2013 Shnider and Levinsons Anesthesia for Obstetrics - 5E

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Shnider and Levinson’s

Anesthesia G R for Obstetrics V FIFTH EDITION

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Shnider and Levinson’s

Anesthesia G for Obstetrics R Maya S. Suresh, MD Professor and Chairman Department of Anesthesiology Baylor College of Medicine Division Chief Obstetrics and Gynecologic Anesthesiology Ben Taub General Hospital Houston, Texas

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Scott Segal, MD, MHCM Chair, Department of Anesthesiology Tufts University School of Medicine Anesthesiologist-in-Chief Tufts Medical Center Boston, Massachusetts

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FIFTH EDITION

Roshan Fernando, MB, BCh, FRCA Consultant Anesthesiologist University College London Hospitals NHS Trust London, United Kingdom

C. LaToya Mason, MD Assistant Professor Department of Anesthesiology Baylor College of Medicine Attending Anesthesiologist Department of Anesthesiology Ben Taub General Hospital Houston, Texas

Roanne L. Preston, MD, FRCPC Clinical Professor Department of Anesthesiology Pharmacology and Therapeutics The University of British Columbia Department Head Department of Anesthesia British Columbia Women’s Hospital and Health Centre Vancouver, British Columbia, Canada

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Acquisitions Editor: Brian Brown Product Manager: Nicole Dernoski Marketing Manager: Lisa Lawrence Vendor Manager: Bridgett Dougherty Designer: Stephen Druding Compositor: Aptara, Inc. Fifth Edition





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Library of Congress Cataloging-in-Publication Data Shnider and Levinson’s anesthesia for obstetrics.—5th ed. / editor, Maya Suresh ; associate editors, Roshan Fernando . . . [et al.]. p. ; cm. Anesthesia for obstetrics Includes bibliographical references and index. ISBN 978-1-4511-1435-5 (hardback : alk. paper) I. Suresh, Maya. II. Shnider, Sol M., 1929- III. Title: Anesthesia for obstetrics. [DNLM: 1. Anesthesia, Obstetrical. WO 450] 617.9′682—dc23 2012039413

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Care has been taken to confirm the accuracy of the information present and to describe generally accepted practices. However, the authors, editors, and publisher are not responsible for errors or omissions or for any consequences from application of the information in this book and make no warranty, expressed or implied, with respect to the currency, completeness, or accuracy of the contents of the publication. Application of this information in a particular situation remains the professional responsibility of the practitioner; the clinical treatments described and recommended may not be considered absolute and universal recommendations. The authors, editors, and publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accordance with the current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any change in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new or infrequently employed drug. Some drugs and medical devices presented in this publication have Food and Drug Administration (FDA) clearance for limited use in restricted research settings. It is the responsibility of the health care provider to ascertain the FDA status of each drug or device planned for use in their clinical practice. To purchase additional copies of this book, call our customer service department at (800) 638-3030 or fax orders to (301) 223-2320. International customers should call (301) 223-2300. Visit Lippincott Williams & Wilkins on the Internet: http://www.lww.com. Lippincott Williams & Wilkins customer service representatives are available from 8:30 am to 6:00 pm, EST.

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CONTRIBUTORS

Katherine W. Arendt, MD Assistant Professor Department of Anesthesiology Mayo Clinic College of Medicine Consultant Department of Anesthesiology Mayo Clinic Rochester, Minnesota

Curtis L. Baysinger, MD Associate Professor Department of Anesthesiology Vanderbilt University School of Medicine Chief, Obstetric Anesthesiology Department of Anesthesiology Vanderbilt University Medical Center Nashville, Tennessee

Valerie A. Arkoosh, MD, MPH Professor of Clinical Anesthesiology Professor of Clinical Obstetrics and Gynecology Department of Anesthesiology and Critical Care Perelman School of Medicine at the University of Pennsylvania Attending Anesthesiologist Anesthesiology and Critical Care Unit Philadelphia, Pennsylvania

