2018 liver anesthesiology and critical care medicine 2nd ed

Gebhard Wagener
Editor

Liver Anesthesiology and
Critical Care Medicine

Second Edition

123


Liver Anesthesiology and Critical
Care Medicine


Gebhard Wagener
Editor

Liver Anesthesiology
and Critical Care
Medicine
Second Edition


Editor
Gebhard Wagener
Department of Anesthesiology, Columbia University Medical Center
New York, NY
USA

ISBN 978-3-319-64297-0    ISBN 978-3-319-64298-7 (eBook)

/>Library of Congress Control Number: 2018935600
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To Laurie, Ben, and Anna, who allow me to enjoy life and
work, and to my parents, who contributed so much to who I am.


Foreword to the First Edition

Liver transplantation has made remarkable progress in the 48 years since the
first human liver transplant, and especially in the last 30 years, since the introduction of cyclosporine made long-term survival after liver transplantation
feasible.

A procedure that was initially untested and experimental became routine
and is now the accepted treatment for end-stage liver disease in many parts of
the world. About 6000 liver transplants are done in the United States every
year, and graft and patient survival is excellent. We are able to administer
transplants to children, do living related and split liver transplants, and only
the shortage of organs limits the expansion of our field.
This progress is not only due to advances in immunosuppression, surgical
techniques, or organ preservation but also due to improvements in anesthetic
techniques. Anesthesia care initially provided by few experts in a small number of centers proliferated and is now often standardized and protocolized.
Advances in anesthesiology enabled the development of surgical techniques
such as caval cross-clamp or partial liver transplantation. There are few procedures in which the close cooperation of surgeon and anesthesiologist is as
essential for the success of the surgery and liver (transplant) surgery would
have never flourished as it did without the teamwork and partnership between
anesthesiologists and surgeons.
Within the last 20 years there has been tremendous progress in clinical
research of liver transplant anesthesia that aims to reduce blood transfusions,
augment organ preservation, and improve overall outcome. Anesthesia for
liver surgery has made a similar astounding progress and now extensive
resections are conceivable that would have been impossible before.
Postoperative critical care medicine as a continuation of the intraoperative
care is now frequently in the hands of anesthesiologists and intensivists specialized in hepatic intensive care, reflecting the increasing knowledge in this
field.
This book aims to summarize the progress in liver anesthesiology and
critical care medicine of the last 20 years and serves as a guide to those who
care for patients undergoing liver transplantation and liver resections. The
authors are the leaders in the field of liver anesthesiology and critical care in
Europe, Asia, and the United States. The foundation of this book is the
increasing fund of knowledge gained through clinical research as well as
through the extensive clinical experience of the authors that they share with
the readers.

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Foreword to the First Edition

This textbook provides the necessary background to understand the complexity of the liver and its pathophysiology. It summarizes the elaborate logistics involved in donor and recipient matching in Europe and the United States
and then describes the routine intraoperative management of liver transplant
recipients and patients undergoing hepatic resections. It addresses common
comorbidities and complications and how they may affect the preoperative
work-up and intraoperative management. The postoperative critical care section describes the routine care after liver transplantation and resection as well
as diagnosis and management of possible complications including pain
management.
This book aims to summarize our current knowledge of liver anesthesiology and critical care. It will serve as a reference for those who routinely care
for patients with liver disease. Those new to our exciting field will gain sufficient knowledge to successfully address many of the complex issues that
may arise during liver anesthesiology and critical care medicine. To those
who have extensive experience in the care of patients undergoing liver (transplant) surgery this book will serve as an authoritative reference and enable an
in-depth immersion into the exciting field of hepatic anesthesiology and critical care medicine.
Pittsburgh, PA, USA

Thomas E. Starzl, MD, PhD (1926–2017)


Preface to the First Edition

Liver transplantation and liver surgery have made enormous strides in the last
20 years. It has been transformed from an often heroic operation requiring
massive amounts of blood transfusions to almost routine surgery with little
blood loss in spite of increasing recipient morbidity. This advancement is

