The Red Book ELSO 5th Edition

Extracorporeal Life Support:
The ELSO Red Book
5th Edition
Thomas V. Brogan, M.D.

Laurance Lequier, M.D.
Roberto Lorusso, M.D., Ph.D.
Graeme MacLaren, M.D.
Giles Peek, M.D.
SUPPORT
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Estab
lished 198
9 N
Senior Editor: Thomas V. Brogan

Editors: Laurance Lequier, Roberto Lorusso, Graeme MacLaren, Giles Peek
Manuscript Editor: Cindy Cooke
Cover Design: Madeleine Eiche
Back Cover: Photo of Dr. Bartlett and former ECLS patient, 2009
Layout: Peter Rycus
©2017 Extracorporeal Life Support Organization, Ann Arbor, Michigan
Previous editions 1996, 2000, 2005, 2012
Printed in the United States of America
ISBN 978-0-9656756-5-9
Dedication
The editors would like to dedicate the 5th Edi-
tion of the Red Book to Peter Rycus. For many
in the ECMO community, Peter Rycus is ELSO,
having worked tirelessly for over two decades. He
maintains the ELSO data registry, helps to edit the
Red Book and ELSO guidelines, and organizes the
website, conferences, and training courses. His is
often the first face many of us see when arriving at
a meeting. He has published more than 70 studies
using ELSO data and provided data to researchers
throughout the world that have been used in many
more studies. Additionally, Peter has been instru-
mental in the establishment of the global ELSO
chapters and has flown all over the world to insure
their success. He represents ELSO with unending
cheer, boundless enthusiasm, and unmatched orga-
nizational skills. Akin to Radar on “Mash,” he usually seems to know what you want before you
do. Members of the ECMO community owe Peter a debt of gratitude for his work. As the editors
of this Red Book, we take this opportunity to express our appreciation.
We would also like to dedicate this edition to the individual ELSO centers who provide
the clinical care needed to provide patients and families with hope and the opportunity
to live beyond hospital discharge. Nurses, ECMO specialists, perfusionists, respiratory
therapists, physicians, surgeons, researchers, and managers create advances in clinical
care and research. ELSO centers provide the data to the Registry that permits benchmark-
ing, quality improvement, and research. Individuals at ELSO centers unselfishly advise
clinicians at other centers under the difficult circumstances we have all experienced. In
recognition of the immense amount of effort and commitment that you, the people who
use ECMO, devote to your patients, we the editors dedicate this Red Book to you. Please
continue your amazing work!
ELSO Member Centers 2017

List of Contributors
Erik E. Abel, PharmD, BCPS Rubia Baldassarri, MD

Cardiothoracic Surgery and Mechanical Azienda Ospedaliero
Circulatory Support Universitaria Pisana, Pisa
The Ohio State University Wexner Medical
Center, Columbus Ryan Barbaro, MD
Division of Pediatric Critical Care
Darryl Abrams, MD University of Michigan, Ann Arbor
Division of Pulmonary, Allergy, Critical Care
Columbia University College of Physicians Robert H. Bartlett, MD, FELSO
and Surgeons Professor of Surgery, Emeritus
New York-Presbyterian Hospital, New York University of Michigan, Ann Arbor
Peta M. A. Alexander, MBBS Patricia Bastero, MD

Cardiac Intensive Care Unit Texas Children’s Hospital
Boston Children’s Hospital, Boston Baylor College of Medicine, Houston
Gail M. Annich, MD John Beca, MD

The Hospital for Sick Children Paediatric Intensive Care Unit
University of Toronto Starship Children’s Hospital, Auckland
Veronica Armijo-Garcia, MD Dorothy M. Beke, RN, MS, CPNP-PC/AC

The University of Texas Health Science Cardiac Intensive Care Unit
Center at San Antonio Boston Children’s Hospital, Boston
Matthew Bacchetta, MD Jan Bělohlávek, MD, PhD

Division of Thoracic Surgery General Teaching Hospital
Columbia University College of Physicians Charles University of Prague
and Surgeons
New York-Presbyterian Hospital, New York
vii
Contributors
Mirko Belliato, MD Daniel Brodie, MD

IRCCS Policlinico Division of Pulmonary, Allergy, Critical Care
San Matteo Foundation, Pavia Columbia University College of Physicians
and Surgeons
Melania Bembea, MD, PhD New York-Presbyterian Hospital, New York
Charlotte R. Bloomberg Children’s Center
Johns Hopkins University, Baltimore Thomas V. Brogan, MD
Seattle Children’s Hospital
Derek Best, RN, RSCN, BN University of Washington School of Medicine,
Royal Children’s Hospital Seattle
Melbourne, Victoria
Kate L. Brown MD, MPH, MRCP
Shazia Bhombal, MD Pediatric Cardiac Intensive Care
Division of Neonatal & Developmental Medicine Great Ormond Street Hospital for Children,
Stanford University School of Medicine, Palo Alto London
James M. Blum, MD, FCCM Hergen Buscher, MD, FCICM, EDIC, DEAA
Chief, Critical Care, Department of Anesthesiology Intensive Care Medicine
Department of Biomedical Informatics St. Vincent’s Hospital, Darlinghurst
Emory University Hospital, Atlanta
Warwick Butt MBBS, FRACP, FCICM, FELSO
Stephen J. Bottrell, CCP Royal Children’s Hospital
Royal Children’s Hospital University of Melbourne
Melbourne, Victoria
Jonathan W. Byrnes, MD
Susan L. Bratton, MD, MPH The Heart Institute
Division of Pediatric Critical Care Medicine Cincinnati Children’s Hospital Medical Center
University of Utah Department of Pediatrics, University of Cincinnati School of Medicine
Salt Lake City
Daniele Camboni, MD
Nicolas Bréchot, MD, PhD Department of Cardiothoracic Surgery
Groupe Hôpital de la Pitié Salpetrière University Medical Center, Regensburg
Assistance Publique-Hôpitaux de Paris
Université Pierre et Marie Curie, Paris Luis Caneo, MD, PhD
Heart Institute
Steve Brediger, RRT-NPS University of Sao Paulo Medical School
Department of Respiratory Care
Boston Children’s Hospital, Boston Gerry Capatos, MBBCh, FCP
Arwyp Private Hospital
Brian C. Bridges, MD, FAAP Johannesburg
Division of Pediatric Critical Care Medicine
Vanderbilt University School of Medicine, Titus Chan, MD, MS, MPP
Nashville Pediatric Cardiac Critical Care Medicine
Seattle Children’s Hospital, Seattle
viii
Contributors
Yih-Sharng Chen, MD, PhD Carl F. Davis, MB, MCH, FRCS

Chief, Cardiovascular Surgery Department of Paediatric Surgery
National Taiwan University Hospital, Taipei Royal Hospital for Children, Glasgow
Roberto Chiletti MD, FCICM Joseph A. Dearani, MD

Department of Paediatric Intensive Care Unit Departments of Cardiovascular Surgery
The Royal Children’s Hospital, Melbourne Mayo Clinic, Rochester
Jonna Clark, MD Lorenzo Del Sorbo, MD

Pediatric Critical Care Medicine Interdepartmental Division of Critical Care
Department of Bioethics and Humanities Medicine
Seattle Children’s Hospital, Seattle University of Toronto
Alain Combes, MD, PhD Matteo Di Nardo, MD

Groupe Hôpital de la Pitié Salpetrière Department of Pediatric Anesthesia and
Assistance Publique-Hôpitaux de Paris Intensive Care
Université Pierre et Marie Curie, Paris Children’s Hospital Bambino Gesù, Rome
Steven A. Conrad, MD PhD, MCCM Rodrigo Diaz, MD, MEd

Muslow Endowed Chair of Clinical Informatics Unidad ECMO
Professor of Medicine, Pediatrics and Clinica Las Condes, Santiago
Emergency Medicine
Louisiana State University Health Sciences Yves d’Udekem, MD, PhD, FRACS
Center, Shreveport Royal Children’s Hospital
Murdoch Children’s Institute
David S. Cooper, MD, MPH University of Melbourne
The Heart Institute
Cincinnati Children’s Hospital Medical Center Amy L. Dzierba, PharmD, BCPS, BCCCP, FCCM
University of Cincinnati School of Medicine New York-Presbyterian Hospital
Columbia University Medical Center, New York
Timothy Cornell, MD
Department of Surgery Aly El-Banayosy, MD
University of Michigan, Ann Arbor Professor of Surgery and Medicine
INTEGRIS Baptist Medical Center, Oklahoma City
Heidi J. Dalton MD, MCCM
Director, Adult and Pediatric ECLS Eddy Fan, MD, PhD
INOVA Fairfax Hospital, Fairfax Interdepartmental Division of Critical Care
Medicine, University of Toronto
Cosimo D’Alessandro, MD
Hôpital de la Pitié Salpetrière Gail M. Faulkner, RGN, RSCN
Assistance Publique-Hôpitaux de Paris Womens & Childrens CMG
Université Pierre et Marie Curie, Paris Glenfield Hospital, Leicester
ix
Contributors
Richard T. Fiser, MD Matthew T. Harting, MD, MS

University of Arkansas for Medical Science Children’s Memorial Hermann Hospital
College of Medicine University of Texas McGovern Medical
Arkansas Children’s Hospital, Little Rock School, Houston
Francis Fynn-Thompson MD Silvia M. Hartmann, MD

Department of Cardiac Surgery Pediatric Critical Care Medicine
Boston Children’s Hospital, Boston Seattle Children’s Hospital, Seattle
James D. Fortenberry, MD Chris Harvey, MB, ChB, MRCS

Pediatrician-in-Chief Heartlink ECMO Centre
Emory University, Atlanta Glenfield Hospital, Leicester
Björn Frenckner, MD, PhD Micheal L. Heard, RN

Professor of Pediatric Surgery Children’s Healthcare of Atlanta
Karolinska University Hospital, Stockholm
Jenna Heichel, MSN, APRN, CPNP-AC
Curt D. Froehlich, MD Division of Cardiac Critical Care
Nemours Alfred I duPont Hospital for Children Children’s National Health System
Wilmington, Delaware Washington, DC
Samir K. Gadepalli, MD Maggie M. Hickey, RGN, RSCN

Division of Pediatric Surgery Deputy ECMO Coordinator
University of Michigan, Ann Arbor University Hospitals of Leicester
Antonella Galeone, MD, PhD Ronald B. Hirschl, MD

Hôpital de la Pitié Salpetrière Division of Pediatric Surgery
Assistance Publique-Hôpitaux de Paris University of Michigan, Ann Arbor
Université Pierre et Marie Curie, Paris
Stephen B. Horton PhD, CCP, CCP, FACBS
Sandro Gelsomino, MD, PhD Royal Children’s Hospital
Cardio-Thoracic Surgery Department The University of Melbourne
Maastricht University Medical Centre, Maastricht
Aparna Hoskote, MBBS, MD, MRCP
Fabio Guarracino, MD Consultant Pediatric Cardiac Intensive Care
Azienda Ospedaliero Great Ormond Street Hospital for Children,
Universitaria Pisana, Pisa London
Isaac Hammond, PA-C Syed Hussain, MD

Pediatric Cardiothoracic Surgery Department of Thoracic and Cardiovascular
Children’s Hospital at Montefiore, Bronx Surgery
The Cleveland Clinic, Cleveland
x
Contributors
Hanneke IJsselstijn, MD, PhD Stephanie Larsen, BS RRT-NPS

Departments of Pediatric Surgery and Department of Respiratory Care
Intensive Care Boston Children’s Hospital, Boston
Erasmus Medical Center – Sophia Children’s
Hospital, Rotterdam Charles Larson MDCM, FRCPC
Department of Paediatric Intensive Care Unit
William Alex Jakobleff, Jr., MD The Royal Children’s Hospital, Melbourne
Montefiore Medical Center
Albert Einstein College of Medicine, Bronx Guillaume Lebreton, MD
Hôpital de la Pitié Salpetrière
Marcus D. Jarboe, MD Assistance Publique-Hôpitaux de Paris
Division of Pediatric Surgery Université Pierre et Marie Curie, Paris
University of Michigan, Ann Arbor
Philippe Léger, MD
Melissa B. Jones, MSN, APRN, CPNP-AC Hôpital de la Pitié Salpetrière
Division of Cardiac Critical Care Assistance Publique-Hôpitaux de Paris
Children’s National Health System Université Pierre et Marie Curie, Paris
Washington DC
Pascal Leprince, MD, PhD
Hussein D. Kanji, MD, MSc, MPH, FRCP Hôpital de la Pitié Salpetrière
Critical Care Medicine Assistance Publique-Hôpitaux de Paris
University of British Columbia, Vancouver Université Pierre et Marie Curie, Paris
Javier Kattan, MD Laurance L. Lequier, MD

School of Medicine Medical Director, PICU
Pontificia Universidad Católica de Chile, Stollery Children’s Hospital, Edmonton
Santiago
Roberto Lorusso, MD, PhD
Shaf Keshavjee, MD Cardio-Thoracic Surgery Department
Toronto General Hospital Maastricht University Medical Centre
University of Toronto Maastricht
Christa Jefferis Kirk, PharmD William R. Lynch, MD

Seattle Children’s Hospital Thoracic Surgery, Department of Surgery
University of Michigan, Ann Arbor
Roxanne Kirsch, MD, MBE, FRCPC, FAAP
The Hospital for Sick Children Graeme MacLaren, MBBS, FRACP, FRCP,
University of Toronto School of Medicine, FCICM, FCCM
Toronto National University Health System, Singapore
Royal Children’s Hospital, Melbourne
Kevin P. Lally, MD, MS
University of Texas McGovern Medical School Marlous J Madderom, PhD
The Fetal Center at Children’s Memorial Dept. of Pediatric Surgery and Intensive Care
Hermann Hospital, Houston Erasmus Medical Center – Sophia Children’s
Hospital, Rotterdam
xi
Contributors
Jos Maessen, MD, PhD Chirine Mossadegh, RN

Cardio-Thoracic Surgery Department Hôpital Pitié-Salpêtrière
Maastricht University Medical Centre Assistance Publique-Hôpitaux de Paris
Maastricht
Justin Muir, PharmD
Patti Massicotte, MD Clinical Pharmacy Manager
Stollery Children’s Hospital New York-Presbyterian Hospital
Edmonton Columbia University Medical Center, New
York
Ciro Mastroianni, MD, PhD
Hôpital de la Pitié Salpetrière Priya Nair, MBBS
Assistance Publique-Hôpitaux de Paris St. Vincent’s Health Network
Université Pierre et Marie Curie, Paris University of New South Wales, Sydney
Wesley A. McKamie, RRT CCP Jose Navia, MD

Cardiac Perfusionist Department of Thoracic & Cardiovascular
Baptist Medical Center, Little Rock Surgery
The Cleveland Clinic, Cleveland
D. Michael McMullan, MD, FACS
Cardiothoracic Surgery Roy Ochiai, MD, PhD
Seattle Children’s Hospital Department of Anesthesiology
University of Washington Medical School, TohoUniversity School of Medicine, Tokyo
Seattle
Mark T. Ogino, MD FAAP
Giulio Melisurgo, MD Nemours Alfred I duPont Hospital for Children
San Raffaele Hospital Wilmington
Vita-Salute University, Milan
Matthew L. Paden, MD
Malaika Mendonca, MD Division of Pediatric Critical Care
Division Chief, Pediatric Cardiac Critical Care Emory University, Atlanta
Sheikh Khalifa Medical City
Federico Pappalardo, MD
Elizabeth A. Moore, MBA, RN, BSN San Raffaele Hospital
University of Iowa Hospitals, Iowa City Vita-Salute University, Milan
Naoto Morimura, MD, PhD Bhavesh M. Patel, MD, FRCP, RDMS

Department of Emergency Medicine Department of Critical Care Medicine
Yokohama City University Graduate School Mayo Clinic Hospital, Phoenix
of Medicine, Yokohama
Meral Patel, MD
Tracy Morrison, MSQA, BSN, RN Division of Pediatric Critical Care
Premier Health Emory University, Atlanta
Miami Valley Hospital, Dayton
xii
Contributors
Giles J. Peek, MD, FRCS, CTh, FFICM, FELSO Melissa Reynolds, PhD
Chief, Pediatric Cardiothoracic Surgery, Colorado State University
ECMO Director Fort Collins, Colorado
Children’s Hospital at Montefiore, New York
Simon G. Robinson, BM, BS
Vincent Pellegrino MBBS, FRACP, CICM Glenfield, Leicester Children’s Hospital
Alfred Intensive Care Unit University Hospitals of Leicester NHS Trust
Alfred Hospital, Melbourne
Peter P. Roeleveld, MD
Antonio Pesenti, MD, FELSO Consultant Pediatric Intensivist
Università di Milano ECMO Director
Fondazione Cà Granda Ospedale Maggiore Leiden University Medical Center
Policlinico, Milan
Juan J. Ronco, MD, FRCPC
Suneel Pooboni, MBBS, MD, DCH, FRCP, Vancouver General Hospital
FRCPCH, FCCP University of British Columbia Vancouver
University Hospitals of Leicester
Leicester, United Kingdom Peter Rycus, MPH, FELSO
Extracorporeal Life Support Organization (ELSO)
Richard Porter, MBChB, FRCA, FFICM, Ann Arbor, MI
EDIC, PGCert
Heartlink ECMO Centre Lindsay M. Ryerson, MD
Glenfield Hospital Department of Pediatrics
University Hospitals of Leicester NHS Trust Stollery Children’s Hospital, Edmonton
Thomas Pranikoff, MD, FACS Sameh M. Said, MD

Surgeon-in-Chief Departments of Cardiovascular Surgery
Brenner Children’s Hospital, Winston-Salem Mayo Clinic, Rochester
Parthak Prodhan, MD, FAAP, FCCM Caroline Sampson, MBBS, BMedSci, FRCA,
University of Arkansas for Medical Sciences FFICM, EDIC
Arkansas Children’s Hospital, Little Rock Heartlink ECMO Centre
Glenfield Hospital
Lakshmi Raman, MD University Hospitals of Leicester NHS Trust
Department of Pediatrics
University of Texas Southwestern Medical Gregory J. Schears, MD
Center, Dallas. Departments of Anesthesiology
Mayo Clinic, Rochester, MN
Marco Ranucci, MD
Department of Cardiothoracic and Vascular Christof Schmid, MD
Anesthesia and ICU Department of Internal Medicine
IRCCS Policlinico San Donato, Milan, University Medical Center Regensburg
xiii
Contributors
Matthieu Schmidt, MD, PhD Rachel Sirignano, MD

Hôpital de la Pitié Salpetrière Division of Pediatric Critical Care
Assistance Publique-Hôpitaux de Paris Emory University, Atlanta
Université Pierre et Marie Curie, Paris
Jon H Smith, MBChB, MRCP, FRCA
Jamie McElrath Schwartz, MD Freeman Hospital
Charlotte R. Bloomberg Children’s Center Newcastle upon Tyne
Johns Hopkins University School of Medicine,
Baltimore Lamia Soghier, MD
Children’s National Health System
Steven M Schwartz, MD, FRCPC The George Washington University School of
The Hospital for Sick Children Medicine, Washington, DC
The University of Toronto School of Medi-
cine, Toronto Thomas Staudinger, MD
Vienna General Hospital
Arlene Sheehan, RN, MS, NNP Medical University of Vienna
Neonatal ECMO Program
Lucile Packard Children’s Hospital Stanford, Denise M. Suttner, MD
Palo Alto Rady Children’s Hospital
San Diego, CA
Ayan Sen, MD, MSc, FACEP, FCCP
Mayo Clinic College of Medicine Justyna Swol, MD
Mayo Clinic Hospital, Phoenix Intensive Care and Emergency Medicine
HELIOS Frankenwaldklinik, Kronach
Lara Shekerdemian, MB ChB, MD, MHA,
FRACP Ravi R. Thiagarajan, MBBS, MPH
Chief of Critical Care Children’s Hospital Boston
Texas Children’s Hospital Harvard Medical School, Boston
Baylor College of Medicine, Houston
John M. Toomasian, MS, CCP, FELSO
Jayne Sheldrake, RN Extracorporeal Life Support Laboratory
Intensive Care Unit University of Michigan School of Medicine,
The Alfred Hospital, Melbourne Ann Arbor
Billie L. Short, MD, FELSO Sebastian Tume, MD

Children’s National Health System Baylor College of Medicine
The George Washington University School of Texas Children’s Hospital, Houston
Medicine, Washington, DC
Shirley Vallance, MPH
Dr Farah Siddiqui, MBChB Intensive Care Unit
University Hospitals of Leicester The Alfred Hospital, Melbourne
Glenfield General Hospital, Leicester
xiv
Contributors
Krisa Van Meurs, MD

Rosemarie Hess Professor of Neonatal and
Developmental Medicine
Stanford University School of Medicine
Lucile Packard Children’s Hospital, Palo Alto
Leen Vercaemst, B.CP, ECCP, RN, RM

Perfusionist, ECMO Coordinator, Coordinator
Perfusion School Leuven
Gasthuisberg Campus, UZ Leuven
Gregor Walker, MB, MD, FRCS

Department of Paediatric Surger
Royal Hospital for Children, Glasgow
Patrick Weerwind, PhD

Cardiovascular Research Institute Maastricht
(CARIM)
Maastricht University Medical Centre
Maastricht
Anne Marie Winkler, MD

Director of Medical Affairs
Instrumentation Laboratory, Bedford
Jennifer Workman, MD
Division of Pediatric Critical Care Medicine
University of Utah Department of Pediatrics,
Salt Lake City
Yu Xia, MD, MS
Department of Cardiothoracic and Vascular
Surgery
Montefiore Medical Center, Bronx
xv
Preface to the 5th Edition
Since the publication of the 4th edition of the Red Book, significant evolution has occurred in
the application of extracorporeal life support (ECLS). The technology has been improved, making
circuits simpler, smaller, and safer. At the same time, a number of studies have examined ECLS in
adults and children, deepening our understanding of when and how it is used. As a consequence,
the number of ELSO centers had expanded to 465 at the end of 2016, and the only continent that
has yet to see substantial growth in the presence of ECLS centers is Antarctica.
To reflect the rapid expansion of ECLS application, we have altered the structure of this, the
5th Edition of the ELSO Red Book. However, like the 4th Edition, the content closely follows the
ECLS guidelines published by ELSO. The book has been divided into large sections covering issues
related to specific patient populations, including detailed discussion of indications and provision
of mechanical support for these patient groups. These sections are preceded by ECLS principles
that relate to all or nearly all patients receiving mechanical support. The final section covers more
particular applications of ECLS, other forms of mechanical support, and organizational issues.
Throughout this edition the terms extracorporeal membrane oxygenation (ECMO) and ex-
tracorporeal life support (ECLS) are used interchangeably. Despite advances in the technology
and new applications of this support mode, the older and less inclusive term ECMO has proven
to have undying character. As such we have chosen to keep ECMO along with the newer and
broader term ECLS.
As with previous editions, and in the spirit of academic collaboration, any figure, table, or text
not previously bound by copyright may be reproduced in scientific publications without further
permission, conditional on the source being referenced. We would like to express our sincere
gratitude to the experts from the ECLS community who have enthusiastically contributed to this
edition of the Red Book and have advanced the science of ECLS. Also, we wish to thank Cindy
Cooke, our manuscript editor and Peter Rycus, the layout editor.
Thomas V. Brogan
Laurance Lequier
Roberto Lorusso
Graeme MacLaren
Giles Peek
xvii
Table of Contents
Dedication............................................................................................................................v
Preface to the 5th Edition............................................................................................... xvii
I. Extracorporeal Life Support: General Principles
1. The History and Development of Extracorporeal Support.......................................1

Extracorporeal Support: Earliest Beginnings..........................................................1
Global Spread of ECMO.........................................................................................6
Perseverance: Experience and Growing Indications in Adult ECMO.................... 9
References..............................................................................................................12
2. The History of ECMO: First Hand Accounts...........................................................17
The History of ECMO: First Hand Accounts.........................................................17
A Conversation with Dr. Robert H. Bartlett...........................................................17
A Conversation with Dr. Jay Zwischenberger........................................................22
3. Evolution and History of Global ELSO................................................................... 25
EuroELSO..............................................................................................................25
Asia-Pacific ELSO.................................................................................................26
Latin American ELSO...........................................................................................27
South and West Asian ELSO ............................................................................... 28
References............................................................................................................. 29
4. The Physiology of Extracorporeal Life Support......................................................31
Cardiopulmonary Physiology................................................................................31
Cardiopulmonary Pathophysiology.......................................................................33
Cardiopulmonary Pathophysiology during ECMO...............................................33
The ECMO Circuit............................................................................................... 34
Modes of Vascular Access and Perfusion..............................................................36
CO2 Removal.........................................................................................................45
ECMO Management when the Native Lung is Recovering..................................46
Summary................................................................................................................47
5. The Circuit.................................................................................................................. 49
Introduction........................................................................................................... 49
Historical Background.......................................................................................... 49
General Principles of Circuit Design.................................................................... 50
Blood Tubing Plasticizers......................................................................................51
ECLS Circuit Components....................................................................................52
Blood Pumps..........................................................................................................52
Pulsatility...............................................................................................................52
Roller Pumps..........................................................................................................53
Roller Pump Servo Regulation............................................................................. 54
Centrifugal Blood Pumps..................................................................................... 54
Centrifugal Pump Inlet Pressure Monitoring Techniques......................................55
Blood Pump Performance......................................................................................56
Regulatory Status...................................................................................................56
Pump Related Complications.................................................................................57
xix
Table of Contents
Commercial Centrifugal Pumps........................................................................... 60

Gas Exchange Devices..........................................................................................63
Commercial Gas Exchange Devices......................................................................65
Gas Exchanger Related Complications................................................................ 70
Heat Exchange and Heat Regulation.....................................................................71
Heat Exchanger Related Complications................................................................72
Circuit Priming......................................................................................................73
Circuit Monitoring.................................................................................................73
Summary................................................................................................................75
References..............................................................................................................76
6. Adverse Effects of ECLS: The Blood Biomaterial Interaction...............................81
Introduction............................................................................................................81
Normal Hemostasis ..............................................................................................82
Activation of the Coagulation Pathway.................................................................82
Activation of the Fibrinolytic Pathway..................................................................83
Developmental Hemostasis....................................................................................83
Coagulation Pathway Activation and Inflammatory Response............................ 84
Activation of the Coagulation System during ECLS.............................................87
Activation of the Innate Immune System...............................................................87
Endothelial Function in Hemostasis and Circuit Modifications........................... 88
References............................................................................................................. 90
7. Anticoagulation and Disorders of Hemostasis......................................................... 93
Introduction............................................................................................................93
Anticoagulation......................................................................................................93
Anticoagulation Monitoring...................................................................................95
Anticoagulation Laboratory Schedule and Blood Product Replacement.............. 98
Hemorrhagic and Thrombotic Complications...................................................... 99
Conclusions........................................................................................................... 99
References........................................................................................................... 100
8. Transfusion Management during Extracorporeal Support................................. 105
Blood Product Transfusion during Extracorporeal Support................................105
Use of Coagulation Factor Replacement............................................................. 111
References............................................................................................................117
II. Extracorporeal Life Support: Neonatal Respiratory Disease
9. Neonatal Respiratory Diseases............................................................................... 123

Introduction..........................................................................................................123
Congenital Diaphragmatic Hernia (CDH)...........................................................123
Meconium Aspiration Syndrome (MAS).............................................................123
Persistent Pulmonary Hypertension of the Newborn...........................................126
Pneumonia/Sepsis................................................................................................127
Surfactant Deficiency – Hyaline Membrane Disease......................................... 128
Surfactant Deficiency – Term Infants in Respiratory Failure............................. 129
References........................................................................................................... 130
xx
Table of Contents
10. Congenital Diaphragmatic Hernia and ECMO................................................... 133

Introduction..........................................................................................................133
Diagnosis.............................................................................................................133
Management........................................................................................................ 134
Mechanical Ventilation....................................................................................... 134
Inhaled Nitric Oxide............................................................................................135
Sildenafil..............................................................................................................135
Fetal Interventions...............................................................................................136
Management Adjuncts.........................................................................................137
ECMO..................................................................................................................137
Summary..............................................................................................................143
References........................................................................................................... 144
11. Indications and Contraindications in Neonates with Respiratory Failure.........151
Introduction..........................................................................................................151
Patient Selection Criteria.....................................................................................151
Indications............................................................................................................151
Contraindications.................................................................................................152
Weight <2 kg....................................................................................................... 154
Gestational Age <34 wks.................................................................................... 154
Intracranial Hemorrhage......................................................................................155
Irreversible Organ Damage..................................................................................156
Chromosome Abnormalities................................................................................156
Pre-ECMO Ventilation Days...............................................................................156
References............................................................................................................157
12. ECLS Cannulation for Neonates with Respiratory Failure................................ 159
Setup................................................................................................................... 159
VV- or VA- ECMO?............................................................................................ 160
Choice of Cannula and Vessel............................................................................ 160
Cannulation Technique........................................................................................161
Post Cannulation Imaging....................................................................................165
References............................................................................................................167
13. Congenital Comorbidities among Respiratory Neonatal ECLS Patients.......... 169
Background......................................................................................................... 169
Congenital Anomalies......................................................................................... 169
Malignancies........................................................................................................172
Infections.............................................................................................................173
Neurologic...........................................................................................................175
Inborn Errors of Metabolism...............................................................................176
Genetic Abnormalities.........................................................................................176
Prematurity...........................................................................................................177
Conclusion...........................................................................................................177
References........................................................................................................... 178
14. Medical Management of the Neonate with Respiratory Failure on ECLS........ 183
Fluids, Electrolytes, and Nutrition.......................................................................183
Respiratory.......................................................................................................... 184
xxi
Table of Contents
Cardiovascular.....................................................................................................186
Infection...............................................................................................................187
ECMO Circuit Considerations in the Neonatal Patient...................................... 188
Hematologic........................................................................................................ 190
Neurologic System...............................................................................................191
Summary............................................................................................................. 194
References............................................................................................................195
15. Nursing Management of the Neonate with Respiratory Failure.........................201
Nurse or Technician?...........................................................................................202
Background..........................................................................................................202
Respiratory...........................................................................................................202
Prone Positioning on ECMO...............................................................................203
Ventilator-Associated Pneumonia (VAP).............................................................203
Sedation...............................................................................................................203
Cardiovascular.................................................................................................... 204
Neurological........................................................................................................ 204
Fluid Balance–Renal/Elimination........................................................................205
Gastrointestinal (GI) Concerns and Nutrition......................................................205
Hematological Management/Bleeding................................................................206
Bleeding and Anticoagulation Management........................................................206
Hygiene and Skin Care........................................................................................206
Family Support....................................................................................................207
Conclusion...........................................................................................................207
References........................................................................................................... 209
16. Weaning & Decannulation of Neonates with Respiratory Failure on ECLS..... 211
Weaning................................................................................................................ 211
Special Circumstances.........................................................................................212
Neonatal ECMO Trial off....................................................................................212
Decannulation......................................................................................................213
References............................................................................................................215
17. Outcomes, Complications, & Follow-up of Neonates with Respiratory Failure.217
Introduction..........................................................................................................217
Early Survival Outcomes.....................................................................................217
Late Survival Outcomes...................................................................................... 218
Complications with Impact on Long-term Outcomes........................................ 218
Long-term Medical Outcomes............................................................................ 219
Long-term Neurodevelopmental Outcomes........................................................ 220
Outcomes in Congenital Diaphragmatic Hernia..................................................222
Recommendations for Long-term Followup....................................................... 224
References............................................................................................................227
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III. Extracorporeal Life Support: Pediatric Respiratory Disease
18. Pediatric Respiratory Diseases Predisposing to ECLS.........................................231

Epidemiology of ECLS for Respiratory Support.................................................231
Acute Respiratory Failure....................................................................................231
Status Asthmaticus ..............................................................................................232
The Immunocompromised...................................................................................233
Mediastinal Masses..............................................................................................233
Pulmonary Hemorrhage ..................................................................................... 234
Perioperative Support for Airway Surgery ........................................................ 234
Severe Air Leak ................................................................................................. 234
ECLS for Bridge to Lung Transplant and Preoperative Rehabilitation ............. 234
Burns....................................................................................................................235
Respiratory Support of Patients with Congenital Heart Disease.........................235
Prolonged Respiratory ECLS...............................................................................235
Summary..............................................................................................................235
References............................................................................................................237
19. Indications & Contraindications in Children with Respiratory Failure........... 239
Introduction......................................................................................................... 239
Indications........................................................................................................... 239
An Approach to an Unknown Cause of Respiratory Failure............................... 244
Summary............................................................................................................. 244
References............................................................................................................245
20. ECLS Cannulation for Children with Respiratory Failure.................................247
Introduction..........................................................................................................247
Preferred Routes..................................................................................................247
Technique............................................................................................................ 248
Complications......................................................................................................252
References........................................................................................................... 254
21. Comorbidities among Pediatric Patients with Respiratory Failure................... 255
Epidemiology.......................................................................................................255
General Considerations........................................................................................256
Pediatric Respiratory Failure-Risk Factors for In-Hospital Mortality.................256
Coexisting Conditions.........................................................................................257
Genetic Abnormalities........................................................................................ 258
Complications and Therapies.............................................................................. 259
Hospital Volume...................................................................................................261
Prediction of Mortality Risk Prior to ECLS Initiation.........................................261
Conclusion...........................................................................................................262
References............................................................................................................263
22. Management of the Pediatric Respiratory Failure Patient on ECMO...............267
Introduction..........................................................................................................267
Patient Management........................................................................................... 268
Extubation on ECMO..........................................................................................276
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Diagnostic Tools in ECMO..................................................................................277

Other Interventions............................................................................................. 278
Complications..................................................................................................... 278
Followup............................................................................................................. 278
Conclusion.......................................................................................................... 278
References........................................................................................................... 279
23. Nursing Management of the Child with Respiratory Failure on ECLS............ 283
Introduction..........................................................................................................283
Daily Assessment.................................................................................................283
Daily Patient Care............................................................................................... 284
Wound Care..........................................................................................................286
Daily Activities....................................................................................................287
Conclusion.......................................................................................................... 288
References........................................................................................................... 289
24. Weaning and Decannulation of Children with Respiratory Failure on ECLS...291
Strategies for Withdrawal of ECLS Support.......................................................291
Withdrawal of ECLS Support as Palliative Withdrawal of Care.........................292
Weaning Support and Trialing.............................................................................292
Technique for Decannulation of Patients on Venovenous ECLS.........................293
Continuing Venous Access after Decannulation................................................. 294
Approaches to Inadvertent Decannulation.......................................................... 294
References............................................................................................................296
25. Outcomes, Complications, & Followup of Children with Respiratory Failure.297
Introduction..........................................................................................................297
Outcomes.............................................................................................................297
Long-term Outcomes.......................................................................................... 299
ECMO Complications......................................................................................... 300
References........................................................................................................... 304
IV. Extracorporeal Life Support: Neonatal and Pediatric Cardiac Disease
26. Neonatal and Pediatric Cardiovascular Diseases Predisposing to ECLS...........307

Introduction..........................................................................................................307
Indications and Outcomes................................................................................... 308
ECMO in Patients with Functionally Univentricular Circulation.......................312
Outcome and Risk Factors for Death...................................................................313
Conclusions......................................................................................................... 314
References............................................................................................................315
27. Extracorporeal Cardiopulmonary Resuscitation in Children.............................321
Introduction..........................................................................................................321
ECPR Definition..................................................................................................321
ECMO for Failed CPR.........................................................................................321
ECPR Utilization and Epidemiology...................................................................322
Survival to Hospital Discharge after ECPR.........................................................322
Patient Selection for ECPR..................................................................................323
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Duration of CPR and ECPR Outcomes...............................................................323

Neurologic Injury in ECPR.................................................................................323
ECPR in Specific Populations............................................................................. 324
ECMO Equipment and Organizing an ECPR Team ...........................................325
Long-term Outcomes Following ECPR...............................................................327
Summary..............................................................................................................327
References........................................................................................................... 328
28. ECMO for Adults with Congenital Heart Disease................................................331
Introduction..........................................................................................................331
Specific Cardiac Defects Requiring ECMO .......................................................331
Indications for ECMO Support in ACHD............................................................333
Management Strategies....................................................................................... 334
Tips/Pitfalls for ECMO in Patients with Previous Sternotomies........................ 334
Results and Outcomes Following ECMO for ACHD..........................................335
References............................................................................................................337
29. Indications and Contraindications in Children with Cardiovascular Disease.. 339
Preoperative Stabilization................................................................................... 339
Perioperative Support......................................................................................... 340
Mechanical Support beyond the Perioperative Period........................................ 340
Low Cardiac Output Syndrome.......................................................................... 340
Bridge to Transplantation.....................................................................................341
Posttransplantation Support.................................................................................342
Procedural Support..............................................................................................342
ECPR...................................................................................................................342
Respiratory Support.............................................................................................343
References........................................................................................................... 344
30. Neonatal/Pediatric Cardiac Cannulation..............................................................347
Neonatal/Pediatric Cardiac Cannulation..............................................................347
Neck Cannulation................................................................................................347
Transthoracic Cannulation.................................................................................. 348
Venting................................................................................................................ 350
Not Venting..........................................................................................................351
Troubleshooting...................................................................................................351
Conclusion.......................................................................................................... 354
References............................................................................................................355
31. Comorbidities and Outcomes in Pediatric Patients for Cardiac Disease...........357
Background..........................................................................................................357
Preexisting Comorbidities....................................................................................357
Acquired Comorbidities.......................................................................................361
Summary..............................................................................................................363
References........................................................................................................... 364
32. Medical Management of Neonates & Children with Cardiovascular Disease...367
Introduction..........................................................................................................367
Utilization of Cardiovascular ECLS....................................................................367
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Management of Common Issues for the Cardiac ECLS Patient ........................ 368
Cardiovascular Assessment and Monitoring...................................................... 370
Ventilator Management........................................................................................371
Inotrope/Vasoactive Medications.........................................................................372
Other Organ System Considerations Specific to the Cardiac ECLS Patient.......372
Psychological Support.........................................................................................373
Conclusion.......................................................................................................... 374
33. Nursing Management of Children with Cardiovascular Disease...................... 379
Introduction......................................................................................................... 379
Nursing Assessment ........................................................................................... 379
Cardiac Anatomy Considerations....................................................................... 380
Respiratory Considerations................................................................................. 380
Prevention of Infection....................................................................................... 380
Neurologic Considerations..................................................................................381
Rehabilitation.......................................................................................................382
Integumentary Considerations.............................................................................382
Nursing Roles in Rapid Deployment...................................................................383
Family Support....................................................................................................383
Reference.............................................................................................................385
34. Weaning Pediatric Cardiac ECMO........................................................................387
Introduction..........................................................................................................387
When to Attempt Weaning...................................................................................387
Predictors of Successful Weaning....................................................................... 389
Weaning Trial...................................................................................................... 389
Speed of Weaning............................................................................................... 390
Optimizing for Decannulation............................................................................ 390
Decannulation..................................................................................................... 390
Failure to Wean....................................................................................................392
Conclusion...........................................................................................................393
References........................................................................................................... 394
35. Outcomes/Complications/Followup of Children with Cardiovascular Disease.395
Introduction..........................................................................................................395
Early Survival Outcomes.....................................................................................395
Single Ventricle Patients......................................................................................396
Heart Failure and Transplantation........................................................................396
Longer-term Survival...........................................................................................397
Early Neurological Outcome...............................................................................397
Longer-term Neurodevelopmental Outcome.......................................................397
Long-term Quality of Life (QOL).......................................................................397
Followup............................................................................................................. 398
Conclusions......................................................................................................... 399
References............................................................................................................401
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V. Extracorporeal Life Support: Adult Respiratory Disease
36. Adult Respiratory Diseases Predisposing to ECLS.............................................. 405

Introduction..........................................................................................................405
Initial Diagnostic and Management Approaches to Respiratory Disease ...........405
Imaging and Acute Respiratory Distress Syndrome (ARDS)..............................406
Gas Exchange......................................................................................................406
Hemodynamic Stabilization and Echocardiography in Acute Hypoxemia.........407
Immunosuppressed Hosts....................................................................................407
Imitators of ARDS.............................................................................................. 409
Open Lung Biopsy.............................................................................................. 410
Summary.............................................................................................................. 411
References............................................................................................................412
37. Indications & Contraindications in Adults with Respiratory Failure............... 415
Introduction..........................................................................................................415
ECLS for Rescue from Refractory Hypoxemia...................................................416
ECLS for Rescue from Refractory Hypercapnia................................................ 418
ECLS for Rescue from Ventilator-Induced Lung Injury..................................... 419
ECLS Consideration in Patients with Potentially Reversible Diseases...............421
Potential ECLS Contraindications.......................................................................422
Conclusions..........................................................................................................423
References........................................................................................................... 424
38. ECLS Cannulation for Adults with Respiratory Failure.................................... 429
Introduction......................................................................................................... 429
Cannulation Decision Making for Adult Respiratory Failure............................. 430
Technical Aspects of Cannulation for Adult Respiratory Failure........................433
References............................................................................................................436
39. Comorbidities among ECLS Patients with Respiratory Failure........................ 439
Introduction......................................................................................................... 439
Comorbidities and Patient Outcome from ECLS............................................... 439
Comorbidities Identified in Adult VV-ECLS...................................................... 440
Impact of Comorbidities on Outcome in Non-ECLS Adults...............................442
Specific Common Comorbidities and Their Interaction with ECLS...................442
Summary............................................................................................................. 444
References............................................................................................................445
40. Medical Management of the Adult with Respiratory Failure on ECLS............ 449
Introduction......................................................................................................... 449
Ventilatory Support............................................................................................. 449
Prone Positioning................................................................................................ 450
Bronchoscopy..................................................................................................... 450
Airway Hemorrhage............................................................................................ 450
Tracheostomy.......................................................................................................451
Awake Extubation................................................................................................451
Cardiovascular Support: Vasopressors and Inotropes..........................................451
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Right Heart Failure..............................................................................................452

Venoarterial Support.............................................................................................452
Arrhythmias..........................................................................................................452
Sedation Management.........................................................................................452
Delirium...............................................................................................................453
Intracerebral Hemorrhage....................................................................................453
Renal Support..................................................................................................... 454
Nutrition.............................................................................................................. 454
Endocrine Support.............................................................................................. 454
Hematological Abnormalities............................................................................. 454
Infection as the Indication for Respiratory ECLS Support................................. 454
Infection Complicating ECLS Support................................................................455
Conclusion...........................................................................................................456
References............................................................................................................457
41. Nursing Care of the Adult Respiratory ECLS Patient........................................ 459
Introduction......................................................................................................... 459
ECLS Specific Nursing Care.............................................................................. 459
Checklists and Preventative Care....................................................................... 459
Cannula Care...................................................................................................... 460
ECLS Circuit Observations and Monitoring of Circuit Function....................... 460
Console Settings, Safety, and Responses............................................................ 460
Renal Replacement............................................................................................. 460
Emergency Responses.........................................................................................461
General Nursing Care of the ECLS Patient ........................................................461
Neurological Assessment and Sedation Practice (and Awake ECLS).................461
Patient Moves and Pressure Area Care................................................................461
Prevention of Bleeding........................................................................................462
Hygiene and Infection Prevention.......................................................................462
Nutrition...............................................................................................................462
Bowel Management.............................................................................................463
Staff Support........................................................................................................463
Role Allocation....................................................................................................463
References........................................................................................................... 464
42. Weaning and Decannulation of Adults with Respiratory Failure on ECLS...... 465
Introduction..........................................................................................................465
VV-ECLS Physiology..........................................................................................465
Initiation of VV-ECLS.........................................................................................466
Maintaining VV-ECLS........................................................................................466
Recirculation........................................................................................................467
Weaning VV-ECLS............................................................................................. 468
Liberation and Decannulation............................................................................. 468
Other Modes of Support..................................................................................... 469
The Patient Who Cannot be Weaned................................................................... 469
Conclusion.......................................................................................................... 469
References........................................................................................................... 470
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43. Outcomes and Complications of Adult Respiratory ECLS..................................471

Short-term Outcome of ARDS Patients on VV-ECLS........................................471
Long-term Outcomes after ECLS for Severe ARDS...........................................472
Main ECLS Related Complications and Their Impact on Outcome...................472
Mortality Risk Factors and Outcome Prediction for ECLS Candidates............. 474
Volume-Outcome Effect and ECLS Activity Organization................................. 474
Conclusion...........................................................................................................475
References............................................................................................................476
VI. Extracorporeal Life Support: Adult Cardiac Disease
44. Adult Cardiovascular Defects, Diseases, and Procedures................................... 479

Acute Myocardial Infarction............................................................................... 479
Postcardiotomy....................................................................................................481
Acute Myocarditis............................................................................................... 484
Acute Pulmonary Embolism................................................................................486
Cardiogenic Shock in Other (Rare) Non Surgery-Related Etiologies................ 488
Cardiocirculatory Support or Bailout Assistance .............................................. 488
Preoperative Support .......................................................................................... 489
Acutely Decompensated Chronic Cardiomyopathy ........................................... 490
Conclusions..........................................................................................................491
References............................................................................................................493
45. Extracorporeal Cardiopulmonary Resuscitation in Adults.................................501
Introduction..........................................................................................................501
Definition of ECPR..............................................................................................502
Organizational Issues Related to ECPR Implementation....................................502
Facilities and Equipment Appropriate for ECPR.................................................503
The Ideal ECPR Patient.......................................................................................503
ECPR Cannulation Technique............................................................................ 504
Optimal Cannula Diameter..................................................................................506
Reperfusion Technique and Initial ECLS Flow Setting.......................................506
Complications during Implantation and Initial Launching..................................506
Rhythm Analysis, Conversion of Ventricle Fibrillation.......................................507
Postresuscitation Care Monitoring...................................................................... 508
Studies on ECPR in IHCA.................................................................................. 508
Studies on ECPR in OHCA................................................................................ 509
Studies on ECPR in the Pediatric Population..................................................... 510
ECPR as a Stepwise Approach to Refractory CA............................................... 510
Weaning from ECLS after ECPR........................................................................ 510
Ethical Issues in ECPR....................................................................................... 510
Future................................................................................................................... 511
References............................................................................................................512
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46. General Considerations for VA-ECMO Implantation..........................................517

Peripheral VA-ECMO is Fast and Easy to Implant.............................................517
Peripheral VA-ECMO is Efficient as a Circulatory Support Device...................517
ECMO is Cost Effective......................................................................................517
ECMO Does Not Unload the Left Ventricle....................................................... 518
ECMO Decreases the Transpulmonary Flow..................................................... 518
ECMO is Associated with a High Rate of Complications.................................. 518
ECMO Requires the Patient to Stay in Bed........................................................ 518
ECMO and Hemodynamic Criteria.................................................................... 519
ECMO and Neurological Status......................................................................... 519
ECMO and Cardiac Arrest.................................................................................. 519
ECMO vs. Other Short-Term Circulatory Support Devices............................... 520
VA-ECMO and Contraindications...................................................................... 520
Conclusion.......................................................................................................... 520
References............................................................................................................521
47. Cannulation for ECMO in Adult Patients with Cardiac Failure....................... 523
Peripheral Cannulation .......................................................................................525
References........................................................................................................... 530
48. Adult Cardiac ECLS Acute Complication and Comorbidity Management...... 533
Introduction..........................................................................................................533
Acute Complications during ECLS......................................................................533
Multimorbidity Patients ..................................................................................... 539
Summary............................................................................................................. 540
References............................................................................................................542
49. Medical Management of the Adult with Cardiovascular Disease........................551
Introduction..........................................................................................................551
General ICU Management ..................................................................................551
Monitoring of the ECMO Circuit........................................................................552
Daily Echocardiography Monitoring...................................................................552
Management of Pulmonary Edema under VA-ECMO........................................553
Blood and Coagulation Issues..............................................................................553
Cannula Site Related Complications.................................................................. 554
Nosocomial Infections........................................................................................ 554
Drug Pharmacokinetics....................................................................................... 554
Weaning from VA-ECMO....................................................................................555
Conclusion...........................................................................................................555
References............................................................................................................556
50. Nursing Management of Adults with Cardiovascular Disease............................561
Introduction..........................................................................................................561
Management of the ECMO Device.....................................................................561
Preventing Complications....................................................................................562
Adopting the Specifics of ECLS to Patient Regular Monitoring.........................565
References........................................................................................................... 568
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51. The Weaning Process and Decannulation in Adult Cardiac Patients................ 569
Weaning............................................................................................................... 569
Echocardiography in the Weaning Process......................................................... 570
Decannulation......................................................................................................571
VA-ECMO Decannulation...................................................................................572
Emergent ECMO Decannulation .......................................................................572
Conclusion...........................................................................................................572
References............................................................................................................573
52. Neurologic and Pulmonary Complications in Adult ECLS................................ 575
Introduction..........................................................................................................575
Factors Determining Neurologic Outcome..........................................................575
Incidence of Neurologic Injury............................................................................576
Factors and Incidence of Pulmonary Complications...........................................577
Return to Work Expectations and Quality of Life.............................................. 579
Conclusion.......................................................................................................... 580
References............................................................................................................581
VII. Extracorporeal Life Support: Special Indications
53. Pregnancy and Extracorporeal Life Support....................................................... 583

Physiological Changes During Pregnancy...........................................................583
Adult Respiratory Distress Syndrome (ARDS) in Pregnancy.............................585
Severe Cardiac Disease in Pregnancy..................................................................585
Special Considerations for ECMO Therapy during Pregnancy...........................585
Complications of ECMO.................................................................................... 588
Specific Complications of Pregnancy to Consider during ECMO..................... 589
Experience with ECMO in the Puerperium Period............................................. 590
References............................................................................................................591
54. Trauma and Extracorporeal Life Support........................................................... 593
Introduction..........................................................................................................593
Indications for ECLS in Trauma Patients........................................................... 594
Conclusions..........................................................................................................596
References............................................................................................................597
55. Transport of the Patient Supported with ECMO................................................ 599
Inter-Hospital Transport...................................................................................... 599
Special Transport Situations................................................................................607
Conclusion.......................................................................................................... 608
References........................................................................................................... 609
56. ECMO for Septic Shock......................................................................................... 613
Introduction..........................................................................................................613
Indications........................................................................................................... 614
Cannulation Strategies.........................................................................................615
Central Cannulation............................................................................................ 618
Management on ECMO...................................................................................... 619
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Outcomes.............................................................................................................621
Conclusions..........................................................................................................622
References............................................................................................................623
57. Extracorporeal Life Support for Severe Cardiotoxic Drug Poisoning...............627
Introduction..........................................................................................................627
ECLS for Poisoning-induced Cardiovascular Failure ........................................627
Venovenous ECLS for Poisoning-induced Respiratory Failure ..........................632
Conclusion...........................................................................................................632
References........................................................................................................... 634
58. ECMO as Bridge to Lung Transplantation.......................................................... 639
Introduction......................................................................................................... 639
Cannula Configurations...................................................................................... 639
Patient Selection and Timing of ECMO Initiation...............................................642
Patient Management Strategies............................................................................642
ECMO Use in the Intraoperative and Posttransplantation Settings.....................643
Outcomes of ECMO as BTT.............................................................................. 644
Limitations to Bridge to Transplant.................................................................... 644
Conclusions......................................................................................................... 644
References............................................................................................................645
59. ECLS in Heart Transplantation............................................................................ 649
Introduction......................................................................................................... 649
Pretransplant ECMO........................................................................................... 649
ECLS after Heart Transplantation........................................................................655
References........................................................................................................... 659
60. Immunodeficiency and ECLS................................................................................ 665
Introduction..........................................................................................................665
Support in Pediatric and Adult Patients with Solid Organ and Blood Cancer.....665
ECLS Utilization in Patients with Malignancy....................................................665
Indications, Contraindications and Specific Considerations................................666
ECLS in Patients Treated with Hematopoietic Stem Cell Transplant (HSCT)....667
Technical Considerations ....................................................................................667
Use of ECLS to Manage Respiratory Failure after HSCT...................................667
Use of ECLS to Manage Heart Failure after HSCT .......................................... 668
Vascular Access................................................................................................... 668
Management of Coagulation after HSCT........................................................... 669
ECLS in Adult Human Immunodeficiency Virus (HIV) Patients....................... 669
ECLS in Patients with PJP: the South Africa Experience.................................. 669
ECLS Candidate Selection for HIV+/PJP+ ....................................................... 670
Antiretroviral Drugs (ARVs) and ECLS............................................................. 670
ECLS in Adult and Pediatric Autoimmune Diseases.......................................... 670
References............................................................................................................673
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VIII. ECLS: Procedures and Adjunctive Extracorporeal Therapies
61. Procedures on ECLS............................................................................................... 679

Introduction......................................................................................................... 679
Decision Threshold-Three Questions................................................................. 680
General Principals............................................................................................... 680
General Measures................................................................................................681
ECMO Circuit Related Procedures......................................................................681
Diagnostic Procedures.........................................................................................682
Surgical Procedures General................................................................................683
Trauma and Burn Patients....................................................................................685
Specific Surgical Procedures in Respiratory ECMO...........................................687
Specific Surgical Procedures in Cardiac ECLS...................................................687
Conclusion.......................................................................................................... 688
62. Extracorporeal Elimination....................................................................................697
Acute Kidney Injury (AKI) during ECLS............................................................697
Apheresis during ECLS........................................................................................701
References........................................................................................................... 708
63. Extracorporeal Carbon Dioxide Removal............................................................ 713
Introduction..........................................................................................................713
Considerations for ECCO2R...............................................................................713
Contraindications and Limitations.......................................................................715
Physiological Targets...........................................................................................715
Circuit Configurations.........................................................................................716
Anticoagulation Strategy and Impact of Low Extracorporeal Blood Flow.........716
Management Considerations in the Event of Circuit Failure..............................717
Weaning ECCO2R...............................................................................................717
Conclusion...........................................................................................................717
References........................................................................................................... 718
64. Other Forms of Extracorporeal Cardiovascular Support...................................721
Introduction..........................................................................................................721
Intraaortic Balloon Pump.....................................................................................722
IMPELLA............................................................................................................723
Levitronix CentriMag......................................................................................... 724
Anticoagulation....................................................................................................725
Right Ventricular Failure.....................................................................................725
Mobilization.........................................................................................................726
Weaning................................................................................................................726
References........................................................................................................... 728
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IX. Extracorporeal Life Support: Organization
65. Implementing an ECLS Program...........................................................................731

Identify the ECMO Service.................................................................................731
Identify Your Customer........................................................................................732
Identify the Employees and Equipment Needed .................................................733
Develop the Key Processes................................................................................. 734
Mistake-Proof the Processes................................................................................735
Develop Measures, Improvement Goals and Controls........................................735
Continuously Improving and Sustaining a Program............................................736
References........................................................................................................... 738
66. Centralization and Regionalization of ECLS Resources......................................741
Background..........................................................................................................741
Relationship of Centralization to ECMO.............................................................741
The ECMO Center...............................................................................................742
Outlying Centers and Critical Care Transport.....................................................743
ECMO Transport..................................................................................................743
Summary..............................................................................................................745
References............................................................................................................746
67. Education and Training...........................................................................................747
Introduction..........................................................................................................747
Educational Process............................................................................................ 748
Establishing ECMO Competency....................................................................... 749
ECMO Training Program.................................................................................... 750
ECMO Training Course Curriculum .................................................................. 750
Didactic (Classroom) Course...............................................................................751
Training Labs...................................................................................................... 754
Water Drills..........................................................................................................755
Animal Lab...........................................................................................................755
High Fidelity Simulation.....................................................................................755
ELSO ECMO Training Course............................................................................756
Maintaining Competency Standards....................................................................757
Maintaining ECMO Competency....................................................................... 758
Summary............................................................................................................. 759
References........................................................................................................... 760
Addendum 67-1....................................................................................................762
68. Quality of Care in Extracorporeal Life Support................................................. 765
Introduction..........................................................................................................765
Summarizing the Evidence for Interventions to Improve Outcomes..................766
Identify Local Barriers to Implementation of Changes.......................................767
Performance Measurement..................................................................................767
Implementation of the Interventions................................................................... 768
Data Collection and Measuring Quality............................................................. 768
Quality in Small vs. Large ECLS Programs....................................................... 769
New Technology................................................................................................. 769
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Summary............................................................................................................. 769
References........................................................................................................... 770
69. The Economics of ECMO....................................................................................... 773
Introduction..........................................................................................................773
Fundamental Considerations................................................................................773
Measuring the Overall Cost of ECMO............................................................... 774
International Models of ECMO Finance.............................................................776
The Future of ECMO.......................................................................................... 778
References........................................................................................................... 779
70. The Ethics of ECLS..................................................................................................781
Introduction..........................................................................................................781
Expanding Utilizations of ECLS: Application and Resource Allocation............781
Complex Medical Decision Making in ECLS: Starting and Stopping ECLS.....783
Research in ECLS: Ethical Challenges and Controversy....................................787
Practical Considerations..................................................................................... 788
Conclusion.......................................................................................................... 788
References........................................................................................................... 790
71. Strategies for Medication Management in ECLS................................................ 795
Introduction..........................................................................................................795
Pharmacokinetics.................................................................................................795
Pharmacokinetic Changes in Critical Illness and ECLS......................................797
Experience and Recommendations Based on Medication Class........................ 798
General Dosing Strategy .....................................................................................803
References............................................................................................................806
72. The Registry of the Extracorporeal Life Support Organization........................ 809
Registry Data Collection .................................................................................... 810
Registry Reports.................................................................................................. 811
Current Registry Data Summary.........................................................................812
Neonatal Trends...................................................................................................812
Pediatric Trends...................................................................................................812
Adult Trends.........................................................................................................812
Cardiac Trends.....................................................................................................813
Summary..............................................................................................................813
References........................................................................................................... 814
Glossary.......................................................................................................................... 815
Appendix 1: Pediatric ECLS Cannula Characteristics...............................................817
Appendix 2: Adult ECLS Cannula Characteristics (Edwards)................................. 818
Appendix 3: Adult ECLS Cannula Characteristics (Medtronic)............................... 819
Appendix 4: Adult ECLS Cannula Characteristics (Maquet)................................... 820
Appendix 5: Adult ECLS Cannula Characteristics (Sorin)........................................821
Appendix 6: Adult ECLS Cannula Characteristics (Medos)..................................... 822
Appendix 7: Double Lumen ECLS Cannula Characteristics ................................... 823
Index ............................................................................................................................... 825
xxxv
1
The History and Development of Extracorporeal Support
James D. Fortenberry, MD, MCCM, Roberto Lorusso, MD, PhD
“During that long night, helplessly watching blood driven by a syringe to the right heart
the patient struggle for life as her blood became to generate artificial circulation in an animal
darker… the idea naturally occurred to me that model. Results were promising, but limited by
if it were possible to remove continuously some lack of anticoagulation, leading Richardson to
of the blue blood…put oxygen into that blood... note, “I infer that resuscitation [and artificial
and then to inject continuously the now-red circulation]…is a possible process, and that it
blood back into the patient’s arteries, we might demands only the elements of time, experiment
have saved her life”. and patience for its development of a demon-
strable fact of modern science.”2 In the 1920’s
-John Gibbon MD Russian physician Sergei Brukhonenko and
Extracorporeal Support: Earliest Beginnings
Surgeon John Gibbon eloquently described

above the anguish and powerlessness he felt as
a young research fellow in 1931 over the loss
of a young patient to a pulmonary embolism.1
The memory of that single patient was the
impetus for Dr. Gibbon to embark on an effort
dedicated to the proposition that mimicking or
replacing normal human body cardiopulmonary
functions during an acute illness could save
lives. However, the remarkable story of the
development of extracorporeal support can be
traced as far back as 1693, when Jean Baptiste
Denis performed experiments cross-transfusing
the blood of a human with the “gentle humors
of a lamb” to determine if living blood could be
transmitted between two species (Figure 1-1).
Benjamin Ward Richardson MD, noted British Figure 1-1. Woodcarving of experiments circa
1693 by Jean Baptiste Denis to drain human
physician and anesthetist, conducted experi- blood into a sheep.
ments in the 1860s using injected oxygen and
1
Chapter 1
collaborators developed a total body perfusion a bubble oxygenator he invented with Richard
system, called the “autojector,” using excised DeWall. The remarkable chronicles of early
donor animal lungs for blood oxygenation, and extracorporeal development were captured by
later a bubble oxygenator, to perform successful Dr. Lillehei in the first edition of the ELSO
animal experiments with isolation of the heart.3 “Red Book.”4,5
Dr. Gibbon began his journey to further While use of extracorporeal support proved
advance the field of extracorporeal support in feasible in limited settings in the operating
humans in the 1930s. Collaborating with his theater, more prolonged use past several hours
wife Mary at Jefferson Medical School in Phila- outside of the OR remained problematic. Early
delphia, Dr. Gibbon developed a freestanding attempts in the ICU for extracorporeal sup-
roller pump device for extracorporeal support. port were limited by the nature of available
The initial Gibbon heart-lung machine was the artificial lung devices and blood gas interfaces,
size of a spinet piano that created thin films which tended to induce blood component dam-
of deoxygenated blood passing over a screen age from the direct exposure to oxygen gas.6,7
exposed to oxygen.1,4 Twenty-two years would Bubble oxygenators did not create an interface
pass before Dr. Gibbon was able to use the de- between blood and gas, producing hemolysis
vice in the operating theater. On May 6, 1953 he within hours.
performed the first successful extracorporeally The next steps in the development of ex-
assisted repair of an atrial septal defect in 18 tracorporeal support were a testimony to the
year-old Cecilia Bavolek (Figure 1-2). collaboration between biomedical engineers,
The esteemed cardiac surgeon C. Walton physiologists, physicians, and surgeons to cre-
Lillehei, MD (Figure 1-3) further advanced ate devices that could provide support for more
extracorporeal circulation in the operating room extended time periods inside and outside the OR
in 1954 when he performed cardiac surgery via without massive hemolysis and plasma leakage.
cross circulation and then progressed to using Two basic innovations drove this breakthrough:
Figure 1-2. John H. Gibbon MD and patient Cecilia Bavolek, who underwent the landmark repair in
1953 of an atrial septal defect utilizing an extracorporeal circuit. The two pose before the Plexiglas-
covered “lung” ten years after the procedure. Right: original device, approximately the size of a spinet
piano (source: Jefferson University Archives).
2
the invention of silicone and the ability to al- culating flow, significantly less heparin would
low prolonged circuit-blood exposure through be required.7 They showed circuits could be
controlled anticoagulation.8 The development of used for days without clot formation or hemor-
synthesis of silicone rubber by Kammermeyer rhage.11,12 Bartlett and Drinker also described
in 1957 revolutionized the artificial lung. 8,9 and developed an approach to continuously
Silicone possessed the strength to withstand titrating coagulation and heparin dosing via the
hydrostatic pressure and yet remain permeable activated clotting time, a time honored approach
to gas transfer. Collaborative innovators, in- that has remained in place for over 40 years.7
cluding Drs. Theodor Kolobow, Al Gazzaniga, The benefits of extracorporeal support
Phil Drinker, and Robert Bartlett pioneered during a procedure and recovery postopera-
experiments in developing a silicone membrane tively in children with congenital heart disease
lung that allowed prolonged circulation1. Kolff encouraged physicians to expand its operating
and Kolobow independently identified and ad- room use. Baffes et al.13 first reported the use
vanced the use of silicone membranes for gas of extracorporeal support for surgery itself,
exchange, and Kolobow identified the enhanced followed by experiences from other centers. In
gas exchange activity of a spiral-wrapped 1972, Bartlett, Gazzaniga, and associates first
silicone membrane.9,10 The use of the silicone successfully used cardiac ECMO for 36 hours
“membrane oxygenator” also led to the use of in a 2-year old infant with cardiac failure fol-
the term extracorporeal membrane oxygenation lowing a Mustard procedure for correction of
(ECMO). Bypass became feasible in animal transposition of the great vessels; they subse-
models for days at a time.11 quently reported a growing series of cases.14 In-
Bartlett and Drinker also recognized that dications in these patients related to low cardiac
the cardiac patient in the operating room needed output due to ventricular failure or pulmonary
“infinite” anticoagulation due to stagnation in vasospastic crisis following surgical repair of
open surgical repair, but with long-term cir- complex heart lesions.
Figure 1-3. Bubble oxygenator invented and first use in 1954. Left: Inventor Richard DeWall with
device. Right: Dr. C. Walton Lillehei, cardiovascular surgeon and innovator in cardiopulmonary bypass.
3
Chapter 1
With this improved technology, extracor- bedside from the laboratory, and sought consent
poreal support was extended outside of the from the infant’s mother, who had delivered her
operating theater. Dr. J.D. Hill reported on the after crossing the Mexican border into Orange
first successful cannulation and prolonged extra- County, California. She signed the consent and
corporeal circuit use in a patient in an intensive then disappeared, leaving her baby behind. The
care setting in 1972.15 The patient was a 24-year nursing staff named the child Esperanza, Span-
old male with a ruptured aorta and posttraumatic ish for “hope.”18 She received ECMO support
acute respiratory distress syndrome following for 72 hours, and then was decannulated with
a motorcycle accident, and who was supported recovery, and a subsequent life with children
with a membrane lung developed by Morrie of her own (Figure 1-5).19,20 Bartlett’s success
Bramson. The patient received venoarterial and further experience helped drive growing
support for 75 hours, with subsequent decan- successful expansion of use in neonates around
nulation and survival. Adult ECMO support the world. From 3 survivors among 16 patients
efforts continued, although survival rates were treated by Bartlett and coworkers, clinical
initially low. outcomes persistently improved,21-23 which
Meanwhile, the use of ECLS in newborns
and neonates also expanded. Dorsons and White
reported experience with trials of extracorporeal
support16, 17 in moribund patient cases at the end
of life, demonstrating the capability of the sup-
port system to provide adequate oxygenation.
Surgeon Dr. Robert Bartlett (Figure 1-4),
who has been called the father of modern extra-
corporeal support, made a therapeutic decision
in 1975 that brought this burgeoning technology
to neonates with primary respiratory conditions.
Faced with a newborn infant dying from meco-
Figure 1-5 Left
nium aspiration pneumonia and resultant pul-
monary hypertension, Bartlett and colleagues
brought an ECMO oxygenator to the NICU
Figure 1-5 Right
Figure 1-5. Top: Esperanza, the first infant

successfully placed on ECMO for primary
respiratory failure. Bottom: Esperanza and
Figure 1-4. Dr. Robert H. Bartlett. The Father daughter with Dr. Bartlett at ELSO conference.
of ECMO.
4
promoted the interest and application in the in neonates. Centers performing ECMO grew
surgical and intensive care community. Pub- from only 18 worldwide to over 100 centers
lished reports showed ongoing improvements in the early 1990s. Thanks to technological
in outcomes, increasing survival rates 75% for advances, neonatal and pediatric application of
neonatal diseases previously associated with ECMO became a common practice.
only 10% survival. A second prospective trial effort took ad-
Expansion of the use of ECMO in neonates vantage of ECMO and traditional, non-ECMO
ran counter to typical use of new medical and therapy being provided in separate intensive
technologic interventions, which had typically care units. Dr. Pearl O’Rourke, a pediatric criti-
advanced first in adults. With growing interest, cal care physician at Boston Children’s Hospital
the medical community sought randomized, (Figure 1-6), led a two phase RCT. The study
controlled trial (RCT) evidence of the benefits design included a phase one approach with
of neonatal extracorporeal support over stan- a traditional 50/50 randomization of patients
dard therapies. Dr. Bartlett and colleagues at the until one arm had four deaths, followed by a
University of Michigan initiated an ECMO RCT phase two utilizing an adaptive design to favor
with an intriguing statistical twist to give pref- the “winner” of the first phase. Overall, 19/20
erence in the trial to a therapy which appeared (97%) of ECMO patients survived compared to
superior. Their “randomized play the winner” 60% of standard control patients.25 The study,
approach began with randomization but gave published in 1989, engendered controversy in
increased preference based on the success or the medical community and in the media.26,27
failure of the previous patient. During the study, Ironically, an outcry arose from many medical
the first patient receiving ECMO, survived. The professionals and the lay press that randomiza-
next patient, randomized to standard care, died. tion to standard therapy without ECMO was
Increased preference went to ECMO, and the unethical, implying a loss of equipoise and
next ten patients, all receiving ECMO, survived subtly demonstrating recognition that ECMO
(p=.0000001). The study24 was published in had become a standard of care.
1985 to significant controversy and discussion, The long-desired RCT evidence for out-
including concern that control patients did not come benefit in neonatal ECMO for persistent
undergo informed consent. The findings, how- pulmonary hypertension was provided by a
ever, encouraged growing use of ECMO support study performed in the United Kingdom from
1993 to 199528 that remains to date the largest
randomized ECMO trial. The study, authored
by Drs. David Field, Richard Firmin, and col-
leagues, enrolled 55 centers and took advantage
of the country’s regionalized medical/ ECMO
system, with randomization either to stay in the
referral center for standard therapy or transfer
to the regional ECMO center. A significant
survival difference (60% in ECMO patients vs.
40% with standard therapy; number needed to
treat: 3-4) supported the superiority of ECMO
in neonatal respiratory failure, and etched the
value of ECMO in stone.
Figure 1-6. Dr. Pearl O’Rourke, principal
investigator of early neonatal ECMO random-
ized trial.
5
Chapter 1
Global Spread of ECMO of Michigan, and University of Pittsburgh) were

represented at one of the meetings. By 1986,
Even absent the elusive “perfect” trial, sup- nineteen institutions provided ECMO support to
port for, and use of ECMO in neonates grew neonates.30 A voluntary alliance of these active
globally. Neonatal ECMO served as a role centers emerged. In 1989, a steering committee
model for rapid propagation of medical tech- formed (Table 1-1 and Figure 1-8) and created
nology for treatment of disease, and served as the bylaws to form the Extracorporeal Life
a demonstration model in a National Institutes Support Organization (ELSO). The purpose
of Health workshop for diffusion of technology of ELSO was to pool common data on ECMO
in 1990 (Figure 1-7), outlining the meteoric rise use, compare outcomes, and exchange ideas for
from concept to clinically accepted, if still con- optimal use of ECMO support. ELSO meetings
troversial, therapy. The NIH workshop Chair, attracted representatives from the small number
Dr. Anne Lennarson-Greer, noted, “The diffu- of institutions performing ECMO to present
sion of an innovation is a highly social process. their experience. The growing interest in ECMO
The spread of even a simple technology...is led to the development of a week-long meeting
characterized by many interpersonal contacts totally dedicated to ECMO directed by Dr. Billie
and differentiated social roles.”29 Short and sponsored by DC Children’s National
The concept of rapid technology diffusion Medical Center. Attendance was broadened by
as a social enterprise aptly described ECMO a growing international community experi-
well before the days of social media. Dissemina- ence. The community of international ECMO
tion of information for ECMO accelerated with experience also grew with the first European
the initiation of meetings and networks dedi- symposium on extracorporeal lung support in
cated to ECMO issues. Multiple centers sprang Paris in 1991. This meeting was associated with
up nationally and internationally, often with the foundation of the European Extracorporeal
movement of physicians and staff to develop a Life Support Organization (EESO). In 1994, the
new center, and always with collaboration from international ECMO conference represented the
the experienced centers. For instance, in 1983, first combined meeting of ELSO and EESO.
only three institutions regularly performing ELSO became the epicenter for the develop-
ECMO (Medical College of Virginia, University ment of thought and definition of the operation
of an ECMO center and guidelines which could
Table 1-1. Charter Members of First Extra-

corporeal Life Support Organization Steering
Committee, 1989
Members Location
Robert Bartlett Ann Arbor, MI
William Kanto Augusta, GA
Fred Ryckman Cincinnati, OH
Larry Cook Louisville, KY
Martin Keszler Washington, DC
Billie Lou Short Washington, DC
P. Pearl O’Rourke Seattle, WA
J. Devn Cornish San Diego, CA
Figure 1-7. Graphic representation of devel- Charles Stolar New York, NY
opment and propagation of ECMO, from NIH Michael Klein Detroit, MI
Report of the Workshop on Diffusion of ECMO Phyllis McClelland Ann Arbor, MI
Technology, 1993. Sandy Snedecor Ann Arbor, M
6
Figure 1-8. Top: Attendees at Charter Meeting of the Extracorporeal Life Support
Organization, October 1989. Bottom: Attendees at 25th Anniversary Meeting of
ELSO, September 2014.
7
Chapter 1
be utilized by a growing number of centers. In outcomes with the national and international
addition, it became the steering organization centers. International ELSO Registry involve-
for future randomized trial work. Awards for ment grew from 80 centers in 1990 to over 467
ELSO Centers of Excellence were developed active centers in 2016, and well over 350 centers
to provide center recognition around ELSO contributing data (Figure 1-9). From Registry
recommendations. The Award of Excellence inception to date in 2017, the Registry database
has received recognition by entities such as the has captured over 86,000 patients and provided
annual US News and World Report survey as a data for hundreds of publications and countless
marker of institutional quality. queries for centers seeking experience around
Key efforts of ELSO included the publica- ECMO use in a specific condition. The Regis-
tion of manuals and textbooks to help codify try is the largest repository of extracorporeal
approaches to ECLS care. The need for a col- support data in the world and is considered the
lated text of ECMO knowledge was recognized. gold standard for reporting U.S. and interna-
Two members of the steering committee, Drs. tional ECLS outcomes. Use of neonatal ECMO
Robert Arensman and Devn Cornish, edited the peaked in 1992 at around 1500 annual cases.
inaugural edition of this textbook, now known The development of additional new therapies
as the “Red Book,” in 1992. The Red Book such as inhaled nitric oxide likely contributed
has now entered its 5th edition in 2016 as a to a decline in the numbers of neonates requir-
collaboration of experts in the global ECMO ing ECMO, to current levels half of those at the
community. peak of neonatal use.
A critical element of propagation of ECMO Efforts to use ECMO for pediatric cardiac
technology was the development of a standard- and respiratory failure rose with the success of
ized international patient database to track neonatal ECMO and its availability in growing
results and provide evaluation of indications numbers of centers. A variety of case series
and outcomes in a large population, a huge supported the efficacy of ECMO in pediatric
improvement over traditional small case series respiratory failure.32,33 However, the relatively
experience. This early database, which transi- low numbers of pediatric patients suitable for
tioned into the ELSO Registry,31 allowed for ECMO across the country precluded a definitive
participating institutions to collate and compare trial. A multicenter RCT was attempted in the
350 9000
300 8000
7000
Number of Centers
Number of Runs
250
6000
200 5000
150 4000
3000
100
2000
50 1000
0 0
1990
1992
1994
1996
1998
2000
2002
2004
2006
2008
2010
2012
2014
Centers
Cases
Figure 1-9. Growth of ELSO Centers 1989-2016 (ELSO Registry centers actively providing data
annually to 2015). Over 467 centers were ELSO members worldwide in 2016.
8
1990s by Fackler and Heulitt, but was stopped dard therapy utilizing a computerized protocol
due to enrollment difficulties, and lower than for ventilator management. The study again
expected mortality in the study population.34 showed no difference in outcomes. Study design
In the absence of a pediatric RCT the most sig- concerns included the lack of experience with
nificant case-control study35 demonstrated im- extracorporeal use in some centers as well as
proved outcomes associated with use of ECMO. extremely high blood loss in ECMO patients.
To date, no new pediatric RCTs are on the Despite these disappointing study results, phy-
horizon. Efforts in pediatrics became focused sicians such as Dr. Luciano Gattinoni42 and Dr.
on delineating optimal timing and indications Bartlett persevered in its use in adults, reporting
for support,36 pushing the envelope for pediatric significant survival improvement compared to
indications,37,38 and determining relationships historical controls.
between center volumes and outcome.39 Advances in ECMO experience, equipment,
and expertise paved the way for another RCT in
Perseverance: Experience and Growing adult respiratory failure, the 2009 United King-
Indications in Adult ECMO dom CESAR trial, under the leadership of Dr.
Giles Peek.43 The CESAR trial took advantage
Since the initial efforts of Dr. Gibbon, clini- of the regionalized ECMO system which had
cians sought to utilize the benefits of ECMO to allowed the success of the neonatal UK trial,
allow recovery in adult cardiac and respiratory with patients randomized to either remain at
failure. However, the road to acceptance of a standard treatment center or be transferred
ECMO’s benefit in adults was a slow one. The to a regional ECMO center. The study also
first attempt at an ECMO RCT was actually an utilized venovenous (VV) cannulation, with its
NIH-supported adult trial directed by Zapol inherent advantages. Patients receiving care at
et al. comparing venoarterial (VA) ECMO to the ECMO center demonstrated significantly
standard therapy for severe respiratory fail- improved intact survival compared to standard
ure.40 The study, while well intentioned, was center treatment. The study results, while con-
hampered by a variety of factors, including the troversial due to some methodological limita-
choice of moribund patients for study entry, tions, served to support the growing interest in
participation of the majority of centers with no adult therapeutic potential.
previous ECMO experience, and the utilization The timing of release of the CESAR results
of VA cannulation patients potentially requiring shortly preceded the 2009 worldwide H1N1
only respiratory support. The trial utilized the influenza pandemic. The acute, severe, fulmi-
relatively poor-performing technology available nant nature of respiratory failure with H1N1
at the time, and lung protective strategies were led providers to seek ECMO as a therapeutic
not utilized in either arm. The study demon- option, with encouraging findings supporting
strated very poor survival (approximately 10%) potential ECMO benefit.44,45 The convergence
in both study arms. These findings, although helped supercharge international growth of
clearly underlining the complexity of the clini- ECMO use. Both ELSO Registry reports31,46 and
cal scenario (66% mortality in total population studies of independent national data registries47
and 90% in severe ARDS patients), put a chill demonstrated a marked rise in adult cannulation
on subsequent extension of ECLS in adult rein subsequent years, with a continued upward
spiratory failure. trajectory to present.
A later adult RCT in 199441 randomized This rise in use of extracorporeal support
patients with ARDS to receive either extracor- was fuelled by several major advancements
poreal CO2 removal with VA support or stan- in equipment, including improvements in
9
Chapter 1
oxygenator components, ECLS circuit and removal opened the door for potential sup-
configuration, and vascular access. Femoro- port for a large number of adults with chronic
femoral cannulation with reduced cannula sizes, obstructive pulmonary disease55 ECMO teams
prevention of limb ischemia through selective also pushed the envelope in expanding indica-
distal perfusion, active drainage of limb ve- tions for extracorporeal support previously
nous flow, and attention paid to left ventricular considered contraindications, with reports of
unloading all played a critical role in enhanced improved outcomes in trauma, malignancy, and
ECLS management, reduced complication sepsis on ECMO.56,57 The use of ECLS for acute
rates, and improved outcome. Vascular access extracorporeal support during cardiopulmonary
techniques transitioned from surgical cutdown resuscitation (ECPR) also became a burgeoning,
and insertion towards emphasis on peripheral if somewhat controversial indication for support,
access employing Seldinger technique, with with growing use in both children and adults.58-60
thin, small size, percutaneous cannulas, often Global growth of ECMO use has charac-
characterized by nonthrombogenic surfaces. terized recent decades. ECLS use in Europe
Cannula design (double lumen cannula for VV- has been both longstanding and innovative. In
ECMO48,49 or low profile cannula for arterial particular, the enhanced use in adult respira-
access) and the routine application of a distal tory and cardiac failure has been propagated
limb perfusion in case of femoral artery can- in great part by experience and expertise in
nulation for peripheral venoarterial approach European centers. International center growth
were additional breakthroughs for successful also resulted in the establishment of ELSO
ECMO application with significant reduction global chapters tied to every continent. Eu-
in postprocedural complications. These in-
novations increased use of VV cannulation, Table 1-2. Chronology of Steering Committee
with transition to predominance of VV use for Chairs-ELSO and Global ELSO Chapters.
pediatric respiratory failure in 2012.31 Years Chair
Coating and heparin-bonded circuit sur- ELSO
2016-2018 Michael McMullan
faces,50 together with the miniaturization and
2014-2016 James Fortenberry
integration of pump systems, led to the develop- 2012-2014 William Lynch
ment of more simplified, portable, and efficient 2010-2012 Steve Conrad
ECLS systems. The most significant recent step 2007-2010 Mike Hines
2004-2007 Heidi Dalton
was the development of the polymethyl pentene 2002-2004 Joseph Zwischenberger
membrane oxygenator, which allowed achiev- 2000-2002 Ronald Hirschl
ing a low priming volumes, oxygenator pressure 1997-2000 Charles Stolar
1994-1997 Michael Klein
drop, high oxygenation efficiency, and long-
1993-1994 Billie Lou Short
lasting membrane performance.51 Preferential 1989-1993 Robert Bartlett
use of centrifugal pumps for pediatric and adult Euro ELSO
support also grew. 2014-2017 Roberto Lorusso
2012-2014 Giles Peek
Several trends in management also altered Asia Pacific ELSO
ECMO care. In Europe, efforts to allow pa- 2013-2017 Graeme MacLaren
tients to remain awake and enhance mobility Latin American ELSO
2015-2017 Luiz Caneo
were popularized, particularly by the ECMO
2013-2015 Rodrigo Diaz/Javier Kattan
team at the Karolinska Institute,52 allowing for (Co-chairs)
longer runs, bridging for transplant, and the South and West Asia ELSO
2018 Venkat Goyal
capacity for ambulatory ECMO.53,54 Primary 2017 Malaika Mendonca
use of ECMO for extracorporeal carbon dioxide 2014 -2016 Suneel Poobani
10
roELSO was chartered in 2011 as a sequel to Table 1-3. Fellowship of the Extracorporeal
the previous European Extracorporeal Support Life Support Organization: Members of Inau-
gural Classes.
Organization (Table 1-2). Asia Pacific ELSO
soon followed, being chartered in 2013, and Inaugural Class Members 2015
Latin American ELSO and the South and West Robert Bartlett MD
Asia ELSO chapters soon followed also in 2013, Konrad Falke MD
all with the support of then-ELSO chair Steve Luciano Gattinoni MD
Conrad. These vibrant organizations allowed John Gibbon MD
accelerated growth of international ECMO Robert E. Gross MD
patient capture in the Registry, robust scientific J. Donald Hill MD
conferences, expanded training courses, and Theodor (Ted) Kolobow MD
Pearl O’Rourke MD
enhanced global networking among ECMO
Billie Short MD
providers and centers. Individual membership
John Toomasian CCP
in ELSO was also initiated in 2016 to draw in Class of 2016
members from around the world, whether or not Warwick Butt MD
their institution was an ELSO center. Robin Chapman RN
The next chapter in the development of J. Devn Cornish MD
extracorporeal support remains to be written, Jean-Yves Chevalier MD
but it was the authors of the preceding works Richard Firmin MD
who set the stage. In 2015, ELSO established Masahiro Nagayo MD
Fellowship in the Extracorporeal Support Orga- Giles Peek MD
nization, an honorary designation to recognize Antonio Pesenti MD
Peter Rycus MPH
these pioneering contributors to the ECMO
Charles Stolar MD
story (Table 1-3). Much more work remains to
Warren Zapol MD
be done to improve ECMO technology, predict Joseph (Jay) Zwischenberger MD
outcomes, and fine tune best indications.47,61 As
we seek to fulfill Dr. Gibbons’ quest for lifesav-
ing support, we should be encouraged by the
inspiring words of Sir Winston Churchill, “The
future is unknowable, but the past should give
us hope.”62
11
Chapter 1
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tial extracorporeal gas exchange in alert
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12
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24. Bartlett RH, Roloff DW, Cornell RG, FW, Thompson AE, Sweeney MF. The
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25. O’Rourke PP, Crone RK, Vacanti JP, et al. 1996;24(2):323-329.
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conventional medical therapy in neonates WB, Rollins MD, Bratton SL. Extracorpo-
with persistent pulmonary hypertension of real membrane oxygenation for pediatric re-
the newborn: a prospective randomized spiratory failure: survival and predictors of
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26. Knox RA. A Harvard study on newborns 370.
draws fire. Boston globe, August 7, 1989:25. 37. Gow KW, Heiss K, Wulkan ML, et al.
27. Marwick C. NIH Research Risks Office Extracorporeal life support for support of
reprimands hospital institutional review children with malignancy and respiratory
board. JAMA. 1990;263:2420. or cardiac failure. The Extracorporeal Life
28. UK Collaborative ECMO Trial Group. UK Support Organization Experience. Crit Care
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extracorporeal membrane oxygenation. 38. MacLaren G, Butt W, Best D, Donath
Lancet. 1996;348(9020):75-82. S, Taylor A. Extracorporeal membrane
29. Wright L, Ed. Report of the Workshop on oxygenation for refractory septic shock
Diffusion of ECMO Technology; National in children: one institution’s experience.
Institutes of Health, 1993 Pediatr Crit Care Med. 2007; 8(5):447-451.
30. Custer JR, Bartlett RH. Recent research in 39. Barbaro RP, Odetola FO, Kidwell, K, et
extracorporeal life support for respiratory al. Association of hospital-level volume of
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real Life Support Organization registry. Am ous and ambulatory paracorporeal artificial
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901. 49. Javidfar J, Wang D, Zwischenberger JB, et
40. Zapol WM, Snider MT, Hill JD et al. Extra- al. Insertion of bicaval dual lumen extracor-
corporeal membrane oxygenation in severe poreal membrane oxygenation catheter with
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spective study. JAMA. 1979;242(20):2193- 205.
6. 50. Harig F, Feyrer R, Mahmoud FO, Blum U,
41. Morris AH, Wallace CJ, Menlove RL, et von der Emde J. Reducing the post-pump
al. Randomized clinical trial of pressure- syndrome by using heparin-coated circuits,
controlled inverse ratio ventilation and steroids, or aprotinin. Thorac Cardiovasc
extracorporeal CO2 removal for adult Surg. 1999; 47(2):111-118.
respiratory distress syndrome. Am J Resp 51. Lim MW. The history of extracorporeal ox-
Crit Care Med. 1994;149(2 Pt 1):295-305. ygenators. Anaesthesia. 2006;61(10):984-
42. Gattinoni L, Pesenti A, Bombino M et al. 994.
Role of extracorporeal oxygenation in adult 52. Frenckner B, Palmer K, Linden V. Extra-
respiratory distress syndrome management. corporeal respiratory support and minimally
New Horiz. 1993;1(4):603-612. invasive ventilation in severe ARDS. Mi-
43. Peek GJ, Mugford M, Tiruvoipati R et nerva Anestesiologica 2002; 68:381
al. Efficacy and economic assessment of 53. Turner DA, Cheifetz IM, Rehder KJ, et al.
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44. Davies A, ANZIC ECMO Investigators et al. ECMO for adult respiratory failure: current
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15
2
The History of ECMO: First Hand Accounts
Giles Peek, MD, James D. Fortenberry, MD
The History of ECMO: First Hand Accounts Dr. Robert H Bartlett: The way we got
started with this thing that became ECMO was
The words of those directly involved in through cardiac surgery. I was a resident at the
the development and early days of translating Boston Children’s Hospital in the 1960s, and
extracorporeal support to the bedside provide the mortality at the time for complex congenital
compelling insights that facts alone cannot ex- heart lesions was about 50%. We knew if these
press. Dr. Giles Peek (Figure 2-1) sat down with babies could live for a day or two, they would be
two of those pioneers, Dr. Robert Bartlett and alright. In retrospect it was what we would call
Dr. Joseph (Jay) Zwischenberger (Figure 2-2) to myocardial stun. So, we asked about whether
hear their stories. What follows is an edited tran- we could use the heart lung machine from the
script of their conversations at the EuroELSO operating room to keep these babies on the
Congress in Glasgow Scotland in May, 2016.
A Conversation with Dr. Robert H. Bartlett
Dr. Giles Peek: What were your first memo-

ries of ECMO?
Figure 2-2. Drs. Robert Bartlett and Jay

Figure 2-1. Dr. Giles Peek headed towards Zwischenberger trading surgical instruments
another peak. for musical versions.
17
Chapter 2
pump for a few days. My surgical chief and extracorporeal membrane circulation in animals.
mentor, Dr. Robert E. Gross said, “Of course Studies remained in the laboratory.
that is impossible because of problems with At that point, I moved to the University
the heart lung machine. It is very damaging to of California at Irvine Medical Center, with
blood, and causes lots of problems after an hour a brand new medical school that opened the
or two, but why don’t you work on it?” That is day I arrived, together with Al Gazzaniga, my
why we always toast Dr. Gross at ELSO func- surgical partner. In retrospect, it was a great
tions, “To Dr. Robert E. Gross, without whom opportunity because there was no one around
none of this would be possible!”. “Why don’t to say, “We don’t do it that way.” So we did
you work on that problem?” he said, so we set what we thought would be good for our patients.
out to work on it. There was an empty building where we built a
We knew that the problem with the heart laboratory and began more studies of prolonged
lung machine was the lung, which was simply extracorporeal support. We switched our model
bubbling oxygen through blood and we and to sheep because they were much more suited
other people had demonstrated that that was the to chronic awake experiments, will stand there
limiting factor. At about that time silicone rub- passively for days at a time as long as you feed
ber became available with the unique properties them, unlike the dog. So we got to the point
of transferring respiratory gases. With another where we could do this successfully without
resident named Lou Plzak we built some mem- any deleterious side effects in sheep for days
brane envelopes out of silicone rubber, hooked at a time.
it up to a dog, and ran venous blood through it. In 1971, we actually got a call from a surgi-
It worked beautifully for about a minute and cal friend in Santa Barbara who said, “Is your
then it stopped working altogether. That was machine ready? I have a kid here who is dying
interesting. We presented this at Dr. Francis of respiratory failure.” We said we were not, but
Moore’s research conference and at the same let’s call Don Hill he is up there in San Francisco.
conference an engineer named Phil Drinker was Don had, at that time, treated six patients, all
presenting his work. He was trying to minimize unsuccessfully, using the Bramson oxygenator-
hemolysis and had a machine that mixed blood -a huge device, but it worked. So Don came to
up ferociously, but as long as no oxygen was in- Santa Barbara and put this young man on. We
volved, no hemolysis. I spoke with Dr. Drinker went up to watch what he was doing. After about
to see what we could do with gases. We got a two days of support this young man recovered.
membrane oxygenator with efficient externally His problem was trauma and ARDS following
induced mixing, and were able to exchange trauma with a ruptured thoracic aorta which had
oxygen and CO2. That oxygenator allowed us been repaired but was in respiratory failure. So
to begin the study of prolonged extracorporeal he recovered and it was really the first success-
circulation. So we developed models in the dog ful case. The case was published in 1972.
and other animals and got to the point where we In 1972, Al and I were doing cardiac sur-
could, in fact, maintain extracorporeal circula- gery in addition to everything else in this little
tion for days on end--unprecedented at the time. hospital. We had a little boy that Al had done a
There were two other labs working on the same Mustard procedure on and he was failing postop.
project. One was that of Donald Hill, a cardiac This was a 2-year-old boy, so we brought our
surgeon in San Francisco, and the other was Ted oxygenator equipment from the laboratory and
Kolobow, a researcher at the NIH who both de- hooked it up in the hospital and put this little
veloped membrane oxygenators and prolonged boy on. He was on for a couple of days and
recovered. Those early cases demonstrated
18
what we suspected but no one really knew: if and to actually come to understand that that
you could support the circulation and respira- was what was happening; that must have been
tion for a short time, the native heart or lung amazing.
could recover. A few other people started doing Dr. Bartlett: We didn’t understand it, but we
similar things and by 1975 there were about 25 learned about it. The little girl was the first child
successful cases reported in the literature--some of a girl herself from Mexico who had crossed
in children, some in adults with respiratory into the country illegally to deliver her baby.
failure or with cardiac failure. The mother was told that her baby was certainly
In 1975, we treated our first newborn in- going to die and that the doctors were going to
fant with respiratory failure. Why did we do try something that has never worked before but
that? Well, as I said, we were the surgeons for they don’t have much hope for it. So the mother,
the hospital. We did the pediatric surgery and scared off by all the forms and questions, and
the cardiac surgery and the traumas and the running the risk of being deported, kissed the
hernias and the hemorrhoids and everything baby goodbye and disappeared. We never saw
in between, so it was not unusual for the neo- her mother again. And so the nurses named this
natologists to call us. At the time, left to right baby Esperanza which means “hope” in Spanish.
shunting through the ductus arteriosus was a She was well supported on VA-ECMO, but
common problem in newborn infants, and we every time we tried to turn down the pump flow
would be doing 3 to 4 ductus ligations a week. she got very hypoxemic and looked terrible. In
So that is why they would ask us to see these the mid-1970s patent ductus arteriosus was a
patients. We went to see this beautiful full term common problem. This was before prostaglan-
baby whose PO2s were in the teens, clearly dy- din inhibitors and other agents and we ligated
ing of hypoxemia and respiratory failure. She the ductus in many babies. So, that must be the
had some meconium aspiration, but that didn’t problem here, but we wanted to demonstrate
explain it. Based on our experience with that that before just charging in--after all we had this
cardiac case a few years before and trials with baby on bypass. To visualize the patent ductus,
other newborn cases which were unsuccessful, this was before echo, we did a cineangiogram,
we said, “Sure, we will try it again because we injecting dye into the arterial perfusion catheter,
have demonstrated that it will work.” We can- expecting to see it go from the aorta into the
nulated that baby on VA-ECMO through the lungs. What we saw was just the opposite. In
vessels in the neck, a technique which we had fact, no blood was getting into the lungs and
developed in the laboratory--not something we the dye was being washed out at the level of the
just did on the spur of the moment. That child aorta so the flow was going right to left, fetal
ultimately recovered and was the first neonatal circulation. I must admit, we didn’t believe
respiratory failure patient to survive. We later that so we did what any other Gross-trained
learned that there is a syndrome called persistent surgeon would do with unusual cath data. We
fetal circulation or pulmonary hypertension of just decided to go to the operating room to see
the newborn in which normal pulmonary vaso- what we could see.
constriction, which exists in the fetus continues Well, she had a huge ductus alright, but it
after birth with profound right to left shunts appeared that blood was flowing right to left. We
through the ductus and the foramen ovale, with thought, “That can’t be right, but it’s a ductus,
secondary hypoxemia. let’s ligate it.” So we did and of course if she
Dr. Peek: We understand that phenomenon had not been on VA bypass she would have died
very well now. But at the time there was no on the spot, because in retrospect she had very
concept of persistent pulmonary hypertension, high pulmonary vascular resistance. So, when
19
Chapter 2
we ligated the ductus, her pulmonary artery catheter in her right lower lung. I said, “Oh,
expanded with high pressures. I didn’t know thank you very much. I have been looking for
what was going on so we put a catheter in her that little girl!” So that is how we reestablished
pulmonary artery through a little pursestring contact with her. Esperanza is now 45 years old
suture, using a handy piece of silicone rubber and has a daughter of her own and a piece of
tubing. The PA pressure was twice systemic- silicone rubber tubing in her right lower lung.
-why should this be in a newborn with perfectly In retrospect, her problem was PPHN. It
normal cardiac anatomy? We assumed she had turns out that there was one paper in the pediat-
some kind of malformation of her distal pul- ric literature that was published the year before.
monary arteries down in the lungs somewhere, We went on to treat one newborn and another
and a fatal condition. So, we left the monitoring and another. They would get better in a day or
catheter in the chest. two. The use of ECMO for neonatal respira-
I planned to just turn her ECMO off but I tory failure proved to be remarkably successful
didn’t want to do it in the operating room. I mostly because these babies had completely
wanted to wait until the middle of the night, turn normal lungs. They just needed a day or two
her off in the ICU and see what the pathologist to accommodate their pulmonary circulation.
told us was wrong with her lungs. These are the Dr. Peek: So, obviously ECMO with the
stories that aren’t published. I went in about 12 early circuits was more challenging than what
hours later to turn her off, considering it another we have today. It was ideal for a short-lived
failure, but two things had happened. First of all, disease like PPHN. It was the perfect treatment.
her pCO2 had dropped precipitously with new But how did you get from those patients to the
exhaled CO2 gas. Secondly, the PA pressures older children and the adults? What were the
had dropped to less than systemic levels. So, we challenges you had to overcome?
decided to continue ECMO. She continued to Dr. Bartlett: Well, the biggest challenge
improve and we were able to wean off of ECMO, was not the mechanics of the system. It was
then quickly wean off the ventilator after that. the perception of the public. In 1975, the year
So, after we are off ECMO and off the ven- we treated Esperanza, and based on the very
tilator then we had to take the catheter out of the early successes, the NIH sponsored a prospec-
pulmonary artery. As I pulled it out it was about tive randomized trial of extracorporeal support
4cm shorter that what I had put in. So we took a in adult respiratory failure. It went on for three
chest x-ray and in her right lower lobe is a piece years and it was ultimately published in 1979.
of silicone rubber. Otherwise, she was fine. We It was through that study group the technique
had a dilemma, what should we do? What we got to be called ECMO. Somebody made up
decided was to just leave it there. She was fine that term because membrane oxygenation was
and she lived with it and, in fact, we lost track of the focus of it. In retrospect, it was a poorly
her altogether. She was eventually adopted by designed trial, done at the wrong time with
the foster family that took her in. That family immature technology. Everything about it was
moved to Missouri a long way from California badly done. I can say that because I was one
and I lost track of her. I moved to Michigan, of the designers of the trial and one of the par-
she was in Missouri. Fourteen years later I got a ticipants in that study. There were nine centers,
call from a pediatrician in Missouri saying there only three of whom had ever done a clinical
is a girl here in my office and she is telling me ECMO case before that. There was no break-in
a story and I can’t believe it. He said she has a period. There was no way to learn the technol-
left thoracotomy, she has an incision in her neck ogy. There was no standard anticoagulation
and I took a chest x-ray and she has a piece of regimen. Most people bled to death. There were
20
lots of problems with the trial and it was stopped SVC). It was safer because it didn’t involve
after 90 patients because of futility. There was access to the arterial circulation and supported
10 percent survival in both the ECMO and the the patients perfectly well. So, other groups
control groups. gradually started treating adults with respiratory
The paper was published with the conclu- failure. In the meantime, the major growth in
sion that ECMO offers no advantage in the this procedure was in cardiac support. Initially it
treatment of ARDS. This was a correct inter- was used in patients who were immediate post-
pretation of results from a badly done study. cardiotomy, patients whose heart did not work
We cared for several adult patients that were in well or perhaps weaned directly from cardio-
that trial, in fact, one of the only survivors. That pulmonary bypass onto ECMO for a while. The
study essentially stopped research on ECMO results were quite good, with about 50 percent
on adult patients for the next 20 years. But we survival compared to death otherwise. It then
continued to do it in adults, and Luciano Gat- grew into other types of support for myocarditis
tinoni continued to do it in Italy, but until 1990 and myocardial infarction, things like that.
there was basically no other research going on Dr. Peek: Obviously, one of the problems
in adults. We did expand it to older children and with ECMO was that you couldn’t move the
to cardiac surgery children where it worked very technology very easily in the early days. The
well, but it was the results of that NIH sponsored patients were very sick and would have to come
trial that slowed everything down for a couple to you in the hospital. But you had the concept
of decades. that you could take ECMO to the patient.
Dr. Peek: So, when you were beginning Dr. Bartlett: Yes, we started with transports,
to do these adults in Michigan, do you think it actually. Our first transports were in 1973, 1974
was just gradually learning each aspect of the in the California days. We continued that when
treatment and improving rather than a “eureka we went to Michigan in 1980, but developed a
moment?” much bigger team and had a much bigger op-
Dr. Bartlett: No, there was definitely no eu- eration including a very sophisticated transport
reka moment. It was just one step after another. system. Many of the patients who were referred
All the children as well as adults with respiratory to us were too sick to transport by conventional
failure were placed on VA bypass. In fact, most means so we learned to take the ECMO machine
of the adults were on VA through the neck using to the patient to cannulate the patient wherever
and ligating the carotid artery and the jugular they were and bring them back. In fact, that
vein. We had learned that it was safe to do it in got to be a major source of our patients. We
babies. We learned after about 50 cases that if much preferred to transport the patient not on
you ligate the carotid artery in an adult patient ECMO and put them on once they got to our
who is in cardiac arrest, stroke resulted about 15 hospital, but there were many patients that were
percent of the time. So we eventually stopped just too sick to do that. Over the first ten years
doing that and used the femoral artery in prefer- or so at Michigan we transported about 100
ence. The carotid actually works perfectly well patients. The results were actually better in the
for adults. So, we treated a lot of adults. About a transported patients and, looking back on it, the
hundred adult patients up until 2005, something reason was that they were usually patients that
like that, and had about a 50-60 percent survival got very sick very quickly. We would find them
depending on the primary diagnosis. So, we on the first day or so of illness rather than 5 to
knew that it would work well in those patients. 7 days later after some outside centers trying to
We eventually switched to VV access us- recruit their lung in the process.
ing two separate venous catheters (IVC and
21
Chapter 2
Dr. Peek: For sure. And obviously when cannulation and the femoral vein fell apart and
you take it out of hospital and on the road it then it fell apart some more, and eventually it
becomes exponentially more complex, so you dissected and the patient died. It turned out
have all kinds of issues with the technology. the patient had Ehler-Danlos syndrome but we
Dr. Bartlett: Well, there are lots of problems. didn’t know it at the time. The combination of
It is just a matter of planning ahead and learning trying to do VV-ECMO (and in this syndrome)
to do that so we, in two suitcases, could take and watching a femoral vein in a child tear all
the entire ECMO system plus all of the operat- the way up the vena cava and knowing that ty-
ing equipment. We went with two nurses and ing up the carotid was quite a challenge. Back
two surgeons and the pilot to go to a place and in those days we were highly frightened by all
we developed a technique if we went for 60 that. We were so worried about the stroke rate.
miles we would go by ground. We would get We hadn’t quite worked out what was the con-
the patient, bring them back. If it was from 60 tributor to the incidence of strokes. We didn’t
to about 200 miles we would go by helicopter. know if it was the anticoagulation, we didn’t
If it was more than 200 miles we would go by know if it was prematurity. We didn’t know if
fixed-wing aircraft. it was tying off the carotid so we lost a lot of
Dr. Peek: Thank you, Bob. sleep over the idea of the procedure.
So when I became the second ECMO
A Conversation with Dr. Jay Zwischenberger surgeon at Michigan in January of 1984 Bob
Bartlett came up to me and said, “Zwisch, I just
Dr. Peek: Jay, thank you very much for want you to do two things in the lab. Number
talking with us. I wonder if you can tell us one, I want you to come up with a heparin
what it was like coming up with the concept bonded circuit that allows us not to have to use
and the idea of building the double lumen can- heparin and I want you to come up with a double
nula and basically changing the paradigm from lumen catheter.” Well, actually I worked hard
VA-ECMO to VV-ECMO. on both, and history has written the heparin
Dr. Zwischenberger: Well, like all good bonded circuit went through several iterations.
ideas, it isn’t a lightning bolt or an “aha” mo- We did an ionic bonding which then evolved
ment, it evolves from a single idea in a discus- into covalent bonding, which then evolved into
sion session to the point to where you actually multilayering and complex layering like what
try to make it work. My first exposure to VV- you see now. We sit here in 2016. That is not
ECMO was with a pediatric surgeon named resolved.
Mike Klein who was at the University of Michi- But in 1984, what I was able to do was
gan working with Bob Bartlett. Mike had be- partner with an engineering resident named
come very enamored of the idea that VV-ECMO Ken Drake on the catheter. Ken was a “good
would be less invasive than VA because back ‘ole boy” who loved to work with his hands
in 1983 Dr. Bartlett had just come to Michigan and was sort of a mechanical engineer. I had
and he was trying to talk everybody into doing done work on a farm and I had restored antique
ECMO. So it took a couple of the young sur- cars so I was a tinkerer and a fixer upper and
geons to embrace this, otherwise, Bartlett would a hands-on kind of guy as a surgery resident.
have to do this all by himself. Mike Klein was The two of us got together and we decided to
one of the early adopters and he became a major design a double lumen catheter. Well, because of
contributor to ECMO. our background, we both went to the hardware
I was a resident at the time and I scrubbed store and we bought a whole array of stainless
in with Mike on a patient. We were doing VV steel tubing, ranging from small to fairly large.
22
He had a machine shop in his basement and the was my mentor and I loved him dearly, his
two of us would get together and we came up contribution was just that. And I have to credit
with different combinations and permutations John with my first publication. So I presented at
of reinfusion cannulas and drainage cannulas. ASAIO and people came up and said, “Wow--a
Our thought at the time was to have a concentric double lumen catheter that really works!” So,
configuration. That is a small cannula inside we were then inspired by that to keep doing
a big cannula. We tried at first a double barrel experiments.
approach like a double barrel shotgun but that This was back in the late 1980s when the
was hard to put in and always resulted in a fig- FDA went through a period where virtually
ure eight configuration. We hadn’t yet learned nothing was being approved [for clinical use].
to make eccentric tubing so we decided to do There was about a two year period where there
concentric tubing of a tube in a tube. was a very risk-averse atmosphere, virtually
Well, believe it or not, over a month we had nothing new happened and virtually all new
tried virtually every combination and permuta- technology was exported to Europe--Giles you
tion of cannula that you could buy or construct lived through that. This period was when the ex-
by soldering stainless steel and having one plosion of research and development took place
drain and one reinfuse, and we came up with in Germany and Europe. The United States
the empiric ratio of two to one. If the venous became more of the prototyping site and then
catheter was twice the internal diameter of the Europe would develop it in the first patients and
reinfusion catheter, that was a sweet spot for then it would come back to the United States.
drainage and reinfusion. And, as history is That paradigm exists today--at least in my world
written, that sweet spot is the same today. All of cardiothoracic surgery.
double lumen catheters basically use that two We went through a 3-year period trying to
to one configuration. We did it empirically find a company that would make the double lu-
and then Bartlett’s group went on to create the men catheter. We were very unsuccessful with
mathematics to create the “M” number. But the major companies and we virtually almost gave
M number was generated off of all that data of up on the idea that we would ever have a double
drainage catheters and reinfusion catheters that lumen catheter that we would have to continue
we did with the stainless steel tubing. with the old cutting the chest tubes and putting
Then we constructed a soldered machined them in the jugular vein and the carotid artery
double lumen catheter out of stainless steel: the until a small company called Kendall came to
first properly oriented, properly proportioned us and offered to make the catheter. The only
drainage and reinfusion catheter. We made a caveat was that we couldn’t have any intellec-
beautiful soldered catheter and then we worked tual property rights. So Dr. Bartlett, Ken Drake,
with John Toomasian, who was the director of and I made the decision that we would give the
the lab at that time, and Al Petkus, a veterinarian. intellectual property to the Kendall Company if
And we did a whole series of animals where we they would just make the catheter. They agreed.
did VV support. We supported those animals for That first catheter went through several compa-
8 hours without a ventilator on total VV support. nies acquiring the technology and changed its
It was my first presentation at the American name several times. But that catheter was the
Society of Artificial Internal Organs (ASAIO), standard of care for almost 20 years. And I am
and John helped me with the first presenta- pleased to see it happen.
tion and paper. After all this work, Dr. Bartlett As we tried to educate people on double
looked at it and said, “Well Zwisch, that looks lumen catheters the most difficult part was that
simple. That’s no big deal.” So, although he it was designed with a significant (20 percent)
23
Chapter 2
recirculation. We knew that, but when you used Dr. Zwischenberger: The bicaval cannula
it on patients and it started to recirculate it would that evolved 20 years later was based on a lot of
make the critical care physicians crazy because those early drawings where we thought through
they couldn’t get the kind of gas exchange that all the combinations and permutations. I was a
they wanted to get in order to have “perfect” cardiac surgeon by trade so I was used to bicaval
numbers. They couldn’t get an oxygen satura- cannulation anytime we had to open the atrium
tion of greater than 90 percent. They couldn’t or do major valvular surgery on the tricuspid or
get the numbers they had grown accustomed to mitral valve. So, that was an accepted technol-
look for. So, we had to educate people that a ogy to me. We also felt that the Kendall catheter,
saturation of 80% and a pCO2 and a pH that was no matter how big you make it, would never be
normal was a perfectly viable blood gas for a useful for adults with respiratory failure because
newborn with respiratory failure. But that was of the recirculation and because of the possibil-
a huge educational process in those days. ity of developing pulmonary hypertension.
Dr. Peek: Still ongoing… So, we felt strongly that we had to get a
Dr. Zwischenberger (laughing): Yes. The cannula that allowed total pulmonary support.
natural tendency if the oxygen saturation wasn’t Now, there was a lot of new evidence up to that
perfect was to turn up the flow which created point. We had tried the intravenous oxygenator
two problems; first a further increase in recircu- (IVOX). We knew that partial support even
lation and second, hemolysis. So it would, by though it was enticing didn’t really work that
definition, frustrate the caregiver because higher well. We had already tried arteriovenous CO2
VV-ECMO flow was more recirculation and less removal. We knew that it would work in a
support than lower VV flow without recircula- limited patient population but wasn’t universally
tion. We gave lots of talks and demonstrations applicable. So, we wanted to come up with a
labs and we would give simulations [to help universal catheter that would work on adults
with understanding]. and we also wanted it to potentially be ambula-
VV-ECMO with a single double lumen tory. Even then, back in the late 1990s, we felt
cannula was slow to be adopted, but those who strongly that ambulation was how the human
learned how to position the catheters and use it had evolved. We had evolved as hunter gather-
correctly were wild enthusiasts. There was a ers. We evolved as erect, ambulatory animals
period when about half of the ECMO programs and the idea of critical care with the patient se-
supported ECMO with a double lumen catheter dated, flat on their back, intubated, with a Swan
and about half wouldn’t even try it. And, the Ganz catheter, an art line and a Foley catheter
better results were initially being obtained with and sedated and paralyzed and aspirating we
VA. But over time, the VV enthusiasts showed just didn’t think that that was going to be the
that the outcomes were better in respiratory fail- future. And with my collaborator, Dong-Fang
ure. There were less bleeding complications and Wang, we created the bicaval cannula, a big next
cerebral vascular problems. There was a general step in allowing patient mobility.
feeling that the VV patients got better quicker Dr. Peek: We are running out of time, but
and 35 years later, it is hard to show that. But not out of stories. Thank you Jay.
that was the general feeling at the time and that
is what allowed VV use to continue.
Dr. Peek: Is that what led you to want to
develop the bicaval cannula--the thought of get-
ting through the recirculation and giving people
a better cannula?
24
3
Evolution and History of Global ELSO
Graeme MacLaren, MBBS, FRACP, FRCP, FCICM, FCCM, Rodrigo Diaz, MD, MEd, Malaika
Mendonca, MD, Giles Peek, MD, FRCS, CTh, FFICM, Suneel Pooboni, MBBS, MD, DCH, FRCP,
FRCPCH, FCCP, Peter Rycus, MPH
Following the influenza A(H1N1) pan- committee was duly elected. As the inaugural
demic and publication of the CESAR study1 in chair, I quickly realized that this was a BIG
2009, the use of ECMO for adult respiratory job and I really had no idea how to achieve our
failure increased exponentially.2 In 2012-2013, objectives, or indeed exactly which objectives
the annual number of adult ECMO cases world- of education, research, communication, and
wide reported to ELSO overtook pediatric and the Registry were the most important. But in
neonatal cases for the first time. As ECMO use the words of the song “With a little help from
increased in adults, many ECMO-naïve centers my friends,” the first spectacular annual Euro-
outside North America expressed an interest in ELSO conference was organized by Roberto
adopting this technology. This attention helped Lorusso in Rome 2012, with 878 delegates.
rekindle interest in forming regional ELSO This was followed by a sophisticated meeting
chapters across the globe in order to better ad- in Stockholm organized by Bjorn Freckner in
dress local needs. The inaugural chairs of these 2013 with 910 delegates. In 2014, Alain Combes
chapters recount how they evolved. welcomed us to Paris in the springtime where
1200 colleagues attended. 2015 saw EuroELSO
EuroELSO in the historic city of Regensburg with Thomas
Mueller hosting over 1300 ECMOlogists. The
Giles Peek attendance of so many delegates far exceeded
our expectations and more than vindicated Dr
I don’t recall exactly where Dr. Bartlett Bartlett’s inspirational directive. This does
sandbagged me, but indeed it was a “great make each successive meeting more stressful for
idea,” as he put it. As a long-time member of the the conference organizers as they try to attract
ELSO steering committee, I had often vocally more delegates than the previous year.
complained to my North American colleagues We gradually developed our “European”
that ELSO was (mainly) a North American way of working which was perhaps more de-
organization, even though it had a global remit. volved than that of the parent organization. The
“Giles, we need a local ELSO organization annual conference chair was given absolute au-
in Europe,” said Dr. Bartlett, “It’s a great idea,” thority over the conference and this has allowed
he continued. I had to agree. So in 2011 we had each chair to stamp his mark on the successful
a preliminary meeting at La Pitié-Salpêtrière but subtly individual annual meetings which
Hospital in Paris and the EuroELSO steering followed in Stockholm, Paris, Regensburg,
25
Chapter 3
and Glasgow. We included our nursing and I am thankful to Dr. Bartlett for giving me
perfusion colleagues as full voting members the inspiration and opportunity to build the
of the steering committee and we established EuroELSO team. Now, having stepped down
the semi-permanent nonvoting officers of the as Chair, I am immensely proud to see them
steering committee, the treasurer, and secretary, go forwards under the leadership of Roberto
to keep the administrative and financial mat- Lorusso to achieve so much more than we could
ters of EuroELSO on an even keel. Each and have dreamed of in 2011.
every member of the committee has played an
instrumental part in making EuroELSO the suc- Asia-Pacific ELSO
cessful “organisation” it is. As British English
is the official language of EuroELSO, this word Graeme MacLaren
is spelled with an ‘s’, not a ‘z’.
The growth of ECMO within Europe has A group of ECMO Directors from the
paralleled the global experience. By the end of Asia-Pacific region met in Rome 2012 for the
2014, there were 65 EuroELSO member centers, first EuroELSO conference. Given how well
20% of the world total, reporting 1488 cases attended and successful the meeting was, it
for the year (21% of the total). Comparing Eu- seemed worthwhile to set up a similar chapter
ropean with global data from the January 2016 in the Far East and Oceania.
ELSO report shows some interesting trends In July 2012, a preliminary meeting in
(Table 3-1). Note that all groups of patients Melbourne, Australia, was held to develop the
are somewhat under-represented compared concept further, hosted by Dr. Vin Pellegrino.
to the number of centers but the proportion of Steve Conrad, then the Chair of ELSO, attended.
adult respiratory cases is much higher. It will From the beginning, people seemed prepared to
be interesting to watch this develop over the go to great lengths to make sure it worked. For
following years. example, four doctors from Japan flew down
just for the meeting and left the next day. There
was unanimous agreement about the potential
Table 3-1. EuroELSO vs. Global ELSO
January 2016 value of the chapter and a ballot was conducted
across the Asia-Pacific ELSO centers to elect
the inaugural steering committee. Rather than
Europe n (%) Global n use the same structure as the parent organiza-
Neonatal Respiratory 3274 (11%) 28723 tion, the APELSO steering committee decided
Cardiac 673 (11%) 6269 to have a different format, with an emphasis
on education. The first meeting in Beijing in
ECPR 83 (7%) 1254
October, 2013, was very successful and was
Pediatric Respiratory 1417(20%) 7210 followed by an equally successful conference
Cardiac 1128 (14%) 8021 in Kyoto in July, 2015. Dr. Cun Long stepped
down as conference chair and was replaced by
ECPR 287 (10%) 2788 Dr. Ryoichi Ochiai. After the Kyoto meeting, Dr.
Adult Respiratory 2759 (30%) 9102 John Fraser became the conference chair for the
Cardiac 1129 (14%) 7850 third meeting, to be held on the Gold Coast in
Australia in October 2017.
ECPR 463 (18%) 2379
From the beginning, the primary aim of
Total 11213 (15%) 73596 APELSO has been education. From 2014 on-
wards, Simon Sin, Peter Lai, and colleagues
26
from Queen Mary Hospital, Hong Kong, have were elected, Javier Kattan and Rodrigo Díaz.5
run annual ECMO workshops, all selling out Their aim was to establish the chapter steer-
months in advance. At the inaugural workshop, ing committee and together institute its legal
a steering committee meeting was held and foundations, enact the bylaws, start mutual
again demonstrated the lengths some members collaboration, and bring international standards
were prepared to go to: two doctors flew down and education in ECMO care to the region.
from Beijing for the meeting and left the next Now there are more than 25 ELSO centers in
day, while a Korean doctor flew to Hong Kong the chapter that have reported more than 600
to attend the two-hour meeting, arrived just cases, more papers are being published by
as we started, then returned to the airport and local authors, and collaboration in education
flew home. is growing. The First ECMO Specialist Train-
Over the last few years, APELSO has laid ing Course was held in 2013 in Brazil at the
the foundations to help promote ECMO and Heart Institute, University of Sao Paulo Medi-
educate clinicians in the region about how best cal School.6 Since 2014, the Latin American
it may be performed. In the future, we hope to Chapter team, together with different national
provide more resources to clinicians from lower and international teachers, have done an annual
income countries. VV Adult ECMO Course in Santiago. In 2015,
an “MCS in Cardiogenic Shock Course” was
Latin American ELSO started in Bucaramanga. Efforts are being made
to establish training courses in other countries
Rodrigo Diaz of the region.
In December 2014, the first Latin American
Latin America started to do ECMO in the ELSO Chapter Congress was held and more
early 1990s.3 These were just sporadic cases than 500 attendees shared experiences at this
until 2003, when the first hospital in South meeting. Luiz Caneo from Brazil was elected
America joined ELSO, Pontificia Universidad the Chapter`s chairman.
Católica de Chile in Santiago, led by the neona- Latin America has unique characteristics,
tologist Javier Kattan. After training in the U.S., and we have to be able to share experiences,
4
his group started a successful and regionalized adapt techniques to our needs, and maintain the
experience in pediatric and neonatal care. Five best standards of care focused in education, data
years after that, another center in Santiago be- registry, and publication of our experience. In
came the second hospital reporting to ELSO. In 2015, a first center in the region got the Center
2009, hospitals in Colombia, Brazil, and Mexico of Excellence Award and three centers in the
all joined ELSO. region are regularly doing mobile ECMO: Mon-
Over the last five years, programs have terrey in Mexico, Bucaramanga in Colombia,
grown quickly and centers contributing to the and one center in Santiago, Chile,6 and more
ELSO Registry now come from several coun- cases are being reported each year. In Chile, a
tries, including Argentina, Costa Rica, and Peru. joint commission of the Intensive Care Society
In December 2012, the Latin American and the government established formal criteria
chapter was founded with the assistance of Peter for ECMO and made it obligatory to report the
Rycus, William Lynch, Steve Conrad, and Mike results to a national database.
Hines. More than 200 people attended the first
Latin American Symposium on ECMO and
started the international collaboration based
on ELSO’s vision and mission. Two co-chairs
27
Chapter 3
South and West Asian ELSO bites; patients with organophosphate poisoning;
and ARDS secondary to malaria, tuberculosis,
Suneel Pooboni and Malaika Mendonca PJP pneumonia, or newer varieties of viral
pneumonias.
The suggestion of establishing a global The region includes countries where access
chapter covering West Asia and Gulf Coun- to sophisticated healthcare is possible without
tries, which were already cooperating in terms any limitations to cost, and others where the
of training, came early in discussions between provision of basic healthcare remains the main
ELSO representatives and the ECMO Society priority. The area also includes countries torn
of India, which was established in 2010. Early apart by war. Healthcare funding is very diverse,
in 2013, the South and West Asian Chapter of with South Asia consisting of populations of
ELSO (SWAC ELSO) was formally created dur- mixed income groups with healthcare fund-
ing the 4th ECMO Society of India conference ing coming from a mix of private companies,
in New Dehli, with the help of Peter Rycus and government sponsorship, and individual health
Steve Conrad. The executive body was elected insurance, while healthcare in West Asian coun-
during the same meeting, with Suneel Pooboni tries is mostly based on government funding. In
being elected as Chairperson. this context, our focus has been on the exchange
The first two SWAC ELSO annual confer- of experience and knowledge among the centers
ences were held in India (Hyderabad in 2014, already performimg ECMO and those who wish
Bangalore in 2015). The increasing presence to start. Courses, workshops, and continous
and engagement from people in the Gulf region education are the priorities of the chapter.
then brought the third annual conference to Abu SWAC ELSO, as with all the other chapters,
Dhabi, UAE, in 2016, which led to sharpened has the important mission to knit together a
awareness of ELSO as an organisational body, community of diverse but motivated specialists.
and an increase in centers registering from Exciting times lie ahead.
outside India. During this steering committee
meeting, people from different countries were
assigned to be members of subcommittees, and
Malaika Mendonca was elected as co-Chair
with Suneel Pooboni. The already vast region
was further extended to include Africa, in par-
ticular the Republic of South Africa.
As a young chapter, SWAC is still in the
transition phase of defining roles and respon-
sibilities of its subcommittees, its bylaws and
financial alignments.
The chapter covers a diverse area, with a po-
tential catchment population of nearly 2 billion
people. Although centers of only 11 countries
have registered membership in ELSO by the end
of 2016, their participation is developing rapidly.
The nature and diversity of the SWAC area
leads to specific challenges and indications for
ECMO rarely seen in other regions, such as
myocarditis due to scorpion stings or snake
28
References
1. Peek GJ, Mugford M, Tiruviopati R, et

al. Efficacy and economic assessment of
conventional ventilator support versus
extracorporeal membrane oxygenation for
severe adult respiratory failure (CESAR):
a multicentre randomised controlled trial.
Lancet 2009; 374:1351-63
2. Extracorporeal Life Support Organization
ECLS Registry Report. International Sum-
mary, Ann Arbor, 2016
3. Castillo L, Bugedo G, Hernández G, Mon-
tes JM, Ilic JP, Labarca E et al. Soporte res-
piratorio extracorpóreo: nuestra experiencia.
Rev Méd Chile 1996; 124: 45-56.
4. Kattan J, Gonzalez A, Castillo A.
Oxigenación con membrana extracorpórea
neonatal-pediátrica. Rev Chil Pediatr 2013;
84 (4): 367-378.
5. Diaz R. ECMO and ECMO Mobile. Me-
chanical Cardiopulmonary Support. Rev.
Med. Clin. Condes - 2011; 22(3) 377-387.
6. Caneo LF ; Neirotti R. ECMO: Improving
our Results by Chasing the Rabbits. Braz
J Cardiovasc Surg 2015;30(6):657-9
7. Kattan J, Diaz R. Latin ELSO Chapter: the
Latino American experience. Presented at
25th ELSO meeting, September 2014. Ann
Arbor, MI, USA
29
4
The Physiology of Extracorporeal Life Support
Robert H Bartlett, MD, Steven A. Conrad, MD, PhD
ECLS (ECMO) is the use of mechanical is controlled by a center in the brain, and in-
devices to support heart and/or lung function creases or decreases depending on activity and
in severe heart or lung failure, unresponsive other factors.
to optimal conventional care. With circulation Metabolic rate increases with activity, fever,
and respiration supported by ECMO, damaging and drugs and hormones, and decreases with
heart and lung treatment can be stopped (eg, sleep, paralysis, and cooling. Metabolic rate
vasopressors, high ventilator settings) while increases as much as five times in extreme
the failing organs are treated, recover, or can be exercise. When the metabolic rate changes, the
replaced. Managing patients with ECMO differs delivery of substrate and oxygen changes in
actively from conventional care, and requires proportion, accomplished by a change in cardiac
a thorough understanding of cardiopulmonary output. The amount of oxygen available in the
physiology, pathophysiology, and ECMO physi- bloodstream for metabolism is normally five
ology. This chapter includes a brief review of times the amount actually used by the tissues. A
normal and abnormal cardiopulmonary physiol- complex system of reflexes and hormones keeps
ogy, and the physiology related to mechanical this all in balance, referred to as homeostasis.
replacement of circulation and respiration. Oxygen gets into the blood through the
lungs and arrives in tissues via perfusion of
Cardiopulmonary Physiology
Figure 4-1 summarizes the essentials of nor-

mal cardiopulmonary physiology. All tissues
of the body function by combining substrates
(food) with oxygen, producing heat, energy,
CO2, and water in the process called metabolism.
Metabolism is related most closely to oxygen
consumption, and is determined by measuring
the amount of oxygen consumed per minute,
which is called VO2. The rate of metabolism
for adults at rest is approximately 3 cc/kg/min
or 120 cc/min/m2 for a typical adult (children
Figure 4-1. A summary of oxygen consump-
4 cc/kg/min, infants 5 cc/kg/min). Metabolism tion, delivery, and metabolism.
31
Chapter 4
the capillaries. About 20-25% of the oxygen is tant (and as a single value, perhaps the only
removed for metabolism (although the oxygen important) measurement of oxygen in blood.
extraction ratio varies from organ to organ) In clinical practice the amount of dissolved
so 75-80% of the oxygen is still in the venous oxygen is less than 1% of the content, so the
blood on the way back to the heart and lungs. second half of the equation involving PO2 is
Carbon dioxide is produced during metabolism; usually ignored. Figure 4-3 shows the relation
the amount (VCO2) is essentially the same as the among these measurements. Notice that there
amount of oxygen consumed (3 cc/kg/min). CO2 is twice as much oxygen in arterial blood at a
comes out of the blood in the lungs and into the normal hemoglobin (content 20 ml/dl) than in
exhaled air. The amount of oxygen consumed anemic blood (content 10 ml/dl), even though
and CO2 produced is different for each organ the oxygen saturation and PO2 are the same in
but the average for all organs is measured by both samples.
O2 and CO2 exchange in the lungs (Figure 4-2). The amount of oxygen delivered to metabo-
These principles apply to all ages and sizes, lizing tissue is the oxygen content in arterial
and size specific parameters are normalized to blood times the blood flow (cardiac output),
weight or BSA. Typical adult values are used called the oxygen delivery (DO2).
in the examples in this chapter.
DO2 (cc/min) = CO2 (cc/dl) x CO (1/min)
Oxygen in Blood x 10 (dl/l)
The oxygen content is the amount of oxygen For an adult the normal DO2 is 600 cc/min/
bound to hemoglobin plus the amount dissolved m (20 cc/dl × 3 l/min/m2 x 10).
2
in plasma related to PO2: The normal amount of oxygen consumed

by tissues at rest is 120 cc/min/m2, abbreviated
CO2 (cc/dl) = Hb (gm/dl) x SO2 x 1.34 (cc/gm) as VO2. Figure 4-4 displays the relationship
+ PO2 (mmHg) x .003 (cc/dl/mmHg) between these concepts. The DO2 is controlled
Oxygen content is difficult to measure di-

rectly so it is typically calculated and reported
by blood gas analyzers. It is the most impor-
Figure 4-3. Oxygen in blood is measured as

PO2, oxyhemoglobin saturation, and oxygen
content. Oxygen content is the only measure-
Figure 4-2. Oxygen delivery/consumption ment of the amount of oxygen in blood, hence
(DO2/VO2). Typical adult values are shown. the most important measurement.
32
by homeostatic mechanisms to be 5 times VO2, Cardiopulmonary Pathophysiology

so in a resting adult 20% of the available oxy-
gen is used for metabolism, leaving 80% in the The relationship between DO2 and VO2
venous blood. Therefore, the normal arterial can be affected by disease states, primarily
oxygen values of a patient breathing air are PO2 those that affect oxygenation and cardiac out-
90 mmHg, saturation 100%, O2 content 20 cc/ put. If the DO2 is decreased compared to VO2
dl. Normal venous oxygen values are PO2 40 (eg, in low cardiac output states, anemia, or
mmHg, saturation 80%, content 16 cc/dl. The hypoxemia), VO2 continues at the same rate,
VO2 increases with exercise, catecholamine thus more oxygen is extracted per dl of blood,
release or administration, and sepsis. The DO2 leaving less oxygen in venous blood. Normal
adjusts to VO2, maintaining the ratio at 5:1. DO2 aerobic metabolism continues in this setting.
is limited primarily by cardiac output. If VO2 However, when the DO2 is less than twice the
increases relative to DO2 (or if DO2 is impaired), VO2, oxygen supply is inadequate to maintain
a higher fraction of the arterial oxygen content aerobic metabolism and anaerobic metabolism
is removed by the tissues, so the content in the ensues, producing lactic acid rather than CO2. A
venous blood decreases from the normal 16 cc/ DO2:VO2 ratio less than 2:1 leads to supply-de-
dl to lower levels. This is well tolerated until pendency hypoxia and systemic acidosis, with
the DO2/VO2 ratio is below 2:1 (50% extrac- resultant organ failure (Figure 4-4). A goal of
tion). At that point there is not enough oxygen managing any critically ill patient is to maintain
available to maintain oxygen-dependent (aero- DO2:VO2 close to normal (5:1), or at least more
bic) metabolism, and metabolism switches to than the critical 2:1. So it is important to know
anaerobic processes which causes exhaustion the VO2 and DO2 when planning management.
and lactic acidosis. The VO2 below this level
then becomes dependent on the supply of O2. Cardiopulmonary Pathophysiology during
Anaerobic metabolism is tolerated for a few ECMO
hours at most, leading to cardiovascular and
metabolic collapse if it persists. ECMO is used when heart or lung failure is
so severe that DO2:VO2 is less than 2:1, or when
the interventions needed to keep DO2 twice
VO2 are inherently damaging (eg, high airway
pressure, high FiO2, or vasoactive drugs at
high doses). In its simplest form (venoarterial),
ECMO maintains normal DO2:VO2 by draining
most of the venous blood, pumping it through
a membrane oxygenator, and into the systemic
circulation. Most of the blood bypasses the heart
and lungs and the artificial organs replace the
function of the diseased heart and lungs. This
is shown in Figure 4-5, in a neonate, as an ex-
Figure 4-4. DO2/VO2 relationships during ample. On ECMO, safe DO2:VO2 is restored
normal and elevated metabolic rate. DO2 and the damaging ventilator settings and drugs
adjusts to changes in VO2 over a wide range, are discontinued. This provides time for the
maintaining DO2 5 times VO2. If DO2 drops
below 5:1, aerobic metabolism continues, but organ dysfunction to be diagnosed and treated,
if DO2/VO2 is less than 2:1, anaerobic metabo- leading to organ recovery in most cases.
lism and shock occurs.
33
Chapter 4
The ECMO Circuit Centrifugal pumps create suction which can

lead to hemolysis when the suction pressure is
Cannulation high, so centrifugal pumps are operated under
conditions to avoid high suction pressures. Gen-
Blood flow through the extracorporeal cir- erally, pressures no more negative than about
cuit is limited primarily by the size of the venous -50 mmHg are targeted.
drainage catheter. Resistance to blood flow var-
ies directly with the length of the catheter and Membrane Lung (Oxygenator)
inversely with the fourth power of the radius
of the catheter. Consequently, the shortest and Modern membrane lungs achieve gas ex-
largest internal diameter catheter that can be change by perfusing venous blood through a
placed in the right atrium via the access vein network of thousands of small hollow fibers.
will allow the highest rate of extracorporeal The tubes are filled with continuously flowing
blood flow. Blood drains through the venous gas (the “sweep gas”), either 100% oxygen or
tubing to a pump that directs the blood through an air/oxygen mix, while blood flows exterior
the membrane lung and back into the patient. to the fibers. The hollow fibers are made of
a material that allows gases to diffuse across
Blood Pump the membrane wall, but prevent liquids from
passing through. Oxygen and CO2 diffuse
Blood pumps are designed to direct the between the gas and the blood as a function
venous drainage through the membrane lung, of the gradient between the partial pressures
then return it into the patient. Pumps can be on each side. When the gas is 100% oxygen,
centrifugal, servo-modified roller, or peristaltic. the gradient driving gas transfer is from 600
Centrifugal pumps modified for long-term use to 40 mmHg for O2, and 45 to 0 for CO2. Even
are the most commonly used. Rupture of the though the gradient is much larger for oxygen,
circuit can occur when the post pump pressure the solubility and diffusivity of CO2 is much
exceeds 300 mmHg, so pumps are modified to greater, so the amount of O2 and CO2 exchanged
prevent overpressure. is roughly equal when to ratio of blood flow to
gas flow is 1:1.
Oxygen Transfer in Membrane Lungs
The maximal O2 transfer capacity of any

membrane lung is determined by the gas ex-
change surface area and the amount of disrup-
tion of laminar flow as blood passes through the
device. Laminar flow allows equilibration of
blood of lower PO2 at the membrane interface,
reducing the gradient for diffusion. Laminar
flow is disrupted by small secondary flows as
the blood moves through the irregular blood
flow path, mixing fully saturated red cells with
deoxygenated red cells and maintaining the
gradient. The amount of mixing by secondary
Figure 4-5. A simple diagram of VA-ECMO,
shown in a newborn. flows is one of the most important factors in
34
determining the maximal oxygenating capacity. CO2 Transfer

All these factors are summarized in the concept
of “rated flow.” When venous blood is perfused The amount of CO2 cleared by any mem-
at a low flow through a membrane lung there is brane lung is the inlet minus outlet CO2 content
sufficient time for equilibration and the hemo- difference (DI-O CO2). At 1:1 gas to blood flow
globin saturation of the outlet blood is 100% ratio this will be about the same as oxygen. But
saturated. As flow increases, a point is reached when the sweep to blood flow ratio is increased
when the blood passes through so fast that all to as high as 8:1, a much larger DI-O can be
the red cells are not oxygenated, and the outlet achieved and much more CO2 can be removed.
saturation drops below 100% saturation. The Therefore when a membrane lung is used pri-
flow of venous blood which exits the membrane marily for CO2 removal, high gas:blood ratios
lung at 95% saturation is defined as the “rated are used and CO2 clearance can be achieved at
flow” (standard venous blood is defined as a much lower blood flow than when the goal is
Hb 12 gm/dl, and saturation 70%, Figure 4-6). oxygenation. The sweep gas flow rate is set by
Oxygenators for ECMO are chosen based on the operator based on the desired PaCO2. These
the rated flow for oxygenation. The size of the phenomena are demonstrated in Figure 4-8.
oxygenator is matched to the oxygen require-
ment of the patient. Other Components
As long as a membrane lung is perfused at
a rate below rated flow, the amount of oxygen The cannulas, pump, and membrane lung
delivered to the blood by any membrane lung are connected by conduit tubing. It might seem
is the outlet minus inlet O2 content difference desirable to have the circuit as close to the
(DO-I) times the flow. Normal DO-I differ- patient as possible, but usually the connection
ence is 5 cc/dl. Figure 4-7 shows the amount lines between the patient and the circuit are
of oxygen delivered related to blood flow for about 6 feet long because it is easiest to care
different DO-I. for both the patient and the circuit when they
Figure 4-6. The concept of “rated flow.” Ve-

nous blood perfused through a membrane lung
exists at 100% saturation until a limitation is
reached and blood exists at less than 100% Figure 4-7. The amount of oxygen supplied by
saturation. The capacity of membrane lungs a membrane lung is the flow times the out-in O2
is described as “rated flow.” content difference. Blood flow is in deciliters.
35
Chapter 4
are separated. One reason is because the pump with left ventricular blood which has traversed
and lung are mounted on a bulky cart which also the lungs. Hence, the content of oxygen and
carries the pump motor, a large battery, a water CO2 in the patient’s arterial blood represents a
bath for circulating warm water through the heat combination of blood from these two sources,
exchanger, an oxygen tank and gas regulator for and the total systemic blood flow is the sum
travelling, and the monitors and displays. Moni- of the extracorporeal flow plus the amount of
tors and alarms can include venous and arterial blood passing through the heart and lungs.
blood gases, pre and postpump pressure and Hemodynamics of VA access are dem-
flow, and blood temperature. There are access onstrated in Figure 4-9. As venous blood is
sites for infusion and blood sampling. drained from the right atrium and perfused into
the aorta, the total blood flow remains constant
ECMO Circuit Physiology but the pulse contour decreases since there is
less blood ejected from the left ventricle. When
The circuit blood and gas flow are set by the extracorporeal flow is 100% of the venous
the operator to match the needs of the patient. return the systemic pulse contour is flat. This
The amount of O2 and CO2 transfer is estimated is the situation in VA access for heart surgery
based on all the information above, then ad- (cardiopulmonary bypass, CPB). In CPB, the
justed to achieve the physiologic goals. Usually superior and inferior vena cavae are occluded
the circuit is set to totally support the circula- proximal to the drainage cannulas, so that all
tion and respiration initially, then decreased as the venous return (except the coronary sinus)
physiologic goals are met. goes through the circuit. In VA-ECMO the flow
is maintained at about 80% of venous return, so
Modes of Vascular Access and Perfusion 20% passes through the heart and lungs. The
reason is to avoid stagnant flow and clotting
Venoarterial ECMO in the pulmonary vessels and chambers of the
heart (which can occur, even with systemic an-
In venoarterial bypass (VA), the functions
of both heart and lungs are replaced by artificial
organs, either totally or partially. During partial
VA bypass perfusate blood mixes in the aorta
Figure 4-9. Physiology of VA perfusion. As

extracorporeal flow increases, pulmonary flow
decreases and pulse pressure decreases until
total extracorporeal flow is reached. During
Figure 4-8. CO2 removed when gas to blood VA-ECMO extracorporeal flow is ideally at
flow is 1:1, 4:1, and 8:1. Data for 2 membrane 80% of total flow, so the pulse pressure is
lungs is shown (PL1 and PL2). about 10 mmHg.
36
ticoagulation). Even in severe heart failure, the VA-ECLS Compared to CPB

heart can usually pump a small amount of blood
when 80% of the circulation is provided by the While the principles of gas exchange and
ECMO circuit. In practice, this proportion of blood flow are the same, there are several
extracorporeal to cardiac flow is represented important differences between the conduct of
by a pulse contour of about 10 mmHg. The best ECLS and operating room bypass. Table 4-1
way to assess heart function in VA-ECMO is by summarizes some of the more important differ-
echocardiography. ences. Because the purpose of operating room
If the heart is completely nonfunctional, all CPB is to permit operations on the heart, total
the venous return drains into the extracorporeal venoarterial bypass is always used, with airtight
circuit and there is no arterial pulse contour. The occlusion of the venous drainage catheters and
patient is on total CPB (as during cardiac sur- arterial access, usually directly into the aorta.
gery). This is tolerated for a few hours (enough Because there is total stagnation of blood in
time to operate on the heart, then restore circula- the pulmonary circulation and some chambers
tion), but in ECMO this leads to two problems. of the heart, total anticoagulation is required,
First, the left side of the heart gradually fills with achieved by giving a huge dose of heparin to
blood from bronchial and Thebesian venous make the whole blood clotting time infinitely
flow. This causes increased pressure in the left long. This anticoagulation, and uncontrolled
ventricle, atrium, and pulmonary circulation. blood flow into the operative field from the
When that pressure reaches 20-25 mmHg, coronary sinus, bronchial veins, and Thebesian
pulmonary edema occurs and the LV becomes veins, results in continuous bleeding which is
overdistended. This must be treated by draining managed by aspiration and filtration of the shed
blood from the left side of the circulation into blood with return to the venous reservoir (so
the circuit. This is done by creating an atrial called cardiotomy suction or autotransfusion).
septal defect, or by placing a drainage cannula To minimize this bleeding into the field, and to
in the LA (or pulmonary artery). The second minimize any risks associated with high blood
problem is that blood in the cardiac chambers flow, it is common practice to manage systemic
and pulmonary circulation will clot, even with perfusion at abnormally low levels of blood flow
systemic anticoagulation. This is treated by (2-2.4 L/m2/min) and abnormally low hemato-
using higher levels of systemic anticoagulation, crit (typically 20%). This combination of low
and adding urgency to going from ECMO to a blood flow and low hematocrit leads to very low
VAD and restoring pulmonary circulation. systemic oxygen delivery, which could result in
oxygen debt and metabolic acidosis, except that
total body hypothermia is usually implemented,
maintaining the ratio of delivery to consump-
Table 4-1. Comparison of CPB in the operating room and VA-ECMO in the ICU.
CPB vs. ECMO*

Major Differences OR CPB ECMO
Open Reservoir Yes No
Heparin (ACT) >600 180
Autotransfusion Yes No
Arterial Filter Yes NO
Patient Asleep Awake
Environment OR, Hours ICU, Days
*Venoarterial bypass, same devices, physiology
37
Chapter 4
tion in the normal range of 5:1. Therefore a must be instituted. The patient is anesthetized
very efficient heat exchanger and a large water and paralyzed rendering neurologic evaluation
bath are required for cardiopulmonary bypass impossible. Everyone caring for the patient
for heart surgery. measures success or failure in hours of CPB.
Aside from these differences in perfusion In contrast, ECLS is managed in the ICU
technology, the entire approach to management by a team expecting days or weeks of continu-
of extracorporeal circulation differs markedly ous care. The patient is maintained awake or
comparing CBP to ECLS. Cardiopulmonary awakened at regular intervals to evaluate neuro-
bypass is conducted in the operating room with logic function. Feeding, ventilation, antibiotic
the sole intention of operating upon the heart. management, renal function are all-important
There is an appropriate sense of urgency to aspects of ECLS care. The use of inotropic
minimize the time on bypass. Complications drugs and high ventilator settings is minimal,
including myocardial damage, renal failure, and weaning from bypass may proceed over a
liver failure, hemolysis, and abnormal bleeding period of hours or days. The patient commonly
increase proportionate to the amount of time lacks heart, lung, or renal function for days, and
on bypass. Unlimited amounts of bleeding in futility is conceded only after many days of vital
the operating field are tolerated and managed organ failure.
by autotransfusion, with the realization that the
effect of heparin will be reversed by protamine Gas Exchange in VA Access
at the end of the procedure. An hour or two of
rewarming and attempts to come off bypass is During VA-ECMO, fully saturated blood
considered an exceedingly long and tedious from the circuit is perfused into the aorta and
interval. Sometimes huge doses of catechol- mixes with blood from the left ventricle. If the
amines are given to encourage a sluggish heart lungs are functioning well, the mixed blood is
simply in order to come off bypass. If the pa- well oxygenated and has normal PCO2. The
tient cannot be weaned off bypass in a few hours, patient can be weaned from the ventilator and
a mechanical support system (ECMO or VAD) managed awake. If the lungs are functioning
Figure 4-10. VA-ECMO with jugular-carotid Figure 4-11. VA-ECMO with femoral-femoral
access. access.
38
poorly or not at all, the systemic blood gases Hemodynamic Effects of VA-ECMO
will reflect the mixture of the cardiac and extra-
corporeal flows, resulting in lower oxygenation By reinfusing blood directly into the arterial
proximal to the site of mixing. If the mixing system, VA-ECMO augments the cardiac output
is in the proximal aorta, blood to the brain and provided by the native heart. Since the heart and
coronary circulation is well oxygenated. This is lungs are bypassed, cardiac output decreases as
demonstrated in Figure 4-10. In femoral artery extracorporeal flow increases, shifting systemic
access the mixing takes place in the mid aorta, blood flow from pulsatile to nonpulsatile flow.
so the upper body is perfused by the blood from As long as venous return remains adequate,
the left ventricle. This can result in differential total systemic blood flow increases since cir-
circulation with the lower body perfused by cuit flow is higher than the output of the left
fully saturated red blood while the upper body ventricle. VA-ECMO thus augments systemic
is perfused with desaturated blue blood. This is oxygen delivery through both increased oxygen
referred to as the Harlequin or red feet blue head content and blood flow, and improves systemic
syndrome (also known as differential cyanosis blood pressure via higher blood flow through
or differential hypoxia). This is demonstrated in resistance vessels.
Figure 4-11. The management of the Harlequin An adverse but unavoidable result of VA-
syndrome is to perfuse some of the post oxy- ECMO is increased left ventricular afterload
genator blood into the right atrium (combining associated with the higher arterial blood pres-
VA with VV perfusion). This is accomplished sure that can impact myocardial recovery, but
by inserting an infusion cannula via the jugular despite this the myocardium typically recovers
vein, or by perfusion of a second lumen in the since preload is reduced and coronary blood
drainage line as shown in Figure 4-12. flow is maintained.
Managing VA-ECMO Based on These

Principles
In VA access the parameters described in

Figures 4-9, 4-10-12 are monitored, and VO2
and DO2 are calculated from these measure-
ments. That information informs the adjusting
of ECMO variables and patient variables to
maintain DO2:VO2 at 3:1 or higher.
1. Plan the circuit based on the best estimation

of the metabolic rate (adults, 3-4 cc/kg/
min for both O2 and CO2) and the drainage
flow which can be achieved from the larg-
est drainage cannula which can be placed.
Plan for total support, realizing that there
may be some native lung function and total
Figure 4-12. VA-ECMO with some arterial-
ized returned to the right atrium to treat the support may not be necessary. For a septic
differential circulation syndrome when lung 80 kg adult you will need 5 L/min flow, and
function is compromised. Arterial blood is an oxygenator with rated flow over 5 L/min
“Y’d” off the infusion line, through a second
lumen in the drainage cannula. to supply 300 cc O2/min.
39
Chapter 4
2. On ECMO go to the highest flow to de- Venovenous ECMO

termine the maximum drainage capacity
following the pulse contour. If the drainage In venovenous ECMO (VV), the perfus-
cannula is large enough, total bypass (non- ate blood is returned to the venous circulation
pulsatile flow) will result. Then decrease the and mixes with venous blood coming from the
flow until the pulse contour is 10-15 mmHg. systemic organs, raising the oxygen content and
Vasoactive drugs should be decreased to low lowering CO2 content in the right atrial blood.
or absent levels. If there is no LV function This mixed blood, now higher in oxygen con-
establish left atrial drainage. tent, passes into the right ventricle, the lungs,
3. When the patient is stable (usually 6-12 and into the systemic circulation. VV access
hours), determine the variables of O2 kinet- is achieved by draining venous blood from the
ics, using the formulas described above. If IVC via the femoral vein and reinfusing into the
oxygen supply is adequate (DO2:VO2 over RA via the jugular (Figure 4-13), or by drain-
3) no changes are necessary. If oxygen sup- ing from the IVC and SVC and reinfusing into
ply is inadequate (DO2:VO2 under 3) and the RA via a separate lumen in a double lumen
the patient is anemic, transfuse to a higher cannula (Figure 4-14).
hemoglobin (12-14 gm%) This will result in Hemodynamics during VV access are not
arterial saturation around 90% and venous affected by the circuit. Since the volume of
saturation around 65% (DO2/VO2=3-4). blood removed is exactly equal to the volume
4. Manage the patient based on continuous of blood reinfused; there is no net effect on
venous and arterial saturation monitoring. central venous volume or pressure, right or
Plot the position on Figure 4-4 frequently. left ventricle filling, or hemodynamics. The
Calculate the variables if oxygen supply content of oxygen and CO2 in the patient’s
seems excessive or inadequate. arterial blood represents that of right ventricle
5. When the native heart begins to recover blood modified by any pulmonary function that
(pulse contour increases when flow is de- might exist. The systemic blood flow is the
creased) turn down the flow, keeping the native cardiac output and is unrelated to the
venous saturation >70%. When the native extracorporeal flow.
heart function is adequate, conduct a trial
off bypass. When heart function is satisfac-
tory, decannulate the patient.
Figure 4-13. VV-ECMO for respiratory sup- Figure 4-14. VV-ECMO with a double lumen
port. 2-Cannula access. cannula.
40
Gas Exchange in VV-ECMO outlet minus inlet O2 content. Because the outlet
blood is typically 100% saturated and PO2 is
In VV-ECMO, some of the systemic ve- over 500 mmHg the dissolved oxygen can be
nous return is drained into the ECMO system, as much as 10% of the oxygen content.
oxygenated, and returned to the right atrium. Blood flow is limited by the resistance to
Some of the systemic venous return goes di- flow in the drainage cannula, the suction pro-
rectly to the right atrium where it mixes with duced by the pump or siphon, and the geometry
the ECMO perfusate blood. The mixed blood of the cannulated vessel (usually the vena cava
passes through the right ventricle, native lungs, or right atrium). Typical maximum flow at 100
left heart and into the systemic circulation. In cm/H2O suction for common sizes of venous
severe respiratory failure, the native lungs cannulas is 4-5 liters per minute.
contribute little or none to gas exchange, so the
arterial oxygen and CO2 levels are the result of Relation of Extracorporeal Oxygenation to
mixing the oxygenated ECMO blood with the Systemic Oxygen Delivery
deoxygenated native venous blood. As a result,
the arterial saturation ranges from 60% to 90%, Assuming that there is no native lung func-
depending on the relative amount of ECMO tion, the systemic arterial content, saturation,
flow, native venous flow, lung function, and and PO2 will result from mixing the flow of
cardiac output. The desaturated arterial blood oxygenated blood from the membrane lung with
results in normal systemic oxygen delivery the flow of venous blood which passes into the
as long as the cardiac output and hemoglobin right ventricle, not into the ECMO drainage can-
concentration (oxygen content) are adequate. nula, (hereafter referred to as the native venous
These relationships are often confusing to ICU flow). The amount of oxygen in systemic arterial
staff, because the usual goal of management is blood is the result of the mixture of these two
to keep the arterial saturation over 90%. flows (Figure 4-15).
Oxygenation
To illustrate the principles, the discussion

begins with the assumption that there is no na-
tive lung gas exchange (which is often the case
in ECMO patients). In a membrane lung (as in
the native lung) oxygenation is a much greater
problem than CO2 removal, so the initial focus
is on oxygenation. The circuit and blood flow
are planned for total oxygen supply (VO2) at
rest or during moderate exercise. For adults
this is 120 cc/min/m2 (3 cc/kg/min), or 250-
300 cc of oxygen/min for average adults. The
membrane lung must be large enough to transfer
this amount of oxygen. All devices currently on
the market can achieve this (see “rated flow”).
The oxygen supply from the membrane lung is
dependent on the blood flow, the hemoglobin Figure 4-15. Mixing of perfusate with native
concentration, and the difference between the venous flow during VV-ECMO.
41
Chapter 4
Calculations Related to Mixing Two Flows Systemic Arterial PO2, Saturation, and Con-
tent During VV ECMO
When two blood flows of different oxygen
contents mix, the resultant oxygen content is Use of these equations in VV patient
the average of the amount of oxygen in each physiology are shown in Figure 4-18. In these
of the two flows (not the average of the partial examples, one variable is changed while oth-
pressures). The amount of oxygen contributed ers are held constant to illustrate the principles.
by each flow is the oxygen content (in cc/dL) Clinically, all these variables may change
in the blood times the flow rate (in dL/min). simultaneously and at different rates. For sim-
The equation summarizing these events is in plicity of the examples, we assume no native
Figure 4-16. The same calculation can be done lung function, and approximate the points on
using saturation rather than oxygen content. the graphs. We do not account for dissolved
This calculation using saturation is done for oxygen in calculation of O2 content, although
simplicity and is not an exact representation of it can be significant when the PO2 is over 300.
the amount of oxygen content but is useful at Example 1: Typical VV physiology. Sup-
the bedside (Figure 4-17). The combinations pose the extracorporeal flow for an adult with no
of flow and oxygen (expressed as saturation) lung function is 4 l/min and the systemic PO2 is
variations are shown in Figure 4-18. Of the 50 mmHg, saturation 88%, O2 content 12.3 cc/
variables in the equation, all are known except dl. The Hb is 10.5 gm/dl and the venous blood
the flow of venous blood which does not go saturation is 64%. The patient’s oxygen con-
through the extracorporeal circuit (the native sumption is 200 cc/min. The oxygen content of
venous flow). The native venous flow can blood leaving the membrane lung is determined
be back calculated from the systemic arterial primarily by the concentration of hemoglobin.
oxygen content or saturation. The total venous At hemoglobin concentration of 10.5 gm/dl and
return (cardiac output) is the sum of the native 64% saturation, the drainage (inlet) O2 content
venous and circuit flow. is 9 cc/dl and the outlet content at 100% satura-
Figure 4-16. The relationship among flow and

O2 content are shown in the equation. During
ECMO all the variables are known except na-
tive venous flow (F2) and total flow (cardiac Figure 4-17. The relationships among flow
output). Native venous flow can be calculated. and O2 content using the data in Example 1.
Cardiac output is F2 plus F1. This assumes no The same calculations are shown using satura-
lung function and no recirculation. tion rather than content.
42
tion is 14 cc/dl. The amount of oxygen supplied is lower. The systemic oxygen delivery is 920
to the patient is the outlet minus inlet content cc/min. The DO2/VO2 is 4.6. There has been
(which is 5 cc/dl), times the flow (40 dl/min) a gain in systemic oxygen delivery because of
equals 200 cc oxygen supplied per minute. The the higher cardiac output, despite a decrease in
native venous flow is calculated at 2 L/min (per arterial saturation and content. If the patient’s
equation in Figure 4-17) so the cardiac output is systemic oxygen consumption is 200 cc/min,
6 L/min (native plus circuit venous flow). DO2 systemic oxygen delivery is perfectly adequate
is the arterial content (12.3 cc/dl) x 60 dl/min = and full aerobic metabolism is supported, even
738 cc/O2/min. DO2/VO2 ratio is 3.64. The O2 though the arterial PO2 is 45 mmHg and arte-
content of native venous blood is the same as rial saturation is 84%. No changes are required
the drainage content (9 cc/dl). The final com- but the ICU staff need to understand that the
plete equation is 40 dl/min x 14 c/dl divided by hypoxemia does not require intervention. Un-
60 dl/min, plus 20 dl/min x 9 dl divided by 60 derstanding this concept can be difficult when
dl/min=12.3 cc/O2/dl (corresponding to a PO2 the plan is to keep the arterial saturation over
of approximately 50 mm/Hg). The calculation 90%. (Point B, Figure 4-18)
using saturation is 4 L/min x 100% + 2 L/min x Example 3: Anemia. The patient in Ex-
70% ÷ 6 L/min which yields a systemic arterial ample 1 is moderately anemic (Hb 10, 5 gm%)
saturation of 88% (Point A, Figure 4-18) but stable. Suppose the hemoglobin suddenly
Example 2: Increased cardiac output at drops to 8 gm%. The venous drainage is fixed
fixed ECMO flow. If, in the same patient, the at 4 L/min by the resistance of the drainage
cardiac output (venous return) increases to 8 L/ cannula, and cardiac output is 6 L/min. The
min and the circuit flow is fixed at 4 L/min there outlet content at 100% sat is 10.7. The amount
will more native venous return at 64% sat mix- of oxygen supplied by the membrane lung is
ing with the fully saturated ECMO flow. The 10.7 minus 9 which is 1.7 cc/dl, so the mem-
systemic arterial content will decrease to 11.5 brane lung is supplying only 68 cc/min. The
and the saturation will decrease to 84% corre- native venous flow is 20 dl/min and content is
sponding to PO2 of 45 mmHg. The total amount 9 cc/dl. The arterial content has gone from 11.5
of oxygen going to the patient is the same (200 to 9.8, the arterial sat to 80% and the DO2 has
cc/min), but the systemic saturation and PO2 gone from 738 cc/min to 588. This results in a
DO2/VO2 ratio of 2.9 (assuming no difference
in metabolic rate). However, since only 68 cc
of oxygen is being added per minute, and the
oxygen consumption is 200 cc/min, venous
(inlet) content and saturation decrease quickly.
When the inlet content falls to 5.7 (saturation
50%) the membrane lung O-I difference is 5 cc/
dl and the oxygen supplied is 200 cc/min. The
mixture of the fully saturated blood at 40 dl/
min and the 50% saturated native venous flow
results in arterial saturation of 75% and arterial
content 9 cc/dl. The systemic oxygen delivery
is 540 cc/min and the VO2/DO2 ratio is 2.7. The
patient can remain in steady state with arterial
Figure 4-18. Mixing of flows in VV-ECMO. saturation 75% and venous saturation 50%, but
Data from Examples 1-4 are shown. any further decrease in hemoglobin or increase
43
Chapter 4
in metabolic rate will result in supply depen- flow from 4 to 5 L/min (maintaining Hb 10.5).
dency and lactic acidosis (Point C, Figure 4-18). The DO2 increases to 792 cc/min, and the DO2/
Example 4: Increased metabolic rate. VO2 is 3.9. The third alternative for example 4 is
Suppose the patient in Example 1 becomes to paralyze and cool the patient, decreasing the
hypermetabolic (VO2=250 cc/min). The size of VO2 back to 200 cc/min. A fourth consideration
the venous cannula determines that the circuit is to add another membrane lung to increase
flow is at maximum at 4 L/min so the circuit the gas exchange surface, but O2 supply is still
oxygen delivery is limited to 200 cc/min. The limited by the blood flow, so this will not help.
cardiac output is 6 L/min. Going through the The tradeoff between extracorporeal flow
same arithmetic, the patient will fall behind and hemoglobin is demonstrated in Figure 4-19.
at the rate of 50 cc of oxygen per minute and This example shows a 80 kg man with oxygen
venous content and saturation will steadily de- requirement of 240 cc/min, but the relationships
crease (70% to 45%, for example). As venous remain the same for any size patient. Under
saturation and content decrease, the oxygenator most circumstances, the risks of increasing
will still increase the outlet saturation to 100% extracorporeal flow are greater than the risks
and oxygen content to 14 cc/dl, so the circuit of transfusion.
outlet minus inlet oxygen difference (oxygen
supply) will go up as the venous saturation Oxygenation in VV-ECMO
goes down (from 5 to 6 for example). Systemic
saturation will decrease because the saturation The combination of venous access cannula,
and content of the native venous blood going membrane lung size, and hemoglobin concen-
through the heart and lungs will decrease. At tration should be planned to match or exceed
venous content 7.5 the O-I content difference resting VO2 (120 cc/m2/min for adults). The
is 6.5 and the oxygen supplied is 260 cc/min. membrane lung will supply the most oxygen
Steady state is reached with arterial saturation at at a normal hemoglobin (15 gm/dl). All the
about 75% and PaO2 35 mmHg. The DO2/VO2 important variables related to blood flow and
is 2.1 and any increase in activity will lead to oxygenation can be measured or calculated. It
anaerobic metabolism which will produce lac- is essential to know the patient’s oxygen con-
tate rather than CO2, and lactic acidosis results.
In time, this will lead to multiple organ failure
and death (Point D, Figure 4-18).
How can systemic oxygen delivery be in-
creased in Examples 3 and 4? Turning up the
ventilator FiO2 or airway pressure will not help.
Furthermore, the whole objective is to avoid in-
creasing FiO2 and pressure from the mechanical
ventilator. There are four alternatives. The first
is to increase the hemoglobin concentration to
normal. When hemoglobin goes from 10.5 to
15, systemic oxygen delivery goes to 930 cc/
min, arterial saturation returns to 95%, venous
saturation goes to 80%, and the patient is stable
and well supported. The DO2/VO2 is 4.6. The Figure 4-19. The tradeoff between hemo-
globin and flow. The relationships to deliver
second alternative is to increase the suction or 240 cc O2 per minute are shown, but the same
add another cannula and increase the circuit calculations can be done for any oxygen supply.
44
sumption and systemic oxygen delivery to decreases, and becomes markedly elevated when
cide the best way to manage the extracorporeal cardiac output drops below extracorporeal flow.
circuit. Hypoxemia (PaO2 40-60, SaO2 70-90) Increases in recirculation during extracorporeal
always occurs with venovenous support and is support can result from dislodgement of can-
adequate to maintain normal oxygen delivery. If nulas, such as closer approximation of single-
systemic oxygen delivery falls to a critical level lumen cannulas from inadvertent advancement,
(near twice consumption), circuit oxygen supply or accidental withdrawal or advancement of a
must be increased by: 1) transfusing to a higher dual lumen cannula, in which the distal drainage
hemoglobin or; 2) adding additional venous port moves into the right atrium, or the reinfu-
drainage access to increase the flow. There is sion port advances into the inferior vena cava,
a tradeoff of risk between transfusion and in- respectively.
creasing circuit flow which favors transfusion
of RBCs. Membrane lungs function optimally Hemodynamics during VV-ECMO
at a normal hematocrit.
Unlike venoarterial support, VV-ECMO
Recirculation during VV-ECMO does not provide any direct hemodynamic sup-
port since there is no reinfusion of blood into
Since VV-ECMO reinfuses blood drained the arterial system. Venous return and pulsatility
from the vena cavae or right atrium back into are unaffected since drainage and reinfusion are
the central venous system, the potential exists in equilibrium.
for some of the returned blood to be drained Despite the lack of direct support, however,
by the circuit before it mixes with the native myocardial function and cardiac output typi-
venous flow. Recirculation reduces the effec- cally improve during VV support. Reduction in
tive extracorporeal flow by the recirculated mechanical ventilatory support that is allowed
amount. For example, if total circuit flow is 5 from improved gas exchange reduces right
L/min and recirculation is 20% (1 L/min), then ventricular afterload and improves RV func-
only 4 L/min of oxygenated blood is available tion. Improved oxygenation of the pulmonary
to the patient. vascular bed can mitigate hypoxic vasocon-
Determinants of recirculation include the striction. Higher oxygen saturation of left ven-
type and placement of cannulas, and the extra- tricular blood results in improved myocardial
corporeal flow in relation to cardiac output and oxygenation and reversal of hypoxia-induced
vena caval native blood flow. Two-site single myocardial depression. Reduction in acidosis
lumen cannulation is always associated with from correction of hypercarbia and reversal
some recirculation, since the vena caval flow of anaerobic metabolism also contribute to
is less than the circuit drainage, necessitating improved myocardial function.
blood from the atrium containing oxygenated This indirect support is usually sufficient
blood from the circuit being drained as well. to reduce or eliminate requirements for cardio-
Three-site single lumen cannulation, in which vascular pharmacologic agents. Improved organ
both vena cavae are drained, reduces recircula- perfusion can help reverse renal, hepatic, and
tion. Similarly, the dual lumen bicaval cannula other organ failure.
provides drainage from both vena cavae, and is
associated with low recirculation. CO2 Removal
Recirculation fraction is also related to
overall circuit flow relative to cardiac output. CO2 production is equal to O2 consumption
As cardiac output decreases, the fraction in- (when the Respiratory Quotient is 1), so the
45
Chapter 4
amount of CO2 exchanged per minute is essen- of gas exchange in the placenta and fetus. Be-
tially the same as the amount of oxygen (120 cause of the blood flow requirements for gas
cc/min/m2 for adults). Because CO2 is much exchange support, the arteriovenous route is not
more soluble and diffusible in blood than O2, a reasonable approach to total extracorporeal
CO2 clearance will exceed oxygenation in any respiratory support, except when the patient can
circumstance, so all the circuit management is tolerate a large arteriovenous shunt and increase
based on oxygenation. If CO2 clearance is the in cardiac output (such as a premature infant).
only or the major goal, much lower blood flow However, AV flow through a membrane lung
can be used and hemoglobin concentration is can provide significant CO2 removal, decreasing
not important. The amount of CO2 elimination the need for mechanical ventilation.
is a function of the membrane lung surface
area and the gradient between the inlet PCO2 ECMO Management when the Native Lung
(typically 50 mmHg) and the sweep gas (0). The is Recovering
systemic PCO2 is the result of mixing circuit
outlet blood (PCO2 typically 30 mmHg) with All the preceding discussion describes a
native flow (typically 45 mmHg). Like oxygen- situation when there is no native lung function.
ation, the actual amount of CO2 removed by the As the native lung begins to recover, some oxy-
membrane lung is the inlet CO2 content minus gen and CO2 exchange will occur. The effect
the outlet content times the flow. However, CO2 will be to improve systemic arterial oxygenation
content is difficult to measure or calculate, so and PaCO2 with no change in the extracorporeal
actual CO2 removal is measured as the % CO2 flow rate and hemoglobin. It is tempting to
in the exhaust gas times the gas flow. Unlike increase ventilator settings and FiO2 in order to
oxygenation, measuring or calculating the ac- take advantage of this recovery, but this may add
tual amount of CO2 exchanged by the circuit is to lung injury and delay lung recovery. ECMO
not critical; the sweep gas is simply adjusted to is continued during rest ventilator settings, and
maintain the desired systemic PCO2 (typically when arterial PCO2 drops below 40 the sweep
40 mmHg). gas to the membrane lung can be proportionally
One phenomenon unique to ECMO is the decreased. When the systemic arterial satura-
effect of water accumulation on the gas side tion exceeds 95%, the extracorporeal flow can
of the membrane lung. This is the only cir- be gradually decreased (changing the ratio of
cumstance in which CO2 clearance is less than circuit to native venous flow). When the ex-
oxygenation. Understanding the reason is a tracorporeal support has decreased from total
good exercise in understanding how membrane support to approximately 50%, extracorporeal
lungs work. support can be briefly discontinued (at moderate
ventilator settings) to test native lung function.
Arteriovenous CO2 Removal When native lung function is sufficient for total
patient support, ECMO can be discontinued.
Arteriovenous (AV) extracorporeal circula- Because reestablishing vascular access in
tion is commonly used for hemodialysis but not ECMO can be difficult, it is wise to continue
for cardiac or pulmonary support. The AV route ECMO support for a day or two beyond this
can be used for gas exchange provided the arte- point to allow more lung recovery, unless there
rial blood is desaturated, and the cardiovascular is a pressing reason to take the patient ECMO
system can tolerate the arteriovenous fistula (systemic bleeding or CNS complications).
with a large enough flow to achieve adequate
gas exchange. This is, after all, the mechanism
46
Managing VV-ECMO Based on These 5. When the native lung begins to recover (the
Principles arterial saturation is >95%) turn down the
flow, keeping the venous saturation >70%,
In VV access, the parameters described in and the sweep flow, keeping the PaCO2 at
Figures 4-13-15 are monitored and VO2, DO2 40. When native lung function is adequate,
are calculated from these measurements. That trial off ECMO then decannulate.
information is used to adjust the ECMO vari-
ables and the patient variables to maintain DO2/ Summary
VO2 at 3:1 or higher.
1. As in VA access, plan the circuit based on Managing a patient on ECMO requires
the best estimation of the metabolic rate a thorough understanding of normal and ab-
(adults, 3-4 cc/kg/min for both O2 and normal cardiopulmonary physiology, and a
CO2) and the drainage flow which can be thorough understanding of the ECMO circuit.
achieved from the largest drainage cannula Based on this understanding, the ECMO system
(or cannulas) which can be placed. Plan for is used to replace part or all of heart and lung
total support, realizing that there may be function, maintaining normal systemic physiol-
some native lung function and total support ogy while the damaged organs can recover or
may not be necessary. For a septic 80kg be replaced.
adult you will need 5 L/min flow, and an
oxygenator with rated flow over 5 L/min to
supply 300 cc O2/min.
2. On ECMO go to the highest flow to deter-
mine the maximum drainage capacity, then
turn down the ventilator to rest settings
(FiO2 0.3, CPAP 10-15 cm H2O) and wean
off the vasoactive drugs. The hypermetabo-
lism will decrease to baseline. The lungs
may go to total consolidation. Adjust the
sweep gas to keep the PaCO2 40 mm Hg.
3. When the patient is stable (usually 6-12
hours) determine the variables of O2 kinet-
ics, using the formulas described above. If
oxygen supply is adequate (DO2:VO2 over
3) no changes are necessary. If oxygen sup-
ply is inadequate (DO2:VO2 under 3) and
the patient is anemic, transfuse to a higher
hemoglobin (12-14 gm/dl). If DO2 is still
inadequate, change the drainage cannula to
a larger size and increase flow.
4. Manage the patient based on continuous
venous and arterial saturation monitoring.
Plot the position on Figure 4-4 frequently.
Calculate the variables if oxygen supply
seems excessive or inadequate.
47
5
The Circuit
John M. Toomasian, MS, CCP, Leen Vercaemst, RN, ECCP, Stephen Bottrell, CCP,
Stephen B. Horton, PhD, CCP, FACBS
Introduction blood contact gas exchange device with an open

venous cardiotomy reservoir for return of shed
The extracorporeal life support (ECLS) blood from the operative field, the ECLS circuit
circuit consists of the set of artificial organs and required a closed circuit with a gas exchange
equipment that provides mechanical support of device that had no direct air-blood contact. A
the failing heart and/or lungs for days, weeks, or “true” membrane-type gas exchange device
months. A proper circuit design provides a foot- would function for days, weeks, or months.
print to meet the expected metabolic demands Several membrane lungs were used during
of the patient including adequate oxygen (O2) the early clinical history of ECLS including the
delivery and carbon dioxide (CO2) removal. The Landé-Edwards and Bramson membrane lungs.2,
circuit may also provide access for additional 3
However, the gas exchanger that allowed for
therapeutic modalities such as hemofiltration, routine use was the spiral wound reinforced
continuous renal replacement therapy, and car- silicone rubber membrane lung developed by
diovascular intervention. The circuit requires Theodor Kolobow in the 1960s.4 This device
management by trained specialists who are had a long blood path which resulted in a high
readily available to respond and troubleshoot resistance to blood flow, often generating a 200-
any circuit related irregularity. This chapter 300 mmHg device pressure gradient. Priming
describes the fundamental components of an was complex and required a carbon dioxide
ECLS circuit, based on the ELSO Guidelines flush and the use of a vacuum. The membrane
that served as an update from the material from was made from silicone rubber, a highly gas
Chapter 8 of the 4th edition of the Redbook.1 permeable barrier. Gas transfer occurred by
simple molecular diffusion. The device was
Historical Background manufactured in several sizes based on effective
surface area by SciMed, Avecor, and Medtronic.
ECLS involves several mechanical plat- Some devices had an integrated heat exchanger.
forms developed to support the circulation, The device was used for 50 years, until produc-
allowing time for the affected organ system to tion was discontinued in 2012. Despite its few
recover. The traditional circuit was adapted shortcomings, the Kolobow membrane lung had
from devices and techniques used during stan- an outstanding and reliable performance record
dard cardiopulmonary bypass (CPB). Unlike that was the gold standard for gas exchangers.
traditional CPB that used a direct contact gas-
49
Chapter 5
The earliest circuits used roller pumps, as for short-term intraoperative use for CPB (not
centrifugal pumps were only design concepts. to exceed 6 hours). Many CPB components are
The classic roller pump was described by many used in an “off-label” application for extended
but was often credited to Debakey.5 Roller use at the discretion of the treating physician,
pumps used for ECLS were produced in many in a manner that may be outside the indication
sizes and manufactured by various compa- for use. Experience with off-label use has been
nies including: American Optical, Travenol, applied to select patient groups for extended
Polystan, Stockërt, Cobe, Rhone Poulenc, and periods of time. Governmental restrictions for
Sarns. Roller pumps were driven by either belt device use vary by country. For instance, the
or direct drive and presented a unique set of European CE Mark may have different labelled
challenges, especially related to management clearance criteria than the identical device used
of the circuit pressure. A catastrophic blowout in the U.S. The descriptions in this chapter do
occurred if the positive pressure (outlet) side not reflect any specific manufacturer’s recom-
was clamped or occluded. If the pump inlet mendations.
pressure became excessive (negative), air could
enter. Regulating the blood inflow to the circuit General Principles of Circuit Design
became significant. Prior to any servo control
mechanisms, the venous return could only be The ECLS circuit is made from biomaterials
gauged visually and pump speed adjusted manu- and plastics commonly used in traditional CPB.
ally. This was tedious, dangerous, and impracti- The patient and the circuit are typically antico-
cal for use outside the operating room. When agulated to prevent thrombosis. Each circuit can
the roller pump flow exceeded the venous return, vary in sophistication and complexity; however,
the positive blood displacement characteristics each new level of complexity requires the
of the roller pump would easily entrain air into knowledge to troubleshoot and rectify problems
the circuit. To minimize this risk, a small com- that may result. The ECLS circuit may contain
pliant silicone rubber chamber was inserted into a number of access sites that can measure or
the circuit proximal to the pump. If the chamber monitor specific patient parameters such as
was full, blood flow was not impaired and the extracorporeal blood flow(s), circuit pressures,
pump would operate at its set speed. However, oxygen saturation(s), hemoglobin or inline
when pump flow exceeded drainage (ie, kinked blood gases, and other metabolic parameters.
venous drainage line, cannula malposition, or Variations of this design exist and depend on
hypovolemia), the chamber would empty and patient size, physiologic needs, and institutional
partially collapse, tripping a micro-switch that philosophy. When designing the circuit, a goal
stopped or slowed the roller pump.6 As ECLS would be to minimize or eliminate additional
expanded and grew in the 1980s, this design blood components in the prime solution. The
was described, copied, and modified throughout tubing that connects the patient to the essential
the world. This system has been the historic circuit components should not be lengthy, but
template for newer ECLS circuit configurations adequate in length to allow for patient move-
that have been used since the mid 2000s and has ment and transport. Resistance to flow increases
been eloquently described in earlier editions of as tubing length increases.10 Larger volume
the Redbook.7-9 circuits expose the blood to additional foreign
In the United States, all medical devices surface areas that may promote greater inflam-
are “cleared” for use by the U.S. Food and Drug matory response and chance of thrombosis.11
Administration (FDA) for specific indications. Circuits that contain longer than required tubing
The majority of components are manufactured lengths with an excessive number of stopcocks,
50
The Circuit
connectors, and access sites risk more circuit Blood Tubing Plasticizers
related complications. Each connector causes
turbulent blood flow, potential blood element The majority of conduit tubing is made
damage, and creates an area of stagnation that from a formulation of polyvinylchloride (PVC)
can induce clot formation. The “ring thrombus” mixed with a plasticizer. The amount of plasti-
is commonly observed at a tubing-connector cizer determines the tubing durometer or flex-
junction. Luer lock connections have a potential ibility. Known as Di-2(ethyl hexyl) phthalate
to entrain air or leak blood. The access port of (DEHP), DEHP is used to make PVC flexible.
any Luer connector should be positioned point- However, in recent years, concerns have been
ing upwards to avoid thrombus formation that expressed regarding the release of DEHP into
often occurs if the connector is positioned at a the circulation. The FDA has previously is-
lower place, allowing blood cells to collect and sued a public notification regarding exposure
clot. Double luer connectors increase access and to DEHP.14 The lipid content, temperature, and
can be considered when multiple access sites the duration of exposure all affect the leaching
are required. Luer connectors can be used at the of DEHP. Adverse effects have been reported
patient “bridge” site, eliminating the need for in laboratory animals, with the greatest con-
Y-connectors used with a bridge or “diamond” cern being its effects on the male reproductive
configurations. This also eliminates stagnant system.15 The FDA concluded that health risks
areas that are subject to potential thrombosis. from DEHP exposure exist and non–DEHP
With simple design objectives, gas ex- containing substitute products should be used
change devices have been developed that in male neonates, pregnant women, and peripu-
maximize exterior hollow fiber technology with bertal boys when available. Leaching of DEHP
modern compressed surface polymers such as does occur in ECMO circuits, although coated
polymethylpentene (PMP) or polyolefin (PO). circuits decrease or eliminate DEHP leaching
These materials exchange gas as efficiently as from pre-primed circuits.16
their predecessors and can be designed to have The European Commission on Food and
less surface area resulting in a lower device Health also published opinions on DEHP in
pressure gradient. The new generation centrifu- 2002, 2008, and 2014. Opinions in 2008 and
gal pumps are much more efficient than their 2014 stated “there is no conclusive evidence
predecessors and when used in conjunction that DEHP exposure via medical treatments has
with the new lower resistance gas exchange harmful effects in humans.” However, “the new
devices provide support without the problems information indicates that there is still a reason
of hemolysis and mechanical failure commonly for some concern for prematurely born male
observed by their predecessors.12 More sophis- neonates, because of the high human exposure
ticated computer controlled servo-regulated during certain medical procedures.”17 Male
systems exist and when used in conjunction neonates treated in intensive care units are
with newer thin wall cannula designs (including considered at a higher risk of DEHP exposure
double lumen catheters), many of the problems during medical procedures “due to their physi-
observed with older ECLS systems have been cal conditions, the immaturity of many systems
significantly reduced. Integrated component and organs, as well as their small size.” The
systems have continued the trend towards sim- 2014 opinion statement also mentioned that
plicity, with a smaller footprint. Biocompatible “DEHP-containing plasticized PVC devices
circuits also continue to make slow progress to are important for many treatments and justified
reduce some of the deleterious effects of the because of the benefits of these procedures.”
circuit surfaces on blood elements.13
51
Chapter 5
There are active efforts to find safe and suitable result of these potential adverse effects, a num-
alternatives to DEHP in medical devices. ber of modifications to the bridge have been
employed, including an open bridge (regulating
ECLS Circuit Components flow with a thumb clamp), placing a clamp on
the bridge to occlude flow totally, and a bridge
The circuit consists of three primary com- that is closed with stopcocks that can be opened
ponents: blood pump, gas exchange device, and when needed. 22 A bridge is usually not required
heat exchanger. The components are connected during VV support.
by standard medical grade tubing. The circuit
also includes catheters for vascular access, ac- Blood Pumps
cess sites, monitors, and safety devices. With
each additional component added, such as The ECLS blood pump controls the required
an isolated heat exchanger, circuit shunts (ie, blood flow for the patient. They differ in design,
bridges, recirculation lines), connector based capacity, hemocompatibility, durability, avail-
oxygen saturation measurement systems, moni- ability, and hardware features. The choice of
tors, bubble detectors, and alarms, the circuit a pump depends on many factors including
becomes more complex. Added complexity may local expertise and experience, console and
require additional training and limit operation hardware features, regulatory issues, econom-
to a trained circuit specialist. The tubing length ics, and availability. Pumps belong to two basic
and diameter will contribute to the resistance to subgroups: occlusive (positive displacement)
blood flow. Achieving the desired flow is deter- that include modified roller pumps with inlet
mined by the vascular access site(s), drainage pressure control and nonocclusive (rotary) that
tubing diameter, cannula size(s), resistance, and are centrifugal, diagonal, and axial with inlet
pump properties. Tubing size is chosen to allow pressure control, or peristaltic. Rotary pumps
free venous drainage with minimal resistance. require preload and afterload adjustment;
The blood flow through one meter of tubing whereas positive displacement pumps displace
at 100 mmHg pressure gradient for common volume as a function of pump speed regardless
internal diameter tubing (inches) is: 3/16”: 1.2 of preload or afterload conditions. Figure 5-1
L/min; ¼”: 2.5 L/min; 3/8”: 5L/min; ½”:10L/ shows the international trend in blood pump
min.18 A small caliber tubing connection or usage from 2005-2015 from the ELSO Registry
“bridge” that joins the drainage and reinfusion data that includes transition from roller pumps
lines may be incorporated into the circuit at a to centrifugal pumps, currently the predominat
position close to the patient. A bridge may be pump type except in neonates. The chart shows
constructed from tubing or high flow stopcocks the percent breakdown of pump type use per
and small caliber tubing (such as 1/8”-1/4” year and the number of cases in each patient
according to circuit size). As a stagnant area subgroup (neonatal, pediatric, and adult).
the bridge can contribute to thrombosis when
clamped for prolonged periods. The bridge Pulsatility
allows for the patient to be separated from the
circuit in situations such as trial periods off sup- Traditional blood pumps used for ECLS
port, weaning, or an emergency. Periodically the support deliver blood flow in a continuous,
bridge is opened and “flashed” allowing blood nonpulsatile mode. Though not typically used,
to shunt through the connection to reduce clot in theory pulsatile flow has advantages. Pulsa-
formation. Several studies have demonstrated tile perfusion modes have been used to support
the adverse effects of this practice.19-21 As a patients on CPB undergoing primary surgical
52
The Circuit
procedures or long-term ventricular support. Roller Pumps

The greatest limitation to pulsatile support is
the capability to generate a mechanical physi- Prior to the advent of modern centrifugal
ologic pulse wave. The debate over pulsatile pumps, the roller pump was commonly used
vs. nonpulsatile flow continues with no clearly for ECLS. The venous drainage inlet to the
demonstrated superiority of either type. The roller pump required gravity drainage, which
use of a pulsatile extracorporeal membrane resulted in a siphon to the pump. To create this
oxygenation platform (PECMO) has shown siphon effect, the pump had to be in a depen-
an increase in coronary blood flow when using dent position, relative to the patient separated
R-wave triggered pulse (at a 1 to 2 ratio) in an typically by 100-150 cm. The roller pump was
experimental porcine model.23 Some reported servo regulated, so the gravity siphon did not
benefits include improved microcirculation cause an extreme in pressure negative enough
and therefore better end organ function result- to produce cavitation and red cell trauma. As
ing in improved myocardial, cerebral, renal, a positive displacement pump, the roller pump
and splanchnic perfusion.24-26 Mechanical generates forward flow as a function of the tub-
challenges include energy loss from circuit ing size and pump speed. They often become
components, synchronicity, and hematological advantageous with lower flows and blood flow
effects. Energy losses can occur from both the management requires rates in the 10-25 mL
oxygenator and circuit, supporting the impor- range. If standard PVC tubing is used in the
tance of proper circuit selection.27 raceway, it can usually withstand a 48-hour
period of support without failure when properly
occluded. Rupture resistant PVC tubing has
been used to extend the longevity of the pump
raceway conduit. By altering the plasticizer con-
tent, raceway tubing is made more durable and
can tolerate the repetitive compression caused
by the occlusive roller pump. Rupture resistant
PVC, or polyurethane tubing, can extend perfor-
mance for several weeks; however, the risk of a
raceway rupture always remains a concern.28, 29
Roller pumps work remarkably well, but require
constant monitoring and troubleshooting.30, 31
Roller pumps may be operated for extended
periods and are considered hemocompatible
depending on the occlusive settings within the
housing. Apart from potential blood damage
from improper or over-occlusion, the compres-
Figure 5-1. Extracorporeal Life Support Or- sion of the pump rollers against the tubing could
ganization Registry data showing the trend potentially release substances or particulate
in international gas exchange device use from emboli into the circuit. The process of advanc-
2005-2015. The number of cases is reported by
neonatal, pediatric and adult subgroups and the ing a new tubing segment into the raceway or
total number of cases. Pump usage is based on “walking” the raceway tubing minimizes this
the percentage of the total number reported per potential complication.
year. The trend shows a transition from roller
pumps to centrifugal pumps in all subgroups
except for neonates.
53
Chapter 5
Roller Pump Servo Regulation outlet pressures to achieve flow. A flow meter
measures the blood flow rate exiting the pump.
Roller pumps must be servo regulated to Centrifugal pumps generate flow by a spin-
prevent excessive levels of negative inlet pres- ning rotor which applies suction to the blood in-
sure that may result in air being entrained into let and then propels the blood outward from the
the circuit. This requires the incorporation of pump housing by generating a positive pressure.
a reservoir (“bladder”) or pressure buffer be- This occurs without any tubing compression and
tween the patient drainage line and the pump allows for longer continuous pump operation
to avoid excessive negative pressure when the without replacement, as well the ability to clamp
pump flow exceeds the return. Blood flow is or occlude the circuit tubing without violating
modulated downward or stopped, based on a the circuit’s integrity. The first centrifugal pump
set pressure parameter.32 The drainage line used for ECLS was the Bio-medicus constrained
should be of sufficient diameter and length to vortex pump. The pumphead consisted of a
optimize a passive gravity siphon, which can be series of concentric cones that created a cen-
enhanced by elevating the patient. The desired trifugal force which directed blood forward to
blood flow rate, when using a roller pump is a dedicated outlet. A fixed shaft anchored the
a function of the size of tubing selected and cones and a seal was incorporated within the
rotations per minute (rpm). Tubing selection is blood path resulting in a stagnant blood zone
often based on expected maximum flow rates. at the pumphead base. A consequence of this
For flows ranging up to 1.5-2.0 LPM, 1/4” size design was localized heat generation that was
tubing is often selected. For flows up to 3.0 poorly dissipated and at high rpm. The use of
LPM, 3/8” size tubing can be used in the roller early centrifugal blood pumps in conjunction
pump housing. For flows exceeding 4.0 LPM, with high resistance gas exchange devices re-
1/2” size tubing is commonly used. quired high rpm to generate forward flow. High
levels of plasma free hemoglobin due to heat
Centrifugal Blood Pumps generation, sheer stress, and resultant hemolysis
were observed in some patients.38-42 Hemolysis
Pumps are classified as either axial (Im- is one major factor considered in pump design,
pella), diagonal (Medos DP3), or centrifugal for hemolysis is thought to be caused, in part, by
(CentriMag, Rotaflow, Revolution). Centrifu-
gal pumps generate a higher pressure, but use
relatively lower rpm compared to axial pumps.
The blade design includes characteristics of
blade thickness, pitch/angle number, and dis-
tance from the pump housing that all effect
performance characterization.33-37 Performance
characteristics of axial, diagonal, and cen-
trifugal pumps are diagramed in Figure 5-2.
Greater motion and pressure per rpm (hydrau-
lic power) is generated as the device changes
Figure 5-2. Performance characteristics of
design (movement from axial to radial design) axial, diagonal and centrifugal pumps. Greater
while the operational rpm increases as the size motion and pressure per rpm (hydraulic power)
of the device decreases. Axial pumps operate is generated as the device changes design
(movement from axial to radial design) while
at relatively higher rpm to provide adequate the operational revolutions increase as the size
of the device decreases.
54
The Circuit
the shear and the time exposed to shear forces. hemolysis becomes excessive or thrombosis
The disposable pumphead has a magnetic rotor is suspected. Many of the problems related to
that couples directly to a shaft or bearing. The localized heat generation and hemolysis have
blood is contained within the disposable pump- subsided with proper understanding and use
head. When connected, the pumphead couples of these pumps. Pivot bearing (Figure 5-3)
to the motor with magnets. As the motor spins, and bearing free magnetic levitation designs
the pumphead spins to the rpm generated by the (Figure 5-4) along with the incorporation of
pump motor. Localized heat is generated around low resistance, short blood path gas exchange
the seal and if there is sufficient washout around devices, have allowed for safer use in more
the seal, heat induced thrombosis is minimized. recent years.44
Newer centrifugal designs are more ef-
ficient primarily due to a key design feature Centrifugal Pump Inlet Pressure Monitoring
described by Mendler.43 This design features a Techniques
hole located adjacent to the impeller that allows
blood to continually wash the area around the The circuit can become more streamlined
rotor, reducing or eliminating any stagnant areas. with shorter line lengths to reduce the forces
This design decreases the mechanically induced generated by the centrifugal pump. Shorter
hemolysis observed in earlier centrifugal pump line lengths may enable better blood drain-
designs. However, when used outside a safe age. One method of measuring the negative
flow high pressure head window, these devices pressure in the drainage line incorporates a
become less hemocompatible. Use of high flow compliance-like chamber/bladder into the line.
centrifugal pumps in neonates and children The Better Bladder™ (Circulatory Technology,
requires downsizing of the tubing to fit the 1/4” Inc., Oyster Bay, NY) is a safety device made
circuit adding more shear stress and turbulence from PVC with a flexible balloon within a rigid
contributing to blood cell damage and local chamber. The pressure between the bladder and
thrombus formation. Free hemoglobin should rigid chamber can be measured and reflects the
be monitored and the pumphead replaced if negative pressure in the drainage tubing.45,46 The
Figure 5-3. Pivot bearing centrifugal pump. Figure 5-4. Cross sectional view of a mag-
The pump eliminates a central shaft and seal netically levitated pump. Bearing less design
by using a blood flushed bearing, thereby allows for no contact with the pump impeller
avoiding stagnant zones, and reducing areas as the impeller is suspended in a magnetic field.
of high shear and turbulence. (Figure courtesy (Figure courtesy of Piyumi Fernando)
of Piyumi Fernando)
55
Chapter 5
device is positioned between the patient and the resistance can be observed with smaller can-
pump inlet and requires a pressure transducer nulas and circuits resulting in similar or higher
to monitor the pre-pump pressure. The Better- pressure heads as with higher flow systems.
Bladder™ provides compliance in the venous Hence, blood cell contact time within the pump
line to reduce large negative pressure spikes at increases substantially and the red blood cells
the pump inlet and allows for noninvasive pres- may be damaged at a much faster rate. Low
sure measurements while removing the risk of flow range pumps typically provide flows up
accidental air entrapment. Abrupt cessation of to 2 LPM. They can be considered in low flow/
venous flow can cause a large negative pressure high pressure situations, such as neonatal/pe-
spike at the inlet and outlet of the centrifugal diatric support or extracorporeal CO2 removal
pump. Measurement of the inlet pressure allows settings. These pumps are available with 1/4”
time for a pressure regulated centrifugal pump inlet and outlet connections. Currently there are
to be adjusted downward, reducing the steady two lower range flow pumps available: the first
state negative pressure, especially if it is exces- generation Medtronic Bio-medicus BP50, and
sive and collapses the vasculature around the the PediVAS magnetic levitated pump. They are
drainage cannula. Lowering the negative pres- recommended for use up to 1.5 LPM and 1.7
sure in the drainage line would be reflected at LPM, respectively. Use in neonates can cause
the cannula site and cause less potential intima more blood damage compared to use in adults
damage. A large negative pressure spike at the and compared to roller pumps.47,48 The newer
outlet of the centrifugal pump will also result lower flow pump designs, such as the PediVAS
in negative pressures inside the oxygenator, al- seem to ameliorate this complication.
lowing retrograde flow from the patient, or air
entry in the oxygenator if used in combination Regulatory Status
with porous or ruptured membrane fibers.
The regulatory status of centrifugal pump
Blood Pump Performance technology varies by country. Many circuit
components, including centrifugal pumps, are
The desired blood flow rate in centrifugal used off label from their designated indications.
blood pumps relates primarily to two categories In the U.S. all centrifugal blood pumps are
of expected maximum flow rates: high flow cleared by the FDA for use in CPB for up to 6
range and low flow range. High flow range hours. Use for extended support is conducted
pumps traditionally provide flow from 1-8 entirely off label. The CentriMag is cleared for
LPM (although some pumps can generate up 30-day use as a VAD but not in an ECLS set-
to 10 LPM). Centrifugal pumps with 3/8” inlet ting, when a gas exchange device is included
and outlet connections are considered high inline. In contrast, CE (Conformité Européene)
flow range pumps, meaning they have a low marking offers longer periods of validated use in
hemolysis index for a high range of flow with a the ECLS setting, which is mostly based upon
physiological pressure head. These pumps can manufacture recommendations. Newer gen-
be used safely at lower flow rates as the pressure eration centrifugal pump designs have initially
head will lower in relation to the decrease in been used outside the U.S. The recommended
the flow rate. However, these pumps lose their use of many devices is much longer in Europe
optimal performance characteristics when their compared to the U.S. For example: Medos
optimal flow/pressure head window changes DP3 (7 days), Maquet Cardiohelp (30 days),
when high rpm are required for lower flows, Lifebox (28 days, with the Livanova Revolution
such as neonatal or pediatric support. Higher centrifugal pump).
56
The Circuit
Pump Related Complications more fragile and the clinical relevance of their
destruction is being increasingly investigated
Hemolysis and recognized.50 Blood cell damage by centrif-
ugal blood pumps depends on the design of the
Hemolysis is defined in the ELSO Reg- pump, the rotational speed, suction pressure, the
istry as the appearance of free hemoglobin in pressure head and presence of air and/or clots.
the blood plasma in concentrations exceeding The comparison of hemolysis and blood
50 mg/dL. The plasma hemoglobin should be handling related to centrifugal and conventional
<10 mg/dL under most conditions.49 Eleva- roller pumps has showed centrifugal pumps
tions >50 mg/dL should be investigated for may not be as hemolytic as roller pumps when
cause. Elevated free hemoglobin may relate to used properly.51,52 In order to investigate a new
intermittent venous line chattering, extremes in centrifugal pump design, three pumps were
negative pressure generated by the centrifugal compared: Rotaflow, Bio-medicus BP50, and a
pump, air-blood interface related to cardiac conventional roller pump. The Bio-medicus and
surgery (if the patient is immediately on ECLS Rotaflow pumps showed similar results until
postcardiotomy), partial circuit or component 24 hours when the Bio-medicus became more
thrombosis, as well as high shear stresses re- hemolytic. The difference became significant at
lated to turbulent flow. Hemolysis can also be day 6 (p <0.0001). The roller pump had the most
a consequence of water and blood mixing if the pronounced rise in hemolysis after 24 hours,
integrity of the heat exchanger membrane has which continued to the end of the experiment.
been violated. Subclinical hemolysis does not The trial confirmed clinical experience in that
necessarily indicate RBCs are undamaged, be- the Bio-medicus pump should be exchanged
cause normally the constituents of red cells are after 5 days of use as a precautionary measure
removed by efficient elimination mechanisms. or earlier if indicated.47
When the rate of destruction exceeds the rate
of elimination, free hemoglobin levels increase. Cavitation and Excessive Negative Pressure
Free circulating hemoglobin causes nephro-
toxicity and binds rapidly and irreversibly to Any centrifugal pump can generate a siphon
endogenous NO, inducing a range of potential and an excessive negative pressure. With nor-
unfavorable side effects, such as increased mal operation, the negative pressure exerted by
vascular resistance, increased thrombin genera- the pump should not exceed a negative 100-200
tion, platelet dysfunction, and clotting disorders. mmHg, even if the inlet line becomes temporar-
Shear forces may also contribute to hemolysis. ily occluded. As the pump speed increases, the
When exposed to a shear stress environment of inlet pressure can vary from a small positive
below the threshold cell rupture, erythrocytes pressure to a significant subatmospheric pres-
can be sublethally damaged, which is a revers- sure. When exposed to extreme negative pres-
ible phenomenon, depending on the duration sure with interruption in the venous drainage, a
and intensity of exposure to subatmospheric perfect storm results and a negative pressure ex-
pressure and/or blood/air interface. The RBC ceeding negative 750 mmHg may occur. Under
does not lyse, but stiffens and becomes rigid, these conditions, a phenomenon known as out-
making it more difficult to enter the microcir- gassing or cavitation occurs. Cavitation pulls
culation and exchange or release oxygen in the the dissolved gases (oxygen, CO2) out of solu-
lungs and end organs. Erythrocytes resist shear tion when the negative pressure is higher than
stress better than other blood cells. Leucocytes, the pressure at which gases dissolve in blood.
platelets, and von Willebrand proteins are much Cavitation causes localized negative pressure
57
Chapter 5
fields. As gas comes out of solution it lyses red is performed manually to avoid these potential
cell membranes. Once the negative pressure risks. Although not commercially available,
resolves, the gas will go back into solution, but centrifugal pumps can be servo regulated to a
the free hemoglobin remains in the circulation. prescribed negative pressure.56
Under most circumstances, the suction pressure The effect of the position of inlet pressure
generated by centrifugal pumps is tolerated with was measured at different sites in the drainage
no cavitation or hemolysis. A negative pressure line.57 A linear relationship was found between
less than -600 mmHg typically does not induce the sites along the inlet line, as anticipated
cavitation or cause hemolysis unless the red by Poiseuille’s Law. Measurement closer to
cells are preconditioned by an air interface such the centrifugal pump gives a greater absolute
as that observed with cardiotomy suction dur- pressure than by measuring at the cannula con-
ing CPB.53 When used at high rpm, centrifugal nection. However, measuring the pump inlet
pumps may generate a negative pressure in pressure at the cannula connection eliminates
excess of -600 mmHg, which may temporarily the need for the additional prepump connec-
occlude the return resulting in the drainage line tor, thus avoiding another potential interface
surging or “chattering.” Chattering is related to where thrombus could form. This has allowed
several possibilities: hypovolemia, changes in alteration of the maximum flow for cannulas
patient and cannula position, changes in intra- by choosing a specific inlet pressure point on
thoracic pressure by coughing, etc. As a result, the obtained graphs as a reference. The same
blood flow usually falls. Each interruption may study also examined tubing lengths and found
cause cavitation, especially with high pump that increasing tubing length from 1.2 m to 2.4
rpm. With sudden interruption in blood flow and m dramatically increased the subatmospheric
with the pump rotor spinning at high speed, the pressure the blood experiences (Figure 5-5).
pump head ejects blood but no volume refills There was an average of 200 rpm to obtain the
the voided space. Instantaneously a vacuum same flows equating to an increase of turbulence
forms within the pumphead, cavitation occurs, in the pumphead, kinetic energy dissipated as
and the blood in the pump head is hemolyzed. heat, and eventual hemolysis.58, 59
When this occurs, the pump rpm should be
reduced to determine the cause of the intermit-
tent occlusion, and implement a solution. The
appearance of gaseous microemboli (GME)
has been observed from negative pressures of
-250 mmHg and onwards. When the negative
pressure further increases, the volume and size
of the GME also increases. Although gaseous
microscopic air will redissolve in blood when
moving into a positive pressure zone, and the
oxygenator may trap some of this gas, GME ac-
tivity can be detected at the oxygenator outlet.54
Air from cavitation when reentering a positive
pressure zone may also damage the pump.55
The ideal method to reduce the risks related to Figure 5-5. Changes in blood flow as a func-
cavitation is to slow the pump rpm to lower the tion of tubing length. Longer tubing lengths
significantly increase the inlet pump pressure
suction pressure exerted on the pump’s inlet line. to obtain the same flow rate to the centrifugal
Currently, adjustment of the pump speed control pump.
58
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Ultimately, the question relates of whether essential.60 Pumps may also produce inadequate
there exists a recommended negative pressure forward flow if air is entrained in the pumphead,
that should not be exceeded. In cases of stable for air does not have the required driving force
flow without line chatter or flow interruptions, to establish forward flow. Regardless of the
the pressure has been anecdotally reported as pump type, methods are required to maintain
high as -200 mmHg. Therefore, the pump inlet pumphead operation in event of either failure
pressure should be managed to achieve optimal or a power loss, either by manual methods or a
blood flow with minimal hemolysis, especially backup power supply.
when frequent interruptions in flow or periods
of inconsistent venous drainage occur. Under- Power Failure
standing the concepts of venous line compliance
and pump inlet pressure are essential to avoid The pump should have a battery life of at
the potential hemolytic effects of a centrifugal least one hour for full operation. A system to
pump with any flow variation. One key to un- manually crank the pump in the event of power
derstanding these principles is to measure the failure, or a backup system should exist, if there
venous drainage pressure in order to establish a is no method to manually hand crank the pump.
tolerable threshold of sub-atmospheric pressure. The pump should alarm in situations where low
or reverse flow occurs or if the power fails.
Thrombosis
Retrograde Blood Flow
Thrombus generation observed in early
generation centrifugal pumps was primarily Retrograde flow can occur if the distal
related to heat generation around the fixed shaft. pressure exceeds the pump generated pressure.
This issue has improved with the newer designs. Under these conditions forward flow will cease
However, thrombus generation can still occur if and blood flow may reverse. This is likely to
inadequate pumphead wash-out occurs. A small occur at lower flow ranges or if a shunt (eg,
thrombus may also be aspirated from the venous bridge) is open. The risk of retrograde flow can
line and enlarge inside the pumphead. These be reduced by a flow alarm or a shut off valve.
thrombi will cause hemolysis and might lead In a simulated model of pediatric ECLS, retro-
to pump failure by obstruction of blood flow grade flow was demonstrated to occur at low
to the impellers, especially in the small pumps rotational speeds in the Levitronix CentriMag,
or diagonal designs. Medtronic Biomedicus, and Maquet Rotaflow
pumps. At lower pump speeds, the CentriMag
Pump Failure pump exhibited the earliest occurrence and the
greatest degree of retrograde flow.61
Pump failure may occur in all magnetic
driven centrifugal pumps when there is impeller Air Embolism
imbalance within the pumphead. This can hap-
pen due to magnetic field disturbances, air entry As centrifugal pumps can generate exces-
or small clots that disrupt the pumphead balance. sive negative pressures, the possibility exists
Often the pump will make a noise, hemolysis that air can be generated from cavitation or by
will occur, and the pump might stop abruptly. inadvertent air entry through a loose connection
There have been a few reported incidents with between patient and pump. Air entry via open
different pump designs so a protocol for emer- intravenous lines, stopcocks, and uncovered
gent pump changeout and patient support is drainage cannula holes has been reported. Sensi-
59
Chapter 5
tive bubble counting devices can detect air at pumps and centrifugal pumps without impel-
the outlet of oxygenator in cases of excessive lers can generate shutoff pressures of 400-500
negative suction, indicating that cavitation mmHg, while centrifugal pumps with impellers
related air is not all captured in the bubble trap might create pressures up to 800-900 mmHg.
of the oxygenator.54 Larger amounts of air can Nevertheless, positive pressure generation by
be trapped in the centrifugal pump forward centrifugal pumps is limited to approximately
flow. A rotating pump in an empty housing can 400 mmHg in physiological situations, when
lead to heating, dislocation, and pump failure, increases in rpm are discontinued as soon flow
depending on the design. does not respond.62 The isolated positive pres-
sure is not harmful to blood cell integrity but
Outlet Pressure the turbulences and shear stresses which can
be induced at these high pressures, depending
Outlet pressure or outflow line pressure on the size and configuration of cannula and
refers to the pressure generated by the pump. tubing, are the main stimuli to blood trauma. If
When the pump’s outlet line is occluded, the small or curved tip cannula are in situ, such as
outlet pressure increases, but should not exceed LV vent cannula or limb cannula, then pressures
400 mmHg. Although pump generated pressures of >300 mmHg can cause damaging turbulence
greater than 400 mmHg do not inherently cause and shear force which will result in hemolysis.63
hemolysis, a centrifugal pump’s speed may sig-
nificantly increase heat generation as a function Commercial Centrifugal Pumps
of rpm. The ability of any pump to dissipate
heat is an important factor inherent in its design. There are a number of commercial centrifu-
There is also concern for the integrity of blood gal pumps that have been used for extended
tubing connectors when line pressure exceeds ECLS whose characteristics are summarized
400 mmHg. Outlet pressure can also be servo in Figure 5-6. Individual device availability
controlled to minimize the risk of generating an and regulatory status varies from country to
extreme positive pressure. Centrifugal pumps country and by certifying agency. Indications
can also generate high positive (shut off) pres- for use may also vary by country. The regula-
sures when the outlet is clamped at high pump tory status of each device described is not listed
speeds and under zero flow conditions depend- due to the wide variation and changing status
ing on the pump design. Smaller, diagonal of each device.
Figure 5-6. Characterization and performance parameters of commercial

centrifugal blood pumps.
60
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Maquet Rotaflow by a 1 mm steel strut (Figure 5-3). The blood

gap between the impeller and housing is conical
The Rotaflow centrifugal pump (Maquet on either side. The outflow exits into a circular
Cardiopulmonary AG, Hirrlingen, Germany) recuperator and a spiral volume chamber. All
(Figure 5-7) was introduced in 1995. This pump blood contacting parts are made of acrylic and
was able to reduce heat generation from the polycarbonate resins.
bearing and seal and improved hydraulic effi-
ciency with minimal blood damage. In testing, Livanova Revolution Centrifugal Pump
the Rotaflow pump showed strong hydraulic
efficiency compared to other devices.45 The The Revolution centrifugal pump (Liva-
disposable pumphead features a low friction nova, Arvada, CO) features a sealless, low
one-point pivot bearing that supports a multi- friction bearing (Figure 5-8). The pumphead is
finned impeller. The pumphead is controlled controlled by the Livanova Centrifugal Pump
by a remote drive motor tethered to a control (SCP) System that can be integrated with the
console. An ECLS ICU console incorporates safety devices of the S5™ and C5™ systems.
additional safety features that minimize inad- When certain conditions are detected (low
vertent manipulation of the speed control or level, bubble, or retrograde flow), this feature
power switch. The unit is manually controlled allows for some servo-regulatory controls that
and not servo regulated. The pumphead is com- are unavailable with other centrifugal pump
pact with a priming volume of 32 mL and has technologies. The Revolution 5 version that has
an outer diameter of 85.5 mm, a height of 48 been qualified for 5 days of use is available in
mm, and a weight of 60 gm. It is constructed some countries.
to exploit the potential of the radial magnetic
drive in eliminating a central shaft and seal us- Medtronic BPX-80 and BP-50
ing a blood flushed bearing, avoiding stagnant
zones, and reducing areas of high shear and The Medtronic BPX pump design (Medtron-
turbulence. The drive magnets are embedded in ic, Minneapolis, MN) features a patented verti-
a shrouded impeller with four blood channels. cal outlet and a smooth vortex cone design that
A single pivot bearing supports the impeller at provides superior micro air retention. This pump
its bottom, in which the sapphire ball bearing is has been used widely during clinical open heart
held in the center of the completely open rotor surgery, but is associated with higher hemolysis
Figure 5-7. Rotaflow centrifugal pumphead Figure 5-8. Revolution centrifugal pumphead
(Maquet Cardiopulmonary, Hirrlingen, Ger- (Livanova, Arvada, CO, USA).
many).
61
Chapter 5
with extended use.41 The current BPX80 has 3/8” CentriMag Magnetic Levitated Pump
inlet and size outlet connectors and has a prim-
ing volume of 80 ml with a recommended blood The CentriMag pump technology (St. Jude
flow up to 8 LPM. The BP50 has 1/4” inlet and Medical, St. Paul, MN) is based on the prin-
outlet connectors and has a priming volume of ciples of magnetic levitation. The CentriMag
48 mL with a recommended blood flow up to features bearingless technology which contains
1.5 LPM. Both pumphead versions are available no seals. The pump rotor is levitated within the
with Carmeda heparin coating and may be used disposable pumphead housing by a magnetic
with any Biomedicus pump console. field so that when the motor is powered up, the
resultant magnetic field aligns and maintains
Medtronic Affinity Centrifugal Pump the rotor in a position in which no direct contact
to any other part of the pumphead housing oc-
The Medtronic Affinity centrifugal pump curs. When the pump is engaged the magnetic
(Medtronic, Minneapolis, MN) has a smooth field fluctuates allowing the rotor to spin at
cone and low profile fins enabling blood flow to the rate set by the control console. The risk
10 LPM with a ceramic heat resistant pivot shaft. of thrombus formation is reduced by uniform
The pumphead has a 40 mL priming volume unidirectional flow and less stagnation, while
and interfaces with the Medtronic Biomedicus reduced shear stress attenuates hemolysis. The
console. The external motor driver rotates in CentriMag adult unit can produce flows up to 10
the opposite direction than the traditional Bio- LPM. The pediatric version, referred to as the
medicus pumphead. The Affinity pumphead is PediVAS (PediMag U.S.) can produce flows up
offered with two surface coatings: Carmeda to 1.5 LPM. Both pumpheads are operated by
heparin coating and the nonheparin Balance the same console and hardware. These pumps
Biosurface (UK) (Figure 5-9). require flow probes to enable the system. The
pumphead cannot be manually hand cranked,
so a backup system is required (Figure 5-10).
Figure 5-9. Medtronic Affinity centrifugal Figure 5-10. CentriMag™ Maglev System (St.
pumphead (Medtronic, Minneapolis, MN). Jude Medical, St. Paul, MN).
62
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Medos Delta Stream flow mode controls the pump speed to avoid
inadvertent retrograde flow. The system cannot
The Medos Deltastream DP3 pump (Me- be manually hand cranked.
dos Medizintechnik AG, Stolberg, Germany)
(Figure 5-11) is a hybrid of centrifugal and Gas Exchange Devices
axial technologies that utilizes higher rpm but
shorter transit time to generate blood flow. The Rated Flow
DP3 has 3/8” inlet and outlet connectors for
adult use (a design with 1/4” size connectors for The gas exchange device is designed to add
pediatric use is pending). The pumphead prim- oxygen and remove CO2. The device must be of
ing volume is 16 mL and generates a flow range adequate size to provide for the total anticipated
of 0-8 LPM at a pump speed from 100-10000 metabolic requirements of the patient. The gas
rpm. The pumphead incorporates a ceramic exchange device should be able to transfer
bearing and magnetic coupling with an optional the amount of oxygen being consumed by the
pulsatility mode (rate 40-90 beats/min). The patient, as well as the amount of CO2 being
MDC console is portable, lightweight (10 kg), produced by the patient. The surface area and
and contains two batteries (90-minute power/ blood path mixing determine the maximum
battery) that allow the pump to be operated oxygenation capacity of any gas exchanger.
independently from the driving console. The A standard referred to as “rated flow” allows
detachable touch screen monitor can display op- for direct comparisons of all gas exchange de-
erational parameters such as flow, rpm, pressure, vices. The rated flow is the blood flow rate at
and temperature. The controlling hardware has which venous blood, with a saturation of 75%
three integrated pressure channels with nega- and hemoglobin of 12 gm/dL will exit the gas
tive pressure regulation, zero flow mode, and exchange device with a saturation of 95%.64
air bubble detection, as well as a display of the
charging condition of both batteries. The zero Oxygen Delivery
Patient metabolic needs determine the

amount of oxygen delivery required. The maxi-
mal oxygen delivery of a gas exchange device
is the amount of oxygen delivered per minute
when running at rated flow. This is determined
by calculating the difference in oxygen content
between the outlet blood and the inlet blood to
the gas exchanger. This difference is typically
4-5 cc O2/dL. Multiplying this by blood flow
rate through the gas exchanger yields the oxy-
gen delivered by the gas exchanger in cc O2/min.
A gas exchange device with a rated flow of 2.0
L/min will offer a maximal oxygen delivery of
100 cc O2/min. A device with a rated flow of 4.0
L/min will offer a maximal oxygen delivery of
200 cc O2/min. Based on the anticipated oxygen
Figure 5-11. Medos Deltastream pump sys- delivery requirements, the appropriate size gas
tem ((Medos Medizintechnik AG, Stolberg,
Germany). exchange device can be chosen.
63
Chapter 5
Sweep Gas Pressure Gradients
The gas ventilated through the gas exchange Early generation gas exchange devices
device is referred to as the sweep gas. For most were characterized by a long blood path and
applications, sweep gas will be 100% oxygen. a high pressure gradient. These early designs
There are occasions during cardiac support or included flat sheet silicone rubber membranes
by institutional preference when the sweep gas and the “blood inside” hollow fiber bundle
will be a mixture of oxygen and compressed configurations. Design modifications lead
room air, thus requiring an oxygen-air blender. to a hollow fiber concept with “gas inside”
In some instances, when the pCO2 must be main- and blood circulating outside the fibers. This
tained, carbogen gas (5% CO2, 95% O2) or 100% configuration resulted in significantly lower
CO2 gas (in small amounts) may be titrated into pressure gradients in the blood path.65 This de-
the sweep gas. In some institutions, a gas flow sign has been applied to all subsequent device
rate equal to the blood flow rate (1:1) is used designs regardless of hollow fiber material. The
to begin support. The gas to blood flow ratio is first widely used biomaterial was microporous
then adjusted to maintain the systemic pCO2 at polypropylene. Although this material could
a desired range (ie, 36-44 mmHg). Increasing be manufactured as a flat sheet, fiber technol-
sweep gas flow rate increases CO2 clearance ogy provided more effective surface area and
but does not affect oxygenation. Decreasing was relatively inexpensive to manufacture.
the sweep gas flow rate elevates the pCO2, but Engineering designs to maximize secondary
usually does not affect oxygenation. Water va- flows and mixing in the blood path, optimizing
por can condense within the gas compartment gas exchange, and lowering the device pres-
of the membrane lung and may be cleared by sure gradient have improved performance and
intermittently increasing sweep gas flow to a allowed for smaller sized devices. The lower
higher rate. If there is excessive water that has resistance made these newer generation gas ex-
not been purged, the pCO2 may rise. ECLS can change devices more practical for long duration
be used for CO2 removal in addition to full meta- use. Microporous polypropylene hollow fiber
bolic support. In most gas exchange devices, gas exchange devices are limited in longevity
the amount of oxygen added and CO2 removed because over time, plasma will leak across the
is the same at a gas to blood flow ratio of 1:1. fiber eventually causing device failure.66,67 Gas
Since membrane gas exchangers clear CO2 more transfer normally occurs across a protein layer
efficiently than adding oxygen, CO2 can be recovering the fibers micropores. Over time, ex-
moved with blood flows as low as 0.75 L/min/ posure to phospholipids in the blood causes the
m2. In cases when CO2 regulation is required, surface tension at the blood/gas interface in the
the gas exchange device size can be smaller than micropores to decrease. As the surface tension
the device required for full support. Ventilation decreases, plasma begins to weep through the
to maximize CO2 removal is typically greater micropores into the gas side of the membrane.
than 4:1 on the gas to blood flow ratio rate. It As a result, gas exchange efficiency falls.68 This
must be noted that some manufacturers limit the membrane failure has limited the widespread
recommended gas to blood flow ratios in their use of polypropylene devices for extended use.
instructions for use. Polymethylpentene (PMP) fibers that
became available in the early 2000s showed
promise as a plasma leakage resistant fiber.
Polymethylpentene is a chemical cousin to
polypropylene fibers that when the outer surface
64
The Circuit
is compressed it displays a more leak resistant the sweep gas pressure exceeds the blood path
property than the microporous polypropylene. pressure. This may occur if the device blood
Although PMP has been described as more of a path pressure becomes negative, which can
“solid” membrane, in fact PMP is microporous. occur with an unregulated centrifugal pump.
During manufacture, the fibers are compressed Air can also be pulled across the membrane
to form an outer surface or “skin” with proper- surface when blood flow ceases and the device
ties similar to that of a solid membrane. Even is positioned above the level of the patient’s
though the PMP membranes are “solid-like,” heart. In this circumstance, blood within the gas
gas can still be entrained across the PMP ma- exchange device can drain by gravity into the
terial into the blood path if a large negative dependent blood tubing, subsequently pulling
pressure is applied. Therefore, it is important air across the fibers and “de-priming” the device.
to maintain positive pressure on the blood path To minimize the risk of air embolization through
side. The PMP fibers, produced by Membrana the gas exchanger blood path, pressures must
GmbH (Wuppertal, Germany), have similar be maintained higher than the gas side pres-
gas exchange characteristics as polypropylene sure.70 Pressure pop off valves may be placed
but it is more challenging to handle, so PMP is in the gas supply line to insure the gas pressure
typically matted and either wound or stacked remains low. Sweep gas pressures may be servo
in relatively short blood path configurations. regulated and the gas exchange device should
Current PMP hollow fiber devices have low be kept below the patient’s heart to minimize
pressure gradients and the fibers mimic a “solid air embolism risk. As newer generation gas
hollow-fiber” technology with minimal plasma exchange devices and centrifugal pumps have
leakage.69 Polymethylpentene devices were allowed the transport of patients within and
first described in two pilot clinical studies. The between hospitals, the gas exchange device may
device was reported as showing feasibility and inadvertently be repositioned above the level
longevity in long-term ECLS support. The Me- of the heart while venous drainage pressures
dos HiLite LT was used in six patients in whose are subatmospheric. If blood flow were stops
transfusion rates were significantly lower and by either a line kink, patient cough, or clot
plasma leakage was not observed.12 Similarly, formation within gas exchange device, risk of
no plasma leakage occurred in 23 patients with air embolism exists.
Maquet diffusion membrane device that was
used for up to 46 days in conjunction with a Commercial Gas Exchange Devices
centrifugal pump.69 However, plasma leakage
has been observed in clinical application. The Figure 5-12 shows the utilization of mem-
initial experience with PMP devices demon- brane lung types from 2005-2015, based on data
strated promise in durability, inflammatory submitted to the Extracorporeal Life Support
response attenuation, and decreased transfu- Organization Registry. The data incorporates
sion requirements making these gas exchange all patient groups and is expressed as a per-
devices well suited for long-term ECLS use. centage of the total number of cases reported
Since their introduction, other PMP devices per year. The trend shows the growth in PMP
of varying sizes have entered the marketplace. gas exchanger use and the gradual phase out
of the silicone rubber units worldwide. Many
Gas Exchanger Induced Air Embolism commercial membrane lungs are available
for clinical use and some are described in the
Gas bubbles can pass across the gas ex- sections below. The regulatory status for each
change device membrane into the blood path if individual device varies from country to country
65
Chapter 5
and by certifying agency. In the U.S., most gas PMP hollow fibers and contains an integrated
exchange devices are cleared for up to 6 hours heat exchanger. The design effectively prevents
of use. In Europe, CE marking may be extended formation of microbubbles and protects against
to days or weeks. The regulatory status of each bacterial contamination from the gas side. The
device is not listed, due to that wide variation Quadrox iD has a low pressure drop across
and changing status of each device. There are the fiber bundle. The designs for bundling the
several commercial gas exchange devices used fibers within the oxygenator and the flow pattern
for extended ECLS whose technical character- through the device are key factors in decreasing
istics are summarized in Figure 5-13. the priming volume.71
Maquet Quadrox- iD Medos Hilite LT
The Maquet Quadrox- iD diffusion mem- The Medos Hilite LT (Medos Medizintech-
brane device (Maquet Cardiopulmonary AG, nik AG, Stolberg, Germany) is produced in
Hirrlingen, Germany) comes in adult and in- three sizes with an integrated heat exchanger.
fant/pediatric sizes (Figure 5-14). The device The device is characterized by a low pressure
is constructed of plasma resistant hydrophobic differential between blood inlet and outlet and
Figure 5-12. Data from the Extracorporeal Life Support Organization showing the trend in international
gas exchange device use from 2005-2015. The number of cases is reported by neonatal, pediatric and
adult subgroups and the total number of cases . Gas exchanger use is based on the percentage of the
total number reported per year. The trend shows a transition from silicone rubber devices towards
polymethylpentene devices in all subgroups.
66
The Circuit
Figure 5-13. Performance characteristics of commercial membrane lungs.
Figure 5-14. Maquet Quadrox iD Adult and ID Pediatric membrane lungs. (Maquet Cardiopulmonary,
Hirrlingen, Germany).
67
Chapter 5
a smaller priming volume than the Quadrox- It has also served as an artificial lung to bridge
iD. The HiLite LT devices are suitable for use patients to lung transplant with or without a
with all pump types. The Medos LT device is blood pump.74, 75 The iLA Activve system is used
illustrated in Figure 5-15 and is available with in conjunction with a blood pump and comes
or without a surface coating. in three sizes. The individual platforms support
a range of metabolic conditions from isolated
Novalung Lung Assist Device CO2 removal to full metabolic support.
The iLA Activve and iLA platforms (No- Livanova EOS ECMO
valung GmbH, Heilbronn, Germany) consist
of multiple versions of different gas exchange Livanova (London, UK) produces two sizes
devices for support of respiratory failure. The of extended use gas exchangers. The Lilliput 2
Novalung Membrane Ventilator, a low resis- ECMO gas exchanger is a pediatric unit made
tance temporary artificial lung that can provide with PMP fibers.66 The device has a phosphoryl-
CO2 transfer across its membrane fibers with or choline surface coating and has been validated
without the use of a blood pump, is designed for up to 5 days of extended support. The device
primarily for extracorporeal CO 2 removal. requires the use of a blood pump. The D 905
Total CO2 management can be achieved allow- EOS ECMO unit (Figure 5-16) is a larger adult
ing for protective mechanical ventilation lung sized device that is phosphorylcholine coated.
management strategies. Clinical use has shown The device has been validated for 5 days of use
benefits and good feasibility in a wide number outside U.S.
of etiologies including ARDS and COPD.72, 73
Figure 5-15. Medos HiLite LT membrane

lung (Medos Medizintechnik AG, Stolberg, Figure 5-16. Livanova EOS ECMO membrane
Germany). lung. (Livanova, London, UK).
68
The Circuit
Nipro Biocube at top of the unit to assist in priming and gross

air removal. The device is coated with a propri-
Nipro Corporation, (Osaka, Japan) pro- etary synthetic albumin surface coating called
duces three sizes of plasma tight hollow fiber Rheopax. The Paragon series comes in six sizes
membrane gas exchange devices with or with- with different flow ratings and an intended use
out an integrated heat exchanger. The membrane for up to 15 days (Europe only).
material is a polyolefin. The device utilizes a
biocompatible heparin based coating with an Integrated Pump/Oxygenator Systems
ionic coupling to promote durability and anti-
thrombogenic properties (Figure 5-17). The incorporation of a pump and gas ex-
changer into a single unit optimizes portability.
Eurosets Oxygenators The Maquet Cardiohelp HLS module integrates
three major ECLS circuit components (gas
Eurosets (Medolia, Italy) manufacture three exchanger, pump, and heat exchanger) into a
sizes of PMP oxygenators (Figure 5-18) that single product (Figure 5-20). The product has
have been validated for 14 days of use (Europe integrated sensors to detect inlet saturation,
only). The gas exchanger is coated with a lipid hemoglobin/hematocrit, and temperature. Three
based phosphorylcholine coating and contains pressure parameters can be measured. The
an integral heat exchanger. HLS module comes in two sizes: HLS Module
Advanced 5.0 (blood flows up to 5.0 LPM)
Paragon Oxygenators and HLS Module Advanced 7.0 (blood flows
up to 7.0 LPM). The system is coated with the
The Paragon oxygenator series (Chalice Maquet Bioline thromboresistant surface and
Medical, Nottinghamshire, UK) is a stand-
alone unit constructed with PMP fibers, spe-
cifically designed for long-term applications
(Figure 5-19). The Paragon device has a vent
Figure 5-18. Eurosets membrane lung series.