Yaakov Beilin, MD Professor and Vice Chair for Quality Departments of Anesthesiology and Obstetrics and Gynecology Mount Sinai School of Medicine Co-Director of Obstetric Anesthesiology Department of Anesthesiology Mount Sinai Hospital New York, New York

Sarah L. Armstrong, FRCA Consultant Anaesthetist Anaesthetic Department Royal Surrey County Hospital Guildford, United Kingdom Emily J. Baird, MD, PhD Assistant Professor Department of Anesthesiology and Critical Care University of Pennsylvania Director of Obstetric Anesthesia Department of Anesthesiology and Critical Care Hospital of the University of Pennsylvania Philadelphia, Pennsylvania

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Mrinalini Balki, MD Associate Professor Department of Anesthesia and Pain Management University of Toronto Staff Anesthesiologist Mount Sinai Hospital Toronto, Canada

Venkata D. P. Bandi, MD Associate Professor of Medicine Department of Medicine Pulmonary, Critical Care, and Sleep Medicine Section Baylor College of Medicine Associate Director, Medical ICU Ben Taub General Hospital Director, Intensive Care Unit Texas Children’s Hospital–Pavilion for Women Houston, Texas

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Brenda A. Bucklin, MD Professor Department of Anesthesiology University of Colorado School of Medicine Aurora, Colorado William Camann, MD Associate Professor Department of Anesthesiology Harvard Medical School Director, Obstetric Anesthesia Department of Anesthesiology Brigham and Women’s Hospital Boston, Massachusetts Christopher R. Cambic, MD Assistant Professor Department of Anesthesiology Feinberg School of Medicine Northwestern University Staff Anesthesiologist Department of Anesthesiology Prentice Women’s Hospital Chicago, Illinois David C. Campbell, MD, MSc, FRCPC Professor and Chairman Department of Anesthesiology, Perioperative Medicine and Pain Management University of Saskatchewan Chairman Department of Anesthesiology Saskatoon Health Region Saskatoon, Saskatchewan, Canada

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Contributors

Thomas Chai, MD Assistant Professor Department of Pain Medicine University of Texas MD. Anderson Cancer Center Houston, Texas

Pamela Flood, MD Professor Department of Anesthesia and Perioperative Care Department of Obstetrics, Gynecology and Reproductive Science University of California, San Francisco Director of Obstetric Anesthesia Department of Anesthesia and Perioperative Care Moffitt Long Hospital San Francisco General Hospital San Francisco, California

Shobana Chandrasekhar, MD Associate Professor Department of Anesthesiology Baylor College of Medicine Houston, Texas

Michael Frölich, MD, MS Associate Professor Department of Anesthesiology Chair-Elect, Faculty Senate The University of Alabama at Birmingham Director, Fellowship Program for Obstetric Anesthesiology UAB Hospital Birmingham, Alabama   

Katherine L. Cheesman, MBBS, FRCA, BSc Consultant Anaesthetist Department of Anaesthesia Guy’s & St. Thomas’ NHS Trust London, England Edward T. Crosby, MD, FRCPC Professor Department of Anesthesiology University of Ottawa Staff Anesthesiologist Department of Anesthesiology The Ottawa Hospital Ottawa, Ontario, Canada Christina M. Davidson, MD Assistant Professor Department of Obstetrics and Gynecology Division of Maternal Fetal Medicine Baylor College of Medicine Chief of Service Department of Obstetrics and Gynecology Ben Taub General Hospital Houston, Texas

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Oscar A. de Leon-Casasola, MD Professor of Anesthesiology and Medicine Department of Anesthesiology University at Buffalo Chief of Pain Medicine Department of Anesthesiology Roswell Park Cancer Institute Buffalo, New York

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Julio B. Delgado, MD Staff Psychiatrist Dual Diagnosis Attending Physician Department of Psychiatry Lake City VA Medical Center Lake City, Florida