reflected in improved long-term mortality rates in the face of preferentially
allocating more marginal organs to sicker recipients.
Many little steps and advances are responsible for this achievement, not
least improvements of anesthetic techniques and postoperative care. These
little steps may not be immediately obvious but were necessary to accomplish
such a progress. Clinical and preclinical research in liver anesthesiology and
critical care medicine in the last 10 years has thrived, and a new generation of
anesthesiologists and intensive care physicians is willing to scrutinize their
clinical practice using clinical research tools instead of relying only on experience. This has created a fascinating and productive interaction within the
small group of anesthesiologists and intensivists who care for these severely
sick patients.
This book summarizes their current knowledge by bringing together the
leading experts of our subspecialty. It not only condenses a large amount of
clinical research but also includes opinions and experiences when evidence is
insufficient.
It is an in-depth review of the field and presents the current best knowledge. It aims to be the definitive resource of liver anesthesiology and critical
care medicine. Experienced and busy practitioners will find essential information to manage complex conditions of liver disease. The novice anesthesiologist or resident will be able to use this book as a thorough and comprehensive
introduction to our field and rapidly gain extensive knowledge as well as
obtain practical advice for those complex and scary situations that can occur
so frequently during liver transplantation.
This book provides a comprehensive review of the pathophysiology of
liver disease, pharmacology, immunology, and its implications for the anesthesiologist and intensivist. Anesthesiologic and postoperative care of liver
transplant recipients requires a thorough appreciation of the intricacies of
liver disease and its complications. Extrahepatic manifestations of liver disease are addressed in chapters separated by organ systems. Routine management as well as common intra- and postoperative complications are described
in detail to provide the knowledge required to care for these patients.

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Preface to the First Edition

x

Liver transplantation is expanding internationally and a large body of
work and experience originates from centers in Europe and Asia. Experts
from the United States, Europe, and Asia have contributed to this book to give
a global perspective of liver transplant anesthesiology.
A separate section reviews the anesthetic and postoperative management
of patients undergoing liver resection. New surgical approaches have allowed
us to perform more extensive and intricate resections that pose new challenges to the anesthesiologist and intensivists. Surgical techniques and their
physiologic repercussions are described in detail, and management strategies
for routine as well as complex cases and their possible complications are
offered.
We hope this book will alleviate the apprehension often associated with
caring for these sick patients and encourage many readers to engage in liver
anesthesiology and critical care medicine.
New York, NY, USA

Gebhard Wagener, MD


Preface to the Second Edition

The first edition of this book was published six years ago. Since then liver
anesthesiology and critical care medicine has rapidly evolved in pace with
new developments in surgery and transplantation. Laparoscopic and
laparoscopic-­assisted liver surgery that was rarely used before is now routine
in many centers and its use for living donor hepatectomies will greatly
increase acceptance of liver graft donation. Anesthetic management is very
different for this type of surgery, and anesthesiologists need to understand the

risks and benefits of these new technologies. Left lobe living liver donation
for adult recipients is now frequently used and will expand the potential
donor pool and reduce the risk for morbidities for the donor. This would not
have been possible without a better understanding of the regulation of liver
blood flow and improved treatment for early graft dysfunction in the ICU. Pain
procedures have evolved and the use of novel, ultrasound-guided regional
analgesic techniques improved patient comfort and recovery.
The advent of highly successful treatment of hepatitis C with new antiviral
drugs may one day reduce the number of liver transplants. However in the last
six years the need for organs kept rising, resulting in lower quality grafts
assigned to sicker recipients. This greatly complicates the anesthetic and
critical care management of these patients.
Liver anesthesiology and critical care medicine has matured into a subspecialty in its own right with national and international societies and meetings. The anesthesiology section of the International Liver Transplant
Society continues to thrive with an annual educational meeting and an
extraordinarily instructive and useful educational website ( />education/). Independent subspecialty societies such at the Liver Intensive
Care Group of Europe (LICAGE) and the newer Society for the Advancement
of Transplant Anesthesia (SATA) in the United States meet regularly to
share advances in the field, develop guidelines, and facilitate scientific progress. Many centers now offer fellowships in liver transplant anesthesiology
and societies are currently developing fellowship guidelines to potentially
gain approval by the Accreditation Council for Graduate Medical Education
(ACGME) in the United States.
To reflect these remarkable changes in our field, all chapters in this book
have been revised for this edition. We also added multiple new chapters, for
example, about chronic liver disease, regulation of liver blood flow, evaluation of liver function, and evidence in liver anesthesiology. Among others the

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Preface to the Second Edition

chapter on pain underwent a major revision and now includes detailed
description of regional analgesic techniques.
We hope that this book remains a useful companion for those who start in
this exciting field as well for the experienced liver anesthesiologist and
intensivist.
New York, NY, USA

Gebhard Wagener, MD


Acknowledgments

I sincerely thank the authors of this book for their excellent contributions.
They have spent many hours of diligent and hard work creating delightful,
intelligent, and insightful chapters that were a pleasure to read and edit.
I would also like to thank their families for the time the authors missed with
them while writing these chapters. Dr. Jean Mantz, one of the authors and a
true leader in our field, died last year; I feel privileged to have known such an
outstanding doctor.
This book would not have been possible without the encouragement, support, and advice of Dr. Margaret Wood who has unwaveringly supported me
throughout my career and all my colleagues and friends at Columbia
University Medical Center. I am immensely grateful to all of you.
I would further like to thank my editors from Springer Science + Business
Media, Asja Parrish, Rebekah Collins, and Saanthi Shankhararaman, who
have been indefatigable and immensely patient with me. Thank you.
Thank you, Taryn Lai and Nina Yoh for your help, insights and advice
with so many aspects of this book (and life!). Also thank you to Tara RichterSmith and Erin Hittesdorf who have reviewed and corrected syntax, style and
references of many of these chapters and were essential in finishing this book.