(Eurosets, Medolia, Italy).
Figure 5-17. Nipro 6000P membrane lung. Figure 5-19. Paragon membrane lung series.
(Nipro Corporation, Osaka, Japan). (Chalice Medical, Nottinghamshire, UK).
69
Chapter 5
has different regulatory clearances depending Gas Exchanger Related Complications

on country. The module can be positioned on a
portable cart and may be used for patient trans- Plasma Leakage
port. The system can be operated with a minimal
number of controls. These systems may be able Plasma leakage has been a problem in
to provide more feedback servo regulation of microporous polypropylene hollow fiber de-
essential parameters (ie, venous inlet pressure, vices which lose their hydrophobic character
venous saturation, CO2 exhaust gas, sweep rate, over time during long-term applications. The
and pressure gradient monitoring). The benefits advent of PMP fibers has greatly diminished
of simplicity must be weighed against cost in this problem, although it can still occur. Poly-
an integrated system. Any integrated system methylpentene fibers are hybrid in nature and
should be potentially easy to set up, prime, and microporous and layered by a true membrane,
initiate, as well as allow for patient transport. preventing plasma from leaking through the
This type of system would simplify the use for pores. Most PMP devices are made from plasma
multiple patients in a large volume center. Such leak resistant fibers. These fibers have been
a system should be easier to implement in an developed not to avoid but to improve plasma
emergent setting (ie, ECPR, catheterization lab leakage as this is in function of the thickness of
rescue) and allow for support while the patient the nonporous fiber skin, which again needs to
was assessed for the best treatment options. be limited in favor of gas transfer capacities.67
There have been a few reports from plasma
leakage in PMP devices.76 The fibers can be
overstretched due to winding on spools for ship-
ment, causing microtears through which plasma
leakage can occur. One report explains that PMP
fibers become less permeable to gas and plasma
as soon as an albumin layer forms on this mem-
brane, sealing the fibers. This explains why the
fibers are more porous to gas when dry primed
with crystalloid solution as opposed to blood. If
the albumin coating over the PMP micropore
is inadequate, which in part may be due to an
altered protein composition in certain patients,
plasma leak may occur after some time.77 It is
important to recall that PMP is a microporous
material even though the presence of the dense
skin largely prevents air entry in the blood and
the plasma breakthrough times are much longer
in respect to the common microporous fibers.78
Additionally, transfer of volatile anesthetic gas,
Figure 5-20. Maquet Cardiohelp. (Maquet such as Isoflurane, is impaired in PMP mem-
Cardiopulmonary, Hirrlingen, Germany). brane devices.79
70
The Circuit
Device Thrombosis Heat Exchange and Heat Regulation
Despite anticoagulation strategies and the ECLS constantly exposed the blood to the
theoretic benefits of passivated bio-surfaces, ambient temperature of the environment. The
oxygenator thrombosis occurs nonetheless. The circuit should be capable of maintaining the
ELSO Registry reports (2015) an average of patient at normothermia (37o C). The oxygen in
10% oxygenator clots in cardiac ECMO with a the sweep gas comes from a cold liquid oxygen
higher incidence in neonates (13%) as opposed source and the evaporative vapor-losses across
to adults (10%). In respiratory support, a higher the membrane dissipate heat, also cooling the
incidence from 17% in neonates to 14% in patient. Therefore, a heat exchanger may be
adults has been observed. 80 Oxygenator clots integrated into the gas exchange device, but can
can be detected by a variety of parameters, such be a standalone component. ECLS patients, es-
as increasing transmembrane pressures, rising pecially infants and small children may require
D-dimers, decreased gas transfer, hemolysis, active warming to maintain normal body tem-
and direct observation. If these parameters are perature with a heater cooler device. Warming
monitored regularly, then the device may be the gas source or employing topical warming
replaced in a controlled setting instead of an methods in small patients (ie, warm air blanket)
emergent change out when the device suddenly may also prove effective. For larger patients,
fails. Although sudden thrombosis does not usu- direct blood warming may be implemented, but
ally occur, there should be protocols for urgent is often not required and is discontinued if tem-
oxygenator change-out.81 perature autoregulation is maintained. While
the heat exchanger is typically used to maintain
Oxygenator Failure and Wet Membrane temperature, it can also cool for neuroprotection,
to decrease patient metabolic demands, or to
Oxygenator failure is defined as ‘the need to treat fevers. Heat exchangers require an exter-
change out the device.’ More correctly, the gas nal recirculating water bath which circulates
exchanger is failing as soon the measured gas water through a coil or network of fibers in the
transfer does not meet the manufacturer speci- blood path. The coil, or fiber network, is often
fied capacity of the device. Oxygen transfer can integrated within the shell of the gas exchange
be calculated by measuring the oxygen content device. The temperature of the circulating water
of the blood at the oxygenator outlet minus the bath is regulated to control the patient or blood
oxygen content at its inlet and should be accord- path temperature. In general, the temperature of
ing to the published data for a given blood flow the water is maintained between 36 to <38.5º C
and hemoglobin. An oxygenator membrane can (depending on the heat exchange efficiency and
become wet via air condensation inside the heater cooler) to achieve normothermia.
oxygenator because a temperature difference Heat exchangers are typically integrated
exists between the gas and blood, causing the into the device just prior to the gas exchanger
membrane to become less permeable to CO2. portion, although heat exchange can be main-
Hyperventilation of the gas exchanger with tained by a separate heat exchange component.
high gas flows for a short period can resolve Heat exchangers have evolved from devices
the problem while warming the ventilation gas used in CPB, which employs controlled hypo-
to 37o C have been suggested to prevent this thermia. In a CPB application, the heat exchang-
wetting phenomenon. er must have high efficiency and the ability to
cool or heat the blood in a relatively short time
period. However, in a typical ECLS circuit, the
71
Chapter 5
heat exchange performance requirement is not Heat Exchanger Related Complications

as high, for normothermia is usually maintained.
In some situations, especially in adult patients, A breach in the heat exchanger can rarely
a heat exchanger may not be required, for the complicate ECLS, however, the consequences
patient can often regulate their own tempera- can be fatal and thus heat exchanger integrity
ture. In smaller patients, especially infants, a must be monitored and changed if compromise
heat exchanger is required, as the oxygen that is suspected. Although direct contact between
ventilates the gas exchanger comes from a cold the recirculating water path and the circulating
compressed source and the cold oxygen gas blood occurs rarely, if blood or proteins are
can cool the blood unless it is rewarmed by a present in the circulating water or unexplained
heat exchanger. Regardless, a heat exchanger hemolysis occurs, a water to blood heat ex-
is typically incorporated into the circuit, un- changer leak should be suspected. Water should
less ECLS is used for treatment such as CO2 be circulated through the heat exchanger before
removal. In those instances, the extracorporeal priming to detect heat exchanger leakage, but
flow is relatively low and a heat exchanger is this is not always possible (eg, in case of pre-
not required. Heat exchange is accomplished by primed circuits) and doesn’t guarantee an intact
the recirculation of water over a heat transfer heat exchanger as a perforation may occur at any
material in the heat exchange compartment of time point during ECLS. One report described
the gas exchange device. A heater-cooler water the timely detection of membrane oxygenator
recirculation device is set to a desired tempera- heat exchanger failure by taking blood gases of
ture in order to maintain normothermia. The the circuit blood priming, thus detecting hypo-
nonsterile water from the heater-cooler device chlorite in the blood.82 An additional technique
is separated from the blood by material made for timely detection of heat exchanger failure
from stainless steel, aluminum, or polyurethane. uses air pressure to pressurize the water cham-
These areas are glued or welded to secure the ber and to observe an attached manometer for
sterile blood path from the nonsterile water path. any fall in pressure. This detective method can
There are several water based heater-cooler be performed before setup and priming.83 De-
units that have been used to maintain the ECLS pending on the type of recirculation device, wa-
circuit temperature including: Cincinnati Sub ter is either delivered through the heat exchanger
Zero Hemotherm, Maquet HCU series, Terumo or drawn into it; the latter provides extra safety
HX2, and Livanova 3T. Although these units and leakage can be detected when red colored
are typically used for hypothermic application, water is observed in the semitransparent heater
they have been used for long-term support. cooler tubing. Electrostatic charge building up
Smaller modular units such as the Medtronic from roller pumps can create a spontaneous
Biocal 370, Seabrook, and Cincinnati Sub Zero discharge, compromising the integrity of the
ECMOtherm devices were widely used, but no heat exchanger fibers.84
longer produced. Newer units exist to maintain In 2011, in response to customer complaints,
normothermia and include: Cincinnati Sub Zero a manufacturer issued a warning noting oxygen-
Cardio-Temp, Cardioquip, Novalung Nova- ators, which are primed for a prolonged period
therm, and Maquet HCU series. Other devices with sodium chloride solution, risk developing
such as the Microtemp LT are not labelled for microholes in the heat exchanger.85 In 2014,
ECLS use indications, but have been used to infections related to the use of contaminated
maintain the desired temperature. water recirculation devices were reported in
patients on CPB. These infections were caused
by the slow growing bacterium Mycobacte-
72
The Circuit
rium chimaera. It was hypothesized that the When blood is added to the prime, heparin is
contaminated water was aerosolized by the also added as anticoagulation (1 unit per mL
device’s cooling fan and that the M. chimaera prime). Calcium is added to replace the calcium
bacterium resulted in infections in surgical pa- bound by the citrate in the banked blood. If time
tients. Considering the water in the water bath permits, the circuit electrolyte composition and
is not sterile, the circuit will become contami- ionized calcium are verified prior to starting
nated. When not in use, the water bath should support. For emergency use or ECPR, the prime
be cleaned and treated with a liquid antiseptic. can be crystalloid. The hemodilutional effects
Worldwide, institutions have since been sup- of using a clear prime can be treated after the
plied with manufacturer recommendations for onset of support by administering diuretics, the
prevention that include regular disinfection and addition of a hemoconcentration device and/or
maintenance of heater-coolers.86 transfusion.
Circuit Priming Circuit Monitoring
The ECLS circuit is primed under sterile The circuit is monitored to provide levels
conditions with an isotonic balanced electrolyte of safety, measure circuit function, and alert the
solution resembling normal extracellular fluid health care personnel of abnormal conditions.
including 4-5 mEq/L potassium. The prime is The circuit can be equipped to measure several
recirculated through a reservoir until all bubbles parameters.
are removed. In some instances, de-airing can
be expedited by saturating the blood path with Blood Flowmeter
100% CO2 gas before adding the priming solu-
tion. Before connecting to the patient, the circuit Extracorporeal blood flow is monitored
prime can be warmed to 37o C by a dedicated most commonly with an ultrasonic flow de-
heater cooler device. Microporous gas exchange tector/probe. The flowmeter may be separate
devices (including PMP) de-air quickly because or integrated into the pump. Integrated flow
gas in the blood path is purged through the ma- monitors are common with modern centrifugal
terial. The pump generates a positive pressure pumps. Flow can also be calculated based on
that forces gas through the pores. Conversely, pump capacity and revolutions per minute,
if the blood path pressure becomes negative, air commonly done when using a roller pump. The
may be entrained in the blood path through the ELSO guidelines describe the ranges for blood
same mechanism. The circuit can be primed at flow based on tubing size.88
the time of use, or several days before use. The
circuit may be maintained in a primed condition, Circuit Pressures
safely, for 30 days.87 Support may be instituted
with a crystalloid prime (based on an adequate Pressure is commonly measured to de-
pre-ECLS hemoglobin), but many centers add termine the gradient across the gas exchange
human albumin (12.5 gm) to “coat” the plastic device or to measure the siphon effect (nega-
surfaces and add an oncotic component. For tive pressure) in the venous drainage line. An
adults and large children, a crystalloid prime is increase in the device pressure gradient may
practical and safe. However, infants and smaller indicate a kink in the outlet tubing or pos-
children often require a blood or blood compo- sible device thrombosis. Measuring post gas
nent prime. For infants, packed RBCs are added exchanger pressure is necessary to determine
to bring the hematocrit of the prime to 35-40%. the gradient across the device and to measure
73
Chapter 5
the return pressures to the patient. There could access for CRRT. Blood access sites should be
be associated alarms (lowest acceptable inlet avoided between the patient and the pump inlet
pressure, highest acceptable outlet pressure) or because of the risk of entraining air. Although
control points for circuit servo regulation based it is acceptable to use the circuit for blood
on these pressure measurements. Inlet and outlet sampling and infusions, patient vascular access
pressures, relative to the gas exchange device may be used to give infusions, transfusions, or
and the pump, are common points for pressure blood samples.
measurement. Measurement of centrifugal
pump inlet pressure may be valuable when try- Circuit Alarms
ing to minimize cavitation associated hemolysis.
Audible alarms should identify pressures
Hemoglobin Saturation Measurement or parameters that have exceeded preset safety
settings. Alarms can reflect transmembrane
The hemoglobin saturation of circuit blood device pressure gradients, negative or positive
may be measured by inserting an indwelling pressure in the blood path, excessive gas inlet
catheter through a specialized optical connector, pressure, and central power failure. Throm-
applying a wraparound fitting and sensor that bosis or clotting within the device can cause
encompasses the tubing or inserting a special- increasing membrane lung pressure gradient
ized connector that measures the saturation opti- and/or a drop in the flow rate. Pump speed can
cally. Hemoglobin saturation is most useful on be controlled by defining limits of maximum
the venous side of the circuit. With VA-ECLS and minimum flow with alarms to alert provid-
venous hemoglobin saturation approximates ers. Measuring and controlling the centrifugal
that of mixed venous saturation, reflecting over- pump inlet pressure may prevent extremes in
all metabolism and adequacy of support. With negative pressure, minimizing the risk of cavi-
VV-ECLS, recirculation of arterialized blood tation and hemolysis. Bubble detectors may be
falsely elevates the oxyhemoglobin saturation of used on the blood return line to protect patients
the venous blood making it less representative from microemboli or catastrophic air embolus.
of metabolism and adequate support. Measured Both pressure and bubble detector alarms can
venous saturations become more inaccurate as be used to clamp lines and regulate the blood
the recirculation fraction increases. Measuring pump, although air must be removed manually,
the hemoglobin saturation of arterialized blood often while disconnecting the patient temporar-
exiting the gas exchange device can offer help- ily from support.
ful information about its performance. Blood
gases may be measured from pre and post gas Emergency Circuits
exchanger sites either by continuous monitoring
or batch sampling. A fully primed, emergency support circuit
should be available within minutes of the
Circuit Access Sites cannulated patient. These circuits should also
include safety features to prevent excessive
Most circuits have blood access sites pre negative pressure on the inlet side and high
and post gas exchanger. The number of access positive pressure on the outlet side to avoid
sites varies as a function of the patient and in- errors during emergent cannulation and attach-
stitution, but their number should be minimized. ment. Emergency implementation may require
Two sites are usually included: pre and post gas transport inside or outside of the center.
exchanger. Additional sites may accommodate
74
The Circuit
Summary
The ECLS circuit is designed to provide

complete mechanical support for an expected
duration of days, weeks, or months. Each circuit
can vary according to patient, size, diagnosis,
and expected length of use. The ECLS circuit
consists of three primary components: blood
pump, gas exchange device, and heat exchanger.
The components are connected by standard
medical grade tubing. The circuit also includes
catheters for vascular access, access sites, moni-
tors, and safety devices. The circuit components
are selected to support a blood flow rate of 3.0
L/m2/min. In general, target flow rates are: 100-
150mL/kg/min (neonates), 80-100mL/kg/min
(pediatrics), and 60cc/kg/min (adults). In VV
support, blood flow rates are typically higher
than VA, 120ml/kg/min for neonates ranging
downward to 60-80 mL/kg/min for adults. Pa-
tients with single ventricle cardiac lesions or
sepsis may require higher flow rates.89,90 The
best indicator of adequate systemic perfusion is
a mixed venous saturation greater than 65-70%,
measured directly or noninvasively from the
venous drainage line. Ideally the circuit should
be simple, with only essential access sites, so
that minimal manipulations are required to sup-
port the patient. It is realistic to contemplate
a simple and smaller footprint for the ECLS
system of the future with integrated feedback
controls. The future ECLS system may follow
the care patterns of patients with implantable
ventricular assist devices, which require less
bedside maintenance and offer durable support
for extended periods. Although it may be years
before ECLS is used outside of the hospital
setting, cases of chronic obstructive diseases or
patients with elevated CO2 may provide the first
use of the ECLS circuit in an ambulatory setting.
75
Chapter 5
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J Extracorp Technol 1998; 30:30-34. plasma leakage in a polymethylpentene
66. Thiara APS, Hoel TN, Kristiansen F, et al. oxygenator during extracorporeal life sup-
Evaluation of oxygenators and centrifugal port. Perfusion 2009; 24: 51-.2
pumps for long-term pediatric extracor- 77. Gill MC, O’Shaughnessy K, Dittmer J. A
poreal membrane oxygenation. Perfusion pediatric ECMO case of plasma leakage
2007; 22:323–326.
79
Chapter 5
through a polymethylpentene oxygenator. 88. ELSO Guidelines Version 1.3 November

Perfusion 2015; 30: 600-3. 2013 Page 9.
78. Membrane Technology: Membranes for 89. Alsoufi B, Shen I, Karamlou T, Giacomuzzi
Life Science. Klaus-Viktor Peinemann, S C, Burch G, Silberbach M, Ungerleider R.
Pereira Nunes, J. Wiley & Sons, Feb. 2011; Extracorporeal life support in neonates, in-
57-59. fants, and children after repair of congenital
79. Wiesenak C, Wiesner G, Keyl C, et al. In heart disease: Modern era results in a single
vivo uptake and elimination of isoflurane institution. Ann Thorac Surg 2005; 80:15-
by different membrane oxygenators during 21.
cardiopulmonary bypass. Anesthesiology. 90. Horton S, d’Udekem Y, Shann F, Butt W,
2002; 97: 133-8. Bennett M, Best D, Brizard C, Extracorpo-
80. ELSO Registry Report. ELSO. Ann Arbor, real membrane oxygenation via sternotomy
Michigan 2015. for circulatory shock. J Thorac Cardiovasc
81. Dornia CA, Philipp A, Bauer S, et al. D- Surg. 2010; 139: e12-3.
dimers are a predictor of clot volume inside
membrane oxygenators during extracorpo-
real membrane oxygenation. Artif Organs.
2015; 39: 782-7.
82. Hawkins JL. Membrane oxygenator heat
exchanger failure detected by unique blood
gas findings – Case report. J Extra Corpor
Technol. 2014; 46: 91-3.
83. Hamilton C, Stein J, Seidler R, et al. Testing
of heat exchangers in membrane oxygen-
ators using air pressure. Perfusion. 2006;
21:105-7.
84. Snijders J, De Btuijn P, Bergmans M, Bas-
tianen G. Study on causes and prevention
of electrostatic charge build-up during
extracorporeal circulation. Perfusion. 1999;
14: 363-70.
85. Notice safety warning from the Sorin
group. Available at www.scps.org.uk/pdfs/
sorin-12:12:11.pdf
86. Non-tuberculous Mycobacterium (NTM)
Infections and Heater-Cooler Devices In-
terim Practical Guidance: CDC’s Division
of Healthcare Quality Promotion -Updated
October 27, 2015
87. Walczak R, Lawson DS, Kaemmer D, et al.
Evaluation of a pre-primed microporous
hollow fiber membrane for rapid response
neonatal ECMO. Perfusion 2005; 20:269-
275.
80
6
Adverse Effects of Extracorporeal Life Support: The Blood Biomaterial Interaction
Gail M. Annich, MD, Ryan Barbaro, MD, Timothy T. Cornell, MD, Melissa Reynolds, PhD,
Patricia Massicotte, MD
Introduction to a significant area of artificial biomaterial cir-

cuitry for a few hours or less. Large amounts
Current extracorporeal life support (ECLS) of anticoagulation are required to prevent clot-
applications have evolved from the early days ting, and essentially all elements in the blood
of cardiopulmonary bypass (CPB), first success- become activated during this time. Activation
fully applied more than a half century ago by Dr. refers to the conversion of blood zymogens to
John Gibbon. There have been many challenges active enzymes, expression of blood cellular
bringing extracorporeal perfusion from the op- receptors, initiation of cell signaling, and re-
erating room into the intensive care unit. CPB lease of vasoactive and cytotoxic substances.
caused an acute inflammatory response and was A relatively small artificial surface area gets
fraught with problems related to coagulation, exposed to circulating blood in VADs though,
bleeding, and other organ dysfunction, and initially, the amount of blood exposed to the
therefore was not considered to be a technol- wound varies until the device has been placed.
ogy appropriate for long-term circulatory or In ECLS systems exposure of part of the blood
respiratory support. Significant advancements volume to a large surface area of artificial bio-
in the materials, components, and techniques of material circuitry remains consistent throughout
ECLS have been realized over the past 50 years. its use, but little to no wound blood is circulated,
However, the inability to completely control the unless the patient has had recent surgery such
interaction between blood and the biomaterials as cardiac or congenital diaphragmatic hernia
of extracorporeal circuitry and the subsequent repair or trauma. In surgery or trauma the
inflammatory and coagulation reactions result injured vessels put the patient at increased risk
in these same challenges to the use of ECLS for bleeding, but that injury activates blood,
today and in the future. increasing the risk of circuit thrombosis as well;
Although likened to CPB, ECLS differs therefore, some anticoagulation is necessary to
significantly from open heart surgery or ven- prevent clotting within the extracorporeal cir-
tricular assist devices (VADs). The two main cuit, but less than that required in CPB because
differences are the extracorporeal support dura- the stimulus to blood component activation is
tion and the amount of blood exposed to non- less. The basic mechanisms of blood protein
endothelial surfaces per unit of time. CPB for and cellular activation during different applica-
cardiac surgery collects blood from the surgical tions of extracorporeal perfusion are identical,
field, an acute wound, and exposes that blood but the intensity of these reactions vary depend-
81
Chapter 6
ing upon the duration of the stimuli, the type of tion (coagulation) and/or thrombus degradation
anticoagulants, patient variability, and type of (fibrinolysis).
artificial circuitry.
Spontaneous bleeding and thrombosis Activation of the Coagulation Pathway
rarely occur in children and young adults. The
negatively charged membranes of the vascular The classic ‘coagulation cascade’ model
endothelium maintain the fluidity of blood via of hemostasis described a series of reactions
a complex interaction between plasma pro- involving activation of various factors along
teins and platelets. This normal physiologic extrinsic and intrinsic pathways. According to
hemostasis is disturbed when blood comes this model, stimulation of either the extrinsic or
into contact with any nonendothelial surface. intrinsic coagulation pathway leads to a com-
During ECLS, the continuous contact between mon pathway, resulting in the production of
circulating blood and the foreign surface of the thrombin and subsequent formation of a stable
circuit shifts the hemostatic balance to hyper- fibrin clot. This ‘coagulation cascade’ model
coagulability with patients and extracorporeal suggests that the coagulation factors themselves
circuit components at risk for thrombosis. To were responsible for controlling hemostasis,
regain hemostatic balance and prevent throm- while various cells provided a phospholipid
bosis, administration of antithrombotic therapy surface for the procoagulant reactions to occur.
is necessary. The most widely used antithrom- The cell-based model of hemostasis replaces
botic therapy for ECLS is the anticoagulant, the classic ‘coagulation cascade’ model, and
unfractionated heparin (UNFH). Unfortunately, proposes that cells play active roles in con-
the use of UNFH can result in bleeding in the trolling coagulation.1 Cell-based coagulation
systemic circulation and despite its use, clot- takes place on different cell surfaces in three
ting in the extracorporeal circuit. The bleeding overlapping steps: initiation, amplification, and
and thrombosis that occur regularly during the propagation (Figure 6-1).
course of ECLS can ultimately result in sig- The initiation phase occurs on a tissue
nificant clinical complications, including death. factor-bearing cell or cellular fragments.2 A
This chapter will primarily focus on the effect of large number of cells including endothelial cells,
the artificial surface and the blood/biomaterial vascular smooth muscle cells, and fibroblasts
interaction that occurs during ECLS. It will tissue factor (TF). TF antigen also circulates
also touch upon what normal hemostasis is and in peripheral blood, delivered to sites of vas-
the expected variability seen in the neonatal
population.
Normal Hemostasis
Normal physiologic hemostasis depends

upon maintaining a fine balance between
thrombosis and hemorrhage. Coagulation and
fibrinolysis are the two pathways responsible
for hemostasis. These pathways consist of a
number of protein components which when
activated by a stimulus, interact with red blood
Figure 6-1. Cell-based coagulation occurs on
cells and platelets and result in thrombus forma- different cell surfaces in three overlapping
steps: initiation, amplification, and propagation.
82
cular injury by neutrophils, monocytes, and Fibrin deposits are eliminated because fibrin
macrophages. TF becomes available through attracts plasminogen and tissue plasminogen
a number of different mechanisms including: activator (tPA), which converts plasminogen to
exposure on damaged vessel wall (surgery, trau- plasmin. The increasing plasmin concentrations
ma), through aberrant expression by activated cause thrombus degradation by digesting fibrin
monocytes or endothelial cells when stimu- (fibrinolysis) into soluble fragments, including
lated by sepsis (various different organisms), D-dimer. The fibrinolytic pathway is modulated
or inflammation (cytokines). The activated by the inhibitor protein plasminogen activator
factor VII-TF complex successively activates inhibitor 1 (PAI-1) to prevent degradation of all
a number of coagulation proteins resulting in thrombi, including important hemostatic plugs,
thrombin (fIIa) generation. which prevent hemorrhage. Stabilization of
The small amount of thrombin generated in coagulation counteracts fibrinolysis through
the initiation phase is essential for procoagulant thrombin-activated fVIIIa, which converts
progression to the amplification phase. In the loosely interlaced fibrin into a tightly knitted
amplification phase, platelets and cofactors (f) aggregate.
(fV, fVIII, fXI) become activated to prepare for
more significant thrombin generation. During Developmental Hemostasis
the propagation phase, fIXa, accelerated by
fVIIIa, binds to activated platelets causing fur- Hemostasis remains “balanced” in infants
ther fX activation. The complexing of fXa with and children despite very different levels of
fVa, to membrane surfaces leads to a burst of constituent proteins and inhibitors of coagu-
thrombin (fIIa) generation resulting in the cleav- lation (decreased factors XII, XI, X, IX, VII,
age of fibrinogen to fibrin monomers, which II and protein C and S and AT; increased α2
polymerize to consolidate the initial platelet macroglobulin) and fibrinolysis (decreased
plug into a stable fibrin clot. tPA, plasminogen and increased PAI-1) which
approach adult levels at different developmental
Activation of the Fibrinolytic Pathway stages up to puberty. These normal physiologic
differences in hemostasis are termed “develop-
The fibrinolytic pathway continuously regu-
lates cell-mediated coagulation (as described
above). The fibrinolytic pathway (constituent
proteins: tissue plasminogen activator (tPA) and
plasminogen) becomes activated via thrombin
generation. This regulation occurs in three
phases as well: termination, elimination, and
stabilization (Figure 6-2). Tissue factor path-
way inhibitor (TFPI), along with protein C and
S, antithrombin (AT) and α2macroglobulin par-
ticipate in the initial termination of coagulation
and ultimately prevent formation of pathologic
thrombi.
TFPI inhibits TF, fVIIa and fXa, while AT
inhibits thrombin, fIXa, fXa, fXIa and the TF-
VIIa complex. Protein S acts as a cofactor for Figure 6-2. Regulation of the Fibrinolytic Sys-
protein C-mediated fVa and fVIIIa inhibition. tem: termination, elimination, and stabilization.
83
Chapter 6
mental hemostasis”.3 Epidemiologic studies only partially, either because of disease or lack
demonstrate that infants and children have de- of inflow. Mechanisms that normally maintain
creased venous thrombosis compared to adults physiologic homeostasis become disrupted,
as a result of unique protective mechanisms (in- which results in increased acuity to the already
creased α2macroglobulin, decreased thrombin physiologically compromised patient.
generation and altered vessel wall properties).
However, high risk cohorts of children with an Pathophysiology of the Blood/Biomaterial
increased incidence of thrombosis exist, includ- Surface Interaction
ing children who undergo ECLS.
Contact with synthetic, nonendothelial cell
Initiation of ECLS: Coagulation Pathway surfaces, shear stresses, turbulence, cavitation,
Activation and Inflammatory Response and osmotic forces directly damage blood.6
Plasma proteins and lipoproteins are progres-
Exposure of blood to the nonbiologic sively denatured during ECLS,1,2 increasing
surfaces of an extracorporeal circuit initiates a plasma viscosity and protein solubility, produc-
complex inflammatory response involving both ing macromolecules, and increasing protein
the coagulation and the inflammatory response reactive side groups. Plasma IgG, IgA, IgM,
pathways (Figure 6-3).4 This response leads to and albumin decrease more than expected
capillary leak which can cause temporary dys- from hemodilution.7 Red blood cells (RBCs)
function of every organ. In fact, the response to develop reversible echinocytic changes, but
extracorporeal circulation is remarkably similar, some are hemolyzed by shear forces and acti-
clinically and biochemically, to that seen in vated complement.8,9 Roller pumps cause more
the systemic inflammatory response syndrome hemolysis than centrifugal pumps, although
(SIRS) and acute respiratory distress syndrome with improved technology this has grown less
(ARDS).5 During ECLS, blood is circulated via problematic.10 Platelets and white blood cells
a mechanical pump in parallel with the heart, in- (WBCs) are also injured during perfusion, but
dependent of physiological controls. The heart, the consequences of activation of these cells far
in contrast, responds to physiologic controls but outweigh the effects of direct injury. In addition,
the effect of shear rate on platelets and other
components of coagulation are also critically
important. The higher the shear rate, the more
platelet deposition and generation of fXa by
augmentation of TF:VIIa complex. While at
lower shear rates, less platelet deposition but
more fibrin deposition occurs.
Multiple blood cells and plasma protein
systems become activated as part of a series
of cellular and enzymatic reactions that occur
during initiation and maintenance of ECLS.
Figure 6-3. Simplistic representation of the The response involves the contact and comple-
blood-surface interaction during ECLS. This ment systems, coagulation, fibrinolysis, and
shows the components relevant to thrombosis activation of most cell lines including platelets,
and even though complement and leukocytes
are considered to be involved with inflamma- neutrophils, monocytes, lymphocytes and en-
tion, they are also very relevant participants in dothelial cells.11
thrombosis formation.
84
Platelets GPIIb-IIIa (CD41/CD61) is the dominant

platelet receptor. Resting platelets with inac-
Platelets are the mainstay for hemostasis tive GPIIb-IIIa have a low affinity for binding
and preservation of vascular wall integrity. adsorbed fibrinogen. Once activated, confor-
Platelets respond to minimal stimulation and mational shape changes of the platelet occur,
become activated when they encounter a throm- and the high-affinity binding site of GPIIb-IIIa
bogenic stimulus such as injured endothelium, is exposed, binding soluble fibrinogen, which
subendothelium, or artificial surfaces. Normal in turn leads to platelet aggregation and platelet
platelets participate in the balance of hemosta- leukocyte aggregates by the crosslinking of 2
sis through the following activities: activation, GPIIb-IIIa receptors or by the crosslinking of
adhesion, secretion of active substances, and GPIIb-IIIa with Mac-1 on the leukocyte. These
aggregation. Collagen exposure and von Wil- crosslinks are made by fibrinogen.
lebrand Factor (vWF) released by the damaged Platelet activation and adhesion, as de-
blood vessel results in platelet adhesion. In high scribed above, occur during both CPB and
shear stress conditions (arteries and microves- ECLS, as well as with vascular access catheters
sels) high molecular weight vWF mediates and grafts. Both adherent platelets and platelet
platelet adhesion by binding to collagen and microparticles are procoagulant in nature, and
the nonactivated platelet through the platelet therefore provide continual, ongoing stimulus
receptor glycoprotein (GP) Ib-IX-V. GPIb for the above described physiologic platelet
mediates platelet interactions with VWF. The responses. During ECLS, platelet adhesion
adherence of platelets via GPIb to adsorbed and aggregate formation reduce the circulating
vWF depends upon shear stress, which provides platelet count; however, high consumption and
the conformational change in VWF needed to formation of microemboli, rather than occlusive
allow binding.12 In low shear stress conditions thrombi, can occur even in the event of minimal
(large veins) platelet adhesion occurs through adhesion to the circuitry surface. As ECLS
direct interaction via GP VI with collagen. continues, adherent platelets detach, leaving
Platelet secretion occurs from intracellular fragments of platelet membrane behind; these
granule collections and results in a number of will also detach and circulate. The circulating
actions due to agents released including: platelet pool during ECLS consists of decreased
numbers of morphologically normal platelets,
• Increasing platelet adhesion and aggrega- increased numbers of platelets at various stages
tion (released: adenosine diphosphate, vWF, of activation (eg, pseudopod formation, de-
fibrinogen and thrombospondin) granulation and membrane receptor loss), and
• Participation in coagulation (released: fV, new larger platelets released from the bone mar-
fibrinogen) row. Bleeding times increase in the presence
• Increased vascular tone and contraction of structurally normal appearing platelets13 and
(released: serotonin) as ECLS continues beyond 24 hours, platelet
• Increased cell proliferation and migration consumption continues.
(released: platelet derived growth factor,
PDGF) Leukocytes
• Fibrinogen binds to activated platelets
through the receptor GPIIb-IIIa and acts Neutrophils, monocytes, and lymphocytes
as a bridge between platelets resulting in are the main groups of cells involved in the in-
aggregation. flammatory responses during ECLS. Exposure
of patient blood to the extracorporeal circuit
85
Chapter 6
results in activation of innate immunity. Cir- rendering a host susceptible to infection and
culating leukocytes, including peripheral blood infectious sequelae such as sepsis and multiple
mononuclear cells (PBMCs), are stimulated in organ dysfunction syndrome (MODS).24
part by tissue factor activation,14 complement,4,15
and endotoxin,16 releasing numerous circulating Endothelial Cells
proinflammatory cytokines (eg, TNF-a, IL-1b)
that activate circulating neutrophils facilitating Endothelial cells maintain the fluidity of
their adhesion to the vascular surfaces of numer- blood and the integrity of the vascular system.
ous organs.17 Leukocyte activation also releases Endothelial cells produce prostacyclin, heparin
an array of potent oxygen metabolites and pro- sulfate, tPA, and TFPI, which help regulate
teolytic enzymes. The material characteristics the coagulation pathway. Endothelial cells
of artificial surfaces modulate the absorption of produce protein S, a necessary cofactor for
proteins to the surface and therefore the level normal protein C function; protein C is a natural
of activation. anticoagulant. Endothelial cells also produce
Neutrophil counts decrease immediately vasoactive substances and cytokines such as
after ECLS initiation because of dilution and nitric oxide (NO), prostacyclin, endothelin-1,
recover slowly thereafter. The principal ago- IL-1, IL-6, and platelet activating factor (PAF)
nists for activating neutrophils during ECLS as well as inactive substances such as histamine,
include kallikrein and C5a.18 Both CPB and norepinephrine, and bradykinin.25 Prostacyclin
ECLS cause accumulation of activated neutro- concentrations increase rapidly at the start of
phils in pulmonary perivascular and interstitial CPB and then begin to decrease.26
tissue. This accumulation produces increased
capillary permeability, interstitial edema, and Complement
large alveolar-arterial oxygen differences dur-
ing and after perfusion.19 During open heart The alternative complement pathway, as
surgery, monocytes are activated to express opposed to the classic complement pathway,
TF, in both the wound and extracorporeal is primarily activated by foreign surfaces of
circuit, but activation in the circuit is delayed microbial organisms or elements, particles, or
for several hours.20 Extracorporeal perfusion biomaterial surfaces as part of this procoagulant
decreases the total number of lymphocytes and activation and inflammation.27 The alternative
specific subsets of lymphocytes, particularly B pathway does not require antibody or immune
lymphocytes, natural killer cells, helper T-cells, complexes for activation. Complement activa-
and T-suppressor lymphocytes.21 Lymphocyte tion via the alternative pathway occurs sponta-
counts usually recover within 5 days of weaning neously at a low rate, but a hydrolyzed C3 is
from ECLS; slower recovery is associated with formed, factor B becomes activated, and then
a poor prognosis.22 initiates the cleavage of C3 to form C3a and
This proinflammatory response has been C3b. During ECLS or CPB, with a biomaterial
thought to be responsible for the physiologic surface to bind C3b covalently to its hydroxyl
derangements observed early after the blood or amine groups, factor B and D binding occurs,
contacts the extracorporeal circuit. A compen- and the alternative C3 convertase (C3bBb) is
satory, antiinflammatory response syndrome formed, creating a positive amplification loop.
(CARS) also exists that is aimed at countering
the proinflammation.23 While CARS is a neces-
sary response, an exaggerated or dysregulated
CARS response can impair immunity thus
86
Activation of the Coagulation System during ther contributing to the inflammatory response
ECLS to extracorporeal circulation.33
The fibrinolytic system has the important
Plasma proteins are adsorbed onto the bio- role of limiting the extent of clot formation
material surface of the extracorporeal circuit and eventually dissolving it. The presence of
to form a monolayer of bound proteins within circulating thrombin stimulates endothelial cells
seconds of contact.28 The physical and chemical to produce tPA, which participates in the cleav-
composition of the polymer determines which age of plasminogen to plasmin.34 Plasmin lyses
proteins are most likely to adhere to that sur- fibrin to dissolve clot and inhibits fibrinogen
face, which may not be the proteins of greatest and factors V, VII, IX, and XI. The cleavage
concentration within the plasma. Adsorbed reaction to form plasmin produces D-dimers,
fXII and fibrinogen undergo conformational which have been shown to be elevated dur-
changes, triggering activation of the contact ing the course of neonatal ECLS as a marker
system. The contact system consists of four of ongoing fibrinolysis.35 Evidence for early
primary plasma proteins: fXII, prekallikrein, activation of both the contact and fibrinolytic
high molecular weight kininogen (HMWK), systems has been demonstrated by peak concen-
and C-1 inhibitor. FXIIa, HMWK, fXI, fIX and trations of fXIIa and fibrin degradation products
fVIIIa work together to produce the tenase com- in neonates early after the initiation of ECLS.36
plex.29 The tenase complex binds fX to produce Such significant activation of the coagulation
fXa. Activation of coagulation occurs through system results in a pattern of consumptive
TF expression on activated cells (monocytes, coagulopathy with half of infants and children
macrophages, neutrophils, activated endothelial in one study having demonstrated deficiencies
cells, smooth muscle cells, apoptotic cells), or in both platelets and coagulation factors soon
cellular components (platelet microparticles after the ECLS initiation ECLS, even with the
or circulating vesicles). TF is a cell-bound use of fresh frozen plasma (FFP) in the circuit
glycoprotein expressed in the vascular sub- priming volume.37
endothelium, and many other cells including Despite the activity of plasmin and the
activated monocytes.30 TF complexes with fibrinolytic system described above, the use of
fVII in conjunction with a phospholipid surface an extracorporeal circuit results in continued
forming the TF:VIIa complex which in turn acti- activation of the coagulation system and genera-
vates fX to Xa.31 FXa facilitates the conversion tion of thrombin. Endogenous antithrombotic
of prothrombin to thrombin, and fibrinogen to activity becomes overwhelmed and this neces-
fibrin as described in more detail earlier. sitates the use of an exogenous anticoagulant
Platelets adhere to the circuit surfaces and to maintain the integrity of the extracorporeal
become activated, which leads to platelet aggre- circuit.
gation and further activation of the coagulation
system. Platelet activation and consumption Activation of the Innate Immune System and
occurs upon ECLS initiation causing decreases Resultant Immune Dysregulation
in platelet number and function within the first
hour of ECLS.32 Platelet activation and con- Activation of the coagulation system and
sumption continues throughout the course of thrombin generation does not occur in isolation
ECLS often requiring regular platelet transfu- but in conjunction with the activation of the in-
sions. With platelet activation neutrophils also nate immune system. The initial activation of
become activated producing cytokines and fur- the innate immune system by the ECLS circuit
cumulatively contributes to the SIRS response
87
Chapter 6
that can clinically manifest as hemodynamic Endothelial Function in Hemostasis and

instability and capillary leak. Thus, depending Circuit Modifications
on the degree of the innate immune response,
a slight increase in hemodynamic support may Understanding the normal function of the
be necessary following the first few hours after coagulation system and the normal inflamma-
initiation of ECLS. The initial SIRS response is tory response, and pairing this with the patho-
counterbalanced by a compensatory antiinflam- physiology of the blood biomaterial interface
matory response (CARS) meant to reestablish are crucial to maintaining stability in patients
homeostasis and reset the innate immune sys- on ECLS. Future success will rely upon a
tem. However, a prolonged CARS response multidisciplinary team that can create circuitry,
may lead to an acquired immunosuppressed regardless of surface type, that minimizes
state placing the patient at risk for nosocomial thrombogenesis and preserves platelet and
infections. hemostatic functionality. Heparin-bonded or
Increased attention is being placed on surface-treated circuits (a number of different
understanding the immunology of this CARS formulations are available) have not success-
phase, a key feature of which is the presence of fully inhibited the coagulation and inflammatory
“deactivated” monocytes.38 These monocytes response to the foreign surface, although many
that do not produce TNF-a to ex vivo endotoxin centers use them to limit or eliminate the need
challenge in patients with septic shock as com- for anticoagulation during cardiopulmonary
pared to the response in unaffected patients.39,40 bypass and/or ECLS. Some have shown that the
This deactivated state is also associated with a use of these circuits reduces platelet activation,
decrease in the cell surface MHC-II molecule, fibrinolysis, and the inflammatory response.44
HLA-DR. In time, the term “immunoparalysis” Others have demonstrated decreased blood loss
was coined to refer to the combination of de- and need for blood product replacement when
creased ex vivo LPS responsiveness and HLA- using heparin-bonded circuits.45, 46 However,
DR expression (less than 30% normal).41 The the beneficial effects of coated circuits may be
presence of these parameters following CPB has measured in hours and thus too short lived to
been preliminarily observed.42,43 The one study be of benefit in longer runs of ECLS that can
investigating the impact of immunoparalysis last for days to weeks to months.
following CPB in children examined HLA- A surface modification strategy for ECLS
DR expression in 82 children and showed that would be to make it as nonthrombogenic as
HLA-DR expression less than 60% at 72 hours vascular endothelium. A surface modifica-
after CPB predicted the development of sepsis tion strategy for ECLS would be to make it as
with an odds ratio of nearly 13.43 Although the non-thrombogenic as vascular endothelium
incidence of immunoparalysis while on ECLS (Figure 6-4). Among other things, endothe-
remains unknown, the potential for an acquired lial cells produce prostacyclin and nitric oxide
immunosuppressed state must be acknowledged (NO) which inhibit thrombin induced platelet
and attention to proper antibiotic usage, ad- adhesion and activation as a way to maintain
equate nutrition and practices for the prevention the fluidity of blood.47-49 In the presence of
of nosocomial infections are warranted. NO, platelets become reversibly anesthetized,
and therefore do not become activated during
contact with the extracorporeal circuit. The
half-life of NO is extremely short in plasma, as
hemoglobin quickly eliminates it (<1 second)
allowing for rapid reversal of its inhibitory
88
effects on platelets returning them to normal

function. The creation of NO releasing poly-
mers has been successfully demonstrated in a
rabbit model of extracorporeal circulation.50-52
The results exceeded expectations allowing for
precise NO-release/control at the surface and
determination of the exact NO flux required at
the surface to prevent platelet activation and ad-
hesion during extracorporeal circulation without
systemic anticoagulation. More recently incor-
poration of a direct thrombin inhibitor within
the circuit as well, has created a complete local
anticoagulation effect at the blood/biomaterial
interface which is not seen systemically, thus
maintaining normal physiologic hemostasis
within the animals.53
The use of ECLS for critically ill patients
now represents an important support technol-
ogy. Advances in ECLS technology have made
it safer as the patient population who require it
has expanded and grown more complicated with
a higher acuity. UNFH remains the mainstay
of anticoagulation but continues to have impor-
tant limitations and risks discussed in detail in
Chapter 7 of this book. Ultimately mimicking
the endothelium and obviating the need for sys-
temic anticoagulation altogether would signifi-
cantly reduce the risks in this patient population.
Mastering and controlling the blood biomaterial
interaction appears close at hand.
Figure 6-4. The endothelium maintains the

delicate balance between thrombosis and an-
ticoagulation during normal hemostasis.
89
Chapter 6
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EC. Red blood cell damage by shear stress. small intestinal mucosal ischemia during
Biophys J. 1972;12(3):257-273. cardiopulmonary bypass. Measurement by
7. Clark RE, Beauchamp RA, Magrath RA, diamine oxidase and peptidoglycan. Eur J
Brooks JD, Ferguson TB, Weldon CS. Cardiothorac Surg 2004. 25(2): p. 275-80.
Comparison of bubble and membrane 17. Levy, JH, Tanaka KA, Inflammatory re-
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Thorac Cardiovasc Surg. 1979;78(5):655- Thorac Surg 2003. 75(2): S715-20.
666. 18. El Habbal MH, Carter H, Smith L, Elliot
8. Woodman RC, Harker LA. Bleeding com- MJ, Strobel S, Neutrophil activation in
plications associated with cardiopulmonary paediatric extracorporeal circuits: effect
bypass. Blood. 1990;76(9):1680-1697. of circulation and temperature variation.
9. Salama A, Hugo F, Heinrich D, et al. De- Cardiovasc Res. 1995;29:102-107.
position of terminal C5b-9 complement 19. Ratliff NB, Young WG Jr, Hackel D, Mikat
complexes on erythrocytes and leukocytes E, Wilson JW. Pulmonary injury secondary
during cardiopulmonary bypass. N Eng J to extracorporeal circulation. An ultra-
Med. 1988;318(7):408-414. structural study. J Thorac Cardiovasc Surg.
10. Kawahito K, Nose Y. Hemolysis in dif- 1973; 65:425-432.
ferent centrifugal pumps. Artif Organs. 20. Barstad RM, Ovrum E, Ringdal MA, et
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11. Bowen FW, Edmunds HL Jr. Coagula- procoagulant activity during coronary
tion, anticoagulation and the interaction of artery bypass surgery is reduced with
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heparin-coated extracorporeal circuit. Br 29. Yeh T Jr., Kavarana MN. Cardiopulmonary

J Haematol. 1996; 94(3):517-525. bypass and the coagulation system. Prog-
21. DePalma L, Yu M, McIntosh CL, Swain ress Ped Cardiol. 2005;21:87-115.
JA, Davey RJ. Changes in lymphocyte sub- 30. Edgington TS, Mackman N, Brand K, Ruf
populations as a result of cardiopulmonary W. The structural biology of expression and
bypass. The effect of blood transfusion. J function of tissue factor. Thromb Haemost.
Thorac Cardiovasc Surg. 1991;101(2):240- 1991;66(1):67-79.
244. 31. Edmunds LH Jr., Colman RW. Thrombin
22. Kawahito K, Kobayashi E, Misawa Y, et al. during cardiopulmonary bypass. Ann Tho-
Recovery from lymphocytopenia and prog- rac Surg. 2006;82(6):2315-2322.
nosis after adult extracorporeal membrane 32. Robinson TM, Kickler TS, Walker LK,
oxygenation. Arch Surg. 1998;133(2):216- Ness P, Bell W.. Effect of extracorporeal
217. membrane oxygenation on platelets in new-
23. Zimmerman, J.J., Congenital heart disease, borns. Crit Care Med. 1993;21(7):1029-
cardiopulmonary bypass, systemic inflam- 1034.
matory response syndrome, compensatory 33. Fortenberry JD, Bhardwaj V, Niemer P,
anti-inflammatory response syndrome, and Cornish JD, Wright JA, Bland L. Neutro-
outcome: evolving understanding of critical phil and cytokine activation with neonatal
care inflammation immunology. Crit Care extracorporeal membrane oxygenation. J
Med 2002. 30(5): p. 1178-9. Pediatr. 1996;128(5Pt1):670-678.
24. Mokart D, Capo C, Blache JL, et al. Early 34. Levin EG, Marzec U, Anderson J, Harker
postoperative compensatory anti-inflamma- LA. Thrombin stimulates tissue plasmino-
tory response syndrome is associated with gen activator from cultured human endothe-
septic complications after major surgical lial cells. J Clin Invest. 1984;74(6):1988-
trauma in patients with cancer. Br J Surg, 1995.
2002. 89(11): p. 1450-6. 35. Urlesberger B, Zobel G, Zenz W, et al.
25. Vane JR, Anggard EE, Botting RM. Regu- Activation of the clotting system dur-
latory functions of the vascular endothe- ing extracorporeal membrane oxygen-
lium. N Eng J Med. 1990; 323(1):27-36. ation in term newborn infants. J Pediatr.
26. Faymonville ME, Deby-Dupont G, Larbuis- 1996;129(2):264-268.
son R, et al. Prostaglandin E2, prostacyclin, 36. Plotz FB, van Oeveren W, Bartlett RH,
and thromboxane changes during nonpulsa- Wildevuur CR. Blood activation during
tile cardiopulmonary bypass in humans. J neonatal extracorporeal life support. J Tho-
Thorac Cardiovasc Surg .1986;91(6):858- rac Cardiovasc Surg. 1993;105(5):823-832.
66. 37. McManus ML, Kevy SV, Bower LK, Hick-
27. Valhonart H, Swinford RD, Ingelfinger JR, ey PR. Coagulation factor deficiencies dur-
et al. Rapid activation of the alternative ing initiation of extracorporeal membrane
pathway of complement by extracorpo- oxygenation. J Pediatr. 1995;126(6):900-
real membrane oxygenation. ASAIO J. 904.
1999;45(1):113-114. 38. Volk, HD, Thieme M, Heym S, et al.,
28. Horbett TA. Principles underlying the role Alterations in function and phenotype of
of adsorbed plasma proteins in blood inter- monocytes from patients with septic dis-
actions with foreign materials. Cardiovasc ease--predictive value and new therapeutic
Pathol. 1993;2:137S-148S. strategies. Behring Inst Mitt, 1991(88): p.
208-215.
91
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39. Asadullah, K, Woiciechowsky D, Döcke 48. Skogby M, Friberg G, Adrian K, Mellgren

WD, et al., Very low monocytic HLA-DR K, Pharmacological inhibition of plasma
expression indicates high risk of infection- coagulation and platelet activation during
-immunomonitoring for patients after experimental long-term perfusion. Scand
neurosurgery and patients during high dose Cardiovasc J 2003;37(4):222-228.
steroid therapy. Eur J Emerg Med 1995. 49. Jacobson J. Nitric oxide: platelet protec-
2(4): p. 184-190. tant properties during cardiopulmonary
40. Volk, HD, Reinke P, Krausch D, et al., bypass/ECMO. J Extra Corpor Technol.
Monocyte deactivation--rationale for a new 2002;34(2):144-147.
therapeutic strategy in sepsis. Intensive 50. Annich GM, Meinhardt JP, Mowery KA et
Care Med 1996. 22 Suppl 4: p. S474-481. al. Reduced platelet activation and throm-
41. Volk, H.D., P. Reinke, and W.D. Docke, bosis in extracorporeal circuits coated with
Clinical aspects: from systemic inflamma- nitric oxide release polymers. Crit Care
tion to ‘immunoparalysis’. Chem Immunol Med. 2000(4);28:915-920.
2000;74:p. 162-177. 51. Batchelor MM, Reoma SL, Fleser PS, Nut-
42. Hummel M, Döcke WD, Friedel N, et al. hakki VK, Callahan RE, Shanley CJ, Politis
Monitoring of the cellular immune system JK, Elmore J, Merz SI, Meyerhoff ME.
in patients with biventricular assist de- More lipophilic dialkyldiamine-based dia-
vices awaiting cardiac transplantation. Clin zeniumdiolates: synthesis, characterization,
Transplant 1994. 8(1): p. 59-66. and application in preparing thromboresis-
43. Allen, ML Peters MJ, Goldman A, et al. tant nitric oxide release polymeric coatings.
Early postoperative monocyte deactivation J Med Chem 2003;46(24):5153-5161.
predicts systemic inflammation and pro- 52. Skrzypchak AM, Lafayette NG, Bartlett RH,
longed stay in pediatric cardiac intensive Zhou Z, Frost MC, Meyerhoff ME, Annich
care. Crit Care Med 2002. 30(5): p. 1140- GM. Effect of varying nitric oxide release
1145. to prevent platelet consumption and pre-
44. Palatianos GM, Foroulis CN, Vassili MI, et serve platelet function in an in vivo model
al. A prospective, double-blind study of the of extracorporeal circulation. Perfusion
efficacy of the bioline surface-heparinized 2007;22(3):193-200.
extracorporeal perfusion circuit. Ann Tho- 53. Yu J, Brisbois E, Handa H, Annich GM,
rac Surg. 2003;76(1):129-135. Meyerhoff ME, Bartlett RH, Major T.
45. Marcolin R, Bombino M, Fumagalli R, The immobilization of a direct thrombin
Pesenti A Venovenous ELS with hepa- inhibitor to a polyurethane as a nonthrom-
rin bonded circuits. Int J Artif Organs. bogenic surface coating for extracorporeal
1995;18(10):624-626. circulation. J. Mater Chem. B Biol Med
46. Tayama E, Hayashida N. Akasu K, et 2016;4(13):2264-2272.
al. Biocompatibility of heparin-coated
extracorporeal bypass circuits: New hepa-
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2000;24(8):618-623.
47. Radomski MW, Palmer RMJ, Moncada S.
The anti-aggregating properties of vascular
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1987;92(3):639-646.
92
7
Anticoagulation and Disorders of Hemostasis
Brian C. Bridges, MD, Marco Ranucci, MD, Laurance L. Lequier, MD
Introduction half-life of 30 to 60 minutes.2,3 The antico-

agulation effect of heparin is mediated via its
One of the greatest challenges of providing interaction with antithrombin (AT) and tissue
ECLS is achieving and maintaining therapeutic factor pathway inhibitor (TFPI).4 Although AT
anticoagulation. While the field of ECLS has inhibits all serine proteases except factor VIIa
advanced greatly, most of the complications and protein C, most of its anticoagulant effect
involved with this support remain unchanged, is through inhibition of thrombin and factor Xa.
and continue to involve clotting of the artificial The inhibition of thrombin prevents the con-
circuit and patient bleeding. In this chapter we version of fibrinogen to fibrin, and ultimately,
will discuss the types of anticoagulation used the formation of a cross-linked fibrin clot. The
for ECLS, the monitoring of anticoagulation, UNFH-AT complex increases the inhibition of
blood product replacement, and the strategies coagulation proteins by 1000 fold compared to
for dealing with hemorrhagic and thrombotic AT alone.5 Patients with congenital or acquired
complications. AT deficiency often fail to achieve therapeutic
anticoagulation with UNFH.6 The administra-
Anticoagulation tion of UNFH also results in a several-fold
increase in the release of TFPI from the endo-
thelium. TFPI is a major in-vivo inhibitor of
Unfractionated Heparin coagulation that binds and inhibits both factor
Xa and factor VIIa/tissue factor catalytic activity.
Historically, unfractionated heparin Dilute prothrombin time assays reveal that TFPI
(UNFH) has been the anticoagulant of choice contributes about one third of the anticoagulant
for the vast majority of ECLS. Heparin has been effect of heparin, with the rest of the effect at-
in clinical use since 1937 when it was first used tributed to antithrombin.7
to prevent pulmonary embolism in postsurgical A bolus dose of UNFH ranging from 50 to
and postpartum patients.1 It remains widely 100 units/kg is given after the exposure of the
used, relatively inexpensive, and easily avail- vessels and before insertion of the cannulas for
able. UNFH is a mixture of mucopolysaccharide ECLS. Patients with transthoracic cannulation,
chains of various lengths that range from 5,000 severe coagulopathy, or active bleeding can
to 30,000 daltons. UNFH undergoes hepatic receive an UNFH bolus at the lower end of this
metabolism, renal excretion, and has a plasma range. Subsequently, UNFH is administered as
93
Chapter 7
a continuous intravenous infusion. Some ECLS this testing is complex and not readily available
centers have a minimum and maximum UNFH at most medical centers.14
infusion rate that typically ranges from a mini-
mum of 10 to 15 units/kg/hr to a maximum of Direct Thrombin Inhibitors
40 to 60 units/kg/hr.
Administration of anticoagulants place Direct thrombin inhibitors (DTIs) represent
patients at risk of bleeding. However, UNFH an alternative to UNFH anticoagulation for
also carries the risk of heparin-induced throm- ECLS. DTIs have been used in both adult and
bocytopenia (HIT). Patients with HIT typically pediatric patients with HIT, heparin resistance,
have a greater than 50% decrease in platelet and non-HIT thrombocytopenia. Unlike UNFH,
count that occurs 5 to 14 days after the initiation DTIs directly inhibit thrombin without requir-
of heparin.8 HIT occurs due to the formation of ing the cofactor AT. Intravenous DTIs currently
IgG antibodies to the platelet factor 4/heparin available on the market include bivalirudin and
complex on platelet surfaces. These antibodies argatroban.
cause platelet activation, platelet consumption, Bivalirudin is a 20–amino acid synthetic
the release of prothrombotic microparticles, polypeptide analog of hirudin, which binds to
and thrombin generation.9 HIT is strongly as- the active site of thrombin. It has a half-life
sociated with arterial and venous thromboses of approximately 25 minutes, with only 20%
that carry a high morbidity and a mortality renal elimination, the majority being cleared by
risk of 17% to 30%.10 HIT can occur with all proteolytic enzymes.16,17 The successful use of
forms of heparin, but the risk with UNFH is bivalirudin anticoagulation for ECLS has been
higher than that seen with low molecular weight published in case reports, series, and clinical
heparin.11 HIT is considerably more common studies.18-22 The reported maintenance dose
in adult patients than pediatric patients. While ranges from 0.045 to 0.48 mg/kg/hr. An initial
the incidence of HIT can be 0.9% to 4.9% of bolus dose is unnecessary when converting
adult patients treated with heparin,12 it is esti- from UNFH to bivalirudin after ECLS initiation.
mated to be as low as 0.33% for non-neonatal, Bivalirudin is intravascularly cleaved in areas
pediatric patients undergoing cardiopulmonary where blood stagnates. Therefore, it should be
bypass, and potentially nonexistent in neonatal avoided in the presence of echocardiographic
patients.13 In a retrospective cohort study at a signs of intracardiac blood stagnation (“smoke
tertiary children’s hospital, the prevalence of effect”).23 Dose adjustments are required for
HIT was 0.06% and HIT with thrombosis was patients with decreased creatinine clearance.
0.05% for patients treated with UNFH.14 Monitoring of anticoagulation with bivalirudin
The diagnosis of HIT can be difficult, espe- relies on the activated partial thromboplastin
cially true for the patient supported with ECLS, time (aPTT) (target 50-60 seconds) and the
as most of these patients are anticoagulated with activated clotting time (ACT). Viscoelastic
UNFH and have thrombocytopenia requiring tests have been used to target a prolonged clot
platelet transfusion. HIT antibody assays are formation time.21
readily available in most medical facilities, but Argatroban competitively inhibits thrombin
these tests have a high false positive rate, and by binding its active site to form a reversible
only a minority of critically ill patients with complex.16 It undergoes hepatic metabolism,
positive platelet factor 4/heparin antibodies and the half-life is approximately 45 minutes.
will develop HIT.15 The confirmatory serotonin The use of argatroban anticoagulation for ECLS
release assay is much more specific, with a re- has been published in case reports and series
ported sensitivity and specificity of >95%, but for adult and pediatric patients with suspected
94
or diagnosed HIT.24-30 The maintenance dose different commercially available instruments

is reported between 0.1-0.7 µg/kg/min with that measure ACT.33,34
anticoagulation monitoring based on the aPTT Traditionally, ACT has been used to initi-
(50-60 seconds) and ACT. Potential advantages ate and titrate UNFH for ECLS. The UNFH
of DTIs over UNFH are the prevention and infusion is typically started once ACT reaches
treatment of HIT and the preservation of platelet 300 seconds or less. The initial standard He-
and AT levels. The main disadvantages include mochron® ACT range is 180 to 220 seconds or
the lack of antidotes and, for bivalirudin, the risk 160 to 180 seconds with the ISTAT® analyzer
of local, intravascular clearance with thrombus with kaolin cartridge. This ACT range can then
formation in areas with blood stagnation. be adjusted based on factors including patient
When UNFH is replaced by a DTI, the ini- bleeding, circuit clotting, or the measured anti-
tial dose should begin on the lower side of the factor Xa level.
reported range (0.05 mg/kg/hr for bivalirudin
and 0.1 µg/kg/min for argatroban) progressively Activated Partial Thromboplastin Time
increasing the dose until the target aPTT is
reached and maintained. DTIs represent a viable The aPTT assesses the intrinsic and final
alternative to UNFH for ECLS anticoagulation common pathway of coagulation and so is
that deserves additional study. influenced by coagulation factors, heparin, and
AT levels, and the presence of a lupus inhibitor.
Anticoagulation Monitoring It has been the traditional means of measuring
and titrating anticoagulation with UNFH. In a
retrospective study of pediatric ECLS patients,
Activated Clotting Time titration of UNFH using aPTT versus ACT led
to decreased hemorrhagic complications but
The ACT has long been the standard mea- increased circuit clotting complications.35 As de-
sure of anticoagulation for both cardiopulmo- scribed previously, aPTT is the accepted means
nary bypass and ECLS. It provides a measure of for titrating therapy with intravenous DTIs.
the clotting of whole blood. Advantages of ACT Of note, children have developmental dif-
are that it can be done at the bedside, requires a ferences in coagulation, and aPTT does not
drop of blood, and results are available within a perform as reliably in neonatal and pediatrics
few minutes. ACT continues to be the most com- patients compared to adults.36,37 For neonatal
monly performed test of anticoagulation among and pediatric ECLS patients, aPTT values cor-
ECLS centers. In an international survey study relate poorly to anti-factor Xa levels and UNFH
of ELSO centers, 97% reported using ACT for levels.38-40 In a prospective observational cohort
patients supported with ECLS.31 of pediatric ECLS patients, anti-factor Xa lev-
Despite its ease, ACT has limitations. ACT els had a stronger correlation to UNFH dose
measures the time to clotting for a sample of than the ACT or aPTT.39 Another prospective
whole blood. A prolonged ACT could be due pediatric ECLS study found a positive correla-
to excessive anticoagulation, thrombocytope- tion between anti-factor Xa levels and heparin
nia, coagulopathy, or any combination of these dose but a poor correlation of anti-factor Xa
factors. In addition, variability in the ACT for levels to aPTT or ACT.39 Additionally, the aPTT
a single sample of blood occurs, even when often becomes unreliable in critical illness, be-
using the same measuring device.32 Finally, con- ing affected by acute phase reactants such as
siderable variability in results exists between C-reactive protein (CRP) and factor VIII. The
aPTT is falsely prolonged in patients with el-
95
Chapter 7
evated CRP but falsely decreased with elevated levels and hyperbilirubinemia can result in the
factor VIII levels.41 Inflammatory states occur underestimation of UNFH activity as measured
commonly among various patient populations by the anti-factor Xa assay.44 Table 7-1 provides
supported with ECLS. recommendations on the use of anti-factor Xa
assays to titrate UNFH infusions and to adjust
Anti-factor Xa Assay the goal ACT range.
The anti-factor Xa assay has become an Thromboelastography/Thromboelastometry

important means of titrating UNFH for ECLS.
In a survey study of ELSO centers, 65% of re- Thromboelastography measures the time
spondents reported using anti-factor Xa assays needed to form a fibrin clot, the strength of the
as part of monitoring ECLS anticoagulation.31 clot (determined by the cross linking of platelets
The anti-factor Xa assay can be measured with and fibrinogen), and the eventual breakdown of
or without the addition of AT to the specimen. the fibrin clot (fibrinolysis) in whole blood and
A sample with subtherapeutic anti-factor Xa has been used since the 1940s. With thrombo-
activity due to AT deficiency can have the elastography, disorders related to abnormalities
activity artificially increased with the addition in clotting factors, abnormal platelet function,
of AT. Typically therapeutic levels range from or excessive fibrinolysis can be detected. Some
0.3 – 0.7 IU/mL. ECLS centers use an alternative, but similar
The anti-factor Xa assay measures the an- method of testing whole blood, known as
ticoagulation activity of UNFH, and depends thromboelastometry. Thromboelastography
only on heparin and AT levels. Pediatric ECLS can be especially useful in ECLS patients with
patients with higher anti-factor Xa levels had excessive bleeding or clotting. When thrombo-
decreased circuit/oxygenator change.42 In a elastography is normal with refractory bleeding,
retrospective, single center study of ECLS pa- a surgical source should be considered. Throm-
tients, an anticoagulation laboratory protocol boelastography is typically performed with
that used anti-factor Xa assays to titrate UNFH heparinase to determine the underlying coagu-
led to significantly decreased blood product use, lation profile of the heparinized ECLS patient.
hemorrhagic complications, and increased cir- The effect of UNFH can be accounted for using
cuit life.43 However, elevated free hemoglobin anti-factor Xa assays, or some centers elect to
Table 7-1. UNFH Titration and ACT Goal Range Based on Anti-factor Xa Levels.
Anti-factor Xa Anti-factor Xa Level UNFH Rate ACT Goal

Goal Range (units/mL) Change Range
(units/mL) (seconds)
< 0.3 ↑10 – 20% ↑10 – 20 seconds
0.3 – 0.5 0.3 - 0 .5 No Change No Change
> 0.5 ↓10 – 20% ↓10 – 20 seconds
< 0.4 ↑10 – 20% ↑10 – 20 seconds
0.4 – 0.6 0.4 – 0.6 No Change No Change
> 0.6 ↓10 – 20% ↓10 – 20 seconds
< 0.5 ↑10 – 20% ↑10 – 20 seconds
0.5 – 0.7 0.5 – 0.7 No Change No Change
> 0.7 ↓10 – 20% ↓10 – 20 seconds
96
perform thromboelastography both with and for this use is mixed. A retrospective study of
without heparinase to determine the effect of neonatal and pediatric ECLS patients revealed
UNFH.45 Table 7-2 provides recommendations increased in AT levels with AT concentrate ad-
on approaches to abnormalities observed with ministration, but no other clinically significant
thromboelastography and thromboelastometry, changes, including UNFH infusion rate, ACTs,
performed with heparinase for those patients chest tube output, or packed red blood cell
anticoagulated with UNFH. (PRBC) transfusion volume.48 In another single
center pediatric ECLS study, supplementation
Antithrombin Level with AT concentrate for activity levels of <70%
resulted in higher anti-factor Xa levels without
AT is the most important inhibitor of co- differences in UNFH infusion rates, but greater
agulation in vivo. For ECLS patients, a primary circuit failures.49 Ryerson et al. conducted a
deficiency of AT may exist or can may occur retrospective study of pediatric ECLS patients
secondary to excessive peritoneal drain or chest that demonstrated supplementation with AT
tube losses. AT can be replaced in two ways: concentrate was associated with an increase in
giving fresh frozen plasma (FFP) or commer- anti-factor Xa levels, decreased UNFH dose
cially available AT concentrate. AT concentrate requirements, and no acute adverse events.50
is available as a product pooled from human FFP contains a relatively small amount of
plasma or as a recombinant AT formulation. AT, approximately 1 unit of AT per ml.51 Thus,
Healthy infants do not achieve normal adult a large volume of FFP is needed to change AT
levels of AT until approximately six months of levels, increasing blood product exposure and
life. Term neonates have an AT level of approxi- fluid overload. For patients with a low AT level
mately 60% of adult values.46 The “off label” for age, heparin resistance, and sub-therapeutic
use of AT concentrate for ECLS has increased anti-factor Xa level, supplementation with AT
greatly over the past decade,47 but the evidence may help. For patients with coagulopathy or
Table 7-2. Thromboelastography/thromboelastometry with Heparinase Guidelines.
Abnormality Approach
R >10 min (low clotting factors) or Administer FFP or prothrombin complex
CT (extem) >100 sec concentrate
MA <54 mm or Administer platelet concentrate

MCF<45 mm
and normal fibrinogen levels (decreased
platelet function/count)
Low fibrinogen at Administer cryoprecipitate/fibrinogen

Functional Fibrinogen (<150 mg/dL) test concentrate
or FIBTEM (<6 mm) test
*Usually associated with a prolonged R
time, so treat prolonged R time with FFP
first, and if the angle is still low, then
administer cryoprecipitate as above.
EPL >15% or LY30 >7.5% and CI ≤1 Consider treatment with antifibrinolytic for
CLI30 <85% primary fibrinolysis
97
Chapter 7
uncontrolled bleeding, FFP may be a preferable Loading dose of AT (units) =

means of replacing AT levels. The administra-
[100-baseline AT activity level]×wt(kg)
tion of AT concentrate should be avoided in
2.3
ECLS patients with uncontrolled bleeding.
Finally, AT concentrates carry a great financial
cost. Maintenance dose AT (units/hr) =
For patients requiring AT concentrate, the [100-baseline AT activity level]×wt(kg)
dose depends on the formulation. For the pooled 10.2
AT product Thrombate®, the following formula,
based on the manufacturer’s recommendation, Some centers use the loading dose for
is used: Atryn® and only start infusions if the AT level
does not respond to repeat loading doses. Other
AT dose in units (IU) = ECLS centers begin the infusion after initial
[desired AT – current AT] × weight (kg) loading dose. Consideration for adjusting the
1.4 weight used for the above calculation can be
done based on the volume of the ECLS circuit.
Some centers account for ECLS circuit vol- When using Atryn®, the first AT level should
ume in addition to this calculation, while others be obtained two hours after initiation of therapy,
do not. Those that account for the volume of with adjustments made as necessary. If a patient
the circuit equate every 75 ml of ECLS circuit requires a continuous AT infusion, consultation
as 1 additional kilogram of body weight. With with hematology should be considered.
Thrombate®, some centers bolus the product
over 30 minutes, and others run the dose over Anticoagulation Laboratory Schedule and
12 to 24 hours. After AT replacement with Blood Product Replacement
Thrombate®, AT levels can be rechecked 6 to
8 hours after the dose. If the level is still low, a Tables 7-3 and 7-4 list general guidelines
repeat dose may be administered. for a recommended schedule of anticoagulation
For centers using the recombinant AT prod- laboratories and goals for blood product replace-
uct Atryn®, the manufacturer recommends the ment for ECLS. The patient’s clinical condition
following formula for dosing:
Table 7-4. Blood Product and Factor Replace-
ment.
Anticoagulation Lab Guidelines
Platelets Platelet transfusion to maintain counts
Table 7-3. Laboratory Schedule. >80,000 μL to 100,000 μL
INR FFP transfusion to maintain INR <2.0
Fibrinogen Cryoprecipitate to maintain fibrinogen

Anticoagulation Lab Guideline >100 mg/dL OR
ACT Q1h – Q2h >150 mg/dL if bleeding or prior
aPTT Q6h – Q12 surgical intervention
Anti–factor Xa Assay Q6h Hematocrit PRBCs to maintain hematocrit >30%
Platelets Q6h - Q12h (consider higher goal for neonates and
children with cyanotic congenital
INR Q6h - Q12h
heart disease or lower goal for stable,
Fibrinogen Q12h - Q24h adult patients)
CBC Q6h - Q12h Antithrombin >50%-80% (>0.5-0.8 u/mL), consider
Antithrombin Level Daily - PRN AT replacement if on maximum dose
Thromboelastography Daily – PRN for bleeding of UNFH and unable to obtain
or clotting complications therapeutic anti-factor Xa assay
98
and underlying pathophysiology should dictate Conclusions

adjustments of laboratory determinations and
blood product administration. Laboratory test- The number and complexity of patients
ing can be decreased and blood product trans- supported with ECLS continues to increase.
fusion reduced in patients who have reached a With this growth comes an even greater need for
stable clinical status. Blood product transfusion improved surfaces for blood-circuit interaction,
carries with it infectious and non-infectious safer anticoagulation, and enhanced anticoagu-
risks and will be covered in Chapter 8 lation monitoring. Consultation with hematol-
ogy specialists and laboratory medicine should
Hemorrhagic and Thrombotic Complica- be considered for managing complex issues
tions regarding anticoagulation for ECLS or for any
ECLS patient with unexplained hemorrhagic or
Hemorrhagic complications produce sig- thrombotic complications.
nificant morbidity and mortality among ECLS
patients. Their prevention requires correcting
coagulopathy and thrombocytopenia, careful
titration of anticoagulation therapy, and repair
of surgical sources of bleeding.
The ELSO Registry defines a significant
clotting complication as requiring a change in
a portion of the circuit or entire circuit. In the
July 2015 ELSO International Registry Report
across all age groups and indications, circuit
clots have been reported in nearly 40% of all
ECLS runs, with the oxygenator being the site
with the greatest number of reported clots.52
Inadequate anticoagulation, low flow states, and
patient hypercoagulability lead to increased risk
of thrombosis. Areas of stasis or turbulence in
the ECLS circuit are prone to clot formation.
Even when thrombotic complications are not
evident during an ECLS run, thrombosis is
commonly observed during postmortem ex-
aminations of ECLS patients. A single center
report of postmortem examinations of pediatric
ECLS patients revealed significant thrombosis
in 69% of patients overall and 85% of patients
with a history of congenital heart disease.53 In
a report of autopsy findings of postcardiotomy
adult ECLS patients, over 70% had previously
unrecognized thromboembolic complications.54
99
Chapter 7
References thromboprophylaxis: a meta-analysis.

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P. Unfractionated heparin therapy in infants lence, thrombotic risk, and application of
and children. Pediatrics. 2009;123(3):e510- the 4Ts scoring system. The Journal of
518. pediatrics. 2015;166(1):144-150.
5. Pratt CW, Church FC. Antithrombin: 15. Warkentin TE. Heparin-induced throm-
structure and function. Semin Hematol. bocytopenia. Curr Opin Crit Care.
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6. Finley A, Greenberg C. Review article: 16. Hirsh J, O’Donnell M, Weitz JI. New anti-
heparin sensitivity and resistance: man- coagulants. Blood. 2005;105(2):453-463.
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ological function of tissue factor pathway A, Bhathiwal RS, Sharma D. Bivalirudin
inhibitor and interaction with heparins. in venovenous extracorporeal membrane
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induced thrombocytopenia: recognition, 19. Nagle EL, Dager WE, Duby JJ, et al. Bi-
treatment, and prevention: the Seventh valirudin in pediatric patients maintained on
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Thrombolytic Therapy. Chest. 2004;126(3 cal care medicine : a journal of the Society
Suppl):311S-337S. of Critical Care Medicine and the World
9. Warkentin TE. Heparin-induced thrombo- Federation of Pediatric Intensive and Criti-
cytopenia: pathogenesis and management. cal Care Societies. 2013;14(4):e182-188.
Br J Haematol. 2003;121(4):535-555. 20. Pieri M, Agracheva N, Bonaveglio E, et al.
10. Jang IK, Hursting MJ. When heparins Bivalirudin versus heparin as an antico-
promote thrombosis: review of heparin- agulant during extracorporeal membrane
induced thrombocytopenia. Circulation. oxygenation: a case-control study. J Car-
2005;111(20):2671-2683. diothorac Vasc Anesth. 2013;27(1):30-34.
11. Martel N, Lee J, Wells PS. Risk for heparin- 21. Ranucci M, Ballotta A, Kandil H, et al.
induced thrombocytopenia with unfraction- Bivalirudin-based versus conventional
ated and low-molecular-weight heparin heparin anticoagulation for postcardiotomy
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extracorporeal membrane oxygenation. 30. Johnston N, Wait M, Huber L. Argatro-

Critical care. 2011;15(6):R275. ban in adult extracorporeal membrane
22. Koster A, Weng Y, Bottcher W, Gromann oxygenation. J Extra Corpor Technol.
T, Kuppe H, Hetzer R. Successful use of 2002;34(4):281-284.
bivalirudin as anticoagulant for ECMO in 31. Bembea MM, Annich G, Rycus P, Olden-
a patient with acute HIT. The Annals of burg G, Berkowitz I, Pronovost P. Vari-
thoracic surgery. 2007;83(5):1865-1867. ability in anticoagulation management
23. Ranucci M. Bivalirudin and post-cardioto- of patients on extracorporeal membrane
my ECMO: a word of caution. Critical care. oxygenation: an international survey. Pedi-
2012;16(3):427. atric critical care medicine : a journal of the
24. Phillips MR, Khoury AI, Ashton RF, Cairns Society of Critical Care Medicine and the
BA, Charles AG. The dosing and moni- World Federation of Pediatric Intensive and
toring of argatroban for heparin-induced Critical Care Societies. 2013;14(2):e77-84.
thrombocytopenia during extracorporeal 32. Uden DL, Payne NR, Kriesmer P, Cipolle
membrane oxygenation: a word of cau- RJ. Procedural variables which affect acti-
tion. Anaesthesia and intensive care. vated clotting time test results during extra-
2014;42(1):97-98. corporeal membrane oxygenation therapy.
25. Dolch ME, Frey L, Hatz R, et al. Extracor- Critical care medicine. 1989;17(10):1048-
poreal membrane oxygenation bridging to 1051.
lung transplant complicated by heparin- 33. Seay RE, Uden DL, Kriesmer PJ, Payne NR.
induced thrombocytopenia. Exp Clin Trans- Predictive performance of three methods
plant. 2010;8(4):329-332. of activated clotting time measurement in
26. Beiderlinden M, Treschan T, Gorlinger neonatal ECMO patients. ASAIO journal.
K, Peters J. Argatroban in extracorporeal 1993;39(1):39-42.
membrane oxygenation. Artificial organs. 34. Bosch YP, Ganushchak YM, de Jong DS.
2007;31(6):461-465. Comparison of ACT point-of-care measure-
27. Scott LK, Grier LR, Conrad SA. Heparin- ments: repeatability and agreement. Perfu-
induced thrombocytopenia in a pediatric sion. 2006;21(1):27-31.
patient receiving extracorporeal membrane 35. Maul TM, Wolff EL, Kuch BA, Rosendorff
oxygenation managed with argatroban. Pe- A, Morell VO, Wearden PD. Activated par-
diatric critical care medicine : a journal of tial thromboplastin time is a better trending
the Society of Critical Care Medicine and tool in pediatric extracorporeal membrane
the World Federation of Pediatric Intensive oxygenation. Pediatric critical care medi-
and Critical Care Societies. 2006;7(5):473- cine : a journal of the Society of Critical
475. Care Medicine and the World Federation
28. Young G, Yonekawa KE, Nakagawa of Pediatric Intensive and Critical Care
P, Nugent DJ. Argatroban as an alterna- Societies. 2012;13(6):e363-371.
tive to heparin in extracorporeal mem- 36. Chan AK, Black L, Ing C, Brandao LR,
brane oxygenation circuits. Perfusion. Williams S. Utility of aPTT in monitoring
2004;19(5):283-288. unfractionated heparin in children. Throm-
29. Mejak B, Giacomuzzi C, Heller E, et bosis research. 2008;122(1):135-136.
al. Argatroban usage for anticoagulation 37. Ignjatovic V, Furmedge J, Newall F, et al.
for ECMO on a post-cardiac patient with Age-related differences in heparin response.
heparin-induced thrombocytopenia. J Extra Thrombosis research. 2006;118(6):741-745.
Corpor Technol. 2004;36(2):178-181.
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38. Khaja WA, Bilen O, Lukner RB, Edwards cine and the World Federation of Pediatric
R, Teruya J. Evaluation of heparin assay Intensive and Critical Care Societies. 2014.
for coagulation management in newborns 44. Kostousov V, Nguyen K, Hundalani SG,
undergoing ECMO. American journal of Teruya J. The influence of free hemoglobin
clinical pathology. 2010;134(6):950-954. and bilirubin on heparin monitoring by
39. Liveris A, Bello RA, Friedmann P, et al. activated partial thromboplastin time and
Anti-factor Xa assay is a superior corre- anti-Xa assay. Archives of pathology &
late of heparin dose than activated partial laboratory medicine. 2014;138(11):1503-
thromboplastin time or activated clotting 1506.
time in pediatric extracorporeal membrane 45. Alexander DC, Butt WW, Best JD, Do-
oxygenation*. Pediatric critical care medi- nath SM, Monagle PT, Shekerdemian
cine : a journal of the Society of Critical LS. Correlation of thromboelastography
Care Medicine and the World Federation with standard tests of anticoagulation in
of Pediatric Intensive and Critical Care paediatric patients receiving extracorpo-
Societies. 2014;15(2):e72-79. real life support. Thrombosis research.
40. Bembea MM, Schwartz JM, Shah N, et al. 2010;125(5):387-392.
Anticoagulation monitoring during pediat- 46. Andrew M, Paes B, Johnston M. Devel-
ric extracorporeal membrane oxygenation. opment of the hemostatic system in the
ASAIO journal. 2013;59(1):63-68. neonate and young infant. The American
41. Teruya J. Coagulation Tests Affected by journal of pediatric hematology/oncology.
Acute Phase Reactants Such as CRP and 1990;12(1):95-104.
Factor VIII. Paper presented at: Interna- 47. Wong TE, Huang YS, Weiser J, Brogan
tional Conference on Hematology and TV, Shah SS, Witmer CM. Antithrombin
Blood Disorders; September 23 - 25, 2013; concentrate use in children: a multicenter
Research Triangle Park, NC USA. cohort study. The Journal of pediatrics.
42. Irby K, Swearingen C, Byrnes J, Bryant J, 2013;163(5):1329-1334.e1321.
Prodhan P, Fiser R. Unfractionated heparin 48. Niebler RA, Christensen M, Berens R,
activity measured by anti-factor Xa levels is Wellner H, Mikhailov T, Tweddell JS.
associated with the need for extracorporeal Antithrombin replacement during extracor-
membrane oxygenation circuit/membrane poreal membrane oxygenation. Artificial
oxygenator change: a retrospective pediat- organs. 2011;35(11):1024-1028.
ric study. Pediatric critical care medicine 49. Byrnes JW, Swearingen CJ, Prodhan P, Fiser
: a journal of the Society of Critical Care R, Dyamenahalli U. Antithrombin III sup-
Medicine and the World Federation of Pe- plementation on extracorporeal membrane
diatric Intensive and Critical Care Societies. oxygenation: impact on heparin dose and
2014;15(4):e175-182. circuit life. ASAIO journal. 2014;60(1):57-
43. Northrop MS, Sidonio RF, Phillips SE, et 62.
al. The Use of an Extracorporeal Membrane 50. Ryerson LM, Bruce AK, Lequier L, Kuhle
Oxygenation Anticoagulation Laboratory S, Massicotte MP, Bauman ME. Admin-
Protocol Is Associated With Decreased istration of Antithrombin Concentrate in
Blood Product Use, Decreased Hemor- Infants and Children on ECLS Improves
rhagic Complications, and Increased Circuit Anticoagulation Efficacy. ASAIO journal.
Life. Pediatric critical care medicine : a 2014.
journal of the Society of Critical Care Medi- 51. Mintz PD, Blatt PM, Kuhns WJ, Roberts
HR. Antithrombin III in fresh frozen plasma,
102
cryoprecipitate, and cryoprecipitate-deplet-

ed plasma. Transfusion. 1979;19(5):597-
598.
52. Extracorporeal Life Support Organization.
Registry Report. Ann Arbor: University of
Michigan; July 2015.
53. Reed RC, Rutledge JC. Laboratory and
clinical predictors of thrombosis and
hemorrhage in 29 pediatric extracorporeal
membrane oxygenation nonsurvivors. Pe-
diatr Dev Pathol. 2010;13(5):385-392.
54. Rastan AJ, Lachmann N, Walther T, et
al. Autopsy findings in patients on post-
cardiotomy extracorporeal membrane
oxygenation (ECMO). Int J Artif Organs.
2006;29(12):1121-1131.
103
8
Transfusion Management during Extracorporeal Support
Anne Marie Winkler, MD
Blood Product Transfusion during in an otherwise uncomplicated ECMO run was

Extracorporeal Support 100,000/ml (range 50,000-200,000) for pediatric
only programs versus 100,000/ml (range 20,000-
Blood transfusion during extracorporeal 100,000) for adult only and mixed adult/pedi-
support typically occurs for several reasons, atric programs (p=0.034). Lastly, the median
including circuit priming, restoration of oxygen fibrinogen threshold for fresh frozen plasma
carrying capacity, maintenance of a hemostatic (FFP) or cryoprecipitate transfusion did not
balance, and treatment of hemorrhagic com- differ between pediatric only, and adult only
plications. The variability of blood products and mixed adult/pediatric centers, 150 mg/dL
included in the circuit prime was captured in a (range 60-200) vs. 145 mg/dL (range 50-200),
recent international cross-sectional survey with respectively (p=0.33). As a result, transfusion
119 of 121 ELSO-reporting centers responding.1 requirements during ECLS are high. A single
Of those centers, 92% of circuit primes included pediatric center, during an 8-year period in Latin
packed red blood cells (RBC), 50% fresh frozen America, reported the following mean transfu-
plasma (FFP), one center whole blood, and an- sion volumes in 98 patients of whom 87 were
other center including platelets, in addition to neonates: RBC 34.9 ml/kg/day, FFP 12.9 ml/kg/
other solutions. As a result, the majority of pa- day, platelets 34.3 ml/kg/day, and cryoprecipi-
tients are exposed to at least one blood product tate 1.2 ml/kg/day.2 Blood utilization during
during extracorporeal support. Additionally, 91 ECLS has also been reported in adults. A U.S.
of 117 (78%) respondents from the same survey center reported a median number of 19 RBC, 3
had an institutional protocol for blood product FFP, and 2 apheresis platelet units transfused to
management with transfusion thresholds differ- a cohort of 132 adults with increased require-
ing for pediatric only programs as compared to ments in those patients who underwent VA-
adult only or mixed adult/pediatric programs. ECMO and those with bleeding events.3 Similar
Of the 81 pediatric only program respondents, utilization has been published from a single
the median hematocrit threshold reported for adult center in Singapore who reported median
RBC transfusion for a typical ECMO patient of 11 RBC, 4 FFP, 15 platelet concentrate, and
was 35% (range 25-40%) compared to 30% 15 units of cryoprecipitate transfused to a cohort
(range 20-40%) for adult and mixed adult/ of 42 adults in a 15 month time period.4 This
pediatric programs (p<0.001). The median section will discuss the currently published
platelet count threshold for platelet transfusion data to support RBC, FFP, cryoprecipitate, and
105
Chapter 8
platelet transfusion in critically ill patients of a RBC transfusion. As a result, hospitals

including a discussion of the effect of red cell typically transfuse the “oldest” inventory units
storage on patient outcomes, and association of first in order to not outdate an expensive, often
RBC transfusion with patient outcomes during limited resource. Nevertheless, exceptions
extracorporeal support. to this practice exist, such as in intrauterine
and neonatal transfusion, but each hospital
Red Cell Transfusion may have individualized policies and practice.
Throughout storage, RBCs acquire deleterious
The majority of RBC products are manu- metabolic and structural changes which include
factured from whole blood donations, while the increased levels of lactate, pH less than 6.5,
minority are collected by RBC apheresis. The reduced adenosine triphosphate and nicotin-
initial step of component manufacturing from amide adenine dinucleotide levels, depletion of
whole blood donation includes centrifugation, 2,3-diphosphoglycerate, impairment of sodium
which leads to packing of the RBCs. Subse- and potassium exchange, increased oxidative
quently, the supernatant composed mostly of stress by oxidation of hemoglobin to methe-
platelet rich plasma is expressed leaving the moglobin, disruption of the RBC cytoskeletal
packed RBC component, which can be used for membrane, and microvesicle formation.5 How-
transfusion. A RBC unit contains approximately ever, the association of this RBC storage lesion
130-240 mL RBCs, 50-80 grams of hemoglobin, with clinical outcomes remains controversial.
and 150-250 mg of iron; however, the total Initial observational studies demonstrated as-
volume and hematocrit depend on the antico- sociations of RBC age with risk for increases in
agulant preservative solution used. Currently, infection, thromboembolic events, multiorgan
additive solution (AS) containing products have failure, ventilator time, ICU and hospital length
the longest shelf-life and can be stored up to of stay (LOS), and mortality.6 Unfortunately,
42 days, representing the largest inventory of most of these studies were fraught with bias
RBC products in a hospital transfusion service and confounding. As a result, several large,
inventory. AS products have a higher volume randomized, controlled clinical trials have been
and lower hematocrit compared to citrate- completed and two others are ongoing.7-11 The
phosphate-dextrose-adenine solution (CPDA-1) results of the completed studies are summarized
RBCs, which can be stored up to 35 days. His- in Table 8-1, but none have found a difference in
torically, RBC products used for transfusion to clinical outcomes following transfusion of fresh
pediatric patients contained CPDA-1 because or old RBCs across a variety of clinical settings.
of the concern of large amounts of adenine and In addition, any potential effect of RBC storage
mannitol in AS containing units (AS-3 units may not be applicable in ECMO centers that
are the exception), and the potential for renal limit storage age for their patients to avoid the
toxicity; however, most evidence suggests that potential adverse effects of hyperkalemia.
transfusion volumes of 5-15 mL/kg of AS RBCs RBC products can also undergo modifi-
are safe for this population. cations including leukoreduction, irradiation,
RBC anticoagulant preservative solutions washing, and/or volume reduction. Leukore-
are approved for use by the Food and Drug duction lowers the residual leukocytes to less
Administration (FDA) based upon testing to than 5x106 per product and appears to be associ-
demonstrate a minimum recovery of 75% of ated with decreased incidence of febrile nonhe-
RBCs 24 hours after transfusion and less than molytic transfusion reactions, human leukocyte
1% hemolysis in the RBC unit. However, there antigen alloimmunization, and cytomegalovirus
is no requirement to assess the clinical efficacy transmission, although there may be other ben-
106
efits of leukoreduction. The majority of RBC etic progenitor cell transplantation, Hodgkin’s
products in the U.S., Canada, and Europe are lymphoma, transfusion from blood relatives, or
universally leuko-reduced, but this depends transfusion of HLA matched platelets. However,
upon a center’s blood supplier and should be indications for which irradiation is deemed ap-
confirmed. Irradiation of cellular blood prod- propriate by most authorities include preterm/
ucts obviates the risk of transfusion associated low birth weight infants, infants/children with
graft vs. host disease, which is a rare but almost congenital heart disease, patients with acute
universally fatal complication of transfusion. leukemia, non-Hodgkin’s lymphoma or other
Irradiation either by gamma rays or x-rays hematologic malignancy, aplastic anemia, or
damages the lymphocytes thereby prohibiting patients with solid tumors receiving intensive
them from proliferating. While some centers chemotherapy and/or radiation.
universally irradiate blood products, it typically Red cell transfusions are indicated for de-
depends upon the clinical indication, which is creased oxygen carrying capacity and/or tissue
typically defined by the hospital transfusion hypoxia as a result of inadequate circulating red
service. Indications for which irradiation is cell mass. Unfortunately, hemoglobin concen-
considered required include suspected or known tration alone is a poor measure of circulating
immunodeficiency syndromes, hematopoi- RBC mass because of the physiologic com-
Table 8-1. Key randomized, controlled clinical trials investigating clinical outcomes with red cell
storage.
Number of Mean Age of Blood Percent

RBC
Study Subjects Study Population (Fresh vs. Nonconformance Primary Outcome
Randomization
Randomized Standard) to RBC Group
Fergusson et al7 377 Premature infants 7 days or less vs 5.1 days 15.2% in fresh •52.7% of infants in
with a birth weight standard practice vs. group, 0% in the fresh RBC
less than 1250 gram (dedicated donor 14.6 days standard group compared to
sand required 1 or unit per patient 52.9% in the
more RBC up to the standard RBC
transfusions expiration of the group experienced
unit) composite primary
outcome (mortality
and major neonatal
morbidities
associated with
acute organ
dysfunction or
failure)
Steiner et al8 1481 Individuals 12 years 10 days or less 7.8 days 11% in the fresh •No difference in
of age or older, vs 21 days or vs. group and 13% MODS or mortality
weight40 kg or more more 28.3 days in the standard
undergoing complex group
cardiac surgery with
median sternotomy;
patients 18 and older
were required to have
a likelihood of
receiving a RBC
transfusion of 60% or
more during or within
24 hours of surgery
Lacroix et al9 2510 Critically ill adults 8 days vs 6.1 days 16% in fresh •No difference in 90
who had a RBC standard issue vs. group, 0% in day mortality
transfusion ordered 22 days standard between fresh
within 7 days of ICU (p<0.001) (37%) and standard
admission and were (35.3%) RBC
expected to require transfusion
mechanical
ventilation for at least
48 hours
RBC=red blood cell; MODS=multiple organ dysfunction syndrome
107
Chapter 8
pensatory mechanisms that preserve oxygen been published in pediatric patients, the Trans-
transport such as reduced blood viscosity to fusion Requirements in the Pediatric Intensive
increase blood flow to tissues, redistribution of Care Unit (TRIPICU) study, which enrolled
blood flow, increased unloading of oxygen to hemodynamically stable, critically ill children
tissues, and maintenance of blood volume due 3 days, 14 years of age who had at least one
to expansion of plasma volume. Because of hemoglobin concentration of 9.5 g/dL within the
this and observations made in Jehovah’s Wit- first 7 days after admission to the PICU; patients
ness patients who declined transfusion based on who received ECMO were excluded.24 Using
religious beliefs and in underdeveloped coun- a hemoglobin threshold of 7 g/dL and a target
tries where RBCs were unavailable or limited, range of 8.5-9.5 g/dL in the restrictive group as
readjustment of transfusion practice to a lower compared to a threshold of 9.5 g/dL and a range
hemoglobin threshold has been investigated.12-17 of 11-12 g/dL in the liberal group, there was a
In 2012, a Cochrane systematic review of pro- 44% reduction in the number of RBC transfu-
spective randomized trials compared restrictive sion administered without an increase in the rate
vs. liberal transfusion strategies in 19 trials in- of new progressive multiple organ dysfunction
cluding 6264 patients.18 The authors found that syndrome including death. Subgroup analyses
a restrictive transfusion strategy reduced the risk of the TRIPICU study have been performed in
of receiving a RBC transfusion by 39% without postsurgical and cardiac surgery patients and
an increase in adverse events, ICU or hospital have demonstrated similar conclusions.25,26
LOS, and 30-day mortality. The authors con- To date, no prospective studies investigat-
cluded that the existing evidence supported the ing hemoglobin threshold in patients receiving
use of restrictive transfusion triggers in most extracorporeal support have been performed.
patients. For RBC transfusion, five prospec- Current ELSO guidelines recommend mainte-
tive randomized trials have been conducted to nance of the hematocrit over 40% to optimize
investigate restrictive vs. liberal transfusion oxygen delivery while allowing the lowest
thresholds in adult patients in critical care, car- reasonable blood flow. However, a single
diothoracic surgery, hip fracture repair, acute center retrospective study investigated RBC
upper gastrointestinal bleeding, and septic transfusion practice and the relationship with
shock, and the results have been summarized changes in mixed venous saturation (SVO2) and
in Table 8-2.19-23 The seminal Transfusion cerebral regional tissue oxygenation measured
Requirements in Critical Care or TRICC trial by near infrared spectroscopy (NIRS) while
was the first study to demonstrate that in criti- maintaining a hematocrit threshold of 36%.27 Of
cally ill, euvolemic patients a restrictive RBC the 617 individual transfusions to 45 pediatric
transfusion approach (hemoglobin threshold patients, most RBC transfusions did not result
of 7 g/dL and maintenance between 7-9 g/dL) in a statistically or clinically significant change
was at least as effective and possibly superior in either SVO2 (95%) or NIRS (91%) suggesting
to a liberal strategy (maintenance hemoglobin that most transfusions were administered when
concentration of 10-12 g/dL). In addition, the the patient was not oxygen delivery dependent.
restrictive strategy (threshold 7 g/dL), resulted Three studies also investigated the association
in a decrease of 54% in RBC transfusions and between RBC transfusion and mortality in this
a decline of 33% in RBC exposure. As a result population. A single U.S. center reported fac-
of these findings, clinical practice guidelines tors influencing outcomes following ECMO
have adopted recommendation of a restric- support in 58 patients requiring ECMO after
tive transfusion strategy using a hemoglobin repair of a congenital heart defect.28 From the
threshold of 7-8 g/dL. A similar study has also subgroup of decannulated patients, total RBC
108
volumes of greater than 1000 mL/kg were as- efficacy of transfusion in this population. In
sociated with increased mortality (p=0.02) and addition, the association of RBC transfusion
the probability of death was augmented with and mortality needs to be further investigated in
increasing RBC transfusion volumes. Simi- well-designed studies before definitive conclu-
larly, Smith et al. reported a 24% increase in sions can be made.
the odds of in-hospital mortality for each RBC
transfusion volume of 10 ml/kg/day of ECMO Plasma, Cryoprecipitate, and Platelet
support (p=0.018) in a cohort of 484 pediatric Transfusion
patients.29 An association of RBC transfusion
and mortality has also been reported in adult Similar to RBC products, plasma can be
ECLS patients.3,30 While many centers target manufactured from either whole blood or au-
the transfusion thresholds described above, a tomated apheresis. Plasma products FFP, F24
lack of evidence to guide transfusion thresholds (plasma frozen within 24 hours of phlebotomy),
exists in the setting of ECLS and additional and thawed plasma (plasma that originates from
studies are needed to establish evidence based either FFP or F24 that has been thawed and
thresholds for transfusion support and diag- refrigerated for more than 24 hours) are typi-
nostics to guide transfusion therapy to assess cally considered clinically equivalent products
Table 8-2. Key randomized, controlled clinical trials investigating restrictive vs. liberal transfusion
strategies.
Hb Average Hb Number of
Number of Concentration Concentration Patients
Study Subjects Study Setting Threshold at Transfusion Transfused Primary Outcome
Randomized (Restrictive vs. (Restrictive vs. (Restrictive vs.
Liberal) Liberal) Liberal)
Adult Patients
Hébert et al 838 Intensive care 7.0 g/dL 8.5 g/dL vs. 67% •30 day mortality was 18.7% in the
unit vs. 10.7 g/dL vs. restrictive group compared to 23.3%
10.0 g/dL 100% in the liberal group (p=0.11) while in-
hospital mortality was lower in the
restrictive group (22.2% vs. 28.1%,
p=0.05)
Hajjar et al 512 Elective 8.0 g/dL 9.1 g/dL 47% •Restrictive strategy was noninferior to
cardiopulmona vs. vs. vs. liberal in the primary composite
ry bypass 10.0 g/dL 10.5 g/dL 78% endpoint (30 day mortality,
(p<0.001) (p<0.001) cardiogenic shock, ARDS, or acute
renal injury require dialysis or
hemofiltration) occurring in 11%
versus 10%, respectively (p=0.85)
Carson et al 2016 Primary 8.0 g/dL 7.9 g/dL 41% •Rates of death or inability to walk
surgical repair vs. vs. vs. without human assistance at 60 days
of a hip 10.0 g/dL 9.2 g/dL 97% were similar in the restrictive versus
fracture with (p<0.001) (p<0.001) liberal group, 34.7% versus 35.2%
cardiovascular (p=0.90)
risk factors
Villaneuva et al 921 Acute upper 7.0 g/dL 7.3 g/dL 49% •45 day mortality was reduced in the
gastrointestina vs. vs. vs. restrictive group (5%) compared to the
l bleeding 9.0 g/dL 8.0 g/dL 86% liberal group (9%, p=0.02)
(p<0.001) (p<0.001)
Holst et al 1005 Intensive care 7.0 g/dL Daily lowest Hb 64% •43% of the restrictive group and 45%
patients who vs. differed between vs. of the liberal group died at 90 days
fulfilled 9.0 g/dL groups* 99% after randomization (p=0.44)
criteria for (p<0.001) (p<0.001)
septic shock
Pediatric Patients
Lacroix et al 648 Intensive care 7.0 g/dL 6.7 g/dL 46% •No difference in the risk of new or
unit vs. vs. vs. progressive MODS in both the liberal
9.5 g/dL 8.1 g/dL 98% and restrictive groups (12% in each
(p<0.001) (p<0.001) group, p=0,84)
*Numerical means/medians not reported
Hb=hemoglobin; MODS=multiple organ dysfunction syndrome
109
Chapter 8
although subtle differences exist. Outside of the a therapeutic dose. The therapeutic dose of
U.S., both FFP and F24 may be termed FFP. FFP platelets varies by clinical indication, but the
contains approximately 70-100% of each clot- optimal dose of platelets for prophylactic trans-
ting factor per mL of plasma and 1-2 grams of fusion is unknown. In adults, transfusion of an
fibrinogen. At a dose of 10-15 mL/kg, clotting apheresis platelet should increase the platelet
factor activity should increase by approximately count by 30,000-60,000/ml. In neonates and
30% in the absence of activation. Compared to pediatric patients, a 10 ml/kg dose should in-
FFP, F24 has lower levels of coagulation factors crease the platelet count by 50,000-100,000/ml.
V and VIII; however, neither is considered clini- Exposure of blood to the artificial surface of
cally significant. Similarly, thawed plasma has an extracorporeal circuit results in initiation of
decreased coagulation factor activity of factors coagulation, cellular activation, and increased
V, VII, and VIII compared to FFP and F24 and inflammation, which disrupts normal homeo-
likewise is not considered to be clinically dif- stasis in an already acutely ill patient.31-37 In
ferent since mean factor activities remain above addition, sheer stresses and turbulence gener-
the necessary amount for surgical hemostasis. ated during ECLS further contribute to this
Cryoprecipitate is manufactured by slowly activation, and to platelet or fibrin deposition
thawing FFP, which forms a precipitate that is during high or low sheer force, respectively.
collected and refrozen; the remaining superna- Moreover, fibrinogen and other coagulation
tant becomes cryo-poor or cryo-reduced plasma factors are absorbed onto the artificial surface
that has limited clinical use. Per AABB Stan- over the first 24 hours of ECLS.38 Platelets ac-
dards, each unit of cryoprecipitate must contain quire both quantitative and qualitative defects
at least 150 mg of fibrinogen and a minimum during ECLS. Specifically, sheer stress results
of 80 IU factor VIII although units typically in exposed collagen and release of vWF, which
contain more and additional components in- results in subsequent platelet adhesion via GPIb
cluding von Willebrand factor (vWF), factor and expression of GPIIb/IIIa receptors, and may
XIII, and fibronectin. Transfusion of one unit be exacerbated by release of free hemoglobin.39
of cryoprecipitate will typically increase the As a result, platelets further bind to the absorbed
fibrinogen concentration by 50 mg/dL per 10 fibrinogen and platelet counts fall to less than
kg of body weight. While commonly used for 40% of normal within the first few hours of
transfusion for fibrinogen replacement, cryopre- ECLS.40 Impaired platelet aggregation has also
cipitate can also be incorporated to make fibrin been reported during ECLS.41-44 Lastly, high
glue; however, FDA approved fibrin sealants are sheer rates result in uncoiling of vWF making
commercially available. it susceptible to cleavage by ADAMTS-13
Platelet products include those manufac- (a disintegrin and metalloproteinase with a
tured from whole blood (whole blood derived thrombospondin motif) thereby resulting in
platelets, random donor platelets, platelet con- loss of high molecular weight multimers and
centrates) and apheresis (apheresis platelets, decreased binding of vWF, which character-
single donor platelets, plateletpheresis) dona- izes the acquired von Willebrand syndrome
tions. In the U.S., apheresis platelets represent (AVWS).45,46 As a result, transfusion of FFP,
91.1% of total platelet products produced. Per cryoprecipitate, and platelets is needed during
AABB Standards, 90% of whole blood derived ECLS to maintain hemostasis; however, there
platelets must contain >5.5 x 1010 platelets while have been no prospective studies investigating
90% of apheresis platelets must contain >3.0 x their use in critically ill patients including those
1011 platelets. As a result, 4-6 units of whole receiving ECLS.
blood derived platelets must be pooled to make
110
The most common indications for plasma tions have local guidelines based upon expert
transfusion include reversal of coagulopathy opinion and a systematic review found insuf-
in bleeding patients or for prophylactic use in ficient evidence to make recommendations for
patients undergoing procedures; however, a or against platelet transfusion in critically ill
paucity of well-designed studies define plasma preterm infants, children, and adults.54
transfusion practice.47 Despite the lack of data, While many centers target the transfusion
plasma transfusion is a common procedure oc- thresholds described above, there is a lack of
curring in approximately 10% of critically ill evidence to guide transfusion thresholds in the
patients. A recent multicenter study identified setting of extracorporeal support and additional
that the majority of adult plasma transfusions studies are needed to establish evidence based
occur in patients who have a mildly elevated thresholds for transfusion support and diag-
international normalized ratio (INR) with 22.5% nostics to guide transfusion therapy to assess
given for an INR of less than 1.6 and 33% for efficacy of transfusion in this population.
an INR of 1.6-2.0.48 In addition, patients who
received plasma transfusion received low doses Use of Coagulation Factor Replacement,
with 58% not reaching a posttransfusion INR Blood Derivatives, and Antifibrinolytic
of less than 1.6, which has been confirmed in Therapy during Extracorporeal Support
other adult and pediatric studies.49-51 In a similar
study performed in pediatric patients across 101 Recombinant Factor VIIa
pediatric ICUs in 21 countries, 34% of patients
who received plasma were neither bleeding nor Recombinant factor VIIa (NovoSeven®RT,
scheduled for a procedure; only 22% received Novo Nordisk, Bagsværd, Denmark) is a lyophi-
plasma for critical bleeding.52 Moreover, de- lized powder of recombinant human coagulation
creases in INR or activated partial thromboplas- factor VIIa (rFVIIa) which, when complexed
tin time (APTT) were seen for values greater with tissue factor, can activate factor X to factor
than 2.0 or 60 seconds, respectively. As a result, Xa, as well as factor IX to factor IXa. The tenase
plasma transfusions do not correct a laboratory complex then converts prothrombin to thrombin,
coagulopathy in critically ill adults and children. which leads to the formation of a hemostatic
However, it should be mentioned that coagula- plug by conversion of fibrinogen to fibrin and
tion tests may not be the best surrogate as they subsequent cross linking by factor XIII. Throm-
fail to predict bleeding, but alternative tests bin generation may also occur on the surface of
with correlations with clinical outcomes remain activated platelets enhancing platelet adhesion
unavailable. A single study demonstrated that and aggregation. Initially approved in the U.S.
a fixed dose of FFP decreased syndecan-1 and by the FDA, rFVIIa is currently indicated for
factor VIII suggesting that plasma may have an the treatment of bleeding episodes and periop-
endothelial stabilizing effect in 33 critically ill erative management in adults and children with
adult patients.53 While promising, it is unknown hemophilia A or B with inhibitors, congenital
what other biologic effects plasma transfusion factor VII deficiency, and for patients refractory
may have especially in the setting of ECLS. to platelet transfusion with Glanzmann’s throm-
Thrombocytopenia occurs commonly in basthenia with or without antiplatelet antibodies,
critically ill patients and is present in 8.3-67.6% in addition to treatment of bleeding episodes
of adult ICU patients, and 20-50% of neonates.54 and perioperative management in adults with
As a result, patients commonly receive platelet acquired hemophilia. However, a retrospec-
transfusions, which remain the primary treat- tive audit of the Premier Perspectives database
ment despite a lack of evidence. Most institu- from 615 nonfederal U.S. hospitals from 2000
111
Chapter 8
through 2008 demonstrated a 143-fold increase volumes for a defined period of time postad-
in use over the study period.55 Specifically, off- ministration. Table 8-3 presents a summary of
label use of rFVIIa represented 96% of cases published case series.58-66
with adult cardiac surgery (12,086 cases) and In clinical trials, thrombotic adverse events
trauma (11,689 cases) representing the most occurred in 0.2% of patients treated with rFVIIa
rapidly emerging indications despite the limited with hemophilia A or B and 4% of patients
data to support its use. Pediatric cardiac surgery with acquired hemophilia; the risk of throm-
accounted for an estimated 1684 cases of the boembolic complications in patients receiving
73,737 total number of cases from 2004-2008. rFVIIa for off-label uses remains unknown.
Off-label use of rFVIIa in pediatric patients Currently, NovoSeven®RT carries a warning
has also been examined. A single center in the of possible increased risk of development of
U.S. reported decreased blood product admin- thromboembolic events due to circulating tissue
istration 24 hours after rFVIIa administration factor or predisposing coagulopathy in patients
in 135 patients who received 997 doses of with disseminated intravascular coagulation,
rFVIIa for a variety of indications, of which 3 advanced atherosclerotic disease, crush injury,
patients also received ECMO.56 In the second septicemia, or concomitant treatment with ac-
study from a 75 hospital registry in Australia, tivated or nonactivated prothrombin complex
388 patients less than 16 years of age received concentrates, and in uncontrolled postpartum
rFVIIa mostly for active bleeding (97%); the hemorrhage. In a review of the FDA’s Ad-
remaining 11 patients received rFVIIa for sur- verse Event Reporting System, there were
gical prophylaxis.57 Of note, 26 patients were 168 reports of 185 thromboembolic events, of
receiving ECMO at the time of rFVIIa admin- which 151 occurred in patients who received
istration. From this cohort, it was reported that rFVIIa for unlabeled indications.67 Moreover,
there was a statistically significant reduction in thromboembolic complication was the probable
the volume of RBC, FFP, platelets, and cryopre- cause of death in 72% of cases. In addition, a
cipitate transfused 24 hours after administration metaanalysis of 35 randomized controlled trials
of rFVIIa, consistent with previous reports from including 2815 subjects who received rFVIIa
observational studies. However, 21 patients for off-label indications demonstrated a 10.2%
(5.4%) experienced a thromboembolic adverse thromboembolic event rate, compared to 8.7%
event with a higher rate reported in those who of subjects who received placebo (p=0.16);
were receiving ECMO support (19% vs. 4%, however, the rate of arterial thromboembolic
p=0.009). events was higher (5.5%) when compared to the
While use of rFVIIa during ECLS was placebo group (3.2%, p=0.003) and this effect
described in case reports and case series, no was more pronounced in subjects 65 years of
randomized controlled trial has yet been re- age and older.68 The thromboembolic risk of
ported in this population. Despite the limited rFVIIa administration has not been established
data, 63/94 (67%) ELSO centers reported use in the setting of ECLS and case reports of fa-
of rFVIIa when asked if e-aminocaproic acid, tal thrombosis after administration of rFVIIa
rFVIIa, tranexamic acid, aprotinin, or other have been published.69-72 As a result, careful
products where used to manage anticoagulation, consideration must be given to administration
hemorrhage, or thrombosis in ECMO patients.1 of rFVIIa in ECLS patients as they have mul-
Similar to previous studies, case series of off- tiple risk factors for thrombosis. In addition, it
label use of rFVIIa during ECLS demonstrated is unknown whether the disturbed hemostatic
reduced blood loss, most commonly measured balance during ECLS may enhance thrombo-
by chest tube output, and reduced transfusion
112
Table 8-3. Case series reporting pediatric and adult patients who received rFVIIa for refractory bleed-
ing while receiving ECLS.
Median Median
Median Adverse Survived
rFVIIa Number Effect on Blood Product Adverse Patient
Study #s age Circuit to
Dose of Doses Requirements or Bleeding Events
(years) Events Discharge
(µg/kg) Received
Pediatric Patients
Wittenstein et al 4 0.625 2 • Blood loss was reduced by 83% None None 4
(p=0.025) 6 hours after 1st rFVIIa
infusion
• Transfusion requirements
decreased by 81.9% for RBC
(p=0.045), 90% for FFP
(p=0.062), 92% cryoprecipitate
(p=0.005), and 79.7% platelets
(p=0.024) 6 hours after 1st
rFVIIa infusion
Agarwal et al 12 9.5 36.5 1.6 • Significant reduction (59.4%) in 1 thromboembolic 2 circuit 9
(1-4) chest tube bleeding (P=0.0017) 6 event thromboses
hours after rFVIIa infusion
• Significant reduction in RBC
(42%), FFP (59.3%), platelet
(55.2%), and cryoprecipitate
(11.5%) transfusion 6 hours after
rFVIIa infusion*
• One patient was nonresponsive to
rFVIIa therapy
Veldman et al 7 4 83 (61- 3 • Chest tube output decreased by None 2 oxygenator 4
106) (2-3.5) 63.7% (p=0.097) 2 hour after one failures, 2
dose of rFVIIa circuit
• Reduction in transfusion thromboses
volumes for RBC (23%) and FFP
(35%) but not platelets after 2
hours after 1st dose of rFVIIa
Niebler et al 17 0.1 45-90 1.5 • Decreased chest tube output and 4 thromboembolic 2 oxygenator 5†
(1-3) transfusion support (p<0.05) up events* failures,
to 12 hours after rFVIIa 2 circuit
administration obstructions
• 50% reduction in total blood
product transfusion (p<0.05) for
up to 12 hours after rFVIIa
administration
Walker et al 6 NR 94 2.7 • Significant reduction in blood None None NR
(55-107) loss as measured by chest tube
output (p=0.04) 6 hours post
rFVIIa infusion
• Nonsignficant reductions in
RBC, FFP, platelet, and
cryoprecipitate transfusion
Long et al 7 1.75 98.2 2 • Reduction of blood loss 6 hours 1 thromboembolic 1 oxygenator 3
(67-171) (1-4) after the final dose of rFVIIa by event (intra-gastric failure
35.6% (p=0.13) clot)
• No reduction in the RBC or other
blood product transfusions
• When patients who underwent
successful surgical management
hemorrhage were excluded, RBC
transfusions increased
Adult Patients
Schneider et al‡ 5 48 90 2 • Reduction in the transfusion None None 2
(54-105) (1-2) volume of RBC (61%) and FFP
(22%) 12 hours after rFVIIa
administration
Repessé et al 15 47 77 1.4 • Chest tube output decreased by None 2 circuits 6
(55-144) (1-4) 58.7% (p=0.008) 24 hours after changes
rFVIIa administration within 48
• Transfusion requirements hours for
decreased by 75% for RBC and fibrin
84% for FFP (p=0.008) 24 hours deposits and
after rFVIIa administration related
hemolysis
Anselmi et al 30 57.5 NR NR • Final efficacy rate of rFVIIa in 1 5 circuit 12
stopping bleeding as 93.3% changes due
• Requirements for transfusion or to hemolysis
blood products decreased and fibrin
markedly for up to 12 hours post deposits
rFVIIa infusion
*Statistically significant compared to historical controls
†Not statistically different from historical controls
‡A total of 12 patients were published; however, only 5 were adult patients receiving ECMO
RBC=red blood cell; FFP=fresh frozen plasma; NR=not reported
113
Chapter 8
genicity with administration of rFVIIa or other either FFP or rFVIIa and their use has mostly
procoagulant coagulation factor products. been replaced by 4F-PCC. Currently, there are
two 4F-PCCs, Kcentra® or Beriplex®P/N (CSL
Prothrombin Complex Concentrates Behring GmbH, Marburg, Germany) and Octa-
plex® (Octapharma, Lachen , Switzerland), only
Two types of prothrombin complex concen- one of which, Kcentra®, is available in the U.S.
trates are currently available for use, activated Both 4F-PCCs are human plasma derived con-
(aPCC) and nonactivated (PCC). Activated centrates of vitamin K dependent coagulation
PCC, licensed in the U.S. as antiinhibitor coagu- factors, II, VII, IX, X and proteins C and S, and
lant complex or FEIBA (Baxalta, Westlake Vil- as such are indicated for the urgent reversal of
lage, California) is currently FDA approved for acquired coagulation factor deficiency induced
control or prevention of bleeding, perioperative by VKA therapy in adult patients with acute
management, or routine prophylaxis to prevent major bleeding or need for an urgent surgery
or reduce the frequency of bleeding in patients or invasive procedure.75 Outside of the U.S.,
with hemophilia A or B. The aPCC is a human 4F-PCC may also be used for the treatment
plasma derived concentrate with FVIII inhibitor of bleeding and perioperative prophylaxis of
bypassing activity that contains nonactivated bleeding in congenital deficiency of any of the
factors II, IX, and X, and activated factor VII. vitamin K dependent coagulation factors only
Similar to rFVIIa, thromboembolic adverse if a purified specific coagulation factor product
events have been reported especially at high is unavailable, in addition to, in cardiac surgery,
doses or in patients with thrombotic risk fac- trauma, and liver disease. However, the efficacy
tors.73 To date, the efficacy of aPCC in patients and safety of PCC in the setting of ECLS has
receiving ECLS remains unestablished and a not been established.
single report describes massive intracardiac and A metaanalysis of 27 studies including
circuit thromboses in a 56 year old man placed use of PCC in patients treated with VKAs
on ECMO following lung retransplantation who demonstrated a low but quantifiable risk of a
received two doses of rFVIIa followed by aPCC thromboembolic event with either 3F-PCC or
for refractory bleeding.72 4-PCC.76 The incidence of thromboembolic
Nonactivated PCCs are classified as either 3 events reached 1.4%, with a thromboembolic
factor PCC (3F-PCC) or 4 factor PCC (4-PCC) event rate of 1.8% with 4F-PCC and 0.7%
based on the concentration of FVII. Currently, with 3F-PCC administration. Beriplex®P/N
there are two available 3F-PCCs in the U.S., has been licensed in Europe since 1996, and
Bebulin® (Baxalta, Westlake Village, Califor- pharmacovigilance data have been reported for
nia) and Profilnine® (Grifols Biologicals Inc., 1,294,500,970 IU of Beriplex®P/N.77 From ap-
Los Angeles, California) both of which derive proximately 647,250 applications, 21 suspected
from human plasma concentrates containing thromboembolic events occurred with no cases
nonactivated factors II, IX, X, and low levels of of viral transmission; however, these data may
FVII (typically not in excess of 35 IU/mL) and be biased by underreporting of events. In ad-
are FDA indicated for prevention and control of dition, data from the phase IIIb clinical trials
bleeding episodes in patients with hemophilia B. comparing the safety and efficacy of Kcentra®
Other 3F-PCCs are available for use outside of for VKA reversal demonstrated less fluid
the U.S. and have been reviewed elsewhere.74 overload with 4F-PCC compared to FFP trans-
While 3F-PCC has been used off-label mainly fusion.78-80 As a result, careful consideration
for vitamin K antagonist (VKA) reversal, FVII must be given to administration of either aPCC
concentrations had to be supplemented with or PCC in patients requiring ECLS as these
114
patients have multiple thrombosis risk factors this, in ECLS, albumin may be used for other
until the efficacy and safety can be established indications including in the circuit prime.
in this population. Plasma proteins can be absorbed onto an
artificial surface upon contact with blood. This
Albumin absorbed protein layer composed of albumin,
immunoglobulins, fibrinogen, and other clot-
Albumin, the most abundant protein in ting factors can be a surface to which platelets
human plasma, accounts for 80-85% of the adhere and form thrombus. As a result, albumin
osmotic pressure thereby maintaining and is routinely added to priming solutions used in
regulating plasma volume. Albumin also acts extracorporeal circuits to minimize this effect.
as a carrier for other physiologic molecules and In vitro data from ECMO circuits have dem-
administered drugs. Although recombinant onstrated preservation of platelet counts and
albumin remains under investigation, current decreased platelet activation as demonstrated
albumin solutions are purified from human plas- by plasma b-thromboglobulin levels in circuits
ma either from whole blood or plasmapheresis primed with albumin.82 In vivo data for patients
donations. Albumin solutions must have 96% undergoing coronary bypass surgery demon-
of the protein composition consisting of albu- strate higher platelet counts and reduced chest
min, but the product may contain nonalbumin tube drainage in 20 subjects who received 2.5
proteins, endotoxins, trace metals, prekallikrein grams of 5% albumin in the circuit prime; plate-
activator, bradykinin, sodium, potassium, and let function as assessed by PFA-100 (Siemens
stabilizers such as sodium caprylate and/or Healthcare Diagnostics, Inc., Tarrytown, New
sodium acetyltryptophanate. Preparation and York) collagen/epinephrine and collagen/ad-
products vary, but albumin is most commonly enosine diphosphate cartridges did not differ.83
provided in 5% and 25% concentrations. Typi- Moreover, in another survey, 98 of 119 (82%)
cally, albumin infusions are used therapeutically ELSO reporting center respondents included
to maintain intravascular volume and increase albumin in their ECMO circuit prime.1
osmotic pressure; however, albumin infusion
vs. use of nonprotein colloids such as dextran Antifibrinolytic Therapy
or hydroxyethyl starch or crystalloid solutions
have not been investigated in well designed Antifibrinolytic therapy reduces bleeding
studies. Specifically in a single publication of associated with activation and dysregulation
30 neonates with pulmonary hypertension due to of fibrinolysis in major surgery (cardiac, liver,
meconium aspirations syndrome on VA-ECMO, neurosurgery, and obstetric hemorrhage) and
half received 3.8% albumin for fluid replace- trauma. For many years aprotinin, a bovine,
ment.81 In this study, neonates who received nonspecific serine protease inhibitor, was the
colloid had less edema, but there was no differ- most popular antifibrinolytic agent; however,
ence in ECMO run times, duration to extubation, following publication of the BART trial (Blood
or mortality. In addition, there was concern Conservation Using Antifibrinolytics in a Ran-
about impaired renal function in neonates who domized Trial) which showed higher mortality
received albumin and the authors could not in patients receiving aprotinin compared to the
provide a final recommendation regarding the lysine analogues, tranexamic acid and e-ami-
type of volume replacement in neonates. As nocaproic acid, aprotinin was withdrawn from
a result, administration of albumin should be the market.84,85 Nonetheless, Canada and some
based on individual patient status. Despite European countries have lifted the suspension
of aprotinin, but its use remains controversial
115
Chapter 8
especially outside of noncomplex cardiac sur- curring on ECMO, decreased RBC transfusions,
gery. As a result, the synthetic lysine analogues, and improved survival (100% versus 56%). In
TXA and e-aminocaproic acid, are now the most addition, two thromboses were reported; how-
widely used antifibrinolytic agents. Both drugs ever, these complications were similar in the
block the lysine binding sites of plasminogen, group not treated with tranexamic acid.
preventing activation to plasmin and lysis of At present, data to support routine use of
polymerized fibrin. While some data suggest antifibrinolytic therapy during ECLS is lack-
an increased risk of myocardial infarction with ing; however, prophylactic perioperative use
aprotinin, no data support a prothrombotic or as an adjunct therapy to blood product and
state with the lysine analogues; however, sei- coagulation factor therapy may help reduce
zures have been associated with high doses of bleeding. While the risk of thrombosis may not
tranexamic acid.85 be significantly increased, fatal thrombosis has
The use of e-aminocaproic acid, 100 mg/ been reported in a neonate with CDH treated
kg bolus prior to cannulation followed by 30 with e-aminocaproic acid.91 As a result, larger
mg/kg/hr until decannulation, during ECLS studies are needed to determine the efficacy and
was first described in 42 infants at high risk safety of antifibrinolytic therapy during ECLS.
for bleeding. 86 Neonates who received e-
aminocaproic acid had significantly less extra-
cranial bleeding compared to controls and no
intracranial hemorrhage compared to controls.
This effect was more pronounced in the cardiac
and congenital diaphragmatic hernia (CDH)
subgroups. In addition, the e-aminocaproic
acid group had lower transfusion requirements
but increased thrombotic complications; two
circuits had to be changed and two patients
developed right atrial thrombi around central
venous lines, but the findings did not reach
statistical significant. As a followup study, a 10
year review of e-aminocaproic acid use at the
same institution87 compared to ELSO Registry
controls, did not confirm the initial findings
of reduced intracranial hemorrhage and red
cell transfusion requirements. These findings
reflected those of another center, but reduced
surgical site bleeding (12% vs. 7%, p=0.005) in
patients who received e-aminocaproic acid still
occurred, an effect that was more pronounced
in the cardiac surgery subgroup.88 In adults,
successful use of e-aminocaproic acid has been
reported in a case series of four ECLS patients.89
Data have also been published in a cohort of
20 CDH patients using tranexamic acid.90 The
10 patients treated with tranexamic acid had
significantly less perioperative blood loss oc-
116
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1034. fect of fresh-frozen plasma transfusion on
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Prospective observational study of hemo- with mild coagulation abnormalities. Trans-
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42. Cheung PY, Sawicki G, Salas E, Etches PC, 139.
Schulz R, Radomski MW. The mechanisms 51. Soundar EP, Besandre R, Hartman SK, Ter-
of platelet dysfunction during extracorpo- uya J, Hui SK. Plasma is ineffective in cor-
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neonates. Crit. Care Med. 2000;28(7):2584- ill children: a retrospective observational
2590. study. J Intensive Care. 2014;2(1):014-
43. Mutlak H, Reyher C, Meybohm P, et al. 0064.
Multiple electrode aggregometry for the as- 52. Karam O, Demaret P, Shefler A, et al. Indi-
sessment of acquired platelet dysfunctions cations and Effects of Plasma Transfusions
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Cardiovasc. Surg. 2015;63(1):21-27. Care Med. 2015;191(12):1395-1402.
44. Saini A, Hartman ME, Gage BF, et al. Inci- 53. Straat M, Muller MC, Meijers JC, et al. Ef-
dence of Platelet Dysfunction by Thrombo- fect of transfusion of fresh frozen plasma
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119
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54. Lieberman L, Bercovitz RS, Sholapur and efficacy of recombinant activated factor
NS, Heddle NM, Stanworth SJ, Arnold VII for refractory hemorrhage in pediatric
DM. Platelet transfusions for critically ill patients on extracorporeal membrane oxy-
patients with thrombocytopenia. Blood. genation: a single center review. Perfusion.
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55. Logan AC, Yank V, Stafford RS. Off-Label 64. Schneider AG, Perez MH, Tozzi P, et al.
Use of Recombinant Factor VIIa in United Recombinant factor VIIa for intractable
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Med. 2011;154(8):516-522. circulatory assist devices. Intensive Care
56. Alten JA, Benner K, Green K, Toole B, Med. 2010;36(9):1620-1621.
Tofil NM, Winkler MK. Pediatric off-label 65. Repesse X, Au SM, Brechot N, et al.
use of recombinant factor VIIa. Pediatrics. Recombinant factor VIIa for uncontrol-
2009;123(3):1066-1072. lable bleeding in patients with extracor-
57. McQuilten ZK, Barnes C, Zatta A, Phil- poreal membrane oxygenation: report on
lips LE. Off-label use of recombinant 15 cases and literature review. Crit. Care.
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59. Agarwal HS, Bennett JE, Churchwell KB, JN, Braun MM. Thromboembolic ad-
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61. Niebler RA, Punzalan RC, Marchan M, corporeal membrane oxygenation. Ann.
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75. Kinard TN, Sarode R. Four factor prothrom- LG, Mellgren G, Wadenvik H. The effect
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78. Sarode R, Milling TJ, Jr., Refaai MA, et 86. Wilson JM, Bower LK, Fackler JC, Beals
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thrombin complex concentrate in patients acid decreases the incidence of intracra-
on vitamin K antagonists presenting with nial hemorrhage and other hemorrhagic
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121
Chapter 8
nocaproic acid (Amicar) in the prevention

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122
9
Neonatal Respiratory Diseases
Billie L. Short, MD, Lamia Soghier, MD
Introduction Meconium Aspiration Syndrome (MAS)
Neonatal respiratory diseases that result in Meconium is a bacterial free material con-
respiratory failure and require extracorporeal taining residuals of gastrointestinal secretions
membrane oxygenation (ECMO) therapy after in the gut of the fetus. It can be seen in the fifth
failed ventilation and vasodilator therapies in- month of gestation. In utero passage occurs in
clude the following: congenital diaphragmatic up to 25% of deliveries, with higher percent-
hernia (CDH), meconium aspiration syndrome age seen in postterm infants and those with in
(MAS), persistent pulmonary hypertension of utero stress. Meconium in the amniotic fluid
the newborn (PPHN, note PPHN can be a com- can be detected in 8-25% of all births after 34
ponent of all neonatal respiratory diseases, this weeks gestation. Of those, approximately 10%
category is idiopathic, ie, without other causes), inhale the meconium into the lungs and develop
neonatal pneumonia, sepsis with respiratory respiratory distress known as meconium aspira-
compromise, hyaline membrane disease action syndrome (MAS).2,3 The majority of these
companied by PPHN, and other congenital lung infants do quite well with minimal respiratory
disorders. The use of ECMO to treat these dis- support, but those with severe respiratory failure
ease states is limited to the infant within the first
10-14 days of life, who is ≥34 weeks gestation
or 2000 grams, without a major bleeding com-
plication, including a significant intraventricular
or intracranial hemorrhage.1 This chapter will
discuss the pathophysiology of these disease
states and focus on potential treatment modali-
ties prior to the need for ECMO. Figure 9-1
shows the breakdown of these diagnoses in the
ECMO population.1.
Congenital Diaphragmatic Hernia (CDH)

Figure 9-1. Neonatal diseases treated with
Congenital diaphragmatic hernia (CDH) is ECMO, from the January 2016 ELSO Registry
Report. Presented as percent of the total new-
covered in full in Chapter 10. born population treated with ECMO.
123
Chapter 9
may require ECMO therapy. An early study by conium aspiration chiefly affects infants born
Paranka et al.4 indicates that when oxygenation at term and postterm. Delivery postterm is a
does not improve consistently by 6 hours of ven- major risk for MAS. Therefore, delivery prior
tilation infants should be referred to an ECMO to 41 weeks gestation is recommended to reduce
center, as a high percentage will continue to this risk. Meconium directly alters the amniotic
worsen and require ECMO. Singh et al. found, fluid, reducing antibacterial activity and subse-
in their review of over 7000 patients with MAS, quently increasing the risk of perinatal bacterial
9% required acute transfer to a higher level of infection. Aspiration induces hypoxia via four
care.3 major pulmonary effects: airway obstruction,
surfactant dysfunction, chemical pneumonitis,
Pathophysiology and pulmonary hypertension (see Figure 9-2).
The first intestinal discharge from newborns Airway Obstruction

is meconium, which is a viscous, dark green
substance composed of intestinal epithelial Complete obstruction of the airways by
cells, lanugo, mucus, and intestinal secretions meconium results in atelectasis. Partial obstruc-
(eg, bile). Factors that promote the passage in tion causes air trapping and hyperdistention of
utero include in utero stress, placental insuf- the alveoli, commonly termed the ball-valve
ficiency, maternal hypertension, preeclampsia, effect (see Figure 9-3). Air trapping caused by
oligohydramnios, hypoxic delivery events the meconium can result in a pneumothorax,
(eg, cord compression), maternal drug abuse, pneumomediastinum, or pneumopericardium.
especially tobacco or cocaine.
Meconium-stained amniotic fluid may be
aspirated before or during labor and delivery.
Because meconium is rarely found in the am-
niotic fluid prior to 34 weeks’ gestation, me-
Figure 9-2. Schematic of the pathophysiologic Figure 9-3. Schematic showing the result of
events associated with MAS. meconium partial or full obstruction resulting
in either airtrapping/emphysema or atelectasis/
collapse of the lung.
124
Neonatal Respiratory Diseasest
Surfactant Dysfunction hampers the ability to ventilate. The recommen-

dation for rapid resuscitation with positive pres-
Meconium deactivates surfactant and may sure ventilation for depressed meconium infants
also inhibit surfactant synthesis, contributing to supersedes the need to place an endotracheal
the development of diffuse atelectasis.5,6 tube (NRP 17th Edition). The majority of MAS
patients have mild respiratory distress usually
Chemical Pneumonitis and Secondary Infec- only requiring nasal cannula oxygen therapy.
tion For severe cases, conventional ventilation may
be required. High frequency ventilation, spe-
Enzymes, bile salts, and free fatty acids in cifically high frequency oscillatory ventilation
meconium irritate the airways and parenchyma, (HFOV), may improve respiratory status in
causing a release of cytokines, which initiate about 50% of patients; however, it is not toler-
a diffuse pneumonitis that may begin within a ated in many patients.4 Inhaled nitric oxide
few hours of aspiration. Although meconium (iNO) may be beneficial for those who have a
is sterile, its presence in the air passages can component of pulmonary hypertension noted
predispose the infant to pulmonary infection as- on cardiac echocardiogram.9 The pathophysiol-
sociated with the chemical pneumonitis. Chemi- ogy of MAS is characterized by a combination
cal irritation and inflammation may persist for of atelectasis and hyperinflation caused by the
a several days. meconium particles either partially or totally
blocking the airways (see Figure 9-4, a & b),
Persistent Pulmonary Hypertension of the making ventilation techniques difficult. In
Newborn (PPHN) some cases, patients respond to high ventilator
rates and low inspiratory times (TI), while oth-
To complicate matters further, many infants ers respond to low rates and long TI. When all
with MAS have either primary or secondary perventilation techniques fail, infants with MAS
sistent pulmonary hypertension of the newborn have excellent outcomes with ECMO therapy.
(PPHN). This can be an acute event at birth with Venovenous (VV) ECMO can be used in many
inhalation of meconium resulting in hypoxia, MAS patients, even those requiring pressor
or because of chronic in utero stress resulting support.10
in thickening of the pulmonary vessels. PPHN
further contributes to the hypoxemia caused by
meconium aspiration syndrome.
Treatment
Delivery room management of the meco-

nium stained infant has changed over the years.
Because of the high risk to postterm infants,
delivery prior to 41 weeks gestation is now the
norm.6 Studies, although small in number, have
Figure 9-4 a & b. (a) X-ray of an infant with
shown that intubating and suctioning the trachea MAS with the major pathophysiology related
does not change outcome.7,8 The current Neo- to lung collapse/atelectasis; (b) X-ray of an
natal Resuscitation Program NRP recommen- infant with MAS with the major pathophysiol-
ogy related to over expansion and pulmonary
dation allows for suctioning of meconium only interstitial emphysema.
when it causes an obstruction to the airway that
125
Chapter 9
Outcome pathic PPHN). These patients have normal

ventilation but severe hypoxemia. Causes
A large retrospective analysis demonstrated are usually unknown but may result from
the overall mortality rate for meconium aspira- early closure of the ductus arteriosus, or
tion syndrome to be 1.2% in the United States.3 chronic medications the mother may be tak-
The mortality rate for meconium aspiration ing, including serotonin reuptake inhibitors
syndrome resulting from severe parenchymal (SSRI) or prostaglandin inhibitors (aspirin,
pulmonary disease and pulmonary hyperten- indomethacin). The idiopathic form of
sion is as high as 20%. Other complications PPHN is seen in about 10-20% of the cases
include air block syndromes (eg, pneumothorax, of PPHN, and if severe can ECMO therapy.
pneumomediastinum, pneumopericardium) and, 3. Hypoplastic vasculature as seen in the CDH
pulmonary interstitial emphysema which occur patient. These are the most difficult patients
in 10-30% of infants with meconium aspiration to treat because not only do they have hypo-
syndrome. When ECMO is employed, infants plastic lungs but they also have a remodeled
do very well with a 94% survival rate reported pulmonary vasculature bed which causes
by the ELSO Registry (January, 2016). The severe pulmonary hypertension. Many of
neurologic disabilities of survivors are not due these infants require ECMO therapy be-
primarily to the aspiration of meconium, but cause of the severity of their disease.
rather by in utero pathophysiology, including
chronic hypoxia and acidosis. Lethal forms of pulmonary hypertension
in the newborn are found in several genetic
Persistent Pulmonary Hypertension of the disorders, including alveolar capillary dysplasia
Newborn (ACD) with misalignment of lung vessels, sur-
factant B deficiency, and other genetic disorders
When the normal cardiopulmonary transi- such as Fryns syndrome, characterized by CDH,
tion fails after birth, the condition is call per- hypoplastic lungs and abnormal brain develop-
sistent pulmonary hypertension of the newborn ment. ACD should be considered in patients
(PPHN). Severe PPHN has been estimated to who receive ECMO but cannot be weaned suc-
occur in 2/1000 live births with a mortality cessfully.11 The diagnosis requires either lung
between 5-10%. PPHN can be characterized biopsy or may often be made at autopsy.
by one of three types:
Pathophysiology
1. Abnormally vasoconstricted pulmonary
vasculature due to lung parenchymal dis- In utero the pulmonary vascular bed is
eases such as MAS, respiratory distress vasoconstricted to facilitate blood flow away
syndrome, or pneumonia.9 This type of from the fetal lung through the foramen ovale
PPHN is considered the result of acute and patent ductus arteriosus (See Figure 9-5).
events without remodeling of the pulmo- This normal state in the fetus occurs because the
nary vessels. Note: MAS can also be the placenta and not the lungs is the gas exchange
result of chronic hypoxia in utero with in organ. After birth, acute changes in blood flow
utero passing of meconium. This type has a and shear stress result from the clamping of the
component of remodeling of the pulmonary umbilical cord. This results in blood flow now
vasculature. directed into the lungs, producing in a 10-fold
2. The lung with remodeled pulmonary vas- increase in flow. This increase along with the
culature, but normal parenchyma,( ie, idio- rhythmic movement of the chest wall and lung
126
tissue and a dramatic rise in the PaO2 stimulate Treatment

the production of vasodilator agents in the lung,
including nitric oxide, prostacyclin, and ad- PPHN treatment includes mechanical ven-
enosine, while turning off the vasoconstrictors, tilation of the underlying lung disease for cases
endothelin and platelet activating factor. All including MAS and pneumonia, while treating
of these factors result in a marked reduction in the pulmonary hypertension with agents such as
the vascular resistance in the lung, allowing the iNO.9,12 Attempts at alkalinization are no longer
foramen ovale to close, followed soon by the warranted as hyperventilation techniques have
closure of the PDA. If normal transition does been shown to cause lung injury, and alkaline
not occur as described above, the infant will drips such as bicarbonate drips have not been
develop hypoxia due to right-to-left shunting shown to improve outcome. Typically, low
through the fetal shunts bypassing the lungs volume conventional ventilation with iNO is
as in utero, (ie, PPHN). Pulmonary vascular used and if unsuccessful, HFOV is attempted.
resistance can equal or exceed systemic vascular Preductal saturations between 88–95% have
resistance in these cases. shown a good measure of oxygenation, while
postductal PaO2 levels are accepted down to
50 mmHg. Indications for ECMO usually are
preductal saturation levels <88 with postductal
PaO2 <50 mmHg. Maintenance of blood pres-
sure can be an issue usually requiring dopamine
and/or epinephrine therapy although some cen-
ters prefer dopamine/dobutamine combination.
Milrinone can be added as a pulmonary vasodi-
lator, but cardiac output must be able to adjust
for the systemic vasodilation that may occur.13
Outcome
Survival rates for infants with idiopathic

PPHN not requiring ECMO are almost 100%,
but for those who receive ECMO the survival
rate is 77% (ELSO Registry, January 2016).
Most deaths are related to intracranial com-
plications thought to be caused by the severe
hypoxemia pre-ECMO.
Pneumonia/Sepsis
Figure 9-5. A schematic of the fetal circula-
tion from Wikimedia Commons, originally
from 20th U.S. edition of Gray's Anatomy of Neonatal pneumonia and/or sepsis can be a
the Human Body, originally published in 1918 devastating condition because lung ventilation
(not copyrightable). Fetal shunts at the foramen
ovale and patent ductus arteriosus remain open disorder combined with the shock and coagu-
postnatally in cases where stress occurs at birth lopathy that can develop. The most common
resulting in the persistent pulmonary hyper- organisms involved in neonatal sepsis and pneu-
tension of the newborn (PPHN), a syndrome
that can be idiopathic or associated with other monia are group B beta hemolytic streptococcus
disease states. (GBS) or gram-negative organisms.14,15 Many
127
Chapter 9
of these patients will not appear ill at delivery Surfactant Deficiency – Hyaline Membrane
but develop respiratory distress and shock after Disease
birth. Mothers who carry GBS are treated at
the time of delivery; significantly reducing the The late preterm infant (34-36 weeks ges-
risk to the newborn for developing sepsis and/ tation) may present with hyaline membrane
or pneumonia with this gram-positive organism. disease, but also have underlying pulmonary
Treatment for GBS has increased the risk for hypertension or sepsis/pneumonia making their
overgrowth of gram-negative organisms and respiratory status tenuous.
for infections with gram-negative organisms
in the newborn. Pathophysiology
Pathophysiology Surfactant, secreted by type II alveolar cells

in the lungs, is composed of proteins and several
These infants develop respiratory failure phospholipids that lower the surface tension
and shock shortly after birth. PPHN is a com- of alveoli. Surfactant deficiency is the patho-
mon factor in the pathophysiology, along with physiologic basis of hyaline membrane disease
cardiac failure, so treatment can be difficult. (HMD), characterized by massive atelectasis.
The major constituent of surfactant is lecithin,
Treatment comprising 50-75% of all the phospholipids. It
first appears in significant quantities at 22-24
Most patients are treated with conventional weeks gestation and continues to increase with
therapy, but may advance to high frequency gestation. Most infants produce surfactant by
oscillator ventilation (HFOV) and iNO therapy, 35 weeks gestation, but those who do not can
along with blood pressure support including develop significant lung disease. Many of these
volume replacement and pressor support. When infants will develop PPHN because of hypoxia
these fail, patients are considered ECMO candi- at birth. Infants who are considered for ECMO
dates.16 Treatment of coagulopathy is essential, typically have severe surfactant deficiency
both pre-ECMO and during ECMO to reduce along with PPHN.17,18
the risk for bleeding complications, especially
intracranial hemorrhages. Treatment
Outcome After the availability of artificial surfactant

in the mid 1990s, the typical treatment in this
Survival for neonates with pneumonia or population is surfactant replacement, conven-
sepsis is less than conditions such as MAS, tional ventilation, advancing to HFOV, and if
primarily due to the systemic inflammation and PPHN is diagnoses, adding iNO. The addition
coagulopathy of the disease state. Intracranial of surfactant, HFOV, and iNO to our treatment
hemorrhage is the most common cause of death. regimen has almost eliminated the need for
The ELSO database reports a 73% survival in ECMO as a therapy for these infants (ELSO
neonatal sepsis and 58% in neonatal pneumonia Registry, January 2016; see Figure 9-6).
(ELSO Registry, January 2016).
128
Outcome ventilation. Therefore recommendations for

use in the term infant with respiratory distress
The survival for the RDS population that is to use it when the FiO2 is <50% or OI <25.
requires ECMO is 84% as reported by the
ELSO Registry. The major cause of death in
this population is intracranial hemorrhage and
not pulmonary failure.
Surfactant Deficiency – Term Infants in Re-

spiratory Failure
Studies in term infants in respiratory failure

have shown surfactant deficiency not related to
alveolar production, as with the preterm popula-
tion, but secondary to our ventilation techniques,
resulting in surfactant production being turned
off or deactivated by proteins such as those
seen in MAS and lung injury with protein
leakage.19-21 Lotze et al. showed that surfactant
replacement could reduce ECMO use in this
population but only with early use.20 When
meeting ECMO criteria, surfactant therapy did
not reduce the need for ECMO and in some
cases caused desaturation and worsening of
Figure 9-6. Graph of cases overtime of newborn diseases treated with ECMO. Note the
marked reduction in the treatment of the RDS population with ECMO. This has resulted
from the newer pre-ECMO therapies such as surfactant and HFOV.
129
Chapter 9
References 9. Steinhorn RH. Neonatal pulmonary hy-

pertension. Pediatr Crit Care Med. 2010
1. Suttner DM, Short BL. Neonatal respiratory March; 11(2 Suppl): S79–S84.
ECLS. In: Annich G, Lynch WR, MacLaren 10. Rais-Bahrami K, Van Meurs K. Venoarte-
G, Wilson JM, Bartlett RH, eds. Extracor- rial versus venovenous ECMO for neonatal
poreal cardiopulmonary support in critical respiratory failure. Semin Perinatol. 2014
care. Ann Arbor, MI: 2012: 225-249. Mar;38(2):71-77.
2. Dargaville PA, Copnell B. The epidemiol- 11. Tibballs J, Chow CW. Incidence of alveo-
ogy of meconium aspiration syndrome: lar capillary dysplasia in severe idiopathic
incidence, risk factors, therapies, and out- persistent pulmonary hypertension of the
come. Pediatrics. 2006; 117(5):1712-1721. newborn. J. Paediatr. Child Health. 2002;
3. Singh BS, Clark RH, Powers RJ, Spitzer AR. 38:397–400.
Meconium aspiration syndrome remains a 12. The Neonatal Inhaled Nitric Oxide Study
significant problem in the NICU: outcomes Group. Inhaled nitric oxide in full-term
and treatment patterns in term neonates ad- and nearly full-term infants with hypoxic
mitted for intensive care during a ten-year respiratory failure. N Engl J Med. 1997;
period. J Perinatol. 2009; 29(7):497-503. 336:597-604.
4. Paranka MS, Clark RH, Yoder BA, Null 13. McNamara PJ, Shivananda SP, Sahni M,
DM. Predictors of failure of high-frequency Freeman D, Taddio A. Pharmacology of
oscillatory ventilation in term infants with Milrinone in neonates with persistent pul-
severe respiratory failure. Pediatr. 1995; monary hypertension of the newborn and
95(3):400-404. suboptimal response to inhaled nitric oxide.
5. Lotze A, Whitsett JA, Kammerman LA, Pediatr Crit Care Med. 2013; 14:74–84.
Ritter M, Taylor GA, Short BL. Surfactant 14. Mukhopadhyay S, Puopolo KM, Neonatal
protein A concentrations in tracheal aspirate Early-Onset Sepsis: Epidemiology and Risk
fluid from infants requiring extracorporeal Assessment. NeoReviews. 2015; 16 (4):
membrane oxygenation. Journal of Pediat- 221e-228.
rics. 1990; 116:435-440. 15. Webber SI, Wilkinson AR, Lindsell D,
6. Shahed EL, Dargaville AL, Ohlsson PA, Hope PL, Dobson SR, Isaacs D. Neo-
Soll A. Surfactant for meconium aspiration natal pneumonia; Arch Dis Child. 1990
syndrome in term and late preterm infants. Feb;65(2):207-11.
Cochrane Database of Systematic Reviews. 16. Maclaren G, Butt W. Extracorporeal mem-
2014, Issue 12. brane oxygenation and sepsis. Crit Care
7. Chetti S, Adhisivam B, Bhat BV. Endotra- Resusc. 2007 Mar; 9(1):76-80.
cheal suction for non-vigorous neonates 17. Polin RA, Carlo WA , and the COMMIT-
born through meconium stained amniotic TEE ON FETUS AND NEWBORN, Sur-
fluid: A randomized controlled trial. J. Pe- factant Replacement Therapy for Preterm
diatr; 2015;166:208-213. and Term Neonates With Respiratory Dis-
8. Wiswell TE, Gannon CM, Jacob J, et al. tress. Pediatrics 2014;133:156–163.
Delivery room management of the appar- 18. Donn SM, Dalton J. Surfactant replace-
ently vigorous meconium-stained neonate: ment therapy in the neonate: beyond re-
results of the multicenter, international spiratory distress syndrome. Respir Care
collaborative trial. Pediatr 2000;105:1-7. 2009;54(9):1203–1208.
19. Shahed AI, Dargaville P, Ohlsson A, Soll
RF. Surfactant for meconium aspira-
130
tion syndrome in full term/near term

infants. Cochrane Database Syst Rev.
2007;(3):CD002054.
20. Lotze A, Knight GR, Martin GR, et al.
Improved pulmonary outcome after ex-
ogenous surfactant therapy for respiratory
failure in term infants requiring extracor-
poreal membrane oxygenation. J Pediatr.
1993;122(2):261–268.
21. Tan K, Lai NM, Sharma A. Surfactant for
bacterial pneumonia in late preterm and
term infants. Cochrane Database Syst Rev.
2012;(2):CD008155.
131
10
Congenital Diaphragmatic Hernia and ECMO
Matthew T. Harting, MD, MS, Carl F. Davis, MD, Kevin P. Lally, MD, MS
Introduction in a diaphragmatic defect, allowing abdominal

viscera to reside in the thoracic cavity. Roughly
Congenital diaphragmatic hernia (CDH) 95% of CDH defects occur in a posterolateral
is an abnormality of diaphragm development position, with 80% on the left side.3 CDH re-
that allows abdominal contents to herniate into sults in abnormal pulmonary parenchymal and
the thoracic cavity in utero. CDH was first de- vascular development.4,5 Pulmonary pathogen-
scribed in 1679 by Lazarus Riverius, who noted esis in CDH arises as a primary, secondary,
an incidental CDH during an autopsy of a 24 or “dual-hit” process, whereby an underlying
year old patient. In 1754, Dr. George Macaulay common pathway leads to both pulmonary and
described the classic clinical and postmortem diaphragmatic abnormalities, compression of
findings of CDH in newborn infants with right the developing lung by herniated contents stunts
and left-sided diaphragmatic defects in the pulmonary embryogenesis, or both factors
philosophical transactions of the Royal College playing a role.6,7 A major complicating factor in
of Physicians. Both specimens reside in the Uni- children with CDH is pulmonary hypertension
versity of Glasgow. In 1761, Giovanni Battista secondary to abnormalities in the pulmonary
Morgagni described a myriad of diaphragmatic vasculature.8,9 CDH may also occur along with
defects, including the anterior-medial CDH that chromosomal defects and/or cardiac anomalies.
now is known as a Morgagni hernia. Finally, A study in 2010 demonstrated that low vitamin
in 1848, Victor Bochdalek identified several A (retinol) levels, along with decreased retinol
patients at postmortem with posterolateral binding protein levels, were associated with
diaphragmatic hernias that now bear his name. patients with CDH. This suggests that the patho-
The incidence of CDH is approximately genesis of CDH may be related to dysfunction
1 in 2,000 to 4,000 live births. Male children of vitamin A homeostasis.10,11
are more commonly affected, with a 1.5:1
male:female ratio. The risk of recurrence for Diagnosis
future pregnancies is estimated at 2%. These
frequencies are consistent in the United States CDH is increasingly diagnosed in the pre-
and throughout the world.1,2 The pathogenesis natal period by fetal ultrasound and is report-
of CDH remains incompletely understood, with edly detected in up to 75% of cases, dependent
potential genetic or teratogenic, among other un- upon geographic location and institution.12
known origins. The disease universally results Sonographic findings include absence of the
133
Chapter 10
stomach in the abdomen (or presence in the Other diagnostic tests that are indicated
thorax) and/or bowel loops in the thoracic cavity, following birth include chromosomal analysis
along with a shift of the heart into the opposite (if not performed prenatally) and echocar-
hemithorax. The position of the liver may also diography, considering the high incidence of
help identify CDH and predict disease severity, chromosomal abnormalities and cardiac defects.
with significant increases in mortality associated Head ultrasound confirms that no neurologic
with liver herniation into the chest.13-15 abnormality exists that might contraindicate
If the diagnosis is not made in the prenatal extracorporeal support.
period, early clinical signs of CDH may include
cyanosis and respiratory distress manifesting Management
in the postnatal period. However, symptoms
may range from absent (or asymptomatic) to Infants with CDH may demonstrate worsen-
profound respiratory failure. Physical finding respiratory distress after birth, with progres-
ings reveal a flat or scaphoid abdomen, with sion to hypoxemia, hypercarbia, and acidosis.
decreased breath sounds on the affected side of Management with endotracheal intubation and
the thorax. A chest radiograph may confirm the mechanical ventilation is usually indicated.
presence of loops of intestine in the hemithorax Care should be taken to avoid lung overdisten-
(Figure 10-1). Additional findings may include sion, even with the initial intubation. Bag-mask
cardiac/mediastinal shift toward the contralat- ventilation following delivery may cause in-
eral thorax and/or a nasogastric tube visible creased stomach and intestinal air, which could
within, or angled toward, the chest. further compromise pulmonary function. A
nasogastric tube should be placed early. Blood
pH and gas exchange status should be assessed.
Also, preductal (right hand) pulse oximetry is
helpful in monitoring infants with CDH.
Mechanical Ventilation
Infants with CDH can develop hypoxemic

and/or hypercarbic respiratory failure in vary-
ing degrees. The advent of neonatal mechanical
ventilation in the 1960s allowed infants with
previously fatal CDH to survive following
surgical repair of their defect. With increasing
knowledge of newborn physiology, neonatal
CDH patients with pulmonary hypertension
and extrapulmonary shunting were identified.
Studies demonstrated that pulmonary vascular
resistance (PVR) could be modulated with ma-
nipulation of pH and pCO2, and the use of hy-
perventilation strategies became widespread.16
Although hyperventilation was effective in
Figure 10-1. Chest radiograph of an infant
with a left CDH. Note the bowel in the left reducing PVR, this practice resulted in signifi-
hemithorax, the trajectory of the nasogastric cant ventilator associated lung injury (VALI)
tube, and the mediastinal shift to the right. secondary to aggressive ventilation strategies.
134
Congenital Diaphragmatic Hernia and ECMOt
Wung et al. demonstrated that in some CDH and VALI. This approach is prevalent and seems
patients mortality was related to VALI.17 Other to optimize survival. Most centers utilize con-
investigators advocated gentle ventilation along ventional ventilation (with low pressure HFOV
with permissive hypercapnia as a strategy to as an alternative or rescue strategy), define
reduce mortality.18 Most ECMO centers utilize pressure limits to avoid over distention and
a strategy that focuses on minimizing VALI by subsequent VALI, and tolerate adequate blood
allowing spontaneous ventilation with minimal gases, while ensuring cardiac function and end
set respiratory rates, minimal pressure, permis- organ perfusion remain satisfactory.26,27
sive hypercapnia, minimal sedation, and avoid-
ance of pharmaceutical paralysis. This strategy Inhaled Nitric Oxide
has resulted in selected survival rates at some
centers near 90%.19,20 Hyperventilation and a Pulmonary hypertension (pHTN) in patients
normocapnia target as a strategy for infants with with CDH is multifactorial. These patients have
CDH has largely been abandoned. decreased pulmonary vascular arborization,
High frequency oscillatory ventilation increased medial thickness of pulmonary arter-
(HFOV) has had mixed outcomes as a venti- ies, and blunted oxygen-induced vasodilation.8
lation strategy in CDH. Paranka et al. found Inhaled nitric oxide (iNO) selectively dilates
little benefit from HFOV in CDH using a high- pulmonary arteries, improving oxygenation.
pressure lung recruitment strategy.21 However, However, the data regarding the efficacy of iNO
other authors have shown that HFOV can be an in CDH remain unclear. When used as a rescue
effective mode of therapy as an initial treatment therapy for postoperative patients with CDH
for acute respiratory failure in CDH by avoid- and severe respiratory failure, iNO does not im-
ing lung hyperinflation, therefore minimizing prove survival or reduce the use of ECMO.28-30
VALI.22-24 Using historical controls, a European In contrast, a recent prospective study of 218 pa-
study compared conventional ventilation (CV) tients over 10 years from the CDH Study group
to HFOV and found improved survival, espe- found, that in high-risk infants with diaphragm
cially in patients who survived to surgery.23 agenesis, there was a trend toward increased
A recent multicenter, randomized clinical iNO utilization (from 30% to 80%) along with
trial of HFOV versus CV (Ventilation in Infants decreased ECMO use. The authors reported a
with Congenital diaphragmatic hernia: an Inter- trend towards increased survival when compar-
national randomized clinical trial or VICI trial)25 ing the first two years of the study with the last
Conventional Mechanical Ventilation Versus two years (47% to 59%).31 Also, iNO may be
High-frequency Oscillatory Ventilation for useful in patients with CDH following ECMO
Congenital Diaphragmatic Hernia: A Random- therapy.32 iNO continues to be used in many
ized Clinical Trial (The VICI-trial Secondary centers as an adjuvant therapy in managing
analyses found that patients who received CV CDH-associated pulmonary hypertension and
had decreased length of ventilation, less ECMO right heart failure.
support, less inhaled nitric oxide, sildenafil, and
vasoactive medication use, and were less likely Sildenafil
to fail the initial ventilator management strategy.
In summary, while no particular mode of Sildenafil, a phosphodiesterase-5 inhibitor,
ventilation has been shown to be superior for has been used in severe neonatal pulmonary
the management of infants with CDH, clinical hypertension (including in CDH) to allow
data suggest that management strategies should weaning of iNO and extubation.33,34 In severe
be designed to limit lung distention, barotrauma, pulmonary hypertension, oral sildenafil acts as
135
Chapter 10
an adjunct to iNO. Dose and duration (up to two between 1999 and 2001 that compared en-
years) of sildenafil in CDH have been variable doscopic TO (n=11) with standard postnatal
due to lack of practical, standardized measures therapy (n=13) in patients with isolated left
to follow pulmonary vascular resistance in the sided liver-up CDH. The trial was halted as
postdischarge period.35 survival was 77% and 73%, respectively.43 In
Intravenous (IV) sildenafil use has been Europe, the Fetal Endoscopic Tracheal Occlu-
reported since 2009 in non-CDH newborn sion (FETO) consortium has continued to per-
PHT, which improved oxygenation beyond that form endoscopic TO in greater than 150 cases.
achieved with iNO alone.36 Continuous silde- In this study group, TO is offered to patients
nafil infusions (usually 100 mcg/kg/hour) have with liver herniation or a lung to head ratio of
been reported in nine infants with CDH, before <1.0 in the third trimester.44 Investigators have
and after repair.37 In a series from Glasgow, IV reported survival over 50%, which is greater
sildenafil use was associated with improved than expected in this high-risk group compared
oxygenation (FiO2 and OI) at 24 and 72 hours. to historical controls. In 2010, the Tracheal Oc-
A loading dose was avoided due to theoretical clusion To Accelerate Lung growth (TOTAL)
concerns of systemic hypotension. However, trial, an international randomized trial compar-
no systemic hypotension has been observed ing percutaneous FETO under local anesthesia
with sildenafil infusions. An additional case to expectant management among fetuses with
series of three infants (two with CDH) receiv- isolated left CDH and moderate or severe lung
ing intermittent IV sildenafil concluded that it hypoplasia, was launched and as of early 2016
was well tolerated and potentially beneficial.38 continues enrollment. As of late 2015, several
A pharmo-kinetic/pharmo-dynamic study of IV U.S. centers have FDA approval to use this
sildenafil is in progress (Rotterdam) to investi- approach. At this point, fetal intervention for
gate appropriate dosing in newborns. Although severe CDH is investigational and should only
no consensus exists, a reasonable strategy is to be undertaken at experienced centers within the
use IV sildenafil as a second line pulmonary trial guidelines and as a participating center of
vasodilator after iNO and to convert to oral an ongoing (TOTAL) trial.
sildenafil as part of a weaning strategy postop- Experience with ex utero intrapartum treat-
eratively and potentially postdischarge. ment (EXIT procedure) with ECMO (EXIT
to ECMO) for severe cases of CDH (liver
Fetal Interventions herniation and LHR <1.4) has been reported.
EXIT to ECMO seemed to be a promising ap-
Fetal surgery for CDH was first described proach which could allow a smooth transition
in 1990 by Harrison et al.39 Initial attempts at from placental to postnatal support, avoiding
fetal intervention were performed in an open barotrauma, hypoxia, acidosis, hemodynamic
fashion. Patients with and without liver hernia- instability, and/or cardiac arrest. Indications
tion were selected for intrauterine diaphragm were LHR <1.4 with liver-up on ultrasound and/
repair. Those with liver herniation had dismal or percent predicted lung volume less than 15%.
outcomes secondary to compromise of venous Early results of 18 patients (11 received EXIT
return. 40,41 Subsequent data demonstrated to ECMO) identified potential improvements in
equivalent outcomes from fetal and postnatal survival, with a 64% long-term survival versus
intervention in patients without liver hernia- 25% among controls (non-randomized).45 A
tion.42 Today, the most commonly performed subsequent report noted a survival of 28.6%
fetal intervention is tracheal occlusion (TO). A (7 patients) with the EXIT to ECMO approach
prospective randomized trial was conducted versus 50.0% (10 patients) utilizing a non-EXIT
136
management approach.46 Together, these reports nized.61 PFC-induced lung growth (PILG) is
had a combined survival with EXIT to ECMO used to stimulate lung growth. In a prospective,
of 50% (9/18) compared to 54% (9/17) without randomized, single center (though underpow-
EXIT to ECMO. Given these data, there is no ered) trial of 16 CDH patients on ECMO, PILG
current role for the EXIT to ECMO strategy in was safe and lung size doubled but no survival
the management of CDH. advantage was identified.62
Management Adjuncts ECMO
Antenatal medical therapy has also been ECMO for the treatment of CDH was first
investigated. Corticosteroids have had mixed reported in 1977 by German et al.63 Three in-
results. A study of three fetuses treated with fants with severe respiratory failure received
antenatal betamethasone (large dosing) with no ECMO after repair, resulting in one survivor.
comparison group, reported 100% survival.47 A Since then, ECMO has become widely adopted
randomized trial found no difference in survival among infants with CDH. In the 1970s and
when comparing fetuses that received prenatal 1980s CDH was treated as an emergent surgi-
steroids verses control. A cohort study com- cal condition; thus, infants who were placed on
pleted concurrently with the randomized trial ECMO postoperatively often had experienced
also confirmed no benefit to steroids in patients barotrauma, with concomitant VALI, from early,
treated at the 34th week of pregnancy.48 high ventilator pressures. In the late 1980s, the
Surfactant replacement has also been inves- role of pulmonary hypertension in CDH was
tigated as a postnatal therapy. Infants with CDH recognized and clinicians transitioned to a de-
have evidence of surfactant deficiency related to layed surgical strategy, waiting until the infant
abnormal kinetics, decreased total lung volume was hemodynamically stable and/or pulmonary
(area where surfactant resides or pool size),49 hypertension had stabilized. Some authors have
and decreased surfactant phosphatidylcholine reported improved survival with this strategy,
synthesis. 50 However, a large prospective but randomized trials are lacking.64
observational study showed worse survival
and increased complications associated with ECMO Criteria
surfactant replacement.51,52 Further, surfactant
replacement therapy did not improve length of ECMO is commonly reserved for patients
ECMO run, number of days intubated, oxygen who are failing optimal medical management.
requirement, or survival for CDH patients on When incorporated with a strategy of pressure-
ECMO.53 limited (gentle) ventilation and permissive
Perfluorocarbons (PFC) such as Perfluooc- hypercapnia, early use of ECMO may help
tylbromide (Perflubron™) and Perfluorodecalin minimize VALI. Unfortunately, entry criteria
have been shown to increase postnatal lung that accurately predict high mortality prior to
growth via alveolar distension in both preclini- the initiation of ECMO in infants with CDH
cal54-56 and nonrandomized clinical trials.57,58 have not been published. Multiple parameters
PFC have substantial oxygen-carrying capac- have been used to predict those who may benefit
ity,59 low surface tension, and possibly antiin- from ECMO (Table 10-1).65-69 However, none of
flammatory effects.60 Partial liquid ventilation these criteria has been validated in multicenter
(PLV) is a specific technique where PFC are studies. General indications (Table 10-2) and
used with mechanical ventilation, though no contraindications (Table 10-3) for ECMO are
cumulative survival benefit has been recog- listed.70,71 Many centers use a specific limit
137
Chapter 10
on ventilator parameters to avoid VALI and Efficacy of ECMO

transition to ECMO support when a patient
does not respond appropriately. Limiting peak Reversibility of the underlying pulmonary
inspiratory pressure (≤26 cm H20), HFOV to a derangement in CDH is a key criterion when
MAP of 14-15 cm H2O), and maintaining pH considering ECMO therapy. However, this
>7.2 (usually PaCO2 <70 mmHg) are criteria criterion presents a challenging dilemma as the
often used. degree of respiratory failure in CDH depends on
ECMO use in CDH varies according to the the severity of the existing pulmonary hyperten-
location of providers. ECMO is utilized more sion, pulmonary hypoplasia, and the degree of
frequently in the United States compared to the VALI. Pulmonary hypertension is potentially
United Kingdom (30.7% vs. 15.4%, rate ratio, reversible, but can progress in some children
1.81; 95% CI 1.64-2.00).72 ECMO survival for to right heart failure. Pulmonary hypoplasia oc-
CDH infants was 45.8% in the US and 52.9% curs along a spectrum of severity and the rate of
in the UK. However, overall CDH survival was improvement or alveolarization over the course
higher in the U.S. Multiple confounding factors of 2-4 weeks remains unknown.
prevent interpreting the association of ECMO The intrinsic problems related to CDH have
with these outcomes.72 led to poor outcomes compared to other neona-
The CDH Study Group shows that a ma- tal indications for ECMO. The overall survival
jority of patients are placed on ECMO before of infants with CDH reported to the ELSO is
CDH repair. An earlier report from the CDH approximately 51%, the lowest among all eti-
Study Group showed that 770 of 2,077 received ologies of neonatal respiratory failure requiring
ECMO therapy, with only 15% undergoing can- ECMO. Furthermore, a recent study by Stevens
nulation before surgery. These data highlight et al. of the ELSO Registry demonstrated a de-
the trend toward employing ECMO earlier. In crease in overall survival from 64% in 1990 to
1995 ECMO was used postoperatively in 20% 52% in 2001.77 However, other studies showed
of total ECMO cases, decreasing to only 5% an overall improvement in survival with the
postoperative use in 2001.73 Currently, ECMO use of ECMO.78-80 Two studies demonstrated
is predominantly used as a component of pre- similar CDH survival to discharge, but dra-
operative stabilization.74-76 matically different rates of ECMO use (50% vs.
Table 10-1. Relative criteria for initiating Table 10-2. Indications to initiating ECMO
ECMO in the CDH patient. support in the CDH patient.
Author Criteria for Initiating ECMO Indication Assessment

Sebald 65 OI >40 for 4 hours or PaO2 <40 for 2 hours
Hypoxia Preductal saturations
Boloker 20 Preductal O2 saturation <80% refractory to
ventilator manipulation (PIP >30 with consistently <80-85%
convention ventilation, MAP of 20 on Acidosis Metabolic (lactate >5
HFOV) mmol/L or pH <7.20) or
Somaschini 66 OI >40 or PaO2 <40 respiratory (pH <7.20 due
Nagaya 67 Emergent: OI >40 or PaO2 <40 or PaCO2
>100 for 2 hours to hypercarbia)
Preventative: FiO2 >0.9 or MAP >12 for 24 Hypercarbia Persistent PaCO2 >70
hours leading to pH <7.20
Vd Staak 68 A-aDO2 >610 for 8 hours or OI >40 for 3 Hypotension Poor tissue perfusion,
of 5 consecutive blood gases
Howell 69
A-aDO2 >610 for 8 hours or OI >40 for 2 urine output <0.5
hours cc/kg/hr; unresponsive to
IV fluid and inotropic
support
138
1%). These data suggest that interventions other Patients with right-sided CDH have been
than ECMO may be responsible for improved identified as requiring increased use of ECMO
outcomes.19,81 A long-term study from Germany (54% in one study), but had better than expected
recently described their 20 year experience with ECMO survival (80% survival, compared to
ECMO, reporting 62% overall survival in CDH 63% predicted by CDH Study Group equation).
patients with improved survival associated with Mortality in this cohort was also linked to the
early referral to an ECMO center in the first 24 presence of cardiac anomalies.83
hours of life (77% vs. 54%).80 Considering the above observations, emerg-
For preterm infants with CDH the data ing prenatal approaches to and evaluation of
are mixed. A recently published study from pulmonary development may improve patient
the CDH registry found that in 1127 infants selection, optimizing morbidity and mortality
with CDH, ECMO utilization was lower in the associated with ECMO in infants with CDH.
preterm group than in term infants (25.6% vs. Pulmonary hypoplasia, an important factor that
33.0%). Among all patients with CDH, ECMO affects outcome of CDH, represents a challeng-
use was associated with increased mortal- ing condition to accurately assess prenatally.
ity with an odds ratio (OR) of 3.13 (95% CI, Surrogate indicators of lung development in-
2.76-3.55), as was prematurity (OR 1.68; 95% clude the observed to expected lung:head ratio
CI, 1.34-2.11) reflecting the severe patient measured with repeated fetal ultrasound during
population receiving ECMO, the underlying pregnancy and total fetal lung volume assessed
pulmonary pathology associated with prema- by maternal magnetic resonance imaging in the
turity (respiratory distress syndrome and bron- 2nd and 3rd trimesters of pregnancy.
chopulmonary dysplasia), and the increased Postnatally, the use of alveolar arterial
risk of ICH. The infants who received ECMO oxygen gradient, preductal hemoglobin satu-
and survived to repair had improved chances rations, postductal arterial PaO2, oxygenation
of overall survival. Eight infants ≤32 weeks index (OI), and hypercarbia have been utilized
gestation (average weight 2.3 kg) were man- by some centers to create algorithms for iden-
aged with ECMO support and six underwent tification of children with the best chance of
diaphragmatic repair and survived.82 survival and who would benefit most from
ECMO therapy (Table 10-1).
CDH has a wide spectrum of severity, sta-
Table 10-3. Contraindications to initiating bilization strategies vary among centers, and
ECMO support in the CDH patient. comparing center outcomes is fraught with limi-
tation. The CDH Study Group has been working
Relative Contraindications since 1995 to develop treatment-independent
Significant congenital anomalies (major risk assessment tools that would allow accurate
cardiac anomalies) assessments of outcome between centers ac-
Lethal chromosomal abnormalities cording to the severity of disease. Gender, race,
(Trisomy 18) or other lethal birth weight, Apgar scores, immediate distress
malformations at birth, CPR, estimated gestational age (EGA),
Grade III/IV intracranial hemorrhage side of CDH, and prenatal diagnosis have been
Weight <2 kg
considered. Of these immediately available data,
Gestational age <32-34 weeks
birth weight and Apgar scores are the most
Prolonged mechanical ventilation
predictive of outcome using logistic regression
requiring prolonged high pressure
analysis. Amongst patients in the low risk group,
74% survival was demonstrated, compared to
139
Chapter 10
16% in the high-risk group.1 However, other to receive ECMO (assuming they do not have
authors have been unable to confirm these re- contraindications).
sults.84 Furthermore, 5 minute Apgar scores may
not be available in every case if the patient has Mode of ECMO in CDH
been intubated immediately.
A recent CDH Study Group report identi- Traditionally, infants with CDH requir-
fied predictors of survival in infants with CDH ing ECMO were placed on venoarterial (VA)
who received ECMO. In ECMO treated patients, ECMO. This practice was based on the assump-
survivors were born at a greater estimated ges- tion that these patients are, or can rapidly be-
tational age (38 ± 2 weeks vs. 37 ± 2 weeks, p come, hemodynamically unstable and may not
<0.001), had greater birth weights (3.2 ± 0.5 vs. tolerate venovenous (VV) ECMO. Furthermore,
2.9 ± 0.5 kg, p <0.001), were less likely to be concerns about inadequate venous drainage and
diagnosed with CDH prenatally (53% vs. 63%, insufficient oxygen delivery, when compared to
p <0.01) and were on ECMO for a shorter length VA-ECMO, reinforced the previous notion that
of time (9 ± 5 days vs. 12 ± 5 days, p <0.001).85 VA-ECMO was the mode of choice in CDH.
Others have also tried to identify factors However, several studies have found VV to be
that predict progression to ECMO and survival an acceptable mode of ECMO for infants with
in CDH infants. One group found that lung CDH. 91-93 Based on concerns about inadequate
area to head circumference ratio (LHR <1.0) venous drainage, obscured anatomy, and vessel
and gestational age (GA) at delivery (OR 1.3, size, there remains a bias in some centers to
95% CI 1.0-1.6) predicted use of ECMO and utilize VA-ECMO in infants with severe, right-
survival.86 While a recent report identified sided CDH (Figure 10-2). On the other hand,
pre-ECMO PaCO2 as a predictor of survival, Dimmitt et al. found no difference between
another group described difficulty identifying patients with right and left-sided hernias in
pre-ECMO predictors of survival.87,88 failure of VV-ECMO or the need for conversion
In 2014, a simple, generalizable scoring to VA-ECMO. Furthermore, infants who did fail
system was developed to assess newborn infants
with CDH and categorize them as low, indeter-
minate, and high risk of death.89 The following
equation was created, with a range of 0-8:
1 (birth weight <1500 g) + 1 (Apgar <7)
+ 2 (missing Apgar) + 2 (severe pulmonary
hypertension*) + 2 (major cardiac anomaly) +
1 (chromosomal anomaly) = Total CDH score
*Right to left shunt or suprasystemic pulmo-
nary pressures on echocardiogram
This score is easy to calculate and identi-
fies mortality risk: score 0 (low, <10%), score
1-2 (intermediate, 25%), and score ≥3 (high,
50%). This model was validated, both within
this manuscript (separate dataset) and, subse-
quently, externally.90 Although the ability to Figure 10-2. Chest radiograph of an infant with
predict ECMO was not tested, those in the high a right CDH on VA-ECMO. Note the extreme
mortality risk group are certainly more likely shift of the heart and mediastinum to the left.
This patient had a 5 mm right internal jugular
vein on preoperative ultrasound.
140
sized VV cannula can be placed (Figure 10-3).

Interestingly, Frenckner et al. found that infants
with CDH tend to have smaller diameter vessels
than other infants, which could make cannula
placement for ECMO more difficult.95 However,
it is unlikely that vessel size alone has driven
the greater use of VA-ECMO in CDH patients.
Fisher et al. have described difficulties in right-
sided CDH with failure of the venous catheter
to pass to the right atrium and two occurrences
of azygos vein cannulation with one mortality.96
Table 10-4 lists the advantages (known and
theoretical) of each approach.
Figure 10-3. Chest radiograph of an infant
with a left CDH on VVDL ECMO. Note the
angulation of the cannula to the right. CDH Surgery on ECMO
VV-ECMO and required conversion to VA had The question of optimal surgical timing
similar outcomes to those placed on VA initially, arose when ECMO became part of preoperative
rendering a trial of VV-ECMO safe and reason- stabilization. Operations performed on ECMO
able.93 A recent update from the ELSO Registry are high risk because of the potential for bleed-
in 2009 found that, after multivariate regression ing complications. Early reports of surgical
analysis, mortality and complication rates were repair of CDH while on ECMO described
equivalent between VA and VV-ECMO. Renal significant hemorrhagic complications that
97
complications and inotrope use were more contributed to low survival rates. However,
prevalent in patients receiving VV-ECMO, but later studies showed that surgery can be per-
patients who were on VA-ECMO had higher formed safely with modest hemorrhagic risk if
rates of neurologic morbidity.94 Considering the circuit coagulation status is monitored closely.
above observations, it would be prudent to as- Aminocaproic acid, an inhibitor of fibrinolysis,
sume that many infants with CDH can be treated has been used in patients undergoing operative
with VV-ECMO provided that an adequately repair on ECMO with good results. Downard
Table 10-4. Advantages of venovenous (VV) and venoarterial (VA) ECMO

in CDH.
Advantages of VV-ECMO Support Advantages of VA-ECMO Support

Provides oxygenated blood to Provides cardiac / hemodynamic
pulmonary vasculature and support
myocardium
Does not disrupt the carotid artery Initiation usually not limited by small
vessel diameter
Preserves pulsatile flow Decreases preload
Stabilizes preload and afterload Management more straightforward –
less susceptible to flow and position
challenges
Decreased risk of cardiac stun No need to urgently convert mode of
support
Minimal neurologic embolism risk
141
Chapter 10
et al. showed that 5% of infants treated with edema and early reduction of thoracic pressure),
aminocaproic acid required reexploration for many centers favor early repair. Dassinger et al.
bleeding on ECMO compared to 26% of those have reported a series of 34 infants undergoing
patients who did not receive the drug.98 This early CDH repair on ECMO with 71% survival
has resulted in the increased use of aminoca- and 8.8% reexploration rate for bleeding.101
proic acid along with strict control of circuit Kays et al. found that among left-sided, liver-
coagulation during surgery for CDH on ECMO. up patients with an “opportunity” for repair
Furthermore, Downard et al. found no increased (ie, not placed on ECMO within 12 hours of
risk of large vessel thrombus or cerebral infarc- life), those repaired prior to ECMO had a 92%
tion, although there was an increased need for survival versus 65% among those who arrived
ECMO circuit change.98 to ECMO unrepaired.102 Reasonable strategies
The optimal timing of repair of CDH on include expeditious repair prior to ECMO, early
ECMO remains unclear due to inadequate study repair on ECMO, late repair on ECMO, or repair
and variability amongst centers. Data from the after (if able to wean off) ECMO.
CDH Study Group showed that of the infants
placed on ECMO, 54% underwent surgery on Long-term Outcome of Infants with CDH
ECMO, 30% had surgery following ECMO, and Treated with ECMO
16% never underwent repair. Survival was 83%
in patients who had repair after ECMO, com- Long-term morbidity among children with
pared to 49% in those that had repair on ECMO, CDH has increasingly been recognized. Infants
and 0% for those who did not undergo repair. with CDH who received ECMO support ap-
The length of hospital stay was shorter (64 vs. pear to have a higher risk and greater severity
76 days) and need for oxygen therapy lower of neurological morbidity compared to those
(56% vs. 64%) in children with CDH repaired who did not receive ECMO and those who re-
after ECMO rather than on ECMO. Considering ceived ECMO for other, non-CDH diagnoses.
timing of surgery performed on ECMO, the data Stolar et al. reported 89% of infants receiving
are mixed. Operations have occurred in the first ECMO therapy for non-CDH diagnoses were
24 hours of ECMO to as long as greater than cognitively normal. On the other hand, only
three weeks into therapy. Not surprisingly, in- 60% of infants with CDH treated with ECMO
fants who underwent surgery later demonstrated had a similar outcome.103 Another important
lower survival.99 A recent update from the CDH concern is increased survival at the cost of
Study Group found that after Cox regression increased neurologic morbidity. McGahern et
analysis, surgical repair of CDH on ECMO was al. reported survival of 75%, with 67% of the
associated with decreased survival (48.2% vs. survivors exhibiting neurologic compromise.104
77.1%) relative to repair after ECMO therapy Considering these data, it has been argued that
(hazard ratio, 1.41, 95% CI 1.03-1.92). This was poor neurologic outcome may be related to se-
found to be significant even after controlling for verity of illness, but other independent ECMO
factors associated with severity of CDH,100 but factors cannot be excluded.
meaningful comparisons without confounding Gastroesophageal reflux (GER) is also an
are impossible. Quite clearly, patients who extremely common condition among CDH
can be liberated from ECMO have a far better patients, and has an incidence of up to 50% in
prognosis, while those who cannot and have some series. One study has described a patient
not undergone an “early” repair are relegated cohort followed for ten years with a high in-
to a late repair, or remain unrepaired and do cidence of nutritional problems. The authors
not survive. For several reasons (prior to tissue described high rates of GER, failure to thrive,
142
and severe oral aversion requiring gastrostomy and lowest rate of functionally normal children
tube placement.105,106 Infants with CDH may (37.5% compared to 52.6% in children with
also require surgical management of their GER. meconium aspiration).110 Another recent study
In one of the previously mentioned studies, described the use of ECMO as a risk factor for
21% of patients received fundoplication, with neurodevelopment, psychomotor, and neuro-
the highest rate amongst those requiring patch cognitive disabilities.111 Considering these data,
repair of their hernias.105 Furthermore, hernia re- practitioners should (and will) continue to better
currence rates have been increasingly reported, define the role of ECMO in the management
with recurrence most prevalent in those patients of CDH. Refined selection criteria for ECMO,
who underwent patch repair.106 early identification of the most severe patients
Recent prospective study of lung function who may not benefit from ECMO support, and
in 14 CDH infants over 12 months found that advances in our understanding and manage-
those who had undergone ECMO had increased ment of pulmonary hypertension are likely to
functional residual capacity at 12 months com- improve morbidity and mortality rates. Further
pared to normal values. Forced expiratory flow investigation will continue to delineate the role
was within the normal range at this time point. and value of ECMO among patients with CDH.
However, only 12 patients were available for
followup at 12 months.107 Another retrospective Summary
study found that, in CDH patients following
repair, abnormal lung function tests gradually Infants with CDH can develop severe re-
normalized during the first two years of life. spiratory failure requiring ECMO therapy. Over
The authors found that FRC improved and time ECMO has evolved into a component of
maximum expiratory flow rate normalized.108 preoperative stabilization as a lung-protective
A study from the UK reported outcomes strategy to prevent ventilator associated lung
on patients treated with ECMO between 1991 injury. While advances have been made in
and 2000. Of 73 infants with CDH treated ECMO management for infants, these neonates
with ECMO, 46 (63%) were able to be weaned remain difficult to treat, with the lowest rate of
from ECMO, 42 (56%) survived to hospital survival, and high rates of long-term morbidity.
discharge, and only 27 (37%) lived to one year Some centers have developed selection criteria
or longer. Of the 27 survivors, only 7 were free to identify patients who will receive ECMO;
of complications.109 These outcomes are indeed however, reliable and reproducible algorithms
troublesome, yet survival was not likely pos- that are translatable between institutions remain
sible without ECMO. Stevens et al. have shown elusive. Ongoing investigation will continue
that the incidence of complications while on to focus on early (and this includes prenatal)
ECMO increased over the 25 years of evalua- identification of patients with high mortality,
tion and is possibly associated with increases in concomitant identification of patients who will
the average duration of ECMO therapy.77 The require (benefit from) ECMO, novel therapies
authors suggested that improvements in ventila- for the vascular/parenchymal consequences of
tor management have resulted in more severely CDH (optimally delivered while on ECMO),
ill patients being placed on ECMO, resulting in intra/inter-institutional standardization, long-
longer duration and increased morbidity. term followup/management of morbidity, and
A recent study from the Netherlands consid- multiinstitutional collaboration.
ered the motor and cognitive status at five years
of patients who had received ECMO. The CDH
cohort demonstrated the lowest survival (58%)
143
Chapter 10
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2016;110(1):66-74. real membrane oxygenation: the first year.
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Federation of Pediatric Intensive and Criti- 81. Azarow K, Messineo A, Pearl R, Filler R,
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73. Lally KP, The Congenital Diaphragmatic matic hernia--a tale of two cities: the Toron-
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83. Bryner BS, Kim AC, Khouri JS, et al. Right- 48.
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84. Downard CD, Jaksic T, Garza JJ, et al. and circulatory compromise. The Journal
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Hirschl RB. Factors associated with surviv- genital diaphragmatic hernia. J Ped Surg.
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hernia requiring extracorporeal membrane 93. Dimmitt RA, Moss RL, Rhine WD, Benitz
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88. Hoffman SB, Massaro AN, Gingalewski C, alternative route for ECMO cannulation. J
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89. Brindle ME, Cook EF, Tibboel D, Lally 97. Lally KP, Paranka MS, Roden J, et al. Con-
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2003;38(8):1212-1216. et al. Prospective longitudinal evaluation of
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150
11
Indications and Contraindications for ECLS in Neonates with Respiratory Failure
Denise M. Suttner, MD
Introduction clinical trials that proved the efficacy, the goal

was to prevent patients from dying. In that era,
Extracorporeal membrane oxygenation criteria for ECMO included extreme abnormali-
(ECMO) has been used to support tens of ties in Oxygenation Index (OI), alveolar-arterial
thousands of lives in neonates with respira- oxygen difference (A-aDO2) and hypoxemia.4-6
tory failure. According to the Extracorporeal During this period, criteria were set to select the
Life Support Organization (ELSO), neonates sickest neonates, with a projected mortality of at
continue to have the best survival across all least 80%. Standard medical therapy included
patient diagnoses. Since Dr. Robert Bartlett’s hyperventilation, hyperoxia, alkalization, rou-
first reports of survival of the sickest neonates tine neuromuscular blockade, and intravenous
after ECMO support, several clinical studies vasodilators.
have shown its efficacy. It is now considered Understanding of optimal medical manage-
standard of care for the newborn in respiratory ment in newborns with respiratory failure has
failure or shock who has failed to respond to changed tremendously over the years. Inhaled
less invasive therapies.1-3 nitric oxide (iNO), surfactant, and high-frequen-
cy ventilation (HFV) are now used routinely,
Patient Selection Criteria while hyperventilation, hyperoxia, and several
other therapies have become obsolete. These
changes in practice make the degree-of-illness
Indications measures difficult to translate from one epoch
to another. For example, correlating OI on
ECMO is standard of care for infants meet- conventional ventilation with that calculated
ing criteria outlined in this section. ECMO on HFV is potentially inaccurate. Furthermore,
therapy should be considered in term and late predictors of mortality and morbidity can be
preterm infants with hypoxic respiratory failure institution dependent. For these reasons, univer-
who have failed to improve with other medical sal acceptance of any one criterion for ECMO
interventions. Currently, the more complicated initiation is limited. As in the past, one objective
decision is the optimal initiation time; what in instituting ECMO continues to be increased
defines “failure to improve on other medical survival. However, ECMO has evolved from a
therapies?”. Three decades ago, when the “last ditch effort” intervention. With improved
ECMO pioneers developed entry criteria for the technology and a better understanding of its
151
Chapter 11
risks and benefits, the rationale to cannulate is other respiratory conditions treated with ECMO.
based on decreasing morbidity as well as pre- Overall, MAS patients had a significantly higher
venting death. Tools that predict morbidity are survival rate and significantly fewer complica-
lacking and therefore many simply use “failure tions per patient in each category compared
to respond to other therapies” as their indication to other patients.8 This information supports
for ECMO. Beyond this, the most commonly the consideration of unique, relaxed ECMO
used quantifier of disease severity for neonatal entry criteria for the MAS patient. Grist el al.
HRF remains the OI. reviewed neonatal patients to determine whether
cannulation timing correlated to increased mor-
Oxygenation Index Calculation: tality. Elevated CO2 gradient, anion gap, and
Viability Index (AGc+p(v-a)CO2) correlated
OI = MAP x FiO2 x 100 with a higher mortality (p <0.05). The authors
Post ductal PaO2 concluded that starting ECMO too late may
cause reperfusion injury that reduces survival.9
MAP = (Mean Airway Pressure) Thus, it is recommended that any neonate with
respiratory failure and an OI of >25 be cared
The initial trials used an OI >40 as enroll- for in an ECMO center where timely initiation
ment criteria. Presently many centers still use can occur if the patient’s condition warrants
an OI range of 40-45 as the primary indica- ECMO. Not all critically ill newborns will meet
tion for ECMO support. Schumacher et al. the strict criteria of an OI calculation. To this
documented that patients who received ECMO end, additional criteria for ECMO support are
when the OI was >25 but <40 had shorter and shown in Table 11-1.10
less costly hospital stays with a trend toward Therapeutic options including surfac-
improved outcome. This study contained small tant and iNO have decreased the need for
numbers of patients, but indicates that earlier ECMO in neonates with respiratory failure
cannulation may reduce the morbidity associ- (Figure 11-1).11-13 However in 2014, more
ated with treatments for respiratory failure.7 than 800 neonates received ECLS because of
Radhakrishnan et al. compared the morbidity of inadequacies of other therapeutic strategies.11
patients with MAS with that in patients with all While patients should be given the opportunity
to respond to less invasive therapies, delaying
ECLS cannulation is unacceptable. Regional
Table 11-1. Neonatal ECMO entry criteria for ECMO centers should work with the non-ECLS
respiratory failure or shock.10
centers in their area to establish a standard
protocol regarding transfer criteria in order to
Entry Criteria
prevent untimely delays.
Oxygenation index (OI)* >40 for 0.5-6hr
Oxygenation index (OI)* >20 with lack of improvement
despite prolonged (>24hr) Contraindications
maximal medical therapy or
persistent episodes of
decompensation. Certain patients with complicating pa-
Decompensation (PaO2 <40) PaO2<40 mmHg for 2-12hr thologies should not be considered for ECLS
Unresponsive to intervention
regardless of the degree of respiratory failure.
Metabolic acidosis and shock pH <7.25 for 2hr or more with
hypotension Examples of patients in this category include
Progressive pulmonary hypertension Evidence of right ventricular those with lethal chromosomal disorders (such
dysfunction or continued high
inotropic requirement
as trisomy 13 or trisomy 18), severe preexisting
*Calculation as shown in text
brain damage, or significant intracranial hemor-
152
Indications and Contraindications for ECLS in Neonates with Respiratory Failuret
rhage (grade III or IV). Neonates with irrevers- a cross-sectional study using a data collection
ible, extrapulmonary organ injury are ineligible survey to evaluate differences in practice related
for ECMO unless they are being considered for to ECLS criteria. The lowest birth weight and
transplantation. Even with technical progress, gestational age at which respondents would
ECMO remains a high risk and resource intense consider placing a neonate on ECLS were
intervention; it should only be utilized in those frequently below recommended thresholds.
patients with a high likelihood of a meaning- Wide variability was found in respondents’
ful survival. Pre-ECMO review of the history willingness to place neonates on ECLS in the
and physical are critical prior to cannulation presence of conditions such as intraventricular
to determine if there are contraindications for hemorrhage and hypoxic ischemic encepha-
ECMO. When feasible, pre-ECMO testing and lopathy (HIE). The number of respondents who
consultation should be done if major contrain- would never seek to override parental refusal of
dications are of concern (Table 11-2). ECLS equaled the number who would always
Specific concerns regarding candidacy for do so.15 This variability is likely explained by
ECLS should be discussed with the relevant more experience with ECLS, advancement in
medical subspecialists prior to cannulation capabilities, and the increasing complexity of
addressing the risks (including those of using the patient population. In the end, each patient
valuable resources) versus the potential benefits. must be evaluated individually by a team of
As ECLS technology improves and medical caregivers, and the decision based solely on
therapies advance, candidacy becomes fluid what is in the patient’s best interest.
and more neonates should be considered can-
didates (Table 11-3).14 Some historical absolute
contraindications are now considered relative
contraindications. Chapman et al. performed
1600 30000
1400
25000
1200
20000
1000
800 15000
600
10000
400
5000
200
0 0
#Cases Cumulative
Figure 11-1. Annual and cumulative neonatal respiratory ECLS cases.12
153
Chapter 11
Weight <2 kg (VV) support in patients <2 kg is not possible

since the smallest dual-lumen VV cannula cur-
For the past three decades, weight <2 kg rently available is 13Fr. Therefore, one must
has been a relative contraindication to ECLS. weigh the risks to venoarterial (VA) ECMO
Despite years of experience, the lowest accept- (see Chapter 12) especially in such a high risk
able weight for cannulation remains debatable. patient. Although technically feasible, with
In other words, “how low really is too low for limited long-term followup on patients <2 kg,
ECMO?”. In 1999, Hardart found that weight the question remains whether it is appropriate.
was not an independent factor for developing Currently, patients <1.6 kg have no option for
ICH, as previously thought.16 In 2004, Roz- traditional ECLS and for those >2 kg it can be
mierek et al. hypothesized that ECMO was lifesaving. More investigation, particularly with
effective and safe in babies under 2 kg and regard to long-term developmental followup, is
sought to examine outcome. Neonatal patients needed in the 1.6 to 2 kg population before it
(<30 days old) in the ELSO Registry (n=14,305) should become widely used in these patients.
were divided into those <2 kg (n=663) and
those >2 kg (n=13,642). Overall, survival rate Gestational Age <34 wks
reached 76% but was lower in infants less than
2 kg (77%, ≥2 kg vs. 53%, <2 kg, p<.0001). Some centers feel comfortable providing
Survival was significantly lower for patients ECLS to infants <34 weeks if they are deemed
with diaphragmatic hernia (CDH), bleeding, ‘good candidates’ but this degree of prematurity
and ICH. In contrast to the findings by Hardart, remains a relative contraindication. The prohi-
the incidence of ICH in <2 kg was 6% versus bition to ECLS support in premature infants
4% in those >2 kg (p<.05). Regression analysis is based on studies that established a strong
determined that the lowest weight at which a inverse correlation between gestational age
survival rate of 40% could be achieved was 1.6 (GA) and intracranial hemorrhage (ICH). Car-
kg.17 A 40% survival compares to that seen in diorespiratory support for premature infants has
patients with congenital heart disease receiving been used for a half century. In the mid 1960s,
ECLS. Small cannula sizes may make ECLS ECMO was used as an ‘artificial’ placenta in a
feasible for some patients <2 kg. Venovenous group of premature infants.18 Sufficient cardio-
respiratory support was achieved; however, all
Table 11-2. The pre-ECMO evaluation for infants died secondary to ICH. Similar results
neonatal respiratory failure.
were seen in in the initial trials of ECMO. Dr.
Evaluation
Bartlett et al. reported16 premature infants un-
Review prenatal and delivery history
Complete physical examination Table 11-3. Contraindications to neonatal
Chest and abdominal radiograph respiratory ECMO.
CBC, differential, platelet count
Serum electrolytes with BUN and creatinine Absolute Relative
Transaminase levels Lethal malformations or lethal

Birth weight <2 kg
congenital anomalies
Renal ultrasound when labs or history suggests Severe irreversible brain damage Gestational age <34 weeks
renal disease Irreversible organ damage
Grade II or greater intracranial
Coagulation factors (PT, PTT, fibrinogen) (unless considered for organ
hemorrhage (ICH)
transplant)
Cranial ultrasound Disease states with a high
probability of a poor prognosis
Echocardiogram
Ventilation with 100% oxygen
Neurologic evaluation for ≥14 days
154
der 35 weeks gestational age of whom only four diagnoses or gestational age were also excluded,
(25%) survived.19 ICH occurred in all premature and only data from the first ECMO course was
infants, prompting the authors to recommend used for the analysis. There were 14,528 neo-
against the use of ECLS in premature infants natal ECMO runs which met inclusion criteria.
with respiratory failure. This concern for ICH Late preterm infants experienced the highest
established during the early trials remains the mortality on ECMO (late preterm 26.2%, early
primary reason for withholding ECLS from term 18%, full term 11.2%, p<.001) and had
premature infants. longer ECMO runs; they also had higher rates
However, ECLS management has changed of ICH (late preterm 12.3%, early term 7.6%,
dramatically over time. Management of the full term 3.6%, p<.0001) and other neurological
neonates who suffered ICH differed dramati- complications on ECLS. Furthermore, they ex-
cally from current management. Of the 16 perienced increased mechanical, metabolic, and
patients, 4 had conditions that would now be infectious complications on ECLS. The authors
considered ECLS contraindications and 5 had concluded that late preterm infants had poorer
major technical complications that have become outcomes on ECLS than their more mature
rare. Optimal anticoagulation was unclear and counterparts, underscoring their developmental
thus several of these premature infants had immaturity and vulnerability.24 Effective treat-
activated clotting times of >700 seconds. The ment of respiratory failure in premature infants
authors suggested that advancement in cur- remains an unsolved problem. Despite signifi-
rent practice strategies would likely produce a cant advances, given the complication rate in
survival of 50% or greater.20 Furthermore, the the more premature population, alterations in
ELSO data base from 1988 to 1991 showed a traditional ECLS may still be necessary before
dramatic decrease in the rate of ICH and death acceptance in patients <34 weeks gestation is
compared to that a decade earlier; during this widespread. The development of an artificial
period there was a 37% incidence of ICH in placenta that maintains fetal circulation is an
patients 32-35 weeks gestation compared to appealing alternative.24,25
100% first reported.21 Hardart reviewed the
ELSO Registry for ICH rates in patients ≤37wks Intracranial Hemorrhage
from 1992 to 2000. Gestational age (GA) did
not predict ICH unless combined with postnatal Grade III or IV ICH hemorrhage can be
age (PNA) to calculate postconceptional age detected by head ultrasound and this degree
(PCA). Statistical significance of ICH oc- of hemorrhage is associated poor long-term
curred across PCA age (p=.004) rather than GA prognosis.26 Thus, ECMO should not be offered
alone (p=.09): 26% of patients or ≤32 weeks in this population. Additional expansion of the
PCA developed ICH as compared with 6% of hemorrhage, further compromising neurologic
patients with PCA of 38 weeks (p=.004).22 A prognosis, is likely with the anticoagulation as-
review of 21,218 neonatal ECMO cases in the sociated with ECLS. Patients with pre-ECLS
ELSO Registry from 1986 to 2006 evaluated grade I or II ICH have been successfully man-
GA and outcome. Infants were divided into aged on ECMO without extension of hemor-
three groups: late preterm (34 0/7 to 36 6/7), rhage. Even in this less severe situation, diligent
early term (37 0/7 to 38 6/7), and full term (39 monitoring of hemodynamics, clotting factors,
0/7 to 42 6/7). Neonates with CDH, and other platelets, bleeding times, anticoagulation, and
major congenital disorders including cardiac imaging is required.27-29
defects, chromosomal, and genetic abnormali-
ties, were excluded. Those with unavailable
155
Chapter 11
Irreversible Organ Damage ways available in a timely fashion or adequately

informative to withhold ECMO, it is appropriate
Although patients with irreversible organ and acceptable to proceed with ECLS support.
damage should not be offered ECLS unless they In these circumstances reevaluation and discus-
are eligible for transplantation, determination of sions with consultants and parents should occur
irreversibility of organ function can be difficult. shortly after cannulation. If ECLS support is
Time permitting, appropriate testing should be not in the patient’s best interest, it should be
done to document the degree of injury. An ex- discontinued.
ample is a patient with severe renal dysfunction,
eg, oliguria and increasing creatinine. A renal ul- Chromosome Abnormalities
trasound prior to cannulation can help determine
if the patient has renal agenesis contributing Patients with physical findings suggestive
to hypoplastic lungs which changes the ECLS of trisomy 13, trisomy 18, or other syndrome
calculus. With advances in therapeutic capa- should have a pre-ECMO dysmorphology
bilities, determining irreversible organ damage evaluation. In those situations where time does
and eligibility for transplantation requires input not allow for a definitive diagnosis, the decision
from experts in the organ of interest. to initiate ECLS may be valid. However, once
Frequently, infants with hypoxic ischemic the diagnosis is confirmed a discussion with
encephalopathy (HIE) suffer hypoxic respira- the family about withdrawal of ECMO support
tory failure and some will meet institutional should take place.
ECMO criteria.30 Even in a small program, the
ECMO team will eventually have to make the Pre-ECMO Ventilation Days
decision of whether to offer support to a patient
who has a perinatal injury suggestive of a poor Evaluation for the appropriateness of
neurologic outcome. Despite hypothermia ECMO should involve a consideration of the
treatment, morbidity and mortality from HIE pre-ECMO ventilation days. In some reports,
remain high. Because of the acute state of ill- the number of days of ventilation required prior
ness, one of the more difficult evaluations to to ECMO has been shown to significantly de-
perform prior to initiating ECLS is a thorough crease survival. Zabrocki et al. reviewed over
neurologic evaluation. When time allows, head 3,000 pediatric ECMO patients from 1993-2007
imaging with MRI combined with an EEG may and found no association between pre-ECMO
prove helpful.31 Beyond exclusion of a grade III ventilation under 14 days and survival.32
or IV ICH, no clear set of measures defines how
severe the damage must be in order to exclude
an infant from ECLS. In cases where there
is strong evidence of hypoxic injury on MRI,
abnormal EEG findings, significant metabolic
acidosis, and low Apgar scores, strong consid-
eration for withholding ECLS should occur.
Surprisingly, in 2009, a data collection survey
revealed that only 48% of ECLS doctors would
never offer ECMO to a neonate with severe
hypoxic ischemic encephalopathy.15
Because pre-ECMO evaluations to deter-
mine irreversibility of organ damage are not al-
156
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cut-points in neonatal and pediatric respira- 19. Bartlett RH, Andrews AF, Toomasian
JM, Haiduc NJ, et al. Extracorporeal
157
Chapter 11
membrane oxygenation for newborn re- into incidence, timing and risk factors.
spiratory failure: forty-five cases. Surgery. Intraventricular hemorrhage in asphyxi-
1982;92(2):425-433. ated newborns treated with hypothermia: a
20. Bui KC, LaClair P, Vanderkerhove J,et al. look into incidence, timing and risk factors.
ECMO in premature infants. Review of BMC Pediatr. 2015;15:106.
factors associated with mortality. ASAIO 29. Ancel PY, Livinec F, Larroque B, et al. Ce-
Trans. 1991;37(2):54-59. rebral palsy among very preterm children
21. Hirschl RB, Schumacher RE, Snedecor in relation to gestational age and neonatal
SN, et al. The efficacy of extracorpo- ultrasound abnormalities: the EPIPAGE
real life support in premature and low cohort study. Pediatrics. 2006;117(3):828-
birth weight newborns. J Pediatr Surg. 835.
1993;28(10):1336-1340. 30. Massaro A, Rai-Bahrami K, Chang T, et al.
22. Hardart GE, Hardart MK, Arnold JH, et al. Therapeutic hypothermia for neonatal en-
Intracranial hemorrhage in premature neo- cephalopathy and extracorporeal membrane
nates treated with extracorporeal membrane oxygenation. J Pediatr. 2010;157(3):499-
oxygenation correlates with conceptional 501.
age. J Pediatr. 2004;145(2):184-189. 31. Mariani E, Scelsa B, Pogliani L, et al.
23. Ramachandrappa A, Rosenberg ES, Wag- Prognostic value of electroencephalograms
oner S, et al. Morbidity and Mortality in in asphyxiated newborns treated with hypo-
Late Preterm Infants with Severe Hypoxic thermia. Pediatr Neurol. 2008;39(5):317-
Respiratory Failure on ECMO. J Pediatr. 324.
2011;159(2):192-8.e3. 32. Zabrocki LA, Brogan TV, Statler KD, Poss
24. Reoma JL, Rojas A, Kim AC, et al. Devel- WD, Rollins MD, Bratton SL. Extracorpo-
opment of an artificial placenta I: pumpless real Membrane Oxygenation for Pediatric
arterio-venous extracorporeal life support Respiratory Failure: Predictors of Mortality.
in a neonatal sheep model. J Pediatr Surg. Crit Care Med. 2011;39:364-370.
2009;44(1):53-59.
25. Bryner B, Gray B, Perkins E, et al. An
extracorporeal artificial placenta supports
extremely premature lambs for 1 week. J
Pediatr Surg. 2015;50(1)44-49.
26. Bolat F, Kılıç SÇ, Oflaz MB, et al. The
prevalence and outcomes of thrombocy-
topenia in a neonatal intensive care unit: a
three-year report. Pediatr Hematol Oncol.
2012;29(8):710-20.
27. Von Lindern JS, van den Bruele T, Lopriore
E, Walther FJ. Thrombocytopenia in neo-
nates and the risk of intraventricular hemor-
rhage: a retrospective cohort study. BMC
Pediatr. 2011;11:16.
28. Al Yazidi G, Boudes E, Tan X, Saint-
Martin C, Shevell M, Wintermark P. In-
traventricular hemorrhage in asphyxiated
newborns treated with hypothermia: a look
158
12
ECLS Cannulation for Neonates with Respiratory Failure
Carl Davis, MB, MCH, FRCS, Gregor Walker, MB, MD, FRCS
Setup and a system should be in place for this to be

done rapidly and safely.
The setting in which a neonate needs to be
cannulated for ECMO support is usually stress-
ful and therefore it is vital that systems are in
place that make the procedure as “routine” as
possible and minimize the need for “off the cuff”
decisionmaking. Safe and efficient cannulation
requires a number of teams (ie, neonatal medical
and nursing, OR, surgical, perfusion, ECHO,
laboratory) to function as one.
Immediately prior to cannulation, a “team
pause,” or timeout, where the lead clinician
outlines the patient details, the circumstances
leading to the decision to cannulate, and a plan
for cannulating the patient provides a “road
map” which increases team focus and improves
outcomes.1 The important steps of this are out-
lined in Figure 12-1. The authors have found
that the team pause ensures all personnel and
equipment are present (or readily available)
and that everyone understands their role and
the sequence of events planned for a success-
ful cannulation. Starting ECMO flow rates (gas
and blood), blood products, resuscitation drugs,
and the proposed loading dose of heparin are
confirmed. Likely problems are anticipated and
vocalized so all team members can prepare.
Even with modern low volume ECMO
circuits, in neonates, a blood prime is necessary Figure 12-1. Team Pause Checklist for ECMO
cannulation at the Royal Hospital for Children,
Glasgow.
159
Chapter 12
VV- or VA- ECMO? a selection of cannulae immediately available,

so alternative sizes can be chosen once the ves-
Once it has been decided that a baby needs sels have been visualized.
ECMO support, the next decision is whether Single lumen cannulae suitable for VA-
it should be venovenous (VV) or venoarterial ECMO require a large internal lumen with a thin
(VA). In neonates, VV is almost always via but strong wall. This requires the cannula to be
a double lumen cannula (VVDL). Although wire reinforced. Arterial cannulae suitable for
VVDL-ECMO does not provide direct cardiac neonatal use have only an end hole while venous
support, the delivery of well oxygenated blood cannulae also have side holes for better drainage.
to the right atrium invariably improves cardiac Suitable arterial cannulae include the 8 and 10F
output even in unstable neonates requiring high Bio-Medicus (Medtronic, Inc., Dublin Ireland)
dose inotropic support.2 The authors prefer to and suitable venous cannulae include the 8, 10,
support all neonates with VVDL-ECMO where 12, and 14F Bio-Medicus. This range covers
possible. Each center will need to determine babies from approximately 1.6 to >5.0 kg. For
their comfort with commencing VV-ECMO in practical purposes, the only vessels suitable in
such patients. However, VVDL can be convert- the neonate to accept such large cannulae are
ed to VA when VV support proves inadequate. the internal jugular vein (IJV) and the common
Occasions where VA support is required carotid artery (CCA). The right side is the ac-
include smaller infants (<2.5 kg) where the right cess side of choice but left neck cannulation is
internal jugular vein is unlikely to accommodate also possible.
the smallest VVDL cannula (presently the 13F For venovenous ECMO support in neonates,
OriGen cannula). Low cardiac output state as the only viable option is a dual lumen cannula
the result of sepsis or a cardiac anomaly usually inserted via the right IJV (RIJV) into the right
requires VA support. atrium. The recently introduced OriGen 13F
Traditionally, neonates with CDH have re- and 16F dual lumen PEBAX® wire reinforced
ceived VA-ECMO support, partly because they “atrial” cannulas (Origen Biomedical, Austin
are often unstable at the time of cannulation, TX) are suitable for infants between 2.5 to >5.0
but also because the duration of support can kg and can be used with either roller or cen-
be lengthy and VA cannulae are felt to be more trifugal pumps. The authors use a 16F cannula
reliable in long runs. Also, the neck veins in in babies weighing >3.4 kg.
CDH tend to be smaller than equivalent weight Until recently, dual lumen cannulae were
neonates3 and are displaced from their normal unsuitable for centrifugal systems as they
anatomical position, particularly in right-sided were not reinforced to cope with the negative
CDH.4 This becomes more critical in VV than pressures generated by the centrifugal system
VA-ECMO. However, VV-ECMO can and (roller pumps depend on passive drainage by
should be considered in selected cases. gravity). OriGen still supplies a 15F polyure-
thane, non-reinforced dual lumen VV cannula
Choice of Cannula and Vessel that is suitable for use with roller pumps only.
Covidien (now Medtronic Inc., Dublin, Ireland)
The surgeon should ensure there is a choice also makes a non-reinforced 14F dual lumen
of suitable cannulae available at the time of catheter. Only reinforced cannulae are suitable
cannulation. Based on weight and required flow, for use with centrifugal pump systems.
each center should have a chart that helps with Bicaval cannulae are unsuitable for neo-
cannula selection based on known cannula pres- nates as the 13F Avalon Elite Bicaval (Maquet
sure/flow characteristics. It is advisable to have Cardiovascular, LLC., Wayne NJ) dual lumen
160
ECLS Cannulation for Neonates with Respiratory failure
cannula was withdrawn because of a high in-

cidence of complications.5 Although the 16F
version is available, it should be reserved for
older children. There is no role for cephalad
cannulae in neonatal VV-ECMO.6
Cannulation Technique
Patient Position and Preparation
As a rule, neonatal cannulation is under-

taken in the NICU on an open bassinette. The
patient is paralyzed, sedated, and given suitable
analgesia. The patient is placed with their head
towards the surgeon, with a small roll under
the shoulders to extend the neck and with the
head turned to the left to maximally expose the
right side. A small amount of Trendelenburg
(head down) position is recommended until the
vessels are cannulated. Care must be taken to
ensure adequate vascular access and a well se-
cured endotracheal. Resuscitation drugs should
be prepared and available. In open cannulations,
atropine should be available as irritation of the
vagus nerve can cause bradycardia. Also, lido-
caine can be used topically to relax vessels that
go into spasm if handled. A diathermy (Bovie)
pad should be placed on the patient.
Echocardiography should be available,
particularly for VVDL-ECMO, as it is essential
to visualize the cannula in the heart to confirm Figure 12-2. Top: Echocardiographic views
good position and direction of the return jet of a VVDL cannula is a good position. Note
(Figure 12-2). For VA cannulation, confirma- the Eustachian valve is just beyond the catheter
tion of cannula position following cannulation and can cause problems with venous drainage
if the cannula is too low. Middle: Demonstrat-
is best practice and essential if any difficulty ing optimal direction of the return jet towards
achieving full and consistent ECMO flows the tricuspid valve. Bottom: Pseudo-long-axis
ensue. The arterial cannula can be viewed view. The jet is directed appropriately to the
tricuspid valve. In this patient, the TV is not
proximal to the aortic arch, and care should be open, which is why the jet splays.
taken to avoid a lower position as this can cause
aortic valve malfunction. In CDH patients, it
is particularly useful to see the venous cannula
enter the right atrium to avoid malplacement.4
161
Chapter 12
VVDL Percutaneous Technique Steps 10. The authors’ practice is to advance the
introducer about 5 cm beyond the can-
1. Prepare and position patient as described nula tip, and to grip this as the introducer/
above. cannula are advanced over the guidewire
2. After a standard prep and drape, portable into the right internal jugular vein. It is
ultrasound is used to locate the RIJV. A essential to ensure that the ECMO can-
Seldinger technique is used with a small nula does not slip forward or backwards
(22-gauge) needle and a fine (0.018”) on the introducer until the 5 cm of the
guidewire to access the vein with the aid introducer has been inserted into the right
of US guidance. Most VVDL cannulae internal jugular vein. During this process
come with an insertion kit although, for it is also essential to keep a firm grip on
initial access, the authors favor the 4F the guidewire to ensure this is held steady
access system produced by Merit Medi- and not also introduced further.
cal (Prelude® Sheath Introducer). The 11. With the introducer held steady, the can-
presence of the guidewire in the right nula is gently slid forward on the static
atrium, demonstrated by echocardiogra- introducer with a slight left-right wrist
phy, confirms correct venous placement. rotation action (“wiggling”) to facilitate
3. The 0.018” guidewire should be upsized advancement. It is imperative that the
to the more robust 0.035” guidewire be- introducer not be advanced beyond 5 cm
fore advancing dilators/cannulae. to avoid atrial injury and possible cardiac
4. Make a small incision in the neck around tamponade.
the guidewire to facilitate dilator/cannu- 12. When the cannula is in the right atrium
lae introduction. (as seen on echocardiography), the intro-
5. Depending on the cannula size, one ducer and guidewire are simultaneously
or two introducer/dilators are used to removed, backflow of blood is confirmed
dilate the skin, subcutaneous tissue and and the venous tubing is clamped with a
venotomy. tubing clamp. A finger over the connec-
6. As each dilator is withdrawn, some gentle tor prevents blood loss prior to clamping.
pressure on the neck by an assistant will 13. A second tubing clamp is used for the
stop any bleeding. “arterial” tubing and the cap is removed. If
7. When exchanging dilators, ask for confir- the patient has low intravascular volume,
mation that the tip of the guidewire has a small amount of pressure on the liver
not changed to avoid the guidewire being will bring blood up into the tubing.
inadvertently withdrawn, or advanced 14. The authors recommend clamping the
into the right ventricle (or through the venous tubing from the right and the “ar-
atrial wall). terial” tubing from the left as best practice.
8. Prepare the cannula by placing the appro- 15. The cannula needs to be orientated such
priate introducer down the venous limb of that the “arterial” tubing is anteromedial
the cannula. Ensure the arterial (return) and the venous tubing posterolateral.
limb of the VVDL cannula is capped. 16. Ensure the tubing is free of air bubbles,
9. A heparin bolus of 50-100 U/kg is given particularly at the junctions of the con-
at this stage (if ECMO flows are not nectors.
established within 20 minutes, another 17. The ECMO circuit is connected. The
bolus should be given). authors always connect the return tubing
162
to the “arterial” limb first, ensuring this VA Open Technique

tubing comes from the oxygenator.
18. Good position of the cannula is confirmed 1. Prepare and position patient as recom-
on echocardiography at optimal ECMO mended above.
flow to ensure the return jet is directed at 2. Either make a 2-3 cm transverse incision
the tricuspid valve. as described above or an oblique inci-
19. The cannula is fixed firmly in place with sion parallel with sternomastoid can be
2.0 Ethibond or silk sutures. An occlusive used (the former has a better cosmetic
dressing is applied. appearance).
3. The sternomastoid muscle is separated
VVDL Semi-open Technique and retracted to display the carotid sheath,
which is opened.
1. Positioning and prepare as above. 4. It is best to isolate the RCCA initially,
2. A transverse 2 cm incision over the right leaving the RIJV undisturbed. It is found
sternomastoid muscle about 1 cm above medial and deep to the internal jugular
the clavicle is used. vein, and once identified, it should be
3. The sternomastoid fibres are separated slung with two 2-0 silk loops. Ensure the
using retractors just enough to visualise vagus nerve is identified and untouched
the anterior surface of the IJV. No deeper to avoid bradycardia.
dissection is undertaken to preserve the 5. Without occluding the RCCA, a heparin
natural tissue support for the internal bolus 50-100 U/kg is given (if ECMO
jugular vein. flows are not established within 20 min-
4. The 24-gauge catheter is introduced utes, another bolus should be given)
through the skin a few centimetres above 6. Ligate the RCCA cephalad with 2-0 silk
the incision and inserted into the IJV over a short silicone bootie. The ends are
under direct vision. The 0.035” guide- left long and clipped as they form a useful
wire is introduced through the needle method of retracting the vessel and will
and advanced into the right atrium under be used later for final cannula fixation.
echocardiographic control. 7. A bulldog clip is placed on the artery as
5. The remainder of the cannulation fol- centrally (low) as possible and an arteri-
lows the guidelines for the percutaneous otomy formed with an 11 blade. This is
technique above apart from the need for best done by lifting the anterior surface of
formal closure of the wound. the artery with nontoothed forceps and by
incising the artery with a scalpel angled
Rarely, the percutaneous (and semi-open) 45 degrees towards the operator.
technique is unsuccessful, particularly if there 8. The lubricated cannula with introducer
is a large haematoma around the vein. In these in place is gently inserted into the arte-
cases, a formal neck exploration and isolation riotomy, taking care not to damage the
of the RIJV is required. Follow the steps noted intima (vessel dilators may help). The
below for insertion and securing of the venous bulldog clamp is released by the assis-
cannula. tant as the cannula is advanced. Expect a
small amount of bleeding at this point but
this will stop as the cannula is advanced.
It is helpful to pull up on the cephalad tie
to straighten and ensure correct tension
163
Chapter 12
on the artery as the cannula is inserted advanced to achieve a low atrial position;
and advanced. aiming for the level of the nipple is a rea-
9. Advance the cannula gently. Usually, 3 sonable landmark, although accurate po-
cm is an adequate length for the intravas- sitioning with echocardiography is good
cular component of the arterial cannula. practice. (2/3 distance between insertion
Be careful not to advance the cannula site and xiphisternum is a reasonable
too far as it may injure the aortic valve. initial guess).
(1/3 distance between insertion site and 19. The introducer is removed and tubing
xiphisternum is a reasonable initial guess). clamp applied as above. Some pressure
10. Remove the introducer and place a finger of the liver may be required to fill the
immediately on the end to prevent blood cannula with blood.
loss before a tubing clamp is applied. 20. The venous cannula is tied in place as de-
11. Tie the second silk loop down onto the scribed for the arterial cannula above. The
artery and cannula over another silicone authors prefer to use different coloured
bootie. The authors’ practice is to place a silicone booties for artery and vein.
second silk tie around the vessel/bootie/ 21. Final fixation is achieved by tying the
cannula for reassurance. ends of the cephalad ties (artery and vein)
12. Next, the IJV is isolated with two silk ties around the appropriate cannulae. Then,
and ligated cephalad in similar fashion one of the ends is tied to one of the 4 long
to the artery. ends of the ties around the cannula cen-
13. A bulldog clip is placed onto the vein trally. This helps to ensure the cannulae
close to the clavicle. cannot be displaced accidentally.
14. A venotomy is made in the same fashion 22. The ECMO circuit is connected to the
as the artery. cannula tubing using a bubble-free
15. Gently place the introducer and venous technique. It is the authors’ practice to
cannula into the venotomy, holding the always attach the arterial/return cannula
venotomy open with nontoothed forceps. to the ECMO circuit first. Either way, the
Take care with the vein, as it is more surgeon must visually trace the tubing
fragile than the artery and can tear. Gentle (arterial in this case) handed to him/her
cephalad traction is helpful. back to the oxygenator to ensure that it is
16. Once the tip of the introducer/cannula is correctly orientated. This reduces the risk
in place, the bulldog is released by the of inadvertently connecting the ECMO
assistant and the cannula advanced. circuit in reverse configuration.
17. The venous cannula has a number of side 23. Once optimal flow is achieved, the
holes and there will be bleeding from wound is closed in layers after ensuring
these until they are all in the vein lumen. hemostasis.
Until all the side holes are in place, air 24. The cannulae are fixed firmly to the skin
embolism remains a risk. Head-down with 2-0 Ethibond sutures and the wound
position and full paralysis helps prevent is dressed. The surgeon and team should
this complication. not leave until ECMO flow is adequate
18. Great care must be taken to ensure the and the patient has been positioned with
vein is not damaged as the cannula is the head being brought back to a more
advanced, especially as it passes behind central position to facilitate venous drain-
the clavicle. Do not attempt to force it in; age on the contralateral side.
it must “glide” in. The cannula should be
164
Post Cannulation Imaging
For all the above methods, a plain chest

radiograph should be obtained following
the procedure to determine catheter position
(Figures 12-3 through 12-5). The following
should be considered when inspecting the CXR:
• The perforated distal plastic section of the

Biomedicus venous cannula (size 8-14F)
is radiolucent but the tip has a metal “dot”
that is opaque on x-ray and should be sited
1 cm above the diaphragm.
• The entire intracorporeal section of the
Biomedicus arterial cannula is radiopaque,
and the tip should be sited approximately 1
cm below the clavicle.
• Some of the older reinforced OriGen can-
nulae are only partially radiopaque but the
tip is about 5 cm beyond the visible com-
ponent on x-ray.
• Recent reinforced OriGen cannulae are
radiopaque to the tip.
Figure 12-3. Optimal position of Bio-Medicus Figure 12-4. Top: Nonreinforced Origen
venous and arterial cannulae. Note the radi- VVDL cannula in good position. Bottom: Rein-
opaque “dot” at the distal end of the venous forced OriGen VVDL cannula with radiopaque
cannula reinforcement of the cannula.
165
Chapter 12
Decannulation breath-hold in a paralyzed (or sedated) patient.