M. Joanne Douglas, MD, FRCPC Clinical Professor Department of Anesthesiology, Pharmacology and Therapeutics University of British Columbia Research Director Department of Anesthesia British Columbia’s Women’s Hospital and Health Centre Vancouver, British Columbia, Canada Roshan Fernando, MB, BCh, FRCA Consultant Anesthesiologist University College London Hospitals NHS Trust London, United Kingdom

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Andrea J. Fuller, MD Assistant Professor Anesthesiology Department University of Colorado School of Medicine Aurora, Colorado

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Rodolfo Gebhardt, MD Associate Professor Department of Pain Medicine The University of Texas Acute Pain Director Department of Pain Medicine MD. Anderson Cancer Center Houston, Texas

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Ravpreet Singh Gill, MD Assistant Professor Department of Anesthesiology University of Tennessee Health Science Center Anesthesiologist Department of Anesthesiology Regional Medical Center Memphis, Tennessee Laura Goetzl, MD, MPH Associate Professor Department of Obstetrics and Gynecology Medical University of South Carolina Charleston, South Carolina Stephanie R. Goodman, MD Associate Clinical Professor Department of Anesthesiology Columbia University Associate Attending Department of Anesthesiology Columbia University Medical Center New York, New York Thomas A. Gough, MBChB, MRCP, FRCA Specialist Registrar Barts Health NHS Trust The Royal London Hospital London, United Kingdom

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Contributors

Stephen H. Halpern, MD, MSc, FRCPC Professor Departments of Anesthesia, Obstetrics, and Gynecology University of Toronto Division Head, Obstetrical Anesthesia Department of Anesthesia Sunnybrook Health Sciences Centre Toronto, Canada

Suzanne Wattenmaker Mankowitz, MD Assistant Professor Department of Anesthesiology Columbia University Faculty Department of Anesthesiology The New York–Presbyterian Hospital New York, New York

Joy L. Hawkins, MD Professor Associate Chair for Academic Affairs Department of Anesthesiology Denver School of Medicine, University of Colorado Director of Obstetric Anesthesia Department of Anesthesiology University of Colorado Hospital Aurora, Colorado

David G. Mann, MD Assistant Professor Departments of Anesthesiology and Pediatrics Baylor College of Medicine Attending Anesthesiologist Department of Anesthesiology Texas Children’s Hospital Houston, Texas

Paul Howell, BSc, MBChB, FRCA Consultant Anaesthetist St. Bartholomew’s Hospital London, United Kingdom McCallum R. Hoyt, MD, MBA Assistant Professor Department of Anesthesiology, Perioperative and Pain Medicine Harvard Medical School Division Chief, Gynecologic and Ambulatory Anesthesia Department of Anesthesiology, Perioperative & Pain Medicine Brigham and Women’s Hospital Boston, Massachusetts Bhavani Shankar Kodali, MD Department of Anesthesiology Brigham and Women’s Hospital Boston, Massachusetts

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Ruth Landau, MD Professor Department of Anesthesiology and Pain Medicine University of Washington Chief, Director of Obstetric Anesthesia Department of Anesthesiology and Pain Medicine University of Washington Medical Center Seattle, Washington Ellen M. Lockhart, MD Associate Professor Department of Anesthesiology Washington University St. Louis, Missouri

Dennis T. Mangano, MD Founder and Director Ischemia Research and Education Foundation Founder and Director McSPI Research Group San Mateo, California

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C. LaToya Mason, MD Assistant Professor Department of Anesthesiology Baylor College of Medicine Attending Anesthesiologist Department of Anesthesiology Ben Taub General Hospital Houston, Texas

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Kenneth L. Mattox, MD Distinguished Service Professor Department of Surgery Baylor College of Medicine Chief of Staff, Chief of Surgery Ben Taub General Hospital Houston, Texas