I am sincerely grateful to my colleagues, residents, students, and nurses
that I have had the pleasure to work with for many years and, most ­importantly,
to my patients, who taught me so much about disease, life, and death.

xiii


Contents

Part I Physiology, Pathophysiology and Pharmacology
of Liver Disease
1Physiology and Anatomy of the Liver. . . . . . . . . . . . . . . . . . . . .    3
Teresa Anita Mulaikal and Jean C. Emond
2Chronic Liver Failure and Hepatic Cirrhosis . . . . . . . . . . . . . .   21
Lauren Tal Grinspan and Elizabeth C. Verna
3Acute Hepatic Failure  41
Andrew Slack, Brian J. Hogan, and Julia Wendon
4The Splanchnic and Systemic Circulation in Liver Disease. . .   63
Nina T. Yoh and Gebhard Wagener
5Drug Metabolism in Liver Failure. . . . . . . . . . . . . . . . . . . . . . . .   69
Simon W. Lam
6Evaluation of Liver Function. . . . . . . . . . . . . . . . . . . . . . . . . . . .   79
Vanessa Cowan
Part II Anesthesiology for Liver Transplantation
7History of Liver Transplantation. . . . . . . . . . . . . . . . . . . . . . . . .   89
John R. Klinck and Ernesto A. Pretto
8Recipient and Donor Selection and Transplant Logistics:
The European Perspective. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .   101
Gabriela A. Berlakovich and Gerd R. Silberhumer
9Recipient and Donor Selection and Transplant

Logistics: The US Perspective. . . . . . . . . . . . . . . . . . . . . . . . . . .   109
Ingo Klein, Johanna Wagner, and Claus U. Niemann
10Surgical Techniques in Liver Transplantation. . . . . . . . . . . . . .   121
Holden Groves and Juan V. del Rio Martin
11Intraoperative Monitoring. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .   135
Claus G. Krenn and Marko Nicolic

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xvi

12Evidence for Anesthetic Practice in Liver
Transplant Anesthesiology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .   149
Ryan M. Chadha
13Caval Cross-Clamping, Piggyback and 
Veno-Venous Bypass. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .   155
David Hovord, Ruairi Moulding, and Paul Picton
14Hemodynamic Changes, Cardiac Output Monitoring
and Inotropic Support . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .   163
Anand D. Padmakumar and Mark C. Bellamy
15Coagulopathy: Pathophysiology, Evaluation,
and Treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .   173
Bubu A. Banini and Arun J. Sanyal
16Physiology, Prevention, and Treatment
of Blood Loss During Liver Transplantation. . . . . . . . . . . . . . .   195
Simone F. Kleiss, Ton Lisman, and Robert J. Porte
17The Marginal Liver Donor and Organ
Preservation Strategies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .   207
Abdulrhman S. Elnaggar and James V. Guarrera

18Pediatric Liver Transplantation . . . . . . . . . . . . . . . . . . . . . . . . .   221
Philipp J. Houck
19Combined Solid Organ Transplantation
Involving the Liver. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .   233
Geraldine C. Diaz, Jarva Chow, and John F. Renz
20Liver Transplantation for the Patient
with High MELD. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  247
Cynthia Wang and Randolph Steadman
21Perioperative Considerations for Transplantation
in Acute Liver Failure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .   257
C. P. Snowden, D. M. Cressey, and J. Prentis
22The Patient with Severe Co-morbidities: Renal Failure. . . . . .   269
Andrew Disque and Joseph Meltzer
23The Patient with Severe Co-morbidities:
Cardiac Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .   281
Shahriar Shayan and Andre M. De Wolf
24Pulmonary Complications of Liver Disease. . . . . . . . . . . . . . . .   293
Mercedes Susan Mandell and Masahiko Taniguchi
25The Patient with Severe Co-morbidities: CNS Disease
and Increased Intracranial Pressure. . . . . . . . . . . . . . . . . . . . . .   307
Prashanth Nandhabalan, Chris Willars, and Georg Auzinger