Pressure is applied to the exit site and, while still
Decannulation (see Chapter 16), after per- applying pressure, a single absorbable suture is
cutaneous and semi-open VVDL cannulation is used to close the skin. This is an important step
straightforward; simply requiring the cannula to stop bleeding from the site (and will shorten
to be withdrawn after discontinuing ECMO and greatly the time needed to apply pressure!).
clamping the tubes. Again, care must be taken Decannulation after VA-ECMO requires a
to avoid air embolism, so it is advisable to have formal operation with paralysis, sedation, and
the patient in a head-down position and a short analgesia. The wound is reopened. The site
of vessel cannulation is exposed to achieve
vascular control proximally and distally with
2-0 silk loops around the vessels. The previ-
ously placed silicone booties protect the vessels
when incising the silk ties with a scalpel and
this facilitates vessel repair. The highest risk of
air embolus is during venous cannula removal
due to the numerous side holes; so the authors
recommend removing this cannula first to allow
rapid reinstitution of ECMO support in the case
of air embolus. While removing the venous can-
nula the medical team should give a ventilator
“inspiratory hold” to minimize the chance of
venous air embolism. A Satinsky vascular clamp
is used to occlude the central vein as the can-
nula is removed. Once the venous cannula has
been removed +/- repaired, the arterial cannula
is removed in identical fashion.
It is the authors’ practice to repair the ves-
sels (especially the RCCA) in all but the longest
runs. Bulldog clamps are placed cephalad and
centrally on the vessels to gain control. The
arteriotomy (and venotomy where appropriate)
is closed with 6-0 or 7-0 polypropylene. Ensure
the lumen of the vessel is filled with heparinized
saline and remove the cephalad clamp, allow the
artery to fill with blood before the central clamp
is removed. If the vessels are in poor condition
(usually after long runs) they should be tied
off with nonabsorbable ties. The neck wound
is closed in layers with absorbable sutures ac-
cording to personal preference.
Figure 12-5. Top: Biomedicus venous and
arterial cannulae in a patient with left CDH.
Bottom: OriGen VVDL cannula in a patient
with left CDH.
166
References
1. Haynes AB, Weisner TG, Berry WR et al. A

surgical safety checklist to reduce morbidity
and mortality in a global population. N Eng
J Med 2009;360:491-499.
2. Roberts N, Westrope C, Pooboni SK et
al. Venovenous extracorporeal membrane
oxygenation for respiratory failure in
inotrope dependent neonates. ASAIO J
2003;49(5):558-571.
3. Frenckner B, Palmar K, Linden V. Neonates
with congenital diaphragmatic hernia have
smaller neck veins than other neonates – an
alternative route for cannulation. J Pediatr
Surg 2002;37(6):906-908.
4. Fisher JC, Jefferson RA, Kuenzler KA, Sto-
lar CJ, Arkovitz MS. Challenges to cannula-
tion for extracorporeal support in neonates
with right-sided congenital diaphragmatic
hernia. J Pediatr Surg 2007;42(12):2123-
2128, 2007
5. Speggiorin S, Robinson SG, Harvey C,
et al. Experience with the Avalon bicaval
double-lumen veno-venous cannula for
neonatal respiratory support. Perfusion
2015;30(3):250-254.
6. Skarsgard ED,Salt DR,Lee SK. Extracor-
poreal Life Support Organization Registry.
Venovenous extracorporeal membrane
oxygenation in neonatal respiratory fail-
ure: does routine, cephalad jugular drain-
age improve outcome? J Pediatr Surgery
2004;39(5):672-676.
167
13
Congenital Comorbidities among Neonatal Extracorporeal Life Support (ECLS)

Patients with Respiratory Failure
Javier Kattan, MD, Mark T. Ogino, MD
Background Congenital Anomalies
With the evolution in the past few decades Pulmonary

of neonatal intensive care treatments and extra-
corporeal life support (ECLS), more complex Disease categories for pulmonary comor-
and severe cases have been selected to receive bidities can be grouped as: surfactant protein
ECLS with the consequent increase in mortality deficiencies, alveolar capillary dysplasia,
and morbidity rates in newborns who receive anomalies of airways and lung parenchyma,
ECLS suffering from hypoxic respiratory failure thoracic dystrophies, and disorders of the
(HRF) and persistent pulmonary hypertension diaphragm (Figure 13-1 and 13-2). These and
of the newborn (PPHN). Special attention to other pulmonary anomalies are reviewed in
neonatal comorbidities during ECLS will help Chapter 9 and 10.
clinicians anticipate complications, improve Chronic Lung Disease/Bronchopulmonary
survival, and decrease short and long-term mor- Dysplasia. No systematic studies of neonates
bidities. An understanding of comorbidities is with CLS/BPD exist but case reports of suc-
essential to improve selection criteria for ECLS cessful support with ECLS have been reported.
for complex newborn cases. A review of the In a review of the ELSO Registry, Smith et al.
ELSO Registry by Zabrocki et al. reported the showed that survival to discharge in neonates
impact of comorbidities in the Pediatric ECLS who are cannulated after day 7 of life was sig-
cohort’s survival statistics.1 Comorbidities re- nificantly lower (61% vs. 83%) than in neonates
lated to ECLS in neonatal HRF and/or PPHN cannulated at 1 week of age or less.2 However
can be congenital or acquired in origin. The the older neonates had a lower rate of intracra-
congenital comorbidities will be the primary nial hemorrhage than the younger group.
focus of this chapter and the acquired comor-
bidities will be discussed in chapters specific to Cardiac
the organ system.
The most common cardiac diagnoses within
the ELSO Registry include myocarditis, cardio-
myopathy, intractable arrhythmias with hemo-
dynamic compromise, pulmonary hypertension,
and unique ventricular circulation.3 Respiratory
169
Chapter 13
ECLS support can be complicated by difficult patients. Neonatal cardiac patients placed on
to diagnose cardiac or vascular comorbidities ECLS were reviewed by Grist et al. to deter-
in neonates that may present as severe PPHN. mine the first adjusted anion gap (AGc), the
Poor outcome in these patients relates to the first venoarterial carbon dioxide (CO2) gradi-
high incidence of cardiovascular collapse and ent (p[v-a]CO2), and the first Viability Index
end-organ dysfunction; therefore, early echo- (AGc + p[v-a]CO2 = VI) on ECLS.6 Some key
cardiography is recommended for neonates clinical indicators were identified for increased
with presumed PPHN. Ten percent of ECLS mortality: an AGc ≥ 23 mEq/L, a p[v-a]CO2 ≥
referrals, all with presumed PPHN, were found 16 mmHg, and a VI ≥ 28. An elevated AGc and
to have congenital heart disease (CHD).4 The VI correlated with a significantly higher risk
most common diagnoses being transposition of for mortality, with survival to discharge being
the great arteries, total anomalous pulmonary 20% or less.6
venous return, then left-sided heart obstructive
lesions.4 Computed tomographic angiography Gastrointestinal
and cardiac catheterization can be used in CHD
patients receiving ECLS to define extra and Abdominal wall defects are related to PPHN
intracardiac anatomy in the chest (see Chapter or lung hypoplasia and have sufficient severity
10).5 Mortality in the CHD group diagnosed to develop HRF and hemodynamic instability.7
while on ECLS was 50%, compared with 11% Although omphalocele and gastroschisis may
for correctly identified CHD patients.4 This produce HRF due to PPHN the use of ECMO
observation reaffirms the importance of basing to support these patients seems rare.8
neonatal ECLS support in centers with cardiac Abdominal compartment syndrome (ACS),
surgical services.4 an acquired comorbidity associated with ab-
ECLS intervention prior to severe organ dominal wall defect repair or other abdominal
failure may improve survival in neonatal cardiac surgeries, can lead to compromise in venous
Figure 13-1. VA-ECLS in a newborn with PPHN, finally diagnosed as an alveolar capillary dysplasia
by a biopsy. A) X-ray on ECLS; B) & C) histology showing vascular and capillary misalignment.
170
Congenital Comorbidities among Neonatal ECLS Patients with Respiratory Failure
blood return ECLS support.9 This ACS occurs or PPHN.14 Frequent causes of CRD include uri-
especially in patients with massive capillary nary obstruction (eg, posterior urethral valves),
leak and post abdominal surgery patients with renal dysplasia, and vesicoureteral reflux. In
an increasing abdominal distension. Timely the past, the prognosis in these high-risk cases
placement of a peritoneal dialysis catheter and was extremely poor, although successful sup-
drainage of peritoneal fluid can improve venous port with ECLS in neonates with CRD has been
return and improve oxygen delivery by improv- reported.14,15 Factors associated with success-
ing ECMO flows.10,11 ful long-term outcome include renal disease
amenable to surgical correction, aggressive
Renal Disease nutritional support, and a reliable social sup-
port system.14,15
Acute kidney injury (AKI) frequently Wightman et al. recently investigated the
complicates neonatal critical illness resulting prevalence and survival to discharge of neonates
especially in newborns with HRF and PPHN with underlying kidney disease who received
on ECLS (approximately 50%), significantly in- ECLS from 1989 to 2012. They analyzed the
creasing ECMO duration and mortality rate.12,13 28,755 neonates from the ELSO Registry and
Renal replacement therapy due to acute kidney reported that survival was lower in neonates
injury while on ECLS is independently associ- with kidney disease (49% vs. 82% pulmonary
ated with neonatal mortality12,13 (see Chapter 62). failure without CDH, 25% vs. 51% pulmonary
Oligohydramnios often occurs in associa- with CDH, 21% vs. 41% cardiac diagnosis),
tion with congenital renal disease (CRD) and suggesting that kidney disease be considered
may result in the development of HRF from when evaluating ECLS candidacy.16
pulmonary hypoplasia, delayed lung maturation,
Figure 13-2. Multivariate analysis of factors associated with ECMO or death. (Pediatr Crit Care Med.
2013 Nov;14(9):876-883)
171
Chapter 13
An extensive discussion on treatment op- poorly understood. Wu et al. reported the risk
tions for congenital renal disease extends be- factors and radiologic features of sinovenous
yond the scope of this chapter. The use of RRT thrombosis in neonates of greater than 36
and other renal failure treatment modalities is weeks’ gestational age occurring over an 11-
discussed in chapter 62. year period.17 Of 29 patients, 29% received
ECLS treatment, and 23% had CHD. Genetic
Hematologic thrombophilias were present in four of the seven
infants tested. Eighteen neonates had multiple
Family history of blood dyscrasias should maternal, neonatal, perinatal, or prothrombotic
alert the clinician of possible hemostatic prob- complications. Venous sinus thrombosis was
lems; however, diagnostic confirmation in the often accompanied by infarction (50%) or in-
neonatal period often proves difficult to estab- traventricular hemorrhage (33%).17,18
lish due to the dynamic nature of coagulation
factors associated with postmenstrual age and Immunodeficiency
impact of stress on neonatal factor levels. ECLS
masks hematologic disorders even further due Primary immunodeficiency disorders
to consumption and replacement of coagula- (PID) are rare with an estimated incidence of
tion factors during the ECLS course. Suspicion 1 in 1200 live births in the United States,19,20,21
of a congenital hematologic disorder requires making the probability of encountering such a
monitoring and testing after decannulation condition extremely rare in potential neonatal
and recovery from primary condition leading ECLS candidates. Recognizing PID in the
to ECLS. critically ill neonate is difficult in the absence
Diagnostic categories to consider are of physical findings suggestive of immunode-
hemorrhagic and thromboembolic. Neonatal ficiency syndromes. These syndromes include
diagnoses include: 22q11.2 deletion syndrome, Wiskott-Aldrich
syndrome, and X-linked ectodermal dysplasia.19
• Hereditary Hemorrhage Disorders: Hemo- Newborn screening can detect T-cell PID21 and
philia A/B, Von Willebrand disease may alert the clinician to an early recognition of
• Hereditary Thromboembolic Disorders: these disorders. Disorders of innate immunity,
Prothrombotic disorders, Activated Protein complement deficiencies, humoral and cellular
C resistance, Factor V Leiden mutation, immunity may be a causative factor in recur-
Prothrombin gene mutation, AT3 deficiency, rent infections or infections by nosocomial
Protein C deficiency, Protein S deficiency organisms and need to be considered if the
Disseminated Intravascular Coagulation patient survives ECLS support. Identifying a
(DIC). Patients may experience coagulopathy PID also has important implications for other
or disseminated intravascular coagulation prior family members.
to cannulation. Every attempt should be made
to correct existing coagulation abnormalities Malignancies
before cannulation as the addition of heparin
or other anticoagulants will exacerbate these The peak cancer incidence in children is
defects. Few data exist to predict the impact of the first year of life, and 13% of these cases
such complications on outcomes (see Chapters are diagnosed in the neonatal period.22 The
7 and 8). most common neonatal malignancies include
Venous sinus thrombosis. The etiology neuroblastoma (54%), leukemia (13%), renal
of neonatal venous sinus thrombosis remains tumors (13%), and sarcoma (11%).22
172
Hereditary conditions are associated with infectious agents become clinically significant
tumors, but only Wilms tumor, retinoblastoma, pathogens in this population.26 Some bacterial,
and hepatoblastoma present in the neonatal fungal, and viral agents are described below.
period. Genetic conditions, such as Trisomy
21, are associated with neoplasms including Bacterial
leukemia.23 Survival rates generally are lower
for malignancies presenting in the neonatal Bacterial infections continue to be an im-
period; however, newer drug therapies and portant cause of mortality in the neonate around
interventions have resulted in a wide variation the world, with an incidence of 1 to 10 in 1,000
in survival rates and detailed evaluation of the livebirths.27,28 The most common agents of early
malignancy is required for prognostication and onset sepsis are: Streptococcus group B, Esche-
should be considered to determine a neonate’s richia coli, Listeria monocytogenes, Streptococ-
candidacy for ECLS. cus pneumoniae, Haemophilus, Streptococcus
group A, and Staphylococcus aureus.
Infections Listeria monocytogenes. In an ELSO
Registry report of patients between 1975 and
In neonates with septic shock unrespon- 1991, nine neonates received ECLS for severe
sive to conventional medical management, HRF associated with Listeria monocytogenes
ECLS serves as a viable treatment option. In infection.29 The ECLS duration for patients
1990, McCune et al. reported on 100 neonates with Listeria infection (median, 210 hours) was
treated with VA-ECLS of which 10% were prolonged compared to neonates with other di-
due to septic shock.24 The survival rate for the agnoses, a result likely associated with severe
10 neonates was 100%. Neonates with sepsis necrotizing pneumonia. Six of the nine infants
required greater ventilatory support after ECLS (67%) recovered completely.29
and had a higher incidence of chronic lung Legionella. Moscatelli et al. reported
disease (30% vs. 12%) than neonates receiv- the first neonatal case of hospital-acquired
ing ECLS for meconium aspiration syndrome Legionella pneumonia in a newborn with un-
or respiratory distress syndrome. The study diagnosed tracheoesophageal fistula and HRF
showed that neonates with sepsis also suffered requiring VV-ECLS support before fistula repair.
higher rates of intracranial hemorrhage than Standardized multiplex PCR assay allowed
others supported with ECLS (40% vs. 26%).24 early diagnosis.30
Neonatal and pediatric patients with sepsis have Bordetella pertussis. Pertussis carries a
been successfully supported with venovenous high risk of mortality in very young infants.31
support (see Chapter 56). Skinner et al. dem- The mechanism of refractory cardiorespiratory
onstrated that survival in septic patients was failure is complex and not clearly delineated.
higher in the VV-ECLS group (79%) than in Mean age of patients with pertussis placed on
the VA-ECLS group (64%).25 VA-ECLS had ECLS is approximately 90 days (range: 1 day
increased mortality risk after adjustment for to 3 years). Overall mortality is approximately
age, use of vasoactive agents, and advanced 70%.32
respiratory support. The authors suggest that Surgical sepsis. ECLS can aid resolution
when technically feasible, VV-ECLS can be of not only PPHN, but also cardiopulmonary
considered as the first therapeutic choice in this distress due to neonatal sepsis. Surgical sepsis,
patient population.25 such as in cases of gastric rupture, is one of the
Due to the relative immunocompromised most serious causes of surgical sepsis in the
status of a neonate, common and uncommon
173
Chapter 13
neonatal period and is reported to be success- adenovirus, and metapneumovirus.38 Below we

fully treated on ECLS support.33 will review some especial viral infection requir-
Staphylococcus epidermidis and Staphylo- ing ECLS in neonates.
coccus aureus. Secondary nosocomial infec- Adenovirus. In 1994, Kinney et al. reported
tions in the neonatal period, frequently due to on two infants with fulminant early onset sepsis
Staphylococcus epidermidis and Staphylococ- syndrome and HRF secondary to congenital
cus aureus, have been reported to cause severe adenovirus infection successfully treated with
recurrent PPHN, requiring iNO or ECLS.34 ECLS.39 However, ELSO Registry data showed
survival of only 11% among neonates in-
Fungal fected with adenovirus. Neonatal presentation,
acidosis, sepsis, and increased peak inspiratory
Fungal infection before or during ECLS pressure (PIP) are important pre-ECLS factors
increases the odds of mortality, and the mag- associated with in-hospital mortality when
nitude of this effect depends upon the age considering a trial of ECLS; pneumothorax and
group and timing of infection.35 For patients brain hemorrhage were ECLS-related complica-
with fungal infections before ECLS, 82%-89% tions associated with mortality.40
demonstrated presumed clearance during sup- Cytomegalovirus (CMV). In 1992, Tierney
port. Although the risk of mortality increased et al. reported on disseminated CMV infec-
with fungal infections, ongoing infection does tion after ECLS. In parts of the world where
not appear to be a contraindication to initiation CMV-negative blood remains unavailable,
or continuation of support.35 CMV infection has been described post ECLS.
Aspergillus. Infection/colonization is asso- Leukoreduction of blood products is a possible
ciated with a 22% overall survival-to-discharge solution in these cases; however, clear benefits
rate among children supported on ECLS, includ- have not yet been demonstrated.41
ing neonates. The ELSO Registry data confirm Herpes simplex infection (HSV). In a study
that Aspergillus infection can occur among by Prodham et al. neonates with HSV infection
ECLS patients without known immunodeficien- supported on ECLS demonstrated low hospital
cies.36 A high level of suspicion for Aspergillus survival rates (25%).42 Clinical presentation
infection should be maintained when lung dis- with septic shock was associated with higher
ease in patients on ECLS does not improve.36 mortality for the HSV group and mortality
Candida species. Neonatal invasive can- rates have remained unchanged over the last
didiasis is associated with preterm infants and 35 years.42
carries significant morbidity and mortality.37 Human Immunodeficiency Virus (HIV).
Pre-ECMO Candida species infection is associ- The only reported cases of HIV infected patients
ated with increased risk of mortality; however, on ECLS have been in the adult population.43 In-
Pluim et al. reviewed the ELSO Registry but fants born to a mother with HIV infection have
did not differentiate nosocomial versus invasive a lower risk of viral transmission with interven-
congenital disease.35 tions to prevent transmission, which includes
antiretroviral agent treatment.44 The diagnostic
Viral evaluation for HIV infection is typically delayed
until 2 weeks of age; however, DNA PCR test-
Viral infection can cause severe HRF in ing can be performed on the neonate as early as
neonates. Acute respiratory infections in in- the first day of life for a preliminary diagnosis.44
fants are caused most frequently by respiratory Neonates suspected of HIV infection and who
syncytial virus (RSV), influenza, parainfluenza,
174
would benefit from ECLS should be considered Intraventricular Hemorrhage (IVH)

as candidates with the improved survival rates.
Miscellaneous viral pathogens. Human Although neonates with grade 1 IVH are
parvovirus B19 infection is one of the leading generally considered candidates for cannula-
causes of nonimmune hydrops. ECLS support tion for ECMO there is more concern about
for Parvovirus infection has only been reported newborns with grade II or III bleeds. A survey
for myocarditis in the pediatric age group.45 RSV of neonatologists found that most would offer
is a nosocomial infection that has led to nursery ECLS for a newborn with grade II but not grade
outbreaks.46 Neonates with bronchopulmonary III IVH.53 Few data exist to guide management
dysplasia are at risk for severe HRF that requires decision on these complicated patients.
ECLS support.47 Other viral pathogens that lead
to infections of the fetus and neonate include Myopathies
varicella, rubella, enterovirus, and viral hepatitis.
The agents are known biologic teratogens with In 1994 Sandler et al. reported two unre-
the common target organs being neurologic, lated infants with low Apgar scores, pneumo-
ophthalmologic, dermatologic, and gastroin- thoraces, and severe PPHN who were treated
testinal.48 Primary pulmonary infection, as well with ECLS while receiving chemical sedation
as cardiac anomalies that require immediate and neuromuscular paralysis.54 After decannula-
medical intervention, are rare.48 tion from ECLS, hypotonia and hypoventilation
persisted. Neurologic evaluation confirmed that
Neurologic both infants had a congenital myopathy.54
Neonatal Encephalopathy Vascular Variants
Newborns with acute hypoxic/ischemic Common origin of the carotid arteries

events resulting in cerebral injury after a peri- (COCA) is a normal anatomic variant reported
natal event are at risk for developing HRF from to occur in approximately 11% to 15% of the
meconium aspiration syndrome, idiopathic general population, presuming that patients are
pulmonary hypertension, or pneumonia.49 De- at higher risk for adverse neurologic sequelae
spite evidence to support the continued use of owing to potential occlusion of both carotid ar-
ECLS in these defined groups of neonates, rates teries by the arterial cannula. However, Lamers
of impairment among survivors remain high.49 et al. demonstrated that COCA has no predictive
Therapeutic hypothermia provides neuropro- value in determining PDI and MDI outcomes
tection in mature infants exposed to perinatal and no significance in predicting an increased
asphyxia, although in newborn infants treated risk of adverse neurologic sequelae.55 Therefore,
by ECMO/ECLS, the use of mild hypothermia although a common aortic arch variant, COCA
for the first 48 to 72 hours did not result in im- does not appear to increase the risk of neuro-
proved outcomes up to 2 years of age in a recent logic injury in infants undergoing VA ECLS.55
randomized trial in the United Kingdom.50 Data
upon neonates with moderate to severe hypox- Arteriovenous Fistula
emic ischemic encephalopathy (HIE) supported
with ECMO remain limited but relatively posi- ECLS can sustain severely ill neonates with
tive.51,52 Consequently neonates with potential high output heart failure secondary to intracrani-
HIE should be considered for ECMO when al arteriovenous fistula (AVF). In 2004, Burry et
other contraindications do not exist. al. described the first successful novel approach
175
Chapter 13
to the management of high output heart failure Trisomy 21

secondary to an intracranial high-flow dural
arteriovenous fistula (DAVF), performing an The incidence of PPHN is higher in neo-
embolization (coils and liquid embolic agents) natal patients with trisomy 21 when compared
in conjunction with the use of an ECMO/ECLS with the general neonatal population (1.2% vs.
circuit. This report also documents the first use 0.1%).61 Patients with a cardiac indication for
of an ECLS cannula for intraarterial cerebral ECLS have higher mortality compared with
angiography.56 those supported for respiratory indications.
Despite differences in indications for ECLS,
Inborn Errors of Metabolism patients with Down syndrome (DS) have similar
hospital survival rates as those without DS; thus,
Acute signs of an inborn error of metabo- by itself, the diagnosis should not be considered
lism leading to clinical decomposition can pres- a risk factor for in-hospital mortality for ECLS.
ent in a newborn as severe metabolic acidosis, Recently, Gupta et al. evaluated morbidity and
cardiovascular failure, and respiratory fail- mortality associated with ECLS in infants with
ure.57,58 Organic acidurias, urea cycle disorders, DS and heart disease. The most common car-
maple syrup urine disease, and fatty acid oxida- diac defects in this group included common AV
tion disorders can present with life threatening canal (63%) and tetralogy of Fallot (40%). The
conditions. ECMO can provide cardiac and mortality rate was lower in those with DS than
respiratory support while metabolic imbalances in controls (44 vs. 56 %).62 Cashen et al. also
are corrected and can support hemodialysis to recently reported on 30 years of data from the
rescue newborns with metabolic defects (eg, ELSO Registry including 623 patients with DS
urea cycle defects with life threatening hy- and 46,239 control patients. The prevalence of
perammonemia and HRF).57,58 A neonate with DS was 13.5/1000 patients who received ECLS.
medium chain acyl-coenzyme A dehydrogenase There was no significant difference in survival
deficiency (MCAD) was placed on ECMO after between patients with or without DS (63% vs.
a cardiac arrest from ventricular tachycardia and 57%). In DS patients, independent risk factors
fibrillation and survived to discharge .59 for mortality before cannulation included car-
diac indication and milrinone use. Multivariable
Genetic Abnormalities risk factors for mortality while receiving ECLS
included hemorrhagic, neurologic, renal, and
ECLS has been used in children with ge- pulmonary complications.63
netic syndromes with good results including
high survival and few complications. Uppu et Trisomy 13 and Trisomy 18
al. conducted a retrospective review of children
with CHD and genetic syndromes who received These genetic disorders have characteris-
ECLS and showed that ECMO/ECLS duration, tic physical features which alert clinicians to
hospital LOS, and mortality were similar in consider a genetic evaluation. Cardiovascular
patients with and without underlying genetic and abdominal wall defects and other organ
abnormality. Among genetically abnormal pa- anomalies are commonly associated with these
tients, renal insufficiency and need for dialysis syndromes, also known as Patau syndrome
were associated with mortality. However, only (Trisomy 13) and Edwards Syndrome (Trisomy
56% were discharged home, and the survivors 18), respectively. In the December 2013 ELSO
had a high late mortality of 42%.60 Neonatal Respiratory Failure Supplement to the
ELSO General Guidelines, both of these diagno-
176
ses were listed as “lethal chromosome disorders” ity despite lower rates of CNS hemorrhage
and contraindications to neonatal respiratory than neonates who received ECLS earlier.2
failure.64 Nelson et al. in a 2016 article reviewed Premature infants cannulated after 1 week had
the survival and surgical interventions for these fewer CNS hemorrhages than premature infants
diagnoses and found that 19.8% of those with treated with ECLS starting within the first week
trisomy 13 and 12.6% of infants with trisomy of life.2 Hardart et al. in 2004 made a similar
18 died in the first year of life, but 10 year conclusion based upon a retrospective study of
survival was higher than previously reported the ELSO Registry between the years of 1992
(12.9% and 9.8%, respectively).65 A survey of and 2000 but found that postconceptual age of
ELSO Neonatal ECMO centers reported some ≤32 weeks was the best age predictor of ECMO
centers would consider ECLS support for this related intracranial bleeds.68 Rozmiarek et al.
population of patients.53 reviewed the ELSO Registry and concluded that
ECLS cannulation for infants less than 2 kg may
Chylothorax and Genetics be safe with a IVH incidence of 5.5%, which is
lower than previously reported.69 A data collec-
Congenital chylothorax occurs rarely in tion survey study of neonatal respiratory center
neonate but carries major morbidity and mor- directors reported that 65% of the respondents
tality. The majority of such infants have associ- would consider neonates with a gestational age
ated chromosomal anomalies, malformations of less than 2 kg as potential ECMO candidates,
(80%), and comorbidities that require prolonged and 58.1% setting 35 weeks or greater as the
intensive care and sometimes ECLS support, lowest gestational age.53 The limits continue to
associated to hypoxic respiratory failure. In a be challenged with the placement of low birth
retrospective series of 10 cases of congenital weight and premature infants with complex
chylothorax, 8 infants were diagnosed ante- congenital heart disease on postcardiotomy and
natally, and 3 of these infants had antenatal perioperative venoarterial ECMO.70,71 Careful
pleural drainage. Postnatal management for anticoagulation management in this group of
chylothorax includes drainage of fluid, ventila- patients is essential to minimize the risk of an
tion, albumin, octreotide, and dietary modifica- intracranial accident.
tion with medium-chain triglyceride-enriched
formula. Noonan syndrome and trisomy 21 are Conclusion
the most common underlying genetic diagnosis
for chylothorax.66 Neonates considered for ECLS can have
multiple comorbidities but many of these com-
Prematurity plications may remain undiagnosed at birth.
However, the longest standing and greatest
Current guidelines for ECLS in neonates experience for the use of ECLS exists in this
continue to list prematurity (less than and equal population. The outcomes of ECLS in neonates
to 32 weeks gestation) and birth weight (less with respiratory failure remain excellent. With
than 2 kg) as relative contraindications.64 These careful evaluation of underlying comorbidities
recommendations derive from a 1987 study that and adherence to appropriate ECLS guidelines,
documented decreased survival and an increase neonatal patients will continue to have excellent
in intraventricular hemorrhage (IVH) in this outcomes.
cohort of newborns.67 Smith et al. demonstrated
recently that neonates cannulated for ECLS
after the first week of life had greater mortal-
177
Chapter 13
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by adenovirus infection successfully treated posures in pregnancy: teratology in ado-
with extracorporeal membrane oxygenation. lescent medicine practice. Adolesc Med.
J Pediatr. 1994;125(1):110-112. 2002;13(2):269-291.
40. Prodhan P, Bhutta AT, Gossett JM, et al. Ex- 49. McNally H, Bennett CC, Elbourne D, Field
tracorporeal membrane oxygenation support DJ; UK Collaborative ECMO Trial Group.
among children with adenovirus infection: a United Kingdom collaborative randomized
review of the extracorporeal life support or- trial of neonatal extracorporeal membrane
ganization registry. Asaio J. 2014;60(1):49- oxygenation: follow-up to age 7 years. Pe-
56. diatrics. 2006;117(5):e845-e854.
41. Tierney AJ, Higa TE, Finer NN. Dissemi- 50. Field D, Juszczak E, Linsell L, et al. Neo-
nated cytomegalovirus infection after extra- natal ECMO Study of Temperature (NEST):
corporeal membrane oxygenation. Pediatr a randomized controlled trial. Pediat-
Infect Dis J. 1992;11(3):241-243. rics. 2013;132(5):e1247-e1256.
42. Prodhan P, Wilkes R, Ross A, et al. Neo- 51. Hirakawa E, Ibara S, Tokuhisa T, et al.
natal herpes virus infection and extracor- Single-center experience of extracorporeal
poreal life support. Pediatr Crit Care Med. membrane oxygenation in 61 neonates. Pe-
2010;11(5):599-602. diatr Int. 2016, epub ahead of print.
43. Cawcutt K, Gallo De Moraes A, Lee SJ, et 52. Massaro A, Rais-Bahrami K, Chang T, et al.
al. The use of ECMO in HIV/AIDS with Therapeutic hypothermia for neonatal en-
Pneumocystis jirovecii pneumonia: a case cephalopathy and extracorporeal membrane
report and review of the literature. ASAIO oxygenation. J Pediatr. 2010;157(3):499-501.
J. 2014;60(5):606-608. 53. Chapman RL, Peterec SM, Bizzarro MJ,
44. American Academy of Pediatrics. Human Mercurio MR. Patient selection for neona-
immunodeficiency virus infection. In: Kim- tal extracorporeal membrane oxygenation:
berlin DW, Brady MT, Jackson MA, Long beyond severity of illness. J Perinatol.
SS, eds. Red Book®: 2015 Report of the 2009;29(9):606-611.
committee on infectious diseases. American 54. Sandler DL, Burchfield DJ, Mccarthy JA,
Academy of Pediatrics; 2015; 453-476. Rojiani AM, Drummond WH. Early-onset
45. Vigneswaran TV, Brown JR, Breuer J, Burch respiratory failure caused by severe con-
M. Parvovirus B19 myocarditis in children: genital neuromuscular disease. J Pediatr.
1994;124(4):636-638.
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55. Lamers LJ, Rowland DG, Seguin JH, Rosen- 63. Cashen K, Thiagarajan RR, Collins JW Jr,
berg EM, Reber KM. The effect of common et al. Extracorporeal membrane oxygen-
origin of the carotid arteries in neurologic ation in pediatric trisomy 21: 30 years of
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Surg. 2004;39(4):532-536. Support Organization Registry. J Pediatr.
56 Burry M, Reig AS, Beierle EA, Chen MK, 2015;167(2):403-408.
Mericle RA. Extracorporeal membrane 64. Extracorporeal Life Support Organization.
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tracranial arteriovenous fistula. Case report. elso.org
J Neurosurg. 2004;100(2):197-200 65. Nelson KE, Rosella LC, Mahant S, Gutt-
57. Wen JX, Feldenberg LR, Abraham E, et mann A. Survival and surgical interven-
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14
Medical Management of the Neonate with Respiratory Failure on ECLS
Shazia Bhombal, MD, Arlene M. Sheehan, RN, NNP, Krisa P. Van Meurs, MD
Fluids, Electrolytes, and Nutrition hypotension may have resulted in acute tubular
necrosis. Continuous renal replacement therapy
Initial daily fluid intake on ECMO is usu- (CRRT) is indicated to accomplish fluid and
ally limited to 60-100 ml/kg/day as the usual solute removal.
neonatal ECMO patient is edematous due to Historically, neonates on ECMO were not
substantial fluid overload prior to cannulation. fed enterally due to concerns regarding intes-
In addition to the usual fluid requirements, tinal perfusion prior to ECMO, intestinal isch-
fluid loss occurs from the oxygenator. Studies emia, and the risk of necrotizing enterocolitis.
of insensible fluid loss from the Quadrox D Gut barrier function and intestinal distension
found loss to be 48.0±2.1 ml per liter of sweep due to obstruction are other concerns. A single
flow.1 Sepsis or hypoxic-ischemic injury may center study over a 5-year period demonstrated
also cause significant capillary leak. Transient that neonates on ECMO tolerated enteral feed-
renal dysfunction with oliguria is common ings well without any serious adverse effects.3
but usually spontaneously resolves over the Infants with congenital diaphragmatic hernia
first 48-72 hours. A natural diuresis phase oc- (CDH) were excluded; however, a notable find-
curs as cardiac output improves, capillary leak ing is that 80% of newborns fed enterally were
resolves, and fluid mobilization takes place. receiving inotropic support. Over the duration
Renal function and fluid balance in newborns of the study the use of enteral feedings increased
with severe cardiorespiratory failure managed from 71% to 94%, and the time to initiation of
with venovenous (VV) ECMO was compared to feeds dropped from 67 to 37 hours. A recent
neonates managed without ECMO.2 VV-ECMO survey of enteral nutrition practices in ECMO
was associated with positive fluid balance, lower centers found that the vast majority of respon-
urine output, and higher BUN and creatinine dents reported providing enteral feeding to
values in the first 96 hours of bypass without neonatal ECMO patients; however, significant
any differences in blood pressure or diuretic variability with regard to diagnostic and clinical
use. These changes are likely due to activation parameters was used to guide decision-making.4
of cytokines by the ECMO circuit. Most of the The American Society for Parenteral and Enteral
positive fluid balance was related to packed red Nutrition (ASPEN) published clinical guide-
blood cells and platelet transfusions. Diuretics lines for nutritional support in neonates sup-
are commonly used following ECMO initiation. ported with ECMO in 2010 that recommended
If urine output does not improve, hypoxia and
183
Chapter 14
starting enteral feedings once the newborn had dium content of blood products. Both sodium
stabilized clinically.5 and potassium requirements may be increased
Caloric intake is optimized through the among patients receiving routine diuretics. Cal-
use of total parenteral nutrition (TPN). Protein cium and magnesium requirements may also be
in the form of amino acids is added, although higher than usual. Metabolic alkalosis may be-
renal protein preparations such as Aminosyn RF come evident due to exposure to large amounts
may be necessary if the blood urea nitrogen is of blood products containing the anticoagulant
elevated.6 ASPEN guidelines recommend that citrate-phosphate-dextran.
nutritional support be initiated expeditiously
as optimal weight gain is difficult to achieve Respiratory
in ECMO neonates given their illness, fluid
restriction, and high protein catabolic rates.5 Demographics
Recommended goals are 100-120 kcal/kg/day
and up to 4 grams/kg/day of protein. Excess ECMO for neonatal respiratory failure is
calories are not helpful as they do not decrease utilized for a variety of diagnoses, including
protein catabolism, but can result in increased meconium aspiration syndrome (MAS), CDH,
carbon dioxide production. Many centers use persistent pulmonary hypertension of the
lipid emulsions as part of the TPN regimen, al- neonate (PPHN), respiratory distress syndrome
though some centers limit lipid infusions during (RDS), sepsis, viral or bacterial pneumonia, and
the early days of treatment due to concern about air leak syndrome. Neonates with respiratory
their use in the context of severe respiratory dis- failure, specifically meconium aspiration, had
ease7,8 and clot formation in the extracorporeal previously comprised the largest ECMO uti-
circuit.9 Ranitidine is usually added prophy- lization group in the ELSO Registry, peaking
lactically to TPN at a dose of 2 mg/kg/day to in 1992 at approximately 1500 cases, falling
attempt to limit the significant complication of steadily in the mid 1990s with introduction of
gastritis-associated gastric bleeding exacerbated inhaled nitric oxide (iNO), surfactant, and high
by anticoagulation.10 frequency ventilation, and stabilizing at ap-
Serum electrolytes are monitored at least proximately 800 cases per year (Figure 14-1).11
daily, and glucose every 12 hours. Serum A review of the ELSO Registry database from
sodium levels may be high due to the high so- 1988-1998 by Roy et al. to evaluate effect of
Figure 14-1. Neonatal ECLS diagnosis by year.11
184
changes in management found that while there ECMO management. Rest settings on VV are
was little variation in the demographics such as usually higher than those used on VA. Typical
mean gestational age, gender, or age at time of VA settings are PIP (cm H20) 15-20, PEEP 5,
ECMO cannulation, there was a change in the Rate 15-20, FiO2 0.21, and typical VV settings
proportion of patients with specific diagnoses.12 are PIP 15-25, PEEP 5-10, Rate 20-30, and FiO2
CDH increased from 18% in 1988 to 26% in 0.30-0.50.16 Some advocate for higher PEEP to
1998 of the neonatal respiratory population, prevent alveolar collapse without compromis-
while RDS decreased from 15% to 4%. The ing venous return. An older multicenter study
reported use of high frequency ventilation, found that high PEEP of 12-14 cm H2O vs. low
surfactant, and iNO increased from 0% for all PEEP of 3-5 cm H2O facilitated lung recovery
three treatment modalities in 1988 to 46%, 36%, and resulted in shorter ECMO runs.17 Continued
and 24% respectively by 1997. As treatment for use of surfactant while on ECMO in the setting
MAS evolved, CDH became the leading indica- of neonatal respiratory failure has demonstrated
tion for neonatal ECMO.13,14 ECMO survival is benefit. One small single center study adminis-
94% in the MAS population and 50% in patients tered surfactant or placebo at hours 2, 8, 20, and
with CDH (Table 14-1).11 A review of the ELSO 32 and found significantly decreased duration of
Registry between 2000-2010 found that patients ECMO, improved pulmonary mechanics, and
with irreversible pulmonary dysplasia, such as reduced complications when compared with a
alveolar capillary dysplasia, surfactant protein placebo group.18
deficiency, and pulmonary lymphangiectasia, Patient arterial blood gases, along with
were placed on ECMO at an older chronologic circuit pre and post oxygenator blood gases,
age and for longer duration than typical patients are obtained every 6-12 hours. Daily chest ra-
with PPHN.15 The authors concluded that these diographs are obtained to confirm line, catheter,
patients are often difficult to distinguish from and tube position; assess lung volume changes
those with PPHN. Suspicion of irreversible following significant atelectasis or collapse;
pulmonary dysplasia and potential lung biopsy and to evaluate free air. Air leaks can be man-
should be considered in patients placed on aged with lower ventilator settings including
ECMO at ≥ 5 days of life and on ECMO for >10 low CPAP settings, decreasing until no further
days. Survival to discharge for this subgroup is air leaks are present, with gentle reexpanding
only 3% compared to survival of 81% in PPHN. of lung over longer period of time. A large or
tension pneumothorax, particularly if obstruct-
Ventilation Strategies ing venous return, requires placement of a chest
tube (see Chapter 61). Radiograph findings
While on ECMO, the lungs are allowed combined with frequent or continuous tidal
to rest and recover from the underlying lung volume measurements and blood gases provide
disease and from barotrauma caused by pre- the ECMO practitioner with the data needed to
formulate a weaning plan.
Table 14-1. Neonatal Respiratory ECMO Routine pulmonary clearance is essential
statistics by diagnosis (1990-2014).11 while on ECMO. Endotracheal suctioning is
recommended every 4-6 hours. Changes in
Diagnosis TotalR Avg Run Longest Run Survival secretions should be noted, including watching
uns Time (Hrs) Time (Hrs)
CDH 6784 266 2549 50%
for blood tinged secretions. Pulmonary hemor-
MAS 7352 138 1327 94% rhage was reported in 4.5% of neonatal patients
PPHN 4388 160 1908 76%
RDS 998 151 1093 83% undergoing ECMO.11 Treatment of pulmonary
Sepsis
Other
2450
2941
152
191
1200
1843
68%
61%
hemorrhage varies with the severity of the event
185
Chapter 14
and includes limitation of suctioning, increasing choscopy in patients with persistent atelectasis
PEEP, decreasing anticoagulation parameters, including removal of secretions and identifying
increasing platelet count target, and instillation infectious etiology.22,23 One institution reported
of dilute epinephrine. their experience in patients on ECMO for car-
diac failure with 15% of patients undergoing
Extubation on ECMO bronchoscopy for continued atelectasis despite
ventilator changes and only found minor com-
Extubation while on ECMO has been uti- plications including bleeding in 6% of bron-
lized in the adult population and in children. A choscopies performed.23 Bronchoscopy was
single center experience with extubation on useful in a majority of the cases, with benefits
ECMO reported a decreased need for sedation including subsequent improvement in aeration
as well as possibly faster resolution of pulmo- and new diagnosis of infection. In neonatal pa-
nary inflammation.19 In this small series, 16 of tients with CDH on ECMO, 8 out of 17 patients
511 ECMO patients were extubated for at least received a therapeutic bronchoscopy on ECMO,
24 hours during their ECMO run. Five of the of which the majority demonstrated radiologic
16 patients were newborns. No complications improvement following bronchoscopy.24 Over-
were seen; however, the authors emphasize that all the procedure was well tolerated with only
emergency procedures need to be modified to minimal complications of bleeding, similar to
allow for emergent reintubation. A case report other studies.
described a neonate on ECMO for biventricular
myocardial hypertrophy extubated to high flow Cardiovascular
nasal cannula (Vapotherm) on day 7 until heart
transplant on day 59 of ECMO.20 Hemodynamic Support
Prone Position Neonates with respiratory failure being

considered for ECMO often require inotropic
Prone positioning should be considered or pressor support. Patients with decreased
in patients on prolonged ECMO support, with cardiac function may still be considered for
benefits including reducing the risk of develop- VV-ECMO. Studies have found that use of
ment of pressure ulcers as well as improving inotropes substantially decrease both in patients
aeration to posterior portions of the lungs and in with VV- and VA-ECMO.25,26 Some centers
alveolar ventilation-perfusion matching. While continue low-dose dopamine during VA-ECMO
positioning requires significant coordination, to improve renal perfusion, though there is no
overall it was well tolerated in a center that clear evidence this practice improves outcomes.
reported placing approximately 60% of their One institution evaluated cardiac function in 15
pediatric ECMO patients prone at some point infants on VV-ECMO and found borderline or
during their bypass course.21 The most com- normal cardiac indices prior to ECMO, with
mon complication was bleeding. There were normalization of function on ECMO.27 The au-
no reports of decannulation or endotracheal thors concluded that VV-ECMO did not worsen
tube dislodgement. cardiac function, potentially due to avoidance
of an increase in LV afterload as seen with VA-
Bronchoscopy ECMO, as well as increased oxygen content
provided to coronary arteries with VV-ECMO.
Studies in the pediatric population on Importantly, echocardiography demon-
ECMO have illustrated the usefulness of bron- strates that institution of VA-ECMO can lead
186
initially to increased myocardial dysfunction.28 PA systolic pressure, and arterial blood pressure
Higher flow rates on VA-ECMO increase after- during the ECMO course.28 In general, cardiac
load, which may account for decreased myo- function initially decreases, and then improves
cardial contractility. In extreme cases, patients over 48-72 hours. PA pressures can also be
can develop myocardial stun as evidenced by followed with echocardiography on ECMO,
dampening of the arterial waveform, and patient demonstrating changes in shunt flow when
PaO2 similar to post oxygenator PO2. Usually pulmonary hypertension improves.
transient, cardiac stun often results from arterial Echocardiography also can play a role
flow directing towards the aortic arch, as well as during ECMO weaning, though more so in
decreased coronary oxygenation compared with the setting of VA-ECMO with assessment in
VV-ECMO. When the arterial cannula flows pressures and function, rather than VV-ECMO,
down the ascending aorta, improvement in car- which relies on assessment of improvements
diac function usually occurs following cannula in oxygenation and pulmonary compliance.
adjustment. Myocardial stun by echocardiogra- In a single center prospective study, authors
phy was reported in 4.5% of neonatal respiratory utilized echocardiography while weaning from
ECMO patients in the ELSO Registry.11 VA-ECMO and found that increased morbidity
and mortality could be predicted by failure to
Hypertension increase velocity time integral (VTI), a surro-
gate for cardiac output.31 Similarly, increases in
Hypertension occurs commonly on ECMO; OI predicted poor outcomes.
12% of neonatal ECMO patients had systolic
hypertension requiring vasodilators (2015 Infection
ELSO Registry).11 One institution noted sys-
temic hypertension in 93% of their neonatal Infections acquired during ECMO are
ECMO population, with an associated increase not uncommon and can significantly increase
in intracranial hemorrhage and plasma renin ECMO duration and decrease survival. A re-
activity.29 Prior to a protocol that medically view of ELSO data from 1998-2008 found
managed systemic hypertension on ECMO, that the overall infection rate for neonates was
50% of neonates at the institution had clinically 7.6% with the incidence increasing with longer
significant intracranial bleeds, compared with runs and in VA-ECMO patients.32 Coagulase-
9% after initiation of the protocol. The authors negative Staphylococci were the most com-
found captopril to be the most effective in low- mon organisms, followed by Candida. The
ering blood pressure. commonly identified organisms had associa-
tions with invasive support (eg, central lines,
Echocardiography endotracheal tubes, and urinary catheters).
Thus, continuing strategies to prevent line and
Echocardiography may be a useful tool ventilator-associated infections should decrease
throughout the ECMO course. Prior to cannula- the nosocomial infection rate of these neonates.
tion echocardiography may unmask underlying Although reducing infections on ECMO is im-
cardiac pathology, including total anomalous portant, the benefit of prophylactic antibiotics
pulmonary venous return. It has been utilized remains unclear, although a review of 11 stud-
during or after cannulation to evaluate cannula ies showed no difference in infection rates.33 A
position.30 Echocardiography has demonstrated survey of ELSO centers demonstrated a varying
changes in cardiac performance while on VA- use of antibiotic prophylaxis on ECMO, reflect-
ECMO, including changes in cardiac function, ing this uncertainty.34 At this time, no strong
187
Chapter 14
evidence shows that routine prophylactic antibi- ECMO as evidenced by spikes in pfHB to over
otics decrease nosocomial infections on ECMO. 100 mg/dl.36 pfHB levels decrease after change
out of the pump head. Patients supported with
ECMO Circuit Considerations in the centrifugal pumps should have routine screen-
Neonatal Patient ing of pfHB. If the level exceeds 50 mg/dl, the
cause should be investigated.37 A small study
Cannulation compared neonatal respiratory patients treated
with roller pumps to those treated with new
Cannulation of the neonate poses several generation centrifugal pumps and a Quadrox
challenges, largely because of small neck vessel oxygenator. The study found increased hemoly-
size, and is covered in Chapter 12. sis, increased need for component change, and
a higher mortality in the centrifugal group.38
Pump Selection The authors concluded that neonates are at a
greater risk of hemolysis than older patients due
A survey of neonatal ECMO centers re- to differences in flow and pressure dynamics
vealed a shift from roller head to centrifugal specific to neonatal centrifugal systems. In a
pumps in the past decade.35 Prior to this time larger study using the ELSO Registry, Barrett
roller pumps were used in almost all neonatal et al. compared outcomes of neonates sup-
ECMO programs. In 2002, a small number of ported with centrifugal or roller pumps.39 The
centers surveyed reported routine use of cen- centrifugal pump group had higher rates of he-
trifugal pumps for neonates, while in a 2011 molysis, hyperbilirubinemia, hypertension, and
survey found that nearly 50% of centers sur- acute renal failure than the roller pump group.
veyed reported using centrifugal blood pumps They separated the centrifugal group into older
for neonatal ECMO.35 vs. newer generation pumps and found the
Centrifugal pumping systems have the ben- same morbidities, but at a lower rate with the
efit of smaller circuit size, less blood-prosthetic newer pumps. They recommended avoidance
surface area and inherent protection against of high flow rates (unspecified) in neonates on
cavitation and overpressurization of the circuit. centrifugal pumps, and careful monitoring for
They do not require gravity drainage and can be hemolysis.
placed closer to the patient. In contrast, roller Loss of pump flow is another issue reported
pumps are less expensive (no disposable cen- with centrifugal pumping systems. Centrifugal
trifugal cone) and simpler in design but have the pumps are nonocclusive and flow dependent.
rare complication of raceway rupture. When patient arterial pressure exceeds pump
Hemolysis occurs commonly with cen- arterial pressure, loss of forward pump flow
trifugal pumps, especially with small cannula, and the potential for retrograde flow from the
due to the shearing force on blood components patient arterial circulation back through the
created by the vortex in the pump head. He- circuit, into the patient venous system can oc-
molysis with resulting elevations in plasma free cur. Retrograde flow is more likely to occur at
hemoglobin (pfHb) can cause vasoconstriction lower pump speeds such as during initiation or
and acute kidney injury. Newer generation weaning and with increases in patient arterial
centrifugal pumps have been designed to have resistance such as hypertension. Small children
less stagnation in the pump head with decreased and neonates are at increased risk of retrograde
hemolysis. Despite design improvements there flow because of lower pump flow rates than
remain recent reports of patients supported on adults. A study comparing three centrifugal
centrifugal pumps exhibiting hemolysis during pumps showed that the Bio-Medicus was the
188
least likely to demonstrate retrograde flow at prime blood is not introduced slowly into the
low speeds, followed by the Rotaflow and Cen- systemic circulation. On VA bypass, flow is
troMag.40 Centers that use centrifugal pumps adequate when the venous saturation is greater
to support children or neonates must educate than 70% and the patient is not acidotic or
specialists to monitor circuit venous pressures hypotensive after pressors have been weaned.
closely and to maintain a patient arterial pres- Ventilator support should be decreased to rest
sure greater than pump arterial pressure. settings. On VV-ECMO, support is adequate if
Additionally, shear forces generated by arterial saturation is in an acceptable range on
ECMO pumps activate platelets causing release low ventilator settings and any hypotension or
of platelet derived micro particles (PMPs). Mi- acidosis resolves. Pump flow can range from
cro particles are small cell-derived vesicles that 80-150 ml/kg/min.
promote thrombosis by exposure of membrane In the event that pump flow is inadequate
phosphatidylserine. In a study comparing roller after commencing bypass, cannula position
and centrifugal pumps using simulated circuits should be evaluated by chest radiograph or ul-
primed with swine blood, the generation of trasound. Once cannula position is optimized,
PMPs was 2.5 times greater in the latter sys- suboptimal ECMO support can be addressed
tems.41 This may be of particular importance with a second, cephalad cannula in the jugular
in the neonatal cardiac ECMO population who vein to augment venous drainage. An 8 or 10 Fr
have a high rate of thrombotic complications.11 arterial cannula is used for this technique (not a
venous cannula) as it does not have side ports.
Circuit Prime If the infant on VV bypass remains hypo-
tensive or hypoxic, inotrope/pressors can be
For neonatal ECMO the circuit is primed continued and ventilator pressures and FiO2
with packed red blood cells (PRBCs) and fresh increased to supplement ECMO support. In-
frozen plasma (FFP) to a hematocrit of 35-45%. jurious ventilator settings should be avoided.
The blood prime is heparinized, and then cal- Conversion to VA-ECMO should be considered,
cium added to correct the hypocalcemia caused although it is a challenging procedure. Cannula-
by citrate anticoagulation. Acidosis is corrected tion of the artery can be done on bypass but the
with bicarbonate. The blood prime is warmed infant will need to be supported off-bypass for
to 37 degrees centigrade unless the infant is replacement of the venous catheter. Alterna-
undergoing hypothermia therapy. In that case, tively, the VV catheter can be left in place and
the blood should be warmed to a temperature both lumens used for drainage but commonly,
of 34 degrees C. the arterial lumen clots
Pump Flow Sweep Gas Flow
Once ECMO is initiated, pump flow should Sweep gas flow is initiated in a 1:1 ratio
be increased over a period of several minutes of blood flow to gas flow. If pump flow is 300
in order to determine the maximal flow that ml/min then sweep flow is 0.3 L/min. Sweep
can be achieved. Subsequently, pump flow flow is adjusted to target an arterial pCO2 of
is decreased to meet patient demand. When 40-45 mmHg unless there is significant pre-
initiating VV bypass it is important to increase cannulation hypercarbia. If significant hyper-
pump flow slowly, as prime blood may have carbia is present prior to cannulation, the pCO2
elevated potassium levels that can cause myo- should be slowly brought into the target range
cardial dysfunction and even asystole if the of 45-50. FiO2 of the sweep gas is started at
189
Chapter 14
60-100% then titrated as needed to keep the Hematologic

post oxygenator PaO2 between 150 and 400
mmHg. Carbon dioxide may be added to the Coagulation Abnormalities
sweep gas or sweep flow can be decreased, once
minimal sweep flow for a particular oxygenator Many newborns that are candidates for
is reached, to prevent hypocarbia. ECMO present with coagulation derangements
When initiating ECMO support it is critical secondary to sepsis or hypoxia. Whenever
to correct hypercapnia slowly. Hypocapnia in possible, factor depletion, thrombocytopenia,
the newborn is associated with cerebral va- and hypofibrinogenemia should be corrected
soconstriction and an increased incidence of (see Chapter 8). It is also important to verify
periventricular leukomalacia, intraventricular that the infant received Vitamin K at birth.
hemorrhage, cerebral palsy, and poor neurode- Daily monitoring of coagulation fac-
velopmental outcome. Rapid changes in blood tors, platelet count, and hematocrit are done
gas carbon dioxide levels may also lead to an every 8-12 hours and deficiencies corrected
increase in neonatal brain injury.42 In-line blood (see Chapter 7). ECMO goals include maintain-
gas system is an important adjunct to monitor ing a platelet count greater than 80,000, hema-
circuit carbon dioxide and blood pH levels. tocrit greater than 35-40%, fibrinogen greater
Near-infrared spectroscopy may be useful than 150 mg/dl, and normal PT and INR.
for monitoring cerebral saturation in neonatal
ECMO patients. Anticoagulation
Weaning Anticoagulation of the neonate on ECMO is

challenging due to immaturity of the coagula-
Weaning from VA- and VV-ECMO support tion system and the propensity for intracranial
is indicated with improvement of chest radio- hemorrhage in the neonate. Anticoagulation
graph, tidal volumes, patient venous saturation, practices are covered in Chapter 7. Surface
and patient arterial blood gases. ECMO pump coating with heparin or coating with other poly-
flow is decreased by 10-20 ml/hour as long as mers may decrease the incidence of bleeding or
venous saturation is >65% and arterial satura- thrombotic complications.
tion is >90%, until 50% bypass is achieved. A new generation of anticoagulants, direct
Sweep FiO2 can also be weaned. At that point thrombin inhibitors (DTIs), has been FDA ap-
ventilator rate may be increased. At 30% bypass, proved in the U.S. since 2000. As yet, there are
ventilator FiO2 should be increased and ECMO no retrospective studies of efficacy or safety of
pump flow weaned until a flow rate of 20 ml/ DTIs in children or infants.
kg/min (10% bypass) is reached, where the pa- Baird et al. performed a retrospective review
tient is considered to be “idling” on ECMO. If of 604 pediatric respiratory and cardiac ECMO
blood gases are adequate, decannulation should patients in a single institution and looked at the
be scheduled. If blood gases are marginal, a impact of ACT and heparin dose on survival.43
trial off bypass support should be considered. Increased heparin dose was predictive of sur-
In patients who have had a long bypass run or vival, independent of all other variables. ACT
have serious complications such as intracranial level was not a predictor of survival. It was sug-
hemorrhage, it may be necessary to use high gested that a potential explanation for improved
frequency ventilation, surfactant replacement, survival was fewer thromboembolic complica-
inotropes or steroids, or iNO to wean off. This tions in the patients that received higher doses
is discussed further in Chapter 16. of heparin. These provocative findings have not
190
been reproduced. Figure 14-2 shows the prob- Neuromonitoring on Neonatal ECMO
ability of survival increasing with increased
heparin administration up to 70 units/kg, then Current techniques for neuromonitoring of
a decline with higher doses. The probability of the neonatal ECMO patient include neurologic
survival based on ACT remains the same (58%) exam, head ultrasound, EEG, amplitude inte-
across all ranges of ACT (150-500 seconds).43 grated EEG (aEEG), and near-infrared spec-
troscopy (NIRS). Close and frequent monitoring
Neurologic System of the neurologic exam is warranted on ECMO.
Clinical identification of intracranial injury (eg,
Neonatal ECMO patients have high risk hemorrhage) is unusual and complicated by
of brain injury with resulting adverse neuro- sedation. Routine pain level scoring should be
developmental outcome. Potential injury can implemented and appropriate response evalu-
be attributed to the underlying disease process ated throughout the ECMO course.
leading to ECMO as well as to accompanying Intracranial hemorrhage (ICH), the most
hypoxia, hypotension, and hypocarbia. Can- significant complications in neonates on ECMO,
nulation produces further alterations in cerebral occurs in 7.5%, and the incidence of cerebral
blood flow related to ligation of the right jugular infarction is also noteworthy at 6.9%.11 In an
vein and the right carotid artery, resulting in analysis of the ELSO Registry, gestational age
cerebral ischemia, reperfusion injury, and loss was the strongest predictor of ICH in neonates
of cerebral autoregulation. Neonatal ECMO on ECMO but pre-ECMO factors included
survivors have a significant incidence of neuro- acidosis, primary diagnosis of sepsis, coagu-
imaging abnormalities and neurodevelopmental lopathy, and treatment with epinephrine.44 The
disability (see Chapter 17). Thus, regular as- prevalence of intracranial lesions was found
sessment of the neurologic exam, daily head in another large study to be lower in neonates
ultrasound, and consideration of other neuro- receiving VV-ECMO (12.7% versus 17.4%,
diagnostic modalities are advisable. Prompt p=0.1).45 The strongest predictor of disability
recognition of potentially treatable conditions in ECMO survivors is the extent and severity
is important to optimize outcome. of abnormality on post-ECMO neuroimaging.46
Head ultrasound (HUS) studies should
be performed prior to the initiation of ECMO,
with serial daily HUS commencing 12-24 hours
after cannulation. Khan et al. have reported
that over 90% of intracranial hemorrhages
occur in the first 5 days of ECMO therapy.47
Some ECMO centers perform HUS less fre-
quently after day 5 or perform daily HUS only
in high risk infants or infants with abnormal
HUS pre-ECMO or immediately following
cannulation.47-49 Aminocaproic acid (Amicar),
an inhibitor of fibrinolysis, has been used to
lower ICH in high risk newborns. A study by
Wilson in 1993 using historical controls found
a significant reduction in ICH in a group of
Figure 14-2. Relationship between heparin neonates treated with Amicar and a low rate
dose and the predicted probability of survival.50 of thrombotic complications.50 A later study of
191
Chapter 14
Amicar use in the same institution concluded effects following cannulation, suggesting that
that Amicar did not alter the rate of ICH when adverse outcomes in ECMO survivors were
compared to ELSO Registry data; however, it due to underlying illness and accompanying
did lower the rate of surgical site bleeding.51 hypoxia and hypoperfusion.
New intracranial hemorrhage or extension of Near-infrared spectroscopy (NIRS) has
ICH on ECMO can be promptly recognized on emerged as an effective, noninvasive technique
HUS. Treatment options are limited. Lowering for neuromonitoring in a variety of intensive
anticoagulation targets and increasing platelet care settings. Oxy-hemoglobin (HbO2) and
count are not often successful and discontinuing deoxy-hemoglobin (HHb) have different near-
ECMO support is usually necessary. infrared absorption spectra, and so regional tis-
Earlier detection of neurologic injury per- sue oxygen saturation (rSO2) can be calculated:
mits therapeutic intervention and potentially can rSO2=HbO2/(HbO2 + HHb). The rSO2 reflects
improve outcomes. Conventional EEG is not a regional balance between oxygen supply and
routinely used in the neonatal ECMO popula- demand of the underlying tissue, similar to a
tion unless seizure activity is suspected. The mixed venous oxygen saturation. Interpretation
ELSO Registry reports clinical seizures in 8.8% of NIRS values must be made in the context
of neonates.11 Abnormalities in serial EEGs dur- of other factors that influence cerebral blood
ing ECMO are helpful in predicting mortality flow and oxygenation such as mean arterial
and neurologic morbidity.52-53 Conversely, the blood pressure, carbon dioxide tension, ane-
combination of normal serial HUS and EEG mia, glucose levels, metabolic rate, and drug
without significant abnormalities appears to administration. While an absolute value of
be highly predictive of normal post-ECMO rSO2 associated with neurologic injury has not
neuroimaging.54 been determined, a cerebral rSO2 <40% during
Amplitude integrated EEG (aEEG) is being cardiac surgery may be associated with early
used with increasing frequency in the NICU. postoperative neuropsychological dysfunction,
This device displays both a limited channel EEG changes, intracellular anaerobic metabo-
EEG recording as well as a compressed aEEG lism, and depletion of high energy phosphates,
trace allowing evaluation of the brain’s back- especially when lasting longer than 10 min-
ground activity, change in that activity over utes.56-58 Fractional Tissue Oxygen Extraction
time, and screening for seizures. aEEG has (FTOE) can be calculated from rSO2 and arterial
the advantage of easy and early clinical use oxygen saturation (SaO2) and is a measure of
with minimal impact on patient care. Studies oxygen extraction of the brain tissue. Toet el
comparing standard EEG and aEEG in neo- al. studied newborns with HIE and found that
nates have found good agreement between the the rSO2 increased and FTOE decreased from
two modalities. Pappas et al. performed serial 24 hours onward in infants with an adverse
aEEG recordings at a variety of time points neurologic outcome but remained normal in
prior to ECMO, after cannulation and prior to infants with normal outcomes.59 High rSO2 and
discharge.55 Abnormal aEEG predicted death low FTOE at 24 hours is felt to be a result of
or moderate to severe intracranial injury with secondary energy failure with less utilization
sensitivity of 1.0, specificity of 0.75, positive of oxygen (Figure 14-3). NIRS monitoring
predictive value to 0.86 and negative predictive on ECMO may help to identify poor cerebral
value of 1.0. Interestingly, infants with adverse oxygen delivery and infants at highest risk of
outcome had abnormal tracings before or within adverse developmental outcome.
the first 24 hours on ECMO but no significant
alteration in aEEG background or lateralizing
192
Therapeutic Hypothermia pothermia to 34°C would improve the outcome

at 2 years of age in newborns requiring ECMO
Therapeutic hypothermia has been shown when compared to normothermia.64 The trial
in large randomized controlled trials and meta- concluded that the use of mild hypothermia did
analyses to result in a statistically significant and not result in an improved outcome for newborns
clinically important reduction in the combined requiring ECMO without evidence of moderate
outcome of mortality or major neurodevelop- or severe HIE.
mental disability for term newborns ≥36 weeks
gestation with moderate to severe encephalopa- Sedation and Analgesia
thy.60 Persistent pulmonary hypertension occurs
commonly in infants who are cooled.61 A recent Infants with severe respiratory failure are
cooling trial reported nitric oxide use in 25-34% frequently heavily sedated, narcotized, and
of cooled infants, and 4-9% required ECMO.62 paralyzed prior to ECMO. However, after can-
Neonatal ECMO programs should be prepared nulation, paralysis is not required to prevent
to provide therapeutic hypothermia on ECMO accidental decannulation and should be dis-
for newborns who meet institutional criteria. continued. Similarly, excessive sedation limits
Cooling on ECMO is easily performed using a the ability to interpret the neurologic status and
temperature probe in the blood path proximal to may inappropriately add to concerns regarding
the arterial cannula, adjusting the ECMO heater/ neurologic injury. Prolonged high cumulative
cooling device to reach and maintain a core doses of opioids and benzodiazepines have been
patient temperature of 33-34 degrees C.63 If an associated with tolerance, physical dependency,
esophageal probe is in place, it can be used to and subsequent withdrawal. Strategies to de-
monitor core temperature by connecting it to the crease cumulative doses and duration of use
Blanketrol cooling device in monitor only mode. include daily interruption or even withholding
Alternately, the Blanketrol can be used to servo of continuous sedation. A study of daily inter-
regulate temperature to 33.5 degrees C with the ruption of sedatives in critically ill adult pa-
ECMO heater/cooling device set at a constant tients on mechanical ventilation found that this
temperature. Given the evidence that mild practice significantly decreased the duration of
hypothermia is neuroprotective for newborns ventilation and length of stay without increas-
with hypoxia-ischemia, a randomized controlled ing complications.65 A study of interruption of
trial, the Neonatal ECMO Study of Temperature sedation and analgesia following cannulation
(NEST), was performed to determine if mild hy- was performed in 20 neonates.66 The authors
found that both midazolam and morphine could
be interrupted for a median of 10.3 hours while
maintaining adequate sedation.
No clinical guidelines have been published
for sedation and analgesia for neonates on
ECMO. Commonly used drugs for analgesia
and sedation include morphine and midazolam.
The pharmacokinetics of midazolam, lorazepam,
and fentanyl are altered on ECMO due to se-
questration of the drug by ECMO circuit com-
Figure 14-3. High cerebral saturation at 24 ponents.67 Morphine may be a good choice for
hours of age is associated with poor neurode- patients on ECMO as drug levels are unaffected.
velopmental outcome
193
Chapter 14
Cephalad Jugular Drainage
The use of a cephalad jugular drain in the

setting of VV-ECMO has several theoretical
advantages including augmented venous return,
reduced recirculation, and cerebral venous
decompression. One study found a lower in-
cidence of intracranial hemorrhage in VA and
VV newborns managed with a cephalad drain
compared to a historical cohort.68 A review of
the ELSO Registry found that survival, compli-
cations, and rates of conversion to VA-ECMO
were similar among neonates on VV-ECMO
with or without a cephalad drain.69
Summary
ECMO has been used for four decades

to support newborns with respiratory failure.
The data gathered through the ELSO Regis-
try, randomized controlled trials, and smaller
clinical studies have demonstrated this suc-
cess, especially when compared to other age
and diagnostic groups. Therapies such as iNO,
surfactant, and HFOV have led to a decrease
in the utilization of ECMO for certain neonatal
disease states. This trend has resulted in fewer,
more complicated patients receiving ECMO
treatment, resulting in longer, more complicated
courses. Bleeding and thrombosis remain sig-
nificant sources of morbidity and mortality. The
future challenge for neonatal ECMO centers lies
in developing techniques that limit complica-
tions and improve survival, while treating fewer
and more complex patients.
194
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199
15
Nursing Management of the Neonate with Respiratory Failure on Extracorporeal

Life Support
Gail M. Faulkner, RGN, RSCN, Maggie M. Hickey, RGN
Nursing care of ECMO patients has surveillance of the Extracorporeal Life Support
evolved over the past 26 years. Technology system during clinical operation.”1 The role of
has changed significantly in recent years and ECMO Specialist can be undertaken by nurses,
nursing practices have been adjusted to reflect respiratory therapists, or perfusionists.
this. Neonatal patients on ECMO have special ECMO is usually considered for severely
nursing requirements and practices have been ill neonates and only as a last resort therapy.2
reviewed and aligned to meet the needs of this Therefore, the parents need to be counselled
unique group of patients. accordingly. If ECMO is ineffective, there is
Caring for neonates on ECMO requires a usually no other treatment option available. The
particular skill set with specific education and nursing care of a neonate facing a negative out-
training. Care of the individual neonate depends come from ECMO must reflect this by preparing
on diagnosis, age, type of ECMO support, and and supporting the parents through this process.
clinical condition. Patient stability must be Both parents and staff require full emotional,
considered when performing daily/continuous psychological, and professional support from
assessments. This will change from nursing a all members of the multidisciplinary team. Ef-
stable neonate on ECMO support to managing fective, clear, honest 2-way communication is
a highly stressful situation with an unstable paramount from referral for ECMO, consent,
neonate developing complications of ECMO. and throughout the ECMO run via meetings
This chapter focuses on nursing care strate- to prepare all members of the family and team.
gies based on experience and expertise span- Time must be spent discussing the care
ning 27 years from the Leicester group (Heart and treatment on ECMO for the neonate re-
Link ECMO Centre: University Hospitals of ceiving support, which may be stressful and
Leicester). time consuming. ECMO patients also do not
The nursing care of ECMO patients is outwardly appear to be critically ill, meaning
unique and differs significantly from nursing a parents, family members, and members of the
baby in the NICU. Since the neonate depends multidisciplinary team may find a negative
entirely on ECMO support, patient or circuit outcome from ECMO difficult and challenging.
problems must be addressed promptly to avoid
severe or fatal complications. The ECMO spe-
cialist role is to provide complete care of the
neonate receiving ECMO support – “continuous
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Chapter 15
Nurse or Technician? of supporting a patient while the underlying dis-

ease process is being managed and treated. For
In Europe and certainly in the UK the role of this reason, it is only considered if a patient’s
the ECMO Specialist is undertaken by a nurse. condition is reversible. However, neonates
There are many different models around the with potentially irreversible lung disease due to
world and the structure of each center’s program suspicions of surfactant B deficiency, alveolar
is bespoke to each individual service. Each cen- capillary dysplasia, or pulmonary hypoplasia
ter must review its structure and make changes may be offered ECMO prior to a definitive
to respond to the changing needs of the patient diagnosis of these life threatening conditions.
population it serves. The approach to any suc- Placement onto ECMO allows a diagnosis to
cessful team is teamwork “a dynamic process be confirmed.
involving two or more healthcare professionals The following sections illustrate the care
with complementary backgrounds and skills, of each system when caring for a neonate on
sharing common health goals and exercising ECMO. These only serve as a guide and each
concerted physical and mental effort in assess- individual center must adapt/adopt their own
ing, planning or evaluating patient care.”3 guidelines and protocols specific to their cen-
The partnership between the ECMO coor- ter’s needs.
dinator and ECMO Specialist is unique. To-
gether the team approach must verbalize and Respiratory
implement patient management goals, which
include review and assessment of daily patient/ Management of the ventilated neonate can
circuit parameters (eg, maintaining cardiovas- be complex, as many ventilated neonates are ex-
cular stability, diuretics, ACT management, and tremely sick, unstable, and cannot tolerate even
sedation guidelines). Communication with all simple procedures. Such intervention can result
members of the multidisciplinary team must be in long periods of recovery or further worsening
clear, concise, and consistent. This will enable of their respiratory condition resulting in treat-
all team members to have a clear understanding ment measures being maximized. An increased
of patient management. The nursing manage- oxygen index (OI) >40 is used to indicate the
ment of a neonate on ECMO must be individual, severity of respiratory distress and is used as
goal directed, and holistic. one referral indicator for ECMO.4 However,
the calculation does not account for neonates
Background receiving nitric oxide (NO) or differences in
OI due to high frequency oscillatory ventilation
Neonates on ECMO present with a variety (HFOV). In recent years, neonates are usually
of conditions–PPHN, MAS, sepsis, RDS, CDH. referred for ECMO when the IO exceeds 25.
The use of ECMO to support neonatal patients Neonates cannulated onto VV or VA-
with severe but potentially reversible respiratory ECMO do not rely on their lungs for gaseous
failure was validated by the UK Collaborative exchange. Mechanical ventilation is weaned
ECMO Trial.4 The 7-year followup for this trial5 to ‘rest settings.’ Typical rest settings for a
confirmed that the use of ECMO resulted in neonate are: PIP 20 cm H2O, PEEP 10 cm H2O,
improved survival without increased morbidity. ventilation rate of 10 bpm, and FiO2 0.3/0.4.
The key message is ECMO should not be used The ECMO Specialist must measure blood
as a “rescue” device, but an evidence based gases/continuous oxygen saturations via pulse
option for neonates with severe respiratory/car- oximetry to ensure the neonate is well supported
diorespiratory failure. ECMO serves as a means
202
Nursing Management of the Neonate with Respiratory Failure on Extracorporeal Life Support
and must meet set parameters as prescribed by susceptible to pressure sores on the shoulders.
the ECMO team directly managing the patient. This risk can be alleviated by raising the head
Endotracheal tube (ETT) position must be of the bed, evenly distributing pressure across
reviewed on the latest chest radiograph to assure the shoulders, neck, and head. Elevation of the
appropriate positioning. Patency and security of arm in front of the face (in the free style posi-
the ETT aid in the neonate’s recovery process. tion) can also relieve pressure on the shoulder
Failure to secure ETT fixation adequately is the and neck. Care should be taken that the neonate
most common reason for unplanned extuba- does not slide down the cot, forcing tension on
tion.6 There is a potential risk of trauma due to the ECMO cannulae and potential inadvertent
reintubation. Tube insertion should be carried decannulation. This risk can be further en-
out by an experienced practitioner. Nasal bleed- hanced by the patient making subtle wriggle
ing due to instrumentation can be severe and movements due to under sedation, so optimal
difficult to manage.11 ET suctioning should be sedation is essential.
guided by the neonate’s condition and disease
process.7 Deep suction beyond the end of the Ventilator-Associated Pneumonia (VAP)
ETT should be measured and recorded, elimi-
nating trauma or perforation of the carina. The VAP develops more than 48 hours pos-
use of a ‘yanker’ sucker and suction catheters tintubation.11 Clinical guidelines/protocols and
for nasal suction should be avoided to prevent education aid in preventing VAP and include
trauma to soft tissue. The use of saline for ET implementation of standard infection and
lavage is contentious. Puchalski8 found that control practice: excellent hand hygiene; use
saline does not aid the removal of secretions, and appropriate disposal of personal protective
but may increase the bacterial colonization of equipment eg, gloves, aprons, goggles/masks;
the lower airways. alcohol rub in place at every bed space for use
by all members of the multidisciplinary team
Prone Positioning on ECMO (and parents). Prevention of aspiration is also
vital–the neonate must be nursed in the semi-
Another strategy employed for the man- recumbent position with elevation of the head
agement of severe respiratory failure is prone of the bed to 30-45°, unless contraindicated.
positioning. Prone positioning can improve Gastric distension should be avoided in enter-
gas exchange. Guérin et al.9 describe how their ally fed neonates to prevent VAP. The ventilator
trial showed that patients with severe ARDS/ circuit should only be changed if soiled or dam-
severe hypoxemia (Pa02:Fi02 ratio of <150 mm aged–scheduled changes are not recommended.
Hg, Fi02 of >0.6, and a PEEP of 5 cm H20) can Equipment must be single use only.
benefit from prone treatment when used early
and in relatively long sessions. This is a strategy Sedation
that is used routinely on/off ECMO to improve
gas exchange in Leicester. Sedatives and analgesia are frequently used
When used in combination with VV-ECMO, in the care of the neonate on ECMO to facili-
18 hours of prone positioning improves both tate tolerance of ECMO, protect cannula, and
oxygenation and respiratory system compli- promote patient comfort. Although inadvertent
ance.10 Gravity has its greatest effect in the decannulation or dislodgement of the cannula
prone position, pressing the shoulders into the is potentially fatal Wildschut et al.12 found that
mattress, particularly if the pelvis is elevated interruption of sedatives and analgesics can
with a roll under the hips, making the neonate occur in neonates on ECMO without increased
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Chapter 15
risk of complications. The use of a sedation vascular resistance, vasopressor support may be
assessment tool Comfort B scale aids in ensur- beneficial. The ECMO Specialist must consider
ing patient comfort and achieving optimum maintaining cardiovascular stability and evalu-
sedation. A bedside neurological assessment ate on a continual basis. One measure to ensure
can be made on sick neonates by practicing a appropriate drug delivery and optimal patient
daily sedation hold; sedation can then be recom- management is to administer all vasoactive
menced following a satisfactory assessment. infusions into the patient’s central line access
Neuromuscular blocking agents (NMBA) are rather than the ECMO circuit. In the event of
used in neonates and infants, despite a lack of a circuit emergency the neonate continues to
guidelines and professional standards.13 NMBA receive vasoactive drugs/infusions.
are most often used at ECMO cannulation, or Echocardiography is required on admission,
for other procedures but are becoming less com- periodically during the ECMO run, and prior
monly used via continuous infusion over long to trial off. Echo confirms cannula placement,
periods due to the complications associated evaluates pulmonary artery pressures, and pro-
with their use. vides insight in response to ECMO support and
trial off support.
Cardiovascular
Neurological
The nursing care involves continuous moni-
toring of the patient’s heart rate, oxygen satura- At referral the baseline assessment criteria
tions, blood pressure, mixed venous saturations, must include review of head ultrasound scan
and temperature (core/peripheral). Circulatory before ECMO. Neonates with severe respira-
assessments include warmth of extremities, tory failure are usually heavily sedated and
pulses (may be absent on VA support at high paralyzed prior to commencement of ECMO.
flow), blood volume, colour of extremities, After cannulation, paralysis is discontinued but
urine output, presence/absence of edema, and sedation (eg, morphine/midazolam infusions)
capillary refill time. The ECMO Specialist is continued. Daily neurological examinations
must administer vasoactive infusions via central are required. Routine pain level scoring must
venous access or ECMO circuit, maintain ad- be part of the evaluation of the neonate and ap-
equate blood volume, and position the neonate propriate response evaluated and documented
to promote optimal perfusion of extremities and throughout the patient’s treatment.
minimize edema. Close monitoring of neurological status is
Neonates with severe respiratory failure essential due to the potential for brain injury
commonly receive inotropic agents. Usually caused by pre-ECMO hypoxia, acidosis and
following ECMO initiation, inotropic drugs hypo-perfusion. Reducing sedation may prove
are weaned rapidly. In the majority of neo- challenging to the neonate, team members, and
natal respiratory cases, inotropes are weaned family. The ECMO Specialist must ensure
because systemic perfusion is supported with patient safety and ongoing pump flow at all
VA-ECMO or cardiac performance is improved times, as well as maintaining good position and
with increased myocardial oxygen delivery. patency of the cannulas. The pupillary response
Concern that neonates on VV-ECMO require and fontanel size and fullness are evaluated for
greater inotropic support has been dispelled by evidence of increased intracranial pressure. The
studies that revealed they tolerate weaning of neonate is continuously monitored for evidence
such support as well as VA-ECMO patients after of any seizure activity. Movement of extremi-
cannulation.14 If the neonate has low systemic ties, tone, and visual tracking are also essential
204
parts of the neurological assessment15 made are take and output measures and closely monitors
also essential. electrolytes.20 Other basic interventions include
Intracranial hemorrhage (ICH) commonly maintenance of the urinary catheter daily weight
complicates neonatal ECMO. Head ultrasounds and assessment of intravascular volume, .
are recommended and performed to monitor
function. Khan et al.16 found over 90% of ICH Gastrointestinal (GI) Concerns and Nutrition
cases occur in the first 5 days of ECMO. Elec-
troencephalography (EEG) Cerebral Function Neonates in the NICU need a nutritional
Analysing Monitoring (CFAM) are also invalu- care plan to meet their metabolic demand to
able in predicting mortality/neurological mor- assure repair and growth. A dietetics referral en-
bidity.17,18 The combination of active medical sures appropriate nutritional intake. Neonates
and nursing assessment, head ultrasound, and who are cannulated onto ECMO will have had
EEG appears to be highly predictive of post- some degree of hypoxia, acidosis, low cardiac
ECMO outcome as measured by neuroimaging output requiring inotropes, paralysis and seda-
(MRI/CT).19 tion which are all contributing factors in the risk
Meticulous nursing care can help to prevent of developing gastrointestinal related problems.
further neurological compromise. Anticoagula- Common GI complications include bleed-
tion increases the risk of ICH and the ECMO ing, distension, and dysmotility. Instability prior
Specialist must be vigilant in maintaining ACT to initiation of ECMO can place the neonate at
parameters. team. Over heparinization must risk of bowel ischemia. The ECMO Specialist
be avoided and compliance with prescribed must continually monitor the nature and quan-
ACT management parameters must be followed. tity of gastric aspirates, and assess bowel sounds,
Cannulation of the jugular vein can interfere distension, and tenderness. Decompression of
with venous return, so elevating the head of the the stomach is aided by the use of a nasogastric
bed and keeping the neonate’s head midline may tube. However, in some centers jejunal feeding
help minimize this risk. Neurological recovery is preferred to reduce stomach dysfunction and
may be enhanced by minimal handling, ensuring emesis. Naso/orogastric tubes must be assessed
all cares are performed together, and periods of due to the risks of bleeding from the mucous
designated rest and quiet are preserved. membranes of the nasopharynx/oropharynx.
Careful management of enteral feeding and
Fluid Balance–Renal/Elimination bowel elimination is a vital part of the assess-
ment process.
Renal dysfunction in the neonatal ECMO Neonates need a nutritional care plan to
patient is linked to pre-ECMO hypoxia and hy- help reduce the risk associated with the intro-
potension. Fluid overload occurs commonly be- duction of milk. Breast milk is the preferred diet
fore ECMO and increased volume requirements and should be encouraged. A high risk regime
on ECMO may continue due to capillary leak. where small amounts of ‘gut priming’ or trophic
Diuresis is advised once hemodynamic lability feeds are given may avert unwanted complica-
subsides. With insufficient urine output, CVVH tions. An example of a high risk regime would
can aid fluid management. CVVH is connected be commencing at 0.5 mls per kg and increasing
directly to the ECMO circuit via pigtails post 0.5 mls per kg 12 hourly as tolerated. Monitor-
pump/pre oxygenator (see Chapter 62). Basic ing tolerance by aspiration of the nasogastric
nursing care and patient positioning help pre- tube 4 hourly, documenting the amount, and
vent skin breakdown especially with significant describing the content guides the rate at which
oedema. The ECMO Specialist records all in- feeds are increased or decreased.21 When feeds
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Chapter 15
are not tolerated or when gastric feeds cannot tidisciplinary team. Three basic principles
be given, total parental nutrition (TPN) can underpin the management of bleeding: opti-
be administered directly into central access or mization of anticoagulation, drug therapy, and
ECMO circuit. Assessment of administering survival intervention. The ECMO Specialist
TPN includes close monitoring of blood sugars. must maintain adequate levels of anticoagula-
Therefore, minimizing non-nutritional fluid tion, as prescribed, to prevent clotting of the
administration will help to maximize provision circuit, avoid over heparinization and bleeding.
of carbohydrate, fat, and protein.20 The causes of bleeding on ECMO are usually
related to preexisting coagulopathy, circuit re-
Hematological Management/Bleeding lated platelet and factor consumption, and the
use of heparin. The ECMO Specialist must be
Unconjugated bilirubin accounts for most vigilant in inspecting the ECMO cannula, IV
cases of jaundice in neonates and approximately lines, and chest drain sites for bleeding or clot-
60% of term neonates develop jaundice. 22 ting. Changes to the circuit or patient should
Jaundice is often exacerbated hemolysis in the be communicated to the ECMO team. Minor
ECMO circuit caused by ‘drag’ on the venous bleeding can be controlled by correcting any
drainage as a result of hypovolemia and high coagulopathy and reducing the ACT range.
pump rotor flow rates. Control of massive bleeding usually involves
Visual progression of jaundice may indicate surgical intervention and discontinuation of
the level of bilirubin. However, it should not the heparin infusion temporarily. Lowering the
replace actual bilirubin measurement. A chart ACT places a greater risk of circuit thrombosis
is used to plot the bilirubin level and is used as and may lead to component/circuit change.
a guide for ongoing monitoring and treatment. Prevention is key to reducing bleeding on
Phototherapy is most commonly used in the ECMO. Avoidance of discontinuing IV lines or
treatment of unconjugated hyperbilirubine- tubes and reducing the IV access attempts after
mia. It converts bilirubin to a water soluble cannulation. Subcutaneous and intramuscular
cis-form, increasing excretion.23 Maximum injections must be avoided. Sampling of blood
skin exposure is the key to success and often must always occur via the ECMO circuit or IV/
neonates are nursed naked, with the exception arterial access. Extra care is taken on placement
of a small nappy. Care must be taken to prevent of nasogastric/orogastric tubes, mouth care, and
retinal damage. Eyes can be shielded with soft suctioning as once bleeding starts it can be dif-
opaque ‘goggles,’ which must be tight enough ficult to cease on ECMO support.
to prevent them from slipping off the eyes, but
loose enough to prevent restricted blood flow or Hygiene and Skin Care
potential skin damage. These ‘goggles’ should
be removed at intervals to assess the eyes for A complete assessment of the skin is per-
abrasion, dryness, and signs of infection. formed on admission and at regular intervals
during hygiene needs. This includes assessment
Bleeding and Anticoagulation Management of cannulation site, dressing changes and IV
sites, and particular attention to the back of the
Complications of bleeding and thrombosis head, sacrum, and heels. Ultimately identifying
remain a challenge to the ECMO team and patients at risk is part of the ECMO Specialist’s
represent the most important complication responsibility when assessing patient’s needs.
of ECMO. Successful management requires Frequent repositioning of the neonate pro-
vigilance and skill of all members of the mul- motes prevention of skin damage. Reposition-
206
ing is advised 3-4 hourly. Pressure relieving education with regards to the technology, so if
mattresses are used to reduce the incidence of the neonate develops a complication they may
pressure sores. Dressings to the neck and IV have some preparation, aiding them to make
sites are changed as necessary, not on a rou- difficult decisions regarding withdrawal of care.
tine basis. Nutritional status and maintenance When faced with futility, the parents must never
of adequate tissue perfusion are essential for be made to feel that the decision to stop treat-
improving patient outcome. ment depends on them. This decision belongs
to the multidisciplinary team and the inevitable
Family Support outcome clarified for the parents, to avoid the
lingering belief that their baby will survive and
Interventions when caring for a neonate on recover.29 The ECMO team then supports the
ECMO must focus on family centered care. The family through end of life care, often a difficult
skill to acquire. Providing some control in the
nurse and specialist care not only for the patient,
but for the family as well.24 The family must situation, despite the unavoidable outcome,
be included in all aspects of patient care begin- such as with creating a memory box can provide
ning with the referral process, and throughout such control. Other activities include, taking
the stay in the NICU. Because the environment photographs, making handprints and footprints,
is foreign and the parents separated from their and cutting locks of hair. The parents will be
baby, the team should try to make the entire encouraged to take turns holding their baby
while on ECMO. The care givers themselves
family feel they can actively participate in direct
care.25,26,27,28 The team needs to respond to the also require support through this process. Other
needs of each family. Families commonly feel healthcare professionals with skills in end of
life care include pastoral care, social work
in crisis, finding it extremely difficult to process
information. Nursing interventions, where pos- team, and liaison nurses. These teams provide
sible, should promote positive psychosocial care invaluable resources to aid the ECMO Special-
to decrease these feelings of stress, anxiety, andist/multidisciplinary team members, parents and
loss of control. family members throughout this experience.
The ECMO team has to cope with parental The ECMO Specialist continually evaluate the
distress, suffering, and feelings of powerless- needs of the neonate and parent. They must
ness. The ECMO Specialist and team members inquire about specific care needs, be aware of
must support parents and develop strategies religious practices and beliefs, and ensure that
and interventions to minimize parental stress. parents take regular breaks in order to aid sleep,
They should encourage parents to develop a eat, and rest.
relationship with their baby despite the complex
care. If parents require interpreters, the team Conclusion
members must access this support, so the par-
ents can ask questions and feel fully informed, The role of the ECMO Specialist is possibly
thereby reducing stress and anxiety. ECMO one of the most rewarding roles in intensive
team members should encourage parents to care, requiring a holistic approach to nursing
discuss their feelings, anxieties, and experience the critically ill neonate and family members.
in the NICU. Honesty in discussion is essential. As technology has advanced, the ECMO Spe-
In the event of patient deterioration, hope of cialist undertakes the nursing and technical role,
recovery must be balanced with the prospect leading to complete care of the neonate. The
of a negative outcome. This allows families to nurse–patient and nurse–family relationship
find coping strategies. Parents need to receive are crucial to supporting parents through this
207
Chapter 15
traumatic time while their baby is in the NICU.

Providing emotional support, clear, honest
information, and communicating effectively
enables parents to feel safe, involved, and con-
fident during this time.
The ECMO Specialist role is ever changing
and will continue to evolve over time. Continu-
ing education and development of specialist
skills are essential for continuation of safe,
expert care.
208
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I. Chapter 41. ECMO Extracorporeal Car-
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16
Weaning and Decannulation of Neonates with Respiratory Failure on ECLS
Chris Harvey, MB, ChB, MRCS
Weaning risk of circuit related thrombotic complications.

Knowing the diagnosis and the natural history
Neonatal respiratory extracorporeal life of the underlying condition helps in determin-
support (ECLS) provides the shortest run time ing the appropriateness of a trial off (eg, simple
and the best survival (84% to separation from meconium aspiration usually reaches the point
ECMO and 74% to discharge or transfer) of any of weaning before a neonate with confirmed
of the groups in the Extracorporeal Life Support sepsis or congenital diaphragmatic hernia).
Organization (ELSO) Registry.1 Serial chest radiographs should show clearing
Traditionally, as respiratory function im- of the lung parenchyma with corresponding
proves the ECLS flow and sweep are slowly improvement in lung compliance (Figure 16-1).
weaned until the patient achieves good arterial Echocardiography confirms that the pulmonary
gases on minimal ECLS support, while remain- arterial pressure has decreased to below 2/3 sys-
ing on a lung protective ventilation strategy. temic pressures. Inotropes often commenced
Exactly what constitutes minimal depends upon pre-ECLS in attempt to reduce shunting by in-
the circuit configuration used and the individual creasing the systemic pressure should have been
components within the circuit, especially the substantially weaned and any pneumothorax or
oxygenator. Flows from 30-50 ml/kg/min are active air leak should have resolved. If cannu-
often quoted as expectable minimal levels.2 lated for VV-ECMO the readiness for a trial off
Once stable at minimal ECLS support the pa- ECMO can be assessed simply by increasing the
tient may be trailed off ECLS. The downside in
slowly weaning the ECLS flow is the increased
likelihood of circuit related thrombotic compli-
cations. To counter this problem there may be
a need to maintain circuit anticoagulation at a
slightly higher level with an increased risk of
hemorrhagic complications.
An alternative approach maintains the
ECLS flow at approximately 100 ml/kg/min and
to decide on the appropriateness of a trial off
ECLS by evaluating other clinical parameters. Figure 16-1. CXR postcannulation and at trial
Maintaining flow at higher levels reduces the off showing improvement in lung fields.
211
Chapter 16
FiO2 to 1 on the ventilator, a rapid rise of >5% to approximately 100 ml/kg/min to reduce the
in peripheral saturations indicates likely success. risk of circuit thrombosis. If the arterial blood
gases prove unacceptable, reconnection of the
Special Circumstances sweep gas reestablishes ECLS. As flow through
the entire circuit is maintained long trial offs
Occasionally the decision to progress to (6-24 hrs) are possible, especially if arterial
decannulation is not related to clinical improve- blood gases are borderline. The routine use
ment. In such circumstances the most common of inhaled nitric oxide should be avoided and
reason is bleeding, especially intracranially held in reserve should the respiratory function
where a desire to decannulate to prevent further decrease following decannulation. A PaO 2
bleeding overrides the need for a lung protec- >60 mmHg (8 kPa) with a FiO2 of <50 with a
tive ventilatory strategy. The other scenario in maximal peak pressure of 25 cm H2O suggests
which an alternative approach may be consid- that the patient is ready for decannulation.
ered is the “one way wean.” This would apply to
patient in whom ECLS may not be contributing VA Trial off
to a positive clinical outcome but the patient is
not sufficiently moribund or the outlook with Effective weaning of a respiratory patient
conventional critical care not sufficiently bleak on VA-ECLS differs markedly from that of a
for all treatment to be fully withdrawn. The pa- patient receiving support for cardiac failure.
tient is ventilated and decannulated irrespective With cardiac support, a steady “off ECMO”
of the ventilation or cardiovascular support re- state can be established in a relatively short
quired in the hope that continuing conventional time frame. On commencing a trial off from
treatment may yet still yield a positive outcome. cardiac support an acceptable systemic blood
pressure with minimal change in CVP or LA
Neonatal ECMO Trial off pressure without the need to significantly in-
crease inotropic support or give additional fluid
The most common mode of ECMO in resuscitation can assess suitability for decannu-
neonatal respiratory support remains VA1 as lation rapidly. In addition cardiac function can
small vessel size may preclude the placement be quantified with echocardiography. However
of single double lumen VV cannula and no safe with respiratory VA-ECLS support assessment
and reliable option for multiple single lumen of respiratory function over the short term may
venous cannula exists. The management of VA prove inadequate and longer trial off periods
and VV trials differs substantially. may be required to ensure decannulation is safe
as slow recruitment of additional alveoli may
VV Trial off occur with persistence off ECLS support.
As with VV-ECLS, any respiratory trial off
Performing a trial off with patients receiv- VA ECLS begins with increasing the ventilation.
ing VV is simple. Mechanical ventilation is Common practice is to set the ventilation to the
increased from rest settings but not to a point maximum level that the clinical team would ac-
that may injure the lung. The sweep gas is cept in a patient off ECLS with the expectation
then removed from the oxygenator and arterial that this will be rapidly weaned throughout the
blood gases measured. The ventilator is then trial off. Unlike with VV-ECLS, disconnection
adjusted as with any ventilated patient. If the of the sweep gas is not feasible as this results
flow was weaned to assess the suitability to in a right to left shunt and hypoxemia. Flow
perform a trial off then it should be increased to the patient needs to be interrupted while
212
maintaining flow through the pump and oxygen- from the arterial cannula through the oxygenator
ator. Established practice allows blood to flow in a retrograde fashion and the pump returns
through a bridge inserted between the venous blood through the venous cannula to the pa-
and arterial sides of the circuit and to clamp the tient. The sweep is removed and the rpm of the
ECLS cannula. Some centers prefer a perma- ECLS pump is then used to control the left to
nent bridge within the circuit but a bridge may right shunting of blood. If the pump is set to
be added immediately prior to commencing a zero then the neonatal heart would be unlikely
trial off. Infusions of inotropic drugs and seda- to cope with the drop in afterload. With the
tives must be transferred to the patient. Both the pump acting as a brake, increasing the rpm
venous and arterial cannulae are clamped and reduces the flow and vice versa. Flow through
the sweep gas removed. The cannulae need to the circuit of approximately 100-150 ml/min
be flushed every 10-15 minutes to prevent clot suffices to prevent circuit complications. It
formation. Some centers favor increasing the may be necessary to commence a small dose
rate of anticoagulation or giving a single bolus of epinephrine (<0.1 µg/kg/min) or give a fluid
dose to help prevent cannula thrombosis. The bolus of 10 cc/kg to maintain adequate systemic
complexity of recurrent clamping of the can- perfusion. By utilizing the retrograde technique
nula and bridge and the risk of cannula/circuit much longer trials off ECMO (up to 8 hrs) are
thrombosis generally limits the time of safe trial possible without circuit thrombosis or increased
off ECLS to a maximum of 2 hrs. anticoagulant. In addition renal replacement
In order to prevent circuit and cannula therapy may be continued through the ECMO
complications when trailing respiratory neo- circuit. Although this technique has been uti-
nates off VA-ECLS an alternative method lized with centrifugal pumps by reversing the
has been proposed.3 In a retrograde trial off raceway it could also be performed with roller
the flow probe is reversed and the rpm of the pumps.
centrifugal pump is reduced until the systemic
blood pressure exceeds the pressure generated Decannulation
at the pump (Figure 16-2). Blood then flows
VV Decannulation
Once a trial off ECMO is deemed successful

then the cannula should be removed as soon as
is possible to prevent potential complications.
VV decannulation is easier and less surgi-
cally demanding than VA. It does not matter
whether the cannula was inserted utilizing a
full percutaneous approach or with the aid of
a cut down or semi-Seldinger technique the
removal process is the same. The patient is
sedated and paralyzed to prevent the potential
for inadvertent air entrainment. After antimi-
crobial skin preparation a horizontal mattress
suture is placed around the entry point of the
cannula. All securing sutures are then cut and
Figure 16-2. The reversed flow probe with the cannula is withdrawn. Once the cannula
retrograde flow.
tip has completely exited the skin the mattress
213
Chapter 16
suture is quickly tied (Figure 16-3). Usually a lowing repair; however, there is little difference
single suture suffices for full hemostasis with in long-term neurological outcome in neonates
no need to apply pressure over the cannulation that have their carotid repaired vs. ligated.4-8 If
site. A dressing is then applied. the vessel is ligated, alterations in blood flow
within the circle of Willis compensates.9,10 The
VA Decannulation artery should be ligated with either nonabsorb-
able sutures or MRI compatible surgical clips
Decannulation from VA-ECLS requires as neonates post-ECLS may require scanning
surgical intervention. After appropriate anes- to assess neurodevelopmental concerns.
thesia the cannulation site is reopened. The After the carotid artery has been repaired or
carotid artery and jugular vein are exposed. If ligated then the venous cannula can be removed
the vessels have been cannulated for a short from the jugular vein. The vessel is clamped as
period of time (<10 days) and there is no sus- with the artery and the cannula removed. The
picion of local infection then reconstruction of vein may be reconstructed.11 The thin walled
the vessels should be contemplated. Long-term vein more commonly suffers damage than the
carotid artery patency may be reduced follow- artery so repair can prove more difficult. As
ing prolonged cannulation.4 The carotid artery with the artery, ligation of the vessel is not
should be decannulated first. Vascular clamps associated with increased neurological com-
are applied cranially and any retaining sutures plications.12 However, the need for additional
divided. The cannula is removed and the proxi- central venous access often necessitates that a
mal artery is clamped. If the vessel is in good new line may be inserted into the jugular vein
condition with bidirectional flow then direct at this point.13 This is especially relevant if the
closure is possible with a 7-0 or 8-0 Prolene patient is expected to require renal replacement
suture. Occasionally local damage to the ves- therapy post-ECLS when an appropriate sized
sel necessitates excision of a segment of the dialysis cannula can be inserted. If the vein is
artery and a primary end-to-end anastomosis is damaged during decannulation it may retract
performed. It is essential that the repair is good into the thoracic cavity. When this occurs ad-
with no narrowing. If doubt as to the quality equate hemostasis may be achieved simply by
of the reconstruction exists, then the vessels closing the wound. Exploration of the thoracic
should be ligated. Numerous studies suggest cavity is rarely indicated.
that long-term carotid patency rates are high fol- If the vessels are repaired post-ECMO
anticoagulation is considered to reduce the risk
of postoperative cerebrovascular events.14 It is
the practice in our center to continue heparin at
10 units/kg/hr and to commence aspirin. The
heparin is discontinued after the third dose of
aspirin. Aspirin is then continued for 3 months.
Local complications following decannula-
tion from ECMO are rare. Pseudoaneurysms
have been reported and any local swelling at
the cannulation site should be investigated.15,16
Figure 16-3. Horizontal mattress suture.
214
References ter extracorporeal membrane oxygenation.

Am J Dis Child. 1992;146(2):201-207.
1. ELSO. ELSO Registry International Sum- 11. Pearce FB, Kirklin JK, Knott-Craig CJ,
mary. 2016. et al. Patency of internal jugular vein fol-
2. ECMO Extracorporeal Cardiopulmonary lowing repair after ECMO stabilization
Support in Critical Care. In: GM A, WR prior to Berlin Heart implantation: utility
L, G M, JM W, RH B, eds. 4th Edition ed. of repaired vein for subsequent cardiac
Ann Arbor, MI: Extracorporeal life support catheterization and biopsy. Congenit Heart
organization; 2012:217-223. Dis. 2008;3(6):411-414.
3. Westrope C, Harvey C, Robinson S, Speg- 12. Chai PJ, Skaryak LA, Ungerleider RM, et
giorin S, Faulkner G, Peek GJ. Pump con- al. Jugular ligation does not increase intra-
trolled retrograde trial off from VA-ECMO. cranial pressure but does increase bihemi-
ASAIO J. 2013;59(5):517-519. spheric cerebral blood flow and metabolism.
4. Duggan EM, Maitre N, Zhai A, et al. Neo- Crit Care Med. 1995;23(11):1864-1871.
natal carotid repair at ECMO decannula- 13. Rauth TP, Scott BP, Thomason CK, Bar-
tion: patency rates and early neurologic tilson RE, Hann TM, Pietsch JB. Central
outcomes. J Pediatr Surg. 2015;50(1):64-68. venous catheter placement at the time of
5. Adolph V, Bonis S, Falterman K, Arens- extracorporeal membrane oxygenation
man R. Carotid artery repair after pediatric decannulation: is it safe? J Pediatr Surg.
extracorporeal membrane oxygenation. J 2008;43(1):53-57; discussion 58.
Pediatr Surg. 1990;25(8):867-869; discus- 14. Antithrombotic Trialists C. Collaborative
sion 869-870. meta-analysis of randomised trials of an-
6. Desai SA, Stanley C, Gringlas M, et al. tiplatelet therapy for prevention of death,
Five-year follow-up of neonates with recon- myocardial infarction, and stroke in high
structed right common carotid arteries after risk patients. BMJ. 2002;324(7329):71-86.
extracorporeal membrane oxygenation. J 15. Jacobs JP, Goldman AP, Cullen S, et
Pediatr. 1999;134(4):428-433. al. Carotid artery pseudoaneurysm as a
7. Sarioglu A, McGahren ED, Rodgers BM. complication of ECMO. Ann Vasc Surg.
Effects of carotid artery repair following 1997;11(6):630-633.
neonatal extracorporeal membrane oxygen- 16. Duncan AW, Mawson JB, LeBlanc JG,
ation. Pediatr Surg Int. 2000;16(1-2):15-18. Potts JE, Duncan WJ. Imaging of a carotid
8. Hendrikse J, de Vries LS, Groenendaal F. aneurysm in two patients following extra-
Magnetic resonance angiography of ce- corporeal membrane oxygenation therapy.
rebral arteries after neonatal venoarterial Pediatr Cardiol. 2009;30(7):1000-1002.
and venovenous extracorporeal membrane
oxygenation. Stroke. 2006;37(2):e15-17.
9. Mitchell DG, Merton DA, Graziani LJ,
et al. Right carotid artery ligation in
neonates: classification of collateral flow
with color Doppler imaging. Radiology.
1990;175(1):117-123.
10. Lohrer RM, Bejar RF, Simko AJ, Moulton
SL, Cornish JD. Internal carotid artery
blood flow velocities before, during, and af-
215
17
Outcomes, Complications, and Followup of Neonates with Respiratory Failure
Hanneke IJsselstijn, MD, PhD, Marlous J. Madderom, PhD, Aparna Hoskote, MBBS, MD, MRCP
Introduction will be covered separately in this chapter as

this subgroup has different survival rates and
The use of extracorporeal life support morbidity related to the underlying pulmonary
(ECLS) for life-threatening, reversible car- condition. Moreover, supported by the current
diorespiratory failure revolutionized neonatal literature, we will provide a structured frame-
intensive care management resulting in ex- work and recommendations for longitudinal
cellent survival outcomes.1-4 Hitherto almost followup.
29,000 neonates have been treated with ECLS
for neonatal respiratory failure with an overall Early Survival Outcomes
survival to discharge or transfer of 74% as re-
ported to the ELSO Registry.3,5 The excellent The survival outcome of neonates supported
survival outcomes from neonatal ECLS have on ECLS for acute hypoxemic respiratory fail-
produced a growing population of childhood ure varies with the primary diagnosis, and can
survivors. However, the long-term medical and be as high as 95% in neonates with meconium
neurodevelopmental outcomes remain of some aspiration syndrome (MAS) and as low as 50%
concern,4,6-8 particularly in certain diagnostic in those with CDH.1,3,5, 12 Early survival depends
groups such as congenital diaphragmatic hernia on various factors ranging from pre-ECLS
(CDH).4,9,10 If not appropriately identified and variables (primary diagnosis, gestation, age,
managed, these outcomes may evolve over time hypoxemia, acidosis, hemodynamic instability)
into significant long-term neuropsychological to ECLS related factors (type of cannulation,
sequelae with wide ranging implications for duration, complications) to post-ECLS mor-
the health, education, and integration of these bidity.1,12,13 In a retrospective study of neonates
children into society.11 with persistent pulmonary hypertension (PPHN)
In this chapter, we will review survival supported on ECLS between 2000 and 2010,
outcomes, focusing particularly on recent data Lazar and coworkers identified that prematu-
evaluating long-term medical and neurodevel- rity (37 weeks of gestation), acidosis (pH 7.2),
opmental outcomes after respiratory ECLS in and profound hypoxemia were independently
neonates. Outcomes in neonates with cardiac associated with increased mortality. Further-
disease and those supported after extracorporeal more, prolonged ECLS support (>7 days) was
cardiopulmonary resuscitation will be covered associated with a higher risk of mortality in this
in Chapter 25. Outcomes in neonates with CDH cohort than in patients supported for <1 week.12
217
Chapter 17
Similarly, a United Kingdom (UK) study of 718 most worrying complications include bleeding,
neonates over a 13 year period identified that neurological injury, overwhelming sepsis on
lower birth weight, lower gestational age, older ECLS, and any mechanical complication that
age at ECLS, and higher oxygenation index (OI) needs interruption of the ECLS circuit. These
were associated with increased risk of death in may significantly impact survival and long-term
non-CDH neonates; whereas, in neonates with morbidity, in particular neurological morbidity.
CDH, lower birth weight and younger age at A retrospective analysis of the ELSO Registry
ECLS were significant risk factors for death.1 data of 7,405 neonates treated between 2005
and 2010 revealed a higher mortality in those
Late Survival Outcomes with neurologic complications as compared to
those without any neurologic complications (62
Few studies describe long-term survival vs. 36%, respectively).16 The authors found that
after neonatal ECLS. Iguchi and coworkers 20% had acute neurological injury (as defined
showed in a single center retrospective study of as occurrence of brain death, seizures, cerebral
741 children (neonatal and pediatric respiratory infarction, or intracerebral hemorrhage identi-
ECLS) that late death is related to comorbidities. fied by ultrasound or computerized tomography
Infants who were alive at 90 days had five-year imaging). Patient factors (eg, birth weight, need
survival estimates that were highest for MAS for cardiopulmonary resuscitation, pre-ECLS
97.9% (95% CI, 92.0-99.5%) and lowest for severity of illness, use of venoarterial ECLS)
CDH 73.6% (52.3-86.5%).14 were associated with increased neurologic
complications.16 The prevalence of intracranial
Complications with Impact on Long-term abnormalities in ECLS-treated neonates de-
Outcomes scribed in the literature varies from 10-59%.17
The worldwide ELSO Registry data captures
All forms of ECLS have associated risks short-term complications including clinically
and not every child supported on ECLS will diagnosed brain death, seizures (clinical or
experience complications, but the most com- electroencephalographically determined), cen-
mon are bleeding (related to systemic antico- tral nervous system infarction or hemorrhage
agulation), infection, acute neurological injury, in patients supported for neonatal, pediatric
mechanical complications, and lastly failure of respiratory, and cardiac ECLS. Survival in the
recovery and death.3 Anticipation and manage- non-brain death cases with neurologic compli-
ment of complications are crucial to successful cations was lower at about 50% of overall sur-
ECLS support. The type and the incidence of vival rate.3 In the latest ELSO Registry report,5
different complications vary with the type and cerebral infarction and hemorrhage (diagnosed
duration of ECLS, age and weight of the child, by ultrasound/computed tomography scan)
and condition of the child prior to ECLS. Few was seen in 6.9% and 6.5% of neonates with
of these factors are modifiable. Recently, a mul- corresponding survival rates of 53% and 43%
ticenter randomized controlled trial conducted respectively. Although these short-term com-
in the UK to study the benefit of systemic hypo- plications are not an accurate representation of
thermia in neonates supported on ECLS showed long-term problems, they identify a cohort of
no benefit of hypothermia versus normothermia, patients with higher risk. Table 17-1 outlines
but did highlight that up to 50% of neonates at the potential determinants of impaired outcome
2 years had some form of neurodevelopmental following neonatal ECLS.
issues as assessed by formal testing with the Mitigating neurological morbidity during
Bayley Scales of Infant Development.15 The and after ECLS support calls for careful neuro-
218
protective management. This management Long-term Medical Outcomes

begins with ECLS treatment (early referral
before acute hemodynamic or respiratory de- Lung Function
compensation or arrest) to neuro-monitoring
and neuro-surveillance on ECLS, and finally Despite the fact that severe respiratory fail-
to appropriate neurodevelopmental followup ure is the most common indication for ECLS in
after discharge so that all issues are identified the neonatal period, lung function at followup
appropriately and managed promptly. Children usually reveals only mildly reduced forced ex-
with neurologic complications are usually piratory flows. In survivors of the only random-
recognized to be at risk for adverse outcome ized controlled neonatal ECLS trial (UK trial)
at an early stage and are referred appropriately recruited between 1993 and 1995, Beardsmore
for postdischarge care. However, for neonatal et al. showed slightly better lung function at
ECLS survivors without evident acute neuro- one year followup in ECLS-treated children
logic events it is important to receive adequate than in children receiving conventional treat-
long-term aftercare. Most studies that have been ment.18 Lung function results of these UK trial
published for this group were cross-sectional survivors did not significantly differ from those
and in small study populations. In the past few of a cohort of ECLS-treated infants born sev-
years, there has seen a shift towards long-term eral years later.19 In neonatal ECMO survivors,
multidisciplinary evaluations. airflow obstruction is usually mild at school
and adolescent age11 and remains stable over
time in those without CDH.20 Unfortunately,
data on lung morphology after neonatal ECLS
treatment are currently unavailable. Risk factors
Table 17-1. Potential determinants of impaired outcome following neonatal ECMO.11
Outcome Parameter Risk Factor

Lung Function/airflow Diagnosis of RDS, diagnosis of CDH, prolonged duration
Obstruction ECMO, chronic lung disease
Exercise Capacity No significant determinants reported
Physical Growth Diagnosis of CDH
Sensorineural Hearing Loss Diagnosis of CDH, prolonged duration ventilation,*
prolonged duration ECMO, sepsis/bacterial meningitis,*
administration of aminoglycosides,* severe birth
asphyxia,* intracranial abnormalities,* clinical seizures
prior to ECMO
Motor Function Development Low parental socioeconomic status, intracranial
abnormalities, duration of hospitalization
Cognition Intracranial abnormalities, low parental socioeconomic
status, diagnosis of CDH?, duration of hospitalization
Neuropsychological Outcome Intracranial abnormalities, highest mean airway pressure
prior to ECMO
Behavior Need for extra help at school
RDS=Respiratory Distress Syndrome; CDH=Congenital Diaphragmatic Hernia
*Not specific for ECMO treatment but for neonatal intensive care treatment
219
Chapter 17
reported in the literature for persistent airflow The prevalence of bilateral sensorineural
obstruction after neonatal ECLS are diagnosis hearing loss (SNHL) ranges from 3 to 26%
of respiratory distress syndrome, CDH, pro- and has mainly been evaluated in neonates who
longed ECLS duration, and chronic lung disease underwent ECLS in the 1980s and 1990s.26-28 In
(CLD) (Table 17-1).11 a more recent Dutch study in 136 five year old
neonatal ECLS survivors born between 1992
Exercise Tolerance and 2005 the prevalence of bilateral SNHL was
3.7%.29 Risk factors seem to be related to the
Maximal exercise endurance at school age pre-ECLS clinical condition (seizures, PaCO2
in ECLS survivors is normal or decreased in <30 mmHg, pH >7.5, use of furosemide)30 and
comparison to healthy peers11 In a longitudinal neonatal intensive care therapies such as the use
study in 120 neonatal ECLS -survivors aged 5 of aminoglycosides, neuromuscular blocking
to 12 years, maximal exercise endurance dete- agents, and loop diuretics rather than ECLS
riorated significantly over time, irrespective of treatment itself (Table 17-1).7,11,28 This is con-
the underlying diagnosis; the proportion of chil- firmed by the equal prevalence of SNHL (12%)
dren with abnormally low exercise endurance found in both ECLS treated and conventionally
(z-score <-1.96) increased from 7% at 5 years to treated neonates of the UK trial.7 New studies
35% at 12 years.21 Maximal exercise endurance are needed to establish whether innovations in
did not have any significant relationships with: intensive care treatment modalities have dimin-
time on ECMO, duration of ventilatory support ished SNHL prevalence after neonatal ECLS.
prior to ECLS, total duration of ventilatory However, late presentation and identification of
support, prevalence of CLD, physical growth SNHL has been described despite normal initial
parameters, spirometry results, and sports par- clinical auditory brainstem responses before
ticipation. Interestingly, the levels of exercise neonatal ICU discharge, which highlights the
capacity estimated by the parents correlated need for early, routine, audiologic evaluations
positively with the measured maximal exercise throughout childhood for all ECLS graduates.
endurance scores.21 Early detection of hearing loss also provides a
significant advantage for language and commu-
Renal Function nication skills31 which is supported by the fact
that in the Dutch study, language development
Neonates with acute kidney injury (AKI) was favorable.29
during critical illness and ECLS-treatment are
at risk of developing chronic kidney disease Long-term Neurodevelopmental Outcomes
(CKD) in childhood.22-24 In a group of 169 neo-
natal ECLS survivors, both with and without Neurodevelopmental sequelae are com-
AKI, at least one sign of CKD (proteinuria or monly described in several ECLS followup
eGFR <90 ml/min per 1.73 m2) and/or hyper- studies.16,32-35 We describe the different neurode-
tension was observed in 54 (32%) children at a velopmental and neuropsychological outcomes.
mean age of 8 years.23
Neuropsychological Development
Somatic Growth
The mental development scores of neonatal
Physical growth is usually normal in neo- ECLS survivors when tested at the preschool
natal ECLS survivors without CDH.11,25 age are generally favorable, with several report-
ing normal development,4,29,35 both with respect
220
to overall cognition, and speech and language and long-term verbal memory, visual-spatial
development. In the UK trial, severe disability memory, and working memory.40 They reported
(defined as developmental quotient <70 on the more withdrawn/depressed behavior, somatic
Griffiths Mental Developmental Scales) was complaints, and social problems. However, they
found in only 4% of ECLS treated infants at 1 also reported positive feelings of self-esteem
year4 and 17% at 4 years of age.7 Interestingly, and an average health status.
one third (33%) of the survivors experienced Neonatal ECLS survivors without severe
hyperactivity or behavioral difficulties at the neurologic impairment usually have a neuro-
latter age.7 psychological profile characterized by average
Studies of children tested at 5 years of age, intelligence, with significantly lower scores
report intelligence in the normal range36-39 with on attention/concentration (linked to work-
one reporting language development above av- ing speed/information processing speed) and
erage population norms.38 However, at this age, memory tasks. Selective memory loss in late
different problems become apparent such as dif- childhood has been identified in neonatal ECLS
ficulties with visual-spatial and memory tasks, survivors without overt neurological impair-
often associated with concomitant behavioral ment. A significant proportion in that study
problems ranging from somatic complaints to had reduced bilateral hippocampal volumes
hyperactivity and reported impaired health.7,36,39 on brain magnetic resonance imaging (MRI)
Few studies have reported on neurodevel- scans.41 These neuropsychological problems
opmental outcome after the age of five years. In are of significant concern because they put
those tested, normal range intelligence scores the children at risk as they age when more
at school age were not an unusual finding.8,37 In demanding tasks require information to be
the UK Trial, the cognitive outcome classifica- processed faster, attention/concentration to be
tion at 7 years of age was normal in 68% of held longer, and greater information to be stored
ECLS survivors and 70% in the conventionally in the (working) memory. These more subtle
treated group.6 However, in the UK trial 39% of learning deficits can be classified as ‘executive
children needed either special support at regular functioning skills,’ skills needed to develop
education or had special educational needs6 and academic, behavioral, and social functioning.
in a nationwide Dutch cohort this occurred in Because these neuropsychological functions
48% of ECLS survivors.8 Both studies reported start to develop in early childhood but continue
problems with visual and spatial information into young adulthood,42 these children are at risk
processing and hyperactivity and attention/ for ‘growing into deficits.’ When intervention is
concentration problems (low working speed).6,8 not provided at young age, neuropsychological
These sometimes subtle neurodevelopmental deficits may cause a downward spiral, leading
deficits that preschool and school age children to academic failure with resultant emotional and
experience can put them at higher risk for behavioral problems.
school failure compared to healthy children.36
Parents reported more somatic problems for Motor Function Development
their 8 year old children compared to healthy
peers.8 On a positive note, these children seem In the preschool group, motor function de-
to possess well developed self-confidence and velopment scores of neonatal ECMO survivors
self-esteem.8 are usually favorable.11,35 In the UK Trial, sig-
In the only study that reported on neu- nificant motor function delay (ie, scores <-2 SD)
rodevelopmental outcome after school age at 1 year of age was observed in 9% of ECLS
adolescence showed problems with short-term patients and in 8% of those treated conven-
221
Chapter 17
tionally.4 However, when motor function tasks study on infant lung function testing in CDH
become more complex at older age neonatal patients at 6 and 12 months showed evidence
ECLS survivors seem to grow into their deficits. of hyperinflation and abnormal airway patency
Whereas motor function has been reported to be indicative of impaired lung growth. Hyperin-
normal in 84% at 1 year, it was normal in only flation was most prominent in ECLS treated
43% of neonatal ECMO survivors at 7 years.4,6,11 infants who developed CLD.20 In ECLS treated
In a longitudinal nationwide study of neonatal CDH patients lung function deteriorates as chil-
ECMO survivors in the Netherlands, motor dren age; mean (SD) z-score FEV1 decreased
function performance was evaluated at 5, 8 and from -0.71 (0.40) at 5 years to -2.73 (0.61) at 12
12 years. Motor function was normal in 74, 75, years.45,46 A smaller but significant deterioration
and 41%, respectively.43 Most problems were of FEV1 has also been described in a longitu-
encountered with gross motor function, ie, ball dinal study in conventionally ventilated young
skills and balance skills.11,43 Interestingly, actual adult CDH patients with mean (SD) z-score
motor function was worse than perceived motor FEV1 decreasing from -0.8 (1.2) to -1.3 (1.4) be-
function. In the same nationwide Dutch cohort, tween ages 12 and 26.47 To date, only one study
Toussaint and coworkers showed that in 135 on long-term development of lung morphology
eight year olds standard deviation scores of per- using hyperpolarized 3He MRI in CDH patients
ceived motor competence, social competence, is available showing microstructural changes
and self-worth were all significantly higher than with significant differences in the ipsilateral and
in healthy children: 0.18(0.94); 0.35(1.03); and contralateral lungs.48 The large number of venti-
0.32(1.08), respectively. Self-reported feelings lation defects and enlarged alveolar dimensions
of social competence did correlate weakly, but occurring in the ipsilateral and the contralateral
significantly with actual motor performance. lung is worrisome (Figure 17-1).
Perceived motor competence and feelings of
self-worth, however, did not correlate. The Exercise Tolerance
same cohort reported that their overall quality of
life was impaired.44 This suggests that neonatal Although maximal exercise endurance in
ECLS survivors may ‘overrate’ their actual mo- ECLS treated CDH patients tended to be worse
tor performance and that monitoring of motor than in other neonatal ECLS survivors, this dif-
performance and educational aids are important ference was not statistically significant.21
to enable timely and successful intervention.
Further studies are needed to determine whether Sensorineural Hearing Loss
parents are able to adequately estimate the mo-
tor performance of their children. Recently published data on SNHL in
CDH patients show contradictory results; the
Outcomes in Congenital Diaphragmatic prevalence of significant SNHL ranged from
Hernia 2.5% to 32%.29,46,49,50 Differences may be partly
explained by age at followup and selection bias.
Illness severity (eg, prolonged ventilation or
Lung Function ECLS) is a predictor of SNHL in this population.
Not surprisingly, CDH patients who re- Neuropsychological Development

ceived ECLS treatment have the most hypo-
plastic lungs resulting in prolonged artificial The pathway of neuropsychological devel-
ventilation and intensive care. A longitudinal opment in CDH survivors is comparable to that
222
of other neonates treated with ECLS. However, concentration/attention problems irrespective of

CDH patients seem to experience the greatest treatment with ECLS.54 ECLS treated CDH pa-
deficits. Still, most studies in centers with tients have significantly lower scores on visual
ECLS facilities reporting on neurodevelopment motor integration compared with other neonatal
in CDH within the first years of life don’t pro- ECLS-patients; however, scores are in the aver-
vide separate data for the ECLS-patients. Over- age range.8 Their perception of general health
all, the cognitive and language development is reduced when compared to the reference
scores at preschool age are normal to mildly norm,44 but they also report a well-developed
delayed51,52 and receipt of ECLS is, among other self-confidence.44,54
factors indicating disease severity, reported as
an independent predictor of impaired mental Motor Function
development.52,53
Among 8 year olds, intelligence is found Preschool motor development scores in
in the average range8,54,55 with a mean (SD) CDH patients are usually reported to be normal
IQ of 91.7 (19.5) and 111.6 (20.9) in ECLS or below normal52,56 but improve between 1 and
treated and non-ECLS treated CDH patients, 3 years of age.51 In a population of 47 CDH
respectively.54 These 8 year olds experience patients of whom 26% received ECLS, mild
Figure 17-1. Microstructural findings in the lungs of a congenital diaphragmatic hernia survivor
Hyperpolarized 3 He MR images of an 18-year old CDH patient with a left-sided diaphragmatic defect,
treated with neonatal ECMO; (top row) ventilation-weighted images demonstrating multiple ventilation
defects and (bottom row) maps of 3He apparent diffusion coefficient (ADC) showing elevated ADC
in the ipsilateral lung compared to the contralateral lung consistent with enlargement of mean dimen-
sions of the confining lung microstructure at the alveolar level. (Images provided by Helen Marshall
and Jim Wild, POLARIS, Academic Radiology, University of Sheffield, UK).
223
Chapter 17
to severe motor function delay was reported in disability. Since predictability of outcome in-
45% and 19% at 1 and 3 years, respectively. At creases when the outcome at young age is more
5 years 47% of ECLS treated CDH patients had severe,60 followup of these patients should focus
normal motor function, the remaining 53% had on providing optimal management of their dis-
motor delays mainly in the gross motor func- abilities and preventing further complications.
tion domains.55 Where all ECLS patients show In addition, honest evaluation of the costs and
a deterioration of motor performance through benefits of ECLS treatment for this group of
the years (5-8-12 years), the CDH patients children is desirable, as insight into this matter
experience motor problems at all ages43 and is largely lacking.
these problems seem to occur irrespective of Neonatal ECLS survivors without overt
ECLS support.54 neurologic complications usually have favor-
able outcomes in the first years of life, but they
Recommendations for Long-term Followup are at risk for academic, behavioral, and motor
function problems at later age for which they
Most studies use standardized assessment need to be monitored. For this group, more
tools during followup. However, substantial subtle insults to the brain may have led to minor
heterogeneity occurs with different instru- lesions, which interfere with normal brain matu-
ments used for assessments at varying followup ration. Moreover, they are at risk for reduced
intervals after ECLS. No universal reporting maximal exercise capacity, CKD, and, in case
of long-term outcome currently exists in the of CDH, for deterioration of lung function.
ELSO Registry. Restricting focus exclusively Their long-term followup should focus on early
to hospital discharge offers an incomplete un- recognition and offering timely interventions.
derstanding of the relationship between therapy The current ELSO guideline for followup
and disease, and the combined effects on health of ECLS patients has not been reviewed since
in later life. Routine standardized followup pro- 1997.61 Based on data available two decades ago,
grams are offered by very few ECLS programs. followup of the survivors is recommended until
Longitudinal studies from the Netherlands have the age of 5 years focusing on general intelli-
demonstrated unequivocally the value and ben- gence, language development, and visual-motor
efit of early identification and intervention to integration. Because exclusive assessment of
the children and the families.8,39,43 Other ECLS intelligence does not capture the full range of
programs have conducted followup assessments learning deficits that underlie academic and
with a view to understanding the prevalence of behavioral problems, structured assessment of
the problem9,35,36,57-59 or as part of research tri- specific domains of neurodevelopmental skills
als4,6,7,15 but few have long-term followup by a at different ages seems essential. Despite the
multidisciplinary team of specialists. However, awareness of the prevalence of neurodevel-
patients in followup studies are subject to inher- opmental issues over the last two decades and
ent selection bias as there is a higher mortality in recommendations by the ELSO Registry, there
those with neurologic complications on ECLS.5 is currently no framework for standardized fol-
In addition, children who survive with severe lowup of survivors post-ECLS. Internationally
neurodevelopmental disabilities might either agreed recommendations, made in conjunction
refuse to join followup programs or, when they with all ECLS centers, are crucial to reduce
participate, be unable to perform the standard- variability, inform, integrate, and improve fol-
ized tests. These children usually show lifelong lowup care with the aim of engaging families,
morbidity related to cerebral damage (eg, due community health, and educational psychology
to seizures) and profound mental and motor services. With different followup protocols in-
224
cluding neuro-imaging and neuropsychological lyzed, it may lead to the identification of risk
testing, reflecting the degree of variability in the factors for specific patterns of brain injury and
followup data that are acquired, a longitudinal neurological deficit in this population.
followup pathway integrating neurological as-
sessment starting from the time of referral of
the child for ECLS right up to teenage years can
be prepared using the Standardized Clinical As-
sessment and Management Plans (SCAMPs®)
methodology.62 This allows for a consensus-
based care pathway, which can be modified after
analyzing data acquired at periodic intervals. A
recommended pathway would consist of iden-
tifying risk factors from the time of the ECLS
referral and having a structured, longitudinal
followup for all neonates from discharge to
adolescence tailored to the needs of the child
and family. A neonate with an identified risk
factor or who has developed a neurological
complication on ECLS would receive a more
targeted followup. The ideal algorithm would
incorporate followup, neuro-imaging, and se-
quential age appropriate neuropsychological
testing up to adolescence in a risk stratified
process depending on clinical neurological
signs and MRI findings. Considering this is a
time and money consuming process both for
professionals as well as for patients and their
parents, it is recommended to use screening
tools parallel to elaborate structured assess-
ment tools. Evaluation of the predictive value
of these screening tools should eventually lead
to tailor made followup programs that are more
efficient and economical, without compromis-
ing care. Taking into account the recent reported
literature, a proposed protocol for long-term
followup is outlined in Table 17-2.
Having a structured followup right from
the start facilitates involving families early
in the process, which helps them understand
the importance of followup. Furthermore, a
standardized followup pathway would ensure
information and knowledge for local pediatri-
cians and neonatologists to evaluate and support
the infant/child’s ongoing developmental needs.
Finally if this information is collated and ana-
225
Chapter 17
Table 17-2. Proposal for and relevance of long-term followup after (neonatal) ECMO treatment.
Assessments Domains of Interest Relevance/Intervention

INFANCY Growth Referral dietician
0-2 years Hearing assessment Early referral audiology
Neurologic assessment MRI brain Early recognition, rehabilitation
including imaging
Mental development Early referral
Motor development Referral physical therapist
PRESCHOOL Growth (mainly CDH) Referral dietician

AGE
2-5 years Neurologic assessment Rehabilitation
Language development Hearing assessment, referral
speech-language pathologist
SCHOOL AGE Growth (mainly CDH) Referral dietician

≥6 years Lung function Spirometry Evaluate reversibility of airflow
assessment obstruction
Exercise capacity Sports participation and/or exercise
training
Neuropsychological Referral to early school support
assessment
Intelligence (only once
in followup)
Memory Referral to cognitive rehabilitation
Attention/concentration/
information-processing
Behavior assessment Hyperactivity Referral to support/guidance
Somatic problems
ADOLESCENCE Growth (mainly CDH) Referral dietician

>12 years Motor function Gross motor function Referral physical therapist/sports
(eg, ball skills) participation
Exercise capacity Sports participation/exercise training
Neuropsychological Referral to school support
assessment
Career support/choice of profession
Memory Referral to cognitive rehabilitation
Attention/concentration/
information processing
Behavior assessment Hyperactivity Referral to support/guidance
Depressed feelings/
social problems
Somatic problems
226
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230
18
Pediatric Respiratory Diseases Predisposing to ECLS
Silvia M. Hartmann, MD, Thomas V. Brogan, MD
Epidemiology of ECLS for Respiratory Acute Respiratory Failure

Support
The most common diagnosis in the ELSO
The utilization of extracorporeal life support Registry leading to respiratory support with
(ECLS) among pediatric patients with respira- ECLS in children was acute respiratory failure
tory failure has been increasing with approxi- without acute respiratory distress syndrome
mately 300-400 cases/year between 2008 and (ARDS).3 In a review of the ELSO Registry
2012.1 The Extracorporeal Life Support Orga- from 1993 to 2007, almost 20% of a cohort of
nization (ELSO) Registry shows almost 7,000 approximately 3200 children was cannulated
children between 31 days and 18 years of age for this diagnosis.3 Cases of aspiration pneu-
supported with ECLS for respiratory indications monia were considered separately from acute
from its inception to July 2015.2 ECLS has been respiratory failure and made up an additional
applied in children suffering from a broad range 7% of the patients in the same study. The next
of lung diseases. It has been used to “rescue” most common diagnostic category was ARDS,
children with severe hypoxemic respiratory which accounted for 13% of cases in the same
failure but it can also be used in children who cohort. ARDS was examined in subcategories,
are receiving very high ventilator support that in which sepsis-related ARDS was the most
in and of itself may produce severe lung injury. common and represented more than 50% of all
ECLS has been used in an increasingly ARDS cases and 7% of the overall cohort. A
complex group of pediatric patients with combined category of trauma-related and post-
greater frequency. Data from the ELSO Registry operative ARDS was the next frequent cause of
show that many children receiving ECLS for ARDS, which included nearly 40% of the ARDS
respiratory failure have nonpulmonary organ cohort and 5% of the overall cohort.3 Disorders
involvement complicating their acute ECLS occurring in less than 5% of the patients with
course. Additionally, ECLS is finding applica- ECLS respiratory support encompassed status
tion in children prior to transplant surgery or asthmaticus, pertussis pneumonia, pulmonary
as a means of anatomic protection for the large hemorrhage, influenza, submersion injury,
airways following surgery. The goal of this Pneumocystis jirovecii pneumonia, and fungal
chapter is to review the application of ECLS pneumonia.3
in children with pulmonary disease. Pediatric patients with respiratory failure
have been supported with both venoarterial
231
Chapter 18
(VA) and venovenous (VV) ECLS. The cohort combines the first two parameters (cutoff ≥28
from 1993 to 2007 showed 64% of patients sup- leading to higher mortality). The authors of the
ported with VA-ECLS and 34% on VV-ECLS.3 two studies evaluating pre-ECLS labs suggest
A later, but overlapping ELSO Registry cohort, “an early application of ECLS in patients may
from 1998 to 2010 demonstrated an increase improve outcomes.”6, 7
in the use of VV-ECLS in 52% of patients and The degree of disease complexity and under-
VA-ECLS in 46%.4 As double lumen cannulas lying chronic illness among children receiving
for VV-ECLS have become increasingly avail- therapy with ECLS for respiratory failure has
able for children, there has been an increase in increased over the past two decades. Zabrocki
the number of patients with respiratory disease et al. found that 19% of patients in 1993 had
supported with this modality of ECLS.5 comorbidities and that number increased to 47%
The question of timing for ECLS can- by 2007.3 For example, Trisomy 21 was an his-
nulation for respiratory support compared to toric relative contraindication for ECLS. With
ongoing conventional mechanical ventilation or changing attitudes towards ECLS candidacy,
oscillation has no single correct answer. In one 623 patients with Trisomy 21 have received
review of the ELSO Registry, 49% of patients ECLS for both respiratory and cardiac indica-
were managed on conventional mechanical tions between 1983 and 2013 with increasing
ventilation and another 38% on high frequency numbers in more recent years.8 No difference
oscillatory ventilation.3 Ventilator mode had in mortality occurred between patients with or
no impact on survival. The median time to without Trisomy 21 treated during the same
cannulation was 3.5 days in the ELSO Registry period.8 Overall, data from the ELSO Registry
review3 and 5.4 days in a review of one center’s show that the most common comorbidities in
experience with 2000 patients.4 Zabrocki et children receiving ECLS for respiratory indica-
al. found that 43% of patients were cannulated tions included renal failure (10%), followed by
within three days of invasive mechanical venti- chronic lung disease (9%), and congenital heart
lation.3 Fewer patients were cannulated later in disease (8%).3 A notable group was those with
the course of their respiratory illness with 24% an immunocompromised state that made up 7%
cannulated between days 3-7, 17% between of this 3200 patient cohort.3 Even though more
days 7-14 and 8% after greater than 14 days complex patients have been receiving ECLS,
of cannulation. The group with two weeks or the survival rate has remained consistently
more of mechanical ventilation had a distinctly around 57%.3
lower survival rate (38%) compared to those
cannulated earlier (55-61%).3 Many patients Status Asthmaticus
receiving respiratory ECLS have significant
hypoxia with two studies describing median ECLS has been applied to children with se-
oxygenation index greater than 40.3,4 In a single vere status asthmaticus producing excellent sur-
institutional review, pre-ECLS pH >7.20 and vival outcomes. A review of the ELSO Registry
oxygenation index <35 were associated with from 1986 to 2007 reported 64 patients with
survival but pre-ECLS duration of mechani- severe status asthmaticus support treated with
cal ventilation or pH were not associated with ECLS.9 Patients in this cohort typically had se-
outcome.6 In another single institution study of vere hypercarbic respiratory failure with median
neonates and children, non-survivors had higher pH 6.96 (IQR 6.78-7.28) and PaCO2 123 mmHg
first adjusted anion gap on ECLS (cutoff ≥23 (IQR 70-237). The degree of hypercarbia did
mEq/L), first venoarterial pCO2 gradient (cut- not affect survival, which reached 94%. Due to
off >16 mmHg) and a Viability Index, which limitations of Registry data, authors were only
232
able to look at additional therapy received prior patients.11 Almost 50% had infections prior
to ECLS in a subset of patients treated at a single to ECLS and an additional 20% acquired an
institution.9 Of the 13 patients, 100% received infection during the ECLS run.11 The most
intravenous β-2 sympathetic agonists, 92% re- common cause of death in this study was ir-
ceived ketamine, 69% received helium:oxygen reversible organ failure in 60%. Overall, 35%
mixture, 23% received theophylline and 62% of the cohort survived to hospital discharge.11
received inhalational anesthetics.9 ECLS was ECLS should be a therapy offered to many im-
used primarily as a rescue therapy after the munocompromised patients that otherwise have
other asthma therapies had failed. Once the a disease compatible with long-term survival
patient is cannulated, some authors suggest because there is a reasonable chance to survive
that PaCO2 levels should be dropped relatively to hospital discharge. Patients with immune
slowly in those that have severe hypercarbia to suppression are specifically at risk for Pneumo-
avoid cerebral complications. A rate of PaCO2 cystis jirovecii (formerly Pneumocystis carinii)
fall of 20 mmHg/hour has been suggested as pneumonia. A survival rate of 48% among 25
reasonable by expert opinion. Additionally, patients was recently published.3
9/64 (14%) patients had cardiopulmonary arrest More reservations may be voiced regarding
prior to ECLS therapy.9 Given the encouraging the candidacy of patients receiving ECLS after
outcomes of patients with status asthmaticus, HSCT as survival in these children has not been
therapy with ECLS should be considered early nearly as good as patients with hematologic
in the course of patients with severe hypercarbia or solid organ malignancy. One study looked
to avoid the undesirable outcomes after cardio- specifically at patients after HSCT who required
pulmonary arrest. respiratory support with ECLS.12 Many of these
patients had herpesvirus infections or typical
The Immunocompromised respiratory viruses with adenovirus, parainflu-
enza, and RSV being common in this cohort.
Patients with an immunocompromised state, Coinfections of viruses and bacteria were rela-
when considered as a group, comprise a surpris- tively common (6/29 or 21%) and 3/29 (10%)
ingly large subset of children receiving ECLS patients were observed to have concurrent viral
therapy for respiratory failure. In the ELSO and fungal infections.12 In this group only 2
Registry, patients with cancer, hematopoietic (7%) patients survived.12 A challenge with small
stem cell transplant (HSCT), solid organ trans- numbers in retrospective cohorts of patients
plant, primary or acquired immunodeficiency with HSCT is that oncologic care and expected
make up 6-7% of the cohort.3,10 Outcomes survival may improve over shorter time periods
varied depending on the specific nature of the than those represented by the studies themselves.
immunocompromised state. Survival was the The cohorts described above span at least two
lowest in patients who had had a HSCT, with decades, over which time hematopoietic stem
5% survival in a cohort of 22, and the highest cell transplant care has evolved. It is likely that
in patients after solid organ transplantation with insight into which HSCT patients could benefit
35-39% survival.3,10 Patients with cancer had from ECLS will improve.
an intermediate survival of 30%.3 In another
ELSO Registry review, 107 patients with both Mediastinal Masses
hematologic and solid organ malignancies were
examined. Although patients in this cohort ECLS may be used in conditions where
received both cardiac and respiratory support, the presence of an anterior mediastinal mass
80% (86/107 patients) were respiratory ECLS can cause extrinsic airway compression with
233
Chapter 18
high risk of cardiopulmonary arrest during to surgical repair for physiologic stabiliza-
intubation. Case reports have described suction,22 postoperatively for optimal healing of
cessful cannulation onto VA-ECLS without the surgical site without mechanical irritation
induction of general anesthesia or intubation from endotracheal tubes and risk of rupture of
using ketamine sedation to maintain spontane- suture lines from positive airway pressure, or
ous respiration.13,14 used postoperatively to manage dehiscence.23
Some patients have received repair of airway
Pulmonary Hemorrhage anomalies while on ECLS.22
Severe pulmonary hemorrhage represents a Severe Air Leak

concern for many clinicians considering ECLS
because of the need for anticoagulation, but it Severe air leak disease can complicate pul-
has been successfully treated with either VV- monary infections or intrathoracic surgery and
or VA-ECLS. Both modalities allow for lower in some cases, may not be relieved adequately
pulmonary artery pressures and time for healing by surgical drainage. In these situations, low
of the pulmonary parenchyma as treatment for mean airway pressure is desirable to allow the
the underlying condition is instituted. Although site of injury to heal but this may not be com-
a relatively small cohort of pediatric patients patible with adequate gas exchange. ECLS has
from the ELSO Registry (n=51), survival among been employed to provide respiratory support
children with pulmonary hemorrhage is rela- with minimal ventilator settings. Two cases of
tively good at 69%.3 Most of the information VV-ECLS for the indication of severe air leak
regarding treatment of pulmonary hemorrhage have been reported recently in the literature.
with ECLS is from small case series and case re- One patient had complicated bacterial trache-
ports. Many of these studies reported lowering itis,24 and the other with airway damage second-
anticoagulation targets, eg, aiming for a lower ary to a foreign body.25
activated clotting time15 or activated partial
thromboplastin time (APTT) than normal.16 ECLS for Bridge to Lung Transplant and
The largest case series included eight children Preoperative Rehabilitation
treated with VA- or VV-ECLS with 100% sur-
vival. 15 The underlying etiologies of severe pul- ECLS respiratory support is most often
monary hemorrhage leading to the use of ECLS used as a bridge to recovery for children. How-
vary in the literature. Successfully treated cases ever, there are growing pediatric applications
include Wegener’s granulomatosis,17,18 diffuse of ECLS used as a bridge to lung transplant,
alveolar hemorrhage complicating HSCT (17),19 generally in patients with chronic respiratory
and idiopathic pulmonary hemosiderosis. 20 diseases such as cystic fibrosis. A single case
Open lung biopsy to aid diagnosis of unclear report describes a previously healthy teen with
etiologies of severe pulmonary hemorrhage severe community acquired pneumonia who
can be performed during ECLS with a bleeding received ECLS as a bridge to lung transplant
complication rate of 5-10%.21 after failure of recovery.26 A recent innovation
in the care of patients awaiting lung transplant
Perioperative Support for Airway Surgery has been to emphasize active rehabilitation with
patients on ECLS. This change in preoperative
Infants and children with severe airway management has been associated with shorter
abnormalities have been supported with either postoperative mechanical ventilation time as
VA- or VV-ECLS. ECLS has been used prior
234
well as decreased ICU and hospital length of with conversion to VA-ECLS is a function of
stay.27 severity of illness or related to the intervention
of changing ECLS modalities.
Burns
Prolonged Respiratory ECLS
ECLS support has been used in children
with burns and smoke inhalation injury. A re- A small but significant number of children
view of 29 studies showed no survival benefit supported with ECLS have a prolonged need
with ECLS but that ECLS runs of less than 200 for ongoing ECLS. Prolonged courses have
hours were associated with better survival than been defined as greater than 21 days of ECLS
longer runs. Additionally, patients who suffered support. A study of more than 3200 patients
scald burns had greater survival than those with utilizing respiratory ECLS showed that 389
flame burns.28 The studies reviewed included patients (12%) had prolonged courses.31 The
patients of all ages. In a single institution study survival for this cohort was significantly lower
of children who experienced burns, the survival than those who were supported with ECLS
rate for the 12 patients was 67%. This cohort for 14 days or less (38% vs. 61%, p <0.001).
had severe burns with an average total body Survival does decline with longer duration of
surface area burned of 50.2% and average full- ECLS therapy but does so gradually, with no
thickness burns of 41.8%.29 In this group, higher distinct duration of ECLS at which survival
ventilator settings were associated with lower dramatically decreases. For example, approxi-
survival rate. mately 25% of patients supported for more than
45 days survived to discharge.31 Notably, this
Respiratory Support of Patients with same cohort reported nine patients with ECLS
Congenital Heart Disease duration of more than 52 days with no survivors,
although other groups have reported survivors
The presence of congenital heart disease is of even longer ECMO runs. Prognostication
another group of children who receive ECLS for patients with prolonged ECLS support and
for respiratory support. In the Zabrocki et al. the decision to continue ECLS support remains
review of the ELSO Registry, 6% (n = 195) difficult. Given this uncertainty, it is prudent not
of patients had congenital heart disease with to discontinue care arbitrarily but only if major
the presence of two ventricles and 2% (n=75) complications arise that preclude adequate long-
had single ventricle lesions.3 These groups had term quality of life.
survival rates of 52% and 60%, respectively.
Another ELSO Registry cohort of 133 neonatal Summary
and pediatric patients treated with VV-ECLS
for acute hypoxemia resulted in survival to A wide array of pediatric respiratory dis-
discharge in 42% of patients. In this cohort, eases has been shown to be amenable to ECLS
25% required conversion to VA-ECLS, which support. Studies suggest that early use of ECLS
was associated with a higher mortality of nearly may improve outcomes. However, due to the
75%.30 Patients with congenital heart disease advances in supportive, respiratory and ECLS
may be supported with VV-ECLS but patient practices, as well as technology, it remains
selection is likely critical for success, as is the difficult to define the optimal timing for initia-
need to individualize cannulation strategies. It tion of ECLS support. Chapters 21 and 25 in
is challenging, with information from retrospec- this edition describe complications occurring
tive cohorts, to determine if the higher mortality with pediatric respiratory ECLS. A review at
235
Chapter 18
seven years of the United Kingdom random-

ized control trial of ECMO versus conventional
mechanical ventilation in term neonates with
respiratory failure32 showed similar neurologic
complications in the two groups but lower pul-
monary morbidity in the ECLS arm of the
study.32,33 Although the UK trial was performed
in the 1990s, no similar followup data are yet
available for pediatric patients. Moving forward,
such studies may help define the relative risks
and benefits of ECLS and provide more precise
timing for its initiation. Hence, the use and
timing of ECLS remain a local determination.
The authors recommend careful data gathering
at each institution in order to better define the
chances of successful outcome.
236
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and acute respiratory distress syndrome. poreal membrane oxygenation case report
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SL, Turner DA, Rehder KJ. Extracorporeal Lancet. 1996;34(9020)8:75-82
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238
19
Indications and Contraindications for ECLS in Children with Respiratory Failure
Simon G. Robinson, BM, BS
Introduction considerations guided by current societal norms.

Balanced against this is if the boundaries had
ECMO has evolved greatly over the past 40 not been pushed in the beginning, we would
years. Initially only patients with low survival not have developed the specialty of today. As
expectations were supported with ECMO. The such, this chapter discusses principles, research,
encouraging outcomes allowed development and consensus but is not a strict rulebook. For
and refinement of techniques, equipment, and challenging cases, cross disciplinary discussion
circuit technology that improved survival sig- and consultation with other ECMO centers is
nificantly. Simultaneously, improvements in recommended.
conventional medical therapies have meant that
indications and contraindications have evolved Indications
and are likely to continue.
The basic deciding principles for providing ECMO support should be considered in all
ECMO support are as follows: eligible neonates and children who are failing to
• There is a known or suspected reversible respond to more conventional medical therapies,
pathology which can be treated while pro- bar those at the extremes of prematurity or with
viding ECMO support. (Special extenuating lethal congenital anomalies. The indications
circumstances include the availability and discussed in this chapter are not exhaustive but
likely outcome of organ transplant that may focus on the pediatric patients who may benefit
allow ECMO to be appropriate as a bridg- from extracorporeal therapy. The individual
ing therapy.) diseases that most commonly require ECLS
• The risks associated with ECMO are less support are covered in a separate chapter, but
than those of not providing extracorporeal in terms of relating the condition to indications,
support. they are briefly detailed below.
When considering ECMO support, multiple Conditions

factors need to be considered to ensure that
ECMO is offered appropriately and not where Among pediatric patients, the ‘other’ cat-
the situation is futile. These factors include egory of diverse conditions represents the most
relative and absolute contraindications, an common underlying cause for ECLS. This
approach to an uncertain diagnosis, practical explains the focus on the principles within this
limitations, resource allocation, and ethical
239
Chapter 19
chapter rather than the underlying condition associated with prediction of a high mortality,
determining which children will benefit from but given that these are historical thresholds and
ECLS support. The next most common disease healthcare continues to evolve, the sensitivity of
processes supported are viral pneumonia and each individual marker as a predictor of ECLS
non-ARDS respiratory failure, followed by benefit remains unclear. The appropriateness
bacterial pneumonia, ARDS, and aspiration and availability of transplantation and bridg-
pneumonitis. The highest survival figures for ing services should always be considered in
children receiving ECLS support are among addition to the principles detailed here when
patients with status asthmaticus, aspiration determining whether ECLS will be offered.
pneumonitis, and respiratory syncytial virus
(RSV)-induced pneumonia.1 Oxygenation Failure
Principles behind Pediatric ECLS Indications While neonatal oxygenation failure occurs
most commonly due to insufficient pulmonary
With the underlying disease process not blood flow with pulmonary hypertension, pedi-
being as useful a determinant of ECLS benefit atric indications are mostly due to pathologies
among the pediatric population, it is helpful to that limit alveolar gas exchange with the blood
consider factors in addition to the extent of gas (Table 19-1).
exchange achieved for the current level of me- Quantifying the degree of oxygenation
chanical ventilation. Other pre-ECLS therapies failure as an indicator for ECMO support is
which act as guiding factors include the speed most commonly assessed using the oxygenation
of deterioration, current status of reversible index (OI) in the neonatal population; whereas,
associated factors (eg, lung recruitment, fluid the PF (PaO2/FIO2) ratio is used in adult prac-
balance), and the success of other rescue thera- tice but omits the mean airway pressure as a
pies. Consideration of these multiple variables variable:
is also required since widespread consensus of Oxygen Index (OI) = MAP x FiO2 x 100
when ECLS is beneficial is absent.2 Post-ductal PaO2 (mmHg)
No single widely used validated marker
of respiratory failure exists for the pediatric P/F Ratio = PaO2
population. As such, by using the available FiO2
tools and information detailed below a picture
can be built, similar to the individual pieces of
a jigsaw puzzle, to identify the larger image.
Thresholds have developed for each marker
Table 19-1. A comparison of the most common

conditions requiring ECLS support among
neonates and children.
Neonatal Pediatric
CDH (30%) Viral Pneumonia (20%)
MAS (25%) Non-ARDS, Respiratory failure (20%)
PPHN (20%) Bacterial Pneumonia (8%)
Sepsis (5%) ARDS (6%)
RDS/Pneumonia (1.5%) Aspiration Pneumonia (1%)
Other (18.5%) Other (45%)
CDH=Congenital diaphragmatic hernia, MAS=Meconium Aspiration Figure 19-1. Oxygen Index at time postintuba-
Syndrome; PPHN=Persistent Pulmonary Hypertension; tion and its relationship to outcome in Pediatric
RDS=Respiratory Distress Syndrome; ARDS=Acute Respiratory Respiratory Failure.6
Distress Syndrome
240
Both variables can be considered to help Alveolar-Arterial Oxygen Gradient (AaDO2)

gauge where on the pediatric respiratory failure
spectrum a deteriorating child falls, but neither AaDO2 = FiO2 (Barometric Pressure – Water
are used as strong clinical determinants of when Vapour Pressure) – PaCO2 – PaO2
to provide ECLS support in this population. RQ
There is also no single value that acts as a set Barometric Pressure = 760 cmH2O at sea level
marker of when mechanical support should be Water Vapour Pressure = 47 cmH2O
offered. This is due to consideration of disease RQ (Respiratory Quotient) = 0.8
process, logistics of patient location in relation
to ECMO, whether the patient is improving or
deteriorating, or whether there is further medi- In the pediatric population, an AaDO2 of
cal management. However, for the purpose of >470 was noted to be 81% predictive of death
clinical trials and healthcare commissioning, without ECLS support.4 A similar mortality of
cut-offs have been chosen. Many neonatal trials 80% correlated with an AaDO2 of >610 for 8
used an OI of ≥40 but with a recommendation hours in the neonatal population.
for referral for discussion at a lower level.3 A The Murray scoring system was utilized
PF Ratio of <80 on ≥90% oxygen and a Murray during the adult CESAR trial as an entry crite-
score of 3-4 are typical adult scores for ECMO rion. The Murray Score equals the sum of each
initiation.4 parameter for which data exist divided by the to-
In the pediatric population, steady state tal number of parameters included (Table 19-2).
oxygenation index from day two of illness As ECLS techniques are refined and tech-
forward (as opposed to worse OI) has been nology advances, ECLS is becoming safer
shown to be a predictor of mortality.5, 6 The with fewer complications and associated co-
increased reliability of OI from 12 hours post morbidities. This has moved the initial bound-
intubation onwards is well demonstrated in a ary of when to offer ECLS from a patient in
study of pediatric patients with acute hypoxic extremis or a moribund condition, to one of the
respiratory failure (Figure 19-1).6 However, critically unwell and unresponsive to medical
across the literature, no clear threshold has been therapies patient. This boundary is continu-
identified that accurately predicts mortality or ously moving and broadening to include more
clearly guides institution of ECLS. conditions. Over 20 years ago, Schumacher et
While other markers of oxygenation failure al. published a paper identifying a nonsignifi-
have been used historically, none are employed cant trend towards fewer intensive care days
as readily as the oxygenation index and P/F ratio. and reduced costs in term neonates offered
However, they may be beneficial as additional ECMO at a lower oxygenation index of 25-40.7
tools to guide ECLS selection. These include: Since most post-ECLS neonatal morbidity is
Table 19-2. The components of the Murray Score. The total score equals the sum
of the parameters divided by the number of parameters for which there are data.
Murray Score 0 1 2 3 4
P/F ratio (mmHg) ≥ 300 225-299 175–224 100–174 <100
PEEP (cmH2O) ≤5 6-8 9-11 11-14 ≥ 15
Compliance (ml/cmH2O) ≥ 80 60-79 40-59 20-39 ≤ 19
CXR quadrants infiltrated 0 1 2 3 4
P/F=PaO2/FiO2; PEEP=Positive end expiratory pressure; CXR=Chest x-ray
241
Chapter 19
related to the underlying condition rather than Contraindications

extracorporeal support itself, the reasons for
ECMO not being instituted earlier are unclear There are very few absolute contraindica-
but likely multifactorial.8 Schumacher’s paper tions to providing ECMO support and they all
did not demonstrate any increased morbidity relate to reversibility of the underlying diag-
or mortality and could be used to support this nosis. Conditions that fit the following criteria
argument, but the sample size was small and it would be deemed inappropriate for ECMO
was during a different era of neonatal medical support:
therapies. More recent evidence and research • The ‘No chance’ situation. ECMO support
involving larger neonatal and pediatric patient simply delays death but does not prevent it
populations is lacking. nor relieve suffering (eg, lethal congenital
Clearly communicated guidance for local anomalies such as trisomy 13 or 18).
non-ECMO centers is advised to ensure patients • The ‘No purpose’ situation. Although
are referred promptly and ensure equity of care ECMO support may allow survival, the
for all. This will allow for adequate planning, be degree of physical or mental impairment
it for transfer of potential patients, mobilization would be unacceptable.
of a mobile ECLS team, or consideration of • The ‘No ability’ situation. ECMO support
other treatment strategies that may negate the not possible due to practical limitations.
need for ECLS.
Practical limitations when instigation of
Ventilation Failure ECMO would be of unlikely benefit in non-
neonatal children are as follows:
This is less common than oxygenation fail- • Large intracranial bleed with mass effect
ure. Studies such as the neonatal collaborative • Cardiac arrest without adequate CPR
UK ECMO trial utilized a PaCO2 of >90 mmHg • Irreversible underlying cardiac or lung
(>12 KPa) for more than 3 hours as an entry pathology (unless considered amenable to
criterion but this should be taken in the context transplantation)
of reversibility and baseline level of underlying • Greater than two weeks of high pressure
lung disease. To account for this, others use a ventilation
persistent pH of <7.0 due to hypercarbia with • Pulmonary hypertension and chronic lung
high-pressure ventilatory support. The presence disease
of chronic lung disease is not an absolute con- • Chronic multi-organ dysfunction
traindication but further parenchymal damage is • Incurable malignancy
likely to have occurred from further high-pres- • Allogenic bone marrow recipients with
sure ventilation and the chances of reversible pulmonary infiltrates
disease are significantly reduced. The presence
of pulmonary hypertension in the presence of Relative Contraindications
chronic lung disease would make the long term
benefit of ECMO support highly unlikely, un- Relative contraindications include: vessel
less transplantation was a realistic option. In a anomalies or previously clipped/ligated vessels
similar fashion to oxygenation failure, no single from prior ECMO, unavailability of femoral
figure is or should be strictly adhered to when vessels due to infant size, and localized infection
deciding whether to offer mechanical support. Open and frank discussion with the family
should occur in all cases but particularly when it
is unclear whether ECMO will be of long-term
242
benefit. The best interests of the child should ECMO varies between institutions but typically
always be forefront in driving decisionmaking. ranges from 1-7 days.
Conditions that previously had poor survival fig- Increased duration of mechanical ventila-
ures on ECMO have improved due to advances tion pre-ECMO has historically been a contrain-
in technique and technology but there remains dication, with varying thresholds by institution,
a grey area of uncertainty. but mostly advising against prolonged mechani-
A retrospective analysis of the ELSO da- cal support (e.g. 10 days for those <2 years and
tabase in 2011 identified those with the worst after 7 days for older children). The 1993 study
survival chances, but that does not mean that by Moler et al. identified a fall in survival with
they should not be offered ECMO support if increased duration of mechanical ventilation.11.
their underlying disease process is potentially However, this occurred in an era prior to the
reversible.9 The mortality predictors were age widespread adoption of lung protective ventila-
10-18, hepatic or renal failure, pertussis infection and the study details peak airway pressures
tion, fungal pneumonia, ARDS secondary to of 49.5±13.1 cm H2O. More recent literature
sepsis, and immunodeficiency. Those with challenges these thresholds and practice has
comorbidities are also known to have a reduced changed to be more flexible with lengthened
survival but again that does not mean that periods of pre-ECMO ventilation.12 Figure 19-2
they should not be supported with ECMO if a details the length of pre-ECMO ventilation and
reversible disease process is identified. This in the lack of relationship with patient survival
part explains the unchanged overall pediatric on patients studied between 1999 and 2008 by
survival, since despite an increased survival Mehta at al. The significantly larger retrospec-
rate among those without comorbidities, the tive ELSO database review between 1993 and
number of patients with comorbidities who 2007 by Zabrocki and the 1999 to 2008 review
were supported increased from 19% in 1993 to of the same database by Domico still identified a
47% in 2007.9 reduced survival with prolonged ventilation but
When considering mechanical support for
infants with acute respiratory failure on top of
a baseline of home oxygen dependency due to
previous prematurity, survival is reduced. While
a retrospective single institution analysis of 64
infants identified oxygen dependency as an
independent risk factor for death, survival was
still 64% and no single parameter nor combina-
tion of parameters reliably predicted death in a
manner that would preclude ECLS.10
Small intracranial bleeds may not contra-
indicate ECMO if there is no significant mass
effect and neurosurgical advice is supportive.
The risk of significant hemorrhagic extension Figure 19-2. Relationship between pre-ECMO
duration of mechanical ventilation and survival.
and a subsequent anticoagulation strategy both Mean duration was 2.7 (±4.2) days for survi-
require significant consideration. ECMO sup- vors and 3.6 (±5.6) days for non-survivors.
port following neurosurgical intervention would Horizontal line depicts an arbitrary threshold of
7 days for pre-ECMO mechanical ventilation
be unusual in the subsequent few days. Exactly duration. Solid triangles depict patients with
when the neurosurgical team would support mechanical ventilation over 7 days, before
cannulation.12
243
Chapter 19
this did not reach significance until >14 days.9,13 decisionmaking but wider consultation should
Despite lung protective ventilator strategies, if be considered in challenging cases. If ECMO is
ECMO is to be utilized, earlier institution al- to be instituted, early referral is recommended to
lowing lung recovery is still preferred. However, ensure timely deployment due to the logistical
being ventilated for longer periods prior to challenges ECMO support presents across the
ECMO is no longer such a strong contraindica- healthcare community as a whole.
tion in pediatrics.
While repeated ECMO runs for the same
condition are not contraindicated, they are as-
sociated with a higher mortality rate, increased
complications, and greater risk of a poor neuro-
logical outcome. These factors require consid-
eration in addition to the underlying indication
for ECMO support.
An Approach to an Unknown Cause of

Respiratory Failure
Healthcare does not always fit into neat

boxes with diagnostic labels. Often, the decision
of whether to offer ECMO support comes at a
time where there remains diagnostic uncertainty.
The presence of contraindications will make
this group smaller but if there is a potentially
reversible cause, ECMO support can provide
the additional time required to ascertain treat-
ment options. When there is uncertainty as to the
reversibility of a condition, a diagnosis should
be aggressively sought so as not to continue
ECMO inappropriately when the situation is
futile. While pediatric lung transplantation may
be available in some centers around the world,
this is not yet the norm due to poor organ avail-
ability and low but improving survival rates.
Summary
In summary, while the indications and

contraindications discussed in this chapter can
help to predict the chances of mortality, there
is no single or combination of variables that
can reliably identify a threshold where ECMO
support will not be of benefit. Careful consider-
ation of the potential benefits for the patient and
weighed against the risks of ECMO will aid in
244
References 10. Inwald D, Brown K, Gensini F, et al.

Open lung biopsy in neonatal and pedi-
1. Rehder KJ, Turner DA, Cheifetz IM. Ex- atric patients referred for extracorporeal
tracorporeal membrane oxygenation for membrane oxygenation (ECMO). Thorax
neonatal and pediatric respiratory failure: 2004;59(4):328-33.
an evidence-based review of the past de- 11. Moler FW, Palmisano J, Custer JR. Extracor-
cade (2002-2012). Pediatr Crit Care Med poreal life support for pediatric respiratory
2013;14(9):851-61. failure: predictors of survival from 220 pa-
2. MacLaren G, Conrad, S., Peek, G. Indications tients. Crit Care Med 1993;21(10):1604-11.
for Pediatric Respiratory Extracorporeal 12. Mehta NM, Turner D, Walsh B, et al. Fac-
Life Support. ELSO Guidelines 2015. tors associated with survival in pediatric
3. Mugford M, Elbourne D, Field D. Extracor- extracorporeal membrane oxygenation--a
poreal membrane oxygenation for severe single-center experience. J Pediatr Surg
respiratory failure in newborn infants. The 2010;45(10):1995-2003.
Cochrane database of systematic reviews 13. Domico MB, Ridout DA, Bronicki R, et
2008(3):Cd001340. al. The impact of mechanical ventilation
4. Gaffney AM, Wildhirt SM, Griffin MJ, time before initiation of extracorporeal life
et al. Extracorporeal life support. BMJ support on survival in pediatric respiratory
2010;341:c5317. failure: a review of the Extracorporeal Life
5. Wong JJ, Loh TF, Testoni D, et al. Epidemiol- Support Registry. Pediatr Crit Care Med
ogy of pediatric acute respiratory distress 2012;13(1):16-21.
syndrome in singapore: risk factors and
predictive respiratory indices for mortality.
Front Pediatr 2014;2:78.
6. Trachsel D, McCrindle BW, Nakagawa S, et
al. Oxygenation index predicts outcome
in children with acute hypoxemic respira-
tory failure. Am J Resp Crit Care Med:
2005;172(2):206-11.
7. Schumacher RE, Roloff DW, Chapman R,
et al. Extracorporeal Membrane Oxygen-
ation in Term Newborns: A Prospective
Cost-Benefit Analysis. ASAIO Journal
1993;39(4):873-79.
8. McNally H, Bennett CC, Elbourne D, et al.
United Kingdom Collaborative Random-
ized Trial of Neonatal Extracorporeal
Membrane Oxygenation: Follow-up to Age
7 Years. Pediatrics 2006;117(5):e845-e54.
9. Zabrocki LA, Brogan TV, Statler KD, et al.
Extracorporeal membrane oxygenation
for pediatric respiratory failure: Survival
and predictors of mortality. Crit Care Med
2011;39(2):364-70.
245
20
ECLS Cannulation for Children with Respiratory Failure
Samir K. Gadepalli, MD, Ronald B. Hirschl, MD, Marcus D. Jarboe, MD
Introduction VV-ECLS may be applied in pure respi-

ratory failure even when pressors are being
This chapter focuses on the preferred routes, administered.2 This is because VV-ECLS fa-
techniques, and appropriate cannula placement cilitates a reduction in intrathoracic pressure
for non-neonatal cannulation of children for (because of reduced ventilator pressures), thus
respiratory indications. We will review routes; improving venous return and cardiac output.
techniques for cannula placement, including pH also improves which may improve cardiac
adjuncts such as ultrasound, echocardiography, function. Therefore, when possible, venovenous
and fluoroscopy; and evaluation for and preven- cannulation is still employed even in the setting
tion of complications. of moderate hemodynamic compromise.
For venovenous cannulation, the veins
Preferred Routes commonly employed include the right and
left internal jugular veins and femoral veins.
Preferred routes for cannulation in respira- Originally, two-vessel cannulation was com-
tory illness assume normal underlying cardiac monly employed for access; however, with the
function because most approaches use venove- widespread availability of dual-lumen cannulas,
nous (VV) modes of ECLS. The ELSO Inter- a single venous site is preferentially used when
national Registry data over the past five years a two vessel cannula approach is used, draining
reveal that approximately 460 pediatric patients blood from the femoral cannula drainage and
were placed on VV-ECLS yearly for respiratory reinfusion into the internal jugular vein cannula
indications for an average run of 270 hours, with results in higher arterial saturation as flow is
a 61% survival.1 Although the majority were increased and recirculation is decreased.3
managed using venoarterial (VA) modes, over In general, the jugular veins are preferred
the past few years there has been a clear shift to in children <5 years of age as the femoral veins
VV, with and without the use of double lumen are too small. Traditionally, we reserve femoral
cannulas. Therefore, in this chapter, we focus cannulation for children that are above ~10
primarily on venous cannulation for respiratory kg. The jugular veins can accommodate larger
conditions, acknowledging that conversion to cannula in younger children. In emergency
VA or addition of an arterial cannula may be settings, access to the femoral vein can be dif-
necessary in some circumstances. ficult in young children, while a percutaneous
or cutdown technique can be used to access
247
Chapter 20
the jugular vein quickly. Additionally, the iliac Technique

veins can be used in a younger child if a larger
cannula in the lower extremity is required.4,5 There are two basic techniques used to place
The right jugular vein is preferred over the a VV cannula: percutaneous and cutdown. The
left as the vein provides more direct access to goal of either technique is safe, efficient, and
the superior vena cava (SVC) and right atrium proper placement of the cannula. Surgeon com-
(RA). Furthermore, placement of a large, mini- fort, level of skill, and level of experience plays
mally flexible cannula via the left jugular vein an important role in choosing the appropriate
puts undue stress on the SVC laterally, poten- technique. In addition, whether a standard double
tially increasing the risk for a perforation. lumen catheter or a bicaval catheter is used also
No matter which site is chosen, an appro- plays a role in the approach and the adjuncts
priate size cannula must be inserted to allow used to confirm placement during the procedure.
adequate flow. If the appropriate size cannula
cannot be placed, the flow will not be enough Percutaneous Access
to fully support the child and one should
immediately consider placement of a larger Percutaneous access to the right internal
cannula or an additional drainage cannula at jugular vein (IJ) can be performed with landmark
another location. In general, the largest lumen or with ultrasound guidance. If the surgeon is
and shortest length will decrease the resistance. facile with ultrasound, it provides a level of
Furthermore, venous cannulae have both side visualization and certainty of needle placement
and end holes to prevent occlusion and augment that is not provided with the landmark approach
drainage, whereas arterial cannulae only have (Figure 20-1). The American College of Sur-
an end hole. The cannula are thin walled to al- geons has recommended ultrasound guidance in
low flexibility and to offer minimal resistance; accessing the internal jugular vein in both adults
wire-wound cannulae are important, therefore, and children.
to prevent kinking. The dual lumen bicaval When using ultrasound, two separate
catheter6 has become popular for use in VV- approaches can be used. Each uses a linear
ECLS and, despite disadvantages over two site transducer/probe. At our institution we prefer a
cannulation,7 has gradually become the standard
for the pediatric population.
Upon placement, it is anticipated that
pressors may still be required in a child on
VV-ECLS; in addition, required “rest set-
tings” may be slightly higher than those with
VA support, although in all cases they should
still be lung-protective (PIP <25 cmH2O) to
avoid barotrauma.8 Furthermore, a period of
adjustment may be required as ventilator set-
tings slowly reduce over several hours and the
patient’s intrinsic cardiac function improves. In
younger patients with a bicaval catheter, mal-
position of the catheter is a risk and should be
closely followed with routine radiography and Figure 20-1. Ultrasound of the neck demon-
strates needle in the internal jugular vein with
echocardiography as needed. surrounding adjacent structures such as the
carotid and lung in the same view.
248
micropuncture access set that includes a 7 cm 21 down through the needle into the IJ and down
g access needle, a 0.018” cope wire, and a 3-4 into the superior vena cava (SVC). Fluoroscopy
French (Fr) dilator. We also generally use a stiff can be used to confirm that the wire is in place
wire, such as an Amplatz superstiff, to dilate the and that it does not have any kinks or turns. Once
tract and to facilitate cannula placement. the 0.018 inch wire is in appropriate position, a
Lateral Ultrasound Approach. The first ap- 3-4 Fr dilator is placed over the wire. The 3 Fr
proach is the lateral or in-line approach (Figure portion of the dilator and wire are then removed
20-2a). With the lateral approach the ultrasound with the 4 Fr dilator left in place. The 4 Fr dilator
is placed just cephalad and parallel to the clavicle. will accommodate a larger 0.035” stiff wire, such
The needle is then placed in a vector in line with as an Amplatz. At this point systemic heparin
the ultrasound probe just lateral to the sternoclei- should be given in order to fully anticoagulate
domastoid. With this view the needle, the internal the patient before the dual-lumen venous cannula
jugular, as well as the carotid and the lung can all is placed. A Kumpe catheter can be used to help
be seen in one plane (Figure 20-1). The 21-gauge with guidance of the wire into the inferior vena
entry needle is then advanced under ultrasound cava (IVC).
guidance through the tissue into the lumen of the We routinely use both fluoroscopy and echo-
internal jugular vein. If the ultrasound is placed cardiography (ECHO) in the initial placement
in the correct orientation, the entire length of of the bicaval dual-lumen catheters in pediatric
the needle can be seen throughout this advance- patients. We have seen instances where the wire
ment. This method provides safe placement and migrated into the hepatic vein, but on fluoroscopy
certainty that the needle is placed in the lumen looks to be in the vena cava, or the wire has looped
of the correct vessel. in the right ventricle before turning around and
Once the needle is in the lumen of the inter- coming down to the vena cava which was not
nal jugular vein, the 0.018” cope wire is passed recognized with ECHO.
Standard Ultrasound Approach. Using the
standard approach with ultrasound, the linear
ultrasound probe is placed approximately 2-3
centimeters above the clavicle transversely
across the internal jugular vein (Figure 20-2b).
The ultrasound is used to line up the needle
Figure 20-2. Picture of lateral (a) and standard (b) approaches to access of the internal jugular vein
using ultrasound.
249
Chapter 20
directly over the vein and the needle is then Cannula Placement
followed down to the internal jugular vein and
into the lumen. Given that ultrasound provides a Once access to the vein is obtained, sys-
two dimensional view, it is useful to follow the temic heparin is administered as mentioned.
needle tip by moving the ultrasound probe back The 0.018” wire is exchanged for a stiff 0.035”
and forth across the tip to ensure that it does not wire such as an Amplatz super stiff wire. For
go past the back wall of the vein. Some users the cannula, the wire is advanced into the IVC
prefer to use needle aspiration rather than track- to confirm that it is in the vein. For bicaval
ing the needle tip. We tend to like ultrasound cannula placement it is necessary to place the
after the aspiration. wire into the IVC. At this point the techniques
Once the needle is in the lumen of the IJ, are divergent for the standard double-lumen
the steps are the same as the lateral approach cannulae vs. the bicaval cannula.
using a 0.018” cope wire, a 3-4 Fr dilator, and Standard Double Lumen Cannula. The Am-
exchanging the cope wire for a stiff 0.035” wire. platz wire should be in place and confirmed to
Systemic heparin is given in preparation for be in the SVC/right atrium/IVC. Heparin should
cannula placement. be circulated for 3 minutes. Serial dilation of the
Cutdown Access. A cutdown approach can tract is performed up to the size of the cannula or
also be used. This is very similar to placement slightly larger. Ideally, dilation should be done
of a VA cannula. An incision approximately one with intermittent fluoroscopy. Fluoroscopy is
finger breadth above the clavicle is made and the especially important with the use of a floppy
sternocleidomastoid muscle is split. Dissection guidewire: the stiffer wire tends to direct the
is continued until the IJ is identified. The jugular dilators in the proper direction, which is not
is then exposed and dissected. Systemic heparin the case with a softer or floppier wire. Thus,
is administered and, after a three minute interval, Amplatz wire may prevent perforation of the
the jugular vein is ligated cephalad and two ties SVC or the right atrium.
placed caudad are pulled up and used to occlude After dilation, the catheter is placed over the
the vessel. A venotomy is made and, if preferred, wire into the right atrium, with deeper insertion
stay sutures can be placed at this point. generally providing better flow. However, the
If a bicaval catheter is being used a modified
cutdown technique may be preferred. The ster-
nocleidomastoid is split and the internal jugular
vein is located but only the anterior wall of the
jugular vein is isolated. This allows a needle
to be placed into the internal jugular vein and
a wire to be placed through the needle into the
vein. This method is helpful when a bicaval
cannula is used because a wire must be placed
across the atrium into the IVC in order to direct
the cannula into the IVC. If a cut down is made
with a venotomy, it is difficult to place the wire
without significant blood loss.
Figure 20-3. Ultrasound view of the tip of a

venous cannula in the right atrium from the
sub-xiphoid view.
250
cannula should not enter the tricuspid valve. It then be placed. The tip of the catheter should
is best if the inflow orifice is just above the in- be located in the IVC with the outflow orifice at
ferior vena caval-atrial junction. On fluoroscopy the IVC-RA junction. ECHO can be used to con-
this is typically 1.5-2 vertebral bodies below the firm the exact location of the tip of the cannula
carina. Ultrasound or ECHO can also be used (Figure 20-4). This is particularly important in
to confirm location (Figure 20-3). smaller children since the right atrial junction
Bicaval Cannula. For placement of a bica- with the IVC and the hepatic vein confluence
val cannula, the wire must extend well into the with the IVC can be a very short distance.
IVC. Similar to the standard cannula the wire The outflow orifice should then be pointed
should be an Amplatz super stiff wire to direct towards the tricuspid valve. ECHO can show the
the cannula into the IVC. If there is difficulty in direction and level of the outflow during place-
getting the wire into the IVC, a 4 or 5 Fr Kumpe ment. In addition, DSA (Digital Subtraction
catheter can be used to direct the catheter into Angiography) can also be used with contrast
the IVC. If further difficulty is encountered, an injection (Figure 20-5). For bicaval catheters,
inspiratory hold can help align the IVC with the especially in smaller children, the landing zone
SVC and facilitate the wire entering the IVC. is very small and therefore migration of the
The IVC is generally posterior from the right cannula into the right atrium, right ventricle,
atrium and the Kumpe catheter should be placed and into the hepatic veins is a significant risk.
to accommodate the direction. The distance of the tip of the cannula from the
Once the wire is well into the IVC, serial outflow orifice is also short in a smaller catheter
dilation is performed up to the size of cannula and dislodgement can be a common problem.
or slightly smaller. If at all possible, fluoros- Postplacement cannula monitoring during an
copy should be used to confirm that the wire ECMO run is important to confirm that the
is not bent and the catheter and dilators do not ECMO cannula remains in the appropriate
perforate the wall of the atrium or the side of position.
the SVC. Once serial dilation is performed, a
dilator should be loaded into the bicaval catheter.
This dilator and cannula combination should
Figure 20-5. Fluoroscopy image demonstrat-

Figure 20-4. Echocardiography to confirm ing placement of the dual lumen bicaval
placement when using a dual lumen bicaval cannula in the appropriate location with the
cannula identifying the tip in the inferior vena contrast entering the right atrium when injected
cava. into the “arterial” port.
251
Chapter 20
Complications such as kinking of the cannula or circuit, and

whether the cannula size was appropriate. Fol-
Cannula complications can be differentiated lowing this, we administer volume to improve
into those which occur immediately and those preload, and use imaging of the cannula tip
that are delayed. Immediate complications are with x-ray, fluoroscopy, chest ultrasound, or
those that occur during the placement of the echocardiography to determine whether the
cannula. These include injury to the blood ves- cannula position is appropriate, and to evaluate
sels, lung, heart, and adjacent structures (such for cannula complications including pneumo-
as vascular structures and nerves, bowel and thorax, hemothorax, or tamponade. Finally, we
bladder for femoral and iliac cannulations). De- determine if conversion to VA is appropriate.
layed injuries include injury to the blood vessels, After cannulation, bleeding at the site
malposition and displacement of the cannula, can usually be addressed with a reduction in
bleeding at the insertion site, and hematoma. anticoagulation, application of topical hemo-
Infections of the cannula can also occur. Alto- static agents, or placing a pursestring suture
gether, 15.3% of pediatric runs for respiratory in the skin around the cannula. Kinking of the
failure in the ELSO Registry (includes all modes cannula can be prevented with the use of wire-
of cannulation) reported a mechanical cannula reinforced devices and positioning of the patient.
problem, 18.2% reported cannula site bleeding, Strategies to check for cannula placement can
16.9% reported culture-proven infection, and prevent major injuries from malposition which
less than 0.5% had a limb injury.1 usually present with increased recirculation
During cannulation, we use electrocautery in VV. With both malposition of the cannula
generously to perform the incision and dissec- and with pericardial tamponade, recirculation
tion for cutdown techniques, or ultrasound for is frequently noted. An echo can be useful
a percutaneous approach. During ultrasound to differentiate malposition from tamponade.
identification of the vessel, we measure the Repositioning a cannula is challenging and
vein size to ensure that the cannula is not too one should weigh the benefits of repositioning
large in diameter. This avoids advancement with the risks of perforation, bleeding, injury
of the cannula and is important, as larger sizes to vessels, loss of support, and hemodynamic
can cause trauma to the vessel, including the compromise. In general, if the position of a cath-
potential for disruption of the vein with loss of eter is inadequate and the patient is not ready
the vessel into the mediastinum. Additionally, if to come off ECLS, repositioning is advised to
the patient’s head is hyperextended or rotated avoid complications of vessel injury, hemolysis,
too far to the left, the vein can be obstructed. or barotrauma. When a tamponade is identified,
Moreover, air embolus can occur with improper a cardiac surgical consultation is recommended
flushing of a cannula or patient inspiration. with immediate drainage and repair of intracar-
Therefore, we use extreme care during cannula diac injury via a median sternotomy.
debubbling and paralysis during cannulation. Specific injuries using the Avalon (dual-
Finally, mediastinal shift due to pneumothorax, caval cannula) include malposition, right atrial
effusion, or a mass effect from a diaphragmatic perforation, and arrhythmias.6,9-11 These can be
hernia or parenchymal lung lesion may distort prevented by use of fluoroscopy and echocar-
the vein; additional guidance with fluoroscopy diography12 at the time of placement and vigilant
and/or ultrasound is recommended. evaluation of the CXR with a low threshold
One of the more common complications for use of echocardiography. When migration
after VV cannulation is inadequate support. Our occurs, the catheter can occasionally be repo-
algorithm is to evaluate for mechanical causes sitioned without interruption.11 However, the
252
adjunct use of imaging to guide manipulation

should be strongly considered.
Finally, a standardized process using appro-
priate resources available to the institution and
maintaining competency among a core group
of those performing cannulations cannot be
overemphasized. Use of simulation training13-16
and quality improvement methodology to aug-
ment learning is the next step in the evolution
of ECLS cannulation in pediatrics.
253
Chapter 20
References for venovenous extracorporeal membrane

oxygenation. J Cardiothorac Surg 2012;7:36.
1. Extracorporeal Life Support Organization. 10. Rubino A, Vuylsteke A, Jenkins DP, Fowles
(2016). ECLS Registry Report: International JA, Hockings L, Valchanov K. Direct compli-
Summary (p. 26). Ann Arbor, MI: Extracor- cations of the Avalon bicaval dual-lumen can-
poreal Life Support Organization. Retrieved nula in respiratory extracorporeal membrane
from https://www.elso.org/Registry/Statistics/ oxygenation (ECMO): Single-center experi-
InternationalSummary.aspx ence. Int J Artif Organs 2014;37(10):741–747.
2. Ko M, dos Santos PR, Machuca TN, et al. 11. Tanaka D, Pitcher HT, Cavarocchi N, Hirose
Use of single-cannula venous-venous ex- H. Migrated Avalon Veno-Venous Extracor-
tracorporeal life support in the management poreal Membrane Oxygenation Cannula:
of life-threatening airway obstruction. Ann How to Adjust Without Interruption of Flow.
Thorac Surg 2015;99(3):e63–65. J Card Surg 2015;30(11):865–868.
3. Rich PB, Awad SS, Crotti S, Hirschl RB, 12. Peris A, Lazzeri C, Cianchi G, et al. Clinical
Bartlett RH, Schreiner RJ. A prospective significance of echocardiography in patients
comparison of atrio-femoral and femoro- supported by venous-venous extracorpo-
atrial flow in adult venovenous extracorporeal membrane oxygenation. J Artif Organs
real life support. J Thorac Cardiovasc Surg 2015;18(2):99–105.
1998;116(4):628–632. 13. Allan CK, Thiagarajan RR, Beke D, et al.
4. Ford EG, Atkinson JB. Augmented venous ac- Simulation-based training delivered directly
cess in the problematic ECMO patient: a case to the pediatric cardiac intensive care unit
report. J Pediatr Surg 1992;27(4):527–528. engenders preparedness, comfort, and de-
5. Mathis CA, Powell AE, Holloway RD, Shah creased anxiety among multidisciplinary
S, Goldberg SP, Boston US. Alternative can- resuscitation teams. J Thorac Cardiovasc Surg
nulation strategy for pediatric ECMO. J Card 2010;140(3):646–652.
Surg 2011;26(4):444–445. 14. Anderson JM, Murphy AA, Boyle KB, Yaeger
6. Chimot L, Marqué S, Gros A, et al. Avalon© KA, Halamek LP. Simulating extracorporeal
bicaval dual-lumen cannula for venovenous membrane oxygenation emergencies to im-
extracorporeal membrane oxygenation: sur- prove human performance. Part II: assess-
vey of cannula use in France. ASAIO Journal ment of technical and behavioral skills. Simul
2013;59(2):157–161. Healthc 2006;1(4):228–232.
7. Kuhl T, Michels G, Pfister R, Wendt S, Lange- 15. Chan SY, Figueroa M, Spentzas T, Powell
bartels G, Wahlers T. Comparison of the Ava- A, Holloway R, Shah S. Prospective assess-
lon Dual-Lumen Cannula with Conventional ment of novice learners in a simulation-based
Cannulation Technique for Venovenous Ex- extracorporeal membrane oxygenation
tracorporeal Membrane Oxygenation. Thorac (ECMO) education program. Pediatr Cardiol
Cardiovasc Surg 2015;63(8):653–662. 2013;34(3):543–552.
8. Moler FW, Custer JR, Bartlett RH, et al. Ex- 16. Sanchez-Glanville C, Brindle ME, Spence T,
tracorporeal life support for severe pediatric et al. Evaluating the introduction of extracor-
respiratory failure: An updated experience poreal life support technology to a tertiary-care
1991–1993. J Pediatrics 1994;124(6):875– pediatric institution: Smoothing the learning
880. curve through interprofessional simulation
9. Hirose H, Yamane K, Marhefka G, Cavarocchi training. J Ped Surg 2015;50(5):798–804.
N. Right ventricular rupture and tamponade
caused by malposition of the Avalon cannula
254
21
Comorbidities among Pediatric Patients with Respiratory Failure on ECLS
Susan L. Bratton, MD, MPH, Jennifer Workman, MD
Patient survival after cardiorespiratory to hospitals with ECLS. Risk factors for poor
failure supported by ECLS is predicated on outcome also differ among patient groups (ie,
correct assessment of three issues: 1) selection intraventricular hemorrhage [IVH] in neonates)
of patients with either reversible conditions or which results in what may appear to be conflict-
ones that can be stabilized and later “rescued” ing complication rates and associated mortal-
by organ transplantation, 2) prevention of ad- ity in medical reports. Additionally, because
ditional or ongoing organ injury during ECLS, ECLS is an infrequent intervention, research-
and 3) identification and correction of issues ers often use information from ELSO or other
that could be ameliorated or prevented by large administrative medical data sources (eg,
procedures immediately before or early during Healthcare Cost and Utilization Project, Kid’s
the ECMO course, such as an atrial septostomy. Inpatient Database) in order to evaluate larger
This chapter discusses preexisting comorbidi- patient groups.2
ties, those that develop during acute care prior to These sources of data have some unavoid-
and/or during ECLS and procedures in children able limitations. The accuracy and complete-
that are associated with mortality. ness of administrative database information
for diagnosis and procedure codes frequently
Epidemiology cannot be verified, and although ELSO collects
information on therapies and complications,
At present, survival to hospital discharge for some key factors likely vary substantially by
pediatric patients treated for primary respiratory institution. For instance, acute kidney injury
failure is approximately 60%.1 Unfortunately, (AKI) and renal replacement therapies (RRT)
the epidemiology of ECLS in patients of all are common and strongly associated with mor-
ages is hampered by several factors. Reports tality, but multiple technologies can provide
from both ELSO and single centers describe electrolyte and urea clearance as well as fluid
patients treated with ECLS, but do not identify regulation. Additionally, lack of standardization
those who might have benefitted from ECLS, exists in both clinical practice and semantics of
but did not receive it. Thus it is always possible the definitions and therapies. Serum creatinine
that patients treated with ECLS may differ in (Cr) is not the optimum measure to detect AKI.
important factors from center to center, and may The elevated Cr values that ELSO collects
not be representative of ECLS care in general. are insensitive for infants. The complicated
Demographic factors may simply reflect access interactions between fluid management, tim-
255
Chapter 21
ing of AKI, and RRT cannot be disentangled Reported Outcomes

using the current data available from multiple
centers.2-3 Finally, when weighing risks and Studies regarding ECLS in pediatric pa-
benefits of changing from conventional care to tients frequently report complications, use of
ECLS, mortality prediction models should only support therapies, and mortality. Unfortunately,
include factors present at the time of cannula- data regarding long-term survival and survivor
tion. Factors such as duration of ECLS support functional health status are scarce.8-9 A number
are primarily a consequence of persistent organ of studies report dichotomized outcome groups
failure and are only “predictive” in hindsight based on cognitive function at discharge using
after ECLS is started. For most applications of the Pediatric Cerebral Performance Category10
ECLS, the rate that ECLS is utilized remains with a “good” outcome defined as normal
unknown. These factors must be considered through to moderate cognitive dysfunction,
in the interpretation of pediatric ECLS studies. while death and severe disability are defined
as ”poor.”11-12 This classification is not sensi-
General Considerations tive enough for preverbal infants and important
cognitive and fine motor disabilities may not
be apparent at hospital discharge.11,13 Increas-
Coexisting Conditions ing information about long-term function in
pediatric ECLS survivors is coming to light;
Some coexisting conditions are clearly not however, frequently, investigators reporting
due to ECLS care (eg, cancer, immunosuppres- 5-10 years later on long-term health and cogni-
sion) but increase the risks of both death and tive function do not have granular clinical data
infectious and/or hemorrhagic complications to evaluate risk factors at the time of ECLS and
during ECMO. Others evolve over time and can long-term disability.14
be difficult to attribute fully to either pre-ECLS
care or to complications of ECLS management Pediatric Respiratory Failure-Risk Factors
(eg, AKI). for In-Hospital Mortality
Mode Since 2005, the number of annual ECLS

runs for pediatric respiratory failure reported to
Venovenous support should always be ELSO varies between 250 to 460/year,1 and in
considered strongly for patients with primary recent years VV for this indication exceeded VA
respiratory failure and “manageable” cardiovas- support. Most pediatric patients are supported
cular insufficiency because the risk of central with ECLS for acute respiratory failure .1,15
nervous system injury (CNS) is significantly However, some innovators report using VV
lower.4-6 Increasing use of double lumen venous ECLS as a bridge to transplantation, avoiding
cannulas placed in the internal jugular vein long-term intubation in severely deconditioned
enhances the feasibility of early mobilization patients with end stage chronic respiratory
of cooperative patients compared to patients failure to improve their nutrition and strength.16
with two sites, especially the femoral artery. Zabrocki et al. published the last com-
Intensivists caring for neonates should be aware prehensive review of the pediatric respira-
that risks for IVH decrease substantially by one tory ELSO data in 2011.4 They reported that
week chronologic age.7 although overall survival was unchanged over
almost two decades, in recent years patient
complexity has increased (Figure 21-1). Demo-
256
graphic risk factors had changed since a similar Coexisting Conditions

report by Moler et al. in 1993.17 The association
between increased mortality and increasing age
was no longer evident till preteen years (10 Cancer
years), and prolonged pre-ECMO ventilation
days extended to >2 weeks (Table 21-1). Several case series based on the ELSO
Adjusted odds of mortality varied by prima- Registry for children with respiratory failure
ry pulmonary diagnoses: children with pertussis showed that survival to hospital discharge
or sepsis-associated acute respiratory distress among those with immune deficiencies and
syndrome (ARDS) had significantly greater cancer decreased from 57% to 33-35%.18-19
mortality compared to the reference group Survival rates did not differ between those with
(bacterial and viral pneumonia and trauma- solid tumors compared to hematologic cancer.
induced or postoperative ARDS), while mortal- When assessing the potential benefit of ECMO
ity with asthma or aspiration pneumonitis was for a given cancer patient, additional consider-
significantly lower. Additionally, the mortality ation of prior organ injury due to chemo and
risk associated with comorbid conditions was radiation therapy is important as well as evalu-
relatively larger. These comorbid conditions ation of the malignancy prognosis independent
included: pre-ECMO cardiac arrest, acute renal of ECMO. Successful application of ECMO
failure, acute liver necrosis, cancer, and primary to support both induction chemotherapy20-21 as
immune deficiencies (Table 21-1). well as in patients with substantial past exposure
Figure 21-1. Trend in survival and comorbid conditions among pediatric respiratory failure patients
supported with ECLS. (Used with permission Wolters Kluwer Health Inc., Zabrocki LA, Brogan TV,
Statler KD, et al. Crit Care Med. 2011;39:364-370)
257
Chapter 21
to chemotherapy have been reported as indi- Genetic Abnormalities

vidual and case series.22 However, care of such
patients is complex and the potential for error Reports of greater mortality among cardiac
increases. Multidisciplinary expertise is needed patients with genetic anomalies typically do
for medication dosing due to dilution from the not identify specific genetic abnormalities or
additional circuit blood volume, potential bind- syndromes. Over the past decade an increas-
ing to the circuit, and enhanced clearance if RRT ing number of patients with genetic disorders
is employed.23 The duration of expected time to have been treated with ECLS. A recent study
engraftment or duration of neutropenia should using the ELSO Registry reported on pediatric
also be weighed when deciding if the potential patients with trisomy.25 During the neonatal pe-
ECMO patient has a reversible process. riod, patients with trisomy 21 were more likely
Some providers consider a few select to be treated for primary respiratory failure,
comorbidities such as acute care for a hemato- while cardiac indications were more common
poietic stem cell transplant (HSCT) as absolute as older infants and children. There was no sig-
contraindications to ECLS support. A recent nificant difference in overall survival for trisomy
study of 28 children with a HSCT reported three 21 patients compared to others when treated
(11%) survived to hospital discharge.24 One was with ECLS (63% vs. 57%). There was also no
supported for acute cardiac failure and two had difference in survival between the two groups
respiratory failure. Although providers may when the indication for ECLS was investigated:
interpret this as hopeful or disappointing, such cardiac indications (46% vs. 45%), respiratory
reports remind all that risk factors can change indications (67% vs. 71%), or ECPR.25
with time and advances in care. Given the broad range of genetic conditions
it is difficult to make generalizations whether a
given condition increases the risk of mortality
with ECMO. Similar to patients with cancer, an
evaluation of potential and duration of survival
Table 21-1. Factors independently associated with survival: pediatric respiratory failure supported
with ECLS.
Pulmonary Process OR Extra-Pulmonary OR Clinical Features OR

Disease
Asthma 2.7 Renal Failure 0.45 Age >10 years 0.72
Submersion 2.0 Immune Deficiency 0.42 Pre-ECMO
Ventilation >2 weeks 0.39
Aspiration 1.7 Cardiac Arrest Pre-ECLS 0.44 VV ECMO 1.51
RSV 1.6 Cancer 0.39 pH
Acute Respiratory Failure 0.8 Liver Necrosis 0.23 <7.19 0.65
ARDS Sepsis 0.7 7.19-7.29 0.75
Fungal Pneumonia 0.2 >7.29 1
Reference Group* 1 PaO2/FiO2 1.003
OR=Odds Radio; RSV=Respiratory Syncytial Virus; ARDS=Acute Respiratory Distress
Syndrome; PaO2/FiO2= Ratio arterial oxygen concentration to inspired fraction of oxygen
concentration
*Bacterial pneumonia, viral pneumonia, acute respiratory distress secondary to trauma or
postoperative (mortality)
Adapted from Zabrocki et al.4
258
due to the condition, aside from ECMO, must reported to the ELSO Registry with an overall
be understood as well as making possible expert hospital survival of 38%.3 ECPR was utilized
consultation essential. Additionally as genetic primarily in infants (median age 3 months) with
conditions invariably affect multiple organ cardiac disease (76%). Compared to patients
systems, other coexisting organ dysfunction with other causes of CA (respiratory failure,
must be assessed. Issues specific to a genetic sepsis, or trauma), patients with congenital heart
condition such as connective tissue diseases disease and neonates with respiratory failure
and excessive bleeding (ie, Ehlers-Danlos) were significantly less likely to die. Patients
must be discussed with the medical and surgi- with severe acidosis (pH <6.9) at the time of
cal ECMO staff prior to offering ECMO as a cannulation had additional increased odds of
potential therapy. Finally the child’s baseline hospital mortality. After ECMO initiation, fac-
quality of life must be assessed and transpar- tors independently associated with mortality
ently discussed with providers and the family. included elevated Cr >1.5 mg/dL, persistent
acidosis (pH <7.2), pulmonary hemorrhage,
Complications and Therapies CNS stroke or hemorrhage, and CA during
ECMO. Each factor increased odds of mortality
by two to three fold and were more likely with
Cardiac Arrest increasing ECMO duration.
Cardiac arrest (CA) prior to initiation of Central Nervous System Injury

ECLS support is associated with increased
mortality for patients with pediatric respiratory The ELSO International Summary reports
failure. From 2008-2013 just over 14% had a that 4% of older infants and children suffer
CA prior to ECMO initiation.1 an embolic stroke and 6% have hemorrhagic
ECMO to treat ongoing CA (ECPR) was strokes (Table 21-2).1 However, most centers
described by Thiagarajan et al. using 682 cases do not routinely screen pediatric ECMO sur-
Table 21-2. Complications among pediatric respiratory failure runs reported to ELSO 2016.
Complication % Cases Survival with Complication

Central Nervous System
Neurologic criteria for death 5 -
Brain infarct 4 34%
Brain hemorrhage 6 22%
Renal System
Creatinine 1.5-3.0 mg/dL 9 34%
Creatinine >3.0 mg/dL 4 33%
Dialysis 11 33%
Hemofiltration 23 48%
CAVHD 9 41%
Coagulation/Bleeding
Oxygenator clots 11 2%
Hemofilter clots 5 48%
Cannulation site bleeding 18 54%
Surgical site bleeding 13 48%
Disseminated intravascular coagulation 6 27%
Cardiorespiratory
Inotropes during ECLS 43 45%
Pulmonary hemorrhage 8 30%
CAVHD=Continuous Arteriovenous Hemodialysis
259
Chapter 21
vivors and less symptomatic strokes are likely but may also increase hemolysis due to posi-
more common than those reported to ELSO. 26 tive pressure and increased red cell wall stress
Survival among reported patients is 34% (em- on the additional artificial surfaces. There is
bolic) and 22% (hemorrhagic). Additionally controversy over whether early judicious fluid
5% of pediatric respiratory failure patients are removal is beneficial or harmful for pediatric
declared dead based on neurologic criteria for ECLS patients.29-30
death,1 and 11% die within two days of ECMO A recent metaanalysis that used prior
initiation, suggesting that they may have suf- ECMO studies of all patient ages treated for all
fered neurologic injury prior to ECMO.15 indications estimated that overall, patients who
Pediatric VA ECMO via carotid cannulation received RRT had 89% greater mortality com-
is associated with higher rates of CNS injury pared to those not receiving RRT.31 However,
(22%) (seizures, stroke, IVH), compared to the authors went on to evaluate mortality by
central (17%) or femoral artery cannulation center use of RRT, reasoning that centers with
(15%).5 Age, pre-ECMO high-frequency os- sicker patients would be more likely to have
cillatory ventilation use, pre-ECMO arterial greater RRT use. They compared the relative
pH, pre-ECMO serum bicarbonate level, and risk (RR) of death by receipt of RRT (ie, propor-
pre-ECLS CA were independently associ- tion of RRT patients who died vs. proportion of
ated with CNS injury. Finally, an analysis of non-RRT patients who died) as a way to adjust
7,190 neonates (all indications) supported with for severity of illness and to assess the fraction
ECLS reported that 20% had CNS complica- of mortality attributable to RRT utilization.
tions. Birth weight <3 kg, mild prematurity, They reported a trend of decreased risk of death
pre-ECMO CA, pre-ECMO blood pH ≤7.11, among centers using RRT in >50% of ECMO
pre-ECMO bicarbonate use, prior ECMO runs, cases. Additionally, early implementation of
and VA ECMO were risk factors for neurologic RRT within three hours of ECMO cannulation
complications. Mortality in those with CNS was associated with lower mortality compared
complications was almost twice that of infants to later (RR, 1.31 for <3 hours, RR, 1.92 for 1-3
without (62% vs. 36%).5,7,27 days, RR, 5.00 for >3 days).31
Renal Replacement Therapies Surgery and Hemorrhage
Data submitted to ELSO have several Data submitted to ELSO includes surgical
quantifiable measures of renal insufficiency that procedures that patients received during ECMO
are shown in Table 21-2. As discussed earlier, support (Table 21-2).1 From 2008-2013, 4%
clarity regarding the timing, causes, and sever- of patients had surgeries including abdominal
ity of renal dysfunction for pediatric patients procedures (n=45), intrathoracic (noncardiac)
treated with ECLS remains elusive. Both the procedures (n=49), correction of airway anoma-
underlying causes of cardiorespiratory failure lies (n=1), and neck explorations or tracheotomy
as well as exposure to the additional extracor- (n=41). Hospital survival was 36% for those
poreal circuit biosurface initiate inflammation with abdominal procedures and 49% for patients
and fluid retention. Patients with acute hypoxic with thoracic procedures while survival for
respiratory failure who go on to recover heal neck procedures was not decreased compared
this capillary leak and tolerate diuresis while to nonsurgical patient survival (unpublished
those who remain fluid positive have much data). In pediatric patients with respiratory
greater risk of death.29 Hemofiltration efficiently failure, cannula site hemorrhage was reported in
removes water and decreases intravascular fluid, 18% of patients and surgical site hemorrhage in
260
13%. Surgical site hemorrhage was associated compared to large centers (>50 annual ECMO
with increased rates of mortality (Table 21-2).1 runs), while bronchoscopy was used signifi-
cantly less.15 Although the large centers had
Failure to Improve on ECMO significantly lower rates of renal failure (29% vs.
36% small, 43% medium) they reported greater
Brogan et al. reported that in children re- use of RRT (52% vs. 34% small, 32% medium)
ceiving ECMO support for respiratory failure, than smaller volume centers. Similar to the find-
12% were supported for three weeks or more and ings of the metaanalysis by Seon-Sook et al., use
in this subset of patients overall survival was of RRT at large volume centers exceeded 50%
38%, compared to 61% for those supported for and was associated with improved survival.15
two weeks or less.32 Pre-ECMO factors such as One report using ELSO data not find a
the etiology of respiratory failure, comorbidities, consistent increased risk of patient mortality
or severity of pre-ECMO hypoxemia were not at low volume centers.35 The analysis adjusted
associated with survival among those treated for secondary diagnoses, such as acute renal
for three weeks or more of ECLS and survival. failure and comorbid conditions (not specified)
Complications occurring during ECMO were that were reported to ELSO as ICD9 numbers,
more common among non-survivors. The use which the authors described as markers of ill-
of inotropic infusions, persistent acidosis (pH ness severity. ICD9 codes are reported for the
<7.2) during ECMO and male gender were in- entire hospital course and adjustment for renal
dependently associated with increased odds of failure was intended to negate an additional
death in the subset of children receiving ECLS mortality risk. For children who receive all
for three or more weeks. Among patients who their critical care at an ECMO center even if
do not recover adequate lung function, most acute renal failure developed prior to ECMO,
providers continue full support until complica- it still developed under that center’s care, so
tions result in multiorgan failure and at that adjustment for this would inappropriately lower
point recommend discontinuation of ECMO. the adjusted mortality risk for that center. Obvi-
ously some patients are referred to an ECMO
Hospital Volume center after developing acute organ failure but
many are not. Given that AKI is both common
Recent studies report that hospitals with and associated with substantial mortality risk,
smaller ECLS center volumes have greater these results may be questioned.
in-hospital mortality,15, 33-34 but the relationship
between volume and mortality is complex. Prediction of Mortality Risk Prior to ECLS
Volume is likely a surrogate for other important Initiation
characteristics. A study analyzing factors as-
sociated with both mortality and center volume Two recent reports 36-37 emulating the
among pediatric respiratory failure patients methodological approach used by Schmidt et
found that after adjustment for the primary pul- al,38 Pediatric Pulmonary Rescue with ECMO
monary condition, independent risk factors for Prediction (P-PREP) and Pediatric Risk Esti-
mortality included: initiation of ECLS after two mate Score for Children Using Extracorporeal
weeks of mechanical ventilation, renal failure, Respiratory Support (Ped-RESCUERS), have
and liver necrosis; while bronchoscopy was been developed as prognostic tools to estimate
associated with decreased mortality.15 Renal expected mortality rates with ECLS to support
failure was significantly more common during pediatric respiratory failure (Table 21-3). Both
care at small (<20 annual ECMO runs) centers sets of researchers used subsets of data reported
261
Chapter 21
to ELSO to identify factors independently as- Table 21-3. The Pediatric Pulmonary Rescue
sociated with mortality and the remaining ELSO with Extracorporeal Membrane Oxygenation
Prediction (P-PREP) tool.
cohort (Figure 21-2). Table 21-2 was used in
the Bailly et al. report.36 These authors also 1
Points
validated their model using a cohort from the Venovenous vs. Venoarterial ECMO -4
Mechanical Ventilation >14 days 5
Pediatric Health Information System (PHIS) PaO2/FiO239
data to validate the model in addition to the Mild ARDS vs. acute lung injury 4
ELSO subset. The receiver operator curve Moderate ARDS vs. acute lung injury 5
Severe ARDS vs. acute lung injury 7
(ROC) for the ELSO cohort was 0.66 (95% CI: pH
0.63–0.69) and for the PHIS slightly better (0.69 <7.11 vs. 7.11-7.34 1
[95% CI: 0.67-0.71]). Possible scores range >7.34 vs. 711.-7.34 -1
Primary Pulmonary Diagnosis
from -13 to 53 with greater numbers predicting Asthma -8
increased mortality. For example, a score of -5 Aspiration -5
predicts about 15% mortality, while a scores Respiratory syncytial virus -4
Sepsis 3
of 10 predicts just over 40%, and 20 predicts Pertussis 5
just under 80% (Figure 21-2). A fundamental Comorbid Conditions
issue is whether the comorbid conditions that Pre-ECMO cardiac arrest1 3
Cancer 6
substantially increase risk of death are apparent Acute renal failure 8
prior to ECMO initiation. The practical utility Acute liver necrosis 18
of the score is currently unknown.
The Ped-RESCUERS score differs from
development group and decreased to 0.634 in
the P-PREP with use of more physiologic data
the validation group.
(mean airway pressure, PaCO2, blood pH). Cur-
rently a calculator is available online for use,
Conclusion
pre-ECMO, to aid in risk of mortality assess-
ment (http://www.ped-rescuers.com/). Similar
The estimated risk of mortality in children
to the P-PREP score, only a few pulmonary di-
treated with ECLS for respiratory failure is
agnoses are used in this score: pertussis, asthma,
complex. Certain comorbidities such as under-
and bronchiolitis. The ROC was 0.690 for the
lying malignancy and acute renal failure clearly
increase risk of death. Certain complications
(CNS injury, hemorrhage, failing to improve
on ECMO support) are also associated with
increasing risk of death. Other factors are not
as clear: underlying genetic abnormalities, use
of RRT and other interventions while on ECMO,
plus center volume. The ability to predict death
and very poor outcomes is essential in helping
clinicians decide which patients will benefit
from this intervention. The use of the P-PREP
score may be of use in this way, but more studies
are needed to determine the utility in practice.
Figure 21-2. The shaded band is a 95% point Additional research is urgently needed to assess
wise confidence band. Scores <-5 and >21
are not represented because of small numbers long term neurocognitive and quality of life
of patients. among survivors.
262
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265
22
Management of the Pediatric Respiratory Failure Patient on ECMO
Heidi J. Dalton, MD, Lakshmi Raman, MD
Introduction and perfusion. Studies have shown that failure

to decrease lactate, normalize pH and reduce
ECMO is increasingly applied as the rescue mean airway pressure and ventilator FiO2 within
therapy of choice for acute respiratory distress the first 24 hours is associated with decreased
syndrome (ARDS) refractory to conventional survival.1-3 Flow must provide not only adequate
care and for a variety of other respiratory illness- systemic blood pressure but also adequate oxy-
es in children. In the latest report from ELSO, gen delivery to reverse “oxygen debt.” While
the number of pediatric patients with respiratory there are no devices that can tell us what tis-
failure placed on ECMO was 7355 with overall sue oxygenation is at the mitochondrial level,
survival of 60%. Table 22-1 outlines common many clinicians follow indirect measures that
disease processes and outcomes. This chapter may be helpful. Examples of commonly used
will focus on current patient management for patient and ECMO equipment parameters that
respiratory failure patients on ECMO and ad- are available are:
dress future studies needed to address the gaps • Serial lactate
in knowledge. • Serial pH (maintain >7.30, preferably nor-
The first few hours after placement on mal between 7.35-7.45)
ECMO are vital to establish optimal ECLS • Clinical perfusion (toe temperature, capil-
support as well as improve tissue oxygenation lary filling time)
• Arterial blood pressure (best measured with
Table 22-1. Respiratory Failure ECMO an indwelling line)
Patients. (Adapted with permission from the
International Extracorporeal Life Support • Central venous or pulmonary artery oxygen
Registry, January 2016, Ann Arbor, MI) saturation
• Urine output
Pediatric Respiratory Runs by Diagnosis
Avg Run Longest Run • Neurologic status (if patients are awake,
Total Runs Time Time Survived % Survived
Viral pneumonia 1,564 317 2968 1,021 65% they are likely getting good cerebral per-
Bacterial pneumonia
Pneumocystis
736 284 1411 435 59%
fusion)
pneumonia
Aspiration pneumonia
35
322
373
242
1144
2437
18
220
51%
68%
• EKG: rhythm, signs of coronary ischemia
ARDS, postop/trauma
ARDS, not
191 247 935 119 62% • Echocardiography: estimated volume
postop/trauma
Acute resp failure,
571 305 3086 310 54% status; flows across valves (aortic, pulmo-
non-ARDS
Other
1,331
2,605
259
223
2718
2465
738
1,357
55%
52%
nary); cardiac output (hard to ascertain in
Run time in hours. Survived=survival to discharge or transfer based on number of runs VA support)
267
Chapter 22
• Ultrasound: Gaining increased experience culation is normal, arterial saturations of >80%

and utility for estimating lung volumes, ef- and venous saturations of >70% are common
fusion volumes, cardiac filling, adequacy of goals, although arterial saturations <80% may
blood volume by IVC diameter. also be tolerated. Once physiologic goals are
• Ventilator: tidal volumes, end tidal CO2 set, manipulate the blood flow provided by the
monitoring, pressure and oxygen delivered ECMO circuit to maintain set goals. The FiO2
(discussed more specifically later) delivered to the membrane lung should maintain
Machine related: postmembrane saturation of near 100%. The
membrane lung efficiently removes carbon di-
• Venous (also called outlet or drainage) pres- oxide and the patient’s carbon dioxide level can
sure monitoring be controlled by manipulation of total sweep
• Venous saturation monitoring gas flowing through the membrane lung. In
• Arterial pressure (also called inlet or return) patients who have elevated PaCO2 levels prior
monitoring to ECMO, reduction to normal levels should
• Flow rates (establishing maximum rate that be done slowly to avoid rapid and potentially
can be obtained without generating high damaging alterations in cerebral blood flow.
negative venous pressure; minimum rate Specific patient management perspectives by
that maintains adequate blood pressure and system are as follows:
oxygenation)
• Continuous blood gas monitoring (some Patient Management
centers use this)
Management of the ECMO circuit is cov- Cardiac
ered in detail elsewhere but is also covered
briefly here. Sample clinical pathways for ve- Many patients with severe respiratory
noarterial (VA) and venovenous (VV) support failure will be on vasoactive support prior to
(courtesy of the Alfred Hospital, Melbourne, ECMO. Much of this need (unless intrinsic
Australia) are shown in Figures 22-1 and 22-2. cardiac disease is present) relates to the adverse
Once on ECMO, circuit flow should be gradu- cardiac effects of high levels of ventilator sup-
ally increased to determine the maximum flow port required prior to ECMO. Once mean airway
possible without incurring venous outflow pressure is reduced, venous filling to the heart
limitation and high negative venous pressure. may improve. Coupled with improved oxygen
Flow should then be returned to the level that delivery from ECMO support, the heart often re-
provides desired support. turns to a normal (or even hyperdynamic) state.
For patients on VA support, maintaining a Inotropes can be weaned as systemic blood
patient arterial pulse pressure of at least 5-10 pressure and perfusion improve. Respiratory
mmHg is desired, allowing some blood to enter failure patients commonly develop hypertension
the native pulmonary circulation. Perfusion during ECMO support. This has been described
of the pulmonary bed may prevent ischemia, both in VA and VV patients.4,5 While this can
which can exacerbate existing injury. Native result initially from better circulation of admin-
left ventricular output also predominantly istered vasoactive medications once ECMO is
provides flow to the coronary arteries. Flow begun, hypertension can also develop later in
goals for patients on VA-ECMO often aim for the course. In patients on VA support, reduc-
oxygen saturations of >90-95% and venous tion of cardiac filling pressures from diversion
saturations of 70%. In patients on VV access, of venous blood into the ECMO circuit may
in which flow through the cardiopulmonary cir- cause a reflex increase in heart rate or cardiac
268
Is the circulation pulsatility No

Urgent
maintained or improving?
Extrinsic compression No extrinsic compression

Yes
Early surgical treatment Medical management to

(prevent intra-cardiac maintain some intra cardiac
thrombosis) flow and prevent intra-cardiac
thrombosis
Consider
1. ↑ Inotropes (ECHO guidance)
2. ↑ Anticoagulation
Is ECMO blood flow (in addition to
No 3. ↓ ECMO flows
native cardiac output) adequate
for systemic perfusion?
↑ECMO Flow or
Troubleshoot low ECMO circuit flows
Yes
Treat cause: (e.g. PCI or anti-arrhythmic)
Yes
Is there severe LV failure?
↓ LV load: ↑ PEEP and ↓ MAP
↑ ECMO circuit blood flow

No
Treat cause of lung shunt: (e.g. bronchoscopy and

Is there (R) arm hypoxaemia antibiotics)
Yes
secondary to lung shunt
↑ Lung Support (PEEP and FiO2)
(peripheral ECMO only)
↑ ECMO circuit blood flow
No Consider change of ECMO mode to VV ECMO
No
Is inotropic support minimal or off? Continue ECMO Support
(Inotropes should be minimised for cardiac

recovery)
Yes
Consider weaning trial
Figure 22-1. Venoarterial clinical pathway. (Adapted with permission from the Alfred Hospital, Mel-
bourne, AU; INOVA Fairfax Hospital, June 30, 2016)
269
Chapter 22
Is lung ventilation safe?

TV < 6ml/kg ; PIP < 30; FiO2 < 0.6
No
Establish Safe Lung Ventilation

Yes
Is SaO2 Safe? (88-94)
No
Yes
Check:
1. Sweep Gas
2. Blender
3. Flow Calibrations
Patient Arterial PCO2 Sample
If low SaO2 Persists:

PCO2 high PCO2 PCO2 low
normal Is there access insufficiency?
Yes
Improve Access
↑ Sweep No ∆ ↓ Sweep gas No
gas Sweep
Gas
If low SaO2 Persists:
Increase circuit blood flow (6-7L)
Weaning
Sweep gas If low SaO2 Persists:
CIRCUIT Pre-Oxygenator O2 Sample
Sweep gas off and capped 2-

24 hours
Pre Oxygenator SaO2 Pre Oxygenator SaO2
low (< 60): (High O2 high (>80)
Consumption)
(Recirculation)
Consider:
Consider:
Decannulate if blood gases, 1. Tolerating sat!
vent settings and 2. Hb > 10 Changing cannulae
hemodynamics within 3. Paralysis positions to reduce
parameters 4. ↓Temperature recirculation
5. HFO/NO/PGI2
Figure 22-2. Venovenous clinical pathway. (Adapted with permission from Alfred Hospital, Melbourne,
AU: INOVA Fairfax Hospital, June 30, 2016)
270
output from baroreceptors in the myocardium cardiac ejection preferentially supports the heart
or vasculature sensing an “underfilled” atrium. and brain (upper body). In this circumstance, a
Tachycardia and hypertension can result. Also, cannula may be placed into the right internal
the nonpulsatile flow of VA-ECMO may cause jugular (IJ) vein or right atrium and return from
increases in renin and angiotensin from the the ECMO circuit incorporated into this can-
kidneys detecting inadequate flow (even though nula by means of a Y connector. (Commonly
flow may be normal). Thus, common medica- called venoarteriovenous [VAV] ECMO.) This
tions to treat hypertension during VA-ECMO in- approach directs oxygenated blood from ECMO
clude angiotensin converting enzyme inhibitors into the right heart and improves upper body
or beta-blockers such as esmolol. Nitroprusside, saturation. Care should be taken to monitor flow
or other vasodilators can also be used, although both in this cannula and the femoral arterial site,
caution should be taken as they may reduce as adequate flow into both cannulas is needed to
venous return and limit ECMO flow. They may prevent clotting (the right atrial cannula is usu-
also cause a further decrease in cardiac filling ally larger and gets more flow). Flow restriction
pressures, which may exacerbate the normal with a Hoffman clamp is often used to balance
reaction of the heart and cause more tachycar- blood flow.
dia and increased cardiac output. Hypertension Patients on VV-ECMO with hypoxia to a
that occurs with VV-ECMO is less likely due level that is causing clinical harm at a tissue
to these mechanisms and may reflect volume level can also have trials of increased ECMO
overload or other factors that increase systemic flow, although at higher flow the risk of re-
vascular resistance or cardiac output such as agi- circulation increases. In patients with 2-site
tation, pain, etc. Hypotension in VA-supported cannulation, draining from the femoral venous
patients can be treated with increased flow from cannula and reinfusing into the right atrial site
the ECMO circuit, administration of fluids (if may limit recirculation.
hypovolemic), or may require inotropic support, Learning to accept low oxygen saturations
especially in patients with vasodilatory shock (even to 70-80%), which are often well tolerated
or sepsis. Patients on VV support are dependent in some patients, and monitoring for adequacy
on adequate native cardiac function and the of perfusion in terms of lactate measurements,
need for vasoactive support should be based on cerebral oximetry, and clinical status (eg, ad-
cardiac performance and hemodynamics. equate urine output) are important aspects of
care. While increased inspired oxygen to the
Hypoxia and Related Complications ventilator circuit or escalation of ventilator set-
tings may also improve systemic gas exchange,
Hypoxia and related complications in VA- maintaining nontoxic ventilator support to opti-
supported patients can be reversed by increas- mize the milieu for lung recovery is important
ing flow into the ECMO circuit. Limitation of and hence not an adoptable strategy if it can
venous outflow needed to support oxygenation be avoided.
and hemodynamics in VA support may require Red blood cell transfusion to increase oxy-
placement of additional venous drainage can- gen delivery is sometimes helpful in hypoxic
nulas if simpler measures such as volume patients, although controversy over goal he-
loading or optimizing cannula placement prove moglobin levels exists. Most centers maintain
ineffective. a hemoglobin of 8-12 g/dL. If transfusion is
Femoral VA-ECMO can result in upper ineffective, then reducing oxygen consump-
body hypoxemia (differential cyanosis) if the tion by sedation and/or lowering temperature
patient has severe respiratory failure and native may be helpful. Decreasing cardiac output will
271
Chapter 22
increase the proportion of saturated blood from Renal

the ECMO circuit traversing the native cardiac/
pulmonary circuit and may improve saturation, Renal failure is associated with increased
although adverse effects of low cardiac output mortality. In a recent metaanalysis, 55.6% of
on tissue perfusion must be avoided. Another ECMO patients had acute kidney injury with
venous cannula to provide increased additional 35% of them requiring renal replacement
drainage can also be added. In 2-site cannula- therapy (RRT).6 While there is a current trend to
tion, a 3rd cannula can be added to the femoral maintain strict fluid balance and avoid overload,
site and both lower body cannulas used for especially by the third day of ECMO, care must
drainage. The right IJ or right atrial cannula be taken to not cause hypovolemia or impaired
can then be used in a similar fashion, a venous perfusion. Almost all patients receive diuret-
(or arterial) cannula can be introduced which ics, either in intermittent dosing or constant
is then Y’ed into the oxygenated return limb of infusion. Following intake and output of fluids
the ECMO circuit. Limitation of venous flow and concentrating medications are important
may require additional cannula placement. Hy- aspects of care. Continuous renal replacement
pothermia can be an adopted strategy to reduce therapies (CRRT) are used to maintain fluid
cardiac output and the metabolic demand of the balance, support failing kidneys, and potentially
body. If inadequate oxygenation on VV-ECMO clear proinflammatory cytokines from the blood
and/or patient factors leads to hemodynamic (see Chapter 62). To better define the efficacy
failure, the patient may require conversion to of RRT for patients on ECMO in this recent
VA support metaanalysis, the total ECMO mortality rate
was compared to the use of RRT. If the use of
Infection RRT was less than 30%, mortality rates were
lower. However, increasing the use of RRT from
There are no indications for prophylactic an- 30% to 50% decreased mortality, suggesting that
tibiotics in patients on ECMO. Markers of blood use of renal replacement therapy on ECMO may
stream infections, such as temperature lability actually decrease mortality. Furthermore, based
and inflammatory markers, may not be reliable. on the metaanalysis, the risk ratio of mortality
The need for multiple manipulations to maintain increased if RRT was delayed.7,8 Another recent
temperature in the desired range may be a clue study of 86 children on ECMO compared those
to fever, but patients are not “allowed” to mount who received hemofiltration to those who did
a febrile response since the ECMO circuit can not. The main indication for hemofiltration was
control temperature fairly easily. White blood fluid overload in 67%, renal failure in 21%, and
cell counts may change as a response to initia- electrolyte abnormalities in 11.6%. Patients
tion of ECMO, although the function of white receiving hemofiltration had longer duration
blood cells is thought to return to normal within of ECMO support (127 hours vs. 121 hours,
a few days. Biomarkers such as procalcitonin p=0.05) and received more platelet transfusions.
or CRP may be useful, especially as trending There was no difference in the proportion of pa-
studies. Cultures for suspected infection and tients decannulated or who survived to hospital
appropriate treatment should be instituted as discharge (49% in hemofiltration compared to
needed. Routine circuit cultures, however, are 63% in controls, p=0.19).9
not currently recommended. Data from the ELSO Registry shows that
about 30% of pediatric and adult patients un-
dergoing ECMO undergo renal replacement
either by hemofiltration or dialysis, although
272
elevations of creatinine greater than 1.5 mg/dl membrane lungs affect pharmacokinetics and
were reported in only 15% of pediatric patients. dynamics is under investigation. Therapeutic
Other adjunct extracorporeal therapies such drug level measurements should be done, when
as plasmapheresis/plasma exchange or liver available, to demonstrate adequate dosing (see
support systems have been used successfully Chapter 71).
during ECMO.
Sedation
Nutrition
Maintaining patient comfort, safety of the
Adequate nutrition is essential for healing; ECMO circuit, and minimizing the adverse ef-
provided by total parenteral nutrition, enteral fects of narcotics, benzodiazepines, and other
feeding, or a combination of both. Enteral feed- medications is the goal. Opioids such as fen-
ing has been shown safe and effective during tanyl and morphine are often already in place
ECMO in all groups of patients and may limit at the time of ECMO initiation and continue
the need for total parenteral nutrition and its as first line drugs. Tachyphylaxis to fentanyl
associated complications. With the current (and morphine) can occur over time and rapid
trend to maintain patients awake, extubated, or escalation of these medications can occur. The
with a tracheostomy, oral feeding can also be impact of newer tubing material, coatings, and
established in some patients. In patients unable membrane lung composition may also affect
to tolerate nasogastric (NG) or oral feeding, circulating levels of sedatives, although data
nasojejunal (NJ) placement early in the course on current circuitry and pharmacodynamics and
is useful. Such placement can be done safely kinetics is just beginning to appear. Benzodi-
even with anticoagulation on board. If unable azepines such as midazolam are also frequent
to place blindly, consider early fluoroscopic during ECMO. Given the longer duration of
help to avoid delay in feeding initiation. Caloric ECMO that many patients currently incur, the
goals should be similar to those of critically dosage of sedative medication can become
ill patients and time-to-goal calories should extremely large. Further, weaning sedation in
be reached as soon as possible.10A. One reason ECMO survivors often lengthens hospital stay
often quoted for use of CRRT is to control due to withdrawal complications.11,12 Despite
volume overload related to feedings, although its cost, dexmedetomidine can be helpful in
this remains controversial. It is agreed, however, limiting the need for other medications while
that TPN including use of intralipid should be still providing patient comfort. The need for
limited and enteral nutrition remain the goal. multiple medications, often at high dose, to
Lipid infusion with newer PMP membranes maintain patients “asleep and quiet” is another
has not been associated with oxygenator failure. reason why allowing them to be more awake is
valuable. In an international survey of sedation
Pharmacology practice, fentanyl and morphine were the most
commonly used opioids while midazolam and
Many circulating drug levels may be re- lorazepam were common benzodiazepines.13
duced from hemodilution or adherence to the Answers to queries asked in the survey are
ECMO circuit. With the newer circuit coatings, shown in Table 22-2.
shorter tubing lengths, and oxygenator materials
currently in use, much of the prior research in
this area is likely to be invalid. Many new inves-
tigations are underway. How newer circuits and
273
Chapter 22
Table 22-2. Sedation Practices Questions (Adapted with permission from Buscher H, Vaidiyanathan
S, Al-Soufi S, et al. Sedation practice in venovenous extracorporeal membrane oxygenation: an inter-
national survey. ASAIO J. 2013;59(6):636-641)
Total (n = 102) Nonexpert (n = 84) Expert (n = 18) p
What level of sedation do you most often achieve when your patient is 0.967
on full ECMO support?
Cooperative and tranquil 34 (33) 27 (32) 7 (39)
Response to commands only 18 (18) 15 (18) 3 (17)
Brisk response to light glabellar tap or loud auditory stimulus 8 (8) 7 (8) 1 (6)
Sluggish response to glabellar tap or loud auditory stimulus 27 (26) 23 (27) 4 (22)
No response to glabellar tap or loud auditory stimulus 15 (15) 12 (14) 3 (17)
Compared with other patients in your intensive care unit with similar 0.109
target sedation levels: What do you think is the dose requirement in
ECMO patients?
Generally much more 21 (21 14 (17) 7 (39)
Generally more 38 (37) 35 (42) 3 (17)
Similar 31 (30) 26 (31) 5 (28)
Generally less 10 (10) 7 (8) 3 (17)
Generally much less 2 (2) 2 (2) 0
Do you use a sedation score to prescribe and/or monitor sedation? 0.058
Yes 50 (49) 41 (49) 9 (50)
No 34 (33) 25 (30) 9 (50)
Sometimes 18 (18) 18 (21) 0
Do you reduce/stop sedation daily to assess the patients’ neurology? 0.982
Yes 44 (43) 36 (43) 8 (44)
No 22 (22) 18 (21) 4 (22)
Sometimes 36 (35) 30 (36) 6 (33)
Referring to adult patients on veno-venous ECMO: What 0.059
benzodiazepine do you use most frequently?
Midazolam 81 (79) 63 (75) 18 (100)
Lorazepam 18 (18) 18 (21) 0
Other 3 (3) 3 (4) 0
Referring to adult patients on veno-venous ECMO: What opioid do 0.011
you use most frequently?
Morphine 44 (43) 35 (42) 9 (50)
Fentanyl 46 (45) 41 (49) 5 (28)
Sufentanil 10 (10) 8 (10) 2 (11)
Remifentanil 2 (2) 0 2 (11)
Do you use Propofol routinely? 0.618
Yes 36 (35) 28 (33) 8 (44)
No 65 (64) 55 (65) 10 (56)
Sometimes 1 (1) 1 (1) 0
What other cosedatives do you use in ECMO patients (more than one
answer possible)? 0.651
Ketamine 29 (28) 23 (27) 6 (33)
Clonidine 26 (25) 16 (19) 10 (56)
Dexmedetomidine 42 (41) 37 (44) 5 (28)
Barbiturate 6 (6) 5 (6 ) 1 (6)
Other 5 (5) 4 (95) 1 (6)
None 30 (29) 26 (31) 4 (22)
What proportion of you ECMO patients will be on muscle relaxants 0.701
for longer than 24 hrs at one point during ECMO?
<3% 36 (35) 29 (35) 7 (39)
3 to 33% 30 (29) 23 (27) 7 (39)
33 to 66% 21 (21) 18 (21) 1 (6)
66 to 100% 14 (14) 13 (15) 3 (17)
Don’t know 1 (1) 1 (1) 0
What muscle relaxant do you most commonly use for continuous 0.048
treatment?
Atracurium 11 (11) 7 (8) 4 (22)
Cisatracurium 21 (21) 16 (19) 5 (28)
Pancuronium 8 (8) 6 (7) 2 (11)
Rocuronium 10 (10) 8 (10) 2 (11)
Vecuronium 40 (40) 39 (46) 1 (6)
None 11 (11) 7 (8) 4 (22)
Don’t know 1 (1) 1 (1) 0
274
Neurology sion.22, 23 Other agents such as direct thrombin

inhibitors are also used, especially in patients
Baseline head ultrasounds are routine in who develop heparin induced thrombocytope-
neonates and are often performed the first nia. While many tests (activated clotting time,
several days once placed on ECMO to iden- anti-Xa level, PTT, thromboelastography)
tify bleeding or infarction.14-19 Unlike in the are performed to aid anticoagulation titration,
early years of ECMO, patients with identified none have been shown superior, but some may
hemorrhage that is not massive can receive be more useful than others, depending on the
ECMO support unless confirmed neurologic clinical setting.
devastation appears likely. In older children, Clinicians disagree about the level of
neurologic assessment by ultrasound cannot hemoglobin needed during ECMO but the
be performed due to closed fontanels. Clini- current trend is acceptance of lower levels of
cal neurologic exam is mandatory and another hemoglobin in critically ill patients, including
reason why maintaining a minimally sedated ECMO patients. Many centers now delay trans-
patient is helpful. Any concerns for bleeding or fusion until the hemoglobin falls to 7-10 gm/
infarction should be followed with computed dL, providing the patient had no signs of tissue
tomography. Of note, there are now several hypoxia. The needs of the patient and the risks
case reports of patients with traumatic brain of transfusion are a balance the clinical team as-
injury being supported with ECMO.20 These sesses on an ongoing basis. Conversely, patients
are mainly in the adult population and associ- with hypoxemia may benefit from increased
ated with pulmonary contusion or ARDS. Such oxygen carrying capacity and oxygen content
cases may use little or no anticoagulation with by transfusion. This is probably more important
good outcomes obtained. Many centers also use in patients supported on VV-ECMO, in whom
near-infrared spectroscopy and electroencepha- oxygen delivery is lower than in VA patients.
lography (EEG) to follow patients. One simple The adverse effects of blood transfusion
exam, which should be followed and docu- include infection, lung injury, prolongation of
mented, is pupillary size and reaction. Some ICU and hospital stay, and increased mortality.24
recent preliminary data show that with the use
of a mathematical model of wavelet coherence Endocrine
with mean blood pressures and NIRS saturation,
disturbances in cerebral autoregulation can be Hyperglycemia should be controlled as per
seen and may help to predict intracranial events guidelines for critically ill children. Electrolyte
(Raman L, unpublished data). imbalance, usually hypernatremia, can occur
All survivors should receive a CT or MRI and is easily managed by controlling sodium
prior to discharge to identify abnormalities, intake in fluids and medications. Hyperkale-
which may require serial assessment or benefit mia or hypocalcemia may occur especially on
from early intervention programs aimed at im- initiation of ECMO from rapid transfusion of
proving neurodevelopmental outcome.21 stored blood.
Anticoagulation and Blood Product Ventilation

Replacement
Optimal ventilator management for patients
This is discussed in Chapter 7. In brief, supported for respiratory failure seems to be
heparin remains the most commonly used anti- highly controversial and center dependent. No
coagulant and is administered by constant infu- clear guidelines have been established other
275
Chapter 22
than preventing fluid overload and using non- to the lung, especially to the areas less injured,
damaging ventilator settings. The goal of can result in ongoing ventilator induced lung
ECMO support is to minimize barotrauma injury. Perhaps the most important lesson for
and oxygen toxicity, and promote lung heal- lung management during ECMO learned over
ing. Current recommendations based on the past ten years is to be patient and allow
ELSO guidelines on respiratory management remodeling and recovery to occur. This often
in ECMO for neonates suggest FiO2 of 0.21- takes weeks to months, rather than the 14-day
0.3, peak inspiratory pressure of 15-22, rate of limit previously placed on ECMO duration.
12-20 and I-time of 0.5 seconds. In pediatric Patients with pulmonary hypertension may
patients, use of higher PEEP (10-15 cm H2O) receive therapies such as inhaled nitric oxide
is often recommended to maintain some lung or intravenous pulmonary vasodilators prior
expansion, while low rates, peak pressure <28- to ECMO. Continuation of these medications
30 cm H2O, inspiratory times of 0.8-1 second is controversial. Once the patient is supported
and FiO2 <50% are common. However, in the with ECMO, any benefit from continuation of
current era of prolonged ECMO and a desire to these therapies is likely minimal. Thus, dis-
keep patients awake, recommendations are to continuation of inhaled nitric oxide or other
use lower settings including CPAP or extuba- medications can be recommended. For patients
tion.25,26 with severe right heart failure from pulmonary
In an evaluation from the ELSO Registry, hypertension, especially those provided with
the mode of ventilation (HFOV or conventional) venovenous support, pulmonary vasodilators
did not affect mortality. Pressure control mode may improve right heart function and may have
of ventilation is the most common mode of a role in continuation even during ECMO sup-
ventilation used by centers based on the inter- port. However, if they do not seem to improve
national survey published in 201427 and a recent forward flow or ventilation/perfusion match-
survey from 2016 (Jenks C, unpublished data). ing, then continuation during ECMO may be
The ECMO circuit provides gas exchange, superfluous. They may have a greater role in
so patients should not rely on the ventilator weaning off ECMO or post-ECMO support. The
coupled with the benefits of maintaining the need for adjuncts such as inhaled nitric oxide to
patient in an awake state, use of HFOV during wean off ECMO support, however, may indicate
ECMO seems unnecessary. Patient tolerance that pulmonary vascular resistance remains high
of HFOV commonly requires more sedation. It and risk for post-ECMO failure significant. Un-
also renders examination of breath sounds, tidal less circumstances (excessive bleeding, other
volumes, and other parameters impossible, and complications) push the clinician to wean the
has shown no advantage in recovery. patient from ECMO, following changes in the
Weaning patients who are receiving HFOV patient and assessing the need for adjunctive
following initiation of ECMO to CMV (or medications for weaning appears prudent.
CPAP) seems prudent. Similar thinking applies
for high frequency jet ventilation.28 ECMO Extubation on ECMO
usually removes carbon dioxide efficiently and
the jet is unnecessary. Other adjunct techniques We have discussed the trend away from the
such as APRV and percussive ventilation have days of sedated and paralyzed patients to days
also been reported in single center reports.29 of “awake” ECMO. Although much of the data
Again, if the goal is to allow lung recovery to derives from patients awaiting lung transplant,
occur at its natural pace, then any technique such reports in children are increasing. In a
that results in excessive pressure or volume recent international survey (Jenks, unpublished
276
data) on ventilation practices for patients on useful. In some patients, dyspnea that interferes
ECMO, approximately 40% of the centers with ECMO flow cannot be overcome and the
extubated their patients in the first week of patient requires increased ventilator support or
ECMO and about 26% of the centers extubated sedation (even neuromuscular blockade in some
them 1-2 weeks into their ECMO run. This circumstances). Continued efforts at weaning
represents a large shift when compared to the ventilator support may be useful, however, and
previous survey where only 1% of the centers should be attempted.31
extubated patients on ECMO. Extubation on In centers moving toward extubation as a
ECMO was performed in 32% of the cases if patient care practice, a dedicated team, protocol,
the center provided both pediatric and neonatal and strategy helps establish this practice safely
ECMO and 51% of the cases in adult centers. and efficiently. Steps needed for rapid estab-
Routine use of tracheostomies to maintain an lishment of an airway in the event of ECMO
airway for pulmonary clearance was performed circuit failure, whether the patient will be
by only 12% of centers, although 48% of sites reintubated prior to decannulation, and other
performed tracheostomies in selected patients; specifics should be outlined for each patient.
28% of the centers used their native airway. Of
note, the survey from 2016 noted an almost Diagnostic Tools in ECMO
32-50% increase in patients extubated during
ECMO support, indicating the rising proportion Bronchoscopy and imaging of the chest are
of patients who are extubated during ECMO increasingly used as diagnostic tools in patients
(Jenks, unpublished data). The advantages on ECMO.32 Initial bronchoscopy findings
of extubation include less need for sedative often guide the need for future bronchoscopies
medications, more movement, which limits during the ECMO run. Multiple case series in
skin breakdown and improves muscle strength, both pediatrics and adults demonstrate the value
easier determination of neurologic status, and of bronchoscopies in reducing the duration of
avoiding the harmful effects of positive pres- ECMO.33,34
sure ventilation. Imaging of the chest plays a vital role in the
Some patient who receive ventilation management of patients on ECMO. There has
weaning toward extubation experience severe been greater use of ultrasound (US) due to its
dyspnea. Even in patients in whom oxygenation ease of use at the bedside, thereby avoiding the
and ventilation seem adequate, spontaneous risks of transport. US can be useful in detect-
breathing efforts can result in nasal flaring, ing the existence and complexity of fluids in
retractions, and intrathoracic pressure changes the pleural space. However, since it does not
leading to loss of venous return and poor help in evaluating the underlying lung disease,
ECMO flow. Although the underlying mecha- its value is limited. In a Swedish study from a
nism remains obscure, one theory holds that center with considerable ECMO experience for
patients with severely consolidated lungs and ARDS, CT imaging identified findings requir-
minimal tidal volumes may have baroreceptor ing interventions in 18% of their patients and
responses which initiate breathing efforts de- they also showed that transport to the CT suite
spite adequate oxygenation and ventilation.25,30 was safe.34 Similarly, in a small case series in
In some patients, the visual dyspnea distresses pediatric patients, CT imaging led to interven-
the bedside providers and family members tions in 84% of their patients.33 Other bedside
but the patient seems unperturbed. In other diagnostic tools such as electrical impedance
patients, calming measures to help the patient tomography to identify patients in whom lung
reduce respiratory effort by distraction can be recruitment can be achieved and transpulmo-
277
Chapter 22
nary pressure using esophageal balloons to refuting the findings of increased risk with
titrate PEEP may be useful. centrifugal systems is vital, and working to-
gether with industry to design new equipment
Other Interventions that can potentially improve outcomes should
be a priority.
Prone positioning in ARDS has become a
part of routine management in many patients Followup
with severe ARDS, particularly after the PROS-
EVA study.35 In patients on ECMO with tenuous Perhaps one area deserving much more
oxygenation, multiple case series have shown effort is in followup of survivors of ECMO.
that prone positioning may be used safely and Neonatal followup has been much more efficient
MAY improve oxygenation and lung compli- than in older children, but shows that about
ance.36-38 Caution rules the day, particularly 50% of survivors have neurodevelopmental
in its application in pediatrics with the risks abnormalities.1,44-46 While severe disability oc-
associated with accidental dislodgement of the curs relatively rarely, behavioral, school perfor-
cannula. mance, and socialization problems are evident.
Designing and implementing adequate fol-
Complications lowup systems for ECMO survivors are vital.
Bleeding and thrombosis remain the most Conclusion

common complications with extracorporeal
support.39 Both decrease survival and increase Pediatric respiratory failure supported by
morbidity. Efforts to identify “optimal” an- ECMO is a rapidly emerging field with advanc-
ticoagulation regimens to limit these events es in critical care and circuit technology. Patient
are multiple, but none has shown to be overly management requires meticulous attention to
effective. Limb ischemia from poor perfusion, details to achieve optimal outcome. Minimizing
especially with femoral arterial cannulation, ongoing ventilator induced lung injury to allow
also occurs and neurovascular integrity is an recovery is paramount. Care recommendations
important aspect of patient care. New can- involve limiting sedation and allowing the pa-
nulas and placement techniques may lessen tient to be in an “awake” state and considering
this concern.40 Mechanical complications also ventilator weaning to the extent of extubation is
occur in the form of membrane lung failure, currently a trend. Lack of consensus as to “best
which increases as the duration of ECMO is practice” for multiple areas of patient care exist
prolonged. Circuit thrombosis, pump failure, and such variability makes drawing conclusions
air entrainment, and other potential potentially from single center reports difficult. Questions
lethal events occur but are relatively infrequent. as to optimal ECMO technology, ventilator and
The finding that centrifugal pumps may be as- anticoagulation management, and other aspects
sociated with increased mortality and bleeding/ of care remain. Answering these questions may
thrombotic events, hemolysis, and renal failure require standardization of practice. Future
in children also warrants more investigation, as multicenter prospective studies are needed to
many centers have completely moved to these help guide best practice and optimize outcomes.
systems and away from roller-head devices.41,42
Theoretically and practically, centrifugal sup-
port should be easier, safer and offer many
advantages.43 Exploration into confirming or
278
References 9. Lou S, MacLaren G, Paul E, Best D, Del-

zoppo C, Butt W. Hemofiltration is not asso-
1. Costello JM, Cooper DS, Jacobs JP, et al. ciated with increased mortality in children
Intermediate-term outcomes after paediatric receiving extracorporeal membrane oxy-
cardiac extracorporeal membrane oxygenation. Pediatric critical care medicine
genation--what is known (and unknown). : a journal of the Society of Critical Care
Cardiology in the young. 2011;21 Suppl Medicine and the World Federation of Pe-
2:118-123. diatric Intensive and Critical Care Societies.
2. Kumar TK, Zurakowski D, Dalton H, et al. 2015;16(2):161-166.
Extracorporeal membrane oxygenation in 10. Joffe A, Anton N, Lequier L, et al. Nutritional
postcardiotomy patients: factors influenc- support for critically ill children. Cochrane
ing outcome. J Thorac Cardiovasc Surg. Database Syst Rev. 2009(2):CD005144.
2010;140(2):330-336 e332. 11. Krekels EH, DeJongh J, van Lingen RA,
3. Thiagarajan RR. Extracorporeal membrane et al. Predictive performance of a recently
oxygenation to support cardiopulmonary developed population pharmacokinetic
resuscitation: Useful, but for whom? Crit model for morphine and its metabolites
Care Med. 2011;39(1):190-191. in new datasets of (preterm) neonates,
4. Blowey DL, Duda PJ, Stokes P, Hall M. infants and children. Clin Pharmacokinet.
Incidence and treatment of hypertension in 2011;50(1):51-63.
the neonatal intensive care unit. J Am Soc 12. Anand KJ, Clark AE, Willson DF, et al.
Hypertens. 2011;5(6):478-483. Opioid analgesia in mechanically venti-
5. Dalton HJ, Rycus PT, Conrad SA. Update lated children: results from the multicenter
on extracorporeal life support 2004. Semi- Measuring Opioid Tolerance Induced by
nars in perinatology. 2005;29(1):24-33. Fentanyl study. Pediatr Crit Care Med.
6. Askenazi DJ, Selewski DT, Paden ML, et 2013;14(1):27-36.
al. Renal replacement therapy in critically 13. Buscher H, Vaidiyanathan S, Al-Soufi S, et
ill patients receiving extracorporeal mem- al. Sedation practice in veno-venous extra-
brane oxygenation. Clinical journal of the corporeal membrane oxygenation: an inter-
American Society of Nephrology : CJASN. national survey. ASAIO J. 2013;59(6):636-
2012;7(8):1328-1336. 641.
7. Paden ML, Warshaw BL, Heard ML, 14. Luisiri A, Graviss ER, Weber T, et al. Neu-
Fortenberry JD. Recovery of renal func- rosonographic changes in newborns treated
tion and survival after continuous renal with extracorporeal membrane oxygenation.
replacement therapy during extracorporeal J Ultrasound Med. 1988;7(8):429-438.
membrane oxygenation. Pediatric critical 15. Dalton HJ. Extracorporeal life support:
care medicine : a journal of the Society of moving at the speed of light. Respira-
Critical Care Medicine and the World Fed- tory care. 2011;56(9):1445-1453; discuiion
eration of Pediatric Intensive and Critical 1453-1446.
Care Societies. 2011;12(2):153-158. 16. Andrews AF, Klein MD, Toomasian JM,
8. Han SS, Kim HJ, Lee SJ, et al. Effects of Roloff DW, Bartlett RH. Venovenous
Renal Replacement Therapy in Patients extracorporeal membrane oxygenation in
Receiving Extracorporeal Membrane Oxy- neonates with respiratory failure. Journal
genation: A Meta-Analysis. The Annals of of pediatric surgery. 1983;18(4):339-346.
thoracic surgery. 2015;100(4):1485-1495. 17. Boykin AR, Quivers ES, Wagenhoffer
KL, et al. Cardiopulmonary outcome of
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neonatal extracorporeal membrane oxygen- oxygenation for adult respiratory failure:

ation at ages 10-15 years. Crit Care Med. life support in the new era. Intensive Care
2003;31(9):2380-2384. Med. 2012;38(2):210-220.
18. Mateen FJ, Muralidharan R, Shinohara 27. Marhong JD, Telesnicki T, Munshi L, Del
RT, Parisi JE, Schears GJ, Wijdicks EF. Sorbo L, Detsky M, Fan E. Mechanical ven-
Neurological injury in adults treated with tilation during extracorporeal membrane
extracorporeal membrane oxygenation. oxygenation. An international survey. Ann
Arch Neurol. 2011;68(12):1543-1549. Am Thorac Soc. 2014;11(6):956-961.
19. Muellenbach RM, Redel A, Kustermann 28. Moerer O, Quintel M. Protective and
J, et al. [Extracorporeal membrane oxy- ultra-protective ventilation: using pumpless
genation and severe traumatic brain injury. interventional lung assist (iLA). Minerva
Is the ECMO-therapy in traumatic lung Anestesiol. 2011;77(5):537-544.
failure and severe traumatic brain in- 29. Yehya N, Dominick CL, Connelly JT, et
jury really contraindicated?]. Anaesthesist. al. High-frequency percussive ventila-
2011;60(7):647-652. tion and bronchoscopy during extracor-
20. Biscotti M, Gannon WD, Abrams D, et poreal life support in children. ASAIO J.
al. Extracorporeal membrane oxygenation 2014;60(4):424-428.
use in patients with traumatic brain injury. 30. Anton-Martin P, Thompson MT, Sheeran
Perfusion. 2015;30(5):407-409. PD, Fischer AC, Taylor D, Thomas JA.
21. Bulas D, Glass P. Neonatal ECMO: neuro- Extubation during pediatric extracorpo-
imaging and neurodevelopmental outcome. real membrane oxygenation: a single-
Semin Perinatol. 2005;29(1):58-65. center experience. Pediatr Crit Care Med.
22. Baird CW, Zurakowski D, Robinson B, et 2014;15(9):861-869.
al. Anticoagulation and pediatric extracor- 31. Azoulay E, Citerio G, Bakker J, et al. Year
poreal membrane oxygenation: impact of in review in Intensive Care Medicine 2013:
activated clotting time and heparin dose on II. Sedation, invasive and noninvasive ven-
survival. Ann Thorac Surg. 2007;83(3):912- tilation, airways, ARDS, ECMO, family sat-
919; discussion 919-920. isfaction, end-of-life care, organ donation,
23. Annich GM. Extracorporeal life support: informed consent, safety, hematological
the precarious balance of hemostasis. J issues in critically ill patients. Intensive
Thromb Haemost. 2015;13 Suppl 1:S336- care medicine. 2014;40(3):305-319.
342. 32. Kamat PP, Popler J, Davis J, et al. Use
24. Bateman ST, Lacroix J, Boven K, et al. of flexible bronchoscopy in pediatric pa-
Anemia, blood loss, and blood transfusions tients receiving extracorporeal membrane
in North American children in the inten- oxygenation (ECMO) support. Pediatric
sive care unit. Am J Respir Crit Care Med. pulmonology. 2011;46(11):1108-1113.
2008;178(1):26-33. 33. Goodwin SJ, Randle E, Iguchi A, Brown
25. Raake J, Johnson B, Seger B, et al. Extra- K, Hoskote A, Calder AD. Chest computed
corporeal membrane oxygenation, extuba- tomography in children undergoing extra-
tion, and lung-recruitment maneuvers as corporeal membrane oxygenation: a 9-year
rescue therapy in a patient with tracheal single-centre experience. Pediatr Radiol.
dehiscence following slide tracheoplasty. 2014;44(6):750-760; quiz 747-759.
Respir Care. 2011;56(8):1198-1202. 34. Lidegran M, Palmer K, Jorulf H, Linden V.
26. MacLaren G, Combes A, Bartlett RH. CT in the evaluation of patients on ECMO
Contemporary extracorporeal membrane
280
due to acute respiratory failure. Pediatr pediatric heart surgery. Eur J Cardiothorac
Radiol. 2002;32(8):567-574. Surg. 2011;39(3):392-397.
35. Guerin C, Reignier J, Richard JC, et al. 44. Jen HC, Shew SB. Hospital readmissions
Prone positioning in severe acute respi- and survival after nonneonatal pediatric
ratory distress syndrome. N Engl J Med. ECMO. Pediatrics. 2010;125(6):1217-1223.
2013;368(23):2159-2168. 45. Huang SC, Wu ET, Wang CC, et al. Eleven
36. Guervilly C, Hraiech S, Gariboldi V, et years of experience with extracorporeal
al. Prone positioning during veno-venous cardiopulmonary resuscitation for paediat-
extracorporeal membrane oxygenation ric patients with in-hospital cardiac arrest.
for severe acute respiratory distress syn- Resuscitation. 2012;83(6):710-714.
drome in adults. Minerva Anestesiol. 46. Rais-Bahrami K, Wagner AE, Coffman C,
2014;80(3):307-313. Glass P, Short BL. Neurodevelopmental
37. Kimmoun A, Guerci P, Bridey C, Ducrocq outcome in ECMO vs near-miss ECMO pa-
N, Vanhuyse F, Levy B. Prone position- tients at 5 years of age. Clin Pediatr (Phila).
ing use to hasten veno-venous ECMO 2000;39(3):145-152.
weaning in ARDS. Intensive Care Med.
2013;39(10):1877-1879.
38. Kimmoun A, Roche S, Bridey C, et al.
Prolonged prone positioning under VV-
ECMO is safe and improves oxygenation
and respiratory compliance. Ann Intensive
Care. 2015;5(1):35.
39. Dalton HJ, Garcia-Filion P, Holubkov R, et
al. Association of bleeding and thrombosis
with outcome in extracorporeal life support.
Pediatr Crit Care Med. 2015;16(2):167-174.
40. Rao AS, Pellegrini RV, Speziali G, Marone
LK. A novel percutaneous solution to limb
ischemia due to arterial occlusion from a
femoral artery ECMO cannula. J Endovasc
Ther. 2010;17(1):51-54.
41. Barrett CS, Jaggers JJ, Cook EF, et al.
Pediatric ECMO outcomes: comparison
of centrifugal versus roller blood pumps
using propensity score matching. ASAIO
J. 2013;59(2):145-151.
42. Halaweish I, Cole A, Cooley E, Lynch
WR, Haft JW. Roller and Centrifugal
Pumps: A Retrospective Comparison of
Bleeding Complications in Extracorporeal
Membrane Oxygenation. ASAIO journal.
2015;61(5):496-501.
43. McMullan DM, Emmert JA, Permut LC,
et al. Minimizing bleeding associated with
mechanical circulatory support following
281
23
Nursing Management of the Child with Respiratory Failure on Extracorporeal Life

Support
Micheal L. Heard, RN
Introduction decreased peripheral perfusion and diminished

pulses if a majority of the cardiac output is
Nursing care of pediatric patients on provided by the ECMO pump. Distal extremi-
extracorporeal life support presents specific ties should be carefully assessed because the
challenges that differ from the general pediatric diminished or absent blood flow may cause
intensive care population. Extracorporeal life hypoperfusion syndrome, resulting in black-
support, ECLS or ECMO, may often require ened fingertips and toes. Cannulas placed in
long periods of immobility and higher levels the femoral vessels require hourly perfusion
of sedation which may result in difficulty pro- checks of the affected limb to determine blood
viding basic nursing care effectively. Nurses flow status. Any and all interruptions in the
are responsible for the “facilitation of healing skin will be noted and assessed for changes
and alleviation of suffering” according to the from previous assessments, including new red-
American Nurses Association.1 Intensive care ness, irritation or drainage that may be present.
nurses have specialized training that enables ECMO patients are always at risk for bleeding,
them to work in a highly interactive environ- so a careful assessment and quantification of
ment in collaboration with physicians and vari- blood loss is mandatory.
ous multidisciplinary team members to provide The nurse will complete an assessment
and manage the care of critically ill children. of neurological status; including level of con-
Nurses involved in the care of ECMO patients sciousness, pupillary response, and level of pain.
must be well versed in providing high levels of Any untoward changes in neurological status
care suited to this unique population. require immediate physician notification, as
potentially dire complications may occur with
Daily Assessment ECMO patients such as intracerebral hemor-
rhage. The respiratory system will be reviewed
Initially, the nurse will complete a head- including auscultation of the quality of breath
to-toe assessment of all systems of the patient, sounds, status of secretions, pleural drains pres-
including: vital signs; palpation of pulses and ent, and respiratory assist devices in place. It is
assessment of capillary refill in all extremities; not unusual to have little to no audible breath
physical assessment of skin noting turgor, color, sounds due to the use of rest ventilator settings
and temperature and moisture level. Venoarte- and the disease process with ECMO patients.
rial (VA) ECMO patients commonly will have Careful comparison of breath sounds day to
283
Chapter 23
day throughout the ECMO run may yield clues rial site. An increase in the amount of blood loss
to patient improvement or recruitment. New should be noted and reported to the physician.
or continued presence of bloody secretions or
pulmonary edema should be carefully moni- Daily Patient Care
tored and every attempt should be made not to
aggravate further. Nurses are responsible for the implementa-
Assessment of cardiac function will include tion of the medical care plan as prescribed by
listening of heart sounds and status of the the physician. This includes sampling of blood
cardiac rhythm. Bear in mind that VA ECMO for testing; administration of medications and
patients may have muffled heart sounds due to fluids; and continuous physical assessment and
pump flow requirements. Patients may demon- recording of vital signs. The nurse is respon-
strate little to no pulse pressure, as well as damp- sible for any interventions as directed for test
ened arterial waveform. VA ECMO patients are results, vital sign changes, and medications.
typically supported for their cardiac needs, but Review and documentation of elimination status,
careful assessment of heart function and rhythm including a complete intake and output is an
in venovenous (VV) ECMO patients is required, important aspect of nursing care in the inten-
as the patient must have appropriate cardiac sive care unit. Nurses may also be responsible
function while on VV ECMO. The genitouri- for (possibly in conjunction with a Respiratory
nary system assessment includes the color, odor, Therapist) the assessment and recording of
and amount of urinary output as well as assess- the respiratory ventilation system, respiratory
ment of the external genitalia. The appearance treatments such as inhalation of medications
of hematuria will require additional testing to and pulmonary toilet, and gentle and measured
determine the cause. The ECMO pump may suctioning techniques.
cause hemolysis due to clot formation, friction, Nurses are accountable for the daily tasks
or inadequate preload. Females of menstruating and care of a patient who is unable to complete
age require review of menarche and should be these tasks themselves. Pediatric intensive care
considered for suppression of the cycle to avoid patients may range in age from infants to teen-
possible hemorrhage. A gastrointestinal system agers, which allows for a wide assortment of
review includes a physical assessment of the patients who may be able to participate in their
abdomen including girth, presence and qual- own care. The nurse is responsible for bathing
ity of bowel sounds, the last bowel movement the patient and maintaining a clean environment
and the frequency, and color and consistency for the patient to rest. The American Associa-
of the stool. The amount, color, and quality of tion of Critical Care Nurses recommends that
any nasogastric secretions are also reviewed. the traditional bath basin with soap and water
Again, presence of new blood within the stool or method no longer be used for bathing patients.
gastric secretions requires further investigation This method has been found to promote dry skin
and treatment. Finally, the nurse will review the and may expose the patient to harmful bacteria.
accuracy and status of any and all intravenous The accepted practice includes: providing daily
solutions currently administered to the patient. baths for bed bound patients; using disposable
All lines, drains, and other invasive monitors basins and discarding them after each use;
will be assessed for changes in placement and avoiding use of unfiltered tap water; and using
visual characteristics and function. The nurse prepackaged disposable cloths that contain a 2%
should carefully assess and quantify any bloody solution of chlorhexidine gluconate (CHG) that
drainage present at any intravenous or intraarte- are no-rinse and pH balanced. Additionally, the
patient should have an emollient applied after
284
Nursing Management of the Child with Respiratory Failure on Extracorporeal Life Support
bathing, although some prepackaged wipes in- CHG. Other tools, such as metal instruments or
clude this product. ECMO patients should be cotton swabbed fingers may have some benefit,
very carefully bathed, insuring that any formed, but should be avoided on ECMO patients. If
hard clots are not dislodged or removed, as this the patient has orthodontic devices in place,
may cause new bleeding to occur.2 determine if the device is removable as that is
Oral hygiene is one of the basic nursing preferable to leaving it in place. Otherwise the
skills and has a dramatic impact on the health use of dental wax to protect the inner lips may
and well-being of the patient. Intensive care be beneficial. Finally, lip care is part of oral
patients are at high risk for poor oral health health as well. Lubricants such as petroleum
and the ECMO patient has the additional risk jelly are often recommended, but should be
of anticoagulant therapy and poor nutrition. avoided as they can increase the dryness of tis-
Pediatric patients present several different oral sues. Preferably use water based or aloe based
health dilemmas such as placement of braces lip balms.4
and other orthodontic devices and natural tooth Skin care is considered a tenet of nursing
loss. The nurse must include a comprehensive care. The ECMO patient is at considerable risk
oral assessment in the daily assessment and pro- for pressure ulcers due to the critical nature of
vide for mouth care as prescribed. Frequency of their illness, the use of anticoagulant therapy,
mouth care varies, but it is recommended that it and their relative immobility. The head and
be provided hourly for high risk patients, such neck are frequently edematous due to the lack
as those on oxygen therapy and those who are of mobility. Large cannulas sutured in place,
unconscious. Lack of care between two and endotracheal and oronasal tubes, and other
six hours can significantly reduce the benefits intensive care devices can be a risk factor for
of any oral intervention previously carried pressure ulcers.5 In 2007, the National Pres-
out.3 Mouth care may make use of oral rinses. sure Ulcer Advisory Panel made the preven-
Many mouthwashes contain alcohol which tion and treatment of pressure ulcers in infants
can cause a burning sensation in the mouth and children a key priority.6 In 2015 The Joint
and may increase existing inflammation, and Commission listed prevention of healthcare
are not recommended as part of an oral care associated pressure ulcers a National Patient
protocol. CHG has been shown to be a very Safety Goal.7 The use of the Pediatric Braden
effective antibacterial mouthwash and is effec- Q Scale for pressure ulcer staging will assist
tive in removing dental plaque where mechani- the nurse in the early assessment of pressure
cal tooth brushing is not an option. Saline is ulcers as well as provide appropriate and timely
a nonirritant mouthwash and can be useful in interventions. Basic nursing interventions that
situations where other rinses are not available, may lower the risk of development of pressure
especially since the frequency of mouth care is ulcers include: avoiding injury due to shear
paramount. The use of a toothbrush is effective forces, turning the patient every two hours, use
at removing plaque when used correctly. If a of positioning aids, and changing dirty or wet
patient is conscious and of age, allowing them linen accordingly. Pediatric patients should
to brush their own teeth is beneficial. Nurses have soiled diapers changed as soon as possible.
may have difficulty in using a toothbrush and in Avoiding the use of multiple layers and plastic
assessing how hard to brush. ECMO patients lined protective barriers is recommended to as-
are at risk for oral bleeding due to anticoagula- sist in the flow of oxygen to prevent pressure
tion, so firm bristled brushes should be avoided. ulcers. Pediatric ECMO patients may also have
The use of foam swabs, useful for cleaning the a higher risk of pressure ulcer formation due
oral cavity, are used only if they are soaked in to the use of paralytic medications in order to
285
Chapter 23
provide optimal support of the ECMO machine. signs and symptoms of dry eye, and the use of
Additionally, difficulty in cannula position- normal saline soaked gauze to clean from the
ing may make it very difficult to turn patients inner to the outer canthus every eight hours.
regularly. In these cases, it is recommended the Furthermore, patients who are unable to main-
nurse use fluidized positioners for extremities, tain eyelid closure and have decreased or absent
head and shoulders. The careful manipulation blink reflexes should have an artificial means of
of these positioners every two hours will serve closing the eye and maintaining a barrier against
to reposition the patient so that the same area air currents. Eye lubricant should be used and
does not rest exactly the same on the device. the covers changed every shift.
Finally, the ECMO patient may be placed on a
specialty mattress or overlay; one that reduces Wound Care
pressure, such as an eggcrate, air-filled bed, or
action bed.8 The pediatric patient on extracorporeal life
Assessment and care of the eye is an ad- support is at particular risk for wounds. Most
ditional aspect of nursing care of the patient on wounds are those associated with the insertion
ECMO. Critically ill patients who are mechani- of indwelling devices. Many of these devices
cally ventilated, sedated, or unconscious are at are implanted prior to initiation of ECMO and
high risk for exposure keratopathy or ‘dry eye,’ may have had time to heal and stabilize. How-
as well as other ophthalmic complications, be- ever, the insertion of the ECMO cannula(e) is
cause of decreased tear production and reduced undertaken just before or immediately after
or absent blink reflexes. Intensive care nurses anticoagulation therapy has begun. These
should perform a focused eye assessment every sites are at particular risk for bleeding and for
shift to evaluate for eyelid swelling, conjunc- nosocomial infection. Most ECMO centers
tival redness, corneal hazing and discharge, or have an institutional protocol for dressing
crusting on the eyelid. These are the early signs of intravascular devices as part of a Central
of dry eye that may lead to corneal ulceration or Line-Associated Bloodstream Infection policy
eye infection.9, 10 Additionally, the nurse must (CLABSI). The protocol may include types
assess for the patient’s ability to maintain eye of catheters, assessment tools, frequency and
closure; as the lack of closure may increase types of dressing changes, and prevention
the risk of ophthalmic complications.11 Any techniques that may be used. Maintaining the
sign of abnormality should be reported to the same protocol is important as it will decrease
physician team and an ophthalmologist should the likelihood of compromising an established
be consulted. CLABSI program; however, careful review of
The provision of eye care should be part of the protocol by the ECMO team is important,
the routine care provided to all ICU patients. so that it may be adopted with careful consid-
There are several studies that compare the use of eration of the ECMO patient’s needs. Rigid
eye lubricant drops, ointments, moist chambers, adherence to the protocol may not allow for
and covers. The common standard practice is atypical situations such as excessively hemor-
instillation of a lubricant every two hours. How- rhagic sites. ECMO patients may have other
ever, the use of properly installed polyethylene wounds such as trauma or surgical wounds
covers are more effective at providing a barrier pre-ECMO that may or may not have begun to
against tear evaporation and exposure to air cur- heal prior to heparinization. All breaks in the
rents, thus preventing complications.12 The use skin must be considered wounds and have the
of a specific eye care protocol by nursing staff risk of hemorrhage or infection.
should include the assessment of the eyes for
286
The nurse will assess all cannulation sites Daily Activities

routinely, including integrity and type of dress-
ing, drainage or bleeding, catheter position, Pediatric nursing care of the intensive care
stability, and security. Additionally, the skin ECMO patient can present unique challenges.
around the cannula is assessed for redness, While it is preferable to allow patients to awaken
swelling, and breakdown. Cleaning the can- and move for myriad benefits, certain pediatric
nula site is best done utilizing chlorhexidine patients may not tolerate the activity, or the can-
gluconate. CHG swabs or pads may be used nula position may not facilitate patient move-
to gently clean the incision site. Other clean- ment. The use of sedation and paralytic therapy
ing agents that may be used include betadine should be carefully discussed among the care
and sterile saline wipes. The types of dressing team, with decisions made in the best interest of
used on ECMO cannulas vary greatly, but are the individual patient. That being said, patients
typically thought of as dry dressings. They who are awake and alert require age-appropriate
may be simple gauze or gauze pads. Transpar- stimulation and activities. Infants may enjoy
ent film dressings have a thin layer of plastic music or a mobile, while older children may
that covers a wound area, creating a barrier. appreciate games, books, or television shows.
They allow some oxygen exchange to reduce Pediatric intensive care units may have child
bacteria growth. These dressings are best for life specialists available. They are a valuable
dry, nonexudative sites. Removal of transparent resource to determine the best activities for all
dressings can tear the underlying skin, so cau- ages. Additionally, physical therapy and oc-
tion must be used. Once a site begins to bleed cupational therapists are appreciated members
or drain, the use of these dressings is contrain- of the care team. Their expertise for assuring
dicated due to frequent removal that may result proper body alignment and focusing on condi-
in skin tears. Bloody drainage that is stable is tioning exercises can promote an easier recovery
preferentially left alone until a dressing change period. Certain ECMO patients may be encour-
is required. This will allow the clot to stabilize aged to sit up, stand, or even walk. The right
and prevent further blood loss. Foam dressings conditions may even allow a toddler to ride a
have an adsorptive and protective effect for at tricycle! The nurse should do everything pos-
risk sites or the presence of pressure ulcers. sible to promote a safe environment where each
They are self-adherent and easily cut to fit for pediatric patient may be allowed to participate
specific difficult-to-dress sites. Tape may be in activities that are age appropriate and fun.
used to secure dressings in place. Available in It is also important to maintain a normal
paper, cloth, or plastic, selecting a type that best sleep-wake cycle for these patients. Intensive
fits the need of the dressing, without putting the care units are a noisy environment and lights
skin under unnecessary risk, is important. Many may be left on 24 hours a day.14 Patients on
patients also have sensitivities to tape which ECMO who are medically unconscious will
must be taken under consideration. Cannula benefit from quiet time. Although the ECMO
sites, which are typically in the neck or groin, patient’s bedside may be one of the busiest in
can be difficult to dress. Pediatric patients vary the unit, caregivers should maintain an unobtru-
in size and movement, which must be taken sive demeanor while in the patient room. Ensur-
into consideration when choosing a dressing.13 ing that ‘quiet time’ is observed in the afternoon
and an appropriate ‘lights out for nighttime’
ritual can significantly contribute to decreased
delirium and sleep deprivation hallucinations
and a patient’s healthy healing environment.15
287
Chapter 23
The practice of family centered care is well

established in most pediatric facilities. The
involvement of the family in the care of their
child promotes healthy family relationships and
overall satisfaction with the healthcare team.
The nurse should involve the primary caregivers
in as many aspects of the child’s care as pos-
sible: bathing, hair and mouth care; as well as
activities that allow the caregiver to bond with
their child; such as reading or playing with the
patient. Allowing personal mementos at the
bedside depends on facility policies. Allowing
these items may allow family members to feel
they are connecting to their child in a personal
way. Daily care conferences should include the
family members as they wish, with complete
transparency about the status of their child and
the ECMO run.16
Conclusion
Nursing care of the pediatric ECMO patient

requires specialized training and a high level of
awareness of extracorporeal life support physi-
ology. While usual practices are employed,
there are several unique aspects of care that
must be considered. Of primary importance
is the protection of the patient from harm that
may cause potentially life threatening hemor-
rhage or complications. Awareness of the po-
sition of the ECMO circuit and cannula must
be foremost. Any and all invasive maneuvers
must be carefully evaluated and weighed for
risk versus benefit. The nurse must act as a
patient advocate--allowing only knowledgeable
personnel to intervene and provide care for the
ECMO patient. If there is an ECMO specialist
or perfusionist at the bedside, clear communi-
cation is of the utmost significance. Involving
the entire care team in any discussion regarding
patient status, tasks, and interventions and plans
for the ECMO run will serve to provide the best
possible care to the pediatric ECMO patient.
288
References ill: clinical practice guideline. Aust Crit

Care;21(2):97-109.
1. What is Nursing? www.nursingworld.org. 12. Shan H, Min D. Prevention of exposure
Available at: http://www.nursingworld. keratopathy in intensive care unit. Int J
org/especiallyforyou/what-is-nursing. Ac- Ophthalmol 2010: 3(4):346-348.
cessed December 22, 2015. 13. Hess CT. Clinical Guide: Skin and Wound
2. AACN Updates: Patient bathing practices Care. 6th ed. Ambler, PA: Lippincott, Wil-
protocol. Infection Control Today 2013. liams & Wilkins; 2008.
Available at: www.infectioncontroltoday. 14. AL-Samsan RH, Cullen P. Clinical investi-
com. Accessed January 18, 2016. gations: Sleep and adverse environmental
3. Murphy A. Clinical review - Oral hygiene factors in sedated mechanically ventilated
a priority of care. Available at: https://www. pediatric intensive care patients. Pediatr
inmo.ie/article/printarticle/2764. Accessed Crit Care 2005;6(5):562–567.
January 18, 2016. 15. Xie H, Kang J, Mills GH. Clinical review:
4. DeKeyser-Ganz F, Fink NF, Asher O, Brut- The impact of noise on patients’ sleep
tin M, Nun MB. ICU nurses’ oral-care and the effectiveness of noise reduction
practices and the current best evidence. J strategies in intensive care units. Crit Care
Nurs Scholarship 2009;41(2):132–138. 2009;13(2):208.
5. Schindler CA, Mikhailov TA, Kuhn EM, et 16. Harrison TM. Family-centered pediatric
al. Protecting fragile skin: Nursing interven- nursing care: State of the science. J Pediatr
tions to decrease development of pressure Nurs 2010;25:335–343.
ulcers in pediatric intensive care. Am J Crit
Care 2011;20(1):26–34.
6. Baharestani MN, Ratliff CR. Pressure ul-
cers in neonates and children: An NPUAP
white paper. Adv Skin Wound Care
2007;20(4):208–220.
7. National Patient Safety Goals Effective
January 1, 2015. The Joint Commission.
Available at: http://www.jointcommission.
org/assets/1/6/2015_npsg_lt2.pdf. Ac-
cessed January 18, 2016.
8. Butler CT. Pediatric skin care: Guidelines
for assessment, prevention, and treatment.
Pediatr Nurs 2006;32(5):443–450.
9. Hernandez EV, Mannis MJ. Superficial
keratopathy in intensive care patients. Am
J Ophthalmol 1997;124(2):212-216.
10. Joyce N. Eye care for the intensive care
patients. A systematic review. The Joanna
Briggs Institute for Evidence Based Nursing
and Midwifery, Systematic Review. 2002;
No. 21.
11. Marshall AP, Elliott R, Rolls K, Schacht
S, Boyle M. Eyecare in the critically
289
24
Weaning and Decannulation of Children with Respiratory Failure on ECLS
Thomas Pranikoff, MD
Extracorporeal life support offers critically primarily by lowering airway pressure and FiO2.
ill patients many benefits during their illness. An extreme offshoot of this strategy, now be-
Associated with these benefits are significant ing used in some centers, is elective extubation
risks. Discontinuation of support should be con- while on ECMO. In one study, extubation dur-
sidered when the risk/benefit ratio increases and ing ECMO permitted increased physical activity
patients are able to be cared for by less invasive in cannulated patients and the opportunity to
techniques. After a period of initial stabiliza- prevent the physical deconditioning associated
tion, the question of whether discontinuation of with long ICU stays. Spontaneous, negative
ECLS is possible should be frequently evaluated pressure ventilation may have been effective in
as the patient’s condition improves. promoting spontaneous reaeration, cough, and
secretion mobilization in patients with severe
Strategies for Withdrawal of ECLS Support pulmonary consolidation. Although “rest set-
tings” are likely less harmful than aggressive
At the initiation of extracorporeal support, ventilator settings, it is unknown whether posi-
an estimated length of required support should tive pressure of any sort is harmful or helpful
be made, according to the patient’s disease. in an injured lung. What this study cannot
Patients with sepsis and bacterial pneumonia answer, however, is whether extubation speeds
tend to have longer ECMO runs; whereas or delays resolution of lung injury and alveolar
patients with PPHN, meconium aspiration, reinflation.1
trauma, and viral pneumonia have shorter runs. A study by Marhong et al. using a survey
When improvement of lung function begins to of international centers who contribute to the
appear, a trial off ECLS may be attempted. By ELSO Registry found that 27% of centers have
repeating trials off of support frequently (daily a specific ventilation protocol for patients on
or even more frequently), the earliest time for VV-ECLS. “Lung rest” was the primary goal
decannulation can be determined. In this way, in 77% of respondents and “lung recruitment”
patients are subjected to the potential risks of or a combination of both in 18% of respondents.
extracorporeal support for the least amount of Eighty percent of centers used a PEEP of greater
time. than 5 cm H2O. Most centers (90%) prioritized
The issue of “lung rest” has led some clini- weaning from ECLS over the ventilator. Wean-
cians to utilize ventilation strategies while on ing from ECLS was by reduction of sweep gas
ECLS which are designed to minimize injury in 43% and flow rates in 21%.2
291
Chapter 24
Several strategies have been suggested by despite aggressive medical management facili-
individual centers that may potentially decrease tated by extracorporeal support. Lung biopsy
the time of an ECMO run. In a matched pair may be helpful in this setting.8,9 The decision to
analysis, Hermon et al. compared 7 pediatric discontinue support with the intention to with-
ECMO patients given porcine surfactant with draw care at the end of life is always difficult.
7 who were not. Groups were matched based Since the patient is rarely able to participate in
on age, weight, and underlying diagnosis. The this discussion, the family will assume this re-
most common diagnosis in both groups was sponsibility. The team must give their best view
ARDS. Mean tidal volume improved signifi- of the likelihood of survival, and the ultimate
cantly over time in the surfactant group (100% quality of life that will result. Historically, after
at baseline vs. 186.2% at 10 h after surfactant 14 days of support and no evidence of return
application) compared to the control group of lung function, many centers viewed this
(100% vs. 98.7%; p=0.0053). Similarly, mean situation as futile unless the patient was a lung
compliance values increased significantly over transplant candidate.10,11 However, some centers
time in the surfactant group (100% before have reported prolonged support with meaning-
versus 176.1% at 10 h after surfactant applica- ful recovery after more than 200 days.12,13 Each
tion) compared to the control group (100% vs. center has different capabilities to maintain
97.6%; p=0.0067). Radiographic scores tended patients on ECLS for prolonged periods which
to decrease in the surfactant group within 48 h may range from weeks to months. If the family
following surfactant application. ECMO flow chooses to discontinue ECLS, they should be
tended to decrease in this group within 10 h informed of the likelihood of survival and their
following surfactant application but not in wishes for other types of life support discussed
the control group. Mortality was not affected (eg, continued mechanical ventilation, inotropic
by treatment.3Two other studies showed an support) or whether they wish to discontinue all
improvement in pulmonary mechanics and a support and shift to a palliative mode. Patient
decrease in ECMO duration in term neonates comfort and wellbeing should be supported in
on ECMO who received multiple doses of either situation. If the family decides to discon-
surfactant.4,5 tinue support and shift to palliation, everything
The use of prone positioning to redistribute should be done to facilitate this. For example,
pulmonary blood flow into regions of the lung in an infant or small child the cannulas can be
that are better aerated and to mobilize edema has clamped and wrapped and the circuit cut away
been advocated for patients with ARDS but the to make it less visible and allow family to hold
efficacy remains controversial. Many centers the child. Some parents might elect to have
that care for patients with ARDS with ECMO the cannula removed and then spend time with
have used this technique safely.6,7 their child.
Withdrawal of ECLS Support as Palliative Weaning Support and Trialing

Withdrawal of Care
Indications of lung recovery on venovenous
When patients’ lungs fail to improve or support include increasing saturation of venous
other major complications occur, ECLS may blood returned to the circuit, PaO2, or decreasing
no longer be indicated. Familiar scenarios in- PaCO2 without changes in either extracorporeal
clude multiorgan failure, cerebral hemorrhage, flow or ventilator settings. Increasing lung
or post-arrest global hypoxic cerebral injury. compliance, clearing of the chest radiograph,
Some lung pathologies will fail to improve and increased VO2 and VCO2 measured via
292
the airway are also seen.14 When this process off of support is indicated. A trial off of ECLS
begins, it will usually continue until termination during venovenous support involves discon-
of extracorporeal support is possible unless a tinuing sweep gas flow across the oxygenator
new problem, such as pneumonia or sepsis, while continuing blood flow and anticoagula-
intervenes. tion, and so is safe to continue for prolonged
When lung function begins to improve, periods. This is accomplished by plugging the
“weaning” from support may be possible. It is gas inlet and outlet of the membrane lung to
important to understand that weaning is a diag- prevent gas flow. If room air is allowed to flow
nostic rather than therapeutic maneuver. The across the lung, this can provide considerable
purpose of weaning is to obtain information to support. As noted above, many clinicians will
help make the decision of whether support can omit weaning the blood flow and simply turn
be discontinued and transitioned to mechanical the sweep gas flow to zero. During this time, the
ventilation alone. Since lung rest is the major patient is closely monitored for respiratory rate,
benefit from venovenous support, the decision SaO2, capnography, agitation, heart rate, and
to terminate support must include careful con- blood pressure. Spontaneous ventilation usu-
sideration of the clinical situation at hand. In ally augments lung function, but some patients
the ideal situation, at the time of decannulation, may need additional sedation. The ventilator
ventilator support will be at a level considered is adjusted according to arterial blood gases.
to be safe (low pressure and FiO2). In some Often the goals of support should be modified to
situations, these goals must be modified. For accept levels of PaO2 in the 60-80 mmHg range
example, in a patient with bleeding (eg, postop, and PaCO2 in the 40-60 mmHg range. This
intracranial, gastrointestinal) which cannot be will allow the use of less airway pressure and
controlled by medical means, there needs to be FiO2 to protect the recovering lungs. If the trial
an assessment of the risks of continuing with continues with stable blood gases at acceptable
ECLS vs. discontinuing ECLS while utilizing levels of respiratory support for several hours,
mechanical ventilation at higher FiO2 and air- decannulation can be planned.
way pressures than might be desired.
Weaning can be accomplished in patients Technique for Decannulation of Patients on
on venovenous support by gradually decreasing Venovenous ECLS
circuit flow to a minimal level while increas-
ing ventilator support or noninvasive support Most patients on venovenous ECLS will
for those already extubated. Each circuit will be cannulated percutaneously. Some patients,
have a minimum blood flow below which there mostly newborns, may be cannulated by a surgi-
is a considerable risk of circuit thrombosis. In cal cutdown. For these patients, it is advisable
¼” neonatal circuits, this is usually 100 cc/min. to use a brief general anesthetic with neuro-
The minimum flow of the oxygenator may muscular blockade. This will ensure optimal
be higher than this and should be considered. conditions and prevent negative pressure using
Larger circuits will have higher minimum flow a Valsalva maneuver, which could otherwise
rates. As circuit flow is decreased and respira- cause air embolus when the vein is open or if
tory support increased, sweep gas may need to the side holes are exposed while the cannula
be decreased to maintain PaCO2 in the normal is being withdrawn. The wound is sterilely
range as native lung function improves. prepped and opened. The cannula cutdown site
Once the patient can be maintained on mini- is exposed and clot is removed for visualization.
mal ECLS flow and an acceptable level of venti- A ligature is placed around the cannula and vein
lation or noninvasive respiratory support, a trial and left untied. The circuit is clamped and pa-
293
Chapter 24
tient ventilator settings are adjusted to be sure access for fluids, antibiotics, nutrition, and
that support off ECLS will be tolerated. The other extracorporeal support modalities such as
skin sutures and sutures around the vein are dialysis and plasmapheresis. When consider-
divided and the cannula is rapidly removed by ing decannulation, future access needs should
one person and the previously placed ligature is be assessed and a plan established. Because
tied by a second person. The wound is closed children are often edematous at this point in
after hemostasis is assured. Situations which their illness, using peripheral venous sites can
make this more challenging include tearing of be challenging. We have utilized a technique of
the vein with complete division and not enough guidewire exchange of the venous cannula with
stump left to control (usually the result of a long central venous catheters or dialysis catheters on
ECLS run). For the former, if the vein can be many occasions. We are concerned about the
grasped with a forceps, it can then be either risk of thrombosis and infection with this tech-
simply ligated or suture ligated. For the latter, nique because of the longstanding cannulation
it is sufficient to place a pursestring suture in with a large catheter, but have not experienced
the tissue around the vein to close off the soft problems in our patients. The cannulation site,
tissues since venous pressure is quite low and cannula, connector, and tubing are prepped and
usually easy to control. draped in a sterile fashion. A pursestring suture
For percutaneously cannulated patients, is placed around the skin at the access site and
either sedation or local anesthesia will usually left untied. The circuit and cannula are clamped
suffice. The patient should be placed supine and the line is cut from the connector with a
rather than in a sitting position to lower the scalpel and removed. The line kit is opened
risk of air embolus. The skin and cannula are and the guidewire is prepared. It is important
sterilely prepped and draped. Two options are to have a guidewire of at least twice the length
available for hemostasis. After clamping the of the ECLS cannula (this may not be in the kit
circuit and dividing the skin sutures the cannula and thus should be obtained separately). The
can be rapidly removed (so that air does not cannula connector is controlled with a gloved
enter the side holes and exit the end hole into thumb and the clamp is removed from the
the vein) and direct pressure held over the can- cannula. The thumb is moved just enough to
nulation site. Usually 5-10 minutes of pressure allow entry of the guidewire, but not too much
will provide hemostasis. The alternative is to to allow blood to escape and the guidewire is
place a pursestring suture in the skin close to the advanced. A second person prepares to tie the
cannula exit site in the skin. Monofilament su- pursestring suture and places a single throw of
ture (nylon or polypropylene) slides better and the knot which is tightened to prevent hemor-
is easier to tie. One person can rapidly remove rhage as the cannula is withdrawn, being sure
the cannula while another ties the pursestring; the guidewire remains. The line is then placed
it is unnecessary to hold pressure using this over the guidewire to the appropriate depth
technique. Hematoma formation is unusual due and the pursestring suture is tied to provide
to the relatively low venous pressure. hemostasis. The line is aspirated and flushed to
assure patency and securely sutured to the skin.
Continuing Venous Access after
Decannulation Approaches to Inadvertent Decannulation
Venous access is often challenging in If unplanned removal of the venous cannula

critically ill children, especially after complet- occurs, immediate action is necessary. The
ing ECLS. The ECLS circuit offers plentiful bedside ECLS specialist must be familiar with
294
managing this emergency since they will usu-

ally be the team member at the bedside. The
priorities in this situation are hemostasis and
respiratory support. Direct pressure will pro-
vide hemostasis. Simultaneously, ventilation
must be escalated to provide adequate respira-
tory support. Hand ventilation may provide
this, but using conventional or high-frequency
ventilation may be necessary. Depending on
the amount of lung dysfunction that remains,
two scenarios are possible. The first is that
ventilation and oxygenation are adequate at
acceptable levels of ventilation and FiO2. In
this case, mechanical ventilation should be
continued and weaned as possible, utilizing a
lung preservation strategy. The second scenario
is that, even with high levels of ventilation and
FiO2, the patient is not adequately supported.
In this situation, ECLS should be reestablished
expeditiously, while supporting the patient as
best as possible. If possible, separate teams
should be responsible for each of these tasks.
295
Chapter 24
References 9. Zoeller C, Lau E, Koeditz H, Ure B. Tho-

racoscopic lung biopsy during venovenous
1. Anton-Martin P, Thompson MT, Sheeran extracorporeal membrane oxygenation in
PD, Fischer AC, Taylor D, Thomas JA. childhood. Eur J Pediatr Surg 2011, 21(4),
Extubation During Pediatric Extracorporeal 274-5.
Membrane Oxygenation: A Single-Center 10. Rosenberg A, Haft J, Bartlett R, et al. Pro-
Experience. Pediatr Crit Care Med 2014, longed duration ECMO for ARDS: futility,
15(9), 861-9. native lung recovery, or transplantation?
2. Marhong JD, Telesnicki T, Munshi L, Del ASAIO J 2013, 59(6), 642-50.
Sorbo L, Detsky M, Fan E. Mechanical Ven- 11. Green T, Moler F, Goodman D. Probability
tilation during Extracorporeal Membrane of survival after prolonged extracorporeal
Oxygenation An International Survey. Ann membrane oxygenation in pediatric patients
Am Thorac Soc 2014, 11(6), 956-61. with acute respiratory failure. Extracorpo-
3. Hermon M, Burda G, Male C, et al. Surfac- real Life Support Organization. Crit Care
tant application during extracorporeal mem- Med 1995, 23(6), 1132-9.
brane oxygenation improves lung volume 12. Akkanti B, Hussain R, Nathan S, et al. Pro-
and pulmonary mechanics in children with longed Veno-Venous Extracorporeal Mem-
respiratory failure. Crit Care 2005, 9(6), brane Oxygenation in a Patient with Acute
R718-24. Respiratory Distress Syndrome. ASAIO J
4. Lotze A, Knight G, Martin G, et al. Im- 2015, Dec 30, Epub ahead of print.
proved pulmonary outcome after exogenous 13. Wiktor A, Haft J, Bartlett R, Park P,
surfactant therapy for respiratory failure in Raghavendran K, Napolitano L. Prolonged
term infants requiring extracorporeal mem- VV ECMO (265 Days) for ARDS without
brane oxygenation. J Pediatr 1993, 122(2), technical complications. ASAIO J 2015,
261-8. 61(2), 205-6.
5. Stillerman L, Gunn S, Hart J, Engle W. Ef- 14. Prodhan P, Stroud M, Hassan N, et al.
fects of exogenous surfactant on neonates Prolonged extracorporeal membrane
supported by extracorporeal membrane oxygenator support among neonates with
oxygenation. J Perinatol 1997, 17(4), 262-5. acute respiratory failure: a review of the
6. Kimmoun A, Roche S, Bridey C,et al. Pro- Extracorporeal Life Support Organization
longed prone positioning under VV-ECMO registry. ASAIO J 2014, 60(1), 63-9.
is safe and improves oxygenation and re-
spiratory compliance. Ann Intensive Care
2015, 5(1), 35.
7. Haefner S, Bratton S, Annich G, Bartlett
R, Custer J. Complications of intermittent
prone positioning in pediatric patients
receiving extracorporeal membrane oxy-
genation for respiratory failure. Chest 2003,
123(5), 1589-94.
8. Deshmukh H, Lioy J. The use of early lung
biopsy in detection of fatal pulmonary dis-
ease in the neonate. J Pediatr 2014, 164(4),
934-6.
296
25
ECLS Outcomes, Complications, and Followup of Children with Respiratory Failure
Parthak Prodhan, MD
Introduction with ARF receiving ECMO support. Overall

hospital survival was approximately 50% with
Since the early 1970s, extracorporeal the initial ECMO experience (until the early
membrane oxygenation (ECMO) has been 1990s).2-5 Hospital survival then improved
successfully deployed as a rescue modality (~57%) but has thereafter remained relatively
for pediatric acute respiratory failure (ARF) unchanged.1,6,7 However, some single centers
from diverse etiologies, with a common theme have reported a much higher survival for pedi-
of reversible but refractory hypoxemia and/or atric ARF.8 A more granular assessment of the
hypercapnia. Viral pneumonia is the single most existing data indicates differences in survival
common cause for ECMO deployment and ac- outcomes among some populations. Age dif-
counts for approximately 20% of ARF-related ferences in survival are clearly noted. Older
ECMO deployments in children; whereas, acute children (>10 years) had a lower survival (50%)
respiratory distress syndrome (ARDS) accounts than infants, toddlers, and younger children
for another 10%.1 Our understanding of short- (57%, 61%, and 55%, respectively).6 Among
term outcomes and complications among these the diagnostic categories, hospital survival is
patients has largely come from analyses of highest for status asthmaticus (83%), aspiration
data from the multicenter Extracorporeal Life pneumonia (71%), and respiratory syncytial
Support Organization (ELSO) Registry and virus pneumonia (70%). This contrasts with
some single center reports. The purpose of this lower survival in patients with fungal pneumo-
chapter is to highlight 1) short-term outcomes nia (23%), pertussis (39%), and ARDS related
(survival to hospital discharge), 2) long-term to sepsis (40%). These differences in survival
outcomes (survival, neurodevelopmental status may be related to the inherent reversibility of
and quality of life), and 3) complications while certain disease processes and the absence of
on ECMO support in children with ARF. associated multiorgan failure.6
As pediatric ECMO experience has ac-
Outcomes crued, increasingly more complex children
with comorbid conditions are receiving ECMO
Mortality support for ARF. Comorbid diagnoses among
these patients have increased steadily from 19%
Survival to hospital discharge is an im- in 1993 to 47% in 2007.6 Indeed, if patients with
portant short-term outcome among children comorbid conditions are excluded, survival
297
Chapter 25
among children without any underlying comor- was 76% compared to 71% for >7–10 days of
bid condition has increased significantly from ventilation and 68% for >10–14 days of venti-
57% in 1993 to 72% in 2007. This suggests that lation. It was not until >14 days that the esti-
among children with ARF, any survival benefits mated probability of survival decreased to 50%.
gained from improved ECMO technology and Similar trends were noted for other diagnostic
experience are likely being tempered by the subsets as well. These data suggest that children
increased complexity of patients supported with up to 14 days of pre-ECMO ventilation
on ECMO. The presence of certain comorbid should be considered as viable candidates for
conditions adversely impacts survival. Renal ECMO support and for those who receive >14
failure and liver failure are associated with days of pre-ECMO ventilation consideration
a 33% and 16% survival rate, respectively. for ECMO support should be made on a case-
Similarly, patients with hematopoietic stem cell by-case basis.
transplant, solid organ transplant, and primary Temporal trends assessing ECMO can-
immunodeficiency also have low survival rates nulation strategy indicate a steady increase in
(5%,39%,and 34% respectively).6,9,10 Among venovenous (VV) ECMO and double-lumen
patients with cardiac disease requiring ECMO VV cannulation compared with venoarterial
for ARF, survival for cardiomyopathy/myocar- (VA) ECMO cannulation. From 1993 to 2007,
ditis was 43% and for cardiac arrest prior to VV-ECMO cannulation increased from 35% to
ECMO support was 38%. Surprisingly, survival 46%, and the use of double-lumen VV catheters
was much higher in those with congenital heart increased from 1% to 19%.6 In contrast to ear-
disease with two ventricles (52%), one ventricle lier studies,14 hospital survival with VA-ECMO
(60%), or chronic lung disease (59%).6,11 support was lower (51%) compared to those
Another factor which has clearly emerged with two-catheter VV support (66%) or double-
to affect survival is the duration of pre-ECMO lumen VV catheter support (70%). Similar to
mechanical ventilation.12,13 Despite wide ac- patients initially treated with VA-ECMO, those
ceptance and practice of low tidal volume transitioned from VV- to VA-ECMO had 49%
ventilation strategies to limit ventilator-induced survival. Improved survival in patients receiv-
lung injury, a longer duration of pre-ECMO me- ing VV-ECMO cannulation may reflect patient
chanical ventilation lowers survival. Due to this selection because VV-ECMO offers no direct
fact, an accepted pediatric criterion for patient cardiac support and more critically ill patients
selection in the early part of the ECMO experi- are often placed on VA-ECMO.
ence typically included pre-ECMO mechanical Among children with ARF supported on
ventilation of <7–10 days.2,5 However, recent ECMO, approximately 12% were supported
studies have indicated otherwise.12 Pediatric for ≥21 days on ECMO. In contrast to find-
patients receiving mechanical ventilation for ings published in the mid-1990s,5 recent data
1 to 2 weeks prior to initiation of ECMO have suggests that, for patients requiring prolonged
survival (56%) comparable to those ventilated ECMO, survival varied inversely with duration
for a shorter time period (61%), regardless of of ECMO.15,16 Brogan et al.15 reported a hospital
the underlying diagnosis or mode of ventilation. survival of 38% for those supported for ≥21
In contrast, pre-ECMO ventilation times longer days, 30% after 4 weeks of ECMO support,
than two weeks were associated with much and 27% survived after 45 days of support. No
lower (38%) hospital survival. Similar differ- patient survived >52 days on ECMO. These
ences are noted within patient subsets as well. survival rates are significantly lower than sur-
For example, in a child with viral pneumonia the vival for children supported for <14 days (61%)
survival for 0–7 days of pre-ECMO ventilation on ECMO. In contrast to a clear identification
298
of mortality-related risk factors for the overall Registry, it is not possible to do more than
pediatric ARF patient population, no differ- speculate about the causes for these differences.
ences were found between survivors and non-
survivors among these patients on prolonged Long-term Outcomes
ECLS to pre-ECMO variables (acute pulmonary
diagnosis, comorbidities, adjunctive therapies, Despite the large experience for supporting
or blood gas parameters). children with ARF on ECMO and availability
A small subset of patients may be offered of short-term outcome data, there is a surprising
a second ECMO support deployment.17,18 Al- lack of data on important long-term outcomes
though these patients make up a fraction of beyond the period of hospitalization. However,
overall ECMO deployment in children (<5%), available data do raise the concern of late mor-
it raises important questions on survival and tality in ECMO supported patients. 11, 16, 17
who should be offered a repeat ECMO run. The Pathan et al.11 investigated one-year out-
results from single center experience contrasts comes of children supported on ECMO for
with data from the ELSO Registry. Fisher et respiratory failure and reported that the sever-
al.18,19 analyzed the outcomes of 127 pediatric ity of pulmonary dysfunction (based on the
patients from the ELSO Registry from 1981 to Oxygenation Index) and the presence of shock
2007. They found that the overall survival to were of greater significance in determining pa-
discharge was 44%, comparable to the survival tient outcomes at one year after ECLS than the
of 49% reported in the same period for patients presence of a comorbid condition. They found
supported by a single run, although more com- that one-year followup survival was 58%, which
plications were seen among patients undergoing was not impacted by the presence of comorbidi-
a second run of ECMO support. Independent ties. However, if shock was present the survival
predictors of survival in multiple run ECMO at one year after ECMO support decreased to
were renal complications during the first ECMO 46% and with renal dysfunction the survival at
run and the total number of complications dur- one year was 44%. By diagnostic categories,
ing the second ECMO run. However, in the the one-year followup survival was 65.5% for
Australian experience,17 the overall survival to viral pneumonia, 52% for bacterial pneumonia,
discharge among 26 patients with a second run and 36% for ARDS.
of ECMO was much lower (27%) in a mixed Single center experience with long-term
population of cardiac and respiratory failure. posthospital discharge followup indicates that
There also appear to be differences in out- among children with prolonged ECMO or sec-
comes between ECMO for ARF in children in ond run ECMO the survival is dismal.17,18 In their
the United States compared to European centers. single center experience of patients undergoing
A higher mortality (66%) has been noted among second run ECMO, Bohuta et al.17 showed that
the U.S. ECMO centers for pediatric ARF of four patients with ARF, only two survived to
compared to reports from Europe (56%).1 The hospital discharge. However, one of the hospi-
higher mortality in the US experience may be tal survivors died of respiratory failure during
due to more severely ill patients (as evidenced another hospitalization eight months after the
by higher pre-ECMO ventilator support levels, initial discharge and the other patient died at
lower pre-ECMO oxygenation and higher rates home of severe pulmonary hemorrhage five
of venoarterial ECMO) than with the European months after discharge. Similarly, in another
experience. However, in the absence of mea- single center study, Gupta et al.16 reported 22
sures of severity of illness within the ELSO ECMO runs lasting more than 28 days. Only
45% (n=10) of cases were successfully decan-
299
Chapter 25
nulated from ECMO. Six patients (27%) were various complications noted among children
alive 30 days after decannulation and only four while supported on ECMO.
patients (19%) survived to hospital discharge.
Of the three living children, two have signifi- Hemorrhage
cant neurologic issues with brain atrophy and
developmental delay, and one is awaiting renal Hemorrhage is one of the most frequent
transplantation; all three survivors have chronic complications noted during ECMO support and
lung disease. Both of these single center fol- is associated with decreased survival.20 Older
lowup reports indicate significant long-term children requiring ECMO for pulmonary indica-
sequelae and mortality even after hospital tions had an overall higher prevalence of hem-
discharge among high risk subsets. Unlike re- orrhagic complications than neonates (50% vs.
ports of neurodevelopmental followup among 25%).20 The higher prevalence of hemorrhage
cardiac and neonatal ECMO populations, there in older children when compared to neonates is
are no data on long-term pulmonary, cognitive, noted at various anatomic sites; namely, cannu-
or neurodevelopmental followup among older lation site (18.2% vs. 7.8%), surgical site (12.8%
children with ARF supported on ECMO. This vs. 6.3%), gastrointestinal (4.1% vs.1.7%), and
is a much needed area of investigation among pulmonary (8.2% vs. 4.5%).1 Hemorrhage oc-
children with ARF on ECMO support. curs due to systemic heparinization, consump-
tive coagulopathy associated with blood- bio-
ECMO Complications material interaction and underlying disease state,
platelet dysfunction, and clotting factor dilution.
Complications while on ECMO support If significant bleeding occurs, heparin infusion
are not uncommon and are associated with doses can be decreased (or occasionally stopped
increased morbidity and mortality. These com- altogether) because newer ECMO circuitry that
plications may be related to the underlining is heparin-bonded or surface-coated may allow
disease for which ECMO was indicated, or for a number of hours of minimal to no heparin
from different aspects of the extracorporeal therapy in an effort to control bleeding. Infusion
technology itself. Table 25-1 summarizes the of platelets, clotting factors and, in some cases,
Table 25-1. Mechanical and patient-related complications on ECMO support.
Complications
Thrombotic Clots Mechanical oxygenator failure, raceway rupture, other tubing rupture,
(oxygenator, hemofilter, pump malfunction, heat exchange malfunction, air in circuit, cracks in
bridge, bladder) connectors, cannula related issues
Hemorrhagic Intracranial hemorrhage, gastrointestinal hemorrhage, cannulation site
bleeding, surgical site bleeding, hemolysis, disseminated intravascular
coagulation, pulmonary hemorrhage
Cardiopulmonary Cardiopulmonary resuscitation required, cardiac arrhythmia,
hypertension, tamponade (blood, serous, air)
Pulmonary Pneumothorax, hemothorax
Neurologic Brain death, seizures, infarction, intracranial hemorrhage
Metabolic Related Hypoglycemia, hyperglycemia, hyperbilirubinemia, metabolic acidosis
Infections
Renal failure
Patient-related Mechanical
300
surgical exploration and use of antifibrinolytic Mechanical Complications

agents (aminocaproic acid, tranexamic acid and
aprotinin) may be warranted. Rarely, activated Historically, mechanical failure occurred
factor VII infusion may be required if other opin about 15% of ECMO courses reported to
tions have failed.21 For major pulmonary hemor- the ELSO Registry over a 20-year period,23
rhage, serial bronchoscopy may be warranted with a decreasing trend into the current era.
to clear the airway during the ECMO course. The prevalence of mechanical failure was
higher in children compared to neonates for
Thrombosis oxygenator failure (10.9% vs. 5.7%); raceway
rupture (0.6% vs. 0.3%); other tubing rupture
Thrombosis while on ECMO support occurs (1.7% vs. 0.6%); and pump malfunction (2.3%
because of the inability to modulate the activa- vs. 1.6%). Oxygenator failure occurs most fre-
tion of coagulation initiated within the ECMO quently due to thrombosis on the membrane, or
circuit despite ongoing anticoagulation therapy. plasma leak across it which reduces membrane
It is more likely to occur during periods of low oxygen transfer capabilities. In contrast to older
flow, inadequate anticoagulation, and in areas children, neonates had a higher prevalence of
of increased stasis and turbulence within the cir- air in the circuit (4.7% vs 4.3%), heat exchanger
cuit. It is therefore more common in the venous malfunction (0.7% vs. 0.4%), and pigtail con-
nector cracks (2.4% vs. 1.3%).1 Although rare,
side of the circuit. Clots in pediatric patients are
noted most commonly in the oxygenator (11%) raceway rupture and air in the circuit are sig-
and bladder (5.4%).1 Compared to neonates, the nificant emergencies on ECMO support. Air in
prevalence of thrombosis appears to be lower the circuit may originate with fluid and drug
in older children. Some clots are large and vis- administration, oxygenator failure, cavitation at
ible; however, the majority are subclinical or extreme blood flow rates, or possibly transpul-
occult. Major clots can cause oxygenator failure, monary transfer in patients with pneumothorax
consumption coagulopathy, and pulmonary or or air leak syndrome. Besides these age dif-
systemic emboli. Embolism of clots is infre- ferences, the indication for ECMO and longer
quent but can be devastating when it occurs. In duration of ECMO support also increase the
an autopsy study, systemic thrombosis within probability of mechanical component failure.23
organs was noted in 69% of autopsies, with
significantly more in children with congenital Neurologic Complications
heart disease.21 However, no correlation was
noted between results of coagulation testing or Acute neurologic complications (seizures,
duration of ECMO. Monitoring the circuit for hemorrhage, infarction, and brain death) among
signs of thrombus formation and propagation patients on ECMO support are associated with
growth by vigilant observation of the circuit increased mortality and long-term neurologic
successfully prevents thromboembolism in most morbidity among survivors.24-26 Approximately
patients. Extensive clot formation, particularly 13% of pediatric patients develop these com-
if associated with shear-related hemolysis, may plications.25 These complications are noted
require replacement of the entire circuit. More more frequently in neonates compared to older
recently, heparin-coated ECMO systems have children when ECMO is used for pulmonary
been used to decrease the frequency of this indications (ischemic stroke in 6.9% vs. 4.2%;
complication. intracranial hemorrhage in 7.5% vs 6.3%; clini-
cal seizures in 8.8% vs 5%). Among pediatric
patients, these complications progress to brain
301
Chapter 25
death in 4.7%.1 In all age groups, children who mortality.31 Older children on ECMO for pul-
suffer major neurologic complications have monary indications have a higher prevalence of
lower hospital survival (clinical seizures 36%, culture-proven infections compared to neonates
brain infarct 34%, intracranial hemorrhage (17% vs. 5.8%).1 Infection prevalence doubles
22%). These complications can either be a con- among patients who required ECMO for >14
sequence of the clinical condition that prompted days (30.3%) as compared with those requiring
ECMO, or related to events while on ECMO ECMO for 8–14 days (15.7%) and for ≤7 days
support. In the clinical setting of ongoing (6.1%). Coagulase-negative staphylococcus is
systemic heparinization and frequent presence the most common cause of infection in neonates;
of thrombocytopenia and coagulopathies, risk whereas, Candida species and Pseudomonas sp.
factors for neurological complications include are more common among pediatric and adult
the use of vasopressor/inotropic medications patients, and the prevalence of fungal infection
and the presence of infections, pulmonary rises with longer duration of ECMO support.31
failure, acidosis, elevated creatinine, myocar- There is no consensus on using prophylactic
dial stunning, and CPR during ECMO support. antibiotics or performing surveillance cultures
Complication rates are significantly higher for while on ECMO support although some centers
those supported with VA-ECMO compared to do offer antifungal prophylaxis.32 Broad spec-
VV-ECMO support among those with pediatric trum antimicrobial therapy should be instituted
ARF.25,27 In the setting where clinical param- when there is clinical suspicion for infections
eters are limited because of sedation and use of on ECMO.
muscle relaxants,28 treating physicians should
carefully consider the need for head computed VA-ECMO Specific Complications
tomography29 whenever concerns of neurologic
change arise. For patients with open fontanelles, VA-ECMO cannulation is associated with
frequent ultrasonography of the head should be risks of vessel perforation with hemorrhage,
performed, particularly in the first three days of arterial dissection, distal ischemia, incorrect
ECMO support.30 location, and development of pseudoaneurysm
at the site of insertion. These complications are
Infectious Complications rare (<5%). Femoral cannulation may cause
distal ischemia which, very rarely, can mandate
Patients are at a higher risk for infections amputation. With femoral artery cannulation,
during ECMO support. Factors contributing retrograde flow in the ascending aorta can
to this higher risk include need for invasive impair aortic valve opening, causing stasis of
procedures; prolonged use of support devices blood and thrombosis within the left ventricle.
such as central lines, urinary catheters, and Oxygenated blood infused peripherally into
endotracheal tubes; frequent exposure to broad- the femoral artery from the ECMO circuit may
spectrum antibiotics; and frequent breaches of preferentially perfuse the lower extremities and
the ECMO circuit for laboratory assessments the abdominal viscera while desaturated blood
and to administer ongoing therapies. Further- traversing the diseased lungs perfuses the heart,
more, alterations in the immune response often brain, and upper extremities. As a result, cardiac
accompany ECMO utilization. and cerebral hypoxia could exist. To avoid this
These infectious complications are associ- complication, arterial oxyhemoglobin satura-
ated with a prolonged need for bypass support, tion should be monitored in both the upper ex-
an increased risk of mechanical and patient- tremity and the lower extremity. It can be treated
related complications, and increased hospital with a number of different strategies, including
302
increasing the oxygen content of blood flowing

through the lungs (increased PEEP or FiO2),
placement of an additional venous catheter to
return a proportion of oxygenated blood into
the venous system (VAV-ECMO), moving the
arterial return catheter more proximally into the
right subclavian or carotid artery, or changing
to central ECMO.
Medical Complications
Besides these complications, a patient on

ECMO support is at risk of metabolic com-
plications including electrolyte imbalances,
and hypo- or hyperglycemia. Renal failure is
not uncommon and is covered elsewhere in
this textbook. Gastrointestinal complications
include hemorrhage, feeding intolerance and
hyperbilirubinemia, and biliary calculi second-
ary to prolonged fasting and total parenteral
nutrition (TPN), hemolysis, and diuretics.
303
Chapter 25
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JB, et al: Extracorporeal membrane oxy- AP, Brown KL. Predictors of outcome for
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The impact of extracorporeal membrane Anas NG, Cleary JP, Cappon J, Goldman
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respiratory failure: Survival and predictors vold NJ, Bartlett RH, Custer JR. Venove-
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70 support for pediatric respiratory failure: are
7. Minneci PC, Kilbaugh TJ, Chandler HK, there differences in survival and acute com-
Behar BJ, Localio AR, Deans KJ. Factors plications? Crit Care Med. 2000;28:521-5.
associated with mortality in pediatric pa- 15. Brogan TV, Zabrocki L, Thiagarajan RR,
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for severe pneumonia. Pediatr Crit Care poreal membrane oxygenation for children
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8. Gray BW1, Haft JW, Hirsch JC, Annich Med 2012;13:e249-54
GM, Hirschl RB, Bartlett RH. Extracor- 16. Gupta P, McDonald R, Chipman CW,
poreal life support: experience with 2,000 Stroud M, Gossett JM, Imamura M, Bhutta
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17. Bohuta L, d’Udekem Y, Best D, Alexander Neurosurg Pediatr 2011;7:338-344
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Pasko DA, Baldridge P, Annich GM. Safety due to acute respiratory failure. Pediatr
and efficacy of recombinant activated factor Radiol 2002;32:567-74
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Remenapp RT, Annich GM. Mechanical dren, and adults. Pediatr Crit Care Med
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305
26
Neonatal and Pediatric Cardiovascular Diseases Predisposing to ECLS
David S. Cooper, MD, MPH, Jonathan W. Byrnes, MD, Titus Chan, MD, MS, MPP,
Ravi R. Thiagarajan, MBBS, MPH
Introduction (ToF).3 The patient was weaned from support

within 48 hours, extubated two days later, and
Mechanical circulatory support (MCS) discharged on postoperative day 13.
serves an invaluable role in the care of children As the field of MCS has evolved in children,
with severe cardiac and/or pulmonary failure.1 the indications for use have expanded and out-
The two forms of mechanical circulatory sup- comes have improved. When combined with
port currently available to neonates, infants, an active transplantation program, mechanical
and smaller children include extracorporeal circulatory support can have a significant im-
membrane oxygenation (ECMO) and ventricu- pact on survival. The majority of the pediatric
lar assist device (VAD), with each technique experience consists of use of ECMO.4 The
having unique advantages and disadvantages. January 2016 Extracorporeal Life Support Or-
The intraaortic balloon pump (IABP) repre- ganization (ELSO) Summary5 reported 14,290
sents a third form of mechanical support that neonatal and pediatric cardiac failure cases
has been successfully used in larger children, (26% of cases) since 1989. For neonatal and
adolescents, and adults, but has limited ap- pediatric cardiac failure, survival to separation
plicability in smaller children.1 The use of from ECMO reaches 65% and survival to dis-
ECMO to provide support for circulatory fail- charge is 46%. Despite recent advances in VAD
ure arose as a natural followup to work in the technology, ECMO remains the most common
1970s that established the efficacy of ECMO circulatory assist system in use for children.
in the treatment of respiratory failure. Baffes The advantages of ECMO include its famil-
and colleagues first reported use of prolonged iarity among practitioners, ability to provide
extracorporeal circulation for congenital heart biventricular support and respiratory support,
disease.2 The duration of support was relatively universal availability across all pediatric age
brief for their patients; however, significant in- groups, and relative low cost. Unlike adults in
novations were introduced including the use of whom pure left ventricular (LV) failure is the
an ECMO circuit for resuscitation after cardiac common indication for mechanical support,
arrest and for perioperative stabilization at the cardiopulmonary support is more commonly ap-
time of palliative cardiac procedures. Soeter plied in children with a combination of pulmo-
and colleagues first reported use of ECMO for nary dysfunction, pulmonary hypertension, and
extended periods in a 4-year-old girl with severe right ventricular (RV) dysfunction, particularly
hypoxemia after repair of tetralogy of Fallot in the immediate postoperative period. Extracor-
307
Chapter 26
poreal life support is obviously the mechanical indications, including incurable malignancy,
support of choice for rapid deployment during advanced multisystem organ failure, extreme
cardiopulmonary resuscitation (CPR), known prematurity, and severe central nervous system
as extracorporeal CPR (ECPR, see Chapter 27). damage.8-10 Patients who are not transplant
A number of disadvantages of ECMO include candidates should be considered for support
the need for a dedicated team of specialists, only in carefully selected cases, as any patient
immobilization, requirement for intensive care placed on ECMO may ultimately require car-
monitoring, risks of bleeding, thrombosis, in- diac transplantation for recovery.8 A number of
fection, and multiorgan failure. These attendant conditions previously thought to be at high risk
disadvantages increase over time and hamper for further complications with ECMO support,
the use of ECMO for long-term support. Over including those with functionally univentricular
the last few years, substantial progress has been physiology, have been treated with ECMO with
made in pediatric MCS.6 Ventricular assist de- modest success. The ability to provide MCS
vices are being used with increasing frequency is now considered an expected and important
in children with isolated cardiac failure refrac- adjunct in the treatment of these patients.9-14 In
tory to medical therapy and is the treatment general, rigid contraindications for MCS, other
of choice for long-term bridge to recovery or than those mentioned above, have not been
transplantation (Chapter 59).7 In this chapter, developed. Instead, each case should be evalu-
we focus on the indications and outcomes of ated individually.
ECMO in neonatal and pediatric patients with
critical cardiac disease. Additionally, ECMO Preoperative Stabilization
in patients with functionally univentricular cir-
culation and in the setting of cardiopulmonary Neonates with profound cyanosis, and/or
resuscitation are addressed. cardiogenic shock occasionally require MCS.
Examples include patients with obstructed
Indications and Outcomes total anomalous pulmonary venous (TAPVR)
connection and ToF with absent pulmonary
The indications for ECMO can be divided valve syndrome. Such patients may present in
into two groups, those involving or not involv- extremis, and require preoperative stabiliza-
ing cardiac surgery. The indications related to tion with ECMO. Pulmonary hypertension
cardiac surgery include preoperative stabiliza- refractory to conventional therapy can occur in
tion, failure to wean from CPB, low cardiac neonates with d-transposition of the great arter-
output syndrome in the postoperative period, ies and several reports document the successful
and cardiopulmonary arrest. In the absence of use of ECMO for preoperative stabilization.15,16
cardiac surgery indications for ECMO include Another example is the neonate with severe
cardiopulmonary arrest, myocarditis and cardio- Ebstein’s malformation of the tricuspid valve
myopathy, pulmonary hypertension, intractable and functional pulmonary atresia with ductal-
arrhythmias, and respiratory indications. In dependent flow of blood to the lungs that has
either group, the importance of early ECMO a circular shunt from a wide open duct. Such
support cannot be over emphasized and initia- a patient will benefit from ECMO while the
tion should occur before prolonged periods of pulmonary vascular resistance declines.17
low cardiac output result in end-organ damage.
As the use of ECMO for cardiac patients
has increased, contraindications have evolved.
Certain conditions constitute absolute contra-
308
Postcardiotomy Support an initial period of clinical stability. Overall sur-

vival for all patients reached 58%. Survival to
The role of ECMO to provide postcardioto- discharge was only 23% in patients who could
my support for children with severe cardiopul- not be weaned from CPB, compared to 69% in
monary dysfunction after surgery for congenital patients who were cannulated postoperatively
cardiac disease is well established. Mechanical after an initial period of clinical stability. Morris
circulatory support may be required in the post- and colleagues24 reported on the use of ECMO
operative period, either due to the inability to in 137 children seen from 1995-2001, with an
separate from cardiopulmonary bypass (CPB), overall survival to discharge of 39%. In this se-
or a progressive low cardiac output syndrome ries, 66% received ECMO in the postoperative
due to a number of factors, such as ventricular period. Interestingly, functionally univentricular
dysfunction, pulmonary hypertension, or in- physiology and failure to separate from CPB
tractable arrhythmias. In this group of patients, were not associated with an increased risk of
it is imperative to rule out residual anatomic mortality. Cardiac physiology and the indica-
reasons with echocardiography and, if necessary, tions for support were not associated with the
cardiac catheterization. Booth and colleagues18 incidence of death.
demonstrated that cardiac catheterization could
be safely performed in children while on ECLS. Extracorporeal Cardiopulmonary
The majority of patients requiring ECMO im- Resuscitation (ECPR)
mediately after CPB remain cannulated via the
median sternotomy with a venous cannula in An increasingly common indication for
the right atrium and an arterial cannula in the ECMO in patients with heart disease is as an aid
aorta. Patients requiring support later in their for cardiopulmonary resuscitation. ECMO can-
postoperative course are more likely to be cannulation during active chest compressions has
nulated via the right internal jugular vein and been termed extracorporeal cardiopulmonary
right carotid artery. Importantly, bleeding is resuscitation (ECPR, see Chapter 27). del Nido
a major complication of ECMO after cardiac and colleagues25 initially described the use of
surgery. Re-exploration of the mediastinum is ECMO as ECPR in 11 patients after cardiac sur-
often necessary when transthoracic cannulation gery in 1992. A subsequent report of ECMO uti-
is used, increasing the risk of displacement of lization from the same center showed that ECPR
the cannulae and infection. was the ECMO indication in 38% of all cardiac
Numerous publications have documented ECMO cases.8 Since these initial reports, mul-
the experiences in individual centers.9,10,19-24 tiple other institutions have reported successful
The combined experiences of these centers institution of ECPR, primarily in patients with
demonstrate that ECMO aids survival of many heart disease.11,23,26,27-31 The majority of patients
children with congenitally malformed hearts undergoing ECPR have recently undergone
and refractory cardiopulmonary dysfunction, congenital heart surgery.32,33 Other cardiac
with between 33-60% of patients reaching conditions in which ECPR may be utilized in-
hospital discharge. Walters and colleagues10 clude unoperated congenital heart disease,28,30,34
reviewed 73 children with congenitally mal- myocarditis or cardiomyopathy,23,27,28,30,33-37 and
formed hearts placed on ECMO, analyzing them arrhythmia.27,38,39 An analysis of the American
in three groups: the preoperative support group, Heart Association’s Get With the Guidelines Re-
those who could not wean from CPB and were suscitation Registry examined the differences in
converted to support immediately after repair, patients who underwent ECPR vs. conventional
and the group cannulated postoperatively after CPR only.40 Compared to conventional CPR
309
Chapter 26
patients, ECPR patients had greater surgical E-CPR patients.31,44 In the ELSO Registry , ap-
cardiac illness (vs. medical noncardiac illness), proximately 46% of neonates receiving ECPR
an initial documented rhythm of asystole/pulse- had single ventricular heart disease.39 Similarly,
less electrical activity, preexisting congestive the ELSO Registry shows that 40% of pediatric
heart failure and hypotension, higher rates of patients with all forms of heart disease receiv-
receiving vasoactive infusions, inhaled nitric ing ECPR support were classified as single-
oxide, and electrolyte supplementation. ECPR ventricle lesions.37
patients also had longer periods of CPR than
conventional CPR patients but more likely to Myocarditis and Cardiomyopathy
have a favorable neurological outcome than
conventional CPR. Children with acute fulminant myocar-
The proportion of patients receiving ECPR ditis can benefit greatly from MCS including
varies with institution and population. Two ECMO with eventual myocardial recovery.
studies38,41 described ECPR rates of approxi- Similar to the experience in adults, survival is
mately 9-10% of in-hospital cardiac arrests. In also excellent in children. Hence in children
a single center study, patients in a cardiac ICU with acute myocarditis, persistent low cardiac
(17%) were more likely to undergo ECPR dur- output syndrome despite escalating inotropic
ing a cardiac arrest than patients in a neonatal or support should serve as an indication for MCS.
pediatric ICU (3-4%).41 In the postcardiotomy The ELSO Registry reports that the high-
population, the rate of ECPR can be as low as est survival for any diagnostic group occurs
1.1%38 and as high as 2.3%.42 Among patients among children with myocarditis, with almost
who have undergone the Norwood operation, 60% being successfully weaned from ECMO.5
approximately 8% of patients received ECPR Temporary extracorporeal left ventricular assist
support.34,43 In a similar manner, ECPR can ac- devices (LVADs) have emerged as an alterna-
count for a varying proportion of total ECMO tive therapy with the allure of miniaturized
usage, depending on the patient population and simplified circuits.45 However, ECMO
and institution. In the postcardiotomy ECMO remains the mechanical support of choice in
population, the proportion of ECPR patients patients experiencing cardiac arrest or illness
ranges from 20% 11 to 52% 44 of all ECMO too severe to tolerate sternotomy for temporary
cases. When restricted to patients undergo- LVAD placement. In this subgroup of patients,
ing the Norwood operation, 58% of patients ECMO may be used as a bridge to recovery,
requiring ECMO support received ECPR.43 transplantation, or VAD. In a retrospective
In several reports,23,34,36 56-60% of all cardiac study by Duncan and colleagues,46 the technique
ECMO (including patients with myocarditis and was used in 12 patients with clinical, laboratory,
cardiomyopathy) was utilized as ECPR. Finally, or endomyocardial biopsy-proven myocarditis
when examining all ECMO usage (excluding as a bridge to recovery or transplantation, with
ECMO in the neonatal ICU), ECPR accounted just over 80% surviving. Deaths in this cohort
for 25-30% of all ECMO in single institutional of patients were secondary to post-support
reports.27 nosocomial infections. In more heterogeneous
While the initial description of ECPR groups, other studies47,48 demonstrated survival
did not include patients with single ventricle to discharge of almost 75% for ECMO patients
physiology, subsequent reports of ECPR have with fulminant myocarditis
included these patients.9,11,31 In the postcardi- ECMO can also serve as a bridge to
otomy population, patients with single ventricle transplantation in children with irreversible
physiology accounts for 33% to 74% of all myocardial dysfunction in patients with dilated
310
cardiomyopathy, restrictive cardiomyopathy, Pulmonary Hypertension Refractory to

end-stage congenital cardiac disease, and Medical Therapy
chronic graft dysfunction after transplanta-
tion.49-51 Again, the urgency to provide support Select patients with pulmonary hyperten-
and the ability to tolerate planned sternotomy sion refractory to medical therapy benefit from
dictates the modality of MCS. In the event that extracorporeal life support.57 A classic example
a patient is initially placed on ECMO for un- is preoperative stabilization of obstructed
recoverable myocardial dysfunction, judicious TAPVR when the patient is close to death, and
timing is required for transition to more durable in the postoperative period when the pulmonary
support if there is no recovery observed after vascular resistance may be transiently elevated.
the initial days of support as prolonged ECMO In this group of patients, it is important to rule
(as defined by >14 days) has resulted in inferior out any residual pulmonary venous obstruction
post-transplant survival.52 as a cause of pulmonary hypertension. The
Although limited, indications for ECMO recently published American Heart Associa-
after heart transplantation remain. Indications tion/American Thoracic Society 2015 Pediatric
for support in this setting include failure to Pulmonary Hypertension guidelines recom-
separate from CPB and progressive low cardiac mend the use of MCS, including ECMO, for
output syndrome in the immediate postopera- the management of refractory postoperative
tive period, along with circulatory collapse due pulmonary hypertension in children after car-
to rejection or graft vasculopathy later in the diac surgery (Class 1, level of evidence B).58
post-transplant course.53,54 Right heart failure Mechanical support is controversial for patients
and/or pulmonary hypertension often result with irreversible pulmonary hypertension, such
in the inability to separate from CPB, and as primary pulmonary hypertension, as the like-
hence ECMO may be considered in addition lihood of survival as a bridge to lung transplan-
to temporary right ventricular assist devices. tation or heart-lung transplantation is minimal.
Galantowicz and colleagues55 examined the However, the recent increasing use of lung assist
role of the technique as an adjunct to pediatric devices as bridge to lung transplantation sug-
cardiac transplantation, using it as a bridge to gests that ECMO can be considered to bridge a
transplantation in 20% of patients, in 40% to patient with primary pulmonary hypertension
facilitate resuscitation of the cardiac allograft and refractory cardiopulmonary failure to a
in the immediate postoperative period, while durable lung assist device while awaiting lung
in just under 33%, it complemented therapy for transplantation (see Chapter 58).59
severe rejection in the late postoperative period.
Of the patients, 60% survived, all demonstrating Intractable Arrhythmias with Hemodynamic
normal function of the cardiac allograft. The Compromise
ELSO Registry has reported overall survival
of from 33-66% for this population.5 More re- In select patients with malignant tachyar-
cently a multicenter group reported utilization of rhythmias and bradyarrhythmias, a short trial
ECMO for the treatment of primary graft failure of MCS may help prevent circulatory collapse
with acceptable short term results, but increased while optimizing medical therapy, or prior to
attrition at 5-year followup (40% survival vs. an attempt at radiofrequency ablation. Patients
80% survival in those not requiring ECMO).56 who have benefited from the use of mechanical
support for this indication include those with
lethal arrhythmias secondary to acute myo-
carditis or cardiomyopathy, supraventricular
311
Chapter 26
tachycardia, junctional ectopic tachycardia or mortality for patients with single ventricle
ventricular tachycardia after cardiac surgery, anatomy supported with ECMO, including
and recalcitrant supraventricular tachycardia those who received ECPR.34,37,42,67 However,
in the setting of Ebstein’s malformation.60,61 multiple other reports (also including ECPR pa-
Residual lesions or coronary ischemia in the tients) have not demonstrated increased risk of
postcardiotomy patients must be ruled out. mortality for patients with single ventricle anat-
ECMO has predominated the dysrhythmia omy.13,31,32,36,39,68,69 Indications for ECLS in these
indication, though there are occasional reports children include inability to separate from CPB,
of the effective use of VADs as well. Finally, low cardiac output refractory to conventional
ECMO has been used preemptively in patients therapy, cardiopulmonary arrest, thrombosis of
with refractory arrhythmia and severe cardiopul- the shunt, and elective support. Mascio and col-
monary failure in whom severe hemodynamic leagues70 examined ECMO usage and outcomes
instability is expected during ablation therapy.62 among congenital heart surgical patients in the
Society of Thoracic Surgeons Database. In this
Respiratory Failure study, patients who had undergone the Norwood
operation had the highest rate of postoperative
Patients with congenital cardiac disease mechanical support (17%). However, survival
can develop respiratory failure due to paren- after MCS among Norwood patients (43%) was
chymal lung disease from viral infections, such higher than other surgical procedures such as
as respiratory syncytial virus, or due to severe Ross-Konno (29%), truncus (29%), and TAPVR
tracheobronchomalacia as seen in the sever- repair (41%). Sherwin and colleagues71 recently
est form of ToF with absent pulmonary valve examined the ELSO database for all neonates
syndrome. Patients with cyanotic disease who with hypoplastic left heart syndrome (HLHS)
develop parenchymal lung disease can be sup- who had undergone a Norwood operation and
ported with venovenous ECMO as a bridge to subsequent ECMO support. In this popula-
recovery or surgical palliation.63 Venovenous tion, hospital survival was 31% with failure to
ECMO has been successfully used in children wean from bypass as a significant risk factor for
with cardiac disease in 2 recent publications mortality. Finally, three centers have reported
using ELSO Registry data.64,65 ECMO indica- post-discharge outcomes for patients supported
tions, severity, and type of lung disease were not with ECMO after the Norwood operation.43,72,73
clearly described in these reports. ECMO can The ECMO usage rate across Norwood patients
also be used to provide short-term ventilatory ranged from 13.4% to 20%, with hospital
support to allow time for definitive tracheal sur- mortality ranging from 31% to 44%. In two of
gery in infants and children, in whom it would these studies, ECMO support was associated
otherwise be impossible to achieve adequate with decreased long-term survival compared to
gas exchange because of major airway disease patients who did not require ECMO.72,73 In con-
as seen with long segment tracheal stenosis.66 trast to Norwood outcomes, the ELSO database
demonstrates worse hospital survival (16%) for
ECMO in Patients with Functionally single ventricle patients palliated with a hybrid
Univentricular Circulation procedure.74 ECMO may be particularly useful
in potentially reversible conditions such as acute
Many centers previously considered a thrombosis of the shunt and transient depression
functionally univentricular circulation to be of ventricular function. Allan and colleagues75
a contraindication to ECMO. Single center reviewed their experience with the support of
reports have demonstrated increased risk of infants with shunted functionally univentricular
312
circulations, reporting almost 50% survived to Outcome and Risk Factors for Death
discharge. Patients cannulated for hypoxemia,
particularly with thrombosis of the shunt, had Variable survival statistics have been re-
markedly improved survival compared with ported for pediatric cardiac ECMO. In 2000,
those supported primarily for hypotension or cumulative survival for cardiac ECMO in the
cardiovascular collapse. Ravishankar and col- ELSO Registry was 42%.80 Interestingly, 10
leagues76 examined the use of ECMO follow- years later, the cumulative survival rate remains
ing the first stage of reconstruction for HLHS similar despite advances in management.5 In
and its variants. Almost 40% of their cohort 1991, analysis of the ELSO Registry by Me-
survived to hospital discharge with all patients liones and colleagues listed ongoing cardiac
who experienced shunt thrombosis surviving failure (37%) and major central nervous system
to discharge. damage (15%) as the most common causes of
There is limited experience with MCS in mortality.81 Cardiac failure and complications
patients with cavopulmonary connections.8,77 arising from low cardiac output are, likewise,
In the largest single center retrospective study, the most commonly reported causes of death
Booth and colleagues14 reported on their ex- in more recent reports.14,75,76,79 Thus, attempts
perience following bidirectional Glenn and to improve results achieved with pediatric
Fontan operations. Only one patient with a cardiac ECMO should address optimization
bidirectional Glenn anastomosis survived, al- of ventricular function, avoidance of extended
beit with severe neurological damage. In those periods of low cardiac output, and minimization
with the Fontan circulation, 50% survived to of other end-organ dysfunction. Prompt institu-
discharge, and 33% were alive at followup. tion of ECMO support achieves these goals by
Alsoufi and colleagues69 reported no survivors preserving myocardial, central nervous system,
among patients with Glenn or Fontan physiol- and visceral perfusion. Allowing patients to re-
ogy supported with postcardiotomy ECMO, main in a low cardiac output state on increasing
while hospital survival rates of patients with dosages of inotropic and vasoconstrictive agents
Norwood or shunt physiology ranged from 46- prior to ECMO may lead to end-organ damage
57%, respectively. In one review of the ELSO that may prove irreversible after MCS has been
Registry 103 infants with Glenn physiology, the established. Once initiated, meticulous patient
hospital survival rate reached 41%.78 Receipt of management limits infectious complications
CPR (including ECPR), ventricular morphology, that may progress to multisystem organ failure.
and cannulation site (central versus peripheral) For the salvage of continuing severe cardiac
were not associated with mortality. However, dysfunction, an early and aggressive approach
ECMO for combined cardiopulmonary failure to cardiac transplantation may be the only life-
was associated with increased mortality. Rood saving therapy available.
and colleagues analyzed data from the ELSO Lack of return of ventricular function
Registry on patients receiving ECMO after the within 48-72 hours in postcardiotomy patients,
Fontan operation.79 The overall survival to hos- confers a poor prognosis.9 Return of ventricular
pital discharge was 35% with greater utilization function is defined as the return of a pulsatile
and improved survival over time. These results waveform on the peripheral arterial trace on
suggest that while patients with cavopulmonary maximal levels of support (80% of normal
anastomoses can be supported with ECMO, cardiac output provided by the device). The
survival outcomes may be lower than patients return of a pulsatile waveform on the arterial
with other forms of heart disease. line trace by 72 hours of support was seen in 24
of 25 nontransplanted ECMO survivors (96%).
313
Chapter 26
These data have served as additional prognostic ric cardiac ECMO survivors,88 by parent proxy
information as postcardiotomy patients without reporting, comparing it with that of the general
return of ventricular function within 48-72 U.S. population and other cardiac populations.
hours of support are currently considered for The physical component of health-related qual-
transplantation or termination of support when ity of life scored lower than that of the general
transplantation is contraindicated. Delaying this population but similar to that of patients with
decision while awaiting return of ventricular complex cardiac disease, whereas psychosocial
function beyond the first 48-72 hours of sup- quality of life was similar to that of the general
port is not justified based on these results. Due population and of other pediatric cardiac popu-
to the scarcity of pediatric organ donors, early lations. Older children and adolescents who
consideration for transplantation optimizes the previously required cardiac ECMO perceived
chances of successful organ procurement. While their quality of life to be quite good.
return of ventricular function occurs early or
not at all for ECMO supported patients after Conclusions
cardiac surgery, patients with myocarditis may
require prolonged periods of MCS with ultimate A variety of forms of MCS are available
complete recovery of ventricular function.46,82-85 for children with cardiopulmonary dysfunction
refractory to conventional management. These
Long-term Followup devices require extensive resources, both hu-
man and economic. Extracorporeal membrane
Data regarding neurodevelopmental out- oxygenation can be effectively used in a variety
come86,87 of long-term survivors of ECMO is of settings to provide support to critically ill
emerging (see Chapter 35). Ibrahim and col- patients with cardiac disease. The approach for
leagues87 reported on 37 children who survived children with complex cardiac disease requires
MCS, 26 with ECMO and 11 with a VAD, who the development of innovative measures to help
were followed for an average of more than 4 ensure successful outcomes. Careful selection
years. Only one patient died in either group. In of patients and timing of intervention remains
both groups 80% were reportedly in excellent challenging. Special consideration should be
general condition, and ventricular function by given to children with cardiac disease with re-
echocardiographic evaluation was normal in all gard to anatomy, physiology, cannulation, and
ECMO survivors, and 90% of those surviving circuit management. The principles employed
after VAD support. More than 60% of children presently in the application of ECMO to support
supported with ECMO had moderate to severe the failing circulation in children serve as the
neurologic impairment, whereas only 20% of foundation for developing innovative circula-
those surviving after VAD support demonstrat- tory support techniques for the future.
ed the same degree of neurologic impairment.
These results may suggest an advantage for
use of the VAD, possibly because of decreased
requirements for anticoagulation, with less
risk for intracranial hemorrhage. These results
must be interpreted with caution, as the group
supported with ECMO had a greater proportion
of critically ill neonates, with more complex
underlying cardiac conditions. Costello and
colleagues assessed the quality of life of pediat-
314
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Requiring Postoperative Extracorporeal Prolonged extracorporeal life support for
Membrane Oxygenation After Norwood Pal- bridging to transplant. Perfusion 1997;12:93-
liation. Pediatr Cardiol 2013;34(3):570–575. 98.
74. Roeleveld PP, Wilde RD, Hazekamp M, et 83. Holman WL, Bourge RC, Kirklin JK.
al. Extracorporeal Membrane Oxygenation Circulatory support for seventy days with
in Single Ventricle Lesions Palliated Via the resolution of acute heart failure. J Thorac
Hybrid Approach. World J Pediatr Congenit Cardiovasc Surg 1991;102:932-934.
Heart Surg. 2014;23;5(3):393-397. 84. Kato S, Marimoto S, Hiramitsu S, et al. Use
75. Allan C, Thiagarajan R, del Nido P, et al. of percutaneous cardiopulmonary support
Indication for initiation of mechanical cir- of patients with fulminant myocarditis and
culatory support impacts survival of infants cardiogenic shock for improving prognosis.
with shunted single-ventricle circulation Am J Cardiol 1999;85:623-625.
supported with extracorporeal membrane 85. Kawahito K, Murata S, Yasu T, et al. Useful-
oxygenation. J Thorac Cardiovasc Surg ness of extracorporeal membrane oxygen-
2007;133:660-667. ation for treatment of fulminant myocarditis
76. Ravishankar C, Dominguez T, Kreutzer J, et and circulatory collapse. Am J Cardiol
al. Extracorporeal membrane oxygenation 1998;82:910-911.
after stage I reconstruction for hypoplastic 86. Hamrick S, Gremmels D, Keet C, et al.
left heart syndrome. Pediatr Crit Care Med Neurodevelopmental Outcome of Infant
2006;7:319-323. Supported with Extracorporeal Membrane
77. Klein MD, Shaheen KW, Whittlesey GC, et Oxygenation after Cardiac Surgery. Pediat-
al. Extracorporeal membrane oxygenation rics 2003;111:671-5.
for the circulatory support of children after 87. Ibrahim A, Duncan B, Blume E, et al. Long-
repair of congenital heart disease. J Thorac Term Follow-up of Pediatric Cardiac patients
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78. Jolley M, Thiagarajan RR, Barrett CS, et al. Ann Thorac Surg 2000;69:186-92.
Extracorporeal membrane oxygenation in 88. Costello JM, O’Brien M, Wypij D, et al.
patients undergoing superior cavopulmonary Quality of life of pediatric cardiac patients
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2014;148(4):1512-1518. membrane oxygenation. Pediatr Crit Care
79. Rood KL, Teele SA, Barrett CS, et al. Ex- Med 2012;13:428-434.
tracorporeal membrane oxygenation support
after the Fontan operation. J Thorac Cardio-
vasc Surg 2011;142(3): 504-510.
319
27
Extracorporeal Cardiopulmonary Resuscitation in Children
Ravi R. Thiagarajan, MBBS, MPH, Steve Brediger, RRT-NPS, Stephanie Larsen, BS RRT-NPS,
Francis Fynn-Thompson, MD, Peta MA. Alexander, MBBS
Introduction ECPR Definition
Few children who experience cardiac arrest, The ECMO Registry of Extracorporeal
both in-hospital (IHCA) and out-of-hospital Life Support Organization (ELSO) defines
(OHCA) settings, survive to hospital discharge ECPR as “Extracorporeal Cardiopulmonary
with good neurological outcomes.1-5 Extra- Resuscitation, in which ECLS was used as part
corporeal Membrane Oxygenation (ECMO) of the initial resuscitation from cardiac arrest.
initiated during CPR (ECPR) in some patients Hemodynamically unstable patients placed on
who failed to respond to conventional cardio- ECLS emergently without cardiac arrest are
pulmonary resuscitation (CPR), has improved NOT considered ECPR.”15 Patients who have
survival to hospital discharge.6-13 Increasing use return of native circulation (ROSC) and are
of ECMO to support patients with critical car- not receiving chest compressions at the time of
diorespiratory failure, improved ECMO tech- ECMO deployment do not meet the definition
nology, and ability to quickly deploy ECMO of ECPR. Throughout this chapter we refer to
have resulted in increasing application of ECPR ECPR as ECMO cannulation during CPR with
worldwide. The 2015 International Consensus ongoing chest compressions.
Statement on CPR and Emergency Cardiovas-
cular Care states that ECPR be considered for ECMO for Failed CPR
infants and children with cardiac diagnosis who
have in-hospital cardiac arrest, at centers with ECMO initiated during CPR can provide
resources and expertise to deploy ECPR (weak blood flow and gas exchange during the “low-
recommendation, low quality evidence).14 flow phase” of CPR resulting in improved
Many ECMO programs now offer ECPR for end-organ and brain perfusion during CPR
patients who fail to respond to conventional (Figure 27-1).16 Figure 27-1 demonstrates that
CPR. However, wide practice variability exists ECMO support cannot reverse ischemic injury
with little consensus on appropriate candidates, sustained during the “no-flow” or for much of
optimal timing, and best management practices the “low-flow phase” of CPR. Thus, prompt
for ECPR patients. This chapter describes cur- recognition and initiation of CPR to minimize
rent knowledge about neonates and children ischemic end-organ injury sustained during
supported with ECPR. the “no-flow” phase is required for success.
Furthermore, good quality CPR with minimal
321
Chapter 27
interruptions to chest compressions during the Thus ECPR remains a low volume event in
“low-flow” phase prior to ECMO deployment most institutions. Although all patients with
can reduce end-organ injury and improve ECPR cardiac arrest may be eligible for ECPR, in
outcomes. These issues explain improved ECPR most writings on the topic, ECPR is more com-
survival in patients with in-hospital compared monly used in children and adults compared to
to out-of-hospital cardiac arrest. Finally, ECPR neonates; and in those with cardiac compared
provides opportunities for investigation and to other diagnostic groups.9,11-13 Figure 27-2
treatment of the condition resulting in cardiac shows trends in ECPR utilization reported to
arrest. the Extracorporeal Life Support Organization’s
Wide variability continues among centers (ELSO) ECMO data registry.
offering ECPR on definition of “failed CPR,”
or when ECMO should be deployed after start Survival to Hospital Discharge after ECPR
of CPR. Some centers deploy ECMO when no
ROSC occurs after 10-15 min of CPR, while Survival to hospital discharge in children
others deploy ECMO earlier. Variability in tim- supported with ECPR has been described in
ing of ECPR deployment may also be influenced many retrospective cohort studies of ECPR
by underlying patient diagnosis and expected (Table 27-1), and ranges from 33-75%. Ran-
outcome of CPR as well as local logistic factors. domized clinical trials evaluating the efficacy
of ECPR compared to conventional CPR are
ECPR Utilization and Epidemiology unavailable. Current studies describing ECPR
survival have not included patients with car-
The ELSO International Summary, Janu- diac arrest receiving conventional CPR only
ary 2016, shows that ECPR compromised for comparison. In a recent propensity score
9% (n=6,421) of 73,596 cases reported to the matched cohort of children <18 years of age and
ECMO Registry from 400 centers worldwide.15 receiving CPR for >10 min duration, Lasa et al.
Data from other registries, eg, Get With The showed that use of ECPR increased survival to
Guidelines - Resuscitation Registry (GWTG- hospital discharge (odds ratio [OR]: 1.7) with
R) showed that only 16% (n=591) of 3,756 good neurological function (OR:1.8) compared
children <18 years of age who received CPR to conventional CPR alone.13 Because ran-
for >10 minutes were supported with ECPR.13 domized controlled trials to evaluate survival
Pre-Arrest
Total ECMO patients ECPR patients
1000
2500
900
No Flow
No: of ECMO Runs
800
No: of ECPR Runs
2000
Untreated Cardiac Arrest 700
1500 600
500
1000 400
Low Flow ECPR 300
Chest Compressions Flow (Cardiac Output)
500 200
Gas Exchange
100
Post-Resuscitation 0 0
Therapies 19921994199619982000200220042006200820102012
Post-Resuscitation Phase
ECLS year
Figure 27-1. Cardiac arrest phases and ECPR. Figure 27-2. Trends in ECPR use in children
and reported to the ELSO 1992–2013.
322
benefits from ECPR are difficult to conduct, was associated with improved survival. Thus
novel research methods, such as propensity based on current knowledge, patients who have
score analysis, offer the best hope for future successful outcomes following ECPR often
evaluation of ECPR. have a reversible cause for cardiac arrest, good
end-organ function prior to cardiac arrest, and
Patient Selection for ECPR receive good quality CPR. Patients with less
successful outcomes have prolonged duration
The limited time available for making de- of critical illness, significant metabolic acidosis,
cisions during active CPR complicates patient and end-organ injury prior to cardiac arrest,
selection for ECPR. Retrospective studies cited and may not have received good quality CPR.
in this chapter have evaluated factors associ- Cardiac patients with congenital heart disease
ated with mortality and can help with patient supported with ECPR in the postoperative pe-
selection. In a cohort of 682 ECPR patients, riod have good survival in most studies and are
Thiagarajan et al. found improved survival good candidates for ECPR.
in ECPR in those with cardiac and neonatal
respiratory disease without severe metabolic Duration of CPR and ECPR Outcomes
acidosis prior to ECMO support.12 In addition,
complications arising from ECMO increased There are conflicting data on the impact of
mortality. This study also examined factors as- duration of CPR on mortality and neurological
sociated with early (≤72 h after ECMO start) sequelae.8,9,11,17 Some studies describe survival
mortality after ECPR deployment. Brain death to hospital discharge with intact neurologic
(85%) and severe metabolic acidosis (pH <6.9) function when ECPR was initiated after 60
were both common in patients with early mor- minutes of CPR. However, one study demon-
tality, indicating pre-ECMO severity of illness strated increased mortality when CPR duration
and CPR quality contributed to death in these exceeded 30 minutes.17 Thus duration of CPR
patients. Raymond et al. found that presence alone cannot be used to exclude patients. Fi-
of pre-ECMO renal insufficiency, metabolic nally, although it is intuitive that CPR quality
acidosis requiring treatment, metabolic or rather than duration may be more important for
electrolyte abnormalities were all associated successful survival after ECPR, every attempt
with increased mortality.11 Cardiac diagnosis should be made to deploy ECPR as soon as pos-
sible because ensuring prolonged good quality
CPR may prove difficult.
Table 27-1. Survival to hospital discharge in
children supported with ECPR.
Neurologic Injury in ECPR
Author Year Diagnosis Institution Total Survival
del Nido6 1992 Cardiac Pittsburg 11 64% Neurologic injury occurs commonly fol-
Dalton7
Duncan10
1993
1998
Cardiac
Cardiac
Pittsburg
Boston
29
11
45%
54%
lowing ECPR. Barrett et al., using a cohort of
Morris9 2004 All Philadelphia 64 33% ECPR patients from the ELSO Registry, showed
Thiagarajan12 2007 All ELSO 682 38%
Alsoufi30 2007 All Toronto 80 34%
that 22% suffered acute neurologic injury.18
Huang46 2008 All Taiwan 27 41% Brain death, seizures, cerebral infarction and
Tajik31 2008 All Multicenter* 288 40%
Chan19 2008 Cardiac ELSO 492 42% bleeding were common. Mortality was high
Kane8
Raymond11
2010
2010
Cardiac
All
Boston
GWTG-R
172
199
51%
44%
in patients with acute neurologic injury (89%).
Wolf20 2012 Cardiac Atlanta 150 56% Pre-ECMO metabolic acidosis was associated
McMullan47 2014 Neonates ELSO 641 39% with increased risk of neurologic injury, sug-
Lasa13 2016 All GWTG-R 591 40%
*Metaanalysis, All patients: includes cardiac and noncardiac diagnosis
gesting again that CPR quality and potentially
323
Chapter 27
timing ECMO deployment may be factors pre- interventional cardiac catheterization proce-
disposing to neurologic injury and mortality in dures.27 In these patients, ECPR for cardiac
ECPR patients. arrest for rupture of structure is associated with
poor prognosis.
ECPR in Specific Populations Cardiac arrest unresponsive to conventional
CPR in patients with acquired heart disease, and
ECPR in Children with Cardiac Disease in those with cardiac dysfunction as a result of
noncardiac systemic illness can also be success-
ECMO to support children with cardiac fully with supported ECPR. Children with car-
arrest in the postoperative period after repair or diac arrest due to acute fulminant myocarditis
palliation of congenital heart disease (CHD) is have excellent survival following ECPR, and
the most common indication for ECPR.8-10,19,20 are thus good candidates for ECPR.28,29
Etiology of cardiac arrest in this population
is multifactorial including cardiac failure due ECPR in Children with Noncardiac Disease
to cardiac arrhythmia, tamponade, pulmonary
hypertension, and hypoxemia due to acute Experience with ECPR in children with
pulmonary blood flow obstruction, as well as noncardiac disease remains limited. Morris et
myocardial dysfunction or residual structural al. reported that only 2 (10%) of 21 children
lesions after congenital heart surgery unrespon- with medical diagnosis compared to 19 (44%)
sive to conventional management. Neonates of 43 with cardiac diagnosis survived to hospital
and children undergoing complex CHD surgery discharge after ECPR.9 The medical diagnosis
appear to be at higher risk of cardiac arrest and cohort in this report contained potentially high-
are commonly supported with ECPR. risk diagnostic groups including pulmonary
Children with single ventricle CHD, those hypertension (n=3), hypoplastic left heart syn-
with genetic syndromes and noncardiac struc- drome (n=2), and heart/lung and lung transplant
tural anomalies, and those with severe pre- patients (n=2). Of 682 ECPR patients studied by
ECMO metabolic acidosis all have increased Thiagarajan et al., 183 (27%) had a noncardiac
mortality.8,19 However patients with cardiac ar- diagnosis.12 Diagnostic groups included sepsis,
rest due to acute onset of reversible hypoxemia pediatric and neonatal respiratory failure, and
(eg, Blalock-Taussig shunt occlusion) have accidental injury (trauma and toxic ingestions).
excellent survival and should be considered as Survival was significantly lower in the ECPR
good candidates for ECPR.21-23 Patients with patients with noncardiac compared to cardiac
Bi-directional Glenn and Fontan circulations diagnosis (27% vs. 42%). However, patients
experiencing cardiac arrest have high risk for with neonatal respiratory failure supported
neurologic injury because positive intrathoracic with ECPR had significantly lower mortality
pressure from mechanical ventilation and the compared to other noncardiac diagnosis groups.
presence of atrioventricular valve regurgita- In a report on ECPR survival by Raymond et al.,
tion limits cardiac output generated during using data from the GWTG-R registry, patients
chest compression.24-26 In addition, high central with noncardiac diagnosis including pneumo-
venous pressure present in these circulations nia (no survivors) and sepsis (19%) had poor
reduces cerebral perfusion and ischemia. Thus survival. Similarly, Alsoufi et al. report poor
these patients may be considered high-risk survival (11%) with respiratory failure.30
candidates for ECPR. Finally, ECPR has been Reasons for poor survival in ECPR patients
used effectively in patients with CHD suffer- with noncardiac disease cannot be discerned
ing cardiac arrest during the course of complex from currently published literature. Reduced
324
survival in these patients may be related to hypothermia (initial body temperature 24–260
severe precardiac arrest illness and cardiac C). Of the 9 patients 2 survived to hospital dis-
arrest in non-ICU settings (compared to pa- charge and were neurologically intact. Because
tients recovering from cardiac surgery). In a coagulopathies and bleeding complicates severe
metaanalysis of 288 children supported with hypothermia, the authors titrated anticoagula-
ECPR, Tajik et al. showed that survival was tion carefully to minimize these risks. Other
highest in patients supported with ECPR in the reports on the topic report similar results.37-39
postoperative period.31 These patients likely Accidental hypothermia often complicates
had cardiac arrest in monitored settings such victims of unintentional drowning. Burke et al.
as intensive care units, where skilled personnel reviewed survival in 247 patients supported
to provide CPR and safely deploy ECPR were with ECMO following unintentional drown-
readily available. Based on current informa- ing. 40 Overall survival was 51%, however
tion, decisions to deploy ECPR in noncardiac drowning victims who had cardiac arrest and
patients should be based on patient factors and needed ECPR had poorer survival (23%). The
availability of a skilled ECPR team. reasons for poor survival could not be evaluated
in this report but may be related to OHCA.
ECPR Use in Out of Hospital Cardiac Arrest,
Accidental Hypothermia, and Drowning ECMO Equipment and Organizing an ECPR
Team
Out of hospital cardiac arrest is associ-
ated with poor survival. ECPR has been used Equipment needed for deploying ECPR
to support in adults presenting to Emergency include cannula, circuit, and oxygenator. ECPR
Departments (ED) receiving CPR after OHCA. requires rapid mobilization of equipment to
However, the current experience with this re- the bedside or site of cardiac arrest for ECMO
mains limited and survival poor.32-34 Information cannulation. Thus all ECMO equipment and
on the use of ECPR in children presenting to surgical instruments for cannulation should be
ED with cardiac arrest remains limited. Posner stored in an easily accessible location and in
et al. report on 2 children with cardiac disease containers that can be easily moved to the site
presenting to the ED in full cardiac arrest. ECPR of cardiac arrest. Where ECPR is deployed var-
was initiated in the ED and one survived to hos- ies between institutions. However, monitored
pital discharge.32 Poor survival may be related environments such as intensive care units and
to quality and duration of out of hospital CPR. procedural suites are ideal for safe deployment
ECPR has been used to support cardio- of ECPR.8
pulmonary resuscitation in children and adults
with accidental hypothermia and drowning.35-40 ECMO Cannulation
Emergency institution of cardiopulmonary by-
pass (CPB) or ECMO has been used to provide ECPR equipment should contain venous
rewarming and cardiopulmonary support in and arterial ECMO cannula catering to all
patients with severe accidental hypothermia. patient sizes, and for peripheral or central
Skarda et al. report a series of children man- ECMO cannulation. Cannulation sites include
aged with CPB and ECMO for rapid rewarming chest (right atrium and aorta) and peripheral
and ECPR.35 Using an existing institutional vessels (internal jugular veins, carotid arteries,
protocol for management of environmental hy- and femoral arteries and veins). Children who
pothermia with ECMO and/or CPB,36 9 patients have undergone recent cardiac surgery via ster-
were placed on ECMO after severe accidental notomy are usually cannulated through the chest.
325
Chapter 27
Conduct of CPR during open chest cannulation ECMO circuit priming and deployment should
may be associated with interruptions to CPR be readily available. Availability of 24/7 in-
and reduced survival.19 Finally, children with house ECPR teams among institutions offering
cardiac disease who have undergone multiple ECPR varies, and whether the presence of an
previous cardiac catheterization procedures for in-house team improves ECPR survival remains
diagnosis or intervention may have peripheral unknown. Clear roles for ECPR team members
vessel occlusions. Thus knowledge of occluded should be delineated during ECMO deployment.
vessels may help prevent delays in ECMO can- An event manager, usually the Intensive Care
nulation by avoiding accessing these sites for Unit physician, should be established to ensure
cannulation. the maintenance of good quality resuscitative
measures including CPR during ECMO can-
ECMO Circuit nulation.
Protocols for rapid mobilization of the
ECMO circuit configuration, pump (roller ECPR team and conduct of ECMO cannulation
or centrifugal), and oxygenators vary widely during CPR should be established and followed.
between centers. Centrifugal pumps are be- These protocols should be widely disseminated
ing increasingly used for ECMO. Circuits and the ECPR team should be well trained to
configured using centrifugal pumps can be manage mechanical circuit failure and ECMO
miniaturized, and are more mobile compared complications. Examples of team member com-
to roller pump circuits. However improved position, definition of roles and tasks for team
patient outcomes in patients supported with members, and an ECPR deployment algorithm
centrifugal pump ECMO has not been demon- currently in operation in the Cardiac Intensive
strated.41,42 Since flow generated by centrifugal Care Unit at Boston Children’s Hospital are
pump is afterload sensitive, epinephrine and/ shown in Table 27-2 and Figure 27-3.
or other vasoconstrictors used as part of CPR ECPR is a low volume high-risk event, thus
may reduce centrifugal pump output. The use of ensuring adequate training for all members
hollow fiber oxygenators has reduced the need of the ECPR team is crucial (see Chapter 67).
for maintaining wet primed circuits as these Medical simulation has been widely used for
devices are easier to prime. these purposes both for skill and/or team-based
Many centers prime ECMO circuits using training for ECPR. Such training has shown
clear prime solutions (eg, Normasol) during enhanced team performance, patient safety, and
rapid deployment for ECPR.8 Easy access to outcomes.44,45 A process for debriefing all ECPR
a blood bank is essential for centers that use events must be available in all ECPR programs.
blood primed circuits for ECPR. Care should
be taken to avoid hyperoxia when starting Table 27-2. Boston Children’s Hospital CICU
ECMO flow to minimize hyperoxia mediated ECPR team composition.
reperfusion injury. The ECMO circuit can be
43
Task Responsible Team Member
used to provide therapeutic hypothermia for Event Manager CICU physician; CICU Charge Nurse
STAT ECMO Page CICU Charge Nurse
neuroprotection following CPR. Blood Bank Notification CICU Charge Nurse
ECMO Cannulation & Surgical Issues CICU Surgeon
ECMO Circuit & ECMO issues ECMO specialist
ECPR Team CPR Team Roles
CPR Medication Administration
Assigned by Event Manager
Nurse assigned to patient
Heparin Administration Nurse assigned to patient
Documentation Assigned by Event Manager
A skilled ECMO team forms the basis for Time Out #1: Patient Identification Cannulating Surgeon
and Cannulation site identification
successful outcomes in ECPR. A surgical team Time Out #2: Identification of correct Cannulating Surgeon and ECMO
for cannulation and ECMO personnel for rapid Patient to ECMO circuit connections
CICU=Cardiac Intensive Care Unit
Specialist
326
Systems and personnel deficiencies identified who received CPR for >60 min prior to ECPR
during event debriefing should be corrected. and survived had intact neurological function.9
Creation and regular evaluation of ECPR quality In another study 89 survivors from a cohort of
metrics (eg, time from CPR to full ECMO sup- 199 ECPR patients with from the GWTG-R
port) can be useful for monitoring and planning registry, 56 had good neurological status at dis-
program performance improvement. charge.11 In a single center study of 172 children
with cardiac disease undergoing ECPR, Kane
Long-term Outcomes Following ECPR et al. report 75% of survivors had none or only
mild neurological impairment at discharge.8
Long-term neurological, functional, and Posthospital discharge functional and cogni-
survival outcomes for children supported with tive outcomes and quality of life information
ECPR are not well reported. Some studies have in ECPR survivors is not available and should
included neurological status at discharge in be the focus of future evaluation of this therapy.
cohorts of ECPR patients. Morris et al. report
no change in Pediatric Cerebral and Overall Summary
Performance Categories (PCPC, POPC) in 50%
of survivors, and 3 of 6 patients in this cohort ECMO is increasingly used to support
children with cardiac arrest failing to respond
to conventional CPR therapies with good sur-
Cardiac Arrest
CPR Initiated vival. ECPR is commonly used in children with
Ice Packs to the Head
heart disease and in-hospital settings. Prompt
5 min CPR
recognition of cardiac arrest and providing good
No ROSC quality resuscitation are critically important
STAT ECMO page*
to improve survival and neurologic outcomes
among patients supported with ECPR. ECPR
Optimize CPR
Team Members Assembled deployment algorithm and team based educa-
Blood Bank Notification
ECMO/Surgical Equipment to Bedside
tion are essential to ensure success and safety
in ECPR programs.
TIME OUT #1 (Surgeon)

Patient Identification
Cannulation Plan**
ECMO Cannulation completed
TIME OUT #2
(Surgeon and ECMO Specialist)
Identify correct Arterial &
Venous connections
ECMO FLOW
Goal 100ml/kg/min or 2L/min
Post-resuscitation Management
* STAT ECMO pages Cannulating Surgeon and ECMO specialist

** Peripheral Vessel Cannulation: Check Vascular Occlusion Sheet
Figure 27-3. Boston Children’s Hospital

cardiac ECPR deployment algorithm.
327
Chapter 27
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hypoplastic left heart syndrome. Pediatr Thorac Cardiovasc Surg. 2007;134:952-959
Crit Care Med. 2006;7:319-23. e2.
23. Jolley M, Yarlagadda VV, Rajagopal SK, et 31. Tajik M,Cardarelli MG. Extracorporeal
al. Extracorporeal membrane oxygenation- membrane oxygenation after cardiac ar-
supported cardiopulmonary resuscitation rest in children: what do we know? Eur J
following stage 1 palliation for hypoplastic Cardiothorac Surg. 2008;33:409-17.
left heart syndrome. Pediatr Crit Care Med. 32. Posner JC, Osterhoudt KC, Mollen CJ, et
2014;15:538-45. al. Extracorporeal membrane oxygenation
24. Salvin JW, Laussen PC, Thiagarajan RR. as a resuscitative measure in the pediatric
Extracorporeal membrane oxygenation for emergency department. Pediatr Emerg Care.
postcardiotomy mechanical cardiovascular 2000;16:413-5.
support in children with congenital heart 33. Johnson NJ, Acker M, Hsu CH, Desai N,
disease. Paediatr Anaesth. 2008;18:1157- et al. Extracorporeal life support as rescue
62. strategy for out-of-hospital and emergency
25. Rood KL, Teele SA, Barrett CS, et al. Ex- department cardiac arrest. Resuscitation.
tracorporeal membrane oxygenation sup- 2014;85:1527-32.
329
Chapter 27
34. Le Guen M, Nicolas-Robin A, Carreira S, 43. Sznycer-Taub NR, Lowery R, Yu S, et

et al. Extracorporeal life support following al. Hyperoxia Is Associated With Poor
out-of-hospital refractory cardiac arrest. Outcomes in Pediatric Cardiac Patients
Crit Care. 2011;15:R29. Supported on Venoarterial Extracorporeal
35. Skarda D, Barnhart D, Scaife E, et al . Ex- Membrane Oxygenation. Pediatr Crit Care
tracorporeal cardiopulmonary resuscitation Med. 2016;17:350-8.
(EC-CPR) for hypothermic arrest in chil- 44. Allan CK, Pigula F, Bacha EA, et al. An
dren: is meaningful survival a reasonable extracorporeal membrane oxygenation
expectation? J Pediatr Surg. 2012;47:2239- cannulation curriculum featuring a novel
43. integrated skills trainer leads to improved
36. Scaife ER, Connors RC, Morris SE, et al. performance among pediatric cardiac sur-
An established extracorporeal membrane gery trainees. Simul Healthc. 2013;8:221-8.
oxygenation protocol promotes survival 45. Su L, Spaeder MC, Jones MB, et al. Imple-
in extreme hypothermia. J Pediatr Surg. mentation of an extracorporeal cardiopul-
2007;42:2012-6. monary resuscitation simulation program
37. Walpoth BH, Walpoth-Aslan BN, Mattle HP, reduces extracorporeal cardiopulmonary
et al. Outcome of survivors of accidental resuscitation times in real patients. Pediatr
deep hypothermia and circulatory arrest Crit Care Med. 2014;15:856-60.
treated with extracorporeal blood warming. 46. Huang SC, Wu ET, Chen YS, et al. Extra-
N Engl J Med. 1997;337:1500-5. corporeal membrane oxygenation rescue for
38. Wollenek G, Honarwar N, Golej J.. Cold cardiopulmonary resuscitation in pediatric
water submersion and cardiac arrest in patients. Crit Care Med. 2008;36:1607-13.
treatment of severe hypothermia with 47. McMullan DM, Thiagarajan RR, Smith KM,
cardiopulmonary bypass. Resuscitation. et al. Extracorporeal cardiopulmonary re-
2002;52:255-63. suscitation in term and premature neonates.
39. Eich C, Brauer A, Timmermann A, et al. Pediatr Crit Care Med. 2014; 15: e9- e16.
Outcome of 12 drowned children with at-
tempted resuscitation on cardiopulmonary
bypass: an analysis of variables based on
the “Utstein Style for Drowning”. Resus-
citation. 2007;75:42-52.
40. Burke CR, Chan T, Brogan TV, et al. Ex-
tracorporeal life support for victims of
drowning. Resuscitation. 2016;104:19-23.
41. Barrett CS, Jaggers JJ, Cook EF, et al. Out-
comes of neonates undergoing extracorpo-
real membrane oxygenation support using
centrifugal versus roller blood pumps. Ann
Thorac Surg. 2012;94:1635-41.
42. Barrett CS, Jaggers JJ, Cook EF, et al.
Pediatric ECMO outcomes: comparison
of centrifugal versus roller blood pumps
using propensity score matching. ASAIO
J. 2013;59:145-51.
330
28
Extracorporeal Membrane Oxygenation for Adults with Congenital Heart Disease
Sameh M. Said, MD, Gregory J. Schears, MD, Joseph A. Dearani, MD
Introduction shock postcardiotomy. A wide variety of ACHD

diagnoses can result in heart failure, requiring
Since the 1990s, extracorporeal membrane mechanical circulatory support. These include
oxygenation (ECMO) has been used to treat the conotruncal anomalies (eg, tetralogy of Fal-
adult patients with cardiogenic shock. ECMO lot, pulmonary atresia,) or Ebstein’s anomaly
has been shown to be lifesaving and provide that are most commonly associated with right-
excellent hemodynamic support. It has the ad- sided heart failure, or other ACHD lesions, such
vantage of quick deployment in emergency situ- as atrioventricular septal defects, left-sided
ations, especially for those with biventricular obstructed lesions that may be associated with
failure. A considerable number of patients with left or right-sided heart failure. The following
congenital heart disease survive to adulthood are examples of special applications of ECMO
due to the improved therapeutic techniques, but support in ACHD:
reoperation becomes necessary. A fair number
of these adults develop complications related Single Ventricle and Failed Fontan Circulation
to decompensated heart failure or cardiogenic
shock. Cardiac surgery in high-risk adults with Patients with single ventricle physiology
congenital heart disease (ACHD) may require and failed Fontan present significant challenges
extracorporeal membrane oxygenation (ECMO) to ECMO support. Poor outcome has been as-
in the postoperative period as well. ECMO can sociated with ECMO used for heart failure after
be useful in this patient group because of the the procedure but when used for other indica-
ability to fully bypass the right ventricle which tions, better outcomes ensue.1
often has diminished function. ECMO can ECMO can be used in adult patients with
also be useful to support patients with Fontan single ventricle palliation in the following cir-
circulation. cumstances:
• Progressive myocardial failure in those who
Specific Cardiac Defects Requiring ECMO previously underwent a modified Fontan
procedure;
In ACHD, ECMO can be used in either the • Cardiorespiratory arrest during interven-
pre- or postoperative periods. It can be used tional procedures in the cardiac catheteriza-
to optimize the patient’s hemodynamic status, tion laboratory;
overcome heart failure or treat cardiogenic
331
Chapter 28
• Adults who previously had an older ver- ventricle is ejecting. Echocardiography helps to
sion of the Fontan connection such as ensure adequate decompression of the systemic
atriopulmonary connection and underwent ventricle. Careful monitoring for superior vena
conversion to intracardiac lateral tunnel or cava syndrome and hepatic congestion is critical
extracardiac conduit Fontan. in these patients. Measures to avoid potential
Cannulation strategies in Fontan patients in- compartment syndrome in the lower extremity
clude femoral vessels alone, neck vessels alone, include not oversizing the femoral venous can-
neck vessels combined with femoral vessels, or nula and preserving antegrade blood flow in the
central cannulation. femoral artery. Compartment syndrome typi-
Success in these patients depends on proper cally results from inadequate femoral arterial
patient selection, timing, technique of can- perfusion or adequate antegrade arterial perfu-
nulation, and the ability to protect other organ sion with inadequate femoral venous outflow.
systems while on ECMO support. Recovery of
good myocardial function, sinus rhythm, and Congenitally Corrected Transposition of Great
atrioventricular valve function are associated Arteries
with improved outcome. Placement of ECMO
for cardiopulmonary resuscitation (ECPR) in A retrospective multi-institutional study
Fontan patients is associated with poor outcome, clearly demonstrated an increasing incidence
probably because of the difficulty in providing of systemic ventricular dysfunction and clinical
adequate conventional CPR in these patients, as congestive heart failure (CHF) with advancing
the intrathoracic pressure increases which oc- age in patients with TGA. Even in those with
curs as a result of compressions can restrict ef- cc-TGA and no significant associated lesions,
fective pulmonary blood flow and oxygenation. more than one third developed CHF by the
Compressions also result in increased cerebral fifth decade of life. In patients with significant
venous pressure, which may impair cerebral associated defects and prior open heart surgery,
perfusion. By the time cannulation occurs, ir- two thirds of patients had CHF by the age of 45
reversible end-organ damage may have ensued. 2 years, 3
and cardiac transplantation may be their
ECMO should be considered earlier in these first operation at that time. Potential theories
patients before irreversible end-organ damage behind this include:4
occurs. The main contributing factors to poor

outcome in adults relate to the inability to main- Malalignment of the Interventricular Septum
tain adequate venous drainage and systemic
perfusion which results in neurologic injury. Suboptimal function of the systemic ven-
Using more than one venous cannula from more tricle (morphologic right ventricle) either at
than one site should augment the venous return, rest or with exercise is well established. Coex-
but these patients often have multiple central istence of abnormalities of the left-sided atrio-
venous occlusions from previous monitoring ventricular valve (morphologic tricuspid valve
lines related to prior operations, or percutaneous (TV)) structure and function also predisposes
interventions. We recommend during the initial the patient with cc-TGA to more rapid clinical
resuscitation efforts to cannulate the internal deterioration. The development of systemic
jugular vein to ensure decompression of the ventricular (RV) failure can occur primarily,
superior vena cava and maximize cerebral per- without previous surgical intervention, and is
fusion pressure and avoid neurologic injury. A usually associated with dysplasia of the TV,
single venous cannula in patients with a Fontan causing tricuspid regurgitation. RV failure
circulation usually proves inadequate even if the may also occur secondarily after conventional
332
repair (physiologic repair) of associated cardiac addition to the volume loading secondary to
defects such as VSD or relief of PS or atresia tricuspid regurgitation, may also contribute to
when the RV remains in the systemic circulation. RV failure.6, 7
The deterioration in RV function associated with ECMO can be used in these patients to
tricuspid regurgitation may develop insidiously support the failing systemic ventricle postopera-
over many years without associated cardiac tively until myocardial recovery or transplanta-
anomalies. When associated with dysplasia or tion occurs, or postoperatively as a method of
Ebsteinoid malformation of the TV, deteriora- support until recovery occurs from late double
tion may be rapid. Once tricuspid regurgitation switch operation.
has developed, the volume loading of the RV,
accentuated by any shunts or VSD, can cause Awaiting Cardiac Transplantation
further TV annular dilatation, creating more
regurgitation and worsening systemic ventricu- ECMO has been used to improve pulmo-
lar function and subsequent heart failure. The nary hypertension in those patients waiting
development of morphologic RV failure without for heart transplantation8 (see Chapter 59) but
previous surgical intervention is almost always it remains unknown if it improves in overall
associated with dysplasia of the TV. Right ven- outcomes.9
tricular dilatation, in association with volume
loading from tricuspid regurgitation, displaces Indications for ECMO Support in ACHD
the ventricular septum into the morphologic LV,
which leads to displacement of the septal com- ECMO can provide both circulatory and
ponents of the TV, which, in turn, accentuates respiratory support as a bridge to recovery or
the regurgitation. In secondary morphologic RV sometimes to transplantation. ECMO can also
failure following conventional closure of VSD be used during cardiac arrest (ECPR). Severe
or relief of PS, the decrease in the morphologic heart failure unresponsive to maximal medi-
LV pressure and realignment of the septum cal therapy or the use of an intraaortic balloon
toward the pulmonary ventricle can have the pump (IABP) represent the main indications to
same effect by creating tricuspid regurgitation. consider ECMO. The following represent our
This is thought to be the mechanism of the inclusion criteria:
development of tricuspid regurgitation and RV
failure, which is supported by the observation • Mean arterial blood pressure < 60 mmHg,
that PA banding to train the morphologic LV • Elevated left atrial pressure (>20 mmHg),
reduces tricuspid regurgitation by realignment • Low cardiac index (< 2 L/min/m2),
of the ventricular septum. If this is the mecha-
5
• Rising lactates with evidence of end organ
nism of morphologic RV failure, then tricuspid involvement,
regurgitation and RV failure can be expected to • Failure to respond to optimized vasoactive
occur after conventional repair. support,
• Neurologically intact with reasonable likeli-
Role of Ischemia hood of either reversibility or qualification
for either long term mechanical support or
The RV working as a systemic ventricle transplantation.
at systemic pressures with the resultant hy- For postcardiotomy patients, ECMO should
pertrophy of the myocardium may not receive be considered with failure to wean from car-
sufficient coronary blood flow. This results in diopulmonary bypass despite high inotropic
ischemia of the RV myocardium, which, in support with or without IABP placement.
333
Chapter 28
Contraindications to ECMO Support in ACHD Chapter 7). We routinely obtain thromboelas-

tography (TEG) with and without heparinase
Among patients with multisystem organ to judge intrinsic coagulation and the heparin
failure ECMO is not usually associated with effect. For postcardiotomy patients, we usu-
good outcome, most likely due to the severe ally wait until chest tube drainage is low (<2
end-organ damage that occurred prior to its cc/kg/hr for at least 4 hours) prior to initiation
initiation. Therefore, it is best to consider ear- of intravenous anticoagulation. Depending
lier ECMO prior to irreversible organ damage on the severity of the bleeding and extent of
occurs. mediastinal dissection, anticoagulation may be
In patients with sepsis (see Chapter 56) withheld for the first 12-24 hours if full ECMO
ECMO management may prove difficult due to flow can be achieved. Incremental increases in
the associated systemic vasoplegia and inability anticoagulation goals over the first several days
to maintain circuit flows that sustain satisfactory can help lessen hemorrhage and the need for
mean arterial pressure. Other contraindications transfusion. For longer support, the addition
include irreversible neurological damage or of a second agent such as bivalirudin is often
other prohibitions for transplantation with no helpful to provide more comprehensive, titrat-
hope of myocardial recovery. Finally, severe able anticoagulation. Heparin-coated circuits
aortic valvular regurgitation, and unwitnessed may provide some additional benefit as well.
cardiac arrest or prolonged cardiorespiratory Patients who have failed to be weaned from
resuscitation (>60 minutes) represent additional ECMO will be evaluated for transplantation
contraindications. when no other contraindications exist.
ECMO should be considered as a bridge
to conventional operation or postcardiotomy Tips/Pitfalls for ECMO in Patients with
recovery, and patients with ACHD should be Previous Sternotomies
considered for ECMO support if myocardial
recovery is expected with or without surgery. Vascular Access
Management Strategies Femoral vessels are usually the first choice

for cardiogenic shock and in emergency situ-
Echocardiography is used routinely to con- ations especially since the majority of these
firm cannulae position and ensure the absence ACHD patients have had at least one prior ster-
of LV distension. It also helps in monitoring notomy or femoral artery monitoring. This can
during the duration of support to assess myo- be performed percutaneously or by cut-down.
cardial recovery. Central cannulation is our first choice for post-
The initial pump flow should support at least cardiotomy shock to avoid the issues related to
2.5 L/min/m2 with the goal of mixed oxygen peripheral cannulation. The axillary artery with
saturation of 70%. Inotropic support should be or without a chimney graft represents a good
reduced or withdrawn to decrease myocardial alternative to femoral artery particularly if the
oxygen demand. Mechanical ventilation with latter is occluded or too small for cannulation.
low tidal volume is applied. Bleeding is the
main complication of ECMO support. Meticu- Left Ventricular Distention
lous hemostasis is necessary as these patients
that have typically undergone prior surgery. Left atrial or systemic ventricular cannula
Once hemostasis is achieved, anticoagulation drainage can be added to the systemic venous
is started aiming at an aPTT of 60-80 sec (see line to decompress the left side of the heart and
334
should be considered with evidence of left atrial Central Cannulation (Open vs. Closed Chest)
hypertension-pulmonary edema or systemic
ventricular distention. Adequate anticoagula- Central cannulation can obtain full car-
tion and prompt removal of a left-sided cannula diopulmonary support with excellent flows
with myocardial recovery are necessary to re- and avoids the issues related to peripheral
duce the likelihood of systemic arterial emboli. cannulation described above. Sternal closure
is preferred if it is expected that the duration of
Issues with Peripheral Cannulation ECMO support will be long in order to facili-
tate the patient’s mobility and avoid problems
Limb Ischemia related to being sedentary. In this situation,
An important concern related to peripheral the cannulae are tunneled away from the ster-
cannulation is compromised limb perfusion. notomy incision.
A small arterial cannula (8-10 F size) can be
added to the arterial inflow, inserted distal to Results and Outcomes Following ECMO for
the femoral arterial cannulation site. A chimney ACHD
graft (Dacron T-graft) can also be employed as
an alternative to preserve distal extremity per- While ECMO technology and management
fusion. It may prove unsuitable in emergency has improved dramatically in the last decade,
situations but sometimes we switch from direct the use of ECMO support in adults still produces
femoral artery cannulation to a chimney graft multiple complications. The most frequent
after stabilizing the patient. We typically use include bleeding, and peripheral access issues.
an 8 mm Dacron graft sewn in an end-to-side The most common causes of death include
manner to the femoral artery and then connect it multisystem organ failure (MSOF), heart failure,
to the arterial inflow limb of the ECMO circuit. or sepsis.
We reviewed the records for all ACHD
Hyperperfusion Syndrome patients who received mechanical circulatory
support (MCS) following cardiotomy from Jan-
Although most vascular issues due to pe- uary 2001 to December 2013 at our institution.
ripheral cannulation relate to limb ischemia During the study period, 4,220 operations were
from inadequate arterial perfusion, overflow performed in ACHD patients at Mayo Clinic, of
syndrome or hyperperfusion syndrome can also whom 25 (0.6%) required postoperative MCS
occur. This syndrome differs from compartment (15 males; median age 41 years, range 19-75).
syndrome although both share the increase in The median number of prior sternotomies was
extremity compartmental pressure. This syn- 2 (range 1-4). The mean systemic ventricular
drome, described in up to 25% of patients due to EF preoperatively was 47% (range 10-66%);
development of significant swelling and venous 68% of patients were in NYHA class IV heart
inadequacy, has been reported more commonly failure. Underlying diagnoses included pul-
with axillary artery cannulation with the side monary atresia with intact ventricular septum
graft technique.10 Several potential mechanisms (24%), tetralogy of Fallot (16%), Ebstein’s
underlie this syndrome; however, they are anomaly (12%), cc-TGA (12%), and septal
centered on either arterial inflow obstruction defects (12%), with tricuspid atresia, truncus
or venous return obstruction.11 arteriosus, and congenital valve abnormalities
constituting the remaining diagnoses (24%).
The most common operations performed in-
cluded valve-related (repair or replacement)
335
Chapter 28
with/without maze arrhythmia surgery (52%),

Fontan conversion (20%), coronary bypass
grafting with valvular operations (12%), and
heart transplant (8%). Indications for MCS
were left-sided (systemic) heart failure (32%),
right-sided (sub-pulmonary) heart failure (24%),
biventricular heart failure (36%), persistent
arrhythmia (4%), and hypoxemia (4%). Both
ECMO and IABP were used in 68% of patients,
while 32% used ECMO alone. The mean dura-
tion of MCS was 195.8 hours (range 20-850
hours). The most common early complications
included coagulopathy (60%), renal failure
(56%), and arrhythmia (48%). Overall, 48%
of patients survived to hospital discharge. All
deaths were due to either multi-organ failure
or the underlying cardiac diagnoses, with one
patient dying from overwhelming sepsis. Me-
dian available follow up for survivors was 38.5
months (maximum, 106 months). New York
Heart Association functional class was I/II in
6/9(67%) of late survivors.
336
References 9. Liden H, Haraldsson A, Ricksten SE, Kjell-

man U, Wiklund L. Does pretransplant left
1. Suzuki Y, Yamauchi S, Daitoku K, Fu- ventricular assist device therapy improve
kui K, Fukuda I. Extracorporeal mem- results after heart transplantation in pa-
brane oxygenation circulatory support tients with elevated pulmonary vascular
after congenital cardiac surgery. ASAIO J. resistance? Eur J Cardiothorac Surg. 2009;
2009;55(1):53–57. 35(6):1029-1034.
2. Booth KL, Roth SJ, Thiagarajan RR, Al- 10. Chamogeorgakis T, Lima B, Shafii AE, et
modovar MC, del Nido PJ, Laussen PC. al. Outcomes of axillary artery side graft
Extracorporeal membrane oxygenation cannulation for extracorporeal membrane
support of the Fontan and bidirectional oxygenation. J Thorac Cardiovasc Surg.
Glenn circulations. Ann Thorac Surg. 2013;145(4):1088–1092.
2004;77(4):1341-1348 11. Mosquera VX, Solla-Buceta M, Pradas-Irún
3. Graham TP Jr, Bernard YD, Mellen BG, et C, Fernández-Arias L. Lower limb over-
al. Long-term outcome in congenitally cor- flow syndrome in extracorporeal membrane
rected transposition of the great arteries. J oxygenation. Interact Cardiovasc Thorac
Am Coll Cardiol. 2000;36(1): 255-261. Surg. 2014;19(3):532-534.
4. Said SM, Burkhart HM, Schaff HV, Dearani
JA. Congenitally Corrected Transposition
of Great Arteries: Surgical Options for
the Failing Right Ventricle and/or Severe
Tricuspid Regurgitation. World J Pediatr
Congenit Heart Surg. 2011;2(1):64-79.
5. Acar P, Sidi D, Bonnet D, et al. Maintain-
ing tricuspid valve competence in double
discordance: a challenge for the pediatric
cardiologist. Heart. 1998;80(5):479-483.
6. Tulevski II, Zijta FM, Smeijers AS, et
al. Regional and global right ventricular
dysfunction in asymptomatic or minimally
symptomatic patients with congenitally
corrected transposition. Cardiol Young.
2004;14(2):168-173.
7. Espinola-Zavaleta N, Alexanderson E, At-
tie F, et al. Right ventricular function and
ventricular perfusion defects in adults with
congenitally corrected transposition: cor-
relation of echocardiography and nuclear
medicine. Cardiol Young. 2004;14(2):174-
181,
8. Zimpfer D, Zrunek P, Sandner S, et al.
Post-transplant survival after lowering fixed
pulmonary hypertension using left ventricu-
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2007;31(4): 698-702.
337
29
Indications and Contraindications for ECLS in Neonates and Children with

Cardiovascular Disease
Lindsay Ryerson, MD, FRCPC, D. Michael McMullan, MD, FACS
Indications and contraindications for ECLS with obstructed TAPVR. Although preoperative
in neonates and children with cardiovascular ECLS for these patients may be required to pre-
disease have evolved during the past 45 years. vent cardiovascular collapse before surgical in-
Advances in ECLS circuit design and greater tervention can be arranged, conventional ECLS
recognition of ECLS benefits for indications be- does not improve pulmonary venous drainage or
yond early postoperative support have resulted pulmonary vascular resistance (PVR). A single
in steady growth in the number of pediatric institutional review of 26 patients (6.5% of the
patients who receive cardiac ECLS. ELSO total ECLS population) who received ECLS
Registry data indicates that ECLS was used to as a bridge to surgery found that it effectively
provide cardiac support for over 1,400 pediat- rescued patients with complex congenital heart
ric patients in 2015.1 Indications for ECLS in disease and failing circulation prior to surgical
these patients may be broadly categorized as intervention.2 Overall survival in this group of
perioperative support and support remote from patients reached 62%. Hypoxemia and cardio-
the surgical intervention. genic shock in patients with arterial transposi-
tion or hypoplastic left heart syndrome (HLHS)
Preoperative Stabilization with inadequate atrial shunting were the most
common indications for support. Neonates with
Mechanical circulatory support (MCS) is arterial transposition and persistent pulmonary
required in a subset of neonates prior to initial hypertension represent a unique and high-risk
surgical repair/palliation. The primary goal of population. ECLS may provide cardiopulmo-
ECLS support aims generally to optimize the he- nary support until PVR falls and the arterial
modynamic state to maximize oxygen delivery switch operation can be safely performed.3-5
and promote recovery of the cardiopulmonary Neonates with Tetralogy of Fallot and ab-
system and other organ systems prior to surgi- sent pulmonary valve with refractory respiratory
cal repair. The use of ECLS in this setting may compromise despite mechanical ventilation are
improve candidacy of some patients for com- also candidates for preoperative ECLS stabiliza-
plex surgical repair but its use for preoperative tion.6 Similarly, patients with severe Ebstein’s
support in patients with obstructed total anoma- anomaly and functional pulmonary atresia who
lous pulmonary venous return (TAPVR) is to present with low cardiac output secondary to
be discouraged. The primary therapeutic goal a circular shunt, intractable dysrhythmia, or
should be expedited surgical repair in patients cyanosis secondary to inadequate pulmonary
339
Chapter 29
blood flow may benefit from VA or VV-ECLS to initiate ECLS during the early postoperative
stabilization during the period of transitional period can be challenging due to the evolv-
circulation until PVR declines and a stable ing clinical state of the patients against the
source of pulmonary blood flow is established.7,8 backdrop of multiple simultaneous therapeutic
interventions. No consensus exists regarding
Perioperative Support optimal timing for initiation of perioperative
ECLS. Some reports suggest absence of a
Myocardial dysfunction due to the meta- clear relationship between timing of ECLS
bolic stress of cardiopulmonary bypass (CPB) initiation and clinical outcome, whereas others
and ischemia/reperfusion injury generally re- describe improved survival in patients who
sponds to inotropic support, afterload reduction, receive early ECLS support, including those
and pulmonary vasodilators. However, patients who transition to ECLS in the operating room,
subjected to prolonged periods of CPB and compared to those who receive support later in
extended periods of myocardial arrest can expe- the postoperative period.10-15 The threshold for
rience severe postoperative myocardial dysfunc- initiating perioperative ECLS varies by center
tion that may prevent successful separation from and patient population. Reported center-specific
CPB. Children who have preexisting ventricular utilization rates generally range from 1-7% of
dysfunction or structural cardiac abnormali- postcardiotomy patients.16,17 ECLS provides
ties may be at greatest risk. Once correctable perioperative support for approximately to
residual anatomic lesions have been excluded, 10% patients with HLHS who undergo neonatal
ECLS can provide short-term cardiopulmonary Norwood palliation.18 Irrespective of the patient
support for patients who are unable to separate population, earlier initiation of ECLS facilitates
from CPB. In addition to improving systemic unloading of vulnerable myocardium, preven-
perfusion, MCS appears to facilitate myocardial tion or reduction of acidosis, and reduced risk
recovery by reducing ventricular wall stress, of cardiovascular collapse.
reducing myocardial oxygen consumption, and
increasing myocardial oxygen delivery.9 In most Mechanical Support beyond the Perioperative
cases, the cannulation strategy utilized for CPB Period
suffices during and after the transition to ECLS.
Although venoarterial ECLS is the most com- Although the vast majority of neonatal and
monly used modality in neonatal and pediatric pediatric cardiac ECLS occurs in patients with
cardiac patients during the perioperative period, structural congenital heart disease who undergo
venovenous ECLS may be used to provide re- surgical repair or palliation, patients without
spiratory support for patients who experience structural heart disease may receive ECLS for
refractory hypoxemia due to CPB-related lung to heart failure.
injury or intraoperative pulmonary hemorrhage.
Ongoing myocardial dysfunction following Low Cardiac Output Syndrome
successful separation from CPB may result in
a refractory low cardiac output state several Cardiomyopathy (8.3%) and myocarditis
hours after surgery. During the early postop- (4.5%) are the most common nonstructural eti-
erative period ECLS can improve end-organ ologies of heart failure in neonates and children
oxygen delivery and prevent hemodynamic reported to the ELSO Registry.1 Overall survival
collapse while reducing the need for poten- in this population is approximately 67% and
tially arrhythmogenic pharmacologic inotropic appears to be greatest in older pediatric patients
therapy and vasopressor support. The decision and in those who do avoid signs of end-organ
340
Indications and Contraindications for ECLS in Children with Cardiovascular Disease
injury such as renal insufficiency.19,29 ECLS significantly higher for children who require
may be necessary in many as 50% of pediatric ECMO as a bridge to transplant (Hazard Ratio
patients who present with acute fulminant myo- 3.1) than those who receive mechanical venti-
carditis.21 Cardiogenic shock and dysrhythmia lator support or no invasive support.28 When
represent the primary indications for MCS in used as a short-term bridge to transplantation,
the majority of these patients. Other indications ECLS survival to transplantation approximates
for neonatal cardiac ECLS include myocardial 45%.29 However, approximately one third of
infarction22 and unstable or refractory dysrhyth- patients who are successfully transplanted die
mia.23-25 Rhythm related low cardiac output prior to hospital discharge. Patients with single-
states may result from tachycardia induced ventricle forms of congenital heart disease and
cardiomyopathy or myocardial depressant those who require prolonged pretransplant
effects of antiarrhythmic medications.24 Neo- ECLS (>14 days) are at greatest risk of dying.
nates who present with left ventricular dilation Survival is much higher in patients with severe
(left ventricular end diastolic z-score >2.0) in primary or secondary cardiomyopathy bridged
the setting of supraventricular tachycardia in- to transplantation with ECLS.30,31
duced cardiomyopathy have increased risk for Data from a large, propensity score-matched
receiving MCS to prevent circulatory collapse study showed that overall survival rates are sig-
and facilitate pharmacologic control of rhythm nificantly higher in pediatric patients who are
abnormalities.23 ECLS is also occasionally used bridged to transplantation with a ventricular
to provide support for patients who experience assist device (VAD) than ECMO.32 However,
cardiovascular collapse due to accidental or patients with complex forms of congenital heart
intentional poisoning26 and for patients who disease were excluded from the primary analy-
experience life-threatening systemic low car- sis, largely limiting general applicability of the
diac output state due to acute right heart failure observed survival advantage to patients with
related to pulmonary hypertensive crisis.27 predominately cardiomyopathic and inflam-
The use of MCS in the management of matory forms of heart failure. Although VADs
end-stage heart failure has dramatically evolved appear to provide a superior form of bridge to
during the past two decades. Short-term ex- transplantation in older children and in children
tracorporeal devices and durable implantable with nonstructural heart disease, survival rates
ventricular assist devices are now standard heart in patients with functional single ventricle heart
failure therapies in adults and late adolescent disease who require VAD support remain poor.
children. Technologic advances in highly ef- This is especially true for neonates and patients
ficient implantable centrifugal and axial flow with shunted sources of pulmonary blood flow.33
pumps have proven difficult to miniaturize for In addition, the apparently encouraging survival
use in small children, infants, and neonates. rate in patients who are bridged with the VAD
Consequentially, ECLS remains an important is tempered by the fact that 29% of patients ex-
component of mechanical heart failure therapy perienced a stroke and 97% experienced some
in some patient populations. form of serous adverse event during support. In
addition to worse pretransplant outcomes, pedi-
Bridge to Transplantation atric patients who are bridged to transplantation
with ECMO also experience significantly worse
Optimal timing and indications for MCS as short-term and long-term posttransplant sur-
a bridge to transplantation have not been clearly vival compared to patients who do not require
established in the highly heterogeneous pediat- MCS prior to transplantation and those who are
ric patient population. Waiting list mortality is bridged to transplantation with a VAD.34
341
Chapter 29
There is general agreement that ECMO most common indications for cardiac cath-
serves successfully as a bridge-to-decision eterization on ECMO include assessment of
and as a bridge-to-bridge (bridge-to-VAD).35 operative results and percutaneous left heart
When used in the setting of acute hemodynamic decompression. Early detection and correction
decompensation, including ECPR, ECMO of residual cardiac lesions appears to shorten
provides a readily available and rapidly initi- ECMO duration and improve survival so the use
ated form of MCS. In most cases, the degree of catheter based diagnostic procedures should
of myocardial recovery, if any, is unknown at be considered when noninvasive diagnostic
time of initiation. During this period of clini- studies fail to identify a reason for inability to
cal uncertainty, ECMO is useful as a bridge to separate from ECMO.38,39 ECMO is also useful
decision regarding transplant candidacy as for providing cardiopulmonary support during
neurologic function and end-organ recovery high-risk catheter based interventions beyond
are assessed. Consideration should be given the perioperative period and has proven to be a
to transitioning potential transplantation can- safe alternative to CPB during complex airway
didates to VAD support (bridge-to-bridge) if surgery and repair of pulmonary artery sling.40
myocardial recovery does not occur within 7-14
days. While this approach is associated with im- ECPR
proved survival in most patients, it is less clear
whether VAD support is better than ECMO for Clinical outcomes tend to be better in chil-
supporting infants with single ventricle heart dren who receive extracorporeal cardiopulmo-
disease to transplantation. nary resuscitation (ECPR, see Chapter 27) for
underlying cardiac disease than those who have
Posttransplantation Support a noncardiac etiology of acute cardiopulmo-
nary failure.41 Patients with underlying cardiac
Early posttransplant dysfunction may pre- disease are typically being monitored in an in-
vent separation from CPB at transplantation or tensive care setting and have adequate vascular
lead to life-threatening low cardiac output state access. These patients tend to be younger, less
during the early posttransplant period. ECMO likely to have preexisting organ dysfunction,
can provide mechanical support for these pa- and more likely to experience ventricular dys-
tients in whom survival reaches approximately rhythmia than asystole prior to cardiac arrest.42,43
50%.1 Neonates appear to have greater risk for Potential benefits of ECPR include improved
death than older children. Irreversible graft myocardial oxygen delivery, reduced myocar-
dysfunction is the most common reason for dial workload, reduced vasopressor and ino-
discontinuing support in this patient population. tropic therapy, reduced pulmonary barotrauma
The use of ECMO to as a bridge to recovery for and intrathoracic pressure, improved end-organ
patients who experience severe acute rejection perfusion and oxygen delivery, reversal of aci-
remote from transplantation is less successful dosis, and targeted temperature control. Current
and many patients will ultimately require re- resuscitation guidelines from the American
transplantation.36 Heart Association support the use of ECPR in
pediatric patients with a cardiac diagnosis who
Procedural Support experience in-hospital cardiac arrest in a center
with ECLS expertise.44
Catheter based interventional and diag-
nostic procedures can be safely performed
on patients receiving ECMO support.37 The
342
Respiratory Support rate following ECPR approaches 30% in pre-

term babies and is as high as 21% in neonates
Some children with underlying cardiac <34 weeks gestational age.46 Weight <2 kg has
disease may require VV-ECLS for respiratory historically been a relative contraindication
failure refractory to conventional or advanced to ECMO but a survival rate of 10% has been
forms of mechanical ventilation. Hypoxemia/ reported in neonates with HLHS weighing <2.5
hypercarbia secondary to underlying paren- kg when placed on ECMO47 which rises to 33%
chymal lung disease or tracheobronchial abnor- for infants weighing <3 kg at time of cardiac
malities may respond to decreased mean airway ECMO support.48 Although an absolute lower
pressure, improved myocardial oxygenation, limit of gestational age or weight for ECMO
and reduced inotropic support requirements as- candidacy remains unestablished, any poten-
sociated with VV-ECLS. Approximately 1.6% tial survival benefit must be weighed against
of children with an underlying cardiac diagnosis increased risk of neurologic injury in younger
are supported with VV-ECLS, with an overall and smaller infants.
survival rate of 42%.45 Some patients receiving
VV-ECLS may require conversion to VA-ECLS
to improve gas exchange or provide additional
support in the setting of hypoxia related myo-
cardial dysfunction.
Contraindications
Neonatal and pediatric patients typically re-

ceive ECMO support for severe, life-threatening
clinical states that are refractory to less invasive
supportive therapy. Consequentially, consensus
regarding absolute contraindications to ECLS
in these high-risk patients is lacking. There is
general agreement that patients with otherwise
lethal congenital conditions or severe irrevers-
ible brain injury should not receive ECMO.
However, many factors that have historically
been considered absolute contraindications to
ECLS, such as extremely low gestational age
and milder forms of intracranial hemorrhage,
are now considered relative contraindications.
Contemporary data from the ELSO Registry
indicates that the overall survival rate for pre-
mature infants (<37 weeks gestation) who re-
ceive cardiac ECMO is 31%, compared to 41%
survival in term infants.1 Survival falls to 19%
for neonates <33 weeks gestational age. A step-
wise improvement in survival and reduction in
neurological injury is observed with increasing
gestational age. Similarly, the reported survival
343
Chapter 29
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8(1):67-70 istotle score predicts outcome in patients
9. Priddy CM, Kajimoto M, Ledee DR, et al. requiring extracorporeal circulatory support
Myocardial oxidative metabolism and pro- following repair of congenital heart disease.
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18. Ohye RG, Sleeper LA, Mahony L, et al. toxicology investigators consortium (toxic).
Comparison of shunt types in the norwood J Med Toxicol 2016; 12(1):95-99
procedure for single-ventricle lesions. N 27. Wong JY, Buchholz H, Ryerson L, et al.
Engl J Med 2010; 362(21):1980-1992 Successful semi-ambulatory veno-arterial
19. Rajagopal SK, Almond CS, Laussen PC, et extracorporeal membrane oxygenation
al. Extracorporeal membrane oxygenation bridge to heart-lung transplantation in a
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young adults with acute myocarditis: A 15(8):2256-2260
review of the extracorporeal life support 28. Almond CS, Thiagarajan RR, Piercey GE,
organization registry. Crit Care Med 2010; et al.Waiting list mortality among children
38(2):382-387 listed for heart transplantation in the united
20. Madden K, Thiagarajan RR, Rycus PT, states. Circulation 2009; 119(5):717-727
Rajagopal SK. Survival of neonates with 29. Almond CS, Singh TP, Gauvreau K, et al.
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21. Teele SA, Allan CK, Laussen PC, et al. from the organ procurement and transplant
Management and outcomes in pediatric network and extracorporeal life support
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643 e631 30. Fiser WP, Yetman AT, Gunselman RJ, et
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CF. Role of ecmo in neonatal myocardial membrane oxygenation (ecmo) as a bridge
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Ed 1996; 74(2):F143-144 Transplant 2003; 22(7):770-777
23. Salerno JC, Seslar SP, Chun TU, et al. 31. Gajarski RJ, Mosca RS, Ohye RG, et al. Use
Predictors of ecmo support in infants with of extracorporeal life support as a bridge to
tachycardia-induced cardiomyopathy. Pe- pediatric cardiac transplantation. J Heart
diatr Cardiol 2011; 32(6):754-758 Lung Transplant 2003; 22(1):28-34
24. Dyamenahalli U, Tuzcu V, Fontenot E, et 32. Fraser CD, Jr., Jaquiss RD, Rosenthal DN,
al. Extracorporeal membrane oxygenation et al. Prospective trial of a pediatric ven-
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in newborns and infants: Short-term and 33. Weinstein S, Bello R, Pizarro C, Fynn-
medium-term outcomes. Pediatr Crit Care Thompson F, et al. The use of the berlin
Med 2012; 13(1):47-52 heart excor in patients with functional
25. Cohen MI, Gaynor JW, Ramesh V, et al. single ventricle. J Thorac Cardiovasc Surg
Extracorporeal membrane oxygenation 2014; 147(2):697-704; discussion 704-695
for patients with refractory ventricular ar- 34. Davies RR, Russo MJ, Hong KN, et al.
rhythmias. J Thorac Cardiovasc Surg 1999; The use of mechanical circulatory support
118(5):961-963 as a bridge to transplantation in pediatric
26. Wang GS, Levitan R, Wiegand TJ, et al. patients: An analysis of the united network
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35. Morales DL, Almond CS, Jaquiss RD, et 43. Ortmann L, Prodhan P, Gossett J, et al.
al. Bridging children of all sizes to car- American Heart Association’s Get With the
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north american experience with the berlin in-hospital cardiac arrest in children with
heart excor ventricular assist device. J Heart cardiac disease: A report from get with the
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36. Perri G, Hasan A, Cassidy J, et al. Mechani- 124(21):2329-2337
cal circulatory support after paediatric heart 44. de Caen AR, Berg MD, Chameides L, et al.
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2012; 42(4):696-701 2015 american heart association guidelines
37. Booth KL, Roth SJ, Perry SB, et al. Cardiac update for cardiopulmonary resuscitation
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Am Coll Cardiol 2002; 40(9):1681-1686 45. Kim K, Mazor RL, Rycus PT, Brogan TV.
38. Agarwal HS, Hardison DC, Saville BR, Use of venovenous extracorporeal life
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147(1):434-441 46. McMullan DM, Thiagarajan RR, Smith
39. Callahan R, Trucco SM, Wearden PD, et al. KM, Rycus PT, Brogan TV. Extracorporeal
Outcomes of pediatric patients undergoing cardiopulmonary resuscitation outcomes in
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40. Huang SC, Wu ET, Chi NH, et al. Periopera- J, Gajarski R. Outcomes of hypoplastic
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Eur J Pediatr 2007; 166(11):1129-1133 1181
41. Alsoufi B, Al-Radi OO, Nazer RI, et al. Sur- 48. Bhat P, Hirsch JC, Gelehrter S, et al. Out-
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42. Raymond TT, Cunnyngham CB, Thompson
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346
30
Neonatal/Pediatric Cardiac Cannulation
Giles J. Peek, MD, FRCS, CTh, FFICM, Isaac Hammond, PA-C
Neonatal/Pediatric Cardiac Cannulation Neck Cannulation
Introduction The subject of cervical cannulation is dis-

cussed in some detail in Chapters 12 and 20 and
When cannulating babies and children for will not be repeated in this chapter but a few
cardiac support we must consider a number specific pieces of advice for cardiac patients
of factors both specific to patient needs and will be added.
the skills of the operator while adhering to the Firstly, consider whether VV-ECMO is
principals of adequate extracorporeal flow, good sufficient for your patients’ needs. On occa-
decompression of the heart, and strict asepsis. sions patients can suffer acute problems with
In addition to these factors, maintenance of pulmonary blood flow which in turn leads to
hemostasis and prevention of polyneuropathy/ myocardial suppression or even cardiac arrest.
myopathy are important and must also be This can occur following surgery, for instance,
considered. For this reason, neck cannulation with a blocked BT shunt or with a transient in-
is almost always superior to transthoracic can- crease in PVR in a circulation with full mixing
nulation if the support is to be prolonged as it at atrial level. In these situations VV-ECMO
allows the chest to be left closed and the patient alone can be sufficient support until the prob-
to be awakened either partially or completely. lem is resolved surgically or the PVR returns to
There is some evidence that neck cannulation is normal. In most circumstances provision of an
associated with improved outcome.1 However, adequate common atrial oxygen saturation (ie,
to initiate ECMO (especially in an emergency) above 75%) will result in excellent myocardial
for shorter periods, and where extraordinary function. VV-ECMO also provides perfect sup-
flow rates are needed transthoracic cannulation port for reconstruction of a failed BT shunt or
is used. It is essential to always check that the complex pulmonary artery stenosis. A double
patient has sufficient anticoagulation prior to lumen cannula can be inserted via the right in-
ECLS initiation either by virtue of heparin for ternal jugular vein using either a percutaneous
CPB or by giving a standard ECLS loading dose or exposure assisted technique.2 If the chest is
of heparin (75-100 u/kg). open, the cannula position can be verified by
palpation of the right atrium and inferior vena
cava, depending on cannula design (Origen vs.
Avalon).
347
Chapter 30
In most cases VA-ECMO is required, this with vascular surgical techniques to consider
can be achieved via the standard technique of using this approach and you should consider
ligating the right neck vessels around the can- obtaining assistance from someone who does.
nulae which are brought out through the incision. In the meantime, tunnel the lines and ligate the
This technique has the virtue of speed but is less vessels around them.
than ideal if the patient needs prolonged support If the chest is open and the patient is already
(months rather than weeks) which may be need- on ECMO, the graft can be anastomosed to the
ed if bridging to another device or to transplant. innominate artery or left carotid if needed and
In this setting it is better to tunnel the cannulae the cannula can be introduced by feel into the
to separate stab incisions cephalad to the lower descending aorta. The advantage of this is that
transverse neck incision. The cannulae can be any particulate emboli are kept away from the
ligated into the vessels in the normal manner brain and the high velocity jet of blood ema-
with non-adsorbable braided ligatures such as nating from the cannula is kept away from the
silk. Outside the newborn period the venous aortic valve. It is my impression that the Venturi
cannula can often be inserted percutaneously effect draws blood around the aortic arch and
without ligating the jugular which can help in is slightly better tolerated in cases where there
preserving the vessel for the future. Another is significant AR. The cannula can still be tun-
useful technique is to anastomose a vascular neled from the neck and decannulation can be
graft end to side onto the right carotid artery achieved through the stab incision alone without
and introduce the cannula through this graft, having to reopen the chest.
positioning the cannula tip in the innominate
artery. The graft can then be ligated around the Transthoracic Cannulation
cannula. It is important to cut the graft such that
it does not protrude beyond the skin tunnel, in This is where most patients will start off on
this way it does not become colonized and when ECMO, usually because they have undergone
it is time to decannulate the stab incision at the a cardiac operation and failed to wean from
top of the tunnel can be opened, the cannula bypass or have suffered low cardiac output or
can be removed, the graft can be oversewn or cardiac arrest postoperatively. There will usu-
ligated, and the artery remains undisturbed and ally be a combination of myocardial edema and
patent at the other end of the graft. swelling, extremely poor/absent contractility
Gore-Tex is used for smaller vessels up to and bleeding. The cannulation must take ac-
6mm, and Dacron above this. It is useful to spray count of these aspects as well as adhering to
fibrin glue onto the suture line before letting the three golden rules:
blood into the anastomosis to prevent bleeding
from needle holes. If the patient has yet to be • Adequate extracorporeal flow
heparinized, then blood can be let into the graft • Good decompression of the heart
and allowed to clot for 2-3 minutes in the needle • Strict asepsis
holes before heparin is given. It is important to The best venous drainage will be achieved
wash the graft out with heparinized saline and with the shortest, fattest cannula that will fit
to allow back bleeding and anterograde bleed- comfortably in the right atrium, with sufficient
ing through the graft to wash out any clot after atrium around it to allow the blood to reach the
the heparin is given. Either proline or Gore-Tex cannula. In babies and small children this is best
sutures can be used according to preference. achieved with a wire reinforced right angle can-
If you cannot follow these technique tips then nula with a basket (bullet) tip inserted through
you probably do not have sufficient familiarity the right atrial appendage. Similar cannulae
348
are available from a number of manufacturers Larger children and adolescents may
including DLP. A 2 kg baby will usually ac- achieve better drainage with a two-stage venous
cept a 12-14 Fr cannula, sometimes a 16 Fr if a cannula which has drainage holes in the right
septectomy has been performed. The tip should atrium and IVC, it is secured in the same man-
sit in the middle of the right (common) atrium; ner described above. The larger sizes of these
the correct size can be easily judged by eye cannulae often have half inch connectors which
when offering the cannula up to the heart. The obviously need to be taken into account if your
cannula is then brought out at the bottom of the ECMO circuit has a 3/8” venous line.
sternotomy. In most cases no attempt is made The arterial cannula is usually inserted into
to tunnel the venous cannula at this point as it the ascending aorta, it may already be in situ
is not yet clear how long the ECMO run will from CPB. Depending on the design of the by-
be. The cannula is initially secured in the right pass arterial cannula, the surgeon may elect to
atrial appendage with a pursestring suture, this keep this cannula or to change it if the design
may already be in place for cardiopulmonary only has a short intraaortic segment. It is my
bypass. The pursestring is in turn secured with practice to use a straight wire wound cannula
a rubber or plastic or rubber tourniquet (snug- such as the Biomedicus cervical arterial cannula
ger), which is tied to the cannula. This, then, is and position the tip in the descending aorta from
usually secured with a hemostat when on bypass. the ascending aortic entry point. The cannula is
It is less than ideal to have these foreign bodies secured using the same technique used for the
protruding from the chest when the baby is in venous cannula.
the PICU so the tourniquet should be secured In some patients, when anterograde head
either by passing the pursestrings through a perfusion has been used during CPB, for
button and tying them or by clipping it with instance the Norwood-Sano procedure, the
titanium hemoclips. It is my practice to rely arterial cannulation for CPB is achieved using
on this pursestring for cannula removal but not a 3.5-4.0 mm Gore-Tex conduit anastomosed
for either hemostasis or cannula security. This end-to-side to the innominate artery. This con-
function is provided by a separate 4-0 Ethibond duit is usually left long and the arterial cannula
pursestring, which can be reinforced with Teflon is inserted into it with the tip sitting outside
pledgets at all 4 cardinal points if there is signifi- the chest. At the end of the operation when the
cant bleeding, this suture is initially tied around heart is decannulated this conduit is cut down
the cannula at the entry point to the atrium and to about 10-15mm in length, secured with a
then tied around the cannula. This technique titanium hemoclip across the base then folded
is also useful when cannulating for ECPR if over and clipped again before the bight of the
tourniquets are unavailable. The right pleura is conduit is transfixed with a 6-0 Prolene suture to
then widely opened, an intercostal chest tube is prevent the clip from slipping off. This conduit
inserted and the tourniquet is placed in the right is secured in this way to allow recannulation
pleural cavity anterior to the right lung, (ie, it is if ECMO is subsequently required. After ad-
not left sticking out of the chest). ministration of heparin, a side biting vascular
In an emergency almost any cannula will clamp is applied to the innominate artery, the
work for venous drainage via the right atrial hemoclips and suture are removed, a hemostat
appendage including a straight Biomedicus is applied to the uppermost corner of the conduit,
cervical venous cannula or even a cervical arte- a #1 silk ligature is passed around the conduit
rial cannula or a chest tube. It can be changed and snared with a tourniquet, the clamp is then
to the correct cannula later on. released while the arterial cannula is introduced
using the left hand through the conduit and the
349
Chapter 30
tip positioned at least as far as the innominate has the additional advantage of preventing the
arterial lumen, but ideally in the descending swelling of the arm which can occur with side
aorta. Finger pressure from the right hand can graft perfusion of the axillary artery; a much
limit the bleeding to some degree. As soon as easier alternative than banding the distal artery
the tip of the cannula is in the desired position to limit the flow. Decannulation is achieved by
the ligature is tightened, allowing the obturator removing the cannula, folding over the con-
to be removed and the cannula connected to the duit, and transfixing it then oversewing using
ECMO circuit. Once a venous line is inserted 3-0 or 4-0 Prolene. This technique can also be
flow can be initiated. The arterial cannula can used to treat the Harlequin syndrome of upper
then be definitively secured by a further ligature body cyanosis which can occur during femoro-
tied initially around the conduit and then around femoral VA-ECMO. It is seen when the heart
the cannula. It is often necessary to move the recovers and starts ejecting before the lungs
alignment of the conduit and innominate ar- have recovered, thereby perfusing the upper
tery and “twiddle” the cannula to negotiate it body with deoxygenated blood while the lower
through the anastomosis, the innominate artery, body luxuriates in oxygenated blood from the
and the aortic arch. If this is not possible, flow circuit. Of course a more elegant solution to this
can be initiated with the cannula in the conduit problem is addition of a percutaneous “arterial”
and a better position can be obtained later once cannula in the jugular vein to establish hybrid
the patient has been resuscitated. In situations VA-V-ECMO.
where a patient with this type of arterial can-
nulation cannot be weaned from CPB, it is best Venting
to shorten the conduit and advance the cannula
into the descending aorta. If there is sufficient If the left heart needs venting and it is not
cardiac output to come off bypass for a few done effectively, the heart will not recover. Even
minutes the cannula can be tunneled from the if the aim is to bridge to transplant this omission
neck. If not, then the cannula is brought out at can lead to sometimes fatal pulmonary conges-
the top of the sternotomy incision. tion and hemorrhage. The reason that the left
In larger patients undergoing aortic arch ventricle cannot recover if not vented is down
surgery an 8 mm Dacron graft may be used to the basic physiology of myocardial perfusion.
in the same way, anastomosed either to the This perfusion comes from the coronary arteries
innominate artery or often to the right axillary/ and will only occur when the coronary perfusion
subclavian artery. Instead of introducing a can- pressure exceeds the LV cavity pressure. During
nula through the graft, a 3/8”-1/4” connector normal physiology this occurs in diastole. If the
is used to join the arterial line to the conduit. heart is not ejecting, the LV will fill until the LV
This works well for CPB but during ECMO is cavity pressure is equal to the arterial pressure at
prone to kinking if the patient moves, and to which point myocardial perfusion fails. In most
infection if the Dacron is left hanging out of cases the mitral valve will become incompetent
the wound. It should therefore be cut short so before this pressure is reached, decompressing
that it doesn’t protrude from the wound and an the ventricle into the left atrium. This can be
arterial cannula advanced through it. An 8 mm very helpful as this blood can be drained from
graft is approximately 24 Fr in diameter and the atrium by means of a septostomy or a left
will usually accept a 19-21 Fr cannula with ease. atrial cannula, thereby venting the left heart. If
The cannula should be sized so that it does not the atrium is not decompressed the blood backs
completely obstruct the subclavian or innomi- up into the lungs initially causing pulmonary
nate artery. Apart from asepsis this approach edema and subsequently pulmonary capillary
350
rupture, pulmonary hemorrhage, and death. The Not Venting

easiest route for cannulation of the left atrium
is via the right superior pulmonary vein. This If the heart is ejecting it will not need to be
is often used for venting during surgery. In a vented. This can usually be determined by the
newborn a 10 Fr right angle or 12 Fr Pacifico pulsatility of the arterial line trace accompanied
cannula can be easily positioned with the tip in by echocardiographic evidence such as the
the left atrium via this approach. It is secured aortic valve opening and closing and antegrade
in the same manner described above. The vent flow through the aortic valve. These signs can
is then connected to the venous line with a Y- be easily elicited on transthoracic, transesopha-
connector. If the lungs are working this blood geal or epicardial echocardiography. If the left
will have 100% oxygen saturation and samples ventricle is distended it is probably better to
for estimation of MVO2 should be taken from vent anyway, especially if the likely trajectory
the venous line above the Y. In some cases, the is short-term deterioration rather than recovery.
mitral valve remains competent, this is usually In larger patients the addition of intraaortic bal-
in the setting of an atrial septostomy where the loon counterpulsation can help the heart to eject
left atrial pressure remains low and the mitral as well as augment coronary perfusion. The
annulus does not dilate. In this setting the left arterial return from the ECMO circuit should
ventricle must be vented directly, or the mitral be positioned proximal to the IABP.
valve rendered temporarily incompetent. This If in doubt, vent.
is easily done via the right superior pulmonary
vein where a LV vent catheter can be introduced Troubleshooting
across the mitral valve, thereby opening it, as
well as aspirating blood from the LV, which is Bleeding
then seen to shrink visibly and become pinker
as perfusion is reestablished. Some of these Correct management of anticoagulation
catheters have air inlets designed for use during is covered in Chapters 7 and 8 in fact pretty
CPB, it is best to secure these with a Tegaderm much the rest of the book (apologies to Douglas
dressing to prevent them falling off as they are Adams), so I will not reiterate these chapters
not designed for ECMO use. If the patient does save an admonition to personally check that
not have a median sternotomy or an atrial com- everything medical has been done to treat co-
munication it is often possible to prevail upon a agulopathy prior to surgical exploration. This
friendly interventional cardiologist to undertake is essential both to avoid unnecessary surgery
a catheter septostomy. Alternatively, the left but more importantly to allow the surgeon to
ventricle can be vented directly through the apex see the surgical bleeding points. This is not
via a small left anterior thoracotomy. Pledgeted possible if all the Dacron is sweating blood
sutures should be used to secure the vent. and all the needle holes are behaving like a
Percutaneous double lumen RVAD cannu- watering can. Once the coagulation system has
lae are currently under development. Inserted been optimized this “medical” bleeding will
in the right jugular vein, these devices have a stop and the surgeon can then concentrate on
drainage port in the right atrium and a reinfu- controlling what remains. The exception to this
sion port in the pulmonary artery; depending rule is when there is hemodynamic compromise,
upon the exact design, it may be possible to either hypovolemia or tamponade in which case
drain from the distal lumen thereby decom- exploration should be immediate. Note that
pressing the left atrium through the pulmonary tamponade of venous drainage occurs at lower
circulation. intrathoracic pressures than those needed for
351
Chapter 30
tamponade during normal cardiac physiology. by giving aliquots of approximately 0.25 mg/kg
In addition, obstruction of venous drainage can (usually 1 mg for a newborn, up to a maximum
occur due to inflow obstruction (IVC distor- of 25 mg for an adolescent) of protamine until
tion) if there is massive mediastinal shift due to the ACT drops below 250-200 seconds. The
pleural bleeding. The usual surgical techniques usual sequence is to give a dose of protamine, al-
of hemostasis (see Chapter 20) are employed low three minutes for mixing, draw an ACT and
including packing the chest with swabs. Once once 250 seconds is exceeded give another dose
all of the operative sites have been checked and repeat. By not waiting for the ACT to fin-
any further bleeding will be coming from the ish counting, approximately 250-1000 seconds
cannulation sites. The best way to stop bleed- are cut from each protamine-ACT cycle which
ing around a cannula is to remove it, so if the has massive advantages in getting the bleeding
heart is recovering and the vent site is bleeding, under control. Once the ACT has fallen into the
remove the vent. It is permissible to have one 200s the residual heparin can be allowed to clear
attempt at placing additional pledgeted sutures normally. The patient can be started on antifibri-
around cannulae that are bleeding, but if this nolytics such as aprotinin or Amicar. Doses of 1
has already been tried and the bleeding persists, ml/kg to load and 1 ml/kg/hr infusion for apro-
further suturing is likely to be both ineffective tinin and 15-30 mg/kg/hr infusion for Amicar, a
and damaging to the tissues. Better, if possible, loading dose (100 mg/kg) is usually omitted as
to convert to extrathoracic cannulation, remove the patient is usually already loaded on bypass
the transthoracic cannulae and close the chest when Amicar is given routinely. The coagu-
if tolerated. Bleeding will often get better in lopathy must now be treated by simultaneous
the dark of a closed chest due to apposition of replacement of whole blood equivalent (ie, red
tissues. Provision of adequate chest tubes both blood cells, fresh frozen plasma, platelets and
in number and caliber to evacuate any shed cryoprecipitate). Zero Balance Ultra-Filtration
blood is essential. If it is the vent site that is (ZBUF) can be a useful tool to make space for
bleeding and it cannot be removed or controlled the products, although hemorrhage also makes
with sutures consideration should be given to space for blood and product replacement. Gauze
venting across the atrial septum. Balloon atrial swabs should be packed around all suture lines
septostomy can be performed with epicardial and a systematic program of repacking, suture,
echo guidance through the right atrium or a activated thrombin (Floseal, Baxter) application
Blalock-Hanlon procedure can be used.3 and repacking continued until hemostasis is
When initiating ECLS for failure to wean secured. It is sufficient to have hemostasis with
from CPB there is almost always massive bleed- packs in at this stage as chest reexploration is
ing by reason of a prolonged bypass run, often mandatory in any case due to the transthoracic
with several periods of cross clamping, cooling, cannulation. The importance of the coordination
and DHCA. This leads to massive coagulopathy of all team members (including the blood bank)
and edema of the tissues with attendant fragility in this strategy cannot be over emphasized as
and congestion. It is important to have a system there is a “Golden Window” where hemostasis
for dealing with this entirely predictable sce- can be achieved if this procedure can be fol-
nario. The combination of heparin from bypass lowed rapidly and in parallel. The total volumes
and in the ECLS circuit prime and coagulopathy of blood and products needed may be much
mean that no further heparin is needed and a less if all are available immediately rather
heparin infusion is not initiated for at least 6 than doled out piecemeal in a miserly fashion.
hours, until the bleeding has settled. Heparin In larger patients it may be more difficult to
can be slowly and cautiously partially reversed correct the clotting factor deficiency with FFP
352
alone and clotting factor concentrate (Octoplex) can be sutured. Sometimes disconnecting the
can be useful. Thromboelastography can be a venous line from the cannula is necessary to
useful tool to aid decision making. Sometimes allow the cannula to fill (as the anesthesiologist
a problem occurs in triggering the appropriate gives volume to the patient) or to evacuate foam
thrombin-burst to achieve hemostasis, this is from the venous line as it is filled from below.
evidenced by a lack of clot forming in the chest, A heavy silk ligature snared or tied around the
continued bleeding, a prolonged R-time on TEG cannula in the right atrial appendage can be
(usually around 12+ minutes) followed by a used to seal this area. Once the circuit is deaired
normal trace after splitting, and no appreciable ECMO should be reinitiated very slowly and
heparin effect when comparing concurrent flow increased gradually, watching the heart and
plain and heparinase samples. In this setting atrial pressure to assure it does not become too
administration of recombinant activated fac- empty. If no obvious source can be found and
tor VII (NovoSeven) at a dose of 90 mcg/kg the problem persists the pericardium can be kept
repeated hourly until the bleeding settles can be filled with saline to allow ECMO to continue
effective. Circuit thrombosis is an unusual but while a solution is sought. If no source of en-
serious potential complication of NovoSeven trainment can be found, then the air is coming
administration especially if a prosthetic valve is out of solution (cavitation). Limiting the inlet
present and the heart is at complete stand-still,4 pressure by controlling the pump speed and
therefore it is recommended that a replacement using a venous compliance chamber such as
circuit should be primed and instantly available the Better-BladderTM (Circulatory Technology,
when NovoSeven is being given. Inc., Oyster Bay, NY) can solve this problem.
Cavitation is especially likely to arise either
Air Entrainment when the venous cannula is poorly positioned
or oversized or in situations where there is little
Modern centrifugal pumps can exert sig- or no atrial compliance (for instance after an
nificant negative pressure on the venous line, if extracardiac Fontan).
there are any small tears in the atrium or central
lines with open taps then air can be entrained Poor Venous Drainage
into the venous line of the ECMO circuit. Of
course the circuit should also be checked for This is caused by the cannula either being
open taps or cracked connectors. The left atrial too small, too big, not in the right place, or the
vent air inlet (if present) should be checked first blood being somewhere else. A combination of
to ensure it is closed as it is the prime suspect. echocardiography (epicardial or transesopha-
Some cardiac surgeons are unaware of the dif- geal), the Mark-1 human eyeball and index
ference between an ECMO circuit and a bypass finger can often detect if the cannula position
circuit and will actually open the air inlet or is inadequate. This could occur, for instance,
put a needle in the venous line (both standard if the cannula was positioned too deeply and
techniques during CPB), so always have high the tip was slipping down the IVC, or into the
index of suspicion when a vent is present. coronary sinus or across the tricuspid valve. In
Air entrainment can be sufficiently severe the case of straight extrathoracic cannulae it is
to lead to foam in the circuit, this is difficult tempting to put the biggest possible cannula,
to remove. After clamping the venous cannula but sufficient space must be left around the tip
and the venous line the atrium should fill (as- of the cannula to allow the blood to reach it. In
suming there is some cardiac activity) and the other words, the cannula must sit comfortably
defect will then become a bleeding point which
353
Chapter 30
within the vessel, not stretch the vessel wall

tightly around itself.
Sometimes the left SVC to coronary sinus
is the dominant vein returning blood to the
heart and this blood can only be accessed via a
direct right atrial cannulation. Sometimes there
is so much collateral formation that the amount
of blood returning via the thebesian veins is
so large than left atrial/ventricular venting is
required purely to obtain sufficient venous
drainage.
Conclusion
Safe, timely and reliable cannulation and

after-cannulation support is essential to the
provision of effective ECLS in pediatric cardiac
patients. While this is true of all ECLS, the chal-
lenges of this patient group are considerable and
reliance of the patient on ECLS often absolute.
In order to achieve this goal, it is essential that
the pediatric cardiac surgeon and pediatric
perfusionist are integral members of the ECLS
team and have a firm understanding of ECLS
physiology and circuitry. Being an expert in
the operating room when using CPB is a good
foundation to build an ECLS program, but does
require some additional building bricks. The
key principals of successful cardiac ECLS can-
nulation are adequate extracorporeal flow, good
decompression of the heart, and strict asepsis.
Don’t forget to give the heparin!
354
References
1 Balasubramanian SK, Tiruvoipati R, Amin

M, et al. Factors influencing the outcome
of pediatric cardiac surgical patients dur-
ing extracorporeal circulatory support. J
Cardiothorac Surg. 2007;2-4
2. GJ Peek, RK Firmin, HM Moore & AW
Sosnowski. Cannulation of Neonates for
Extracorporeal Life Support. Ann Thorac
Surg. 1996;61:1851-1852
3. Marathe SP, Talwar S.Surgery for transposi-
tion of great arteries: A historical perspec-
tive. Ann Pediatr Cardiol. 2015;8(2):122-
128
4. Chalwin RP, Tiruvoipati R, Peek GJ. Fatal
thrombosis with activated factor VII in a
pediatric patient on extracorporeal mem-
brane oxygenation. Eur J Cardiothorac Surg.
2008;34(3):685-686
355
31
Comorbidities and Their Impact on Outcome in Pediatric Patients on ECMO

for Cardiac Disease
Lara S. Shekerdemianm, MD, Patricia Bastero, MD
Background important potential determinants of outcome

after ECMO for cardiac disease can be broadly
The survival for children with heart dis- categorized according to indication for ECMO,
ease on extracorporeal membrane oxygenation timing of ECMO initiation, cardiopulmonary
(ECMO) has steadily improved over the past physiology, and understanding of center-spe-
two decades, despite placing increasingly com- cific experience and team readiness, as well as
plex patients on support, including a significant predetermined and acquired comorbidities in
proportion with single-ventricle physiology, individual patients. In this chapter we consider
endstage heart failure, noncardiac comorbidi- the impact of comorbidities on outcome in pa-
ties, or during cardiopulmonary resuscitation. tients with heart disease who receive ECMO.
Indeed in the current era, the operation associ- Comorbidities and their impact on outcome
ated with the highest mechanical support rates logically lie in two broad categories: pre-ECMO
is the Norwood operation for hypoplastic left comorbidities that include preexisting patient
heart syndrome (HLHS).1 factors as well as pre-ECMO in-hospital ones,
Survival to hospital discharge after cardiac and ECMO-specific acquired comorbidities.
ECMO is currently between 40% and 50%.2,3 An inevitable overlap occurs between these,
However, crude survival is only one marker even a ‘chicken and egg’ phenomenon as the
of success, so quality of survival in terms of presence of a pre-ECMO comorbidity may
functional outcome must also be considered. directly increase the likelihood of developing
Data pertaining to quality of life after ECMO ECMO-related complications, and hence an
are limited to small single-center series, using inferior outcome.
a variety of questionnaire based tools, but in
general point to a degree of decreased quality Preexisting Comorbidities
of life (particularly health related) compared to
non-ECMO patients, though within acceptable Patient factors that impact the outcome after
limits in financial models.4,5 Garcia Guerra et ECMO are often non-modifiable, and as such
al. reported the health-related quality of life cannot be influenced by any aspect of clinical
(PedsQL) scores after pediatric cardiac ECMO care. However, a clear understanding of the ac-
are lower than the scores for children who un- tual or potential impact or contribution of these
derwent surgery for congenital heart disease in factors, and clarification of fact from ‘urban
infancy but did not require ECMO.6 The most
357
Chapter 31
myth’ is very important for all those participat- disease. This includes underlying cardiac diag-
ing in decisionmaking and care of these patients. nosis, nature of acquired heart disease, or type
of surgery, all of which can influence aspects of
Patient Demographic Factors decisionmaking regarding candidacy overall, as
well as optimal cannulation techniques. In the
Birthweight, Gestation, and Race current era, few, if any diagnostic contraindica-
tions to instituting ECMO support exist, though
Several single-center studies have indicated outcomes may potentially vary according to
a significant relationship between birthweight or these factors.
weight at the time of cannulation and outcome
after ECMO in neonates with congenital heart Newborns with Complex CHD
disease.7,8 A recent review of the ELSO Registry
of 1898 newborns with congenital heart disease Newborns undergoing stage 1 palliation or
(CHD) who received ECMO, concluded that other complex biventricular repairs, including
a birthweight of less than 3kg was associated the arterial switch with VSD with or without
with an increased risk of neurologic injury (odds arch repairs, together constitute the largest
ratio 1.5), and that in turn, this was associated patient group. In a recent review of all ECMO
with increased in-hospital mortality.9 Similarly, for CHD from the Society of Thoracic Surgeons
in a review of the ELSO Registry, extracorpo- (STS) database, this population accounted for
real cardiopulmonary resuscitation (ECPR) in 31% of the entire CHD ECMO population,
641 neonates, the majority of whom had heart with 17% undergoing support after Norwood
disease showed survivors had a higher weight operations.1 Interestingly, mortality was highest
at cannulation, as well as more advanced ges- for infants after truncus repair or Ross-Konno
tational age, than non-survivors. In this cohort, procedures (both 71%), while hospital mortal-
survival for those with a corrected gestational ity for ECMO after the Norwood operation or
age of less than 37 weeks was only 23%, com- Damus-Kaye-Stansel palliations was 57% and
pared to 43% in those at 40 weeks or greater.10 40%, respectively. Despite greater physiological
Not surprisingly, cerebral hemorrhage, also an complexity and overall surgical mortality and
independent risk factor for death, was signifi- perceived postoperative fragility, an important
cantly more common in less mature infants. message from this large study is that patients
Gender and race represent additional non- requiring ECMO after staged palliation do not
modifiable factors that may impact outcome af- in fact represent the highest risk patient group
ter ECMO in children with heart disease. While in terms of mortality.
one single-center study suggested that males Patients with the Glenn or Fontan Circulation
had higher survival following ECMO in the
setting of staged palliation,7 this was not borne Infants and children after surgical pallia-
out in a larger ELSO review of a similar patient tions with cavopulmonary anastomoses (Glenn
population. The data relating to race do appear or Fontan circulations) represent a complex
more robust, suggesting that the Caucasian race physiological group, in whom stable sup-
may be protective in this setting.7,11 port with ECMO can be difficult to establish.
Moreover, the indications for ECMO are often
Diagnostic Group less than straightforward in these patients who
may suffer severe clinical deteriorations due to
An important factor when considering car- recognized or unrecognized anatomic (surgical)
diac ECMO in children relates to the underlying problems including residual lesions, as well
358
Comorbidities and Their Impact on Outcome in Pediatric Patients on ECMO for Cardiac Disease
as elevated pulmonary vascular resistance or not as convincing as we might expect, and this
severe diastolic dysfunction. Historically these is at least in part related to the terminology or
surgical groups have had grim prognoses in classification.
terms of mortality and quality of survival. In According to the most recent ELSO Regis-
an early review from the ELSO Registry, sur- try International Summary (July 2015), when
vival to center discharge for Fontan patients categorizing ECMO by age group, survival
after ECMO was only 18%.12 A single-center in neonates after ECPR matched that for all
review of 6 Glenn and 14 Fontan patients in cardiac disease (both 41%) whereas survival
2004 reported intact, transplant-free survival in patients aged 1 month to 16 years was lower
in only 4/20 patients at a median followup of after ECPR (41% vs 51% for ECPR and car-
35 months. All but one Glenn patient died in diac disease, respectively).2 When grouping
hospital, and the sixth (who also subsequently all pediatric age groups together: survival after
had a heart transplant) sustained severe neuro- ECPR was 39%, and for cardiac ECMO, 46%.
logical injury.13 However, ECPR does not specifically apply
More recent reviews suggest modest im- to the CHD population and can be applied to
provements in outcomes over time in patients patients without underlying heart disease. Thus,
with cavopulmonary connections. This may when considering this dataset differently, the
relate, in part, to a better appreciation for re- survival after cardiac ECMO in neonates are
versible indications, early intervention with 40% and 31% for all CHD and cardiac arrest
remediable contributors, as well as refinements respectively, and for older children, 49.5%, and
in technology and cannulation techniques. A 38.4% for CHD and cardiac arrest respectively
review from the ELSO Registry (1987-2009) suggesting that within the cardiac population,
for Fontan patients revealed an overall survival cardiac arrest prior to or during ECMO can-
to discharge of 35%, with survival in the 2002- nulation significantly impacts survival.
2009 epoch of 42%. However, neurological Single institution data, while clearly limited
injury was present in 20% of patients, and was by smaller numbers, provide greater detail and
the single most powerful predictor of mortality, overcome some of the obscuring of definitions,
with an odds ratio of greater than 5.14 Similarly, while also providing the opportunity to learn
mortality rates for patients on ECMO after from ‘expert centers.’ Kane and colleagues re-
Glenn operations has improved, with a review ported a survival to hospital discharge of 51%
from the ELSO Registry between 1999 and after ECPR in children with heart disease, in an
2012 demonstrating overall survival to center institution with a longstanding commitment to
discharge of 41%. Again, significant neurologi- a programatic, standardized approach to ECPR,
cal injury was present in a high proportion of the clearly defined candidacy, early ‘triggers,’ and
cohort, including 14% of survivors.15 the presence of an inhouse specialist team.16
When considering ECPR as a comorbidity,
Pre-ECMO Cardiac Arrest diagnostic groups must be considered too, as
While intuitively one might expect that a differences exist by patient categories. Patients
cardiac arrest requiring cardiopulmonary resus- with single ventricle physiology now represent
citation (CPR) prior to ECMO, or active CPR a significant proportion of all cardiac ECMO,
during ECMO cannulation (which by many is and a growing percentage of the ECPR popu-
referred to as extracorporeal cardiopulmonary lation. An ELSO Registry review of patients
resuscitation or ECPR) would represent a co- with HLHS receiving ECPR showed survival
morbidity that would adversely impact survival, to center discharge of 36%, which is somewhat
the current data to support this hypothesis are lower than for outcomes after cardiac ECMO as
359
Chapter 31
a whole.17 This does not suggest that it is a futile on subsequent quality of outcome. An early
therapy, but provides important data to share ELSO review of ECMO in pediatric patients
with families and other providers, and perhaps aged 1 month to 18 years demonstrated that
provides further encouragement to consider the need for CPR prior to cannulation was as-
ECMO early in this high-risk group. sociated with an increased risk of neurologic
The heart failure cohort represents a minor- injury on ECMO (odds ratio 2.5).19 In a more
ity of the ECPR group, but nonetheless warrant recent ELSO Registry review neonates with
mention here. Traditionally acute cardiogenic CHD requiring ECMO, the need for CPR was
shock in the absence of CHD (myocarditis, the strongest predictor of adverse neurological
cardiomyopathy) has been associated with ac- outcome (odds ratio 1.7 for stroke or intracranial
ceptable survival after ECMO as either a bridge hemorrhage on ECMO). In turn, adverse neuro-
to recovery, or to other long-term devices (or in logical outcome was associated with death prior
the rare event, directly to transplant). In a re- to discharge from the ECMO center.9
cent single-center review of ECPR, Philip et al.
reported survival to discharge of patients with Syndromes and Chromosomal Abnormalities
myocardial failure of 40%, but importantly no As the breadth of indications for ECMO
child with restrictive cardiomyopathy survived support expands, and concomitantly the con-
after ECPR. While a relatively rare diagnosis, traindications decrease, the appropriateness
the difficulty of maintaining adequate perfusion of ECMO, or the question of whether patients
during CPR and even excellent ECMO support with known genetic syndromes, chromosomal
for this complex physiology impacts outcome.18 abnormalities or major extracardiac malfor-
Clearly limitations in interpreting this mations, all more common in patients with
data include the definition of ECPR which has CHD, affect risks and outcomes. In an elegant
been variably applied to include all CPR prior population-based analysis that included more
to ECMO or ongoing CPR until commencing than 12 million infants born between 1998 and
ECMO support. Additionally, the underlying 2008, the prevalence of genetic syndromes,
diseases include CHD as well as acute cardio- nonsyndromic malformations and overall con-
genic shock with or without primary heart dis- genital anomalies were 2%, 11.4%, and 13.6%
ease. Regardless of these limitations, mortality respectively in the CHD population, and 0.3%,
overall is not dismal, and may approach the 6.7%, and 7% respectively, for non-CHD con-
survival after cardiac ECMO as a whole. The trols.20 Furthermore, the presence of genetic
reasons for this are most likely multiple, and syndromes and additional noncardiac anomalies
include the availability of a primed ECMO impact in-hospital morbidity and mortality,21 as
circuit or a rapid response ECMO team around well as long-term mortality 22 and overall neu-
the clock; simulation-based team training in rodevelopmental performance 23,24 after surgery
emergency ECMO cannulation, and early ini- for complex CHD.
tiation of the ECMO response in the setting of A limited number of reviews consider the
cardiac arrest. Additionally, careful attention to spectrum of ‘genetic syndromes’ and their
or avoidance of other factors that can exacerbate impact on outcome after ECMO. One large
brain injury including management of coagu- single-center review of 377 cardiac ECMO
lopathy, CO2 and pH, and careful temperature runs included 43 runs in 42 children with a
control may ameliorate outcomes. known genetic syndrome. Although hospital
As already stated, outcomes cannot and survival reached 56% in the syndromic group
should not be limited to survival, and the exist- (which was comparable to the nonsyndromic
ing literature clearly defines the impact of CPR patients), late attrition was common with only
360
24% of the patients with genetic syndromes be- Similarly, the existing literature refutes the
ing alive at long-term followup.25 In a different assumption that DiGeorge Syndrome confers
single-center review of ECPR, the presence of increased risk in patients on ECMO. In an ex-
noncardiac structural or chromosomal anoma- tensive review of the ELSO database, Prodhan
lies were associated with a threefold increase et al. reported that patients with 22q11 dele-
in hospital mortality.16 tion requiring ECMO after repairs of common
conotruncal defects and other lesions commonly
Trisomy 21 (Down Syndrome) and Del22q11 associated with Di George, did not suffer in-
(Di George Spectrum) creased risk of postoperative complications
Trisomy 21 and 22q11 deletion together including infections, or mortality.28 Clearly
represent the two genetic syndromes most com- this query could not be expected to examine
monly associated with CHD. While one might where in the extensive ‘Di George spectrum’
assume that these syndromes are associated each patient lies, in terms of multisystem dis-
with increased postoperative morbidity and ease, immune competence and other variables;
mortality, the existing data show that morbidity nonetheless it is important to take note of these
and mortality should be considered separately. observations in the decisionmaking process.
In a retrospective review from the STS
database, which included 4,350 children with Acquired Comorbidities
trisomy 21 and 41,229 without, patients with
trisomy 21 had increased postoperative lengths The survival rates of neonatal and pediatric
of stay after surgery for CHD, infectious and cardiac patients to ECMO decannulation vary
respiratory complications, and heart block, but between 62% and 67%, and to hospital discharge
similar mortality rates.26 A recent ELSO review range from 41% to 51%. Limited long-term data
reported that the hospital mortality for children suggest that 90% of the children discharged
with trisomy 21 receiving ECMO after correc- alive survive to medium-term followup. Thus,
29
tive heart surgery was 44%, compared with 56% factors which impact hospital mortality seem to
in non-Down syndrome controls with a similar be key determinants of long-term survival after
range of surgical diagnoses.27 It would therefore cardiac ECMO. It is now well recognized that
appear that Trisomy 21 does not confer any additional comorbidities, particularly renal or
additional mortality risk in children receiving neurological injury (Table 31-1) acquired during
ECMO for cardiac support. the ECMO course, impact in-hospital mortality
and indeed contribute to longer-term morbidity.
Table 31-1. Category and incidence of neurological and renal injury in cardiac ECMO patients.2
0 – 30 days 31 days – < 1 year 1 year - < 16 years
Neurologic
CNS bleed (US/CT) 11.2% CNS bleed (US/CT) 6.2% CNS bleed (US/CT) 4.1%
Seizures (Clinical) 6.5% Seizures (Clinical) 8.3% Seizures (Clinical) 4.2%
CNS infarct (US/CT) 4.8% CNS infarct (US/CT) 4.8%
Brain death (Clinical) 6.1%
Renal
Hemofiltration 26.1% Hemofiltration 23% Hemofiltration 20.4%
Creatinine 1.5-3.0 10.7% Creatinine 1.5-3.0 8.1% Creatinine 1.5-3.0 12.9%
Dialysis 9% Dialysis 10.1%
361
Chapter 31
Neurological Injury of neonates, 11 % of infants, and 7.4% of older

children while on cardiac ECMO support.32
Neurological injury, the most devastating The incidence of nonconvulsive seizures is
complication of ECMO, represents a common likely higher but poorly understood as routine
reason to withdraw ECMO support in cardiac EEG monitoring is rarely performed in ECMO
patients. Neurological injury that is acquired patients.33
(or recognized) on ECMO is associated with As well as being associated with reduced
higher mortality9,30 and more frequently oc- survival, neurological injury ECMO indepen-
curs in patients after ECPR.19 All neurological dently predicts of long-term neurodevelopmen-
complications in ECMO patients (hemorrhage, tal morbidity. Up to 50% of ECMO survivors
infarction, and seizures) occur more frequently with neurological injury show a degree of
in the pediatric population than in adults, and physical impairment or disability, which may
are most prevalent in the youngest patients. In improve over time, but other subtle learning and
the absence of clinical suspicion, with the ex- language deficits can emerge.34. Small single-
ception of serial ultrasounds in young infants, center studies have shown a relation between
the absolute incidence of neurologic injury seizures and lower IQ scores, this being associ-
in ECMO patients is difficult to gauge. Fur- ated with cerebral palsy and/or developmental
thermore, MRI scanning, which would be the delay.34
gold standard investigation for confirming or
excluding acquired structural brain injury, is Kidney Injury
impossible during ECMO. Continuous electro-
encephalography (EEG) recording is rarely, if Acute kidney injury (AKI) and fluid overload
ever, done routinely. frequently complicate ECMO courses and are
Stroke, a devastating complication of associated with poor outcomes. Renal failure
ECMO, can often necessitate discontinuation or occurring when on ECMO is associated with
withdrawal of support. A recent ELSO Registry longer duration of ECMO and higher mortal-
review reported an incidence of hemorrhagic or ity rates.35,36 Critically ill children with heart
ischemic stroke of 12% in pediatric patients on disease are at intrinsic risk of preexisting renal
ECMO after cardiac surgery.30 Stroke occurs impairment, which can be due to longstanding
most commonly in neonates and is associated circulatory compromise with reduced systemic
with increased in-hospital mortality. Addition- oxygen delivery in the presence of acute, chronic,
ally, it is associated with lower weight-for-age, or acute-on-chronic heart failure, complex cir-
longer ECMO runs (greater than 167 hours), culatory physiology or intrinsic congenital or
and carotid artery cannulation but not with acquired renal abnormalities.
surgical complexity.30,31 Other independent Renal failure has been consistently associ-
risk factors for neurological injury include the ated with poor outcomes in children on ECMO
administration of bicarbonate before going on support for cardiac support. In a review of ECMO
ECMO, the ongoing need for vasopressors and in patients with single ventricle physiology from
inotropes during support, and conversion from an administrative database, the presence of
a ventricular assist device to ECMO.19 acute renal failure was associated with a more
With respect to abnormal EEG patterns than threefold increase in mortality.37 In another
including seizures, the same limitations apply review from the ELSO Registry of ECPR in
when attempting to address the question of how newborns after Stage 1 Palliation, renal failure
commonly these occur on ECMO. An extensive on ECMO was associated with a twofold increase
ELSO review reported clinical seizures in 8.1% in mortality.17
362
Renal replacement therapies (RRT) (see followup be considered in survivors of ECMO

Chapter 62) a term that loosely applies to a spec- who received RRT.
trum of therapies including continuous simple
ultrafiltration, continuous hemofiltration, hemo- Other
diafiltration, or hemodialysis, are commonly used
during ECMO support. In the majority of ECMO Neurologic and renal injury acquired dur-
patients, RRT is relatively easy to institute in that ing ECMO support represent the most common
it can be applied in tandem with the ECMO cir- acquired comorbidities, and should routinely
cuit, utilizing the ECMO flows, and without the warrant long-term followup in survivors. Other
need for additional dialysis cannula placement. issues also affect selected survivors and warrant
The indications for RRT vary broadly, including brief consideration. Sensorineural hearing loss
simple fluid removal as a preemptive measure or has been a concern among neonatal ECMO sur-
in the management of fluid overload, as well as vivors,41 impacting language and learning abili-
supporting deteriorating renal function or AKI. ties, therefore representing a comorbidity with
Regardless of the absolute indication for potential for neurodevelopmental, behavioral,
RRT, or the mode of support, this adjunctive and quality of life consequences. Chylothorax
therapy is consistently associated with increased is an additional acquired comorbidity that can
hospital mortality for children requiring ECMO have devastating consequences in the long term.
for heart disease. In their single institution review This is typically secondary to superior vena cava
of 153 children undergoing cardiac ECMO, Wolf (SVC) obstruction due to thrombus (occurring in
et al. reported that the need for continuous veno- up to 45% of neonates on ECMO). This occurs
venous hemofiltration was associated with longer more typically after peripheral ECMO cannula-
ECMO runs and a threefold increase in hospital tion, resulting in impaired growth, malnutrition,
mortality.38 A recent multicenter report identified chronic respiratory disease, and/or immunode-
that the need for ‘all’ renal replacement therapy ficiency states. 42
was associated with nearly a twofold increase
in mortality in children with CHD receiving Summary
ECMO.35 Although the presence of AKI is as-
sociated with worse outcomes, it appears to be ECMO is a complex high-risk therapy that
potentially recoverable in a majority of survivors, is offered to the most critically ill infants and
with a single-center review reporting apparent children with heart disease, many of whom
recovery of renal function among the majority of would otherwise not survive. Over the past three
the survivors.39 However, the ‘recovery of renal decades, the outcomes have steadily improved,
function’ commonly refers to normalization of while the spectrum of patients treated and their
creatinine, or return of native urine output, and complexity and the range of coexisting comor-
caution should be applied to extrapolating true bidities have increased. There is no doubt that
long-term recovery from these observations. outcomes for cardiac ECMO are impacted by
Zwiers et al. followed all neonates in their institu- a broad range of patient comorbidities, some of
tion who underwent ECMO support for multiple which are preexisting, others occurring before
indications at up to 18 years of age, and found or during ECMO support. While the available
that those in the ‘failure’ category on the RIFLE information can be used to help define candi-
scores while on ECMO had 4.3-fold increased dacy and at short term prognosis, the impact
risk of developing chronic renal disease and hy- of comorbidities on longer-term survival and
pertension.40 This suggests that long-term renal functional outcome warrants further study.
363
Chapter 31
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tava S. Prevalence of associated extra- mediate-term outcomes after paediatric car-
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membrane oxygenation after heart surgery:

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366
32
Medical Management of Neonates and Children with Cardiovascular Disease
Roxanne Kirsch, MD, FRCPC, Steven M. Schwartz, MD, FRCPC
Introduction Utilization of Cardiovascular ECLS
The medical care of the patient on ECLS There are a few overarching pathways
or other forms of mechanical circulatory sup- for which ECLS is used to support cardiac
port (MCS) continues to be challenging. With patients. Most commonly, ECLS is used as
ongoing evolution in technology and a grow- a bridge to recovery. Failure to separate from
ing variety of diseases for which ECLS is used, cardiopulmonary bypass after surgery, or a sub-
an in-depth understanding of unique patient sequent unremitting low cardiac output state is
anatomy, physiology, and the impact of ECLS a common scenario. Here, time for ventricular
physiology on patient physiology is essential recovery, or opportunity for additional surgical
for all team members.1,2 or interventional therapies may allow success-
This chapter will address pertinent medical ful separation from ECLS. ECLS may provide
considerations for patients requiring ECLS for time for diseases such as myocarditis or intrac-
cardiovascular indications such as ventricular table arrhythmias to improve while supporting
failure. Consideration of current clinical state, vital organ function.4 Stabilization with ECLS
patient age, level of clinical stability, underlying prior to surgical intervention may be necessary
disease, comorbidities related to that disease, in certain cases with very unstable physiology.
knowledge of potential cardiac surgical inter- If recovery is unlikely despite ECLS support, or
ventions, potential for organ replacement, and additional interventions to improve physiology
type of durable MCS that might be possible are not possible, ECLS may be used to bridge
if indicated are important aspects of caring to alternate durable MCS or organ replacement
for these patients.3 The goals of medical care therapy. Finally, ECLS can be used as emergent
need to be tailored according to the indication rescue therapy in the setting of cardiopulmonary
for ECLS with attention to improving physiol- arrest. Each of these uses will involve varia-
ogy, addressing common challenges, applying tions in expectations for recovery, methods of
knowledge of outcomes where possible, and enhancing recovery, expected timelines, and
addressing the needs of the patient and family. will impact the likelihood of a successful ECLS
course (see Chapter 35). They also provide
challenges that may be unique to the cardiac
ECLS patient such as cardiac stun, postsurgical
bleeding, need for changes in ECLS support
367
Chapter 32
for certain physiologies, adjusted expecta- becomes increasingly distended with resultant
tions of measured values to reflect the cardiac left atrial hypertension and pulmonary edema.
anatomy and physiology, and need to define Importantly, the elevated intracavitary pressure
and treat residual lesions and hemodynamic will decrease myocardial perfusion pressure
burdens. Cardiac patients generally require a and can cause subendocardial ischemia. This
relatively short duration of ECLS, which affects can further damage an already compromised
the approach to managing the ECLS course. myocardium. The practitioner at the bedside
In all situations, management is directed at must monitor for signs of developing left atrial
maximizing myocardial perfusion to aid cardiac hypertension, particularly if no vent is in place
recovery, addressing important residual lesions and there is not an atrial or ventricular level
if present, and maintaining or improving end communication. Signs may include pulmonary
organ function. edema on chest radiograph, new bleeding from
endotracheal tube, or loss of systemic pulse
Management of Common Issues for the pressure that was previously present. Echo-
Cardiac ECLS Patient cardiographic findings of LV or LA dilation,
poor function, and transseptal gradients can be
Myocardial Stun misleading and underestimate the LA pressure.
Therefore, many centers will advocate for early
Although cardiac stun can happen with decompression.5-7
any initiation of ECLS support, it occurs more Without a surgically placed vent, catheter
commonly in the patient with myocardial dys- based creation and dilation of the atrial sep-
function prior to MCS. The sudden decrease tum can be performed to decompress the left
in preload with the addition of afterload to the heart.6-,9 Some published studies suggest that
poorly functioning heart will often induce a early decompression shortens ECLS course and
time period of worsened cardiac function with improves LV recovery.6,7 However, it should be
minimal to no pulse pressure. This expected noted that long-term LV function, neurologi-
phenomenon requires diligent monitoring to cal function, and survival in patients with LA
ensure adequate myocardial perfusion and as- decompression for ECLS needs further study.
surance of adequate ECLS flows to support end
organ function and allow time for improvement. Bleeding
The generally expected time course for recovery
of cardiac stun is 3-7 days. Commonly, patients on cardiovascular
ECLS suffer voluminous bleeding. In a mul-
Ensuring Adequate Ventricular Decompression ticenter analysis, nearly half of children with
cardiac disease on ECLS had hemorrhagic com-
ECLS does not inherently decompress the plications associated with increased mortality
systemic ventricle in a two-ventricle circulation risk.10 Additionally, neonates who undergo CPB
unless there is an atrial or ventricular com- experience greater risk of needing ECLS with
munication or a specific cannula to vent the excessive postoperative bleeding.11 Risk factors
systemic atrium. Even with full venoarterial for hemorrhagic complications during ECLS
support, there will be blood return to the left include mediastinal exploration prior to ECLS,
ventricle. In a setting of a poorly functioning greater surgical complexity, early postopera-
ventricle either due to underlying disease pro- tive cannulation, and longer bypass time.10,12
cess, or ventricular arrhythmia, the ventricle can Hemorrhage from surgical sites and generalized
no longer empty the blood returning to it and it seepage puts the patients at risk for tamponade,
368
even with an open sternum. Bleeding also im- Although early initiation of ECLS may be help-
pedes the ability to provide appropriate ECLS ful, the observation that ECLS initiated due to
flows. Early postoperative bleeding may resolve failure to separate from CPB is associated with
over 12-24 hours with aggressive support for higher mortality13 may reflect that the inability
volume losses and meticulous attention to cor- to ever separate from bypass sometimes results
recting factors that contribute to bleeding such from a different set of problems than does the
as thrombocytopenia. Decisions regarding the inability to maintain cardiac output several
need for or timing of mediastinal reexploration hours later. Use of ECLS for single ventricle
have to consider the potential to disturb clot patients has increased over time and is costly.13,17
that is appropriately forming vs. the importance Further study to define the best use of ECLS in
of uncovering surgically correctable causes of the single ventricle population is still required.
bleeding. Commonly, anticoagulation targets Regardless of the evolution of this data,
are also altered and on occasion prothrombotic understanding physiology in the single ventricle
products, such as activated factor VII may be patient on ECLS is imperative to appropriately
given (see Chapter 8). It is important to have supporting the patient. Often patients with
the capability for rapid replacement of the the Blalock-Taussig (BT) shunt require higher
ECLS circuit should circuit thrombosis result. ECLS flows (150-200 mL/kg/min). The goal
Once better hemostasis has been achieved for here aims not a specific amount, but rather ade-
several hours and patient hemodynamics im- quate flow to maintain the circulation, which has
proves, anticoagulation is generally increased systemic and pulmonary perfusion in parallel,
for circuit maintenance. It is not uncommon to rather than in series. Also, the team must recog-
have increased thrombus in the ECLS circuit nize that the mixed venous saturation from the
or early membrane failure after large volume ECLS circuit does not represent cardiac output,
blood product replacement for bleeding, and circuit function, or recirculation since the com-
this needs expectant monitoring. mon atrial chamber decompresses the systemic
ventricle. The pulmonary venous return will
Single Ventricle Physiology on ECLS Support be well oxygenated because of the flow from
arterial cannula down BT shunt to the lungs,
ECLS support has been used in single ven- and the mixed venous saturations are higher
tricle circulations (see Chapter 29 and Chapter than in those with two ventricle physiology. If
35).13-16 A multicenter database study suggests the lungs and BT shunt are working normally,
overall 59% weaned from ECLS, and 31% it is possible to support the patient using the
survived to hospital discharge. Risk factors ECLS circuit without an oxygenator, sometimes
for mortality in that study included black race, called “no-MO,” used as a paracorporeal VAD.
mechanical ventilation prior to ECLS, longer Alternately, one can review shunt patency by
ECLS duration, and once on ECLS, develop- “capping” the oxygenator and removing all gas
ment of multiorgan complications or acidosis. exchange of the circuit. With this, in the set-
In addition failure to separate from CPB as an ting of good arterial cannula position, adequate
indication for ECLS also showed decreased sur- lung volumes, and appropriate ventilation
vival.13 This is generally consistent with previ- strategies, gas exchange should be adequate
ous series that have shown better outcomes with and blood gases demonstrate appropriate PaO2
reversible problems (such as shunt thrombosis) and PCO2 for a single ventricle circulation. If
and short ECLS course,14,15 and it is felt that this trial is unsuccessful, shunt patency should
perhaps early deployment and patient selection be discussed and addressed where appropriate
may be important determinants of outcome.13,16 prior to attempts to separate from ECLS support.
369
Chapter 32
Another strategy to manage the parallel rather be performed via a full sternotomy, a limited
than in-series circulation present is to surgically right 4th space anterior thoracotomy or via the
constrict the BT shunt. This approach adds McEverdy approach to the IVC. The femoral
some risk of shunt thrombosis, perhaps even vessels should not be used in a child of this age
after removing the constriction. It is now well due to their small size.
understood that the shunt must be left open
during ECLS as previous attempts to manage Residual Cardiac Lesions
the shunt by totally occluding it resulted in
100% mortality, although partial occlusion can When a postoperative cardiac patient
be effective. Finally, for any patients with a BT requires ECLS support, additional investiga-
shunt cannulated for ECLS via the ipsilateral tion for residual lesions should be considered.
internal carotid artery, there is risk of slippage These studies may have been undertaken prior
of the arterial cannula into the shunt, which will to initiating support, but residual issues that
be reflected as sudden loss of all cardiac output could not be fully addressed due to patient
supported by the circuit. instability or may have led to ECLS must be
ECLS support utilized in the cavopulmo- investigated. However the ECLS circuit can
nary connection and the Fontan circulations,15,16 hamper the search for useful data. Cardiac
(see Chapter 29 and Chapter 35) has included MRI is not technically possible. The presence
venovenous support to provide improved oxy- of open sternum, dressings, or cannula position
genation while awaiting decrease in PVR with can obscure echocardiographic windows. Fur-
anticipation for improved flow through the thermore, hemodynamic measurements by echo
cavopulmonary connection(s), or venoarterial or catheterization may be unreliable in the face
more commonly used to stabilize the patient of the limited intracardiac flows or ventricular
prior to take down of Fontan or Glenn surgeries. filling on ECLS. Flow through the aortic can-
In both instances, management of the patient nula may produce or exacerbate aortic insuffi-
requires vigilant observation for development ciency. Therefore certain diagnostic procedures
of superior vena cava (SVC) syndrome or im- or maneuvers may require temporary reduction
portant venous congestion due to failure of flow or cessation of ECMO flow.
through the pulmonary bed that can be difficult
to recognize with maintenance of oxygenation Cardiovascular Assessment and Monitoring
by the membrane and or support of cardiac out-
put in the patient on VA-ECLS. The anatomy Rhythm and Heart Rate
of those with a bidirectional Glenn shunt re-
quires a choice of the venous cannulation site Often during a period of cardiac stun, or
for mechanical support. Use of the SVC can in the inflamed heart, patients may experience
decompress the cerebral venous system and sup- low voltages on continuous telemetry or severe
port oxygenation but may provide little cardiac bradycardia. With adequate ECLS flows, these
output support. Cannulation of the atrium can abnormalities should not prove problematic and
support both oxygenation and cardiac output return of appropriate heart rate or sinus rhythm
to a greater degree due to the larger amount can signal cardiac recovery. Additionally, and
of blood returning to the heart from the lower particularly in the postoperative patient, epi-
body, but may not decompress the SVC with cardial pacing may be required to demonstrate
SVC syndrome unless the underlying cause improvements in ventricular function that can
is ventricular dysfunction associated with a be difficult to assess with atrioventricular dys-
high atrial pressure. Atrial cannulation can synchrony.
370
Dysrhythmias that would otherwise cause actual cardiac filling volume.18 Fluid manage-
hemodynamic instability or cardiovascular col- ment therefore involves not only optimal goals
lapse generally are not as problematic while on for the patient, but attention to circuit function.
ECLS. However, converting the patient back Increasingly negative venous pressure, low flow,
to sinus rhythm generally reduces myocardial or circuit “chattering” may occur in the circuit
demands and promotes ventricular recovery.18 when the patient is intravascularly depleted.
Volume repletion may improve circuit func-
Blood Pressure tion, but a reassessment needs to be made not
only of fluid status, but for potential causes of
Patients on ECLS present challenges in impaired venous return such as tamponade or
blood pressure monitoring. Pulsatile MCS decannula obstruction.18
vices have a relatively normal arterial waveform,
but continuous flow ventricular assist devices Ventilator Management
or ECLS with poor ventricular function show
a flat waveform with little pulse pressure. It Cardiac and Pulmonary Considerations
should, nonetheless reflect mean arterial pres-
sure. For the ECLS patient, arterial waveform Respiratory care of ECLS patients with an
changes can also reflect blood loss, impaired open lung strategy and good pulmonary toilet
pump flow or function, hypertension related for patients with cardiovascular failure opti-
to volume overload, or other issues.18-21 For all mizes lung function and maintains the ability
MCS devices, determining adequacy of support to separate from ECLS when cardiac recovery
is accomplished by assessing hemodynamic has occurred--generally within days. Patients
status, vital signs, capillary refill, warmth and may suffer pulmonary edema as a manifestation
color of extremities, urinary output, and neuro- of inadequate left ventricular decompression;
logical status.18,22 however, noncardiogenic lung edema from fluid
retention and capillary leak after large volume
Central Venous Pressure and Fluid blood product transfusions, inflammatory re-
Management sponse to bypass, and reperfusion after periods
of low output can occur. While many cardiac
A simple way of estimating intravascular patients benefit from a lower positive end-expi-
volume status is trending central venous pres- ratory pressure (PEEP) ventilation strategy, dur-
sure (CVP). This is an important determina- ing ECLS support, a higher PEEP (generally 10
tion since all MCS devices are dependent on cm H20) can maintain lung volume and prevent
adequate preload. If device flow is impaired microatelectasis. This is utilized while being
and CVP low, volume replacement is gener- careful to avoid stretch and therefore a smaller
ally required. But when device flow falls with tidal volume is often beneficial. Whether using
a high CVP, a search for tamponade or right volume control or pressure control modes of
heart failure should ensue. If device flow is ventilation, the target tidal volumes aims for a
maintained with high CVP, hypervolemia may maximum of 6-8 mL/kg with peak inspiratory
be present and should be treated. These gen- pressures 18-20 cm H20 and low rates (gener-
eralizations must be qualified by recognizing ally 10 breaths per minute), recognizing that
the limitation of CVP. This number not only the targeted values may be inappropriate in
represents volume status, but also is affected patients with open sternum, or those with poor
by cardiac and vascular compliance. Studies lung compliance secondary to atelectasis, pul-
note the poor correlation between CVP and monary hemorrhage, or intrathoracic hematoma.
371
Chapter 32
Settings need to be reassessed on a continuous transient encephalopathy in adults; a condition

basis and adjusted based on evolving patient improved by lowering device flow.23 Similarly,
status and goals of ECLS support.18 severe hypertension occurs commonly upon ini-
The majority of cardiac patients on ECLS tiation of MCS, at least in infants,24,25 although
have normal lung function and compliance and linkage to intracranial hemorrhage has been
maintaining ventilator settings used in the ab- variable. Alternatively, when flows are clearly
sence of ECLS may prove optimal to improve adequate and the patient remains hypotensive,
cardiopulmonary interactions. Furthermore, the use of vasoconstricting agents often improve
impact of ventilator strategies on venous return, organ perfusion pressure.18
pulmonary vascular resistance (PVR), and sys-
temic ventricular afterload need to be carefully Other Organ System Considerations Specific
considered and may dictate different targets in to the Cardiac ECLS Patient
airway pressure or PaC02.18 In select situations,
it may be appropriate to extubate the patient Infections
without lung pathology, or allow spontaneous
breathing with pressure support. General considerations for appropriate
monitoring and treatment of infection, renal
Inotrope/Vasoactive Medications dysfunction, or neurologic complications reflect
those of the noncardiac ECLS population. How-
Supporting Cardiac Function ever, a few unique issues should be mentioned.
Low white blood cell count occurs commonly
Although the ECLS circuit effectively after large volume transfusion of packed red
replaces cardiac function, it is important to blood cells, platelets, and plasma and may not
support cardiac function and recovery beyond adequately reflect the presence (or absence) of
“rest” on the ECLS circuit. As discussed ear- infection. Vigilant monitoring is required with
lier, maintaining left atrial decompression is attention to potential for endocarditis or endo-
important. Inotropic support such as low-dose vascular infection particularly in the presence of
epinephrine and/or milrinone may be useful mechanical valves or synthetic grafts or stents.
to promote native cardiac function. These, of
course need to be balanced with potential car- Renal
diac toxicities, although their short-term use for
ECLS patients has not been studied.18 Renal dysfunction may be exacerbated in
the cardiac patient due to impediments to renal
Supporting Organ Perfusion blood flow prior to ECLS cannulation, and
use of nephrotoxic drugs. Unfortunately, fluid
Vasoactive agents such as norepinephrine, removal generally improves myocardial compli-
vasopressin, phentolamine, and nitroprusside ance and cardiopulmonary interactions, so renal
may serve as adjuncts to MCS to support blood recovery may be a lower priority in the cardiac
pressure and organ perfusion. Particularly for ECLS course to allow for earlier separation
centrifugal devices, increased afterload reduces from ECLS. Ongoing debate and much litera-
pump flow potentially necessitating vasodilator ture examine the association of poor outcomes
agents to ensure adequate flows and systemic and CRRT in ECLS patients.26-30 Investigations
support. are difficult to interpret as these patients have
The rapid restoration of cerebral perfusion high disease severity and clearer indications for
with VAD insertion has been associated with
372
when CRRT can help the cardiovascular patient Endocrine

on ECLS remain unclear.30
Glycemic control has been the subject of
Neurologic several large trials in critically ill adults and
children but controversy regarding the optimal
Neurologic monitoring with head ultra- approach persists. With regard to pediatric
sound (for patients with open fontanelles) and patients on ECLS, a recent study revealed that
assessing for risks of strokes or hemorrhage is both hyperglycemia and hypoglycemia, together
important for the cardiac ECLS patient. Neuro- recognized as dysglycemia, were not associated
logic complications may occur more commonly with increased mortality after adjustment for
in the congenital heart disease patient popula- weight, severity of illness, pre-ECLS lactate,
tion as many have baseline or prior neurologic and ECLS indication.34 The patients in this
injury or dysfunction in association to their heart study were disproportionately neonates and
disease that can impact decisions about moni- the ECLS use suggests that they had critical
toring and investigations after ECLS initiation. and unresolved medical issues. Other work
Seizures during the postoperative phase are has shown that the marginal contribution of
associated with poor late developmental out- hyperglycemia to adverse outcomes after pedi-
come31 and continuous EEG monitoring may be atric heart surgery is less for neonates and those
considered in patients who underwent neonatal with residual cardiac lesions.35 Taken together,
bypass, where seizures commonly follow.32,33 these studies suggest that tight glycemic control
Patients with a longer duration of hypotension for cardiac patients on ECMO is, at most, of
and poorly perfused states or those who have secondary importance.
had cardiac arrest may require EEG monitoring
due to risk of posthypoxic seizures. However, Nutrition
no evidence exists that treatment of subclinical
seizures changes neurologic outcome for these Few data regarding appropriate caloric
patients and further investigation is required. targets or optimal nutritional routes for patients
on ECLS exist. Recent work suggests that
Analgesia and Sedation early parenteral nutrition may be detrimental
in critically ill children.36 Studies have assessed
Strategies for minimizing use of sedation the success of enteral rather than parenteral
allow spontaneous breathing, participation nutrition.37-40 Hanekamp reported that with a
in care, and interaction with staff and family concerted effort 87% of neonates on VA-ECLS
members.3 Minimizing sedation is a growing received enteral nutrition and just over half of
trend for patients on ECLS, although this occurs those reached 40% of overall caloric goals by
more commonly with VADs. In many centers day 3 of ECLS. In general, published reports
common use of neuromuscular blocking agents suggest minimal risk to enteral feeding and po-
occurs for ECLS patients, but some centers tential benefit as well as cost savings in adults
are moving away from this practice. Potential on ECLS.37,38
benefits include better neurologic assessment
and possibly less long-term muscle weakness.1,3 Psychological Support
Having a child in intensive care exacts

an emotional toll on family that may increase
further with the need for ECLS support. It is
373
Chapter 32
important to maintain multidisciplinary sup-

port and open communication to the family to
identify issues of significance to them. Goals of
therapy should be discussed early and reviewed
regularly.18 Furthermore, the potential that
ECLS proves unsuccessful for patient recovery
needs to be communicated early. Discontinuing
ECLS support when the patient cannot reverse
the underlying disease is difficult and chal-
lenging (see Chapter 70). The involvement
of palliative care services may assist in family
support and aid the identification of important
care goals.
Conclusion
Managing patients with cardiovascular

disease using ECLS presents many challenges.
With a thorough understanding of the problems
unique to the population, knowledge of patient
specific anatomy and physiology, combined
with an understanding of ECLS and the inter-
action of this therapy with patient physiology
management is improved and the potential for
successful decannulation maximized.
374
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7. Hacking DF, Best D, d’Udekem Y, et al. circulation supported with extracorporeal
Elective decompression of the left ven- membrane oxygenation. J Thorac Cardio-
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Elective decompression of the left ven- rac Cardiovasc Surg. 2006;131:1114-21.
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Chapter 32
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2016;17:194-202. diac patients on extracorporeal membrane
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2013;14(5):S43-50. al. Recovery of renal function and sur-
19. O’Shea G: Ventricular assist devices: What vival after continuous renal replacement
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about postoperative management. AACN oxygenation. Pediatr Crit Care Med. 2011;
Adv Crit Care. 2012; 23:69–83. 12:153–158.
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devices. Crit Care Nurs Q. 2011; 34:200– Fluid overload and fluid removal in pedi-
207. atric patients on extracorporeal membrane
21. Litton KA: Demystifying ventricular assist oxygenation requiring continuous renal
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Extracorporeal membrane oxygenation, ceiving extracorporeal membrane oxygen-
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nutrition in critically ill children. N Engl J
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37. Pettignano R, Heard M, Davis R, et al: To-
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38. Hanekamp MN, Spoel M, Sharman-Koend-
jbiharie I, et al. Routine enteral nutrition
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39. Nellett M, Gregory MP, Lefaiver CA: Pilot
study evaluates nutrition for patients receiv-
ing mechanical circulatory support in the
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40. Umezawa Makikado LD, Flordelís Lasierra
JL, Pérez-Vela JL, et al: Early enteral
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Nutr. 2013;37(2):281-4.
377
33
Nursing Management of Neonates and Children with Cardiovascular Disease on