Contents


Contents

xvii

Part III Anesthesiology for Liver Surgery

26Hepatobiliary Surgery: Indications, Evaluation
and Outcomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .   333
Jay A. Graham and Milan Kinkhabwala
27Liver Resection Surgery: Anesthetic Management, Monitoring,
Fluids and Electrolytes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .   349
Emmanuel Weiss, Jean Mantz, and Catherine Paugam-Burtz
28Anesthetic Aspects of Living Donor Hepatectomy . . . . . . . . . .   367
Paul D. Weyker and Tricia E. Brentjens
29Complications of Liver Surgery. . . . . . . . . . . . . . . . . . . . . . . . . .   377
Oliver P. F. Panzer
30The Patient with Liver Disease Undergoing
Non-hepatic Surgery. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .   389
Katherine Palmieri and Robert N. Sladen
Part IV Critical Care Medicine for Liver Transplantation
31Routine Postoperative Care After Liver Transplantation. . . . .   415
Jonathan Hastie and Vivek K. Moitra
32Immunosuppression. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .   431
Enoka Gonsalkorala, Daphne Hotho, and Kosh Agarwal
33Acute Kidney Injury After Liver Transplantation . . . . . . . . . .   445
Raymond M. Planinsic, Tetsuro Sakai, and Ibtesam A. Hilmi
34Early Graft Failure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .   451
Avery L. Smith, Srinath Chinnakotla, and James F. Trotter
35Sepsis and  Infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .   455
Fuat Hakan Saner
36Respiratory Failure and ARDS. . . . . . . . . . . . . . . . . . . . . . . . . .   469
James Y. Findlay and Mark T. Keegan
Part V Critical Care Medicine for Liver Surgery
37Postoperative Care of Living Donor for Liver Transplant. . . .   485
Sean Ewing, Tadahiro Uemura, and Sathish Kumar
38Liver Surgery: Early Complications—Liver Failure,

Bile Leak and Sepsis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .   497
Albert C. Y. Chan and Sheung Tat Fan
39Pain Management in Liver Transplantation . . . . . . . . . . . . . . .   507
Paul Weyker, Christopher Webb, and Leena Mathew
Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .   525


Contributors

Kosh Agarwal, MD Institute of Liver Studies, Kings College Hospital,
London, UK
Georg Auzinger, EDIC, AFICM  Department of Critical Care/Institute of
Liver Studies, King’s College Hospital, London, UK
Bubu A. Banini, MD, PhD  Division of Gastroenterology and Hepatology,
Department of Internal Medicine, Virginia Commonwealth University,
Richmond, VA, USA
Mark C. Bellamy, MA, MB, BS, FRCP(Edin), FRCA, FFICM  St. James’s
University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds, West
Yorkshire, UK
Gabriela A. Berlakovich, MD, FEBS Division of Transplantation,
Department of Surgery, Medical University of Vienna, Vienna, Austria
Tricia E. Brentjens, MD Department of Anesthesiology, Columbia
University Medical Center, New York, NY, USA
Catherine Paugam-Burtz, MD, PhD  Department of Anesthesiology and
Critical Care Medecine, Beaujon, HUPNVS, Assistance Publique-Hôpitaux
de Paris (AP-HP), Paris, France
University Paris VII, Paris Diderot, Paris, France
Ryan M. Chadha, MD  Anesthesiology and Perioperative Medicine, Mayo
Clinic Florida, Jacksonville, FL, USA
Albert C. Y. Chan, MBBS, FRCS  Department of Surgery, The University

of Hong Kong, Queen Mary Hospital, Hong Kong, People’s Republic of
China
Srinath Chinnakotla, MD  Department of Surgery, University of Minnesota,
Minneapolis, MN, USA
Jarva Chow, MD Department of Anesthesiology, Loyola University,
Chicago, IL, USA
Vanessa Cowan, MD  Transplant Institute, Beth Israel Deaconess Medical
Center, Boston, MA, USA

xix


xx

D. M. Cressey, BSc (Hons), MBBS, FRCA  Department of Perioperative
Medicine and Critical Care, Freeman Hospital, Newcastle Upon Tyne, UK
Geraldine C. Diaz, DO Department of Anesthesiology, University of
Illinois at Chicago, Chicago, IL, USA
Andrew Disque, MD Department of Anesthesiology and Perioperative
Medicine, David Geffen School of Medicine, University of California at Los
Angeles, Los Angeles, CA, USA
Abdulrhman S. Elnaggar, MD Department of Surgery, Columbia
University Medical Center, New York, NY, USA
Emmanuel Weiss, MD, PhD  Department of Anesthesiology and Critical
Care Medecine, Beaujon, HUPNVS, Assistance Publique-Hôpitaux de Paris
(AP-HP), Paris, France
University Paris VII, Paris Diderot, Paris, France
Jean C. Emond, MD  Department of Surgery, Columbia University Medical
Center, New York, NY, USA
Sean Ewing, MD  Department of Anesthesiology, University of Michigan