ECLS
Melissa B. Jones, MSN, APRN, CPNP-AC, Jenna Heichel, MSN, APRN, CPNP-AC,
Dorothy M. Beke, RN, MS, CPNP-PC/AC
Introduction the patient skin color, temperature of distal

extremities, capillary refill time and presence of
Venous-arterial extracorporeal life support edema, in addition monitoring of urine output,
(VA-ECLS) allows children time for recovery near-infrared spectroscopy (NIRS), and mixed
from congenital heart surgery or acute decom- venous saturation monitor on circuit. Heart
pensated heart failure from a cardiomyopathy or rate and rhythm may be trended, but does not
myocarditis. In addition to its use as a bridge to significantly influence oxygen delivery when
recovery, cardiac ECLS may serve as a bridge the patient is fully supported on VA-ECLS. A
to heart transplant or a long-term ventricular malignant ventricular dysrhythmia warrants
assist device. Children with cardiac disease treatment given that it may lead to inadequate
requiring VA-ECLS have complex needs and decompression of left side of the heart, causing
require astute nursing care. Careful nursing left atrial hypertension and pulmonary edema.
assessment and synthesis of several data points Both heart rate and rhythm should be optimized
are critical to recognizing inadequate oxygen when weaning from ECLS. Blood pressure
delivery, establishing appropriate and timely and presence or absence of a pulse pressure is
interventions, and preventing ECLS related important to monitor. A patient without a pulse
complications. pressure will display a mean pressure on the
Cardiac ECLS may be deployed urgently arterial line tracing.1 Low mean blood pressure
for a slowly deteriorating patient or emergently may indicate inadequate preload, low systemic
in a cardiac arrest setting during cardiopul- vascular resistance, sepsis, inadequate flow, or
monary resuscitation (ECPR). Well-defined poor cardiac function. Therapies to treat low
nursing roles in an emergency deployment, and mean blood pressures must target the underly-
meticulous routine nursing care of the patient ing etiology. Vasoactive medications may be
on ECLS are essential to positive outcomes. needed, particularly during ECLS weaning to
augment cardiac output. High mean arterial
Nursing Assessment blood pressure might be noted immediately after
ECPR cannulation when epinephrine from the
Nursing assessment and synthesis of lab resuscitation is circulated. High mean blood
data identify adequacy or inadequacy of oxygen pressures may preclude adequate flow, and
delivery when a patient is receiving ECLS and therefore warrant treatment with vasodilator
during the weaning phase. Nurses examine medications to reduce afterload.1 The presence
379
Chapter 33
of pulse pressure, or pulsatility, suggests ejec- Cannulation and establishing adequate

tion from the ventricle. A higher pulse pressure ECLS flow after the superior cavopulmonary
when weaning flow can be reassuring and may anastomosis or the Fontan operation can be
indicate readiness for decannulation. challenging. Two venous cannulas may be
Arterial blood gas and lactate measurements needed after the superior cavopulmonary anas-
are used to evaluate gas exchange and identify tomosis, one to decompress the superior vena
a metabolic or lactic acidosis. Evaluation of cava, and one for the inferior vena cava and to
end-organ function, specifically creatinine establish adequate flow.
and electrolytes to assess renal function, and
liver enzymes and coagulation studies to as- Respiratory Considerations
sess hepatic function, are routine and important
markers to trend. Though the focus of ECLS in the cardiac
patient is to support the heart, goals should
Cardiac Anatomy Considerations also include providing lung rest and avoiding
injurious effects of mechanical ventilation since
The venous cannula in patients with two the ECLS circuit usually delivers adequate oxy-
ventricle physiology, without intracardiac shunt- genation and ventilation. Nurses should expect
ing decompresses the right side of the heart; low ventilator settings to prevent volutrauma or
however, some blood circulates to the lungs barotrauma. Concurrently, higher positive end
and returns to the left side. The patient may expiratory pressure is used to avoid atelectasis,
develop left atrial hypertension and pulmonary as this may become a nidus for infection and
edema if there is minimal or no ejection from preclude weaning of flow when the heart has
the left ventricle (LV). The bedside nurse must recovered. The bedside nurse routinely as-
monitor for a narrow pulses pressure, suggesting sesses chest rise, breath sounds, and the nature
minimal or no pulsatility, increasing the risk of of endotracheal tube secretions.
inadequate decompression of the left heart. In
addition to pulmonary edema, an inadequately Prevention of Infection
decompressed left ventricle results in LV disten-
sion, increased wall stress, increased myocardial Prevention of nosocomial infections re-
oxygen demand,2 and decreased myocardial mains a primary aspect of daily nursing care,
perfusion. If this develops, pulmonary edema with infection rates reportedly 15 per 1,000 days
will be evident on chest radiograph, and the pa- on ECLS.1 As patients on mechanical circula-
tient may need a left atrial vent placed or atrial tory support have multiple invasive devices,
septostomy to allow left to right decompression. nurses must maintain meticulous care to prevent
Single ventricle patients with an arterial to bacterial entry. Infection may not present with
pulmonary artery shunt on ECLS may prefer- a fever, as the ECLS circuit controls patient
entially shunt blood from the arterial cannula temperature; therefore, clinical changes and
to the lungs and not the systemic circulation. laboratory data should be monitored closely to
Closely monitoring for adequate oxygen de- recognize early signs of infection.
livery is critically important in this setting. In a review of 141 pediatric patients sup-
Although the set flow rate may seem adequate, ported on ECLS across a 4-year period, O’Neill
it may prove inadequate to reach tissues if more and colleagues found that 26% developed
blood is being shunted to the lungs than to the nosocomial infections; among these patients,
body. 78% were cardiac patients supported on VA-
ECLS.3 Notably, 36% of patients with an open
380
Nursing Management of Neonates and Children with Cardiovascular Disease on ECLS
chest developed infections compared to 19% sary for a variety of reasons (see Chapter 71),
of patients with a closed chest. Risk factors forincluding development of tolerance, variability
infection while on ECLS include patients with in metabolism and clearance, altered organ
an open chest, prolonged ECLS course, cardiac blood flow in a nonpulsatile circulation, bleed-
disease as opposed to respiratory failure, and ing requiring frequent transfusions, or renal
the need for a major procedure while supported replacement therapy.4 The pharmacokinetics
on ECLS.3 of narcotics and sedatives can further be altered
Standardized nursing interventions should by the ECLS circuit due to the large volume of
be implemented to prevent nosocomial infec- distribution and drug sequestration in the circuit
tions. Ventilator associated pneumonia (VAP) tubing affecting drug absorption and clearance.4
may be minimized by elevating the head, The nursing team should also utilize nonphar-
routine mouth care utilizing an antimicrobial macological modalities to ensure patient com-
cleanser, and airway clearance with suctioning. fort, such as patient diversion, clustering cares,
Maintenance of urinary catheter care and daily and music therapy.1 While it remains patient
evaluation for possible discontinuation can help dependent, there is a growing trend to minimize
prevent urinary tract infections. To minimize paralytic as well as narcotic usage to reduce
central line associated blood stream infections muscular weakness and promote improved
(CLABSIs), nurses should perform proper neurologic evaluation.1
hand hygiene, and sterile dressing changes Guidelines for narcotic and sedative man-
with occlusive dressings. Many centers utilize agement in patients on ECLS currently remain
an antimicrobial patch (Biopatch®, Ethicon program specific. DeBerry et al. surveyed 46
US, LLC. Somerville, NJ) placed at the site centers to evaluate current practices when
of entry and designed to release chlorhexidine sedating patients on ECLS therapy. The sur-
gluconate (CHG) to prevent bacterial entry. vey results showed that fentanyl was the most
Finally, patients with chest cannulation often common first-line drug utilized and thought to
receive broad-spectrum antibiotic coverage to produce the most reliable effects (see Chapter
prevent a surgical site infection due to the high
71).5 Although studies show that as high as
risk from this cannulation.1 Equally prolonged 68% of fentanyl can bind to the ECLS circuit,
prophylaxis may simply facilitate the growth it remains frequently used due to its rapid
of resistant organisms highlighting the impor- onset of action, short half-life, and minimal
tance of meticulous wound care and infection hemodynamic effects. Fifty seven percent of
prevention. centers describe a targeted sedative level as
“movement with stimulation,” 35 % target goal
Neurologic Considerations of “spontaneous movement,” and 22% describe
the patient sedation goal “without movement.”
Patients usually need narcotics and/or Interestingly, 70% of the surveyed centers re-
sedatives while on ECLS to promote comfort ported that they do not routinely utilize muscle
and minimize pain. Nursing assessment of relaxants, administering them only as needed.5
the patient pain or discomfort is essential for Though frequent neurologic examinations
implementing the appropriate interventions. are challenging and sometimes limited because
Dependent on the hemodynamic status, can- of sedation requirements on ECLS, they are
nula placement, and activity level, short-term critically important given the risk of stroke or in-
neuromuscular blockade may be warranted tracranial hemorrhage, particularly in neonates.
to maintain patient safety. Increased doses of Primary neurologic examination for patients on
medications while on ECLS may be neces- ECLS includes evaluation of pupil size, reactiv-
381
Chapter 33
ity to light, and equality, fontanelle assessment stretching to preserve range of motion and
(if applicable), response to tactile and painful heel-lift boots to prevent foot drop is important.
stimuli, and cough and gag reflexes. Nurses There is a growing trend, mainly for patients on
should apply artificial eye lubrication to prevent venovenous ECLS that promotes mobilization,
corneal abrasions if the patient is paralyzed and and even ambulation, to avoid debilitation and
unable to produce natural lubrication. Cerebral ultimately shorten recovery times post-ECLS
NIRS has emerged as a helpful tool to trend ce- therapy.2 Patient complexity and safety should
rebral oxygenation and perfusion.1 Changes in be evaluated with a multidisciplinary approach
heart rate and blood pressure may also indicate when determining rehabilitation interventions.
patient level of responsiveness. The nurse should ensure day and night ori-
Neurological complications including entation, particularly for older patients by dim-
cerebral infarction and intracranial bleed oc- ming the lights at night, using natural light when
cur commonly in patients on ECLS, with a possible during the day, clustering care, and
reported rate at 12.9%.6 Nurses assist techni- avoiding excessive noise stimulation. Playing
cians in obtaining neurologic imaging such as soft music may help mitigate extraneous noise
head ultrasounds, computed tomography (CT) and provide patient comfort. Creating a daily
scans, or electroencephalograms (EEGs). The schedule and routine with patient interventions
increasing use of portable CT scan devices has and anticipated therapy also promotes patient
allowed improved imaging opportunities to be orientation. Early identification of delirium
safely obtained at the bedside. facilitates timely and appropriate interventions.
Rehabilitation Integumentary Considerations
Prolonged immobilization results in muscle While nutrition, fluid status, and perfusion
and bone atrophy leading to weakness and contribute to healthy skin integrity, the nursing
contractures. In fact, large losses of both team has a paramount role in preventing skin
muscle strength and mass begin as early as breakdown. Pressure ulcers occur in over 10%
10 days of immobilization on ECLS.7 Early of critically ill children with an increased rate
rehabilitation increases ventilator-free days, in those patients receiving ECLS.6 Hospitaliza-
results in shorter hospitalizations, and improve tion treatment costs for pressure ulcers range
outcomes at discharge.7 However, even the from $37,800 to $70,000 with total annual costs
most comprehensive of ECLS guidelines do reaching $11 billion in the U.S.8 Turning or
not have standardized rehabilitation programs changing patient position can be difficult while
for such patients. Therefore, the nursing team on ECLS, particularly cannula site hemorrhage,
should coordinate with both the intensive care or high positioning of the ECLS cannulas.
unit (ICU) team, and physical and occupational Meticulous care should be maintained by the
therapists, to create an individualized approach nurses in conjunction with the ECLS Specialist
to safely encourage early range of motion and when turning patients to avoid cannula move-
muscle strengthening. ment and bleeding; however, position changes
Additional complications of immobiliza- are essential to alleviate key pressure points,
tion may include nerve compression injury, and thus prevent pressure ulcer formation and
skin breakdown, and decreased bone mineral shear friction.
density.6 Hand and foot splints maintain joints Additional nursing interventions may help
in anti-deformity position and static stretching reduce the rate of skin breakdown and promote
to prevent contractures. Similarly, soft tissue wound healing. Skin friendly products should
382
be utilized to support turning and limit skin blood products, and set up a sterile field and
breakdown, including sacral patches, gel pads equipment for the surgeons to cannulate.
under pressure points, as well as fluidized po- ECPR is a low frequency, high risk pro-
sitioners (Z-flo TM Medline Industries Inc. Mundelein, cedure requiring seamless coordination of the
IL), and turning wedges. Specialized air-filled ICU team and ECLS team. The two major goals
mattresses designed to reduce the incidence of include providing excellent CPR and quickly
pressure ulcers by redistributing pressure may reestablishing circulation with ECLS.9 Special-
be utilized. Turning patients with hemodynamic ized training and simulation of these events are
instability or with critical cannula placement vital to the success of an ECLS program. Su et al.
presents a significant safety risk. Therefore, found that delineating roles and simulating rapid
frequent, subtle position changes to “off-load” deployment with the entire team significantly
pressure points, is needed.8 The most significant reduced the time from CPR to ECLS flow.10
elements in development of a pressure ulcer is Nursing experience also impacts the success
prolonged pressure over a bony prominence of the deployment. In a retrospective review,
such as the occiput, coccyx or hip, and contact Gaies et al. found that unsuccessful resuscita-
with medical devices including the ECLS can- tion, (no ROSC or ECLS cannulation), was
nulas.8 Patients should be positioned on clean, more likely when the cardiac intensive care unit
dry linen and avoid lying on medical devices nurse had less than one year of nursing experi-
and equipment.1 Nurses should perform fre- ence.11 Education and simulation opportunities
quent evaluations of skin integrity and work focusing on role definition and teamwork are
closely with the wound care team for effective key to developing high functioning, well-
prevention and proper management of skin coordinated teams.
breakdown.
Family Support
Nursing Roles in Rapid Deployment
One of the fundamental aspects of nursing
Bedside nurses are often the first to recog- care when managing an ECLS patient centers on
nize and respond to a deteriorating patient by providing compassionate family support. The
activating the team for resuscitation (see Chap- predominant emotions for these families are fear
ter 27). The goal of the resuscitation includes, of and anxiety.12 Nurses must orient parents to the
course, rapid return of spontaneous circulation equipment, provide expectations for care and
(ROSC); however, if that proves impossible, provide regular family education. Family stress-
than the decision can be made to deploy ECLS.9 ors may include language or cultural barriers,
Once decided, several nurses are needed for distress from being away from other children for
successful extracorporeal cardiopulmonary an extended period of time, financial concerns
resuscitation (ECPR). Clearly defined roles and limited resources.1 The nursing team assists
and delineation of responsibilities ensures that families in coordination of care with chaplain
tasks are completed and not duplicated. One services, social work, and child life specialists.
nurse may be responsible for assigning roles to Nurses are in a position to involve parents in
the team, and specific roles may include nurses patient care and help them find ways to comfort
to prepare medications, administer medications, their child. Regular family meetings with the
perform chest compressions, monitor adequacy bedside nurse and other members of the inter-
of compressions, record the events, prepare the disciplinary care team should be encouraged to
defibrillator, prepare the patient for cannulation, set realistic family expectations, and provide
ensure the timely availability of appropriate timely information related to patient condition.
383
Chapter 33
Families should be encouraged to participate in

daily patient rounds with opportunities to ask
questions and express concerns to promote both
trust and family involvement in decisionmak-
ing.13 Discussions regarding future plans and
expected outcomes as well as life after ECLS
should be emphasized, as studies have shown
that these concerns are frequent and prevalent
in these families.12 Nursing management of
patients on ECLS can be both physically and
mentally demanding, requiring a well-trained
nursing team as well as integration from all
disciplines to create a unified approach.9
384
Reference 10. Su L, Spaeder MC, Jones MB, et al. Imple-

mentation of an extracorporeal cardiopul-
1. Schwartz SM, Schmidt A. Medical and monary resuscitation simulation program
nursing care of the child on mechanical reduces extracorporeal cardiopulmonary
circulatory support. Pediatric Crit Care Med resuscitation times in real patients. Pediatric
2013;14(5 Suppl 1):S43-50. Crit Care Med. 2014;15(9):856-860.
2. Raleigh L, Ha R, Hill C. Extracorporeal 11. Gaies MG, Clarke NS, Donohue JE, et
Membrane Oxygenation Applications in al. Personnel and unit factors impacting
Cardiac Critical Care. Semin Cardiothoac outcome after cardiac arrest in a dedicated
Vasc Anesth 2015;19(4):342-352. pediatric cardiac intensive care unit. Pedi-
3. O‘Neill JM, Schutze GE, Heulitt MJ, atric Crit Care Med. 2012;13(5):583-588.
Simpson PM, Taylor BJ. Nosocomial 12. Curley MA, Meyer EC. Parental experience
infections during extracorporeal mem- of highly technical therapy: survivors and
brane oxygenation. J Intensive Care Med nonsurvivors of extracorporeal membrane
2001;27(8):1247-1253. oxygenation support. Pediatric Crit Care
4. Shekar K, Roberts JA, Mullany DV, et Med. 2003;4(2):214-219.
al. Increased sedation requirements in pa- 13. Michelson KN, Clayman ML, Haber-Barker
tients receiving extracorporeal membrane N, et al. The use of family conferences in
oxygenation for respiratory and cardiore- the pediatric intensive care unit. J Palliat
spiratory failure. Anaesth Intensive Care Med. 2013;16(12):1595-1601.
2012;40(4):648-655.
5. DeBerry BB, Lynch JE, Chernin JM,
Zwischenberger JB, Chung DH. A sur-
vey for pain and sedation medications
in pediatric patients during extracorpo-
real membrane oxygenation. Perfusion.
2005;20(3):139-143.
6. Thiagarajan RR, Teele SA, Teele KP, Beke
DM. Physical therapy and rehabilitation
issues for patients supported with extra-
corporeal membrane oxygenation. J Pediatr
Rehabil Med 2012;5(1):47-52.
7. Zebuhr C, Sinha A, Skillman H, Buckvold
S. Active rehabilitation in a pediatric extra-
corporeal membrane oxygenation patient.
PM R 2014;6(5):456-460.
8. Clements L, Moore M, Tribble T, Blake J.
Reducing skin breakdown in patients receiv-
ing extracorporeal membranous oxygen-
ation. Nurs Clin North Am 2014;49(1):61-
68.
9. Ryan J. Extracorporeal membrane oxygen-
ation for pediatric cardiac arrest. Crit Care
Nurse. 2015;35(1):60-69.
385
34
Weaning Pediatric Cardiac ECMO
Charles Larson, MDCM, FRCPC, Roberto Chiletti, MD, FCICM, Yves d’Udekem, MD, PhD, FRACS
Introduction factors associated with the weaning process

itself. Therefore, ECMO weaning remains an
Survival to decannulation of pediatric art rather than a science and the clinician must
cardiac ECMO is 67% (ELSO Registry report rely on common sense, expert opinion, and
January 2016). Although various definitions experience to navigate this process.
have been used, successful ECMO weaning is
generally defined as survival after discontinua- When to Attempt Weaning
tion of ECMO without the need for reinitiation
of mechanical support for the next 48 hours. A The Decision Depends on Local Factors
previous adult definition used a timeframe of
30 days,1 which may not be as valid in children; The timing of ECMO weaning balances a
pediatric patients not uncommonly require re- number of risks. The performance of the team
peated elective mechanical support for repair of in ECMO support and in intensive care sup-
congenital heart lesions, and factors unrelated port determines these risks. A team confident
to ECMO support frequently determine 30-day in supporting children for prolonged periods
mortality. without significantly adding to the burden of
In most instances, ECMO support is re- complications will support a patient longer,
moved at a stage when the patient remains and the opposite holds true. The capacity to
fragile in their course of recovery. Therefore, the provide senior level intensive care to critically
timing and manner of weaning ECMO support ill patients off ECMO, influenced for instance
crucially impact the chances of survival. Today, by variable night cover, will also influence the
little evidence has been published to help the timing of ECMO weaning.
clinician identify which parameters predict
patient readiness to be separated from ECMO The Decision Depends on the Length of
and even fewer recommendations exist in terms Support
of speed of weaning and acceptable amount
of inotropic support on the best strategy to Most myocardial recovery occurs in the first
achieve decannulation. Studies have helped to two weeks of support. Additional gains become
prognosticate death following ECMO support, less likely past this period, a fact that should
but most of the identified parameters relate to prompt conversations about how long support
underlying patient characteristics rather than should be offered and whether transition to VAD
387
Chapter 34
is indicated, as a bridge to recovery or cardiac of these patients may benefit from longer sup-
transplantation. port to recover.
ECMO and identification of a culprit le-
The Decision Depends on the Indication for sion. ECMO can be indicated as a bridge to
Support identification and repair of a lesion. Examples
include undiagnosed critical aortic valve ste-
The clinical course of myocardial dysfunc- nosis and intractable cyanosis despite balloon
tion is a major determinant of the expected tim- septostomy in patients with transposition of
ing of recovery and ultimate removal of ECMO. the great arteries and pulmonary hypertension.
Recovery from primary myocardial dysfunc- In the course of ECMO support after cardiac
tion, as in the case of myocarditis, occurs over surgery, residual lesions may be identified, such
weeks to months or not at all, and may require as vessel or valvar obstruction or residual shunt-
conversion to VAD as a bridge to recovery or ing. In these instances, the patient can often be
transplantation. With the current commercially immediately weaned after repair of the residual
available VAD devices, it is increasingly clear lesion, depending on the patient’s myocardial
that, in any age group, ECMO may not be the and respiratory function.
best form of mechanical support beyond two Recovery from postoperative events. Indica-
weeks if sufficient myocardial recovery has not tion for support may be a sudden adverse event
occurred.2 Mortality in pediatric patients with in the early postoperative period such as bleed-
myocarditis supported with ECMO increases by ing or tamponade following line removal, shunt
some 15% for each additional week of support, obstruction, airway compromise, or refractory
and survival beyond 4 weeks of support was arrhythmia. ECMO may be necessary as part of
not observed in a large ELSO database review.3 the resuscitation. The timing of ECMO weaning
Recovery from myocardial dysfunction after will depend on resolution of the insult and the
cardiac surgery. Myocardial injury after open degree of organ ischemia from the event.
heart surgery consists of inflammatory, isch-
emia-reperfusion and surgical insults. The peak The Decision Depends on the Team’s
effect of these factors on myocardial function is Perception of Prognosis
felt to be within the first 24 hours,4 although the
evidence to support this assumption is sparse. ECMO is often emergently initiated with-
As a general rule, we would not consider ECMO out a full understanding of the deterioration’s
removal until the patient has received at least 48 precipitants. It may become apparent that fur-
hours of support with adequate tissue oxygen ther support is futile based on the underlying
delivery, LV decompression, hemostasis, cor- disease or ECMO complications. The percep-
rection of metabolic disturbances, and exclusion tion of prognosis often differs between team
of residual lesions. members, and these decisions benefit from a
Recovery from cardiac surgery with preex- team approach.
isting myocardial injuries. ECMO is at times
necessary to recover from lesions predating sur- The Decision may Depend on the Capacity to
gery such as late presentation of transposition of go back on Support
the great arteries and intact ventricular septum
with deconditioned systemic ventricle, coronary In some instances, the vascular access for
abnormalities, and left ventricular outflow tract ECMO support has been compromised. An
obstruction with ventricular dysfunction. Some example is the infant with a previous healed
sternotomy supported by neck cannulation.
388
Recannulation of the same neck vessels could Currently, no biomarkers have been shown
prove difficult or impossible. In this situation, to be predictive of myocardial recovery in pa-
greater certainty of successful weaning may be tients on ECMO for cardiogenic shock.7
necessary before ECMO removal.
Weaning Trial
Predictors of Successful Weaning
For clinical parameters and echocardiog-
Weaning ECMO should only commence raphy to reflect accurately adequate cardiac
with signs of myocardial recovery and adequate function off mechanical support, they should
resolution of complicating factors such as the be evaluated as part of a weaning trial with
systemic inflammatory response and pulmonary optimized myocardial loading conditions and
dysfunction. Signs of myocardial recovery multidisciplinary input. Under echo guidance,
include increasing pulse pressure, increasing flows are incrementally decreased with admin-
systolic pressure, rising ETCO2 (in children istration of volume and restoration of normal
without systemic to pulmonary shunts) and ventilation. To minimize the risk of clot forma-
improving function on echocardiography.1,5,6 tion, we generally do not decrease flows to less
Function measured by echocardiography while than 200 ml/min except very briefly. However,
on full ECMO flows does not predict myocar- the risk of circuit clot formation when reduc-
dial performance under conditions of increased ing ECMO blood flow depends upon multiple
preload and decreased afterload encountered factors, including the level of anticoagulation,
after decannulation, and should only be used existing clot burden, circuit size, and circuit
as a trend. Echocardiography under low flow complexity. The use of a bridge and clamp-
conditions as part of a weaning trial has been ing the cannulae proximal to the patient allow
shown to be predictive of successful ECMO complete separation from support for brief pe-
decannulation in adults with cardiogenic riods; however, bridges can increase the risk of
shock,1 and represents a cornerstone of most circuit clots by being sites of low and turbulent
pediatric weaning protocols. The target is not flow. Patients whose systemic to pulmonary
near-normal or normal ventricular function shunts that have been partially or completely
but rather enough function to allow adequate occluded as part of the extracorporeal support
organ oxygen delivery, a cutoff that remains strategy represent a special case of weaning. In
ill-defined in the pediatric population and may such cases, readiness to wean must be judged
vary between patients. without decreasing flows, as this will lead to
In patients whose support includes a left desaturation.
atrial vent or atrial septostomy, lower left atrial Throughout the weaning, adequacy of
vent flows and a drop in circuit mixed venous ventricular function is assessed by echocar-
oxygen saturation can herald left ventricular diography, cardiac output, oxygenation, and
recovery; the ability of the left ventricle to in- ventilation. If myocardial recovery is judged
crease native ejection when the left atrial vent is sufficient, the patient is optimized for decan-
clamped or removed are also signs of myocar- nulation. No pediatric studies have examined
dial recovery. Venting should be removed as a echocardiographic predictors of successful
step before weaning off ECMO. We have been ECMO weaning, and the applicability of adult
suspicious that thromboembolic events may oc- findings is limited by differences in patient size,
cur at the time of ventricular recovery, provoked difficult image acquisition in small patients with
by suck down of the ventricular cavities. open sternums, and variable cardiac anatomy. In
a study of 21 adults supported with VA-ECMO
389
Chapter 34
for cardiogenic shock, qualitative assessment of oxide should be initiated. The patient should be
ventricular function and dilatation by continu- euvolemic. We would recommend that patients
ous transesophageal echocardiography during with single ventricle physiology have a hemo-
an extensive weaning protocol that included globin above 14 g/dl. Lungs should be recruited
volume and inotropic challenges, was predictive with attention to tidal volumes and the chest
of successful decannulation.8 In a study of 51 radiograph. The endotracheal tube should be
adults supported with VA-ECMO for cardiogen- sized and appropriately positioned to facilitate
ic shock, positive predictors of ECMO weaning secretion clearance and proper ventilation with
included left ventricular ejection fraction >20- an acceptable leak. Metabolic abnormalities
25%, velocity time integral >10 cm and lateral should be corrected, with special attention to
mitral annulus peak systolic velocity >6 cm/s.1 potassium, calcium, magnesium, phosphate,
Some teams advocate the use of Pump and glucose. Pacing wires should be attached
Controlled Retrograde Trial Off (PCRTO) to the pacemaker and their function tested. An-
VA-ECMO in order to reduce the risk of clot ticoagulation should be titrated to minimize the
formation in the circuit. The additional benefit risk of clot formation in the circuit during the
of this technique is that it imposes an additional reduction in blood flow. Thrombocytopenia and
cardiac output burden on the patient’s heart and hypofibrinogenemia must be corrected in an-
therefore provides reassurance that the patient ticipation of surgical manipulation. In patients
has recovered sufficiently to decannulate.9 supported with continuous renal replacement
therapy via the ECMO circuit, the necessary
Speed of Weaning vascular access should be ensured if ongoing
renal support is anticipated.
It is unclear how a rapid wean in ECMO
flows vs. a slower increase in myocardial load- Decannulation
ing conditions might affect the chances of suc-
cessfully weaning off ECMO. Particularly in Organization
cases of longstanding preoperative ventricular
dysfunction or deconditioned ventricles being VA-ECMO decannulation can be done in
“retrained” with ECMO; one could wonder ICU or the operating room. Personnel, equip-
whether a more progressive increase in myo- ment, medications, and blood products are orga-
cardial workload might be favorable, although nized for the decannulation procedure. Compli-
there is little evidence to support such an asser- cations such as low cardiac output, pulmonary
tion. Conversely, in instances of rapid recovery hypertension, bleeding, arrhythmias, and the
of ventricular function, a rapid wean is recom- need to reinitiate ECMO must be anticipated.
mended. In the extreme case of partially clipped All patients should have a defined plan in the
systemic to pulmonary shunts, weaning must be event of clinical deterioration after discontinu-
done from full support. ation of ECMO, including whether reinitiation
of ECMO is indicated.
Optimizing for Decannulation The timing of decannulation should take
into consideration the availability of resources
Optimization should start several hours in the event that reinitiation of ECMO is
prior to any weaning trial. Low-dose inotropes required. In particular, in institutions where
and vasopressors should be started with enough surgeons cannulate and are not in-house over-
time to reach the patient. In patients at risk of night or where a perfusionist is required in the
pulmonary hypertensive crises, inhaled nitric early stages of ECMO reinitiation, decannula-
390
tion should take place early in the day. Spare dissection, and undue bleeding may destabilize
cannulae should be available in the room in the patient, and should be avoided especially in
case recannulation is necessary. A spare circuit unstable patients.
should be prepared if the current one seems At this stage, heparin infusion is stopped
compromised by accumulation of clots in the and flows are further weaned. The patient is
tubing. (Table 34-1) observed for a period lasting between a few
minutes and up to 20 minutes. This duration
Surgical Perspectives of observation depends on the confidence in a
successful wean, the anticoagulation status, the
When the same circuit will be used to re- existence of a shunt, and whether clots have
cannulate for ECMO if necessary, the tubing been observed in the circuit. During this time,
beyond the connector attached to the cannulae the snares are prepared for cannulae removal. As
should be prepped and placed in the operative soon as the team feels confident of a success-
field. Skin incisions are reopened for periph- ful outcome, the cannulae are removed. If the
eral cannulation and the membrane is removed circuit appears reusable, both parts of the cir-
for central cannulation. The cannulation sites cuit are reconnected and recirculation of blood
are accessed before ECMO flows are weaned. through the circuit is initiated immediately upon
Swabs can be taken for gram stain and culture. cannulae removal.
Clots are removed, especially around the can- Chest closure can be contemplated in cer-
nula insertion sites. In peripheral cannulation, tain situations where ventricular function was
some dissection of the vessels above and below never more than minimally compromised. In
the cannulation site may be necessary. The all other cases, the chest should be left opened
principles guiding the surgeon at the time of and the pursestrings for cannulation should be
ECMO decannulation should be to cause mini- snared and left in the chest. In some instances,
mal harm. Manipulation of the heart, extensive bleeding around the cannulation sites neces-
sitates ligation of the cannulation pursestrings,
in which case it may be wise to position new
Table 34-1. Sample decannulation checklist. pursestrings. If the patient has been supported
more than 2-3 days, the tissues at the edge of
Decannulation Checklist the wounds may no longer be viable and should
be debrided at the time of wound closure. If
Inotropes and vasopressors in line
the chest remains open, debridement should
Anesthetic and resuscitation drugs prepared be left until chest closure to avoid blood loss
Temporary pacemaker attached to wires and checked and instability.
For peripheral cannulation, vessel recon-
Euvolemic state, volume expanders drawn up
struction takes place at this stage. Depending
Packed red blood cells available on cannulation technique, reconstruction may
Platelets 80x109/L and fibrinogen 1.5g/L involve simple tying of the pursestring, direct
Endotracheal tube checked
closure of the incision, or oblique incision of
both vessel ends with end-to-end anastomosis.
Adequate pulmonary recruitment Exceptionally, when reconstruction appears
Normal electrolytes infeasible vessels are tied off. Attention should
Established plan if decannulation fails be paid to the cranial segment of the vessels.
Spare cannulae of the same size in the room Before reconstruction, care should be taken to
Spare ECMO circuit prepared
391
Chapter 34
let this end of the vessel bleed back to avoid trajectory of ECMO related complications,
embolization of an occult clot. multiorgan failure and death.
Risk factors for mortality in ECMO patients
Medical Management include renal failure, lactatemia and acidosis at
24 hours of support, bleeding, and initiation of
Unless the plan does not include offering ECMO in ICU vs. directly from cardiopulmo-
further mechanical support after decannulation, nary bypass (see also Chapter 32).11,12 These
the patient should not be weaned off ECMO on variables reflect inadequate tissue oxygen de-
maximal inotropic and vasopressor support, as livery prior to initiation of, or during ECMO,
patients often require an increase in hemody- and suggest that modifications to the timing of
namic support in the hours following decan- initiation of ECMO, the level of support, and
nulation. In the 4-6 hours after decannulation, meticulous hemostasis help to maximize the
the patient is kept sedated and paralyzed, and odds of successful decannulation.
blood gases are monitored hourly. Certain patients with marginal ventricular
function and difficulty weaning off VA-ECMO
Failure to Wean may benefit from levosimendan given 24-48
hours prior to a weaning trial. Levosimendan is
Some children demonstrate an inadequate a calcium sensitizer with inotropic and vasodi-
trajectory of cardiovascular and pulmonary latory properties, and does not impair diastolic
recovery to achieve successful ECMO wean- function or increase myocardial oxygen con-
ing. Such children need an early and aggressive sumption. Due to active metabolites, effects per-
approach to investigation and management of sist for 7-9 days after dosing.13 Levosimendan
residual lesions, inadequate support, infection, reduces other inotrope requirements in pediatric
and pulmonary disease. Echocardiography, patients with severe heart failure.14 In a study
chest ultrasound, CT angiography, cardiac of six adults on VA-ECMO, levosimendan ad-
catheterization, and electrophysiology stud- ministered 24 hours prior to weaning facilitated
ies can reveal lesions amenable to surgical or ECMO removal and reduced inotropic require-
interventional correction, such as effusions, ments after decannulation compared to histori-
valvar regurgitation, outflow tract obstruction, cal controls.15 In our institution, levosimendan
coronary abnormalities, determinants of bal- is routinely administered to patients who fail a
ance of pulmonary and systemic blood flow, first ECMO wean due to marginal ventricular
and arrhythmias. In a contemporary series of function.
119 pediatric patients supported on ECMO In patients with primary myocardial dys-
after cardiac surgery, 28% had hemodynami- function, such as myocarditis or cardiomyopa-
cally significant residual lesions that required thy, who fail to show adequate recovery, VAD
correction for successful decannulation.10 Of support should be considered within 10 days.
these residual lesions, over 70% were detected Forcing a wean off mechanical support in such
by cardiac catheterization but not echocardiog- patients risks end-organ damage secondary to
raphy. Additionally, early detection of residual low cardiac output, which can exclude them
lesions within the first 3 days of ECMO support from future VAD or transplant candidacy. Con-
was associated with a higher rate of successful versely, continuing ECMO support exposes
decannulation and better survival to hospital patients to excess risk of complications.
discharge. These findings illustrate that with- Pulmonary edema and pneumonia can delay
out timely diagnosis and correction of residual successful weaning.16 In the setting of recovered
lesions, patients risk following a predictable myocardial function with persistent severe
392
pulmonary disease, conversion to VV-ECMO

should be considered, especially in the setting
of peripheral VA-ECMO.
Conclusion
Separating from ECMO is a complex pro-

cess that is affected by multiple patient, circuit,
and system factors, and requires careful plan-
ning and assessment starting from the time of
ECMO initiation. Early initiation of ECMO and
meticulous attention to the adequacy of support
facilitates successful weaning success. In chil-
dren who fail to follow the expected course of
myocardial recovery, an early and aggressive
approach to the diagnosis and management of
residual lesions should be undertaken. Finally,
to avoid complications, children who fail to be
weaned off ECMO within 10 days should be
considered for alternative forms of support if
indicated.
More research is required to elucidate
which parameters predict successful separation
from VA-ECMO, including clinical, imaging,
and biological markers. Additional investiga-
tion of strategies and therapies to facilitate
ECMO weaning is required.
393
Chapter 34
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brane oxygenation (ECMO) weaning after 9. Westrope C, Harvey C, Robinson S, Speg-
assistance for refractory cardiogenic shock. giorin S, Faulkner G, Peek GJ. Pump con-
Intensive Care Med. 2011;37(11):1738- trolled retrograde trial off from VA-ECMO.
1745. ASAIO J. 2013 Sep-Oct;59(5):517-9.
2. d’Udekem Y, Shime N, Lou S, MacLaren 10. Agarwal HS, Hardison DC, Saville BR, et al.
G. Recurrent or Prolonged Mechanical Residual lesions in postoperative pediatric
Circulatory Support. Pediatric Critical Care cardiac surgery patients receiving extracor-
Medicine. 2013;14:S69-S72. poreal membrane oxygenation support. J
3. Rajagopal SK, Almond CS, Laussen Thorac Cardiovasc Surg. 2014;147(1):434-
PC, Rycus PT, Wypij D, Thiagarajan RR. 441.
Extracorporeal membrane oxygenation 11. Kumar TKS, Zurakowski D, Dalton H, et
for the support of infants, children, and al. Extracorporeal membrane oxygenation
young adults with acute myocarditis: A in postcardiotomy patients: factors influ-
review of the Extracorporeal Life Support encing outcome. J Thorac Cardiovasc Surg.
Organization registry*. Crit Care Med. 2010;140(2):330-336.e332.
2010;38(2):382-387. 12. Duncan BW, Hraska V, Jonas RA, et al.
4. Wernovsky G, Wypij D, Jonas RA, et al. Mechanical circulatory support in children
Postoperative course and hemodynamic with cardiac disease. J Thorac Cardiovasc
profile after the arterial switch operation in Surg. 1999;117(3):529-542.
neonates and infants A comparison of low- 13. Pathak A, Lebrin M, Vaccaro A, Senard JM,
flow cardiopulmonary bypass and circula- Despas F. Pharmacology of levosimendan:
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35. effects. J Clin Pharm Ther. 2013;38(5):341-
5. Park B-W, Seo D-C, Moon I-K, et al. Pulse 349.
pressure as a prognostic marker in patients 14. Namachivayam P, Crossland DS, Butt WW,
receiving extracorporeal life support. Re- Shekerdemian LS. Early experience with
suscitation. May 2013:1-5. Levosimendan in children with ventricular
6. Naruke T, Inomata T, Imai H, et al. End-tidal dysfunction*. Pediatric Critical Care Medi-
carbon dioxide concentration can estimate cine. 2006;7(5):445-448.
the appropriate timing for weaning off from 15. Affronti A, di Bella I, Carino D, Ragni
extracorporeal membrane oxygenation for T. Levosimendan May Improve Weaning
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2010;51(2):116-120. ASAIO Journal. 2013;59(6):554-557.
7. Luyt C-E, Landivier A, Leprince P, et al. 16. Chaturvedi RR. Cardiac ECMO for biven-
Usefulness of cardiac biomarkers to predict tricular hearts after paediatric open heart
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8. Cavarocchi NC, Pitcher HT, Yang Q, et al.
Weaning of extracorporeal membrane oxy-
394
35
Outcomes, Complications, and Followup of Neonates and Children with

Cardiovascular Disease
Kate L. Brown, MD, Aparna U. Hoskote, MD
Introduction velopmental outcomes, and quality of life are

not collected by ELSO; and for children with
Over the last decade, extracorporeal mem- cardiovascular disease on ECLS, are less well
brane oxygenation (ECMO) to support children delineated than for neonatal ECMO survivors.
with cardiovascular disease has increased rela- Evidence based protocols for the evaluation and
tive to respiratory indications in particular for followup of children at risk of developmental
neonates,1 and while the ECMO rate within disorders, informed by outcome data, are impor-
congenital heart surgery programs averages tant for the purposes of quality improvement.9
2-3%,2 children with more severe forms of Awareness of the possibility of neurological
congenital heart disease,2 undergoing complex injury in the intensive care unit setting may
cardiothoracic surgery such as stage one for enable the use of neuroprotective measures.
hypoplastic left heart syndrome2 or cardiotho- Protocols for followup of children with cardio-
racic transplants3 and children in cardiac arrest vascular disease undergoing ECMO should be
termed ECPR4 are increasingly represented prioritized, given that the accumulation of more
within this population. Outcomes of ECMO detailed outcome data will inform future use of
for children with cardiovascular disease are in ECMO, enabling children with developmental
general worse than for respiratory indications, needs to access early intervention and support
and many ECMO complications that are linked services more readily.
to poor outcome appear more frequently in
children with cardiovascular diseases, includ- Early Survival Outcomes
ing infections,5 bleeding and thrombosis,6 renal
failure,7 and acute neurological events8; hence, The overall survival rate to hospital dis-
a clear understanding of ECMO outcomes in charge in children with cardiovascular disease
this high-risk population, risk factors for poor supported with ECMO varies by age, indication
outcome, and strategies to improve outcomes for ECMO, the timing of deployment, the type of
are increasingly important. cardiac disease, and the operative repair or pal-
While short-term survival rates to hospital liation.2 Overall survival to hospital discharge
discharge are available from the Extracorporeal rates for children with cardiovascular disease
Life Support Organization (ELSO) Registry,1 supported with ECMO based on ELSO Registry
data regarding important longer-term outcomes data1 are 51% in children (aged >30 days to 18
including cardiorespiratory function, neurode- years) and 41% in neonates (aged <30 days).
395
Chapter 35
The ELSO Registry shows patients with cardiac with Fontan physiology experienced early
disease who receive ECPR have worse out- survival of 36%. Based on the ELSO Registry,
comes than those supported without prior CPR 230 ECMO patients with Fontan circulation
(41% in both neonates and children). Single experienced 35% survival to discharge19 and
center reports of survival following ECMO 103 ECMO patients with Glenn circulation had
in children undergoing cardiothoracic surgery 41% survival to discharge.20 These poor out-
have shown higher survival rates than those comes in cavopulmonary connection patients
published in the ELSO Registry10-12 possibly may be linked to pre-ECMO cardiorespiratory
reflecting local practice protocols or case mix in and other organ dysfunction, multiple venous
those centers that have publicized their results. cannulations of sites to provide adequate car-
Evidence suggests that larger volume programs diac decompression, and persistence of high
that potentially gain greater experience with this systemic venous pressure despite adequate
high-risk population may achieve better early ECMO support; these contribute to ECMO
survival rates.13 complications and multiple organ dysfunction.
Single Ventricle Patients Heart Failure and Transplantation
ECMO support after neonatal stage one ECMO used for patients with acute fulmi-
palliation (S1P) for hypoplastic left heart syn- nant myocarditis is associated with the highest
drome is now the most frequent postoperative survival rates in children with cardiac disease,
indication for ECLS, with a rate of 17% in the ranging between 61 and 80%.21,22 The reversible
Society of Thoracic Surgeons (STS) database, nature of myocardial dysfunction and short time
but a high early mortality of 57%.2 Single center frame for recovery makes ECMO a very suit-
reports state that ECMO indications include able mechanical support strategy for patients
support of low cardiac output, acute hypoxemia, with cardiogenic shock after myocarditis. The
cardiac arrest, and arrhythmia, with poorer exception to this rule is the neonatal enterovi-
outcomes linked to cardiac failure, organ dys- ral myocarditis which appears to have a worse
function, and ECMO complications.14-16 In S1P prognosis23 with survival of only 33% based on
patients with an arterial shunt, effective use of the ELSO Registry.
ECMO necessitates management of the shunt The availability of newer ventricular assist
for pulmonary blood flow during ECMO.17 A devices that provide longer durations of support
series of patients receiving ECMO following have improved outcomes for children requir-
S1P with an aortopulmonary shunt reported ing mechanical circulatory support as a bridge
that complete shunt occlusion was associated to cardiac transplantation.24 Previous reports
with dismal survival.17 Higher ECMO flows in of ECMO as the primary bridging device are
the range of 150–200 ml/kg/min may improve mixed. Almond et al.25 using ELSO Registry
outcomes, however, if cardiac output remains data showed that ECMO duration of >14 days
insufficient despite increased ECMO flows, prior to transplantation increased risk of in-hos-
then constriction of the aortopulmonary shunt pital mortality, with only 40 to 50% of patients
to limit pulmonary blood flow and encourage successfully bridged to transplant. Mortality risk
systemic blood flow and tissue oxygen delivery may also be increased in patients successfully
may be undertaken.15,17 transplanted because they acquire considerable
Booth et al.18 reported a series of ECMO morbidity during the waiting period on ECMO
patients with cavopulmonary connections who that affects posttransplant outcomes.26,27 A re-
experienced early survival of 17% and those cent report from the Pediatric Heart Transplant
396
Outcomes, Complications, and Followup of Neonates and Children with Cardiovascular Disease
Study (PHTS) Database cautioned that prioriti- report focused specifically on neonatal cardiac
zation of donor hearts to children wait listed on patients reported a rate of CNS injury of 14%,
ECMO required careful consideration because with higher risk in low weight babies, those with
of the high pre and posttransplant mortality.28 worse acidosis, and following ECPR.8 Early
Children undergoing cardiac transplanta- rates of CNS complications must be viewed as
tion had relatively high rates of ECLS (14-17% minimal estimates for the following reasons:
of transplants)3,29; the most common indication
being acute graft dysfunction. Early survival • ELSO Registry data are limited by the
exceeds that of many other cardiovascular in- voluntary nature of reporting.
dications since many grafts (56 to 60%) recover. • The time horizon over which data are col-
lected is short term.
Longer-term Survival • The context in which data are collected is
acute, intensive care based.
To compound the relatively high early mor- • Methods of evaluation are not systematic
tality rate faced by children with cardiovascular and unbiased.
disease on ECMO, evidence suggests additional
late mortality of 4% to 12%.10,30-34 A cohort of Longer-term Neurodevelopmental Outcome
169 children with various types of congenital
heart disease supported on ECMO had a 5-year Published studies related to longer-term
survival rate of 32% with 6% postdischarge neurodevelopmental outcomes of children
mortality.35 Reported causes of late death in with cardiovascular disease are displayed in
these patients related either to the severity of Table 35-1. Fewer data are available than for
the underlying heart condition or was to linked neonatal respiratory survivors. Studies indicate
comorbidities.35 Longer-term outcomes may be that a significant amount of pathology is present
worse in single ventricle patients: a cohort of 64 in survivors with neurodevelopmental problems
children with hypoplastic left heart syndrome ranging from 20%30 up to 73%39 depending on
supported on ECMO had a 25% survival rate the study design, inherent case mix and local
to completion of Fontan.36 practice patterns for each study. Most studies
are single center based, incorporate mixed age
Early Neurological Outcome and mixed diagnosis cohorts, followed up at a
wide range of time intervals post support, and
Study of ELSO Registry data indicates that use a range of evaluation methods, which limits
acute neurological events arise in 12.9% of interpretation of the results.
patients.37 Given that central nervous system
(CNS) complications on ECMO are linked to Long-term Quality of Life (QOL)
the use of ECPR, left ventricular assist devices,
venoarterial support, bicarbonate and inotropes, QOL evaluation has gained increased em-
such complications are inherently more likely phasis in recent years, with the development
in children with cardiovascular disease. An of new methods for assessment in children
ELSO Registry based assessment of acute and increased interest in functional outcome
CNS complications after ECPR, which pre- of survivors.40 Assessment of QOL remains
dominantly reflects cardiac patients, reported challenging in children under the age of 8 years
acute neurological events in 22%, including for who measures are more limited. Available
11% brain death, 7% cerebral infarction, and studies documenting quality of life in children
7% cerebral hemorrhage.38 An ELSO Registry with cardiovascular disease post-ECMO are
397
Chapter 35
listed in Table 35-2. Studies indicate that QOL visual construction and perception, attention,
may be limited in some long-term survivors of executive functioning, fine motor skills, gross
ECMO for cardiovascular disease. motor skills, and psychosocial maladjustment
(internalizing and externalizing problems).
Followup Similar neurodevelopmental issues may be
found in survivors after ECMO. The 2012
Children growing up with congenital heart American Heart Association (AHA) scientific
disease have significantly increased risk for statement on the evaluation and management
neurodevelopmental disabilities in the areas of of neurodevelopmental outcomes in children
intelligence, academic achievement, language with congenital heart disease9 recommends
(development, expressive, and receptive), that all ECMO patients should be referred for
Table 35-1. Studies of long-term neurological outcome in cardiac ECMO patients.
Reference Proportion Time Frame of Method of Outcome Description

available at Followup Outcome
Followup Evaluation
Ibrahim 200030 25/67 (37%) Median 43 (range Telephone 80% Good or

11 to 92) months Questionnaire excellent, 12% fair
and 8% poor outcome
Hamrick 200331 14/53 (26%) Assessment at 1, Age appropriate 72% normal motor
1.5, 2.5 and 4.5 neuropsychiatric outcome, 50% normal
years tests cognitive outcome
Chow 200432 28/90 (31%) Mean 4.5 years Telephone 54% normal
(range 4 months Questionnaire neurological outcome
to 9 years)
Wagner 200739 22/49 (45%) Mean 6.1 (+/-4.4) Age appropriate 73% moderate to
years neuropsychiatric severe impairment
test
Taylor 200741 69/211 Median 7.2 years Pediatric 61% good outcome,
(33%) (range 3.9 months Cerebral 22% mild disability,
to 12.6 years) Performance 13% moderate
Category disability, 4% severe
disability
Lequier 200834 16/39 (41%) 2 years post Age appropriate Mental delay in 50%.
ECMO neuropsychiatric Motor or sensory
tests disability in 12.5%.
Chrysostomou 63/95 (66%) 1.7 years post Pediatric 66% good outcome,
201342 ECMO Cerebral 22% mild disability,
Performance 10% moderate
Category disability, 2% severe
disability
Ryerson 201543 50/98 (51%) Mean age 52.9 Age appropriate Mean IQ in non
months neuropsychiatric syndromic survivors
tests 79.7, 25% had IQ >
2SD below mean
398
formal medical and developmental evaluation Conclusions

and future reevaluation, whether or not any
developmental concerns are present.9 Evalua- Given the complex and high-risk nature
tion of neurodevelopmental status may include of ECMO and underlying diverse health care
CNS imaging, electroencephalography (EEG), needs of children with heart disease, the evalu-
and the assessment of intelligence quotient (IQ), ation of outcomes becomes a crucial part of
academic achievement, neuropsychological patient care. Registry data that contain not only
outcome, and motor skills. In addition, evalu- high quality short-term survival data, but more
ation of speech and language, auditory abilities, detail concerning acute CNS complications, as
as well as behavioral and emotional function- well as longer-term functional, neurodevelop-
ing proves useful in this high-risk population. mental, and quality of life data are an ideal to
A schematic display of proposed followup is work towards. A clearer understanding of the
shown in Table 35-3. precise mechanisms, timing, and consequences
of the diverse brain injuries in these children
is essential to the development of interven-
Table 35-2. Studies of quality of life outcome in cardiac ECMO patients.
Reference Proportion Timeframe of Method of Outcome Description

available at Followup Outcome
Followup* Evaluation
Mahle 200533 14/32 (44%) 1 year post Health Utilities Quality of life mean
support Index - 2 score 0.75 (+/- 0.19)
compared to full score
1.0
Taylor 200741 69/211 (33%) Median 7.2 Health State 71% good, 23%
years (range 3.9 Utility Index moderate and 6% poor
months to 12.6 quality of life
years)
Costello 201144 41/397 (only Median 7 years Child Health Physical summary
44% of eligible (range 1.1 to 14 Questionnaire mean: 42.4 (+/- 16.4)
survivors) years) normal 53.0 (+/- 8.8)
Psychosocial
summary mean
similar to normal.
Wray 201145 26/33 (79%) Median 3.1 Pediatric Physical and
years (range 1.0 Quality of Life psychosocial scores
to 6.3 years) Inventory equivalent to non-
bridged transplant
(slightly lower than
normal).
Garcia Guerra 47/98 (47%) Median age 4 Pediatric Mean summary scores
201446 years Quality of Life 64.9, significantly
Inventory lower than chronic
health conditions and
congenital heart
disease not treated
with ECMO
*Unless stated the patients not assessed were reported deceased.
399
Chapter 35
tions aimed at preventing them or mitigating

their effects, not to mention the importance of
accurate prognostication for parent counsel-
ing when having discussions about limiting
or withdrawing life sustaining therapies. The
variability within current followup pathways
for children surviving ECMO warrants urgent
review and standardization. Referral for neuro-
developmental surveillance as well as tracking
of long-term cardiorespiratory function should
be routine aspects of long-term followup of
ECMO patients in the future.
Table 35-3. A proposed framework and recommendations for followup of neonates and children with
cardiovascular disease.
Timing of Tests Domain Test Intervention
Predischarge at any age Growth • Anthropometry • Dietician referral and input

Neurodevelopment • Neuro-imaging if any acute • Focused care with input from
neurological event specialist nurses and liaison with
• Baseline age-appropriate community
neurodevelopmental screen • Structured followup
Infancy Assessments may be Growth Anthropometry • Dietician referral and input
1 month to 1 year performed at 6 months,
9 months or at 1 year Neurodevelopment • Physical examination • Neurology/neonatologist/Pediatrician/
as per AHA • MRI Brain if any new Community pediatrician referral and
recommendations neurological deficit support (depending on local practice)
• Age-appropriate neurodevelop- • Physiotherapist
mental screen
Hearing Hearing tests • Audiology assessment and input
Vision Vision tests • Ophthalmology/Optometrist referral
Preschool 2 year Growth Anthropometry • Dietician referral and input
If age at ECMO falls within this age Mental and motor • Formal assessment tool –as per • Pediatrician/Community pediatrician
range, then adapt with the AHA development, vision local practice (depending on local practice)
recommended assessment times (9 • Age-appropriate parent filled • Physiotherapist
mos, 18 mos, 24 mos, 30 mos, 4 questionnaires
years). • Vision Tests
Hearing Hearing tests • Audiology assessment and input
Language Speech and Language assessment • Speech and Language input
4-5 years Growth, mental and • Formal assessment tool as per • Pediatrician/Community pediatrician
motor development, local practice (depending on local practice)
speech and language, • Age-appropriate parent filled • Physiotherapist
behavior questionnaires • Speech and Language Therapist
• Child Behavior Checklist
School 5-12 years Growth, mental and • Formal assessment tool as per • Pediatrician/Community pediatrician
If age at ECMO falls within this age motor development, local practice (depending on local practice)
range, then adapt with the AHA speech and language, • Age-appropriate parent filled • Physiotherapist
recommended assessment times (8 behavior, memory questionnaires • Speech and Language Therapist
years) • Child Behavior Checklist • Cognitive rehabilitation
• Additional help at school
Self-esteem Quality of life score • Psychology referral
Adolescent >12 years Growth, • Formal assessment tool as per • Pediatrician/Community pediatrician
If age at ECMO falls within this age neuropsychological tests, local practice (depending on local practice)
range, then adapt with the AHA intelligence, motor, • Age-appropriate parent filled • Physiotherapist
recommended assessment times behavior, memory questionnaires • Speech and Language Therapist
(middle school (11–14 years of age) • Child Behavior Checklist • Cognitive rehabilitation
and high school (15–18 years of • Additional help at school
age).
Quality of life/Self- Quality of Life Score • Psychology referral
esteem
400
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403
36
Adult Respiratory Diseases Predisposing to ECLS
Hussein D. Kanji, MD, MSc, MPH, FRCPC, Juan J. Ronco, MD, FRCPC
Introduction Initial Diagnostic and Management

Approaches to Respiratory Disease
Over the course of three decades we have
struggled to improve the outcome of patients Severe hypoxic respiratory failure has sig-
with acute respiratory distress syndrome nificant mortality.1 Elucidating the etiology may
(ARDS). Only recently we have begun to make require multiple data points, including history
progress in the management of these complex and physical examination, to confirm the diag-
cases resulting in decreased mortality. The nosis and its chronicity. Whether the current
principal paradigm related to the observed out- illness represents progression of an underlying
come is to achieve lung rest and abate ongoing condition, an acute exacerbation of an existing
inflammation and tissue damage after primary disease, or a novel acute respiratory ailment, the
or secondary lung insult. In this context ECLS current illness will guide management decisions
has resurfaced as perhaps the ultimate strategy and inform prognostication. Acute exacerbation
to achieve this therapeutic goal. In addition, the may be caused by reversible infectious, environ-
decrease in iatrogenic lung injury, along with a mental, or inflammatory conditions. Therefore
systematic improvement in the delivery of care early recognition and appropriate treatment is
in ICU have played a major role in decreasing necessary. The history can provide important
mortality, although it remains difficult to quan- diagnostic data such as an infectious prodrome,
tify which components of care contribute most travel, purulent or bloody secretion, and con-
to the observed improved outcomes. Similar to stitutional symptoms. Assessment of the host
the progress made in critical care, the iatrogenic immune status will inform consideration of
complications of ECLS are better managed due opportunistic infections (see section on Immu-
to progress in cannulation techniques, circuits, nocompromised host). History should guide
pumps, anticoagulation strategies, and efficient diagnostic testing and form the basis for the
system delivery. While there are volumes of pretest probability for diagnostic evaluations.
text characterizing ARDS, in this chapter we All patients with severe respiratory disease
take a dynamic approach to respiratory condi- and impaired gas exchange should have a chest
tions producing hypoxemic respiratory failure radiograph and CT scan,2 cultures (bacterial,
to allow clinicians to diagnose and intervene fungal, and mycobacterial), and viral studies
expeditiously. to rule out infectious causes. Management
decisions should be based upon findings from
405
Chapter 36
these investigations. If a diagnostic conundrum 50% of patients within 24 hours of being defined
still exists, the expected course deviates from as ARDS.
predicted, or there is a paucity of diagnostic The guiding principle among patients with
data, an open lung biopsy may be considered. severe gas exchange impairment includes
These elements will be discussed in greater restoring adequate oxygen delivery through
detail subsequently. physiological matching between ventilation
and perfusion while maintaining adequate
Imaging and Acute Respiratory Distress cardiac output. Specifically, the aim of PEEP,
Syndrome (ARDS) positioning and recruitment maneuvers, is to
redistribute ventilation to areas where perfusion
Radiography, computed tomography (CT), is proportionally in excess. Likewise, the use
and ultrasonography have pivotal roles both in of pulmonary vasodilators such as nitric oxide
the diagnosis and management of ARDS, pro- and epoprostenol aim to redistribute perfusion
viding insight into the extension and severity of to areas with relatively preserved ventilation.
respiratory illnesses while functionally assess- The average adult has an anteroposterior
ing the lung volume and response to recruit- chest diameter of approximately 15 cm (verti-
ment interventions such as PEEP.3-6 In addition, cal height), and the density of edematous lung
CT has been instrumental to comprehend the in severe ARDS is approximately 0.7 g/cm3.
pathophysiology of lung disease and abnormal Thus, the magnitude of the compressive force
gas exchange.7 For example, contrast CT of collapsing the lung would be in the order of
the chest demonstrating flow into consolidated 15 x 0.7=10.5 cm H20, which should be the
lung provides visual inference to anatomical minimal pressure required to counteract the
shunt or significant V/Q mismatch as well as compressive forces of the most dependent lung
impaired pulmonary hypoxic vasoconstriction regions. When setting PEEP, additional forces
(HPV). When obtaining chest CT in patients to counteract the elastance of the chest wall
with ARDS the lung must be fully inflated to should not be overlooked, rendering a total
appreciate both the histological-architectural ar- PEEP of approximately 15 cm H2O when the
ray features and the distribution of lung disease. chest wall elastance is normal.12
This may occur with large pleural effusions, at- The prerequisite for lung recruitment is the
electasis, or inadequate recruitment maneuvers. presence of a collapsed and or recruitable lung
In contrast to CT, chest radiography has low owing to gravity-related compressive forces due
sensitivity and specificity for the diagnosis of to weight produced by lung edema, surfactant
ARDS.8 Sensitivity is lower for focal compared deficit, and gas reabsorption. Applying positive
to diffuse disease distribution limiting the value pressure during the expiratory phase counteracts
of bedside radiography due to under recognition gravity-dependent compressive forces due to
of this syndrome. lung weight. Since the distribution of compres-
sive forces follows a gradient from sternum to
Gas Exchange vertebrae in the supine position, lung collapse
is near zero close to the sternum and maximal
Hypoxemia is a defining feature of respira- near the vertebrae.
tory diseases, but the initial degree of hypox- Interventions such as PEEP adjustment and
emia is a poor predictor of outcome unless recruitment maneuvers may diminish cardiac
quite severe (PaO2/FiO2 <50) or persistent.9-11 output (Q) and aggravate hypoxemia by impair-
On standard ventilator settings the severity of ing the function and loading conditions of the
hypoxemia improved significantly in at least right ventricle.13,14 In turn, this can potentially
406
exacerbate a seemingly benign right-to-left beside echocardiography has replaced the need
extrapulmonary shunt in the setting of a patent for pulmonary artery catheterization in most
foramen ovale, producing catastrophic declines cases, providing data points to titrate therapy
in arterial and mixed venous oxygen saturation to optimize the initial treatment of shock and
(SvO2).15,16 Interventions that exacerbate this enhance gas exchange. Echocardiography can
phenomenon, specifically those that impair Q, aid in the detection of acute core pulmonale,
must be avoided or recognized and corrected to presence of right-to-left shunt, and assist in the
limit the drop in SvO2. Other factors that affect titration of PEEP. In addition, clinical evidence
decreased SvO2 and the degree of hypoxemia suggests that once adequate hemodynamic
include anemia and increased metabolic rate. stability has been assured, a strategy of strict
Interventions to restore gas exchange play control of positive fluid balance and use of di-
an initial role in management of patients with uretics not only hastens resolution of pulmonary
severe acute hypoxemic respiratory failure edema and shortens the duration of mechanical
(AHRF) in whom ECLS is a consideration. ventilation but also might improve survival.21
An appropriate therapeutic trial is necessary Echocardiography-guided fluid management
to ascertain the severity of gas exchange and has been shown to direct recommendations of
cardiac output derangement. The use of ap- vasopressors and lower the volume of initial
propriate PEEP, position, and recruitment can fluid prescription and improve overall mortality
improve oxygenation indices sufficiently to in the subacute phase of shock.22 Individualized
convert patients from severe to mild or moder- therapy, fluid, PEEP and vasopressor prescrip-
ate classification of ARDS, obviating the need tion resulting in lessened iatrogenic harm is
for ECLS. necessary in patients with severe AHRF.
Hemodynamic Stabilization and Immunosuppressed Hosts

Echocardiography in Acute Hypoxemia
“To strive, to seek, to find, and not to yield”
ARDS is associated with cardiovascular and (Ulysses, Alfred Lord Tennyson)
oxygen delivery and consumption abnormali- Over the last decade substantial improve-
ties similar to those found in severe sepsis and ment has occurred in the outcome of patients
septic shock.17 Cardiac dysfunction (related to receiving treatment for hematological, onco-
sepsis and induced by stress/catecholamines) logical, autoimmune diseases, recipients of
often complicates management of patients with solid organ transplants, and patients infected
AHRF. In patients with pneumonia-induced sep- with HIV (see Chapter 60).23-25 More aggressive
tic shock, diffuse bilateral pulmonary infiltrates, and targeted treatments with chemotherapy and
and refractory hypoxemia requiring initial biological agents, improved use and monitor-
large-volume fluid resuscitation, myocardial ing of immunosuppressive and antiretroviral
dysfunction has been observed contributing to therapies are responsible in part for the observed
physiological instability. Occasionally, when improved success. Intensive care units have
patients present with severe hemodynamic also contributed by caring for a growing number
instability, the use of VA-ECLS early in the of patients with complications related to such
course of the disease has been associated with diseases and or their treatments.
a decrease in mortality.19,20 Important factors to consider in immu-
Echocardiography plays a significant role nocompromised patients impacting the host
in the initial assessment of hemodynamic status include the contributing diseases, (eg, hemato-
and fluid resuscitation. Contemporary use of logical or solid organ tumors, transplants); the
407
Chapter 36
type of immunodeficiency including neutrope- graphs in this setting and synergistic when ac-
nia, phagocytosis, cellular or humoral mediated companied by broncho-alveolar lavage (BAL)
immune deficiencies; respiratory complication and or lung biopsy in a diagnostic strategy.28
timing as it relates to the course of the underly- Specific abnormalities that aid the diagnosis are
ing illness (eg, days after hematopoietic stem focal or diffuse ground glass infiltrates, nodules
cell transplant); and lastly, the plethora of treat- (peribronchovascular or centrilobular distribu-
ments including chemotherapy, radiotherapy, tions, halo sign), tree in bud pattern, septal
biological agents, corticosteroids, etc. and their thickening, alveolar consolidation, cavitation,
side effects. Together these factors make it vir- and pleural effusions. Combination of CT with
tually impossible to render a single category and angiography can improve diagnostic specificity
approach to the immunosuppressed patient but in patients with pulmonary mold infections.
a multimodal dynamic approach that evaluates Fiberoptic bronchoscopy (FOB) with BAL
the underlying cause and type of immune com- is minimally invasive and safe, permitting
promise, timing of respiratory decompensation, sampling of distal airways targeted to abnormal
and review of antineoplastic or immunosuppres- CT findings. The diagnostic yield as part of a
sive therapies that could be personalized to each comprehensive strategy and attendant altera-
patient.24 The differential diagnosis of AHRF tions in management vary depending on the un-
in this population is broad but is summarized derlying cause of the immune abnormalities.28
in the following categories: 1) infectious, 2) Culture-dependent and independent methods
due to the underlying illness and its progres- for identifying common respiratory pathogens,
sion, 3) related to complications of treatment,
and 4) related to transfusion and or circulatory Table 36-1. Etiology of insult in immuno-
overload. A systematic search for evidence of compromised stratified by infectious and
noninfectious.
indirect mechanisms of lung injury secondary to
extrapulmonary complications (line infections, Infectious Causes Noninfectious Causes
Gram Positive and Gram Pulmonary edema (cardiogenic
intraabdominal, neurological, skin, mucosal or Negative Bacteria (Pseudomonas and noncardiogenic)
musculoskeletal involvement, and tumor lysis aeruginosa, Staphylococcus
aureus)
syndrome) must occur. With respect to pulmo- Fungi (Aspergillus, Candida, Presentation and/or progression of
fusarium, zygomycetes, underlying disease
nary drug toxicity we find it useful to refer to an scedosporium)
Viruses (CMV, VZV, HSV, Peri Engraftment Respiratory
updated online repository of drug-induced lung EBV, Human Herpes Virus 6, Distress Syndrome (PERDS)
diseases (www.pneumotox.com), and to search and community acquired
respiratory viruses: influenza,
Posttransplant
Lymphoproliferative Disorder
PubMed and the FDA AE reporting system. parainfluenza, RSV, adenovirus, (PTLD)
human metapneumovirus,
Table 36-1 summarizes the causes of respiratory rhinovirus, enterovirus)
failure in immunosuppressed non-HIV patients. Pneumocystis Jiroveci
Mycobacteria (Mycobacterium
Drug toxicity (acute or delayed)
Bronchiolitis Obliterans
With acute leukemia the degree of hypox- tuberculosis and nontuberculous syndrome/chronic graft vs. host
mycobacteria) disease
emia can be overestimated. Metabolically Parasites (Toxoplasma, Transfusion-related acute lung
active high white blood cell counts consume Strongyloides) injury
Bronchiolitis obliterans/organizing
oxygen, avidly leading to decreased arterial pneumonia
Idiopathic pneumonia syndrome
oxygen tension especially if such measurements Radiation toxicity (acute or
are delayed (white blood cell larceny). This delayed)
Secondary alveolar proteinosis
phenomenon is characterized by a wide gap be- Delayed pulmonary toxicity
syndrome
tween pulse oximetry and cooximeter measure- Diffuse alveolar hemorrhage
ments of the oxygen saturation of hemoglobin. (DAH)
Congestive heart failure
As stated earlier, high resolution CT scans Pulmonary venoocclusive disease
Modified from Differential Diagnosis of Pulmonary Infiltrates in the
are more sensitive and specific than chest radio- Immunosuppressed Non-HIV Patient (not in order of importance)26,27
408
opportunistic organisms, and noninfectious occurrence of “idiopathic ARDS” in control

causes in BAL specimens are summarized in and intervention groups (average of 9.6 and
Table 36-2. Finally, open lung biopsy has a 10.9% respectively), suspecting that within this
role after thorough diagnostic evaluation does category there is a case mix of patients with a
not provide a clear diagnosis and therapeutic wide variety of diagnoses, responses to treat-
strategy. ment, and outcomes.
Under these circumstances, alternative
Imitators of ARDS diagnoses must be considered. Expeditious
diagnostic techniques (eg, BAL, lung biopsy)
“When intelligence explores unfamiliar enabling rapid implementation of specific thera-
domains, it falls back on “weak methods,” in- pies (such as corticosteroids, cyclophosphamide,
dependent of domain knowledge. People satisfy rituximab and or plasmapheresis) should begin
instead of searching for the best.”29 without awaiting a therapeutic response to
Occasionally, critical care physicians con- antimicrobials and other therapies. These
31-33
front cases of severe AHRF presenting with noninfectious etiologies are recognizable by
diffuse bilateral pulmonary infiltrates on a chest their signature on high resolution CT scan,
radiograph fulfilling the definition of ARDS, BAL, or histology. Table 36-3 lists the diseases
but lacking a predisposing cause in the his- that mimic ARDS. Additional considerations
tory. Indeed, a study 665 patients with ARDS enumerated above are paramount to confirm the
requiring mechanical ventilation reported a diagnosis but extend beyond the scope of this
prevalence of 7.5% of patients fulfilling the chapter. 34-38
Unfortunately, disease reversibility
Berlin criteria for ARDS with no clinical risk in some of the processes may be limited. Thus
factors for ARDS.30 We reviewed the prevalence suitability for ECLS may be challenged and a
of idiopathic ARDS in randomized controlled diagnostic algorithm can guide management
trials from 2000 to 2008 and found a similar and interventions in these cases.
Table 36-2. Diagnostic evaluation of bron- Table 36-3. Mimickers of ARDS.

choscopic specimens in immunosuppressed
patients.
Mimicker
Pathogen(s) Test
Bacterial, Gram stain, acid-fast, Acute exacerbation forms of usual interstitial
Mycobacterial, culture, PCR pneumonitis (UIP) or nonspecific interstitial
Nocardia, actinomyces pneumonitis (NSIP)
Legionella, Mycoplasma PCR, culture (urine Vasculitides (including pulmonary renal
antigen) syndromes)
Fungi Stain, culture and PCR, Alveolar hemorrhagic syndromes*
Galactomannan Hypersensitivity pneumonitis
Viruses Multiplex PCR, culture, Acute eosinophilic pneumonia
cytology (serum PCR for Connective tissue diseases
CMV)
Malignancy (intravascular lymphoma,
P. jiroveci Stain, cytology,
lymphangitis carcinomatosis)
immunofluorescence, PCR
Toxoplasmosis PCR Acute interstitial pneumonitis (AIP)
Diffuse Alveolar Cytology (>20% *Including alveolar filling with RBCs,
Hemorrhage hemosiderin laden without septal inflammation, resulting from
macrophages) anticoagulants, thrombolytic therapy, and/or
Organizing Pneumonia Cytology (lymphocyte thrombocytopenia (bland pulmonary
predominance) hemorrhage). Not in order of frequency or
Malignancy Cytology, flow cytometry importance.
409
Chapter 36
Open Lung Biopsy of tissue necrosis, eosinophils, diffuse alveolar

hemorrhage, and/or a background of fibrosis
The pathology underlying the clinical and (acute on chronic fibrosis) point to a specific
radiological presentation descriptive of ARDS cause of the syndrome. An alveolar filling pat-
results from diffuse parenchymal injury, which tern where alveoli are filled with cells (immature
in turn invokes a stereotypic inflammatory re- fibroblasts, macrophages, neutrophils, and or
sponse in the lungs followed by repair.39 Many siderophages) or noncellular proteinaceous
factors contribute to lung injury, namely the acu- material, points toward organizing pneumonia
ity, severity, duration, and type of the injury will in any of the above settings for DAD. Though
influence the cellular composition of the tissue the standard definition of ARDS attempts to
response. Observed changes in histopathology capture the pathological diagnosis of diffuse
depend greatly on biopsy timing relative to the alveolar damage, both autopsy and open lung
onset of the insult. Inflammatory processes tend biopsy results demonstrate that the two are
to overlap with regard to clinical, radiological, not synonymous. Specifically, DAD can have
physiological, and histopathological features, other causes such as connective tissue diseases
adding to the complexity and heterogeneity in that are not considered classic risk factors for
“defining” the syndrome. ARDS.40 We have seen patients with ARDS in
Acute lung injury (interstitial edema, in- whom biopsies revealed minimal histopatho-
traalveolar fibrin and reactive type II cells) is logical changes. Baring sampling error, this
the histopathological pattern associated with situation suggests a biopsy perfromed early
acute clinical lung disease.39 Several subtypes in illness progression, and/or the presence of
of acute lung injury are recognized histopatho- cardiogenic pulmonary edema. Clinical history
logically (diffuse alveolar damage [DAD], and CT results should be reviewed for further
acute eosinophilic pneumonia, acute fibrin- insights into the diagnosis.
ous and organizing pneumonia [OP], diffuse In addition, the history of the illness lead-
alveolar hemorrhage). When specific findings ing to ARDS, patient immunological status,
are incomplete (ie, no hyaline membranes), the and high resolution chest CT provides gross
generic term “acute lung injury” is appropriate. anatomical-pathological information that com-
When intraalveolar hyaline membranes are bined with histopathology often aids diagnosis.
present it is termed “diffuse alveolar damage We suggest that similar to the management of
(DAD).” DAD is a common histopathological interstitial lung disease, an approach incorpo-
pattern of injury in acute diffuse lung disease, rating input from clinicians, thoracic surgeons,
particularly in ARDS patients and those who chest radiologists, and lung pathologist in the
are immunosuppressed. Conditions associated form of a multidisciplinary conference, should
with DAD include acute idiopathic interstitial be conducted in each individualized case where
pneumonia (AIP), infections, toxic inhalants an open lung biopsy is considered.
and aspiration, drug reactions, shock, connec- The indication and optimal timing of open
tive tissue diseases, acute radiation reactions, lung biopsy in respiratory conditions leading
acute hypersensitivity pneumonitis, and alveolar to hypoxic respiratory failure remains a source
hemorrhage. DAD can also occur in patients of controversy. Clinicians must weigh the
with idiopathic pulmonary fibrosis and other risk of this intervention with the likelihood of
chronic ILDs, possibly as a natural component diagnosis when BAL is noncontributory and/or
of the disease evolution and following an acute reveals process(es) responsive to steroids or an-
exacerbation. In addition to acute lung injury tiinflammatory therapy. Confronted with a lack
with hyaline membranes (DAD), the presence of evidence-based guidelines, the intensivist
410
must apply intelligent-based medicine instead

and personalize the indication of an open lung
biopsy on a case-by-case basis. The practice
of blind steroid administration in the setting
of ARDS is fraught with potential side effects
including immunosuppression. Furthermore,
without a tissue diagnosis the appropriate du-
ration of therapy is unclear.41 Complications of
open lung biopsy in nonresolving ARDS have
been demonstrated to be quite low. Limited
data describe complications of lung biopsy on
ECLS.42 Evidence suggests that lung biopsies
influence decisionmaking in the majority of
cases of ARDS, and when contributory, signifi-
cant associated survival benefit accrues.43,44 We
recommend lung biopsy when the diagnosis re-
mains unclear or the disease trajectory deviates
from the presumed clinical course in the context
of disease timing and radiographic findings.
Summary
Respiratory disease and acute hypoxic re-

spiratory failure represent a voluminous topic
and this chapter serves simply as an introduc-
tion. The approach to such patients must remain
dynamic, concomitantly instituting investiga-
tion and management. Specifically, the objec-
tive must continue to abate iatrogenic injury,
optimize oxygenation, and hemodynamics,
whilst considering multiple etiologies, mimics,
and host immune response. ECLS effectively
improves oxygenation and allows “lung rest.”
However, successful therapy is built upon
recognition and treatment of the inciting insult.
ECLS can provide the time for diagnosis, treat-
ment, and recovery while minimizing further
lung injury. In summary, a concise, goal ori-
ented approach such as the one suggested herein,
can serve as a roadmap for clinicians to achieve
stabilization, elucidation of the pathology, and
optimize individualized therapy.
411
Chapter 36
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414
37
Indications and Contraindications for ECLS in Adults with Respiratory Failure
Lorenzo Del Sorbo, MD, Eddy Fan, MD, PhD
Introduction diagnosis of a potentially reversible disease; and

3) the absence of contraindications.2,7,10-12 With
In 1972, the first successful application of these principles in mind, we will discuss the
extracorporeal life support (ECLS) in an adult criteria used by experienced ECLS centers to
with respiratory failure was reported.1 In this optimize benefits and minimize risks of ECLS
case, venoarterial extracorporeal membrane in patients with respiratory failure.
oxygenation (VA-ECMO) was initiated as a
rescue measure in a 24-year old patient who ECLS Considerations in Patients with
developed trauma-related acute respiratory High Risk of Death Despite Optimization
distress syndrome (ARDS) refractory to the of Conventional Management
conventional treatment of that era: tidal volume
1 liter, positive end-expiratory pressure (PEEP) Mechanical ventilation (MV), the standard
8 cmH2O, fraction of inspired oxygen (FiO2) therapy to support gas exchange and improve
100%. After 75 hours, ECMO support was survival in patients with respiratory failure, may
discontinued and the patient recovered. not suffice in the worst cases or may potentiate
Today, with the exception of clinical trials, and worsen lung injury (ventilator-induced lung
ECLS is still considered in patients with respira- injury [VILI]) by producing induces alveolar
tory failure as a potential rescue intervention.2 overdistension and cyclic tidal recruitment.13,14
Both remarkable improvements in technology3 The most severe patients experience increased
and several clinical investigations4 have con- mortality.13,14
tributed to the diffusion of ECLS in different In patients with respiratory failure, ECLS
contexts and with different indications.5-8 While is a support mode based on solid physiological
large randomized controlled trials demonstrat- rationale. ECLS effectively maintains adequate
ing the efficacy of ECLS in improving patient- gas exchange, replacing the respiratory function
important outcomes are lacking,9 the decision through an artificial lung, thereby unloading the
to use ECLS is typically based on the balance respiratory system, allowing recovery.3,4,8,10,15
of potential risks and benefits in each individual However, ECLS carries significant risks and
case.2 However, the principles guiding the selec- evidence-based thresholds to guide initiation of
tion of candidates with respiratory failure for ECLS have not been established. Therefore, out-
ECLS include: 1) a high risk of death despite side of clinical trials, it is typically considered as
optimization of conventional treatment; 2) the rescue treatment only when patients are at high
415
Chapter 37
risk of death despite conventional therapy.2,16 hypoxemia. If vasodilatory shock complicates

Since the main goal of ECLS in patients with respiratory failure, VV-ECMO might remain the
respiratory failure is to improve ventilation and mode of choice while vasopressors would be
oxygenation, it can be utilized with the follow- administrated to manage low systemic vascular
ing major objectives (Figure 37-1): 1) as rescue resistance (see Chapter 56). In addition, with
from refractory hypoxemia; 2) as rescue from right ventricular dysfunction secondary to re-
refractory hypercapnia; or 3) as rescue from spiratory failure, function may improve with the
injurious mechanical ventilation. rapid reversal of hypoxemic vasoconstriction
with VV-ECMO. However, if concomitant left
ECLS for Rescue from Refractory Hypoxemia ventricular or biventricular failure complicates
respiratory failure resulting in end organ hypo-
Common causes of respiratory failure with perfusion, VA-ECMO, or a hybrid configuration
refractory hypoxemia requiring ECLS include (eg, venoarterial-venous ECMO (VAV-ECMO)
acute respiratory distress syndrome (ARDS), would be more appropriate (Figure 37-1).
primary graft dysfunction following lung trans- Ideally, ECLS for refractory hypoxemia
plantation, acute pulmonary embolism, acute should be initiated in patients, whose predicted
eosinophilic pneumonia, alveolar hemorrhage, hypoxemia-related morbidity and mortality out-
and large bronchopleural fistula. Among these weigh the risk of ECLS-related complications.
causes, ARDS has been the focus of most stud- Early referral for ECLS is crucial, allowing for
ies in ECLS in patients with respiratory failure. proper assessment and timely cannulation of the
High extracorporeal blood flow is crucial in patient. However, there is a paucity of data and
achieving oxygenation during ECLS, venove- the exact timing remains unclear.9 In particular,
nous ECMO (VV-ECMO) is the configuration none of the three randomized clinical trials
most often applied in patients with refractory convincingly demonstrated the efficacy of the
Figure 37-1. Scheme of possible configurations based on the main pathophysiological indications
for ECLS.
416
routine application of ECLS in patients with tients with a mortality risk >50%, identified by
ARDS as compared to conventional therapy.17-19 a PaO2:FiO2 <150 mmHg when the FiO2 >90%
Therefore, several professional organizations and a Murray score of 2-3 (Figure 37-2).20
have released different recommendations char- In the Conventional ventilatory support
acterized by distinctive definition of refractory versus Extracorporeal membrane oxygenation
hypoxemia and thresholds for ECLS initiation for Severe Adult Respiratory failure (CESAR)
(Table 37-1). randomized controlled trial,17 eligibility criteria
In the Extracorporeal Life Support Organi- included severe but potentially reversible respi-
zation (ELSO) guidelines,2 ECLS is indicated in ratory failure, a Murray score ≥3.0, or uncom-
patients with a mortality risk >80%, identified pensated hypercapnia with a pH <7.20 despite
by a partial pressure of arterial oxygen to frac- optimum conventional treatment. Patients were
tion of inspired oxygen ratio (PaO2:FiO2) <80 also considered for ECMO with a Murray score
mmHg when the FiO2 is >90% and a Murray ≥2.5 to facilitate the transportation in case of
score of 3-4. However, ECLS could also be rapid deterioration.
considered in less severely ill hypoxemic pa-
Table 37-1. Criteria for initiating VV-ECMO as rescue treatment in patients with ARDS according to
different ECMO-expert clinical groups.
Clincial ELSO(2,16) ECMOnet(20) CESAR(17) EOLIA

Group/Reference NCT01470703
Indication to ECMO Mortality risk > -OI > 30 -Potentially -P/F < 50 with FiO2 >0.8
80%: -P/F < 70 with PEEP ≥ reversible respiratory X >3 hrs,
-P/F < 80 with FiO2 15 cmH2O for patients failure -P/F <80 with FiO2 >0.8
> 0.90 in an ECMO center -Murray Score ≥ 3.0 for >6 hrs,
-Murray score of 3-4 -pH < 7.25 X > 2 hrs -pH < 7.20 despite -pH<7.25 for >6 hrs (RR
-Hemodynamic optimum increased to 35/min) with
instability conventional MV settings
treatment adjusted to keep Pplat <32
cmH2O
Consideration for -Mortality risk > P/F < 100 with PEEP ≥ Murray score ≥2.5
ECMO 50%: 10 cmH2O for patients
-P/F < 150 with awaiting transfer to an
FiO2 > 0.90 ECMO center
-Murray score of 2-3
Contraindications to -Conditions -Intracranial bleeding -Peak inspiratory -MV ≥ 7 days
ECMO incompatible with -Other contraindication pressure >30 cmH2O -Age < 18 years
normal life to anticoagulation -FiO2 >0.8 -Pregnancy
-Preexisting -Previous severe -Ventilation for > 7 -BMI > 45 kg/m²
conditions affecting disability days -Chronic respiratory
quality of life (CNS -Poor prognosis of -Intracranial bleeding insufficiency treated with
status, end stage underlying disease -Contraindication to long duration oxygen or
malignancy, risk of -Mechanical ventilation anticoagulation respiratory assistance
systemic bleeding > 7 days. -Contraindication to -Previous history of HIT
with continuation of -Malignancy with fatal
anticoagulation) active treatment prognosis within 5 years
-Age -Patient moribund
-Futility: patients -SAPS II > 90
who are too sick -Non drug-induced coma
(e.g., following cardiac arrest
immunosuppression) -Irreversible neurological
, have been on pathology
conventional therapy -ECMO cannulation not
too long (MV >7 possible
days)
BMI=body mass index; Cesar=Efficacy and economic assessment of conventional ventilatory support versus extracorporeal
membrane oxygenation for severe adult respiratory failure; CNS=central nervous system; ECMOnet=Italian ECMO network;
EOLIA=Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome; HFO=high frequency
oscillation; MV=mechanical ventilation; NO=nitric oxide; PaO2/FiO2: arterial partial pressure of oxygen to fraction of inspired
oxygen ratio; PEEP=positive end expiratory pressure; RR=respiratory rate
417
Chapter 37
According to the Italian ECMO network ECLS for Rescue from Refractory
(ECMOnet),21 indications for ECMO in ARDS Hypercapnia
patients with suspected H1N1 infection com-
prised one of the following: oxygenation index Patients with obstructive lung diseases,
(FiO 2:PaO 2 x mean airway pressure) >30; such as asthma and chronic obstructive pul-
PaO2:FiO2 <70 mmHg with PEEP ≥15 cmH2O monary disease (COPD), may experience acute
for patients already admitted to an ECLS center; exacerbations with severe hypercapnic respira-
PaO2:FiO2 <100 mmHg with PEEP ≥10 cmH2O tory failure. Hypercapnia results from acute
for patients awaiting transfer to an ECLS center; worsening of expiratory flow limitation caused
pH <7.25 for at least 2 hours; and hemodynamic by the increased small airways resistance,22-23
instability. with consequent development of dynamic al-
Finally, in the ongoing Extracorporeal veolar hyperinflation and intrinsic PEEP.24 In
Membrane Oxygenation for Severe Acute Re- the most severe cases, these may be refractory
spiratory Distress Syndrome (EOLIA; Clinical- to conventional therapies and MV, becoming
Trials.gov NCT01470703) randomized clinical life threatening.
trial, patients are eligible if the meet any of the ECLS, and in particular ECCO2R, repre-
following three inclusion criteria: sents an attractive therapeutic approach in this
setting. By reducing tidal volume and respira-
• PaO2:FiO2 <50 mmHg with FiO2 >0.8 for tory rate, ECCO2R may interrupt the vicious
>3 hours despite optimization of MV set- circle of dynamic hyperinflation, reestablishing
tings and use of adjunctive rescue therapies appropriate oxygen delivery, and providing
(eg, inhaled nitric oxide [iNO], recruitment time for the bronchospasm to resolve.25-26 This
maneuvers, prone position, high-frequency hypothesis has been clinically investigated in
oscillatory ventilation) patients with status asthmaticus (Table 37-2).
• PaO2:FiO2 ratio <80 mmHg with FiO2 >0.8 Definitive thresholds to guide initiation of
for >6 hours, despite optimization of MV ECLS in this context have not yet been estab-
settings and adjunctive rescue therapies lished. Current indications suggested by the
• pH <7.25 for >6 hours with respiratory rate ELSO guidelines include CO2 retention due to
increased to 35 breaths/min, resulting from asthma or extreme hypercapnia associated with
MV settings adjusted to keep the plateau the inability to achieve safe inflation pressures
airway pressure <32 cmH2O (plateau airway pressure ≤30 cmH2O).2
ECLS has also been applied in patients with
COPD exacerbation with the goal of avoiding
or facilitating the weaning from invasive MV,
Murray score 0 points 1 point 2 points 3 points 4 points

cXR n.0 n.1 n.2 n.3 n.4
(quadrants with consolidation)
Hypoxemia ≥300 225-299 175-224 101-174 ≤100
(PaO2/FiO2)
PEEP (cmH2O) <5 6-8 9-11 12-14 >15
Compliance >80 60-79 40-59 20-39 <19
(ml/cmH2O)
The final score is calculated by the addition of the component parts divided by 4
Figure 37-2. Components of the Murray score.
418
which has been associated with an increased ECLS for Rescue from Ventilator-Induced
mortality, especially when initiated after failure Lung Injury
of noninvasive ventilation.27
As shown in Table 37-3, alternative crite- In routine clinical practice, lung protective
ria have been considered to start ECLS in this MV to minimize VILI include pressure- and
context. In a recent study, ECLS was started in volume-limited strategies and the application
patients at risk of failing noninvasive ventila- of adequate PEEP.14 However, it remains un-
tion with pH ≤7.30 and PaCO2 >20% of the clear whether current recommendations are
baseline value despite treatment for at least 2 adequately safe, or if further reduction of thresh-
hours with noninvasive ventilation, associated olds would provide greater protection and ad-
with respiratory rate ≥30 breaths/min and use of ditional improvements in survival of ARDS.29,30
accessory respiratory muscles.28 Although this Ideally, injured lungs should be “rested” without
is a promising approach for the management undergoing any mechanical stress or strain, and
of patients with severe COPD exacerbation, provided with sufficient time for the lung to heal.
no randomized trials have been performed to ECLS may represent the ideal strategy to rescue
evaluate its potential efficacy. Moreover, the patients with respiratory failure from VILI. By
rate of complications associated with ECLS in providing extracorporeal gas exchange, ECLS
this context has been shown to be substantial.27 allows the use of MV with less injurious settings,
especially in patients with very low respiratory
system compliance.31
Table 37-2. Selected case series of ECLS for near fatal asthma.
Modality # of Patients and Outcome

MacDonnell ECMO and 1 patient, survived
KF, 198159 IMV
First description
of ECLS for
asthma
Hebbar KB, VV-ECMO -64 patients;
200960 or -age 10 years (1-17)
ELSO report on VA-ECMO -Gas exchange parameters with IMV
ECLS for and IMV before ECLS:
severe pH 6.96 (6.78-7.28)
refractory status PaCO2 123 mmHg (70–237)
asthmaticus in PaO2 126 mmHg (59–636)
children -Duration of ECLS: 94 hours
-Survival rate 94%
Mikkelsen ME, VV-ECMO -24 patients; age 31.3±12.3 years
200961 or -Gas exchange parameters with IMV
ELSO report on VA-ECMO before ECLS:
ECLS for and IMV pH 7.17±0.16
severe PaCO2 119.7±58.1 mmHg
refractory status PaO2/FiO2 ratio 244±180
asthmaticus in -Duration of ECLS: 111.9±71.2 h
adults -Survival rate 83.3%
Brenner K, ECCO2R 2 patients, both survived
201462 and IMV
ECCO2=extracorporeal carbon dioxide removal; IMV=invasive
mechanical ventilation; VA=venoarterial; VV=venovenous
419
Chapter 37
The application of either VV-ECMO or low tients with moderate/severe ARDS, facilitating
flow extracorporeal carbon dioxide removal an “ultra”-protective MV strategy may further
(ECCO2R) techniques may accomplish the goal improve patient-important outcome.33
of sustaining oxygenation and CO2 removal Recently, clinical studies have focused on
while minimizing VILI. ECCO2R does not the specific role of ECCO2R in patients with
provide oxygenation but may allow significant ARDS to enhance lung protection during MV
reductions in alveolar ventilation and tidal vol- (Table 37-4).33 However, the only random-
umes with less invasive technology compared ized controlled trial investigating the effect of
to ECMO.32 Currently no definitive clinical data an “ultra”-protective MV strategy with 3 mL/
exist to support the initiation of ECLS with the kg predicted body weight (PBW) combined
particular goal of minimizing VILI. However, with ECLS failed to demonstrate a mortality
as it is challenging to identify a safe threshold of benefit.33 Further data on the efficacy of the
alveolar distending pressure, future trials should combination of a very low tidal volume MV
evaluate whether the application of ECLS in pa- strategy with ECLS treatment in ARDS will
Table 37-3. Criteria to start ECLS for COPD exacerbation in

selected case series.
Modality # of Patients and
Criteria for ECCO2R
Pesenti A, 199063 ECCO2R 1 patient;
First description of and IMV
ECLS for COPD Unable to wean from IMV
exacerbation
Abrams DC, 201364 ECCO2R 5 patients;
ECLS to facilitate and IMV
weaning from IMV IMV and preintubation arterial
blood gas with pH <7.35 and
PaCO2 >55 mm Hg
Burki NK, 201365 ECCO2R 20 patients with COPD: 7 at risk of
ECLS during NIV to failing NIV, 13 on IMV;
prevent IMV, and
during IMV to facilitate NIV for at least 1 hour and
weaning PaCO2 >55 mmHg and pH <7.25,
or pH <7.30 and PaCO2 >55 mm
Hg, with PaCO2 decrease <5
mmHg from baseline
Difficult weaning from IMV

Karagiannidis C, 201566 ECCO2R 5 patients on IMV;
Veno-venous
extracorporeal CO2 Failure of at least 2 spontaneous
removal improves breathing trials in 48 hours
pulmonary hypertension
in acute exacerbation of
severe COPD
Del Sorbo L, 201527 ECCO2R 25 patients with COPD at risk of
ECCO2R in And NIV failing NIV;
Hypercapnic Patients At
Risk of NIV Failure: A pH ≤7.30 and PaCO2 >20% of the
Matched Cohort Study baseline value despite the treatment
With Historical Control for at least 2 hours with NIV
and RR ≥30 breaths/min or use of
accessory respiratory muscles
AV=arterovenous; ECCO2-R=extracorporeal carbon dioxide removal;
IMV=invasive mechanical ventilation; NIV=noninvasive mechanical
ventilation; RR=respiratory rate
420
be provided by the results of an ongoing multi- most common indications for ECLS are acute
center randomized controlled trial: Strategy of forms of respiratory failure, such as ARDS,
UltraProtective Lung Ventilation With Extracor- or acute exacerbations of chronic respiratory
poreal CO2 Removal for New-Onset Moderate diseases, such as asthma and COPD. Currently,
to seVere ARDS (SUPERNOVA; ClinicalTrials. the only circumstance where ECLS may be
gov NCT02282657). considered for irreversible respiratory failure
is to provide life support to patients awaiting
ECLS Consideration in Patients with lung transplantation: ECLS as bridge to lung
Potentially Reversible Diseases transplantation.38-41
Futility should be ruled out when consider-
At present, ECLS cannot be considered ing ECLS. The ELSO guidelines recognize futil-
standard of care in patients with respiratory ity as a contraindication for ECLS in “patients
failure due to the lack of high-quality evidence who are too sick, have been on conventional
demonstrating efficacy. 9 Therefore, ECLS therapy too long, or have a fatal diagnosis.”16
remains a temporary strategy to be considered Nevertheless, the definition of reversible or
on a case-by-case basis for rescue situations. futile conditions may be very challenging in
However, general consensus exists that ECLS clinical practice, raising important ethical is-
would be inappropriate as a destination therapy, sues regarding the indication to start ECLS
and hence it should be currently considered only and also its duration. The certainty of disease
as a bridge to recovery.2,7,12,35-37 As such, the use irreversibility is elusive, rendering decisions
of ECLS as bridge to recovery implies that the about ECLS application or discontinuation dif-
clinical conditions of patients requiring ECLS ficult. Indeed, successful recovery of patients
must be potentially reversible. Therefore, the supported with ECLS for ARDS is expected
Table 37-4. Selected trials on ECLS to prevent VILI in patients with ARDS.
Clinical Study ECLS Criteria to Start ECLS MV Strategy Combined with

Technique ECLS
Gattinoni L, 198056 ECCO2R Refractoriness to Intermittent mandatory
Treatment of acute conventional IMV ventilation
respiratory failure with RR=3 breaths/min
low-frequency positive- peak-pressure <45 cmH20
pressure ventilation and
ECCO2R
Zimmermann M, 200957 AV-ECCO2R PaO2/FiO2 70-200 Vt ≤6 ml/kg PBW
Pumpless extracorporeal mmHg Pplat ≤30 cmH2O
interventional lung assist PEEP ≥10 cmH2O RR ≤25 breaths/min
in patients with ARDS: pH <7.25 High PEEP strategy
a prospective pilot study
Terragni P, 200958 ECCO2R 28 ≤ Pplat ≤30 cmH2O Vt=4 mL/Kg PBW
Tidal Volume Lower RR=40 breaths/min High PEEP strategy
than 6 ml/kg Enhances pH ≤7.25
Lung Protection
Bein T, 201333 ECCO2R MV <7 days Vt=3 ml/kg PBW
The prospective Pplat >25 cmH2O
randomized Xtravent- Absence of severe
study hemodynamic instability
SupernovaNCT02 282657 ECCO2R PaO2/FiO2 200-100 Vt=4 mL/kg PBW
mmHg PEEP resulting in:
PEEP ≥5 cmH2O 23 ≤ Pplat ≤25 cmH2O
RR=20-35 breaths/min
ARDS=acute respiratory distress syndrome; AV=arterovenous; ECCO2-R=extracorporeal carbon
dioxide removal; MV=mechanical ventilation; PaO2/FiO2=arterial partial pressure of oxygen to
fraction of inspired oxygen ratio; PBW=predicted body weight; PEEP=positive end expiratory
pressure; Pplat=Inspiratory plateau airway pressure; RR=respiratory rate; Vt=tidal volume
421
Chapter 37
to occur after an average of several weeks, but kg/m²; chronic respiratory insufficiency treated
cases of protracted support up to months have with oxygen therapy of long duration and/
been reported.41-43 or long-term respiratory assistance; previous
history of heparin-induced thrombocytopenia
Potential ECLS Contraindications (HIT); malignancy with fatal prognosis within
5 years; moribund patient; SAPS II greater than
Due in large part to the technological evo- 90; non drug-induced coma following cardiac
lution of ECLS equipment, the management of arrest; irreversible CNS pathology; decision to
patients supported with extracorporeal respira- limit therapeutic interventions; lack of vascular
tory support has become easier,3 altering ECLS access. The lack of adequate vascular access
contraindications. Thus, indications for ECLS may not be acknowledged as a contraindica-
have been expanding including diagnoses for- tion, but needs to be carefully evaluated, being
merly considered absolute contraindications, a critical limitation to the ECLS feasibility and
such as alveolar hemorrhage or neurogenic pul- efficacy.4
monary edema following intracranial aneurysm Investigators have tried to identify clinical
rupture.45-49 According to the current ELSO parameters independently associated with a
guidelines, there are no absolute contraindica- poor prognosis for ECLS patients with refrac-
tions for respiratory ECLS, only considerations tory respiratory failure, primarily ARDS.49-52
of its risk/benefit balance to be evaluated on a Although these investigations do not address
case-by-case basis.2 However, the following the issue of the identifying contraindications to
clinical conditions are considered as relative ECLS, they may help in decision making to de-
contraindications, as they carry a poor prognosis fine risks and benefits of extracorporeal respira-
despite the institution of ECLS:2,10,12,16,37 tory support. The largest of these investigations
examined 2355 adult patients from the ELSO
• High risk of systemic bleeding or recent/ Registry with acute respiratory failure sup-
expanding CNS hemorrhage ported with ECLS.52 Factors present at ECLS
• Comorbidities including terminal malig- institution including older age, cardiac arrest
nancy, advanced CNS injury, and immu- before ECLS, CNS dysfunction, renal dysfunc-
nosuppression tion immunocompromised status, associated
• Older age (recognizing that there is not a nonpulmonary infection, iNO use, bicarbonate
defined age threshold) but an increasing risk infusion, longer duration of pre-ECLS MV,
of death with increasing age higher PaCO2, and higher PIP were independent
• MV delivered with high Pplat >30 cmH2O risk factors associated with hospital mortality.
and high FiO2 >90% for more than 7 days Bacterial pneumonia, viral pneumonia, aspira-
tion pneumonia, asthma, trauma and burn, and
Similar contraindications were considered the use of neuromuscular blocking agents were
in the CESAR trial: peak inspiratory pressure protective factors.
greater than 30 cmH2O or FiO2 >0.8, pre-ECMO Finally, recent expert opinion reported
MV >7 days, intracranial bleeding, contraindi- the most common clinical situations where
cation to limited anticoagulation, and contrain- ECLS application is unlikely to be success-
dication to continuation of active treatment.17 ful.37 Among these, it is worth highlighting
Moreover, in the ongoing EOLIA trial, the two important issues. The first includes ECLS
following exclusion criteria have been estab- volume, as centers with high ECLS volumes
lished: pre-ECMO MV >7 days; weight greater demonstrate lower mortality.35, 54 The second
than 1 kg/cm; body mass index greater than 45 is the diagnosis of refractory septic shock with
422
preserved cardiac function (see Chapter 56). In

this setting, even ECLS at high flow may insuf-
ficient to reestablish adequate oxygen delivery
and match the high metabolic demand due to
increased cardiac output. In a recent series of 32
patients treated with ECLS for refractory septic
shock, the hospital mortality rate reached 78%.
Interestingly, the presence of severe myocardial
injury based on elevated troponin was associ-
ated with a lower risk of hospital mortality.55
Data support the application of VA-ECMO in
patients with severe septic-induced cardiogenic
shock refractory to high doses of vasopressors.56
However, more robust evidence is needed to
define the role of ECLS in septic patients.
Conclusions
Despite the lack of evidence-based criteria,

ECLS application in patients with respiratory
failure is expanding due to the increasing sim-
plicity and safety of its management. However,
since ECLS remains complex, high risk, and
resource intensive, it should be used in centers
with sufficient experience and expertise. Ad-
ditionally, rigorous clinical trials are needed to
further define the indications and contraindica-
tions of this technology.
423
Chapter 37
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Extracorporeal membrane oxygenation in 55. Park TK, Yang JH, Jeon K, et al. Extracor-
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427
38
ECLS Cannulation for Adults with Respiratory Failure
William Lynch, MD
Introduction dual lumen cannula placed with fluoroscopy

guidance. This single site cannulation strategy
This chapter focuses on issues related to makes ambulatory ECLS possible and practical.
cannulating an adult in respiratory failure for VA-ECLS in adults typically requires femoral
VV-ECLS. Cannulation techniques (percuta- artery cannulation with venous drainage being
neous, open, semi-open), preferred routes of from the femoral vein, right internal jugular vein,
access (arterial and venous, venous only, single or both. Femoral artery cannulation commonly
site cannulation, multiple sites) and cannula requires distal arterial reperfusion to protect the
selection are described. Primary respiratory leg from ischemia. The axillary artery is also
failure (pneumonia, aspiration) and secondary an option with the advantage of keeping can-
respiratory failure (trauma, postoperative) are nulas out of the groin, again making ambulation
considered together as either hypoxic respirato- practical and safe. Axillary artery cannulation
ry failure or pure hypercarbic respiratory failure. requires open surgical technique. Arterial can-
A section is dedicated to respiratory failure in nulation of the femoral arteries can be done
the setting of severe sepsis. This chapter mirrors percutaneously but often is done with open
the outline of the ELSO Guidelines for Adult surgical technique. Decannulation of arteries
Respiratory Failure.1 commonly requires surgical repair of the artery.
Respiratory failure can produce hypoxia, Femoral artery and/or vein cannulation makes
hypercarbia, or a combination of the two. ECLS ambulation impractical and arguably unsafe.
for hypoxic failure requires flows similar to Consider the following scenario describ-
native cardiac output, sometimes referred to ing an adult with ARDS. Hypoxic respiratory
as “high flow” ECLS, while support for hyper- failure is initially supported with mechanical
carbia requires flows of about 10-20% of the ventilation. As support is escalated, uncomfort-
cardiac output, or relatively “low flow” ECLS. able modes of ventilation are used and sedation
Hypoxia is typically supported with VV-ECLS is necessary. Patients commonly require volume
when cardiac function is adequate. If cardiac resuscitation and sometimes paralysis. Vasoac-
function is compromised, VA-ECLS providing tive infusions are added to maintain adequate
biventricular support and pulmonary support, is cardiac output. Sometimes permissive hyper-
an option. VV-ECLS can be offered with single capnia is allowed. The patient remains hypoxic
site cannulation. This typically is right internal and hypercarbic. As a consequence, pulmonary
jugular, percutaneous cannulation, using bicaval vascular resistance is high and the right ventricle
429
Chapter 38
struggles. High intrathoracic pressures, second- VV-ECLS does not offer cardiac support, it may
ary to the ventilator, diminish cardiac return and reverse many of the disturbed hemodynamics
further disturb hemodynamics. that are a consequence of hypoxia and hyper-
This patient is now hemodynamically un- carbia, as well as mechanical ventilation which
stable with marginally supported hypoxic and causes increased intrathoracic pressure and
hypercarbic respiratory failure. What do you do associated need for sedation.
next? The ECLS strategy you choose is based
on the pathophysiology of the disease threaten- Cannulation Decision Making for Adult
ing the patient. Is this just hypoxia? If so, “high Respiratory Failure
flow” VV-ECLS may be indicated. Does the
patient suffer primarily from hypercarbia? In Respiratory failure is multifactorial. The
this case, “low flow” VV-ECLS only may be clinical picture will be your guide in making
required. Could this be sepsis, in which case decisions about mode of support, size of can-
VA-ECLS potentially requiring very high flows nulas, and anatomic placement of the cannulas.
may be needed. Is this a pulmonary embolus Decisionmaking begins with recognizing the
necessitating use of VA-ECLS? Essentially you pathophysiology of the disease and then choos-
are trying to decide if this patient has sufficient ing the appropriate mode of ECLS. These are
cardiac function to be supported with VV-ECLS, the real decisions and once made, cannula type,
realizing that VV-ECLS will not directly sup- size, and site of insertion is determined. Then
port cardiac function. For this particular patient, cannulating is a technical exercise and ECLS
the ECHO shows a dilated RV and inotropic and initiation is only logistics.2-5
vasopressor infusions are needed to support a Patient conditions that will drive cannula-
marginal blood pressure. This hemodynamically tion decisionmaking are described below.
fragile patient seems to require VA-ECLS.
This patient, while critical and questionably Hemodynamically Supportable Respiratory
unstable, tolerates a move to the operating room Failure
where fluoroscopy is used to guide placement of
a bicaval cannula via the right internal jugular VV-ECLS is the preferred mode of extra-
vein. VV-ECLS is initiated. Bright red oxygen- corporeal support, for adult respiratory failure
ated blood is instilled into the right ventricle and when cardiac function is adequate or moderately
is ejected through the pulmonary vasculature. depressed. A typical patient will be on signifi-
The pulmonary hypoxic vasoconstriction is cant ventilator support; 80-100% FiO2; 10-20
reversed; the pulmonary vasculature relaxes; cmH2O PEEP; peak airway pressure of 30-40
right ventricular strain is relieved and hemody- cmH20; respiratory rate of up to 40 breaths per
namics improves. Systemic oxygenation climbs. minute. Sedation is necessary, perhaps even
Coronaries deliver blood with increased oxygen paralytics. Some vasoactive infusions might be
capacity to struggling myocytes. Ventricular used to augment cardiac output and maintain
function responds and hemodynamics further blood pressure. If the patient seems stable, VV-
improve. Oxygen delivery and CO2 clearance ECLS support is an appropriate place to start.
are accomplished by VV-ECLS and dependence Ideally, a dual lumen cannula should be placed
on mechanical ventilation wanes. Ventilation in the right internal jugular but this requires
pressure and rate can be lowered, decreasing transporting the patient to a room capable of
intrathoracic pressure, allowing cardiac venous fluoroscopy. Transporting these patients can be
return to rise. All of this results in improved he- challenging and often times the safest strategy is
modynamic function. In this example, although to travel using the ICU ventilator. Transitioning
430
to a transport ventilator can interrupt the airway, Unstable Respiratory Failure with Supportable
release the PEEP, de-recruit the lung and result Hemodynamics
in an unrecoverable condition. Clamping the
endotracheal tube is wise when making any Some respiratory failure patients are pre-
break in the circuit. carious and unstable. Some patients are so
Echocardiography guidance is acceptable fragile that they will not tolerate changes in
for placing the dual lumen cannula, however bed positioning. These patients cannot be safely
critical aspects of cannulae positioning can be transported to a fluoroscopy suite, so a bedside
missed by echo.6-9 Real time fluoroscopy allows cannulation is indicated. If VV-ECLS is the
visualizing the wire and the entire length of the indicated mode, two-site VV-ECLS cannulation
cannula during cannulation. Even with the wire is the safest option. In this clinical scenario, it
appropriately positioned below the diaphragm can be more challenging to attempt a bedside
in the inferior vena cava, the cannula can still echocardiography guided dual lumen cannula.
enter the right ventricle, the coronary sinus, or The typical strategy would include the right
the hepatic veins. Any of these cannulation internal jugular vein and one or both femoral
misadventures can be unrecognized on echo, veins. Echocardiography is helpful to posi-
leading to an unrecoverable complication. If the tion long cannulas placed in the femoral veins,
patient is stable enough to move, it is advanta- designed to have the tip near the right atrium.
geous to go to a fluoroscopic capable suite for
dual lumen cannula placement. A fluoroscopy
capable operating room offers advantages if
it becomes necessary to convert to an open
surgical cannulation. Otherwise, a catheteriza-
tion lab or interventional radiology suite will
be adequate. Those new to cannulating should
only use fluoroscopy when placing the current
generation of adult dual lumen VV cannulas.10
Figures 38-1 and 38-2 show a chest x-ray of a
patient after placement of the bicaval cannula.
Figure 38-2. Anatomical landmarks labeled.

31 French Avalon Elite bi-caval cannula. The
cannula is straight and the tip is below the
diaphragm. If the tip bowed to the left or the
right, there would be concern for placement
into a hepatic vein. The reinfusion port is 10
cm proximal to the tip and is where the cannula
tapers. The SVC drainage is about 14.5 cm;
about 4.5 cm from the taper.
This adult is 5’9” (175 cm). The carina is at
the level of the 6th thoracic vertebral body
(T6). The tricuspid valve should be level with
the 8th thoracic vertebral body (T8). This can-
Figure 38-1. Chest x-ray after placement of 31 nula is designed to have reinfusion jet directed
Fr Avalon Elite dual lumen bi-caval cannula towards, and across, the tricuspid valve.
431
Chapter 38
Venous drainage from the femoral cannula with most common approach is the femoral artery
return to the internal jugular vein cannula is the and vein. The internal jugular vein is also an
most common technique. Successful support acceptable site for venous drainage. Femoral ar-
can also be offered with venous drainage from terial cannulas can cause lower extremity malp-
the internal jugular vein as well, returning oxy- erfusion, by obstructing distal arterial perfusion,
genated blood to the femoral cannula.11 Figures causing ischemia, compartment syndrome, and
38-3 and 38-4 show a chest x-ray of a patient loss of leg. Distal perfusion can be supported by
with two venous cannulas. placing an 8-12 Fr cannula in the femoral artery,
and directing flow in an antegrade fashion to the
Unstable Respiratory Failure with Unstable leg. An alternative approach can be retrograde
Hemodynamics perfusion of the leg, accomplished by placing
a 4-8 Fr cannula in the posterior tibial artery.12
In this presentation, it will be important to Flow of 100-150 cc/min is sufficient to perfuse
decide if the clinical status is due to isolated the leg.
respiratory failure, sepsis, a pulmonary em-
bolus, perhaps there is a tension pneumotho- Hypercarbia without Hypoxia
rax. Respiratory failure that has progressed to
hemodynamic instability and malperfusion is Hypercarbia is a consequence of under ven-
unlikely to be isolated respiratory failure. If it tilation and is more frequently being managed
is, perhaps the decision to move to ECLS has with extracorporeal techniques. Clearance of
taken too long. Ideally, the initiation of ECLS CO2 can be efficiently and quickly achieved
for isolated respiratory failure should never be with extracorporeal techniques, requiring about
an emergency. 25% of blood flow necessary for VV-ECLS used
VA-ECLS is the indicated mode when sig- to support hypoxia. There are two approaches.
nificant hemodynamic support is required. The One is venovenous, using a dual lumen cannula,
Figure 38-3. Venovenous ECLS using two can- Figure 38-4. The long venous drainage cannula
nulas. A 23 Fr long drainage cannula is placed has the tip in the hepatic cava, near the atrial
in the right femoral vein. A short 21 Fr cannula caval junction. The reinfusion cannula is near
is placed in the right internal jugular vein. the confluence of the right internal jugular vein,
the innominate vein and the right atrium.
432
a pump and a membrane gas exchange device. appropriate for adult support (20 Fr, 23 Fr, 27 Fr,
The other approach is utilizing an arteriovenous 31 Fr). These larger diameter cannulas are the
shunt, a pair of cannulas and a membrane gas same length, 31 cm, and offer flows limited by
exchange device. This is commonly referred the diameter. Most adults have a right internal
to AVCO2R removal. Groin vessels are most jugular vein large enough to accommodate the
commonly used and awake ambulation is im- 27 Fr and 31 Fr sizes. ECLS flow will always be
practical.13 limited by venous drainage, when the cannula
is appropriately positioned.
Respiratory Failure and Sepsis Percutaneous Seldinger technique should
be the primary approach. The Avalon Elite has
Hypoxia, hypercarbia, metabolic and/ a separate dilator and wire kit appropriate for
or mixed acidosis, hypotension, and cardiac these 31 cm length cannulas. The wire is 210
dysfunction are seen in sepsis. VA-ECLS can cm and is relatively flimsy. Stiffer wires of the
offer gas exchange, biventricular support and same length can be helpful and these are avail-
augment blood pressure. VA-ECLS for malp- able in most fluoroscopy suites. Ultrasound
erfusion in sepsis seems rationale, but remains should be used to identify the internal jugular
controversial, as it is not always certain if and initiate access. The jugular diameter can
improving tissue perfusion is always possible. be measured, helping to choose ideal cannulae
VA-ECLS has been reported as effective in size. Fluoroscopy is used to assure wire place-
children and continues to appear in the literature ment is in the hepatic cava, as opposed to the
related to adult sepsis.14-16 Sepsis physiology right ventricle, coronary sinus, or hepatic veins.
represents a spectrum and there is little guid- Fluoroscopy is used as dilations take place and
ance to help identify generalizable indications as the cannula is inserted. While the wire might
and contraindications. Large studies would help be in the appropriate position, the stiffer cannula
guide clinical thinking; however, studies of this can still pass into the ventricle, coronary sinus,
nature are impractical and not on the horizon. and hepatic veins, carrying the wire along in
VA-ECLS for severe refractory sepsis is a com- its path. Injury to these structures can be a life
plicated undertaking and should be considered threatening complication.
by experienced ECLS programs.17-20 The skin incision should be slightly smaller
than the diameter of the cannula, so that the
Technical Aspects of Cannulation for Adult final placement will be closely approximated
Respiratory Failure to the edge of the skin incision, minimizing
bleeding at the insertion site. Serial dilations
The decision to cannulate has been made. are necessary to create a tract, from skin to
The necessary mode is based on the patient’s vein, to receive the cannula. Gentle steady pres-
pathophysiology. Technical considerations of sure is required. The cannula has a tendency
the various modes are described below. to buckle if the tract is too tight. Creating the
tract takes patience and can be accomplished
VV-ECLS Cannulation-Single Site, Dual in a controlled, slow fashion. Creating the tract
Lumen will be a distraction from proper wire position-
ing. It is common that while focusing on the
Dual lumen cannulation via the right inter- dilations, the wire will either pull back or loop
nal jugular vein, guided with fluoroscopy, is pre- in the ventricle. Once satisfied with the dila-
ferred. The Avalon Elite® dual lumen bicaval tion, review wire positioning with fluoroscopy.
cannula is currently available and in four sizes It remains common practice to systemically
433
Chapter 38
anticoagulate the patient prior to cannula inser- chosen, there is likely a positioning problem.
tion. 50-100 units/kg of unfractionated heparin This should be identified at the time of cannula-
is a typical dose and is about 1/3 the dose used tion not upon return to the ICU. Open surgical
for cardiopulmonary bypass. Waiting for the approaches are possible for adult cannulation
heparin to circulate makes sense. Checking but few clinical scenarios would require this
baseline coagulation parameters prior to can- strategy.
nulating should be done. Multiple strategies of
anticoagulation exist (see Chapter 8) and will VV-ECLS Cannulation-Two Site, or Multiple
not be discussed in this chapter.
The cannula is designed to have the distal Multiple site VV cannulation is possible
drainage tip in the hepatic cava. The reinfusion and practical but should be reserved for patients
jet is designed to be oriented towards, and at who are not candidates for single site dual lumen
the level of the tricuspid valve. The cannula approach. This can be safely done at the bedside
tip is easier to see radiographically, after the without any visualization techniques; however,
introducer is removed. However, once the in- ultrasound is usually helpful. Previously placed
troducer is removed, it is difficult, and unsafe, central lines can be used and exchanged over a
to advance the cannula. The most common wire. Venous access typically is the right inter-
reason for advancement of the cannula is that nal jugular vein and a femoral vein. A common
the tip is in the right ventricle. The introducer approach is placing a long 23-28 Fr cannula for
should be replaced and the tip advanced under venous drainage from the patient in a femoral
fluoroscopy. A cannula placed too deep can be vein with arterialized return going to the right
easily pulled back without having to replace the internal jugular cannula. Since the vena cava is
introducer. Figure 38-1 is a chest x-ray docu- a right-sided structure, the right femoral vein
menting appropriate cannula position. Figure is preferred for placement of the long cannulas
38-2 identifies anatomic landmarks of a typical but the left femoral vein is a reasonable and
adult patient and the cannula. Daily chest x-rays safe alternative. The right internal jugular vein
can help identify changes in cannula positioning. cannula can be relatively small (17-23 Fr), real-
Taking a picture of the cannula site at the skin izing that the pressure generated by the pump
can be used as an additional tool for nurses to will overcome the resistance of a small diameter
monitor changes in cannula position. Activity cannula. Short cannulas should be used in the
on ECLS is encouraged and cannula position internal jugular position. These cannulas should
changes are possible. be placed using ultrasound guided Seldinger
Once the cannula is appropriately posi- techniques. Surface or transesophageal echocar-
tioned, VV-ECLS support can be initiated. diography can be used to optimize the position
Flow should be slowly established (0.5 -1.0 L of the long venous drainage cannula, ideally
liter/min) in order to minimize hemodynamic with the tip outside the right ventricle.
instability. Once oxygenated blood is being This two-cannula approach can be hindered
infused via the cannula, flow can be increased. by recirculation. Recirculation can be identified
Flow should be increased to identify the maxi- by falling arterial saturations with increasing
mum flow achievable. Adult support typically pump flows. Supporting a diagnosis of recircu-
requires 60-80 cc/kg/min (3-6 liters/min) sup- lation will be an associated increase in “mixed
porting metabolic needs of about 3 cc O2/kg/ venous” saturations, commonly estimated by
min, when hemoglobin is close to normal. At measuring the saturation of the venous drain-
the time of cannulation, if you are not able to age blood, not the true mixed venous, which is
achieve the anticipated flow rate for the cannula measured distal to the pulmonic valve. Recir-
434
culation is only an issue if the ECMO support Surgical technique can be used to place the
is felt to be marginal (patient arterial saturation arterial cannula. The femoral artery is exposed
<75%, PaO2<45 mmHg, when Hgb 14-15 gm/ and the cannula can be directly placed via an
dL). Once cannulation is accomplished, ECLS arteriotomy. Proximal and distal arterial control
flows should be increased so that maximum flow is achieved using typical vascular surgical tech-
can be identified. If support is marginal, an ad- niques. A purse-string suture can be placed in
ditional venous drainage cannula can be placed the artery, around the arteriotomy. A snare can
in the remaining femoral vein. This should be a be used to secure the arteriotomy. The wound
short cannula of 21-23 Fr caliber. Figures 38-3 can be closed over the insertion site or the
and 38-4 show chest x-rays of patient supported wound can be packed open.
venous cannulas in the right internal jugular The “semi-Seldinger” technique is also an
vein and the right femoral vein. In this particular option for the arterial cannulation. The femoral
case, venous drainage from the patient is via the artery is exposed. A needle is pierced through
long femoral cannula. The “arterialized” return the skin inferior to the incision, entering the
blood is via the right internal jugular venous anterior vessel wall under direct vision. A tract
cannula. Flow could be reversed and support is serially dilated and the cannula is passed. The
would be comparable. Open surgical techniques cannula insertion is palpable in the artery, via
are possible but unlikely necessary. the wound, providing most of the advantages of
the open surgical approach. This semi-Seldinger
VV-ECLS for CO2 Removal technique can offer improved hemostasis. This
is a common technique for VA cannulation used
The technical details described for VV- in neonates.
ECLS cannulation using the dual lumen cannula
apply when placing a dual lumen cannula for VA-ECLS
CO2 removal. The large cannulas (20-31 Fr)
can be used but flow will be excessive. Most This approach is described in detail else-
adults would require 0.5-1.0 LPM blood flow where in the text (see Chapter 47).
to remove the metabolic production of CO2.
Smaller cannulas can be easier to place with less
risk. Dual lumen cannulas 15-16 Fr can suffice.
AV-ECLS for CO2 Removal
Arteriovenous approach for CO2 removal

require 0.5-1.5 LPM flow.13 This can be ac-
complished with a 12-14 Fr arterial cannula
and a 16-18 Fr venous cannula. Both the arterial
and venous cannulas can be safely placed with
percutaneous Seldinger techniques. Ultrasound
should be used for placement. Arterial cannulas
of this size can be easily removed by pulling
and holding pressure, similar to removing a
balloon pump. Surgical removal is not com-
monly required.
435
Chapter 38
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39
Comorbidities among ECLS Patients with Respiratory Failure
Vincent Pellegrino, MBBS, FRACP, CICM
Introduction the need for ECLS will be considered in this

chapter. Chronic respiratory conditions likely
Comorbidities, or preexisting chronic to be associated with irreversible lung failure,
health conditions, that increase the risk of de- such as pulmonary hypertension, cystic fibrosis,
veloping severe respiratory failure and impact and pulmonary fibrosis, where the use of ECLS
negatively on patient outcome and resource uti- is considered as a pathway to lung transplant,
lization include a broad range of illness common will not be considered. Immunosuppressing
in adults. Common chronic health conditions, conditions are considered in greater detail in a
which are likely to be present in patients with dedicated Chapter 60.
severe forms of respiratory failure considered
for ECLS support and which will be considered Comorbidities and Patient Outcome from
in this chapter can be broadly classified as: ECLS
• Degenerative or progressive illnesses asso- Advancing age and comorbidities due

ciated with advancing age including arterial to arterial vascular disease, cardiac failure,
vascular diseases and chronic organ failures chronic lung disease chronic renal failure, im-
(cardiac, kidney, liver and lung) munosuppressing conditions, and the presence
• Malignancies of malignancy all mitigate the ability of the
• Illnesses which result in immunosuppres- lung to recover from severe injury, shorten life
sion expectancy, and would be considered relative
• Morbid obesity exclusions to the beneficial application of ECLS
in adult populations.
As ECLS utilization increases and greater Local care practice and resource limitation
experience is gained it is likely that more and vary across health systems and ultimately drive
more patients with severe acute forms of respi- the selection process for providing ECLS prac-
ratory failure and with comorbidities are receiv- tice. As critical care practice evolves, outcomes
ing and being considered for ECLS. improve, and the reach of therapies is extended,
The effect of comorbidities on patient out- the need for up to date information becomes
come following ECLS, the impact of comor- more urgent. While clinicians are often chal-
bidities on providing ECLS, and the association lenged to weigh the impact of comorbidities
between the presence of some comorbidities and and advancing age when considering patient
439
Chapter 39
selection for ECLS for respiratory failure sup- estimating the risk of death. These variables are
port, limited data exist to guide decisionmaking. then combined in an algorithm, which is then
The only recently completed randomized applied to the derivative population (internal
controlled trial of ECMO in severe adult respi- validation) and then tested on a new population
ratory failure, the CESAR trial, did not report (external validation). The larger the data set and
advanced comorbidities as exclusion criteria.1 the greater the number of centers including data,
Rather patients were excluded on the basis of the more likely these factors will be externally
being “moribund or having contraindications valid. They are limited by being based on out-
to continuation of care.” Data were not col- comes of patients who received ECLS, not those
lected on the presence of comorbidities in the considered for ECLS.
randomized groups, thus it remains uncertain The ELSO database is an international col-
whether an interaction between comorbidity lection of patient ECLS data and provides much
and outcome with ECMO occurred using this greater power to measure interaction between
powerful trial design. patient factors and outcome. The data fields in
We can look for evidence of the effect the ELSO database for comorbidity data collec-
of comorbidities on outcome from ECLS for tion include age, body mass index (BMI), and
severe respiratory failure from a number of immunocompromised state, which is defined as
sources including ECLS case series and the hematological malignancies, solid tumors, solid
ELSO database with risk prediction modeling organ transplants, HIV, and cirrhosis. Renal
and current validated non-ECLS risk prediction and cardiac dysfunctions are defined as either
models for conditions associated with severe acute or chronic impairment before or during
respiratory failure in adults. ECLS and central nervous system dysfunction
includes acute and chronic conditions such as
Comorbidities Identified in Adult VV-ECLS trauma, stroke, and epilepsy. The opportunity to
Case Series and the ELSO Database examine the relationship between comorbidities
and outcome is limited by the common inclu-
The impact of patient factors (such as pre- sion of chronic and acute renal, cardiac, and
existing medical conditions) on outcome can neurological insufficiency.
be measured in ECLS case series using multi- Table 39-1 summarizes the comorbidities
variant analysis. This allows factors associated studied in all mixed adult VV-ECLS case series
with outcome to be identified independent of since 2005, greater than 50 patients, where ad-
confounding effects.2 Information obtained vanced age and the presence of comorbidities
from such studies is often limited by small were analyzed for an effect on mortality.3-9
sample size, homogeneity (case selection), and In summary these studies almost exclu-
nomination of data fields, retrospective data sively deal with hospital mortality and ignore
collection and nonstandardized data definitions. other patient centered outcomes. Conclusions
Findings should be used with caution in differ- that can be drawn include:
ent patient settings to those of the original data
set and smaller single center case series lack • Age is a ubiquitously collected variable
power to detect a large number of independent and advancing age is strongly related to
associations. increased mortality, which is noted beyond
An extension of this approach is the de- the ages of 45-50. This was noted in virtu-
velopment of Risk Prediction Models, which ally all studies.
allows patient illness and treatment variables • The association of an immunocompromised
associated with outcome to be combined when state and higher mortality has been noted in
440
multiple studies. The definition of immuno- chanical ventilation and ECLS with H1N1
compromised state is reasonably consistent influenza. Where associations between BMI
between studies (see Table 39-1) but spans and mortality exist in ECLS case series, a
a wide variety of conditions (hematologi- protective effect was noted.
cal malignancy to high dose, short-term • The presence of significant neurological
corticosteroid use), which are likely to be disease, often a contraindication for ECLS,
associated with different mortality effects. cannot be studied in small case series. The
• BMI and obesity (BMI >30) was not as- ELSO database includes a field for neu-
sociated with increased mortality, although rological dysfunction, which comprises
it was a risk factor for the development of pre-ECLS illness but also includes cere-
severe respiratory failure requiring me- bral complications arising in association
Table 39-1. Mixed adult respiratory ECLS case series with more than 50 patients since 2005 where
the effect of advanced age and comorbidities were evaluated (largest to smallest size).
Author Study Period # Pts Study Population Comorbidities Analyzed Risk Effect of advanced age or co-morbidity
(Title) Prediction on mortality
Model (Y/N) (Weighting)
Schmidt 2000-2012 2355(1) ELSO Adult Age Yes Age 18-49 (Score 0)(2)
(RESPscore) Respiratory Immunocompromised (see Age 50-59 (Score -2)(2)
database text for definition) Age ≥60 (Score -3)(2)
BMI > 30 Immunocompromised (Score -2)(2)
BMI >30 not associated with hospital
CNS dysfunction(3) mortality
Renal dysfunction(3) CNS dysfunction (Score -7) (3)
Cardiac dysfunction(3) Renal dysfunction: independently
associated hospital mortality Odds Ratio
0.77 (but not included in the score)
Cardiac dysfunction not associated with
hospital mortality
Brogan 1986-2006 1473 ELSO Adult Age No Age: Highly significantly associated with
Respiratory Weight mortality across early and late cohorts
database
Enger 2008-2013 304 University Medical Age Yes Age (per 5 years) Odds ratio hospital
Center Regensburg Immunocompromised(4) mortality 1.193 (CI 1.1 - 1.2)
Immunocompromised Odds ratio 2.6 (CI
1.3 – 5.2)
Schmid 2007-2010 176 University Medical Age No Age
Center Regensburg
Schmidt 2008-2012 140 3 French Centers Age Yes Age <45 (score 0)(6)
(PRESERVE BMI Age 45-55 (score 2) (6)
score) Immunocompromised(4) Age >55 (score 3) (6)
Charlson Score(5) BMI >30 (score -2) (6) associated with
McCabe and Jackson Score(5) increased survival
Immunocompromised (score 2) (6)
Co-morbidity scores were strongly
associated with outcome in the univarate
analysis, but were not found to be
independently associated with outcome
in this study population
Roch 2009-2013 85 Marseille, France Age Yes Age <45 (Score 0)(8)
BMI Age >45 (Score 1)(8)
Comorbidities(7) BMI (and BMI>30) not associated with
mortality
Comorbidities: no effect on outcome
Aubron 2005-2011 52 Melbourne, Age No Age not found to be associated with
Australia Chronic respiratory failure mortality
+Cystic Fibrosis Chronic respiratory illnesses not found to
Immunocompromised be associated with mortality
Immunocompromised state not found to
be associated with mortality
(1)
2355 with complete data on first ECMO run
(2)
Greater negative scores associated with increased mortality. Total score range -22 to 15 with a total score of 0 indicating a 50% risk of hospital mortality
(3)
Includes both acute and chronic illnesses
(4)
Immunocompromised state included is similar to ELSO category (does not include cirrhosis) and does include high-dose or long-term corticosteroids or other
immunosuppressive therapy
(5)
Summary score of 21 common Comorbidities. Each condition allocated a point score of 1-6 points. Metastatic solid tumor = 6 points (max)
(6)
Higher score indicates greater risk of death at 6 months post ICU discharge (Total score range 0 – 14) with scores of -1 and -2 converted to 0
(7)
8 separate Comorbidities were listed: Chronic lung disease, diabetes, transplantation, malignancy, immunocompromised, HIV, drug addiction
(8)
Greater positive scores associated with increased mortality. Total score range 0-4
441
Chapter 39
with ECLS. The presence of neurological assign risk to patients presenting to hospital
dysfunction appears highly associated with with CAP.13,14 Comorbidities included in this
poor survival.3 score were: age, neoplastic disease, chronic
• Many degenerative comorbidities such as liver disease, congestive heart failure, cere-
chronic lung, heart, kidney, and liver failure brovascular disease, and chronic renal failure.
and those due to vascular disease are not All comorbidities were associated with higher
routinely captured in ECLS case series or mortality and rates of ICU and hospital admis-
the ELSO database but likely contribute sion. Neoplastic diseases and liver disease had
to clinical outcomes. Validated summary the highest weightings for increased mortality.
scores of comorbidities such as the Charl- Although less well validated, specific risk pre-
son and McCabe Scores best represent the diction tools for mortality prediction for CAP
burden of these illnesses.10-12 Only one patients in intensive care, which incorporate
ECLS study (140 patients) has used such chronic health variables have demonstrated the
an approach to measure the independent presence of advanced age, chronic respiratory
relationship between common comorbidi- disease, immunosuppression, and a comorbidity
ties and outcome in a multicenter study and classified by the McCabe Classification likely
failed to find an independent association.7 leading to death within five years, as strong
independent predictors of hospital mortality.15,16
Ideally, scoring systems to capture co- In ARDS, risk prediction most commonly
morbidity burden of patients considered for rests only on oxygenation indices.17 Where other
ECLS would have simple and accurate data risk prediction variables have been incorporated
capture from hospital records and be updated into risk prediction models they have incorpo-
and revalidated over time. Linking such data to rated APACHE chronic health states and do not
ECLS use across many centers and including it directly measure the effect of comorbidities.18,19
in large databases such as ELSO may greatly A recent ICU mortality risk prediction for
improve risk prediction by incorporating effects Australasia, which includes APACHE chronic
of comorbidities. health variables, has measured the contribution
of age and chronic health conditions for all
Impact of Comorbidities on Outcome in ICU patients as almost 25%.20 These studies
Non-ECLS Adults with Severe Respiratory support the strong negative effect of comorbidi-
Failure ties on survival and health resource utilization.
To some extent these finding would apply to
Of all patients with severe respiratory patients receiving ECLS support for similar
failure, patients receiving ECLS make up a underling conditions.
small proportion. Research into the association
between the presence of comorbidities and pa- Specific Common Comorbidities and Their
tient outcome from common causes of severe Interaction with ECLS
respiratory failure such as community acquired
pneumonia (CAP) and ARDS in non-ECLS Obesity
populations have used either a ubiquitous ICU
scoring system such as APACHE (Acute Physi- The proportion of obese adults (BMI >30)
ology and Chronic Health Evaluation) or other is increasing in many countries and this trend
scoring systems discussed below. is expected to continue. In the first wave of the
The pneumonia severity index (PSI) is a 2009 H1N1 influenza pandemic, morbid obesity
widely cited and validated scoring system to (BMI>40) increased the hospitalization rate,
442
receipt of invasive mechanical ventilation, and, receiving ECLS for respiratory failure, except
along with immunosuppression and chronic some patients with renal failure.33,34 Some health
lung disease, acted as a risk factor for severe providers advocate for aggressive treatment in
disease.21-26 Crude mortality rates from acute this cohort despite high mortality.
respiratory failure with invasive mechanical
ventilation is lower for morbidly obese patients Chronic Renal Failure
than nonobese patients and being underweight is
associated with higher mortality.21,27 Morbidly There are no reports of patient outcome
obese patients have been noted to be younger with advanced renal failure in adult ECLS case
with fewer accompanying comorbidities. After series of respiratory failure. The number of pa-
adjusting for age and other confounders, mortal- tients with endstage renal failure (ESRF) and
ity does not differ significantly for obese and chronic kidney disease (CKD) is increasing due
morbidly obese patients with severe respiratory to rising incidences of diabetes and hyperten-
failure supported with invasive mechanical sion and these patients have a higher incidence
ventilation or ECLS compared to nonobese of developing critical illness.35 Chronic renal
adults.21,28,29 failure patients have a higher mortality follow-
In addition, morbid obesity provides chal- ing ICU admission but this appears due to a
lenges to the provision of ECLS for severe much higher number of comorbidities associ-
respiratory failure in adults.30 Ultrasound guid- ated with ESRF rather than an effect of renal
ance for cannulation of femoral vessels may be failure per se. A systematic review found that
impossible or difficult and double-lumen jugular survival of patients with ESRF admitted to ICU
cannulation is more common in these patents.28 with respiratory failure was less than in those
Although achieving adequate ECLS blood flow patients developing acute renal failure during
to meet oxygenation targets in morbidly obese their ICU admission, but that long-term survival
patients often proves difficult, it was not asso- was reduced following ICU admission and that
ciated with reduced survival.28 Morbid obesity cardiac failure and infections remain the com-
was also associated with higher rates of renal monest causes of death.36 As such, the presence
failure in H1N1 cases and altered inflammatory of advanced renal disease would be expected
mediator profile.31 Morbid obesity may also to be associated with reduced hospital survival
impact patient transport platforms used for following ECLS support for reversible causes of
interhospital transport of ECLS cases. severe respiratory failure and elevated mortality
rates following ICU admission and increase the
Malignancy risk of secondary infection.
The presence and treatment of malignancy Chronic Liver Disease

create many forms of severe respiratory failure
for which mechanical ventilation may provide Reporting of ECLS support for patients
limited benefit. Younger patients with these with advanced forms of chronic liver disease
conditions, but without other comorbidities, are (CLD) remains rare and many centers would
often considered for ECLS support.32 Reports exclude such patients from ECLS support other
on ECLS outcomes remain few, some centers than in the early post liver transplant setting.37,38
have for decades provided ECLS to younger Early and long-term survival rates reported in
patients with respiratory failure associated severe CLD admitted to ICU, without the use
with hematological malignancy and reported of ECLS, strongly suggest that in the cases
survival rates much lower than other cohorts of refractory respiratory failure, enduring pa-
443
Chapter 39
tient benefit would be unlikely with the use of timeliness and adequacy of ECLS support, as
ECLS.39,40 In carefully selected cases of refrac- well as complications from ECLS. The ability
tory respiratory failure with lesser forms of to make better-informed clinical decisions in
CLD, ECLS could be considered but it would the future will require risk prediction models
be presumed to impose higher risks of sepsis incorporating improved patient data collection
and bleeding complications. including past medical problems. Comorbidi-
ties and age contribute heavily to mortality risk
Summary prediction in critically ill populations but are
currently not incorporated into such models for
Degenerative processes associated with ad- ECLS patients.
vancing age including arterial vascular disease
and chronic failure of the lungs, kidney, and
liver are poorly captured in descriptive ECLS
case series. Estimates of their negative effect
on outcome can be made from broader studies
examining their effect on outcome from critical
illness not involving ECLS. While in all cases
the presence of advanced forms of these comor-
bidities would have an adverse effect on survival
and recovery, their presence alone would not
necessarily contraindicate ECLS support, but
would have to be considered in conjunction with
other factors. Of these conditions, advanced
forms of chronic liver disease would appear be
the strongest deterrent to the use of ECLS for
severe respiratory failure.
The adverse effects of immunosuppres-
sive conditions and malignancies on patient
outcome are commonly captured in ECLS and
severe respiratory failure case-series; however,
definitions of immunosuppressive conditions
vary slightly and incorporate a broad range of
conditions of ranging severity. Selection and
subsequent management of such patients sup-
ported with ECLS is extremely challenging
and should be the domain of highly specialized
ECLS centers.
Obesity does not seem to have a negative ef-
fect on outcome from severe respiratory failure
with or without ECLS particularly with single
organ failure.
Finally, the effect of comorbidities on out-
come from severe respiratory failure is likely
to interact with other factors known to effect
outcome such as age, acute illness severity,
444
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447
40
Medical Management of the Adult with Respiratory Failure on ECLS
Caroline Sampson, MBBS, Richard Porter, MBChB
Introduction ing time for recovery and reduction of further

damage to the lung secondary to aggressive
The medical management of the patient ventilator strategies (ventilator induced lung
with severe respiratory failure receiving VV injury). A large systematic review confirmed
extracorporeal support is complex and can that potentially injurious mechanical ventilation
be very challenging. Ideally, the patient with parameters were reduced with the initiation of
severe respiratory impairment, not the ECLS ECLS. That mortality was lower in groups of
circuit, should be the center of attention. ECLS patients who had a lower intensity of applied
specific treatment should incorporate routine ventilation following ECLS initiation.4 A mul-
intensive care unit (ICU) management, alter ticenter retrospective study also demonstrated
treatment strategies, and avoid complications. that not only were protective mechanical venti-
Optimal care of VV-ECLS patients requires lation strategies routinely employed following
teamwork, attention to detail, and enhanced ECLS initiation, but that higher levels of PEEP
clinical experience. were independently associated with improved
survival.5 Further prospective trials defining
Ventilatory Support optimal targets for tidal volume, plateau pres-
sure, PEEP, and FiO2 are warranted.
During institution of extracorporeal respi- In practice at our institution, the default
ratory support, mechanical ventilation settings initial “rest ventilatory” settings for ECLS pa-
often exceed the guidelines of lung protective tients include using a bilevel airway pressure
ventilation in an attempt to achieve acceptable mode with an inspired pressure of 20-25 cmH20
arterial oxygen saturations. Therefore, it is im- and a positive end expiratory pressure (PEEP)
perative that all patients should be ventilated of 10 cmH20, with a rate of 10-12 breaths per
within lung protective parameters; aiming for minute. Parameters will vary depending on the
a tidal volume of ≤6 ml/kg ideal body weight underlying reason for ECLS support, such as
with plateau airway pressures ≤30 cmH20 to prolonging expiratory times in patients with
avoid any further ventilator initiated lung injury acute bronchospasm and using higher levels of
(VILI). This has demonstrated, in numerous PEEP in obese patients. We aim to reduce FiO2
trials, to confer a mortality benefit in ARDS.1-3 to 30% accepting PaO2 ≥45 mmHg. In some
Extracorporeal respiratory support temporarily patients, particularly with higher body mass
replaces the native pulmonary function allow- indexes or high cardiac output states, a partial
449
Chapter 40
ventilatory strategy is necessary using inspira- Bronchoscopy

tory pressures up to 30 cmH20 and PEEP up to
14 cmH20. We also keep FiO2 <60% to minimize Bronchoscopic examination and lung la-
oxygen toxicity and absorptive atelectasis.6 vage should be regularly undertaken, both to
At times, we employ alternative ventilation obtain broncheoalveolar lavage specimens for
modes in patients who remain hypoxic despite microbiological examination and as a therapeu-
full ECLS support, including airway pressure tic intervention to clear excessive secretions,
release ventilation (APRV) and high frequency exudate, or blood. A skilled operator should
oscillatory ventilation (HFOV). Following the always perform bronchoscopy in anticoagulated
publication of the OSCAR and Oscillate trials ECLS patients.
in 2013, the efficacy of HFOV has been ques-
tioned, but we find it a potentially useful mode Airway Hemorrhage
to reduce and control mean airway pressures in
patients with bronchopleural fistulae, allowing Airway haemorrhage in itself is an infre-
healing and spontaneous resolution of signifi- quent indication for ECLS support. Significant
cant air leak syndromes.7,8 airway bleeding may occur spontaneously
Signs of recovery can commence within during ECLS support, particularly in patients
a week but sometimes are delayed by several with bronchiectasis, cavitating pneumonias,
weeks or in rare cases more than a month. Of- or mycobacterial infections. Bleeding often
ten the first indicator is an improvement in complicates airway procedures such as trache-
compliance with increased tidal volumes. If ostomy or bronchoscopy. Major bleeding can
ultra-protective ventilation strategies are used, be tamponaded by directly clamping either a
an increase in airway pressures may be neces- single or dual lumen endotracheal tube with
sary to recruit more lung tissue. Only when total reliance on ECLS support for gas exchange.
ventilation parameters become compatible with Intubation with a dual lumen endotracheal tube
survival without ECLS but with lung-protective is preferable with unilateral bleeds to prevent
strategies, should discontinuation of VV-ECLS contralateral airway soiling, but should be at-
be attempted. tempted only if it is safe and achievable within
a short time scale. Patients managed in this way
Prone Positioning will need to be deeply sedated and paralysed,
as spontaneous ventilatory efforts can generate
Prone positioning shows improvement high negative inspiratory pressure, potentially
in oxygenation, and more recently a survival leading to negative pressure pulmonary edema.
benefit in ARDS.9 Although logistically more An alternative technique employs continuous
difficult during extracorporeal support, expe- positive airways pressure (CPAP) set at 5 cmH20
rienced centers have facilitated lung recovery above central venous pressure. This should al-
and hastened VV-ECLS weaning using prone low the bleeding to tamponade, and may permit
positioning.10 We prone position VV-ECLS a degree of oxygenation. Patients with cardio-
patients as a rescue technique for hypoxia and, vascular instability, fluid depletion, or right
in certain cases, to mobilize secretions. This ventricular dysfunction may not tolerate high
is particularly helpful with radiographically levels of CPAP and we would not recommend
demonstrable dense posterior consolidation levels greater than 20 cmH20. For patients with
and especially when respiratory physiotherapy continued bleeding or hemodynamic instability,
sessions are nonproductive. urgent CT angiography is required to delineate
the site of bleeding. Surgical or interventional
450
radiologic intervention may be warranted to improved oral dietary intake, communication

achieve control of clinically significant hemor- and morale, and possibly easier mobilization
rhage. For patients with diffuse alveolar hemor- and physical rehabilitation. This technique is
rhage secondary to vasculitides or connective particularly useful in status asthmaticus patients.
tissue disorders, bleeding may be controlled When the initial bronchospasm is breaking, the
with “rest” ventilator settings and treatment of very presence of a tracheal tube can aggravate
the underlying disorder with steroid immuno- airway reactivity and extubation provides an
suppression and/or plasmapheresis without the easy way to break this cycle. Potential difficul-
need for the techniques described above. ties with extubation include those patients with
high work of breathing and poor secretion clear-
Tracheostomy ance. This technique should only be attempted
in experienced centers. Only a minority of
Good evidence exists for ARDS patients on patients may be suitable for such a strategy with
mechanical ventilation that continuous muscle experienced centers reporting 7% of their cases
relaxation should be limited to the first 1-2 days extubated during VV-ECLS.12
of ventilation and light sedation is preferred. To
facilitate long-term ventilation and weaning, a Cardiovascular Support: Vasopressors and
tracheostomy is often performed. It remains Inotropes
unclear if this practice should be followed in
patients on ECLS. Early institution of a trache- Commencement of VV-ECLS usually re-
ostomy is practiced in some centers, but any sults in decreasing vasopressor and inotropic
evidence of benefit or potential risks remains requirements. The reduction in intrathoracic
unpublished.11 We aim for early tracheostomy in pressures achieved with lung rest settings and
all patients we expect to need ECLS support for improved myocardial oxygen delivery from
five days or longer, usually with a percutaneous the commencement of ECLS provides indirect
technique under direct bronchoscopic vision cardiac support. In patients with intravascular
on the ICU. Assuming sufficient ECLS flow depletion, maintaining adequate preload with-
rates, heparin anticoagulation is discontinued out the concern of worsening lung function also
peri-procedure and for the first six hours fol- contributes to optimization in cardiovascular
lowing tracheostomy, then reintroduced at a status.
lower rate initially. Sedation is weaned rapidly If vasopressor requirements remain high,
to get the patient breathing spontaneously using hydrocortisone at 50 mg every 6 hours may
a pressure support mode of ventilation as soon be either continued or commenced. Although
as possible. studies did not demonstrate an improvement
in outcome, hydrocortisone may reduce pe-
Awake Extubation riods of cardiovascular instability.13 In the
event of significant peripheral vasoconstric-
In a small cohort of patients, awake ex- tion, we consider milrinone or enoximone,
tubation is performed while receiving ECLS to improve perfusion. All patients presenting
and a strategy to wean mechanical ventilation for VV-ECLS should undergo comprehensive
before liberation of extracorporeal support has echocardiographic examination to demonstrate
been suggested in case reports. If appropri- any significant cardiac abnormalities that may
ate, extubation confers a number of benefits need treatment.
including: decreased need for sedation and
risk of ventilator-associated pneumonia (VAP),
451
Chapter 40
Right Heart Failure Arrhythmias
Right heart failure is a feared complication In the event of persistent bradycardia or

on VV-ECLS. Our first line strategies are to use heart block, we have a low threshold for pace-
epinephrine and/or milrinone to provide sup- maker insertion. Tachyarrhythmias are treated
port. With failure to improve by these measures, aggressively both chemically and with DC
atrial septostomy can be considered. However, cardioversion. On VV-ECLS we have a low
significant intractable right heart failure is as- threshold to use DC cardioversion for AF as it
sociated with high mortality and consideration can increase the risk of recirculation. During
should be given to palliation in these patients if cardioversion we temporarily reduce the ECLS
acutely treatable conditions are excluded. circuit flows.
Venoarterial Support Sedation Management
In patients with ongoing inotropic sup- Lighter sedation allows communication

port requirements consideration is given to VA with the patient, assessment of pain, and early
support. We would insert an additional arterial recognition of a cerebral insult. Compared to
cannula using a Dacron graft to the femoral over sedation, lighter sedation is associated with
artery or by percutaneous means to convert to less drug accumulation, which may reduce the
VVA-ECLS. If required to achieve flows an ad- ICU length of stay, duration of ventilation, and
ditional drainage cannula can be inserted. The the risk of delirium with the associated increase
decision for initiation of VA support is made mortality.14 We routinely utilise the Richmond
on a case-by-case basis, as overall fatality rates Agitation Sedation Scale (RASS) to guide
following this support are high. overall sedation practice (Table 40-1).15,16 We
target a RASS score of -1 to 0. The choice of
agent is difficult and with VV-ECLS patients in
the early phase deeper sedation and paralysis
may be required prior to moving towards the
Table 40-1. Richmond Agitation–Sedation Scale (RASS).
1. Observe patient
If restless or agitated +4 Combative Overtly combative or violent; immediate danger to staff
score from +1 to +4. If +3 Very agitated Pulls on or removes tubes or catheters; aggressive
alert or calm score 0. If +2 Agitated Frequent non-purposeful movement, patient-ventilator
not alert progress to dysynchrony
stage 2. +1 Restless Anxious but movements not vigorous or aggressive
0 Alert and calm
2. Assess response from verbal stimulation – state patients name and ask to open eyes and look at speaker.
Repeat one time if necessary.
If response from voice -1 Drowsy Not fully alert, awakens and sustains eye opening and
then assess from -1 to - contact for > 10 secs
3. If no response move -2 Light sedation Awakens and briefly sustains eye contact and opening
to stage 3. for < 10 secs
-3 Moderate sedation Any movement in response to voice but no eye contact
3. Physical stimulation by shoulder shake or sternal rub (if safe)
Assess response to -4 Deep sedation Movement or eye opening to physical stimulation
physical stimulus. -5 Unrousable No response to physical stimulation
452
more awake patient. At our center, we adjust including clonidine or dexmedetomidine, and
sedation to target the more awake patient as antipsychotics such as olanzapine and risperi-
per Figure 40-1. done, can also be used. Rivastigmine, however,
should be avoided as it is associated with a
Delirium higher mortality.17 Dangerous agitation, which
may cause ECLS circuit compromise, requires
We use the Confusion Assessment Method urgent management. We would routinely give
for the ICU (CAM-ICU) to assess for delirium.16 propofol boluses to gain control and adjust the
This requires a sedation level greater than -3 underlying sedation management.
by RASS scoring (responsive to verbal com-
mands). To be positive there must be evidence Intracerebral Hemorrhage
of a change in mental function from baseline or
fluctuation of mental status, including inatten- Intracerebral hemorrhage is a relatively rare
tion and either disorganized thinking or an al- but often fatal complication of ECLS therapy.
tered level of consciousness. We use haloperidol Deterioration in neurological function should
as the first line for delirium. Alpha 2 agonists, instigate an urgent CT scan of the brain. The
•Morphine and midazolam – as intravenous infusions
Initial 48 •May require paralysis – agent of choice is atracurium as

infusion
•Aim for spontaneous breathing and resposnsive to voice
hours (RASS 0 to -1)if clinically feasible by end of 48 hours period

•This is achieved by stopping paralysis ASAP and actively
reducing morphine and midazolam
•If ongoing sedation requirements still present use:
Following •Remifentanil infusion

•Propofol infusion if hypnotic agent required (ideally boluses
to control dangerous agitation)
48 hours •If ongoing agitation or delirium use haloperidol regularly

•Aim to stop propofol and remifentanil over 48 hours – if
needed clonidine can be used to facilitate this
Difficult •Dexemeditomidine if above techniques have failed to
Agitation
achieve awake and spontaneously breathing patient - by
consultant initiation only
Figure 40-1. Management of sedation.
453
Chapter 40
presence of intracerebral hemorrhage should be prophylaxis for stress ulcers with ranitidine or
discussed with neurosurgical specialists; how- proton pump inhibitors if previously received.
ever, in our experience, treatment is often not First line treatment for minor upper GI bleeds
possible and the outlook poor. Heparin infusion is an omeprazole infusion with gastroscopy if
should be stopped immediately if intracranial bleeding is significant or ongoing.
hemorrhage is suspected.
Endocrine Support
Renal Support
Routine measurement of cortisol levels is
Although no difference occurred in mortal- no longer undertaken.13 We commence hydro-
ity between liberal vs. conservative fluid man- cortisone in the event of significant vasoplegic
agement in the FACCT study, lower duration of shock as described above. We target glucose
mechanical ventilation and length of ICU stay levels of less than 10 mmol per liter using in-
were seen.18 We target negative fluid balance in sulin infusion if required. Tight glucose control
patients as soon as feasible, based upon cardio- is no longer indicated.21
vascular stability. Our initial approach includes
the use of diuretics, (eg, furosemide). We favor Hematological Abnormalities
continuous infusion to reduce the ‘swings’ in
fluid status, permitting a more controlled di- In the event of persistent abnormalities in
uresis. If patients do not respond adequately to the blood count or suspected immunosuppres-
diuretics, continuous renal replacement therapy sion, we perform a blood film. Consideration
(CRRT) can be initiated via connection to the for bone marrow aspiration should be given
ECLS circuit or separately inserted vascular as we have identified unknown leukemias in
access catheters. Insertion of central venous patients failing to improve on VV-ECLS. Per-
access risks complications in anticoagulated sistent thrombocytopenia raises the possibility
patients, so we use the circuit if such devices of heparin-induced thrombocytopenia. Chapter
are not already in situ prior to commencement 7 covers this heparin complication.
of VV-ECLS.
Infection as the Indication for Respiratory
Nutrition ECLS Support
The aim is to commence full enteral nutri- The most common indication for respira-
tion as early as possible. A number of studies tory ECLS support is primary lung infection
have shown that enteral nutrition is well toler- (bacterial, fungal or viral) or ARDS as part of
ated by most patients on ECLS, albeit with a systemic sepsis spectrum. During 2014-2015,
frequent interruptions and slightly less delivery 72% of the patients in our center had infection
of calories and protein than desired.19,20 The as their initial diagnosis. Initial antibiotic cover-
majority of patients with feeding intolerance age should be broad spectrum to cover all likely
are managed with pro-kinetics if required. As organisms in collaboration with local microbi-
a second line, additional metoclopramide fol- ology guidelines, and knowledge of antibiotic
lowed by erythromycin may be used. In the resistance patterns from the referring hospital.
event enteral nutrition cannot be achieved A macrolide antibiotic is usually added to cover
within a timeframe of 5-7 days, we then com- atypical organisms. In peak influenza season,
mence total parenteral nutrition (TPN) via a we treat all patients with antiviral medications
dedicated lumen or line. All patients receive active against the current circulating viral strains
454
until investigations prove them to be influenza Infection Complicating ECLS Support

negative. It is imperative to maintain dialogues
with referring centers so that any positive or Exposure of whole blood to an extracorpo-
negative microbiological results reported after real circuit induces the systemic inflammatory
transfer are communicated to the ECLS center response syndrome (SIRS) with activation of
in a timely fashion. ECLS patients should have the complement cascade and release of pro-
daily input from local microbiological teams. inflammatory cytokines namely interleukin
On admission, all patients in our center have 6, 8 (IL-6, IL-8) and tumour necrosis factor
a full septic screen comprising: (TNF-α) (See Chapter 6). This is most marked
• Blood, urine, and sputum specimens for at the initiation of ECLS support or following
microscopy, cultures, and sensitivity circuit changes. Much of the adult ECLS data
• Serum for atypical pneumonia screen (my- has been extrapolated from animal, neonatal,
coplasma, chlamydia, Coxiella) or cardiopulmonary bypass data with the latter
• Urine for legionella antigen detection having confounding variables such as ischemia-
• Full blood born virus screen (HIV and reperfusion injury and nonpulsatile flow.22-24
hepatitis B and C) Infection surveillance therefore remains chal-
• Throat swab for respiratory viral PCR lenging as many normal parameters, including
(including influenza A&B, respiratory temperature and inflammatory markers, are
syncytial virus and parainfluenzae strains) unreliable in the context of circuit induced-SIRS
• Methicillin Resistant Staphylococcus Au- reaction and heater-cooler control of patient
reus (MRSA) screen temperature. Evidence in adult VA-ECLS pa-
• Any other investigations dictated by the tients suggests that CRP and procalcitonin levels
patient’s condition, including wound swabs, can differentiate infectious vs. noninfectious
stool or blood cultures from existing in- inflammation with cut off values of 98 mg/L
dwelling vascular access catheters, sputum and 1.89 ng/ml respectively particularly if the
for acid-alkali fast bacilli etc. two are combined, but this conflicts with data
from the pediatric ECLS population.25,26
We do not take routine surveillance blood Following the initial SIRS response, ECLS
cultures from ECLS circuits unless indicated by induces a relative immune-paresis, increasing
clinical or radiological signs of new infection, the risk of further septic episodes. We maintain
nor do we use prophylactic antibiotics, other a high index of suspicion for new infection in
than preprocedure antibiotics. Likewise, we do our ECLS patients. A full septic screen is sent,
not routinely change vascular access devices including bronchioalveolar lavage specimens
without suspicion of line sepsis to minimize for microbiological examination. The choice
risks from undertaking central and arterial ac- of antibiotic coverage with suspected new epi-
cess in anticoagulated patients. Experienced sodes of sepsis should cover unusual and resis-
operators, with meticulous attention to aseptic tant organisms, again guided by local patterns
technique, must undertake any attempts at of pathogens and resistance. Fungal infections
vascular access in ECLS patients. Measures to are common and we have a low threshold for
reduce the incidence of VAP should be strictly adding an antifungal agent with suspected new
adhered to, including selective oral decontami- or unresolving infection. Aggressive source
nation with chlorhexidine, nursing the patient control in imperative and CT scanning may be
30⁰ head up, and the use of endotracheal and required to rule out empyemas, abdominal, or
tracheostomy tubes with supraglottic suction pelvic collections. Systemic anticoagulation
devices. should not delay urgent radiological or surgical
455
Chapter 40
drainage of collections and heparin is usually

discontinued peri-procedure.
Conclusion
Meticulous attention to the daily medical

management of VV-ECLS patients is vital to
obtain the best possible outcomes for these
complex, resource intensive patients, but this
exercise is rewarding and worthy of these ef-
forts.
456
References 10. Kimmoun A, Guerci P, Bridey C, Ducrocq

N, Vanhuyse F, Levy B: Prone positioning
1. Network TARDS. Ventilation with lower use to hasten veno-venous ECMO wean-
tidal volumes as compared with traditional ing in ARDS. Intensive Care Med (2013)
tidal volumes for acute lung injury and the 39:1877–1879
acute respiratory distress syndrome. The 11. Braune S, Kienast S, Hadem J, Wiesner
Acute Respiratory Distress Syndrome Net- O, Wichmann D, Nierhaus A, Simon M,
work. N Engl J Med 2000;342(18):1301–8. Welte T, Kluge S. Safety of percutaneous
2. Brower RG, Lanken PN, MacIntyre N, et al. dilatational tracheostomy in patients on
Higher versus lower positive end-expiratory extracorporeal lung support. Intensive Care
pressures in patients with the acute respi- Med. 2013; 39:1792–1799
ratory distress syndrome. N Engl J Med 12. Schmid C, Philipp A, Hilker M, Rupprecht
2004;351(4):327–36. L, Arlt M, Keyser A, Lubnow M, Müller
3. Sakr Y, Vincent J-L, Reinhart K, et al. High T: Venovenous extracorporeal membrane
tidal volume and positive fluid balance are oxygenation for acute lung failure in adults.
associated with worse outcome in acute J Heart Lung Transpl.
lung injury. Chest 2005;128(5):3098–108. 13. Sprung CL, Annane D, Keh D, et al. Hy-
4. Marhong J, Munshi L, Detsky M, Telesnicki drocortisone therapy for patients with septic
T, Fan E. Mechanical ventilation during shock. N Engl J Med 2008;358(2):111–24.
extracorporeal life support (ECLS): a sys- 14. Riker RR, Fraser GL. Altering intensive
tematic review. Intensive Care Med. 2015 care sedation paradigms to improve pa-
Jun;41(6):994-1003 tient outcomes. Anesthesiology Clinics
5. Schmidt M, Stewart C, Bailey M, et al. 2011;29(4):663–74.
Mechanical Ventilation Management Dur- 15. Sessler CN. The Richmond Agitation-Seda-
ing Extracorporeal Membrane Oxygenation tion Scale: Validity and Reliability in Adult
for Acute Respiratory Distress Syndrome: Intensive Care Unit Patients. Am J Respira
A retrospective International Multicenter Crit Care Med 2002;166(10):1338–44.
Study. Crit Care Med. 2014;43(3):654-664. 16. Riker RR, Picard JT, Fraser GL. Prospective
6. Santos C, Ferrer M, Roca J, Torres A, evaluation of the Sedation-Agitation Scale
Hernández C, Rodriguez-Roisin R. Pul- for adult critically ill patients. Crit Care
monary gas exchange response to oxygen Med 1999;27(7):1325–9.
breathing in acute lung injury. Am J Respira 17. van Eijk MMJ, Roes KCB, Honing MLH,
Crit Care Med 2000;161(1):26–31. et al. Effect of rivastigmine as an adjunct
7. Young D, Lamb SE, Shah S, et al. High- to usual care with haloperidol on dura-
frequency oscillation for acute respiration of delirium and mortality in critically
tory distress syndrome. N Engl J Med ill patients: a multicentre, double-blind,
2013;368(9):806–13. placebo-controlled randomised trial. Lancet
8. Ferguson ND, Cook DJ, Guyatt GH, et al. 2010;376(9755):1829–37.
High-frequency oscillation in early acute 18. Wiedemann HP, Wheeler AP, Bernard GR,
respiratory distress syndrome. N Engl J et al. Comparison of two fluid-management
Med 2013;368(9):795–805. strategies in acute lung injury. N Engl J Med
9. Guérin C, Reignier J, Richard J-C, et al. 2006;354(24):2564–75.
Prone positioning in severe acute respi- 19. Ferrie S, Herkes R, Forrest P. Nutrition
ratory distress syndrome. N Engl J Med support during extracorporeal membrane
2013;368(23):2159–68. oxygenation (ECMO) in adults: a retrospec-
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Chapter 40
tive audit of 86 patients. Intensive Care

Med. 2013;39(11):1989-1994.
20. Ridley EJ, Davies AR, Robins EJ, et al.
Nutrition therapy in adult patients receiv-
ing extracorporeal membrane oxygenation:
a prospective, multicentre, observational
study. Crit Care Resusc. 2015;17(3):183-
189.
21. Finfer S, Chittock DR, Su SY-S, et al. In-
tensive versus conventional glucose control
in critically ill patients. N Engl J Med
2009;360(13):1283–97.
22. Warltier DC, Laffey JG, Boylan JF, Cheng
DCH. The Systemic Inflammatory Re-
sponse to Cardiac Surgery. Anesthesiology
2002;97(1):215–52.
23. Day JRS, Taylor KM. The systemic
inflammatory response syndrome and
cardiopulmonary bypass. Internat J Surg
2005;3(2):129–40.
24. McILwain RB, Timpa JG, Kurundkar
AR, et al. Plasma concentrations of in-
flammatory cytokines rise rapidly during
ECMO-related SIRS due to the release of
preformed stores in the intestine. Lab Invest
2009;90(1):128–39.
25. Pieri M, Greco T, De Bonis M, et al. Diagno-
sis of infection in patients undergoing extra-
corporeal membrane oxygenation: A case-
control study. The Journal of Thoracic and
Cardiovascular Surg 2012;143(6):1411–1.
26. Rungatscher A, Merlini A, De Rita F, et al.
Diagnosis of infection in paediatric veno-
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reactive protein. Eur J Cardiothorac Surg
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458
41
Nursing Care of the Adult Respiratory ECLS Patient
Jayne Sheldrake, RN, Shirley Vallance, MPH
Introduction trained nurses having received specific educa-

tion and training including ongoing assessments
Over the last decade, many adult ECLS and competency evaluations.
centers have progressively incorporated re-
spiratory ECLS care into the scope of practice ECLS Specific Nursing Care
of specially trained ICU medical and nursing
staff and moved away from having dedicated ECLS patients require the same initial as-
noncritical care staff overseeing care by the sessment and scrutiny as other ICU patients.
bedside. The incorporation of circuit monitoring This thorough assessment is an essential com-
and care into the nursing scope of practice in ponent of the daily routine. Patients on ECLS
particular, has facilitated the growth in ECLS require additional initial assessments/checks
for respiratory failure in the critical care envi- carried out by the nurse when commencing
ronment and is expected to grow further with care for the patient each shift. The additional
the increasing interest in partial ECLS support patient checks include circuit and equipment
of respiratory failure.1 checks and neurological and vascular assess-
Bedside nursing management of ECLS pa- ment and observations.3 Circuit checks include
tients plays an essential role in patient outcomes. taking blood samples for hemolysis screening
The nurse role demands continual vigilance to alongside other patient pathology tests. Checks
identify and respond to changes in the patient of the circuit and review of circuit integrity are
and circuit function, but also performs an es- a vital component of preventative management
sential role in the prevention of complications. and initial and ongoing review by the primary
The bedside nurse is often the primary responder caregiver, the bedside nurse.
and care coordinator and often the first to iden-
tify complications in any or indeed all of these Checklists and Preventative Care
areas. Standard nursing care practices should
be implemented for these patients with several A circuit and equipment checklist, which
areas requiring additional focus/assessment and includes checks for power source and battery
checks while the patient is on ECMO support.2 function, gas delivery, cannula dressing posi-
This chapter covers the delivery of daily tions and security, circuit settings, and availabil-
nursing care of the adult patient receiving ECLS ity of spare and emergency equipment, should
for severe respiratory failure for critical care be completed at the beginning of each shift.
459
Chapter 41
Completing checks with the outgoing nurse is and ability to set alarms appropriately as well
best practice. Any identified problems should be as trouble shooting the system. Hourly checks
managed in a timely manner to minimize risk or should include mode of ECMO support, docu-
further complications. Backup equipment and mentation of patient parameters such as blood
knowledge of how to access and use these sup- flow, venous blood oxygenation, circuit pres-
ports are imperative. A backup console should sures, fresh gas flow, and fraction of oxygen
be available. Alternatives sources for power and delivered. Timely circuit interventions include
oxygen delivery should be part of the checklist. adjusting alarm limits, pump speed settings, and
Knowledge of personnel available and how to alterations of gas flow in response to patient
contact them is also an important strategy for changes. Adjustments to circuit settings require
preventative management. specific training and physiological understand-
ing of the circuit and patient gas exchange.
Cannula Care Changes in circuit/membrane pressures are
often the first sign of circuit dysfunction that
The key initial assessment of the circuit could potentially result in suboptimal ECLS
and cannula ensures patient safety. Pulses dis- support, as well as minor or catastrophic com-
tal to any cannula should be checked initially plications. Maintenance of the console power
and hourly thereafter. The cannula assessment source and backup blood pumping options are
includes visual assessment of cannula sites vital. The bedside nurse plays a crucial role in
and securing devices. The positioning of the the detection of pump/console failure and the
cannula should be measured and documented. rapid commencement of emergency support.
The dressing integrity should also be reviewed. Patient position, room size, the presence of ad-
ditional equipment, such as a continuous renal
ECLS Circuit Observations and Monitoring replacement (CRRT) machine, and connection
of Circuit Function of the circuit to a heater can make disengaging
and moving the pump head challenging. Nurs-
Preventative management to identify any ing staff play a crucial role in cubicle layout and
complications early is essential. Regular blood must maintain sufficient access to the circuit to
tests for bleeding, hemolysis, and fibrinoly- allow timely emergency interventions.
sis screening in addition to anticoagulation
monitoring should be carried out according to Renal Replacement
local practice. The initial circuit assessment/
observations should be completed at the start Continuous renal replacement (CRRT)
of the shift and then at least hourly. Correct provides a stable mode of renal support for
management of circuit function depends greatly adults with respiratory failure and allows ex-
on regular sampling and reviewing of the blood cellent control of fluid balance.4,5 Connection
tests and results. and disconnection of the CRRT machine to the
circuit has been incorporated into the scope of
Console Settings, Safety, and Responses practice of the bedside nurse. Accessing the
CRRT machine from the ECLS circuit increases
Nurses should review and document the the longevity of the hemofiltration life and opti-
console settings and alarms. As the primary mizes fluid CRRT management.6 Connections
caregiver, the nurse can identify early, any of the CRRT machine onto the positive pressure
changes in the console settings and alarms. region of the ECLS circuit and returning CRRT
This monitoring requires an understanding of blood to a pre-oxygenator side of the oxygenator
460
decreases the risk of patient complications such risk of the patient pulling or compromising lines
as air emboli. and circuit integrity.
References to the management of awake or
Emergency Responses ambulating patients on VV-ECLS support have
increased in the literature. Different strategies
As the first responder the bedside nurse are needed for the awake or sedated patient. A
should receive training in emergency response. substantial number of VV-ECLS patients VV-
Console failure, circuit rupture, accidental ECLS are not suitable for ‘awake’ ECLS or
decannulation and massive bleeding need im- participation in their own care. Reasons may
mediate response while calling for medical include hypoxemia despite VV-ECLS, and/or
assistance. Emergency procedure training of the need for neuromuscular blockade or deep
the bedside nurse must include appropriate sedation due to the severity of their lung injury.7
clamping and unclamping of the circuit, disen- A sedated ECLS patient requires the same care
gaging the pump head and initiating the backup focus as other ICU patients in a sedated state.
system, establishing alternative gas supplies The bedside nurse spends a great deal
and adjustments of pump speed in the event of of time with the ‘awake’ ECLS patient and
access insufficiency (inadequate venous return their families. Literature suggests that patient
to the circuit resulting in unstable circuit flows). participation aids recovery and is influenced
Competencies should incorporate emergency by the level of sedation.8 Other benefits of pa-
responses and regular training with wet lab tient participation include increased transplant
simulation training if available. recovery and decreased postoperative hospital
length of stay.9 An additional focus needs to
General Nursing Care of the ECLS Patient be on psychological support for the patient and
their families.
By requiring additional checks, ECLS ex-
tends the timeframe required to carry out hourly Patient Moves and Pressure Area Care
observations and documentation, a primary
nursing duty. As a result, time management is an A necessary, thorough patient assessment
essential strength for the nurse to competently requires additional resources and staffing to
care for the patient prioritizing needs and asking ensure safe implementation of interventions.
for additional resources when required. An individual, often called a ‘spotter,’ allocated
solely for handling the ECLS circuit, can be
Neurological Assessment and Sedation used. An “ECLS only” area, where the ECLS
Practice (and Awake ECLS) circuit rests off the bed can decrease risk of pull-
ing or entanglement. Removing any items (ie,
ECLS carries an increased risk of neu- urinary catheter, other drains) that could poten-
rological insult and poor outcome therefore tially compromise the ECLS circuit decreases
neurological assessment is imperative.3 This the risk of the ECLS circuit tubing compromise.
risk increases partly due to the anticoagulation Notifying the medical team that the patient is
required to assist smooth running of the ECLS being turned or moved maintains patient safety
therapy. Pupil assessment becomes critical and and ensures assistance is availability of assis-
needs to be carried out regularly. Sedation aims tance if required, often including a member of
should be discussed and agreed upon during the medical team caring for the patient.
the multidisciplinary ward round to allow the Prevention strategies should be applied
bedside nurse to provide safe care with minimal to specific areas identified as high risk of skin
461
Chapter 41
breakdown.10 Dressings placed between patient Hygiene and Infection Prevention

skin and circuit tubing prophylactically can
decrease the development of pressure injury. Interventions for patient hygiene need to
Repositioning the circuit tubing hourly also be adapted to suit the ECLS population and de-
decreases risk. A small adjustment of the circuit crease risk of bleeding/complications. Shaving
on the lower limbs, particularly if edematous, should be performed with a clipper or dry shaver
can help prevent pressure injury. A nonadhe- only. Brushing teeth can cause significant
sive dressing to cushion the circuit tubing on trauma and bleeding. If a toothbrush is used it
the patient will also assist. Rotating the bed, if should be a small soft brush head. Mouthwash
possible, can also relieve pressure. Placement and oral suctioning should be minimal and as
of a heel wedge elevates vulnerable skin areas clinically indicated. Care should be taken to
prone to breakdown, decreasing risk of injury. minimize bleeding. Brushing should be stopped
These pressure prevention strategies can be if bleeding occurs. Oral swabs can also be used.
incorporated into the hourly assessment of the Washing solutions with any alcohol content,
ECLS cannula and circuit. such as Chlorhexidine, can be detrimental to
ECLS circuit integrity. Hygiene interventions
Prevention of Bleeding often require additional staffing and should be
carried out as part of the clustered care along-
Anticoagulation puts the ECLS patient at side patient assessment and pressure area care.
risk of bleeding from any intervention. Preven-
tion of bleeding complications, no matter how Nutrition
minor, aids positive outcomes. Only an ECLS
trained individual should carry out necessary Nutrition assessment, goals and plan, and
procedures. Common procedures such as NG delivery of care follow standard practice for
tube placement, urinary catheterization, periph- other ICU patients. There is no difference in glu-
eral venous cannulation, and similar interven- cose management, electrolyte control, and stress
tions usually performed by the nurse should ulcer prevention from any other ICU patient.11
be assisted by ECLS medical staff. Ensuring Little published literature clearly defines the
blood products remain available with a current nutritional needs in the adult ECLS population.
group (or type) and are saved is an essential One study found adults on ECLS received 55%
component of the bedside nursing role. Check- of their nutritional requirements compared to
ing the coagulation screen and identifying areas 71% once decannulated. This study was not lim-
for review aids in prevention of bleeding. The ited to VV-ECLS, but reviewed all adult ECLS
timely administration of blood products, which groups.12 Ensuring adequate enteral nutrition
depends on severity and site(s), may require can be difficult due to the stoppage of feeding
additional staff assistance. A dressing impreg- for procedures, poor absorption confounded
nated with a procoagulant may be placed on the by sedation and other medications, late onset
bleeding site. Sighting of the cannula remains of enteral support, and increased metabolism
a priority, but often difficult when bleeding related to the stress response. Still, performing
occurs. Manual pressure is a useful tool to nutritional assessment to define nutritional goals
minimize bleeding but both the limb and the can also be quite a challenge. Accurate weights
cannula site need frequent observation, at 15 performed regularly and other assessment
minute intervals, to identify complications that methods such as a metabolic cart, may prove
may require more aggressive management. difficult and time consuming, often requiring
additional resources. The nurse and dietician
462
should collaborate to facilitate safe and accurate for this patient group and with outside psycho-
assessment and delivery of nutritional needs. logical support should be essential components
of any ECLS program.
Bowel Management
Role Allocation
Bowel management is crucial but challeng-
ing as the critically ill have increased risk of Role allocation is instrumental when com-
ileus, bowel obstruction, or fecal incontinence, mencing any procedure identified as complex
which can hinder skin integrity and promote or high risk. The low volume of ECLS patients
infection. Application of topical skin barriers decreases familiarity, often enhancing stress
optimizes skin integrity but frequent cleaning associated with these complex patients. A
for incontinence decreases their effect.10 Fecal team leader allocates roles for any high risk
management systems may minimize these risks procedure. Each individual should fully un-
but their introduction has its own risks. The risks derstand their role allocation and place in the
of these devices should be reviewed prior to in- team approach. The roles should be allocated
sertion. Signs of or history of bleeding, clotting, with individual strengths and limitations in
and coagulation profile are also reviewed and mind.13 Interhospital transports should only be
optimized prior to insertion. A rectal bag is less embarked upon if essential for diagnosis and
invasive and may decrease complications and treatment decisions (see Chapter 55). Adequate
may prove a better choice in some cases. Review staffing and role allocation optimize safety in
and assessment for the most appropriate bowel such a complex procedure.14
management system can be carried out on the ECLS patients are unique in a few areas.
skin pressure care assessment when additional Only in these areas, should the clinical nursing
resources to reposition the patient are already management differ. The benefits and risks have
being utilized. to be carefully considered prior to any interven-
tion no matter how small.
Staff Support
The nurses caring for this patient group are

highly skilled and experienced in critical care
but often represent a small group within a larger
team. This can result in those nurses caring
almost exclusively for ECLS patients with little
break from acute and high intensity workload.
As discussed, ECLS patients are physically de-
manding, exposing the nurse to high physical
demands for most of the shift. CRRT and other
adjuncts increase this physical burden.
The family dynamics of the patient with
a complex admission can also increase the
nursing workload. Awake ECLS patients add
further challenges. Many support personnel,
such as social workers and psychologists, can
help minimize these additional work stressors.
Providing these nurses with breaks from caring
463
Chapter 41
References Ostomy Continence Nursing, 2007. 44(2):

p. 163-175.
1. Leligdowicz A, Current Opinion in Critical 11. Compton R, Straub M, Frey J, Zidek W,
Care. Critical Care Medicine, 2015. 21(1): Schafer JH. Pressure ulcer predictors in
p. 13-19. ICU patients: nursing skin assessment
2. Gay, Critical care challenges in the adult versus objective parameters. J Wound Care
ECMO patient. Dimensions of Critical Care 2008. 1017(10): p. 417-424.
Nursing 2005. 24(4): p. 157-162. 12. G, L., Nutritional support in adult patients
3. Risnes I, Nome T, Sundet K, et al. Cerebral receiving extracorporeal membrane oxy-
Outcomes In Adult Patients treated with genation. Critical Care and Resusitation,
extracorporeal membrane oxygenation. . 2010. 12(4): p. 230.
AnnThorac Surg 2006. 81: p. 1401-6. 13. Stubs D, Pellegrino V, Smith K, et al. Re-
4. Yap HJ, Fang JC, Huang CC. Combination fractory cardiac arrest treated with mechani-
of continuous renal replacement therapies cal CPR, hypothermia, ECMO and early
(CRRT) and extracorporeal membrane reperfusion (the CHEER trial). Resuscita-
oxygenation (ECMO) for advanced cardiac tion, 2015. 86(Jan ): p. 88-94.
patients. Renal Failure, 2015. 25(2): p. 183- 14. Shields J, Krau S. Nurses’ knowledge of
193. Intra-hospital Transfer. Resuscitation, 2015.
5. Chen H, Yin NN, Zhou ZX. Combination 50(2): p. 293-314.
and continuous renal replacement therapy
in critically ill patients: a systematic review.
Critical Care Epub 2014. 18(6): p. 675.
6. Crosswell AB, Matthew J, Roodenburg O.
Vascular access site influences circuit life
in continuous renal replacement therapy.
Critical Care and Resusitation, 2014. 16(2):
p. 127-130.
7. Needham D. Early physical medicine
and rehabilitation for patients with acute
respiratory failure: a quality improvement
project. Arch Phys Med Rehab, 2010. 91(4):
p. 536-542.
8. Javidfar J. Current Opinion Organ trans-
plantation, 2012. 17(5): p. 496-502.
9. Fuehner T, Hadem J, Wiesner O, et al.
Extracorporeal Membrane Oxygenation in
Awake Patients as Bridge to Lung Trans-
plantation. Am J Respir Crit Care Med,
2012. 185(7): p. 763-768.
10. Benoit RA. The effect of a pressure ulcer
prevention program and the bowel man-
agement system in reducing pressure ulcer
prevalence in an ICU setting. J Wound
464
42
Weaning and Decannulation of Adults with Respiratory Failure on ECLS
Hergen Buscher, MD, FCICM, EDIC, DEAA
Introduction venous return, drainage cannula size, and posi-

tion which require optimizing by augmenting
As with mechanical ventilation, the aim of native cardiac output, cannula size, and position.
extracorporeal life support (ECLS) should be In addition, the recirculation fraction should be
to minimize support to the lowest level needed minimized. In the absence of significant lung
to achieve the therapeutic goal. ECLS treatment capacity to oxygenate blood subphysiologic
goals may change from providing oxygenation, arterial oxygen saturations (often measured in
to clearing carbon dioxide, to allowing for lung the range of 85-90%) are expected. An attempt
protective ventilation, or even extubation, dur- to increase blood flow to improve this situation
ing support. In this regard the weaning process may increase recirculation, hemolysis, and fluid
starts at the time of cannulation and should be overload, add to venous drainage problems,
separated from the process of liberation where or require additional cannulae. Importantly a
the aim is decannulation, only after certain cri- single liter per minute of oxygen exceeds the
teria have been achieved. Unlike in mechanical average oxygen consumption of an adult and is
ventilation, where over the last number of years theoretically enough to fully saturate the blood
criteria for relative safe and lung protective passing through an ECLS circuit.2,3
ventilation have been introduced, the optimal Most adult ECLS centers use pure oxygen
level of ECLS remains still unknown. as gas. Air-oxygen mixture should saturate
blood to 100% in well-functioning oxygenators
VV-ECLS Physiology and therefore an increase in oxygen concentra-
tion does not contribute to an increase in oxy-
The preferred mode for respiratory support gen delivery. It remains unclear if this ‘safety
is VV-ECLS.1 The main adjustments are blood margin’ increases the risk of oxygen toxicity
flow, sweep gas flow, and gas composition. The to the pulmonary system. There is insufficient
indications include severe hypoxia (oxygen- evidence to recommend a specific oxygen
ation failure), hypercarbia (ventilation failure), concentration in VV-ECLS as long as the blood
or most commonly a combination of the two. To leaving the oxygenator is fully oxygenated.1
treat oxygenation failure most of venous to right In contrast, clearing venous carbon dioxide
ventricle needs to pass through the oxygenator (CO2) does not significantly depend on blood
when the lungs provide no significant contribu- flow but mainly is a function of gas flow. Ap-
tion to gas exchange. Blood flow is limited by proximately 90% of CO2 is transported in the
465
Chapter 42
blood as bicarbonate.4 For that reason, less mental in some settings such as spontaneously
than 500 ml of blood contains all CO2 produced breathing patients or suspected brain injury. A
per minute and very little blood flow is needed stepwise increase in gas flow in association
to clear that amount. The gas flow should be with a reduction in minute ventilation may be
adjusted to achieve a normal pH rather than necessary. Since bolus heparin doses are often
a normal pCO2 since many patients may have administered during cannulation the bleeding
a chronic respiratory acidosis with metabolic risk may be increased at this point.
compensation. A slight increase in gas flow
beyond this may aid a patient suffering from Maintaining VV-ECLS
tachypnea and respiratory distress.
The most common problem during ECLS
Initiation of VV-ECLS is poor venous drainage. Venous drainage de-
pends on the size and position of the cannula,
After cannulation, a significant amount of venous filling (depending on venous return
blood volume will be drained from the patient and preload), and ECLS pump speed. Any of
toward the extracorporeal circuit and will be these parameters can cause suboptimal drain-
replaced by the priming fluid of the circuit. age. If we ensure that the VV-ECLS cannula
This most often consists of a crystalloid solu- is optimally positioned, adding an additional
tion, which will lead to hemodilution of the drainage cannula may be needed to address
blood volume. Often patients experience he- poor venous drainage but this extra cannula
modynamic compromise as a result of severe often results only in moderate increases in blood
hypoxia and consequently may suffer from flow (see Chapter 38). Increasing ECLS pump
brief but significant hypotension. It is impor- speed will increase blood flow but may increase
tant to insure that hemodynamic support with recirculation and hemolysis, although this is less
vasopressors or a fluid bolus can be delivered. likely with optimal venous drainage.5 Of course,
Preexisting intravascular hypovolemia may this strategy relies on adequate venous return.
be exacerbated by ECLS and optimal pump Once this critical volume is reached the drained
function may be compromised by poor venous vein may collapse leading to a sudden drop of
drainage. If the drainage cannula is confirmed blood flow to zero. The acute hypoxia will be
to be in an optimal position further fluid boluses substantial and only a reduction in pump speed
may be needed. will free up the drainage cannula.
Once instituted, ECLS support delivers ox- Figure 42-1 illustrates the importance of
ygenated blood to the patient and often resulting not increasing ECLS pump flow beyond a
in improved hemodynamic function. Changes sustainable drainage (area A). Plateauing of
in ventilatory settings allowing lung protective the relationship (area B) may not be observed
or even ultra-lung protective ventilation result since venous filling is a dynamic process and
in reduction in intrathoracic pressure with im- can change quickly, for example secondary to
proved preload and RV afterload. Unloading of increased intrathoracic pressures (eg, coughing).
the RV by a combination of reduced ventilator Increasing venous filling by administration
pressure and reduced pulmonary resistance of fluid boluses is a common reflex when blood
secondary to the correction of hypoxia and hy- flow is deemed to be inappropriate. However,
percarbia may play the main role in this observa- this benefit is usually temporary and ultimately
tion. ECLS also very effectively corrects severe can lead to fluid overload.
respiratory acidosis. Rapid reversal or over A restrictive approach to fluid management
correction of respiratory acidosis may be detri- in ARDS improves survival and therefore the
466
same strategy needs to be applied during ECLS. post oxygenator PaO2 or need for increases in
Trying to maintain high levels of blood flow sweep gas flows. There is no single marker or
by fluid administration ultimately reduces the score for device failure and it remains a matter
chance of organ recovery. Reducing the blood of clinical judgement to determine if an ex-
flow targets or improving venous drainage by change is needed, keeping in mind that patients
additional cannulation are preferred options. who are completely dependent on ECLS should
ECLS circuit failure occurs rarely in adults undergo an elective exchange rather than an
but early signs need to be addressed to avoid urgent procedure which usually results in severe
a catastrophic event. Modern oxygenator and respiratory and/or hemodynamic instability.
pumps can last for weeks or in some cases
months without exchange and signs of failure Recirculation
often develop slowly so that elective changes
can be planned for (see Chapter 5). A sudden Recirculation of already oxygenated blood
loss of function should be an uncommon prob- into the drainage cannula complicates VV-
lem in modern adult ECLS practice. ECLS. Again, higher ECLS pump speed and
Risk factors for component failure include blood flow may increase this problem. As a con-
prothrombotic conditions including low or sequence, oxygen delivery does not increase in
no anticoagulation, trauma, or underlying proportion to flow while complications includ-
thrombophilic disease. Routine care includes ing hemolysis and poor drainage occur more
regular monitoring and documentation of clot commonly. No simple bedside test measures the
formation and of changes in biochemical mark- recirculation fraction nor can it be completely
ers of hemolysis and thrombosis such as free avoided during VV-ECLS. Optimal placement
hemoglobin, d-dimers, fibrinogen, and platelets. of drainage and return cannula, in a two-site
Thrombin fragment and thrombin-anti-thrombin VV-ECLS configuration, and proper position-
complexes may increase while factor XIII may ing of bicaval dual-lumen VV-ECLS cannula,
drop, but these are not part of standard monitor- are both essential to minimize recirculation.7
ing in most centers.6 Failing oxygenators may The most frequent clinical sign associated with
gradually loose function noted by a decrease in recirculation is desaturation, which can be acute
and life threatening. An experienced team of
nurses, ECLS specialists, respiratory therapists,
and medical staff at the bedside is essential to
deal with this swiftly to avoid poor outcome.
Addressing drainage problems, circuit
failure, and recirculation early will avoid the
majority of these episodes. Additionally, in the
absence of oxygenation by the lungs desatura-
tion always occurs when native cardiac output
significantly exceeds ECLS blood flow. Clinical
situations where this may be accelerated include
Figure 42-1. Function of blood flow to pump
pain, delirium, and sepsis. These syndromes are
speed. Area A - linear increase of blood flow not always easy to diagnose during ECLS and it
with pump speed. Area B - Ineffective increase takes experience to address them expeditiously
in pump speed secondary to poor venous filling. (see Chapter 40).
Area C - acute drop in blood flow secondary to
venous collapse. Not to scale.
467
Chapter 42
Weaning VV-ECLS with no gas flow on VV-ECLS, decannulation

can be attempted.
A successful stepwise weaning of sweep
gas flow may therefore indicate the recovery of Liberation and Decannulation
the ventilator function (CO2 clearance) but not
necessarily the recovery of oxygenation. Over The weaning of mechanical ventilation
prolonged ECLS support the ability of an oxy- drives the timing for liberation from extracor-
genator to clear CO2 can decline and increasing poreal support. The targeted level of ventilator
amounts of gas flow become necessary. When support deemed appropriate to allow for the
this change is observed in association with other removal of the extracorporeal system varies from
indicators of oxygenator failure a system change patient to patient. However, the majority will be
may be indicated. For VV-ECLS the following ventilated at the time of liberation, well within
procedure should be followed: once the level of lung protective ventilation with a PaO2/FiO2 ratio
ventilator support is deemed to be appropriate above 100 mmHg without extracorporeal support.
and safe, the extracorporeal gas flow can be It should also be possible to achieve almost nor-
reduced in a stepwise fashion to zero with close mal CO2 clearance (pH >7.3). Factors which may
monitoring of arterial oxygenation and CO2 lev- have negative impact on the respiratory function
els. It usually becomes necessary to increase the including infections or other organ failure should
respiratory rate and FiO2 settings used to rest the be well controlled before decannulation, since
lungs while on full ECLS support. Some centers reinstitution of ECLS often proves more complex.
wean extracorporeal blood flow parallel to the In some situations, continuing with ECLS to the
gas flow, to a set minimum flow; however, no point of liberating a patient from mechanical
changes in blood flow are absolutely necessary, ventilation first is appropriate. Little evidence
since during the provision of VV-ECLS without exists in which group of patients, perhaps with
gas flow, the drained venous blood will return the exception of patients waiting for lung trans-
to the venous system without any change in plantation, would benefit from this strategy and
oxygen content. Protocols that include wean- more trials on this subject are desperately needed.
ing of extracorporeal blood flow may add the An elevated aPTT is a risk factor for post
risk of thromboembolic complications at a time decannulation complications.8 Heparin free
when anticoagulation may also be reduced in ECLS in adult patients on modern extracorporeal
preparation for decannulation. devices has been reported for up to 25 days and
Over the following hours, sometimes ex- many centers routinely stop anticoagulation be-
tending to days, the patient needs to be closely fore decannulation.9 Percutaneously placed can-
monitored for signs of weaning failure. Some nula can be removed after clamping the circuit
extracorporeal devices have a built in mixed with the help of local compression for 20 to 60
venous saturation monitor. A steep drop in minutes. The use of a pursestring suture is often
saturation may indicate weaning failure. When recommended. After prolonged ECLS runs and
a pulmonary artery catheter is present, the same in patients with minimal subcutaneous tissue or
phenomenon can be observed as well as signs signs of tissue infections at the cannula site surgi-
of acute cor-pulmonale. Echocardiography may cal consultation may be needed. Clot formations
also be helpful. Signs of poor tissue oxygenation around venous cannula have been described and
such as lacticemia or new organ impairment risk for thromboembolic complications during
may indicate that further extracorporeal support decannulation exists.10
is needed. Once a patient has stable hemody- In case of a sudden hemodynamic deterio-
namic parameters and adequate oxygen delivery ration the possibility of a pulmonary embolism
468
must be considered and venous ultrasound pos- A small proportion of patients may qualify
tremoval is indicated in any case. If a cannula was for lung transplantation and early contact with
placed with an open approach or an arterial can- the appropriate transplant center is indicated (see
nula is in place the decannulation strategy should Chapter 58). In a recent review of the interna-
be discussed with the team who performed the tional lung transplantation database ~4% of all
procedure as an open repair may be indicated. transplants received ECLS first.14 Two scenarios
Patients on VA support and respiratory failure are common. Patients with chronic disease who
need to follow the VA weaning protocol with have already been placed on the transplant wait-
special consideration for systemic oxygenation ing list may have an acute deterioration and need
and differential hypoxia (see Chapter 51). ECLS support. These patients are unlikely to be
weaned from ECLS successfully and ventila-
Other Modes of Support tor weaning and extubation may be desirable
once it has been confirmed that transplantation
In the recent past low flow extracorporeal remains an option. On the other hand, patients
systems have been introduced for extracorporeal on extracorporeal support with the intention to
CO2 removal, (ECCOR, see Chapter 63).11 These bridge to recovery may fail to show significant
systems are either pump driven venovenous or improvement. No clear cutoff time exists after
pumpless arteriovenous in configuration. During which a referral for lung transplantation should
weaning and liberation no change in blood flow be considered. The appropriateness of this op-
is needed. Reduction in gas flow leads to less tion depends on the patient’s condition, age, and
effective CO2 removal and ceasing it altogether premorbid state as well as on local availability
mimics decannulation. The relation between CO2 of lung transplantation and wait times. Since
removal and gas flow is not linear and attention full recovery after prolonged ECLS runs has
needs to be taken to monitor native CO2 clearance been observed and long-term survival times
during weaning. after transplantation may be shorter the deci-
sion for transplantation can only be made on
The Patient Who Cannot be Weaned an individual basis in discussion with the local
transplant center.13
According to the 2015 ELSO report, respi-
ratory support averaged approximately 12 days, Conclusion
which exceeds that needed for cardiac support.
Much longer support times of over 100 days have Since up to a third of adult patients on re-
been reported and indeed according to a recent spiratory support may not be able to be weaned,
analysis of the database, duration of support the appropriateness of ECLS should be reviewed
alone does not predict futility.12 Full lung recov- regularly and similar to other invasive life sup-
ery has been demonstrated after many weeks port including mechanical ventilation or renal
on support.13 However, complications related to replacement therapy, should be continued only if
intensive care and extracorporeal support itself a reasonable chance of a positive outcome exists.
can accumulate and can make prolonged runs The withdrawal of extracorporeal life support
very difficult. for futility needs to follow local ethical guide-
ELSO reports suggest that about 2/3 of all lines with ongoing discussions with family and/
adult runs wean successfully. In the CESAR trial or patient. Organ donation post withdrawal of
only 9% of all patients died of persistent respira- extracorporeal life support should be considered.
tory failure while the majority of deceased pa-
tients developed extrapulmonary organ failure.4
469
Chapter 42
References of Critical Care Medicine. 2014;16 (1):69-

72.
1. ELSO Guidelines for respiratory support 10. Kalem V, Buchwald D, Strauch J, et al.
Vers 1.3 (searched January 2016) https:// Surgical extraction after thrombosis around
www.elso.org/Resources/Guidelines.aspx the Avalon dual lumen cannula. Ann R Coll
2. Schmid C, Philipp A, Hilker M, et al. Ve- Surg Engl. 2014;96(1):106-8E.
novenous extracorporeal membrane oxy- 11. Abrams D, Brenner K, Burkart K, et al.
genation for acute lung failure in adults. J Pilot Study of extracorporeal carbon di-
Heart Lung Transplant. 2012;31(1):9-15. oxide removal to facilitate extubation and
3. Javidfar J, Brodie D, Iribarne A, et al. Ex- ambulation in exacerbations of chronic
tracorporeal membrane oxygenation as a obstructive pulmonary disease. AnnalsATS.
bridge to lung transplantation and recovery. 2013;10(4):307-14.
J Thorac Cardiovasc Surg2012;144(3):716- 12. Lacono A, Groves S, Garcia J, Griffith B.
21. Lung transplantation following 107 days of
4. Peek GJ, Mugford M, Tiruvoipati R et extracorporeal membrane oxygenation. Eu-
al. Efficacy and economic assessment of ropean Journal of Cardio-thoracic Surgery.
conventional ventilator support versus 2010; 37:969-71.
extracorporeal membrane oxygenation for 13. Muller G, Guillon A, Garot D, Mercier E,
severe adult respiratory failure (CESAR): Perrotin D. Strategies for the withdrawal of
a multicentre randomised controlled trial. extracorporeal membrane oxygenation for
Lancet. 2009;374(9698):1351–63. severe acute respiratory failure support: a
5. Toomasian JM, Bartlett RH. Hemolysis and new challenge? Anaesthesia and Intensive
ECMO pumps in the 21st Century. Perfu- Care. 2012;40(2):359.
sion. 2011; 26(1):5-6. 14. Gulack BC, Hirji SA, Hartwig MG. Bridge
6. Protti A, L’Acqua C, Panigada M. The deli- to lung transplantation and rescue post-
cate balance between pro-(risk of thrombo- transplant: the expanding role of extracor-
sis) and anti- (risk of bleeding) coagulation poreal membrane oxygenation. J Thorac
during extracorporeal membrane oxygen- Dis. 2014;6(8):1070-9.
ation. Ann Transl Med. 2016;10.210-37.
7. Abrams D, Bacchetta M, Brodie D. Recircu-
lation in venovenous extracorporeal mem-
brane oxygenation. ASAIO. 2015;61(2):
115-21.
8. Yeo HJ, Kim HJ, Jang JH, Kang LH, Cho
WH, Kim D: Vascular Complications
Arising from Hemostasis with Manual
Compression Following Extracorporeal
Membrane Oxygenation Decannulation.
2016;31(2):123-6.
9. Herbert DG, Buscher H, Nair P. Prolonged
venovenous extracorporeal membrane oxy-
genation without anticoagulation: a case of
Goodpasture syndrome-related pulmonary
haemorrhage. Critical Care and Resuscita-
tion: Journal of the Australasian Academy
470
43
Outcomes and Complications of Adult Respiratory ECLS
Matthieu Schmidt, MD, PhD
Short-term Outcome of ARDS Patients on est PaO2/FiO2 ratio of 56 mmHg, a lowest pH

VV-ECLS of 7.2, and a modified acute lung injury score
of 3.8.3 However, other studies have reported
Outcomes of patients with severe ARDS better outcomes of A(H1N1) influenza-related
treated with the latest extracorporeal life support ARDS compared to other ARDS etiologies.4,5
(ECLS) technology, which includes a centrifu- Lastly, similar short-term outcome has been
gal pump, a polymethylpentene membrane oxy- reported in two recent cohorts by Schmidt et
genator, and tubing with biocompatible surface al. In the first cohort, the PRESERVE cohort,5
treatment show mortality rates ranging from 36 in which 140 patients from three French ICUs
to 56 %. The first large international multicenter were studied retrospectively, Schmidt et al.
database, using 20-year data from the ESLO report a 64% survival rate at ICU discharge
Registry on 1,473 patients with a median age and 60% survival at 6 months. This cohort in-
of 34 years, reported an all-cause mortality rate cludes 95% of VV-ECLS with a median time
of 50%.1 Risk factors associated with a poorer between intubation and ECLS cannulation of
outcome were advanced age, days on mechani- 5 (1–11) days for bacterial pneumonia (45%)
cal ventilation prior to ECLS, and decreased and A(H1N1) influenza-related ARDS (26%).
patient weight. More recently, the randomized Interestingly, 68% patients were transported via
controlled trial CESAR of patients with severe, a mobile ECLS team and their prognosis was
potentially reversible ARDS reported 63% of comparable to those who received VV-ECLS
survival without severe disability at six months support in their initial center hospital. In the
in the ECMO group.2 Patients had a mean age second cohort, 2,355 patients from the inter-
of 40 years and a mean APACHE II score of national ELSO Registry were analyzed,4 57%
20. Sixty percent had a primary diagnosis of of whom survived to hospital discharge after a
pneumonia. In 2009, the positive results of the median of 170 hours on ECLS with VV mode
CESAR trial and the A(H1N1) influenza pan- used for 82%. ECLS therapy was initiated after
demic led to an exponential increase in ECLS a median of 57 hours of mechanical ventilation
use in severe ARDS. The short-term outcome with high positive end-expiratory pressure level,
of patients with A(H1N1) influenza-related neuromuscular blocker agents (49%), inhaled
ARDS treated with ECLS appeared positive nitric oxide (20%), and high-frequency oscilla-
(ie, 71% ICU survival) considering the severity tory ventilation (10%).
at cannulation characterized by a median low-
471
Chapter 43
Long-term Outcomes after ECLS for Severe ARDS patients supported with ECLS remains
ARDS unacceptably high. Indeed, ECLS support can
cause severe and potentially life-threatening
ECLS patients often experience prolonged complications.
ICU and hospital length of stay (LOS), often
exceeding 1 month.1,6 Thus, evaluation of the Bleeding Complications
impact of this therapy on long-term pulmonary
function, quality of life (QoL), and psycho- Bleeding remains a major ECLS complica-
logical status appears crucial in the decisional tion, with intracerebral bleeding being the most
process to use ECLS in ARDS patients. To date, dreaded, and still widely impacts short-term
the long-term prognosis after ECLS for ARDS outcome and the overall cost. The main mecha-
remains underreported. Frenckner et al. de- nisms involved include anticoagulation, throm-
scribed long-term outcome in 21 patients for the bocytopenia, and consumption of coagulation
first time,7 most of whom had limited fibrosis factors. In addition, impaired platelet function11
lesions on CT scan and pulmonary function tests and acquired von Willebrand syndrome increase
(PFTs) within normal limits. Similarly, patients the risk of bleeding for ECLS patients.12 In a
in the ECLS arm of the CESAR trial2 exhibited review of ECLS complications among 1763
comparable or better health related QoL scores patients, serious bleeding occurred in 33%.13
(measured by the SF 36 questionnaire) than Similarly, bleeding occurred in 29% of patients
those reported by patients in the conventional on ECLS during the A-(H1N1) influenza pan-
arm.8,9 Exertional dyspnea was reported by demic.3 Lastly, the incidence of intracerebral
50% and 40 % of 12 influenza A (H1N1) ECMO bleeding for adult patients on VV-ECLS in the
patients and 25 controls, respectively.10 Anxiety last ELSO database reports was 3.8%. Aubron
and depressive symptoms were reported by 28% et al. reported that red blood cells transfusion
and 56% of patients respectively, whereas 40% reached approximately 1 unit per day and 17%
were at risk of posttraumatic stress syndrome of patients underwent surgery for bleeding is-
(PTSD).10 However, the one-year QoL in ECLS sues.14 However, a restrictive transfusion policy
patients was poorer than a sex and age-matched on ECLS seems possible with implementation
general population.10 Lastly, the largest study of a lower objective for systemic anticoagula-
published to date was reported by Schmidt et tion, a fixed transfusion threshold of 7 g/dL,
al.6 on a population of 84 6-month survivors. and an auto-transfusion during decannulation.15
In that series, 36% of the patients reported
exertional dyspnea, whereas 30% were still Thromboembolic Events
receiving pulmonary treatments after a median
of 17-month followup. Health related quality of Given the significant morbidity and mor-
life (HRQL) evaluation in 80% of the 6-month tality attributed to bleeding, anticoagulation
survivors revealed satisfactory mental health targets have generally declined over the last
but persistent physical and emotional related 5–10 years, which may increase the risk of
difficulties. thromboembolic events. In 2006, Rastan et al.
reported autopsy results performed on 78 out
Main ECLS Related Complications and of 154 patients, who died after postcardiotomy
Their Impact on Outcome ECLS, describing major discrepancies between
clinical and postmortem examination. The true
Based on cohort series previously described, incidence of thromboembolic events, which ap-
overall in-ICU or in-hospital mortality of proached 50%, was highly underestimated by
472
clinical evaluation.16 The risk of such events ARDS, a total of 146 ECMO procedures were
increased with the ECLS duration, especially performed on 139 patients. Thirty-six patients
beyond 6 days and was still frequent despite had a total of 46 infections (30.1 infectious
systemic anticoagulation. Presently, ECLS is episodes per 1,000 days of ECLS).21
predominantly provided using miniaturized cen- Catheter-related, cannula, and bloodstream
trifugal pumps, low resistance oxygenators, and infections, as well as ventilator associate pneu-
heparin-bonded circuit components. All have monia (VAP) prevalence were all collected in
contributed to lower anticoagulation require- recent studies. Although the frequency varied
ments. The prevalence of post-decannulation between studies, the most commonly infected
deep vein thrombosis (DVT) in the cannulated site was the lung. Indeed, the frequency of VAP
vessel in adults who received VV-ECLS for se- among ECLS patients was higher in the recent
vere respiratory failure has been highlighted.17,18 study of Schmidt et al. (55% of all patients)
Of 127 patients requiring ECLS for ARDS, underlying the discrepancies of the surveillance
9.5% reported partial vein thrombosis of the system between ECLS centers and the contro-
cannulated vessels.18 More recently, the preva- versial use of antibiotics prophylaxis to prevent
lence of DVT in cannulated vessels following NIs with ECLS patients. Lastly, from a clinical
ECLS was estimated at 8.1/1,000 cannula days point of view, the time to NI occurrence is im-
in a cohort of 81 survivors. Routine venous portant. For instance, mean time to the first NI,
Doppler ultrasound following decannulation is first VAP, and infection of the femoral cannula
warranted in this population. insertion site were 8±11, 7±12, and 12±6 days,
respectively.20 NI occurrence during ECLS
Infectious Complications was consistently independently associated with
death in ICU. Also the risk of NIs increases
The high incidence of nosocomial infec- with patient severity at ICU admission and with
tions (NIs) during ECLS contributes to poor longer duration of ECLS support.20,21 To date,
outcomes. Altered immunity, cannulation of specific strategies for the prevention of ECLS-
great vessels, and insertion of invasive devices associated infections have not been rigorously
(endotracheal tube, central venous catheter, studied. Research on preventive strategies on
urinary catheter) increase the risk of develop- ECLS such as antibiotic prophylaxis, routine
ing NIs. Few studies have reported infections surveillance cultures, or the use of chlorhexi-
complications in adults receiving ECLS and in dine gluconate-impregnated sponges in cannula
most of them, indication for ECLS was both dressing is warranted.
respiratory and cardiac failure. A recent report
based on the ELSO Registry showed that the Hemolysis
adult infection rate was higher than newborns
(30.6 vs. 10.1 per 1000 ECLS day), especially Minor hemolysis commonly occurs during
for patients requiring ECLS for cardiogenic VV-ECLS. A study of 207 pediatric patients
shock (37 per 1000 ECLS day).19 Schmidt et with ECLS reported at least one episode of
al. reported a total of 142 (64%) NIs (75.5 per hemolysis in 66% patients.22 Hemolysis was
1000 ECLS day) among 220 patients who un- classified as mild (<0.5 g/L), moderate (0.5-
derwent >48 hours ECLS support for refractory 1.0 g/L) or severe (<1.0 g/L) in 47, 12, and 7%
cardiogenic shock.20 This prevalence was higher patients, respectively. Patients with hemolysis
than that of the ELSO Registry and other studies experienced longer duration of ECLS run and
from single centers. For instance, in a mixed required more blood products. After controlling
Australian population of cardiogenic shock and for age, weight, pediatric index of mortality,
473
Chapter 43
and diagnosis, patients with severe hemolysis while maintaining Plateau pressure <30 cmH20
were more likely to die in the ICU and in hos- were independent risk factors for mortality in
pital (odds ratio, 6.34; 95% CI, 1.71–23.54; the PRESERVE score.6 Lastly, a greater degree
p=0.006). A retrospective study of 154 adult of organ failure was frequently associated with
patients receiving VA and VV-ECLS, showed poor outcomes as well.6,25-27
that patients who demonstrated hemolysis In order to provide tools to help clinicians
within 24 hours post-ECLS cannulation de- select appropriate candidates for ECLS, these
fined by plasma free hemoglobin >50 mg/dL, pre-ECLS mortality risk factors have been
occurred in 3.9% of survivors and 15.9 % of combined into predictive survival models6,26-29
non-survivors (p=0.002) and a Cox proportional such as the RESP26 or the PRESERVE6 scores.
hazard analysis identified hemolysis as an in- For instance, the RESP-score26 constructed on
dependent predictor of mortality (OR=3.4, 95% data extracted from a large multicenter interna-
confidence interval: 1.3-8.8, p=0.01).23 Further tional population (n=2355), computes 12 simple
study to investigate causes of hemolysis on pre-ECLS parameters to provide a relevant and
ECLS and to confirm its influence on morbidity validated tool predicting survival after ECLS for
and mortality are warranted. acute respiratory failure.
Mortality Risk Factors and Outcome Predic- Volume-Outcome Effect and ECLS Activity
tion for ECLS Candidates Organization
A high rate of complications and significant Recent analyses of large pediatric and
long-term physical and neuropsychological adult databases suggested a significant rela-
impairment6,24 have prompted the defining of tionship between ECLS center patient volume
pre-ECLS risk factors for death in these patients. and prognosis.30-32 These data suggest that the
Older age consistently appeared as an indepen- best results occurred in expert centers treating
dent risk factor of mortality. Better prognosis a sufficient number of patients and in coun-
seems to be associated with patients younger tries where ECLS activity was organized and
than 45 years of age6 whereas an age ≥60 years regulated, as in the United Kingdom,33 Italy,34
seems to markedly impact the survival rate.25 Australia, and New Zealand.35 A recent position
Similarly, pre-ECLS comorbidities, such as paper36 by an international group of physicians
immunocompromise, were consistently asso- with expertise in ECLS for severe respiratory
ciated with a poorer survival rate and should failure advocated regional and inter-regional
be considered in the decision to initiate ECLS. organization of ECLS activity through networks
Also, the timing of ECLS also seems crucial as of hospitals around an ECLS referral center with
it impacts prognosis.6,26 Pre-ECLS duration of a mobile ECLS unit37-39 to retrieve the most se-
mechanical ventilation ≥7 days has also been vere ARDS patients. This group also suggested
associated with a poorer outcome; whereas that at least 20 ECLS cases should be performed
prone positioning and neuromuscular block- per year at each referral center.36 Furthermore,
ade prior to ECLS were both protective in two high volume and expert referral centers might
studies.6,26 Although refractory hypoxemia is a provide better prevention and management of
frequent indication for ECLS in ARDS, very severe complications, which might occur during
low pre-ECLS pulmonary compliance seems long ECLS runs.
to have a greater impact on survival. Thus, pre-
ECLS plateau pressure >30 cmH20 and inability
to increase pre-ECMO PEEP above 10 cmH20
474
Conclusion
Although the use of ECLS for severe re-

fractory ARDS has markedly increased since
2009, the hospital mortality of these patients
remains high (from 35 to 45%). In addition,
despite major technological improvement of
the devices, this technology remains marred
by numerous complications, which might occur
during long ECLS runs. This specific manage-
ment reinforces the need to perform ECLS in
high volume and expert referral centers. In
addition, greater knowledge of the impact of
such complex therapy on long-term pulmonary
function, quality of life, and psychological sta-
tus is warranted.
475
Chapter 43
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7. Frenckner B, Palmer P, Linden V. Extracor- drome. Ann. Thorac. Surg. 2015;99(2):590-
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Rycus P. Infections acquired during ex- 27. Roch A, Hraiech S, Masson E, et al. Out-
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Butt W. Hemolysis in pediatric patients 30. Campbell BT, Braun TM, Schumacher RE,
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24. Hodgson CL, Hayes K, Everard T, et al. et al. Increased extracorporeal membrane
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477
Chapter 43
pediatric patients. J. Thorac. Cardiovasc.