Health System, Ann Arbor, MI, USA
Sheung Tat Fan, MD, PhD, DSc Liver Surgery Centre, Hong Kong
Sanatorium and Hospital, Hong Kong, People’s Republic of China
James Y. Findlay, MB, ChB, FRCA  Department of Anesthesiology and
Critical Care Medicine, Mayo Clinic, Rochester, MN, USA
Enoka Gonsalkorala, MD Institute of Liver Studies, Kings College
Hospital, London, UK
Jay A. Graham, MD  Department of Surgery, Albert Einstein College of
Medicine, Bronx, NY, USA
Lauren Tal Grinspan, MD, PhD Department of Medicine, Columbia
University Medical Center, New York, NY, USA
Holden Groves, MD, MS  Columbia University Medical Center, New York,
NY, USA
Department of Anesthesiology, Columbia University Medical Center, New
York, NY, USA
James V. Guarrera, MD, FACS Division of Liver Transplant and
Hepatobiliary Surgery, Rutgers New Jersey Medical School, University
Hospital, New York, NJ, USA
Jonathan Hastie, MD Department of Anesthesiology, Cardiothoracic
Intensive Care Unit, Columbia University Medical Center, New York, NY,
USA

Contributors


Contributors

xxi

Ibtesam A. Hilmi, MB, ChB  Department of Anesthesiology, University of

Pittsburgh Medical Center, Pittsburgh, PA, USA
Brian J. Hogan, BSc, MBBS, MRCP, FEBTM, FFICM  Institute of Liver
Studies, Kings College London, Kings College Hospital, London, UK
Daphne Hotho, MD Institute of Liver Studies, Kings College Hospital,
London, UK
Philipp J. Houck, MD  Department of Anesthesiology, Columbia University
Medical Center, New York, NY, USA
David Hovord, BA, MB, BChir, FRCA Department of Anesthesiology,
University of Michigan Medical School, Ann Arbor, MI, USA
Jean Mantz, MD, PhD Department of Anesthesiology and Critical Care
Medicine, HEGP, APHP, Paris, France
Mark T. Keegan, MB, MRCPI, MSc, D ABA  Department of Anesthesiology
and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA
Milan Kinkhabwala, MD  Department of Surgery, Albert Einstein College
of Medicine, Bronx, NY, USA
Ingo Klein Department of General- and Visceral-, Vascular and Pediatric
Surgery, University of Wuerzburg, Medical Center, Wuerzburg, Germany
Simone F. Kleiss, MD Section of Hepato-Pancreato-Biliary Surgery and
Liver Transplantation, Department of Surgery, University of Groningen,
University Medical Center Groningen, Groningen, The Netherlands
John R. Klinck, MD, FRCA, FRCPC Division of Perioperative Care,
Cambridge University Hospitals, Cambridge, UK
Claus G. Krenn, MD  Department of Anaesthesia, General Intensive Care
and Pain Medicine, Medical University of Vienna, General Hospital Vienna,
Vienna, Austria
Simon W. Lam, PharmD, FCCM  Cleveland Clinic, Cleveland, OH, USA
Ton Lisman, PhD  Section of Hepato-Pancreato-Biliary Surgery and Liver
Transplantation, Department of Surgery, University of Groningen, University
Medical Center Groningen, Groningen, The Netherlands
Mercedes Susan Mandell, MD, PhD Department of Anesthesiology,

University of Colorado, Aurora, CO, USA
Leena Mathew, MD  Department of Anesthesiology, Columbia University
Medical Center, New York, NY, USA
Joseph Meltzer, MD  Division of Critical Care, Department of Anesthesiology
and Perioperative Medicine, David Geffen School of Medicine, University of
California at Los Angeles, Los Angeles, CA, USA