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37. Beurtheret S, Mordant P, Paoletti X, et al.
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39. Linden V, Palmer K, Reinhard J, et al. High
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1637.
478
44
Adult Cardiovascular Defects, Diseases, and Procedures that Predispose to ECLS
Roberto Lorusso, MD, PhD, Mirko Belliato, MD, Patrick Weerwind, PhD,
Sandro Gelsomino, MD, PhD, Jos Maessen, MD, PhD
Acute Myocardial Infarction course.11-14 The updated 2015 American Col-

lege of Cardiology Foundation/American Heart
Currently, the optimal therapy for acute Association/Society for Cardiovascular Angi-
myocardial infarction (AMI) is primary percuta- ography and Interventions guidelines for PCI
neous coronary intervention (PCI), and despite recommend the implementation of a mechanical
early revascularization, 6% to 10% of patients hemodynamic support for patients in cardio-
with AMI with ST-segment elevation present re- genic shock who cannot be stabilized rapidly
fractory cardiogenic shock (RCS). The mortality by pharmacological treatment during PCI.15
rate in this clinical scenario ranges from 40% to Multiple reports of percutaneous mechanical
80%, and with a rather constant incidence over circulatory support devices for patients with
time.1-6 RCS is usually defined as systolic blood post-AMI refractory acute cardiac dysfunction
pressure <90 mmHg, a cardiac index <2.0 lt/ have been published,16-19 but among them, the
min/m2, and evidence of end-organ hypoperfu- popularity of VA-ECMO is growing due to the
sion ultimately leading to multiorgan failure relative ease of implementation; provided that
(MOF) despite aggressive pharmacological in- a specialized professional team with adequate
terventions such as vasopressors and inotropes.7 expertise in this super-specialized field is in-
When RCS is established and pharmacological volved.16-19
treatment is not sufficient or MOF is imminent, Of paramount importance is the timing of
the use of mechanical circulatory support should ECMO start. In fact, VA-ECMO should be
be considered, such as the intraaortic balloon established as soon as possible (preferably ˂60
pump (IABP), percutaneous or more sophisti- minutes from RCS appearance), particularly
cated ventricular assist devices (VAD), or extra- if the initial attempts with fluid resuscitation
corporeal membrane oxygenation (ECMO).7-10 and pharmacologic support fail to produce any
If there are no contraindications and if the time significant hemodynamic improvement, and
limits are respected, venoarterial ECMO (VA- preferably prior to PCI.20 In that clinical phase
ECMO) should be rapidly implanted because the repeated use of cardiac ultrasound (trans-
it can concomitantly and effectively support thoracic or transesophageal echocardiography)
heart and lung function, interrupt the refractory and/or pulmonary catheter pressure monitoring
deterioration of organ perfusion, prevent the oc- could be helpful to timely assess the evolution
currence of cardiac arrest, and may ultimately of the biventricular impairment and monitor
facilitate PCI and improve the periprocedural cardiac loading conditions.
479
Chapter 44
From the ECMO configuration standpoint, support.30 Nevertheless, some recent reports
the most common setup is VA-ECMO with a pe- have shown the reduction of cerebral blood
ripheral percutaneous approach (femoral artery flow in patient with concomitant VA-ECMO
and vein). Surgical cutdown at the groin might and IABP support.31 At this moment it is still
be preferable when there is cardiac arrest,20-22 not clear what is the best tool or strategy to
although the debate on this topic is ongoing. The unload the left ventricle. It is well known that
application of VA-ECMO in the AMI-related VA-ECMO may indeed increase ventricular
RCS scenarios is increasing,23-25 but the optimal wall stress and perpetuate ongoing myocardial
timing of VA-ECMO implantation, particularly ischemia, which is also caused by reduced oxy-
in relation to coronary reperfusion, is still un- genated blood reaching the coronary circulation
der debate. Many authors have reported better in this condition. In patients with AMI and
outcomes in high-risk patients approached by ECMO, myocardial protection has priority, and
VA-ECMO first and then followed by PCI.26-28 It careful consideration of left ventricular (LV)
seems clear that the application of ECMO sup- venting and unloading is an important part of
port during elective high-risk PCI procedures patient management. Therefore, concomitant
should considered at the start of the intervention, placement of an IABP or other percutaneous
but in any case, this should be done without devices, and other solutions like transpulmonary
hesitation if the patient is unstable, as described drainage and surgical transdiaphragmatic apex
by Yeh and colleagues.27 In this study, patients cannulation should be considered early.32-34
with AMI-induced refractory ventricular ar- The overall survival rate in patients receiv-
rhythmia were successfully supported prior to ing VA-ECMO for RCS is not yet well defined,
and during PCI with ECMO, which was re- but in a systematic review of 84 studies in-
moved in the presence of stable hemodynamics cluding 1,494 patients with cardiac failure, the
immediately after the procedure or maintained median survival rate was 39.5%, and 50% in
for a few hours until the hemodynamic situation the subgroup of patients with RCS due to AMI
had improved in hemodynamically unstable who were treated with ECMO.17 In this context,
patients to avoid the risk of the development possible favorable prognostic factors are to
of an untreatable RCS.27 be considered before performing VA-ECMO,
Contraindications for ECMO in AMI pa- like the absence of cardiac arrest, the effect of
tients are usually the same for ECMO use in combining IABP with VA-ECMO, and PCI.
other settings, but it is noteworthy that some Successful early revascularization provided
authors suggest that advanced age should not better long-term survival of patients with AMI-
be considered an exclusion criterion to perform related RCS compared to emergency coronary
VA-ECMO in elderly patients.29 The ECMO artery bypass grafting (CABG).
team should focus on the cardiac anamnesis, A team approach with input from specialists
reversibility of heart injury, or on the therapeutic in advanced heart failure and VAD/transplant
options.28,29 surgeons can facilitate decision making. In gen-
A very important issue in AMI patients eral VA-ECMO may be considered as a “bridge-
requiring VA-ECMO support is providing ad- to-decision” or as “temporary heart replacement
ditional support with an IABP. In patients at therapy” in the event of RCS, despite recovery
high risk for RCS with little or no residual left of other vital organs (bridge to transplant or
ventricular function, the use of an IABP may re- destination therapy).35 Finally, the “bridge-to-
duce left ventricular afterload, increase coronary decision” scenario may encompass the option
blood flow, aid the recovery of the arterial wave, of shifting to VAD, performing a heart trans-
and may enhance the weaning from VA-ECMO plantation, waiting for myocardial recovery,
480
or making an ethical decision of withdrawing emergency surgery in the ICU or ward are
hemodynamic support, if other therapeutic op- other frequent indications for ECMO implanta-
tions are not suitable in case of lack of recovery. tion.1,38-46 Graft failure or persistent pulmonary
Recently, some authors have highlighted the hypertension are also potential contributors to
detrimental role of tracheal intubation, sedation, the need for ECMO support after heart trans-
and mechanical ventilation, due to the increased plant.47-50
risk of pulmonary infectious complications and Access for cannulation varied among
muscle deterioration.36 For that reason, the use published series. The timing and indication of
of ECMO in awake patients without tracheal ECMO implant influence the type of approach,
intubation also seems promising in patients with central cannulation more frequently ap-
submitted to ECMO support because of AMI plied intraoperatively 39,43 taking advantage
sequelae.37 of the cannula used for CPB. In contrast, the
In conclusion, VA-ECMO has become more peripheral route, either percutaneous or with an
and more popular in patients with AMI and RCS, open access, is more commonly used in case of
being an innovative and possibly lifesaving tool, delayed ECMO implant.39,40,43 Several groups
especially when a device is implanted early and have also adopted intraoperative peripheral
is combined with other therapeutic measures. cannulation to allow sternal closure and reduce
the risk of bleeding.1,42 There are obviously pros
Postcardiotomy and cons for each type of cannulation. Central
cannulation might be advisable when the can-
The prevalence of ECMO implantation nulas used during CPB can be left in place, in
following cardiac surgery procedures varies be- the presence of low body weight which usually
tween 0.5% and 2.6% of operated patients1,38-46 is linked to small femoral vessel size, in case
(Table 44-1). Preoperative predictors for ECMO of severe femoral atherosclerosis, for better left
use in postcardiotomy patients are difficult to heart decompression, in case of a renal graft on
define. Smedira, by analysing 107 patients one side and IABP placed contralaterally, and
submitted to postcardiotomy ECMO, found finally to improve coronary and upper body
several consistent presurgical factors which may oxygenation.1 In contrast, the disadvantages
indicate that a patient has a high risk for such a of central cannulation are the need for reopen-
condition.38 Young age, higher creatinine, long ing the sternum for cannula removal, higher
history of coronary artery disease with previous risk of bleeding around the cannula insertion
myocardial infarction, repeat operation, recent site, uncomfortable channelization of the can-
previous operation, unstable clinical status, and nulas outside the body (subxiphoid), slight
an emergency operation with incomplete revas- hemodynamic and venous return interference
cularization without left mammary artery are during weaning due to the presence of the
potential predictors of the need for temporary venous cannula compressing the right atrium,
cardiocirculatory support at the end of or after increased left ventricular afterload with risk
cardiac surgery procedures38. for permanent aortic valve closure at high
The most common postcardiotomy sce- ECMO flows, and an increased risk of cerebral
nario is represented by intraoperative failure of neurologic events secondary to ECMO circuit-
weaning from cardiopulmonary bypass (CPB) related emboli.51 Femoral cannulation, either
due to left or biventricular dysfunction, or re- with a percutaneous or open technique, might
fractory hypoxemia with or without associated be more advantageous because it allows sternal
global cardiac hypocontractility. The onset of closure, better control of cannulation sites in
cardiogenic shock or cardiac arrest following case of bleeding, no need for sternal reentry
481
Chapter 44
after ECMO weaning, reduced risk of cerebral intensive care unit with immediate health care
embolization, and limited LV increase afterload personnel intervention, prompt availability of
as compared to central cannulation. One of the ECMO system), postcardiotomy patients appear
cons of peripheral cannulation is the “Harlequin to have a worse prognosis when compared to
Syndrome” in which the lower part of the body patients submitted to ECMO implant in other
is more oxygenated, with the potential of arterial settings, and this prognosis is almost the same as
vascular damage, leg ischemia (see cannulation in patients undergoing cardiocirculatory support
chapter for further details), and higher risk for for cardiac arrest.11,14,24
infection. There are few studies in the literature Predictors of mortality on ECMO after car-
which compare the two methods of vascular diac surgery include pre, intra and perioperative
access. No major advantage has been found in factors. Regarding preoperative factors (Table
terms of oxygenation/ventilation, end-organ 44-1), the need of cardiopulmonary resuscita-
perfusion, and hemodynamics with central can- tion, age >60 years, and duration of CPB were
nulation as compared to femoral cannulation in linked to reduced survival rates. Regarding peri-
postcardiotomy patients.51 operative predictors, high lactate levels, con-
The duration of ECMO in these patients is tinuous hemofiltration, and duration of ECMO,
usually shorter than in other ECMO settings, were linked to likelihood of in-hospital death.
with expected recovery within 48-72 hours Concerning the intraoperative aspects, isolated
from implant.38 Published series have described CABG appears to be a favourable prognostic
ECMO support ranging from 48 to more than factor, although not confirmed by all series40;
140 hours (Table 44-1). It has repeatedly been whereas, longer CPB duration, perioperative
shown that shorter duration of ECMO is linked lactate >4 mml/L,52 and incomplete sternal clo-
to better survival rates.1,38-46 Some institutions sure are factors which seem to increase mortality
suggest keeping ECMO support time limited to if ECMO is applied after surgery (Table 44-1).
2-3 days, and then switching to more durable Interestingly, the relation between age and
assist devices or, if indicated, to heart trans- the use of ECMO in the postcardiotomy set-
plantation.38 ting was investigated by several groups, and
Complication rates and types do not differ contradictory findings have been reported.1,38-46
from ECMO experiences in other settings, with It seems, however, that although a higher mor-
bleeding and acute renal failure as the most tality rate can be expected,53,54 there are no
common events.39 Of note is that cerebral com- contraindications to the application of such tem-
plications appear more common in this setting, porary support in older patients.45 Furthermore,
with neurological adverse events ranging from although mid- and long-term followup has been
6.3% to 29%,38,39,43,44 but frequently above 17%, poorly investigated, it has been shown that hos-
as compared to a brain injury rate of 15% in pital survivors from ECMO implant, regardless
the total group of adult VA-ECMO patients in- of their age, have rather satisfactory mid- and
cluded in the ELSO Registry (unpublished data). long-term outcomes, with cumulative survival
Regarding weaning from ECMO assistance, rates higher than 50% at five years.11,38,39
published series have shown rates ranging from Postcardiac transplant graft failure deserves
30% to 60% of cases. However, survival to a short commentary. It has been shown that
hospital discharge is substantially lower than posttransplant cardiac graft failure occurs in 2%
the percentage of weaned patients and ranges to 26% of transplanted patients,47-50 with a clear
from 16% to 43.6%.1,38-46 Despite apparently benefit from an early implant with regard to
more favourable conditions (in-hospital event, patient survival.51 ECMO weaning may achieve
conditions occurring in the operating room or very satisfactory results, with more than 80% of
482
the patients weaned, and with relatively short is certainly warranted, more liberal application
ECMO duration.47 LV unloading, in this setting, of LV venting still remains a controversial issue
appears to be critical, and, although careful at- and its actual benefits are yet to be demonstrated
tention based on the extreme susceptibility of conclusively.
the transplanted graft to any kind of ischemia47
Table 44-1. Published series of extracorporeal membrane oxygenation implanted in postcardiotomy

patients.
ECMO Survival to
Pts Prevalence° Duration Weaning Hospital Predictors of
Author Ref
(nr.) (%) (mean±SD, hrs (%) Discharge Hospital Mortality
if available) (%)
132±139^^ Acute renal failure
Ko 1 76 2.6% 118±57§§ 46,7% 26.3%** requiring dialysis on
99±33# ECMO
Smedira 38 97 0.48% 48-72¶ 39.2%¶¶ 35% na
Age>70 years,
Diabetes, Obesity,
Preop chronic renal
Rastan 39 517 1.2% 78,7±68.4 63.3% 24.8% failure, Operative
lactate >4 mmol/L,
Logistic Euroscore
>20
Older age,
Higher preoperative
albumin, Diabetes
Elsharkawy 40 239 0.58% na na 36%
history, CABG
surgery, Longer
CPB time
Age >60 yrs,CVVH,
Total Bilirubin>6
Wu 42 110 2.6% 143±112 60.9% 43.6%
mg/dl, ECMO
duration >110hrs
Preop atrial
fibrillation, Chronic
renal failure, Lactic
Saxena 43 45* na 103±74.3 53.3% 24.4% acidosis on ECMO,
Persistent
coagulopathy on
ECMO
Age >65 years,
85±12.5^
Fiser 44 51 0.9% 31% 16% LVEF< 30% after
64.7±9.2§
48 hours on ECMO
CK-MB relative
Zhang 45 32 na 64.8±40.8 43.7% 25% index as the ratio of
CK-MB to total CK
Incomplete sternal
Unosawa 46 47 na na 61.7% 29.7% closure, ECMO
support >48 hours
Pts=patients; °=In relation to global cardiac surgery activity; ¶=Institute strategy implies to keep ECMO for 48-72
hours and then switch to VAD or heart transplant; ¶¶=18 patients underwent heart transplant; *=this publication
deals with elderly patients (>70 years of age) only; CVVH=continous venovenous hemofiltration;
CABG=coronary artery bypass surgery; CPB=cardiopulmonary bypass; ^=heart transplant patients; §=non-heart
transplant patients; ^^=died on ECMO; §§=weaned from ECMO, but died in hospital; #=survivors to hospital
discharge; **=Other patients were bridged to VAD or heart transplant
483
Chapter 44
Acute Myocarditis in these patients since cardiac recovery is ex-

pected in the majority of the affected patients
Acute myocarditis (AM) frequently has a within a relatively short time.59-71,75 In AM and
benign course with rather rapid cardiac recovery particularly in AFM, careful daily monitoring
and favourable early and midterm outcome.55 of cardiac function and related aspects is war-
Rarely, however, a more malignant course, ranted. Significant stasis of blood in the left
namely acute fulminant myocarditis (AFM), atrium or left ventricle may occur due to ex-
might occur with rapidly refractory hemody- tremely poor contractility, making appropriate
namic compromise ultimately leading to patient peripheral perfusion almost entirely dependent
death if no mechanical cardiocirculatory sup- on ECMO flow, a condition which often leads
port is promptly instituted.56-71 The etiology of to permanent aortic valve closure or reduced
acute myocarditis is often undefined, but viral blood flow across the mitral valve due to high
or other infective agents apparently represent intraventricular pressure. Left chamber venting
the most frequent cause.55-59,70 Endomyocardial may, therefore, be warranted more often than in
biopsy is considered the gold standard in the other ECMO settings.71,76
diagnostic workup, although this procedure Complications are frequent, as in all ECMO
remains largely underutilized and has shown settings, and may have a significant negative
low negative predictive value.55-58,69,71 Markers impact on in-hospital outcome.59-72
of myocardial damage provide relevant infor- The use of associated immunosuppres-
mation about the extent of ongoing cardiac sive therapy on ECMO is still controversial,77
compromise and chance of recovery.72,73 High although a benefit of such a complementary
troponin-I levels have been shown to be as- treatment in case of poor response to cardiocir-
sociated with a more malignant form of AM culatory support has been reported.78
(less than one month duration) suggesting that Despite severe myocardial involvement
myocardial necrosis is an early event requiring cardiac recovery in AM usually takes place
a prompt diagnosis and aggressive treatment to within 7 to 10 days,59-71,75 although this period
limit such an overwhelming process.72 may be longer. Published VA-ECMO weaning
McCarthy and colleagues have interestingly rates after cardiac recovery in AFM range from
linked AFM to a more favourable outcome as 66% to 100% with survival to hospital discharge
compared to nonfulminant pattern of AM.74 In ranging from 60% to 100% (Table 44-2). The
their experience only two patients needed me- extent of end-organ and myocardial compro-
chanical circulatory support indicating a more mise, as previously measured by the amount
benign form of AFM in that patient cohort.74 of cardiac-related enzyme release or lactate
Generally speaking, a lethal outcome, unless levels at the time of ECMO implantation, and
aggressively and rapidly treated primarily with the time-to-normalization of end-organ perfu-
cardiocirculatory assistance, is likely in AFM. sion as expressed by a significant reduction of
Indeed, severe dysfunction of both cardiac lactate levels, have been directly related to the
ventricular chambers is almost invariably pres- probability of cardiac improvement, ECMO
ent.60,61,64,66,69,71,75 The efficacy of VA-ECMO in weaning, and in-hospital survival.68,71,73 Re-
such cases has been consistently proven and cently data from 147 patients included in the
is advisable based on the ease and speed of ELSO Registry have been reported, showing
implantation, on the immediate biventricular as a hospital discharge of 61%, with pre-ECMO
well as respiratory assistance, and on a limited arrest, need for higher ECMO flows at 4 hours
resource consumption as compared to other postimplant, central nervous system injury, re-
assist devices.59-71 ECMO is an invaluable tool nal failure, arrhythmia, and hyperbilirubinemia
484
being independent predictors of in-hospital to prolonged ECMO support and therefore

death at multivariable analysis.62 have higher complication rates.60,71,75 How-
In a small proportion of patients, a switch ever, favourable early and midterm outcomes
to more durable and sophisticated devices or to in patients supported with VAD or with heart
heart transplant is mandatory due to lack of car- transplantation have also been reported.68
diac recovery (Table 44-2). The overall outcome Following heart recovery and hospital dis-
of patients transplanted in these circumstances charge, AM recurrence is uncommon and can
is still less than optimal,71,75 probably because effectively be treated with medical therapy.68,70,71
patients requiring such surgical treatment are Mid and long-term results of patients submitted
often in suboptimal clinical condition with to VA-ECMO for AM or AFM are good, unless
end-organ failure and are usually exposed temporary myocardial disease resulted in per-
Table 44-2. Published series of extracorporeal membrane oxygenation in acute fulminant myocarditis.
ECMO Pts Switched Survival to

ECMO
Duration to LVAD or Hospital Postop Survival
Author Ref Pts Weaning
(mean±SD, hrs, Heart Discharge (%)(mean followup)
Pts (%)
if available) Transplant Pts (%)
Aoyama 61 52 42 (80.7%) 186±134 na 31 (59.6%) na
Diddle 62 147 101 (69%) 138 9^ 90 (61%) na
80%
Pages 63 6 5 (83%) 312±96 1* 5 (83%)
(1 year)
Chen 65 15 14 (93%) 129±50 2* 11 (73%) na
171.5±121 (incl 6* - 3^ (incl

Hsu 66 51 na 31 (61%) na
pediatric pts) pediatric pts)
100%
Ishida 67 20 12 (60%) na 0 12 (60%)
(2.6±2.1 years)
100%
Mirabel 68 35 na 240 4^ 24 (69%)
(1.5 years)
Asaumi 69 6 4 (67%) 130 1* 4 (67%) na
100%
Maejima 70 8 na na 0 6 (75%) (range 1.4 - 5.9
years)
65.9%
Lorusso 71 57 43 (75.5%) 237±456 2* - 3^ 41 (71.9%)
(5 years)
131 (txp pts 100%

Su 75 14 9 (64.2%) 2^ 10 (71,4%)
excluded) (4 years)
Pts=patients; LVAD=left ventricular assist device; SD=Standard Deviation;*=pts switched to LVAD;
^=pts swtiched to heart transplant
485
Chapter 44
manent LV dysfunction. In these cases, a less combination with coronary ischemia. Because
favourable prognosis, similar to other chronic of ventricular interdependence, RV dilatation in
heart failure conditions, is expected following acute severe PE leads to paradoxical interven-
hospital discharge.71 tricular septal shift that deforms the LV cavity
In summary, ECMO for AM in its most ma- and results in diastolic LV function impairment
lignant form represents an extremely effective and compromised LV filling leading to reduc-
tool to counteract or limit the life-threatening tion of LV output, systemic hypotension, and
progression of ongoing myocardial damage ultimately to severe haemodynamic instability.84
and dysfunction, and despite a rather high rate Respiratory insufficiency in PE is mainly
of complications, myocardial recovery can be caused by circulatory imbalance.85 Low cardiac
expected in a relatively short time, with very output results in ventilation-perfusion mismatch,
few patients requiring more aggressive thera- leading to hypoxemia. The ventilation of lung
pies. The long-term outcome is also favourable, units with absent or reduced perfusion induces
although it remains less defined in patients increased dead space ventilation with the re-
switched to VAD or heart transplant as well as sultant increase of the end-tidal to arterial CO2
in those showing persistent LV dysfunction at gradient, and finally hypercapnia.
hospital discharge. The therapeutic options according to the
American Heart Association80 include thrombo-
Acute Pulmonary Embolism lytic therapy. This is a reasonable choice with
an acceptable risk of bleeding complications
Pulmonary embolism (PE) is one of the for MAPE, and may be considered also for less
most undiagnosed conditions in hospitalized pa- massive PE with clinical evidence of an adverse
tients, with an overall mortality rate up to 15%.79 prognosis, with severe right ventricular (RV)
Rapid, efficient strategies of investigation and dysfunction and hemodynamic instability or
management are necessary. When massive acute increasing respiratory failure. Surgical embo-
pulmonary embolism (MAPE) occurs, acute lectomy and catheter-based techniques should
right ventricular failure and cardiogenic shock be considered in patients with contraindications
often result in early death. The American Heart to systemic thrombolysis or continued instabil-
Association and the European Society of Car- ity after thrombolysis, and may be mandatory
diology guidelines define massive PE as acute for less massive PE with worsening respiratory
PE with sustained hypotension (systolic blood failure or severe RV dysfunction.
pressure <90 mmHg or a systolic pressure drop The choice of the definitive treatment
>40 mmHg for at least 15 minutes or requiring should always be made on the basis of local
inotropic support).80,81 hospital expertise and experience with a patient-
Both circulation and gas exchange are centered approach.
compromised during acute PE. Pulmonary The use of ECMO is a potentially lifesav-
arterial obstruction of more than 30–50% of ing therapeutic option that can provide clinical
the total cross-sectional area of the pulmonary stability allowing definitive treatment if the
arterial bed82 and subsequent release of vaso- patient is critically ill due to severe cardiogenic
active substance (serotonin, thromboxane A2) shock, previous cardiac arrest, severe acidosis,
lead to acute pulmonary hypertension.83 Such a or untreatable hypoxemia. ECMO can be used
hemodynamic state causes a pressure overload as standalone treatment without any further
and an increase in right ventricle (RV) afterload definitive therapy, and some cases of success-
causing RV failure, which is considered to be ful use of ECMO as standalone treatment have
the primary cause of death in severe PE, often in been recently reported.85,86
486
The rationale of ECMO as a support for The successful use of standalone ECMO in
RV failure in MAPE, in a venoarterial con- some cases, without any other definitive therapy,
figuration, is to divert the blood from right to can possibly be explained by the effect of con-
left circulation bypassing the pulmonary bed tinuous and effective systemic heparinization. It
which relieves the RV pressure overload, does has been shown that autolysis of the thrombus,
not cause further elevation of the pulmonary allowing RV recovery, is possible within five
pressures, and increases left-sided pressures.87 days in the absence of hypercoagulable disor-
VA-ECMO allows the unloading of the ders such as factor V Leiden disease, antiphos-
acutely overloaded right atrium and ventricle, pholipid syndrome, and malignancy states.90
thereby improving LV output due to ventricular ECMO for selected patients with massive
interdependence.88 Beside stabilizing the hemo- PE is associated with favourable outcomes.
dynamic status, VA-ECMO relieves hypoxemia, Indeed, the ELSO Registry reports the survival
which ensures adequate organ oxygenation and of patients supported by ECMO for respiratory
allows therapeutic anticoagulation until clot dis- and cardiac failure to discharge or transfer back
solution. Patients requiring ECMO have exten- to the referring hospital to be 56% and 30%,
sive pulmonary thromboemboli, and therefore respectively.91 Patients presenting in cardiac ar-
the aggressive use of catheter-based interven- rest have worse outcomes (survival 29%),92 but
tion appears to have beneficial effects in case other data93 suggests that patients with massive
of MAPE, making quick weaning of the patient PE presenting in cardiac arrest are more likely
from the extracorporeal support possible.89 to survive with good neurological outcomes
The most used approach for VA-ECMO, in (survival 51%) with a measured cerebral per-
up to 80% of the patients, is femoral cannulation. formance in category 1 or 2.
This technique allows rapid cannulation at the Maggio and collaborators89 developed an
bedside so the correction of the abnormal physi- algorithm for the management of suspected
ological status can start immediately, thereby PE with impending or existing RV failure. The
preventing severe organ failure by providing most interesting part of that algorithm is the
full cardiorespiratory support until clot dissolu- placement of inferior vena cava filters, prefer-
tion occurs with systemic heparinization or by ably before the patients could be weaned from
the definitive therapy. ECMO but before decannulation. For this the
Venovenous ECMO can only be used if the use of a drainage cannula placed in the internal
patient does not have any severe hemodynamic jugular vein is necessary.
impairment but only major hypoxia and this ECMO use in the context of massive PE
strategy needs to take into account the possible should be considered, balancing possible
presence of residual thrombus in the deep vein benefits and the chance of recovery without
(femoral or jugular) or in the right atrium. significant neurological sequelae on one hand
An interesting solution could be venoar- and the potential risks on the other hand.
terial-venous ECMO (VAV-ECMO) that can The major complication of ECMO use in PE
support circulation and oxygenation. This tech- is massive bleeding and this occurs as a result
nique can totally solve the Harlequin Syndrome of systemic thrombolysis, of persistent changes
when the patient’s heart still has a residual in the coagulation due to the hepatic shock, or
ejection function. VAV-ECMO is not simple of uncontrolled fibrinolysis that induces a dis-
to configure and it needs extensive monitoring seminated intravascular coagulopathy.94
of the blood flow in both inlet branches and In conclusion a rapidly implanted ECMO
outlet pressure (to avoid arteriovenous shunting support system can be a lifesaving treatment in
between the two outlet cannulas). the setting of massive MAPE and the risks of
487
Chapter 44
this therapeutic strategy are well justified by the Other challenging and life-threatening
good results in the category of patients with a conditions are represented by malignant ar-
very high risk for morbidity and mortality. rhythmias or electrical storms which may be
sometimes refractory to aggressive pharmaco-
Cardiogenic Shock in Other (Rare) Non logical agents or to repeated electrical shocks,
Surgery-Related Etiologies which are used for hemodynamic stabilization
and recovery of normal cardiac electrical activ-
In patients with life-threatening hemody- ity.102,103
namic instability, VA-ECMO can be considered Although uncommon, these experiences
when shock persists despite volume administra- suggest that ECMO might be considered a
tion, the use of inotropes and vasoconstrictors, valuable option to counteract cardiocirculatory
and IABP implantation. There are several dysfunction due to variable etiologies which
rare, but life-threatening conditions which are are refractory to medical therapy, as well as for
characterized by refractory cardiocirculatory treating acute circulatory impairment which can
impairment which might benefit from prompt be the consequence of poisoning.
and temporary assistance of the circulation.
A series of 12 patients affected by endo- Cardiocirculatory Support or Bailout
crine-related cardiogenic shock have been Assistance During Interventional Cardiology
reported by Chao and collaborators.95 In this
series, endocrine emergencies included car- Interventional cardiology is certainly an
diocirculatory crisis secondary to pheocromo- emerging setting for ECMO application.104,105
cytoma (4 patients), thyroid storm (5 patients), Indeed, temporary cardiocirculatory support has
and diabetic ketoacidosis (3 patients). The been used for various indications, ranging from
clinical features were different depending on prophylactic support in high-risk PCI or trans-
the underlying endocrine disorder, but were catheter procedures, to bailout approach in case
equally compromising the cardiocirculatory of cardiac arrest or shock during or following
system with severe and RCS. In all patients, cardiological interventions. Arlt and colleagues
the cardiac function and the general conditions have reported the use of ECMO in ten patients
showed a fast recovery, whereby only a short in cardiac arrest which occurred during PCI or
period of ECMO support was necessary.95 The transcatheter aortic valve implantation (TAVI)
use of ECMO to successfully counteract RCS with a percutaneous approach.106 All patients
in a pheochromocytoma crisis has been reported had heart activity rapidly restored, and two
in other cases.96-98 TAVI patients were converted to surgical aortic
ECMO has been shown to be life-saving valve replacement while on ECMO, whereas in
and highly effective also in the presence of all PCI cases ECMO allowed the completion of
Takotsubo-like or related syndromes.99-100 This the coronary intervention during cardiocircula-
well known stress-induced and related myocar- tory assistance. In this series of patients with a
dial dysfunction is associated with disparate mean age of 73 years the survival to hospital
conditions, ranging from intraoperative to discharge was 50%, with one patient eventually
pregnancy or pharmacologycally solicited hy- undergoing heart transplantation. Causes of
perreactive myocardial response.99-101 Duration death were multiorgan failure in 3 cases (43%),
of ECMO support may also vary remarkably bowel ischemia in 2 (28%), and nonreversible
in these circumstances from a few hours to a cardiac failure in 2 (28%). The Regensburg
few days.99-101 group has published a series of eight patients un-
dergoing TAVI who were submitted to ECMO
488
because of complications, and nine patients high. These conditions may be perioperative
had TAVI while on prophylactic ECMO. They refractory hypoxemia, severe acidosis with
showed that ECMO may also be valuable in profound cardiovascular impairment, ongoing
bail-out cases, but the mortality remains high severe cardiac damage or left and right severe
in these circumstances.107 ventricular dysfunction which might further
Interestingly, ECMO might be used also as be exacerbated by the myocardial ischemia
a temporary support to improve different trans- inevitably generated by open heart surgery. A
catheter procedures in case the patients require short period of hemodynamic and metabolic
emergent cardiac defect correction, but have stabilization and compensation prior to the
concurrent multi-organ failure which cannot be surgical procedure might be beneficial in these
treated surgically. Temporary ECMO support circumstances, bring the patient in a better clini-
during Mitraclip (MitraClip®, Abbott Labora- cal and metabolic condition to undergo surgery,
tories, Abbott Park, Illinois, U.S.) application and reduce or prevent intra or perioperative
has been shown to be feasible and effective.108 complications.
Short-term mechanical assistance was also There are several case reports about the
shown to be beneficial in the presence of inces- use of prophylactic ECMO in the presence of
sant ventricular fibrillation.109 In these cases, post acute myocardial infarction ventricular
ECMO might act as cardiocirculatory support septal defect.110-113 It is of note that delaying the
during electrophysiological procedures, and surgical correction might improve the chance
with a special circuit configuration (Y-connector of a successful surgical repair because of better
in the arterial cannula to allow passage of the tissue strength, but this delay could increase the
ablation catherer, and keeping higher ECMO right and left ventricular dysfunction which can
flows during the interventional procedure) be associated with the intracardiac defect. Rohn
might be effectively applied even in these criti- and Hobbs have independently reported about
cal circumstances. the use of ECMO as a preoperative bridge to
These experiences are anecdotal and, as definitive surgical repair of postinfarction ven-
such, do not represent evidenced-based indica- tricular septal defect (VSD),110-115 and Tsai and
tions, but offer a new perspective in handling colleagues have used ECMO support as a bridge
a compromised circulation in an emergency to definitive surgery in a patient with recurrent
situation when a cardiac intervention is neces- VSD following initial surgical repair.114
sary to interrupt a vicious cycle and a surgical A bridge to cardiac surgery with ECMO
procedure cannot be performed because of a might be applied also in other surgery related
prohibitive risk. conditions like acute mitral insufficiency due to
papillary muscle rupture,115 or left ventricular
Preoperative Support (postinfarct ventricular free wall rupture.116,117 ECMO can be used also
septal defect, papillary muscle or left free as a stand alone support to allow recovery of
wall rupture, acute endocarditis) left ventricular free wall rupture without surgi-
cal repair118.
Other potential scenarios of ECMO use Acute endocarditis may be the cause of
in cardiovascular medicine are represented by acute severe cardiocirculatory compromise ei-
acute cardiac defects with severe RCS with or ther due to valve insufficiency and cardiac dys-
without respiratory impairment which might function leading to hemodynamic deterioration
benefit from surgical correction, but the risk or to a refractory septic state. ECMO, besides
for operative or perioperative complications septic shock, may have a role as prompt sup-
and a fatal outcome is considered to be too port in case of cardiopulmonary deterioration
489
Chapter 44
(also in septic shock) and bridge the patients often in the middle-aged population and is more
to the surgical correction of the endocarditis- likely to affect men. It has a considerable annual
related valve abnormalities.119,120 ECMO may mortality rate, ranging from to 5% to 10%.122
be particularly valuable in those patients who Sudden death accounts for up to 50% of all
present with biventricular dysfunction, often deaths and is most often due to rapid ventricular
with multivalvular infectious involvement. In tachycardia or ventricular fibrillation and less
such circumstances ECMO may provide pre often due to bradyarrhythmias or asystole.123
and perioperative support, particularly for the Patients affected by CCM may progress
dysfunctional right ventricle which often is the through a variable time-related asymptomatic
cause of the unfavourable outcome. Despite ef- phase of cardiac dysfunction, which can usually
fective cardiocirculatory assistance the removal be well controlled by medical therapy, but after
of the source of the infection and the correc- a certain amount of time they may develop epi-
tion of concurrent valve dysfunction must be sodes of acute heart failure, or the heart evolves
promptly addressed and carried out since the toward an end stage cardiac dysfunction.122
persistence of such conditions and maintain- These patients are at a higher risk for death
ing a conservative approach usually leads to as compared to other patients with acute RCS
intractable septic shock and ultimately to the since this situation is usually associated with
death of the patient121. exhausted cardiac reserve and long-lasting dys-
function of other organs, namely liver, kidney,
Acutely Decompensated Chronic and gut. Furthermore, long-lasting aggressive
Cardiomyopathy pharmacological therapy make these patients
also poor or nonresponders to maximal medical
The term chronic cardiomyopathy (CCM) therapy in the presence of acute decompensa-
refers to a number of diseases that affect the tion. Cardiogenic shock remains a life-threat-
heart by compromising the cell and the related ening emergency with a overall mortality rate
interstitium, ultimately leading to severe con- ranging from 50% to 80%.124
tractile impairment characterized by a rather The treatment of RCS in the presence of
long-lasting course. Cardiomyopathy can have CCM is more challenging than in the situa-
different causes: it can be genetic; it can occur tion of primary acute heart failure. Mechani-
as result of metabolic or nutritional disorders; be cal circulatory support is, in most of these
secondary to long-term hypertension, coronary circumstances, the only form of therapy that
disease, or cardiac valve dysfunction; and even may be lifesaving. Patients can be in preshock
be pregnancy related. Sometimes, however, car- condition due to long-lasting cardiac and end-
diomyopathy occurs with no discernible cause, organ hypoperfusion. VA-ECMO definitely
and is than called idiopathic cardiomyopathy. represents a valuable and immediate support
There are three main types of cardiomyopathy: to improve hemodynamics, gas exchange, and
hypertrophic, dilated, and restrictive. This sec- consequently organ perfusion. It has been dem-
tion will deal only with dilated CCM, either onstrated that VA-ECMO implantation quickly
ischemic or idiopathic, as this is the most com- restores hemodynamic function. Lactate, cre-
mon for potential ECMO use. atinine, and transaminases serum levels will be
Dilated CCM is a severe myocardial disease reduced, leading to less need for vasopressor
characterized by dilatation and impaired func- and inotropic agents; in this way the perfusion
tion of the left or both ventricles, which affects of the organs is improved and the myocardial
>36.5 individuals per 100,000.122 Although this oxygen consumption is reduced.125 Tarzia and
type can affect people of all ages, it occurs more colleagues have recently shown that patients
490
treated with VA-ECMO for acutely decom- should be optimized to improve the bridge-to-
pensated CCM had a higher rate of end-organ bridge function to more aggressive therapies
dysfunction, needed more frequently inotropes like VAD or heart transplant.129,130 VA-ECMO
and also higher doses, had more renal failure may also help to ascertain the suitability of
(67% vs. 38%), and hepatic failure (48% VAD implantation and cardiac transplant, and
vs. 19%), and needed higher ECMO flow to to obtain clinical stability prior to considering
achieve good organ perfusion, as compared to VAD insertion as “destination therapy,” and
the group of patient with acute primary RCS.126 reduce mortality and morbidity following VAD
Furthermore, recovery was achieved only in the or cardiac transplant procedures.126,127,129,130 Mar-
acute group. They suggested that patients with asco and colleagues have compared 23 patients
an acute failure of CCM need an early ECMO who received VA-ECMO prior to VAD with
implantation and, probably, multiorgan support 35 patients who had VAD without previous
if the low cardiac out state is already established circulatory support, and have shown how the
at the start of ECMO. These authors showed ECMO-related group had more comorbidities
that in the CCM group (27 patients), 85% of and end-organ dysfunction prior to VAD im-
the patients were switched to VAD (52%) or plant, but the final outcome was comparable to
to heart transplant (33%), as compared to the the other group. This indicates that ECMO may
patients with acute heart failure of which 8% lead to clinical improvement prior to the subse-
underwent a heart transplant, 24% had a bridge- quent procedure and improve the final outcome
to-bridge procedure and 49% recovered.126 by reducing the expected higher morbidity and
Furthermore, the long-term survival of the two mortality130.
groups did not differ (77% at one month, 56% The use of ECMO allows survival to be
at six months, and 51% at one year in the acute maximized in patients who are otherwise
heart failure group, and 71%, 56%, and 55% untreatable and face an extremely severe prog-
in the CCM group, respectively).126 These data nosis in CCM, regardless of the etiology of the
are in contrast with the series of Bermudez and cardiomyopathy. In the context of chronic pro-
collaborators, who showed a comparable early gressive cardiac failure, ECMO may represent
outcome, but a remarkably less favorable results the ultimate rescue strategy, and could save
at midterm in the CCM group as compared to the patient’s life by functioning as a bridge-to-
patients supported for a primary acute failure bridge tool, or bridge to transplant. If the patient
(64%, 48% and 48% at 30 days, one year and is not a candidate for one of these two options,
two years in the acute group, versus 56%, 11% the caregiver’s team should carefully reconsider
and 11%, in the CCM group, respectively).127 the indication for implantation of ECMO sup-
The most common and safe cannulation port. This is to avoid the indiscriminate use of
approach is peripheral implantation as a bifemo- this highly technological tool and encourage
ral VA-ECMO. Central cannulation is still an instead its use at the right time and in the right
option, but has a higher rate of complications, patients so they can have a chance for survival
due to the prolonged cardiac support and a and a longer life.131
higher risk for limb ischemia. The use of axil-
lary artery cannulation for blood return might Conclusions
be considered and could, in these cases, give
better access.128 It has become increasingly evident that
As mentioned, myocardial recovery in pa- ECMO represents a valuable tool in the pres-
tients with CCM is rather unlikely and, therefore, ence of severe cardiac compromise, with or
VA-ECMO and associated medical therapies without concomitant respiratory dysfunction,
491
Chapter 44
in adult patients. Beside traditional settings like

AMI, postcardiotomy, and acute or decompen-
sated chronic cardiac diseases, other clinical
conditions represent potential and promising
scenarios for ECMO use, including prophylac-
tic or preoperative ECMO support to allow the
safe performance of various procedures, bailout
cardiocirculatory assistance during catheter-
based interventional cardiology, or temporary
support during acute heart failure of variable
etiologies. Refinement of patient selection and
management, timing of implantation and dura-
tion of support, and a team approach, together
with ongoing technological and pharmaceutical
(see alternatives to heparin) improvement, will
provide further development and new applica-
tions of these systems. This will lead to better
ECMO use outcomes in adult patients who need
hemodynamic support in conventional or novel
clinical settings of cardiovascular medicine.
492
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ogy on outcome. J Thorac Cardiovasc Surg.
2015;150:333-40
127. Bermudez CA, Rocha RV, Toyoda Y, et
al. ECMO for advanced refractory shock
in acute and chronic cardiomyopathy. Ann
Thorac Surg. 2011;92:2125-31
128. Biscotti M, Bacchetta M. The “Sport
model”: ECMO using the subclavian artery.
Ann Thorac Surg. 2014;98:1487-9
129. Hoefer D, Ruttmann E, Poelzl G, et al.
Outcome evaluation of the bridge-to-bridge
concept in patients with cardiogenic shock.
Ann Thorac Surg. 2006;82:28–33
130. Marasco SF, Lo C, Murphy D, et al. Extra-
corporeal life support bridge to ventricular
assist device: the double bridge strategy.
ASAIO J. 2016;40:100-6.
131. Abrams D, Combes A, Brodie D. What’s
new in extracorporeal membrane oxygen-
ation for cardiac failure and cardiac arrest in
adults? Intensive Care Med. 2014;40:609-
12
500
45
Extracorporeal Cardiopulmonary Resuscitation in Adults
Jan Bělohlávek, MD, PhD, Yih-Sharng Chen, MD, PhD, Naoto Morimura, MD, PhD
Introduction citation, however, remains the early return of

spontaneous circulation (ROSC). Prolonged
Survival after cardiac arrest (CA) remains CA and CA without ROSC bears dismal prog-
poor. Worldwide, neurologically favorable noses.6 In patients without ROSC, the chance of
survival in patients resuscitated by emergen- survival when transport to the hospital occurs
cy services for out-of-hospital cardiac arrest during CPR falls below 4%.7,8
(OHCA) is only 2-11%, eventually 12-19% in Therefore, substituting failed ROSC by an
patients with initially shockable rhythms1 and extracorporeal device presents an attractive ap-
slightly better for in-hospital cardiac arrest proach in refractory CA. The concept of using
(IHCA) of 22%.2 Still, in certain subgroups of an extracorporeal pump for artificial circulation
patients with witnessed cardiac arrest, shockab- is old9 and has been tested initially in moribund
le rhythms, high quality post cardiopulmonary patients with challenging survival. Fifteen long-
resuscitation (CPR) care, including targeted term survivors out of 39 patients urgently cannu-
temperature management, early coronary related for ECLS at the bedside within 15 minutes
perfusion, treatment of electrolyte disorders, of CA were reported by Mattox in 1976.10 Fifty-
seizures, and pneumonia, neurologically favo- four studies with 675 patients in CA treated by
rable outcome as high as 25-30% can be rea- percutaneous cardiopulmonary bypass between
ched. 1 Moreover, other interventions including 1966 and 2005 reported survival to discharge of
reduction in no-flow time by early bystander 42% (IQR 15.4%, 75%).11 However, most prob-
CPR, telephone assisted bystander CPR, early ably these results underreported poor outcomes.
defibrillations using automated external defi- 11
These initial reports and crucial advances in
billators (AEDs), adequate compression depth technology, availability of miniaturized simple
and rate of CPR, compression to ventilation ECLS devices useful for transporting patients,
ratios, appropriate oxygenation, use of targeted compatible extracorporeal circuits, novel percu-
temperature management, catecholamines to taneous cannulas suitable for rapid implantation,
improve cardiac output, thrombolysis and early and ongoing efforts to improve outcome of CA
percutaneous coronary intervention (PCI) have became the prerequisites for the implementation
been adopted into routine care and tested with of extracorporeal mechanical support technique
an aim of improving cardiac arrest outcomes.3 to CPR, ie, development of extracorporeal
Large studies have employed mechanical chest cardiopulmonary resuscitation (ECPR). ECPR
compression devices.4,5 The main aim of resus- has been recognized in European Resuscitation
501
Chapter 45
Guidelines 2015 as a rescue therapy for those patient with venoarterial ECMO. Alternatively,
patients in whom initial advanced life support for ECMO or ECLS, other terms including
measures are unsuccessful or to facilitate specif- percutaneous or emergency CPB and eventu-
ic interventions (eg, coronary angiography and ally portable or percutaneous cardiopulmonary
PCI or pulmonary thrombectomy for massive support, are used interchangeably.
pulmonary embolism).12 The American Heart
Association (AHA) guidelines are more cau- Organizational Issues Related to ECPR
tious regarding the recommendation for ECPR Implementation
because of the ongoing paucity of available
data.13 A recent metaanalysis compared ECPR ECPR usually occurs in tertiary care insti-
to conventional CPR and showed a favorable tutions provided by a dedicated ECMO team.
effect on 3-6 month survival with good neuro- The ECMO team consists of professionals from
logical outcome in ECPR subjects. However, intensive care, cardiology, cardiac surgery, and
the effect of ECPR on survival to discharge in other specializations collaborating with special-
OHCA has not been clearly shown indicating ized nurses and perfusionists. In-hospital coor-
the need for strict criteria for implementation dination between the ECMO and CPR teams
of ECPR in such a setting.14 must include rules to activate the ECPR team in
This chapter aims to provide an overview a 24/7 coverage model. ECMO team members
on the current role of ECPR in clinical practice, must be well trained in venoarterial cannulation,
serving as a practical guide for performing circuit management, and early postresuscita-
ECPR. tion care (see Chapter 67). An ECLS-trained
physician and perfusionist or specialist provides
Definition of ECPR 24-hour coverage for ECLS patients. Physicians
trained in vascular ultrasound for the insertion,
ECPR applies ECLS in patients who remain maintenance, and surveillance of ECMO can-
in CA despite conventional CPR, or when inter- nulae and distal perfusion cannula should also
mittent ROSC occurs, but repetitive CA reoc- be available. Intensive care unit (ICU) care
curs. In other words, ECPR is used in refractory
CA, when chances of obtaining and sustaining
ROSC are poor. Unfortunately, definitions of re-
fractory CA vary from 10 to 30 minutes of CPR
without ROSC.15,16 The optimal duration of
refractory CA prior to ECPR remains unknown,
but both for IHCA and OHCA, maximal time
of approximately 15 minutes of CPR seems to
be reasonable.17,18
Cannulation to ECPR ensures complete
mechanical support suitable to provide tem-
porary circulation and gas exchange. Cannu-
lation usually occurs via the femoro-femoral
venoarterial route, because of easy accessibility, Figure 45-1. A typical scheme of a femoro-
(Figures 45-1 and 45-2). Alternative approaches femoral VAl ECMO circuit setting including
include the femoro-subclavian, jugulo-subcla- distal perfusion cannula for prevention of limb
ischemia used for ECPR. IVC=inferior vena
vian or jugulo-femoral routes. The term ECPR cava; RA=right atrium; arrows depict blood
is used to describe an intention to treat a CA flow direction.
502
Extracorporeal Cardiopulmonary Resuscitation
must be adjusted to ECMO use, ie, intensive cardiology, cardiac surgery, general intensive
care unit nurses should be specifically trained care, and emergency departments. Supportive
in ECLS and circuit management. The nurse-to- departments necessary for ECPR patients com-
patient ratio during the postresuscitation phase prise: biochemistry with emergently available
should be 1:1, depending on the local regula- common laboratory tests (arterial blood gases,
tions or resource availability. The ECLS team lactate, hemoglobin, glucose often available
should be self sufficient and able to set up the also bedside); radiology including vascular ul-
ECLS circuit quickly. The specialist team may trasound, vascular embolizations, CT imaging
also be responsible for managing equipment used to adopt adjustments specific for ECMO
and supplies, regular service administration, patients;24 blood bank, pharmacy, coronary an-
troubleshooting, daily rounds, education, pa- giography and PCI service. Essential equipment
tient database administration, quality control,17 readily available for use at the site of ECPR
and coordination of neurological, psychiatric, (or on the “ECPR trolley“) should consist of
psychological and rehabilitation care. Adjust- ECMO cannulation sets, ECMO cannulas (15
ments may be implemented depending on the to 21 Fr for arterial and 19 to 29 Fr for venous
site where ECPR is provided. ECPR for IHCA is access), 150 cm catheterization wires including
usually provided in the ICU or operating room. stiff wires for adequate support, catheterization
Experiences mainly from France and Germany sheats 5 to 8 Fr for vessel access establishment,
show tha for OHCA, ECPR occurs primarily in eventually useful for distal perfusion, stopcocks,
the cathlab or emergency departments.18-23 Ac- basic surgical instruments required for open
cordingly, the ECMO team has to be prepared access to femoral vessels and other routine
both for in-hospital and inter-hospital transport material used for invasive procedures including
of ECLS patients. sterile dressing, drapes, etc.
A preassembled dry-primed or wet-primed
Facilities and Equipment Appropriate for ECLS machine should remain available 24/7,
ECPR with regularly checked technical and battery
status. ECLS machine can be situated at the
Complex intensive care serves as a prereq- ICU, cathlab, emergency department, or within
uisite to provide ECPR service and involves the operating room areas. The team should be
trained to deploy the device for full use within
5-10 minutes from decision to proceed with
ECPR. An overview of essential prerequisites
to perform ECPR is summarized in Table 45-1.
The Ideal ECPR Patient
Patients who might be excellent candidates

for ECPR consideration (Table 45-2) have a CA
with initially shockable rhythm, a witnessed
arrest with immediate CPR with no sustained
ROSC within 10-15 minutes of advanced life
support by an emergency medical service/CPR
Figure 45-2. An ECPR patient on the ICU. The team, and age less than 75 years.25,26 The final
patient had severe aortic stenosis and coronary
artery disease leading to ECPR for refractory decision on whether to proceed with ECPR
OHCA. falls to the ECMO team and is based on estab-
503
Chapter 45
lished criteria. Within an ongoing randomized on a case-by-case basis.27 The short time for
trial, a strict protocol and inclusion/exclusion such a decision renders the complex decision
criteria both for enrollment of the patient into that encompasses ethical, social, financial, and
the “ECPR” study itself and also for a final logistical even more challenging. Definitely,
decision whether to connect an ECLS is used inappropriate ECLS cannulation may produce
(Tables 45-3 and 45-4).18 An age limit in ECPR serious consequencies28 while potential organ
remains controversial. The ELSO Registry donation has been used as an indication to pro-
analysis, with its inherent reporting biases, ceed with ECPR.29
has an acceptable hospital discharge rate of
22% in the elderly; however, indication for ECPR Cannulation Technique
ECPR in older patients must be considered
During ECPR, the ECMO team leader
Table 45-1. Essential prerequisites to perform assesses patient suitability for cannulation
ECPR. (Table 45-4), the quality of CPR (position and
ECPR effects of mechanical chest compression de-
For IHCA For OHCA
Resuscitation team for hospital Resuscitation team at the site
24/7 where OHCA is referred to 24/7
Early alert system to notify Early alert system to notify
ECMO team leader about IHCA cardiac center/emergency
Table 45-2. Criteria of patients suitable for
department coordinator about ECPR consideration.
OHCA
Coordinated collaboration with Coordinated collaboration with
CPR team leader EMS crew/dispatcher during Criteria
transport with ongoing CPR Witnessed sudden arrest (public place, EMS
(mechanical chest compressions) crew, emergency department, ICU, cathlab,
ECMO team ready within 15 minutes at the site of ECPR
24/7 available preassembled ECLS device and perfusionist/specialist
operating theatre)
Ability to transport a patients Ability to admit patients with Assumption of cardiac etiology and reversible
with ongoing CPR in the hospital ongoing CPR via mechanical cause (acute coronary syndrome, pulmonary
(mechanical chest compressions chest compressions embolism, myocarditis, shockable rhythm, etc.)
used)
Ability to cannulate and perform invasive procedures (coronary
High-quality CPR started immediately after the
angiography) under ongoing CPR (includes technical skills and collapse
equipment) Intermittent ROSC
Readily available: echocardiography, vascular ultrasound, basic No major comorbidities
laboratory examinations, optional monitoring of cerebral tissue
saturation Age under 70 years (individual, case by case
Trained ICU team available at the site of ECPR consideration)
Table 45-3. Inclusion and exclusion criteria for a randomized study

of ECPR.18
Inclusion Criteria Exclusion Criteria
Age ≥18 and ≤ 65 years OHCA of presumed noncardiac cause
Witnessed OHCA of presumed cardiac Unwitnessed collapse
cause
Minimum of 5 minutes of ACLS Suspected or confirmed pregnancy
performed by emergency medical service
team without sustained ROSC
Unconsciousnessa ROSC within 5 minutes of ACLS performed by EMS team
ECLS team and ICU bed capacity in Conscious patient
cardiac center available
Known bleeding diathesis or suspected or confirmed acute
or recent intracranial bleeding
Suspected or confirmed acute stroke
Known severe chronic organ dysfunction or other
limitations to therapy
“Do not resuscitate” order or other circumstances that make
180 day survival unlikely
Known pre-arrest cerebral performance category CPC ≥ 3
OHCA=out-of-hospital cardiac arrest; ACLS=advanced cardiac life support; ROSC=return of spontaneous circulation;
EMS=emergency medical service; CPC=cerebral performance category.
a
Defined as no response to verbal or painful stimuli during ACLS
504
vice), and neurological status. Small pupils are Panel A:

considered to be a favorable prognostic factor,30
similarly lactate values below 5 mmoL/L,31
however, lactate values are usually higher in
ECPR patients. Alternatively, some reports in-
dicate brain near infrared spectroscopy (NIRS)
can be a potentially valuable tool in assessing
patients under CPR.32 When care includes
EPCR, a perfusionist or specialist primes the
ECLS pump, femoral vessels are visualized
by ultrasound, and the patient is draped in a
sterile fashion to begin cannulation. Generally,
cannulation during ongoing CPR is challenging,
puncture of the vessels may not be easy, and ad-
vancement of the wire must be done cautiously
but rapidly. Occasionally, it may be difficult
to distinguish between the artery and the vein,
Panel B:
therefore cannulation under fluoroscopy may
be required. The direction the wires advances
helps assess whether artery or vein has been
punctured. Another alternative includes insert-
ing a regular catheterization sheath to perform
brief angiography, which not only distinguishes
artery from vein but helps to choose the cannula
diameter and excludes possible peripheral arte-
rial disease (Figure 45-3). Position of the venous
cannula can be confirmed under fluoroscopy or
by echocardiography. Later positional changes
without an inserted wire should be avoided.
After cannulas are safely inserted and retrograde
flow from the cannulas is brisk (an easy aid to
confirm correct intraluminal position), the ex-
Table 45-4. Inclusion and exclusion criteria

for initiation of ECLS in a randomized study
on ECPR.18 Figure 45-3. ECPR patient: previously healthy
55-year old man with ongoing CPR for OHCA
from ventricle fibrillation resulting in CPR.
Inclusion Criteria Exclusion Criteria Panel A: femoral artery cannulation, with
No ROSC or ROSC with ongoing Signs of death or irreversible organ two sheaths accidentally inserted into the
shock (defined as sustained damage
hypotension less than 90 mmHg of same artery (arrows). One was subsequently
systolic pressure or the need for removed, the other one exchanged for arterial
bolus doses of vasopressors to
maintain circulation)
ECLS cannula. No bleeding occurred. Panel
Admission to catheterization lab not Known bleeding diathesis B: angiography of the left coronary artery after
more than 60 minutes after the institution of ECLS flow, non-beating heart,
collapse/initial call to EMSa
proximal LAD occlusion (upper arrow), signifi-
Consensus of ECMO team members Inadequate arterial and/or venous
on ECLS initiation access for femoro-femoral cannulation cant atherosclerotic lesion on distal circumflex
ROSC=return of spontaneous circulation artery (lower arrowhead).
a
If the exact collapse time was not known, an initial call to EMS was considered
505
Chapter 45
tracorporeal circuit is attached. Patient receives institute target hypothermia quickly. However,
full anticoagulation, unless contraindicated this intervention is not based on established evi-
(suspicion of bleeding), usually with a bolus dence. Starting with a lower sweep gas oxygen
of unfractionated heparin of 75-100 IU/kg fol- concentration is based on studies suggesting the
lowed by continuous infusion to keep activated harmful effects of hyperoxia after ROSC.37,38
clotting time close to 200 seconds, or an aPTT at Titration to target peripheral saturation of 90-
50-70 seconds (see Chapter 7). In some centers 95% seems reasonable, bearing in mind that in a
or instances, ECPR with surgical cutdown and majority of ECPR patients pulse oximetry may
exposure of the femoral vessels is used, and be inaccurate. Thus brain tissue regional satura-
might be preferrable in case of difficult echo tions by NIRS provide better in-line (sampling
visualization or lack of fluoroscopy imaging. every 6 seconds or similar depending on device
used) control with target values around 60-70%.
Optimal Cannula Diameter Beginning with inspired oxygen of 50-60%
and later increases based on above monitoring
Choosing cannula diameter size can prove appears reasonable. Blood flow is usually set
difficult but important because changing them to 4 L/min and eventually increased gradually.
after cannulation is stressful and potentially Thiagarajan et al. analyzed the ELSO Registry
dangerous. When considering the appropriate for ECPR and found an initial pump flow of 3
cannula diameter, an important factor is the L/min in both survivors and nonsurvivors and it
presence of peripheral arterial disease. A smaller remained constant after 24 hours.39 Sweep flow
diameter cannula to prevent damage or tearing initially matches that of the blood flow.
of the femoral or iliac artery can prevent this
potentially fatal complication. Consequently, Complications during Implantation and
smaller cannula may not need a distal perfusion Initial Launching
to prevent cannulated limb ischemia and some
centers, including the Regensburg group, prefer Several serious complications may occur
this approach.33 Target ECLS flows relate to during percutanous cannulation. Unsuccesful
cannula diameter. For a targeted flow of 3.5-4 cannulation itself occurs with usually fatal
L/min an arterial cannula of 15-17 Fr should consequencies due to refractory CA. Surgical
suffice. For higher flows, larger cannulas are exploration of the groin, as mentioned, serves as
needed. The authors prefer larger cannulas to an alternative; however, severe atherosclerotic
reach a flow of more than 60-70 mL/kg/min, 5 femoral/iliac artery disease may preclude even
L/min or more in larger patients, however no a surgical approach. Alternative approaches
firm data support any single approach. usually for arerial cannulation should be imme-
diately tried if femoral cannulation is unfeasible.
Reperfusion Technique and Initial ECLS The axillary approach with a 15 Fr cannula is
Flow Setting probably best and if succesful, allows enough
reperfusion into the ascending aorta but may
The ECLS circuit, unless wet primed be- need later conversion to a different site. Pro-
forehand, is usually primed with cold crystal- longed cannulation over 30 minutes usually
loid for a cold flush reperfusion technique,34-36 means an overall time of CPR over 60 minutes,
although evidence is scarce and based on often associated with poor neurological out-
experimental settings. Intravenous cold fluid come or death. Vessel injury or rupture must be
boluses during ECLS initiation may help cor- avoided by a careful technique during all stages
rect hypovolemia to assure ECLS flow and of cannulation, espcially during wire insertion.
506
The guiding principle is to be perfectly sure that sign is highly oxygenated blood in the venous
the wire is properly inserted in the vessel lumen. cannula due to complete recirculation. A new
Simultaneous distal cannulation of the same cannula must be inserted into an appropriate
vessel (Figure 45-3) may happen and usually vessel (Figure 45-4).
does not cause signficant problems. One sheath/
wire is either removed when a large cannula is Rhythm Analysis, Conversion of Ventricle
inserted into the vessel, or better left in situ for Fibrillation (VF) and Further Investigation
later safe removal.
Despite proper arterial cannulation, arte- ECPR patients on ECLS may present a vari-
rial wall dissection may occur, causing vessel ety of heart rhythms. In patients with refractory
narrowing or obstruction after removal of the ventricular fibrillation (VF) as a cause of CA,
cannula. This must be detected early and cor- ventricle arrhythmia usually persists. It remains
rected. If not, it may cause severe limb ischemia. unclear when another trial of conversion to
Venous cannulation is easier but improper sinus rhythm should be performed. However,
position (not enough deep or too deep) may if the anticipated cause of refractory VF is an
cause cannula dysfunction or inappropriate acute coronary occlusion or chronic severe
ECLS flow. Generally, if the ECLS flow proves coronary artery disease, PCI on ECLS should
adequate despite suboptimal cannula position, preceed defibrillation (pH and potasium correc-
change of the cannula position is not recom- tion should also be performed). Other malignant
mended. Cannula insertion of the same vessel rhythms or other causes of refractory CA should
(usually the vein) may prove fatal if not imme- be identified as soon as possible. The causes of
diately recognized and corrected. The telltale refractory CA differ from causes of usual CA
and, unfortunately, may often be irreversible
(aortic rupture, other severe bleeding, intracra-
nial hemorage). It is straightfoward to continue
with coronary angiography following institution
of ECLS. If the cause is not established with pul-
monary angiography or aortography, and other
causes including pericardial tamponade have
been excluded by bedside echocardiography,
then CT scan of the brain and chest/abdominal
exams should be performed.
Frequent laboratory examination is of para-
mount importance in ECPR. Initial examination
should exclude severe electrolyte imbalances,
Figure 45-4. Accidental double cannulation assess organ functions, and allow thorough
of the femoral vein during ECPR. A 44-years
old male with primary pulmonary arterial monitoring, mainly by means of lactate, blood
hypertension with cardiac arrest cannulated gases, and hemoglobin levels. Not only at ECLS
on ICU. The arterial cannula was erroneously start, but also the trend in blood levels of lactate
inserted into the femoral vein, complication
was immediately identified by a presence of values and base excess40 and other variables
recirculation (bright red blood in venous limb) (hemoglobin) may correlate with outcome in
and corrected by insertion of a cannula into the ECPR. Blood gas monitoring every 15 to 30
femoral artery. Two cannulas in the femoral
vein were left in situ, attached by Y-connector minutes after cannulation helps manage the
and used for simultaneous drainage of inferior dynamic changes that can occur.
vena cava.
507
Chapter 45
Postresuscitation Care Monitoring Studies on ECPR in IHCA
Monitoring during venoarterial ECMO Multiple observational studies (Table 45-5)

differs from that of other ICU patients. Blood report encouraging results of ECPR in IHCA
pressure must be monitored invasively, due to with neurologically favorable survival in up to
nonpulsatility. Pulsatility is defined as a pulse 35% of cases.45-49 In an analysis of 135 IHCA
pressure over 15 mmHg.41 Right radial artery cases (50), average CPR duration lasted 56 min-
for blood pressure monitoring and blood gases utes, 56% received subsequent intervention to
examination is mandatory. In any interpretation treat the underlying etiology, weaning rate was
of monitored data, it must be kept in mind that 59% and 34% patients survived to discharge
the final result comes from a combination of with 89% having acceptable neurologic status.50
spontaneous and extracorporeal circuits and Patients were resuscitated in the ICU (61%),
is influenced by the ratio of those two flows. cath lab (16%), and emergency room (19%).
Therefore, cerebral and peripheral tissue NIRS Importatnly, this study also demonstrated a
may help monitor not only the brain and periph- declining chance of survival with prolonged
eral perfusion, but also overall hemodynamic duration of CPR. The probability of survival
status and further identify deteriorations requir- was approximately 50%, 30%, and 10% when
ing hemodynamic interventions or other inves- CPR lasted 30, 60, or 90 minutes, respectively.
tigations.42,43 Patients with nonpulsatile flow or Similar results of increased short-term and
with severely impaired left ventricle function long-term survival benefit over conventional
may develop pulmonary edema or left ventricle CPR in patients with in-hospital cardiac arrest
thrombosis which may require left ventricle of cardiac origin treated by ECPR have been
venting or intraaortic balloon counterpulsation, confirmed in a propensity analysis.51
(see Chapters 48 and 64).44 Target temperature Therefore, based on available studies, ECLS
and protective ventilator management on ECLS for in-hospital CA has become a standard of care
is also a part of routine care. in many tertiary institutions, despite the fact that
no randomized study confirmed its effectivity.
Table 45-5. Characteristics and outcomes of selected ECPR studies in IHCA.
Study, Citation Design N Age (yrs) Time to Neurologically

Country Male (%) ECLS (min) Favorable Survival
Chen et al. (2008)46 Prospective 59 18-75 <30 42%
Taiwan 30-45 30%
45-60 30%
>60 18%
(33% overall)
Lin et al. (2010)69 Prospective 59 59 40 24%
Taiwan 85%
Shin et al. (2011)48 Retrospective 85 60 42 28%
Taiwan 62%
Chou et al. (2014)70 Retrospective 43 61 60 35%
Taiwan 93%
Zhao et al. (2015)47 Retrospective 24 59 36 33%
China 79%
Blumenstein et al. (2016)49 Retrospective 52 72 33 21%
Germany 54%
508
Studies on ECPR in OHCA in Japan, Korea, Taiwan, France, Germany, and

Italy. Currently, two randomized trials of ECPR
Use of ECPR in OHCA may appear even in OHCA are ongoing in Prague and Vienna
more attractive than in IHCA. OHCA patients (NCT01511666 and NCT01605409).52,53 Most
are generally younger, previously healthy, and studies suffered a high risk of confounding bias
the cause of CA is usually of cardiac origin. due to the observational design.29 Nonetheless,
Sudden CA is often caused by a single reversible patients included were usually under 75 years
condition in contrast to polymorbid in-hospital of age, no-flow times were below 5 minutes
patients suffering IHCA. On the other hand, pre- and low-flow periods were variable ranging
hospital logistics in the care for OHCA victims up to 140 minutes, mainly close to 60 minutes.
plays a major role in selecting suitable patients Prognostically favorable indicators included
for ECPR. Trials assessing ECPR in OHCA are witnessed arrests, shockable rhythms, and re-
listed in Table 45-6. These trials were observa- versible causes of CA. Treatments provided in
tional, not randomized, and performed mainly addition to ECLS included PCI, targeted tem-
Table 45-6. Characteristics and outcomes of selected ECPR studies in

OHCA.
Study, Citation Design N Age (yrs) Time to Neurologically
Country Male (%) ECLS (min) Favorable Survival
Nagao et al. (2000) 71
54
Prospective 36 25%a
Japan (70) 61
Nagao et al (2010)72 57-62
Prospective 171 66 12%
Japan (83-91)b
Le Guen et al (2011) 16
42
France (90)
Megarbane et al (2011) 73
46
France (77)
Avalli et al (2012)74 46
Retrospective 18 78 5%
Italy (94)
Haneya et al (2012) 75
48 70
Retrospective 26 15%
Germany (65)
Fagnoul et al (2013) 76
48
Prospective 14 22%
Belgium (58) 58c
Leick et al (2013)54
Retrospective 28 MR - 29%
Germany
Maekawa et al (2013) 30
54
Japan (83)
Tazarourte et al (2013) 77
39
Retrospective 27 140 d
4%
France (56)
Kim et al (2014)56 53
Korea (75)
Mochizuki et al
51
(2014)79 Retrospective 32 84 16%
(78)
Japan
Sakamoto et al, (2014) 57
56.3 - 12%
Prospective 260
Japan (90)
Stub et al (2014)
Prospective 11 20e 27%
Australia
Wang et al (2014) 78
Prospective 50.7
31 68 26%
Taiwan observational (75)
Choi et al. (2016) 58
56
Retrospective 320 44 9%
Republic of Korea (81)
N=number of patients in study
a
outcome combined with hypothermia treatment in non-ECLS patients
b
reported in quartiles related to hypothermia therapy
c
time from cardiac arrest to ECLS separately for OHCA not reported
d
mixed population of ECPR patients: resuscitative ECLS and organ preservation
e
Cannulation time
509
Chapter 45
perature management, and intraaortic baloon reperfusion: the CHEER trial,63 Prague OHCA
counterpulsation. Outcomes in studies varied study.18
substantially with neurologically favorable sur-
vival ranging from 4% to 29%, mainly around Weaning from ECLS after ECPR
15-25%.16,54 Recent systematic review of stud-
ies on ECPR in OHCA states overall survival Weaning follows a similar path of all veno-
in 833 patients in 20 studies of 22% including arterial ECMO (see Chapter 51); however, close
13% with good neurological recovery.29 How- neurological monitoring and prognostication
ever, ECPR in OHCA remains challenging must occur. Patients after prolonged CPR may
with many unresolved issues including optimal suffer irreversible cardiac damage and favor-
patient populations, variables associated with able neurological outcome may strenghten the
a favorable neurological outcome, cost-benefit efforts to proceed with more advanced mechani-
analysis of this resource demanding strategy, cal circulatory support or heart transplantation.
etc. Different approaches to minimize no-flow Thus, early extubation of an ECPR patient still
and low-flow states include prehospital mobile dependent on ECLS may be very helpful in
ECPR deployment55 compared to early transport this regard.64,65 In the ELSO Registry, ECMO
under high-quality ongoing CPR (ie, mechani- duration in these patients has been reported to
cal) with ECPR commencement after hospital range up to 60-70 hours.39
admission.18 Hopefully, ongoing randomized
trials will help to define the future role of Ethical Issues in ECPR
ECPR in OHCA.Efforts to increase survival in
refractory OHCA should outweigh the risk of ECPR is associated with potential harm to
neurologically impaired survivors.56-58 Of note, patients and/or their relatives. Although recov-
organ donation is an important issue in ECPR ery of the heart often occurs, a coma or vegeta-
for OHCA and should be acknowledged as a tive state could result.57 It has earned the title
relevant outcome in ECPR studies.29 of a “bridge to nowhere“ in which the patient
awakens, but has no cardiac function and is not
Studies on ECPR in the Pediatric Population a transplant or destination therapy candidate.66
ECPR can prolong the time to death in patients
In children, the survival rate after CA with unfavorable outcome, potentially harming
ranges from 9 to 47% for in-hospital events and patients and their relatives. Moreover, ECLS
0%–29% for events outside the hospital. The dependency may lead to the decision to turn off
survival rate for pediatric ECPR was reported the device, which is stressfull for both the team
to be 33-51%, which was higher than for con- and family members.
ventional CPR (see Chapter 27).59-62 ECPR is definitely considered an impor-
tant advance in the treatment of cardiac arrest.
ECPR as a Stepwise Approach to Currently, it seems ethically appropriate to use
Refractory CA ECPR when a likelihood of clinical benefit
exists, clinicians have adequate training and
ECPR itself does not assure favorable out- expertise, and institutions can provide subse-
come in refractory CA. Connecting a patient quent care.28
to ECLS must follow a protocolized approach
during CPR, therefore several centers have
developed policies encompassing mechanical
CPR, targeted temperature control, and early
510
Future
Extracorporeal CPR does not yet represent

the standard of care. Ongoing randomized stud-
ies have to elucidate whether ECPR is worth
implementing into routine practice. Moreover,
technological advances should enable improved
end-organ support. Miniaturization may en-
hance the use of wearable/implantable devices.
In emergency preservation and resuscitation, in-
vestigators may go beyond ECPR and overcome
the current drawbacks of this approach.67,68
511
Chapter 45
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516
46
General Considerations for VA-ECMO Implantation in Adults with

Cardiocirculatory Impairment
Pascal Leprince, MD, PhD, Ciro Mastroianni, MD, PhD, Antonella Galeone, MD, PhD,
Cosimo D’Alessandro, MD, Guillaume Lebreton, MD
Venoarterial ECMO (VA-ECMO) is used where cardiac surgery is not available and when
to stabilize hemodynamics in patients expe- a patient cannot be transferred. In such a situ-
riencing severe cardiogenic shock (CS) of ation, bringing the ECMO team to the patient
several etiologies. Because the indications for can be lifesaving. Moreover, since cannulation
VA-ECMO are already treated in Chapter 44, can be either percutaneous or surgical, it can be
the following paragraphs will focus on another performed by a surgical team or interventional
aspect of indication which includes two topics: cardiologists, intensivists, etc. This shortens the
timing (ie, when patients are cannulated too timing for the decision process and improves
early or too late) and the place of ECMO among local availability.
other temporary circulatory support devices.
Both topics require review of the advantages Peripheral VA-ECMO is Efficient as a
and inconvenience of VA-ECMO. Circulatory Support Device
Peripheral VA-ECMO is Fast and Easy to ECMO can fully support the circulation,
Implant up to 5-6 liters/min, depending on the cannula
diameter, independent of heart function (ie, no
These two words (fast and easy) are prob- need for residual cardiac function or adequate
ably the two major positive characteristics right ventricular function). Moreover, the
qualifying ECMO as an emergency or rescue presence of an oxygenator makes the circula-
device. Indeed, ECMO in the field of cardio- tory efficiency independent of the oxygenation
genic shock, could be compared to an external status of the patient. This is very useful in this
emergency defibrillator used for life-threatening population of cardiogenic shock patients who
cardiac rhythm disturbances. The main benefit do experience a high rate of pulmonary edema.
of ECMO relates to the fact that patients can be
cannulated rapidly for ECMO at the bedside and ECMO is Cost Effective
requires only surgical material when performing
an open cannulation. Another major advantage At present, cost has become increasingly
of ECMO is that patients can be cannulated in important in patient care. Cost effectiveness is
the cardiac ICU without need to transfer the even more crucial in rescue situations for two
patient to an operating room. However, this reasons. First, such situations are associated
becomes especially critical in medical centers with a high risk of death, despite optimal care.
517
Chapter 46
Thus, in the current era of cost control, the blood flow. In this situation, complete throm-
amount of money spent has to be balanced with bosis of the pulmonary vascular bed can occur.
the quantity of life saved. For instance, the use This is why, in our institution, central ECMO
of ECMO in out of hospital refractory cardiac is prohibited. As soon as we have to open the
arrest (OHCA) well illustrates this concept. In chest, we used biventricular Levitronix support.
this situation, ECMO is associated with a 10
to 15% rate of survival,1 even in well selected ECMO is Associated with a High Rate of
patients. No health system can afford to spend Complications
thousands and thousands of dollars for such
results, even if the outcome for survivors cannot Although life-saving, ECMO can be asso-
be contested. Second, physicians have greater ciated with potentially devastating complica-
involvement in cost control and thus, employing tions.4 Vascular, neurological, infectious, and
a high cost device, carries greater weight. pulmonary complications can indeed lead to
patient death or impair recovery and long-term
ECMO Does Not Unload the Left Ventricle quality of life in survivors. Many complications
are related to patient severity and the urgency of
The main drawback of peripheral VA-EC- cannulation. Although earlier cannulation may
MO is that it does not unload the left ventricle decrease the rate of complication, the relation-
(LV) and actually increases LV afterload. This ship between timing of ECMO and the severity
might impair the chance of recovery of LV of the patient’s status before cannulation has not
function and is one of the main components in yet been determined. Early cannulation makes
the development of pulmonary edema while on most sense when there is a higher chance for
ECMO support. Of course, this risk can be pre- short term recovery and decannulation. The
vented by the use of an intraaortic balloon pump best example is fulminant myocarditis or drug
or other techniques for unloading,2,3 which each poisoning situations where patients can become
have their own potential complications. More- hemodynamically unstable in very short order
over, when the LV remains unloaded, stagnation but can rapidly recover good ventricular func-
of blood in cardiac cavities which can lead to tion within one week. On the other hand, using
clot formation and in the extreme, to a full ECMO as a bridge for transplantation does not
thrombosis of left side cavities, particularly in make sense since patients can experience com-
case of acute myocardial infarction. plications which can preclude transplantation or
worsen outcome.
ECMO Decreases the Transpulmonary Flow
ECMO Requires the Patient to Stay in Bed
Although the LV is not unloaded while on
ECMO, the right ventricle (RV) is well pre- Femoral VA-ECMO requires the patient
served. However, the higher the ECMO flow, to remain on bedrest. Even mobilization for
the lower the filling of the right ventricle and nursing care can be dangerous. This negatively
as a consequence, the transpulmonary flow is impacts muscle strength, impairing the chance
lower. Although ECMO reduces pulmonary vas- for recovery. This furthers the argument to use
cular pressures it may have a negative impact on ECMO in an emergency but not as a bridge to
lung perfusion and thus increase the risk of lung transplantation.
injury and infectious complications. These risks
are greater with a larger central cannula that
fully unloads the RV, with nearly no pulmonary
518
General Considerations for VA-ECMO Implantation in Adults with Cardiocirculatory Impairment
ECMO and Hemodynamic Criteria ECMO and Neurological Status
Peripheral VA-ECMO should be used in Very often patients with severe cardiogenic
cardiogenic shock only if the clinical status shock receive sedation and mechanical ventila-
contraindicates or is not compatible for a vention. Moreover, many of them have experienced
tricular assist device (VAD) or total artificial cardiac arrest. In such situations, the question
heart (TAH) implantation. of neurological integrity should be raised but
The definition of cardiogenic shock in- may be difficult to answer. Potentially, the only
cludes systolic blood pressure below 90 mmHg, option to evaluate neurologic status is to can-
cold extremities, skin color, and low urine nulate for VA-ECMO. Neurological status may
output. These patients can be classified as In- then be assessed when good circulatory sup-
termacs class 1 and beyond. Intermacs class 2 port is established and sedation can be weaned.
patients can be ECMO candidates when time Thus, starting ECMO without insight into
for cannulation to VAD implantation appears neurological status at the time of cannulation
inadequate. It is difficult to define a threshold for makes sense. Furthermore, the team should
the use inotropic drugs and clinical parameters have a low threshold to discontinue ECMO if
that necessitate using mechanical circulatory a patient, once stabilized on ECMO, appears to
support (MCS). However, worsening hemody- have severe neurological lesions not compatible
namic deterioration or shock (as defined previ- with an acceptable quality of life. Of course, in
ously) despite use of two inotropes/vasopressor the case of brain death, the patient should be
(10 mcg/Kg/min dobutamine, 0.4 mcg/Kg/min considered for organ donation (even cardiac
epinephrine or norepinephrine) and elevated graft donation in case of recovery).
serum lactate levels should be considered strong
indication for emergent MCS. ECMO and Cardiac Arrest
Because it is difficult to predict when a
patient on inotropic support is going to de- Refractory cardiac arrest is the extreme
compensate, ECMO can provide a backup situation in which the borderline between ef-
tool. Manuscripts have shown good results of ficiency and futility is minimal. Studies show
transplantation after ECMO.5 However, the data that peripheral VA-ECMO is associated with
supporting this strategy remain limited 5,6 and good survival in patients experiencing in-
thus one should consider survival and ECMO hospital refractory cardiac arrest as long as the
related complications which can produce long- cardiac arrest is witnessed, CPR is high quality,
term sequela. and time from arrest to ECMO is short. 7 Of
At the opposite extreme, with severely course, the story differs for patients experienc-
unstable patients receiving very high doses of ing an out-of-hospital cardiac arrest. In order
inotropes/vasopressors and/or with profound to avoid futility, the two major parameters to
metabolic impairment (pH lower than 7, lactate consider include durations of no-flow and low-
higher than 16), the futility of ECMO use should flow states. In this situation, no-flow duration is
be discussed. However, examples of good often impossible to define and if it is the case,
outcome in patients in whom initial conditions ECMO is generally contraindicated except if
would have appeared as noncompatible with the patient is hypothermic or shows signs of
survival exist and therefore doubt should go to life during resuscitation. There is no clear cut
the benefit of the patient. low-flow duration, but in a study by Cheng et
al.,8 60 minutes was definitely associated with
poor results. However, due to the rarity of such
519
Chapter 46
a situation, the decision process is still on a case mobile unit should deny a patient already under
to case basis. CPR resuscitation at the time of phone call.
Age is often considered a potential con-
ECMO vs. Other Short-Term Circulatory traindication. Maximum age threshold varies
Support Devices depending on the patient and the underlying
disease. Postcardiotomy VA-ECMO can be jus-
ECMO is the most versatile of the short- tified in older patients when the situation is well
term circulatory support devices for the reasons controlled and the potential for recovery is high.
described previously: it can be placed without A word of caution regarding patients un-
any adjunctive visualization method such as dergoing mitral valve surgery as they have a
echocardiography or fluoroscopy; cannulation high risk of thrombosis due to the decrease of
can be percutaneous or surgical depending on transmitral flow. In this situation, particularly if
the physician available; it can provide a full there is no left ventricular ejection, it is better
circulatory support; it works for LV, RV, or to assure a transpulmonary flow by using a bi-
biventricular failure. Of course, if one center ventricular support with two centrifugal pumps,
can afford to have several systems, temporary one right and one left.
short-term LVAD like the Impella c-VAD,
the tandem heart, or the PHP are preferred in Conclusion
patients experiencing moderate shock due to
LV dysfunction, as they unload the LV and ECMO is a very efficient circulatory sup-
thus might help recovery. This is even more port device, but every attempt action should
true if the patient is managed in the cath lab be made to avoid the use of ECMO. In the
by interventional cardiologists who will feel setting of chronic heart failure, patients should
more confident implanting such devices. On be undergo transplantation and/or use of VAD
the other hand, in severe cardiogenic shock, prior to any deterioration. This is equally true
the percutaneous LVAD might not be efficient in patients experiencing myocardial infarction
enough to stabilize the patients. in whom cardiogenic shock is recognized early
enough so they can be assisted with a temporary
VA-ECMO and Contraindications LVAD instead of ECMO. Similarly, primary
care centers should consult referral centers in
Because VA-ECMO as a rescue MCS that order to discuss patients on a case by case basis
can provide a chance of survival for unstable and should refer the patient before dramatic
patients, contraindications should be considered hemodynamic compromises require ECMO as
with caution and the patient deserves the benefit the only solution.
of the doubt. Moreover, the decision to can-
nulate to ECMO does not require an outcome
plan. Thus, few contraindications remain and
the main one is probably the impossibility to
cannulate, such as in severe multivessel disease
or situations in which ECMO is inefficient
such as uncontrolled hemorrhagic shock. As
mentioned earlier, cardiac arrest per se is not a
contraindication but unknown duration of no-
flow or extended duration of low-flow should
serve as contraindications. Similarly, an ECMO
520
General Considerations for VA-ECMO Implantation in Adults with Cardiocirculatory Impairment
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3. Cheng A, Swartz MF, Massey HT. Impella
to unload the left ventricle during periph-
eral extracorporeal membrane oxygenation.
ASAIO J. 2013;59(5):533-536.
4. Cheng R, Hachamovitch R, Kittleson M,
et al. Complications of extracorporeal
membrane oxygenation for treatment of
cardiogenic shock and cardiac arrest: a
meta-analysis of 1,866 adult patients. Ann
Thorac Surg. 2014;97(2):610-616.
5. Ting M, Wang CH, Tsao CI, et al. Heart
transplantation under mechanical circula-
tory support for acute fulminant myocar-
ditis with cardiogenic shock: 10 years”
experience of a single center. Transplant
Proc. 2016;48(3):951-955.
6. Hayanga JW, Aboagye JK, Hayanga HK,
Luketich JD D’Cunha J. Extracorporeal
membrane oxygenation as a bridge to lun-
gre-transplantation: Is there a role. J Heart
Lung Transplant 2016;35(7):901-905.
7. Chen YS, Lin JW, Yu HY, et al. Cardiopul-
monary resuscitation with assisted extra-
corporeal life-support versus conventional
cardiopulmonary resuscitation in adults
with in-hospital cardiac arrest: an observa-
tional study and propensity analysis. Lancet.
2008;372(9638):554-561.
8. Le Guen M, Nicolas-Robin A, Carreira S,
et al. Extracorporeal life support following
out-of-hospital refractory cardiac arrest.
Crit Care. 2011;15(1):R29.
521
47
Cannulation for ECMO in Adult Patients with Cardiac Failure
Syed T. Hussain, MD, José Luis Navia, MD
The indications for extracorporeal mem- for longer duration. ECMO can rapidly restore
brane oxygenation (ECMO) are well established. systemic blood flow during cardiogenic shock.
ECMO can replace the function of both heart ECMO has undergone significant techno-
and lungs.1-8 The basic ECMO circuit consists logical advancement over the last decade, and
of a centrifugal pump, coupled with a hollow the evolution has taken place in both the cen-
fiber membrane oxygenator and oxygen blender, trifugal pumps and oxygenators that constitute
and a heparin-coated circuit (Figure 47-1). the main components of most adult ECMO
ECMO circulates and oxygenates the blood circuits. Evolution of ECMO technology has
and also acts as a temporary substitute for the improved the ease with which patients are
entire circulatory system. ECMO functions cared for, especially those with postcardiotomy
under the same principles of cardiopulmonary cardiogenic shock; however, it has done little
bypass (CPB), with duration of support being to impact the overall survival rates, reflecting
the most important difference. While CPB is that comorbidities associated with patients still
typically employed for hours during cardiac sur- drive outcomes.9
gery, ECMO is designed to support circulation Venoarterial (VA) ECMO is used primarily
for cardiogenic shock due to profound left ven-
tricular (LV) or right ventricular (RV) failure.1-5
The typical scenarios for VA-ECMO are cardiac
arrest due to various etiologies, postcardiotomy
shock, cardiac emergencies such as recent myo-
cardial infarction with shock, as a bridge to left
ventricular assist device, or acute heart or lung
transplant allograft dysfunction. The specific
indications for ECMO are discussed elsewhere
in the book. In this chapter, various cannulation
techniques and their indications are discussed.
Access for initiation of ECMO can be chal-
lenging and cannulation technique should be
based on type of support needed, patient’s age
Figure 47-1. ECMO system used at the Cleve- and size, and specific clinical situation. The de-
land Clinic: a centrifugal pump, oxygenator,
and heat exchanger. cision regarding the place for ECMO cannula-
523
Chapter 47
tion (ICU, operating room, etc.) should be based sure. The choice of the cannula size should be
on clinical scenario and ability to transport the based on the patients’ body surface area and the
patient safely to the OR with adequate ventila- required blood flow. For adults, typical cannula
tion and hemodynamic support.1-5 For patients sizes range from 16-20 Fr for arterial, and 18-
with postcardiotomy shock, central cannulation 28 Fr for venous.1-3,9,10 The venous return could
is typically used, because it is easy to switch the also be achieved through a long venous cannula
CPB circuit to ECMO with the existing cannu- placed in the femoral vein. Central cannulation
las. Alternatively, in cases in which immediate is often set up in postcardiotomy cases, and
support is necessary, such as acute cardiogenic switching from CPB to ECMO is an easy proce-
shock after myocardial infarction, peripheral dure. After stopping the CPB flow, the existing
access by way of a peripheral vessel using the cannulas are clamped and disconnected from
Seldinger technique or open arteriotomy may the CPB circuit, and then reconnected to the
be easier, and quicker (Figures 47-2, 47-3). The ECMO circuit. All air must be evacuated from
latter avoids the need for repeat sternotomy for the system. We do not routinely insert a pulmo-
decannulation and reduces risk of bleeding and nary vent or left atrial pressure monitoring line.
infection; however, limb ischemia and unsatis- The purse string suture should be hemostatic and
factory upper body perfusion are potential risks. the tourniquets would be kept in the chest (or
A rapid assessment of the specific clinical attached to the skin) in cases of central aortic
scenario and patient-related factors are required cannulation. This obviously requires return to
to select the best strategy and cannulation site. operating room for decannulation. The lines
Central ECMO cannulation may be used in have to be secured meticulously to avoid ac-
patients who require postcardiotomy support cidental catastrophic dislodgement. Axillary
through right atrial (for venous return) and artery cannulation is another option to allow
ascending aortic cannulation (for arterial out- chest closure and provide antegrade flow and
flow). The size of the venous cannula limits the combines the advantages of central cannulation
extracorporeal flow and the size of the arterial and peripheral approach for ECMO. This will
cannula determines the ECMO system pres- be discussed in more detail later in the chapter.
Central cannulation allows better ECMO
flow and ventricular unloading as it allows use
of a larger size cannula, especially in patients
with a large body surface area in which periph-
Figure 47-2. The setup for venoarterial periph- Figure 47-3. Venoarterial ECMO with cannula-
eral ECMO with cannulation of right femoral tion of left femoral artery and vein. Notice the
artery and vein. A distal perfusion cannula is perfusion cannula distal to the arterial cannula,
attached to the arterial limb of ECMO circuit. and attached to the arterial limb of the circuit
via a Luer lock.
524
eral cannulation may not deliver adequate flow. the femoral vessels if time allows, but in most
ECMO flow is limited by the maximum size of clinical situations it may not be feasible.
the vessel for access and the size and position of If ECMO is being placed during CPR, it
the cannula used.9.10 In patients with BSA >2 m2, is preferable to have two personnel trying
peripheral ECMO flow may not be sufficient to simultaneously, working on both groins to try
prevent multiorgan failure. Central cannulation locating the femoral artery and vein. If possible,
also provides antegrade oxygenated blood flow we prefer the right femoral vein for venous
to the coronary and cerebral circulation. With cannulation and left femoral artery for arterial
peripheral ECMO, the cardiac output of the cannulation, both due to venous anatomy and
failing heart competes with retrograde ECMO minimize leg ischemia by avoiding the arterial
flow from the femoral aortic cannula, producing and venous cannulation in the same leg. Fol-
admixing in the thoracic aorta, and perfusing lowing the Seldinger technique, the guidewire
arch and coronaries with desaturated blood.1,3 is advanced from the femoral vein towards the
Major disadvantages of central cannulation are right atrium and from the femoral artery into
need for open chest and higher risk of bleeding, the aorta. The vessels are progressively dilated
although the need for open chest may also be using progressive dilators, and the cannulas are
unrelated to ECMO. There is also higher risk introduced over the wires. We typically give
of mediastinal infection. Prolonged central about 5000 units of heparin bolus once the wires
cannulation can cause serious injury to aorta are in place (Figure 47-4).
and right atrium. The venous cannula tip is aimed to be in
the mid right atrium and ideally in the SVC-RA
Peripheral Cannulation junction for optimum drainage. The arterial can-
nula is inserted for its whole length and lies in
Peripheral cannulation is probably the the iliac artery. The cannulas are connected to
most common approach for ECMO initiation the ECMO circuit after making sure the lines
in noncardiac surgical situations like primary are meticulously deaired. It is very important to
cardiogenic shock, cardiopulmonary arrest, secure the cannulas to the skin with multiple su-
acute myocardial infarction, etc., when immedi- tures. In case of hemodynamic instability, rapid
ate ECMO support is needed. In adults, femoral
artery and vein cannulation, either performed
percutaneously or by direct cutdown on the ves-
sel, is the preferred approach when peripheral
ECMO initiation is chosen, because of the large
size of the adult femoral vessels (unless there is
a suspicion or history of significant peripheral
vascular disease) and technical ease (Figures
47-2, 47-3). Although presence of bounding
femoral pulse can facilitate the identification
of the femoral vessels, the vast majority of
patients that require VA-ECMO for cardiac
failure are unlikely to have bounding pulses. Figure 47-4. Peripheral arterial and venous can-
Occasionally, with the use of catecholamine nula used for venoarterial ECMO. The arterial
cannula has Luer lock mechanism. The bottom
during resuscitation or during external cardiac figure shows the kit required for percutaneous
massage, a femoral pulse may be palpated. An puncture of the artery, along with the guidewire
ultrasound can facilitate the identification of and dilators.
525
Chapter 47
conversion to open technique is necessary if the encountered during a more lateral deltopectoral
initial attempts at percutaneous insertion fail. approach.3,14-16
Since leg ischemia is a major concern, distal The complications reported with axillary
leg perfusion cannula should be routinely in- artery cannulation include hypoperfusion of the
serted. A 6-8 Fr distal perfusion cannula placed ipsilateral arm and damage to the artery, both
in the superficial femoral artery, and spliced reduced with the use of an interposition graft.17
into the arterial perfusion limb of the ECMO The most significant adverse effect associated
circuit is used to establish adequate perfusion with using axillary artery side graft technique
of the leg.3 If the ECMO indication was emer- as an outflow site for VA-ECMO is hyperperfu-
gent, this usually has to wait for the patient to sion syndrome in nearly 20% of patients, with
stabilize and then an attempt to insert a distal almost half of them requiring some type of
perfusion catheter/cannula downstream to the intervention to treat compartment syndrome.14
arterial cannula is made, usually percutaneously The reasons for the development of hyperperfu-
under ultrasound guidance and connected to the sion syndrome are multiple and can be broadly
arterial limb of the ECMO circuit. If the ECMO divided into two categories: 1) those causes
is done electively, the guidewire for the distal resulting from arterial outflow obstruction; and
perfusion cannula should be inserted initially as 2) those associated with venous outflow obstruc-
it is easier to locate the femoral pulse distally tion. Among the arterial obstructive causes,
before the before the arterial ECMO cannula. narrowing of axillary artery causing reduction
Modifications to improve arterial flow in of lumen and resulting preferential flow down
the cannulated limb may include sewing an 8 the arm can cause hyperperfusion. A similar
mm graft on the femoral artery or cannulating pattern can be expected with prolonged axillary
contralateral venous and arterial vessels, and graft use on the axillary artery in patients with
decrease peripheral limb ischemia, particularly atherosclerotic aortic arch disease and/or acute
when femoral artery is small or diseased. type A dissections in which the head vessels are
The disadvantages of peripheral cannula- involved. Venous obstructive causes can include
tion via femoral artery are interference of distal
flow to the cannulated limb, resulting in leg
ischemia, and potentially unsatisfactory upper
body oxygenation.11-13 Use of a side graft on
the axillary artery is an option for ECMO arte-
rial cannulation.3,14-16 The advantages include
lack of atherosclerosis of axillary artery, even
in patients with iliac femoral disease, central
support with antegrade flow in the aorta, poten-
tially minimizing atherosclerotic embolization,
and the preferential delivery of oxygenated
blood to the heart and brain. The axillary ar-
tery is exposed below the clavicle, and after
administration of 5000 units of heparin, and
8 mm vascular graft is sewn in end-to-side
fashion and connected to the arterial limb of
the ECMO circuit (Figure 47-5). We prefer a Figure 47-5. ECMO axillary circuit: venous
inflow through the right femoral vein, and arte-
more medial approach to the axillary artery as rial inflow through interposition graft over the
it avoids the surrounding brachial plexus roots right axillary artery.
526
bleeding into the surrounding space, causing a cannulation method was not a predictor of in-
compressive hematoma, or if drainage to the hospital outcomes.
arm is impeded by either a venous cannula or The arterial cannulation strategy should
deep vein thrombus, or both. The initial man- depend on the specific clinical scenario. In
agement of hyperperfusion syndrome should our practice, for patients with ongoing chest
be guided depending on its etiology. If arterial compression, percutaneous femoral artery can-
causes are suspected, the initial management nulation is the most commonly used technique
should include: 1) elevating the arm and; 2) for VA-ECMO support (Edwards Fem-Flex II
decreasing ECMO flow. If these maneuvers fail arterial, 16, 18 or 20 Fr. Edward Lifesciences,
to relieve the syndrome, and concerns regarding Irvine, CA).10 For postcardiotomy cases, central
the condition of the arm continue to occur, an aortic cannulation is the first choice. However,
effort to relocate the outflow for VA-ECMO if either the axillary artery was already exposed
should be pursued. If the cause of hyperperfu- before sternal reentry in redo sternotomy, or
sion syndrome is venous obstruction, therapy used for complex arch cases requiring deep
should be aimed at addressing the etiology hypothermia with antegrade cerebral perfu-
causing the decreased venous return, including sion, axillary artery is used. Venous drainage is
evacuation of the hematoma and wide drain- achieved with either a long 20 Fr, 24 Fr, or 24
age achieved with sump catheters. In cases in Fr cannula (Edward Lifesciences, Irvine, CA,
which a cannula is placed in the axillary vein Figure 47-4) placed in the common femoral vein
for VA-ECMO drainage, another vein should or the right atrium when the chest is left open
be selected for cannulation—preferably the after median sternotomy.10
femoral vein. For patients in whom deep ve- Early detection of limb ischemia and or
nous thrombosis is suspected, or diagnosed by compartment syndrome is paramount to mini-
radiologic modalities, no alternative is possible mizing the adverse effects. With the absence of
other than changing the arterial cannulation pulsatile flow, bedside Doppler examination of
site, as previously described. It is important distal arterial waveforms is an impractical and
to note that the venous outflow can also be an unreliable method of monitoring limb perfu-
impeded in cases of cardiac tamponade and sion. Effective monitoring of distal perfusion
relieving this problem will also assist in upper by pulse evaluations is difficult in patients on
extremity drainage. The incidence of brachial ECMO as they are in shock, on a circuit that
plexopathy is very low and is not permanent.14 provides nonpulsatile flow, and are often receiv-
Chamogerorgakis et al.14 reported their expe- ing vasopressors, leaving uncertainty regarding
rience with 81 patients supported on ECMO the adequacy of distal perfusion. Additionally,
using arterial inflow by a side graft sewn to the large time gaps can occur between evaluations.
axillary artery. One hundred sixty-six patients To minimize injuries to the lower extremities,
underwent femoral arterial cannulation and 61 improvement is needed in monitoring tissue
patients underwent femoral arterial cannulation. perfusion to diagnose complications before they
The most common complication in the axillary become irreversible. Transcutaneous continu-
artery group was hyperperfusion syndrome of ous near-infrared spectroscopy monitoring of
the ipsilateral upper extremity in 24.7%, and tissue oxygenation for the early detection of
bleeding from the outflow graft in 17.3% of limb complications in extracorporeal membrane
patients. Lower extremity ischemia and fasci- oxygenation has been recently described.18,19
otomy were more frequent after femoral arterial This technique has the potential to hasten surgi-
cannulation (16% and 10.8% respectively). The cal correction of perfusion deficits and prevent
development of compartment syndrome and
527
Chapter 47
limb complications in patients with ECMO confirmed by pulsatility on the arterial wave-
(Figure 47-6). Our practice is to place a distal form, or by observing aortic valve opening on
perfusion cannula in all patients, and if a limb the echocardiogram. If a mechanical valve is
complication is suspected clinically or by a uni- present, then maintaining opening and closing
lateral drop in tissue oxygen saturation O2, we of the valve avoids thrombus formation. Echo-
ensure the cannula is not kinked or thrombosed. cardiogram should be done within 6 hours of
If the issue cannot be resolved, we then take the initiating ECMO, if not done during insertion
patient to the operating room for placement of a to assess the left ventricular decompression.
chimney graft or an alternative inflow position ECMO unloads the right ventricle but does
such as the axillary artery. We use a perfusion not completely unload the left ventricle, even
cannula as a first-line treatment instead of the though the LV preload is reduced. Lack of LV
chimney graft because bleeding at the suture decompression on full ECMO flow may re-
lines of the chimney graft can be problematic. quire additional measures including additional
ECMO flow should be high enough to allow inotropic support, intraaortic balloon pump
“cardiac rest” and maintain adequate hemody- (IABP), Impella insertion, or separate venous
namics and organ perfusion (Target MAP 65-70 drainage catheter in the main pulmonary artery
mmHg; SVO2 >55%). Total cardiac output is (retrograde transpulmonary LV decompression).
typically 60 ml/kg/min in adults. It is important Patients with severe ventricular dysfunction
to allow some blood flow to go through the with poor ejection should ideally have a left
right and left chambers to avoid stasis within ventricular vent placed to prevent ventricular
the cardiac chambers. Ventricular ejections are distension or thrombosis. For postcardiotomy
patients, IABP decreases afterload that can
adversely affect the injured heart, and it adds
pulsatility to the continuous flow generated by
the centrifugal pump. We routinely place Luer
locks in the arterial and venous connectors dur-
ing ECMO insertion to allow easy hemofiltra-
tion and continuous venovenous hemodialysis
(CVVHD). CVVHD permits control of fluid
balance by continuous ultrafiltration and can
be adjusted for volume removal and also allows
for dialysis if needed.
Prior to placement of large bore perfusion
cannulas and initiation of ECMO, a heparin bo-
lus of 60 u/kg is usually administered to achieve
ACT 180-200 s. Since many postcardiotomy
patients may not have had the heparin reversed,
no additional heparin is given. Post-ECMO
continuous heparin infusion, unless contrain-
dicated (uncontrolled surgical bleeding, recent
Figure 47-6. Lower extremity ischemia moni- surgery, stroke etc.), is started at 8-10 unit/kg/
toring in peripheral ECMO using transcutane- hr and titrated to maintain a PTT between 45-55
ous near-infrared spectroscopy. Sensors are s or ACT between 180-200 s. This maintains a
placed on the calf of both lower extremities for
continuous monitoring of tissue oxygenation to balance that reduces both the rate of bleeding
allow early detection of leg ischemia. and clot formation inside the pump head and
528
in the heart cavity. Any evidence of clotting

in the pump head or tubing requires a change
of these components. For actively bleeding
patients, anticoagulation is delayed until the
appropriate coagulation deficit is corrected
and the bleeding is under control (<100 cc/hr).
Most postcardiotomy patients placed on ECMO
should be started on heparin infusions within
24 hours; other patients placed on ECMO by
percutaneous placement should be started on
heparin infusion earlier. Since ECMO reduces
platelet levels, platelet count should be checked
regularly and transfused to maintain counts over
50,000/mm3.
Cannulas used centrally will require an
operative procedure and return to the operating
room for removal. Although cannulas placed
in the axillary artery or femoral vessels can be
removed at bedside, thereby reducing bleeding
and lower risk of infection for these critically ill
patients, it is preferable to remove them in the
operating room as repair of vessels may be re-
quired when large cannulas have to be removed.
529
Chapter 47
References technology impacted outcomes in adult

patients developing postcardiotomy cardio-
1. Pranikoff T, Hines MH. “Vascular access for genic shock? J Card Surg 2012;27:246-52.
extracorporeal support.” ECMO. Extracor- 10. Kohler K, Valchanov K, Nias G, Vuyl-
poreal cardiopulmonary support in critical steke A. ECMO cannula review. Perfusion
care, 4th ed. Michigan: ELSO (2005): 133- 2013;28:114-24.
148. 11. Bisdas T, Beutel G, Warnecke G, et al. Vas-
2. Navia JL. “Mechanical circulatory support”. cular complications in patients undergoing
McCarthy PM, Young JB, eds. Heart failure: femoral cannulation for extracorporeal
a combined medical and surgical approach. membrane oxygenation support. Ann Tho-
John Wiley & Sons, 2008. rac Surg 2011;92:626-31.
3. Sangalli F, Patroniti N, Pesenti A, eds. 12. Foley PJ, Morris RJ, Woo EY, et al. Limb
ECMO-Extracorporeal Life Support in ischemia during femoral cannulation for
Adults. Springer, 2014. cardiopulmonary support. J Vasc Surg
4. Shekar K, Mullany DV, Thomson B, 2010;52:850-3.
Ziegenfuss M, Platts DG, Fraser JF. Extra- 13. Kanji HD, Schulze CJ, Oreopoulos A, Lehr
corporeal life support devices and strategies EJ, Wang W, MacArthur RM. Peripheral
for management of acute cardiorespiratory versus central cannulation for extracorpore-
failure in adult patients: a comprehensive al membrane oxygenation: a comparison of
review. Crit Care. 2014 May 9;18(3):219. limb ischemia and transfusion requirements.
5. Marasco SF, Lukas G, McDonald M, Mc- Thorac Cardiovasc Surg 2010;58:459-62.
Millan J, Ihle B. Review of ECMO (extra 14. Chamogeorgakis T, Lima B, Shafii AE, et
corporeal membrane oxygenation) support al. Outcomes of axillary artery side graft
in critically ill adult patients. Heart Lung cannulation for extracorporeal membrane
Cir. 2008;17 Suppl 4:S41-7. oxygenation. J Thorac Cardiovasc Surg
6. Rastan AJ, Dege A, Mohr M, et al. Early 2013;145:1088-92.
and late outcomes of 517 consecutive 15. Navia JL, Atik FA, Beyer EA, Ruda Vega
adult patients treated with extracorporeal P. Extracorporeal membrane oxygenation
membrane oxygenation for refractory post- with right axillary artery perfusion. Ann
cardiotomy cardiogenic shock. J Thorac Thorac Surg 2005;79:2163-5.
Cardiovasc Surg 2010;139:302-11, 311.e1 16. Moazami N, Moon MR, Lawton JS, Bai-
7. Smedira NG, Moazami N, Golding CM, ley M, Damiano R Jr. Axillary artery
et al. Clinical experience with 202 adults cannulation for extracorporeal membrane
receiving extracorporeal membrane oxy- oxygenator support in adults: an approach
genation for cardiac failure: survival at to minimize complications. J Thorac Car-
five years. J Thorac Cardiovasc Surg diovasc Surg 2003;126:2097-8.
2001;122:92-102. 17. Sabik JF, Nemeh H, Lytle BW, et al. Can-
8. Doll N, Kiaii B, Borger M, et al. Five-year nulation of the axillary artery with a side
results of 219 consecutive patients treated graft reduces morbidity. Ann Thorac Surg
with extracorporeal membrane oxygenation 2004;77:1315-20.
for refractory postoperative cardiogenic 18. Keshavamurthy S, Shafii AE, Soltesz E.
shock. Ann Thorac Surg 2004;77:151-7; Spectroscopic limb monitoring in periph-
discussion 157. eral extracorporeal membrane oxygenation.
9. Pokersnik JA, Buda T, Bashour CA, Gonza- Asian Cardiovasc Thorac Ann 2015;23:347-
lez-Stawinski GV. Have changes in ECMO 8.
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19. Steffen RJ, Sale S, Anandamurthy B, et

al. Using near-infrared spectroscopy to
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genation. Ann Thorac Surg 2014;98:1853-4.
531
48
Adult Cardiac ECLS Acute Complication and Comorbidity Management
Bhavesh M. Patel, MD, FRCP(C), RDMS, Ayan Sen, MD, MSc, FACEP, FCCP, Aly El-Banayosy, MD
Introduction require attention to avoid associated complica-

tions; however, very little evidence is available
Acute complications that occur during to guide management while on ECLS.
adult cardiac ECLS are usually related to the
underlying disease, the ECLS procedure, or the Acute Complications during ECLS
interaction between the two. The most common
complications include major bleeding, acute Bleeding
kidney injury (AKI), new infections, lower
extremity ischemia, acute neurologic events, Major bleeding is the most commonly re-
hemolysis, left ventricular overload with asso- ported complication, with an estimated preva-
ciated pulmonary edema, and dysrhythmias.1-8 lence of 30-42% among ECLS patients, 25-63%
Among the critically ill adult population, of which require operative management.1,2,24,25
chronic comorbid conditions are also common.9 Intracranial bleeding is a source in 3-8% of pa-
Twenty-five percent of adults less than age 65 tients, with other locations being intrathoracic,
and 75% of older adults carry multimorbidity, intraabdominal, gastrointestinal, retroperitoneal,
a co-occurrence of two or more chronic condi- and at all invasive procedural sites.5,25,26 The
tions,10 associated with a significantly increased significant nature of bleeding may be attributed
risk of adverse drug reactions, morbidity, and to the systemic therapeutic anticoagulation re-
mortality.11-16 The most common comorbidities quired to prevent clot formation on ECLS or an
in ECLS patients include respiratory dysfunc- acquired coagulopathy from blood exposure to
tion (chronic obstructive pulmonary disease, artificial surfaces and shear stresses, in addition
acute pneumonia, pneumothorax, or severe to the trauma induced by invasive procedures.
hypoxemia), renal failure, infection, central Management requires balancing the control
nervous system dysfunction, and liver dysfunc- of bleeding with the risk of ECLS-associated
tion,17,18 all associated with a worse outcome.19-21 thrombosis and thromboembolism. New cir-
While chronic organ failures, severe brain cuits and oxygenators require lower levels of
injury, malignancy, and extremes of age gener- anticoagulation which is typically achieved with
ally make a patient a poor candidate for ECLS, intravenous unfractionated heparin infusion
many chronic illnesses such as diabetes, obesity, titrated to a target activated coagulation time
hypertension, and cardiovascular disease are (ACT) of 180-220 and activated partial throm-
encountered in patients on ECLS.13,18,22,23 These boplastin time (aPTT) of 1.5-2.5 x normal.27 In
533
Chapter 48
situations of life threatening active bleeding, (ARDS), when inflammatory effluent from the
anticoagulation is discontinued and reversed lung induces acute kidney injury via systemic
using protamine, blood products, and antifibri- toxicity or biotrauma.45 ECLS-related renal
nolytics guided by point of care (POC) testing. injury may occasionally be the result of hemo-
Hypothermia and acidosis should also be cor- lysis byproducts, hemoglobinuria, microemboli,
rected, and ECLS pump flow rates maintained pump speed, and inflammatory effects of blood
higher until bleeding is controlled.27 If activeexposure to the circuit and membrane.46-49 Renal
bleeding cannot be controlled with conventional perfusion may also be influenced by the ECLS-
methods, some advocate that judicious use of associated dysregulation of the renin-angioten-
recombinant FVII may be safe in ECLS patients sin-aldosterone and atrial natriuretic peptide
(n=30),28 while source control is considered systems.50 Whether the nonpulsatile ECLS
with a surgical or interventional radiology con-blood flow adversely affects renal perfusion,
sultation. The circuit and membrane oxygenator however, is still controversial.51,52 Local blood
should be observed closely for development flow and regional perfusion may be affected
of clot. In situations where anticoagulation is by cannula positioning. Ultrasound assessment
required for coronary stents or prosthetic mitral
of volume responsiveness to improve perfu-
valves, authors suggest control of bleeding for sion can overcome the challenges of using the
12-24 hours prior to sequential reinitiation of traditionally unreliable central venous pressure
POC-guided low dose systemic anticoagulation (CVP).53,54 Rarely, retrograde aortic dissection
followed by an antiplatelet agent after another occurs and involves the renal arteries.2
12-24 hours. Defining and monitoring the degree of
AKI during ECLS can be done using RIFLE,55
Acute Kidney Injury AKIN,56 or KDIGO49 criteria, which largely
utilize urine output and creatinine change over
Acute kidney injury (AKI) occurs in an es- time. All of these demonstrate that a worse
timated 47-56% of adult patients supported by outcome is associated with worsening AKI.
cardiac ECLS and has an associated mortality of The clinical application of plasma biomarkers
33% with another 35-46% requiring dialysis.1-3 of acute kidney injury, such as neutrophil gela-
A review of patients in the international ELSO tinase-associated lipocalin, is being studied and
Registry between 2003 and 2013, demonstrated may be of benefit for prognostication and evalu-
a 3% prevalence of chronic kidney disease ation of renal injury while on renal replacement
(CKD)43 and a 14% prevalence of preexisting therapy (RRT).57,58 Treatment and prevention
AKI (defined as a creatinine >1.5 mg/dL (>132 of AKI requires optimization of oxygen deliv-
umol/L) with or without renal replacement ery by maintaining an adequate hemoglobin,
therapy.17 While the exact mechanism of ECLS- oxygen saturation, and blood flow, along with
associated AKI is not well understood, factors reduction of oxygen consumption via judicious
including kidney disease pre-ECLS and system- sedation strategies, fever control, pain control,
ic hypoperfusion are certainly major contribu- and prevention of hyperadrenergic states. Using
tors. In the Acute Decompensated Heart Failure the lowest possible ECLS flow and pump speed
National Registry (ADHERE) patients admitted with appropriately sized and positioned can-
for acute decompensated heart failure (HF), nulas to keep central venous oxygen saturation
30% had a history of renal insufficiency, with levels above 60%, clear lactate, and maintain
21% having a serum creatinine concentrations an adequate urine output, minimizes the detri-
>2.0 mg/dL.44 Adverse organ cross talk is also mental effects of ECLS-associated hemolysis
seen in Acute Respiratory Distress Syndrome and blood shear stresses49,59,60 This concept of
534
‘blood protective flow’ to protect the blood from studies have significant heterogeneity in the
hemolysis during ECLS is analogues to ‘lung definitions.1-3,64,65 Risk factors for developing
protective ventilation’ being used to protect the infections while on ECLS include older age,
lung from overdistention during mechanical increased disease severity, duration of therapy,
ventilation for ARDS. positive pre-ECLS culture, and mechanical
CKD patients may need a higher mean arte- complications during ECLS.20,64,65 The most
rial pressure to ensure adequate blood flow to common sources of infections include vascu-
the kidneys, although overshooting should be lar access, bladder catheters, pulmonary and
prevented as it can induce ischemia-reperfusion surgical wounds, with pneumonia, bacteremia,
injury. A MAP of 70-85 is usually sufficient to and wound infection being the most common
avoid flow limitation.61 Optimizing the patient’s presentations at a median of 5, 8, and 23 days
fluid status is important and remains challenging post-ECLS initiation, respectively.64 Signs of
even with the use of serial echocardiograms and infection (systemic inflammatory response
ultrasound assessments of the inferior vena cava syndrome [SIRS]) including tachypnea, tachy-
(IVC). Empiric fluid challenges may be expedi- cardia, hypotension, temperature variation, leu-
tious and pragmatic, but detrimental, as increas- kocytosis, and thrombocytopenia are challeng-
ing evidence suggests excessive fluid may be ing to distinguish from ECLS-related immune,
harmful.54,62 In situations of IVC congestion, the hematologic, and metabolic changes. As a result,
use of diuretics is beneficial to decongest the monitoring for other subtle changes that ac-
kidney and improve renal perfusion pressure.63 company sepsis is necessary. Increasing carbon
Use of nephrotoxic medications must also be dioxide results from the increased metabolism
avoided. If necessary, dose adjustments should associated with sepsis and requires increasing
be based on estimated glomerular filtration rate the ECLS sweep to compensate. Increased
(GFR), volume of distribution or measured insulin resistance as a result of circulating cat-
blood levels (for drugs with available assays). echolamines requires increasing doses of insulin
Similar dose adjustments should be made for in a previously stable patient. Vasodilation and
all drugs that are renally excreted. The overall third spacing from sepsis-associated capillary
aim is renal preservation and recovery; how- leak results in hypotension and ‘chatter events’
ever, use of renal replacement therapy (RRT) is frequently requiring decreased ECLS flow rates
frequently necessary. Classic RRT indications while undergoing fluid resuscitation. Sepsis as-
in patients on ECMO include uremia, acidosis, sociated coagulopathy resembling disseminated
electrolyte abnormalities, and fluid overload intravascular coagulation (DIC) can be difficult
(most common). CKD patients already on to distinguish from circuit associated sterile
hemodialysis and considered appropriate for thrombosis. Tanaka et al. looked at a procalcito-
ECMO support should be initiated on CRRT nin based algorithm (cutoff levels >2.0 ng/mL)
after ECMO initiation to avoid rapid fluid shifts to supplement the clinical signs of infection and
and hemodynamic perturbations. Finally, CKD found this had a sensitivity of 90% and speci-
patients have increased risk of venous thrombo- ficity of 89% in this small retrospective adult
embolism and synthetic erythropoietin or ana- cohort study (n=41),66 and other studies have
logues are not recommended once on ECMO. shown this to be useful in pediatrics.67
Candida, methicillin resistant Staphylococ-
New Infections cus aureus (MRSA) and nonlactose fermenting
gram negative bacilli (Pseudomonas, Stenotro-
New infections arise in 7-30% of patients phomonas) infections are increasingly common,
and are associated with a 27% mortality but and appropriately broad spectrum antimicrobial
535
Chapter 48
coverage tailored to local antibiograms is rection, as well as monitoring distal blood flow
ommended.20,64,65 Antibiotic pharmacokinetics post cannulation in order to distinguish between
are differentially affected by ECLS circuit arterial embolism and low flow.32,33 When ves-
sequestration, and this may effect patient sel caliber is too small to safely accommodate
outcome.68,69 For example, meropenem may the cannula size necessary for adequate ECLS
require higher dosing and continuous infusion flow, distal perfusion catheters (anterograde via
whereas vancomycin is unaffected.70,71 Infection distal superficial femoral artery or retrograde
prevention checklists and ‘ECLS bundles’ are via dorsalis pedis) or a cutdown approach with
recommended for insertion and maintenance arterial vascular grafts may be employed to
of medical appliances; however, routine use of permit both anterograde and retrograde flow
antibiotic prophylaxis is not recommended.72 within the artery.31,34-37 Though difficult to moni-
Despite optimal care, vasodilatory septic tor or quantitate, resting superficial femoral
shock can develop in patients receiving cardiac artery blood flow can be measured, and in the
ECLS and preexisting sepsis is present with normal lower extremity is estimated at 150 ml/
cardiogenic shock in up to 13% of cases in min with an ankle pressure of >50 mmHg.38,39
some series.17-19 ECLS flow should be increased For patients at high risk of peripheral ischemia,
to compensate for the additional metabolic de- the addition of near-infrared spectroscopy
mand targeting a cardiac index of >2.2 L/min/ (NIRS) and meticulous clinical examination
m2 and central venous oxygen saturation >70%. with calf circumference measurements may
73
Peripheral ECLS cannulas can be inadequate also be of value by providing an early warning
to achieve target blood flow without excessive of limb hypo/hyperperfusion that may require
blood shear; thus, some advocate addition of intervention.40,41 Despite attempts at optimiz-
a second venous drainage cannula or conver- ing distal perfusion, compartment syndrome
sion to central cannula configuration. Patients may occasionally require urgent fasciotomy
who develop infections while on ECLS can be and less commonly requires distal limb am-
expected to have increased complications and putation.42 Other vascular injuries associated
a higher mortality.65 with arterial cannulation have occurred in 18%
of patients (n=101) and include lacerations,
Lower Extremity Ischemia arterial dissection, pseudoaneurysms, stenosis,
and lymphoceles, all of which require surgical
In patients with lower extremity arterial can- intervention.31
nulation, meta analytic studies demonstrate that
11-17% develop distal ischemia, with 9-10% Acute Neurologic Events
requiring fasciotomies, and 3-5% requiring am-
putation.2,3,29 The risk of vascular complications Reported rates of acute neurologic com-
is higher in patients with peripheral vascular plications vary widely from 2%-50%, with the
disease, which may be present in 4% of those ELSO Registry reporting seizures in 2% and
over the age of 40 and particularly prevalent acute intracranial hemorrhage in another 2%
among patients who are diabetic, hypertensive, of adult patients receiving cardiac ECLS.4,5,24
hyperlipidemic, have chronic kidney disease, or The etiology of new ischemic events is believed
are active smokers.30,31 Large diameter cannulas to be related to air or clot emboli; hence, the
necessary for ECLS may occlude anterograde importance of systemic anticoagulation and air
flow in native vessels contributing to distal filters for all intravenous lines.4,5,46 Neuropro-
ischemia. Vascular ultrasound can be useful for tection with normothermia (36-37° C), eugly-
sizing the femoral vessels during cannula selec- cemia (140-180 mmol/L), and optimization of
536
cerebral oxygen delivery is prudent. Cerebral Central cannulation is optimal for cerebral
blood flow can be monitored with transcranial oxygen delivery but is associated with compli-
Doppler (TCD) sonography,79,80 although this cations inherent to thoracotomy. With peripheral
does not monitor for effects of differential cannulation, adequate oxygenation of cerebral
hypoxia.81 Differential hypoxia occurs when blood flow depends upon ECLS blood flow,
oxygen desaturated blood ejected from the left arterial cannula location, native cardiac function
ventricle mixes with oxygen rich retrograde and native lung function. Early in cardiac ECLS
blood flow from the ECLS circuit resulting in when native cardiac output is poor, systemic
the potential to deliver poorly oxygenated blood and cerebral arterial perfusion is maintained
to the coronary arteries and ascending arch of primarily by continuous ECLS blood flow. As
the aorta. Also termed Harlequin syndrome, this native cardiac output improves, however, dif-
phenomenon was shown in one study to occur in ferential hypoxia may worsen cerebral oxygen
8% of peripheral cannulations.82 Right radial ar- delivery. This can be managed by improving
terial catheterization and use of pulse oximetry the pulmonary shunt through mechanisms
on the right hand may be the best ways to ob- that include manipulation of the mechanical
tain a surrogate estimate of ECLS-oxygenated ventilator, reduction of native cardiac output
blood delivered via femoral artery cannula to by decreasing inotropes or increasing diuresis,
the cerebral circulation (see Figure 48-1).83 The improvement in ECLS blood flow by increasing
addition of cerebral NIRS to monitor changes in pump rate or adding an extra venous drainage
cerebral perfusion may provide further guidance cannula, or the addition of a venous return
in select patients (Figure 48-1).84 cannula (conversion to venous-arterial venous
[V-AV] configuration).85 Intraaortic balloon
pump support may also improve cerebral blood
flow during cardiac recovery when arterial
pulse pressure is increased above 10 mmHg.80
While an initial target MAP of 65 mmHg may
be necessary, adjustments should be considered
according to regional organ tissue perfusion
pressure estimates.61
Neuroprognostication can be challenging
in patients on ECLS with unexplained altered
mental status. Neuroimaging with cranial
computed tomography (CT) frequently demon-
strates significant findings that change direction
of care but may be underutilized due to patient
transportation logistics.86 Electroencephalog-
raphy (EEG) monitoring is recommended in
critically ill patients with unexplained altered
mental status, as up to 16% of them may have
nonconvulsive seizures.87,88 Plasma brain injury
biomarkers such as neuron specific enolase and
S100b show promise for neuroprognostication
but most data is from pediatrics at this time.89-91
Figure 48-1. Monitoring in the VA-ECMO
patient.
537
Chapter 48
Hemolysis the right ventricle, through the lungs to the left

ventricle. With a competent aortic valve and
Hemolysis is seen in approximately a poor LV function, peripheral ECLS pressurizes
quarter of adult cardiac ECLS patients and the aorta, resulting in proportionately excessive
is associated with increased morbidity and LV afterload. Without LV ejection into the aorta,
mortality.1,60 The fractured red blood cells re- the LV overdistends and rapidly results in severe
lease free hemoglobin into the plasma which pulmonary edema, pulmonary hemorrhage, and
scavenges endothelial nitric oxide resulting in an increased risk of LV and aortic root throm-
microvascular vasomotor dysregulation and bus formation. Detection of this phenomenon
may promote thrombosis by von Willebrand requires assessment of arterial line pulsatility
factor-mediated platelet adhesion.74 The degree (as a pulse pressure of <15 mmHg correlates
of hemolysis is routinely monitored by plasma with a loss of aortic valve ejection),94 bedside
free hemoglobin (PHb) levels, lactate dehydro- echocardiography to evaluate LV ejection and
genase (LDH) levels, and change in urine color. function, as well as recognition of elevated
PHb levels trending up over 100 mg/dL require pulmonary capillary wedge pressures, changes
further investigation including measurement of in end tidal carbon dioxide,95 and loss of lung
serum bilirubin and haptoglobin levels. Hyper- compliance on the mechanical ventilator.32,96
triglyceridemia may result in overestimation of Mechanical LV venting may be necessary if
PHb measurement and should be considered in LV unloading is not successful with inotropic
patients receiving propofol.75 Sudden increases support (in patients with nonischemic cardio-
to levels over 1000 mg/dL strongly suggest myopathy), pharmacologic afterload reduction,
pump head thrombosis, and if associated with or intraaortic balloon pump afterload reduc-
a decrease in platelets, heparin induced throm- tion. Peripherally inserted LV venting options
bocytopenia should be considered.47,76 Other include the Impella 2.5 CP® or 5 LD® pumps
technical causes of increased hemolysis include (Abiomed, Danvers, MA) with a pump across
disproportionately high velocity blood flow the LV outflow tract, a percutaneous transseptal
through cannulas generating excessive nega- left atrial catheter drain, or a percutaneous pul-
tive pressures, centrifugal pump speeds >3500 monary artery catheter drain.6,97,98 Central can-
RPM, and an increased pressure gradient across nulation typically consists of venous drainage
membrane oxygenator.59 Roller pumps have from the right atrium and arterial return to the
been associated with higher levels of hemolysis, ascending aorta, with the occasional addition of
but no difference has been observed between a LV vent via the right superior pulmonary vein.7
centrifugal pumps.77,78
Acute Dysrhythmias
Left Ventricular Overload and Pulmonary
Edema Acute dysrhythmias occur in 47% of adult
cardiac ECLS patients and are associated with
The prevalence of adult cardiac ECLS- a 27% mortality.1 Ventricular fibrillation and
associated left ventricular (LV) overdistention ventricular tachycardia may be associated with
and pulmonary edema was 11% in a small sudden LV distention but can be well tolerated
adult study, but has been reported to occur in on VA-ECMO. If acute myocardial infarction
over 60% of pediatric ECLS cases.92,93 Because is suspected, options for percutaneous inter-
VA-ECMO is a partial cardiopulmonary bypass vention may need to be reviewed.99 Otherwise,
system, some blood that is not captured by the typical treatments include confirming optimal
venous drainage cannula continues through myocardial oxygen delivery on VA-ECMO,
538
increasing mechanical ventilator support in case cardiac venous return and ECLS venous drain-
of differential hypoxia, correction of electrolyte age flows in difficult to predict ways depending
and acid-base abnormalities, treatment of sep- upon a patient’s active or passive ventilation
sis, antidysrhythmic rate control with the least pattern.106 With consideration for chronic hy-
negative inotropic agent that is hemodynami- pertensive and diabetic microvascular diatheses,
cally tolerated (beta blockers, calcium channel the target MAPs may need to be higher (MAP
blockers, sotalol, amiodarone, lidocaine), and >75 mmHg) to maintain adequate tissue perfu-
electrical cardioversion. sion pressure and organ function. Optimization
of oxygen delivery may be aided by the use of
Multimorbidity Patients cerebral and limb NIRS.107 In addition, moder-
ate glycemic control with a target of 140-180
Two well described global multimorbidity mg/dL (7.7-10 mmol/L) and avoidance of
patterns are the metabolic triad of obesity, diabe- hypoglycemia is recommended.108,109 Use of
tes, and hypertension and the cardiorespiratory insulin infusions may minimize large glyce-
triad of chronic obstructive pulmonary disease mic variability which may be associated with
(COPD), reactive airways disease and coronary increased mortality110 while avoiding subcuta-
artery disease (CAD).100 Little is known about neous punctures and associated erratic insulin
how these multimorbidity patterns affect care absorption from vasoconstricted subcutaneous
and outcome of patients receiving ECLS. tissues. With attention to the care of morbidly
Extreme obesity (body mass index >40 kg/ obese critically ill patients, it may be possible
m2) adversely effects all major organ systems to improve their outcomes over time.111,112
and in particular cardiovascular, respiratory, COPD affects 10% of adults and is fre-
and metabolic function.101,102 Management of quently associated with other smoking related
ECLS in the obese patient is complicated by comorbidities such as reactive airway disease
difficulty with imaging due to fluoroscopy and and CAD.100,113,114 COPD is associated with
ultrasound power, table weight limitations on airflow limitation, chronic airway inflammation,
CT scanners, unpredictable lipophilic drug bio- cough, and increased secretions. Goals of man-
availability, and challenges with hemodynamic aging mechanically ventilated COPD patients
monitoring and vascular access.103-105 The higher include resting respiratory muscles, maintaining
prevalence of obesity hypoventilation syndrome bronchial hygiene, avoiding hyperventilation,
and obstructive sleep apnea with associated pul- minimizing the risk of barotrauma, and avoid-
monary hypertension, elevated blood pressures, ing impairment of ECLS flows that result from
and increased biventricular ventricular mass dynamic hyperinflation. Initially the use of
and cardiac output further bring challenges to short acting bronchodilator and anticholinergic
the management of the obese patient on ECLS. nebulizers and sedation is required to avoid
Initiation of peripheral VA-ECMO may require air trapping and hyperventilation. The use of
surgical cutdown procedures for cannulation, systemic steroids and antibiotics needs to be
larger cannulas to achieve adequate blood flow, considered for acute exacerbations manifested
higher blood flow rates to adequately support by increased secretions and worsening airflow
basal oxygen consumption, and careful attention obstruction.115 Airway clearance techniques
to wound care and pressure points for preven- range from manual percussive chest physical
tion of decubitus ulcer formation and infection. therapy to intrapulmonary percussive ventila-
In addition, higher intrathoracic mechanical tion therapy to fiberoptic bronchoscopy,116(Print
ventilation pressures and intraabdominal pres- though there is no clear evidence to support
sures may be present and can influence native routine use in COPD exacerbations except in
539
Chapter 48
patients with bronchiectasis.115 Managing pro- acute complications and chronic comorbidi-
longed exhalation and reactive airways becomes ties. An approach to monitoring and managing
challenging as patients emerge from sedation the complex interactions between the patients’
and during weaning from ECLS. Recognizing acute illnesses, chronic diseases, and ECLS is
and managing dynamic hyperinflation (intrinsic necessary to improve short and long-term out-
positive end expiratory pressure) via waveforms comes (Table 48-1). As multimorbidity becomes
on mechanical ventilator and end tidal CO2 more common, recognition of common patterns
monitor prevents associated complications such may assist providers in anticipating and avoid-
as increased work of breathing, barotrauma, ing complications.
and hemodynamic compromise.117,118 Unfortu-
nately, inhaled beta agonist bronchodilators are
frequently associated with tachycardia, which
can detrimentally increase myocardial oxygen
demand, especially in multimorbid patients with
CAD. This becomes particularly important in
peripherally cannulated patients with differen-
tial hypoxia where coronary arterial blood may
be inadequately saturated (as described previ-
ously). Usual monitoring for cardiac ischemia
is performed with serial electrocardiograms,
cardiac serum biomarkers, and echocardiogra-
phy. Aspirin and antithrombin therapy remain
the usual management, as well as minimizing
myocardial oxygen demand. Beta blockers may
be considered in this situation; however, their
pulmonary side effects may limit their use in
multimorbidity.119 Insertion of an IABP was
previously considered conventional therapy for
augmenting myocardial diastolic perfusion dur-
ing cardiogenic shock. This, however, has fallen
out of favor since the SHOCK II trial.120 While
the use of an IABP was not shown to improve
microcirculation during ECLS in a recent small
study, it can decrease LV end-diastolic pressure
and pulmonary capillary wedge pressure.121 In
evaluation of ongoing myocardial injury and
prognostication of postcardiotomy cardiogenic
shock, daily creatine kinase isoenzyme MB
(CK-MB) relative index may be valuable.122,123
Summary
Adult cardiac ECLS can support patients

with cardiopulmonary compromise; however,
careful attention must be paid to managing
540
Table 48-1. Approach to Monitoring and Managing the VA-ECMO patient. (Permission to use granted
under Creative Commons Attribution License.)
Monitor for Treatment

Rhythm Dysrhythmias such as ventricular fibrillation that Antiarrhythmics
may prevent ventricular ejection Cardioversion
Pacing
Ablation
MAP Hypotension (MAP=COxSVR)
(i) Inadequate VA-ECMO flow (i) See “Flow” below
(ii) Inadequate DVR (ii) Start vasoconstrictor
Pulsatility Lack of pulsatility on arterial waveform caused by
(i) poor myocardial function If poor myocardial function, consider:
(ii) excessive VA-ECMO support decreasing VA-ECMO flow
(iii) inadequate preload starting or increasing inotrope
(iv) RV failure starting or increasing vasodilator
May result in IABP
(i) thrombus Myocardial decompression
(ii) myocardial ischemia
(iii) pulmonary edema (assess CXR, wedge(
Flow (L/Min) Low flows (assuming centrifugal pump)
(i) Inadequate preload (i) Volume:
(a) hypovolemia (may see hemolysis, crystalloid/colloid/transfusion
chattering) Release of mechanical obstruction
(b) mechanical obstructive (ii) Exchange oxygenator, relieve cannula
(ii) Excessive afterload (thrombus, kink, SVR) kink, vasodilator to decrease SVR
(iii) Inadequate RPM (iii) Increase RPM
Gas Exchange Inadequate PaO2 inadequate or excessive CO2
elimination
(i) VA-ECMO settings (i) If hypoxemia, increase FiO2 or flow.
(a) FiO2 If hypercarbia, increase sweep. If
(b) VA-ECMO flow hypocarbia, decrease or add CO2
(c) Sweep gas flow rate (ii) Increased AP and inadequate
(ii) Oxygenator function arterialization of postoxygenator gases
(a) Pre and postmembrane pressures suggest oxygenator malfunction
(b) Pre and postoxygenator gases (iii) Increase pulmonary venous O2
(iii) Upper body hypoxemia (femoral-femoral content
cannulation Adjust ventilator settings. Treat etiology
of pulmonary dysfunction. Increase VA-
ECMO flow. Change to axillary/carotid
cannulation. VA-V-ECMO. VV-ECMO
Oxygen Delivery: Decreased SvO2 and increasing lactage suggest
SvO2 and Lactate inadequate oxygen delivery (DO2=COxCaO2)
(i) VA-ECMO flow (i) Increase VA-ECMO flow
(ii) Hemoglobin (ii) Transfuse
(iii) SaO2 (iii) Ensure adequate gas exchange
Excessive oxygen consumption (ER=VO2/DOs)
(i) Febrile (i) Antipyretics
(ii) Shivering (ii) Consider agents such as meperidine or
dexmedetomidine
Distal limb Ischemia Loss of pulses Femoral-femoral cannulation
Cyanosis and coolness of limb DP or PT anterograde perfusion catheter
Anticoagulation Adequate heparinization by PTT
Temperature Normothermia unless therapeutic hypothermia
541
Chapter 48
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549
49
Medical Management of the Adult with Cardiovascular Disease on Extracorporeal

Life Support
Alain Combes, MD, PhD
Introduction on the thermodilution technique will provide

inaccurate values in VA-ECMO patients. If the
Venoarterial extracorporeal membrane patient’s heart is still pumping blood through
oxygenation (VA-ECMO) is an easily appli- the circulation, the arterial line should be placed
cable and widely accepted treatment option for in the right radial artery and the oximetry probe
temporary circulatory assistance in patients with on the right hand to detect upper body hypoxia,
cardiogenic shock refractory to conventional a situation called “Harlequin” or “North-South”
medical therapies.1 This procedure provides syndrome, which occurs when native lungs do
prolonged cardiac and respiratory life support not provide adequate blood oxygenation and a
allowing myocardial recovery, or bridging to flow competition occurs between the heart and
cardiac transplantation, or the implantation of the ECMO device returning blood through the
a left ventricle assist device. Although signifi- femoral artery.2
cant advances in extracorporeal circuitry have Patients on VA-ECMO may not require
improved the risk-benefit profile, the medical ventilatory support, especially when the system
management of patients under VA-ECMO still has been installed under local anesthesia and the
requires great expertise that can be best pro- patient suffers isolated cardiac failure without
vided in highly experienced centers.1,2 significantly impaired gas exchange. For those
This chapter will review the general and in whom invasive mechanical ventilation was
specific ICU management of critically ill pa- initiated, ventilatory strategies that minimize
tients who received VA-ECMO for refractory ventilator-associated lung injury are recom-
cardiac failure. mended and weaning from ventilation attempted
as soon as possible. Consequently, continued
General ICU Management sedation is not required to support most VA-
ECMO patients and should be discontinued at
Patients on VA-ECMO should be managed the earliest opportunity. Alternatively, analgesia
in an intensive care environment.1,2 Standard should be titrated to provide comfort and allow
monitoring should include monitoring of pain-free interventions and nursing care.
cardiac rhythm, invasive arterial and venous Acute kidney injury is common in patients
blood pressures, temperature, pulse oximetry, supported with VA-ECMO. If needed, renal
and urine output. It should be noted that most replacement therapy (see Chapter 62) will
cardiac output measurement devices based permit optimization of the fluid balance and
551
Chapter 49
allow the administration of adequate nutrition, RV and LV preload decrease while LV afterload
intravenous drugs, and blood products without increases because the retrograde aortic ECMO
inducing fluid overload.3-5 Connecting a renal flow competes with the blood flow ejected from
replacement device to the ECMO system is pos- the LV.1,2,12,13 This situation may induce several
sible; however, lines should always be inserted complications. First, it may create or aggravate
after the ECMO blood pump, where pressures aortic regurgitation contributing to further LV
are positive, to minimize risks of air embolism dilation and mitral regurgitation resulting in
through the circuit.3 severe pulmonary edema. Second, it may also
Nutrition of patients on ECMO is not dif- result in a loss of pulsatility and closed aortic
ferent from other ICU patients. Enteral nutrition valve that might contribute to stasis and throm-
should be should be initiated in the first days bosis in the ascending aorta and ventricular
of ECMO support, and approximately 25 kcal/ cavities. Doppler echocardiography should be
kg/day should be achieved within a week of repeated frequently in such situations to adjust
initiation. Parenteral nutrition may be required blood flow on the ECMO machine, guide as-
in patients who cannot tolerate enteral feeding.6,7 sociated inotropic support, and anticoagulation.
Daily physiotherapy should be encouraged It may also help positioning a left-ventricle
in VA-ECMO patients, although cannulation of venting device such as the Impella catheter (see
the femoral artery usually precludes out of bed Chapter 64).14
mobilization.8,9 Indices of LV and RV function should be
evaluated daily, particularly in patients who
Monitoring of the ECMO Circuit might recover from severe heart failure.15-17
These indices include LV ejection fraction and
The ECMO circuit should be monitored LV outflow tract velocity-time integral, tissue
several times daily by the medical and nursing Doppler lateral mitral annulus peak systolic
team caring for the patient and at least once ev- velocity, RV size and function (tricuspid an-
ery 24 hours by a perfusionist or another ECMO nular plane systolic excursion, tissue Doppler
specialist.1,2 Circuit and cannula surveillance systolic velocity at tricuspid annulus), signs of
is intended to verify the correct functioning paradoxical septum, tricuspid regurgitation, and
of the device and identify complications early, assessment of pulmonary artery pressure.
including fibrin deposits or clots on the ECMO Importantly, Doppler echocardiography is
membrane, clots in the cannulas or pump, bleed- the only reliable method to assess cardiac output
ing, signs of inflammation or infection at the in ECMO-supported patients, since thermodi-
cannula insertion sites, unexpected drops in lution techniques are inaccurate because a sig-
ECMO outflow, or the appearance of clinical or nificant amount of injected solution is drained
biochemical signs of intravascular hemolysis. If from the right atrium to the circuit and because
any of these complications occur, a combined pulse-contour techniques are not possible in
multidisciplinary consultation should be con- case of low pulsatility.
ducted to establish the best therapeutic approach. Other complications detected by echocar-
diography in VA-ECMO patients are pericardial
Daily Echocardiography Monitoring effusion and tamponade, inadequate position of
the venous cannula or hypovolemia with col-
Doppler echocardiography should be per- lapse of the IVC around the cannula that might
formed at least daily in patients on VA-ECMO result in low ECMO flows.11
to monitor RV and LV function and to detect
complications.10,11 During peripheral VA ECMO,
552
Medical Management of the Adult with Cardiovascular Disease on Extracorporeal Life Support
Management of Pulmonary Edema under tography which is a point-of-care functional test

VA-ECMO that measures viscoelastic properties of blood,
and evaluates the whole clotting system and
Because the ECMO system reinjects oxy- fibrinolysis might also provide some important
genated blood countercurrent into the descend- information,28 although no robust scientific
ing aorta, it increases in left ventricular afterload evidence exists to date showing its ability to
and, in 15–20% of the patients, is associated decrease coagulation-related complications in
with severe hydrostatic pulmonary edema. The ECMO patients.
latter is even more frequent in patients with little Hemorrhagic complications are among the
or no residual LV ejection on ECMO. In this most frequent adverse events on VA-ECMO.29
context, hydrostatic pulmonary edema is further Minor bleeding in the nose, mouth or throat, or
aggravated by mitral regurgitation induced by at cannula or lines insertion site is common and
LV dilation and increased LV end-diastolic usually easily controlled with local pressure.
pressure, resulting from poor LV unloading.18 Major bleeding is a less frequent but potentially
Decreasing afterload by reducing ECMO flow life threatening. Gastrointestinal bleeding, mas-
to around 3 L/min and improving LV ejection sive ENT hemorrhage, or intracranial hemor-
with IV inotropes are first line therapeutic op- rhage occur in less than 5% of the patients.30
tions. Insertion of an intraaortic balloon pump Management of severe bleeding in VA-ECMO
to restore pulsatility and to decrease cardiac patients includes immediate stopping of IV anti-
afterload has also been associated with lower coagulation, correction of coagulation disorders
LV end-diastolic dimension and pulmonary using blood products, and surgical correction
artery pressures.19 Other therapeutic options20 of the bleeding cause, if any. Administration of
are direct left ventricular unloading using the recombinant factor VIIa was reported to be safe
Impella® device,21,22 percutaneous atrial septos- and efficient in controlling massive bleeding,
tomy,23,24 percutaneous insertion of a transseptal especially in cardiothoracic surgery patients
left atrial cannula, or switch to central ECMO supported by ECMO.31
with intrathoracic cannulation of the left ven- Fibrinolysis and thrombocytopenia that
tricle and aorta.25 frequently occur in ECMO patients are as-
sociated with bleeding complications and
Blood and Coagulation Issues might require circuit change. Heparin induced
thrombocytopenia is a rare complication of
The ideal anticoagulant for patients on heparin treatment related to platelet activating
ECMO that would be effective, easy to monitor, antibodies that should be diagnosed clinically
and to antagonize and with no drug interac- when extensive thromboses are associated with
tion unfortunately does not exist. Therefore, thrombocytopenia.32 A high clinical suspicion
unfractionated heparin remains the mainstay of heparin induced thrombocytopenia should
of continuous anticoagulation in these patients lead to immediate interruption of heparin infu-
due to its quick onset of action and the ability sion, removal of all heparin coated devices, and
to rapidly reverse its action.26 Monitoring of institution of alternative anticoagulant such as
heparin relies mainly on the aPTT and anti-Xa argatroban.33
activity, since the ACT was shown to provide Intravascular hemolysis is a complication of
unreliable values in patients receiving moderate ECMO when highly turbulent flow, thrombosis,
to low dose heparin.27 The usual target is 50 to or cavitation occurs within the circuitry. Signifi-
70 seconds and 0.2 to 0.5 IU/ml for the aPTT cant hemolysis is best detected by measuring
and anti-Xa activity, respectively. Thromboelas-
553
Chapter 49
LDH, haptoglobin, and especially plasma free time of ECMO cannulation. Infected patients
hemoglobin. had longer durations of mechanical ventilation,
ECMO support, and hospital stays.41 The most
Cannula Site Related Complications common organisms responsible for infection
include coagulase negative staphylococcus,
Limb ischemia and compartment syndrome Staphylococcus aureus, Pseudomonas aerugi-
are of major concern in venoarterial ECMO.34-37 nosa, Enterobacter, Klebsiella, enterococcus,
In order to minimize the likelihood of ischemia, E. coli and Candida albicans.41-45 The risk of
cannula size should be selected based on the nosocomial infection is increased with longer
amount of support needed and the size of the ECMO support, in cases of associated mechani-
artery.38 Insertion of a distal reperfusion cannula cal ventilation, or if the patient has an autoim-
into the superficial femoral artery should be mune disease or receives immunosuppressant
considered to perfuse blood to the extremity.30 drugs.41-45 Standard measures to decrease the
In a metaanalysis of 20 studies of ECMO for risk of nosocomial infections should be ap-
cardiogenic shock or cardiac arrest,39 cannula- plied scrupulously. Blood, tracheal, or distal
related complication rates (95% CI) were lung secretions, cannula insertion site and urine
reported as follows: lower extremity ischemia, cultures should be performed rapidly if an infec-
16.9% (12.5-22.6); fasciotomy or compartment tion is clinically suspected. Empiric antibiotics
syndrome, 10.3% (7.3-14.5); lower extremity should be prescribed promptly to patients who
amputation, 4.7% (2.3-9.3). In other series of have signs of sepsis or septic shock.
VA-ECMO patients, significant bleeding30,40
and infection41 at femoral cannula sites were Drug Pharmacokinetics
reported in 10-30% and 10% (3.4 episodes per
1000 ECMO days), respectively. Patients on ECMO require multiple medica-
tions including sedatives, analgesics, antibiot-
Nosocomial Infections ics and sometimes immunosuppressive drugs.
Pharmacokinetics of drugs administered during
Nosocomial infections occurring while ECMO is complex and very difficult to predict;
on ECMO may have dreadful consequences. notably due to a larger volume of distribution
Indeed, risks of developing infections are mark- in patients treated, to the adsorption of drugs
edly increased in these very sick patients, with on PVC tubing and/or membrane oxygenator
disease-induced compromised immune systems leading to an increase in drug clearance, to
who have many indwelling medical devices drug interactions and associated renal replace-
(ie, large ECMO cannulas, endotracheal tube, ment therapy.46,47 The degree of drug uptake
intraaortic balloon pump, and central venous by the circuit depends on physicochemical
catheter). In a series of 220 patients who under- characteristics of drugs.48-49 For example, lipo-
went ECMO support for >48 hours for a total philic drugs and highly protein-bound drugs
of 2,942 ECMO-days,41 64% developed noso- (eg, voriconazole propofol, Dexmedetomidine,
comial infections. Ventilator-associated pneu- and fentanyl) are significantly adsorbed in the
monia, bloodstream or cannula infections, and circuit, while hydrophilic drugs (eg, β-lactam
mediastinitis infections occurred respectively antibiotics, glycopeptides, oseltamivir, and ami-
in 55%, 18%, 10%, and 11% of the patients. noglycosides) are mostly affected by hemodilu-
Increased critical condition at ICU admission tion and other pathophysiologic changes that
was associated with subsequent development of occur during critical illness. Therapeutic drug
nosocomial infections, but not antibiotics at the monitoring is therefore of utmost importance
554
when drug dosage available, to prevent toxicity stolic velocities) did not discriminate between
and monitor efficacy. ultimately weaned and not weaned patients.
Alternatively, Cavarocchi et al.51 showed in a
Weaning from VA-ECMO series of 21 patients that ECMO was safely
removed if both LV and RV functions tolerated
Weaning success from VA-ECMO is de- volume challenge and demonstrated inotropic
fined as device removal and no further require- reserve. Lastly, another study demonstrated
ment for mechanical support due to recurring that an increase in strain and strain rate of 20
cardiac failure over the following 30 days.17 % at minimal ECMO flows, with a concomitant
The first consideration for weaning is that the increase of EF, could predict successful wean-
etiology of cardiac failure is compatible with ing,16 while the strain and strain rate remained
myocardial recovery.15,30 For example, patients unchanged in patients that could not be weaned.
with terminal dilated cardiomyopathy who After VA-ECMO removal, vena cava thrombo-
needed ECMO support should be bridged to sis should also be searched by echography.52
cardiac transplantation or to a temporary VAD,
unless a very specific decompensation factor Conclusion
(such as rapid supraventricular arrhythmia,
severe septic shock) can be cured. Second, the Cardiac ECMO is still a high risk and
patient should have recovered a pulsatile arte- complex therapy for which complications are
rial waveform with consistent opening of the frequent. To optimize patient outcomes, VA-
aortic valve for at least 24 hours, should be ECMO should be performed responsibly under
hemodynamically stable, with baseline mean the supervision of a multidisciplinary medical-
arterial pressure > 60 mmHg in the absence or surgical team.
with low doses of catecholamines, and should The continuous medical management of
have recovered from major metabolic distur- these patients in the intensive care unit is of
bances. Third, pulmonary function should not utmost importance to achieve satisfactory clini-
be severely impaired. If PaO2/FiO2 <100 mmHg cal outcomes.
when FiO2 of the ECMO gas flow is set at 21%,
bridging the patient from VA- to VV-ECMO
should be considered.15
An ECMO weaning trial consisting in de-
creasing ECMO blood flow under close hemo-
dynamic and echocardiographic monitoring to
approximately 1 to 1.5 L/min, will result in an
increase in RV preload and a decrease in LV af-
terload that will allow assessing that myocardial
recovery will permit removal of the device.17
In a series which evaluated this strategy in 51
VA-ECMO patients,17 aortic velocity–time in-
tegration VTI ≥12 cm, left ventricular ejection
fraction >20-25% and tissue Doppler lateral
mitral annulus peak systolic velocity ≥6 cm/s
at minimal ECMO flow support were associ-
ated with successful weaning, while indices of
LV-filling pressure (Mitral E wave and TDI dia-
555
Chapter 49
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559
50
Nursing Management of Adults with Cardiovascular Disease on Extracorporeal Life

Support
Chirine Mossadegh, RN, Gail Faulkner, RGN, RSCN
Introduction Management of the ECMO Device
In the last ten years, extracorporeal mem- It seems obvious, but to ensure the effi-
brane oxygenation (ECMO) has emerged as first ciency of the therapy, the team managing the
line therapy for circulatory failure refractory to patient must understand and be able to analyze
conventional treatment. Peripheral venoarterial the parameters of the device itself. The man-
ECMO (PVA-ECMO) has many advantages agement of the ECMO device is more com-
as salvage therapy compared to other circula- monly called the “circuit check,” which is the
tory assistance systems: it can be implanted responsibility of the ECMO specialist. A check
rapidly at patient’s bedside, even in remote list ensures that the team has not forgotten any
locations with the mobile ECMO team. It al- specific surveillance of the circuit:
lows biventricular assistance with a high and
stable blood flow, combined with a pulmonary • The ECMO cart must be placed near the
assistance, making it suitable for most severe patient bed on brake position.
patients. Once implanted, ECMO allows time • The ECMO system must be correctly con-
to assess the best management strategy for the nected to a secure plug (most commonly a
patient. However, ECMO provides only short- red power outlet). All the ECLS devices
term support. Complications may occur after 7 have a light indicating if ECMO is plugged
to 15 days of ECMO therapy, and the technique in or on battery.
usually does not allow patient rehabilitation, • The gas module must be securely connected
which is crucial for patient improvement. The to the gas sources (wall or tank). The gas
management of these patients is an ongoing module has to be safely connected to the
challenge for an Intensive Care Unit team given oxygenator gas inlet port without any kink
the complexity of the technique. and leak.
There are several sides to the management • The absence of kinks and tensions on the
of adult patients with cardiovascular diseases on whole circuit (cannulae, gas, and power
ECLS: the management of the ECMO device; hoses) must be checked.
preventing complications; and adapting the • Must check and ensure security of the
specifics of extracorporeal life support (ECLS) cannula(e) and check placement with the
to the regular monitoring of the patient in a aid of chest x-ray and reviewed with the
Critical Care Unit MDT.
561
Chapter 50
• A thorough look of all circuit components In a free mode, when an alarm is activated
with a flashlight, looking for thrombin the circuit will keep working but when on
and/or clots. The more complex the circuit Intervention mode, as soon as an alarm is
(bridges, pigtails, stop cocks), the higher the set on, the pump stops working and an im-
risk to develop thrombin and clots. mediate action must be set to resolve the
• Check the security of all connectors and problem. The choice of the mode depends
the presence of tie bands in the appropri- of your human resources. If a nurse or a
ate places. perfusionist is constantly at the patient
• The heater has to be correctly connected to bedside the intervention mode is possible,
the heat exchanger, the water level has to be but if a nurse is taking care of more than
full and the temperature set point adjusted one ECMO patient and cannot intervene
to therapeutic goal. immediately when the pump stops, the free
• Write down the parameters of ECMO sup- mode will be safer.
port to aid guidance and decision making • The equipment needed in case of an emer-
for optimal patient management. gency: clamps, emergency hand crank,
• The circulatory parameters: the Rotation emergency supplies at the bedside must be
Per Minute (RPM) and the blood flow. available; which include appropriate sized
The therapeutic goal is the blood flow. connectors/shears/tubing/rapid access line,
The ECMO specialist in charge of the fluid, tie-gun and tie-straps/sterile gloves,
pump has to control the evolution of the etc.
blood flow in correlation with the RPM.
• The flow rate must be high enough to Vigilance in checking the circuit and atten-
provide adequate perfusion pressure and tion to detail by the ECMO specialist is of para-
venous oxyhemoglobin saturation but mount importance. Effective communication
low enough to provide sufficient preload and escalation to the Duty ECMO consultant/
to maintain left ventricular output. Duty ECMO coordinator must be in a timely
• The ventilatory parameters: the sweep manner to ensure timely decision making.
gas flow should adjust regarding the
PaCO2 and the FiO2 regarding the PaO2. Preventing Complications
• The pressures: some devices are mea-
suring the venous pressure, the arterial ECLS is potentially life-saving for the
pressure, and the ∆P but most ECMO patient in severe cardiogenic shock refractory
teams add pigtails connected to pressure to regular treatment, but it also comes with
monitors. Like the circulatory param- side effects. One of the key points of ECMO
eters, the absolute pressure itself is not management includes preventing and detecting
relevant but its evolution through time. complications. The ECMO specialist role is an
• The pump head must be placed securely extended role and staff must be adequately/ex-
and the ECMO specialist must check for pertly trained to recognize the signs and compli-
disengagement. cations of bleeding, infection, and mechanical
• The alarms: they must be set regarding failure of ECMO components. Specific training
your therapeutic goal. Since the pump is and ongoing assessment is crucial to ensure
nonocclusive, we recommend to maintain clinical competence and skill is maintained to
the blood flow above 2 L/min to avoid any the highest standards to minimize these risks
back flow. The specialist must also know (see Chapter 67). Attention to detail, vigilance
on which mode your ECMO is working. in assessment, and implementation of care in a
562
Nursing Management of Adults with Cardiovascular Disease on Extracorporeal Life Support
timely manner are paramount, along with effec- ECMO the anti-factor Xa can also be a better
tive communication and escalation to the senior indicator of the heparin management.
team in the event of complications. Protocols Bleeding on ECMO can be problematic.
and procedures must be in place to support all The sensitive balance between procoagulants
team members in order to alleviate stress and and anticoagulants must be well understood
improve practice in this highly charged envi- by those who manage patients on ECMO. The
ronment. The partnership between the ECMO ECMO specialist has to check systematically
coordinator, consultant, and specialist is unique. for the presence of bleeding:
Together the team approach must verbalize and
implement patient management goals, which • In the mouth, throat and nose: there can
include review and assessment of daily patient/ be small but continuous bleeding, making
circuit parameters; for example, maintaining mouth care difficult. It is also difficult for
cardiovascular stability, fluid management, ACT families to see their loved ones in such a
management, and sedation guidelines. Commu- state.
nication must be clear, concise, and consistent • At the insertion point of all catheters and
and shared with all members of the MDT. This not only at the ECMO entry point, all IV
will enable all team members to have a clear lines, probes, etc.
understanding of patient management. The • The brain: check the neurological status
nursing care of the patient must be individual, of the patient for any signs of intracranial
goal directed, and holistic. hemorrhage: pupillary response, the level
of consciousness2
Bleeding • The aspect of the lung secretions for the
presence of blood
Bleeding is the most frequent and serious • The aspect of the gastric lavage for the
complication on ECMO, occurring in approxi- presence of blood
mately 34% for adult cardiac ECMO according • The aspect of the urine and stools for the
to the ELSO Registry.1 As an extracorporeal presence of blood
device, ECMO requires continuous systemic In the case of severe bleeding, the admin-
anticoagulation (heparin infusion) to prevent istration of blood products, packed red blood
fibrin and clot formation in the circuit. The cells (PRBC), fresh frozen plasma (FFP), and
implantation can be surgical, with a cutdown platelets is common (see Chapter 8). This forms
and a bolus of 5000 UI of heparin is most compart of the daily parameters prescribed as a
monly injected at the initiation of ECMO flow, guide for the Duty ECMO specialist and ECMO
enhancing the risk of bleeding. In the immedi- team members. If the patient does not respond
ate post-cannulation phase, the challenge is to to transfusion and a decrease of the heparin
balance the control of postoperative bleeding infusion rate, the discontinuation of heparin
with minimizing the formation of clots in the is possible with strict control of the aPPT and
ECMO circuit. The task is worsened by bleeding ACT and a thorough check of the oxygenator
already occurring after an open heart surgery. and cannulas for clots and thrombin.
To prevent bleeding, a very strict control of In a worst case scenario, using recombinant
the hemostasis is necessary: the heparin infusion factor VIIa has be done by several teams with
rates have to be titrated to obtain an aPPT ratio a major decrease of bleedings.3
between 1.8 and 2 depending on the cardiac
patient condition. For patients receiving VA-
563
Chapter 50
Thromboembolic Risk detection is possible by measuring daily free

plasma hemoglobin (normal >50 mg/L) usu-
Effective anticoagulation treatment avoids ally associated with a drop of platelets and red
bleeding but also prevents formation of clots cells counts. Clinically, hemolysis produces a
and thrombin that result from cell lysis caused characteristic reddish color of the urine or the
by the turbulence of the ECMO pump and blood effluent bag if the patient has no urine output.
stagnation. They are easily visualized with a In the most serious cases, other external or
flashlight within the tubing and connectors: dark internal bleedings can occur. Ultimately, with
clots and white fibrin strands often begin near no adequate treatment, the patient develops
stopcocks or other areas of turbulence. All areas disseminated intravascular coagulation. The
of clot identified must be clearly documented treatment consists of replacing the blood loss
and escalated to the Duty ECMO team. with PRBC, platelets, and FFP and potentially
Each hour, the ECMO specialist must changing the ECMO circuit.
carefully monitor the entire circuit with a
flashlight: the cannulas, the connectors, the Differential Hypoxia
pigtails, stopcocks, the pump, and the oxy-
genator. The challenge for the nurse and team Differential hypoxia is also called the Har-
is to assess “normal” clots, which are small lequin syndrome, two circulation syndrome, or
and have no harmful risk to the circuit or the north/south syndrome.
patient. They are frequently seen at the bottom Cerebral hypoxia is a commonly over-
of the oxygenators, where blood stagnation is looked complication of peripheral VA-ECMO.
unpreventable. The “bad” clots are the ones In extreme cardiac dysfunction, if the heart is
becoming an obstacle to the blood flow, the gas not beating and the aortic valve is not opening,
outlet, and causing pressure changes through the ECMO provides 100% of the patient blood
membrane or that may dislodge and travel to the flow and oxygenation. The ECMO blood flow
patient. Again vigilance and attention to detail infused into the femoral artery flows in a direc-
is of paramount importance: detection, docu- tion retrograde to the native blood flow. Upon
mentation, and escalation to prevent untoward return of the heart function, when the heart
incidents and patient compromise. recovers pulsatility and the aortic valve begins
Depending on institutional strategy, the to open, fully saturated blood from the pump
team either changes the component or the mixes with the blood ejected from the native
entire circuit. The assessment of changing an ventricle in the aorta. The location of this mixing
oxygenator must not depend on the presence of cloud depends on the amount of ECMO sup-
clots but mostly on the efficiency of the mem- port provided and the degree of left ventricular
brane to perform gas exchange properly. The function. The mixing cloud begins proximally
pressure (ΔP) monitoring represents adjunctive in the aorta with poor left ventricular ejection
data to assess the occlusion of the component function and/or with increases in ECMO flow.
(oxygenator or pump). However, the mixing cloud moves distally in
the aorta when the ventricle recovers and/or
Hemolysis the ECMO flow is decreased. During severe
respiratory failure due to pulmonary edema,
The spinning and trauma of blood cells the typical VA-ECMO flow rate (80% of full
due to the ECMO flow causes them to break, cardiac output) can result in desaturated blood
producing bleeding and loss of blood com- from the left ventricle perfusing the aortic
ponents. Before clinical signs appear, early arch and coronary arteries and fully saturated
564
infusion blood perfusing the lower body. The Adopting the Specifics of ECLS to Patient
patient’s head appears blue; whereas, the lower Regular Monitoring in a Critical Care Unit
extremities appear pink.
To diagnose differential hypoxia, saturation Pain and Sedation
and blood gases should be measured in the right
radial artery, which reflects the patient’s cardiac Unlike VV-ECMO patients, VA-ECMO
output. To correct and treat this hypoxia, most patients are more commonly awake and even
teams add a jugular cannula to deliver oxygen extubated. Some teams cannulate to ECMO
to the brain. on nonsedated and extubated patients with lo-
cal anesthetics. Pharmacokinetics of pain and
Decannulation sedation drugs such as propofol, midazolam,
or opioids differ on ECMO (see Chapter 71).8
Inadvertent decannulation is the most The circuit traps or binds medication, so higher
feared complication. The key to prevention is dosages of sedation or pain killers may be re-
not necessarily sedating your patient but check quired to obtain the same level of comfort for
the fixation of the cannulas.4 The ECMO spe- the patient. Protocols for management of pain
cialist must visualize the entire ECMO circuit, and sedation should be reassessed for ECMO
check the sutures, and the absence of tension patients to adjust dosages. All members of the
on the cannulas before any mobilization of the MDT must be involved in this aspect of patient
patient. management with periodic review of sedation
agents and their effectiveness.
Limb Ischemia
Infection
The femoral artery is partially or totally oc-
cluded by the return ECMO cannula. To prevent Infection can be a potential issue for ECMO
limb ischemia, it is recommended to insert a patients, especially those receiving central
reperfusion line in the superficial femoral artery cannulation directly accessing the heart. With
and connect it to the reinjection cannula to allow peripheral cannulation, groin infections are
leg perfusion.5-7 frequent. Daily monitoring of white blood count,
The nurse should monitor the leg by com- cell blood culture, and PCT can allow early
paring the temperature of both legs by touch detection although regular blood cultures are a
or using oximetry or NIRS, and the aspect of source of debate.
the leg, its stiffness and color, development The nurse should regularly check the
of blisters, or evidence of foot necrosis. The integrity of the cannula dressing and a daily
reperfusion line must always be visible through assessment of the insertion point of the can-
a translucid dressing, so the nurse can check the nulas looking for redness, swelling, bleeding,
absence of kinks, clots, and/or fibrin. or potential infection.
The same ischemia can occur with axillary The usual institutional protocols can be hard
cannulation. A reperfusion line can be inserted to follow for VA-ECMO patients due to massive
to allow perfusion in the arm. bleeding or the size of the cannulas compared to
a central venous catheter. The ICU team should
adjust their protocols. The use of chlorhexidine
gluconate-impregnated sponges could reduce
the infection rate, diminish the frequency of
565
Chapter 50
dressings up to seven days, and allow a visual tients with poor or no cardiac function, ECMO
on the insertion point as proven in central lines.9 flow generates increased afterload, causing pul-
monary edema. Implanting an IABP at ECMO
Hemodynamic Monitoring initiation can help prevent it.10
The treatment of this edema includes
The ECMO pump is a nonpulsatile device unloading the left ventricle. If conventional
and generates a laminar flow. Right after can- treatment such as the use of diuretics proves in-
nulation, most VA-ECMO patients have poor effective, several approaches are then possible:
or no heart pulsatility and the pump delivers the atrioseptostomy, implanting an Impella®
most if not all the patient blood flow. Hence, (Abiomed), or unloading both ventricles by
the measured arterial blood pressure can appear implanting a central double ECLS.11-14
as a dampened or flat arterial line, with MAP,
SAP, and DAP numbers being identical. When Skin Care
monitoring these patients, the aim is to maintain
the MAP above 65 mmHg. The recovery of a Skin care has always been a challenge for
pulsatile blood pressure can be a sign of left nurses in the ICU. ICU patients are relatively
ventricular function improvement. immobile in bed, often sedated, and thus at high
risk of developing bed sores. Preventing pres-
Fluid Management sure bed sores for ECMO patients resembles
efforts in any other ICU patient. For conscious
Finding the right balance between hypovo- patients, the difficulty is the prohibition of mov-
lemia and fluid overload is more complex for ing one leg, sometimes even both if an IABP
patients undergoing VA-ECMO, especially after has been implanted.
cardiac surgery. Massive blood loss frequently Infection and heparin infusion can also
occurs after heart surgery and ECMO itself provoke skin abrasion or hematoma. For cardiac
can worsened this loss. Hypovolemia induces patients, edema is unavoidable especially after
hypotension and unstable and low ECMO flows. heart surgery. ECMO patients in addition to
The variation of flow also increases fibrin and these preexisting skin alterations must face other
clot formation. potential skin damages: cannula sutures are tight
At the bedside, the nurse should suspect and over time lesions can appear; edema plus
hypovolemia with chattering of the lines as- the pressure of the cannula on the skin can lead
sociated with sudden variations of the ECMO to unavoidable pressure sores.
flow. The nurse must then administer enough Protecting the skin from the cannulas can
volume to maintain an efficient ECMO flow be done with foam dressings or hydrocolloids
(MAP >65 mmHg). already used for regular patients. To fix the
However, giving large volumes in associa- cannulas without damaging more skin, some
tion with muscle relaxants and vasodilators can attachment devices such as the horizontal tube
contribute to large amounts of unavoidable attachment from Hollister® (Hollister, Inc.,
peripheral edema. Fluid overload should be Libertyville, IL) are composed of hydrocol-
treated by diuretics. For unresponsive patients loid, allowing skin protection and an additional
(urine output less than 0.5 mL/kg/hr, positive fixation.
fluid balance >500 mL in the past 24 hours),
renal replacement therapy should be started.
Also, inefficient fluid management often
results in pulmonary edema. In VA-ECMO pa-
566
Mobilizing VA-ECMO Patients from ECMO cannulation the entire scope of

management, and the probability that their
Mobilizing VA-ECMO patients is more loved one might not survive. Staff and family
difficult than a usual ICU patient. At least one members require support from all members of
additional team member (ideally two) must the MDT. Effective, clear, honest, two-way
be at bedside to control the cannulas and the communication is key from referral, consent,
pump. Also the length of the tubing may not and throughout the ECMO run by all members
facilitate mobilization. To prevent adverse of the MDT caring for the patient and fam-
events, the team must have a complete visual on ily. The time spent undertaking this process
the ECMO circuit, check cannulae and tubing can be stressful and time consuming and team
fixation, and move the ECMO cart if necessary members often find a negative outcome from
to avoid any kinks or tension while turning ECMO difficult and challenging. Regular com-
the patient to prevent bed sores or wash him/ munication/meetings to discuss plans of care
her. Extreme caution is necessary. The key is are essential.
to have a nominated team member involved in
the procedure and that person must effectively
communicate the responsibilities of all team
members involved. Vigilance by the ECMO
specialist to prevent rather than treat is essential
to any expert practicing in this role.
Psychological Support
It is of paramount importance for all team

members involved in direct patient care and
management to be trained and competent in all
aspects of ECMO care. ECMO is implanted
when conventional treatment has failed. This is
an emergency therapy, allowing stabilization of
the patient before assessing options, the “bridge
to” therapy:
• Bridge to recovery: the heart recovers and

the ECMO can be withdrawn.
• Bridge to bridge therapy: the patients will
be implanted with a VAD. This is consid-
ered for patients with a possibility of long-
term recovery. It allows the patient to go
back home.
• Bridge to transplant.
• A destination therapy: when ECMO is the
last resort and is ineffective. A procedure for
end of life care must then be set up.
Families and patients need to be counseled

accordingly, they have to know and understand
567
Chapter 50
References 9. Timsit JF, Schwebel C, Bouadma L, et

al. Chlorhexidine-impregnated sponges
1. ELSO. (2015). ECLS Registry Report: and less frequent dressing changes for
International Summary. prevention of catheter-related infections in
2. Luyt CE, Bréchot N, Demondion P, et al. critically ill adults: a randomized controlled
et al. Brain injury during venovenous trial. JAMA. 2009;301(12):1231-1241.
extracorporeal membrane oxygenation. 10. Petroni T, Harrois A, Amour J, et al. Intra-
Intensive Care Med. 2016;42(5):897-907. aortic balloon pump effects on macrocircu-
3. Repessé X, Au SM, Bréchot N, et al. lation and microcirculation in cardiogenic
Recombinant factor VIIa for uncontrol- shock patients supported by venoarterial
lable bleeding in patients with extracor- extracorporeal membrane oxygenation. Crit
poreal membrane oxygenation: report on Care Med. 2014;42(9):2075-2082.
15 cases and literature review. Crit Care. 11. Seib PM, Faulkner SC, Erickson CC, et al.
2013;17(2):R55. Blade and balloon atrial septostomy for left
4. Linden V, Palmer K, Reinhard J, et al. High heart decompression in patients with severe
survival in adult patients with acute respira- ventricular dysfunction on extracorporeal
tory distress syndrome treated by extracor- membrane oxygenation. Catheter Cardio-
poreal membrane oxygenation, minimal se- vasc Interv. 1999;46(2):179-186.
dation, and pressure supported ventilation. 12. Ward KE, Tuggle DW, Gessouroun MR,
Intensive Care Med. 2000;26(11):1630- Overholt ED, Mantor PC. Transseptal de-
1637. compression of the left heart during ECMO
5. Russo CF, Cannata A, Vitali E, Lanfranconi for severe myocarditis. Ann Thorac Surg.
M.(2009)Prevention of limb ischemia and 1995;59(3):749-751.
edema during peripheral venoarterial extra- 13. Cheng A, Swartz MF, Massey HT. Impella
corporeal membrane oxygenation in adults. to unload the left ventricle during periph-
J Card Surg. 2009;24(2):185-187. eral extracorporeal membrane oxygenation.
6. Kasirajan V, Simmons I, King J, Shumaker ASAIO J. 213;59(5):533-536.
MD, SeAnda A, Higgins RS. Technique to 14. Koeckert MS, Jorde UP, Naka Y, Moses
prevent limb ischemia during peripheral JW, Takayama H. Impella LP 2.5 for left
cannulation for extracorporeal membrane ventricular unloading during venoarterial
oxygenation. Perfusion. 2002;17(60):427- extracorporeal membrane oxygenation sup-
428. port. J Card Surg. 2011;26(6):666-668.
7. Greason KL, Hemp JR, Maxwell JM, Fetter
JE, Moreno-Cabral RJ. Prevention of distal
limb ischemia during cardiopulmonary
support via femoral cannulation. Annals
Thorac Surg. 1995;60(1):209-210.
8. Shekar K, Roberts JA, Smith MT, Fing
YL, Fraser JF. The ECMO PK Project: an
incremental research approach to advance
understanding of the pharmacokinetic
alterations and improve patient outcomes
during extracorporeal membrane oxygen-
ation. BMC Anesthesiol. 2013;13:7.
568
51
The Weaning Process and Decannulation in Adult Cardiac Patients
Fabio Guarracino, MD, Rubia Baldassarri, MD
Venous-arterial (VA) extracorporeal mem- the expected goals for which VA-ECMO was
brane oxygenation (ECMO) provides mechani- implemented have been achieved.1,2,4
cal circulatory support for patients in refractory
cardiogenic shock, cardiac arrest, or with acute Weaning
refractory cardiorespiratory illness. Due to the
technical characteristics, high invasivity, risks Well-defined and universally accepted
of complications, and pathophysiologic pat- weaning strategies or protocols are not actually
tern of the extracorporeal circuit, VA-ECMO available. Although the Extracorporeal Life
is a therapeutic strategy and not a therapy. Support Organization (ELSO) guidelines for
VA-ECMO should be terminated after a short adult cardiac failure recommend a protocol for
to medium term duration after the expected weaning from VA-ECMO, the weaning process
goals (eg, a bridge to recovery, bridge to the is still highly dependent on the single center’s
implantation of a ventricular assist device experience and individual clinical practice.5 Ac-
(VAD), bridge to decision, or bridge to trans- cording to the ELSO guidelines, the first step in
plant), for which VA-ECMO was initiated, have ECMO weaning is the prompt recognition of the
been achieved.1 In this context, the timing of clinical signs of cardiac recovery within 1 week
weaning from mechanical support is a crucial of the initiation of the procedure for patients
step in the procedure that primarily depends subjected to VA-ECMO as a bridge to recovery.
on the indications for implantation.1,2 Indeed,
because the anticipated disconnection from Expected early signs of recovery within one
an extracorporeal device can negatively affect week of support
the clinical outcome, delayed weaning from
VA-ECMO and the consequent prolonged Patients on VA-ECMO are commonly sub-
circulatory support significantly increase the jected to continuous clinical and hemodynamic
risk of complications.3 Because VA-ECMO is monitoring to assess either the effectiveness
either an invasive procedure or requires high of the mechanical support or the suitability
doses of anticoagulant drugs for the duration for weaning from ECMO. Weaning should be
of circulatory support, the associated risk of initiated as soon as possible in the presence of
periprocedural complications is very high.1 The hemodynamic stability and adequate peripheral
first consideration in the decision to terminate perfusion indexes with lower doses of inotropic
extracorporeal circulatory support is whether support. Weaning from mechanical support
569
Chapter 51
should be considered when hemodynamic sta- the circulatory support can be further decreased
bility is accompanied by signs of myocardial to 25% of the adequate CO.7,8
recovery and cardiac function improvement
that can be confirmed via echocardiographic Echocardiography in the Weaning Process
assessments of cardiac recovery. The presence
of adequate mean arterial pressure, cardiac Because improvement of left ventricle (LV)
index (CI), and pulse pressure (≥30 mmHg) contractility and opening of the aortic valve
values during conditions of optimized inotropic (AV) are among the most important signs of
support is suggestive of hemodynamic improve- myocardial recovery, the use of echocardiogra-
ment in addition to decreases in the pulmonary phy with the transthoracic (TTE) and especially
artery wedge pressure (PAWP) and the central the transesophageal (TEE) approaches are fun-
venous pressure (CVP) with respect with the damental to the guidance of the weaning process.
baseline values recording at the time of the Although no standardized echocardiographic
initiation of VA-ECMO. protocols guiding weaning from VA-ECMO are
Therefore, the prompt recognition of the available, some echocardiographic parameters
clinical signs of cardiac recovery and adequate have been universally recognized as good pre-
assessments of hemodynamic stability should dictors of successful weaning.3,7 The most used
guide the timing of weaning from VA-ECMO. weaning strategy is based on the reduction of
For these reasons, VA-ECMO should be the pump flow (at a minimum level of 1-1,5 l/
stopped at the appropriate time based on both min for not more than 30 minutes to reduce the
the clinical condition of the patient and the risk of thrombosis of the circuits) while clinical,
indications for device implantation. hemodynamic, and echocardiographic assess-
ments are performed to evaluate the cardiac
With evidence of improved aortic pulsatility performance and the suitability of the discon-
and contraction on echocardiography, the nection from extracorporeal support. When the
inotropes should be optimized and the flow native LV recovers and improves in contractility,
reduced to 50% then 25% of the adequate the reduction of the pump flow is followed by
cardiac output. an increase in the LV ejection fraction (EF). Ac-
cording to the Frank-Starling law, as LV filling
When signs of myocardial recovery and increases due to the reduction of pump flow,
improved cardiac function are present, the flow the improved LV contractility allows for AV
of VA-ECMO can be progressively reduced opening and the ejection of blood through the
to assess the suitability of weaning from the LV outflow tract (LVOT) when the LV systolic
device. An LV EF ≥35-40% on full circulatory pressure surpasses the aortic pressure. In ad-
support and optimized inotropic support is dition to evaluations of the LV EF and the LV
considered to be a good predictor of successful size, adjunctive echocardiographic parameters
weaning.6 If increased myocardial contractility have been suggested as indicators of success-
and improved cardiac function are present, the ful weaning. An EF of up to 20-25% has been
reduction of the pump flow by approximately considered to be a good predictor of effective
50% can be attempted. In conditions of lower weaning from VA-ECMO.6 The measurement
circulatory support, if the cardiac output (CO) of the aortic velocity time integral (VTI) and
is sufficient to maintain adequate end-organ the application of tissue Doppler imaging (TDI)
perfusion and hemodynamic stability, the car- during any step of ECMO flow reduction have
diac function does not worsen, and neither LV recently been considered for the monitoring of
dilatation nor mitral regurgitation occur, then the weaning process. The combination of an EF
570
of up to 20-25%, a VTI ≥10 cm and a systolic Flush the cannulae with heparinized saline
S wave velocity (Sa) ≥6 cm as measured at the continuously or flash from the circuit every 10
level of the lateral annulus of the mitral valve minutes to avoid cannula thrombosis.
with TDI has been considered to be predictive
of successful weaning.6-8 Anticoagulation should be continued during
Echocardiographic evaluation of the right the off trials, and the lines and cannulas should
ventricle (RV) should also be considered dur- be periodically clamped to avoid stagnation and
ing the weaning process. However, it should risk of intracannula thrombosis. When success-
be remembered that acute RV failure can be ful off trials occur, the circuit lines can be cut,
undetectable even when minimal flow occurs. and the cannulas can be locked after hepariniza-
A baseline echocardiographic evaluation tion. Although the cannulas can be left in place
should be performed at the beginning of the for approximately 24 hours after the termination
weaning process and repeated during the proof mechanical support to allow for the reinitia-
gressive reduction of the pump flow to collect tion of the VA-ECMO procedure in unstable
data regarding the changes in myocardial con- patients, the cannulas should be removed as
tractility, cardiac function and eventual acute soon as possible to limit complications.
heart decompensation. Weaning from ECMO is effective when ex-
tracorporeal support can be removed without the
Clamp the circuit and allow recirculation for recurrence of mechanical support for refractory
a trial period of 30 minutes to 4 hours. cardiogenic shock over the 30 days subsequent
to disconnection of the device.6
Weaning from VA-ECMO can be attempted A recent study reported the effectiveness
when a pump flow less than 30% of the native of levosimendan in improving weaning from
cardiac function is sufficient to provide ad- VA-ECMO. The authors reported an increased
equate circulatory support and organ perfusion weaning rate in patients on VA-ECMO who
with low respiratory pressure and inotropic received levosimendan at the time of weaning.9
support. According to the ELSO guidelines, According to the ELSO recommendations, the
weaning from mechanical support should not optimization of the inotropic therapy should be
be performed when the pump flow accounts achieved to enhance cardiac recovery in patients
for as much as 30-50% of the patient’s cardiac who have received extracorporeal circulatory
function.5 support.5
When circulatory support is <30% of the
total cardiac function, off-support trials can be Decannulation
performed. The ventilatory settings and inotro-
pic drug administration should be optimized. After successful weaning from VA-ECMO,
The off trials consist of clamping the drainage vascular decannulation is required to stop the
and infusion lines to allow for slow circulation circulatory support and disconnect the patient
inside the circuit in the arterial venous bridge. from the mechanical device. ECMO decannula-
Then, after a period of 5-10 minutes, the blood tion is a very delicate maneuver that is associ-
lines should be clamped to allow for total cir- ated with significant rates of immediate and
culation and gas exchange. late complications. For these reasons, both the
arterial and the venous cannula must be care-
fully withdrawn at the end of the VA-ECMO
procedure. In peripheral ECMO, cannulation is
percutaneously performed at levels of two large
571
Chapter 51
vessels (ie, for the arterial and venous cannulas). in spontaneously breathing patients and can
The most common sites of implantation are the be prevented by the application of Valsalva
ipsilateral and contralateral femoral arteries maneuver with the patient on the ventilator
and veins. In some cases the jugular vein can or via the administration of short acting
be cannulated.10 In some centers, upper body muscle relaxants.
cannulation is performed via the positioning of In addition to percutaneous VA-ECMO,
the cannulae in the jugular vein and subclavian another strategy for circulatory support is post-
artery.11 Postcardiotomy VA-ECMO is gener- cardiotomy VA-ECMO, which is performed
ally performed in the operating room via the via the placement of intrathoracic cannulae.
intrathoracic cannulation of the right atrium and In these cases, the chest is opened to allow
the ascending aorta. Open chest cannulation can for exploration for the cannulae and surgical
also be performed in patients with inadequate sites. ECMO decannulation is achieved in the
peripheral vascular access. operating room with the surgical removal of the
cannulae and the closure of the chest at the end
VA-ECMO Decannulation of the procedure.
ECMO decannulation is associated with Emergent ECMO Decannulation
high risks of early and late complications, such
as bleeding, hematoma, pseudoaneurysm, and Emergent decannulation can be required
arterial-venous fistula. The vascular complica- when acute vascular complications occur.
tions can be due to altered hemostatic patterns
that typically present in patients on VA-ECMO Conclusion
who are receiving heparin and antiplatelet drugs
to preserve circulatory circuit. Additionally, the Despite the lack of a standardized approach,
large sizes of the cannulas necessary to provide the process of weaning from ECMO always
the high blood flow required by VA-ECMO and requires caution both in selecting the proper
the prolonged maintenance of the cannulation time for the interruption of assistance and
expose the patient to the risk of vascular damage. decannulation. Clinical, hemodynamic, and
The removal of the percutaneous arterial echocardiographic data are of key importance
cannula should be attempted once heparin infu- in the decisionmaking process.
sion has been stopped for almost 30-60 minutes,
and the activated clotting time (ACT) is ≤160
sec. Manual or mechanical compression at the
site of the vascular puncture should be main-
tained for more than 1 hour after the withdrawal
of the cannula.12 Further compression or surgi-
cal repair of the artery can be required in cases
of persistent bleeding. Open surgical repair can
also be necessary in cases of refractory coagu-
lopathy or documented vascular injury.
The removal of the venous cannula
can be complicated by the entrance of air
bubbles into the vein through the access
site. This situation can occur more easily
572
References extracorporeal membrane oxygenation in

adults. Clin Res Cardiol. 2015 Nov 25.
1. Aissaoui N, El-Banayosy A, Combes A. 11. Javidfar J, Brodie D, Costa J, et al. Sub-
How to wean a patient from veno-arterial clavian artery cannulation for venoarte-
extracorporeal membrane oxygenation. rial extracorporeal membrane oxygenation.
Intensive Care Med. 2015;41:902–5 ASAIO J. 2012 58:494–498
2. Abrams D, Combes A, Brodie D. Extracor- 12. Yeo HJ, Kim HJ, Jang JH, Kang LH, Cho
poreal membrane oxygenation in cardiopul- WH, Kim D. Vascular complications arising
monary disease in adults. J Am Coll Cardiol. from hemostasis with manual compression
2014 Jul 1;63(25 Pt A):2769-78. following extracorporeal membrane oxy-
3. Pappalardo F, Pieri M, Arnaez Corada B, genation decannulation. J Card Surg. 2016
et al. Timing and Strategy for Weaning Feb;31(2):123-6.
From Venoarterial ECMO are Complex
Issues. J Cardiothorac Vasc Anesth. 2015
Aug;29(4):906-11.
4. Chung JC, Tsai PR, Chou NK, Chi NH,
Wang SS, Ko WJ. Extracorporeal mem-
brane oxygenation bridge to adult heart
transplantation Clin Transplant, 24 (2010),
pp. 375–380
5. Extracorporeal Life Support Organization:
ELSO guidelines. http://www.elso.org/
resources/guidelines
6. Aissaoui N, Luyt CE, Leprince P, et al.
Predictors of successful extracorporeal
membrane oxygenation (ECMO) wean-
ing after assistance for refractory cardio-
genic shock. Intensive Care Med. 2011
Nov;37(11):1738-45.
7. Victor K, Barrett NA, Gillon S, Gowland
A, Meadows CI, Ioannou N. Critical Care
Rounds: Extracorporeal membrane oxygen-
ation. Echo Res Pract. 2015 Jun 1;2(2):D1-
D11.
8. Douflé G, Roscoe A, Billia F, Fan E. Echo-
cardiography for adult patients supported
with extracorporeal membrane oxygenation.
Crit Care. 2015 Oct 2;19:326.
9. Affronti A1, di Bella I, Carino D, Ragni
T. Levosimendan may improve weaning
outcomes in venoarterial ECMO patients.
ASAIO J. 2013 Nov-Dec;59(6):554-7.
10. Napp LC, Kühn C, Hoeper MM, et al.
Cannulation strategies for percutaneous
573
52
Neurologic and Pulmonary Complications in Adult ECLS
Daniele Camboni, MD, Christof Schmid, MD
Introduction medicine. It is also recognized that the mode

of ECLS deployment plays an important role.
Extracorporeal life support is used to For example, ECLS implanted under mechani-
support patients of all ages with cardiac and/ cal cardiopulmonary resuscitation is associ-
or respiratory failure. The survival benefit is ated with a higher risk for neurologic injury in
sometimes bought at the expense of mostly comparison to an elective and controlled ECLS
reversible and sometimes irreversible complica- implantation in a patient with spontaneous cir-
tions. Among the most important complications culation, as the mechanical chest compression
are neurologic sequelae. A considerable num- and the achieved compromised circulation per
ber of patients suffer neurologic impediments se are associated with neurologic injury.1 The
including seizures, hemorrhage, infarction, or cannulation techniques, basically differentiat-
brain death. Another group of key complica- ing between venovenous (VV) and venoarterial
tions are pulmonary complications. This chapter (VA) configurations, have an influence as well.
provides an overview of the underlying factors It is generally believed that a VA configuration
associated with neurologic and pulmonary is associated with a higher risk for neurologic
complications, as well as outcome, incidences injury, since a VV configuration utilizes the
according to the ELSO Registry, and followup pulmonary vascular bed as a natural particle
data. filter protecting the central nervous system. In-
terestingly, only minor differences are reported
Factors Determining Neurologic Outcome between both support modalities (see Table 52-1
and 52-2) according to the ELSO Registry. For
Neurologic injury depends on a variety of example, the reported rate of brain death in 2015
factors. Pre-ECLS factors including hypoxia, in the VV population comprising of 1568 runs
acidosis, sepsis, hypotension, and low cardiac was 1.9%, and 2.9% in 1769 VA-ECLS runs.
output resulting in an undersupply of the brain This underlines the fact that neurologic injury
play an important role in determining neurologic during ECLS has multifactorial causes includ-
outcome. Also, preexisting neurologic diseases ing thromboembolic events, hemorrhage, and
have a key impact on neurologic outcome after altered coagulation cascade to mention the most
ECLS, as preexisting pathologies tend to be ag- prominent ones. In contrast to the ELSO data,
gravated by extracorporeal support in addition there is also evidence, according to the general
to the necessity and influence of intensive care believe and daily practice, that VV-ECMO is as-
575
Chapter 52
sociated with a lower risk for neurologic injury.2 imaging in critically ill patients during ECLS
VA support may be implanted using peripheral support in addition to the lack of participation
or central cannulation techniques. Central can- of international registries. Patients who sustain
nulation can be differentiated in direct aortic neurologic injury have an increased risk of
arterial cannulation and cannulation of the sub- death even without imaging.4 Therefore, the
clavian or carotid artery with or without the use number of unrecognized neurologic injuries can
of grafts. These different cannulation techniques be assumed to be higher than reported. Rastan et
may have an impact on neurologic outcome, but al. published intriguing autopsy findings in 78
it has never been investigated in a systematic ECMO patients or 50% of the deceased ECMO
manner in ECMO patients. Therefore, one can population. He found in 59 patients (79%)
only assume that the peripheral cannulation prior unrecognized causes of death including
strategy might be associated with a lower clinically undiagnosed cerebral infarction in
risk for neurologic injury in case of residual 7 patients (8%).5 The rate of undiagnosed and
left ventricular ejection, since the retrograde not before postmortem examination evaluated
aortic ECMO flow reaches the brain supplying thromboembolic events was 30%, ie, there
supraaortic vessels only partially. On the other were major discrepancies between clinical and
side, cannulation of the carotid artery, which postmortem causes of death and unrecognized
is mainly done in the neonatal field but also in complications.
adults, is associated with the highest risk for Hemorrhage is generally poorly toler-
neurologic injury.3 Along with the evolving in- ated due to the need for anticoagulation during
dications for ECLS, the support and monitoring ECLS support. Most common hemorrhagic
technology has changed dramatically over the injuries include intraventricular, intracerebral,
past 30 years (eg, centrifugal pumps, dual lumen and subdural hemorrhages. Unfortunately,
cannulas, poly-methyl-pentene oxygenators, intracranial hemorrhage is associated with a
biocompatible circuits), and one can assume a high mortality of approximately 80-90 % ac-
benefit from the technological improvements. cording to the ELSO Registry. Infarction may
be small or large related to the size of emboli
Incidence of Neurologic Injury or to vessel abnormalities of the central vessels.
The incidence of image documented and ELSO
The true incidence of neurologic compli- reported infarction is roughly similar to that of
cations is underestimated due to different fac- hemorrhage (see Table 52-2). VV support is as-
tors including the difficulty to obtain reliable sociated with a slightly higher hemorrhage rate
Table 52-1. Incidence of neurologic complications. Comparison of the years

2006 and 2015 (ELSO Registry data for adults).
Neurologic Complications (VV/VA)

Year 2006 2015
ECMO runs VV 121/VA 141 VV 1568/VA 1769 runs
Brain Death 5.8 / 2.1 1.9 / 2.9 %
Seizures (EEG determined) 2.5 / 1.1 0.2 / 0.9 %
Seizures (clinically determined) 1.7 / 1.4 1.1 / 1.1 %
CNS Infarction 5.0 / 2.8 2.1 / 3.8 %
CNS Hemorrhage 2.0 / 1.4 3.2 / 1.4 %
576
Neurologic and Pulmonary Complications
of 3.8% in comparison to 2.2% in the VA group, retically gas exchange can be managed totally
while cerebral infarction is slightly higher in the by the extracorporeal machine, and some cen-
VA group with 3.8% in comparison to 2.0% in ters do follow this practice. Acute lung injury
the VV group. The ELSO Registry documents leads to pulmonary fibrosis, particularly if the
ECMO runs and corresponding outcome and patient has been on high pressure, high oxygen
the detailed complication rates for more than ventilation for several days. ECMO has the abil-
a quarter century from the year 1991, starting ity to provide gas exchange and deliver oxygen
with less than 20 runs a year, and now reaching to the organism as well as eliminating CO2, but
1500-1800 international adult runs a year. The on the other hand ECMO is also associated with
complication rates are available annually from certain pulmonary complications.
the beginning. Notably, there is a clear reduc- There are a variety of factors leading to
tion of neurologic complication rates over the pulmonary complications in the field of ECMO.
years, which can be seen as a surrogate marker First of all, an ECMO patient is no primarily
for increasing experience in ECMO therapy, bet- different than every other patient requiring
ter patient selection and management, and also extended periods of time of intensive care
for technical improvements. Another group of medicine and long-term mechanical ventilation.
recorded neurologic complications are seizures However, patients requiring ECMO on top of
on ECMO. However, they occur frequently as intensive care medicine and mechanical ventila-
a result of thromboembolic or bleeding events. tion on inotropes can be perceived as the sickest
Its role in adults remains unclear, however, of the sickest (Table 52-3).
adult patients on ECMO developing seizures, Pulmonary complications have a multifac-
either clinically diagnosed or EEG verified, torial origin and three mechanisms can most
have a lower survival to discharge rate 20-40% likely be proposed. First, pulmonary compli-
in comparison to the entire population with a cations can be the consequence of preexisting
survival to discharge rate of 40-60% regardless and probably unrecognized lung injury. Lung
of support modality. injury can easily be overseen and underesti-
mated because of adequate oxygenation and
Factors and Incidence of Pulmonary low pulmonary perfusion on support. A pulmo-
Complications nary complication after ECMO can evolve as
a consequence of the initial cardiogenic shock
Patients on ECMO support are somehow leading to pulmonary congestion. The cardio-
unique in intensive care medicine, since theo- genic shock leads to a multiorgan failure with
Table 52-2. International summary of neurologic complications and corresponding

survival (ELSO Registry Data for Adults from 1991-2015).
Neurologic Complications VV 9102 runs VA 7850 runs

n % Survival % n % Survival%
Brain Death (clinically) 227 2.4 0 354 4.2 0
Seizures (EEG determined) 36 0.4 47 50 0.6 20
Seizures (clinically) 100 1.1 42 135 1.6 24
CNS Infarction (US /CT) 191 2.0 30 322 3.8 23
CNS Hemorrhage (US/ CT) 352 3.8 21 184 2.2 9
CNS=central nervous system; US=ultrasound; CT=computer tomography
577
Chapter 52
impaired liver and kidney function with a cer- complications for ECMO patients. One is the
tain negative impact on the pulmonary function. higher risk for pulmonary embolism caused by
Also, acquired lung injury during extracorporeal thrombotic material in and around the venous
support, like infection due to a compromised cannula. The increased risk for pulmonary em-
immune competence and congestion due to fluid bolism persists after weaning ECMO as mobile
overload, can lead to pulmonary complications. clots remain in the large prior-cannulated veins.
Secondly, patients on ECMO usually re- Another rather unique feature of ECMO pa-
quire blood products due to bleeding issues tients on venoarterial support is left ventricular
as a consequence of cannulation difficulties distension in case of very poor left ventricular
or altered coagulation. Daily transfusions are function with no ejection and consecutive pul-
common in ECMO patients with aggravating monary congestion.
effects on pulmonary function.6,7 It is rather impossible to describe the inci-
Thirdly, VA support leads to pulmonary dence of the above mentioned ECMO related
shunting and reduced transpulmonary blood complications, since these complications are
flow. 8 Pulmonary blood flow is inhomoge- not registered in a systematic manner. Even
neously attributable to existing pulmonary the ELSO Registry cannot provide incidences
pathologies (atelectasis, carnification, fibrosis of pulmonary infection on ECMO, pulmonary
of the lung, etc.) and as a result of mechani- embolism, and so forth. However, the ELSO
cal ventilation. This leads to underperfused Registry provides incidences of relevant
pulmonary regions inducing pulmonary le- pneumothorax and pulmonary hemorrhage.
sions on top of the existing lesion. Koul et al. There is clearly a higher incidence of these
have shown in a large animal model that total rather mechanical complications of the chest
venoarterial bypass for longer periods of time, in VV-ECMO patients (see Tables 52-3 and
up to days, produces pulmonary damage with 52-4) compared to VA-ECMO patients. The
interstitial edema, intraalveolar hemorrhage, incidence of relevant pneumothorax is 9.1 %
and parenchymal necrosis.9 The same authors in the VV population compared to 1.8 % in the
have shown that maintaining pulmonary blood VA population. Similar differences are found in
flow reduced the rate of parenchymal lesions. the incidence of pulmonary hemorrhage (VV:
Higher levels of inflammatory mediators in the 6.3% vs. VA: 3.1%). The diseased organ can
pulmonary alveoli of animals undergoing VA easily explain these differences. VV patients
support were seen when compared to VV sup- suffer from a diseased lung with a higher risk
port. It is noteworthy that all animal lungs were for pneumothorax and hemorrhage. Looking
healthy. However, these findings suggest that at the development of these latter pulmonary
prolonged pulmonary shunting on VA-ECMO complications one can note a clear reduction
support might have deleterious consequences over the last decade (see Table 52-3).
on the lung. In addition, there are some unique
Table 52-3. Incidence of pulmonary complications. Comparison of the years

2006 and 2015 (ELSO Registry Data for Adults).
Pulmonary Complications (VV/VA)

Year 2006 2015
ECMO runs VV 121/VA 141 VV 1568/VA 1769 runs
Relevant Pneumothorax 9.9 / 1.4 5.0 / 2.2 %
Pulmonary Hemorrhage 10.7 / 3.6 4,5 / 2.7 %
578
Return to Work Expectations and Quality tion found only 13 out of 673 records eligible,
of Life of which only 5 studies were included in the
review including only 4 randomized controlled
Longitudinal outcomes after ECMO are trials reaching only a patient cohort size of 389
important but extremely limited and mainly patients. Two out of the four randomized con-
available for neonatal and pediatric patients and trolled trials were conducted in the last century.
not for adults. Functional neurologic outcome Clinical heterogeneity across these studies
cannot be obtained from the ELSO Registry, prevented pooling data for a metaanalysis and
most reports on functional outcome derive from data on long-term outcome for adults is practi-
single centers over a short period.10,11 cally missing. One of the included trials was
However, the ELSO Registry offers a hint the CESAR trial which did not find a significant
about the functional status after ECMO due to difference in health related quality of life after
the registered survival to discharge rate. The six months after study randomization, nor did
survival to discharge rate depends to a vast it show a clear survival benefit at 30 days and
extent on the underlying diagnosis. The highest after 6 month.13 Lung parenchymal changes on
survival to discharge rates are reached in pa- high resolution CT suggestive of fibrosis and
tients with an acute lung failure following fulmi- minor pulmonary function abnormalities remain
nant viral infection (eg, H1N1) and VV support common and can be detected more than one year
with survival rates of 70-80%. There is evidence after VV-ECMO. Furthermore, most patients
that this patient population has a near normal experience a reduction in quality of life due to
quality of life after ECMO removal.10,12,13 The pulmonary sequelae according to Linden et al.13
lowest survival rates are registered for patients Whether these long-term residual abnormalities
requiring ECMO assisted cardiopulmonary apply also for VA-ECMO patients remains un-
resuscitation with survival rates of 25-35%. It clear, but they can be highly assumed.
is also important to point out that the survival This lack of evidence prompted our in-
to discharge rate is generally lower in patients stitution at the University Medical Center of
experiencing a complication in relation to Regensburg to evaluate the long-term outcome
ECMO support. For example, patients on VV of our patient cohort comprising of more than
support developing a cerebral infarction regard- 1000 patients. So far only the results of the
less of diagnosis reach a survival to discharge VA-ECMO population from our institution are
rate of 30%. This did not significantly change available.
over the years. Out of 465 VA-ECMO patients from our
However, it is difficult to extrapolate the institution, including out of and in-hospital
return work rate after ECMO support based on resuscitation cases, a survival rate to discharge
the simple survival to discharge rate. A recently of 37% and a 2 year survival of 45 % of patients
published review by the Cochrane Collabora- reaching survival to discharge after ECMO was
Table 52-4. International summary of pulmonary complications and cor-

responding survival (ELSO Registry Data for Adults from 1991-2015).
Pulmonary Complications VV (9102 runs) VA (7850 runs)

n % Survival % n % Survival %
Relevant Pneumothorax 846 9.1 46 150 1,8 36
Pulmonary Hemorrhage 588 6.3 39 262 3.1 26
VV=venovenous; VA=venoarterial; n=numbers reported; %=% of total runs
579
Chapter 52
calculated over a time period of 10 years. A

quality of life assessment was performed under
the aid of the standardized Euroquol-5D-5L-
Assesment. The data is still unpublished but we
can already distribute that the return to work rate
of discharged patients was roughly one quarter.
On the other hand, 60% were limited in their
mobility and 4% were confined to bed.
Conclusion
ECMO, regardless of support mode, is

associated with neurologic and pulmonary
complications with impact on survival. Despite
a probable underestimation of neurologic and
pulmonary complications, a steady decline in
incidence can be observed over the past decade
as a result of better patient management, more
experience, and better technology.
580
References 9. Koul B, Willen H, Sjöberg T, Wetterberg T,

Kugelberg J, Steen S. Pulmonary sequelae
1. Dankiewicz J, Friberg H, Bělohlávek J, et of prolonged total venoarterial bypass:
al. Time to start of cardiopulmonary resus- evaluation with a new experimental model.
citation and the effect of target temperature Ann Thorac Surg. 1991 May;51(5):794-9.
management at 33°C and 36°C. Resuscita- 10. Schmidt M, Zogheib E, Rozé H, et al.
tion. 2016 Feb;99:44-9. The PRESERVE mortality risk score and
2. Skinner SC, Iocono JA, Ballard HO, et analysis of long-term outcomes after ex-
al. Improved survival in venovenous vs tracorporeal membrane oxygenation for
venoarterial extracorporeal membrane severe acute respiratory distress syndrome.
oxygenation for pediatric noncardiac sepsis Intensive Care Med. 2013 Oct;39(10):1704-
patients: a study of the Extracorporeal Life 13.
Support Organization registry. J Pediatr 11. Taylor AK, Cousins R, Butt WW. The
Surg 2012 Jan; 47(1):63-7. long-term outcome of children managed
3. Rollins MD, Hubbard A, Zabrocki L, with extracorporeal life support: an institu-
Barnhart DC, Bratton SL. Extracorporeal tional experience. Crit Care Resusc. 2007
membrane oxygenation cannulation trends Jun;9(2):172-7.
for pediatric respiratory failure and central 12. Lindén VB, Lidegran MK, Frisén G, Dahl-
nervous system injury. J Pediatr Surg. 2012 gren P, Frenckner BP, Larsen F. ECMO in
Jan;47(1):68-75. ARDS: a long-term follow-up study regard-
4. Lidegran MK, Mosskin M, Ringertz HG, et ing pulmonary morphology and function
al. for diagnosis of intracranial complica- and health-related quality of life. Acta An-
tions in adult and pediatric patients during aesthesiol Scand. 2009 Apr;53(4):489-95.
ECMO: Clinical benefits in diagnosis and 13. Peek GJ, Mugford M, Tiruvoipati R, et
treatment. Acad Radiol. 2007 Jan;14(1):62- al. CESAR trial collaboration. Efficacy
71. and economic assessment of conventional
5. Rastan AJ, Lachmann N, Walther T, et al. ventilatory support versus extracorporeal
Autopsy findings in patients on postcardi- membrane oxygenation for severe adult
otomy extracorporeal membrane oxygen- respiratory failure (CESAR): a multicentre
ation (ECMO). Int J Artif Organs. 2006 randomised controlled trial. Lancet. 2009
Dec;29(12):1121-31. Oct 17;374(9698):1351-63.
6. Agerstrand CL, Burkart KM, Abrams
DC, Bacchetta MD, Brodie D. Blood
conservation in extracorporeal membrane
oxygenation for acute respiratory dis-
tress syndrome. Ann Thorac Surg. 2015
Feb;99(2):590-5.
7. Vlaar AP1, Juffermans NP. Transfusion-
related acute lung injury: a clinical review
Lancet. 2013 Sep 14;382(9896):984-94.
8. Vardi A, Jessen ME, Chao RY, Brink LW,
Levin DL, Johnson RL. Effect of extra-
corporeal membrane oxygenation flow on
pulmonary capillary blood flow. Crit Care
Med. 1995 Apr;23(4):726-32.
581
53
Pregnancy and Extracorporeal Life Support
Farah Siddiqu, MB, BS, Priya Nai, MB, BS
Introduction sidual volume, and functional residual capacity

decrease and by term there is a 20% reduction
The principles of management of severe rein pre-pregnancy levels. The inspiratory reserve
spiratory or cardiac failure in a pregnant patient volume is increased but the vital capacity, lung
and in the puerperium (one month before and up volumes, and forced expiratory volume at one
to 1 month after delivery) differ little from that second (FEV1) remain the same.5 Interestingly,
of a non-pregnant patient.1 Although evidence the respiratory status does not differ in healthy
in this area remains limited, several recent pub- pregnancy with twins when compared to single-
lished case reports and series of Extracorporeal ton pregnancies-this may be due to the reduction
Life Support (ECLS) in this patient group, par- in the functional residual capacity is balanced
ticularly venovenous extracorporeal membrane by the reduction in airway resistance (as a result
oxygenation (VV-ECMO) for refractory respi- of increased relaxin and progesterone in twin
ratory failure during the 2009 H1N1 influenza pregnancies.6 However, women who smoke or
pandemic, suggest growing clinical experience have increased airway resistance may not toler-
and expertise in this complex population.2 ate the reduction in functional residual capacity
Although less than 1% of women require in- of pregnancy too well.
tensive care support for severe cardiorespiratory The majority of these effects start in early
disease during their pregnancy, the maternal pregnancy due to the effects of progesterone.
and fetal mortality is high.3 Managing pregnant Progesterone relaxes the smooth muscle in the
patients is challenging due to the need to con- bronchi and trachea resulting in a reduction in
sider not only the effects of any treatment on airway resistance.7 In addition, progesterone
the developing fetus, but also the physiological increases baroreceptor sensitivity to carbon
changes that occur in normal pregnancy. dioxide, which results in an increase in tidal
volume by 40% and an increase in minute ven-
Physiological Changes During Pregnancy tilation by 15%. The alveolar ventilation is 70%
higher by term. Since the dead space remains
Respiratory4 unchanged, a fall in arterial and alveolar carbon
dioxide tension occurs, the PaCO2 plateaus at
With regard to respiratory function in an 31 torr (4.1kPa), resulting in a respiratory alka-
uncomplicated pregnancy, by the mid second losis.8 The respiratory alkalosis is compensated
trimester, the expiratory reserve volume, re- by an increase in excretion of bicarbonates
583
Chapter 53
by the kidneys resulting in a normal pH. This Aortocaval Compression

relative depletion of the buffering capacity of
bicarbonate renders the pregnant women less In the supine position, the enlarging uterus
able to deal with the acidemia associated with compresses the vena cava from the second half
severe sepsis.9 Due to the increased metabolism of pregnancy.13 This can result in a significant
of the pregnant woman and the developing fetus reduction in venous return and cardiac output
there is an increase in oxygen consumption and (up to 30%), causing the blood pressure to
carbon dioxide production by 60% above non- drop. Additionally, a reduction to blood flow
pregnant values at term.4 to the kidneys and uterus occurs, which can
Histological studies of the respiratory mu- significantly compromise transplacental gas
cosa in pregnant women reveal a significant exchange.14
increase in the glandular activity and thus mucus
production, relative oedema of the respiratory Hematology
mucosa, and an increase in vascularity and
blood flow, resulting in a higher risk of bleeding Pregnancy results in changes to the renin-
into the airways.10 These changes start to take angiotensin- aldosterone pathways resulting in
place from 6 weeks’ gestation and continue into renal sodium retention. This increase in total
the puerperium. body water starts from approximately 6 weeks’
gestation and continues to increase up to 34
Cardiovascular weeks and results in an increase in plasma vol-
ume of up to 45%.15 The red cell mass is only
The first hemodynamic change during preg- increased by 25% resulting in hemodilution.15
nancy is a rise in heart rate, which increases Pregnancy is also a hypercoagulable state due to
by 10-15 bpm from the pre-pregnancy levels.11 an increase in most of the clotting factors (apart
Starting between two and five weeks this change from factors XI and XIII) and fibrinogen. This
continues well into the third trimester. Stroke increases the risk of thromboembolic events.16
volume increases later (10 weeks) peaking at
20-24 weeks and stays at this level (35% higher Immunology
than non- pregnant level) until term, contributed
to by an increase in the preload as a result of an The fetus is genetically foreign to the
increase in the circulating volume and a reduc- mother. In order to prevent rejection, the pla-
tion in the peripheral vascular resistance due centa modulates the maternal immune response
to the effects of the circulating estrogen and which requires tight regulation of angiogenesis
progesterone. Myocardial contractility is prob- and trophoblastic invasion at the uteroplacental
ably slightly increased. The increase in stroke interface. This altered immune response ren-
volume and heart rate results in an increase in ders the pregnant woman more susceptible to
cardiac output by 50% in the first trimester.12 organisms that are controlled by cell mediated
During the third trimester there is relatively immune processes such as viruses, fungi, and
little change in these parameters. After delivery mycobacteria, particularly those women who
there is a very early and dramatic reduction in have preexisting medical disorders.17
volume loading followed by a return towards
normal cardiac output.
584
Adult Respiratory Distress Syndrome signs of decompensation. Cardiac conditions

(ARDS) in Pregnancy commonly associated with cardiac failure dur-
ing pregnancy include cardiomyopathy (preex-
The incidence of ARDS in pregnancy is on isting or new onset peripartum cardiomyopathy),
the order of 1 in 5000 deliveries.3 Due to the valvular disease such as mitral stenosis, aortic
reduced albumin levels (thus reduced oncotic stenosis, and severe mitral or aortic regurgita-
pressure) in pregnancy and the upregulation of tion. Ischemic heart disease is becoming more
the inflammatory response in the maternal lungs, common as women conceive later and the in-
pregnant women may be more susceptible to cidence of obesity in the pregnant population
developing ARDS when compared to their increases. Furthermore, as pregnancy is proar-
non-pregnant state. rhythmic, women with preexisting pathology
Causes in pregnancy are listed in Table 53-1. can develop life-threatening arrhythmias, which
This list is not exhaustive and any cause for can result in acute heart failure. Other examples
ARDS in non-pregnant patients should also be of pregnancy related cardiac disease that can
considered. The diagnostic criteria for ARDS lead to severe cardiac dysfunction include infec-
are not changed in pregnancy. Mortality is tive endocarditis, sepsis, and pericardial disease.
documented at 44% with 23% perinatal deaths.
Special Considerations for ECMO Therapy
Severe Cardiac Disease in Pregnancy during Pregnancy
The Confidential Enquiry into Maternal The physiological changes in the mother
Deaths highlight that cardiac disease in the and the presence of the fetus necessitate certain
United Kingdom is now the leading cause of special considerations for ECMO management
maternal death. As life expectancy increases over and above those generally practiced in the
in patients with congenital heart disease, more care of an adult ECMO patient.
women with complex heart anatomies are
conceiving.18 Cardiac failure can result from Rescue Strategies
exacerbation during pregnancy of preexisting
cardiac disease or as a result of an acute pro- The management of oxygenation with
cess. The plasma volume is increased and the conventional ventilation is the same as the
oncotic pressure is decreased during pregnancy, non-pregnant patient. However, permissive
rendering the patient, particularly with complex hypercapnea is not as acceptable due to the
cardiac disease, more susceptible to pulmonary significant fetal effects that it causes. Inhaled
edema and heart failure. selective pulmonary vasodilators such as nitric
Often chronic heart failure is well tolerated oxide and prostaglandins as well as high fre-
in the first trimester and involves mainly adjust- quency oscillation may be used in pregnancy.
ment of medication and observation for clinical Prone positioning is not feasible or effective in
Table 53-1. Causes for adult respiratory distress in pregnancy.
Complications of Preexisting Conditions Unrelated to

Pregnancy Worsened by Pregnancy Pregnancy
Severe preeclampsia Severe sepsis Smoke inhalation
Amniotic fluid embolus Gastric aspiration Infection such as H1N1
Massive obstetric Cardiac failure influenza outbreak
hemorrhage 2009
Severe sepsis
585
Chapter 53
the late second and third trimester due to the vative anticoagulation regimes with meticulous
gravid uterus.19 monitoring decrease the risk and therefore small
In the case of cardiac failure, the same amounts of postpartum bleeding itself does not
strategies for cardiovascular support such as constitute an absolute contraindication.
optimisation of volume status, inotropes, vaso-
pressors, treatment of pulmonary hypertension, Cannulation Strategies
and mechanical support with intra-aortic bal-
loon counter pulsation, which would be used in The augmented cardiac output of pregnancy
other adult patients should be attempted. necessitates higher flows on VV-ECMO to
ensure adequate oxygenation, which requires
Indications for Therapy using the largest bore cannulae that can be safely
used. Similarly, relatively higher flows may be
The confidential enquiry in maternal deaths required on venoarterial (VA)-ECMO to ensure
(UK) during the H1N1 influenza outbreak in adequate tissue oxygen delivery to the mother
2011 highlighted early consideration of ECMO and the fetus. Appropriate sizing of cannulae
in pregnant patients not responding to conven- with ultrasound measurement of vessels may be
tional ventilation.19 The indications for therapy useful, particularly in this patient group.
are similar to those in other adult patients; tak- Caval compression by the gravid uterus
ing into additional consideration the interests limits effective venous drainage from the infe-
of the unborn fetus ie, pregnant patients are rior vena cava and therefore, dual lumen jugular
considered candidates for ECMO if they have cannulation (Avalon®, Maquet Cardiovascular,
evidence of severe cardiopulmonary failure: LLC,Wayne, NJ) may be advisable for VV-
PaO2/FiO2 ratio less than 100 mmHg after op- ECMO.21 In the case of VA-ECMO, femoral
timal positive end-expiratory pressure (PEEP) cannulation is generally performed although
titration or cardiogenic shock compromising venous drainage may still limit adequate pump
maternal and fetal survival.2 flows. The inability to achieve adequate flows
The majority of ECMO cases undertaken frequently requires the insertion of a second
so far in pregnant women have been for severe venous drainage cannula, both for VV and VA-
ARDS, status asthmaticus, postpartum cardio- ECMO in this patient cohort.
genic shock and amniotic fluid or pulmonary
embolism.2 Early referral to a hospital with Position
ECMO capacity, obstetric care, and neonatal
intensive care is essential, particularly if the pa- Since venous drainage to maintain adequate
tient is not responding to conventional therapy.20 circuit flow can be a significant problem, left
lateral positioning with a wedge under the right
Contraindications hip, which causes a 30 degree inclination to
the left can reduce the aortocaval compression
There are no specific contraindications by the gravid uterus.21 This alone can improve
unique to this patient group. In fact, the general hypotension and augment uterine blood flow.
absence of major comorbid illness, acuity of
the disease process, and relative younger age Respiratory and Hemodynamic Targets
of pregnant women favor the early institution
of ECMO in the appropriate circumstances. Al- Fetal oxygenation requires a maternal
though the risk and implications of bleeding in arterial oxygen tension (PaO2) >70 mmHg
this patient group are more significant, conser- or an oxygen saturation ≥95% and therefore
586
oxygenation targets on ECMO are somewhat and transfusion targets from the University of
higher in this patient group.23 The PaCO2 should Alabama includes targets such as anti-factor
be maintained at 30-32 mmHg when possible, Xa goals of 0.2-0.5, ACT of 160-180, platelet
which is considered normal level in pregnancy. counts >50,000 and antithrombin levels of
Marked respiratory alkalosis (<25 mmHg) may >50%. The lab values are followed closely and
reduce uterine blood flow and cause constriction the heparin is adjusted accordingly (see Chap-
of the uterine artery; this reduces uterine blood ters 7 and 8).2
flow to the feto-placental circulation and results
in fetal hypoxia. Increased PaCO2 can also be Drug Therapy
detrimental as it can result in fetal respiratory
acidosis.22 The pharmacokinetics of drugs is particu-
Hypertension represents an important con- larly complex due the alterations that occur in
cern in pregnant women. The risk of intracere- normal pregnancy25 in addition to those that
bral hemorrhage increases exponentially once occur due to the presence of the ECMO circuit.26
the blood pressure rises above 160/100 (mean The effects of ECMO on pharmacokinetics
arterial pressure of 125 mmHg). Therefore, primarily include sequestration in the circuit,
blood pressure control requires special atten- increased volume of distribution, and decreased
tion. Initial management involves controlling drug elimination. Lipophilic drugs and highly
blood pressure with intravenous hydralazine protein-bound drugs (eg, voriconazole and fen-
or labetalol infusion, particularly in a fully tanyl) are significantly sequestered in the circuit
anticoagulated patient. Magnesium sulphate is and hydrophilic drugs (eg, β-lactam antibiotics,
used to reduce cerebral irritability and the risk glycopeptides) are significantly affected by he-
of eclampsia (seizures).23,24 modilution and other pathophysiologic changes
that occur during ECMO.26
Fetal Monitoring Pregnancy further contributes to a sig-
nificantly increased volume of distribution
As delivery is based on indications to of hydrophilic substrates. Clinically, a larger
improve maternal health, emergency delivery volume of distribution could therefore neces-
due to concerns with fetal health is likely to be sitate a higher initial and maintenance dose of
detrimental to the healthy mother. Therefore, hydrophilic drugs to obtain therapeutic plasma
tests for fetal well-being should usually be concentrations.
limited to assessing viability ie, presence of a Additionally, because of the decrease in
fetal heartbeat. serum albumin concentrations (hemodilution
despite increased production) and other drug-
Anticoagulation binding proteins during pregnancy, drugs that
are highly protein bound may display higher
Heparin does not cross the placental bar- free levels due to decreased protein binding
rier and therefore can be administered using availability and thus higher bioactivity. Di-
conventional targets for maintenance of the goxin, midazolam, and phenytoin are examples
ECMO circuit. However, in general, given the of medications primarily bound to albumin.25
increased risk and implications of major hem- Therapeutic drug monitoring, whenever pos-
orrhage, anticoagulation regimes are generally sible to monitor for under dosing or toxicity is
more conservative in pregnant women, aiming therefore strongly recommended, particularly
for low-normal therapeutic values. An example for this group of ECMO patients.
of an anticoagulation strategy with monitoring
587
Chapter 53
In regards to administration of drugs, a nosocomial infections including bloodstream,

risk benefit decision-making process with the respiratory, urinary tract, and line-related in-
input of specialists with knowledge of the ef- fections.30,31
fects of the medication on the mother and the
fetus should be employed. In these lifesaving Timing and Mode of Delivery
situations maternal health is key, potentially
fetotoxic medication or medication where the Timing of the delivery depends primarily on
effect on the fetus has not been studied can be maternal health. As the pregnancy progresses
justified if there is no safe alternative. the diaphragmatic elevation worsens and with
For example, steroids can potentially result the increasing oxygen requirements of the fe-
in malformations of the fetus if used in the first tus in late pregnancy, sufficient control of gas
trimester.27 Benzodiazepines and opiates, which exchange remains challenging.
are almost universally required during ECMO Any decision to deliver the fetus should
therapy, may result in neonatal depression or be discussed and documented clearly as a
withdrawal polyhydramnios and floppy infant multidisciplinary team including the ECMO
syndrome.28 Many drugs administered in criti- team, adult intensivists, obstetric anesthetists,
cal illness and during extracorporeal circulation obstetricians, and the neonatal teams. Women
have limited or no approval during pregnancy. who received ECMO therapy at early gestations
While essential medications still need to be have recovered and been successfully extu-
delivered, drugs should be chosen according to bated and brought to term, with good maternal
the least risk for maternal and fetal morbidity. and neonatal outcomes. However, in the later
stages of pregnancy, if the causative pulmonary
Complications of ECMO or cardiac pathology appears to have resolved
but satisfactory objective tests of pulmonary or
The major reported complications from cardiac function remain suboptimal, it is reason-
available case reports and series is bleeding. able to deliver the fetus. Delivery may also be
In one small series during the H1N1 pandemic, appropriate if patients experience severe com-
major bleeding occurred in 57.1% (4 of 7) of plications of pregnancy including preeclampsia,
pregnant women while on ECMO, leading to placental abruption, or chorioamnionitis as the
relatively large volumes of packed red blood risk of developing coagulopathies and maternal
cell transfusion (median volume transfused was death is high. Often when planning delivery,
3,500 ml) and was the main cause of death.29 an unheparinized circuit can be run for up to 6
The bleeding sites were intracranial or multiple hours in the case of VA-ECMO and longer in
sites in cases with fatal hemorrhage, and uterine the case of VV-ECMO.32
or pulmonary hemorrhage were more often Once the plan for delivery has been made,
recorded in cases of nonfatal bleeding. Other then consideration regarding the mode of
sites of bleeding included hemothorax, upper delivery becomes crucial. Case reports have
gastrointestinal haemorrhage, nonfatal fetal demonstrated good outcomes with spontaneous
intracranial haemorrhage, vaginal bleeding, and vaginal births while on ECMO. Similarly, in
bleeding from the cannulation and tracheostomy cases of fetal death vaginal birth is appropriate.33
sites. Other published ECMO-related complica- Planned vaginal birth by induction of labor is
tions in this patient cohort include hemolysis, often more challenging due to the patient be-
cannula dislodgment, and ineffective flow rate ing cared for in units without direct maternity
resulting from uterine compression, which im- cover. The risk of intrapartum fetal hypoxia and
proved after emergency cesarean section, and acidosis is high; oxygenation, blood pressure,
588
and pain control are more challenging. Provi- hemolysis, elevated liver function tests and low
sion should be made for emergency operative platelets) is part of the spectrum of preeclamp-
delivery if complications arise.34 Therefore most sia with evidence of hemolysis, elevated liver
units would consider elective cesarean section enzymes (transaminases), and low platelets. In
at a time when the obstetric, cardiothoracic, severe preeclampsia (BP >160/100, greater than
ECMO, anesthetic (both cardiovascular and 3g protein in 24 hour urine collection) cerebral
obstetric anesthetists), and neonatal teams are irritability attributed to cerebral edema, can
present. lead to eclamptic fits. Vigilance for signs of
agitation clonus or brisk reflexes is required
Fetal and Neonatal Considerations with a low threshold for starting magnesium
sulphate (4g loading dose over 20 minutes and
Timing of delivery should generally be ap- maintenance at 2 g/hour). Both fetal and mater-
proached taking into consideration the interests nal mortality in the event of an eclamptic fit is
of the mother; when the delivery is deemed to increased significantly; magnesium sulphate has
improve her respiratory or cardiovascular status. been shown to reduce the incidence of the first
The neonatal morbidity and survival depends and subsequent eclamptic fits. Severe hyper-
significantly on the gestation of delivery. The tension (BP >160/100) is also associated with
Epicure data is a comprehensive review of sur- intracranial hemorrhage if this occurs on a fully
vival both short and long term of infants born at anticoagulated circuit, mortality is high. Severe
the extremes of prematurity.35 Survival is poor at hypertension can be managed with IV labetalol
less than 23 weeks’ gestation. Certainly from 24 or hydralazine. As preeclampsia is related to
weeks’ gestation an experienced neonatal team abnormal placentation, early consideration for
should be present. A course of antenatal steroids delivery is required once the patient has been
(such as dexamethasone 12 mg intramuscularly, stabilized; therefore, timely involvement of the
2 doses at least 12 hours apart) has been shown anesthetic and obstetric teams is crucial.39
to improve neonatal outcome by reducing the
incidence of neonatal respiratory distress and Chorioamnionitis
neonatal intraventricular haemorrhage. Antena-
tal steroid treatment should be considered, if not In cases of rupture of membranes, ascend-
contraindicated, for all women when preterm ing infection may result. Chorioamniotis is a
delivery is being contemplated between 24-36 primary cause of ARDS. In addition, the risk
weeks’ gestation.36 of developing coagulopathy and DIC is high.
Broad spectrum antibiotics should be used early
Specific Complications of Pregnancy to and failure to respond will require consider-
Consider during ECMO ation of delivery or terminating the pregnancy
if unviable.
Preeclampsia
Abruption
Preeclampsia commonly complicates
pregnancy. In severe forms it can be a primary This is defined as bleeding from the placen-
cause for ARDS. However, there is a possibility tal bed. If severe such hemorrhage can result
that it may develop in an already unwell patient. in fetal death, maternal coagulopathy, and DIC;
Therefore, clinical suspicion if the blood pres- in addition, the risk of spontaneous miscarriage
sure is difficult to control, and daily urinalysis is or labor is increased. Therefore, management
required.37,38 HELLP syndrome (an acronym for
589
Chapter 53
of the anemia and coagulopathy should be con- ECMO possibly remains underutilized, poten-
sidered as well as delivery. tially due to the concerns of increased maternal
and fetal bleeding. A recent systematic review
Fetal Death and metaanalysis summarizes the same group
of publications.19
Patients with profound shock or other sig- The experience in the puerperal period is
nificant systemic illness have significant risk heavily concentrated around the 2009 H1N1 in-
of fetal demise. The diagnosis can be made fluenza pandemic with 48 patients (45 VV and
by ultrasound. The retained fetus may cause 3 VA) receiving ECMO. Survival was 92% for
the patient to develop significant coagulopa- the mother and 74% for the fetus. The overall
thy. Therefore, once stabilized, consideration maternal and fetal survival in the 67 patients
should be made to deliver the fetus. Vaginal was 80% and 70% respectively. One has to be
delivery is a reasonable option. Due to the risk mindful of publication bias towards successful
of catastrophic bleeding, once developing signs outcomes, which almost certainly applies to
of labour, temporary cessation of heparin should this patient group.
be considered. Uterotonics should be avail- The most common site of bleeding reported
able to ensure the uterus contracts and controls was around the tracheostomy and ECMO can-
bleeding after delivery. nula. Delivery of the fetus was mostly deferred,
but in one case the fetus was successfully de-
Postpartum Hemorrhage livered by cesarean while the mother remained
on ECMO. As in other adult patients, outcomes
Once the placenta has delivered, significant appeared to be better if the duration of mechani-
bleeding can occur due to atony. Uterotonics cal ventilation was <7 days prior to the initiation
such as boluses of oxytocin, oxytocin infusion, of ECMO.19
Carboprost (PGF2αanalogue) or misoprostol More recently, a retrospective study de-
should be considered. Cell salvage should be scribing the experience of ECMO in 18 pregnant
available and used (only once placenta is de- and postpartum (within 6 weeks of delivery)
livered). Careful consideration should be made patients over a 6.5-year period was published.
to hemostasis and drain placement to estimate Four of these were pregnant at the time of
on going bleeding after. Tranexamic acid, ECMO initiation and 14 were postpartum. The
protamine and recombinant factor VII should majority of patients (17) received ECMO for
be available (see chapter 8).40 ARDS, 14 of who had a VV configuration. The
incidences of bleeding complications as well
Experience with ECMO in the Puerperium as maternal and fetal outcomes were similar to
Period previous studies.41
Overall, the experience to date suggests that
Two recent publications, one describing ECMO therapy can be effective and safe in these
only pregnant patients2 and the other includ- women, with outcomes that compare with other
ing postpartum patients30 have summarized the adult ECMO patients. Certain considerations
publications on ECMO therapy in this patient must be taken into account to ensure optimal
group so far, which are made up of individual outcomes both for the mother and the fetus.
case reports and case series. These two publi-
cations include 45 and 67 patients respectively,
suggesting that to date the experience in this
patient group is relatively limited and also that
590
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C, Cousins L, Schrimmer D. Acute respira- V-V ECMO without anticoagulation: A case
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Use of extracorporeal respiratory support
592
54
Trauma and Extracorporeal Life Support
Justyna Swol, MD, William R. Lynch, MD
Introduction thermia, metabolic acidosis, and coagulopathy

can worsen hemorrhage and hypoxemia from
Emergency room trauma resuscitation in- severe underlying injuries. Major trauma
cludes the treatment of coagulopathy, acidosis, patients experience systemic inflammatory
and hypothermia, the triad of death. All trauma response syndrome (SIRS) in the early posttrau-
patients are resuscitated in the emergency matic phase and can develop hemodynamic in-
department or trauma operating room, and stability with a high risk of multiorgan failure.1,2
Advanced Trauma Life Support (ATLS) guide- ECLS improves oxygenation in patients with
lines are recommended. During resuscitation, parenchymal disruption and/or bleeding. The
the trauma team performs a primary survey extracorporeal device can correct hypercarbia,
(ABCDE intubation, ventilation, circulation, ameliorate metabolic acidosis, help to restore
central venous access, arterial monitoring, Foley the hemodynamics, and rewarm patients in case
catheter with thermistor, and chest tube inser- of hypothermia. The risk of bleeding; impos-
tion), and radiological investigation (trauma sibility of prone positioning in brain, spine and
CT scan). In case of coagulopathy, the massive pelvic injuries; and need for further interven-
transfusion protocol must be initiated until the tions and operations during ECLS, especially in
coagulopathy resolves. Early stabilization with the setting of brain injury, make the extracor-
extracorporeal devices, if needed, allows for poreal therapy of trauma patients challenging.
immediate damage control surgery and delayed Clinicians must weigh the balance between
repairs of injured organs or vessels. the need for anticoagulation and the persisting
The majority of traumatic pulmonary and risk of bleeding. Secondary complications and
chest injuries can be managed without ECLS. organ failure in the later course can also make
However, some severe injuries in major trauma extracorporeal support a useful support mode.
require ECLS for survival. ECLS offers supple- Chest trauma needs to be treated on an
mental capacity in the early resuscitation and individual basis, depending on the location and
treatment of secondary complications of pa- type of chest injury and any co-injuries. Chest
tients with major injuries when primary injuries injuries cause many deaths every year, and
are being evaluated and treated. blunt thoracic trauma is an especially vexing
Trauma patients are often young and have a injury mechanism in major trauma patients.
high risk of complications as well as a complex The blunt force of the injury typically produces
pattern of life-threatening injury (ISS); hypo- an underlying pulmonary contusion, resulting,
593
Chapter 54
in the worst case, in severe respiratory failure be caused by atelectasis, contused lung tissue,
if it has been overlooked or underestimated. or pulmonary hemorrhage.
Clinical findings are often subtle and frequently Traumatic trachea-bronchial and pleural
overlooked due to multiple injuries that direct injuries lead to fistula formation and are as-
attention elsewhere. Faster and more detailed sociated with high mortality and morbidity
diagnosis has been achieved by multislice com- (60%-70%). These injuries are uncommon and
puter tomography.3 Seven independent predic- the diagnosis and surgical treatment can be de-
tors that correlate significantly with increased layed.6 In the case of a fistula, ventilatory man-
risk of pulmonary complications after trauma agement is directed toward keeping the airway
include age, gender, traumatic brain injury pressures below the critical opening pressure.7
(TBI), massive fluid therapy, ISS, Abbreviated In case of damage to the tracheobronchial tree,
Injury Scale (AIS) of chest trauma, and surgical profound hypoventilation can result, and ECMO
interventions.4 cannulation is lifesaving, acting as a bridge to
further reconstructive surgery.8
Indications for ECLS in Trauma Patients Acute airway obstruction by foreign bodies
or particles, accompanied by barotrauma due to
Some trauma patients die of their compli- severe tissue damage, is life threatening. Bron-
cations despite having potentially survivable choscopic clearance of airways and removal of
injuries. ECLS devices have the capacity to particles lodged in smaller airways is challeng-
oxygenate and correct hypercarbia, provide ing and time consuming. ECLS can provide gas
circulatory support, rewarm blood and infuse exchange, facilitating the removal of the foreign
volume, and offer an advanced technology of body by rigid or fiber optic bronchoscopy.9
life support and resuscitation. In case of submersion injury associated with
According to the ELSO guidelines, the use severe hypothermia and submersion, extremely
of ECLS should be considered when the PaO2 abnormal potassium levels and cardiopulmo-
to FiO2 (P/F) ratio is <150, and is indicated nary resuscitation have a poor prognosis.10 Poor
when the ratio is <80. PaCO2 >80 mmHg or oxygenation due to severe pulmonary edema
end-inspiratory plateau pressure >30 cm H2O can be restored by ECLS bridging while wait-
are also considered indications for ECLS in ing for organ recovery. Avalanche victims with
patients with lung failure according to the ELSO profound hypothermia (reported 22°C/71°F)
guidelines. and prolonged cardiac arrest (up to 150 minutes
total duration), if extricated with an air pocket
Venovenous ECMO and free airways, must be treated optimistically,
considering the ECLS indication.11
Venovenous (VV) ECMO should be con- Lung failure is the major cause of mortality
sidered in trauma patients with the following in burn injury. ECMO provides gas exchange,
concerns: acute severe respiratory failure due providing time for lung recovery in the setting
to posttraumatic lung failure (impairments in of inhalation injury with or without cutaneous
gas exchange, severe blunt trauma, contusion, burns.12 Scald burns show a tendency of higher
and related to mass transfusion); inhalational survival than flame burns.13
injury and toxic lung failure; and/or direct dam- Population demographics can influence
age of the lung tissue or injury of the tracheal trauma epidemiology and associated risks of
or bronchial tree resulting in inadequate gas cardiovascular events. Thus aging individuals
exchange.5 Impairments in gas exchange can may suffer severe injury following myocar-
dial infarction. Thus evaluation must include
594
evaluation of underlying cardiac function and Hemostasis and Anticoagulation

coronary perfusion. Conversely, blunt thoracic
trauma can be the cause of acute myocardial In severely injured trauma patients in hem-
infarction.14 orrhagic shock the blood component therapy
Indications for ECLS cannulation include should be initiated according to the local trans-
cardiogenic shock or cardiac arrest (myocardial fusion protocols. Use of heparin-bonded circuits
contusion, cardiac arrest, and impairments in without systemic heparin, decreases the risk of
cardiac output).17 Cardiac rupture is rarely ob- bleeding or coagulopathy in trauma patients. If
served, mainly because most patients die before systemic anticoagulation is necessary, tailored
reaching the hospital. Survival depends on the doses are crucial for a successful outcome (also
rapidity of the patient´s transfer to the cardiac see Chapter 7). Bleeding into the injury sites
surgery center preferably with ECLS reestab- often leads to a fatal outcome. ECLS with a
lishing hemodynamic conditions.15,16 heparin-bonded circuit offers supplemental
Endovascular repair (EVAR) of thoracic capability in the resuscitation and cardiopulmo-
aortic injuries has reduced mortality and mor- nary support in major trauma while the primary
bidity compared with open repairs. Early can- injuries are being evaluated and treated.19
nulation for ECLS preserves systemic organ
perfusion in cases of hemorrhagic shock or Unique Considerations - Traumatic Brain
distal aortic perfusion during aortic grafting.18 Injury
The use of ECLS facilitates the surgery by
supporting gas exchange and cardiac output, The combination of lung failure and severe
maintaining normothermia, and enabling rapid brain injury requires special treatment that
and massive administration of fluids and blood includes extensive monitoring techniques for
products often permitting decreased vasopressor cerebral hemodynamics and metabolism (in-
use in spite of severe cardiac dysfunction.19,20 tracranial pressure measurement, jugular bulb
ECLS may be associated with the high risk oximetry, and estimation of arterial jugular bulb
of bleeding, clotting, infection, limb ischemia, lactate differences) to prevent cerebral hypoxia
and organ failure. In general, the indications and cerebral hyperemia.21 The development of
depend on several factors: lung failure complicates the course of traumatic
brain injured patients. Special therapeutic strate-
• The nature of the injury gies for both may lead to a “conflict of interest”
• Prognosis of the injury and combination (lung protective strategy and permissive hyper-
of injuries capnia against neuroprotective normocapnia
• Possibilities for definitive therapy strategy).21,22
• Comorbidities and patient biological age Coexistent traumatic brain injury (TBI) was
• Severity of the dysfunction considered to be a contraindication for ECLS.
• Status of the central organ, such as the brain, The successful treatment with a beneficial
kidney, and liver neurological outcome suggests that extracor-
poreal devices should not be withheld from
There is no benefit if the situation appears major trauma patients with TBI who present
futile (eg, irremediable neurologic injury) and with life-threatening hypoxemia. 23,24 Brain
incompatible with life. injury is not an absolute contraindication, but
the risk of lethal intracerebral bleeding has to
be considered. A heparin-free ECLS course is
possible.25 Jugular venous cannulation may ob-
595
Chapter 54
struct venous outflow, optional femoro-femoral

cannulation for VV ECMO may be considered.
In case of severe brain injury, ECLS has
been used as organ-preserving support in case
organ donation may be an option.26 ECLS
for organ donation after cardiac death (futile
penetrating injury and exsanguination) may
expand the abdominal organ donor pool of
nonheartbeating donors (NHBDs). ECLS can
also be used to reduce the warm ischemia time
in grafts obtained from uncontrolled NHBD.
Conclusions
Decisionmaking in the treatment of coexist-

ing injuries requires an interdisciplinary consen-
sus between an ECLS specialized intensivist,
trauma surgeon, general surgeon, neurosurgeon,
cardiothoracic surgeon, orthopedic surgeon,
anesthetist, and other physicians involved in
the patient care.
Trauma patients with severe acute respira-
tory failure and/or tracheobronchial injuries, re-
sulting in inadequate gas exchange, submersion
injury, inhalation trauma, burns, and complete
tracheal or bronchial obstruction, resulting in
impaired gas exchange should be considered
for ECLS. Additionally, patients with acute
traumatic cardiac failure (myocardial contusion
and ruptures) resulting in inadequate circulation
(cardiogenic shock or cardiac arrest) or hemor-
rhagic shock should also be evaluated for ECLS.
596
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(extracorporeal membrane oxygenation)
in a traumatic brain injured patient with
severe hypoxemia. Ann Fr Anesth Reanim.
2013;32(10):701-703.
25. Muellenbach RM, Kredel M, Kunze E, et
al. Prolonged heparin-free extracorporeal
membrane oxygenation in multiple injured
acute respiratory distress syndrome patients
with traumatic brain injury. J Trauma Acute
Care Surg. 2012;72(5):1444-1447.
26. Ke HY, Lin CY, Tsai YT, et al. Increase the
donor pool: transportation of a patient with
598
55
Transport of the Patient Supported with ECMO
Björn Frenckner, MD, PhD, Wesley A. McKamie, RRT, CCP, Richard T. Fiser, MD
From time to time the need arises to move ECMO.1 This occurred shortly after the first
a patient supported with extracorporeal mem- published successful use of ECMO by Hill and
brane oxygenation (ECMO), either within a colleagues.2 The team at Wilford Hall U.S.A.F.
facility in order to obtain a particular diagnostic Medical Center published in 1991 the successful
or therapeutic intervention (such as cardiac transport, using military aircraft, of 12 pediatric
catheterization or CT scan), or between fa- patients supported with ECMO over distances
cilities. Inter-hospital transport of a patient on as great as 1400 miles.3 From the late 1980s
ECMO may be necessary in instances in which until recently, the bulk of transport ECMO ex-
the referring facility does not provide ECMO perience in the U.S. had been reported by teams
services, or because the patient supported with from the University of Michigan,4,5 Wilford
ECMO requires other specialized services Hall,3,6,7 Arkansas Children’s Hospital,8-10 and
not available at the referring institution, such Columbia University Medical Center.11 From
as “bridging” to heart or lung transplantation. Europe substantial ECMO transport experience
While transport of patients on ECMO has been was reported by teams from Sweden,12,13 Ger-
reported since the earliest days of extracorpo- many,14,15 France,16,17 and in Asia by Taiwan.18
real support, relatively few centers have large Reported survival rates of patients transported
experience of inter-hospital ECMO transport. with ECMO support have essentially equaled
This chapter hopes to provide useful informa- those for whom ECMO was initiated “in-
tion on the history and published outcomes of house” and compared to international outcomes
ECMO transport, as well as practical informa- reported to the Extracorporeal Life Support
tion on the system requirements for successful Organization (ELSO) Registry.5,9,13 Although
transport of these critically ill, mechanically the initial reports involved neonatal and pedi-
supported patients. atric patients, over the last two decades all age
groups have been successfully transported on
Inter-Hospital Transport ECMO. In recent years, however, interest in
ECMO support of adults with acute, refractory
History and Published Outcomes respiratory failure has further increased follow-
ing the publication of the CESAR trial from
Bartlett and colleagues in 1977 published the United Kingdom19 and following several
the first report of two pediatric patients trans- reports of successful ECMO support of patients
ported between hospitals while supported with with ARDS caused by pandemic H1N1 influ-
599
Chapter 55
enza.20-28 A number of these reports involved such emergencies.21 Transportation of patients

patients successfully transported to a regional already on ECMO is referred to as a Secondary
ECMO center while on ECMO.21,24,26,29,39 This Transport. Obviously, centers with the ability to
resurgence of interest in transport of adults with perform Primary Transports also can do Second-
severe ARDS using ECMO has also coincided ary Transports and we will therefore focus on
with the introduction into clinical use of increas- Primary Transports below.
ingly compact, lightweight ECMO pumps and
circuitry, which will be discussed below. Transport Logistics
Indications for Inter-Hospital ECMO The mission is to transport an extremely