xxii

Vivek K. Moitra, MD Department of Anesthesiology, Surgical Intensive
Care Unit and Cardiothoracic Intensive Care Unit, Columbia University,
College of Physicians and Surgeons, New York, NY, USA
Ruairi Moulding, BSc, MBBS, FRCA Department of Anaesthesia,
Musgrove Park Hospital, Taunton, UK
Teresa Anita Mulaikal, MD  Division of Cardiothoracic and Critical Care
Medicine, Columbia University Medical Center, New York, NY, USA
Prashanth Nandhabalan, MRCP, FRCA, FFICM, EDIC  Department of
Critical Care/Institute of Liver Studies, King’s College Hospital, London, UK
Marko Nicolic, MD Department of Anaesthesia, General Intensive Care
and Pain Medicine, Medical University of Vienna, General Hospital Vienna,
Vienna, Austria
Claus U. Niemann, MD  Anesthesia and Perioperative Care, University of
California San Francisco, San Francisco, CA, USA
Anand D. Padmakumar, MBBS, FRCA, EDIC, FFICM St. James’s
University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds, West
Yorkshire, UK
Katherine Palmieri, MD, MBA Department of Anesthesiology, The
University of Kansas Health System, Kansas City, KS, USA
Oliver P. F. Panzer, MD Department of Anesthesiology, Columbia

University Medical Center, New York, NY, USA
Paul Picton, MB, ChB, MRCP, FRCA Department of Anesthesiology,
University of Michigan Medical School, Ann Arbor, MI, USA
Raymond M. Planinsic, MD  Department of Anesthesiology, University of
Pittsburgh Medical Center, Pittsburgh, PA, USA
Robert J. Porte, MD, PhD  Section of Hepato-Pancreato-Biliary Surgery
and Liver Transplantation, Department of Surgery, University of Groningen,
University Medical Center Groningen, Groningen, The Netherlands
J. Prentis, MBBS, FRCA Department of Perioperative Medicine and
Critical Care, Freeman Hospital, Newcastle Upon Tyne, UK
Ernesto A. Pretto, MD, MPH Division of Transplant and Vascular
Anesthesia, University of Miami Leonard M Miller School of Medicine,
Jackson Memorial Hospital, Miami, FL, USA
John F. Renz, MD, PhD  Section of Transplantation, Department of Surgery,
University of Chicago, Chicago, IL, USA
Juan V. del Rio Martin, MD, FASTS  Hospital Auxilio Mutuo, San Juan,
PR, USA
Tetsuro Sakai, MD, PhD, MHA  Department of Anesthesiology, University
of Pittsburgh Medical Center, Pittsburgh, PA, USA

Contributors


Contributors

xxiii

Fuat Hakan Saner, MD  Department of General-, Visceral- and Transplant
Surgery, Medical Center University Essen, Essen, Germany
Arun J. Sanyal, MD, MBBS  Division of Gastroenterology and Hepatology,

Department of Internal Medicine, Virginia Commonwealth University,
Richmond, VA, USA
Sathish Kumar, MBBS Department of Anesthesiology, University of
Michigan, Ann Arbor, MI, USA
Shahriar Shayan, MD Department of Anesthesiology, Northwestern
Memorial Hospital, Chicago, IL, USA
Gerd R. Silberhumer, MD Division of Transplantation, Department of
Surgery, Medical University of Vienna, Vienna, Austria
Andrew Slack, MBBS, MRCP, EDIC, MD(Res)  Department of Critical
Care, Guy’s and St Thomas’s NHS Foundation Trust, London, UK
Robert N. Sladen, MBChB, MRCP(UK), FRCPC, FCCM  Allen Hyman
Professor Emeritus of Critical Care Anesthesiology at Columbia University
Medical Center, College of Physicians and Surgeons of Columbia University,
New York, NY, USA
Avery L. Smith, MD  Baylor University Medical Center, Dallas, TX, USA
C. P. Snowden, B Med Sci (Hons), FRCA, MD  Department of Perioperative
Medicine and Critical Care, Freeman Hospital, Newcastle Upon Tyne, UK
Randolph Steadman, MD, MS Department of Anesthesiology and
Perioperative Medicine, UCLA Health, Los Angeles, CA, USA
Masahiko Taniguchi, MD, FACS Department of Surgery, Hokkaido
University, Sappora, Japan
James F. Trotter, MD  Baylor University Medical Center, Dallas, TX, USA
Tadahiro Uemura, MD, PhD  Abdominal Transplantation and Hepatobiliary
Surgery, Allegheny General Hospital, Pittsburgh, PA, USA
Elizabeth C. Verna, MD, MS  Transplant Initiative, Division of Digestive
and Liver Diseases, Center for Liver Disease and Transplantation, Columbia
University Medical Center, New York, NY, USA
Gebhard Wagener, MD Department of Anesthesiology, Columbia
University Medical Center, New York, NY, USA
Johanna Wagner Department of General- and Visceral-, Vascular and