Transport sick and unstable patient on ECMO from the
referring hospital to an ECMO center, usu-
The most common indication for transport- ally your own facility. The transport consists
ing a patient supported with ECMO is the need of three parts, namely: 1) transportation of
to move a patient from a center that does not the team including equipment to the referring
provide ECMO to an experienced ECMO center. hospital, 2) procedures at the referring hospital
Conventional transport of these unstable criti- (assessment of the patient, cannulation for and
cally ill patients may be hazardous and deaths initiation of ECMO, stabilization, preparing for
have been described.19,31 High frequency oscil- transport etc.), and 3) transport to the ECMO
latory ventilation (HFOV) and inhaled nitric facility. In most instances transport starts with
oxide (iNO) may also complicate a conventional a phone call from the referring hospital and a
transport. Consequently, patients are often can- decision is made to launch the team for patients
nulated by the transport team at the referring who fulfill ECMO criteria. Once the decision is
hospital and this is referred to as a Primary made, team members are contacted, equipment
Transport.32 is packed, and transport vehicles are organized.
Another common reason for inter-hospital The main priority to reach the referring hospital
transport of an ECMO patient is the need to is to minimize time in order to secure the patient,
move the patient already on ECMO to a cen- while the dominating priority when transporting
ter with certain specialized services, such as the patient to the ECMO center is patient safety.
cardiac or lung transplantation. Some centers Time during the latter part is of less importance.
have the ability to initiate ECMO treatment in
an emergency situation but not to continue for
the whole treatment period. These patients may
thus be transferred to an established ECMO Table 55-1. Properties of ground ambulance,
center. Occasionally, a particular ECMO center helicopter, and fixed wing aircraft (from ELSO
guidelines32). (Courtesy of Carl Chipman, R.N.,
may find it necessary to transport a patient to Arkansas Children’s Hospital)
another center if the number of patients requir- Ground Ambulance Helicopter Fixed Wing
ing ECMO exceeds available ECMO staff and Space for team and Sufficient More limited
Aircraft
Variable
equipment. Certainly a pandemic respiratory equipment
Noise
(4-5 team members)
Relatively little
(3-5 team members)
Very loud
(≥4 team members)
Loud
illness, such as the 2009 H1N1 influenza epi- Distance for
reasonable transport
Up to 400 km
(250-300 miles)
Up to 650 km
(300-400 miles)
Any distance
demic, may place enormous strain on a center’s times

Weight limitations Unlimited Limited Variable
(impacted by (depending on
capability to provide care for large numbers of distance and aircraft and
weather) conditions)
ECMO patients.33,34 Such lessons make a strong Loading and securing Relatively easy
equipment and
Relatively easy Variable
(depending on
case for regionalization of ECMO care and for ECMO circuit/patient equipment and
aircraft model)
proactive planning of potential responses to Cost ++ +++ ++++
600
Transport Vehicle ing a helicopter, though fixed wing aircraft have

been used for longer distances and occasionally
Most often the same vehicle travels to and ground ambulance has been used for transport
from the referring hospital. However, on occa- within the state of Arkansas. Currently, Arkan-
sion, such as when the desired vehicle remains sas Children’s Hospital uses the Sikorsky S-76
unavailable, it may be quicker to reach the aircraft for helicopter transport and a Beechcraft
referring hospital with another vehicle (ground King Air for fixed wing transport. Aircraft
emergency vehicle, taxi plane, etc.) not capable used by other centers with ECMO transport
of patient transportation. Local circumstances experience may range from small jet planes
at different centers may also play a role. like Cessna Citation II13 to massive military
Several factors together dictate the choice transport aircraft.3,7,12 In recent years, increased
of transport vehicle for inter-hospital ECMO use of centrifugal pumps with smaller footprints
transport, including distance, weather, team has resulted in more compact transport ECMO
composition, and vehicle availability. Each circuits, allowing for use of smaller aircraft in
mode of transport has unique advantages and some circumstances. One company currently
disadvantages (Table 55-1). Transportation markets a very compact, lightweight (10 kg),
with fixed wing aircraft also requires ground portable cardiopulmonary support system with
transportation between hospital and airport at self-contained membrane oxygenator, cen-
both ends. In hospitals equipped with helicopter trifugal pump, and arterial and venous pressure
pads the team loads the patient directly into monitoring capability. This system has been
the helicopter, obviating ground transporta- successfully used in air transport of ECMO
tion. The ELSO guidelines recommend ground patients in relatively small aircraft.35 Any air-
transportation for distances up to 400 km (250- craft chosen for inter-hospital ECMO transport
300 miles), helicopter for distances up to 650 must have doors that allow easy patient load-
km (300-400 miles).32 Fixed wing aircraft can ing and unloading (Figures 55-1 and 55-2) and
transport any distance. mechanisms for quickly and easily locking the
At Arkansas Children’s Hospital, most transport ECMO equipment to the floor. All ap-
ECMO transports have been accomplished us- propriate transport vehicles, ground or air, must
Figure 55-2. This patient has just been

Figure 55-1. Arkansas Children’s Hospital unloaded from a Cessna Citation II aircraft.
transport ECMO sled is about to be loaded into Note that the ECMO cart is separate from the
the Beechcraft King Air Aircraft. Note that all stretcher and is standing on the ground. The
equipment is mounted on the sled and that it ECMO physician is holding the tubing between
is all in one piece. the ECMO machine and the patient.
601
Chapter 55
have an electrical source capable of standard On arrival at the referring institution, the
voltage (110 V or 220 V), 60 cycle power to team must assess the patient and review labora-
the ECMO equipment as well as oxygen sup- tory data, radiographs, and any other pertinent
ply (other than transport oxygen cylinders) and clinical data. While in most instances it becomes
suction. Transport vehicles must also possess clear at the time of the referral call that the pa-
adequate climate control. tient is an ECMO candidate, occasionally the
patient deteriorates before the transport team
Personnel arrives to the point that ECMO support is no
longer appropriate (eg, a prolonged cardiac ar-
Different centers have very different com- rest after team takeoff with evidence of severe
position of their ECMO transport teams. This neurologic injury upon team arrival) or new
may depend on different competencies in dif- data may have become available indicating a
ferent professional groups, different traditions, relative contraindication for ECMO. Or, the
and other local circumstances. For example, patient improves significantly so that ECMO
in most centers perfusionists prime the circuit, becomes unnecessary. In such situations, the
while in other centers this is accomplished by a medical physician must possess the experience
nurse (R.N.) or a doctor with special education. to evaluate the patient, derail the initiation of
The ventilator can be managed by a respiratory ECMO support if necessary, and to discuss such
therapist (R.R.T), nurse, or intensivist. Most difficult decisions with the referring hospital
often a pediatric or cardiothoracic surgeon staff and the patient’s family. Assuming that
cannulates the patient, although some centers the patient remains a candidate for ECMO upon
have reported safe percutaneous cannulation for transport physician assessment, he/she must
pediatric ECMO outside of the inter-hospital inform the patient’s family and obtain informed
transport setting.36,37 At least one case report de- consent for ECMO support and for transport
scribed percutaneous ECMO cannulation prior (legal responsibilities vary between different
to ECMO transport.38 However, most published countries) and to assume medical management
series of pre-transport percutaneous ECMO can- of the patient during cannulation, including pro-
nulation have been in adult patients.39-42 vision of further deep sedation during cannula
When configuring the transport team, the placement and administration of a heparin bolus
responsibilities of each member should be around the time of cannula insertion.
clearly defined, including the capability to make The ELSO guidelines provide an example
the final patient evaluation decision regarding of the composition of a transport team.32 This
candidacy for and mode (VA, VV) of ECMO, team consists of a cannulation surgeon, a surgi-
cannulate the patient, assemble and prime the cal assistant, an ECMO physician, an ECMO
ECMO circuit, initiate ECMO treatment, sta- specialist, and a transport R.N./R.R.T. The
bilize the patient, check cannula positions with Arkansas Children’s Hospital ECMO trans-
ultrasound and/or radiograph, and to safely port team includes an ECMO coordinator, a
transport the patient to the ECMO facility. The pediatric surgeon, a surgical assistant, and
team should also be prepared for troubleshoot- an intensive care physician.9 The Karolinska
ing when unexpected difficulties arise. All transport team is relatively similar consisting
responsibilities must be met by experienced of an ECMO physician, an ECMO coordinator,
personnel as there will be no backup. For sec- a cannulating surgeon, and when possible also
ondary transports (when the patient already is on a scrub nurse.13 Other examples of transport
ECMO) competence for cannulation obviously teams are the University of Michigan team with
does not have to be included in the team. a critical care surgeon, a critical care fellow,
602
and two ECMO specialists5 and the Columbia Transport Equipment

University Medical Center transport team with
one cardiothoracic surgeon, one surgical fellow, The realities of space and weight limitations
two perfusionists, and two critical care para- during transport impose significant limitations
medics.11 The Wilford Hall Medical Center has on the amount of equipment that can be car-
used larger transport teams consisting of 10-15 ried, yet the transport team must operate in a
persons, but frequently performed extremely self-sufficient manner. While in some cases
long transports.6 specialized equipment (eg, surgical supplies)
Once on ECMO, the need for aggressive may be available at the referring hospital, it
mechanical ventilation obviously lessens, but is unwise to count on widespread availability
it remains important to maintain lung volumes of very specialized equipment, particularly in
during transport with a consistent level of posi- pediatric sizes. The ECMO transport team may
tive end-expiratory pressure (PEEP), particu- choose to rely on the referring hospital phar-
larly during transport of the patient supported macy for some medications including sedative
with venovenous ECMO in order to prevent the and analgesic infusions for the transport, to
negative effects on right ventricular function of minimize the amount of medication that must
increased pulmonary vascular resistance. be carried. In all cases, the transport team relies
Finally, pilots and ambulance drivers rep- on the referring institution to provide blood
resent crucial members of the ECMO transport products necessary for ECMO circuit priming.
team. ECMO transport can involve long dis- The teams should send the referring intensive
tances and more often than not involves “ground care unit a list of necessary blood products prior
times” at the referring hospital that are much to departure if it is unavailable on your website
longer than most conventional critical care and to request that those blood products be ready
transports. Certainly this is the case if cannula- upon the team’s arrival (Figure 55-3).
tion is necessary at the referring hospital. When A defined process, including role assign-
arranging the transport, care should be taken to ments and checklists, ensures that the ECMO
ensure that pilots and drivers do not violate duty transport team leaves home with all necessary
hour restrictions or crew rest regulations during equipment.32 At both Arkansas Children’s
a lengthy transport. Hospital and Karolinska, the ECMO specialist
Referrring Hospital Check List for Pediatric/Adult ECMO Patients
Blood Bank Requirements (packed in a cooler to go with team if not used at your facility)
• 4 units PRBCs (fresh if possible)
• 1 unit platelet pheresis
• 1 unit FFP
Patient Requirements
• The patient should have a foley placed to a closed drainage system
• The patient’s head should be turned to the left if cannulation is not already attained
(cannulation is done using the right neck in infant and pediatric patients).
**If the patient is too unstable moving can wait untilt ECMO team arrives.**
The ECMO team carries all necessary equipment for cannulation. Please be sure to have a stretcher at
the helipad / ER ambulance entrance to help with transporting equipment.
For questions plese contact the ECMO Coordinator.
Thank you for your assitance. It is greatly appreciated.
Figure 55-3. Example of a list of necessary blood products being faxed to the referring hospital before
arrival of the mobile ECMO team (from Arkansas Children’s Hospital).
603
Chapter 55
and another designated ECMO team member The medical equipment used in ECMO
review the equipment checklist in detail prior transports is basically the same as in-house
to departure to ensure all needed equipment ECMO treatment, although the specific trans-
is loaded. Figure 55-4 shows a copy of the port environment may impose specific require-
Arkansas Children’s Hospital ECMO transport ments regarding size, weight etc. Furthermore,
equipment checklist. Note the inclusion of for all air transports the equipment must be
oxygen cylinders, a transport monitor, point- tested regarding electromagnetic interference
of-care testing devices, and other such “routine” with flight controls and be approved by national
transport equipment, as well as more ECMO- regulatory agencies. It also must sustain the
specific items.
Mobile ECMO Checklist – ECMO Cannulation Pending
Pre-Flight Equipment Checklist – To be completed prior to every transport

Istat and transport bag
Adequate supply of Istat cartridges (ACT, EG7, Glucose, CG4)
Istat Electronic QC device
Ventilator
Sprint Pack (batteries X2) and wall cord
Oxygen high pressure tubing for vent (green curly cord)
Ventilator circuit with HME
Wall plug in box/cord
O2 Cylinders X 2 (One for sweep gas, one for vent)
Green Sleeves for O2 cylinders (attaches tanks to side of stretcher (borrow from transport))
Regulator with micro flowmeter (for sweep)
Regulator with Quick connect (for vent)
Tubing clamps X 8
Extension cord
Sigma IV pumps (preferred over syringe pumps if able) +2 extra pumps
Syringe pumps (as necessary) +2 extra pumps
UPS Cart
Yellow Drug Box/Bag from Pharmacy (ECMO drugs)
Monitor functioning and all necessary probes/leads attached
ECG, POx, IBP Cables, Temp probes X 20
Toolbox (optional after serious consideration)
Straps (patient belt type and securement for equipment)
Portable suction pump
Canister
Suction tubing
Yankeaur
Coordinator Pack stocked for prospective transport
Proper drugs and dose available per patient weight (D25, HCO3, CaCl, MgSO4, 5% albumin).
Proper connectors packed according to circuit size and manipulation
Coordinator Pack Stock list verified
Grey Pack
Membrane Lung
1L Plasmalyte “A”
Appropriate size of spare circuit tubing
Back up blood pump
Appropriate size Better Bladder
Spare tubing
Figure 55-4. Example of a checklist of equipment being brought by the mobile ECMO team (from
Arkansas Children’s Hospital).
604
vibrational and acceleration/deceleration forces equipment weighs 175 lbs (80 kg) with a
of the flight environment. primed circuit. The stretcher reaches 72 inches
Early reports of ECMO inter-hospital (183 cm) in length, 18 inches (46 cm) in width,
transport described the use of roller-head and 30 inches (76 cm) at its maximum height.
ECMO pumps and silicone membrane oxy- Currently the team uses either a Levitronix
genators of various sizes, as was typical of Centrimag (Levitronix Company, Zurich,
pediatric and neonatal ECMO practice.1,3,4,7,10 Switzerland) or Maquet Rotaflow (Maquet
At Arkansas Children’s Hospital, the first 112 Cardiovascular, LLC; Wayne NJ, USA) cen-
patients transported with ECMO from 1990- trifugal pump mounted to the pump mounting
2008 were transported with a roller-head pump bracket located over the patient’s feet. Other
circuit.9 Such circuits required a large blood centers such as Karolinska employ a separate
prime volume and had a large “footprint.” As stretcher and ECMO cart.13 This requires longer
discussed elsewhere, recent years have seen tubing but minimizes the weight of the stretcher
the widespread adoption of small, lightweight holding a patient. For air transports the stretcher
centrifugal pumps and hollow fiber oxygenators with the patient is first lifted into the airplane
that require a smaller priming volume. Since and then the ECMO cart separately afterwards.
2009, Arkansas Children’s Hospital center has During transport the team uses a standard trans-
accomplished transports using such a smaller port patient monitor and the standard transport
centrifugal pump driven ECMO circuit. This ventilator. An iStat (Abbott Point of Care Inc.)
change resulted in an approximate 40% de- device is used during transport to monitor arte-
crease in the amount of priming blood and rial blood gas, electrolyte, and activated clotting
a reduction in the ECMO transport system time (ACT) values. Pre-pump pressure and
weight by approximately 50 pounds (23 kg). preoxygenator and/or postoxygenator pressures
Today most centers use centrifugal pumps for are preferably monitored.
transport5,11,13,43-46 as recommended in the ELSO Again, the ECMO transport team operates
guidelines due to improved functionality and very much on its own and must be self-suffi-
safety in combination with a shorter circuit. cient with regard to all supplies. This does not
As has been previously discussed, recently in- only include medications, intravenous fluids,
troduced and commercially available compact, disposables (syringes etc.), but also backup
portable ECMO systems weigh as little as 10 components of the ECMO circuit (eg, extra
kg.35 oxygenator, pump head, tubing, connectors).
The transport stretcher or sled varies be- An uninterruptible power supply UPS unit is
tween centers. Many centers have developed necessary in case the transport vehicle at the
their own system, where stretcher and the outside facility is not properly equipped with
ECMO components are assembled in one unit. a generator and the power supply gets low.
This configuration shortens the length of tubing Redundancy is a crucial principle in planning
and minimizes the risk for tubing kinking etc. equipment for inter-hospital ECMO transport
during loading and unloading. A commercially to ensure a backup is available for any critical
available ECMO transport system is visible failed component.
on the ELSO web site (www.elso.org). The
Arkansas Children’s Hospital transport ECMO Adverse Effects/Transport Complications
stretcher is constructed utilizing a Lifeport
base with custom made arch reinforcement, Although outcomes (survival to hospital
mounting brackets for infusion pumps, and discharge), as mentioned above, do not differ
electrical power strips (Figure 55-1). The between patients transported on ECMO and
605
Chapter 55
those cannulated in-house,5,9,13,47 two deaths Most equipment is stored in sealed pre-packed
during transport have been described.5,13 Both bags and the rest is quickly packed with the aid
patients were on VV-ECMO and suffered car- of check lists. The transport ECMO program at
diac arrhythmias with circulatory arrest during Arkansas Children’s Hospital, historically one
the transport. of the busier American programs, averages only
A variety of equipment malfunctions dur- approximately 6-8 transport ECMO requests
ing transport may occur.3,4,7-10,12 Adverse ef- annually. Each team member usually performs
fects also occur frequently, reported in 27 % other duties at the time of the referral call. Thus,
of transports,13 and categorized into 5 major the response time of the ECMO transport team
groups: patient, staff, equipment, vehicle, and is NEVER what one would expect of a con-
environment. Most adverse events occurred in ventional pediatric critical care transport team,
the patient category (22%), where loss of tidal and has ranged from 2 hours to 24+ hours (with
volume (13%) was the most common. Other the longer delays tending to be in the cases of
patient events included bleeding, cardiac stun, patients already supported on ECMO at the
hypovolemia etc. In other categories a large referring institution). It is always important to
number of different adverse effects were seen, relay realistic expectations about team response
such as clotting of the ECMO circuit, broken time to the referring physician and institution.
lab device, syringe pump failure, broken heater, As often occurs with critically ill patients,
ambulance traffic accident, and freezing of events often deviate from detailed plans. These
intravenous lines. Broman et al. conducted a deviations can include unexpected change in
retrospective investigation of 452 inter-hospital the patient condition, equipment malfunction,
transports between 2010 and 2015.47,48 Adverse weather delays, or many other possible compli-
effects were seen in 25% of transports. In 2.2% cations. The team must be able to troubleshoot,
the adverse effect was judged as an immediate adapt, and remain calm in trying circumstances.
+threat to the patient (clotting of ECMO circuit, Again, ECMO transport is no place for the inex-
inadequate ECMO, system/pump change, oxy- perienced ECMO specialist or physician to “go it
genator clot, cannula clot, IV line/air into the alone.” ECMO transport often creates gray hair,
circuit) and in 15% as a high risk event (loss and it is a situation that tends to prove the value
of tidal volume, bleeding, circulatory instabil- of earned gray hair.
ity, broken ventilator circuit, reload in ambient Since inter-hospital ECMO transport in-
temperature, broken sweep gas supply, power volves moving the most critically ill, technology-
supply, recirculation). dependent patients, the importance of obtaining
extremely detailed clinical information at the
Practical Points Regarding the Process time of the referral call cannot be over-empha-
sized. A systems-based intake form allows the
The response time for an ECMO transport team the clearest possible picture of the patient
team “take off” after a referral call varies be- before departure. If an ECMO-supported pa-
tween centers. It much depends on the local tient is transported for further intervention such
organization, which in turn depends on the as cardiac surgery or consideration for cardiac
demand for transports. In other words, a busy transplant, detailed discussions with those clini-
transport program can more easily build an cal services should ensue before the transport
organization with a shorter response time. At team ever leaves home.
Karolinska, which currently performs 1-2 trans- ECMO transport is expensive and resource-
ports every week, the transport team goal is to intensive, requiring full institutional support. It
depart within 60 minutes from a referral call. is the picture of a multidisciplinary team coming
606
together to care for the sickest of patients. Clear situations, although credit cards are useful in
lines of communication must remain open among most such situations.
the ECMO team, the transport team, medical and
surgical teams, referring and receiving intensive Long Distance Transports
care units, and hospital administration.
One specific practical issue includes the con- These transports will mostly be internation-
sideration of “ECMO taxi,” or ECMO transport al or intercontinental and have been performed
to a third facility. Occasionally an established by several groups.6,14,49 The importance of bring-
transport ECMO program may be asked to move ing adequate supplies, medication, oxygen etc.
a patient supported with ECMO not back to its cannot be overemphasized. The team should
own institution but to another center. Such a consider the risk for significant delays during
request could occur due to specialized services the transport when calculating supply needs.
available at the destination hospital (eg, evalua- The need for extra staff should be considered.
tion for lung transplantation) or due to the refer- The number of team members with continuous
ring institution or physician’s referral patterns, or responsibilities throughout may need to be
due to potential hardship imposed on the patient’s increased On the other hand the cannulating
family by having to travel great distances. Taxi surgeon is active only during the final assess-
transports have, among other institutions, been ment of the patient and cannulation procedure
performed by the USAF program at Wilford and then stands by for surgical emergencies
Hall, Arkansas Children’s Hospital, and Karo- during the remainder of the transport (Karo-
linska.7,9,13 Again, ECMO transport is extremely linska organization), and can work without an
expensive, and such a “third-party” transport assistant. During intercontinental secondary
service requires much forethought by ECMO transports it can be advisable to bring surgi-
team leaders and hospital administrators regard- cally competent staff for patient safety reasons
ing the financial cost and the personnel cost of in case of emergencies even if the work load is
providing “ECMO taxi.” expected to be nil.47
Special Transport Situations Environmental/Climate Issues
International Transports When patient transports occur in an arctic

environment with extreme cold it is unadvis-
The team must understand the standard of able and may be hazardous to load the patient
electrical sockets and gas outlets at the refer- into the aircraft outdoors. In a temperature
ring hospital and compliable gas and electrical of -30o C (-22o F) stopcocks and infusion
adaptors must be brought. Each transport team lines will freeze within 30 seconds. Neonates
member must carry a passport. The team should and small children will become hypothermic
request the referring hospital to provide the within a few minutes. If a warm hangar is un-
patient’s passport. Medico-legal issues should available, it might be necessary to undertake
be analyzed in advance. In other words, what a long road transport to the receiving facility
legal ramifications exist for the team in the or to the closest airport with a warm hangar.
case of a serious complication or death of the An alternative is a large military transport
patient prior to departure from the referral in- aircraft into which the ambulance is loaded.12
stitution. Lastly, it is advisable to bring local or It should also be noted that practical working
internationally valid currency for unexpected environment in the transport vehicle can tough.
Helicopters and aircraft are frequently noisy.
607
Chapter 55
The space is limited (Figure 55-5) and even cal value in many cases, frequently impacting
minor patient or circuit procedures be difficult treatment.53,55,56
to accomplish. One may conclude that intra-hospital
transports of ECMO patients require extensive
Intra-Hospital Transport of Patients planning and logistics and a well-defined pro-
Supported with ECMO cess but often yield diagnostic information or
therapeutic intervention crucial to patient care.
Before leaving the topic of transporting
patients supported with ECMO, it is important Conclusion
to address the less glamorous but still vital topic
of intra-hospital transport. The need for ECMO Transport of a patient supported with
patients to undergo diagnostic or therapeutic in- ECMO is technically feasible and reproduc-
terventions outside of the ICU arises with regu- ible by a number of centers for over two de-
larity, and the ECMO team must be prepared.50-54 cades. Successful ECMO transport requires
Such a transport should be viewed as an inter- careful planning and coordination of a skilled
vention with potential risks and benefits, but can multidisciplinary team as well as clear com-
be performed safely without complications.54,55 munication between the referring and receiving
The perceived high risk of moving an ECMO institutions. Recent advances in the design of
patients could potentially lead to reluctance to equipment used for extracorporeal life support
transport the patient for an intervention such as make ECMO transport more feasible than ever
a computed tomography (CT) scan, and thus to a for an experienced ECMO team. ECMO is
delay in diagnosis or therapy. In order to move a growing worldwide with an increasing demand
patient supported with ECMO safely within the for transports on ECMO. It has been suggested
hospital (eg, for CT scan, to the cardiac catheter- that networks of hospitals should be created
ization suite, to the operating room), the team around each ECMO center located in tertiary
must have a pre-defined process that includes referral hospitals and that each such network
checklists of necessary equipment, personnel, should create mobile ECMO teams for retrieval
and time required for such a move. Prodhan of patients,57 which currently is the situation in
and colleagues reviewed the experience of the Great Britain (see chapter 66).42
Arkansas Children’s Hospital ECMO team
over a 10-year period in intra-hospital transport
to evaluate the hypothesis that intra-hospital
transport of ECMO patients is associated with
clinically important diagnostic and therapeutic
interventions.55 During the time period studied,
out of a total of 471 ECMO patients, 37 patients
required 57 intra-hospital transports (37 trips
for cardiac catheterization and 20 trips to CT
scan). In the majority of patients transported for
cardiac catheterization, a finding was identified
that was not noted on echocardiogram and/or a
management change (including cardiac surgery)
occurred due to the information obtained during
Figure 55-5. Patient on ECMO inside a Cessna
catheterization. CT scans of brain, thorax, and Citation II aircraft. The environment is not only
abdomen have also shown to have great clini- noisy but also cramped.
608
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612
56
ECMO for Septic Shock
Graeme MacLaren, MBBS, FRACP, FRCP, FCICM, FCCM, Warwick Butt, MBBS, FRACP, FCICM
Introduction • Leucocytosis, leucopenia, or >10% imma-

ture neutrophils
The third international consensus definition
of sepsis in adult patients has been recently The exact values that define many of these
updated to “life-threatening organ dysfunc- parameters vary with age and can be found in
tion caused by a dysregulated host response to the consensus statements of various societies.2-3
infection.”1 The term ‘severe sepsis’ has been Severe sepsis occurs when organ dysfunction,
abandoned and the new definition of septic hypoperfusion, or hypotension are present.
shock is a “subset of sepsis in which underlying Septic shock is defined as severe sepsis with
circulatory and cellular/metabolic abnormalities hypotension and hypoperfusion which per-
are profound enough to substantially increase sist despite adequate fluid replacement. The
mortality.”1 In clinical practice, septic shock in definition of refractory septic shock varies4
adult patients is defined as infection associated but the most comprehensive and apposite is
with 1) persisting hypotension requiring vaso- that of the American College of Critical Care
pressors to maintain a mean arterial pressure Medicine (ACCM): Shock that persists despite
above 65 mmHg despite volume resuscitation goal-directed use of inotropes, vasopressors,
and, 2) a serum lactate level above 2 mmol/L.1 vasodilators, and maintenance of metabolic and
These definitions were written without consider- hormonal homeostasis.5
ation for pediatric sepsis. At the time of writing, Sepsis is one of the leading causes of
it remains unclear whether the pediatric critical mortality and morbidity worldwide. Although
care community will ignore the new definitions, case fatality rates appear to be falling in some
modify and adopt them, or establish new defini- countries, population-based mortality rates
tions of their own. Until then, the older defini- and hospitalization rates with severe sepsis are
tion of sepsis still can be applied to children, increasing.6,7 In high income countries, adult pa-
which is a systemic inflammatory response to tients admitted to the intensive care unit (ICU)
infection. A systemic inflammatory response with a diagnosis of severe sepsis have hospital
consists of two or more of the following: mortality rates between 27–32%.7-10 In the USA,
children hospitalized with severe sepsis have
• Fever or hypothermia mortality rates of up to 10%.10,11 The mortality
• Tachycardia (or bradycardia in infants) in children admitted to ICU with a diagnosis of
• Tachypnea or hypocapnia septic shock is approximately 17%.7 The most
613
Chapter 56
important determinant of the likelihood of death This chapter will outline the indications and
is the development of shock. 12,13
contraindications for ECMO in sepsis, review
Sepsis was historically regarded as a con- the hemodynamic responses to infection in pa-
traindication to ECMO. In the 1990s, however, tients of all ages and the implications these have
a number of studies demonstrated that it could for cannulation strategies, discuss circuit man-
be lifesaving in neonatal and pediatric septic agement in sepsis, and summarize outcomes.
shock,14-17 a view strengthened by recent re- The chapter will focus on the use of ECMO as
ports involving larger numbers of patients.18-20 circulatory support in refractory septic shock,
ECMO for refractory septic shock in neonates which requires more detailed consideration than
is now regarded as a standard indication for isolated respiratory failure from sepsis.
extracorporeal support, with survival rates of
approximately 75-80%.5,19, 21 However, uni- Indications
versal acceptance of ECMO for septic shock
in older patients has been limited by the ret- It was suspected for many years that septic
rospective uncontrolled studies on the subject, patients being placed on ECMO for respiratory
historically poor outcomes in some centers, support of sepsis-induced ARDS or bacterial
lack of comparative evaluation of cannulation pneumonia had worse outcomes than similar
strategies, and perhaps by an under-appreciation patients without sepsis. This has been shown
of the pathophysiological and hemodynamic not to be the case and neither sepsis nor bacte-
responses to infection with changes in age. The remia at the initiation of ECMO are predictors
American College of Critical Care Medicine of poor outcome.22,23 However, the acquisi-
(ACCM) recommends that ECMO be consid- tion of new nosocomial infection during an
ered for refractory septic shock in children, but ECMO run can be detrimental.24-27 Pneumonia
they anticipate survival rates no higher than or sepsis-induced ARDS often present without
50%.5 Whether better survival can be achieved significant circulatory dysfunction, in which
with newer and safer types of ECMO technol- case the indications and cannulation strategies
ogy remains a question awaiting multicenter for ECMO are similar as for other causes of
evaluation. No comparable guidelines exist for hypoxic respiratory failure (see Chapters 9,
adult patients. 18, and 36). Some of these patients may have
Sepsis is predominantly associated with hypotension, caused by many factors including
only one pulmonary pathophysiological re- severe hypoxia, hypercapnia, pulmonary hy-
sponse (ie, acute respiratory distress syndrome; pertension or right heart dysfunction. However,
ARDS) but a multitude of hemodynamic re- these secondary cardiovascular effects usually
sponses including dilation and failure of one improve substantially with adequate venove-
or both ventricles, an increase in pulmonary nous (VV) ECMO, with its attendant effects on
vascular resistance, and a fall in systemic vascu- oxygenation, acid-base balance, carbon dioxide,
lar resistance, all of which may exist in relative temperature, and intrathoracic pressure.
isolation or in combination.4,5 ECMO can be In pediatric septic shock, the indication for
used to support patients with severe sepsis and ECMO is straightforward only in principle: It
any combination of: has been regarded as the therapy of last resort,
• ARDS when shock is refractory and continues to prog-
• Right heart failure ress despite all attempts at ventilation, fluid,
• Left heart failure, and/or pharmacological, and disease-modifying thera-
• Combined cardiogenic and distributive py, or when cardiac arrest has ensued. However,
shock the exact criteria when ECMO should be insti-
614
tuted have not been the subject of prospective in young adults who present with distributive
study and clinicians must rely on clinical expe- shock then develop progressive left ventricular
rience and judgment. The ACCM summarized dysfunction and are placed on ECMO before
one approach in a consensus statement on the cardiac arrest occurs.32
hemodynamic management of pediatric septic
shock.5 The rapidity of shock progression and Contraindications
physiological decline is more important than
the absolute amount of inotropic support, but in The standard contraindications to ECMO
general ECMO should be considered if a child: apply in septic patients, such as preexisting
severe neurological dysfunction or incurable
• Is receiving doses of >1 mcg/kg/min of malignancy.33 An additional consideration is
epinephrine or its equivalent (ie, an inotrope the septic oncology patient. Oncology patients
score28 >100) have been regarded as poor ECMO candidates,
• Has had aggressive fluid replacement and but this view is anachronistic and outcomes are
other pharmacological strategies described acceptable in some instances. One exception
by the ACCM consensus statement5 to this is allogeneic bone marrow transplant
• Continues to deteriorate with worsening recipients, who have dismal outcomes.34 Chil-
hypotension, rising lactates, or rapidly dren who have received stem cell transplanta-
progressive multiorgan dysfunction despite tion and require ECMO have somewhat better
treatment outcomes but survival to hospital discharge
is still only 10%.35 Neutropenic sepsis is not
The speed at which ECMO can be initi- a contraindication to ECMO per se, but it is
ated is institution-dependent and this must be difficult to do because of the other morbidities
borne in mind by clinicians seeking to try every that often coexist in this patient group – such as
possible less invasive strategy in children with thrombocytopenia – and long-term survival may
rapidly progressive shock. Although several not be as good as for other indications. Nonethe-
children have been successfully resuscitated less, successful outcomes have been reported.36
from cardiac arrest caused by progressive sep- The type of infecting organism should not
tic shock and yet completely recovered,18 it be regarded as a major determinant of the appro-
is clearly more desirable to intervene before priateness of ECMO although some organisms,
arrest occurs. The timing of this will depend most notably Bordetella pertussis and herpes
on how quickly an institution can mobilize an simplex virus (HSV) in infants, are associated
emergency ECMO team. Parallels can be drawn with poorer outcomes.37,38 In the absence of
to fulminant myocarditis, where the exact tim- other contraindications, the infecting microbe
ing of mechanical support is based on clinical usually has minimal bearing on whether ECMO
experience and institutional resources, rather is offered or not, and is often not known at the
than by prospectively studied, specific criteria. time.
There have been increasing reports of
ECMO for adult septic shock,29-32 with survival Cannulation Strategies
rates ranging from 15%-71%. Poorer outcomes
have been seen using peripheral venoarterial Cannulation is one of the most important
(VA) ECMO in patients with distributive shock, management issues in ECMO for sepsis and
in patients who have had cardiac arrest as a re- must be individually tailored to the patient’s
sult of septic shock, and in patients older than circulatory and respiratory status. An under-
60 years.29-30 Better outcomes have been seen standing of the pathophysiology of septic
615
Chapter 56
shock coupled with adequate hemodynamic impaired oxygen delivery. The age at which a
information is vital in planning an appropriate child will alter their hemodynamic response
cannulation strategy. from left heart failure (‘cold’ shock) to distribu-
For sepsis-induced isolated respiratory tive shock (‘warm’ shock) is highly variable and
failure requiring ECMO, VV cannulation is cannot be reliably predicted from the child’s age.
preferred because it is associated with better However, by late adolescence and into adult-
outcomes. VV-ECMO avoids the complications hood, the near universal hemodynamic response
of VA-ECMO such as systemic embolization, to sepsis is distributive shock. This response
arterial trauma, and increased left ventricular is characterized by a reduction in ventricular
afterload, while preserving pulmonary blood function, an increase in heart rate, a reduction
flow, pulsatile systemic flow, and oxygenation in vasomotor tone, and often by a reduction in
of blood in the systemic ventricle and thus the oxygen extraction at a mitochondrial level. The
coronary arteries.43,44 VV-ECMO is also pre- categorization of shock requires a combination
ferred in those patients with ARDS that persists of clinical assessment, blood tests (eg, venous
after resolution of shock, when the patient is oximetry, lactate), and echocardiography, with
ready to be weaned off mechanical circulatory or without measurement of cardiac output, and
support but not ready to cease extracorporeal is best done by an experienced intensivist.5
gas exchange because of ongoing respiratory Possible ECMO cannulation strategies be-
failure. In these instances, consideration should come apparent once the hemodynamic pattern
be given to changing to VV cannulation if it is of shock has been identified (Table 56-1). Those
anticipated that lung recovery will require more with right heart failure and concomitant respira-
than 1-2 days of further ECMO. tory failure can be supported with VV-ECMO
If ECMO is being considered primarily as if the shock is not particularly advanced, as the
circulatory support for refractory septic shock, consequent reduction in intrathoracic pressure
then the patient’s hemodynamic response to and optimization of oxygenation and carbon
sepsis must first be established. Septic shock dioxide clearance may be sufficient to improve
has three principle hemodynamic manifesta- myocardial performance and peripheral circu-
tions based on the most compromised part of lation, especially in small children. Otherwise,
the circulation: right heart failure, left heart peripheral VA-ECMO or central ECMO can
failure with poor systemic oxygen delivery, or be used.
distributive shock with poor oxygen extraction.5 In left heart failure, peripheral or high flow
In advanced cases a mixture of these may occur, central ECMO is appropriate. Serial echocar-
eg, adult patients who present with distributive diograms must be performed to monitor left
shock but later develop progressive ventricular heart distension. If this is worsening, then steps
failure, or children with a combination of car- should be taken to alleviate it before left atrial
diogenic and vasoplegic shock.18,20,32 distension and hypertension lead to pulmonary
Right heart failure associated with persis- edema or pulmonary hemorrhage. Increasing
tent pulmonary hypertension of the newborn is circuit flow may limit atrial distension; if un-
the most frequent manifestation of septic shock successful, then percutaneous atrial septostomy
in neonates. Right heart failure from a combina- can be performed on peripheral ECMO, or a left
tion of sepsis-induced ventricular dysfunction atrial vent cannula can be inserted on central
and high positive pressure ventilation can also ECMO, ie, biatrial drainage.
be seen in older patients. After the neonatal If the femoral artery is used in older chil-
period, septic children suffer from left ventricu- dren or adults then some centers advocate the
lar failure with preserved vasomotor tone and routine use of an anterograde perfusion cannula
616
Table 56-1. ECMO cannulation strategies in septic shock.
Hemodynamic Typical Cannulation Advantages Caveats Ref

Pattern Patient Options
45
Right heart Neonate VV - Prevents systemic - Cannot provide complete
failure embolization circulatory support
- Avoids differential - Inappropriate in
cyanosis advanced shock
- Fast
- May use 1 cannula
14,15,18, 65
Peripheral* - Direct circulatory - Limited flows
VA (carotid) support - Slight increase in
- Fast neurological
complications
18
Central* VA - Allows the highest - Requires cardiac surgeon
flow rates to cannulate
- Prevents - Increased risks of
differential bleeding and infection
cyanosis
16-18
Left heart Young Peripheral - As above - As above
failure child VA (carotid - Femoral cannulation
or femoral) requires anterograde
perfusion to avoid limb
ischemia
18,20
Central VA - May be associated - As above
with better
outcomes in
children
18,20
Distributive Older Central VA - Only strategy - ECMO unnecessary /
child or likely to achieve inappropriate unless pre-
adult sufficiently high arrest physiology
circuit flows
18,20
Mixed shock Any age Central VA - As above - As above
(eg, cardio-
genic and
vasoplegic)
18,20
Concomitant Any age Central VA - May be associated - As above
refractory with better
cardiac and outcomes in
respiratory children
66
failure VAV - Avoids risks of - Technically difficult in
central cannulation smaller children
- Facilitates easy - May be associated with
and immediate higher rates of hemolysis
adjustment of the because of the gate clamp
proportion of on the respiratory limb
respiratory and
circulatory support
- Prevents
differential
cyanosis
*Peripheral: Drains deoxygenated blood via jugular vein, femoral vein, or both. Returns oxygenated blood to carotid artery (young
children [<15kg]), femoral artery (older children or adults), or axillary artery (adults)
Central: Drains deoxygenated blood directly from right atrium ± left atrium. Returns oxygenated blood to ascending aorta
617
Chapter 56
to supply oxygenated blood to the affected leg would be useful in these patients. However,
to prevent limb ischemia. An additional consid- ECMO may have a role to play in those with
eration in patients on peripheral VA-ECMO is progressive ventricular dilatation who maintain
that coronary and cerebral arterial blood may be a high cardiac output initially, but later decline
supplied by the left ventricle and not the ECMO and suffer cardiovascular collapse. This sce-
circuit (ie, differential cyanosis). It is thus of nario has been described in adults with bacterial
considerable importance that an appropriate septic shock, but is uncommon.32 Distributive
amount of oxygen is provided by the ventilator shock with early refractory vasodilation may
depending on the severity of respiratory failure, also eventually lead to cardiac arrest. In these
and that a surrogate marker of coronary oxygen- rare patients, central ECMO has been used in
ation (eg, right radial artery blood, near infrared adolescent patients to achieve flows of up to 10
spectroscopy, right hand pulse oximetry) is L/min with good outcomes.20
used to monitor for possible complications.43,44
If there is decreased oxygen saturation in the Central Cannulation
right arm, then increasing peripheral VA flow
(if possible) and thus decreasing flow through Central cannulation is commonly used
the pulmonary circulation may be sufficient in most major pediatric and adult cardiac
to allow for adequate coronary and cerebral transplantation centers for other indications. With
oxygenation; if not, then an additional venous this technique, analogous to cardiopulmonary
drainage cannula may provide sufficient flow bypass, a cardiac surgeon performs a sternotomy
to avoid cerebral injury, either as an additional and cannulates the right atrium directly.
drainage cannula to increase total circuit flow Venous blood is pumped through the circuit
or as a return cannula to oxygenate blood as it and returned through a cannula placed in the
travels through the pulmonary circulation. This ascending aorta. The largest available cannulas
last solution, venoarteriovenous (VAV) ECMO, should be placed so as to maximize laminar
is technically challenging in small children but flow and minimize excessive negative pressures,
easily done in adolescents and adults. which might otherwise promote turbulent flow
Further explanation is necessary regard- leading to shear-stress on blood components
ing distributive shock and any possible role and hemolysis.49 Some ECMO programs use the
of ECMO. Adults with fatal septic shock die roller pump with gravity drainage into a bladder,
as a consequence of one of three mechanisms: but more recently the safety and portability of
multiorgan failure (most common), progressive Mendler-designed centrifugal pumps have seen
ventricular dilatation and cardiogenic shock their use increase. These pumps generate suction
(rare), or early refractory vasodilation (rare).46 which draws blood out of the patient and propels
Although distributive shock is associated with it through the circuit. The intensity of this
high cardiac output and vasoplegia, left ven- pressure requires monitoring, as hypovolemia or
tricular ejection fraction is usually depressed. cannula obstruction will limit inflow and create
In fact, preservation of ejection fraction and an increase in suction, with resultant turbulent
failure of the left ventricle to dilate in response flow, cavitation and potential red cell hemolysis.
to infection is associated with higher mortal- In small children and newborn infants in whom
ity,47 perhaps as a result of preexisting diastolic centrifugal pumps are being used, the pump inlet
dysfunction and poor ventricular compliance. pressure should be measured at the connection
Unlike in children,48 deaths from multiorgan between the atrial cannula and the inlet tubing,
failure in adults are late in the course of illness and should be maintained between -20 mmHg
and there is little reason to believe that ECMO and zero. If the pressure is consistently more
618
negative than -20 mmHg, then it should be 73% of patients who received central ECMO
assumed that the pump revolutions have been survived compared to 38% who received pe-
set too high, the patient is hypovolemic, or the ripheral ECMO (p=0.05).18 Although the study
cannulae are kinked, obstructed, or too small. was a small retrospective study from a single
Suggested cannula sizes and estimated flow center, it highlighted that central ECMO is a
ranges are listed in Table 56-2. In older children valid technique in septic shock. In a subsequent
being cared for in dedicated pediatric hospitals case series from the same center, 17 (74%) of
and requiring higher flows, either a second 23 children supported with central cannulation
drainage cannula can be inserted, or larger sized for septic shock survived to hospital discharge.20
cannulae may have to be sourced from amongst Many of these patients have received long-term
cardiopulmonary bypass cannulae in nearby followup. There have been no survivors with
adult institutions. If possible, the skin should severe disability and the majority of survivors
be sutured around the cannulae to minimize made a complete recovery.18,20,50
bleeding, and the defect between the sternal
edges closed over with a Silastic membrane Management on ECMO
sutured into place.
Possible benefits of this technique in- For patients with circulatory failure on VA-
clude18,20,31,49: ECMO, the goals of ECMO are the same as for
other indications: restore organ blood flow and
• Achieving very high flow rates, which may adequate tissue oxygenation while awaiting
lead to faster resolution of shock recovery, without causing damage to the lungs
• Avoiding differential cyanosis (as all blood or heart. The ECMO pump now becomes analo-
is introduced into the ascending aorta) gous to the heart. Instead of adjusting inotropes
• Complete cardiac and pulmonary support to enhance cardiac output, circuit flows ‘replace’
Possible disadvantages include: the cardiac output and thus must be titrated to
provide adequate oxygen delivery. A term that is
• Requires specialty cardiac surgical services frequently used when referring to ECMO circuit
• Risk of mediastinitis (increases substan- flows is ‘full flow’ and is taken from the cardiac
tially after 5-7 days) surgical operating room. However, this term is
• Risk of local hemorrhage is greater than misleading and should be abandoned in the ICU.
percutaneous techniques Analogous to the concept that no given cardiac
output can ever be considered ‘normal,’51 there
There is some evidence that high flow, is no circuit flow that can be regarded as ‘full-
central ECMO is associated with improved flow.’ The term fails to take oxygen consump-
survival in pediatric septic shock. In one study tion into consideration and falsely implies that
of 45 children with refractory septic shock, there is a universally applicable level above
Table 56-2. Suggested cannula sizes for central ECMO.
Patient Weight Atrial Cannula Aortic Anticipated Flows

(kg) (Fr) Cannula (Fr) (L/min)
<10 14-28 10-16 1-2
10-20 20-36 14-20 3-4
21-40 24-46 18-21 4-6
41-60 28-50 20-24 6-8
>60 36-52 22-24 8-10
619
Chapter 56
which no benefit would be seen from further (eg, sodium nitroprusside or phentolamine)
increases in flow. Instead, circuit flows should should be started to improve centrifugal pump
be goal directed, targeting rapid normalization flow and improve peripheral circulation. Venti-
of lactate, improvement in SvO2 >70%, and lation settings should be reduced to lung-protec-
restoration of age-appropriate mean arterial tive settings (eg, rate 5-10/min, peak inspiratory
pressures. In sepsis, this often requires very pressure <20 cmH2O, PEEP 5-12 cmH2O, FiO2
high flows (eg, >150-200 ml/kg/min). Although <0.5) unless on peripheral VA-ECMO, in which
the ACCM has recommended that flows be case FiO2 must still be set high enough to main-
kept <110 ml/kg/min to minimize the risk of tain coronary oxygenation43,44 (and, as the heart
hemolysis,5 this should be reconsidered in view recovers, cerebral oxygenation).
of more recent information.49 Instead, the target The coagulation cascade is intricately
should be whatever flow is needed to promptly involved in the process of inflammation and
reverse shock and restore tissue oxygenation. In septic patients frequently have disseminated
order to do this safely, appropriate monitoring intravascular coagulation (DIC). Thrombus may
of pump inlet pressures (see above) and regular form in parts of the ECMO circuit or patient’s
measurement of plasma free hemoglobin should blood vessels while profuse hemorrhage occurs
be used to detect excessive pump revolutions or from other areas. DIC should be aggressively
cannula misplacement.18 These goals are more treated with blood products while heparin is
easily executed with central ECMO than with titrated to appropriate activated clotting times
other cannulation strategies. Appropriate flows (ACT), activated partial thromboplastin times
that minimize hemolysis are often less than 110 (APTT), or anti-Xa levels. In sepsis, the target
ml/kg/min, but flows for adequate tissue oxygen ACT is generally 2 times normal unless bleed-
delivery in sepsis are most often in excess of ing is profuse, in which case the target may be
this figure, frequently 150-200 ml/kg./min.18,20,49 temporarily lowered to 1.5 times normal until
Therefore, other circuit considerations, such as the bleeding slows or stops. Aggressive blood
maximizing cannula size and minimizing the product support with fresh frozen plasma (aim-
presence of low flow zones (eg, circuit bridges ing INR <1.3-1.5), cryoprecipitate (aiming fi-
and the number of taps and access points), brinogen >2.5 g/L), and platelets (aiming >100 x
become very important to address in order to 109/L) is routine. Coagulopathy should never be
minimize the risk of hemolysis.49 Hemolysis allowed to replace controlled pharmacological
is a serious complication and every attempt anticoagulation in circuit management. In chil-
should be made to prevent it. One study of 207 dren, a minimum of 10 U heparin/kg/hr should
children on ECMO showed that those patients continue because of circulating procoagulants
with severe hemolysis (plasma free Hb >1 g/L) triggered by the septic process. Smaller doses
had a six-fold independent increase in the risk of are often sufficient in adult patients. Occasion-
dying compared to those who did not.52 Similar ally very large doses of heparin may be required
findings have been seen in adult patients.53 (eg, >30 U/kg/hr). In these patients, antithrom-
Inotropes can usually be weaned com- bin levels may be low, in which case there
pletely or to minimal doses within a few hours may be a role for administering intravenous
of achieving goal-directed circuit flows. Vaso- antithrombin concentrate, aiming for 100-120%
constrictors may be necessary to maintain age of the reference value. In particularly difficult
appropriate mean arterial pressures but it is not cases of DIC and hemorrhage, thromboelas-
unusual to see hypertension ensue around this tography can be useful in identifying the most
time, particularly with the high flows of central important elements of coagulopathy which can
ECMO, in which case short-acting vasodilators then be targeted for treatment.
620
Other measures such as effective empiric Most patients on ECMO for septic shock
antibiotics and immediate treatment of any recover quickly and do not require ECMO for
septic foci are vital. The pharmacokinetics of more than 3-4 days. Failure of the heart to re-
antibiotics for patients receiving extracorporeal cover after seven days should trigger a search
life support have been inadequately studied. As for additional pathologies such as myocardial
failure to provide adequate and timely empiric infarction or bacterial myocarditis, and is usu-
antibiotics has been associated with substantial ally a poor prognostic indicator. Occasionally,
increases in mortality,54,55 initial antibiotics patients suffer from persistent ARDS, necessi-
should be given as early as possible, cover all tating conversion to VV-ECMO when the circu-
likely pathogens, and be at the maximum dose latory component of their illness resolves. This
recommended by standard formularies, espe- scenario is seen particularly with disseminated
cially those with a wide therapeutic index such Staphylococcus aureus and can be challenging
as β-lactam antibiotics.56 to deal with, as necrotizing staphylococcal
The role of other extracorporeal life support pneumonia can cause substantial lung paren-
modalities in sepsis to remove inflammatory chymal destruction. After a trial of prolonged
mediators or modulate the immune response VV-ECMO in some patients with this condition,
is controversial. These techniques, classified the only option other than withdrawal of sup-
as Extracorporeal Blood Purification (EBP), port, may be to perform lung transplantation
include continuous renal replacement therapy directly from ECMO. However, this scenario
(CRRT), plasmapheresis, plasma exchange, and is uncommon and some patients can still be
hemoperfusion.57 CRRT is frequently required successfully weaned.
in septic patients on ECMO to compensate for
sepsis-induced acute kidney injury and provide Outcomes
adequate solute clearance, as well as to prevent
severe volume overload from blood product, nu- ECMO for neonatal sepsis is associated
trient, and drug administration. Although some with survival rates of approximately 75%.21
investigators have seen hemodynamic benefits This age group is unique in having sufficient
in children receiving high-flux CRRT,5 CRRT data to comment on pathogen-specific outcomes.
should not been regarded as standard manage- In one survey sent to 16 ICUs worldwide, 117
ment for septic patients on ECMO unless the septic patients were identified, 107 of whom
patient has incipient renal failure or fluid over- were neonates.39 Survival in patients with Gram-
load.58-59 Plasma exchange and plasmapheresis positive, Gram-negative or viral sepsis was 77%,
have shown some promise in small trials but 60%, and 40% respectively, although the study
again cannot be considered standard therapy was published nearly two decades ago and it is
and await proper evaluation in large prospec- likely that outcomes are better now. One study
tive multicenter studies.48,60,61 Many other forms of neonates on ECMO with herpes simplex vi-
of EBP are undergoing phase II or III trials. rus showed survival to hospital discharge was
One prospective, randomized, controlled trial only 25%.37 The survival rate in infants infected
of intraabdominal sepsis and shock showed with Bordetella pertussis receiving ECMO is
decreased mortality with the use of polymyxin even lower.
B hemoperfusion.62 However, this finding was Data from the ELSO Registry reveal that
a secondary endpoint, just achieved statistical survival in children after the neonatal period
significance, and has not been duplicated in with isolated respiratory failure from bacterial
more recent randomized controlled trials.63 or viral pneumonia are 59% and 65% respec-
tively.21 The corresponding figures for adult
621
Chapter 56
patients are 61% and 66%. Fifty-four percent algorithm of pediatric septic shock management.
of both adults and children with ARDS have Instead of being the therapy of last resort, it may
survived, but this includes all causes of ARDS become a more widely accepted treatment for
and is not specific to sepsis. However, as noted septic shock, instituted earlier in the course of
above, there is no reason to believe that out- illness to prevent the establishment of multior-
comes are different in septic patients.22,23 gan failure.
In pediatric septic shock, historical experi- Septic shock remains a rare indication for
ence suggests that the use of ECMO in children ECMO in experienced centers, yet up to 17%
is associated with survival to hospital discharge of children admitted to ICU with this diagnosis
of 50% at best.5,18 However, the use of high die.7 While not all of these deaths can be pre-
flow, central ECMO with modern circuitry vented, some of these patients probably could
and intensive care is associated with survival be rescued with ECMO. With wider acceptance
rates approaching 75%.18,20 Hopefully, further of sepsis as an indication for ECMO and greater
assessment will support these more recent, im- engagement of institutions to refer to ECMO-
proved survival figures, which are comparable capable centers, we believe this figure may fall.
to survival in neonatal sepsis. Extracorporeal therapy, whether it is ECMO,
The increasing use of ECMO for adult EBP, or both, holds the promise of significantly
septic shock has demonstrated that peripheral improving outcomes in septic shock. The use
ECMO for distributive shock is most likely of ECMO as mechanical circulatory support
unhelpful but that peripheral ECMO for severe for adult septic shock is unlikely to be required
sepsis-induced cardiogenic shock, occasionally except in rare instances of young adults with
seen in younger adults, can save up to 70% of significant ventricular impairment and septic
patients.32 The use of central ECMO for adult shock.
distributive septic shock has been successfully
reported in isolated cases but, thankfully, is
almost never required.64
Conclusions
Our understanding of ECMO for septic

shock has progressed considerably in the last
25 years, through being regarded by many
practitioners in the early 1990s as a complete
contraindication, to modern published case
series demonstrating 75% survival. ECMO
is generally required very early in the course
of sepsis, usually before antibiotics have
taken effect.20 The beneficial effects it exerts
on reversing shock and halting the evolution
of multiorgan failure are usually immediately
apparent, particularly with central cannulation.
As the technological advancements in ECMO
circuitry have made extracorporeal support safer
than ever before, it is interesting to speculate
whether in time ECMO will move higher up the
622
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626
57
Extracorporeal Life Support for Severe Cardiotoxic Drug Poisoning
Nicolas Bréchot, MD, PhD, Philippe Léger, MD, Pascal Leprince, MD, PhD,
Alain Combes, MD, PhD
Introduction cular drugs are of particular concern, represent-

ing 4% of the total exposures, but 13% of deaths.
Poisoning is a frequent and severe condition. Particularly, calcium channel blockers and beta-
Despite major improvements due to specific blockers accounted for 60% of the deaths due
antidotes, refractory cardiovascular dysfunction to cardiovascular drug intoxication. Moreover,
still accounts for a high proportion of deaths in many other substances not referred to as cardio-
poisoned patients. As cardiovascular impair- vascular drugs can have cardiovascular effects,
ment is only transient, there is a strong rationale ie, noncardiovascular pharmaceuticals (anti-
for using extracorporeal life support (ECLS) for psychotics, antidepressants, antihistamines),
this condition. The recourse to the technique drugs (cocaine, amphetamines), rural toxicants
is strongly supported by animal studies, and (organophosphates, pesticides), industrial or
gave promising results in case reports and household toxicants (aluminium phosphide, tri-
small cohort studies in humans. However, the chloroethylene), and plants (digitalis, colchicine,
optimal timing for ECLS implantation remains yew). Specifically, a large panel of substances
inadequately defined. Apart from cardiovascu- have membrane stabilizing properties at high
lar failure, ECLS may be useful in poisoned doses (Table 57-1), which are associated with
patients presenting acute respiratory distress a marked increase in mortality.2
syndrome (ARDS) refractory to conventional Usual presentations of severe cardiotoxic
management. drug poisoning include rapid progression to
severe cardiogenic shock, high degree atrio-
ECLS for Poisoning-induced Cardiovascular ventricular block, asystole, pulseless ventricular
Failure tachycardia, or ventricular fibrillation. Time of
shock onset after ingestion varies largely from
one patient to another, depending on galenic
Epidemiology formulation, ingested dose, and co-ingested
molecules. It is approximately 2 hours for class
The 2014 annual report of the American As- I antiarrythmics,3 6 hours for polycyclic anti-
sociation of Poison Control Centers mentioned depressants, chloroquine, beta-blockers, and
more than two million poison exposures in the immediate release calcium channel blockers,4-7
U.S., more than 600.000 of them managed in and up to 18-24 hours for the modified release
healthcare facilities.1 Among them, cardiovas- form of the calcium channel blocker verapamil.7
627
Chapter 57
Alternatively, cardiovascular failure is unlikely However, mortality is still 10-20% when cardio-
to occur beyond these times. vascular failure occurs,3,6,9 and may reach 90%
when cardiovascular dysfunction is refractory
First Line Management to conventional treatments.3,10
Nonspecific ICU support after drug poison- Role for ECLS

ing includes fluid management and correction
of electrolyte disturbances, catecholamines, at- Considering that myocardial dysfunction
ropine in case of severe bradycardia, and molar observed after poisoning with cardiotoxics is
sodium bicarbonate in case of QRS enlargement transient, there is a strong rationale for using
(Figure 57-1). Mechanical ventilation is initi- mechanical circulatory assistance in the most
ated in case of respiratory or neurologic failure. severe patients. First attempts in humans used
Single-dose activated charcoal may be used up heart surgery cardiopulmonary bypass as a sal-
to two hours after ingestion of life-threatening vage therapy, which led to disappointing results
toxics in patients with intact or protected air- due to a high rate of bleeding complications.11-14
ways.8 However, major technical improvement in
ECMO technique in the last decade has consid-
Specific Antidotes erably decreased complications and venoarterial
Specific antidotes have considerably im- Table 57-2. Main specific antidotes available
proved the prognosis of patients with cardiovas- during drug poisoning.
cular impairment after poisoning (Table 57-2).
Type of Intoxication Antidote
- Glucagon: 2-5 mg IV bolus, then 2-10 mg/h
continuous infusion [37]
Table 57-1. Drugs responsible for membrane - Glucose-insuline: 1 UI/kg IV bolus followed
with 1-10 UI/kg/h infusion+ adequate glucose
stabilizing activity at high doses.25 Beta-blockers
[38-40]
- Discuss intravenous lipid emulsion for
lipophilic agents: 1.5 ml/kg IV bolus then
0.25 ml/kg/min infusion [41]
Pharmacological Class Example of Substances - Calcium salts: 1g IV bolus/15-20 min, 4
Propanolol, acebutolol, doses followed with 50 mg/kg/h infusion
nadoxolol, pindolol, - Glucose-insuline: 1 UI/kg IV bolus followed
Beta-blockers Calcium-channel with 1-10 UI/kg/h infusion+ adequate glucose
penbutolol, labetalol, blockers [38-40]
oxprenolol - Discuss intravenous lipid emulsion for
Flecainide, quinidine, lipophilic agents: 1.5 ml/kg IV bolus then
0.25 ml/kg/min infusion [41]
lidocaine, disopyramide,
Class I Anti-arrhythmics Membrane stabilizing
- 8,4 % sodium bicarbonate: 1-3 mmol/kg IV
cibenzoline, propafenone, bolus if QRS enlargement/arrhythmia.
activity drugs
procainamide Maintain ph<7.55 [42]
- Intravenous lipid emulsion: 1.5 ml/kg IV
Imipramine, amitriptyline, Local anaesthetics
bolus then 0.25 ml/kg/min infusion [43,44]
Polycyclic desipramine, - Anti-digoxin Fab antibodies:
antidepressants clomipramine, dosulepin, Molar neutralization if life-threatening
doxepin, maprotiline condition:
ventricular arrhytmia
Antimalarial agents Chloroquine, quinine bradycardia≤40/min despite atropine
Selective serotonin Venlafaxine, citalopram, infusion
reuptake inhibitors escitalopram hyperkaliemia>5 mmol/L
cardiogenic shock
Dopamine and Bupropion Cardiac glycosides
mesenteric infarction
norepinephrine uptake Half-molar neutralization if high-risk patient:
inhibitors male
age>55 years
Anti-epileptics Carbamazepine, phenytoin underlying heart disease
Phenothiazines Thioridazine atrio-ventricular block
Opioids Dextropropoxyphene bradycardia<60 despite atropine infusion
hyperkaliemia>4.5 mmol/L
Recreational agents Cocaine
628
Extracorporeal Life Support for Severe Cardiotoxic Drug Poisoningt
ECMO is now the first-line salvage therapy group. Interestingly, ECLS-treated animals
in case of drug poisoning. It can be initiated had a drug clearance comparable to normal
at patient’s bedside, even in remote hospitals individuals in this experiment.16 In a model of
with mobile ECMO rescue teams.15 It provides cardiac arrest following desipramine infusion
a high and stable blood flow to reverse organ in dogs, ECLS also rescued all animals (6/6),
dysfunction for the time needed to clear toxics while only 1/6 animals survived in the con-
from the body. ventional treatment group.17 Lastly, in a model
of amitriptyline poisoning in which 20 swine
Animal Studies were receiving 0.5 mg/kg/min amitriptyline
ECLS has been studied to date in three ma- until blood pressure dropped below 30 mmHg
jor animal models of drug poisoning. In a model for 1 min (near-lethal toxicity), ECLS rescued
of lidocaine poisoning in dogs consisting of a all animals (10/10), while 9/10 died in the con-
30 mg/kg IV injection, 8 dogs received ECLS ventional treatment group.18
support during 90 minutes and were compared
to 8 dogs treated conventionally (mechanical Human Studies
ventilation, vasopressors, cardioversion, and To date ECLS has been used as a salvage
antiarrhythmics). All dogs in the ECLS group therapy in humans presenting with cardiogenic
survived, compared to only two in the control shock or arrhythmia refractory to conventional
Figure 57-1. Proposed algorithm for the management of cardiovascular failure in patients
intoxicated with cardiotoxic agents. (Adapted from Baud FJ, et al.25)
629
Chapter 57
treatment (Table 57-3). In 2009, Daubin, et al. and beta-blocker intoxication, ECLS support
reported the outcomes of 17 patients assisted remained significantly associated with lower
with peripheral venoarterial ECMO (PVA- mortality (Adjusted Odds Ratio, 0.18; 95% CI,
ECMO) for acute poisoning.19 Fifteen suffered 0.03-0.96; p=0.04). Interestingly, none of the
from cardiotoxic intoxication including 11 6 ECLS-treated patients who were intoxicated
with membrane stabilizing agents, combined with membrane stabilizing agents died; whereas
with various antipsychotic drugs. All had death occurred in 15 of the 23 patients managed
severe myocardial dysfunction at the time of conventionally in this setting. In a sensitivity
ECMO implantation, were receiving high dose analysis of the 52 intoxicated patients who did
catecholamines, and suffered multiple organ not have cardiac arrest, ECLS remained associ-
failure. Seven were implanted under cardiopul- ated with survival (OR for death 0.28; 95% CI
monary resuscitation due to refractory cardiac 0.05-1.48, p=0.17), although the difference did
arrest, with a mean low-flow time of 101 ± 55 not reach statistical significance. The mean time
min. Time from admission to ECLS was 6.4 ± from admission to ECLS was short (8 ± 7hrs),
7 hrs. Implantation was performed in the oper- as well as ECLS duration (6 ± 2.9 days).
ating room for 13 patients and at the bedside Special attention should be paid to patients
for four. Fifteen patients were weaned from presenting with refractory cardiac arrest follow-
ECMO, and 13 (76%) were discharged alive ing drug poisoning, since they are reported to
without neurological sequelae. Mean ECMO have better outcomes after ECLS support than
duration was short (4.5 ± 2.4 days), but a high patients with cardiac arrest from other etiolo-
rate of complications occurred: 6 episodes of gies. For example, in a cohort of 40 refractory
limb ischemia and 2 cannulation site bleeding. cardiac arrest patients rescued with ECMO,
Authors concluded that despite a high morbid- only 8 (20%) survived with a good neurological
ity associated with the technique, PVA-ECMO outcome, but the survival rate was 67% in poi-
could rescue patients with refractory myocardial soned patients.21 Similarly, of the 4 survivors of
dysfunction associated with drug poisoning. a cohort of 17 refractory cardiac arrest rescued
The largest cohort to date reported in 2012 by ECLS, 3 were cardiotoxic-poisoned patients
the outcomes of 62 patients with severe shock who underwent CPR for up to 180 min before
or persistent (>30 min) cardiac arrest after drug ECMO, and were alive at 1-year followup
poisoning.20 Fourteen of them underwent PVA- without sequelae. Pertinently, two of these pa-
ECMO, whereas 48 were managed convention- tients survived despite elevated plasma lactate
ally. Patients treated with or without ECLS at concentrations before cannulation (39.0 and
ICU admission were on high dose vasopressors 20.0 mmol/l).22 The reasons for better outcomes
and had comparable drug ingestion histories, in this setting remain unknown, although it has
Simplified Acute Physiology Score (SAPS been hypothesized that early hypothermia oc-
II score) (66±18), Sequential Organ Failure curring in many poisoned patients may protect
Assessment (SOFA) score (median: 11 [IQR, the brain.19,23,24
9-13]), Glasgow Coma Scale score (median: 3
[IQR, 3-11]), need for ventilator support (n=56) Future Directions
and extrarenal support (n=23). Survival rate
was 86% in the ECLS group, compared to only The optimal timing for ECMO initiation
48% in patients who received conventional is a crucial issue, which remains undefined in
therapies and none of the patients with persistent poisoned patients. ECLS is still considered a
cardiac arrest survived without ECLS support. salvage therapy for which benefits and risks
In multivariate analysis, adjusting for SAPS II should be carefully weighted. However, concor-
630
Table 57-3.. Summary of clinical cases reporting the use of ECLS after poisoning.
Study Agent Cannulation Type Refractory CA Survival

Cardiovascular Failure
McVey, 1991 [73] Propranolol PVA - +
Rooney, 2009 [45] Acebutolol PVA - +
Escajeda, 2015 [85] Metoprolol PVA + +
Goodwin, 1993 [47] Tricyclic ADS PVA - +
Williams, 1994 [48] Tricyclic ADS PVA - +
Gillart, 2008 [49] Tricyclic ADS PVA + +
* Hendren, 1989 [13] Verapamil CVA + -
Holzer, 1999 [52] Verapamil PVA + +
Maclaren, 2005 [54] Verapamil tricyclic ADS PVA - +
Rygnestad, 2005 [76] Verapamil, sotalol PVA + +
Kolcz, 2007 [53] Verapamil, propranolol CVA + +
* De Rita, 2011 [72] Verapamil, propranolol CVA + +
Durward, 2003 [11] Diltiazem CVA + +
Frazee, 2014 [14] Diltiazem CVA - +
Weinberg, 2014 [29] Amlodipine, Lisinopril PVA - +
Yasui, 1997 [61] Flecainide PVA + -
Corkeron, 1999 [60] Flecainide PVA + +
Auzinger, 2001 [59] Flecainide PVA - +
Reynolds, 2015 [84] Flecainide PVA + +
*Tecklenburg, 1997 [75] Quinidine VA + +
Behringer, 1998 [82] Digoxin PVA + -
Jouffroy, 2013 [90] Colchicine PVA - +
Carvedilol, amlodipine,
Koschny, 2014 [88] PVA + +
amitriptyline, and others
*Haas, 2008 [46] Amiodarone PVA - +
Panzeri, 2010 [78] Yew PVA - +
Fitzpatrick, 1994 [12] Aconite poisoning CVA - +
*Lai, 2005 [50] Arsenic VA + -
* Shenoi, 2011 [51] Bupropion VA - +
* Froehle, 2012 [67] Mepivacaine CVA + +
Megarbane, 2006 [55] Carbamazepine PVA - +
* Marciniak, 2007 [65] Ibuprofen PVA - +
De Vroey, 2009 [57] Cocaine PVA - +
Yoshida, 1998 [58] Disopyramide PVA + +
Lannemyr, 2012 [74] Quetiapine PVA + +
Pasic, 2000 [81] Prajmalium CVA + +
Boisrame-Helms, Colchicum Autumnale
PVA - +
2015 [86] poisoning
Thooft, 2014 [87] Taxus intoxication PVA + +
Hassanian-Moghaddam, 2015 [83] Aluminium phosphide PVA - +
Elkalioubie, 2011 [69] Tramadol PVA + +
Organo
Kamijo, 1999 [70] PVA - +
phosphate
Respiratory Failure
* Scalzo, 1990 [62] Hydrocarbon aspiration PVA - +
* Moller, 1992 [63] Hydrocarbon aspiration PVA - -
* Bille, 2011 [64] Hydrocarbon aspiration PVA - +
* Garrettson, 1992 [66] Lidocaine (ARDS) PVA - +
* Daugherty, 2011 [68] Methadone (ARDS) PVA - +
McCunn, 2000 [56] Carbon monoxide VV - +
Bertram, 2013 [89] Paraquat VV - -
Tang, 2015 [71] Paraquat (ARDS) VV - +
Chian, 2009 [77] Zinc Cholride inhalation VV - +
Pizon, 2004 [79] Opiods (ARDS) VV - +
Chlorexidine gluconate
Ishigami, 2001 [80] VV - +
(ARDS)
*=pediatric case; CA=cardiac arrest; ADS=antidepressants; PVA=peripheral venoarterial; CVA=central venoarterial; VV=venovenous
631
Chapter 57
dant data suggest that early ECMO implanta- the most severe patients. Very early transfer on
tion before multiple organ failure is associated ECMO of patients severely intoxicated with
with far better outcomes than implantation as a cardiotoxics or membrane stabilizing agents to
salvage therapy in dying patients. these referral centers will undoubtedly be as-
Failure to sustain mean arterial pressure >50 sociated with improved outcomes. We propose
mmHg, cardiac index >2 l/min/m² and Doppler an algorithm for the management of patients
echocardiography aortic velocity time integra- with cardiotoxic drugs poisoning in Figure 57-1.
tion (VTI) ≥7 cm despite high doses catechol-
amines are parameters of utmost importance Venovenous ECLS for Poisoning-induced
to guide ECMO decision. Although the dose Respiratory Failure
ingested is usually poorly correlated with the
outcome,25 plasma concentrations can be helpful Poisoning is associated with a high risk of
to predict the risk of cardiovascular impairment secondary acute respiratory distress syndrome,
and sudden cardiac arrest for substances like due to direct toxicity of the poison, aspiration
chloroquine26 or verapamil.27 Serum lactate pneumonia following coma, and multiple organ
measured in the emergency department has also failure after cardiovascular compromise.31-35
been shown to predict the fatality risk for many However, case reports of refractory ARDS res-
drugs,28 but can be falsely reassuring in case of cued with venovenous ECMO are scarce, and
beta-blocker overdose because of the inhibition mostly concern irreversible pulmonary lesions
of beta-adrenergic receptor stimulation.9 due to paraquat poisoning in which ECMO
Another important issue will be to deter- served as a bridge to transplantation (Table 57-
mine the role of ECLS for poisoning-induced 3). Estimating the reversibility of pulmonary
refractory vasoplegia, for which vasopressors lesions is of crucial importance before installing
have low efficacy. Venoarterial ECMO might venovenous ECMO.36 Nevertheless, the overall
contribute to reverse cardiovascular failure in potential of recovery from ARDS appears to be
this setting.29 quite good after poisoning,31-35 as it was reported
ECLS could also interfere with specific for aspiration pneumonia refractory to conven-
antidotes, mainly due to adsorption on the mem- tional treatment supported by VV-ECMO.36
brane, and doses of antidotes under ECMO have
to be better defined. For example, combined use Conclusion
of intravenous lipid emulsion and extracorpo-
real membrane oxygenation may be associated Mortality remains very high in patients
with fat deposition in the ECMO circuits and intoxicated with cardiotoxic and membrane sta-
increased blood clot formation, although the bilizing agents. In the last decade, case reports
clinical implications of this observation remains and small cohort studies reported very promis-
controversial.30 ing results with early initiation of VA-ECMO in
Lastly, since ECMO is a complex, high this setting, even for patients who had refractory
risk, and costly modality, at present it should be cardiac arrest before ECMO. Better definition
conducted in centers with sufficient experience, of the indications and the optimal timing for
volume, and expertise to ensure it is used safely. ECMO will be the challenge of future trials.
Networks of hospitals at the local, regional, or Additionally, since the successful delivery
interregional level should be created around of ECMO requires highly experienced staff
each ECMO center located in tertiary refer- and a minimum number of cases per year, or-
ral hospitals and each ECMO network should ganization of ECMO programs on a regional
ideally create mobile ECMO teams to retrieve or national level is needed to provide the best,
632
safest, and most efficient care possible to this

specific group of patients. A mobile ECMO
rescue team should also be available to retrieve
the most severely intoxicated patients.
633
Chapter 57
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638
58
ECMO as Bridge to Lung Transplantation
Darryl Abrams, MD, Daniel Brodie, MD, Matthew Bacchetta, MD, Shaf Keshavjee, MD
Introduction Cannula Configurations
Invasive mechanical ventilation (IMV) may Venovenous ECMO is the preferred can-
be necessary to support patients with endstage, nulation strategy for patients with respiratory
irreversible respiratory failure who are awaiting failure in the absence of concomitant cardiac
lung transplantation. However, the use of IMV failure or clinically significant pulmonary ar-
has traditionally been associated with poor post- terial hypertension (Table 58-1). Traditional
transplant outcomes, which may be attributable venovenous cannulation involves insertion of
to, among other factors, higher pretransplant a drainage cannula into the inferior vena cava
severity of illness, deconditioning from im- (IVC) via the femoral vein and placement of a
mobility, and ventilator-associated complica- reinfusion cannula into the superior vena cava
tions.1,2 Extracorporeal membrane oxygenation
(ECMO) can support patients in whom IMV is
Table 58-1. ECMO configuration consider-
insufficient to maintain adequate gas exchange, ations for patients awaiting lung transplanta-
although ECMO has also traditionally been tion.
associated with poor posttransplant survival,
likely owing to similar issues of illness severity Physiologic Abnormalities ECMO Configuration
Hypercapnia without Venovenous
and immobility, suboptimal timing of ECMO hypoxemia Arteriovenous
initiation and patient selection, and circuit- Femoral artery to femoral
associated complications (eg, bleeding, throm- vein
Hypoxemia with no Venovenous
bosis), especially when older generation circuit pulmonary hypertension
components were used.1,2 However, temporal Hypoxemia with mild Venovenous, consider
pulmonary hypertension venoarterial
trends suggest that posttransplant outcomes are Hypoxemia with moderate Venoarterial
improving for patients supported with ECMO to severe pulmonary Internal jugular vein to
hypertension subclavian artery
as a bridge to transplantation (BTT)2-5 in the Femoral vein to femoral
context of improved risk-benefit profiles for artery (+/- internal jugular
extracorporeal technology,6,7 advances in can- venous return, i.e.
venoarterial venous)
nulation design and technique,8,9 and changes Venovenous via dual-lumen
in both the timing of initiation of ECMO and cannula with atrial septal
defect or atrial septostomy
the management strategies once patients are Arteriovenous
supported with ECMO.2,3,10-16 Pulmonary artery to left
atrium
639
Chapter 58
(SVC) via the internal jugular vein.17 Although and reinfusion via a single internal jugular ve-
this approach can be performed expediently nous insertion site, femoral cannulation can be
at the bedside without the need for fluoro- avoided altogether.8,9 When properly positioned,
scopic guidance, such a configuration limits drainage ports are located in the IVC and SVC
the patient’s ability to perform active physical and reinfusion flow is directed toward the tricus-
therapy, particularly ambulation, although early pid valve, minimizing recirculation. To ensure
mobilization has been reported with such an proper cannula placement, imaging guidance,
approach.12 It may also lend itself to excess including fluoroscopy and transesophageal
recirculation of reinfused oxygenated blood, echocardiography, is recommended during
thereby compromising its effectiveness.18 cannulation.19
There are multiple alternative cannulation For patients awaiting lung transplantation
strategies based on physiologic and prag- who have concomitant compromise of cardiac
matic considerations in caring for the patient function, a venoarterial configuration may be
(Figure 58-1). An alternative strategy that both necessary.20 This scenario is most commonly
limits recirculation and maximizes the potential encountered in patients with pulmonary arterial
for early mobilization is upper-body venove- hypertension with associated right ventricular
nous cannulation. With the advent of bicaval, dysfunction.21-23 Traditional venoarterial ECMO
dual-lumen cannulae that achieve both drainage involves cannulation of both the femoral vein
Figure 58-1. Algorithm of cannulation strategies for ECMO as bridge to transplant. BTT bridge to
transplant, MOF multiorgan failure, MDR multidrug resistant, PH pulmonary hypertension, ECLS
extracorporeal life support, VV venovenous, VA venoarterial, VVA venovenous arterial, A arterial, ASD
atrial septal defect, PA-LA pulmonary artery to left atrium, SCA subclavian artery, RIJ right internal
jugular vein, DLC dual lumen cannula. Adapted from Biscotti M, Sonett J, Bacchetta M. ECMO as
bridge to lung transplant. Thoracic surgery clinics 2015; 25:17-25, Figure 7.
640
and femoral artery. This configuration may not while avoiding femoral cannulation. However,
achieve adequate upper-body oxygenation in because this strategy requires an open surgical
patients with sufficiently preserved native car- approach to the subclavian artery, it cannot be
diac output and marked impairment in native performed emergently at the bedside for a pa-
gas exchange, as would be expected in those tient needing venoarterial support and may ne-
awaiting lung transplantation, so that deoxygen- cessitate a two-stage procedure. An alternative
ated blood is ejected into the ascending aorta upper-body approach that may be considered in
and aortic arch.20,24 When patients on femoral patients with pulmonary arterial hypertension
venoarterial ECMO have inadequate oxygen- and atrial septal defects is the use of a bicaval,
ation of the coronary and cerebral vasculature, dual-lumen cannula in the internal jugular vein
then conversion to a hybrid configuration that with orientation of the reinfusion jet toward the
returns oxygenated blood to both the femoral defect instead of the tricuspid valve, thereby
artery and internal jugular vein may be neces- creating an oxygenated right-to-left shunt while
sary.24 However, this configuration, known offloading the right ventricle.21,22,27 Patients with
as venoarterial venous ECMO, adds greater an atrial septostomy, either created for manage-
complexity to management and further limits ment of their pulmonary hypertension or for the
rehabilitation. purpose of attempting this strategy, may like-
Alternatively, an exclusively upper-body wise be appropriate for this configuration.28,29
venoarterial cannulation strategy may be con- A pumpless strategy, most suitable in cases
sidered.25,26 Venous blood can be drained from of severe pulmonary hypertension and for which
the right atrium via the internal jugular vein a sternotomy is required, involves insertion of
and reinfused into the subclavian artery via a low resistance oxygenator between the main
an end-to-side graft.21,25 Direct cannulation pulmonary artery and the left atrium.23,30 This
of the subclavian artery is avoided to prevent approach has the added benefit of truly un-
compromise of blood flow to the upper extrem- loading the right ventricle and allowing right
ity. This approach minimizes the amount of ventricular failure and hepatic congestion to
retrograde flow needed to reach the aortic arch, recover. Table 58-2 characterizes the relative ef-
thereby maximizing upper-body oxygenation
Table 58-2. Relative effect of different ECMO configura-

tions on physiology and management.
2-site VV VV via Femoral Upper- Hybrid PA-
VV via DLC VA body configurations LA
DLC with VA (VVA or
ASD VAV)
Upper-body +++ +++ +++ -/+ +++ ++ +++
oxygen
delivery
RV - - ++/+++ +++ +++ ++ +++
unloading*
Effect on - - - +++ ++ ++/+++ -
LV afterload
Mobilization + +++ +++ -/+ +++ -/+ +++
potential
Cannulation + ++ ++ + +++ ++ +++
difficulty
DLC=dual-lumen cannula; ASD=atrial septal defect; mPAP=mean pulmonary arterial
pressure; PA-LA=pulmonary artery to left atrium; RV=right ventricle; LV=left ventricle;
VV=venovenous; VA=venoarterial; VAV=venoarterial venous; VVA=venovenous
arterial
(-)=negligible; (+)=low; (++)=moderate; (+++)=high
*Based on chronic RV loading conditions. The effect of relieving any component of RV
loading due to acute hypoxemia or hypercapnia will be variable.
Adapted from Biscotti M, Sonett J, Bacchetta M. ECMO as bridge to lung transplant.
Thoracic surgery clinics 2015; 25:17-25, Table 1.
641
Chapter 58
fects of the different cannulation configurations transfusion that has the potential to limit suit-
on physiologic parameters and management. able allograft availability.
Optimal timing of ECMO initiation remains
Patient Selection and Timing of ECMO uncertain and is subject to individual transplant
Initiation centers’ practices and experience.35,36 Algo-
rithms for patient selection and configuration
Appropriate patient selection remains as approaches have been proposed.37,38 Ultimately,
crucial an aspect of achieving success with more research is needed to better determine
ECMO as BTT.31 There are no randomized optimal patient selection and timing, includ-
trials evaluating which patients with endstage ing the development of prediction models to
respiratory failure are most likely to benefit identify those patients at greatest risk for death
from ECMO in this setting. Inherently, pa- while still being appropriate ECMO candidates.
tients with the highest expected pretransplant
mortality are also the most critically ill and Patient Management Strategies
would likely benefit the most from ECMO.
However, if the patients are too ill at the time Minimization of Sedation and Endotracheal
of cannulation, ECMO may be insufficient to Extubation
reverse the consequences of severe hypoxemia
or hypercapnia, particularly if they require high The association between IMV and poor
levels of IMV support and are deconditioned or posttransplant outcomes calls attention to the
immobilized because of the need for sedatives need for alternative management strategies to
or neuromuscular blocking agents. The effects support patients with severe respiratory failure
of severe hypoxemia on end organ function, who would otherwise require IMV support. In
such as renal function, may also preclude select patients, ECMO may provide sufficient
transplant if not intervened on rapidly enough. gas exchange to allow the removal or avoid-
Because physical deconditioning is considered ance of IMV altogether.10,12,21,39,40 Endotracheal
by many transplantation centers to be a strong extubation has the potential advantages of re-
relative contraindication to lung transplantation, duced dyspnea, minimization or avoidance of
initiation of ECMO in order to optimize active dynamic hyperinflation from positive-pressure
physical therapy before the development of ventilation, elimination of ventilator-associated
significant weakness may improve outcomes.3,32 complications and the systemic inflammatory
Likewise, patients with endstage respiratory response syndrome associated with maximal
failure, particularly those with severe pulmo- mechanical ventilation that may compromise
nary arterial hypertension, are at high risk for transplant candidacy or worsen the posttrans-
sudden cardiac death.33,34 Initiation of ECMO plant prognosis.10,13 In the setting of ECMO-
prior to the onset of cardiac arrest and irre- supported gas exchange, patients may require
versible extrapulmonary end-organ function less sedation to manage respiratory symptoms.
maximizes the opportunity for successful lung An approach that combines ECMO with avoid-
transplantation. ance of both sedation and IMV is sometimes re-
Although it is important to initiate ECMO ferred to as “awake ECMO,” although the term
prior to the development of contraindications is incomplete because this strategy involves
to transplantation, ECMO itself may introduce more than simply reducing sedation. This ap-
the risk for important pretransplant complica- proach has been shown to be well-tolerated in a
tions, including hemorrhage necessitating blood subset of pretransplant patients.10,40,41 For those
patients who appear to require a secured airway
642
and IMV, consideration should be made for ECMO Use in the Intraoperative and Post-
early tracheostomy to maximize patient com- transplantation Settings
fort and facilitate airway clearance. In patients
with septic lung diseases such as cystic fibrosis, Intraoperative ECMO
tracheostomy, and IMV with frequent bronchial
toilet may minimize decruitment of the lungs ECMO may be employed during lung
and development of uncontrollable sepsis that transplantation as an alternative approach to
would preclude transplantation. Regardless of traditional cardiopulmonary bypass as a means
the amount of ECMO and IMV support required, of providing cardiopulmonary support and
maintaining pretransplant patients awake and controlled, low-pressure lung reperfusion. In
able to participate in physical therapy should fact the use of ECMO for intraoperative sup-
remain a priority. port in lung transplantation is becoming the
preferred method of support in many centers.
Early Mobilization Its use varies by institutional practice and
may be influenced by individual transplant
Proper physical conditioning is of the recipient risk factors, such as the presence of
utmost importance for optimizing patient pulmonary hypertension.50 In comparison with
outcomes posttransplantation. Ambulation in cardiopulmonary bypass, which has tradition-
patients receiving IMV has been demonstrated ally been associated with a marked systemic
to be both safe and effective at minimizing inflammatory response, high anticoagulation
ICU-associated complication.42,43 ECMO, when needs, significant bleeding risk, and increased
combined with a strategy that minimizes seda- risk of primary graft dysfunction,51,52 ECMO has
tion and IMV, is also safe and promotes active been reported to result in lower posttransplant
physical therapy, including ambulation, pre- mechanical ventilation requirements, ICU and
lung transplantation.12,44-46 An interdisciplinary hospital lengths of stay, rates of hemorrhage,
approach, along with carefully planned pro- transfusion requirements, and need for reopera-
cesses, may help minimize complications and tion.53,54 However, overall survival did not differ
maximize effectiveness of physical therapy.12 between groups.53-55
Restrictive Transfusion Strategy ECMO Posttransplantation
ECMO may increase the risk for important Primary graft dysfunction (PGD) is a form
pretransplant complications, including hemor- of acute lung injury that is the leading cause
rhage, with the need for blood transfusions of early death after lung transplantation.56
that may limit the availability of suitable lung ECMO may be used in patients with PGD to
allografts. Lower anticoagulation targets and support gas exchange and minimize pulmonary
conservative transfusion strategies with lower airway pressures in order to facilitate allograft
transfusion threshold can help mitigate these recovery.57 One study evaluating outcomes of
risks.11 An even more restrictive transfusion ECMO-supported severe PGD, compared to
strategy than is usually applied to critically ill non-ECMO-supported transplant recipients,
patients,47-49 balanced against the risks of end- reports reasonable survival rates (82% vs. 97%
organ insufficiency and inability to participate in 30-day survival), particularly when ECMO is
physical therapy, may be appropriate to further instituted early.58 However, long-term allograft
minimize complications of transfusions in the function was significantly worse (peak percent-
pretransplant population. predicted FEV1: 58% vs. 83%, p=0.006).
643
Chapter 58
Outcomes of ECMO as BTT and how to withdraw life sustaining therapy,

and further highlights the importance of patient
Several retrospective, single-center obser- selection for both ECMO and lung transplanta-
vational studies have demonstrated posttrans- tion.60 Whenever possible, recognition of and
plant survival for ECMO-supported transplant discussion about this scenario with the patient
candidates comparable to those not receiv- and surrogates prior to initiation of ECMO may
ing ECMO.3,4,41 A systematic review of 441 facilitate decisionmaking if this situation were
ECMO-supported patients across 14 studies, to occur. Palliative care consultation may also
all of which were performed retrospectively, be appropriate to help with both decisionmaking
reported survival to transplant ranging from and minimization of suffering.
10% to 50% and 1-year posttransplant survival
ranging from 50% to 90%.36 The wide survival Conclusions
ranges highlight the need for careful patient
selection, and differing organ availability across In the context of advances in extracorpo-
transplant centers with consequent variability in real technology, combined with evolving ap-
the length of time required to bridge a patient proaches to both timing of ECMO initiation and
with ECMO. Higher volume centers may have management of patients receiving ECMO, there
better ECMO outcomes,59 though this must be is an increasing body of evidence to suggest that
balanced against the potential for higher ex- ECMO has an important role in bridging care-
pected pretransplant mortality of these complex fully selected patients to lung transplantation
patients at these centers. at centers with expertise in both. Cannulation
and management strategies that facilitate an
Limitations to Bridge to Transplant awake, extubated approach to maximize physi-
cal therapy are recommended when appropriate
ECMO has an emerging role in its ability in order to optimize posttransplant outcomes.
to support patients with advanced, irreversible
respiratory failure who are awaiting lung trans-
plantation. With current technology, pretrans-
plant patients receiving ECMO are committed
to an intensive care environment until trans-
plantation. A significant limitation to ECMO
is the lack of a destination device with which
people can be managed long term, conceptu-
ally similar to a ventricular assist device for
advanced cardiac failure. Given both the limited
availability of donor organs and the potential
for complications that compromise a patient’s
candidacy while awaiting transplantation, a sig-
nificant proportion of patients receiving ECMO
as BTT will not survive to transplantation.3,36,37
The potential for patients to be awake and no
longer a candidate for transplantation, but si-
multaneously dependent on ECMO for survival,
has been called the “bridge to nowhere”, creat-
ing ethical dilemmas including whether, when,
644
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25. Javidfar J, Brodie D, Costa J, et al. Sub- 34. Delcroix M, Naeije R. Optimising the
clavian artery cannulation for venoarte- management of pulmonary arterial hyper-
rial extracorporeal membrane oxygenation. tension patients: emergency treatments.
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26. Biscotti M, Bacchetta M. The “sport mod- journal of the European Respiratory Society
el”: extracorporeal membrane oxygenation 2010;19(117):204-211.
using the subclavian artery. Ann Thorac 35. Biscotti M, Sonett J, Bacchetta M. ECMO
Surg 2014;98(4):1487-1489. as bridge to lung transplant. Thoracic sur-
27. Javidfar J, Brodie D, Sonett J, Bacchetta gery clinics 2015;25(1):17-25.
M. Venovenous extracorporeal membrane 36. Chiumello D, Coppola S, Froio S, Colombo
oxygenation using a single cannula in A, Del Sorbo L. Extracorporeal life support
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as bridge to lung transplantation: a system- of patients on venovenous extracorpo-

atic review. Crit Care 2015;19:19. real membrane oxygenation support using
37. Strueber M. Extracorporeal support as a an ECMO helmet. Intensive Care Med
bridge to lung transplantation. Curr Opin 2014;40(10):1595-1597.
Crit Care 2010;16(1):69-73. 47. Corwin HL, Gettinger A, Pearl RG, et al.
38. Javidfar J, Bacchetta M. Bridge to lung The CRIT Study: Anemia and blood trans-
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brane oxygenation support. Curr Opin practice in the United States. Crit Care Med
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39. Abrams D, Brodie D. Emerging indica- 48. Hebert PC, Wells G, Blajchman MA, et
tions for extracorporeal membrane oxy- al. A multicenter, randomized, controlled
genation in adults with respiratory failure. clinical trial of transfusion requirements
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2013;10(4):371-377. in Critical Care Investigators, Canadian
40. Olsson KM, Simon A, Strueber M, et Critical Care Trials Group. N Engl J Med
al. Extracorporeal membrane oxygen- 1999;340(6):409-417.
ation in nonintubated patients as bridge 49. Vincent JL, Baron JF, Reinhart K, et al. Ane-
to lung transplantation. Am J Transplant mia and blood transfusion in critically ill
2010;10(9):2173-2178. patients. JAMA 2002;288(12):1499-1507.
41. Mohite PN, Sabashnikov A, Reed A, et al. 50. Marczin N, Royston D, Yacoub M. Pro:
Extracorporeal Life Support in “Awake” lung transplantation should be routinely
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Thorac Cardiovasc Surg 2015. Cardiothorac Vasc Anesth 2000;14(6):739-
42. Bailey P, Thomsen GE, Spuhler VJ, et 745.
al. Early activity is feasible and safe in 51. McRae K. Con: lung transplantation should
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43. Schweickert WD, Pohlman MC, Pohlman 2000;14(6):746-750.
AS, et al. Early physical and occupational 52. Diamond JM, Lee JC, Kawut SM, et al.
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cally ill patients: a randomised controlled function after lung transplantation. Am J
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44. Turner DA, Cheifetz IM, Rehder KJ, et al. 53. Machuca TN, Collaud S, Mercier O, et al.
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2011;39(12):2593-2598. 1157.
45. Ko Y, Cho YH, Park YH, et al. Feasibility 54. Biscotti M, Yang J, Sonett J, Bacchetta M.
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46. Pruijsten R, van Thiel R, Hool S, Saeijs M, 55. Bermudez CA, Shiose A, Esper SA, et
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rial extracorporeal membrane oxygenation

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648
59
ECLS in Heart Transplantation
John H. Smith, MD, Sebastian C. Tume, MD, Bill Jakobleff, MD, Yu Xia, MD
Introduction Twenty-five years ago ECMO was the only

widely available and reliable means of sup-
Heart transplantation is considered for porting the circulation for 24 hours to several
heart failure when the expected result will be a weeks. Other medium and long-term support
meaningful survival advantage compared with devices have surpassed it. Although infants
conventional medical or surgical therapy. In the awaiting transplantation still usually receive
last 50 years of cardiac transplantation there support with ECMO, only 12% of adolescents
have been developments in surgical technique, receive ECMO. The ISHLT registry reported
technology, immunology, and logistics, which that 29% of children were bridged to heart
have contributed to improved recipient survival. transplantation with some form of mechanical
The number of patients listed for heart transplan- circulatory support (MCS) in 2012, but only 4%
tation outstrips the organ supply and each year received ECMO alone.5 For short-term support
more potential recipients are added to the list in children, ECMO has the clear advantages
than hearts that become available.1 This dearth of its nearly ubiquitous availability and easy
of organs has forced innovations: deployability and as such provides a ‘bridge to
decision’ or a ‘bridge to a bridge’.
• Transplanting across blood groups in chil-
dren2 Pretransplant ECMO
• Greater willingness to consider marginal
donors Adults
• Investigating the possibility of using hearts
from deceased cardiac donors (DCD).3 Because of the scarcity of organs and
• Development of implantable mechanical lengthy waiting lists, half of all heart transplant
hearts / assist devices4 recipients are bridged to transplant with MCS,
Currently the most influential development almost all of whom receive durable LVADs.
is that of implantable ventricular assist devices Less than 1% of all patients are bridged directly
(VAD) in the treatment of heart failure in adults. with ECMO, although this proportion has in-
With alterations in the cost profile and technical creased slightly in recent years.
6
developments of the devices; combined with In patients with acute cardiopulmonary

better patient selection and followup, these are failure, ECMO is easier to implement and less
transforming the treatment of heart failure. costly than durable MCS. However, long-term
649
Chapter 59
use is associated with an increased risk of thy in the pediatric heart failure study showed
thromboembolic events, infection, and multior- that children could be transplanted successfully
gan dysfunction. Should a patient not qualify for but that ECMO use pretransplant was associated
VAD implantation due to severe hemodynamic with death. Brown showed that although costly,
instability or organ dysfunction, ECMO can sta- ECMO proved a cost effective method of bridg-
bilize the patient, improve end-organ function, ing to transplant in cardiac failure; however, the
and allow evaluation for VAD and transplant. comparison group in this study was derived
The use of ECMO in this “bridge-to-bridge” from the era before durable mechanical support
strategy was initially avoided by some centers was available.16
as it was associated with a decrease in survival Paracorporeal pumps were used in some
following VAD implantation.7 These poor out- centers in the 1990s,18 especially in adoles-
comes may be due to the inability to unload the cents.19 The paracorporeal devices provided
left ventricle resulting in pulmonary edema and a longer duration of support than ECMO.21,22
the resultant increased necessity for right-sided A trial of the Berlin Heart was designed23 us-
support following LVAD in patients initially ing ECMO patients as a comparison group as
supported with ECMO. However, Pagani et al. Almond24 showed in a retrospective study that
found that LVAD survival after ECMO support fewer than half the children supported with
did not differ compared to a group of patients ECMO as a bridge to transplantation survived
undergoing initial LVAD support despite higher to hospital discharge.
initial acuity in the ECMO group.8,9 Lebreton The EXCOR trial clearly demonstrated the
demonstrated that the bridge-to-bridge strategy superiority of the Berlin Heart Excor device
was viable, adding that physiologic improve- over the historical ECMO control group for the
ments on ECMO support were associated with medium and long-term survival of children with
better survival following MCS implantation.10 cardiomyopathy, albeit with a significant risk of
both bleeding and stroke in the study group.25
Outcome The constraint in the organ supply com-
bined with increasing demand for hearts has
In summary, while ECMO may not play lengthened waiting times. 26-28 However, no
a major role in bridging adults directly to single VAD exists that satisfactorily supports
transplantation, it can stabilize a critically ill patients in all age groups. ECMO still has a
patient to allow for further MCS and transplant place in the short-term support and stabilization
evaluation. of children with incipient collapse (eCPR) while
the child’s condition is reviewed and the options
Pediatrics assessed. These usually include:
Bridging to transplant with ECMO was • Recovery from a coexistent problem or

reported in the 90s.11 Del Nido showed that surgery
support could be provided in dilated cardiomy- • Stability with a good neurological outcome
opathy and postoperative heart failure.12 Bar- and assessment for VAD
ziv suggested that support for cardiomyopathy • Severe brain injury or unstable multiorgan
in children achieved acceptable outcomes as failure that precludes further support and
the waiting times were shorter.13 In 2009, both results in a palliative care pathway
Mah14 and Kirk15 reviewing the outcomes re-
spectively in children listed for transplantation
in the U.S. and those with dilated cardiomyopa-
650
Outcome Cannulation for ECMO
Analysis of Pediatric Heart Transplant Patient and vessel size, clinical context, and
Study (PHTS) database 1993-2013 revealed unit experience determine cannulation strategy.
that 8% of children listed for transplant re- An open chest cannulation is done using the
ceived ECMO support. Survival at 12 months aorta and the right atrium, usually after cardiac
after listing and 3 years after transplantation surgery; this option exists for any age, but is
was significantly lower in those on ECMO made more difficult by prior sternotomies.
support compared with those on VAD support In children under 15 kg the neck vessels are
(50% vs. 76%, and 64% vs. 84% respectively). commonly used to provide ECMO. When the
Also, patients younger than 1 year old had the child weighs more than 15 kg we cannulate the
worst survival when transplanted from ECMO femoral vessels. Appropriate cannula sizes are
support. This high risk profile and the poor detailed in the chart in Table 59-1.
outcomes associated with ECMO support have Standard neck cannulation for circulatory
led to aggressive investigation of alternative assist is the normal practice in infants but is
methods of pediatric MCS.28 associated with neurological damage compared
with direct or femoral cannulation in children.32
The Decision for ECMO vs. VAD in the Child This tendency might be lessened by an ‘inkwell’
or Adult Pretransplant cannulation into a graft sewn to the carotid
which would minimize the chance of carotid
De novo Heart Failure occlusion (Figure 59-1).
Femoral cannulation is easy to deploy and
We now assess and triage to VAD should more straightforward during an arrest situa-
patients merit medium term support and be tion but has two disadvantages. The cannula
eligible for transplant. can obstruct arterial flow to the leg; this can
Myocarditis
When a high index of suspicion for this

disease exists then ECMO is easy to deploy and
has been successful.29-31 ECMO should only be
used for a brief interval; after more than 7-10
days we would convert to a VAD although the
use of the cheaper centrifugal pumps in a simple
LV support configuration may be equally effec-
tive, less expensive, and complex.
Emergency Situations
Emergency situations dictate the use of Figure 59-1. Inkwell cannulation of Goretex
ECMO because of ease of deployment and abil- graft applied end to side of carotid artery, this
ity to stabilize the child/adult, allow assessment, child had cardiomyopathy. It is also possible
and bridge to decision. to tunnel the Goretex graft to a remote skin
incision so that it does not become colonized
with bacteria, this makes the cannulation more
durable and decannulation easier.
651
Chapter 59
be monitored by clinical examination and Left-Sided Decompression after ECMO in the

oximetry33 and should be quickly addressed by Context of Heart Failure
antegrade distal perfusion of the limb should
concerns arise.34 (Figures 59-2 and 59-3) When the heart fails, the systemic ventricle
The possibility also exists of differential cannot generate sufficient stroke volume which
flow of oxygenated blood to different parts of decreases cardiac output (CO) and perfusion
the body due to the inadequate mixing of less pressure of the end organs and coronary arter-
well oxygenated blood from the heart flowing ies. In this setting ECMO enhances CO but the
principally to the upper part of the body, the so increase in both the diastolic and mean arterial
called “Harlequin Syndrome.”35 This can be pressures augments afterload on the left ven-
minimized by draining the SVC with the femo- tricle (LV). To eject, the LV must generate a
ral venous drainage cannula, not something that systolic pressure at least equal to aortic diastolic
is routinely attempted.36 Femoral cannulation pressure. Despite the increase in arterial pres-
is not directly associated with cerebral injury. sure and improved CO the LV pressure volume
Table 59-1. Cannula size table taken from Texas Children’s Hospital (Courtesy of S.C. Tume).
Neck Groin Central

Patient
(Medtronic (Maquet (Medtronic Tubing
Weight
Biomedicus) HLS) DLP)
Lt
Venous Arterial Venous Arterial Rt Atrial Arterial
Atrial
< 2kg 8/10 8 14 12 8 1/4
2-2.9 kg 10 8 16 12 8 1/4
3-3.9 kg 12 10 16 12 10 1/4
4-4.9 kg 12 10 18 14 10 1/4
5-5.9 kg 12 10 20 14 12 1/4
6-6.9 kg 14 10 20 14 12 ¼
7-7.9 kg 14 10 20 16 12 ¼
8-8.9 kg 14 12 20 16 12 ¼
9-9.9 kg 14 12 20 16 12 ¼
10-12 kg 14 12 20 16 14 3/8
13-14 kg 14 14 22 18 14 3/8
15-16 kg 14 14 22 18 14 3/8
May need
17-18 kg neck cannula 19 15 22 18 14 3/8
due to size
19-20 kg 19 15 24 18 14 3/8
21-25 kg 19 15 24 18 16 3/8
26-30 kg 21 15 24 18 16 3/8
31-35 kg 21 15 24 18 16 3/8
36-40 kg 23 17 26 18 16 3/8
41-45 kg 25 17 26 20 16 3/8
46-50 kg 25 17 26 20 16 3/8
51-60 kg 29 19 28 20 18 3/8
61-65 kg 29 21 28 20 20 3/8
66-70 kg 29 21 28 20 20 3/8
>70 kg 29 21 30 20 22 3/8
652
relationship shows a significantly larger pres- ited in children because of patient size and
sure volume area (PVA) and MVO2 due to an poor synchrony with higher heart rates.39
increase in LV preload and afterload. In heart • Atrial septostomy or placement of the left
failure the systemic ventricle cannot generate atrium or left ventricle drain
enough pressure to eject and stoke volume is
further compromised. The arterial waveform Atrial septostomy can be performed using
pulsatility becomes diminished. Blood returning a balloon or blade to dilate or perforate the
from the bronchial and Thebesian veins along atrial septum. This is commonly accom-
with the decrease in LV emptying result in a plished in the catheterization laboratory
gradual (usually) filling and then distension of under TEE and fluoroscopy.
the left heart (seen best on cardiac ultrasound) Left atrial drain can be placed by the inter-
with a consequent rise in left atrial and pulmo- ventional cardiologist percutaneously in
nary venous pressure that can result in frank the catheterization laboratory with the use
pulmonary edema.37 of TEE. This allows for direct drainage of
The case for action is clear when frank blood from (Figure 59-4) the left atrium
pulmonary edema occurs. Decisionmaking is and can be incorporated into the ECMO
less easy when the child does not experience circuit.40,41
pulmonary edema and the ECMO works well.
Assessment should include:
• Clinical examination
• Regular cardiac ultrasounds
• Chest radiographs
Should the left side be distended the op-

tions include:
• Inotropes and vasodilators to enhance LV

emptying and reduce afterload promoting
aortic valve opening38
• An intraaortic balloon pump (IABP) may
be used as detailed in the experience of the
Paris group. Use of this mode remains lim-
Figure 59-2. Lower limb perfusion in femoral Figure 59-3. Calf oximetry: a near infrared
VA ECMO for cardiac support. The arrow indi- spectroscopy transducer applied to the calf of
cates the perfusion cannula for the leg. a child on VA-ECMO to check for evidence
of limb ischemia.
653
Chapter 59
Central cannulation and LA drain place- compliance with treatment of pediatric patients
ment. Performed by a surgeon as open and our inability to fully rehabilitate on ECMO,
operation (sternotomy) or via an intercostal most centers elect not to extubate children on VA
incision. (Figure 59-5) ECMO support although the practice appears
to be evolving.
In complex (redo, etc.) cases a left ventricu-
lar apical drain can be placed (Figure 59-6)
Our cardiologists usually decompress the

left atrium in the catheterization laboratory.
Cannulae used are between 8-15 Fr.
Decision to Wean or Transfer to VAD from

ECMO
In the field of cardiac support, ECMO has

become a short-term treatment. If there is no
indication of myocardial recovery within one
week, we would change to VAD support, given
hemodynamic stability, resolving multiorgan
failure, controlled hemostasis, good fluid bal-
ance, appropriate assessment, and consent. The
data in our center suggests that ECMO before
VAD does little harm.42
Ventilator Management
Standard lung protective ventilation strat-

egies are used. Due to concerns about poor
Figure 59-6. Apical ventricular drain in a redo
transplant placed for left-sided decompression.
Figure 59-4. Percutaneous left atrial decom- Figure 59-5. Intercostal placement of venous
pression in a patient on VA-ECMO for conges- cannula and left atrial drain in a redo ECMO
tive heart failure. support.
654
Transfusion to sympathetic volatility and cytokine release,

cold followed by warm ischemic injury, and
We apply normal blood product protocols reperfusion injury. Numerous risk factors have
to maintain oxygen carrying capacity and the been identified (see Table 59-2, after Kobash-
coagulation profile (see Chapter 8). Given the igawa47), but only one validated risk score has
sensitivity of the ‘new’ PRA assay it is hard been reported (RADIAL).52
to know how much, if any, harm we are doing Most studies of PGD were limited by vari-
by further transfusions. As has been frequently able definitions used by different centers. As
noted, patients on VAD appear to produce many a result, ISHLT consensus guidelines were
antibodies. established in 2014 to standardize diagnosis
and more consistent reporting (Table 59-3, after
ECLS after Heart Transplantation Kobashigawa47).
Diagnosis of PGD must be made within
Primary Graft Dysfunction 24 hours of transplant and exclude secondary
causes such as bleeding, technical issues, and
A feared complication of heart transplanta- hyperacute rejection. In pediatric practice, there
tion is primary graft dysfunction (PGD), which are more marked size discrepancies between
occurs in 2-26% of adult heart transplant recipi- donor and recipient hearts.53 There is a similar
ents and in up to a third of pediatric transplants relationship between ischemic time and hypo-
and is associated with increased morbidity and tension after transplantation but a higher chance
mortality.6,43-51 Pathogenesis is complex and the of pulmonary hypertension complicating the
causes numerous, including donor brain death procedure.54,55
and associated hemodynamic instability due
Table 59-2. Risk factors for primary graft dysfunction, after Kobashigawa.47
Donor Risk Factors Recipient Risk Factors Procedural Factors

Age Age Ischemic time
Cause of death Weight Donor recipient sex
mismatch
Trauma Mechanical support Weight mismatch
Cardiac dysfunction Congenital heart disease None cardiac organ
donation
Inotropic support Re-operations Procurement team
experience
Comorbidities Comorbidities, renal or Center volume
liver dysfunction
Cardiac arrest downtime LVAD explant Cardioplegic solution
Drug abuse Ventilator dependent Increased blood
transfusion
Left ventricular Multiorgan transplant Emergency or elective
hypertrophy transplant
Valvular disease Allosensitization
Hormone treatment High PVR
Wall motion abnormalities Infection
Sepsis
Marginal donor allocation Retransplant
Troponin trend
Hypernatremia
655
Chapter 59
Intraoperative Assessment for ECMO tory graft failure, early ECMO provides greater
Requirement cardiac output. (If femoral ECMO cannulation
is used, a femoral IABP may obstruct ECMO
After a period of reperfusion, the assess- flow and increase the risk for peripheral vascular
ment of donor cardiac function is done by visual complications).47,49,50 In the case of a known
inspection, TEE or epicardial echo in smaller marginal donor or increased risk factors such
patients, near infrared spectroscopy (NIRS), as a prolonged ischemic time, ECMO may be
and hemodynamic measurement. Laboratory instituted prophylactically to ensure adequate
adjuncts include arterial blood lactate, base perfusion in the early postoperative period.
deficit, and mixed venous saturation. Patients In pediatric practice we use similar methods
commonly require low dose inotrope and va- of assessment.50,56-62 Patients with good func-
sodilator requirements but those who remain tion, low filling pressures, and low lactates
hemodynamically unstable (CVP >15, SBP <90 will not require ECMO. However, donor heart
mmHg, MAP <70, PCWP >20 mmHg, and CI performance is idiosyncratic and unpredictable,
<2.0) despite several attempts to separate from even donor hearts with good function prior to
bypass with a need for high dose inotropes retrieval and short ischemic times may fail after
should be considered for additional circulatory implantation.
support. Pulmonary artery hypertension post- Assessment depends on the available
operatively should be considered54,55 and these clinical data and team experience. While poor
patients should receive inhaled nitric oxide and function is evident at the time of implantation,
milrinone to improve right heart dysfunction. it may occur after admission to the ICU. Should
In adults, an IABP may be considered for the heart appear suboptimal from the start, for
further therapy; however, in the case of refrac- instance when a ‘marginal donor’ is used as part
Table 59-3. Classification of Primary Graft Dysfunction (PGD), after Kobashigawa.47
PGD Left ventricle: Mild PGD LV one of the i. LV Ejection fraction <40%
PGD-LV criteria must be met ii. RAP > 15 mmHg or PCWP >
20 and CI < 2 L/min /m2 on
low dose inotropes for more
than one hour
Moderate PGD LV must I
have one criterion from I and i. LV Ejection fraction <40%
one from II ii. RAP > 15 mmHg or PCWP >
20 and CI < 2 L/ min /m2 with
hypotension < 70 mm HG for
more than one hour
II
i. on high dose inotropes, score
> 10
ii. newly placed IABP
independent of inotropes
Severe PGD LV Dependence on single or

biventricular support more than an
IABP including ECMO
PGD right ventricle: Diagnosis requires both i and i. RAP > 15 mm Hg, PCWP <
PGD-RV ii, or iii alone 15 and CI < 2 L/ min /m2
ii. TPG < 15 mmHg and PA
systolic pressure < 50 mm Hg
iii. Need for RVAD
656
of a strategy to deal with the waiting list, the with mixture of deoxygenated blood, and poten-
use of ECMO may be routine.63 tial for distal limb ischemia and other vascular
complications. Insertion of a distal perfusion
Cannulation Strategies catheter is highly recommended in this setting.
If this is not done, then careful observation of
Cannulation varies by center and may the limb for compartment syndrome is manda-
depend on surgeon preference and anticipated tory; calf oximetry may be helpful.64
support requirements.47,50 The bypass circuit
can be converted to ECMO by using the atrial Aims of Support
and aortic cannulae, which allow higher flows,
antegrade flow through the aortic arch, and The goal of ECMO after heart transplan-
decreased peripheral vascular complications. tation is to allow for the allograft to rest and
There will be an aortic cannula, an atrial cannula, recover while maintaining adequate organ
and a vent to drain the left side. When antici- perfusion. Hemodynamics should be closely
pating poor function, the surgeon may create monitored and cardiac recovery frequently
an ASD prior to implantation (the adequacy of assessed with echocardiography. Neurologic,
this shunt needs to be assessed on ultrasound renal, hepatic, pulmonary, and other end-organ
postoperatively). perfusion should be maintained, and appropri-
Tunnelling the cannula and closing the ster- ate replacement therapy used when indicated.
num reduce the chance of infection (Figure 59-7). In the immediate postoperative period one
Upon graft recovery, however, decannulation can run without heparin until hemostasis is as-
requires reopening the sternum which allows sured; this strategy requires ready availability
for visual inspection of cardiac function, the of another circuit in case of circuit thrombo-
drainage of pericardial fluid collections, and sis. After restarting anticoagulation, the team
biopsy if acute rejection is suspected.50 should monitor for cerebrovascular events and
Femoral cannulation obviates the need to re- gastrointestinal hemorrhage. If acute rejection
open the sternum, but drawbacks include lower is suspected, endomyocardial biopsies should
achievable flow, retrograde flow down the arch be obtained via right heart catheterization and
immunosuppression augmented as indicated.
Assessing Recovery
Recovery usually occurs between 2-5 days

after implantation.65 Evidence of recovery in-
cludes return of pulsatility in the presence of
adequate but not excessive inotrope use. If the
overall condition of the patient allows, elective
reduction in flow and echo assessment with RV
filling should follow.66 If propitious, weaning
continues to idling and the patient can then be
‘clamped off’ ECMO prior to decannulation.
Decannulation takes place in the operating
Figure 59-7. Posttransplantation. Tunnelled theatre. The chest is left open for 24 hours or
cannulae; venous and left atrial drain on the
left hand margin, tunnelled aortic cannula on more and closed later.67
the right hand margin.
657
Chapter 59
Outcomes allograft vasculopathy. When indicated, ECMO

should be considered soon after presentation to
Prior to the advent of ECMO and other provide support during periods of augmenta-
modes of mechanical support, early graft fail- tion of immunosuppression. Kittleson showed
ure invariably led to mortality in the absence improved outcomes when ECMO is used as
of retransplantation. In recent reports, graft preemptive therapy as opposed to an element of
recovery allowing for decannulation typically cardiopulmonary resuscitation; survival to dis-
occurred within 2-5 days. Successful weaning charge was 79% in the former group, although
of ECMO has been reported in 60-100% of only 26% were alive at one year.74,75
patients and 30-day or survival-to-discharge ECMO deployed to support augmentation
reported between 46-100%.44,49,50,68 In children of immunosuppression may be effective and
who require ECMO after transplantation the allow assessment of recovery, VAD, or retrans-
survival typically reaches 50-60%.60,62,69 If a plantation. The latter is less likely to be success-
patient survives the early period, ECMO-treated ful within one year of the initial transplant, and
PGD is not associated with decreased survival is a cofactor for early death in 6-17 year olds.5,74
at 1 or 5 years.45,51,52
The choice of mechanical assist device vs. Conclusion
ECMO support for severe PGD remains under-
studied. Taghavi found similar survival between ECMO is still used in the acute care of
patients supported with RVAD or ECMO in children with heart failure and will save lives.
isolated right-sided dysfunction but overall graft Newer forms of circulatory support are usually
recovery was improved in the ECMO-treated deployed to bridge to transplant because of
patients.70 PGD has also been successfully man- longer waiting times and have satisfactory out-
aged with the Levitronix Centrimag, although comes. Whether the relatively poor outcomes
a direct comparison with ECMO was not been of bridge to transplant with ECMO are due to
made.71 ECMO or variables such as sedatives, depen-
dency, and inability to rehabilitate is unclear.
Failure to Recover Donor Heart ECMO has a small role in the treatment of
adult heart failure, probably restricted to acute
Should the graft not recover then a critical resuscitation as a ‘bridge to decision’ or ‘bridge
assessment of the anatomy of the donor heart to a bridge’.
with ultrasound, CT, and catheter is required. A
biopsy to assess degree of rejection is usually
easily accomplished on ECMO. If rejection oc-
curs, we augment and review immunosuppres-
sion and assess the comorbidities. A discussion
on the likelihood and feasibility of successful
medium term support to recovery or retrans-
plantation should then take place.72,73
Late Graft Failure
Late graft failure can be supported with

ECMO. Late graft failure usually occurs due
to acute cellular mediated rejection or chronic
658
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Future Cardiol. 2013;9(4):489-495. temporary cohort and performance of the
35. Hoeper MM, Tudorache I, Kühn C, et al. RADIAL risk score. J Heart Lung Trans-
Extracorporeal membrane oxygenation wa- plant. 2013;32(12):1187-1195.
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36. Cove ME. Disrupting differential hypoxia al. Extra-corporeal membrane oxygenation
in peripheral veno-arterial extracorpo- temporary support for early graft failure
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2015;19:280. thorac Surg. 2010;37(2):343-349.
37. Combes A, Leprince P, Luyt CE, et al. 45. D’Alessandro C, Golmard JL, Barreda E,
Outcomes and long-term quality-of-life of et al. Predictive risk factors for primary
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and early reperfusion (the CHEER trial). experience with a review of the literature.
Resuscitation. 2015;86:88-94. Can J Cardiol. 2007;23(5):363-367.
39. Petroni T, Harrois A, Amour J, et al. Intra- 47. Kobashigawa J, Zuckermann A, Macdonald
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extracorporeal membrane oxygenation. Crit 2014;33(4):327-340.
Care Med. 2014;42(9):2075-2082. 48. Lim JH, Hwang HY, Yeom SY, Cho HJ, Lee
40. Cheung MMH, Goldman AP, Shekerdemian HY, Kim KB. Percutaneous extracorporeal
LS, Brown KL, Cohen GA, Redington AN. membrane oxygenation for graft dysfunc-
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diatr Critic Care Med. 2003;4(4):447-449. 49. Listijono DR, Watson A, Pye R, et al.
41. Aiyagari RM, Rocchini AP, Remenapp RT, Usefulness of extracorporeal membrane
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Chapter 59
tation. Ann Thorac Surg. 2010;90(5):1541- 59. Rodrigues W, Carr M, Ridout D et al. Total
1546. donor ischemic time: Relationship to early
51. Seguchi O, Fujita T, Murata Y, et al. Inci- hemodynamics and intensive care morbid-
dence, etiology, and outcome of primary ity in pediatric cardiac transplant recipients.
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54. Mitchell MB, Campbell DN, Ivy D, et al. genation support after pediatric orthotopic
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58. Marasco SF, Esmore DS, Negri J, et al. 1745.
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68. Lima EB, da Cunha CR, Barzilai VS, et

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69. Tissot C, Buckvold S, Phelps CM, et al.
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70. Taghavi S, Zuckermann A, Ankersmit J, et
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2004;78(5):1644-1649.
71. Thomas HL, Dronavalli VB, Parameshwar
J, Bonser RS, Banner NR:Steering Group
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dit.. Incidence and outcome of Levitronix
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72. Kanter KR, Vincent RN, Berg AM, Mahle
WT, Forbess JM, Kirshbom PM. Cardiac
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73. Mahle WT. Cardiac retransplantation in chil-
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74. Kittleson MM, Patel JK, Moriguchi JD, et al.
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75. Perri G, Hasan A, Cassidy J, et al. Extra-
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663
60
Immunodeficiency and ECLS
Matteo Di Nardo, MD, Veronica Armijo-Garcia, MD, Thomas Staudinger, MD,

Gerry Capatos, MD, Heidi Dalton, MD
Introduction disease that may not differ from cancer patients

who were never admitted to the ICU.1,2 Thus, a
Traditionally, Extracorporeal Life Support general reluctance to admit critically ill cancer
(ECLS) has been reserved for patients suffering patients to the ICU can no longer be justified.3
acute cardiac or respiratory failure due to revers-
ible diseases expected to have a good quality ECLS Utilization in Patients with Malignancy
of life after recovery. Concerns whether ECLS
should be offered to immunocompromised Previously, limited use of ECLS for patients
patients have led to many thought-provoking with cancer was most likely influenced by
discussions in the past. Furthermore, the lack cancer-related mortality as well as the ideol-
of specific criteria for ECLS use in the immu- ogy of ECLS being a support modality offered
nocompromised renders patient selection more only to acutely ill patients with no underlying
challenging. This chapter provides current in- chronic illness. Since 2009, reports describing
sights and, where possible, new selection crite- ECLS use for patients (pediatric and adult)
ria for ECLS use in patients with solid and bloodwith malignancy have been published, im-
cell tumors, patients receiving hematopoietic plying increased use in this population, most
stem cell transplantation (HSCT), and patients likely due to improved oncologic survival and
with autoimmune diseases or HIV. more widespread ECLS use in complex patient
populations.6,7 A 2008-2012 analysis of the Ex-
ECLS Support in Pediatric and Adult tracorporeal Life Support Organization (ELSO)
Patients with Solid Organ and Blood Cancer Registry documented that 178 pediatric patients
with malignancy received ECLS, doubling uti-
Survival for adult and pediatric patients lization compared to that reported previously.6
with malignancy over the last 30 years has mark- Furthermore, several pediatric and adult cases
edly improved due to advancements in aggres- of successful use of ECLS as a bridge to thera-
sive chemotherapeutic regimens and supportive peutic interventions or chemotherapy have been
measures. During the last decade, a large body recently published.8,9
of evidence suggests that adult ICU survivors An analysis by Gow and colleagues of 72
regain favorable quality of life, tolerate the adult cancer patients in the ELSO Registry from
continuation of anticancer therapy, and have 1992-2008 reported an overall survival rate of
long-term survival defined by their underlying 32%. Most patients had solid tumors and respi-
665
Chapter 60
ratory failure but ECLS for cardiac indications pre-ECLS arrest compared to 18% in the era
surprisingly yielded better outcomes. Compared prior to 2008.6,7
to the general ECLS population, survival was
significantly lower. Of note, infections occurred Indications, Contraindications and Specific
more commonly in cancer patients, whereas Considerations
bleeding events did not.7 In another study of 14
adult patients with hematological malignancy, Indications and contraindications for ECLS
VV-ECLS was used for ARDS due to pneu- in patients with malignancy reflect those applied
monia in 11 patients. Three patients received to most other patients. However, insights into
VA-ECLS due to septic cardiomyopathy, or life the underlying malignancy should be investi-
threatening circulatory and respiratory failure gated prior to acceptance of candidacy. Such de-
due to massive mediastinal bulky disease. Five tails include but are not limited to 5-year disease
patients received rescue chemotherapy during survival, secondary organ involvement, degree
ECLS. Overall survival reached 50%. All sur- of immune suppression, expected time course
vivors had hematological remission and were for return of white blood cells and ongoing in-
alive at followup after 36 months.10 fections. An analysis by Green et al. from the
A review of children from the ELSO Reg- 1990s found that patients most likely to benefit
istry from 1994-2007 by Gow et al. included from ECLS had a mortality risk of 50-75%.13
107 patients with oncologic disease (HSCT Patients suffering from malignancies with a
patients were excluded) with 35% survival 5-year survival of less than 50%, irrespective of
to discharge.11 More recently, an abstract by their acute critical illness, should be considered
Armijo-Garcia et al. reported 178 ECLS pa- less favorable candidates for meaningful long-
tients with malignancy (also excluding HSCT term benefit from ECLS but this may vary by
patients) from 2008-2012, with 48% survival local practice. Of course, the more severe the
to discharge despite similar complication rates acute illness, the worse the prognostic outcome.
compared to those documented previously. Type A collaborative effort between the critical care
of malignancy (hematologic or solid) did not physician, the oncologist, the ECLS physician,
impact survival.6 Compared to ECLS patients and the family is necessary to make the most
without malignancy, pediatric ECLS cancer considered but difficult decision.
patients from 2008-2012 had increased rates Several other distinct considerations should
of gastrointestinal hemorrhage, leukopenia, be taken into account when using ECLS in
hyperglycemia, myocardial stun, and receipt patients with malignancy:
of inotropes. However, after multivariate re- • A clear understanding of goals of support
gression analysis, none of these complications as well as criteria for potential withdrawal
translated into an increased mortality risk for is critical for both the medical team and the
the patients with malignancy.12 family. A clear communication strategy and
Over the last two decades, survival dur- the skills of the palliative care team may
ing acute, severe illness supported by ECLS prove helpful in situations of withdrawal.
has paralleled improvement in survival from • Typical complications of cancer patients
primary oncologic disease. In the pediatric include infection and bleeding, often due
population with malignancy, this improved to leukopenia and thrombocytopenia. Most
survival is notable in light of increased severity patients receive broad spectrum antibiotics
of illness, as evidenced by the 31% of the pedi- and are susceptible to opportunistic infec-
atric patients from 2008-2012 who experienced tions, making extensive diagnostic tests
inevitable. Use of heparin coated tubing
666
in patients with platelet counts lower than have been reported.6,7 This better outcome can
20000 µL may obviate heparin infusions be explained because autologous transplants
in the first few ECLS days without sig- quickly recover innate and adaptive immu-
nificant impact to circuit function, as long nity without the risk of graft vs. host disease
as adequate flows can be achieved given (GVHD). Pooled data from European adult
the circuit configuration, oxygenator, and centers showed poor outcomes in allogeneic
patient size. Heparin-free ECLS should be stem cell transplanted patients who received
undertaken with more caution in children ECLS, with survival ranging from 10 to 20%.
<10 kg, especially with an adult-sized Importantly, survivors were usually admitted
oxygenator. long after their engraftment (>100 days ).22 No
• ECLS should not be the reason for with- patient was admitted during the peri-transplant
holding life-threatening chemotherapy. period or within 100 days after the engraftment
Chemotherapy can be effective,11 although survived, probably because in the first three
the changes in pharmacokinetics on ECLS months after engraftment patients have not com-
makes the relationship between dose and pleted their immune reconstitution. Therefore,
side effects difficult to predict (see Chapter the use of ECLS for severe respiratory failure
71).14 in this setting is considered a strong contrain-
• If possible, “awake” ECLS may minimize dication by many. Unfortunately, appropriate
infection risks but evidence for this ap- selection of the “best” candidate and proper
proach remains limited.15 timing for ECLS in HSCT patients remain dif-
• Patients with viral or fungal infections and ficult, given the limited clinical experience and
anticipation for prolonged immunosup- reported outcomes.23-25
pression (eg, neutropenia) prior to ECLS
have a guarded prognosis and likely will Technical Considerations
not improve until the immune suppression
has abated. In ECLS candidates with severe respira-
tory or cardiac failure after HSCT, physicians
ECLS in Patients Treated with Hematopoi- should evaluate the underlying disease (eg, he-
etic Stem Cell Transplant (HSCT) matologic disease [benign vs malignant], inborn
errors of metabolism, or immune deficiency);
In the last decade, survival of critically the conditioning regimen (myeloablative vs.
ill patients admitted to ICU who received al- nonmyeloablative); type of HSCT (autologous
logeneic or autologous HSCT has improved, vs. allogeneic); graft source and its manipula-
particularly in children.16,17 The main causes of tion as well as the human leukocyte antigen
ICU admission include respiratory failure and (HLA) matching.
septic shock.18,19 In light of these results, debate
continues regarding the use of ECLS in HSCT Use of ECLS to Manage Respiratory Failure
patients with refractory severe respiratory and/ after HSCT
or circulatory failure. Allogeneic stem cell trans-
plantation is generally considered an absolute Pulmonary infections in HSCT patients
contraindication for ECLS because of its poor (mostly in the early phase after HSCT) are
survival.10,20-22 In contrast, ECLS outcomes often life threatening and difficult to manage.
among patients receiving autologous stem cell Therefore, prompt initiation of broad spectrum
transplantation approach those of patients with antimicrobial therapy is warranted. Specific
hematological malignancies, although few cases antiviral and antifungal therapy is added after
667
Chapter 60
empirically or confirmation of infection.26 loimmune injury to the lung by transplanted

Respiratory failure preceding engraftment is stem cells. ECLS may serve as a bridge to lung
an absolute contraindication because of the transplantation in BOOP and other endstage
inability of the immune system to clear infec- lung diseases.32,33
tion without the support of the innate and the Transfusion related acute lung injury
adaptive immune responses.27,28 ECLS after (TRALI) may occur in HSCT patients after the
engraftment remains at least a relative contra- administration of large amounts of blood prod-
indication and should be used only when the ucts. However, its management rarely requires
patient has achieved a good level of immune ECLS. Transplantation associated thrombotic
reconstitution and when the chance of lung microangiopathy (TA-TMA) is generally as-
recovery appears good within a reasonable sociated with pulmonary hypertension leading
timeframe (~4 weeks of ECLS). The advent of to hypoxemic respiratory failure and right heart
specific therapeutic strategies such as infusion dysfunction, and has a high mortality rate. The
of virus-specific cytotoxic T lymphocytes or exact mechanism remains unknown. No proven
donor T-cells after engraftment has improved therapies have been found and ECLS is not
the outcome of some HSCT patients, providing recommended.
them protection against infections and disease Pulmonary venoocclusive (pVOD) disease
relapse. These newer therapies may expand is a rare cause of pulmonary hypertension fol-
23-25
the range of ECLS use in HSCT patients. lowing allogeneic HSCT. The frequency of
Other noninfectious causes of acute lung pVOD is particularly high in recipients who
injury after HSCT are related to immune have concurrent interstitial pneumonia and
recovery. Early diagnosis and appropriate hepatic veno-occlusive disease. Considering
therapy can help sidestep ECLS use. Idiopathic the absence of a proven therapy for this disease,
pneumonia syndrome (IPS) includes a group of ECLS is not recommended. 26
diseases characterized by noninfectious lung
involvement after HSCT, which may affect the Use of ECLS to Manage Heart Failure after
parenchyma, endothelium, or airway epithelium. HSCT
By definition, IPS requires no active infec-
tions, cardiogenic causes, or renal failure/fluid Congestive heart failure can complicate
overload as causes of respiratory compromise. HSCT, especially in patients receiving au-
The pathophysiology undergirding IPS remains tologous transplantation. Potentially cardio-
unclear, but may depend on the transplant pro- toxic exposures in HSCT include myeloablative
cedure itself (myeloablative conditioning, use conditioning with high dose chemotherapy
of calcineurin inhibitors, GVHD, HLA disparity, (alkylators, anthracyclines, antimetabolites,
allogeneic transplantation, etc.).26 IPS29,30 in- antimicrotubules and antibodies), and total
cludes the peri-engraftment respiratory distress body irradiation. Cardiovascular followup after
syndrome (PERDS), diffuse alveolar hemor- HSCT aids selection of the best candidates for
rhage (DAH) and bronchiolitis obliterans with ECLS as a bridge to recovery or as a bridge to
organizing pneumonia (BOOP). PERDS and a ventricular assist device system.34,35
less severe DAH can often be adequately man-
aged without ECLS. However, severe forms of Vascular Access
DAH31 may require ECLS. BOOP represents a
late complication of HSCT and occurs almost Appropriate cannulae to attain adequate
exclusively in allogeneic recipients with GVHD, flows to meet metabolic and hemodynamic
suggesting that it may represent a form of al- needs may represent a challenge, since these
668
patients usually have at least one long-term of HAART, bacteria also became important
central venous catheter. This kind of catheter, causative agents of ARF. Despite the use of
placed in preparation for the transplant, should HAART, patients with PJ pneumonia (PJP)
be promptly removed to allow the insertion of requiring ICU admission and specifically those
the ECLS cannulae and a short-term central requiring mechanical ventilation for ARF have a
venous catheter should be placed before ECLS. high mortality, approaching 85% in high income
countries, and 100% in resource poor countries.
Management of Coagulation after HSCT However, the overall mortality of hospitalized
PJP patients has not decreased since the intro-
Bleeding frequently complicates HSCT duction of HAART, irrespective of the country.42
since thrombocytopenia occurs during the In the past, HIV patients and particularly
post engraftment period, especially after those with PJP were considered poor candidates
haploidentical stem cell transplantation. for ECLS. However, advances in antiretroviral
therapy (ART) increased HIV patient survival,
Therefore, adequate management of coagu-
thereby impacting the ECLS candidacy of HIV
lation is mandatory. The use of unfraction- patients.43-47 Following the advent of HAART,
ated heparin should be properly tailored treatment compliant HIV positive patients
because the risk of thrombosis increases now attain a nearly normal life expectancy.
in long ECLS runs, especially when daily Therefore HIV has become a chronic illness
platelet transfusions occur. We suggest that in which acute exacerbations of a reversible
platelet counts be maintained over 30,000/ nature should be treated aggressively or when
µL with an ACT level at 170-180 sec or an the initial presentation of HIV is due to an op-
APTT level between 60-70 sec. Fibrinogen portunistic infection (eg, PJP). Resolution of the
levels should be maintained at 200 mg% and acute illness and initiation of HAART appears
antithrombin activity at 100%. Some cen- to restore relatively normal lifespan. ECLS may
form part of the treatment in these situations.48-50
ters report ECLS runs without anticoagula-
tion using high-flow venovenous circuits. ECLS in Patients with PJP: the South Africa
Close observation of bleeding diatheses Experience
and clotting events is obligatory in such
patients. In cases of refractory bleeding, In South Africa, a middle income nation
thrombocytopenia and acquired von Wil- with the highest number of new HIV infec-
lebrand syndrome should be considered.36 tions worldwide,51 PJP is the most common
opportunistic infection causing ARF. Patients
ECLS in Adult Human Immunodeficiency with HIV requiring conventional mechanical
Virus (HIV) Patients ventilation (CMV) have high mortality.52 In the
experience of the group in Cape Town, South
Pulmonary infection and respiratory failure Africa, the use of early ECLS has improved
are the most common causes of ICU admis- outcomes. Of 18 patients with PJP (of 25 total
sion in Human Immunodeficiency Virus (HIV) HIV positive patients treated with VV-ECLS),
positive patients.38-40 Before the Highly Active 11 survived (61%). Although patient numbers
Antretroviral Therapy (HAART) era (before the are small, the 61% survival of PJP patients and
year 2000), Pneumocystis jiroveci (PJ) was the 68% overall survival suggests that ECLS could
primary pathogen responsible for acute respi- be considered as an option in the most severe
ratory failure (ARF).41 After the introduction HIV patients presenting with ARF due to PJP.
669
Chapter 60
Additionally, patients who received more than reported 25% mortality for patients receiving
5 days of ventilation without ECLS had a pre- ARVs, compared to 63% mortality for those
dicted mortality of 90%, suggesting that early not taking them. Therefore, we recommend
ECLS is key for any possible benefit. initiation of ARVs at admission (for the patient
not already on ARVs) for patients with ARF.59
ECLS Candidate Selection for HIV+/PJP+ The combination of antiretroviral therapy and
steroids to treat PJP and/or IRIS has dramati-
Many scoring systems have been used at cally decreased AIDS-associated complications
ICU admission to determine best outcomes for and mortality.
HIV patients.53 From the South African experi- In conclusion, with the advent of new
ence, the most significant predictors of mortality antiretroviral drugs and initiatives to improve
in patients with PJP and ARF were identified diagnostic testing and medication compliance,
during the course of their illness, rather than HIV/AIDS patients can be managed as a com-
at ICU admission. Prolonged mechanical ven- plex, chronic condition. Because these patients
tilation before ECLS, presence of multiorgan have attained a life expectancy comparable to
failure, multi-organism infections, inotropic the general population, more aggressive care
support before ECLS, older age, and cachexia modalities such as ECLS should be considered
were significant predictors of mortality. It is during periods of acute, reversible illness.
noteworthy that CD4 count, PaO2 and the Mur-
ray Score did not predict outcome. ECLS in Adult and Pediatric Autoimmune
Diseases
Antiretroviral Drugs (ARVs) and ECLS
Patients with autoimmune diseases may
Powel et al.41 found that, in a high income suffer acute respiratory failure due to infec-
country, 40% of HIV positive patients pre- tions complicating immunosuppressive therapy
senting with ARF were receiving ARVs and or, more rarely, from direct lung involvement
44% were not. PJP occurred less frequently of autoimmune-mediated inflammatory pro-
in patients compliant with ARVs. Survival for cesses. Thorough investigation for infectious
HIV positive, critically ill patients continues to agents including opportunistic infections and
improve in the current era of ART. Paradoxi- initiation of broad spectrum anti-infectious
cally, antiretroviral therapy has not been directly therapy are warranted at presentation. In cases
linked to improved outcomes in patients admit- of inflammatory processes, appropriate immu-
ted to ICU. Therefore, improved survival may nosuppressive therapy can be lifesaving. ECLS
be due to other contributing factors, including for noninfectious causes of acute respiratory
improved ICU care.54,55 failure due to autoimmune-mediated pulmonary
Initiation of ARVs in the ICU can introduce complications has been rare. A number of case
challenges and additional comorbidities, includ- reports, however, prove that under selected cir-
ing difficulty in drug delivery and absorption, cumstances, ECLS successfully supports such
incorrect dosing, drug reactions, medication patients through their illness.
interactions, effects on viral resistance, and Lung involvement by autoimmune diseases
development of Immune Reconstitution In- can be multifaceted. In patients with systemic
flammatory Syndrome (IRIS).56 Despite these lupus erythematosus (SLE), ARDS rates are
difficulties, initiation of ARVs improves the low (3.5%), usually due to secondary infection.
outcome of critically ill patients, especially Even more rarely, SLE patients suffer lung
those with PJP.43,44,47,57,58 Rodger and colleagues failure due to lupus pneumonitis, vasculitis,
670
or DAH.60 Thromboembolic events including (HLH). 73-74 HLH is a rare life-threatening

pulmonary embolism or myocarditis may impair disorder characterized by severe inflammation
both pulmonary and cardiac performance and, with uncontrolled proliferation and activation of
rarely, lead to cardiogenic shock.61 A thorough lymphocytes and macrophages, secreting large
diagnostic approach to differentiate these syn- quantities of cytokines (“cytokine storm”). The
dromes from infectious complications is manda- hallmark of HLH is the emergence of hemo-
tory including extensive lab workup, CT scan, phagocytosis, a process in which histiocytes
bronchoscopy, and sometimes lung biopsy.62,63 actively engulf blood cells and their precursors.
In cases of pulmonary involvement by the un- The uncontrolled growth is nonmalignant and
derlying autoimmune disease itself, rapid initia- does not appear clonal as in Histiocytosis X.
tion of immunosuppressive therapy (typically HLH can be classified as primary and secondary.
steroids and cyclophosphamide), sometimes The pathophysiology of this syndrome remains
together with plasmapheresis, should be the murky, but involves perforin-mediated cytolytic
priority. In cases of life-threatening respiratory pathways used by natural killer (NK) and CD8
(or, more rarely, cardiac) failure, ECLS may buy T-lymphocytes. Primary HLH is an autosomal
time until recovery. recessive monogenic disorder while secondary
Diffuse alveolar hemorrhage with underly- HLH represents a similar clinical syndrome
ing autoimmune disease such as SLE, polyar- with no known genetic basis. Secondary HLH is
teritis nodosa, or other autoimmune illnesses thought to occur in the context of an underlying
has been successfully managed with ECLS immunologic disease, such as malignancy or an
support.64 ANCA-positive pulmonary vasculitis autoimmune or inflammatory disorder. Second-
(eg, Wegener´s granulomatosis and microscopic ary HLH associated with rheumatic disease is
polyangitis) appears most common.65 Autoim- also referred to as “macrophage activation syn-
mune diseases rarely present initially as DAH, drome” (MAS). Clinical manifestations of both
with an incidence of less than 5%, but the fatal- primary and secondary HLH can be generally
ity rate can reach 50%.66 Bleeding in these cases triggered by an infection, including viral, bacte-
is not a contraindication for ECLS and antico- rial, fungal, and protozoan microorganisms, and
agulation may often be withheld or minimized can be facilitated by immunomodulating thera-
without exacerbation of bleeding.67 Fortunately, pies. Diagnostic criteria for HLH are subtle,71
90% of ANCA-positive vasculitis associated but early diagnosis and treatment may improve
alveolar haemorrhage patients respond rapidly outcomes. Primary HLH is difficult to control
to immunosuppressive therapy.68 and usually requires HSCT. Secondary HLH
Acute SLE-associated myocarditis or mas- appears to respond more readily to immunosup-
sive pulmonary embolism due to antiphospho- pressive therapies but mortality remains high
lipid syndrome or other thrombogenic states in both forms (70% in certain subtypes). The
rarely leads to the need for VA-ECLS. Although use of ECLS to manage this disease remains
ECLS in acute myocarditis can successfully controversial due to its poor results. Virus as-
bridge the patient to recovery,69 pulmonary sociated hemophagocytic syndrome (VAHS)
hypertension due to antiphospholipid syndrome was reported during the 2009 influenza (H1N1)
usually yields high complication and mortality pandemic.75-78. A recent review of the ELSO
rates when managed with ECLS.70 Registry79 reported only 30 children treated for
The use of ECLS to manage pediatric HLH. Survival to hospital discharge was 30%,
autoimmune disease remains uncommon, but no prognostic data could be identified in
limited to brief reports,71-72 usually in the set- patient selection for ECLS.
ting of hemophagocytic lymphohistiocytosis
671
Chapter 60
In conclusion, patients with acute respirato-

ry or cardiac failure complicating autoimmune
diseases represent a poorly studied and complex
population. The decision to support with ECLS
should be discussed with the appropriate teams
(hematology-oncology, rheumatology, infec-
tious diseases) as well as family members while
aggressive therapy for the primary disorder is
instituted.
672
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61
Procedures on ECLS
Peter P. Roeleveld, MD, Giles J. Peek, MD, FRCS, CTh, FFICM
Introduction procedures (lung biopsy, exploratory thora-

cotomy, lobectomy).2 In a retrospective review
The evolution of ECLS circuitry and of adult cardiac ECLS patients, 21% underwent
management techniques over the last 45 years noncardiac surgical procedures.3 High mortal-
has enabled more complex procedures and ity rates occurred in patients who received
operations to be performed safely on patients noncardiac procedures (NCP) on ECLS with a
receiving ECLS. This change has altered patient trend to worse survival than when NCP were
selection as we no longer need to deny patients not performed. Tracheostomy was the most
the chance of ECLS support solely on the basis common procedure followed by laparotomy
of their need for invasive surgery. Neverthe- and fasciotomy. Other documented procedures
less, surgical and interventional procedures on included open cholecystectomy, urologic pro-
ECLS carry the risk of life threatening bleed- cedures, craniotomy with hematoma evacuation,
ing which should not be underestimated. This pericardial window, and vascular procedures.3
chapter initially addresses the basic principles Prolonged experience with surgical inter-
and decisionmaking framework for success- ventions in children on ECLS indicates that such
ful procedures on ECLS and then provides an procedures are technically feasible with the best
overview of such procedures. results achieved when the patient undergoes
With increased use of mechanical circula- rapid postprocedural decannulation.1,4 Hirikati
tory support (MCS), surgical procedures in et al. described 48 procedures in 37 neonates on
ECLS patients have become more frequent and ECLS and concluded that cardiac defects, dia-
more diverse. In 1992, Atkinson et al. found phragmatic hernia, lobar emphysema, and other
that 14% of pediatric ECLS patients received conditions can be safely corrected. However,
surgical procedures (excluding cannulation hemorrhagic and thoracic complications, and
and decannulation).1 A more recent query of multiple surgical interventions were associated
the National Inpatient Database showed that with significantly higher mortality in children
noncardiac surgical procedures were performed on ECLS.1,4 Data demonstrate that few areas of
in 47.8% of adult ECLS patients.2 The most the body and procedures are not amenable to
common procedures included general surgical intervention providing that the proceduralists
procedures (predominantly abdominal explo- are sufficiently expert and take the necessary
ration/bowel resection), vascular procedures precautions.
(control of vascular hemorrhage), and thoracic
679
Chapter 61
Decision Threshold-Three Questions should be called upon within the timeframe

allowable in question 2.
The first question that the proceduralist
must ask is “can the procedure be avoided?” General Principals
This question is more useful than “is the pro-
cedure necessary?” because it focuses attention Preparation and Communication
on what the consequences would be for the
patient if the procedure were not performed. Prior to performing procedures on ECLS
An example of this could be a child on VV- patients, a thorough briefing during which all
ECMO for left sided pneumonia with a large equipment requirements, proposed procedures,
left hemothorax that has been slowly growing areas of responsibility and authority, and po-
for the last week. A chest drain or thoracotomy tential complications with their solutions are
would carry a risk of bleeding, but without the discussed. The specific questions of antibi-
procedure the child is unlikely to inflate the otic prophylaxis, heparin management, and the
pneumonic lung sufficiently to separate from preparation of a primed standby circuit should
ECLS. A caveat to this question is “does this be addressed at this briefing. There should
procedure achieve the therapeutic aim with the always be someone present who is thoroughly
least risk to the patient?” knowledgeable with regard to the hemodynamic
The second question the operator should ask consequences and limitations of the extracor-
is “when is the best time to perform the proce- poreal support.
dure?” In the case given above it is clearly safe
to wait to perform the procedure semi-electively Don’t Let Air into the Circuit
allowing preparation of an ideal team and op-
erating environment. Many procedures will Venting the left atrium, right atrium, ma-
need to be performed emergently (eg, drainage nipulating stopcocks, and cannula bungs can
of a tension hemothorax that impedes venous entrain air into the circuit. In addition, cardiac
drainage). Some procedures can be deferred catheterization can allow air to enter around the
until after decannulation (eg, grafting a burn hemostatic sheath after catheter introduction if
or repairing a fractured bone). This question the venous pressure is low and the pump RPM
relates in part to the balance between the need is creating significant suction.
for the procedure and the need to ensure optimal
operating conditions by transfusing clotting Obtain Absolute Hemostasis (if possible)
factors and platelets, altering heparin infusions,
and administrating antifibrinolytics. With many procedures, residual bleeding
The third question the operator should often persists but usually settles quickly. When
ask is “am I the right person to perform this operating on ECLS one should strenuously
procedure?” Stirling Moss, the famous British attempt to assure total hemostasis including
racing driver of the 1950s and 60s had a rule aggressive packing, draining, and sometimes
that he would never drive at more that 80% of closing the cavity or wound to achieve tampon-
his capacity so that he always had some driv- ade or leaving it open to facilitate exploration.
ing ability in reserve to cope with unforeseen Bleeding from irritation around a tracheostomy
circumstances. The operator should therefore can be easily controlled by removing the tra-
ensure that the proposed procedure falls well cheostomy, intubating the patient orally, and
within their competency. In general terms, for packing the tracheostomy wound. Usually, in
a more complex procedure the best operator
680
Procedures on ECLS
several days the oral tube can be removed and or blood products in case of inadequate ECLS
the tracheostomy tube replaced. support.
General Measures Patient Transport
Specific protocols for performing proce- The team should be notified prior to trans-
dures during ECLS can increase safety and porting patients for procedures. Support from
decrease complications. These procedures can surgeons, perfusionists, and/or the VAD team,
be interventional, surgical, diagnostic, thera- should immediately be available in case of
peutic, or any combination of these. Specific accidental decannulation or other mechanical
procedures require unique approaches. complications during transport (see Chapter 55).
A backup ECLS circuit should remain available
Anticoagulation during transport and the procedure.
Antifibrinolytics (aminocaproic acid/Ami- Anesthetic Considerations

car, aprotinin, and tranexamic acid) successfully
appear to reduce bleeding complications.5-7 Rapid sequence induction/intubation should
Amicar significantly reduced the rate of surgical be considered for VAD patients because of the
site bleeding in 298 pediatric ECMO patients greater risk of aspiration due to the placement
undergoing surgical procedures but was associ- and pressure of the device into the upper left
ated with increased numbers of circuit .5 The abdomen and/or esophagus.8
authors used 100 mg/kg as bolus followed by 30
mg/kg/hr for 72 hrs. No difference in thrombotic Electrocautery
complications (CNS infarct or major vessel
thrombosis) occurred. Tranexamic acid signifi- The interference from electrocautery may
cantly reduced bleeding at the surgical site in disrupt the ECLS circuit. Ideally, the return pad
neonates undergoing congenital diaphragmatic should be placed such that the current will not
hernia repair while on ECLS.7 Aprotinin has pass through the area of the mechanical device.
effectively been used to control bleeding from Bipolar electrocautery should also be used
cannulation sites in adult ARDS patients during whenever possible. Because the “auto” mode
prolonged ECLS (see Chapter 8).6 As stated of the VAD is susceptible to decreased flows
in the ELSO anticoagulation guidelines: “both with electrocautery interference, they should
aminocaproic acid and tranexamic acid are be changed to a “fixed rate” mode.9,10
used in many centers in an effort to prevent
hemorrhagic complications in ECLS patients ECMO Circuit Related Procedures
having surgical procedures.”5
When changing the ECLS circuit, or its
ECLS Management parts, interruption of cardiopulmonary support
should be as brief as possible. Some centers
Alterations in clotting and bleeding pre- have devised ways to replace ECLS without
cipitated by procedures or by manipulating interrupting support by implanting a parallel
anticoagulation can impact ECLS effectiveness. circuit.11 Others simply go as quickly as possible
It may be necessary to prepare, prior to proce- while temporarily increasing standard intensive
dures, to support the patient with conventional care support, such as ventilation and/or inotro-
measures, such as ventilation, inotropes, and/ pes, if necessary. Training for these events can
681
Chapter 61
decrease the likelihood of complications (see Transesophageal Echo

Chapter 67).
Revision of ECLS cannulas may be neces- Transesophageal echocardiography (TEE)
sary to improve positioning, upgrade size, or has become an important diagnostic tool in
removal of cannula related clots. Migration of ECLS, frequently impacting clinical manage-
cannulas can also occur during ECMO, poten- ment.17-19 In VAD and respiratory ECLS pa-
tially compromising flow or causing injury to tients, TEE can determine appropriate cannula
surrounding tissue, including the right ventricle, placement, especially dual-lumen VV-ECMO
right atrium, or inferior vena cava. Therefore, cannulas.20 In cardiac ECLS patients, TEE
malposition of the cannula should be corrected can diagnose (residual) cardiac defects or peri-
expeditiously using fluoroscopic equipment, cardial effusion, evaluate ventricular function,
echocardiography, and/or guidewires.12 determine the need for left atrial decompres-
sion, facilitate (bedside) atrial septostomy or
Diagnostic Procedures interatrial stenting, and guide weaning. 21-23
Systemic anticoagulation does not contravene
Radiologic Procedures performance of TEE.24,25 Contraindications and
complications in ECLS patient are similar to
Ultrasound, roentgenograms, and computed those in non-ECLS patients. Although TEE is
tomography (CT) are standard diagnostic proce- considered safe, even in neonates, and compli-
dures for patients on ECLS. Ultrasound studies cations occur rarely, the benefit-risk ratio should
and most plain radiographs can be performed be examined in each case.17
safely at the bedside. Other radiological inves-
tigations, including CT-scans, require careful Bronchoscopy
attention during transfer to safely complete
the studies.13-15 Clinically significant findings, In patients on VV or VA-ECLS, flexible
leading to changes in patient management were bronchoscopy, bronchoalveolar lavage (BAL),
identified in the majority of chest CT scans of and bronchial washings have been found to be
19 children not progressing after 7-18 days on safe, providing diagnostic information to the cli-
respiratory ECLS.14 When interpreting CT-an- nician and therapeutic benefit to the patient.26-29
giography, one should consider that VA-ECLS Indications include persistent atelectasis, se-
changes filling and blood flow of the cardiac cretions clearance, evaluation of suspected
chambers and pulmonary vessels as well as pulmonary infection with BAL, or foreign
altering the path of the injected contrast.16 In body aspiration.30 No major complications
2006, Lidegran et al. reported the successful use (eg, hemodynamic changes, endotracheal tube
of a mobile ECMO circuit to perform magnetic dislodgement, significant bleeding) were seen
resonance imaging (MRI) in an animal model in three retrospective pediatric reports and one
without interference.13 The ECMO circuit and adult report, without adjusting standard ECMO
the MRI scanner did not interfere with each anti-coagulation.26-28 Spontaneously resolving
other. However, wire-enforced cannulas could blood-tinged secretions occurred after approxi-
not be used. Hitherto, no commercially avail- mately 20-30% of flexible bronchoscopies.
able ECLS system exists which is certified
compatible with MRI. Cardiac Catheterization
Residual anatomic lesions have a strong

negative influence on survival among ECLS
682
Procedures on ECLS
patients after cardiac operations. When echo- a 24 year-old woman with atrial tachycardia
cardiography does not definitely exclude or di- induced cardiomyopathy on VA-ECMO for
agnose residual lesions in these patients, cardiac cardiogenic shock. She reverted to sinus rhythm
catheterization can provide insight into adequa- after successful ablation using radiofrequency
cy of the surgical repair and hemodynamics.31 technique.39 Cheruvu et al. describe a success-
Cardiac catheterization improves outcomes in ful accessory pathway ablation in a 63 year-old
ECPR patients.32 Other indications include as- male on ECMO for cardiogenic shock due to
sessment of coronary anatomy, endomyocardial SVT and atrial fibrillation.40 Rizkallah et al.
biopsy, electrophysiologic study, arrhythmia describe an 18 year-old man with idiopathic
ablation, transcatheter patent ductus arteriosus ventricular tachycardia (VT), who was resusci-
(PDA) or ventricular septal defect (VSD) clo- tated onto ECLS. After stabilization on ECLS,
sure, and left heart decompression.31,33-37 a successful ablation was performed without
In a retrospective study no major complica- complications, with successful decannulation
tions occurred in 28 cardiac catheter studies in 24 hours later.41
22 children on ECLS.31 In another retrospective Vascular access for catheterization in ECLS
study of 60 cardiac catheterizations in ECLS patients can prove challenging, especially in
patients by Booth et al. complications included small children or in adult patients cannulated
two myocardial perforations (3%), one during through the femoral vessels. The use of ultra-
atrial stenting for LV decompression, and the sound-guided percutaneous puncture of femoral
other was presumed to be through the left ven- vessels is advocated. 31 Sometimes surgical
tricular free wall.33 Both patients received man- cutdown is necessary. Some centers have made
agement with epicardial drains. In both studies, adjustments in their ECLS circuits, providing
medical management was adjusted based on access for the cardiac catheter through an ac-
cardiac catheterization data in approximately cessory limb connected to the arterial cannula,
80%.31,33 Callahan et al. described 36 pediatric terminated with a hemostatic valve.42-44
patients undergoing a total of 40 cardiac catheter Cardiac catheterization can be carried out
studies. They noted no complications related to safely during ECLS and may facilitate diag-
patient transport, one nonvascular complication nosis and effective management of residual
(hypotension), and five vascular complications lesions.31,33,38
(compartment syndrome, limb edema, oozing
from cannulation site, temporary pulse loss, ve- Endoscopy
nous thrombus). Survival to discharge was 72%.
Unexpected diagnostic information was found Gastrointestinal (GI) bleeding occurs in 3%
in more than half (52%) of catheterizations.38 to 6% of patients receiving ECLS.45 It may re-
Tachyarrhythmias in children on ECLS quire transfusions and diagnostic or therapeutic
have been safely managed with ablation. Silva interventions such as gastroduodenoscopy and/
et al. describe 39 patients, median age 5.5 or colonoscopy. Endoscopic electrocautery can
months, on MCS because of tachyarrhythmias. safely help control GI bleeding.46
The majority could be treated with antiarrhyth-
mic medication. Thirteen patients (33%) under- Surgical Procedures General
went successful ablation without complications
related to MCS or anticoagulation.35 In adults Vascular Access
with tachycardia-induced cardiomyopathy,
ablation of the aberrant rhythm focus has been The insertion of central venous lines and ar-
safe and successful. Scherrer et al. describe terial catheters can be challenging in the ECLS
683
Chapter 61
patient due to the increased risk of bleeding of PDT were low and comparable to those of
and the presence of edema. Catheter insertion other critically ill patients when performed by
should be performed by experienced caregivers. experienced operators.52
Surgical cutdowns may be a safer or necessary There are two case reports in the literature
option. of tracheostomy in children on ECLS (8, 13, and
17 yrs old).53,54 Two procedures were performed
Thoracotomy Drains on ECLS and the third tracheostomy occurred
6 days prior to ECLS but the patient developed
Pneumothorax and hemothorax occur in bleeding from the site which requiring surgical
up to 10% of patients on ECMO.47,48 Placing correction without further complications. No
a chest tube carries a significant risk of bleed- comments addressed specific surgical tech-
ing complications.49 A recent analysis of the niques or anticoagulation strategies. Agar et
population-based, Kids inpatient database al. describe 11 pediatric patients (median age
(KID) demonstrated that chest drain placement 69.5 months) who underwent tracheostomy; 10
did not affect survival rates.50 The assessment received tracheostomy for prolonged respira-
of the necessity for a chest tube or whether a tory support and one underwent the procedure
patient can be decannulated without the drain to manage tracheal stenosis with no complica-
may prove difficult. Jackson et al. proposed that, tions.55
in children on ECLS, indications for chest tube
placement include situations in which pleural Cesarean Section
collections compromise pump flow or oxygen-
ation, indicating tension physiology, or when Extracorporeal life support is increasingly
they preclude weaning from ECLS.49 being used in patients with peripartum car-
diomyopathy (see Chapter 53).53 Successful
Tracheostomy cesarean section has been reported in women
on ECLS.56-60 In two reports, heparin was dis-
Placement of a tracheostomy can be helpful continued for several hours periprocedurally
during the prolonged ECLS support by enabling and standard (Pfannenstiel) cesarean section
spontaneous breathing, minimizing sedation, was performed without bleeding or thrombo-
and encourage physiotherapy and ambulation. embolic complications.56,57 Both infants were
In 2015, an international survey among 173 approximately 30 weeks gestation and one
adult respiratory ECLS centers on the manage- survived without sequela.56 The other infant
ment of mechanical ventilation, reported that survived with major neurological impairment
71.3% of centers performed tracheostomy on due to intraventricular hemorrhage. Two re-
ECLS.51 Braune et al. reported a retrospective ports described the use of ECLS directly prior
study of 118 percutaneous dilational tracheos- to emergency cesarean section to facilitate
tomies (PDT) in adult ECLS patients.52 Heparin anesthesia and maintain adequate circulation
was paused one hour prior to the procedure in women with peripartum cardiomyopathy.58,59
and restarted directly after. Hematologic and Park et al. used fluoroscopy-assisted insertion of
coagulation parameters were within normally a guidewire during cannulation of the inferior
accepted ranges for ECLS patients. Minor vena cava (IVC) because of concerns of IVC
bleeding from the tracheostomy site occurred injury compressed by the gravid uterus. After
in approximately 30% of cases. The authors cannulation, no heparin was started and an
concluded that with careful optimization of uneventful emergency cesarean section was per-
coagulation management, complication rates formed. Anticoagulation was started 3 days after
684
Procedures on ECLS
delivery.58 The only other report of cesarean bracket fixation to the fractured femur has also
section during MCS describes 3 women with been reported (Table 61-1).68
peripartum cardiomyopathy, supported with Chou et al. describe two burn patients with
an intraaortic balloon pump with no maternal ARDS who underwent several escarotomies on
complications.60 One infant was stillborn, the ECLS. By maintaining ACTs under 140 seconds,
other two survived uneventfully. keeping platelets above 100x109, and infusing
desmopressin, they encountered no hemor-
Miscellaneous rhagic complications.70
Other infrequent general surgical proce- Abdominal Surgery

dures in ECLS patients include reports of liver
transplantation,61 gastrorrhaphy,62 and debride- Laparotomy for bowel resection (eg, in
ment of soft tissue infections.63 trauma patients or neonates with necrotizing en-
terocolitis), abcess removal, relief of abdominal
Trauma and Burn Patients compartment syndrome, or placement of peri-
toneal catheters can be necessary procedures in
Thoracic Trauma patients during ECLS support.71,72
Abdominal compartment syndrome (ACS)
In a recent study of 85 patients in the ELSO can cause abdominal ischemia, limit venous re-
Registry with blunt thoracic trauma, 12 patients turn, and impair the ability to maintain adequate
(14.1%) underwent invasive procedures on ECLS flows. ACS, defined by progressive intra-
ECLS including cranial, thoracic, abdominal, or abdominal distension and intra-abdominal pres-
vascular operations, thoracostomy tube place- sures >15 mmHg in children and >20 mmHg
ments, and tracheostomy placements (see Chap- in adults, has many different causes.73 ACS can
ter 54).64 Hemorrhagic complications occurred be alleviated by decompressive laparotomy or,
in one-third of all 85 patients, including surgi- when significant ascites is present, by placing
cal site bleeding (14%), cannula site bleeding a PD-catheter.71,74-77
(19%), and hemolysis or disseminated intravas- Okhuysen-Cawley et al. described success-
cular coagulation (8%). Subjects with injuries ful placement of a peritoneal dialysis catheter
at high risk for hemorrhage or who underwent via small infraumbilical incision in a child with
invasive procedures were not more likely to
have a hemorrhagic complication.64 Strategies Table 61-1. Technique for lung surgery on
ECLS.
to decrease the risk of bleeding involve with-
holding anticoagulation therapy temporarily or,
if possible, postponing the procedure until after HOW TO PERFORM LUNG SURGERY ON ECMO
separation from ECLS. Increase ECMO flow to maximal possible
Airway and lung surgery can safely be fa- Disconnect the ventilator and deflate both the lungs
cilitated by ECLS, often electively during lung
Perform the surgery
transplantation or pneumonectomy, which is
Maintain arterial saturations at > 75% and appropriate
beyond the scope of this chapter (see Chapter blood pressure for age
58). However, in chest trauma patients with
65-67
airway disruption, ECLS can be used to guar- Hand bag ventilation with 100% FIO2 for a few breaths
can be used when the patient becomes desaturated
antee oxygenation delivery during repair of
Decortication is easier with the lung ventilated rather than
the airway.68,69 Closed reduction and external collapsed
685
Chapter 61
sepsis on VA-ECLS, using aminocaproic acid decisive treatment, patient selection, manage-
peri-procedurally.75 Drainage of ascites led ment of anticoagulation, and early estimation
to immediate improvement in hemodynamics of prognosis.82 Krenzlin et al. described dis-
and oxygenation and successful decannulation couraging results in 11 adults and one child on
occurred after 12 days of ECLS. Prodhan et al. ECLS, requiring craniotomy for life-threatening
described four children on ECLS who devel- intraparenchymal hemorrhage of whom 75%
oped ACS impairing venous return. All four experienced recurrence despite correction of
patients, had restoration of normal flows after coagulation abnormalities. Nine patients (75%)
uncomplicated placement of a PD catheter.71 died in hospital, two survived in a vegetative
Lam et al. described three children with ACS state, and one survived with severe disability.82
compromising ECMO flows that were relieved Wilson et al. described 36 of 330 adult LVAD
by.74 Rollins et al. performed decompressive patients who suffered ICH.83 With suspension
laparotomies without complications, via mid- of anticoagulation, no device failures were
line incision, from the xiphoid process to the seen. Intraparenchymal hemorrhage had the
pubis, using electrocautery in 7 pediatric pa- worst outcome with a 59% 30-day mortality.
tients that significantly improved venous return Traumatic subarachnoid hemorrhages had no
and oxygen delivery.72 deaths at 30 days while traumatic subdural
Other forms of compartment syndrome hemorrhages had a 13% mortality at 30 days.
include limb compartment syndrome requiring Five of their patients with intraparenchymal
fasciotomy, and orbital compartment syndrome hemorrhage underwent a neurosurgical surgi-
requiring orbital decompression, an extremely cal intervention and 4 died. No patient with
rare condition.78,79 In a retrospective study, limb
an initial GCS <11 survived beyond 30 days.83
compartment syndrome requiring fasciotomy The poor outcome of craniotomy for intraparen-
occurred in 7% of patients with femoral artery chymal hemorrhage in ECLS patients has been
cannulation, despite the use of a small reperfu- described in other smaller reports in adults and
sion cannula to obtain antegrade perfusion of the in children.9,84 Evacuation of subdural hemato-
limb. Fasciotomy led to clinical recovery in 5/7 mas carries better prognosis with survival and
subjects and 2/7 eventually required amputation minimal neurological deficit.83-85
of the leg.80 Death related primarily to progression of
intracranial hemorrhage (ICH) and not to throm-
Neurosurgery botic complications.9,83 No specific anticoagula-
tion guidelines exist for this patient population
Evacuation of intracranial blood or clots can and decisions should be based on patient and
be necessary in trauma patients. Friesenecker device specifics.9,85 The general consensus
et al. described an adult trauma patient who calls for immediate reversal of anticoagulation
developed a massive intracerebral hemorrhage and antiplatelet therapy at diagnosis of ICH in
on VA-ECLS. Anticoagulation was adjusted to LVAD patients. Withholding aspirin for 1 week
achieve ACTs of 150 seconds. He underwent and warfarin for 10 days seems sufficient to
successful craniotomy without bleeding com- reduce the risk of hemorrhage expansion or
plications and survived with a GCS of 11.81 rebleeding while minimizing the risk of throm-
With increased use of MCS as a bridge to boembolic events and pump failure for adults
transplantation or as destination therapy, pa- supported with LVAD.83
tients presenting with neurological complica-
tions resulting from MCS are becoming more
frequent. Limited knowledge exists regarding
686
Procedures on ECLS
Specific Surgical Procedures in Respiratory Congenital Diaphragmatic Hernia

ECMO
Repair of congenital diaphragmatic hernia
Thoracotomy can safely be done on ECMO.93 The ideal tim-
ing of surgery is has been the focus of debate
In respiratory ECLS patients, pleural effu- for many years (see Chapter 10). Most centers
sions or empyema may need to be drained using use antifibrinolytics for 24-72 hours to control
chest drains (see above). Furthermore, pulmo- postoperative bleeding.7,93,94
nary abcesses, cysts, bullae, or necrotic tissue
may develop, requiring surgical intervention. Specific Surgical Procedures in Cardiac
Although it would be preferable to postpone ECLS
surgery until after decannulation,86 it may prove
necessary to operate to remove a septic focus Sternotomy/Thoracotomy
or to fully expand the lung despite the risk of
bleeding. Indeed, Bressman et al. reported Blood clots can fill the pericardial or pleural
bilateral thoracotomies in patients receiving space impairing venous return or pump flow,
pulmonary resection due to complications of especially in ECLS patients with central can-
pneumonia. The authors withheld heparin for nulation. Clot debridement may prove neces-
24 hours and reported no complications.87 sary in these patients. In neonates with shunt
dependent circulation, clotting or obstruction
Lung Biopsy of the systemic pulmonary shunt may lead to
acute hypoxia or loss of systemic circulation,
Lung biopsy can be useful to diagnose lung sometimes requiring MCS. Revision of the
pathologies in ECLS patients of all ages and shunt can be safely performed on ECLS or af-
can help guide therapy or decisions to with- ter conversion to bypass, leading to improved
draw treatment.88-92 Lung biopsy is indicated in outcomes.95,96
neonates who show no signs of improvement
after 10-14 days on respiratory ECLS.90 Lung Unloading the Left Ventricle (Left-vent)
biopsy can be safely performed in the intensive
care unit or in the operating suite via commonly When the left ventricle (LV) functions
accepted open surgical techniques, without poorly it can become over distended during
major complications. Most centers, do not use ECLS resulting in acute pulmonary venous
antifibrinolytics, adjust ACT levels to 160-180 congestion and edema, or inadequate myocar-
seconds, maintain platelets >100-150x109, and dial recovery. Treatment is decompression of
fibrinogen >2 g/l. No studies report on broncho- the LV. Elective LV decompression may reduce
scopic transbronchial lung biopsy in pediatric duration of ECLS97 and can be done surgically
ECLS patients probably because of concerns by cannulating the left atrium or a pulmonary
of bleeding. Air leaks rarely occur, probably vein, percutaneously by atrial stenting or bal-
due to low thoracopulmonary compliance, low loon atrial septostomy,36,98-100 or via the trans-
tidal volumes, and low ventilating pressures in diaphragmatic route.101 In adults and children,
patients supported with ECLS.92 echocardiographically guided percutaneous
blade and balloon atrial septostomy can be
performed safely at the bedside.102-104 Barbone et
al. describe introducing a pigtail catheter in the
femoral artery in 4 patients, advancing through
687
Chapter 61
the aortic valve into the LV under TEE guid- Conclusion

ance.105 Ruprecht et al. have reviewed cardiac
decompression during ECLS.106 Few procedures in the lexicon of the
surgeon, interventionist, or obstetrician can-
Intracardiac Operations not be performed safely on ECLS with good
preparation, we must merely await the patient
The removal of intracardiac clots, infective circumstances which embolden the pioneering
endocarditis,107 or surgery for residual lesions protagonists.
usually requires transfer to CPB in the operating
room. Two examples for using the ECLS circuit
for support: 1) a patient on VV-ECMO can
have their BT shunt revised on ECLS, vascular
clamps are applied to the shunt and pulmonary
artery to control blood loss. A cell saver can
be useful; 2) A patient on VA ECMO can have
their coronary arteries grafted using OPCAB
equipment and techniques. (Table 61-2)
Table 61-2. Technique for heart surgery on ECMO.
HOW TO PERFORM HEART SURGERY ON ECMO
Use the ECLS circuit for support The ECMO circuit is used to maintain oxygen
delivery and circulatory support whilst the surgery is
performed.
Use the ECLS circuit for DHCA Simple procedures such as repair of obstructed total
anomalous pulmonary venous drainage can be carried
out by cooling on VA ECLS to around 14 oC.
Cardioplegia is given by hand syringe (if the heart
hasn’t already stopped) and the operation can be
carried out. Care must be taken to prevent distention
of the heart during cooling and rewarming,
sometimes some slow cardiac massage is helpful.
Use of a cell saver is essential.
Convert to CPB • Cool patient to 32 oC whilst opening the chest on
ECLS
• Give 3mg/Kg Heparin and allow to circulate,
check ACT >500 sec.
• Clamp ECLS circuit, connect CPB circuit to ECLS
cannulae, or additional cannulae if necessary. Go
on CPB
• Connect ends of ECLS circuit together and
recirculate, turn the sweep off. Flash sweep for a
few seconds if blood becomes dexoygenated.
Check ACT, blood gas periodically.
• Perform the surgery.
• If patient will not come off CPB then reconnect to
the same ECLS circuit if it is clean. If it was due to
be changed, prime a new one. Deal with bleeding
following recipe in chapter 7.
• If the patient does come off CPB their passivated
ECLS circuit can be kept on standby for 6-12
hours.
688
Procedures on ECLS
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695
62
Extracorporeal Elimination
Meral Patel, MD, Rachel Sirignano, MD, Ryan Barbaro, MD, Matthew L. Paden, MD
Extracorporeal life support (ECLS) was Injury Network’s (AKIN) criteria, and the
traditionally thought of as providing isolated Kidney Disease Improving Global Outcomes
temporary cardiac and/or pulmonary support for (KDIGO) guidelines, have been validated and
patients. However, as providers have become allow classification by both urine output or se-
more comfortable with this technology, the rum creatinine.5-7 Depending on the age, ECLS
patients supported have become more complex, mode, and definition used, AKI occurs widely,
often with multiple secondary organ failures with reports of its presence in 19-71% of neo-
that require supportive therapy. The cardiac nates, 20-72% of pediatric, and up to >70% of
and pulmonary support that ECLS provides adult ECLS patients.8-12 In many of those same
becomes the “platform” upon which multiple studies, an association is established between
organ support therapies can be delivered. In AKI and increased mortality. In addition to
this chapter, we discuss the use of other extra- diagnosing AKI by urine output and creatinine
corporeal therapies, such as continuous renal measures, the concept of fluid overload (FO)
replacement therapy (CRRT) and the use of as another manifestation of kidney dysfunc-
apheresis procedures during ECLS. tion that negatively impacts organ function
and mortality is well established.13-15 In ECLS
Acute Kidney Injury (AKI) during ECLS patients, FO has been associated with impaired
oxygenation, increased duration of ECLS, and
AKI commonly complicates critical illness mortality.16-20 Since both AKI and FO are as-
and is a risk factor for death in critically ill sociated with increased mortality, treatment of
patients of all ages and also for those receiving these comorbidities has been recommended in
ECLS. A complete review of this complicated an attempt to improve ECLS outcomes.
topic is beyond the scope of this chapter, but However, indications for treatment of AKI
assessments of this topic have been completed and FO are not well established. In non-ECLS
for neonatal, pediatric, and adult ICU patients.1-3 patients, consensus recommendations by the
Historically, the literature on AKI has been dif- ADQI on pharmacological and mechanical fluid
ficult to assess, due to multiple differing defini- removal have been published.21,22 With ECLS
tions of the condition.4 Recently, standardized patients, indications for treatment are broadly
scores, such as the Acute Dialysis Quality divided into AKI, FO, electrolyte disturbances
Initiative’s (ADQI) Risk, Injury, Failure, Loss, not amenable to medical therapy, and removal
Endstage (RIFLE) criteria, the Acute Kidney of drugs/toxins. Usage varies greatly by ECLS
697
Chapter 62
center.23 The Extracorporeal Life Support Or- by passing a solution of electrolytes on the
ganization (ELSO) guidelines addressing AKI nonblood side of the filter, in a counter cur-
and FO state, rent direction to the blood flow. This allows
equilibration of solutes and water down their
“the goal of fluid management is to return concentration gradients in the plasma and the
the extracellular fluid volume to normal (dry dialysate to occur. Diffusive clearance is more
weight) and maintain it there. The reason is that effective at small solute removal (individual
edema caused by critical illness or iatrogenic electrolytes, urea, etc.), compared to larger
crystalloid fluid infusion causes lung and myo- molecules. Alternately, convective therapies,
cardial failure, adding to the primary problem… such as continuous venovenous hemofiltration
When the patient is hemodynamically stable (CVVH), utilize the transmembrane pressure
(typically 12 hours) diuretics are instituted and to create a volume of ultrafiltrate by pushing
continued until dry weight is achieved. If the water through the membrane. Convective mass
diuretic response is not sufficient to achieve transfer occurs providing the ultrafiltrate with
negative fluid balance, or if the patient is in small and medium sized solutes, the size of
overt renal failure, continuous hemofiltration is which is determined by membrane properties.
added to the extracorporeal circuit to maintain Commonly used membranes allow convective
fluid and electrolyte balance.”24 clearance of molecules between 500-5000
Currently, Chen et al. provide the most Daltons.
comprehensive evidence based literature review Technically, three main methods for intro-
of the topic of concomitant CRRT and ECLS ducing CRRT into an ECLS circuit exist and
use and review of this work is strongly encour- have been reviewed. The first involves having
27
aged.25 Besides expert opinion, little guidance a separate vascular access point that is not a part
exists in the medical literature regarding criteria of the ECLS circuit and using a commercially
for timing of renal replacement therapy (RRT) available device. This standalone method repre-
initiation, or optimal performance during ECLS. sents the simplest approach in a patient who has
While RRT can be intermittent or continuous, a vascular catheter prior to ECLS cannulation.
CRRT is the most common form used during In this setting, CRRT is managed similar to the
ECLS and will be the focus of the following patient who is not on ECLS, with the exception
sections.23 that reductions or elimination of CRRT circuit
anticoagulation is often possible due to the
Technical Aspects of CRRT during ECLS patient’s ECLS anticoagulation. Placing a new
dialysis catheter after ECLS cannulation is not
Renal support therapies work by isolating routinely recommended due to the increased
blood on one side of a semipermeable mem- risk of bleeding due to ECLS anticoagulation.
brane, the properties of which permit solute The second method to provide concomitant
and volume exchange through it. Seminars in CRRT and ECLS involves inserting a hemofil-
Dialysis provides an entire issue with a review ter in a shunt created post-pump in the ECLS
of CRRT technology, physiology, and modes circuit. The pump flow drives blood through
for a more detailed look at this topic.26 In gen- the hemofilter, producing the ultrafiltrate. The
eral, multiple modes of providing CRRT exist; volume of ultrafiltrate produced is controlled
however, the most commonly used techniques by standard IV pumps and is measured using
rest on the principles of diffusion or convection. a bedside urimeter. The ultrafiltrate can be
Diffusion based therapies, such as continuous discarded, if the user is seeking to provide only
venovenous hemodialysis (CVVHD), work slow continuous ultrafiltration (SCUF), or a
698
replacement fluid containing desired electro- ple factors, including ECLS circuit design, type
lytes can be delivered to provide continuous of ECLS pump, and CRRT device software. In
venovenous hemofiltration (CVVH). The now general, for roller head pump based ECLS, the
treated blood is returned to the ECLS circuit CRRT device can be integrated in the prepump
prepump. This method of “in-line” hemofiltra- venous limb of the circuit. In this manner, the
tion was the first method used to provide CRRT CRRT pumps blood to the CRRT device and
during ECLS, and has the advantages of being returns it to the ECLS circuit. Pressure within
simple, inexpensive, and can be performed by the venous limb is usually adequate to allow the
the ECLS specialist. However, it has multiple CRRT pressure monitoring software to function.
disadvantages. The shunt that returns blood Alternately, in a centrifugal pump based ECLS
prepump creates recirculation to the CRRT cir- circuit, it is recommended that the CRRT de-
cuit, reducing its efficiency, but this is usually of vice be connected postpump to reduce the risk
insubstantial magnitude. Thus ECLS pump flow of air entrainment due to the negative pressure
does not equal patient flow. Consequently, flow in the prepump venous line. Additionally, the
must be monitored distal to the shunt. Using software on many CRRT devices will not allow
this technique for SCUF can contribute to the the device to start with the magnitude of nega-
development of multiple electrolyte anomalies, tive pressures seen in the venous line. In this
especially in the smaller children, and is not scenario, blood returns from the CRRT circuit
recommended. The in-line circuit often has no to the ECLS circuit distal to the postpump ve-
pressure monitoring, which makes identification nous CRRT line, but still pre-oxygenator. This
of hemofilter clotting, rupture, or other malfunc- configuration reduces recirculation through
tion more difficult. The most important disad- the CRRT device, and additionally allows the
vantage of this method relates to inaccuracy in oxygenator to act as a clot and air trap before
fluid balance. The IV pumps that are used to blood returns to the patient. The advantages to
control ultrafiltrate production as well as deliver using a commercially available CRRT device
replacement fluids are not engineered to be used during ECLS include improved fluid balance
in this manner. They are not pumps at all, but accuracy compared to the inline method, built-
rather flow restrictors, and have a significant er- in standard pressure and flow monitoring, lon-
ror rate (~12.5%) when used in this fashion.28 In ger filter life, and a device engineered for the
a laboratory setup of in-line CRRT during ECLS, purpose of providing CRRT.29-31 However, no
the difference between prescribed and measured commercially available CRRT device has been
ultrafiltration rate was as high as 34 mL/hour specifically designed and approved for use dur-
(>800 mL/day).29 Thus, careful monitoring of ing ECLS. The disadvantages of this approach
both volume of ultrafiltrate created, as well as include device costs and training requirements.
replacement fluid delivered, is essential. This
can be accomplished either volumetrically or by Outcomes of CRRT during ECLS
the use of highly accurate scales (+/- 1 gram)
but increases nurse/ECLS specialist workload While the theoretical advantages and dis-
which contributes to the reduction of the use of advantages of the differing methods of CRRT
this technique. during ECLS are presented above, few outcome
Currently, the preferred method to provide data compare these approaches. Santiago et
CRRT during ECLS involves introducing a al. examined children on ECLS who received
commercially available CRRT device into the concomitant CRRT (2 “in-line”, 6 commercial
ECLS circuit. Optimal connection of the CRRT CRRT device, 11 stand alone) and found all
device into the ECLS circuit depends on multi- methods “adequate” for fluid and electrolyte
699
Chapter 62
control.31 Additionally, of the 6 children with ELSO centers in the United States and Canada
a CRRT device incorporated into the ECLS cir- formed the Kidney Injury During Membrane
cuit, they found increased filter life (138.4 hour) Oxygenation (KIDMO) research network to
compared to the 36.8 hours seen in other non- further investigate the relationship between AKI,
ECLS children with standalone CRRT and 27.2 RRT use, and survival in patients <19 years old.
hours seen in CRRT during ECLS adults who They evaluated a cohort of 835 ECLS patients at
used citrate anticoagulation in addition to the their centers from 2007-2011 using the modern
ECLS.31,32 Symons et al. evaluated 458 serial KDIGO definition of AKI. They found that
ultrafiltration fluid balance measurements be- AKI affects the majority (50-69%) of pediatric
tween 12 patients receiving CRRT during ECLS ECLS patients, occurs early (99% identified in
using a commercially available device and 30 the first 48 hours), and is associated with longer
patients with an “in-line” system.30 They dem- duration of ECLS (~48 hours) and mortality
onstrated significantly improved fluid accuracy (OR=2). (Accepted for publication, Pediatric
and a reduction in both ECLS and CRRT dura- Critical Care Medicine. Geoffrey Fleming,
tion with the use of a commercially available Personal communication.) Five case series have
device. They did not see changes in hospital or evaluated the use of ECLS and CRRT in the pe-
ICU length of stay or mortality. diatric cardiac population. All but one showed
The largest set of outcome data that exists statistically worse mortality when CRRT was
for the use of CRRT during ECLS comes from used during ECLS, with a combined odds ratio
the ELSO Registry. “Renal failure” is defined of 6.19 [3.89, 9.87] for all five studies.25
as a complication in the ELSO Registry, with In the adult population, less is known, al-
three increasing levels of injury being coded though there are multiple papers from individual
(creatinine 1.5-3, creatinine >3.0, and either centers that generally show worse survival in
dialysis/hemofiltration/CAVHD required). This patients who require concomitant CRRT/ECLS.
limited definition differs markedly from the RI- Tsai et al. evaluated 104 ECLS and acute
FLE and KDIGO AKI scoring systems. ECLS dialysis patients and found 76% mortality.33
complications are entered in the ELSO Registry Similarly, Wu et al. described a 70% mortality
once per run and no duration information is rate in 102 noncoronary artery bypass graft
obtained. Using this definition, the presence of patients receiving ECLS and dialysis support.34
this complication in each age category of respi- Finally, Keilstein et al. reported 83% mortality
ratory failure is associated with worse survival in 120 patients receiving ECLS and RRT.35 The
(Table 62-1) compared to the overall survival mortality rate in these case series significantly
of these groups (74%, 58%, 58%). Similar data exceeds that seen in the ELSO Registry for all
exist for the cardiac population. Both kidney adults (60%), all adult respiratory (48%), or
injury and the use of RRT are associated with all adult cardiac (70%). The high mortality
increased mortality. A subset of six pediatric could be due to a more pronounced effect of
Table 62-1. Renal complications and survival from 2016 ELSO Registry report.
Neonatal Pediatric Adult respiratory

respiratory failure respiratory failure failure
n (% reported, % n (% reported, % n (% reported,
survival) survival) % survival)
Creatinine 1.5-3 1901 (7, 50) 651 (9, 34) 1490 (16, 45)
Creatinine > 3 373 (1, 37) 306 (4, 33) 874 (9, 45)
Renal replacement therapy 6124 (21, 50) 3170 (44, 42) 3731 (41, 48)
700
AKI in the adult population, higher population mortality of ECLS patients who develop AKI is
of cardiac patients in these case series, center greater than patients without AKI. The details
specific differences, publication bias, or incor- of optimal treatment of AKI, including the use
rect ELSO Registry data. Regardless of the of CRRT during ECLS remain poorly defined,
etiology of the disparity, this combination of rely on expert opinion, and vary between ECLS
diseases leads to substantial mortality. Multiple centers. Use of CRRT does not appear to in-
papers have created prediction models that crease the rate of chronic renal failure at the
identify maximum serum free hemoglobin dur- time of discharge. Additional multiple center
ing ECLS, lactate level prior to ECLS initiation, data and trials with standardized protocols is
SAPS3 score, use of intraaortic balloon pumps, needed to better inform the management of AKI
and APACHE IV score at dialysis initiation as during ECLS.
potential modifiable risk factors for improving
outcome.33,34,36 Now identified, these factors Apheresis during ECLS
provide opportunities to test clinical strategies
to improve patient survival. Apheresis techniques are methods for
Despite limited data, the concern of precipi- separating the blood into its individual compo-
tating chronic renal failure in patients treated nents. Commonly used therapeutic apheresis
with concomitant CRRT and ECLS appears procedures are therapeutic plasma exchange
unwarranted. Five studies with 123 survivors of (TPE), erythrocytapheresis, leukapheresis, and
ECLS/CRRT specifically address renal recov- photopheresis. These therapies have an evolv-
ery.37-41 Only 3 patients (2.4%) did not recover ing history in medical care and comprehensive
renal function (2 transplanted, one with high reviews of this topic are available.43 Apheresis
creatinine, but not dialysis dependent). All 3 therapies now represent the standard of care for
patients presented with complications of newly diseases such as acute stroke in sickle cell dis-
diagnosed primary kidney disease (pulmonary ease or thrombotic thrombocytopenic purpura
hemorrhage from Wegener’s granulomatosis and may play a valuable role in the treatment of
[2] and polyangiitis). Less is known about the other diseases. Use of this established technol-
adult population, with the largest study being ogy has been increasing in critically ill patients,
the description of 100 patients at University especially those requiring ECLS. Concomitant
of Michigan from 1990-1996, of whom 14 ECLS was once considered a contraindication
received CRRT and ECLS, that contains the to apheresis–the patients were just “too sick.”
overall comment that “all but 2 of the 54 survi- Increasingly, physicians are willing to provide
vors are leading normal, healthy lives”.42 Due these therapies during ECLS and even to place
to the lack of strong outcome evidence and patients on ECLS to achieve the cardiorespirato-
long-term followup, continued surveillance of ry stability necessary to complete the clinically
ECLS/CRRT patients appears warranted. indicated apheresis procedure. This chapter
aims to review the limited clinical experience
Summary of Concomitant CRRT and ECLS with apheresis during ECLS and methods to
Use provide these tandem procedures successfully.
Therapeutic cytapheresis, involves the
CRRT use for the treatment of AKI and FO removal of a specific cellular element. In
is commonly practiced by the ECLS community. erythrocytapheresis, red blood cells (RBCs)
Methods of providing these therapies together are removed from the blood and replaced with
are not standardized, and no commercially banked RBCs. The most common use for eryth-
available product exists. In all populations, rocytapheresis is in the setting of complications
701
Chapter 62
from sickle cell disease, but has other rare uses in the extracorporeal circuit. Citrate is most
as well. Leukapheresis is the removal of white commonly used outside of the ECLS setting;
blood cells (WBCs) from the blood. Most however, often the heparin provided for ECLS
commonly, this is done to harvest stem cells for anticoagulation suffices for this circuit as well.
bone marrow transplantation, but also has indi- An extensive review of the mechanisms of these
cations in acute leukemias with hyperviscosity anticoagulation techniques is provided in other
syndrome leading to organ failure and has been chapters of this text.
suggested as a potential therapy for life threaten-
ing pertussis infection. Photopheresis involves Indications
application of ultraviolet light to the blood in
order to modulate immune responses through No ELSO guidelines pertaining to indica-
destruction of WBCs that have absorbed a pho- tions for the use of apheresis procedures on
tosensitizing agent. Currently, this is used in ECLS currently exist. Instead, the decision
graft vs. host disease in hematopoietic stem cell to proceed with apheresis should be based on
transplant (HSCT) patients, but also has a role in evidence of effectiveness for the underlying dis-
both acute and chronic rejection of organ trans- ease and regardless of ECLS support. General
plantation recipients. TPE separates and then indications for apheresis procedures are set forth
replaces the plasma from the blood. TPE aims by the American Society for Apheresis (ASFA).
to remove large molecular weight substances Periodically, AFSA publishes a set of evidence
(such as cytokines and antibodies), or highly based guidelines for the use of apheresis, with
protein bound molecules while also restoring the last being in 2016.45 These guidelines
depleted coagulation factors, proteins, and en- review the medical evidence for apheresis use
zymes to regain the homeostasis necessary for by disease, and present a one page summary of
clinical recovery.44 TPE is the most commonly recommendations. This summary provides a
provided apheresis procedure during ECLS, and list of the therapies, an evidence based grading
will be the focus of this review. system for recommending therapy, biologic ra-
Commercially available apheresis devices tionale for the mechanism of apheresis therapy,
separate the blood into its component parts a critical review of the clinical literature, and
either by centrifugation or filtration. Histori- proposed prescriptions for therapy that include
cally, centrifugation techniques are the most both method and duration. Based on the clini-
commonly used; however, the introduction of cal evidence review, the ASFA indications for
plasma filters that can be used in conjunction TPE are split into categories I-IV. For category
with CRRT devices has increased filtration I, apheresis is considered a first line therapy;
usage over the last decade. One advantage for category II, it is a second line therapy; for
of using dedicated centrifugal apheresis de- category III, data are unclear on the use of
vices is the ability to perform many different apheresis and for category IV, evidence suggests
apheresis procedure types that are not limited apheresis is harmful or ineffective.
to only TPE, as when using the CRRT devices Category I indications for apheresis in
with a plasma filter. A lack of evidence to patients on ECLS may include diffuse alveolar
suggest clinical outcome superiority between hemorrhage secondary to Wegener’s Granu-
centrifugation and filtration exists, and choice lomatosis or Goodpasture’s syndrome, severe
of method is based on local equipment, staffing cryoglobulinemia, atypical hemolytic uremic
resources, and physician experience. Regard- syndrome (HUS) with factor H antibodies, ABO
less of method, an anticoagulant is used to avoid incompatible liver or renal transplant, antibody
excessive thrombosis due to activation of blood mediated transplant rejection, thrombotic
702
thrombocytopenic purpura (TTP), hyperviscos- tor inhibitors, dermatomyositis/polymyositis,

ity syndromes, and fulminant Wilson’s disease. atypical HUS with membrane cofactor protein
Similarly, category II indications which may be mutations, refractory immune thrombocytope-
seen during ECLS include acute disseminated nia, inclusion body myositis, POEMS syndrome
encephalomyelitis, catastrophic antiphospho- (polyneuropathy, organomegaly, endocrinopa-
lipid syndrome, ABO-incompatible HSCT, thy, monoclonal gammopathy and skin changes
atypical HUS with complement mutations, syndrome), ABO incompatible deceased donor
mushroom poisoning/overdose, humoral renal renal transplant, schizophrenia, lupus nephritis,
transplant rejection, severe sickle cell related and either Quinine or Gemcitabine associated
acute chest syndrome, and severe cerebral lu- thrombotic microangiopathy.45 Other relative
pus.45 Perhaps most commonly, based on review contraindications that need to be considered are
of the current literature, TPE has also been related to the effect of citrate when used either
frequently used during ECLS for the manage- as an anticoagulant for the procedure or for the
ment of sepsis with multi-organ dysfunction blood products that are being used during the
syndrome (MODS) and thrombocytopenia as- procedure. Briefly, citrate’s anticoagulation
sociated multi-organ failure (TAMOF).46 These effects are due to the depletion of free, ionized
uses are listed as category III indications in the extracellular calcium upon which many steps in
most recent AFSA guidelines. the coagulation cascade are dependent. How-
As often occurs at the frontier of medical ever, cardiac function may also be negatively
care, there will be diseases and clinical scenar- affected (especially in the neonatal population)
ios where there is either none or little evidence by low ionized calcium. Additionally, because
for the use of apheresis techniques. Essentially of the anticoagulant effect of large amounts of
all cases of concomitant use of apheresis and citrate, bleeding may be exacerbated in patients
ECLS fall into this category. The ASFA guide- who are already bleeding. In both cases, the
lines provide guidance for the clinician in this negative effects of citrate on calcium can be
scenario, referring to assessing the approach by mitigated by infusion of additional calcium.
using a modified set of McLeod’s Criteria which As is common with complicated patients on
help the user demonstrate a biologic rationale ECLS, a thorough weighing of the risks and
for the procedure.45 In cases where guidelines benefits of the procedure, both in the short and
are not present, prior to initiating treatment cli- long time horizons, should guide the provision
nicians should document their reasoning behind of this therapy.
why the chosen apheresis procedure provides
a mechanism of action that would address the Technical Aspects of Apheresis during ECLS
current disease, why that apheresis procedure
will potentially improve the patient’s condition, Similar to the CRRT methods discussed
the proposed therapeutic plan and duration, and above, apheresis procedures can be provided as
how the clinician will assess the efficacy of this stand alone therapy through a separate venous
therapy. access or provided using the ECLS circuit for
venous access. No evidence exists to suggest a
Contraindications superiority to either method, although integra-
tion using the ECLS circuit appears to be more
Based on 2016 evidence based AFSA guide- common in the literature likely due to ease of
lines, apheresis is ineffective or even harmful use and the potential complications of attaining
in patients with amyloidosis, amyotrophic new venous access on an anticoagulated patient.
lateral sclerosis, alloantibody coagulation fac-
703
Chapter 62
For stand alone therapy, apheresis proce- on the apheresis device. For patients already
dures can be done in patients with two large receiving concomitant ECLS and CRRT, the
bore peripheral catheters, but ideally patients apheresis device can be added in series to the
should have a double lumen central venous CRRT limb.48 At Emory University/Children’s
line designed for dialysis that is greater than Healthcare of Atlanta, we attach two 3-way
or equal to 7F or a preexisting subcutaneous stopcocks to the pigtail connection coming from
port designed for apheresis use. Commercially the venous bladder. During the procedure, the
available automated blood cell separators con- apheresis device pulls blood from the first stop-
trol fluid balance and maintain normal plasma cock and returns to the second one, where the
volume to perform the apheresis procedure. blood then continues on into the CRRT circuit
Most apheresis circuits have an extracorporeal and ultimately back to the ECLS circuit. In this
volume of approximately 350 mL. For patients method, the CRRT and apheresis blood flow
who weigh <20 kg, a blood prime similar in rates must remain the same to avoid recircula-
composition to that used for ECLS may be tion and pressure alarms.
employed to avoid dilutional anemia. For Determination of both dose and duration
larger patients, priming with crystalloid suf- of therapy is usually provided by the ASFA
fices. Blood prime should also be considered guidelines. However, apheresis dosage during
in any patient with hemodynamic instability ECLS must be evaluated carefully. The ASFA
or inadequate oxygen delivery. When used as guidelines often base dosages on a multiplier
stand alone therapy, attention should be paid of “plasma volume,” “whole blood volume,”
to patient temperature as hypothermia may be or “red blood cell mass.”45 These numbers are
exacerbated by this additional extracorporeal usually calculated based on weight or body
volume, especially in smaller patients. Warm- surface area. For example, estimated blood
ing of either the apheresis circuit or increasing volume in newborns to 3 month old infants is
the temperature goals for the ECLS circuit 80-90 ml/kg, for children over 3 months old is
may be necessary. Therapeutic aphereses are 70 ml/kg, and about 5 L for an adult. Many of
intermittent, and venous access catheters should these numbers are estimates of Nadler’s equa-
be locked with an anticoagulant solution per a tion which provides a more thorough calculation
center’s usual protocol after the procedure to of total blood volume. It is often assumed that
prevent thrombosis. total plasma volume (PV) is 60% of total blood
Alternately, the apheresis circuit can be volume, based on a hematocrit of 40%. During
connected to the ECLS circuit in a similar con- ECLS, many of the assumptions built into these
figuration to CRRT as described above.47 Again, equations are not necessarily valid and should
careful attention to device placement based on be considered prior to prescribing therapy.
type of ECLS pumping system is required. As During ECLS, you must calculate both the
with CRRT, none of the commercially available total blood volume for the patient as well as
apheresis devices have been engineered or vali- the total extracorporeal circuit volume. Failure
dated for use in the ECLS circuit. A common to do so will provide inadequate dosing of the
complication is a negative pressure alarm on the apheresis therapy. The total extracorporeal
venous limb of the apheresis device. This can circuit volume should include the sum of each
be ameliorated by improving cannula position individual extracorporeal circuit being used
to improve drainage, reducing ECLS flow (if for the patient (ECLS+CRRT+Apheresis+etc.)
clinically acceptable), altering the position of Similarly, total PV should be calculated prior
apheresis drainage from the ECLS circuit, or to each procedure using a recent hematocrit.
changing the parameters for the alarm limits The discrepancies can be extreme, especially
704
with small children. For example, using the is required to evaluate for signs of both potential
standard calculations a 10 kg child would have over and under dosing.49,50
a total blood and plasma volume of 700 mL and Citrate anticoagulation of the apheresis
420 mL respectively. Accounting for an ECLS circuit can be provided during ECLS, but is
volume of 400 mL, CRRT volume of 250 mL, associated with hypocalcemia and hypotension
and apheresis volume of 350 mL, and hema- in a large cohort of both children and adults.47
tocrit of 35%, the same child has a total blood Additional anticoagulation for apheresis is often
and plasma volume of 1700 mL and 1105 mL. unnecessary on ECLS, as ECLS anticoagula-
Not accounting for the extracorporeal volume tion usually suffices for all circuits. Increased
would lead to a >50% underdosing in this child. monitoring of total circuit anticoagulation both
For TPE, depending on disease, the ASFA during and immediately after apheresis should
guidelines usually recommend processing of be considered. Emphasizing again that none of
1-1.5 PV, which are replaced with either al- the commercially available apheresis devices
bumin or fresh frozen plasma (FFP).45 Strict are engineered or validated for use during ECLS,
dosing to the individual mL is not necessary for it is not surprising that issues may arise. For
apheresis procedures, and practically the dose example, many of the commercially available
can be rounded to the nearest unit of product apheresis devices will not run without a bag of
(albumin or FFP). This is because for a solely anticoagulant attached and running. During
plasma based molecule that can be removed by ECLS when this is not needed and additional an-
TPE, it is estimated that you remove 63.2% with ticoagulation may be harmful, a bag of normal
processing of 1 PV, 77.7% with 1.5 PV, 86.5% saline can be substituted for the citrate allow-
with 2 PV, and 95% with 3 PV. If processing ing the apheresis device to mitigate this error.
more plasma results in greater reductions, then Similarly, many of the commercially available
why do the recommendations usually call for apheresis devices calculate estimated blood and
1-1.5 PV therapies? Many of the molecules plasma volumes based on Nadler’s formula and
that we are targeting with TPE are not solely provider entered weight and height. As seen
confined to the blood compartment, and will above, when the much larger values are provid-
redistribute with time necessitating multiple ed based on patient plus extracorporeal volume,
therapies over time. Additionally, the benefit the devices will often alarm over the concern
of increased percentage removal must be bal- that a very large exchange has been ordered and
anced by both the time that it takes to perform either may fail to run, or default to providing the
the therapy as well as the blood product utiliza- procedure over very extended periods of time
tion. When providing apheresis therapies, one (>8 hours). In this situation, either providing
must be mindful that while the focus is on the the therapy over the extended duration is pos-
removal of a target molecule, that many other sible, or more commonly, adjusting the patient
blood components can also be removed. Drug weight that is entered to reflect a patient with a
dosing in particular is exceptionally compli- similar native (non-ECLS) blood volume. For
cated with the use of these multiple methods of example, the 10 kg patient on ECLS described
extracorporeal elimination, such as when using above with a total blood volume of 1700 mL
ECLS, CRRT, and apheresis concomitantly. could be entered as a 24 kg patient and this
While some guidelines and pharmacokinetics would allow processing of a similar volume of
data exist, much additional work needs to be plasma over a much more reasonable time (~2
performed and careful, daily, repeated, clinical hours). In any circumstance where one is con-
assessment of the effect of each prescribed drug sidering overriding or altering manufacturers
recommended usage, a formal protocol should
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Chapter 62
be established and adhered to, with multiple hypotension (22% pediatric, 34% adult) were
independent practitioners checking the calcula- both seen and successfully managed. Looking
tions prior to initiating each procedure. at the remainder of the reported cases in the
literature, the most common indications for use
Use and Outcomes of Apheresis during ECLS were sepsis with either TAMOF or MODS.44,48,51-
54
Nguyen et al. summarized the rationale for
Upon review of the current literature, 172 the use of TPE in this cohort of patients.46 The
reports described patients across the world next most prevalent category of use was for anti-
who have been treated with TPE during ECLS body removal in active autoimmune diseases55-64
(Table 62-2). No randomized clinical trial on and organ transplantation.65-69 Individual case
any disease has been published that contains reports exist for use in ingestions,70-72 hypoxic
the use of apheresis techniques during ECLS. ischemic encephalopathy,73 hemophagocytic
Individual case reports and case series make up lymphohistiocytosis,74 severe hemolysis while
the majority of the published literature. Dyer et on cardiopulmonary bypass for cardiac trans-
al. provides the single largest experience of 293 plant,75 and drug reaction with eosinophilia
concomitant apheresis and ECLS procedures in and systemic symptoms (DRESS) syndrome
76 adult and pediatric patients.47 In this cohort, associated myocarditis.76
the most common pediatric and adult indication There is significant heterogeneity in these
was multisystem organ failure and humoral case reports, due to the variety of rare diseases,
transplant rejection, respectively. They utilized differences in techniques of ECLS (mode,
both ECLS and apheresis teams to provide this equipment, etc.), differences in techniques of
combined therapy, providing anticoagulation to apheresis (centrifugation vs. filtration, dose,
the ECLS circuit with heparin and citrate for the timing of initiation, etc.), and lack of severity of
apheresis circuit. Citrate related complications illness scoring. Combined, these factors make
of hypocalcemia (47% pediatric, 27% adult) and commenting on outcomes such as complica-
Table 62-2. Case reports of therapeutic plasma exchange during ECLS.