Pediatric Surgery, University of Wuerzburg, Medical Center, Wuerzburg,
Germany
Cynthia Wang, MD  Department of Anesthesiology and Pain Management,
VA North Texas Healthcare System, Dallas, TX, USA
Christopher Webb, MD Department of Anesthesiology, Columbia
University Medical Center, New York, NY, USA


xxiv

Julia Wendon, MbChB, FRCP  Institute of Liver Studies, Kings College
London, Kings College Hospital, London, UK
Paul D. Weyker, MD  Department of Anesthesiology, Columbia University
Medical Center, New York, NY, USA
Chris Willars, MBBS, BSc, FRCA, FFICM  Department of Critical Care/
Institute of Liver Studies, King’s College Hospital, London, UK
Andre M. De Wolf, MD Department of Anesthesiology, Northwestern
Memorial Hospital, Chicago, IL, USA
Nina T. Yoh  Columbia University Medical Center, New York, NY, USA

Contributors


Part I
Physiology, Pathophysiology and
Pharmacology of Liver Disease


1

Physiology and Anatomy
of the Liver
Teresa Anita Mulaikal and Jean C. Emond

Keywords

Liver anatomy · Liver segments · External
anatomy · Embryology · Hepatocytes · Liver
function

Introduction
This chapter will review the anatomy and physiology of the liver as it pertains to the anesthetic
management during liver surgery and transplantation. Anesthetic management of the patient
with chronic liver disease requires a thorough
understanding of the alterations induced in cirrhosis that affect many organ systems. For example liver surgery for ablation of tumors may
reduce the functional mass of the liver resulting
in systemic changes that alter hemodynamics and
renal function. In liver transplantation, the body
is deprived of all liver function during the implantation phase and may receive a new liver with
impaired initial function. All types of liver surgery may cause hepatic ischemia and reperfusion
injury that may induce both acute and chronic
T. A. Mulaikal, MD (*)
Division of Cardiothoracic and Critical Care
Medicine, Columbia University Medical Center,
New York, NY, USA
e-mail:
J. C. Emond, MD
Department of Surgery, Columbia University Medical
Center, New York, NY, USA

systemic alterations. Thus, an understanding of
the structure and function of the liver, is critical
for managing the changes in the liver induced
during surgery. This knowledge, applied throughout the peri-operative period by anesthesiologists
with interest and training in liver disease, has
been a major factor in the markedly improved
outcomes of liver surgery during the past
50 years, and especially since the era of liver
transplantation.
The liver is the largest gland in the human
body and the only organ capable of regeneration
[1]. This unique ability has been both the subject
of ancient Greek mythology and modern medicine best illustrated by the myth in which the
injured liver is restored daily as Zeus’ eternal
punishment to Prometheus. While advances in
science allow for the temporary support of renal
function in the form of dialysis, and of cardiovascular and pulmonary function in the form of
extracorporeal membrane oxygenation (ECMO),
there is currently no effective substitute for the
immune, metabolic, and synthetic functions of
the liver other than transplantation (Table 1.1).
The absence of artificial liver support makes a
thorough understanding of hepatic physiology
and pathophysiology imperative to the care of
critically ill patients with liver injury as their
management requires careful protection of remnant function while regeneration occurs.
This chapter will review normal liver anatomy,
histology, and physiology. The first section

© Springer International Publishing AG, part of Springer Nature 2018

G. Wagener (ed.), Liver Anesthesiology and Critical Care Medicine,
/>
3


T. A. Mulaikal and J. C. Emond

4

covers basic liver anatomy and describes
Couinaud’s classification, which divides the liver
into eight segments as a function of its portal
venous and hepatic arterial supply. These segments serve as boundaries for the modern day
hepatectomy. The knowledge of each segment’s
vascular supply, proximity to the vena cava, and
spatial orientation is useful in judging the difficulty of resection and use of surgical techniques
such as total vascular isolation to minimize blood
loss. For example lesions located posteriorly and
adjacent to the vena cava may necessitate total
vascular isolation with broad implications for the
anesthetic management.
The next section will comprise basic liver histology, including a discussion of microanatomy
and cellular function, which have implications
for the regulation of portal blood flow and the
pathophysiology of cirrhosis and portal hypertension. The last section focuses on basic liver physiology, including the immunological role of the
liver, and its metabolic and synthetic functions.

and ventral pancreas while the dorsal foregut
gives rise to the dorsal pancreas, stomach, and
intestines [5]. The ventral endoderm responds

to signals from the cardiac mesoderm to generate the hepatic diverticulum that transforms
into the liver bud and hepatic vasculature [6].
The portal vein derives from the vitelline veins
[4]. The ductus venosus shunts blood from the
umbilical vein, which carries oxygenated blood
from the placenta to the fetus, to the vena cava
thereby supplying oxygenated blood to the
brain. The ligamentum venosum is the remnant
of the ductus venosus, and the ligamentum teres
is the remnant of the umbilical vein.
The extrahepatic and intrahepatic biliary tracts
have different origins. The extrahepatic biliary
tract, which includes the hepatic ducts, cystic
duct, common bile duct, and gallbladder, develops from the endoderm. The intrahepatic biliary
tract, however, develops from hepatoblasts [2].

 acroscopic Anatomy of the Liver
M
and the Visceral Circulation

Embryology
The liver derives from the ventral foregut endoderm during the fourth week of gestation,
responding to signals from the cardiac mesoderm for hepatic differentiation [2–4]. The ventral foregut also gives rise to the lung, thyroid,

Anatomy relevant to surgical management and
liver anesthesia includes the blood supply and
the intrahepatic architecture of the liver. A much
more specific knowledge of liver anatomy is
required to plan and execute surgical resections
and is beyond the scope of this chapter. The

Table 1.1  Functions of the liver
Metabolic
Xenobiotic metabolism
Protein metabolism
 Ammonia
 Detoxification
Lipid metabolism
 B-oxidation F.A.
 Triglyceride
Glucose metabolism
 Gluconeogenesis
 Glycogenolysis
 Glygogenesis

F.A. Fatty acids

Synthetic
Coagulation factor
synthesis
 Procoagulants
 Anticoagulants
 Fibrinolytics
 Antifibrinolytics
Plasma protein synthesis
 Albumin
Steroid hormone synthesis
 Cholesterol
Thrombopoietin
Angiotensionogen

IGF-1

Immunologic
Innate
immunity
Adaptive
immunity
Oral and
allograft
tolerance

Regenerative
Restoration after
hepatectomy or
trauma

Homeostasis
Regulation of
intravascular volume
 Renin-angiogensinaldosterone
Glucose homeostasis
Regulation of portal
inflow
 Hepatic arterial
buffer hypothesis


1  Physiology and Anatomy of the Liver

5

afferent blood to the liver is composed of both
arterial and portal blood and accounts for 20–25%
of the cardiac output, and all the blood exits the
liver through the hepatic veins (Fig. 1.1). The
hepatic artery is derived from the celiac artery
in most cases but may receive some or all of its
supply from the superior mesenteric artery. The
artery divides in order to supply the right and left
lobes and the intraheaptic segments, and the anatomy includes several variants that are relevant in
hepatic resections and biliary surgery. These variants do not affect anesthetic management other
than the recognition that surgical errors may
result in ischemic injury to segments of the liver.
Furthermore, since the biliary tree is primarily
supplied by the arterial system, bile duct ischemia may result in postoperative complications.
The portal blood accounts for the majority of
the hepatic blood flow and unites the venous
return from the entire gastrointestinal (GI) tract
with the exception of the rectum that drains into
the iliac vessels. The foregut, including the stomach, spleen, pancreas and duodenum drain
directly into the portal vein and the splenic vein,
while the small intestine and the right colon drain
into the superior mesenteric vein. This means
Inferior vena cava
Right hepatic vein
Coronary ligament (cut)
Diaphragm (cut)

that the splenic vein contribution to the portal
blood is rich in pancreatic hormones and cytokines while the superior mesenteric vein brings

nutrients, toxins, and bacteria that are absorbed
by the GI tract. In situations of increased portal
vein pressure such as cirrhosis and portal vein
thrombosis, collateral veins known as varices can
develop. These connections between the portal
vein and the systemic circulation become
enlarged and shunt blood away from the liver
(Fig.  1.2). Shunting results in impaired liver
function, most pronounced in alteration of brain
function discussed later in the chapter. Clinically
significant varices may result in GI bleeding in
the esophagus, stomach and duodenum, as well
as the rectum. Other collateral shunts occur in the
retroperitoneum and the abdominal wall, and
may result in a large amount of porto-systemic
shunting without bleeding but other consequences of impaired portal blood flow. In addition to the loss of metabolic ­transformation, the
reticulo-endothelial protective function of the
liver is also bypassed when large shunts are present and may result in bacteremia and sepsis and
contribute to the hemodynamic alterations of cirrhosis discussed below.

Middle hepatic vein
Left hepatic vein
Ligamentum venosum
Falciform ligmament

Lateral segmental branches
of left lobe

Branches to caudate lobe
Right lobe

segmental branches:
Posterior
Anterior

Medial segmental branches
of left lobe

Cystic duct and artery
Left hepatic duct and artery
Round ligament of liver
(ligamentum teres hepatis)
Common hepatic duct
Bile duct, hepatic portal vein, and proper hepatic artery
Right hepatic
artery and duct

Fig. 1.1  Arterial and venous circulation of the liver