Reference N Outcome Result Year(s)/Center Apheresis Anticoagulation Apheresis
Measure Equipment Complications
47
Dyer et al 53 pediatric Resolution of Successful in 2005-2012 Spectra or ECLS Heparin Hypocalcemia
23 adults apheresis 45% USA - UNC Optia Apheresis Citrate Hypotension
293 indications Clot formation in
procedures the ECLS circuit
Sirignano et 30 pediatric Survival 79% Survival 2012-2015 Optia ECLS Heparin Air in line
al51 9 ECLS/21 USA - CHOA only Clot formation
CPB Pump
180 malfunction
procedures Hypocalcemia
Kawai et 14 pediatric PICU 71% survival 2005-2013 If on ECLS Heparin Transient

al44 51 procedures survival Improvement USA - CRRT, Apheresis Citrate hypotension
Organ Failure in organ University of Prisma/ New onset rash
Index failure and Michigan PrismaFlex
Vasoactive vasoactives
Score No CRRT,
Spectra or
Optia
Dellgren et 11 pediatric Survival 8/11 survivors 1990-1999 Spectra CPB Heparin
al69 incompatible Canada only
heart
transplants
11 procedures
Hei et al75 2 pediatric Survival All 5 survived 2002-2007 Prisma CPB Heparin
3 adult Free Reduction in China only
5 procedures hemoglobin free
reduction hemoglobin
706
tions and survival difficult. As has been done

with the ELSO Registry for ECLS, capturing
additional data about patient, prescription, and
device related factors in an international data-
base would allow the accrual of data that may
allow definition of best practices and ultimately
improve outcomes.
Summary of Apheresis during ECLS
Use of apheresis procedures during ECLS is

technologically feasible and rarely used. Guid-
ance related to the appropriateness of apheresis
techniques during ECLS, as well as timing and
dosing information should be aided by using the
ASFA guidelines. When evidence for use is not
present in the medical literature, reliance on the
modified McLeod’s criteria and the underlying
pathophysiology of the disease is necessary.
Variation exists on how apheresis procedures
are performed during ECLS and anticoagula-
tion strategies. To best describe the potential
benefits and harms of this rare combination of
procedures, a worldwide registry approach is
needed.
707
Chapter 62
References during extracorporeal support in the pediat-

ric cardiac patient. ASAIOJ 2009;55:412-6.
1. Selewski DT, Charlton JR, Jetton JG, et al. 10. Lou S, MacLaren G, Paul E, Best D, Del-
Neonatal acute kidney injury. Pediatrics zoppos C, Butt W. Hemofiltration is not
2015;136(2):e463-73. associated with increased mortality in
2. Fortenberry JD, Paden ML, Goldstein SL. children receiving extracorporeal mem-
Acute kidney injury in children : an update brane oxygenation. Pediatr Crit Care Med
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Chapter 62
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712
63
Extracorporeal Carbon Dioxide Removal
Darryl Abrams, MD, Daniel Brodie, MD, Antonio Pesenti, MD
Introduction be considered in patients with acute respiratory

failure without preexisting lung disease or in
Extracorporeal carbon dioxide removal those with acute exacerbations of chronic lung
(ECCO2R) is a form of extracorporeal life sup- disease either as a bridge to recovery (BTR) or
port in which the primary intention of the tech- as a bridge to transplantation (BTT). However,
nique is the removal of carbon dioxide rather because no destination device for carbon di-
than the delivery of oxygen.1,2 For a given blood oxide removal currently exists, careful patient
flow, extracorporeal support more efficiently selection for ECCO2R will optimize outcomes
exchanges carbon dioxide than oxygen, in in this setting, particularly among those patients
large part due to the differences in how carbon with chronic lung disease.
dioxide and oxygen are transported within
blood.1 Extracorporeal membrane oxygenation Considerations for ECCO2R
(ECMO) traditionally requires large bore cannu-
lae to achieve sufficient blood flow rates to meet Acute Respiratory Distress Syndrome
oxygenation needs. In contrast, ECCO2R may
be able to achieve clinically relevant carbon In severe forms of acute respiratory distress
dioxide removal goals at blood flow rates as low syndrome (ARDS), the blood flow of ECCO R
2
as 200-1,500 ml per minute.3 Therefore, when would be insufficient to correct the severe
the main intention of extracorporeal support is oxygenation impairments. However, ECCO R
2
carbon dioxide removal, smaller cannulae may is emerging as a potential strategy in more
be used, which may, in turn, minimize the com- moderate forms of ARDS (Table 63-1).5 Lung
plexity and risk of insertion and maintenance protective ventilation, targeting tidal volumes
of the circuit.4,5 of 6 mL/kg predicted body weight (PBW) or
ECCO2R may be used either to supplement less and plateau airway pressures less than or
invasive mechanical ventilation (IMV) when equal to 30 cm of H O, has been demonstrated
the ventilator alone is insufficient to manage to improve survival2in ARDS and remains the
hypercapnia or to minimize the potentially current standard of care.6 However, both animal
injurious effects of IMV. In selected patients, and human studies have suggested that target-
it may allow for discontinuation of the ven- ing even lower tidal volumes and airway pres-
tilator entirely, or even prevent endotracheal sures may further reduce ventilator-associated
intubation and IMV altogether. ECCO2R may lung injury (VALI).7-10 Post hoc analysis of the
713
Chapter 63
ARMA trial demonstrated a linear relationship renewed interest in demonstrating efficacy of

between plateau airway pressures and decreased such a strategy. Terragni et al. demonstrated a
mortality that held true well below the 30 cm of reduction in inflammatory markers associated
H2O targeted in the study, suggesting there is with VALI by lowering plateau airway pressures
no safe upper limit of plateau airway pressure.8 from an average of 29 cm H2O to 25 cm H2O in
Although lung protective ventilation (tidal vol- the context of ECCO2R-assisted reductions in
umes and plateau airway pressures below the tidal volumes from approximately 6 to 4 mL/
current standard of care) may reduce mortality kg.9 In a subsequent study, Bein et al. random-
beyond what can be achieved with the current ized subjects with moderate to severe ARDS to
low respiratory system, compliance and dead either conventional lung protective ventilation
space fraction may limit the ability to imple- or ECCO2R-assisted very low tidal volume
ment such a strategy because of the develop- ventilation (3 mL/kg PBW).10 Although the
ment of intolerable levels of hypercapnia and study did not show a difference in the primary
acidemia. ECCO2R can facilitate the application outcome of ventilator-free days (VFD), post hoc
of very low tidal volumes by correcting the ac- analysis showed a significant reduction in VFD
companying respiratory acidosis, as has been in the ECCO2R group among those with more
demonstrated in two prospective human stud- severe hypoxemia. Despite these findings, stud-
ies.9,10 This concept of using ECCO2R to manage ies have yet to demonstrate a significant clinical
ventilation and minimize IMV in ARDS is not benefit from ECCO2R-assisted very low tidal
new; Gattinoni and colleagues experimented volume ventilation.15 Additional data is needed
with this strategy since the 1970s.4,11-13 However, to demonstrate both efficacy and an acceptable
early efforts to show a benefit of ECCO2R- risk profile before such a strategy can be rec-
facilitated lung protective ventilation were ommended for use outside the research setting.
unsuccessful, in part because of complications
associated with early versions of the technol- Acute-on-Chronic Lung Disease
ogy.14 With improvements in extracorporeal
circuitry over the last several years, there is ECCO2R may be considered in patients with
acute-on-chronic lung disease when hypercap-
Table 63-1. Considerations and contraindica- nia and respiratory acidosis persist despite the
tions for ECCO2R in respiratory failure. use of IMV, or when endotracheal intubation
and IMV are judged to be too invasive. Acute
Considerations
exacerbations of chronic obstructive pulmonary
ARDS to achieve very low tidal volume disease (COPD) represent the most obvious
ventilation (insufficient evidence to targets for such a strategy, particularly when
recommend) IMV contributes to dynamic hyperinflation
Bridge to recovery from acute exacerbations of and the generation of intrinsic positive end-
hypercapnic respiratory failure expiratory pressure. Several case series have
Status asthmaticus (low level evidence)
Other chronic lung diseases (insufficient
demonstrated the ability of ECCO2R to correct
evidence to recommend) severe, acute respiratory acidosis,16-20 which in
Bridge to transplantation for end-stage turn may improve dyspnea enough to facilitate
respiratory failure extubation and mobilization.16,20 In some cir-
Contraindications cumstances, ECCO2R may provide sufficient
Severe hypoxemia for which higher blood flow gas exchange support to preclude the need for
rates are needed
Terminal exacerbation of end-stage respiratory
IMV altogether, with the advantage of avoiding
failure without eligibility for transplantation ventilator-associated complications.18,21-24
714
Severe, refractory status asthmaticus is modified (eg, additional drainage cannula) to ac-
another obstructive lung disease process for commodate higher blood flow rates (ie, ECLS).
which ECCO2R should be seriously consid- The other major limitation to ECCO2R is the
ered, in particular because of the deleterious lack of a destination device. Patients with termi-
consequences of positive pressure ventilation nal exacerbations of endstage lung disease who
on gas exchange and hemodynamic stability, are ineligible for lung transplantation should
although the data for such use remain limited not be offered ECCO2R. For patients supported
to observational studies.25,26 Exacerbations or with ECCO2R who cannot achieve recovery
progression of chronic lung diseases other or transplantation, the focus of clinical care
than COPD and asthma, when manifested as should shift toward optimizing patient comfort
hypercapnia without significant hypoxemia, and withdrawal of life sustaining therapy, as
may likewise benefit from the initiation of EC- appropriate.29
CO2R, with or without IMV support. However,
in all cases where a significant degree of chronic Physiological Targets
lung disease exists, there must be strong con-
sideration for both the reversibility of the acute The physiological target of ECCO2R should
process, the potential for development of severe be the patient’s arterial blood pH, rather than
hypoxemia, and the eligibility of the patient for the partial pressure of carbon dioxide, because
lung transplantation.27 many patients with chronic lung disease who
There is no universally accepted threshold are candidates for ECCO2R will have chronic
of pH or carbon dioxide for which ECCO2R hypercapnia.16 In most circumstances, and
is indicated. Timing of initiation of ECCO2R without a significant concomitant metabolic
depends in large part on the intention of the acidosis, the sweep gas flow rate should be
therapy (eg, replacement vs. supplementation adjusted to achieve a near-normal pH. However,
of IMV; BTR vs. BTT). Studies intending to in the subset of patients receiving ECCO2R who
better define the optimal patient population and have chronic hypercapnia and a compensatory
threshold gas exchange abnormalities for which metabolic alkalosis, and who may be candidates
ECCO2R should be initiated are ongoing.28 for lung transplantation, the sweep gas flow
rate should be adjusted to achieve a slightly
Contraindications and Limitations alkalemic pH (eg, 7.41-7.45) to allow for a
gradual reversal of the alkalosis in anticipation
Because extracorporeal carbon dioxide re- of transplantation.
moval is more efficient than oxygenation,3,4,11-13 The expected physiological effect of EC-
ECCO2R can be achieved with lower blood flow CO2R is mainly decreased minute ventilation.
rates and smaller cannulae (often referred to as This in turn will increase the risk of alveolar
“catheters” in this setting) than what is required collapse of the native diseased lung, which
for oxygenation. Therefore, extracorporeal cir- is usually managed by maintaining minimum
cuits specifically designed for ECCO2R-level airway pressure. At the same time, a decrease
blood flow will prove inadequate to achieve suf- in alveolar partial pressure of oxygen, driven by
ficient oxygenation in patients with concomitant the decreased alveolar ventilation, may require
severe hypoxemia. Patients who have severe a compensatory increase in fraction of inspired
hypoxemia or are at risk for developing severe oxygen (FiO2) to maintain arterial oxygenation,
hypoxemia are poor candidates for ECCO2R particularly when the baseline FiO2 is in the
(Table 63-1). However, if severe hypoxemia low range.30
develops, certain extracorporeal circuits may be
715
Chapter 63
Circuit Configurations blood flow, though this may require adapters to

connect the smaller tubing to standard circuit
Either venovenous or arteriovenous circuits components.
may be utilized to implement ECCO2R, as both In the context of lower blood flow, the
configurations can remove carbon dioxide at extracorporeal membrane’s surface area and
low blood flow rates.21,23,31 However, it is im- gas exchange efficiency are paramount. Novel
portant to recognize differences between the strategies, including the incorporation of
two strategies. Venovenous ECCO2R requires carbonic anhydrase, blood acidification, and
an extracorporeal pump (typically centrifugal) electrodialysis, are being investigated as means
to generate blood flow.32 Centrifugal pumps of maximizing ECCO2R efficiency by increas-
generate negative pressures that may damage ing the amount of carbon dioxide available for
blood elements, although this phenomenon is removal.37-40 Of note, although neonatal and
less likely at low blood flow rates used in EC- pediatric membranes are rated for lower blood
CO2R. Venovenous ECCO2R has the advantage flows, the surface area of these smaller devices,
of avoiding arterial cannulation, and may be when combined with low blood flow, may be
accomplished with single-site venous access insufficient to achieve the desired carbon di-
when using dual-lumen cannulae.16,33 Upper oxide removal. More data is needed to define
body single-site access is the preferred cannula- the optimal combination of blood flow, mem-
tion strategy for patients in whom ambulation is brane surface area, and ancillary techniques for
anticipated, although femoral venous cannula- adequate carbon dioxide removal for a given
tion is not a contraindication to ambulation.34 disease state.
In contrast, arteriovenous ECCO2R relies on
native cardiac output to generate blood flow Anticoagulation Strategy and Impact of Low
through a pumpless extracorporeal circuit.31 It Extracorporeal Blood Flow
requires femoral arterial cannulation,23 which
may compromise distal limb perfusion and limit Thrombotic risk within the circuit gener-
mobilization. ally increases as extracorporeal blood flow
No consensus on the optimal extracorporeal rates decrease. This may be particularly true
blood flow or cannula sizes for ECCO2R exists. with current ECCO2R technology, which tends
Blood flow and cannula selection depend on to couple low blood flow rates with relatively
the amount of carbon dioxide removal required, high extracorporeal membrane surface area. The
which in turn relates to the underlying disease use of low levels of systemic anticoagulation
state. In patients with exacerbations of COPD,
blood flow rates in the published literature have Table 63-2. Extracorporeal blood flow rates
ranged from 177 mL/min to 1.7 L/min, with and cannula sizes used in studies of ECCO2R.
cannula sizes in venovenous ECCO2R varying
from two 12Fr single-lumen cannulae to 14Fr to ECCO2R Blood Cannula Size
Flow Rate (L/min) (Fr)
23Fr dual-lumen cannulae.16-18,23,35 Cannulae in COPD
arteriovenous ECCO2R have ranged from 13Fr Abrams et al. 1.0-1.7 20-23
Burki et al. 0.43 15.5
to 15Fr for arterial cannulation and 13Fr to 17Fr Del Sorbo et al. 0.18-0.33 14
for venous cannulation, the choice depends, in Gattinoni et al. 0.4-0.6 12 x2
Kluge et al. 1.1 13-15 (arterial)
part, on vessel diameter (Table 63-2).23,36 Like- 13-17 (venous)
wise, smaller tubing diameter (1/4” or 3/16”) Roncon-Albuquerque et al 0.7-1.0
Facilitation of Lung Protective Ventilation in ARDS
19
than what is commonly used for ECMO (3/8” Bein 1.2 15 (arterial)
17 (venous)
or 1/2”) may be considered in the context of low Terragni 0.2-0.4 14
716
increases the thrombotic risk even further. The Conclusion

existing literature reports varying rates of circuit
thrombosis at blood flow rates less than 600 mL/ With advances in extracorporeal technol-
min when activated partial thromboplastin times ogy, ECCO2R has reemerged as a potential
of 1.5 to 2.3 times baseline are targeted.17,18 management strategy for certain subsets of
More data is needed to determine the optimal patients with respiratory failure. The ability to
level of anticoagulation for ECCO2R. perform ECCO2R at low blood flow rates via
smaller cannulae than are required for ECMO,
Management Considerations in the Event of effectively the equivalent of dialysis for the
Circuit Failure lung, could significantly alter the approach
to hypercapnic respiratory failure. However,
In the event of circuit failure, management studies showing both a benefit on meaningful
of patients should rely on conventional manage- clinical outcomes and an acceptable risk profile
ment of hypercapnia while the circuit malfunc- are needed before such a strategy can be recom-
tion is corrected. In endotracheally intubated mended for clinical use.
patients, minute ventilation should be increased
as needed. In nonendotracheally intubated pa-
tients, noninvasive positive-pressure ventilation
should be considered. If noninvasive ventilatory
support is insufficient, tracheal intubation and
IMV should be initiated.
Weaning ECCO2R
In patients receiving ECCO 2R as BTR,

assessments of readiness to wean should be
undertaken as the acute process resolves. In
patients receiving IMV, the sweep gas flow rate
may be reduced in order to maintain normal
pH, while ventilator settings are liberalized
within the limits of lung-protective ventilation
as native lung function improves. In patients
who are breathing without the assistance of
the ventilator, the sweep gas flow rate may be
incrementally lowered with corresponding as-
sessments of both the patient’s respiratory status
and pH by arterial blood gas to ensure adequate
spontaneous ventilation without excess work
of breathing. In patients with ARDS, respira-
tory system compliance should be taken into
consideration as the tidal volumes are liberated,
avoiding excessive plateau airway pressures. In
acute exacerbations of COPD, close monitoring
for dynamic hyperinflation or increased work of
breathing should occur as ECCO2R is weaned.
717
Chapter 63
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Blood oxygenation and decarboxylation 11. Gattinoni L, Kolobow T, Agostoni A, et
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4. Gattinoni L, Kolobow T, Damia G, Agos- in treatment of adult respiratory distress
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Jul 1979;2(4):183-185. The role of total static lung compliance in
5. Abrams D, Brodie D. Emerging indications the management of severe ARDS unrespon-
for extracorporeal membrane oxygenation sive to conventional treatment. Intensive
in adults with respiratory failure. Annals Care Med. 1984;10(3):121-126.
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2013;10(4):371-377. al. Low-frequency positive-pressure ven-
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Dobbs L, Matthay MA. Low tidal volume ratory distress syndrome. Am J Respir Crit
reduces epithelial and endothelial injury Care Med. Feb 1994;149(2 Pt 1):295-305.
in acid-injured rat lungs. Am J Respir Crit 15. Bein T, Weber-Carstens S, Goldmann A, et
Care Med. Jan 15 2002;165(2):242-249. al. Lower tidal volume strategy ( approxi-
8. Hager DN, Krishnan JA, Hayden DL, mately 3 ml/kg) combined with extracor-
Brower RG. Tidal volume reduction in pa- poreal CO(2) removal versus ‘conventional’
tients with acute lung injury when plateau protective ventilation (6 ml/kg) in severe
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1245. 2013.
9. Terragni PP, Del Sorbo L, Mascia L, et al. 16. Abrams DC, Brenner K, Burkart KM, et
Tidal volume lower than 6 ml/kg enhances al. Pilot study of extracorporeal carbon
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obstructive pulmonary disease. Annals corporeal life support for adult respiratory
of the American Thoracic Society. Aug failure due to status asthmaticus. ASAIO J.
2013;10(4):307-314. Jan-Feb 2009;55(1):47-52.
17. Burki NK, Mani RK, Herth FJ, et al. A Nov- 26. Brenner K, Abrams D, Agerstrand C, Brodie
el Extracorporeal CO2 Removal System: D. Extracorporeal carbon dioxide removal
Results of a Pilot Study of Hypercapnic for refractory status asthmaticus: experi-
Respiratory Failure in Patients With COPD. ence in distinct exacerbation phenotypes.
Chest. Mar 1 2013;143(3):678-686. Perfusion. Jul 10 2013.
18. Del Sorbo L, Pisani L, Filippini C, et al. Ex- 27. Biscotti M, Sonett J, Bacchetta M. ECMO
tracorporeal CO2 Removal in Hypercapnic as bridge to lung transplant. Thoracic sur-
Patients At Risk of Noninvasive Ventilation gery clinics. 2015;25(1):17-25.
Failure: A Matched Cohort Study With 28. Sklar MC, Beloncle F, Katsios CM, Bro-
Historical Control. Crit Care Med. Sep 16 chard L, Friedrich JO. Extracorporeal
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19. Abrams D, Roncon-Albuquerque R, Jr., chronic obstructive pulmonary disease: a
Brodie D. What’s new in extracorporeal systematic review. Intensive Care Med. Jun
carbon dioxide removal for COPD? Inten- 25 2015.
sive Care Med. May 2015;41(5):906-908. 29. Abrams DC, Prager K, Blinderman CD,
20. Roncon-Albuquerque R, Jr., Carona G, Burkart KM, Brodie D. Ethical dilemmas
Neves A, et al. Venovenous extracorporeal encountered with the use of extracorporeal
CO2 removal for early extubation in COPD membrane oxygenation in adults. Chest.
exacerbations requiring invasive mechani- Apr 2014;145(4):876-882.
cal ventilation. Intensive Care Med. Dec 30. Gattinoni L, Kolobow T, Tomlinson T,
2014;40(12):1969-1970. White D, Pierce J. Control of intermittent
21. Terragni PP, Birocco A, Faggiano C, Ranieri positive pressure breathing (IPPB) by ex-
VM. Extracorporeal CO2 removal. Contrib tracorporeal removal of carbon dioxide. Br
Nephrol. 2010;165:185-196. J Anaesth. Aug 1978;50(8):753-758.
22. Olsson KM, Simon A, Strueber M, et al. 31. Bein T, Weber F, Philipp A, et al. A new
Extracorporeal membrane oxygenation in pumpless extracorporeal interventional
nonintubated patients as bridge to lung lung assist in critical hypoxemia/hypercap-
transplantation. Am J Transplant. Sep nia. Crit Care Med. May 2006;34(5):1372-
2010;10(9):2173-2178. 1377.
23. Kluge S, Braune SA, Engel M, et al. Avoid- 32. Brodie D, Bacchetta M. Extracorporeal
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extracorporeal carbon dioxide removal in N Engl J Med. Nov 17 2011;365(20):1905-
patients failing noninvasive ventilation. 1914.
Intensive Care Med. Oct 2012;38(10):1632- 33. Javidfar J, Brodie D, Wang D, et al.
1639. Use of bicaval dual-lumen catheter for
24. Fuehner T, Kuehn C, Hadem J, et al. Ex- adult venovenous extracorporeal mem-
tracorporeal membrane oxygenation in brane oxygenation. Ann Thorac Surg. Jun
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tation. Am J Respir Crit Care Med. Apr 1 34. Abrams D, Javidfar J, Farrand E, et al.
2012;185(7):763-768. Early mobilization of patients receiving
25. Mikkelsen ME, Woo YJ, Sager JS, Fuchs extracorporeal membrane oxygenation: a
BD, Christie JD. Outcomes using extra-
719
Chapter 63
retrospective cohort study. Crit Care. Feb

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35. Pesenti A, Rossi GP, Pelosi P, Brazzi L, Gat-
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36. Kohler K, Valchanov K, Nias G, Vuylsteke
A. ECMO cannula review. Perfusion. Mar
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37. Arazawa DT, Oh HI, Ye SH, et al. Immobi-
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Membranes Accelerates CO(2) Removal
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Jun 1 2012;404-404:25-31.
38. Zanella A, Mangili P, Redaelli S, et al.
Regional blood acidification enhances
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6 2015.
40. Abrams D, Brodie D. The clinical manage-
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720
64
Other Forms of Extracorporeal Cardiovascular Support – IABP, IMPELLA, VAD
Federico Pappalardo, MD, Giulio Melisurgo, MD
Introduction tronix CentriMag are the most commonly used

devices for short and intermediate-term support
The Interagency Registry for Mechanically (Table 64-1).2 As a general rule, implantable
Assisted Circulatory Support (INTERMACS) assist devices (intracorporeal left assist devices-
I “crash and burn” and II “sliding on inotropes” LVADs) or total artificial heart are not used in
profiles describe those patients who are in INTERMACS I patients.
critical cardiogenic shock, despite escalating In clinical practice, there are also some pa-
inotropic support.1 In such patients, mechani- tients with the most severe form of ventricular
cal circulatory support (MCS) is required to dysfunction in whom shock is refractory to a
restore hemodynamics and maintain adequate single device (INTERMACS 0). In such pa-
systemic perfusion: ECMO, intraaortic balloon tients a single device approach is not enough
pump (IABP), Impella, and BiVAD with Levi- and the simultaneous use of different devices
Table 64-1. Comparison of devices.
IABP IMPELLA CentriMag-BiVAD

Pump mechanism Pneumatic Axial Centrifugal
Amount of support 0.5-1 l/min 2.5-5 l/min 10 l/min
Arterial or outflow 7-9 Fr femoral or 12-21 Fr femoral or 22 Fr central
insertion axillary artery axillary artery cannulation
Venous or inflow N/A N/A 32 Fr central
insertion cannulation
Maximal duration 10 d 5-7 d 30 d
of support
Contraindications Severe aortic Mechanical prosthetic Mechanical
regurgitation aortic valve prosthetic valves
Aortic dissection Left ventricular thrombus
Complications Bleeding Bleeding Bleeding
Infection Infection Infection
Thromboembolism Thromboembolism Thromboembolism
Limb ischemia Limb ischemia
Hemolysis
Valvular injury
721
Chapter 64
is required to reduce the unacceptably high tricular unloading and slightly increased cardiac
mortality rate. output (0,5-1 l/min). Optimal hemodynamic ef-
We can therefore recognize three clinical fect from the IABP depends on several factors
scenarios: such as balloon diameter in relation to aortic
• Use of ECMO in combination with other diameter, balloon position in the aorta, proper
devices (IABP and/or Impella), in patients timing of balloon inflation in diastole and de-
with shock refractory to other devices flation in systole, patient hear rate and rhythm.
• Use of other devices (IABP and/or Impella) Moreover, patients must have some level of
in combination with ECMO, in patients suf- LV function for the IABP to be effective, since
fering shock refractory to ECMO or ECMO any increase in in cardiac output depends on
related complications the work of the heart itself. For these reasons
• Use of other devices (paracorporeal inotropes are usually necessary during IABP
CentriMag LVAD or BiVAD) in patients support.4
with overt cardiac contraindication to per- IABP support can also last several weeks,
cutaneous peripheral support (eg, severe but requires immobilization and related compli-
aortic regurgitation) cations can limit its prolonged use. The alterna-
tive surgical axillary approach allows patients
Circulatory support devices other than to be mobilized, allowing its prolonged use. A
ECMO differ in terms of cannulation feature, percutaneous technique for placing IABP in
hemodynamic performance, durability, and the left axillary-subclavian artery has also been
pathophysiologic interaction with ECMO. described.5
Complications affecting patients with IABP
Intraaortic Balloon Pump are very low. The most common include limb
ischemia and vascular trauma. However, smaller
Prospective, randomized, and controlled catheters (7 Fr) are now available, allowing
trials have failed to demonstrate conclusive safer use of IABP in patients with small vascular
proof of IABP benefit,3 yet IABP remains the accesses. Thrombocytopenia from platelet de-
most commonly used form of circulatory sup- position on the IABP membrane can also occur.
port in the presence of hemodynamic instabil- There is evidence that in terms of working
ity. Indeed, ELSO guidelines for adult cardiac principle, IABP and ECMO are synergistic and
failure recommend ECMO implantation in complementary to each other.6 IABP utilization
patients with shock refractory to high-dose during ECMO helps to prevent LV distension,
inotropes and IABP, defining the role of IAPB enhancing pulsatility and counteracting the
as first-line support. ECMO induced increase in afterload, and reduc-
IABP is a balloon mounted on a 7.5-8 Fr ing risk of left ventricular thrombosis. Moreover
catheter advanced from the common femoral IABP generates some degree of pulsatility
artery into the aorta through a percutaneous through diastolic augmentation, with potential
femoral approach, with the proximal tip placed beneficial effects on tissue perfusion.7
before the left subclavian artery. IABP can be During the course of ECMO, timing of
easily placed bedside in unstable patients. balloon inflation and deflation should always
Diastolic inflation of the balloon increases be based on ECG triggers, since low or absent
diastolic pressure, while systolic deflation, de- intrinsic pulsatility may limit proper synchro-
creases afterload and promotes left ventricular nization with pressure triggers.
(LV) blood outflow. The net effect is decreased Contraindications for the IABP include
myocardial oxygen consumption, modest ven- significant aortic regurgitation, aortic dissection
722
and clinically significant aortic aneurysm, and most commonly reported complications are
severe peripheral arterial disease. related to vascular access. Hemolysis due to
mechanical erythrocyte shearing has also been
IMPELLA reported.
Patients supported with Impella may re-
The Impella (Abiomed Inc., Danvers, MA) quire ECMO implantation for persistence of
is a nonpulsatile axial flow pump designed to shock. Such rescue ECMO implantation can
propel blood from the left ventricle into the be required either because the chosen Impella
ascending aorta. Impella is deployed across the device is not able to provide adequate flow for
aortic valve in a retrograde fashion under fluo- the patient’s clinical conditions, or because
roscopic or echocardiographic guidance. Three of the occurrence of right ventricular failure.
versions for LV support are available: Impella However Impella RP, a new addition to the
2.5, CP, and 5.0. Impella 2.5 and CP are inserted Impella family, is now available to provide per-
percutaneously via femoral artery: Impella 2.5 cutaneous support for the failing right ventricle.
generates up to 2.5 l/min of flow and requires It is a catheter-mounted axial flow pump (22
a 12 Fr catheter for insertion, while Impella CP Fr) inserted via the femoral vein and deployed
generates up 4 l/min of flow and requires 14 Fr across the pulmonary valve (Figure 64-2). The
catheter (Figure 64-1). Impella 5.0 can generate pump aspirates blood from the inferior vena
5 l/min of flow, but is a 21 Fr device that requires cava, pumping it into the pulmonary artery,
a surgical cut down to the femoral or axillary generating up to 4 l/min flow.
artery.8 Therefore pump selection should be Indeed, patients supported by ECMO may
made at baseline according to the expected flow require Impella implantation to unload the LV9
required by the clinical conditions. since ECMO cannot do so. In the setting of se-
Impella effectively unloads the LV and vere LV dysfunction, the increased cardiac after-
increases forward flow, reducing myocardial load from the retrograde flow of the peripheral
oxygen consumption, and reducing pulmonary cannulation can lead to increases in LV cavity
capillary wedge pressure.4
The Impella is approved for use of up to
five days, but in clinical practice longer time of
support, up to several weeks, has been reported.
Surgical implantation via axillary artery is also
possible and would allow longer support. The
Figure 64-1. A) The Impella micro-axial flow Figure 64-2. Impella RP catheter placement.
pumps. B) Peripheral placement of the Impella (Courtesy of Abiomed, Inc., Danvers, MA;
catheters across aortic valve. (Courtesy of with permission)
Abiomed, Inc., Danvers, MA; with permission)
723
Chapter 64
pressure and to pulmonary venous hypertension, of any aortic valve opening might make the
with subsequent pulmonary edema and vascular procedure extremely challenging during aortic
injury (Figure 64-3). Furthermore, inadequate valve crossing.
unloading of the LV, in association with stasis, During ECMO, assessment of proper
can lead to thrombus formation within the positioning of the Impella axial pump can be
ventricular cavity. This complication is a major challenging through the use of the displayed
determinant of poor outcome, limiting options ventricular pressure tracing due to the absence
for recovery, heart transplantation, or transition of pulsatility. Echocardiography plays an indis-
to a long-term VAD system. Clinicians should pensable role, allowing direct visualization of
actively focus on its prevention. IABP could the pump across the aortic valve.
be considered a simple bedside strategy to Contraindications for the Impella are me-
prevent LV distension, but does not effectively chanical aortic valve or left ventricular throm-
unload the left ventricle once distension has bus. Aortic stenosis is a relative contraindica-
occurred. Traditional management strategies tion. Unlike IABP, severe aortic regurgitation
for LV decompression account for several is not an absolute contraindication, although it
surgical techniques, based on the insertion of a may reduce the net efficacy of the pump.
left atrial or ventricular vent, by sternotomy or
thoracotomy. However such procedures present Levitronix CentriMag
a high risk of bleeding and infection compli-
cations in patients on ECMO; moreover, the CentriMag (Thoratec Inc., Pleasanton, CA)
chest is violated before other potential surgical is an extracorporeal surgically implanted assist
therapies (long-term VAD, total artificial heart, device, with magnetically levitated centrifugal-
or heart transplantation). The Impella is an flow pump that can provide up to 10 l/min.10 The
attractive percutaneous option, because it not pump has no contact between the impeller and
only decompresses the ventricle but also aug- the rest of the pump components, which leads
ments forward flow. Therefore, during ECMO to lower rates of hemolysis and pump throm-
support, Impella implantation should promptly bosis. The CentriMag system is versatile and
be considered in absence of pulsatility within can be used for univentricular or biventricular
the arterial line tracing and in presence of LV support. In LV support, an inflow cannula is
smoke at echocardiography. However, lack placed in the left atrium or ventricle and the
outflow cannula into the ascending aorta. In
right ventricular support, the inflow is placed
Figure 64-4. A) CentriMag blood pump. B)

Schematic diagram of possible CentriMag can-
nulation sites: LA and Ao for LV support vs. RA
Figure 64-3. White lung during ECMO sup- and PA for RV support. (Courtesy of Thoratec,
port. Inc., Pleasanton, CA; with permission)
724
in the right atrium and the outflow cannula in the presence of low pump flow states (eg,
in the main pulmonary artery (Figure 64-4). low pump speed or hypovolemia). Usually,
Cannula positioning requires sternotomy, but anticoagulation initiation can delayed for up to
a less invasive minithoracotomy approach can 24-72 hours postoperatively in order to reduce
also be used. the risk of bleeding, then a low dose of systemic
CentriMag system can provide longer term anticoagulant is started. If bleeding occurs dur-
support compared to the other devices (ECMO, ing support, anticoagulation can be held for up
IABP, Impella).11 In fact although it is approved to 72 hours, but higher pump flows should be
and recommended for short term use, duration maintained.11
of up to three months has been described, with
pumps exchanged every 4 to 6 weeks to prevent Right Ventricular Failure
fibrin formation.12 The pumps can be exchanged
at the bedside or in the operating room. Severe right ventricular (RV) failure can
CentriMag implantation is usually used in complicate acute myocardial infarction and
patients without central neurologic damage who open heart surgery; in particular LVAD im-
have no recovery of end-organ function and plantation and heart transplantation.13 It is an
who might be a candidate for long-term LVAD increasingly common clinical problem associ-
or heart transplantation. As general rule, when ated with significant morbidity and mortality.
this device is required in INTERMACS I pa- Optimal management is not well established
tients, a biventricular support should always be since the RV is known to be more resilient than
considered regardless of the echocardiographic the left ventricle after ischemic and surgical
features of the right ventricle. This clinical insults, but predicting the time needed for its re-
scenario usually portends the need for a long covery remains difficult. Furthermore, recovery
period of time with high flow before a definitive is the only strategy that can be pursued for this
surgical therapy can be applied. condition. These reasons make device selection
The most common complications are infec- challenging, when RV failure is refractory to
tion, bleeding and thromboembolic neurologic medical therapy and MCS is required.
events. The most conventional approach requires
open chest cannulation of the right atrium and
Anticoagulation the pulmonary artery and uses a temporary
RVAD to support the failing right ventricle.14
IABP does not strictly require anticoagula- Such strategy allows complete RV unloading
tion and there is variability in the use of anti- and provides complete anterograde transpulmo-
coagulation during its support. Many centers nary blood flow with adequate preload for the
routinely use anticoagulation, but others do not, LV. Its major limitation is the risk of inherent
particularly with 1:1 pumping.8 bleeding and infectious complications. Percu-
The Impella pump is continuously purged taneous VA-ECMO is another approach, since
with a heparinized dextrose solution to prevent ECMO supports the right ventricle and gas ex-
blood from entering the motor and forming change. However its efficacy is burdened by the
thrombus and systemic anticoagulation is usu- general complications of the device, so its use
ally unnecessary.8 should be limited to patients with concomitant
CentriMag bears a very low risk of pump acute lung failure, when gas exchange has to be
thrombosis; however, the combined surface artificially maintained.
area of pump, cannulas, and tubing are still Impella RP is a novel minimally invasive
susceptible to thrombus formation, in particular percutaneous RVAD, now available for tempo-
725
Chapter 64
rary support of the RV. The recent RECOVER to prevent ventilator-associated pneumonia in
RIGHT prospective trial demonstrate that Im- ventilated patients or to allow for the ability to
pella RP is safe and reliable in patients with se- eat in nonventilated patients. Progressive mo-
vere RV failure refractory to medical treatment, bility with these devices encompasses turning
with immediate and sustained hemodynamic from side to side, and passive/active range of
benefit and favorable outcomes to 30 and 180 motion, avoiding the extremity in which the
days.15 device is located.
In our institution, we have adopted a step When prolonged support is required, an ax-
wise approach, using first a short-term percuta- illary placement approach for IABP or Impella
neous device (VA-ECMO or Impella RP). We should be considered. Surgical central implanta-
proceed to surgical temporary RVAD only when tion of the CentriMag ventricular assist device
recovery is not achieved in a few days and pro- is another option. In fact, an early progressive
longed support is needed. The only exception mobility program permits such patients to be up
might be the postcardiotomy setting. in the chair a few days after implantation and
tolerate up to 30-minute ambulation sessions
Mobilization (Figure 64-5). Safety measures are required dur-
ing ambulation to not compromise the driveline
An early mobility program for patients to the devices.
receiving MCS devices has resulted in suc-
cessful outcomes such as increased tolerance Weaning
to activity and decreased mortality rate. In fact,
complications of prolonged bed rest in the in- Weaning of MCS occurs once noncardiac
tensive care unit are well known.16 Prolonged organ systems have recovered. In patients with
bed rest increases risk of ventilator-associated irrecoverable end-organ and/or neurologic
pneumonia, need for prolonged ventilation,
length of ICU and hospital stays, occurrence
of delirium, and workload of the cardiovascular
system. In particular, in patients assisted by tem-
porary MCS, avoiding deconditioning, muscle
loss, and nutritional depletion is of paramount
importance. In fact, all such conditions dramati-
cally affect future definitive therapeutic options
(heart transplantation or LVAD implantation).
Early progressive mobility goals for pa-
tients receiving MCS devices are no different
than any other ICU patients and allow physical
reconditioning. However, more limitations and
safety considerations exist when mobilizing
these individuals.17
In fact, IABP, Impella, and peripheral VA-
ECMO limit early mobilization because of the
requirement for placement of cannulas within
the femoral vessels. These devices require Figure 64-5. Ambulatory patient during
the patient to adhere to bed rest. However the paracorporeal biventricular support with
reverse Trendelenburg position should be used CentriMag.
726
dysfunction withdraw of mechanical support

should be considered.11 In the weaning process,
MCS support is decreased gradually (hours to
days). If hemodynamics and other organ func-
tion remain adequate, the device is explanted
or if hemodynamics and/or organ function
deteriorate LVAD implantation or heart trans-
plantation need to be considered. For this reason
the weaning process starts as soon as possible,
ideally at the moment of MCS implantation. In
fact all patients who receive a temporary MCS
should be assessed for advanced long-term heart
failure therapies.
When different devices are simultaneously
required for MCS, weaning from the device
which produces increased complications should
be considered first. As a general rule, when
ECMO is used, it should be the first device to
be removed. Such strategy might reduce the
duration of ECMO support, hasten its weaning,
and eventually reduce its related complications.
727
Chapter 64
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6. Ma P, Zhang Z, Song T, et al. Combining Cardiology linics. May 2012;30(2):303-
ECMO with IABP for the treatment of criti- 310.
cally Ill adult heart failure patients. Heart 14. Aissaoui N, Morshuis M, Schoenbrodt M,
Lung Circ. Apr 2014;23(4):363-368. et al. Temporary right ventricular mechani-
7. Gass A, Palaniswamy C, Aronow WS, et cal circulatory support for the management
al. Peripheral venoarterial extracorporeal of right ventricular failure in critically ill
membrane oxygenation in combination patients. J Thoracic Cardiovasc Surg. Jul
with intra-aortic balloon counterpulsation 2013;146(1):186-191.
in patients with cardiovascular compromise. 15. Anderson MB, Goldstein J, Milano C, et
Cardiology. 2014;129(3):137-143. al. Benefits of a novel percutaneous ven-
8. Rihal CS, Naidu SS, Givertz MM, et al. tricular assist device for right heart failure:
2015 SCAI/ACC/HFSA/STS Clinical The prospective RECOVER RIGHT study
Expert Consensus Statement on the Use of the Impella RP device. J Heart Lung
of Percutaneous Mechanical Circulatory Transplant. Dec 2015;34(12):1549-1560.
Support Devices in Cardiovascular Care: 16. Freeman R, Maley K. Mobilization of
Endorsed by the American Heart Assoca- intensive care cardiac surgery patients on
728
mechanical circulatory support. Crit Care

Nurs Quarterly. Jan-Mar 2013;36(1):73-88.
17. Chavez J, Bortolotto SJ, Paulson M,
Huntley N, Sullivan B, Babu A. Promo-
tion of progressive mobility activities
with ventricular assist and extracorporeal
membrane oxygenation devices in a car-
diothoracic intensive care unit. Dimensions
of critical care nursing: DCCN. Nov-Dec
2015;34(6):348-355.
729
65
Implementing an ECLS Program
Tracy Morrison, RN, James D. Fortenberry, MD
Given the complexity and resource inten- This chapter utilizes the Guergueruain ap-
sity of extracorporeal membrane oxygenation proach while adopting a process management
(ECMO) delivery, an institution considering methodology developed by Motorola for project
adding an ECMO service needs to use a planned management and evaluation.2 The methodology
approach when developing and maintaining is also built on six essential steps which have
a comprehensive program. A commitment to been modified to reflect the development of an
beginning ECMO at an institution should be ECMO program:
taken with an understanding that much more
than purchase of a pump and disposables must 1. Identify the type of ECMO service
occur. The program marries technology with 2. Identify the customers
personnel commitment. As a hospital reacts 3. Determine personnel needs and suppliers
to both internal and external environmental 4. Define processes and procedures
threats, the allocation of scarce resources can 5. Eliminate mistakes and optimize processes
create internal competition within the institution 6. Continuously improve and sustain the
for budget allocation. The present healthcare program
environment requires institutional agility when
reviewing current programs or when consider- Identify the ECMO Service
ing implementation of a new program. The
return on investment of an ECMO program for Any institution considering a new ECMO
an institution can be complicated to ascertain. program should perform a needs assessment to
Thus taking a proactive and thoughtful approach identify the patients impacted when it becomes
to stepping into the ECMO world is essential. implemented. The need for a program should
Planning for ECMO at an institution can
be achieved through several paths. A recent
overview provides one excellent approach.1 As
seen in Figure 65-1, the process comprises a six-
step approach. Utilizing a process management
methodology when designing and implementing
a new project has been proven to increase the
overall quality of the project effort.2
Figure 65-1. A six step process for ECMO
planning.
731
Chapter 65
be based on the planned development of new ECPR in an inexperienced program can set the
programs needing ancillary ECMO support (eg, program back significantly.
new pediatric cardiac surgery program), exist-
ing services for which ECMO indications have Identify Your Customer
become established (eg, adult respiratory units
or postoperative cardiac surgery units), or in in- The customer of an ECMO center com-
stitutions where access to ECMO onsite would prises a cast of players. First and foremost is the
provide benefit over external transfer. Collect- patient. As described above, the patient popula-
ing data on the number of previous potential tion must be identified. Ideally ECMO should
annual ECMO patients, based on transfers to be performed in a tertiary ICU with a staff
other centers or patients who expired with an experienced in caring for critically ill patients
inability to transfer to an ECMO center, dem- suffering from respiratory or cardiac failure.
onstrates the urgency to act when presenting a Some centers choose to initiate an ECMO ser-
project proposal to senior leaders. Estimates of vice in one department and develop expertise
expected cases help administrative budgeting and experience before integrating other patient
and planning. For instance, in one pediatric populations into the program. Existing pro-
cardiac surgical study, ECMO volumes were grams within the facility, such as the Neonatal
estimated to be from 1 to 5% of the total annual Intensive Care Unit, can provide infrastructure
pediatric cardiac surgical volume.3 Determina- and expert support during program develop-
tion of minimal annual ECMO volumes needed ment.4 Contacting and visiting an experienced
to achieve or maintain best outcomes has been ECMO with similar patients would be helpful.
a source of much discussion and evaluation4 It would also be beneficial to benchmark with
with conflicting findings, and is discussed in a similar institution that has recently started an
more detail in other chapters (see Chapter 68).
Certainly existing local capacity of higher
volume centers must be considered. However,
processes and education likely play similarly
important roles along with volume. Of note,
approximately 33% of current ECMO programs
are low-volume centers that care for fewer than
6 cases annually.5
Identifying the initial program scope is
critical to success in meeting customer needs.
In general, setting expectations by starting
a program with a focused and limited scope
may prove more effective. Guerguerian et
al.1 provide excellent examples of scope set-
ting (Figure 65-2). In particular, provision of
extracorporeal cardiopulmonary resuscitation
(ECPR) should await experience with more
controlled cannulation and establishment of
in-house capabilities. Achieving success with
the “first cases” goes a long way to building
confidence and buy-in. On the other hand, ex-
periences with uncontrolled attempts to perform Figure 65-2. Examples of scope setting.
732
ECMO program to gain knowledge from their org/Resources/Guidelines) recommends that

lessons learned and things to do differently. ECLS program director and ECLS coordinator
Creating an institutional ECLS steering positions be created for patient management, su-
committee to oversee planning and implemen- pervision of staff training, and equipment main-
tation of the program enables the organization tenance. The ECLS medical director should be
to succeed by utilizing key experts to define a board certified specialist in neonatology, or
the type of ECLS program that best meets pediatric/adult critical care, cardiology, anes-
the needs of the organization.1 Representa- thesiology, cardiothoracic or general surgery,
tion on the steering committee should include or another specialist with documented ECLS
multidisciplinary members from all hospital training and experience.7 The ECLS program
departments that will be internal customers of director is responsible for overall training and
the ECLS program including pharmacy, blood education of specialists, quality improvement,
bank, laboratory, medicine, nursing, surgery, data verification and the credentialing of physi-
respiratory therapy, occupational and physicians.8 The ECLS coordinator should be a reg-
cal therapy, and hospital leadership. Engaging istered nurse or registered respiratory therapist
senior administration from the beginning and with significant experience in critical care or a
sharing patient stories is critical for both philo- certified clinical perfusionist with ECLS experi-
sophical and financial buy-in.6 The committee ence.7 The ECLS coordinator is responsible for
should meet regularly and conduct debriefings staff supervision, training, equipment mainte-
after small changes to intensive learning and im- nance, and data collection.8
provement. Engaging not only fervent ECMO The ECMO specialists and primer provide
supporters but also institutional skeptics ad- care for the patient while on support. The spe-
dresses concerns head on and in advance, rather cialist manages the ECMO circuit and may pro-
than having a program derailed by those with vide for the clinical needs of the patient as well,
disagreement around ECMO benefit. Scenario depending on the staffing model. The ECMO
planning by the steering committee during the primer prepares the ECMO circuit for patient
initial phase of program development helps the use. The primer may be an ECMO specialist,
new ECMO team identify potential strengths, physician, or a perfusionist.8 According to the
weaknesses, and hospital core competencies “ELSO Guideline for Training and Education”
that will benefit or expanded once the ECMO (www.elso.org/Resources/Guidelines), the
program is operationalized.2 This may make the ECMO specialist should have a strong critical
rather large initial expenditures of the ECMO care background with at least one year or ex-
program more palatable to senior leaders as they perience in neonatal, pediatric, or adult critical
can visualize the positive impact of the program care. ECMO specialists come from varied back-
even on patients who do not receive ECLS. grounds including registered nurses, respiratory
therapists, certified perfusionists, physicians,
Identify the Employees and Equipment or specially trained biomedical engineers.9
Needed Registered nurses represent the preponderance
of ECMO specialists, followed by respiratory
A dedicated ECMO team needs to be cre- therapists and perfusionists.10 A specific job
ated to support staff education and training and description should focus on ECMO specific
as well as patient care. Team members include responsibilities and tasks. Spending time on
ECLS medical director, coordinator, special- job design during the planning phase can aid
ists, medical team, and primers. The “ELSO retention and satisfaction of team members.11
Guidelines for ECMO Centers” (www.elso. Specialists serve as the first line of defense for
733
Chapter 65
maintaining safety for patients since more than physically at the patient’s bedside. Guerguerian
73% of ECMO mechanical emergencies are as- et al.1 provide excellent examples of scope
sociated with human error.12 Selecting the right setting at the bedside vs. “rounding” on the
individual for the job then optimizing educa- ECMO machine every couple of hours. Utiliz-
tion and training by using ELSO guidelines ing available hospital perfusion services to help
improves performance and safety. choose equipment serves a new program well.
In addition to specialists and primers, a A standardized approach to equipment selection
successful ECMO program requires at least a will reduce education and training needs, im-
core group of ECMO-trained physicians and proving quality and safety. Details on program
surgeons. Approaches vary by institution, with equipment needs are provided elsewhere in this
some training all ICU physicians to provide book (see Chapter 5). Policies and procedures
ECMO care, and others utilizing a smaller core related to equipment maintenance and cleaning
group. Similarly, for cannulation, center ap- must be formalized with records maintained by
proach varies with some institutions utilizing the institution’s biomedical engineering depart-
only certain surgeons to perform cannulation. ment. The institutional purchasing department
Certification for ECMO delivery has become must become involved from program inception
a topic of increasing discussion. In general, to help with standardizing disposable supplies
ECMO delivery is considered as part of many and reducing costs. Research indicates that com-
physician training programs, and as a core or panies that excel at supply chain management
special competency for physician credentialing exceed in other financial measures of success.2
rather than being provided as a separate certi-
fication. A small number of ECMO fellowship Develop the Key Processes
(one year) programs training a small number
of fellows do exist, but such training should ECMO can be a labor intensive service
not be expected as a standard requirement. and when care requirements mount, varia-
Further efforts to provide external evidence tion between practitioners can impact quality.
of ECMO experience have both pros and cons, Standardization failures can be associated with
and it is likely that focus will be on knowledge inadequate ECMO staff training and educa-
assessment examinations as any first step in tion.13 Utilizing evidence-based guidelines and
the development. Physician credentialing for protocols to standardize care may improve
ECMO delivery is a standard requirement at patient outcomes. 14 Resources available on
most institutions, and approaches for docu- the ELSO website can help a new program to
menting competency vary. Most institutions develop center-specific patient guidelines and
utilize criteria of previous ECMO experience, ECMO protocols. The guidelines available at
participation in an institutional ECMO training www.elso.org/Resources/Guidelines cover ini-
course, and prescribed proctoring of cannula- tial ECMO team setup and training, continuing
tion and/or daily ECMO management to allow education and training, and patient management
for permanent institutional privileging. guidelines (see Chapter 67). Provider consensus
When choosing equipment for any new of care becomes even more important as the new
program, choices should match patient needs ECMO program increases in complexity by add-
with staff experience and planned duties. The ing new populations or services. The complex
proposed staffing model for the new center processes of ECMO care require a high level of
may limit equipment selection as some ECMO standardization to elevate the quality and safety
systems are better utilized with staff continu- level of individual provider performance and
ously monitoring the ECMO machine while permit review of patient outcomes.2
734
Setting up a broad, multidisciplinary train- Mistake-Proof the Processes

ing program may prove challenging for a new
ECMO center. Even in the busiest of programs, In 1999, the Institute of Medicine (IOM)
volumes are still relatively small, making it published the landmark report on medical er-
difficult for specialists to attain and maintain rors and patient safety. The report highlighted
proficiency in the performance of ECMO pa- the costly effects medical errors have on patient
tient management and skill techniques.15 Careful survival, with 44,000–98,000 lives lost in the
attention to the diverse educational backgrounds United States every year due to these errors.18
and needs of the learner when designing initial Humans make mistakes, and approximately
ECMO training improves success.16 Standard- 70% of medical errors are placed at the feet of
izing education by using the Specialist Training their caregivers.19 Quality improvement tech-
Manual published by ELSO in conjunction niques can help a new ECLS program transform
with the training guidelines for new ECMO their processes by using proven techniques to
centers, helps to provide the foundation for design, test, and implement changes to improve
programs to succeed. The manual contains a human responses and decrease patient errors.20
comprehensive chapter on specialist education The concept of mistake-proofing was devel-
and training. Benchmarking with other centers, oped by Shigeo Shingo, the originator of the
while developing your initial training and edu- Toyota production system.11 Mistake-proofing,
cation program, can be worthwhile and save or Poke-Yoke, is designed to be a simple and
valuable time. Some established centers allow inexpensive inspection process to eliminate
practitioners from other institutions to attend errors while a process is being worked or devel-
their ECMO training in-house. A core group of oped. Procedure simplification during program
ECMO team members who attend training at design reduces opportunities for medical error
either an ELSO or non-ELSO sponsored course and optimizes the effectiveness of newly created
should prove advantageous. Using a train-the- policies and procedures. Work standardization,
trainer approach, these team members can return visual aids, and checklists are excellent Poke-
to their institutions and create center-specific Yokes for beginner errors.21 Checklists can
education and training program. Team training be designed around pump set-up, equipment
opportunities can be found on ELSO’s website safety, and procedures, such as cannulation and
at http://www.elso.org/Meetings. decannulation. 22 Many programs also mistake-
Every ECMO center needs a center-specific proof by the use of color coding for drainage
policy and procedure manual. This manual in- and reinfusion tubing, diagrams of line setups,
cludes everything from who meets criteria for and availability of procedure videos to provide
ECMO to directions for changing an oxygenator. additional visual cues for bedside staff. Creat-
The development of the policy and procedure ing computer order sets for common ECMO
manual is critical for the training and education procedures represents another Poke-Yoke that
of the new ECMO team. Standardized policies not only prevents mistakes but also promotes
and procedures effectively prevent human error safety through standardization. 23
when caring for complex patients. New ECMO
team members need to be fluent in center- Develop Measures, Improvement Goals and
specific policies and practice ECMO procedures Controls
in simulations prior to the first ECMO patient.
This helps prevent human error in high stress Quality improvement techniques hone
complex emergency response situations.17 processes by using measurement, evaluation,
and knowledge to study the process, create in-
735
Chapter 65
terventions, and evaluate results.24 The mindset goal of the ELSO award program is to rec-
of quality rests on prevention of errors while ognize and honor ECLS programs that reach
striving for continual improvement. Progress the highest level of performance, innovation,
results from disciplined and structured applica- satisfaction, and quality. A new entry-level ap-
tion of quality improvement methods.25 Many plication process for new ECLS programs called
quality improvement methodologies are easy to Pathway to Excellence in Life Support, reviews
learn, intuitive, and effective. A great resource initial program processes, such as equipment,
for learning improvement methods is www.ihi. personnel, and training. The ELSO guidelines
org/resources/Pages/HowtoImprove. When represent an excellent opportunity for a new
designing quality measures for a new ECMO program to ensure that they meet all the founda-
program, evaluate quality measures that are tion criteria for the Award for Excellence in Life
already being collected for the chosen patient Support during program development. Achiev-
population. Many outcomes such as ventilator ing the Path to Excellence recognition allows
associated pneumonia, are collected on every the ECLS program to progress with patient care
patient and serve as a great quality measure for and the development of a robust quality review
a new program. When designing ECLS specific program that should meet criteria to apply for
measures, decide which components of the the ELSO Award for Excellence in Life Support
ECMO service should be controlled to deliver designation.26
the highest quality possible. Some ideas include Tracking conformity with ECLS work re-
time from decision to cannulation, number of quirements and establishing corrective action
times a circuit is accessed, or number of blood helps preserve stability and standardization
products. of the measured processes. As each deviation
A new center should benchmark with other from the norm is identified, it should be studied
ECMO centers and incorporate best practices so causation can be determined and control
into guidelines and policies during program de- regained. Variation in processes can be detri-
velopment. Joining ELSO and contributing data mental to quality outcomes and financial perfor-
to the Registry provides the opportunity for new mance. Simple audits measure compliance with
ECMO programs to benchmark their outcomes guidelines or procedures. These audits may be
and complications with other more experienced imbedded in the electronic medical record for
centers. The Registry data are compiled semi- ease of collection and be reviewed daily, weekly,
annually with reports sent to individual centers or monthly depending on the measure and the
summarizing center-specific and international volume of ECLS at the center. Early measure-
data. With data from over 73,000 patients col- ments minimize costs and error. Improvement
lected during its four decades, the ELSO Reg- work can focus on improving compliance with
istry provides new centers with the opportunity established protocols and guidelines, then upon
to compare their performance and identify op- reducing variation. The percent of variation
portunities for improvement. Attending ELSO from protocols can be measured over time and
conferences provides additional opportunities displayed on a run chart so key staff can develop
to learn from experts in the field and to network improvements.
with other more experienced centers.
The ELSO Excellence in Life Support Continuously Improving and Sustaining a
Award recognizes ECLS programs worldwide Program
that distinguish themselves by having processes,
procedures, and systems in place that promote While developing and implementing an
excellence and exceptional ECMO care. The ECMO program requires much time and en-
736
ergy, sustaining its success and enthusiasm

may prove even more formidable. Creating
the processes to be self-sustaining is necessary.
Ongoing oversight is essential, particularly
given the often sporadic nature of ECMO cases,
especially in the beginning days of a program.
The initial steering committee should be tran-
sitioned into an ongoing ECMO leadership
council for medical directors and coordinators
to meet routinely to discuss operational issues.
Difficult cases can sap the resolve and spirit of a
team. Creation of standardized rapid debriefing
processes and routine case (morbidity and mor-
tality) conferences to discuss care respectfully
in a peer-review protected fashion is essential. 27
Training programs should be built into the rou-
tine yearly calendars for staff and incoming spe-
cialty resident/fellow trainees who arrive each
year. Again, ELSO center membership helps
sustain the program by permitting benchmark-
ing against global trends and similarly sized
programs. Attendance at ELSO conferences
provides a source for reviewing state of the art
in care, sharing experience, and networking for
care and research innovations.
As a program advances, external validation
takes on increasing importance. The ELSO
Award of Excellence (AOE) program allows
a new center to take the journey to optimiza-
tion, growth, and objective measures of center
quality and effectiveness, beginning with Path
to Excellence recognition (see elso.org). The
AOE program application effectively serves
as a checklist to outline the development of
the overall program and its metrics, guiding
the center’s steps towards applying for AOE
designation in the future.
This chapter has attempted to define the
path of ECMO program building and a basic
roadmap of the journey. In the end, in the words
of Aristotle, “We are what we repeatedly do.
Excellence, then, is not an act, but a habit.”
737
Chapter 65
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Retrieved February 2016, from http://www. 16. Glavin R. Developing your teaching role in
elso.org/Resources/Guidelines.aspx a simulation centre. In: Riley R, ed. Manual
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administrative and training issues, and sus- ford University Press; 2008:115-123
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739
66
Centralization and Regionalization of ECLS Resources
James M. Blum, MD, John Beca, MD, Roy Ochiai, MD
Background studies suggest that an organized trauma system

improves mortality.1-3
The use of centralized resources for special- Similar gains have been seen in the treat-
ized care has been a common tenant of health- ment of stroke using regionalization and cen-
care around the world. Multiple areas of care tralization techniques. Initial certification for
have demonstrated improvement in outcomes stroke centers enabled the quick and expedient
and reduction in costs through the effective tri- evaluation of patients for the possible adminis-
age of patients from remote locations to areas tration of tissue plasminogen activator (tPA).4
of advanced care. While this has always been This involved the ability to obtain a head CT and
the case for advanced, elective specialty care, neurology consult within a three-hour window
the effect of such regionalized and triaged care after the onset of stroke symptoms. With evolu-
has been highlighted in the acute care realms tion in interventional technologies available for
of trauma and stroke.1-5 the treatment of stroke, specialized capabilities
There are 3 levels of trauma centers in of stroke centers now include procedures such
the United States as defined by the American as intraarterial thrombolytic agent and mechani-
College of Surgeons. The highest level cen- cal thrombectomy with time windows extended
ters (level I) provide comprehensive services to 6 hours.5
including standby anesthesiology, emergency
physicians, radiology, subspecialty surgical Relationship of Centralization to ECMO
services, in addition to advanced diagnostics.
Lower level centers provide a subset of services, As both stroke and trauma represent time
including some centers that exclusively provide sensitive, live threatening conditions that have
initial evaluation, stabilization, and transfer had improvement in their outcomes through
services. significant regionalization and centralization, it
Other credentialing bodies, including some seems reasonable that extracorporeal membrane
states, provide trauma center certifications oxygenation (ECMO) support would benefit
based upon different criteria. Meanwhile, some from a similar approach. Much like trauma and
states have no organized trauma system. This stroke care, ECMO requires comprehensive,
has created the ability to study centers with high multidisciplinary teams of providers that can
volume and established systems of care com- provide a continuum of advanced interventions
pared to centers that do not. Data from multiple and procedures.
741
Chapter 66
A center providing ECMO needs compre- center when they are being considered for
hensive services including advanced ventilator ECMO support (see Chapter 68). This allows
support, renal replacement therapies (RRT), 24- for economies of scale, reduction in costs, and
hour critical care physician services, and con- maintenance of proficiency with providers car-
sultative support from a variety of specialties. ing for ECMO patients.
Patients receiving ongoing VA support would The greatest reduction in costs comes from
likely benefit from comprehensive cardiology the individuals providing ECMO support. At
and cardiothoracic services including the abil- smaller centers that provide ECMO, a perfu-
ity to implant long-term mechanical circulatory sionist frequently monitors the circuit. In low
devices (see Chapter 64). volume centers, this introduces the cost of 24-
Additionally, just as with many other as- hour perfusionist coverage and the potential clo-
pects of medicine, ECLS programs with higher sure of operating rooms (OR). This represents
volumes tend to have higher rates of survival two remarkably expensive continuums of care,
than low volume programs.6 Recent research using perfusionists to monitor the patient and
suggests that programs with at least 35 runs/ the opportunity cost of cancelling OR cases.
year had improved survival to discharge. Such High volume centers often train other
centers were also more likely to initiate therapy dedicated practitioners, nurses, or respiratory
sooner on patients that did not have as severe therapists to provide ECMO support, resulting
illness. in lower costs per patient and avoiding resource
The Efficacy and Economic Assessment impact on the cardiothoracic surgery program.
of Conventional Ventilatory Support vs. Extra- Additionally, when these providers are not em-
corporeal Membrane Oxygenation for Severe ployed as ECMO specialists, they are able to
Adult Respiratory failure (CESAR) trial may provide additional services in the hospital from
be viewed as a randomized controlled trial of their primary background training.
keeping patients at local centers for conven- High volume centers also are likely to
tional therapy vs. transporting patients to a invest, develop and refine protocols, undergo
dedicated ECMO centers for severe ARDS.7 frequent training, and institute quality programs
One-hundred eighty patients were enrolled, 90 for process improvements and to examine out-
in each group. The overall outcome of CESAR comes. Lower volume centers may not have
demonstrated improved survival at 6 months the resources to make this investment or have
(63% vs. 47%) for patients that were allocated enough data to detect trends in the care provided.
to transfer to ECMO centers with improved Additional benefits from having patients
functional outcomes. at a common location include increased famil-
iarity with the technology and patient popula-
The ECMO Center tions from primary physicians and consultants.
An understanding of how ECMO affects
Due to the resources required to support the pharmacology of specific medications
patients on ECMO, it is not cost effective and (see Chapter 71) and procedural care is a ben-
likely unsafe for the vast majority of centers to efit from having patients commonly in a single
be providing ongoing therapy on an infrequent center. Surgeons become comfortable perform-
basis. A method of securing adequate volume ing procedures on support and are more will-
to maintain competency in the technology ing to consider bridging patients to long-term
along with the necessary ancillary services is mechanical circulatory support in this situation.
to establish a tertiary or quaternary hospital Additionally, centers that perform lung trans-
as an ECMO center and refer patients to the plants are more likely to consider transplanting
742
patients that are on ECMO.8 This is less likely therapy. Patients with PaO2/FiO2 ratios <60
to occur in centers with low volumes. and high levels of PEEP or advanced ventilator
modes are frequently challenging to transport
Outlying Centers and Critical Care Trans- and have a high risk of intra-transport arrest.
port For patients too unstable for transport, a
variety of advanced modalities that can assist in
While it is unreasonable to expect every the transfer of patients to an ECMO center when
center to provide ECMO on an ongoing basis, conventional critical care support modalities fail
it is reasonable for smaller centers to transfer to provide support. For patients with cardiac
patients to an ECMO center for ongoing care failure, a percutaneous ventricular assist device
when provision of care is straining local knowl- (VAD) can be placed by an interventional car-
edge and resources. If patients are identified diologist9 to allow transfer to a location where
early in the course of their disease, they can potential right heart failure can be treated. While
frequently be transferred using a variety of com- right heart VADs are in development their cost
monly available critical care transport services. and potential complexity of placement makes
However, early identification, timing, and actual their use in place of ECMO uncertain.
transport of individual patients while relatively In patients with respiratory failure on high
stable assures best care. In the CESAR trial 3 ventilator support, iNO may assist transport to
patients died awaiting transport and 2 died in- ECMO center potentially providing improved
tratransport.7 Such expeditious transport is more oxygenation.10,11and mean (SD The use of iNO
challenging when patients deteriorate rapidly has been documented and resulted in safe
The determination of the suitability for transport of 102 patients, many with significant
transport requires consideration of a variety of improvement of arterial oxygenation.10 Details
factors. The transport service, intrinsic capabili- of this study are documented in Tables 66-1
ties of the transport team, and time from depar- and 66-2.
ture to arrival must all be considered. Some
transport services provide critical care trained ECMO Transport
nurses and physicians while others send critical
care certified emergency medical technicians. In patients that are unable to be transported,
Patients with significant cardiac failure can even with advanced forms of respiratory or
be transferred on vasopressor and inotropic cardiac support, cannulation can occur at the
infusions. Placement of an intraaortic balloon referring hospitals and subsequent transfer to
pump may also provide an extra level of sup- an ECMO center. This practice has been docu-
port to enable safe transport to an ECMO center.
Typically, patients that are considered unstable
with mean arterial pressures of <55 mmHg and Table 66-1. Characteristics of patients trialed
with travel iNO (adapted from Teman et al.).
with these vasoactive or balloon pump support
are at high risk of intra-transport arrest. Characteristic Mean(SD or %)
For patients with respiratory failure, it is Age 45.3 (15.7)
best to transfer patients when identified as po- Male 84 (60)
tentially requiring ECMO. Patients with PaO2/ BMI 35.9 (11.7)
FiO2 ratios <100 on more than 10 cm H2O of White 93 (80)
ARDS 110 (79)
PEEP with declining status early in the course of
CHF 22 (16)
mechanical ventilation (<7 days) are frequently Other 7 (5)
considered to be good candidates for ECMO
743
Chapter 66
mented as possible in several manuscripts even ECMO transport is complex, resource in-
in new centers (see Chapter 55).12-15 tensive, and fraught with potential catastrophe.
Teams that provide transport frequently In three manuscripts, mechanical issues with
consist of a small team including an experi- ancillary equipment were common and lead to
enced ECMO specialist or perfusionist, critical life threatening conditions, despite distinctly
care transport nurse or EMT, and a physician. fewer complications with the ECMO circuit
Some teams transport with two of each type of itself.10,13,14 The most common issues occurred
provider.16 Each provider contributes an impor- with oxygen delivery, mechanical ventilation,
tant component of the care team. The ECMO and electrical complications. Movement into
specialist or perfusionist maintains the ECMO and out of unfamiliar locations also introduces
circuit and ensures appropriate anticoagula- the risk of inadvertent decannulation.
tion. The critical care nurse or EMT provides The greatest challenge of ECMO transport
patient management during transport. Opera- is remote cannulation. Engaging a full team for
tion of equipment in an ambulance or aircraft cannulation and subsequent transport requires
can have particular specific requirements and remarkable manpower with technical skill and
needs the insight of an individual experienced the movement of profound amounts of equip-
in the transport vehicle especially in the aircraft ment. When entering a center that does not
that has power and oxygen delivery that vary routinely provide ECMO, devices for vascular
depending on the phase of transport. There are access, cannulae, an ECMO circuit and pump,
also specific governmental regulations regard- and possibly even other supplies including
ing the operation of devices in an aircraft that prep solutions, gowns, gloves, drapes, instru-
an experienced flight nurse or EMT can provide ments, and ultrasound access devices need to
direction with. be brought by the transport team. There may
A physician during the transport may per- also be concerns surrounding emergency cre-
form cannulation or assist a physician at an dentialing at such centers and the delay in the
outside hospital on the technique. The physi- initiation of support between assembling a team
cian can also direct the care during transport, and transport to the remote location.
administering bolus medications (if prohibited One method to address this concern is with
by nursing), and managing bleeding from can- the establishment of centers that can comfort-
nulae sites. Physician attendance for transport ably initiate ECMO support that then transport
is also remarkably useful in the event of a long the patient to the ECMO center. Select surgeons,
duration ground transport or airborne transport interventional cardiologist, and intensivists
where communication with a physician will not have been trained in the techniques required to
be possible. This is particularly true if other initiate ECMO and prepare patients for trans-
members of the transport team are less familiar port. In essence, this creates a “spoke and hub”
with ECMO management. system that mirrors the trauma system in many
Table 66-2. Response to travel iNO therapy (adapted from Teman et al.).
Characteristic Number (%) or Average (SD)
Positive response to iNO 79(69)
Lack of response to iNO 35(31)
PaO2 Prior to iNO 60.7 (20.2) mmHg
PaO2 After iNO initiation 72.3 (40.6) mmHg
P:F Prior to iNO 62.4 (26.1)
P:F After iNO initiation 73.1 (42.6)
744
states, minimizing the resources required at lo-

cal institutions and extracting value in care at
high volume centers.
Such systems are complex and require
collaboration between hospitals and physician
groups. As the acute care environment and
healthcare in general are becoming more system
oriented, previously insurmountable barriers to
such arrangements may be less of a challenge.
However, it is best if centers are able to find
collaborative partners prior to establishing the
required resources to begin initiating ECMO
therapy. Establishing partnerships and preex-
isting transfer agreements ensure the ability to
transport patients and limits the likelihood a
center will initiate therapy and subsequently be
unable to transfer a patient.
Summary
ECMO is an expensive, complex, and labor

intensive service that requires collaboration
between multiple specialties and services. It
is not possible for all centers to provide com-
plete ECMO services. Transport of patients to
dedicated ECMO centers is likely to improve
outcomes and reduce overall costs, improving
value in care. This is most easily addressed in
a “spoke and hub” fashion within organized
health systems that can provide clear criteria for
ECMO therapy across a system. As healthcare
continues to change and hospitals continue
to organize into health systems, this process
should be easier. Prearranged transfer agree-
ments can facilitate seamless care of patients
from one center to another with minimal delay.
745
Chapter 66
References 9. Werdan K, Gielen S, Ebelt H, Hochman JS.

Mechanical circulatory support in cardio-
1. Nathens AB, Jurkovich GJ, Cummings genic shock. Eur Heart J. 2014;35(3):156–
P, Rivara FP, Maier RV. The effect of 167.
organized systems of trauma care on 10. Teman NR, Thomas J, Bryner BS, et al.
motor vehicle crash mortality. JAMA. Inhaled nitric oxide to improve oxygenation
2000;283(15):1990–1994. for safe critical care transport of adults
2. Haas B, Jurkovich GJ, Wang J, Rivara with severe hypoxemia. Am J Crit Care .
FP, Mackenzie EJ, Nathens AB. Survival 2015;24(2):110–117.
advantage in trauma centers: expeditious 11. Buskop C, Bredmose PP, Sandberg M. A
intervention or experience? J Am Coll Surg. 10-year retrospective study of interhospi-
2009;208(1):28–36. tal patient transport using inhaled nitric
3. MacKenzie EJ, Rivara FP, Jurkovich GJ, oxide in Norway. Acta Anaesthesiol Scand.
et al. A national evaluation of the effect 2015;59(5):648–653.
of trauma-center care on mortality. NEJM. 12. Biscotti M, Agerstrand C, Abrams D, et al.
2006;354(4):366–378. One Hundred Transports on Extracorporeal
4. Tissue plasminogen activator for acute isch- Support to an Extracorporeal Membrane
emic stroke. The National Institute of Neu- Oxygenation Center. Ann Thorac Surg.
rological Disorders and Stroke rt-PA Stroke 2015;100(1):34–39; discussion 39–40.
Study Group. NEJM. 1995;333(24):1581– 13. Broman LM, Holzgraefe B, Palmér K,
1587. Frenckner B. The Stockholm experience:
5. Berkhemer OA, Fransen PSS, Beumer interhospital transports on extracorpo-
D, et al. A Randomized Trial of Intraarte- real membrane oxygenation. Crit Care.
rial Treatment for Acute Ischemic Stroke. 2015;19:278.
NEJM. 2014;372(1): 14. Moll V, Teo EY, Grenda DS, et al. Rapid
6. Barbaro RP, Odetola FO, Kidwell KM, et al. Development and Implementation of an
Association of hospital-level volume of ex- ECMO program. ASAIO J. 2016;62(3):354-
tracorporeal membrane oxygenation cases 358.
and mortality. Analysis of the extracorpo- 15. Rambaud J, Léger PL, Larroquet M, et al.
real life support organization registry. Am Transportation of children on extracorpo-
J Respir Crit Care Med. 2015;191(8):894– real membrane oxygenation: one-year ex-
901. perience of the first neonatal and paediatric
7. Peek GJ, Mugford M, Tiruvoipati R, et mobile ECMO team in the north of France.
al. Efficacy and economic assessment of Intensive Care Med. 2015;42(5):940-941.
conventional ventilatory support versus 16. Bryner B, Cooley E, Copenhaver W, et
extracorporeal membrane oxygenation for al. Two decades’ experience with in-
severe adult respiratory failure (CESAR): terfacility transport on extracorporeal
a multicentre randomised controlled trial. membrane oxygenation. Ann Thorac Surg.
Lancet. 2009;374(9698):1351–1363. 2014;98(4):1363–1370.
8. Hayes D, Tobias JD, Tumin D. Center Vol-
ume and Extracorporeal Membrane Oxy-
genation Support at Lung Transplantation in
the Lung Allocation Score Era. Am J Respir
Crit Care Med. 2016;194(3):317-326.
746
67
Education and Training
Mark T. Ogino, MD, Curt D. Froehlich, MD, Elizabeth A. Moore, MBA, RN, BSN
Introduction The “ELSO Award of Excellence in Life

Support” has been established to honor centers
Extracorporeal membrane oxygenation that have met or surpassed the ELSO guideline
(ECMO) procedures are technically complex, recommendations by having robust processes,
high risk, resource dependent, and unpredict- procedures, and systems in place that promote
able in terms of volume and timing. Safe, eco- excellence and exceptional care for ECMO
nomical, and effective use of ECMO requires patients.3 ELSO recognizes those centers that
unique institutional resources and effective have met or exceeded ELSO guidelines by
strategies to maintain optimal quality in the developing quality measures, creating mecha-
delivery of care. A pillar of achieving qual- nisms that deliver safe care, and supporting an
ity care is the presence of an established and administrative structure that promotes excel-
institutionally supported ECMO education and lence in training, education, collaboration, and
training program. communication that contributes to an overall
The Extracorporeal Life Support Organiza- healing environment for families, patients, and
tion (ELSO) has developed “ELSO Guidelines staff. New ECMO centers can apply for the
for ECMO Centers” which outline institutional “Path to Excellence in Life Support,” an entry
requirements for effective ECMO use.1 The level recognition, as a roadmap for developing
“ELSO Guidelines for Training and Continu- a new program while using the established
ing Education of ECMO Specialists” specifies standards of the ELSO Guidelines. The subject
the educational requirements of clinicians matter discussed in this chapter should encour-
responsible for monitoring and maintaining age all ECMO centers to use the “ELSO Award
extracorporeal life support (ECLS) to the pa- of Excellence in Life Support” process as the
tient.2 ELSO recognizes that differences in re- framework in developing an education and
gional and institutional regulations impact each training program of distinction. The engage-
ECMO center, and these variations may result in ment of all clinical disciplines to achieve the
deviation from these guidelines. Nevertheless, designation as an “ELSO Center of Excellence”
these guidelines establish standards for assess- or to begin their journey to excellence with
ing current and future ECMO centers. ELSO the “Path to Excellence in Life Support” will
guidelines are reviewed and revised every three build the foundation for clinical excellence in
years, and are available on the ELSO website extracorporeal life support.
(http://www.elso.org).
747
Chapter 67
Educational Process learning process is known as “Miller’s Triangle”

(Figure 67-1).8 The base of the triangle begins
ECMO education is a challenge due to the with the learner who “knows” the knowledge,
different skill sets that a member of the patient and advances to the second stage where the
care team must achieve before they can be learner “knows how” to apply the knowledge.
considered qualified to deliver ECMO care. The third stage occurs when the learner “shows
The composition of an institution’s ECMO how” to use the knowledge often in a testing
patient care team continues to evolve as dif- environment such as an ECMO training lab.
ferent models of care are developed incorpo- Stages two and three combined describe the
rating advances in technology.4 The ECMO degree of competency achievable in comprehen-
team includes clinicians with responsibilities sive ECMO training courses. The apex of the
to the patient, and/or the ECMO circuit. The triangle is when the learner “does.” This is the
responsibilities can be divided or provided by action phase of the clinical assessment process
a single individual with the appropriate train- in which the learner applies the knowledge in
ing. For the purposes of this chapter, an ECMO the clinical environment. This phase cannot
physician is defined as a critical care physician be tested in an artificial environment since
or surgeon who has had specific ECMO train- unpredictable elements of an actual clinical en-
ing outlined by their institutional credentialing vironment cannot be replicated. The “does” is
guidelines. An ECMO specialist is defined as the decisive test of knowledge mastery. ELSO
the technical specialist trained to manage the recommends that each center develop training
ECMO system and clinical needs of the patient programs that accomplish the first three steps
on ECMO under the direction and supervision of Miller’s Triangle framework, to allow the
of a licensed ECMO trained physician.2 We successful implementation of the “does” phase
have used the term “ECMO team member” to for each learner.
identify all medical professionals who partici-
pates in ECMO management.
ECMO centers create training programs
Expert……
and curriculum from guidelines, policies, pro-

cedures, and a training manual. Since adult DOES
educational theory supports the use of an active (action)
learning environment, the majority of ECMO

centers supplement their traditional didactic SHOWS HOW
courses with practical training to optimize skill (performance)
acquisitions and maintenance as well as techni-
cal and behavioral skills (team interaction, com-
KNOW HOW
munication, leadership skills) that are essential
(competence)
to excellent care.5,6 Effective learning can be
further enhanced by applying new information
KNOWS
to a learner’s professional background and
Novice
previous clinical experience,7 (knowledge)
The framework for clinical education and

assessment was eloquently described by Miller. Figure 67-1. Framework for Clinical As-
The essay figuratively describes the ascent sessment. Miller’s Triangle (Adapted from:
Miller GE. The Assessment of Clinical Skills,
to attaining knowledge using a four tiered Competence, Performance. Acad Med 1990;
triangle as the assessment model; hence the 65:S63-7).
748
The most common method of study utilized “Staff are competent to perform their responsi-
by all learners is to read text, then to reread text bilities.”12 The roles of the ECMO coordinator/
to embed the facts into memory. Conventional manager and medical director in competency
wisdom suggests that repetitive review leads assessment are to determine physician and other
to a feeling of mastery when the facts or con- ECMO team member qualifications and job re-
cepts can be retrieved from memory.5 Brown sponsibilities, determine competencies required
et al. states “mastery requires both the posses- for each job, identify staff development needs,
sion of ready knowledge and the conceptual implement a system competency verification,
understanding of how to use it.”9 Any ECMO and develop an individual remediation plan
education program must apply learning strate- for employees who do not meet the defined
gies that allow the assimilation of knowledge standards.
and its transformation to understanding, and With the diversity in ECMO program orga-
eventually to a skill set. nization, it is recommended each center develop
Defining training objectives designed its own training program based on their patient
for the specific needs of each center must be population, equipment, and assigned responsi-
clearly distinguished and incorporated into an bilities of team members. Since the educational
ECMO center’s training outline. This ensures backgrounds of ECMO team members differ,
the successful conveyance of essential concepts each center must tailor its training program to
during the didactic course. In developing a their staff. For example, respiratory care thera-
course, principles of adult learning to consider pists usually require more time to learn about
include:10 transfusion procedures, IV pumps, and medica-
• Involve the learner in the planning and tions; whereas, nurses may need more education
evaluation of their instruction. in gas physics and circuit component physiol-
• Experience, both positive and negative, ogy. Perfusionists may need to learn more
provides the basis for learning activities. about the effects of long-term extracorporeal
• Generate motivation by having the learner life support and patient care assessment. The
participate in activities with immediate multidisciplinary composition of the ECMO
relevance to their job or personal life. team utilizes the strengths of each discipline to
• Recognize and incorporate previous experi- address the multisystem challenges in the care
ences of the learner. of these complex patients.
The technological achievements in ECMO
Establishing ECMO Competency systems have focused on the safety aspects of
bedside ECMO care. The new ECMO pumps
The ECMO medical director and coordi- are now integrated, simplified, self-monitoring,
nator/manager are responsible for the training and self-regulating. These improvements have
of the team, assuring ongoing competency, led to a new bedside model of care. The Mul-
and guaranteeing that established guidelines tidisciplinary Care Model (MCM), also known
and standards are defined in their institutional as, the “Single Care Giver Model,” uses the
policies and procedures. The Joint Commission bedside nurse to care for the patient and also
(TJC) defines competency as the knowledge, have a shared responsibility in caring and moni-
skills, ability, and behaviors that a person pos- toring the ECMO equipment with the specialist
sesses in order to perform tasks correctly and or ECMO trained multidisciplinary team. A
skillfully.11 TJC standard HR 01.02.01 states, secondary support structure to address ECMO
“The hospital defines staff qualifications” and complications is in place for complex manage-
HR 01.06.01 requires the hospital to ensure that ment issues and emergent interventions.13
749
Chapter 67
Bedside nursing staff (not responsible for ECMO Training Program

ECMO equipment) require additional training
in the care of these patients. This additional ELSO has developed “ELSO Guidelines
training should include a basic understanding for Training and Continuing Education of
of ECMO physiology and equipment. The ECMO Specialists” and “Guidelines for ECMO
ECMO coordinator/manager and unit-based Centers” which can serve as a reference for cur-
nursing educators can work to develop and rent and future ECMO centers. Other ELSO
implement an annual competency class for care training resources include the ELSO “ECMO
of patients on ECMO. The competency class Specialist Training Manual.” ELSO also offers
basic objectives include: ECMO physiology, educational conferences to assist new centers
equipment safety, patient safety, cannula(s) care, with training.
resource management, and emergency patient These guidelines recommend that a new
management. ECMO program offer a didactic (lecture) course,
Representatives from other patient care ser- followed by water drills, and/or animal sessions.
vices involved with the ECMO program should Although high fidelity simulation is not listed
participate in the training. These services may in the guidelines, simulation provides a very
include representatives from blood bank (hospi- effective educational tool for teaching, main-
tal and regional), radiology, ultrasound, cardiac taining and assessing ECMO skills.16 Essential
catheterization lab, operating room, laboratory topics include the review of ECMO equipment
medicine, biomedical engineering, nutritional and basic procedures, emergency procedures
support, physical, occupational, and speech training, and bedside skills. Most programs
therapies. Multidisciplinary exposure to the require additional time with an instructor or a
ECMO patient improves communication among bedside preceptor until the specialist-in-training
hospital services, allowing other caregivers has gained a solid understanding of ECMO
to understand and anticipate the needs of the management principles and are fully competent
ECMO patient. Good team communication is managing acute emergencies.
an essential skill to maintain, and the ECMO For experienced centers the training guide-
training process should include team-building lines are the same, except that animal labs are
activities across all disciplines. Optimal care of not required. Experienced centers include those
ECMO patients requires specialized knowledge that have experience managing ECMO patients
from the multiple disciplines to be integrated. and are training new specialists.2 Incorporating
Integration is best accomplished through fre- didactic and simulation content remains a vital
quent, respectful interaction, and competent component to ECMO training in experienced
communication. In today’s healthcare system, centers as well as bedside orientation with an
working collaboratively with others is as impor- ECMO preceptor.
tant to successful ECMO care as expert clinical
skills are to the individual practitioners. Ac- ECMO Training Course Curriculum: Intro-
cording to data from TJC, a breakdown in team ductory Course for ECMO Providers
communication is a top contributor to sentinel
events.14 Recommended Crisis Resource Man- The primary goal is to design an education
agement (CRM) proficiencies embedded in the program that provides consistent, effective mul-
training program help develop behavioral skills tidisciplinary content where all providers are
required for effective communication across exposed to a single curriculum for initial ECMO
multiple disciplines.15 training. This approach alleviates strict depen-
dence on an individual discipline to troubleshoot
750
complex ECMO complications. Furthermore, Physiology of the Diseases Treated with

specific institutional staffing models provide ECMO
guidance in determining the competency train-
ing necessary for each clinician participating in • Respiratory failure (eg, pneumonia, as-
the care of ECMO patients. Due to the varied piration pneumonitis, ARDS, pulmonary
educational backgrounds of ECMO specialists, embolism, etc.)
each organization must adapt their educational • Pulmonary embolism
program to meet staff needs. • Sepsis
As training of the ECMO team evolves • Postcardiotomy
from initial education to advanced education, • Heart transplantation
the additional curriculum needs to be tailored • Cardiomyopathy and myocarditis
to the specific needs of the individual learners. • Other
For example, training provided to a specialist Pre-ECMO Procedures
responsible for ECMO transport differs mark-
edly from the training needs of an ECMO man- • Notification of the ECMO Team
aging physician, which again does not resemble • Selection of catheters
training to cannulate a patient. However, these • VV or VA
individuals require the same single curriculum • Cannulation procedure (open, percutane-
for initial training and the ability to understand ous)
ECMO physiology and diagnose complications • Initiation of ECLS
related to ECMO. Thus, ECMO education and • Responsibility of team members
training must continually evolve to meet the
needs of the learner. Criteria for ECMO
• Patient selection criteria

Didactic (Classroom) Course • Pre-ECMO evaluation
• Contraindications
There are many topics to include in a di-
dactic course. A sample outline for a didactic Physiology of Venoarterial and Venovenous
course may look as follows: ECMO
Introduction to ECMO • Vessel cannulation (VA, VV, VAV)
• Physiology
• History • Advantages and disadvantages
• Current status
• Risks and benefits Blood Products and Coagulation
• Membrane gas exchange physics and
physiology • Blood products and interactions
• Oxygen content, delivery and consumption • Coagulation cascade
• Shunt physiology • Blood surface interactions and coatings
• Types of ECMO • Heparin pharmacology
• Future applications • SIRS
• Research • Laboratory anticoagulation monitoring
• ELSO Registry studies
• Amicar, Protamine, recombinant clotting
factors
• Disseminated intravascular coagulation
751
Chapter 67
ECMO Equipment and Circuit Components Circuit
• ECMO circuit design • Aseptic technique

• ECMO circuit components (cannula, com- • Pump and gas flow
pliance chamber, pump, venous return • Pressure monitoring
monitor, in-line saturation monitor, pres- • Blood product infusion techniques
sure monitor, heater, hemofilter, bubble • Circuit infusions
detector, flow meter) • Management of anticoagulation
• Oxygenator function and blood gas control • Circuit checks
• ECMO supply cart • Hemofiltration setup
• Other ECLS equipment (CVVH, plasma-
pheresis, etc.) Emergencies and Complications during
ECMO
Cannulation and Initiation of ECMO Support
Medical
• Circuit priming
• Preparing the patient • Intracranial and other hemorrhage
• Initiating ECLS support • Pneumothorax and pneumopericardium
• Cardiac arrest
Daily Patient and Circuit Management on • Arrhythmias
ECMO • Hypotension and hypovolemia
• Hypertension
Patient • Severe coagulopathy
• Bedside care of the ECMO patient (eg. • Seizures
ambulation) • Hemothorax and hemopericardium
• Fluid, electrolytes and nutrition • Uncontrolled bleeding
• Respiratory (eg. ventilator management, • Electrolyte imbalance
tracheostomy, extubation, etc) • Renal failure
• Neurologic Mechanical
• Infection control
• Sedation and pain control • Circuit disruption
• Hematology • Raceway rupture
• Cardiac • Cavitation
• Psychosocial • System or component alarm and failure
• Pharmacologic issues (pump, compliance chamber, venous return
• Lab schedule monitor, oxygenator, heater, flow sensor)
• Documentation and orders • Air embolus
• Inadvertent decannulation
• Clots
Management of Complex ECMO Cases
• Surgery on ECMO
• Postoperative bleeding
• Transport on ECMO (inter/intrahospital)
752
Weaning from ECMO patients with severe respiratory failure. Institu-

tions using ECMO for cardiac support may also
• Techniques and complications include education on the anatomy, circulation,
• Clinical indications of pulmonary and car- surgical procedures and common operations,
diac recovery cardiopulmonary bypass, postoperative man-
• Pump and gas flow weaning techniques agement, pathophysiology of cardiomyopathy
• Ventilator changes during weaning and myocarditis, and principles of transplanta-
• Trial off tion medicine.
• Decannulation from low flow Review of the pre-ECMO setting and
Decannulation management are also recommended, including
pre-ECMO orders, informed consent for ECMO
• Personnel needed and blood transfusions, pre-ECMO laboratory
• Medications required sampling tests along with blood product type
• Potential complications and cross match, neuroimaging studies, and
• Vessel ligation echocardiograms. Room setup, circuit priming,
• Vessel reconstruction ECMO initiation, and necessary documentation
• Percutaneous approach tools are also important topics to be reviewed.
• Post-ECMO complications Some of these topics may also be incorporated
into training labs discussed in the next section.
Outcome of ECMO Patients Each ECMO team member must gain a
• Short and long-term outcomes comprehensive understanding of blood gas
• Institutional followup protocol interpretation and gas exchange. This includes
• Literature review knowledge of the principles involved with oxy-
gen content, delivery, and consumption, and
Ethical and Social Issues carbon dioxide production and elimination in
normal physiologic and extracorporeal support
• Consent process conditions (see Chapter 4). All team members
• Parental and family support must demonstrate an understanding of the cor-
• Withdrawal of ECMO support relational impact ECMO pump flow and sweep
gas flow changes produce upon gas exchange.
Most centers begin their course with an
To reinforce the lung protective aspects of
“Introduction to ECMO” which includes a dis-
ECMO, ventilator and airway management
cussion of the history of ECMO (see Chapters 1
while on ECMO is an important management
and 2). An understanding of past successes and
discussion to include in the curriculum. A thor-
failures provides a better understanding of the
ough demonstration of ECMO physiology and
basis for current practice. Other introductory
oxygen physics by the ECMO team members
discussions may include: different forms of
is highly recommended at the conclusion of the
ECMO support, general indications for ECMO,
ECMO training.
the risks and benefits for specific populations,
Each center should focus the majority of
as well as recent clinical research trials that
its training on site-specific ECMO techniques;
outline the current status of ECLS therapy and
however, a discussion regarding variations
its outcomes.
in support in use at other centers may assist
Other topics recommended for ECMO team
interhospital communication and exchange of
member education include pathophysiology
ideas. Blood product administration, coagula-
of diseases and current medical therapies in
tion management, medications commonly used
753
Chapter 67
in the blood prime and during ECMO, weaning, Training lab sessions are recommended to
and decannulation procedures must also be re- allow additional discussion and demonstration
viewed. In addition, a basic understanding of of ECMO and support equipment, the manage-
intrahospital and interhospital ECMO transport ment of ECMO emergencies, and observation
requirements is recommended. of ECMO team members’ bedside care per-
All ECMO team members must obtain a formance. The recommended list of technical
thorough understanding of ECMO equipment skills for training lab sessions is as follows
and circuit design used in their institution as (institutional variations will exist based upon
well as potential mechanical complications and equipment and circuit configuration):
preventative measures. Institutional guidelines
need to define the essential equipment and Equipment: Component & Function Check
emergency skills each ECMO team member “Circuit Check”
must maintain. These skills may include, but
are not limited to: setting of alarm parameters, • Tubing
recognition of factors that cause alarm condi- • Sampling ports
tions, initiating appropriate response to the • Pump head
alarm conditions, and response to mechanical • Pump controls and alarms
emergencies. • Pressure monitoring
Patient and circuit management lecture • Servo regulation panel
topics cover a broad range of subjects which • Oxygenator
include the fundamentals of daily management • Sweep gas monitoring
of an ECMO patient, and recognition of medi- • Heat exchanger
cal emergencies that may occur during support. • Water heater
ECMO team members in training will also • Other (bridge, compliance chamber, flow
benefit from lectures in ethical and social issues. sensor, arterial filter, bubble detector, etc.)
Training Labs Basic Procedures
• Blood sampling
Technical and behavioral skills necessary • Bedside ACT checks
for effective ECMO team training can be ac- • Pigtail and stopcock changes
complished using different “hands on” training • Blood product administration
methods. These training methods offer a unique • IV infusion and medication administration
opportunity to create, test, refine, and streamline • ECLS documentation
ECMO processes without disrupting patient • ECMO order set review
care or endangering patients. Water drills have • Other (roller pump head occlusion checks)
been utilized to demonstrate functionality of
ECMO components. Animal labs allow ECMO Emergency Procedures
physiology to be demonstrated in an in vivo
model. The introduction of high fidelity simu- • Clamping off ECMO
lation into ECMO training sessions enables the • Massive blood loss from circuit
learner to experience a real time situation with • Tubing replacement
realistic sensory cues that mimic the critical care • Oxygenator failure
setting with an ECMO patient. For the purpose • Air in circuit and de-airing circuit
of this discussion, these “hands on” training • Loss of venous return
sessions will be categorized as “training labs.” • Inadvertent decannulation
754
• Pump head failure and hand cranking Animal Lab

• Power failure
• Circuit and/or component change Animal labs are performed in accordance
with institutional animal care guidelines. The
The recommended introductory course advantage of animal laboratory training is real
training lab topics include a discussion and time coagulation management and blood gas
demonstration of all equipment including an management which are difficult to simulate in
explanation of the circuit configuration and either water drills or ECMO simulation labo-
function, alarm functions, and a routine circuit ratory settings. During these sessions, partici-
assessment, “circuit check.” Basic and emer- pants can practice tasks such as blood product
gency procedures drills can also be developed administration, intravenous solution and medi-
based upon a center’s equipment selection and cation administration, and blood sampling. The
practiced in the training labs. Standard emer- physiologic impact of the pump, sweep gas
gency drills include managing power failures, regulation and heparin infusion adjustments
emergency circuit clamping, hand cranking the can be demonstrated in an in vivo model. Many
pump (if applicable), de-airing a circuit and centers have difficulty accessing a vivarium for
managing accidental decannulation. Individual training, causing a decrease in use of animals
programs will define each team member’s role, for ECMO training. Animal labs have become
thus determining if advanced skills such as increasingly difficult to perform due to cost,
priming, replacing a circuit, oxygenator and/or availability of approved facilities, and rigor-
individual components will be practiced. The ous institutional animal care guidelines; hence,
goals of these training labs are to prepare each alternative “hands on” training methods have
ECMO team member to identify any mechani- been developed.
cal circuit problems and promptly initiate the
appropriate problem solving response. The High Fidelity Simulation
clinician responsible for correcting the problem
will depend on the defined responsibilities of a High fidelity simulation has become a
center’s ECMO team members. widely accepted educational tool for anesthe-
siology, surgery, obstetrics, neonatology and
Water Drills critical care training programs. For decades,
simulation has been used in the military, airline,
ECMO circuits can be assembled, filled and nuclear power industries to train personnel
with fluid, and run in nonclinical settings. This for skill acquisition in routine and emergency
allows for opportunities to mimic many of the situations.17 High fidelity simulation enhances
situations that occur during an actual ECMO run learning through multiple factors including re-
and is commonly referred to as a “water drill.” petitive practice, increasing level of difficulty
Water drills can assist with mastering technical with attainment of skills, addressing multiple
skills necessary for safe ECMO management, forms of learner strategies, permitting clinical
ie, changing broken segments of the ECMO cir- variation in learner responses, and providing im-
cuit. To optimize hands-on experience by each mediate feedback.18 Simulation also addresses
participant, a limited number of participants is the traditional educational method deficiencies
recommended. of technical and behavioral skill development by
immersing the trainee in realistic environments
populated with working equipment (including
a functional ECMO circuit), a patient simula-
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Chapter 67
tor capable of generating authentic physiologic debriefing is a trained facilitator or “debriefer”

cues, and living human beings who respond in a who can direct the discussion and extract maxi-
realistic manner to the events of the scenario. By mum dialog from the learners to achieve the
creating a highly realistic environment where defined learning objectives. Formal training
trainees must respond to problems with both the for simulation-based healthcare education is
circuit and the patient, a more realistic and valu- recommended for a new facilitator to acquire
able learning opportunity is created. Halamek the basic skill sets to develop into a capable,
et al. from the Center for Advanced Pediatric confident, conversant debriefer.29 The pairing
and Perinatal Education at Packard Children’s of a novice debriefer with an expert role model
Hospital at Stanford published two articles and exposure to a variety of simulation settings
describing the use of high fidelity simulation are required to develop the skills and comfort
in ECMO training. The first article described level of the debriefer.30 All ELSO simulation
ECMO simulation as a valid training tool, and faculty members are trained using these recom-
the second demonstrated the superiority of mendations.
ECMO simulation for transmitting technical
and behavioral skills essential for ECMO spe- ELSO ECMO Training Course
cialists.16,19 This group has subsequently made
several modifications to this system allowing Since the inception of the ELSO ECMO
an even more realistic simulation of circuit Training Courses in 2010, over 600 clinicians
performance and patient physiology.20 have participated in the program described as
High fidelity ECMO simulation places the follows:
fidelity, defined as accuracy in details, in the
ECMO circuit.21 This training lab environment ELSO ECMO Course Curriculum
offers an advantage over wet drills and animal
labs due to the added ability to adjust “the pa- Format: Four-day course, eight hours per
tient’s” physiologic parameters in context with day. 32 contact hours
ECMO management decisions. This educa-
tional tool has been introduced in many ECMO Lecture Sessions
centers as an alternative training tool for new, Subject/Topics
as well as experienced specialists and physi-
cians.22-26 ELSO has also instituted high fidelity • History of ECMO
ECMO simulation in its educational programs • Components
utilizing a low cost, easily constructed ECMO • Physiology
simulation model developed by the Hanuola • VV and VA ECMO (includes discussion on
ECMO Program of Hawaii.27 If high fidelity indications)
simulation is available at an ECMO center, the • Cannulation and Initiation
ECMO team should collaborate with the simu- • Patient Management
lation center staff to develop and implement • Circuit Management
training and competency assessment programs. • Anticoagulation
The most important aspect of simulation- • Weaning and Decannulation
based learning is the role of debriefing in • Elective subjects (based upon learners’
enhancing the adult educational experience.28 backgrounds and needs)
As discussed earlier, active participation of • ECMO Economics
the adult learner increases the effectiveness of • Pharmacology
learning.10 An essential element of successful • Ethics and Social Issues
756
• ECMO Team the opportunity to navigate all major circuit and

• Outcomes patient complications noted in clinical practice.
• Case Studies
Maintaining Competency Standards
Simulation Sessions
Subject/Topics Verifying ECMO Competency of ECMO Team

Members
• Physiology
• Patient Management ECMO competency can be verified by ob-
• Circuit Management (including anticoagu- servation in actual clinical settings or in simu-
lation) lated settings. The three skills to consider when
• Crew/Crisis Resource Management (CRM) assessing competency include cognitive (critical
• Cannulation thinking), technical, and behavioral. Verifica-
• Emergency Procedures tion is the objective process of assuring that a
staff member can perform competencies based
Objectives on specific performance criteria used to ensure
• Cognitive Skills accurate and safe practice. Performance criteria
• application of concepts presented in must be outlined in a policy, procedure, standard,
lecture sessions guideline, or reference. Institutional certifica-
• critical thinking tion of ECMO team members is achieved when
• Technical Skills performance criteria for clinical competency are
• psychomotor activities fulfilled. The ELSO guidelines recommend that
• Behavioral Skills all ECMO specialists take an annual oral and/
• communication or written exam.
• CRM A written test can be used to assess knowl-
All sessions incorporate simulation based edge. Critical thinking skills include decision
learning theory and focus on debriefing as the making, prioritizing, troubleshooting, and re-
primary instructional method sponding to actual or potential events. Specific
The course is structured in a mindful way to ECMO problems and the knowledge of how to
allow students an even split of didactic/theory approach them can be simulated in a training
and high fidelity simulation educational time. lab session and an instructor can observe the
The duration of the course is 32 contact hours, ECMO team member’s response and critical
with the course participants divided into two thinking skills.
groups simultaneously repeating the didactic Technical skills include psychomotor ac-
and simulation material to create smaller groups tivities that are part of every job. Training labs
in an effort to maximize adult based learning provide a simulated surrounding to observe
principles. The simulation sessions incorporate the competence of a team member in perform-
key lecture topics into the educational objec- ing the technical skills necessary for the care
tives to better match the application of the of an ECMO patient in routine and emergent
simulation educational material to the learners’ situations. Simulation provides the closest as-
knowledge base, thereby reinforcing relevance sessment of “shows how” competency. True
to their job. competency, the apex of Miller’s triangle,
Learners are guided through the simulation “does,” can only be verified by observation in
lab, with the assistance of highly trained ECMO actual patient situations, under real-life, stress-
simulation instructors, where they are provided ful situations8 (Figure 67-1). Experience from
757
Chapter 67
Advanced Cardiac Life Support training has be used to verify the knowledge and skills of all
shown that retention of skills begin to decay ECMO specialists. Each program should deter-
after six months.30 ECMO team members must mine each the minimum number of pump hours
practice infrequently used skills on a regular for ECMO specialists or patients for physicians
basis. within an established time period to maintain in-
Behavioral skills reflect the ability to stitutional certification. If the number of hours
communicate effectively with individuals and is not met, then a policy outlining a re-training
groups. Professional communication skills program is recommended.
include written, spoken, and nonverbal skills. Most ECMO centers schedule team meet-
Coworkers can identify ECMO team members ings on a regular basis to discuss clinical and
who lack the appropriate interpersonal skills. operational issues, quality assurance review
The difficulty lies in objectively identifying findings, and any other topics pertinent to the
those skills. Some of the communication team. Team meetings also provide an opportu-
behavioral indicators include demonstrating nity to offer continuing education sessions with
courtesy, being respectful, and practicing good case reviews and multidisciplinary morbidity
listening and feedback skills. The behavioral and mortality conferences. The frequency of
skills measured by the Stanford CAPE group in these meetings is determined based on the size
their original study measuring the effectiveness of the team and the volume of ECMO patients
of high fidelity simulation in ECMO training treated. Attendance of team members at these
are as follows:16 meetings is monitored and criteria for minimal
attendance defined to ensure maintenance of
• Familiar with ECMO equipment and bed- institutional certification. Information on pa-
side environment tient follow-up could be included here allowing
• Anticipates and plans for crisis team members to become familiar with patient
• Assumes a leadership role outcomes in order to appreciate the risks and
• Communicates effectively benefits associated with ECMO. Also integrat-
• Distributes workload optimally ing a continuous quality improvement (QI)
• Allocates attention wisely process is essential to the overall delivery of
• Utilizes all available resources ECMO care. QI improves ECMO team training,
• Calls for help early patient safety, patient management, patient care,
• Maintains professional behavior patient satisfaction, ECMO specialist satisfac-
tion, physician satisfaction, and outcomes.
Maintaining ECMO Competency
Institutional Certification of ECMO Team
Since ECMO is a high risk, low volume Members
procedure, centers must establish a process to
ensure that all team members obtain the appro- Each institution is responsible for evaluat-
priate education and experience to retain their ing and certifying its own team members and
skills. Each center must determine a timeline maintaining a written evaluation of the training
for competency evaluation based on their spe- history of those members. Most centers include
cific needs and defined responsibilities of each documentation of course attendance, successful
category of clinicians who are members of the performance at water drills, animal sessions
ECMO team. The ELSO guidelines recommend or simulations, and completion of all required
that training lab sessions be held at a minimum skills lists and competencies in the evalua-
of every six months and an annual examination tions. In addition, each specialist must obtain
758
a passing grade on written and/or oral exams. Summary

Institutional certification can be granted after
successfully completing the training course Although providing ECMO to critically ill
requirements and passing the exam. Sample in- patients is complex, using many health care
stitutional certification requirements for ECMO resources, it can be very rewarding to the institu-
specialists are: tion, staff, and, especially, the infants, children,
adolescents, adults, and families served. An ex-
Institutional Certification Requirements ceptional ECMO program relies upon the initial
• Minimum of 1 year critical care experience and continued education, training, institutional
prior to training certification, and maintenance of quality of the
• Attendance at all didactic sessions multidisciplinary ECMO team. To assist with
• Attendance at all training lab sessions development of these comprehensive programs,
• Participation in ECLS emergency drills the ELSO guidelines exist to provide educa-
• Completion of pump time with a preceptor tional requirements for clinicians responsible
• Completion of technical skills list and/or for monitoring and maintaining ECMO support.
competencies The “ELSO Award of Excellence in Life Sup-
• Successful completion of written/oral exam port” provides the framework for developing an
with passing score education and training program of distinction.
The educational process should be designed
Periodic review of the ECMO team member to follow adult based learning principles and
knowledge and skill level is essential. The fre- be based upon Miller’s triangle for clinical
quency and the skills to be assessed depend on assessment. Training and education must also
center-specific requirements for recertification. address training for new providers and existing
All training expectations and criteria indicat- providers from all disciplines including special-
ing success (eg, a passing score on a test and a ists and physicians. Continuing education and
minimum number of pump hours) need to be assessment of clinical competency should be
established. In addition, yearly requirements for an integral part of the program, including com-
attendance and participation in team meetings petencies of ECMO specialist, physicians, and
will need to be fulfilled. Sample recertification surgeons. Only with robust ECMO education
requirements for ECMO specialists are: and training can a program truly achieve the
Institutional Recertification Requirements “Path to the Excellence in Life Support.”
• Attendance at required team meetings

• Participation in bi-annual ECLS training Acknowledgements: We thank Tracy Mor-
lab drills rison, MSQA, BSN, RN for her critical review
• Passing score on annual written or oral of this chapter.
examination
• Verification of ECLS competency
• Performance of required number of pump
hours per time period
Addendum 67-1 provides a sample insti-

tutional ECMO physician credentialing and
recertification guideline.
759
Chapter 67
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Addendum 67-1 3) Must complete <institution>

Review Course with ECMO
Institutional ECMO Physician Credentialing coordinator to review <institu-
Guideline – SAMPLE - tion> equipment, procedures and
policies
Extracorporeal Membrane Oxygenation 4) Completion requires passing
(ECMO) Resource Physician scores on the written examination
and simulation exercises
The ECMO Resource Physician and ICU B. If ECMO training and experience
attending physician will jointly determine the as attending physician or fellow in
candidacy of the patient for ECMO support. All established ECMO program greater
decisions to offer ECMO support to a candidate than 1 year of appointment to <insti-
will be a two physician decision. If a consensus tution>
cannot be reached, the ECMO Medical Direc- 1) Recommendation from <institu-
tor or designee will be contacted to determine tion> Critical Care ECMO Direc-
eligibility. tor; and
These credentials allow the ECMO Re- 2) Must complete full <institution>
source Physician to coordinate the services of training course
the ECMO Team with the Intensive Care Teams. 3) Completion requires passing
Privileges include the evaluation and selection scores on the written examination
of patients for ECMO, oversight of the cannu- and simulation exercises
lation and decannulation process, management C. ECMO Morbidity and Mortality
of the extracorporeal life support circuit and (M&M)
patient, and provision of routine and emergency Once ECMO Resource Physician
care to patients on ECMO. The minimum clini- credentialing is granted, a presenta-
cal training and/or experience required to apply tion at an ECMO M&M of an ECMO
for this privilege is as follows: case that the individual has been
involved will be scheduled in the first
I. Initial privilege eligibility criteria year of appointment via the ECLS
A. ECMO training and experience as coordinators or designee
attending physician or fellow in II. Reappointment eligibility guidelines
established ECMO program within 1 A. Maintenance of clinical competency
year of appointment to <institution> 1. Participate in supervised can-
1) Recommendation from <institu- nulation and decannulation of 4
tion> Critical Care ECMO Direc- patients within a 2 year period
tor; and 2. Demonstrate competent patient
2) Reference letter from ECMO management for 4 patients within
Medical Director which specifi- a 2 year period
cally addresses the candidate’s 3. Completion requires concurrence
ability to select patients for of the ECMO Program Director.
ECMO support, oversee the Patient management and cannula-
cannulation and decannulation tion/decannulation supervision
process, and manage both routine may be met by involvement with
ECMO care and emergencies; different patients
and
762
B. Maintenance of CME is required by 3. Completion requires passing

completion of one of routes described scores on the written examination
1. Attendance of at least 75% of and simulation exercises
ECMO case debriefings (includes C. Maintenance of Clinical Compe-
M&M) within a one year period tency
2. Participation in an ECLS CME 1. Demonstrate competent patient
activity such as an ECMO Train- management for 4 patients within
ing, annual ELSO conference, a 2 year period.
Keystone ECLS conference, other 2. Completion requires concurrence
accredited ECLS activity or simi- of the ECMO Medical Director.
lar, every three years. CME credit Patient management supervision
documentation will be submitted may be met by involvement with
at recredentialing different patients.
C. If the number of ECMO cases does II. Reappointment Eligibility Guidelines:
not meet the minimum volume per 1. Maintenance of CME is required
year, the ECMO Medical Director by attending at least 25% of ECMO
may extend the time period under case debriefings (including M&M)
consideration within a one year period.
Prescribing ECMO Clinician (MD, Advance

Practice Nurse)
Supplemental privilege for intensive

care hospital privileges. Privileges to pro-
vide routine and emergency clinical care for
the patient on Extracorporeal Life Support
(ECLS).
The minimum clinical training and/or
experience required to apply for this privilege
is as follows
I. Initial Privilege Eligibility Criteria
A. Track 1
1. Completion of the full ECMO
training course
2. Completion requires passing
scores on the written examination
and simulation exercises
B. Track 2
1. Completion of an alternate
ECMO training course approved
by ECMO Program Director; and
2. Completion of review course
with ECMO coordinator to re-
view equipment, procedures and
policies; and
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68
Quality of Care in Extracorporeal Life Support
Melania M. Bembea, MD, PhD, Jamie McElrath Schwartz, MD, Derek Best, RN, RSCN, BN
Introduction ful of the individual patient’s culture, choices,

needs, and values.1
Achieving and maintaining high qual- The first step in achieving these aims is to
ity in an Extracorporeal Life Support (ECLS) evaluate the ECLS center quality of care. This
program is paramount to ensure patients reach quality assessment can be done using the three
the best outcome possible. ECLS is a complex, aspects of care provision first described by Ave-
resource intense, and risky process with unpre- dis Donabedian: structure, processes, and out-
dictable utilization. ECLS programs have a re- comes.2 Adequate structure refers to facilities
sponsibility to patients and hospitals to develop (eg, designated ECLS beds or unit, size of ECLS
a robust system of quality maintenance to sus- program); staffing (eg, nurse or ECLS specialist
tain expertise. Quality improvement should be to patient ratio); physician certification status,
implemented by the ECLS team and supported ECLS specialists and other providers involved
by the hospital for all disciplines involved in in ECLS patient care, or national database
ECLS care (ie, critical care team, surgical team, participation. Processes include compliance
ECMO specialists, perfusionists, blood bank, with published guidelines or internal protocols,
pharmacists, multiple medical specialties such and outcomes include but are not limited to
as hematology, cardiology, pulmonology, and mortality, ECLS-related complications, patient-
others). reported outcomes after hospital discharge, and
A sensible approach for ECLS programs ECLS-related resource utilization.
is to align with the six Institute of Medicine There are multiple strategies for maintain-
“Aims for Improvement” (STEEEP) for health ing quality in an ECLS program. A continuous
care that is 1) safe: avoids patient injuries from evaluation of the scope of care and patient
care intended to help them; 2) timely: minimizes outcomes is integral to this effort.3 While a new
waits and delays; 3) effective: provides services or growing ECLS program spends significant
based on scientific knowledge to all patients effort on planning, development, and imple-
who could benefit, and refrains from providing mentation, the focus of a mature ECLS program
services to those patients not likely to benefit; typically shifts to sustainability (maintaining
4) efficient: reduces waste; 5) equitable: quality skills, reassessment, continuing education),
of care does not vary because of patient charac- quality of care (data collection and reporting,
teristics such as gender, race, or socioeconomic clinical reviews, review of patient outcomes,
status, and; 6) patient-centered: care is respect- strategic planning), and advancement of the
765
Chapter 68
program through research, innovation, and Summarizing the Evidence for Interventions
collaboration.3 to Improve Outcomes
Clinical practice is highly variable among
ECLS centers as documented in several areas of There is a growing literature base regarding
ECLS care.4-6 In the absence of evidence-based ELSO care, but small numbers in individual
clinical practice guidelines, it is recommended center reports and diverse study populations
to standardize practice within each institution leave many unanswered questions for practi-
to decrease variability among providers and en- tioners. Participation in the larger ELSO com-
able impact measurement of practice changes. munity allows for access to guidelines based on
Standardization of care by development of expert opinion and literature review.10 ELSO
institution-specific algorithms and protocols and other professional societies are planning a
has been shown to improve ECLS processes comprehensive set of evidence-based clinical
(eg, significant reductions in extracorporeal car- practice guidelines for ECLS care conforming
diopulmonary resuscitation [ECPR] times after to the Institute of Medicine recommendations,11
implementation of a new ECPR algorithm ac- which will be available in the near future.
companied by multidisciplinary team training)7 Present guidelines address issues as varied as
as well as outcomes (eg, significant reductions management of anticoagulation during ECLS,
in hemorrhagic complications, blood product management of mechanical ventilation, hemo-
usage, and circuit changes after implementa- dynamics, nutrition, or acute kidney insufficien-
tion of a comprehensive ECLS anticoagulation cy, strategies for weaning off ECLS, etc. that
monitoring protocol).8 are publicly available on the ELSO website.10
In this chapter, we will explore how a Individual programs should use such pub-
model of knowledge translation9 applies to lished guidelines to educate staff and create
ECLS programs’ efforts to create and maintain detailed, institution-specific policies and pro-
quality, drawing on resources of a global ECLS tocols. For example, timely ECLS deployment
community and the Extracorporeal Life Support is an important aspect of quality, as it reduces
Organization (ELSO). Five key principles of chances of further hemodynamic or respira-
the model are: tory deterioration and/or progression to cardiac
1. Focus on the ECLS program and the larger arrest. After a review of literature and ELSO
hospital systems rather than individuals guidelines, program members can address this
2. Ownership of improvement projects by the issue systematically to determine which inter-
multidisciplinary ECLS team ventions would have the largest benefit and
3. Centralized support for technical work lowest barriers to use. Multiple issues can be ad-
4. Local adaptation of interventions dressed: 1) ECLS candidacy: is there an ECLS
5. Collaborative culture within the ECLS decision algorithm for identifying patients at
program and larger ECLS community.9 risk for rapid cardiopulmonary deterioration
requiring ECLS support, is there a process to
Process steps for model implementation are: preemptively assess potential cannulation sites
and plan for appropriate cannula size selec-
• Summary of evidence for interventions tion; 2) decision to activate ECLS: is there a
aimed to improve a specific outcome, designated physician who makes the decision
• Identification of local barriers to imple- to activate ECLS (eg, attending intensivist, gen-
mentation eral or cardiothoracic surgeon); 3) location of
• Performance measurement cannulation: what locations within the hospital
• Implementation of the intervention9 would ECLS cannulations take place, does the
766
patient have to be moved prior to cannula- aspects of care provisions noted above.12 Ide-
tion; 4) activation algorithm: is there a simple ally, performance measures that are flexible and
mechanism such as a group page to notify all adaptable across multiple hospitals, regions,
needed providers that a patient needs timely and countries should be agreed upon and used
ECLS cannulation (eg, ICU nurses, ECLS spe- consistently.13 Many such measures are embed-
cialists, operating room staff, pharmacy, blood ded into the ELSO criteria for designation of
bank, specialists involved in the patient’s care, ECLS Centers of Excellence, at silver, gold,
radiology, etc.); 5) supplies and equipment: are and platinum levels.14 These criteria span the
the ECLS cannulation supplies easy to locate, processes, procedures, and systems that are in
are they centralized, is there backup equipment; place or being developed at each center in order
6) pharmacy and blood bank support: are there to improve outcomes, and are classified within
systems in place to prepare medications needed the domains detailed in Table 68-1. For example,
for patient resuscitation, for the circuit prime, timely ECLS deployment process measures
and for the cannulation (eg, heparin bolus), are could include time from ECLS activation to
there systems in place for rapid availability of
blood products (eg, emergency release blood for
new patients, typed and cross-matched blood Table 68-1. Domains of the ELSO Award for
Excellence in Life Support Application (A
for known patients). comprehensive ELSO Award of Excellence
Readiness Tool is available on the ELSO web-
Identify Local Barriers to Implementation site to assist new or growing ECLS centers with
the implementation and maintenance of quality
of Changes improvement programs.14).
Changes aimed at improving quality are Domain

Systems
Components (Selected)
- Availability of specialty medical services,
sometimes met with skepticism from the laboratory, blood bank, operating rooms,
occupational and physical therapy, nutrition,
broader healthcare team. Indeed, in the absence pastoral care, etc
of thoughtful planning, ongoing commitment, - ECLS transport capabilities
- Roles and responsibilities of the ECLS medical
and adequate administrative and time resources, director and ECLS coordinator
Environment - Single- vs multiple-ICU ECLS program
quality improvement projects can easily fail. In - Back-up equipment and circuit components
ECLS in particular, main criticisms of quality Workforce
- Contingency plan for increased census
- Pre-requisites to become an ECLS Specialist (ES)
improvement projects are a lack of evidence- - Patient to staff (ES, nurse) ratio, primer
availability in-hospital or on call
based guidelines and a concern that such - Debriefing and management of staff moral
distress
projects will not ultimately improve patient Training and - Initial and continuous credentialing for ECLS for
outcomes. Therefore, any quality improvement competencies physicians, advanced practice nurses, physician
assistants, nurses, ES
intervention needs to be prefaced by thorough - Water drills and simulation sessions for basic
circuit and emergency management
discussions with the ICU and surgical teams, - Annual pump time requirements, bedside training,
and with supporting services such as clinical Quality
and exam
- Best practices related to workforce management
laboratory, pharmacy, or blood bank. Barriers - Improved value of care delivered
- Maintaining knowledge and incorporating current
need to be identified and addressed preemp- ECLS practice into each center’s clinical practice
tively. Process
optimization
- Process for case reviews (e.g., Morbidity and
Mortality Conference)
- Review and integration of ELSO benchmarking
data
Performance Measurement - Monitoring process for anticoagulation during
ECLS
Patient and - Educational materials provided to families
Performance measures need to be estab- family - Integration of family members into the daily care
of ECLS patients
lished a priori and ideally should encompass - Long-term follow-up process
the six dimensions of quality and the three ECLS=extracorporeal life support; ES=ECLS specialist (individual
designated to care for the ECLS circuit)
767
Chapter 68
surgeon arrival to the bedside, or to circuit Evaluation of quality improvement interven-

readiness, or to successful ECLS support; and tions should be done periodically to compare
outcome measures could include mortality or performance measures for each period with
development of new or progressive multiple baseline measures and with each time epoch
organ dysfunction syndrome on ECLS support. between evaluations. To evaluate interventions,
Performance should be measured at baseline rigorous data collection in institutional or multi-
to estimate the scope and size of anticipated center (eg, ELSO Registry) quality improvement
improvement and to serve as comparison once databases is obligatory and needs to be supported
quality improvement interventions are imple- by dedicated staff with adequate time resources.
mented.9 Programs can develop data collection forms that
are tailored to local needs and/or specific projects.
Implementation of the Interventions In the case of ECLS timely deployment interven-
tion, a quality assurance form could be developed
A cycle of engagement, education, execution, to record: ECLS activation date, time, and loca-
and evaluation should be undertaken to ensure tion; circuit prime start and completion times;
all patients receive the quality improvement time when medications (eg, heparin bolus for the
intervention(s).9 patient, circuit priming medications) and blood
Engagement of the staff can be achieved by products become available at the bedside; time
presenting the program’s baseline performance of insertion of each cannula; time of successful
measure data and explaining opportunity lost ECLS support initiation; as well as any barriers
and potential for improvement, ideally with a encountered at each step and by each discipline
few real-case examples. involved in the tasks enumerated.
Education should be done in a multidisci-
plinary fashion, either peer-to-peer (eg, pharma- Data Collection and Measuring Quality
cist champion to pharmacy team, ECLS specialist
champion to rest of ECLS specialist team, etc.), All ELSO-participating centers are encour-
or as simultaneous interdisciplinary conferences, aged beyond local data collection to enter com-
depending on program size and internal schedul- plete data for each ECLS patient into the ELSO
ing logistics. Registry. The ELSO Registry collects basic
Execution of the project should be focused clinical and laboratory data before, during and
on simplifying interventions and addressing after ECLS support. It allows for each center to
perceived barriers. For the example of timely track its patients’ demographic characteristics,
ECLS cannulation, if the baseline ECLS system pre-ECLS disease characteristics, amount of re-
activation involves multiple phone calls by the spiratory and/or hemodynamic support required
ICU staff to mobilize resources such as surgeons, pre-ECLS, primary indication for ECLS, mode
operating room staff, primers, or blood bank, a and location of cannulation, any ECLS mode
solution such as a group paging system should changes, duration of ECLS support, patient and
be implemented. Similarly, if a computerized circuit related complications during support,
patient order entry is available, developing a reasons for decannulation, mortality at time of
circuit priming medication order set or an ECLS decannulation or prior to hospital discharge, and,
cannulation order set would reduce order entry for survivors, discharge disposition (eg, home,
time. Lastly, centralizing ECLS cannulation sup- rehabilitation hospital, another acute care center,
plies to a single storage space or a mobile ECLS etc).15 Programs can take advantage of the mul-
cannulation cart would diminish times needed to tiple baseline characteristics and outcomes mea-
gather such supplies.
768
sures already collected in the ELSO Registry to of didactic lectures, hands-on circuit training
inform their internal quality improvement needs. via “wet labs,” multidisciplinary simulations,
Another benefit of reporting accurate and and just-in-time training if a patient is deemed at
complete ELSO Registry data is that ELSO high risk for needing ECLS support. Standards
provides an annual report to each participating for maintaining clinical competency should be
center, benchmarking patient and circuit related developed at each center to include a minimum
complications and overall outcomes against required number of hours for bedside ECLS care
centers of similar volume. ECMO centers are and annual written and practical tests for ECLS
divided in three groups, along the 50th and the team members.
75th percentiles (≤5 cases/year, 6-20 cases/year,
and >20 cases/year).16 Data used for bench- New Technology
marking are aggregated for the 10 years prior
to each annual report, to reflect contemporary ECLS technology can change rapidly. The
practice.16 Innovative benchmarking tools that last decade has seen tremendous advances in cen-
take into account case mix adjustment and risk trifugal pump and oxygenator technology, mov-
stratification are being developed at this book’s ing ECLS to a new era of smaller, simpler, and
publication time. more biocompatible circuits. New technology
ECLS programs should strive to evaluate adopted by ECLS centers should be evaluated
quality using several methods, besides ELSO following the same principles and methodologies
Registry data collection and/or internal forms. as those used for quality improvement. Participa-
We know from other fields that adverse events tion in meetings, conferences, web groups, etc.,
and systems problems are detected at different linked to ELSO and other professional organiza-
rates based on the quality measurement tool tions can expose ECLS providers to other centers’
used.17,18 For example, voluntary reporting typi- clinical experience, frequently well ahead of such
cally yields lower rates of adverse events com- published experiences. Technology advances
pared to automated computer-based algorithms are mostly beneficial,23 but an overall process of
for adverse event detection, or compared to indi- creation and maintenance of quality as well as
vidual chart review.17,18 Opportunities should be surveillance for adverse outcomes needs to be
made for staff to report system problems and for maintained for program excellence.24
ECLS program leaders to use multiple modalities
of adverse event detection. Summary
Quality in Small vs. Large ECLS Programs In summary, it is incumbent on all ECLS
programs to have an ongoing process of qual-
Recent data suggest that centers with higher ity improvement utilizing internal and global
ECLS volume experience lower mortality rates resources. Quality processes should employ
when compared to centers with smaller ECLS a systematic approach of evidence summary,
volume, after adjusting for age and severity of intervention implementation, and evaluation.
illness indicators.19-22 Therefore, approaches to Performance metrics should be carefully cho-
maintaining high quality of care in low volume sen based on an internal needs assessment and
programs need to compensate for the lack of should not limit themselves to coarse outcomes
opportunity for hands-on experience present in such as mortality, but strive to cover processes as
high volume programs. This topic is covered well as more granular outcomes such as ECMO-
extensively in other chapters: a robust educa- related complications and long-term functional
tional curriculum should be in place for a mix outcomes in survivors.
769
Chapter 68
References 9. Pronovost PJ, Berenholtz SM, Needham DM.

Translating evidence into practice: A model
1. Berwick DM. A user’s manual for the IOM’s for large scale knowledge translation. BMJ.
‘quality chasm’ report. Health Aff (Mill- 2008;337:a1714.
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2. Donabedian A. Evaluating the quality of med- ELSO guidelines for ECMO centers. https://
ical care. 1966. Milbank Q. 2005;83(4):691- www.elso.org/Resources/Guidelines.aspx.
729. Accessed January 29, 2016.
3. Guerguerian AM, Ogino MT, Dalton HJ, 11. National Academy of Sciences. http://iom.
Shekerdemian LS. Setup and maintenance nationalacademies.org/Reports/2011/Clin-
of extracorporeal life support programs. ical-Practice-Guidelines-We-Can-Trust.
Pediatr Crit Care Med. 2013;14(5 Suppl aspx. Accessed January 29, 2016.
1):S84-93. 12. Copnell B, Hagger V, Wilson SG, Evans SM,
4. Bembea MM, Annich G, Rycus P, et al. Vari- Sprivulis PC, Cameron PA. Measuring the
ability in anticoagulation management of quality of hospital care: An inventory of in-
patients on extracorporeal membrane oxy- dicators. Intern Med J. 2009;39(6):352-360.
genation: An international survey. Pediatr 13. Mears A, Vesseur J, Hamblin R, Long P,
Crit Care Med. 2013;14(2):e77-84. Den Ouden L. Classifying indicators of
5. Camporota L, Nicoletti E, Malafronte M, et quality: A collaboration between dutch and
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6. Glater-Welt LB, Schneider JB, Zinger https://www.elso.org/Excellence/Appli-
MM, Rosen L, Sweberg TM. Nosocomial cationSupportDocuments.aspx. Accessed
bloodstream infections in patients receiv- January 29, 2016.
ing extracorporeal life support: Variability 15. Extracorporeal Life Support Organization.
in prevention practices: A survey of the ELSO registry. https://www.elso.org/Reg-
extracorporeal life support organization istry.aspx. Accessed January 29, 2016.
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[Epub ahead of print] marking. . January 18, 2016.
7. Su L, Spaeder MC, Jones MB, et al. Imple- 17. Jha AK, Kuperman GJ, Teich JM, et al.
mentation of an extracorporeal cardiopul- Identifying adverse drug events: Develop-
monary resuscitation simulation program ment of a computer-based monitor and com-
reduces extracorporeal cardiopulmonary parison with chart review and stimulated
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Crit Care Med. 2014;15(9):856-860. 1998;5(3):305-314.
8. Northrop MS, Sidonio RF, Phillips SE, et al. 18. Cifra CL, Jones KL, Ascenzi J, et al. The
The use of an extracorporeal membrane morbidity and mortality conference as an
oxygenation anticoagulation laboratory adverse event surveillance tool in a pae-
protocol is associated with decreased blood diatric intensive care unit. BMJ Qual Saf.
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plications, and increased circuit life. Pediatr 19. Barbaro RP, Odetola FO, Kidwell KM, et al.
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20. Freeman CL, Bennett TD, Casper TC, et
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membrane oxygenation: Does center vol-
ume impact mortality?. Crit Care Med.
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21. Karamlou T, Vafaeezadeh M, Parrish AM,
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oxygenation center case volume is as-
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membrane oxygenation survival among
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22. Davis JS, Ryan ML, Perez EA, Neville
HL, Bronson SN, Sola JE. ECMO hos-
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23. Sivarajan VB, Best D, Brizard CP, et al.
Improved outcomes of paediatric extracor-
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24. Speggiorin S, Robinson SG, Harvey C, et
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771
69
The Economics of ECMO
Suneel Poobani, MBBS, MD, DCH, FRCP, FRCPCH, FCCP, Luis Caneo, MD, PhD,
Graeme MacLaren, MBBS, FRACP, FRCP, FCICM, FCCM, Lara Shekerdemian, MB ChB, MD,
MHA, FRACP
Introduction include accidental drug or toxin ingestion, en-

venomation or acute tropical or even pandemic
The use of extracorporeal membrane oxy- diseases that may result in potentially revers-
genation (ECMO) is growing rapidly, related, in ible acute cardiopulmonary collapse. However,
part, to better understanding of the associated spending limited resources to benefit a tiny
physiology, training of specialized teams, and minority must be balanced against supporting
the simplification and relative miniaturization of fundamental healthcare needs for the population
the technology, making circuits safer and longer at large; thus, ECMO quite appropriately may
lasting. As a result, the ‘reach’ of ECMO has not be considered a healthcare priority for all.
changed dramatically. The use of ECMO is no ECMO, as an advanced medical therapy
longer confined to a handful of specialist centers requires significant financial and personnel
in economically advanced nations, nor is it lim- resources for effective implementation and safe
ited to a handful of indications with a predict- delivery. While broad applicability of ECMO
able outcome. In the current era, alongside the for all patients who may benefit from it is de-
longstanding and well-understood use of ECMO sirable, the wide variations in the healthcare
to support neonatal hypoxemic respiratory fail- delivery systems and resources among different
ure, have evolved more complex indications nations limit its availability. In the setting of
including cardiac support after neonatal staged limited resources, questions regarding the cost
cardiac palliation, and the recent recognition of effectiveness of the intervention often arise.
its role in the setting of cardiac arrest in the most However, therapies with high initial costs may,
recent American Heart Association Guidelines on an individual level, prove cost effective
for Cardiopulmonary Resuscitation and Emer- in terms of quality-adjusted life years if the
gency Cardiovascular Care.1 therapy proves successful and leads to many
Improvement in sociocultural and socio- productive years.
economic conditions in developing nations has
led to the establishment of previously unavail- Fundamental Considerations
able life sustaining treatments such as ECMO
becoming a reality across the globe. In addition Establishing uniformity in the quality and
to more common indications for support, some standard of the services delivered, resulting in
pathophysiologies pertinent to the developing comparable outcomes while minimizing cost
world where ECMO could have a potential role help make ECMO an acceptable and ultimately
773
Chapter 69
more widely available therapy. This requires that receiving ECMO vs. those treated conventionally
all potential local barriers to success of ECMO, must be evaluated.
for example, local infection control issues or the
rapid availability of blood products, be identi- Cost Effectiveness
fied and addressed early. A successful ECMO
program requires the commitment of the entire To judge the cost effectiveness of this com-
team, with intense and systematic training (see plex, expensive, and resource-heavy intervention
Chapter 67) as well as with the development requires detailed analysis including objective
of evidence-based (or at least the sharing from measures of functional outcome, specifically
larger centers) guidelines and protocols, and related to quality of life, for each patient. A num-
regular audit and quality analyses (see Chapter ber of tools have been developed to help with
68) in order to keep morbidity and mortality rates this evaluation. The quality-adjusted life years
to a minimum.2 (QALYs) tool is perhaps the most commonly
Economic evaluations involve the as- applied for assessing health interventions. It
sessment of costs of at least two potential assesses health-related quality of life at a given
interventions for any condition, defining the time point after an intervention, and has been ap-
determination of the benefits associated with plied in adults and children, in multiple settings
the interventions, and subsequent combination including ECMO and mechanical support.3,4 In
of these costs and benefits to both the individual the UK, the National Health Service (and latterly,
and the system. The assessment of both cost and the National Institute for Health and Care Excel-
benefits enables a more complete consideration lence [NICE]) has, for more than two decades,
of the “value” of an intervention; what additional been using QALYs to measure the overall health
benefit is provided for what additional cost. The benefits delivered by various treatment regimens.
value of a therapy can be described according to To apply such a tool broadly, it is important to
multiple perspectives: those of the patients, the define a target threshold below which the inter-
payers, the hospitals, the medical personnel, or vention can be said to be cost effective in terms
to industry as a whole. Economic evaluations of QALY gained, and above which the model
aid health care professionals and decision mak- would be rejected as being too costly without
ers to decide between competing alternative adequate benefit. But reaching consensus over
interventions. this definition has proved challenging. In 2005
the UK threshold suggested was defined as
Measuring the Overall Cost of ECMO £30,000 (GBP) per additional QALY, which at
this time represented approximately twice the
No single globally applicable tool enables us average salary after tax.5 This implies a value
to accurately model the true ‘cost’ of ECMO, and of a full life of about £2.4 million. In North
this variability relates to local healthcare models America, a similar figure of $50,000 (USD) per
as well as staffing, equipment and consumable QALY has been proposed as a threshold below
costs, and hospital costs of intensive care stay, for cost effectiveness. The disability-adjusted
laboratory resources and associated therapies life year (DALY) tool is, in simplistic terms, the
including renal replacement therapy, drugs, etc. ‘opposite’ of the QALY, and assigns a value to
Notwithstanding, no two ECMO patients are ever health lost (as a result of, or following a given
the same. However, to support and validate the intervention) rather than health gained.
proposal that ECMO be used as a life saving mea- The landmark UK collaborative ECMO trial
sure, the long-term cost effectiveness for those randomized 185 newborns with acute hypoxemic
respiratory failure to either ECMO at one of the
774
nation’s four ECMO centers (n=93), or conven- quality-of-life. The quality-of-life status of sur-
tional management (n=92) and then followed vivors was determined with the Health Utilities
survivors to 7 years of age.6 The overall cost Index Mark II. The mean duration of ECMO
effectiveness of neonatal ECMO was expressed support was 5.1+/-4.1 days. The mean score of
in terms of incremental cost per additional life the Health Utilities Index for the survivors was
year gained and incremental cost per additional 0.75+/-0.19 (range, 0.41-1.0). The median cost
disability-free life year gained. During the 7-year for hospital stay after the institution of ECMO
followup period, neonatal ECMO was shown to was $156,324 (USD) per patient. The calculated
be effective at reducing death or severe disability cost-utility for salvage extracorporeal membrane
when compared to conventional therapy alone. oxygenation in this population was $24,386 per
Mean health service costs during the first 7 years QALY saved, which would be considered within
of life were £30,270 in the ECMO group and the range of accepted cost-efficacy.
£10,229 in the conventional management group,
generating a mean cost difference of £20,041 Personnel and Consumables
per patient that reached statistical significance.
The incremental cost per life year gained was The success of an ECMO program depends
estimated at £13,385. The incremental cost per primarily on solid infrastructure with a team
disability-free life year gained was estimated of highly trained practitioners with identified
at £23,566. At the notional willingness-to-pay leadership, as well as robust equipment. While
threshold of £30,000 for an additional life year, there is an inevitable personnel requirement (ie,
the probability that neonatal ECMO is cost ef- salary), team members will spend their time car-
fective at 7 years was estimated at 0.98, with ing for non-ECMO patients. While no universal
a net benefit of £24,362 for each patient that remuneration model for ECMO personnel exists,
received ECMO. this model of multiple duties provides economic
In the CESAR trial, also in the UK, 180 efficiency, and ensures maintenance of clinical
adults with acute respiratory failure were ran- skills.
domized to receive either ECMO or conventional Sustaining an ECMO program requires
management. ECMO patients incurred average appropriate supplies of all related equipment
3
total costs of £73,979 compared with £33,435 including pumps, circuits, oxygenators, tubing,
for those undergoing conventional management. as well as a variety of monitoring equipment.
The lifetime cost of ECMO per QALY of ECMO Additionally, depending on the projected patient
was £19,252 (95% confidence interval £7622 to volume, backup equipment and access to techni-
£59,200) at a discount rate of 3.5%, and lifetime cal support, repairs, and replacements are also
QALYs gained were 10.75 for the ECMO group required. Contracts will also need to be set up
compared with 7.31 for the conventional group. with vendors to provide support for the complex
Both of these studies demonstrate an economic equipment. The cost of the major items varies sig-
benefit to ECMO over conventional therapy. nificantly across the globe, depending on choice
Over recent years, the use of ECMO in the of equipment, location of vendor, and often the
setting of cardiopulmonary resuscitation has quantity required by the individual ECMO cen-
become common practice. In these patients, the ter. In addition to the cost of consumables, the
likely outcome without ECMO would be death. difficult-to-quantify costs associated with ICU
Mahle et al.7 reviewed their experience with stay and personnel costs must be considered.
salvage cardiac ECMO in 32 patients between
January 2000 and May 2004 to determine the
cost-utility, which accounts for both costs and
775
Chapter 69
Cost vs. Reimbursement are perhaps better aligned with the western world,
ECMO is a centrally funded therapy and there-
The cost of a complex and resource-heavy fore much more accessible to the population as
therapy such as ECMO to the individual patient a whole. In these countries, ECMO is practiced
or his or her family varies enormously across the along the lines of western countries, though the
globe and for many is the ultimate determinant of cost remains high. ECMO practitioners in the
whether or not ECMO can be provided. This vari- Gulf region are working towards modifying
ability is directly related to the healthcare system, their practices to suit their local conditions and
and eligibility for partially or fully reimbursed minimize expenses, in light of the experiences
treatment by either the local jurisdiction (often gained while establishing the ECMO program.
ultimately the taxpayer) or insurance, or charity, In Asia, models of care and the availability of
or some combination of these. Similarly, within ECMO vary considerably. While some countries
some models of healthcare in which ECMO follow Western healthcare models, many do not.
therapy generates direct charges, it can be a For example, in Singapore patients have to pay
source of significant revenue. some out-of-pocket expenses and their ability to
pay is means-tested. The out-of-pocket expenses
International Models of ECMO Finance of each ECMO circuit alone thus range from ap-
proximately US$600 to $10,500, depending on
In the United States, ECMO has its own the patient’s healthcare package and the type of
current procedural terminology (CPT) code, circuitry used. Nonetheless, various additional
making it a billable therapy above routine ICU financial resources are available to patients who
charges and other procedural charges that may cannot afford such treatment and citizens are not
be incurred during ECMO such as dialysis, denied therapy because of inability to pay.
bronchoscopy, surgical procedures, etc. The as- Harvey et al.8 reviewed 18 studies evaluating
sociated charges are based on direct and indirect U.S. and international in-hospital costs of ECMO.
costs, and also include a charge for anticipated Most studies applied cost models to retrospective
bad debt, and a small profit margin. On aver- data collection, while a few did so prospectively.
age, the total charge is roughly three times the The results showed a large variation in the cost of
actual cost (and the average reimbursement). ECMO over multiple cost categories (eg, range
In federally supported Medicare and Medicaid of total in-hospital costs of treatment: $42,554-
programs, and some private carriers, ECMO car- $537,554 (USD) [indexed to 2013 values]). In
ries its own Diagnosis-Related Groups (DRGs) the U.S., the reported costs of ECMO were high-
code, which assigns a generalizable charge and est for congenital diaphragmatic hernia (CDH)
reimbursement to ECMO based on an ‘average repair, followed by cardiac conditions, and the
bundle’. The DRG model provides an incentive lowest for respiratory conditions. Outside the
for improved efficiency (for example related to U.S., the ECMO cost was highest for cardiac
equipment, laboratory samples, duration of sup- conditions and lowest for CDH repair. The au-
port etc.), as the reimbursement is ‘fixed’. In the thors concluded that current literature shows a
UK, where universal access to free healthcare large variation in the in-hospital cost estimates
exists through the National Health Service, there for ECMO. Reliable costing methodologies and
are four designated recognized children’s ECMO cost information will be critical to inform poli-
centers and 5 adult centers. These are nationally cymakers and stakeholders wishing to maximize
funded ‘specialist centers,’ and importantly no the value of advanced medical technologies such
charges are incurred by patients or their families. as ECMO.
In the Gulf region, where health care resources
776
Faraoni D et al.9 assessed the characteris- economic conditions within the SAARC nations
tics associated with higher hospital charges for vary too. India has a heterogeneous population
ECMO to identify using the 2012 Health Care comprised of people from the poorest to the
Cost and Use Project Kid’s Inpatient Database. richest. National healthcare planning is target-
They compared ECMO costs with those for ing schemes to improve the healthcare of the
bone marrow, liver, and kidney transplants entire population, given available resources.
performed during the same year. The median Private healthcare flourishes too, by providing
hospital cost for all children supported with the most modern healthcare facilities including
ECMO was $230,425 (USD), and for ECMO liver, bone marrow, heart transplantations, latest
survivors, $519,450. By comparison, median diagnostic and therapeutic oncological treatment
hospital costs for bone marrow, liver, and kid- facilities, ECMO etc. to name a few. The scope
ney transplants were $207,211, $231,755, and for medical tourism is increasing, by providing
$82,008 respectively. In a multivariable model, healthcare facilities at reduced prices compared
lower ECMO cost was associated with a diagno- to the expenses in the developed world. Some
sis of neonatal respiratory failure or sepsis (OR state governments contribute (to a limited extent)
0.53); whereas, higher costs were associated to the healthcare of the poor that can be under-
with underlying cardiac surgery, the presence taken in any recognized corporate healthcare
of renal failure, thromboembolic complications, setting. With the line between the state owned
smaller sized hospitals, or the region (West or and private facilities being increasingly blurred,
Midwest vs. North-east). Mishra et al.10 analyzed sophisticated healthcare can therefore broaden to
the cost of ECMO in a cohort of 14 consecutive cover the middle- and lower-income groups too.
patients in a single center in Norway. The median Practitioners from these countries who have used
estimated cost for the ECMO procedure was ECMO in their practice while working abroad,
$62,545 (range: 34,121–154,817). The median have managed to train professionals upon their
estimated total hospital costs, including pre- and return and established care centers with ECMO
post-ECMO procedures, were $191,436 (range: facilities with their coordinated efforts. Some
59,871–405,497). charity hospitals in India include ECMO among
their service and have kept costs low. Given the
Funding ECMO in Emerging Economies ingenuity of innovations and some of the equip-
ment being manufactured locally, optimism
When considering emerging economies, exists that the costs of the technology should be
unfortunately the reality exists whereby many of reduced to a reasonable extent in the future. In
these nations, with relatively low GDP outputs Pakistan and Sri Lanka, ECMO usage is much
on healthcare, have the least resources avail- greater in the private sector. With improvements
able to bear the costs of ECMO, and so rely in health infrastructure; tertiary level healthcare
on self-funding and private healthcare, limited facilities such as ECMO should improve in the
insurance options, or external charitable organi- years to come.
zations. Within South-East Asia and South-West In spite of reduced availability of technical
Asia (the Gulf region), significant differences and economic resources, ECMO therapy can
in health economy practices exist. South-East be implemented successfully in developing
Asia includes the countries from the SAARC countries. Flórez et al.11 recently reported a suc-
region (Afghanistan, Bangladesh, Bhutan, In- cessful cost-effective model of care with nurses
dia, Maldives, Nepal, Pakistan, and Sri Lanka). as ECMO specialists supported by a multidisci-
This region includes some of the most populous plinary team in Colombia. This ‘lean’ staffing
nations of the world (eg, India, Pakistan). The model was combined with reduced (and simpler)
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Chapter 69
circuitry and laboratory monitoring, resulting in in ECMO by caregivers remains unrecognized.

favorable outcomes. Park et al.12 have shown a Instead these tasks are simply ‘absorbed’ into
hypothetical analysis of the economic effect of their day jobs. Limited data exist, but ECMO
the use of ECMO in Brazil. They demonstrated cannulation, would carry a charge of around
that costs may be acceptable; however, the Rs.10,000 (INR) (≈ $150 USD) in some hospi-
absence of more robust data concerning the tals, and some of the corporate hospitals charge
morbidity and mortality rates associated with INR. 25,000 (≈ $380) per ECMO day in addi-
these patients, and its actual costs in Brazil, limit tion to regular ICU expenses. This is also not
this evaluation. Cavarocchi et al.13 developed an ideal but suffices as an interim measure, while
ECMO program that did not utilize dedicated institutions gear up to acquire training skills of
ECMO specialists, but instead incorporated the running ECMO and the facilities for retrieval
ECMO circuit supervision into the tasks of the of patients on mobile ECMO improve. In some
bedside ICU care team. In the first year, they charitable hospitals, the cost of an ECMO course
introduced an education platform, new technol- is minimized and totals around INR 5,00,000 (≈
ogy, and dedicated space. In the second year, $7,400). Florez from Colombia quoted hospital
continuous bedside monitoring by perfusionists charges of USD $500 daily for medical and
was removed and new management algorithms nursing management. The average cost of the
designating multidisciplinary providers as first complete hospital stay is approximately USD
responders were established. The total annual $67,000 per patient.11
hospital expenditure for the ECMO program fell With some exceptions, ECMO is not widely
by 61% without compromising patient safety. available in impoverished nations because it is
In India, the few centers that provide ECMO not a priority for the public health systems, as-
fund it through a combination of resources (ie, suming that offering some care is better than no
direct payment, health insurance coverage, or- care, or that reaching a larger number of people
ganizational insurance packages, charity funds, with sub-optimal care is preferable to reach-
and institutions writing off expenses to some ing fewer people with more sophisticated, and
extent). An ECMO patient in the hospital has therefore more expensive, care. This highlights
to bear the expenses of basic intensive care the magnitude of the problems of sheer poverty,
provision besides ECMO-specific costs such inequality, scarce infrastructure, and low human
as blood component transfusions and heparin capital. In general, in the developing countries,
infusions, though all possible efforts to minimize ECMO is only available in the private hospitals
additional costs through aggressive use of lower and tertiary institutions.
transfusion thresholds, avoidance of unnecessary
investigations, and multitasking of caregivers are The Future of ECMO
made. As mentioned by Bartlett and Chapman,14
the projected cost of a 10-day ECMO run and a Many potential mechanisms exist to help
20-day hospital stay in the U.S. hovers around make ECMO a realistic option in various settings.
$100,000. This includes approximately $3,000 While balancing the priorities of a healthcare
per day while on ECMO, and costs relating to system, it is very possible to deliver effective and
the remainder of the hospital stay, equipment, safe ECMO by focusing on efficiency and cost.
laboratory, personnel, and other overhead total- Indeed, this should not only be the focus for de-
ing an additional $70,000. The cost for a similar veloping nations or emerging economies, instead,
scenario in India is significantly lower, in part efficiency and cost effectiveness should be a
because ECMO does not have a true identity as a focus for all actual or potential ECMO providers.
billable procedure, and additional specialization
778
References in children. J Thorac Cardiovasc Surg.

2005;129(5):1084-1090.
1. Brooks SC, Anderson ML, Bruder E, et al. 8. Harvey MJ, Gaies MG, Prosser LA. U.S.
Part 6: Alternative Techniques and Ancil- and International In-Hospital Costs of
lary Devices for Cardiopulmonary Resus- Extracorporeal Membrane Oxygenation:
citation: 2015 American Heart Association a Systematic Review. Appl Health Econ
Guidelines Update for Cardiopulmonary Health Policy. 2015;13(4):341-357
Resuscitation and Emergency Cardiovas- 9. Faraoni D, Nasr VG, DiNardo JA, Thiaga-
cular Care. Circulation 2015;132(18 Suppl rajan RR. Hospital Costs for Neonates
2):S436–443. and Children Supported with Extracor-
2. Freeman CL, Bennett TD, Casper TC, et poreal Membrane Oxygenation. J Pediatr.
al. Pediatric and neonatal extracorpo- 2016;169:69-75.
real membrane oxygenation: does cen- 10. Mishraa V, Svennevigb JL, Bugged JF, et
ter volume impact mortality? Crit Care al. Cost of extracorporeal membrane oxy-
Med.2014;42(3):512-519. genation: evidence from the Rikshospitalet
3. Peek GJ, Elbourne D, Mugford M, et al. University Hospital, Oslo, Norway. Eur J
Randomised controlled trial and paral- Cardiothorac Surg. 2010;37(2):339-342.
lel economic evaluation of conventional 11. Flórez CX, Bermon A, Castillo VR, Sala-
ventilatory support versus extracorporeal zar L. Setting Up an ECMO Program in a
membrane oxygenation for severe adult re- South American Country: Outcomes of the
spiratory failure (CESAR). Health Technol First 104 Pediatric Patients. World J Pediatr
Assess. 2010 ;14(35):1-46. Congenit Heart Surg 2015;6(3):374-381.
4. Brown KL, Wray J, Wood TL, Mc Mahon 12. Park M, Mendes PV, Zampieri FG, et al.
AM, Burch M, Cairns J. Cost utility evalu- The economic effect of extracorporeal
ation of extracorporeal membrane oxygen- membrane oxygenation to support adults
ation as a bridge to transplant for children with severe respiratory failure in Brazil: a
with end-stage heart failure due to dilated hypothetical analysis. Revista Brasileira de
cardiomyopathy. J Heart Lung Transplant. Terapia Intensiva. 2014;26(3):1–10.
2009;28(1):32-38. 13. Cavarocchi NC, Wallace S, Hong EY, et al.
5. Devlin, Nancy; David Parkin (2004). “Does A cost-reducing extracorporeal membrane
NICE have a cost-effectiveness threshold oxygenation (ECMO) program model: a
and what other factors influence its deci- single institution experience. Perfusion.
sions? A binary choice analysis” (PDF). 2015;30(2):148-153.
Health Economics. 2004;13(5):437–452 14. Bartlett RH, Chapman RA. Economics
6. Petrou S, Bischof M, Bennett C, Elbourne of ECLS. ECMO Extracorporeal Cardio-
D, Field D, McNally H. Cost-effectiveness pulmonary Support in Critical Care, 4th
of neonatal extracorporeal membrane Edition, 499-510.
oxygenation based on 7-year results from
the United Kingdom Collaborative ECMO
Trial. Pediatrics. 2006;117(5):1640-1649.
7. Mahle WT, Forbess JM, Kirshbom PM,
Cuadrado AR, Simsic JM, Kanter KR.
Cost-utility analysis of salvage cardiac
779
70
The Ethics of ECLS
Roxanne Kirsch, MD, MBE, Jonna Clark, MD, MA
“Almost every action within the medical rescue them from organ failure when cardiopul-
setting either explicitly or implicitly contains monary arrest appears likely, and emergently
two judgments, one ethical and one scientific, during cardiopulmonary arrest (ECPR).2-4 Four
and there is constant interplay between what broad purposes encompass current ECLS use:
is technically possible and what is morally ECLS as a bridge to recovery (reversible dis-
desirable.”1 ease), ECLS as a bridge to a bridge (goal to
transition to ventricular assist device [VAD]
Introduction or oxygenator), ECLS as a bridge to organ
transplantation, and ECLS as bridge to decision
Technological advancements in extracor- (providing time for recovery, time for diagnosis,
poreal life support (ECLS) change practice and or time to determine candidacy for alternate
improve outcomes such that clinical indications support or organ replacement).5,6 While also
expand almost continuously, making the line used for other innovative practices, such as
between ECLS as standard of care vs. experi- implementation following determination of
mental therapy one in evolution. As with many death based on neurological criteria (brain
intensive care therapies, ECLS is potentially death) to support organ recovery for transplan-
lifesaving, complex, and resource intensive. tation, these ECLS practices occur only at an
It therefore presents challenges that require institutionally based level and remain highly
grounding in bioethical principles in order to controversial.7,8
provide the best possible care for patients. This Within the four broad categories above,
chapter introduces key ethical concepts and as technological advancements and clinical
principles underlying ECLS support, including practices improve, ECLS has been used for
areas of ongoing controversy and evolving prac- novel indications and in the face of complex
tice to provide the clinician with a well-rounded illnesses.5,9-13 In general, the rapid expansion
view of the applied ethics of ECLS. in ECLS utilization has outpaced empirical
outcomes data, making bedside clinical deci-
Expanding Utilizations of ECLS: Application sions challenging. Defining explicit inclusion
and Resource Allocation and exclusion criteria for ECLS is wrought with
uncertainty, requiring subjective interpretation,
Clinicians use ECLS electively to stabilize as demonstrated by the 2013 ELSO guidelines.
patients from ongoing deterioration, urgently to Relative contraindications include: “conditions
781
Chapter 70
incompatible with normal life if the patient chanical circulatory devices, and even intensive
recovers”, “preexisting conditions which affect care beds are not as finite as in resource limited
quality of life”, and “futility: patients who are areas where true rationing (allotting nonrenew-
too sick, have been on conventional therapy too able, finite resources) may need to occur.
long, or have a fatal diagnosis.”14 This empha- When assessing the cost effectiveness of
sizes an attempt to balance sanctity of life with ECLS at the macro level, considerations reflect
quality of life while practicing within a realm of those of other health care therapies. Examining
uncertain outcomes.5,15,16 Ongoing data on clini- quality adjusted life years (QALY) saved can
cal outcomes of expanding and current ECLS help clarify the benefit of a resource-intensive
use will help to inform this balance. and expensive intervention. Some studies have,
However, as medical advancements con- in this way, determined the cost effectiveness of
tinue to cure and treat previously fatal diseases, ECLS support.20,21 However, even using QALY
such as childhood leukemia, endstage liver measures engenders controversy in defining a
failure, or hypoplastic left heart syndrome, the QALY, particularly when referring to patients
range of “normal” lives become increasingly with underlying conditions or disabilities prior
difficult to define. Many people live and thrive to intervention.22 The few studies done with-
with complex medical problems and a quality out using QALYs and comparing outcomes,
of life that differs from others without complex utilization, and hospital costs have produced
medical problems, but on par with their peers, mixed results. While informative, they may
making indications based on anticipated qual- not inform cost effectiveness.21,23-27 Ongoing
ity of life difficult to determine.16-19 In general, work is needed in all areas of health care to
in North America, the default in technology determine cost effectiveness and inform health
utilization errs on the side of potential for life policy and institutional practice in utilizing this
saved rather than to restrict use. Decisions tool. Please also refer to Chapter 69.
to restrict use, for specific indications should Subjectivity in weighing the balance of
ideally be performed away from the bedside, future benefits, burdens, and possible quality
prior to an individual patient presentation, and of life continues to complicate decisions to
applied equally across patients presenting for offer or forgo ECLS. This subjectivity, when
ECLS support. combined with limited outcomes data for rare
At an institutional level, decisions about diagnoses that carry greater uncertainty in
resource utilization may still prove suboptimal. prognosis, creates a large variability in prac-
Each center must weigh the desire to push the tice between centers. While center variation
envelope of care and expand technological sup- importantly pushes the field of ECLS forward
port and capabilities with the intendent expense through innovation,11,19 it leads to demands for
(both morbidity to the patient and financial cost). a multicenter systematic approach to evaluate
Resource allocation is best employed within the ECLS outcomes rigorously and to provide guid-
realms of health policy, with discussion, debate, ance for ethical ECLS practices.16,28 Similar to
and refinement at a national level. Such health other facets of medical care, even with clear and
policy needs to consider the balance of resource concise guidelines, variation in practice will
utilization in other areas of health care, ensure a continue to exist, and use of ECLS will depend
fair allocation principle so as not to discriminate on situation, geographical location, and local
against vulnerable populations who may benefit, institution styles. Yet, as with any innovative
and allow room for innovative use that may therapy, the use of ECLS in novel situations
be of benefit for future patients. In developed should come with transparent communication to
countries, resources including ECLS, other me- the patient or surrogates about the nonstandard
782
The Ethics of ECLS
application, unclear benefit and burdens, chal- the clinical course plays out. While appropriate,
lenges in prognostication, and the need to stop assuming that providing technological support
if no benefit occurs.2,29 meets the best interests of the patient, it is im-
portant to recognize the inadequacies of the true
Complex Medical Decision Making in ECLS: informed consent process.
Starting and Stopping ECLS Additionally, in all instances of informed
consent, surrogate decision making is meant,
Informed Consent and Spectrum of Decision wherever possible, to serve as a substituted
Making judgment, reflecting the decision the patient
would have made if competent. Advanced
Although most intensive care therapies re- directives, or a medical proxy, can help under-
quire complex and challenging decision making, stand this judgment,17 including the priorities
ECLS, particularly when used urgently, presents and acceptable tradeoffs in morbidities. In the
unique challenges to the informed consent absence of a competent patient, (ie, pediatric
process.15,16,30 Informed consent, as one of the patient, cognitively impaired adult), decisions
cornerstones in respect for autonomy (which are made utilizing the best interests standard.
remains strongly guarded in North America), Here, with guidance of the medical team, the
requires: 1) competency of the decision maker; surrogate decides based on their understanding
2) adequate disclosure of information to make of the best interest of the patient.30,34,36,37 Best
an informed decision; 3) a clear understanding interests for the patient as viewed by the medi-
including benefits, risks, and alternatives; and cal team may differ from those viewed by the
4) voluntariness or the lack of coercion.17,31-33 surrogate. Wherever possible, it is of the utmost
Yet, for emergent lifesaving procedures for importance to speak to the patient themselves.
incapacitated patients, (eg, ECLS), surrogate In a course of ECLS, stabilization may be
or two-physician consent suffices, based on the possible to a point that allows communication
presumption that the patient would consent if with the patient and provides the best informed
competent. When no alternatives to ECLS ex- consent, along with the best way to define goals
ist for survival, obtaining true informed consent of therapy. Of course, as with other patients in
from surrogate decision makers is nearly impos- intensive care, a careful assessment of capacity
sible, since therapeutic intervention to poten- is necessary for achieving such consent, since
tially save a life is commonly chosen, whether delirium, sedative effects, and adjustment dis-
full information is known or understood, with orders or acute depression may impede capacity.
very few specific exceptions.15 Surrogates often The role of surrogates in shared decision
favor information biased towards survival rather making varies along the spectrum of uncertainty
than risks and morbidities, including death; and in outcome and potential risk. With greater
they may not fully understand potential com- certainty in outcome, good or poor, physicians
plications.15,30,34 The emotional distress, medical take a greater role in making decisions in order
complexity of interventions, potential for lack to prevent harm to the patient. Generally, if
of full disclosure of information, and possible clear risk of harm to a child is present, includ-
risk for therapeutic misconception (ECLS as ing medical neglect, parental authority is lim-
curative rather than supportive therapy) make ited.37-39 If ECLS outcomes improve in certain
the consent process challenging.15,30,35-37 Hence, instances, this may include prohibiting parental
although written consent is obtained, the expert refusal of ECLS. This would only be relevant
ECLS team makes the decision to initiate sup- in cases where a high certainty of good outcome
port, and provides guidance to the surrogate as exists.40 More often, especially in the instance of
783
Chapter 70
novel uses of ECLS, there is great uncertainty justify not providing them.”41 This terminology
in outcome or morbidity. In this “grey zone” is intrinsically linked to perceptions of immedi-
physicians will generally be less able to pro- ate suffering and potential long-term quality of
vide clear recommendations regarding the best life and depends on the interpretation from the
interest of the patient, and decisions to initiate stakeholder, which can vary among patients,
or forgo ECLS will be more influenced by sur- family members, clinicians, and ECLS centers.
rogate preferences. Further muddying the waters, impressions of
These challenges to actualize true in- quality of life often change across a lifetime,
formed consent in ECLS make it imperative and are frequently higher after recovery from
that communication about risks, benefits, and a disabling illness than they would have been
potential for failure occurs early in the course ranked a priori.18,48-50
and throughout ECLS duration. Transparency Clear communication beginning before
regarding uncertainty in risk, morbidities, and cannulation about intended goals at the outset,
overall prognosis is important, particularly with preparation for failure, and regular review and
novel or infrequent uses of ECLS.2,29 To assist clarification of values, benefits and burdens
families, an approximate timeline for reassess- can diminish the likelihood of conflict. When
ment of the balance of the potential benefits and conflicts regarding futility arise, particularly
burdens can be helpful, including identifica- for a single, prolonged contentious ECLS
tion of key markers indicative of the recovery course, arguments about costs to the system
process (or lack thereof), and emphasizing the and resource utilization are frequently voiced,
temporary nature of the support.2 but not typically helpful considerations. While
such social justice arguments are relevant on the
Medical Futility and Potentially Inappropriate grander scale of ECLS support by the institution,
Therapies region, or country, they cannot be applied to the
individual patient with unique circumstances.
When deciding either to forgo or discon-
tinue ECLS prior to recovery, medical futility Discontinuing ECLS Support Prior to Organ
is often declared. Unfortunately, this term is Recovery: Ethical Permissibility
neither readily definable nor free from subjec-
tivity. For the past four decades, medical futility When time, prior experience, or empirical
has been extensively debated within the medi- evidence demonstrate ECLS will not allow
cal literature.41-46 Futility policies are generally for meaningful survival, stopping is ethically
process based and have largely failed as they appropriate. In North America, forgoing life-
tend to favor physicians overruling family con- sustaining therapies, or requesting the discon-
cerns and do not recognize the moral standing tinuation of life-sustaining therapies such as
of the surrogate.45,47 Current national guidelines mechanical ventilation, dialysis, and artificial
recommend using the term futility only for the nutrition or hydration is ethically and legally
rare circumstances when an intervention can- permissible even when these interventions
not achieve a desired physiologic goal, which are potentially life prolonging, or highly ben-
makes applying the term futility to ECLS dif- eficial.31,51-53 When incapacitated, the surrogate
ficult, as it can often provide physiological sup- decision maker or advance directive addresses
port. Alternatively, the term potentially inappro- this request. For the pediatric patient, forgoing
priate describes “treatments that have at least or withdrawing life support is ethically and
some effect sought by the patient, but clinicians legally permissible based on best interests of
believe that competing ethical considerations the child when the likelihood of ongoing bur-
784
The Ethics of ECLS
dens continues to escalate and the probability loved one (ie, sanctity of life, hope for survival,
of benefit becomes diminishingly low. While or moral opposition to withdrawal of advanced
discontinuing ECLS for any patient may feel medical technology). This recognition should
emotionally different than withdrawing other help to ground discussions and reframe goals
life sustaining therapies, such as the ventilator, of care. Approaching these discussions should
withdrawing ECLS does not differ morally.17,54,55 involve seeking shared interests to achieve a
Applying these ethical and legal permis- path forward, rather than lengthy debates over
sions, reasons for stopping ECLS prior to opposing positions, which often leave teams
recovery include: ECLS fails as a means to and families entrenched on opposite sides of a
recovery, or it fails as a means to achieve decision and the patient left in the middle.
the goal of organ replacement therapy, either
transplantation or durable mechanical sup- Barriers to Stopping ECLS Prior to Recovery
port. To expand, even if ECLS has provided
adequate time for recovery with appropriate Although ethically permissible under cer-
end-organ support, yet recovery has not hap- tain circumstances, the decision to end ECLS
pened and remains unlikely, irreversibility has support and allow a patient to die remains
been demonstrated. At this point, the purpose difficult for many reasons. These decisions
of the ECLS support no longer exists and only do not differ from discontinuing other medical
provides ongoing harms.16,56 In a similar fash- care necessarily, but may highlight certain bar-
ion if the purpose of ECLS is to provide time riers. ECLS in particular, can mask a lack of
to determine candidacy for transplantation or recovery, and team members may feel personal
durable mechanical support, when the patient inhibitions in the active task of stopping ECLS
stops being a candidate for organ replacement support. In many circumstances, the medical
(either following evaluation or due to ongoing team may have difficulty reconciling that the
complications that preclude organ replacement), purpose of ECLS has been lost if options such
the benefit of ECLS ceases. In both instances, as transplant, become impossible. As with
ECLS also may fail due to overall inability to other forms of technology, team angst is often
provide appropriate end-organ support despite increased if the patient is conscious and without
adequate circuit function, or due to major severe neurological deficits when the time to
complications such as intracranial hemorrhage stop is reached. While this in and of itself does
or uncontrollable bleeding where it can no not change the ethical permissibility to stop-
longer be provided safely. These reasons may ping, nor the necessity to stop, it can provide
develop over a short period (days to weeks) or inhibitions to stopping.2,16,51 When possible
longer period (weeks to months) depending on patient input into the decision to discontinue
whether cardiac or pulmonary failure predomi- ECLS helps to reduce team angst and provide
nates. When withdrawal becomes appropriate, optimal medical care. The palliative care or
numerous discussions with the team and fam- advanced care team may help guide these dif-
ily across the time course should occur to aid ficult conversations with the patient and provide
with understanding so that discontinuation does recommendations for the appropriate medical
not surprise the family. The healthcare team management of anxiety, dyspnea, pain and other
additionally needs to recognize that in some symptoms potentially associated with the end
cases there may be a difference between their of life when ECLS is discontinued.
impression of best interests for the patient (ie, to Additionally, after extensive time and
end suffering and prevent doing harm) and the energy has been invested, it can be easy to ex-
surrogate’s impression of best interests for their perience a “sunk cost” effect. Here, additional
785
Chapter 70
time, energy, and technology seem minimal in Addressing the Barriers: Collaborative
the face of what has already been invested, even Communication and Consultation with
if it has minimal to no likelihood of working. Expert Services
Furthermore, debates over indefinable concepts
such as futility, perceived quality of life, uncer- One of the most helpful tools to address
tainty in outcomes, and variation between cen- complex medical decision making and barri-
ters make consensus very difficult to achieve.2,16 ers to stopping ECLS is open and transparent
Beyond reaching consensus within the medical collaborative communication.2,69,70 Setting
team, families and surrogates expect to partici- clear expectations among the clinicians and
pate in decisions to stop ECLS,35,57,58 which can the family early in the course about what can
leave the team worried over the potential for and cannot be accomplished with ECLS is es-
disagreement and may result in the clinicians sential. Recurrent and ongoing assessments
avoiding discussions about the need to stop. and conversations highlighting the purpose of
Additional barriers to stopping come with the intervention, uncertainty in outcome and
the large size of clinical teams involved. Each prognosis, and identifying explicit markers
team member has varied medical expertise, life of success and failure within the context of
experience, and a range of values and beliefs time are necessary to ensure understanding
that impact her or his perception of the ECLS and achieve appropriate consensus. Defining
course. These varied perceptions may amplify endpoints when possible, and maintaining trans-
conflict or uncertainty which may propagate parency regarding potential complications and
confusion for the family. Incomplete or inap- their potential implications, including death, are
propriately biased information can be transmit- key components to limit confusion. The team
ted, and variable or inaccurate perceptions of may need help recognizing that the proximity
family wishes may further impede discussions of death to discontinuation of technology does
of stopping.59 not dictate ethical permissibility. Symptoms of
Finally, the team itself may struggle to ac- severe cardiac or respiratory failure that rapidly
cept failure,60-63 or be inhibited by perceived recur with discontinuation require analgesic
legal or social media ramifications of stop- and anxiolytic management prior to and during
ping.64 Whether consensus is forced or openly discontinuation of ECLS support. The team
achieved within the group affects the degree should review management of patient distress
of angst about a difficult course of ECLS.65-68 before discontinuation.
Such struggles can delay team decisions about The clinical team must provide strong
the appropriateness of stopping. Concerns may recommendations to reduce stress, decisional
lead to avoidance of even discussing a stopping regret, and potential guilt for the surrogate.
point, inappropriately prolonging the course of However, surrogates may not always accept
ineffective ECLS. Recognition of these barri- recommendations.35,36,57,58,71,72 When surrogates
ers prior to a prolonged ECLS course can be disagree over ending a course of ECLS, the
helpful. Ideally, strategies to overcome these provider is tasked with further exploration of
barriers can be implemented before the course the underpinnings of the dissent to help achieve
becomes contentious.10,12 a path forward. If collaborative communication
fails or misunderstandings lead to persistent
conflict, the hospital ethics team should be
consulted. If moral distress persists, or ques-
tions regarding ethically appropriate actions
exist, the ethics consultation may clarify which
786
The Ethics of ECLS
actions are ethically permissible, or enhance ideal research design for studying the efficacy
understanding of various moral positions. of ECLS remains undetermined, some argue
To facilitate open discussions with fam- that a matched pairs design provides the most
ily and the team during a course of ECLS, ethical and informative approach.78 Regard-
early consultation with a pediatric advanced less of design, several studies demonstrate the
care team or adult palliative care team can be importance of incorporating extensive patient
particularly helpful. Pediatric advanced care and family support during the research.20,82,83
teams support children and families through Additional qualitative research also espouses
potentially life-limiting illnesses, emphasizing family support during ECLS, regardless of its
the importance of understanding family values implementation as a research study.28,82,83,84
and beliefs. Palliative care teams provide con- Importantly, informed consent for ECLS
current models of care, where full aggressive differs from that for ECLS as a research
therapy continues while other important care study. In the clinical scenario, the indications,
goals are defined and redefined. These teams likely outcomes, and potential risks or burdens
recognize the need for families to maintain should be disclosed. In the setting of research,
hope for full recovery, while providing guid- equipoise needs to be emphasized as well as
ance to families to develop other important, and the context of the use. The informed consent
potentially more achievable goals to maximize process for using ECLS in a clinical research
quality of life.36,73-77 study is not fundamentally different from that
of any other therapy in research. Ideally, during
Research in ECLS: Ethical Challenges and a clinical research study, the researcher obtains
Controversy consent for research separate from the clinical
practice provided by the clinician. Clarification
As demonstrated throughout this chapter, regarding decisions that fall within a research
additional research studies in ECLS are required protocol vs. those that remain at the discretion
to refine patient selection, clarify outcomes, and of the clinician is necessary. Furthermore, vari-
inform efficient resource allocation. Unfortu- ances from the clinical standard of care need
nately, research evaluating the comparative ef- protections in place to mitigate associated risks.
fectiveness of advanced technologies for acute The patient or surrogate decision maker should
life threatening illnesses is fraught with ethical have a clear understanding of the differences
challenges.78 While prospective randomized between the clinical research team and the
control trials (RCT) remain the gold standard to clinical providers.
determine the efficacy of a medical intervention In general, research in technological in-
or therapy, they are not generally appropriate for novation raises additional ethical challenges in
ECLS. In ECLS, the RCT cannot be blinded, determining when the innovation fits within the
it requires consent from surrogates rather than realm of standard clinical care improvements
patients, portends uncertain risk that may result vs. when it becomes part of a clinical research
in substantial morbidity, and leaves a conven- study or initiative. Often at the forefront of
tional therapy arm exposed to known high medical advancement, as in the case of ECLS,
mortality rates.78 Early RCTs in neonates with the line between the clinical standard of care and
acute respiratory failure in the 1980s resulted research or innovative therapy blurs. On one
in extensive debate regarding study design end of the spectrum, within the realm of clinical
and informed consent.19,79,80-,82 Although these standard of care, in the U.S. the Federal Drug
discussions occurred over two decades ago, Administration (FDA) tightly regulates the use
they highlight persistent challenges.78 While of innovative technology or therapies. At the
787
Chapter 70
other end of the spectrum, where innovative leave patients supported with this technology
technology becomes experimental, patients are for months with the potential to decannulate
protected from harm through careful research and transition to more familiar chronic sup-
study design and institutional review boards ports. Cardiac teams have been challenged
(IRB). Yet, between these two ends of the spec- with the evolving use of VADs that frequently
trum, defining the “grey zone” is not entirely can replace ECLS. Awaiting the development
transparent.19,29 While technological advance of complications that prohibit continuation of
undergirds development of new and better stan- ECLS often serves as a marker for discontinua-
dards of clinical care, implementation of novel tion. This may be appropriate in many instances,
therapies needs to be balanced with transpar- but should not be used as a way to avoid the
ency of risk to the patient. Even if an advance- difficult decision to stop. When there is no
ment may have the potential to provide global purpose to continuing therapy, goals of therapy
advances, the use in a single patient often cannot cannot be met, replacement therapies are no
be justified, as the patient needs to be respected longer possible, or the adult patient requests
in and of themselves and cannot be used solely discontinuation of technology, the teams must
as a means for technologic or research advance- reconcile themselves to stopping. Timelines
ment. When the potential risks to patients, or for reevaluation become important to help the
the degree of uncertainty in outcome increases, team and the family understand the trajectory
greater protections for patients through formal of the current course. Developing methods to
and standardized clinical research protocols support the team during the prolonged or dif-
should be undertaken.29 Some centers have ficult ECLS course, particularly when additional
developed institutional groups that review in- time is needed to achieve team and family align-
novative strategies, surgical and medical, to aid ment on appropriate goals of therapy, becomes
with clarifying whether or not the innovation paramount.
rises to the level of clinical research.
Conclusion
Practical Considerations
In summary, utilization of ECLS continues
The ethical challenges inherent to ECLS to expand and challenge our abilities to obtain
support are not unique. Each novel medical informed consent, determine patients’ best
device or technology has created debate regard- interests, manage shared decision making, and
ing application, extended use, and eventual provide high quality end of life care. It requires
development of chronically used modalities. attention to ethical challenges of resource al-
From the introduction of mechanical ventila- location, novel uses and ongoing innovation
tion to the introduction of outpatient VADs and in technology, and finding appropriate clinical
total artificial hearts, the technological advances research models. Throughout this discussion,
of medicine continue to push us to review the fundamental principles and concepts have been
ethical underpinnings of how we deliver care. outlined and ongoing controversies highlighted
As ECLS continues to become more efficient to provide the practitioner with a view of the
and less burdened with complications, we will ethical considerations in managing ECLS. The
continue to be challenged with appropriate use authors acknowledge that many additional ethi-
in novel situations and with determining when cal challenges and considerations could not be
ECLS becomes ineffective and must be stopped. discussed within the constraints of this book
A developing trend for prolonged ECLS support chapter. We encourage ongoing discussion,
in the case of isolated respiratory failure may
788
The Ethics of ECLS
exploration, and debate of these issues from the

groundwork laid out here.
Acknowledgments: The authors would like
to acknowledge the thoughtful input, sugges-
tions, and wisdom of Dr. Robert Bartlett and Dr.
Pearl O’Rourke in writing this chapter.
789
Chapter 70
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71
Strategies for Medication Management in ECLS
Christa Jefferis Kirk, PharmD, Erik E. Abel, PharmD, BCPS, Justin Muir, PharmD,
Amy L. Dzierba, PharmD, BCPS, BCCCP, FCCM
Introduction binding, lipophilicity, molecular weight, and

degree of ionization at a given physiologic
Given the paucity of data available for pa- pH. Drugs that are hydrophilic (water soluble)
tients requiring intensive care, pharmacotherapy have a lower Vd and their concentrations are
in the critically ill presents considerable chal- primarily influenced by changes in volume
lenges, while the addition of an ECLS circuit status. Highly lipophilic medications penetrate
creates even more complexity. Ever changing into the tissues leaving lower concentrations in
technology decreases the applicability of prima- the blood, increasing apparent Vd.
ry literature while reliance on tertiary references The addition of an ECLS circuit produces
can become outdated. Therefore, it is paramount changes in Vd secondary to hemodilution or se-
to understand alterations in pharmacokinetics questration of drugs. Initially, Vd increases due
and pharmacodynamics related to severe ill- to hemodilution secondary to circuit volume,
ness as well as the effects of ECLS on those additional blood products, and bolus volume
parameters. Having this knowledge provides needed to maintain flows. The impact of this
a powerful base for creating an individualized hemodilution depends upon patient size in rela-
dosing strategy that balances maximal therapeu- tion to the circuit volume. Thus, a larger effect
tic effects while minimizing toxicity. may be seen in an infant vs. an adult. Addition-
ally, patients on ECLS often experience fluid
Pharmacokinetics retention due to circuit-induced inflammation
(see Chapter 6), underlying disease/s/, and renal
Volume of Distribution or liver dysfunction. Finally, redistribution of
fluids into the tissues and substantial protein
A general understanding of volume of dis- losses into the circuit may affect protein bound
tribution is essential to developing a successful medications, impacting their overall Vd as well.
approach to medication management in ECLS. In general, fluid shifts from the ECLS circuit
The volume of distribution (Vd) defines the influence highly protein bound and hydrophilic
theoretical volume needed to dilute a medica- medications more profoundly, potentially neces-
tion, when fully distributed at steady state, to sitating a change in dosing strategy.1,2
a desired concentration. Vd is influenced by
physiological aspects of the body and specific
biochemical properties of drugs such as protein
795
Chapter 71
Protein Binding dose medications safely, as it may seem that

clearance is normal. However, this effect is
In addition to the effects of volume status, often short-lived as most patients have a predis-
alterations in plasma proteins may also affect position to AKI prior to placement on ECLS.4
the Vd of certain medications. Drugs with a More often, clearance becomes moderately or
higher affinity for plasma proteins have lower severely diminished with the addition of ECLS.
Vd. Major blood proteins that bind to drugs Both VV and VA-ECLS are associated with a
include albumin and α1-acid glycoprotein, both decreased glomerular filtration rate (GFR).5
synthesized in the liver. Albumin concentra- Devices which affect flow variability may lead
tions decrease in response to increased vas- to pulseless perfusion of the kidneys. Renal
cular permeability, decreased production, and clearance plays a major role in management of
catabolism in critical illness; whereas, α1-acid medications; however, other methods of clear-
glycoprotein is an acute-phase reactant and in- ance may be affected as well. Maldistribution
creases in response to stress. Changes in protein of blood flow to the liver may create higher
concentrations could affect both the amount of extraction ratios or decrease enzymatic activity.6
free drug available and overall Vd. Systemic
inflammatory response syndrome (SIRS), sepsis, Sequestration
and hypoproteinemia associated with ECLS and
critical illness may all have a large impact on the The addition of an ECLS circuit adds
bioavailability of highly plasma protein bound another layer of complexity to understanding
medications. Recent pharmacokinetic research pharmacokinetics. Components of the ECLS
into antimicrobial dosing in ECLS showed that, circuit are not inert and therefore many medi-
in general, more highly protein bound drugs cations can react to both plastics and silicone;
have both decreased clearance and Vd.3 however, data concerning drug sequestration
within the ECLS circuit are limited. Though
Clearance many methods have been tried to overcome this
issue, it remains problematic when attempting to
The elimination of drugs from the body create effective dosing strategies. The binding
depends on both Vd and clearance. The liver of drugs to circuit components depends upon the
and the kidneys serve as the two major organs chemical characteristics of the drug, design of
responsible for drug elimination while minor the oxygenator, and type of priming fluid. The
losses occur via the biliary track, feces, and membrane oxygenator and polyvinylchloride
lungs. Organ impairment or failures are fre- (PVC) tubing provide a large surface area for
quently encountered in critically ill patients. drug sequestration, leading to decreased bio-
Additionally, ECLS patients may have an array availability of drugs as they become trapped
of pathophysiological changes including acute within the circuit potentially causing treatment
kidney injury (AKI), decreased hepatic blood failure.7,8 A saturation point may exist, lead-
flow, or variations in cardiac output leading to ing to liberation of sequestered drug back into
changes in drug clearance. However, it may circulation; however, this concept has not been
be difficult to untangle changes due to critical well studied. This unpredictable mechanism
illness vs. those associated with ECLS. Many may lead to serious consequences after the
patients may experience an initial increase in placement of a new circuit during initiation or
cardiac output when placed on the ECLS circuit, circuit change.9,10
potentially increasing clearance. This phenom-
enon may create confusion when attempting to
796
Biochemical Properties predict lipophilicity. This value measures the

partition or octanol-water coefficient between
Appendix 1 lists the biochemical properties the hydrophilic and lipophilic properties of
associated with common medications used dur- a specific chemical. Higher log P values are
ing ECLS. It highlights Vd, protein binding, and associated with increased lipophilicity which
log P values. Volume of distribution when listed may indicate a higher likelihood of binding to
in references represents an apparent Vd which circuit components.11 Wildschut and colleagues
means that it estimates the volume of a physical correlated log P values to medication recovery
space in the body. Though this may seem to for seven commonly used medications in ECLS
limit applicability, Vd can be used to estimate (Figure 71-1). Those with higher log P values
how a drug will respond to alterations in fluid were less likely to be recovered postoxygenator
status. Medications with low volumes of dis- which strongly suggests that medications with
tribution are often considered to be hydrophilic, higher partition coefficients have higher affini-
while drugs with higher volumes of distribution ties for circuit surfaces.5,12 In 2015, the ASAP
are highly protein bound or distributed into the ECMO (Antibiotic, Sedative and Analgesic
tissues. Information about protein binding is Pharmacokinetics during Extracorporeal Mem-
readily available; however, it is more challeng- brane Oxygenation) study group reported simi-
ing to determine whether or not a medication lar results for both lipophilic and highly protein
will easily disperse into the extravascular space. bound medications suggesting that, in addition
More recently, practitioners have employed log to having higher Vd, they also bind to the circuit
P values of medications, which more accurately substantially decreasing bioavailability.3
Pharmacokinetic Changes in Critical Illness

and ECLS
Both severe illness and ECLS can have

dramatic and unpredictable effects on pharma-
cokinetics. Table 71-1 illustrates the complex
changes in pharmacokinetics associated with
critical illness while Table 71-2 demonstrates
the additive pharmacokinetic challenges created
by the ECLS circuit. As with Vd, medication
clearance relates to free drug concentration
in the blood and depends mainly upon kidney
and liver function. In fact, elimination half-life
equals the product of Vd and clearance. There-
fore, changes to Vd or clearance may impact
the expected half-life of a drug, the basis for
Figure 71-1. Recovery of drugs in roller pump determination of dosing and frequency. Based
circuits (n=8) vs. their lipophilicity, expressed on the constantly changing patient status, stan-
as log P values. Displayed are the means and
95% confidence intervals for each drug, with dard dosing strategies may lead to treatment
a non-linear sigmoid curve fit (solid line) and failure or toxicity. Therefore, doses must be
its 95% confidence interval (dotted lines). vigilantly adjusted and monitored in critically
(Widschut et al. Intensive Care Med. 2010;
36(12):2109-2116. Reprinted with permission ill patients to ensure safe and efficacious use
from Sage Journals.) of medications.
797
Chapter 71
Experience and Recommendations Based on monly used analgesics and sedatives. Limited
Medication Class data exist on the most appropriate opioids and
sedatives to use in ECLS patients. Benzodiaz-
Analgesics and Sedatives epines are frequently used; however, they are
associated with increased time on mechanical
The overarching goal of optimal analgesia ventilation, prolonged ICU stay, short and
and sedation in patients receiving ECLS in- long-term neuropsychological impairment, and
cludes maximizing comfort, maintaining cath- increased mortality.13
eter position, optimizing flows, and minimizing Morphine has a moderate Vd and can se-
oxygen consumption. Achieving the desired quester in the circuit therefore many references
level of sedation can prove challenging as a indicate that higher doses may be needed. De-
result of pharmacokinetic alterations of com- pending on the circuit type, evidence suggests
Table 71-1. Pharmacokinetic changes in critical illness. (Adapted from: Roberts et al. Crit Care Med
2009; 37:840-51).
↑ drug
↓ clearance Toxicity
concentrations
Organ ↓ drug Treatment

dysfunction Altered concentrations failure
protein
Critical Illness binding ↑ drug
Toxicity
concentrations
↑ cardiac ↓ drug Treatment

↑ clearance
output concentrations failure
Table 71-2. Pharmacokinetic changes during ECLS. (Adapted from: Shekar K et al. J Crit Care. 2012;
27:741.e9-741.e18).
Systemic ↓ medication
inflammation ↑clearance concentration in Treatment failure
↑cardiac output blood
Hemodilution ↓ medication
↑ volume of
concentration in Treatment failure
Fluid shifts distribution
blood
↓ medication
↓ bioavailability concentration in Treatment failure
ECMO Drug blood
sequestration in
circuit Slow release of ↑ medication
molecules from concentration in Toxicity
circuit blood
↓ medication
↑ volume of
concentration in Treatment failure
distribution
blood
Organ
dysfunction
↑ medication
↓ clearance concentration in Toxicity
the blood
798
that the circuit absorbs up to 40% of morphine.14 lipophilic and can be associated with significant
Importantly, the kidneys clear morphine metab- losses in the circuit. Wagner and colleagues
olites which accumulate in patients with dimin- showed up to 73% loss of dexmedetomidine
ished clearance. Accumulation of metabolites when measured pre and post oxygenator in
of morphine can increase the risk of seizures sham circuits.17 However, losses were less in
which is especially problematic for neurological circuits that had been in place longer. This may
assessment during ECLS.15 Limited data exist indicate a need for higher initial doses of dex-
for hydromorphone; however, unlike morphine, medetomidine after ECLS initiation or circuit
clearance does not occur via the kidneys. Both change with a plan to lower the dose slowly over
morphine and hydromorphone effectiveness and the life of the circuit as tolerated. Propofol is
clearance will be affected by alterations in liver known for its lipophilicity and is often avoided
function. Fentanyl is extremely lipophilic and in ECLS due to dosing challenges secondary
has a high Vd. As such, it is recommended to to sequestration. Up to 90% of propofol may
avoid fentanyl in patients on ECLS due to its adhere to the ECLS circuit.16
high affinity for circuit components which may The choice of sedation strategy that main-
lead to ineffective sedation.15,16 tains the clinical safety of the patient while
Metabolites of midazolam, like morphine, avoiding adverse events may prove difficult.
may accumulate due to decreased clearance; Circuit variability, diverse drug properties, and
however, case reports and anecdotal evidence patient lability render the task more herculean
highlight the need for at least a 10-20% increase even with available data. Wildschut and col-
in ECLS patients.15 More recently, Lemaitre leagues highlighted the differences between
and colleagues reported up to 79% decrease in circuits and their effect on sedative medications
drug concentration over 24 hours suggesting in Figure 71-2. Fentanyl and midazolam have
that midazolam may not be a preferred agent in statistically significant variability in medication
ECLS patients.16 Lorazepam is also associated recovered pre and post oxygenator illustrat-
with ~50% loss to the circuit; however, the risk ing the difficulty of applying evidence due to
of propylene glycol toxicity can occur when us- differences in equipment at each institution.5
ing higher doses.14 Dexmedetomidine is highly Additionally, many studies have been done in
70
p < 0.001
60 Neo Roller (n=3)
50 Neo Centrifugal (n=2)
40
Ped Roller (n=2)
p < 0.001
30
Neo Roller OLD (n=2)
20
Adapted from:
10 Wildschut ED et al.
Int Care Med.
2010;36:2109-2116
0
Midazolam Morphine Fentanyl
Figure 71-2. Percentage of medication recovery post-oxygenator in four circuits.
799
Chapter 71
neonates or pediatrics, limiting applicability to Overall, the choice of sedative must be

other populations. Shekar and colleagues pub- adapted to the changing needs and monitored
lished data supporting the anecdotal evidence goals of each patient. Data suggest that mor-
that sedation needs of patients on ECLS tend phine and lorazepam may serve as drugs of first
to increase dramatically over time.15 However, choice for patients with normal renal function.
once decannulated, (graphs in Figure 71-3), However, hydromorphone should be preferred
sedation needs decrease significantly. A more in patients with moderate to severe renal dys-
recent study using an adjusted model to estimate function due to risk of accumulation of me-
the impact of ECLS on the 6-hour maximum tabolites. Many researchers recommend normal
sedative exposure failed to show significance.18 starting doses; however, higher bolus or break-
Despite these studies showing increased anal- through doses with more substantial increases
gesic and sedative requirements during ECLS, in rates of infusions may prove necessary.
it remains unknown whether the increased Over time, sedative and analgesic needs often
requirements depend on circuit-related factors increase due to losses within the circuit and
alone or whether other factors such as tolerance, development of tolerance. Patients receiving
age, or pharmacogenomics also contribute. ECLS for acute respiratory distress syndrome
More recently, researchers have looked into (ARDS) may initially require a deep level of
the ability of ketamine to reduce the amount of sedation; whereas only minimal sedation may
opioids needed. Retrospective reviews show be considered when a patient is extubated on
a reduction in sedative rates needed when co- ECLS. Clinicians should anticipate significant
administered with low-dose ketamine without dose reductions at ECLS discontinuation and
alterations in RASS (Richmond agitation- monitor for signs of delirium and withdrawal.
sedation scale) scores.19,20
Figure 71-3. Sedation needs over time. (Shekar et al. Anaesthesia Int Care. 2012; 40(4):648-658).
Reproduced from Anaesthesia and Intensive Care with the kind permission of the Australian Society
of Anaesthetists.
800
Antimicrobials Vancomycin has a low Vd; therefore, dosing

requirements during ECLS may be unchanged
Due to the substantial risks associated with when compared to those not on ECLS. How-
treatment failure including life-threatening ever, when the ECLS circuit increases the
infections, appropriate antimicrobial dosing in volume of the patient, higher initial doses may
ECLS patients is paramount. Ineffective dos- be needed. Loading doses of 20-30 mg/kg
ing strategies could result from substantial drug may be needed to achieve a desired goal within
losses which might lead to therapeutic failures, twenty-four hours.4 Often, vancomycin inter-
development of resistance, and worse outcomes. vals become extended from standard dosing,
Most dosing regimens are determined in healthy especially in patients with renal dysfunction;
patients with normal physiology; therefore, however, exceptions exist. Similar to vanco-
consideration of antimicrobial properties and mycin, aminoglycosides, including gentamicin
the pharmacokinetic challenges presented by and tobramycin, have smaller Vd necessitating
ECLS often result in multiple dosing adjust- standard or higher initial doses with normal or
ments. Overall, clinical decisions rest on risk extended intervals during ECLS.4 Fortunately,
vs. benefit analysis based on infection severity therapeutic drug monitoring for vancomycin
with a goal of achieving desired antimicrobial and aminoglycosides is widely available and
levels quickly in critically ill patients weigh- should be routinely employed to ensure appro-
ing against possible adverse events. As with priate concentrations.
the sedatives, significant variability in pre and Some medications require no adjustment;
post-oxygenator levels of medications occurs according to limited studies cefotaxime and ce-
(Figure 71-4). fazolin can be administered at standard doses.4
Drug sequestration has been reported to occur
90
80
70
60 Neo
Roller (n=3)
50
Ped
40 Roller (n=2)
30 Neo
Roller OLD (n=2)
20
10
Adapted from:
0 Wildschut ED et al.
Int Care Med.
Cefazolin Meropenem Vancomycin 2010;36:2109-2116
Figure 71-4. Percentage of medication recovered post-oxygenator in four circuits.
801
Chapter 71
with meropenem, though a pharmacokinetic initial therapy while monitoring for potential
evaluation in critically ill patients suggests toxicities. Therefore, whenever possible, moni-
that therapeutic targets can be obtained in tor levels, including both peaks and troughs as
most patients with normal dosing regimens.3,21 appropriate, to help design an effective dose
Another study found no differences in Vd, half- and interval. Often, creative dosing strategies
life, or clearance for meropenem or piperacillin/ are needed, especially when targeting a specific
tazobactam in ECLS vs. non-ECLS patients; microorganism.
however, a significant proportion of all patients
experienced concentrations below therapeutic Other Medications
targets.22 This suggests that despite potential
influences of the ECLS circuit on individual Many cardiovascular medications are ti-
medications, factors associated with critical ill- trated to effect, making dosing in ECLS patients
ness may play a greater role in pharmacokinetic much easier. However, some medications may
or pharmacodynamic alterations. need higher loading doses and more aggres-
Many patients requiring ECLS receive anti- sive rates of infusion. Esmolol may require
fungal or antiviral agents. Preferred antifungal higher than usual bolus doses due to changes
agents include caspofungin or micafungin.23 in Vd with ECLS. Case reports recommend
Fluconazole has a higher Vd during ECLS using a 700 mg/kg loading dose with standard
necessitating higher doses for both treatment infusion rates.29 As with esmolol, amiodarone
and prophylaxis.25 One study in neonates sug- bolus doses may need augmentation; however,
gested doses as high as 12 mcg/kg/day would higher rates of continuous infusion are also
be needed to achieve therapeutic levels. 32 employed. One patient required repeated bolus
Voriconazole is highly lipophilic and should be doses and an infusion rate as high as 20 mg/kg/
avoided during ECLS whenever possible due min to control postoperative junctional ectopic
to the substantial amount of sequestration into tachycardia (JET).30 Commonly used in the
the circuit.9 ECLS may also lower antiviral neonatal population, larger doses of both silde-
levels. Several reports found that regular doses nafil and alprostadil are needed in patients on
of oseltamivir resulted in therapeutic serum ECLS likely due to their larger Vd.30 Although
levels similar to ambulatory patients. While frequently used in ECLS patients, little infor-
ECLS does not appear to affect oseltamivir mation on appropriate diuretic dosing exists.
pharmacokinetics directly, patients with renal Most clinicians find the correct dose via trial
dysfunction experience impaired drug clear- and error. Some literature suggests the need to
ance.24-26 Though associated with lower levels, increase initial bolus doses of both bumetanide
standard dosing of ribavirin has proven effective and furosemide.31,32 This may be due to the fact
in treating ECLS patients.27 Acyclovir has a that both medications have higher log P values
very high Vd, creating significant challenges for predicting losses into the circuit. In fact, data
dosing during ECLS. In fact, when attempting suggest that up to 87% of furosemide may be
to achieve therapeutic drug levels, continuous sequestered.6 Based on this information, it has
infusion of acyclovir may be needed especially been hypothesized that a continuous infusion of
during concurrent continuous renal replacement furosemide would be preferred over intermit-
therapy (CRRT).28 tent bolus doses; however, the data have been
When designing an appropriate antimicro- inconclusive.6,32
bial dosing regimen for patients on ECLS, the Anticonvulsant medications may also be
biochemical properties of each drug should affected by the ECLS circuit. Case reports have
be considered, generally favoring aggressive shown up to 15-35% losses of fosphenytoin
802
into circuits while phenobarbital levels may be especially in pediatric patients.41 Bivalirudin
subtherapeutic with traditional dosing as well.33 has also been used in ECLS at standard starting
Larger loading and maintenance doses will be doses with similar anticoagulation effects as
required to achieve therapeutic levels. Standard heparin.42 Due to its significantly higher binding
doses of levetiracetam have been shown to be affinity for thrombin and its hydrophilic nature
effective in adults, even with the addition of (log P=-7.1), bivalirudin may be preferred for
CRRT.34 Due to the high risk of subtherapeutic use in ECLS; however, additional study and
dosing, the literature suggests using medica- review are needed.
tions with readily available therapeutic drug
monitoring. General Dosing Strategy
Anticoagulants Decisionmaking
The most widely used form of systemic and The challenges of applying the limited data
circuit anticoagulation during ECLS is heparin available make a blanket approach to medica-
(see Chapter 7). Although highly hydrophilic, tion dosing in ECLS patients impractical. Con-
as shown by the log P value of -10.4, up to 50% tinuously changing physiology of critically ill
of heparin may be lost to the circuit secondary patients limits standardization and necessitates
to alterations in protein binding and inactivation vigilant monitoring and adjustment in medica-
by blood products.35 Additionally, heparin is tion management. In the absence of robust phar-
among the most negatively charged physiologic macokinetic data, Vd, lipophilicity, and protein
molecules which may contribute to its indis- binding can be considered for each medication.
criminate binding to other molecules including Furthermore, patient characteristics, fluid status,
the surface of the circuit. Therefore, during and organ function also influence appropriate
ECLS, larger bolus doses and higher infusion dosing regimens.
rates of heparin may be needed, especially if Taking the pharmacokinetic properties of
there are challenges in achieving desired goals. drugs and patient-specific factors into consid-
Direct thrombin inhibitors (DTIs) eration can simplify choosing an initial dosing
(see Chapter 7), such as argatroban or bivali- regimen. In general, standard dosing appears
rudin, are alternatives to heparin for patients appropriate for hydrophilic medications with
with suspected or confirmed heparin-induced lower Vd while medications with higher Vd
thrombocytopenia (HIT). More recently, will be more affected by fluid status. Increased
however, some centers have begun using loading doses should be considered for patients
DTIs for routine ECLS anticoagulation even suffering hypervolemia to achieve therapeutic
in the absence of active concerns for HIT.37-39 concentrations more rapidly. As protein binding
Argatroban is metabolized by the liver and is and lipophilicity increase, higher doses will be
minimally cleared via the kidneys which may needed. Very lipophilic medications or those
lead to a more pronounced nonlinear dose that are highly protein bound should be avoided,
response and a prolonged half-life in the criti- if possible, to prevent prolonged under dosing.
cally ill. Limited data exist; however, theoreti- If unavoidable, significantly higher and more
cal evidence suggests that significantly lower frequent dosing may be required at initiation
argatroban doses may be needed.40 However, and after circuit changes to decrease seques-
more recent data highlight the need for larger tration effects. Lastly, the presence of renal or
bolus doses and standard starting rates with hepatic dysfunction may also affect medication
significant increases in response to low levels, clearance. Manufacturer recommended dosage
803
Chapter 71
adjustments should be considered; however, Understanding Risk

potential alterations in pharmacokinetics (PK)
created by the ECLS circuit may necessitate It is imperative when making decisions
clinically appropriate deviation from their about medication dosing to strongly weigh
guidance. benefit more so than manageable risk. For ex-
Physiologic changes due to critical illness ample, if a patient is receiving ECLS for methi-
and the ECLS circuit can affect dosing needs. cillin resistant Staphylococcus aureus (MRSA)
Table 71-3 identifies pharmacokinetic changes pneumonia, it may be better to give larger initial
that can develop during the changing clinical doses of vancomycin vs. using lower doses to
course of ECLS while Table 71-4 highlights avoid the potential risk of nephrotoxicity. Many
the need to adjust doses and frequency based times, the concern for impaired clearance leads
on biochemical properties of drugs with the pharmacists and providers to act cautiously
dynamics of the ECLS circuit. Factors such as which can result in treatment failure. The ASAP
circuit prime, pump design, pulsatile flow, and ECMO study group has highlighted the primacy
recirculation may all affect Vd and clearance of of pharmacokinetics and their impact on medi-
medications.44 Altered renal and hepatic blood cation management during ECLS to decrease
flow and hypothermia which may develop dur- morbidity and mortality.43 Aggressive dosing
ing ECLS can contribute to decreased clearance with close surveillance for the emergence of
as well.1,6 It is important to consider both the adverse drug reactions should direct medication
physical components of the circuit and the management strategies. Whenever possible,
physiological sequelae created by the circuit therapeutic drug monitoring should be used to
when discussing dosing strategies. ensure appropriate serum concentrations while
Table 71-3. Pharmacokinetic changes during ECLS.

ECMO PK Physiologic Therapeutic Affected
Change PK Changes Implication Medications
Priming/ Hemodilution ↑ Vd ↑ loading dose Hydrophilic
transfusions
Drug ↓ bioavailability ↑ loading dose Lipophilic
inactivation by ↑ maintenance Highly protein
priming fluids doses bound
Circuit factors Sequestration ↓ bioavailability ↑ loading dose Lipophilic
(Effect more ↑ maintenance Highly protein
significant with doses bound
newer circuits) ↑ frequency
Patient factors Systemic ↑ Vd ↑ loading dose Hydrophilic
inflammation ↑ clearance
Sepsis
Organ failure ↑ Vd ↓ frequency Renally or
↓ clearance hepatically
cleared
Table 71-4. Therapeutic implication based on physiochemical properties
Biochemical Physiologic Therapeutic

Properties PK Changes Implication
Drug Factors Hydrophilic (log P <0) ↑ Vd ↑ loading dose
↑/↓ clearance ↑/↓ frequency
Lipophilic (log P >2) Vd unchanged ↑ loading dose
Highly protein bound ↑ sequestration ↑ maintenance doses
(>80%) ↑/↓ clearance ↑/↓ frequency
804
avoiding toxicity. Utilizing the physiochemi-

cal properties of medications in combination
with an understanding of clinical status and a
tolerance for acceptable risk allows the team to
thoughtfully initiate and adjust medications in
the face of severe critical illness.
805
Chapter 71
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808
72
The Registry of the Extracorporeal Life Support Organization
Ryan Barbaro, MD, Peter Rycus, MPH, Steven A. Conrad, MD, PhD, MCCM,
Ravi R. Thiagarajan, MBBS, MPH, Matthew L. Paden, MD
The Extracorporeal Life Support Organiza- vival to hospital discharge, and 52 clinical and
tion (ELSO), founded in 1989, has as one of its mechanical complications. ELSO has grown
principal missions maintaining a database, now from approximately 20 centers to 465 centers
exceeding 80,000 patients who have received at present. These centers vary in size and are
extracorporeal life support (ECLS) stretching found in 60 countries with five ELSO regions
back to 1976 (Table 72-1). The database collects around the globe.
information on patients supported with ECLS The aims of establishing and maintaining
including care provided during the hospitaliza- this database are multiple. The ELSO Registry
tion as well as ECLS support details. The ELSO permits ELSO members the opportunity to
database contains outcome variables including research clinical questions that apply to broad
successful weaning from ECLS support, sur- patient groups or single diagnostic categories.
Table 72-1. ELSO Registry outcomes, January 2017.

Total Survived % Survived to %
Runs (n) ECLS (n) Discharge or
Transfer (n)
Neonatal
29,942 25,205 84 21,948 73
Respiratory
Cardiac 7,169 4,643 64 2,938 40
ECPR 1,532 1,028 67 627 40
Pediatric
8,070 5,424 67 4,632 57
Respiratory
Cardiac 9,362 6,404 68 4,758 50
ECPR 3,399 1,958 57 1,414 41
Adult
12,346 8,242 66 7,157 57
Respiratory
Cardiac 10,982 6,251 56 4,466 40
ECPR 3,485 1,382 39 993 28
Total 86,287 60,537 70 48,933 56
809
Chapter 72
The database provides researchers and clinicians the database began collecting severity of ill-
a chance to investigate the varied populations ness measures prior to ECLS deployment and
and uses of ECLS. The ELSO Registry has also incorporating dates and times associated with
played a role in ensuring the quality of ECLS the development of individual complications.
practice by providing center-specific reports, Newer complication variables such as limb
allowing a center to compare their outcomes ischemia were also added to the Registry. The
to other centers. Starting in 2014, the ELSO database also began formalizing a definitions
Registry additionally provided a benchmarking manual, instruction manual, and plans to start
summary specific for this purpose and allowed a revalidating center data entry measuring centers’
center to compare their results to similar volume inter-rater reliability.
centers, driving quality assurance and clinical
improvement (see Chapter 68). At the time of Registry Data Collection
this writing there are more than 220 manuscripts
listed in PubMed that have included ELSO in Data Variables
the keywords and more than 1,000 studies of
ECMO in 2016. In addition to aiding individual The Registry includes details on several
centers, the ELSO Registry has also been used aspects of ECLS support. Patient demographic
by both industry and regulatory agencies to aid information comprises age, weight, gender, and
in the approval of new devices for cardiorespira- race. For neonates, information on the mode
tory support.1 For example, efficacy of ECMO of delivery, birth weight, maternal age, Apgar
used as a bridge to cardiac transplantation was scores, gestational age, and delivery type are
compared to similar outcomes for children collected. If a congenital diaphragmatic hernia
supported with the Berlin Heart VAD. ECLS (CDH) is present, details on this condition in-
data were provided from the ELSO database cluding laterality are collected.
and this study led to the approval of the Berlin Each patient can have one or multiple ECLS
Heart VAD in the U.S.1 Furthermore, publica- support courses. Data collected from each
tions using ELSO data have helped provide course include diagnoses, procedures, culture
insight into clinical outcomes such as survival results with infectious organisms and specimen
and risk factors for mortality for patients sup- type, pre-support information such as admission
ported with ECLS. time, conditions, and therapies used to support
During the four decades of data acquisi- the patient prior to ECLS. Diagnoses are entered
tion, clinical care of all patient groups and as either primary or secondary (multiple) and
diseases treated has progressed. Consequently, are standardized as ICD-9 codes for data en-
the Registry has had to evolve as well. A de- tered prior to 2016, and ICD-10 codes for data
tailed history of the technological aspects of entered after 2016. A crosswalk of codes was
the Registry is available elsewhere.2 In brief, created which allows queries to gather accurate
initially, the Registry contained four individual information across eras regardless of which
databases; however, with the expansion of the generation of ICD was used. Procedure codes
use of ECMO during the 1990s, the database are standardized as and recorded as CPT codes.
was reengineered to a single relational database Pre-ECLS measurements including blood gases,
with a single uniform entry and predefined cat- ventilator settings, and hemodynamics are
egories and classifications. In 2011 the Registry collected. Dates of support, support type and
incorporated mandatory data fields. In 2016, the mode, cannulation details, and equipment used
Registry added logical entry limits for data to are included. An additional set of measurements
help prevent incorrect data entry. In addition, of blood gases, ventilator settings, and hemo-
810
dynamics are repeated at 24 hours post-ECMO medications, equipment and priming informa-
initiation. tion, return of spontaneous circulation (ROSC)
Complications associated with the ECLS times, and cooling details.
course are recorded using predefined catego-
rized complications. Historically, complica- Registry Reports
tions have been recorded as either occurring or
not. This limitation to the Registry impacted the Historically, the Registry reports were pub-
ability to identify complications that occurred lished twice a year and distributed to member
multiple times. Starting in 2016, each compli- centers, initially on paper and subsequently
cation is recorded with a specific time and date electronically in two formats. The International
stamp which allows the collection of multiple Summary includes ELSO-wide data and is dis-
instances of a complication. Additionally, this tributed to all participating centers (Figure 72-1).
allows centers and researchers to determine Additionally, each center receives a report that
when during the course the complications are details their institution’s data related to each
occurring. Finally, outcome data such as sur- of the patient groups (neonatal respiratory,
vival, discontinuation reason, organ failures, pediatric respiratory, neonatal and pediatric
and discharge information are recorded. cardiac, adult respiratory and cardiac) permit-
ting each center to evaluate their experience
Registry Addenda and outcomes. Additional reports are available
to member centers as well, including trends,
The main Registry form contains general complications, devices, and benchmarking.
information about each ECLS course. In doing Reporting was limited to twice a year, because
so, it lacks more specialized data, which are generating these reports required taking the
important for some ECLS applications. In the ELSO Registry off line necessitating multiple
use of ECLS for cardiac support for example,
specialized information includes descriptions ECLS Registry Report Extracorporeal Life Support Organization
2800 Plymouth Road
Building 300, Room 303
of complex congenital cardiac abnormalities International Summary Ann Arbor, MI 48109
January, 2017
and specifics on the cardiac surgical procedures
performed. These data are unique to cardiac sup- Overall Outcomes
port, and no standardized classification systems Total Runs Survived ECLS Survived to DC or
Transfer
adequately document such parameters. Neonatal

Pulmonary 29,942 25,205 84% 21,948 73%
In 2001 ELSO initiated a cardiac addendum

Cardiac 7,169 4,643 64% 2,938 40%
ECPR 1,532 1,028 67% 627 40%
Pediatric
to the Registry to record additional case-specific Pulmonary

Cardiac
8,070
9,362
5,424
6,404
67%
68%
4,632
4,758
57%
50%
data related to use of ECLS following congeni-

ECPR 3,399 1,958 57% 1,414 41%
Adult
Pulmonary 12,346 8,242 66% 7,157 57%
tal heart disease (CHD) surgery. Additional data Cardiac

ECPR
10,982
3,485
6,251
1,382
56%
39%
4,466
993
40%
28%
collection for the CHD addendum is performed Total 86,287 60,537 70% 48,933 56%
through web based data entry and includes Centers
ELSO-developed diagnosis and procedure

codes, surgical procedure details, functional
evaluation, and outcome.
With the increasing use of ECLS in aid of
cardiopulmonary resuscitation (ECPR), another
addendum was created in 2011 which included Count
Cases
the online Registry release. Data contained in

this addendum document resuscitation times, Figure 72-1. Example of ECLS Report.
Tuesday, January 31, 2017 (c) 2017 Extracorporeal Life Support Organization
Page 1 of 34
811
Chapter 72
hours of data scrubbing, producing hand gener- and perhaps by generalized increase in patient
ated reports for the individual centers. With the complexity.12
2016 changes to the ELSO Registry, the reports
are now available on demand from the ELSO Pediatric Trends
website for member centers, and contain the lat-
est data contained in the Registry. Periodically, Pediatric (>29 days to 17 years) respiratory
the results of the ELSO Registry are formally ECLS has seen consistent growth over the past
published in the medical literature to allow in- two decades. Utilization has increased from 213
sight into the outcomes of these patients to the courses in 1995 to the largest ever number of
wider medical community.3-11 584 deployments in 2015. Despite the increase
in utilization and more complex patients be-
Current Registry Data Summary ing supported,12 pediatric respiratory ECMO
survival has remained fairly stable over that
Based on data distributed to member cen- period at approximately 55-60%. The most
ters in January 2017, data are reported from common indication for pediatric respiratory
318 member centers providing 86,287 ECLS ECLS includes infectious pneumonias. While
courses. Overall survival to discharge is 56%. the predominant mode of cannulation in the
A summary of patient outcomes stratified by Registry remains venoarterial, a trend has been
age and indication are provided in Table 72-1. seen over the last 10 years towards venovenous
use. This change has been attributed to the in-
Neonatal Trends creasing availability of pediatric sized double
lumen cannulas which allow single site cannu-
Refractory neonatal respiratory failure was lation. Average run duration is longer than the
the initial indication for ECLS use. It remains neonates, at approximately 280 hours.
the largest single population of patients in the
ELSO Registry and maintains the highest sur- Adult Trends
vival to discharge. Neonatal respiratory ECLS
use has fallen approximately 50% from a peak ECLS use is increasing rapidly in the adult
of 1515 runs in 1992 to 856 runs in 2015. Much respiratory population. Since 2009, adult re-
of the decline of neonatal respiratory ECLS spiratory ECLS use has grown exponentially
use has been attributed to the development and (Figure 72-2) with 2,192 runs in 2015. The
increasing use of technologies such as high rapid expansion of adult respiratory ECLS has
frequency oscillating ventilation, surfactant, been attributed to positive results during the
and inhaled nitric oxide. Common diagnoses H1N1 influenza epidemic13 and the publication
for neonatal respiratory failure include persis- of the CESAR trial,14 a randomized controlled
tent pulmonary hypertension of the newborn, trial in the United Kingdom demonstrating
meconium aspiration, sepsis, and congenital improved survival without disability in patients
diaphragmatic hernia. Venoarterial ECLS re- randomized to transfer to an ECLS center. Simi-
mains the most common cannulation strategy lar to pediatric patients, infectious pneumonias
for these patients. Average ECLS duration has leading to refractory acute respiratory distress
been increasing from approximately 150 hours syndrome are the most common indications. In
in the 1990s to 210 hours in 2015, which prob- contrast to the younger age groups, venovenous
ably relates to the increase in the proportion ECLS is the predominant mode of cannulation.
of neonates receiving ECLS who have CDH Survival since 2009 has remained consistent
812
between 55-60%, with an average duration of and pediatric cardiac courses ever performed.
ECLS of approximately 280 hours. Similar to the younger patients, approximately
40% survival has been seen in this population.
Cardiac Trends
Summary
The use of ECLS in association with the
management of congenital heart disease both The ELSO Registry has played an essential
in the neonatal and pediatric periods continues role in the growth of ECMO as a mechanical
to increase. Survival in these patients is less device for cardiorespiratory support. It has
than that seen for respiratory ECMO; however, evolved along with the development of ECMO,
it has remained fairly consistent between 40- and has changed to meet the needs of the ELSO
50%. ECPR use in these groups of patients member centers and the wider medical commu-
is also increasing, with approximately 40% nity. The ELSO Registry provides the ability
survival to discharge. Similar to the adult re- for centers to perform quality analysis of their
spiratory patients, the adult cardiac population outcomes, and improve the overall care for their
is undergoing exponential growth as well. As patients. It remains the most comprehensive
an example of the rapid rate of rise, in the last and authoritative database of patients that have
five years the amount of adult cardiac applica- received extracorporeal life support worldwide.
tions is approximately 50% of all of the neonatal
Adult Respiratory Cases
2500 9000
8000
2000 7000
Cumulative Runs
6000
Annual Runs
1500
5000
4000
1000
3000
500 2000
1000
0 0
17 ELSO Registry January 2017
Figure 72-2. Adult respiratory ECMO use by year.
813
Chapter 72
References and pediatric cardiac cases. ASAIO journal

(American Society for Artificial Internal
1. Fraser CD, Jr., Jaquiss RD, Rosenthal DN, Organs : 1992). 2009;55(1):111-116.
et al. Prospective trial of a pediatric ven- 10. Paden ML, Conrad SA, Rycus PT, Thiaga-
tricular assist device. The New England rajan RR. Extracorporeal Life Support
journal of medicine. 2012;367(6):532-541. Organization Registry Report 2012. ASAIO
2. Annich GM, Lynch WR, MacLaren G, Wil- journal (American Society for Artificial In-
son, JM, Bartlett RH, eds. Extracorporeal ternal Organs : 1992). 2013;59(3):202-210.
Cardiopulmonary Support in Critical Care. 11. Thiagarajan RR, Barbaro RP, Rycus PT, et al.
4 ed 2012. The Registry of the Extracorpo- Extracorporeal Life Support Organization
real Life Support Organization. Registry International Report 2016. ASAIO
3. Toomasian JM, Snedecor SM, Cornell RG, journal (American Society for Artificial
Cilley RE, Bartlett RH. National experi- Internal Organs : 1992). 2017;63(1):60-67.
ence with extracorporeal membrane oxy- 12. Zabrocki LA, Brogan TV, Statler KD, Poss
genation for newborn respiratory failure. WB, Rollins MD, Bratton SL. Extracorpo-
Data from 715 cases. ASAIO transactions. real membrane oxygenation for pediatric
1988;34(2):140-147. respiratory failure: Survival and predic-
4. Stolar CJ, Snedecor SM, Bartlett RH. tors of mortality. Critical care medicine.
Extracorporeal membrane oxygenation 2011;39(2):364-370.
and neonatal respiratory failure: experi- 13. Davies A, Jones D, Bailey M, et al. Extra-
ence from the extracorporeal life support corporeal Membrane Oxygenation for 2009
organization. Journal of pediatric surgery. Influenza A(H1N1) Acute Respiratory Dis-
1991;26(5):563-571. tress Syndrome. Jama. 2009;302(17):1888-
5. Stolar CJ, Delosh T, Bartlett RH. Ex- 1895.
tracorporeal Life Support Organization 14. Peek GJ, Mugford M, Tiruvoipati R, et
1993. ASAIO journal (American Society al. Efficacy and economic assessment of
for Artificial Internal Organs : 1992). conventional ventilatory support versus
1993;39(4):976-979. extracorporeal membrane oxygenation
6. Tracy TF, Jr., DeLosh T, Bartlett RH. Ex- for severe adult respiratory failure (CE-
tracorporeal Life Support Organization SAR): a multicentre randomised con-
1994. ASAIO journal (American Society trolled trial. Lancet (London, England).
for Artificial Internal Organs : 1992). 2009;374(9698):1351-1363.
1994;40(4):1017-1019.
7. Bartlett RH. Extracorporeal Life Support
Registry Report 1995. ASAIO journal
(American Society for Artificial Internal
Organs : 1992). 1997;43(1):104-107.
8. Conrad SA, Rycus PT, Dalton H. Extracor-
poreal Life Support Registry Report 2004.
ASAIO journal (American Society for Arti-
ficial Internal Organs : 1992). 2005;51(1):4-
10.
9. Haines NM, Rycus PT, Zwischenberger JB,
Bartlett RH, Undar A. Extracorporeal Life
Support Registry Report 2008: neonatal
814
Glossary
ACT Activated Clotting Time
APTT Activated Partial Thromboplastin Time
ARDS Acute Respiratory Distress Syndrome
AVCOR Arteriovenous Carbon Dioxide Removal
CPR Cardiopulmonary Resuscitation
CPB Cardiopulmonary Bypass
CRRT Continuous Renal Replacement Therapy
CVP Central Venous Pressure
DIC Disseminated Intravascular Coagulation
ECCOR Extracorporeal Carbon Dioxide Removal
ECLS Extracorporeal Life Support
ECMO Extracorporeal Membrane Oxygenation
VA Venoarterial
VAV Venoarteriovenous
VV Venovenous
VVA Venovenoarterial
ECMO I ECMO using traditional roller pumps and silicon membrane oxygenators
ECMO II ECMO using Mendler-designed centrifugal pumps and polymethylpentene
hollow-fiber oxygenators
ECPR Extracorporeal Cardiopulmonary Resuscitation
ELSO Extracorporeal Life Support Organization
FiO2 Fractional Inspired Oxygen Concentration
HFOV High Frequency Oscillatory Ventilation
ICU Intensive Care Unit
IPPV Intermittent Positive-Pressure Ventilation
MAP Mean Arterial Pressure, or
Mean Airway Pressure
NICU Neonatal Intensive Care Unit
NIV Non-invasive Ventilation
PCO2 Partial pressure of carbon dioxide
PO2 Partial pressure of oxygen
PEEP Positive End-Expiratory Pressure
PICU Pediatric Intensive Care Unit
PIP Peak Inspiratory Pressure
Pplat Plateau Inspiratory Pressure
PT Prothombin Time
RPM Revolutions Per Minute
SvO2 Mixed venous oxygen saturation
VAD Ventricular Assist Device
LVAD Left Ventricular Assist Device
RVAD Right Ventricular Assist Device
BiVAD BiVentricular Assist Device
815
Appendix 1: Pediatric ECLS Cannula Characteristics
Appendix 1: Pediatric ECLS Cannula Characteristics
Brand Product Type Size Length Flow ∆ Flow ∆ Flow ∆

(Fr) (cm) (ml/ Pressure (ml/ Pressure (ml/ Pressure
min) (mm min) (mm min) (mm Hg)
Hg) Hg)
Medtronic Bio- Art 8 10 250 20 500 60 750 135
Medicus
NextGen
10 10.5 500 25 750 42 1000 100
12 11 750 18 1000 28 1500 75
14 11.5 1000 12 1500 28 2000 50
Bio- Ven 8 10 250 12 500 50 750 105
Medicus
NextGen
10 10.5 500 18 750 35 1000 60
12 11 750 13 1000 23 1500 48
14 11.5 1000 12 1500 27 2000 45
All pressures were measured using water as the medium. Flows are measured in ml/min. Changes in
pressure are measured in mm Hg.
Abbreviations: Fr = French, Art = Arterial, Ven = venous, ∆ pressure = change in pressure
We gratefully acknowledge this contribution from the Euro-ELSO Working Group on Technological
Innovation.
817
Appendix 2: Adult ECLS Cannula Characteristics (Edwards)
Appendix 2: Adult ECLS Cannula Characteristics (Edwards)

min) (mm min) (mm Hg) min) (mm Hg)
Hg)
Edwards Fem- Art 16 15 1500 20 2000 38 3000 90
Flex II
18 15 2000 18 3000 45 4000 85
20 15 3000 30 4000 50 5000 80
16 15 1500 20 2000 38 3000 90
18 15 2000 18 3000 45 4000 85
20 15 3000 30 4000 50 5000 80
Edwards Quick Ven 22 65 2000 15 3500 40 5000 78

Draw
Fem 25 65 2500 14 4000 32 5000 45
Venous
VFEM Ven 18 55 2000 30 3000 73 3500 100
20 55 2000 17 3000 41 4500 98
22 55 2500 23 3500 43 5000 83
24 68 3000 25 4000 44 5000 65
28 68 3500 15 4000 20 5000 30
Innovation.
818
Appendix
Appendix 3:3: Adult
Adult ECLS
ECLS Cannula
Cannula Characteristics
Characteristics (Medtronic) (Medtronic)

min) (mm min) (mm min) (mm
Hg) Hg) Hg)
Medtronic Bio- Art 15 18 1000 12 2000 42 3000 97
Medicus
Next
Gen
17 18 2000 22 3000 33 4000 95
19 18 3000 28 4000 30 5000 83
21 18 4000 34 5000 52 6000 75
23 18 4000 21 5000 34 6000 50
25 18 4000 14 5000 20 6000 28
Bio- Ven 15 18 1000 12 2000 42 3000 97
Medicus
Next
Gen
17 18 2000 30 3000 60 4000 107
19 18 3000 35 4000 60 5000 90
21 18 4000 40 5000 62 6000 85
23 18 4000 27 5000 42 6000 58
25 18 4000 20 5000 30 6000 42
Bio- Ven 15 50 1000 22 2000 75 3000 160

Medicus
Next
Gen
17 50 1500 27 2500 64 4000 150
19 55 2000 25 3000 52 5000 130
21 55 3000 32 5000 80 6000 110
23 60 3500 30 5000 56 6000 80
25 60 4000 27 5000 38 6000 55
27 60 4000 20 5000 35 6000 41
29 60 4000 14 5000 22 6000 30
Innovation.
819
Appendix
Appendix 4:4:Adult
Adult ECLS
ECLS Cannula
Characteristics (Maquet) (Maquet)

min) (mm min) (mm min) (mm Hg)
Hg) Hg)
Arterial
HLS
Maquet cannula Art 15 15 1500 28 2500 72 3500 155
17 15 2000 27 3000 54 4000 103
19 15 2500 25 3500 46 5000 96
21 15 3000 22 4000 40 6000 88
23 15 3000 16 4500 34 6000 61
15 23 1500 30 2500 90 3000 140
17 23 2000 30 3000 70 4000 130
19 23 2500 30 3500 60 5000 120
21 23 3000 32 4000 61 6000 105
23 23 3000 20 4000 33 6000 72
Venous
HLS
cannula Ven 19 38 2000 23 3500 65 5000 125
21 38 2500 23 4000 53 5500 95
23 38 3000 16 5000 52 6000 85
25 38 3500 20 5000 37 6000 54
21 55 2500 25 4000 58 5000 90
23 55 3000 26 4500 51 5500 92
25 55 3500 23 5000 42 6000 60
29 55 4000 16 5000 26 6000 36
Innovation.
820
Appendix5:5:Adult
Appendix Adult ECLS
ECLSCannula Characteristics
Cannula (Sorin) (Sorin)
Characteristics

Hg)
Sorin FA-19 Art 19 20 3000 35 5000 105 6000 140
FA-21 21 20 3000 19 5000 52 6000 80
FA-23 23 20 3000 12 5000 32 6000 46
Venous
Cannula
200-200 Ven 23 35.6 3000 33 5000 55 6000 90
Venous
Cannula
200-100 22 68.7 3000 60 5000 107 6000 130
Venous
Cannula 23/2
200-150 5 72.5 3000 40 5000 55 6000 72
FV-
319/BF
V-319 19 55 3000 60 5000 130 6000 >160
FV-
323/BF
V-323 23 60 3000 28 5000 65 6000 87
Innovation.
821
Appendix6:6:Adult
Appendix Adult ECLS
ECLS Cannula Characteristics
Cannula (Medos) (Medos)
Characteristics

Hg)
MEFKA
16,
MEFKA
Medos 16L Art 16 168 1500 30 2500 85 3500 170
MEFKA
18 18 168 2000 27 3000 64 4000 118
MEFKA
20 20 168 2500 25 3500 46 5000 103
MEFKA
22 22 168 3000 24 4000 43 6000 90
MEFKA
24 24 168 3500 18 4500 33 6000 55
MEFKA
26 26 168 4000 16 5000 22 6000 30
MEFKV
18,
MEFKV
18L Ven 18 592 1500 39 2500 100 3500 176
MEFKV
20 20 592 2000 36 3000 80 4000 140
MEFKV
22 22 592 2500 31 3500 60 5000 117
MEFKV
24 24 592 3000 28 4000 52 6000 110
MEFKV
26 26 592 3500 24 4500 38 6000 67
MEFKV
28 28 592 4000 20 5000 28 6000 44
Innovation.
822
Appendix 7:
Appendix 7:Double
DoubleLumen ECLS
Lumen Cannula
ECLS Characteristics
Δ Δ Δ Δ
Size pressure pressure Flow of pressure pressure Connector
Brand Product (Fr) Flow (Ven) (Art) medium (Ven) (Ven) size
Avalon
Maquet Elite 13 500 30 97 750 58 205 1/4"
Avalon
Elite 16 750 25 95 1200 55 238 1/4"
Avalon
Elite 19 1200 30 90 2000 75 230 1/4"
Avalon
Elite 20 1000 20 73 2000 90 120 3/8"
Avalon
Elite 23 2000 50 120 3000 97 242 3/8"
Avalon
Elite 27 3000 40 121 4250 80 240 3/8"
Avalon
Elite 31 4250 30 108 6000 70 226 3/8"
Origen 13 500 38 280 600 48 370 1/4"

15 750 50 128 1200 55 288
16 750 40 250 1000 70 402 1/4"

18 1200 52 180 1900 115 400
19 1200 60 305 1400 75 385 1/4"
23 2000 55 197 2500 80 215 3/8"
28 3000 60 210 4250 98 370 3/8"
32 3/8"
All pressures were measured using water as the medium for the Avalon cannula and human whole blood
for the OriGen cannula
Innovation.
823
Index
A Antifibrinolytic Therapy 115

Antithrombin 93,97
Abdominal Compartment Syndrome 170 Aorta 349
Abdominal Wall Defects 170 Aortocaval Compression 584
Access 294 Apheresis 701
Activated Clotting Time 94, 95 Aprotinin 352
Activated Partial Thromboplastin Time 94, 95 Arctic Environment 607
Acute Cardiopulmonary Failure 649 ARDS 231, 240, 267, 405, 406, 409, 416, 471,
Acute Chest Syndrome 703 472, 713
Acute Complications 533 Arteriovenous CO2 Removal 46
Acute Fulminant Myocarditis 484 Asia-Pacific ELSO 26
Acute Hypoxemic Respiratory Failure 407 Aspiration Pneumonitis 240
Acute Kidney Injury 255, 362, 551, 534, 697 Assessment Cannula Sites 287
Acute Myocardial Infarction 479 Assessment Cardiac Function 284
Acute Myocarditis 484 Assessment Gastrointestinal System 284
Acute Neurologic Events 397, 536 Assessment Genitourinary System 284
Acute Renal Failure 257 Assessment Head-To-Toe 283
Additional Drainage Cannula 248 Assessment Neurological Status 283
Adult Educational Theory 748 Assessment Respiratory System 283
Adults with Congenital Heart Disease 331 Autoimmune Diseases 670
Adverse Effects/Transport Complications 605 Avalon Elite® Dual Lumen Bicaval Cannula 433
Age 442 Awake ECMO 642
Air Embolism 59, 65 Award of Excellence 737
Air Entrainment 353 Axillary Artery Cannulation 524
Air Leak 234
Airway Hemorrhage 450 B
Albumin 115
Al Gazzaniga 18 Bacterial Pneumonia 240
Alveolar Capillary Dysplasia 169 Balloon Atrial Septostomy 352
Amicar 352 Benchmarking 769, 810, 811
Amplitude Integrated EEG 191 Benefits 774
Antiarrythmics 627 Berlin Heart 810
Anticoagulation 725 Beta-Blockers 627
Antidotes 628 Better Bladder 55
Anti-factor Xa Assay 96 Bicaval Cannula 251, 431
825
Blalock-Hanlon Procedure 352 Checklists And Preventative Care 459
Blalock-Taussig (BT) 369 Chemotherapy 665
Blood Flowmeter 73 Chest Injuries 593
Blood Protective Flow 535 Chorioamnionitis 589
Blood Pump 52 Chromosomal Abnormalities 360
Blunt Thoracic Trauma 595 Chronic Cardiomyopathy 490
Bowel Management 463 Chronic Liver Disease 442
Bridge-To-Bridge 650 Chronic Renal Failure 442
Bridge To Nowhere 644 Chronic Renal Failure 443
Bridge To Recovery 713 Chylothorax 177
Bridge To Transplantation 639, 713 Circuit Access Sites 74
Bronchiolitis Obliterans 668 Circuit Alarms 74
Bronchopulmonary Dysplasia 169 Circuit Check 561
Bronchoscopy 186, 277, 450, 682 Circuit Components 52
BTT 639 Circuit Management 73
Burns 235, 594 Circuit Modifications 88
Circuit Monitoring 73
C Circuit Pressures 73
Calcium Channel Blockers 627 Circuit Priming 73
Cancer 257 Circulatory Failure 561
Cannulation 159, 247, 640, 651 Clotting Factor Concentrate 353
Cannulation Strategies 657 CO2 Removal 45
Cardiac Addendum 811 Coagulation 82, 87
Cardiac And Pulmonary Considerations 371 Coagulation Factor 111
Cardiac Arrest 257, 259, 501, 519 Coagulopathy 352
Cardiac Catheterization 682 Coexisting Conditions 256
Cardiac ECMO 313 Collaborative Communication 786
Cardiac Surgery 517 Commercial Centrifugal Pumps 60
Cardiogenic Shock 360, 517, 562 Commercial Gas Exchange Devices 65
Cardiohelp 69 Comorbid Conditions 257
Cardiomyopathy 310, 650 Comorbidities , 243
Cardiopulmonary Bypass 37, 481 Compartment Syndrome 526
Cardiopulmonary Pathophysiology 33 Complications 252, 297, 300, 395, 397, 472, 518,
Cardiopulmonary Physiology 31 562
Cardiopulmonary Resuscitation 501 Congenital Diaphragmatic Hernia 183, 217
Cardiothoracic Surgery 395, 396 Congenital Heart Disease , 339, 341, 395, 358,
Cardiotoxics 628 324
Cardiovascular Drugs 627 Congenitally Corrected Transposition Of Great
Carotid Artery 214 Arteries 332
Cavitation 57 Contractility 570, 571
Central Cannulation 618, 622 Contraindications to ECMO in ACHD 334
Central ECMO 524 COPD 418
Centrifugal Blood Pumps 54, 60, 66 Coronary Artery Bypass Grafting 480
CentriMag 724 Cost 741, 773
Centrimag Magnetic Levitated Pump 62 Cost Effectiveness 774
Cerebral Blood Flow 268 Credentialing 733
Cesarean Section 588, 684 Crrt 454, 698
Cesar Trial 775 Cryoprecipitate 109, 110
Chattering 58 Cutdown Access 250
826
Index
D Esperanza 4, 19
Ethical Permissibility 784
Daily Activity 287 Ethics Consultation 786
Daily Patient Care-Nursing 284 EuroELSO 25
Damage 572 Eurosets Oxygenators 69
Decannulation 166, 213,291, 390 EXCOR Trial 650
DEHP 51 Exercise 220, 222
Delirium 453 Extracorporeal Membrane Oxygenation (ECMO)
Development 1, 731 Initiated During CPR (ECPR) 321
Device Thrombosis 71 Extubation 276
Differential Cyanosis 618, 619 Eye Care 286
Diffuse Alveolar Damage 410
Diffuse Alveolar Hemorrhage 668 F
Direct Thrombin Inhibitors 94
Discontinuation of ECMO 390 Family Support 207, 383
Distal Arterial Perfusion 432 Femoral Veins 247
Dual Lumen Cannulation 431, 433 Fentanyl 799
Duration of CPR 323 Fetus 583
Dysrhythmias 538 FFPp 109
Fiberoptic Bronchoscopy 408
E Fibrinogen 105
Fibrinolysis 82
Early Mobilization 640, 643 Fibrinolytic Pathway 83
ECCO2R 418, 420, 713, 716, 717 Finance 776
Echocardiography 552, 570 Flow 616, 618, 619
ECLS Circuit Observations and Monitoring of Fluid Overload 697
Circuit Function 460 Fluoroscopy 430, 431
ECLS Specific Nursing Care 459 Followup 217, 224
ECMO 642, 643, 713, 716, 717
ECMO for Cardiopulmonary Resuscitation G
(ECPR) 332
ECMO Posttransplantation 643 Gas Exchange Devices 63
ECMO Specialist 562, 733 Gas Exchanger Related Complications 70
ECMO Taxi 607 General Nursing Care of ECLS Patient 461
ECMO Team 502, 517, 561 Genetic Abnormalities 176
ECMO Weaning 387 Genetic Anomalies 258
Economic Evaluations 774 Get With The Guidelines - Resuscitation Registry
ECPR 258, 259, 309, 321, 383, 811, 813 (GWTG-R) 322
ECPR Cannulation Technique 504 Glenn or Fontan Circulation 358
ECPR Team 326 Golden Window 352
Education 748 Graft vs. Host Disease 667
ELSO Global Chapters 10 Duidelines 765
ELSO International Summary 322
ELSO Registry 8, 768
Emerging Economies 777
Endocrine-Related Cardiogenic Shock 488
Endothelial 88
Endothelial Cells 86
Endotracheal Extubation 642
Endstage Respiratory Failure 642
827
Index
H Internal Jugular Veins 247

International Transports 607
H1N1 Influenza Pandemic 583, 588 Intraaortic Balloon Counterpulsation 351
Harlequin Syndrome 537, 551, 564 Intraaortic Balloon Pump 479, 653, 722
Heart Failure 360 Intracranial Hemorrhage 191, 205
Hematopoietic Stem Cell Transplant (HSCT) 233, Intra-Hospital Transport 608
667 Intraoperative and Posttransplantation Settings
Hemodynamic 569, 570, 572 643
Hemofiltration 260 Intraventricular Hemorrhage (IVH) 175
Hemoglobin Saturation Measurement 74 Invasive Mechanical Ventilation 639, 713
Hemolysis 54, 55, 57, 188, 473, 538 IVH 260
Hemorrhage 259, 260, 261
Hemostasis 83 J
Heparin 249
Heparin-Induced Thrombocytopenia 94 Jugular Vein 214
Higher Volumes 742
Human Immunodeficiency Virus (HIV) 669
L
Hyaline Membrane Disease 123, 128 Laparotomy 685
Hydrophilic 795, 797, 803 Latin-American ELSO 27
Hygiene And Infection Prevention 462 Left-Sided Decompression 652
Hyperperfusion Syndrome 335, 526 Left Ventricular 480
Hypoplastic Left Heart Syndrome 395, 397 Left Ventricular Afterload 39
Hypoxia 271 Left Ventricular Distention 334
Hypoxic Respiratory Failure 169 Left Ventricular Overload 538
Leg Ischemia 525
I Leukocytes 85
Idiopathic pneumonia syndrome 668 Levetiracetam 803
Immune dysregulation 87 Liberation And Decannulation 468
Immunocompromised 233 Limb Ischemia 335
Immunodeficiency 172 Lipophilic 795, 797, 799, 802
Immunosuppressed hosts 407 Lipophilicity 795, 797
Impella 723 Livanova EOS ECMO 68
Implementation 733 Livanova Revolution Centrifugal Pump 61
IMV 639 log P 797, 802, 803
Inadequate Support 252 Long-Distance Transports 607
Inborn Errors of Metabolism 176 Longer-Term Neurodevelopmental Outcomes 397
Indications for ECMO Support in ACHD 333 Long-Term Followup 314
Infection 173, 272, 454, 613, 614 Long-Term Neurological, Functional, And Sur-
Inflammatory Response 84 vival Outcomes 327
Informed Consent 783 Long-Term Outcomes 297, 299, 472
Inhalational Injury 594 Lower Extremity Ischemia 536
Inhaled Nitric Oxide (iNO) 125, 276 Low-Flow Phase of CPR 321
Initiation of VV-ECLS 466 Luciano Gattinoni 9, 21
Inlet Pressure 55 Lung Biopsy 292, 687
Inotrope 372 Lung Function 219, 222, 224
Inotropic 451, 452 Lung Protective Ventilation 243
Institute of Medicine 765 Lung Rest 293, 380
Inter-Hospital Transport 599 LV Unloading 518
INTERMACS 721
828
Index
M Norwood 340
Nosocomial Infections 380, 473, 554
Magnetic Levitation 55 Not Venting 351
Maintaining VV-ECLS 466 Novalung 68
Major Injuries 593 Nursing Care 201, 283
Major Trauma 593 Nutrition 273, 454, 462
Malignancy 443, 665
Maquet Quadrox- iD 66 O
Massive Acute Pulmonary Embolism 486
Mechanical Chest Compression 501 Obesity 442
Mechanical Circulatory Support 721 Open Lung Biopsy 410
Meconium Aspiration Syndrome 123, 126, 184 Oral Hygiene 285
Mediastinal Masses 233 Organ Supply 650
Medical Futility 784 Oseltamivir Pharmacokinetics 802
Medos Deltastream 63 Outcomes 308
Medos Hilite LT 66 Outlet Pressure 60
Medtronic Affinity Centrifugal Pump 62 Out Of Hospital Cardiac Arrest 325
Membrane Stabilizing 628 Out Of Hospital Refractory Cardiac Arrest 518
Miller’s Triangle 748 Oxygenation Failure 240
Mistake-Proofing 735 Oxygen Content 32
Mobilization 567 Oxygen Debt 267
Monitoring Techniques 55 Oxygen Delivery 32, 63, 379
Morbid Obesity 442 Oxygen Transfer 34
Morphine 798
Motor Function 224
P
Motor Function Development 221 Pacing 370
Multidisciplinary Teams 741 Palliative Care 787
Multimorbidity 539 Paracorporeal Pumps 650
Multiorgan Dysfunction Syndrome 703 Paragon Oxygenator 69
Multiorgan Failure 479 Patient Moves And Pressure Area Care 461
Myocardial 570, 571 Patient Selection for ECPR 323
Myocardial Stun 368 Pearl O’Rourke 5
Myocarditis 340, 651 PEEP 406
Percutaneous Access 248
N Percutaneous Cardiopulmonary Bypass 501
Native Venous Flow 41 Percutaneous Coronary Intervention 479
Near Infrared Spectroscopy (NIRS) 505 Perfusion Cannula 526
Needs Assessment 731 Perfusionist 742
Negative Pressures 58 Peripheral ECMO 525
Neonatal ECMO Trial off 212 Peripheral venoarterial ECMO 561
Neonatal Encephalopathy 175 Persistent Pulmonary Hypertension 123, 125
Neurodevelopmental Outcomes , 217, 395 Persistent Pulmonary Hypertension Of The Neo-
Neurological Injury 362 nate 184
Neurologic Examinations 275, 381 Persistent Pulmonary Hypertension Of The New-
Neurologic Injury 323 born (PPHN) 126, 169
Neuropsychological Development 222 Pharmacokinetic 796, 798, 801, 802, 803
Neurosurgery 686 Phenobarbital 803
Nipro Biocube 69 Physical Therapy 640
No-Flow 321 Plasma 109
Platelets 83, 85, 87
829
Index
Platelet Transfusion 109 Registry Reports 811

Pneumocystis Jiroveci 669 Rehabilitation 234
Poisoning 627, 631 Reimbursement 776
Polymethyl Pentene 51, 65 Renal Failure 261, 272, 700
Polyvinylchloride 51 Renal Insufficiency 260
Postcardiotomy 481 Renal Replacement Therapy 551
Power Failure 59 Reperfusion Technique 506
Preeclampsia 589 Residual Cardiac Lesions 370
Pre-ECMO Cardiac Arrest 359 Residual Lesions 392
Preexisting Comorbidities 255 Resistance 248
Prematurity 177 Resource Utilization 782, 784
Preparation And Communication 680 Respiratory Failure 415
Pressure Gradient 64 Rest Settings 248
Pressure Ulcers 285 Rest Ventilatory Settings 449
Primary Graft Dysfunction 655 Results and Outcomes Following ECMO for
Primary Transport 600 ACHD 335
Prognosis 388 Retrograde Flow 59
Prolonged Immobilization 382 Retrograde Trial Off 213
Prone Positioning 203, 278, 292, 450 Return Of Spontaneous Circulation (ROSC) 501
Propofol 799 Rhythm Analysis 507
Protamine 352 Right Atrial Appendage 348
Prothrombin Complex Concentrates 114 Right Axillary/Subclavian Artery 350
Puerperium 583 Right Ventricular 486
Pulmonary Contusion 593 Risk Prediction Models 440
Pulmonary Edema 553 Robert Bartlett 3
Pulmonary Embolism 486 Robert E. Gross 18
Pulmonary Hemorrhage 234 Roller Pump 50, 53, 188
Pulmonary Hypertension 311 Roller Pump Servo Regulation 54
Pulsatility 52 RRT 255, 258, 260, 261
Pump Failure 59 RSV 240
Pump Related Complications 57
S
Q
SAPS3 701
Quality-Adjusted Life Years 773 Secondary Transport 600
Quality Improvement 765 Sedation 193, 203, 273, 452
Quality Of Care 765 Seldinger Technique 525
Quality Of Life 395, 397, 472 Sensorineural Hearing Loss 220
Sepsis 613, 620, 621, 622, 703
R Septic Shock 613, 614, 619, 621, 622
Rated Flow 63 Sergei Brukhonenko 1
RBC 106 Severe Brain Injury 595
Recirculation 45, 467 Severe Hypercapnic Respiratory Failure 418
Recombinant Activated Factor VII 353 Severity Of Illness 810
Recombinant Factor VIIa 111 Shortest Run Time 211
Reconstruction 214 Short-Term Outcome 297
Recovery 388, 569, 570, 571, 657 Single Care Giver Model 749
Refractory Cardiogenic Shock 479 Single Ventricle 312, 341, 369
Refractory Hypoxemia 416 Single Ventricle and Failed Fontan Circulation
Registry Addenda 811 331
830
Index
Single Ventricle Patients 380 Transpulmonary Flow 518

Skin Care 206, 285, 566 Trends in ECPR Utilization 322
Skin Integrity 382 Triage 741
Smaller Centers 742 Trialing 292
Smaller ECLS Center Volumes 261 Trisomy 21, 176
SNHL 222 Two-site VV-ECLS 431
Social Justice 784 Two Ventricle Physiology 380
South and West Asian ELSO 28
Stability 569, 570 U
Staff Support 463 UK collaborative ECMO 774
Staged Palliation 358 Ultrasound 248
Standardized Followup 224, 225 Unfractionated Heparin 93
Status Asthmaticus 232, 240, 418 Upper-Body 640
Storage 106
Surfactant 128, 292 V
Surrogate Decision Making 783
Survival Rate 395 VA-ECLS 432
Survival To Hospital Discharge 322 VA-ECMO 348
Sweep Gas 64 Vaginal Birth 588
Vancomycin 801, 804
T Vascular Graft 348
Vasoactive Support 268
Tamponade Of Venous Drainage 351 Vasopressor 451
Ted Kolobow 3, 18 Venoarterial ECMO 479, 517
Temperature Management 71 Venous Sinus Thrombosis 172
The Patient Who Cannot Be Weaned 469 Ventilation Failure 242
Therapeutic Hypothermia 193 Ventilator-Associated Lung Injury 713
Thoracotomy Drains 684 Ventilator Management 275
Thrombin 83 Venting 350
Thrombocytopenia Associated Multi-Organ Fail- Ventricular Assist Devices 479, 519, 649
ure 703 Ventricular Decompression 368
Thromboelastography 96 Ventricular Failure 367
Thromboelastometry 96 Ventricular Septal Defect 489
Thrombosis 59 VILI 415, 419
Total Artificial Heart 519 Viral Pneumonia 240
TPE 702 VV-ECLS 347, 430
Trachea-Bronchial 594 VV-ECLS Physiology 465
Tracheostomy 451, 684
Training 749 W
Transcatheter Aortic Valve Implantation 488
Transcutaneous Continuous Near-Infrared Spec- Water Based Heater-Cooler Units 72
troscopy 527 Weaning 211, 292, 555
Transfusion 105 Weaning ECCO2R 717
Transfusion Thresholds 105 Weaning Predictors 389
Transplantation 341, 396 Weaning Trial 389
Transport 743 Weaning VV-ECLS 468
Transport Equipment 603 Wound Care 286
Transport Stretcher 605
Transport Teams 602
Transport Vehicle 601
831

The Red Book ELSO 5th Edition

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The Red Book ELSO 5th Edition

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Extracorporeal Life Support:

The ELSO Red Book

Thomas V. Brogan, M.D.

Senior Editor: Thomas V. Brogan

©2017 Extracorporeal Life Support Organization, Ann Arbor, Michigan

Previous editions 1996, 2000, 2005, 2012

Printed in the United States of America

ELSO Member Centers 2017

Erik E. Abel, PharmD, BCPS Rubia Baldassarri, MD

Peta M. A. Alexander, MBBS Patricia Bastero, MD

Gail M. Annich, MD John Beca, MD

Veronica Armijo-Garcia, MD Dorothy M. Beke, RN, MS, CPNP-PC/AC

Matthew Bacchetta, MD Jan Bělohlávek, MD, PhD

Mirko Belliato, MD Daniel Brodie, MD

Yih-Sharng Chen, MD, PhD Carl F. Davis, MB, MCH, FRCS

Roberto Chiletti MD, FCICM Joseph A. Dearani, MD

Jonna Clark, MD Lorenzo Del Sorbo, MD

Alain Combes, MD, PhD Matteo Di Nardo, MD

Steven A. Conrad, MD PhD, MCCM Rodrigo Diaz, MD, MEd

Richard T. Fiser, MD Matthew T. Harting, MD, MS

Francis Fynn-Thompson MD Silvia M. Hartmann, MD

James D. Fortenberry, MD Chris Harvey, MB, ChB, MRCS

Björn Frenckner, MD, PhD Micheal L. Heard, RN

Samir K. Gadepalli, MD Maggie M. Hickey, RGN, RSCN

Antonella Galeone, MD, PhD Ronald B. Hirschl, MD

Isaac Hammond, PA-C Syed Hussain, MD

Hanneke IJsselstijn, MD, PhD Stephanie Larsen, BS RRT-NPS

Javier Kattan, MD Laurance L. Lequier, MD

Christa Jefferis Kirk, PharmD William R. Lynch, MD

Jos Maessen, MD, PhD Chirine Mossadegh, RN

Wesley A. McKamie, RRT CCP Jose Navia, MD

Naoto Morimura, MD, PhD Bhavesh M. Patel, MD, FRCP, RDMS

Thomas Pranikoff, MD, FACS Sameh M. Said, MD

Matthieu Schmidt, MD, PhD Rachel Sirignano, MD

Billie L. Short, MD, FELSO Sebastian Tume, MD

Krisa Van Meurs, MD

Leen Vercaemst, B.CP, ECCP, RN, RM

Gregor Walker, MB, MD, FRCS

Patrick Weerwind, PhD

Anne Marie Winkler, MD

I. Extracorporeal Life Support: General Principles

1. The History and Development of Extracorporeal Support.......................................1

Commercial Centrifugal Pumps........................................................................... 60

II. Extracorporeal Life Support: Neonatal Respiratory Disease

9. Neonatal Respiratory Diseases............................................................................... 123

10. Congenital Diaphragmatic Hernia and ECMO................................................... 133

III. Extracorporeal Life Support: Pediatric Respiratory Disease

18. Pediatric Respiratory Diseases Predisposing to ECLS.........................................231

Diagnostic Tools in ECMO..................................................................................277

IV. Extracorporeal Life Support: Neonatal and Pediatric Cardiac Disease

26. Neonatal and Pediatric Cardiovascular Diseases Predisposing to ECLS...........307

Duration of CPR and ECPR Outcomes...............................................................323

V. Extracorporeal Life Support: Adult Respiratory Disease

36. Adult Respiratory Diseases Predisposing to ECLS.............................................. 405

Right Heart Failure..............................................................................................452

43. Outcomes and Complications of Adult Respiratory ECLS..................................471

VI. Extracorporeal Life Support: Adult Cardiac Disease

44. Adult Cardiovascular Defects, Diseases, and Procedures................................... 479

46. General Considerations for VA-ECMO Implantation..........................................517

VII. Extracorporeal Life Support: Special Indications

53. Pregnancy and Extracorporeal Life Support....................................................... 583

VIII. ECLS: Procedures and Adjunctive Extracorporeal Therapies

61. Procedures on ECLS............................................................................................... 679

IX. Extracorporeal Life Support: Organization