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Andrew D. Miller, MD Instructor Harvard Medical School Staff Anesthesiologist Department of Anesthesiology, Perioperative and Pain Medicine Brigham and Women’s Hospital Boston, Massachusetts Richard C. Month, MD Assistant Professor of Clinical Anesthesiology Department of Anesthesiology and Critical Care Perelman School of Medicine University of Pennsylvania Attending Anesthesiologist Department of Anesthesiology and Critical Care University of Pennsylvania Health System Philadelphia, Pennsylvania Holly A. Muir, MD, FRPC Assistant Professor Department of Anesthesiology Duke University Vice Chair, Clinical Operations Chief, Division of Women’s Anesthesia Department of Anesthesia Duke University Hospital Durham, North Carolina

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Contributors

Uma Munnur, MD Associate Professor Department of Anesthesiology Baylor College of Medicine Ben Taub Hospital Houston, Texas

Carlo Pancaro, MD Assistant Professor Department of Anesthesiology Tufts University School of Medicine Tufts Medical Center Boston, Massachusetts

Olutoyin A. Olutoye, MD, MSc Associate Professor Department of Anesthesiology and Pediatrics Baylor College of Medicine Staff Anesthesiologist Department of Anesthesiology and Pediatrics Texas Children’s Hospital Houston, Texas

Moeen K. Panni, MD, PhD Professor and Chair of Anesthesiology Professor of Obstetrics and Gynecology Chief of Perioperative Services The University of Mississippi Medical Center Jackson, Mississippi Donald H. Penning, MD, MS, FRCP Professor Department of Anesthesiology University of Colorado-Denver Director of Anesthesia Department of Anesthesiology Denver Health Denver, Colorado

Geraldine O’Sullivan, MD, FRCA Lead Clinician in Obstetric Anaesthesia Department of Anaesthetics Guy’s and St Thomas’ NHS Foundation Trust King’s College London, United Kingdom Alice L. Oswald, MD Assistant Professor Department of Anesthesiology Baylor College of Medicine Department of Obstetric and Gynecologic Anesthesiology Ben Taub General Hospital Houston, Texas Medge D. Owen, MD Professor Department of Anesthesiology Wake Forest School of Medicine Director of Maternal and Infant Global Health Programs Wake Forest School of Medicine Winston-Salem, North Carolina

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Michael Paech, DM, FANZCA Winthrop Professor and Chair of Obstetric Anesthesia School of Medicine and Pharmacology The University of Western Australia Senior Specialist Anaesthetist Department of Anaesthesia and Pain Medicine King Edward Memorial Hospital for Women Perth, Western Australia Quisqueya T. Palacios, MD Associate Professor Department of Anesthesiology Assistant Professor Department of Obstetrics and Gynecology Baylor College of Medicine Director of Patient Safety Division of Obstetric and Gynecologic Anesthesiology Baylor College of Medicine Houston, Texas Peter H. Pan, MD Professor Department of Anesthesiology Wake Forest University School of Medicine Wake Forest University Baptist Medical Center Winston-Salem, North Carolina

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Feyce M. Peralta, MD Assistant Professor–Clinical Department of Anesthesiology The Ohio State University Wexner Medical Center Columbus, Ohio

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May C. M. Pian-Smith, MD, MS Assistant Professor Department of Anesthesia Harvard Medical School Obstetric Anesthesiologist Department of Anesthesia, Critical Care and Pain Medicine Massachusetts General Hospital Boston, Massachusetts Mihaela Podovei, MD Instructor in Anesthesia Harvard Medical School Staff Anesthesiologist Department of Anesthesiology, Perioperative and Pain Medicine Brigham and Women’s Hospital Boston, Massachusetts Stephen D. Pratt, MD Assistant Professor Department of Anesthesia Harvard Medical School Chief, Division of Quality and Safety Department of Anesthesia, Critical Care, and Pain Medicine Beth Israel Deaconess Medical Center Boston, Massachusetts Roanne L. Preston, MD, FRCPC Clinical Professor Department of Anesthesiology Pharmacology and Therapeutics The University of British Columbia Department Head Department of Anesthesia British Columbia Women’s Hospital and Health Centre Vancouver, British Columbia, Canada

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Contributors

Jaya Ramanathan, MD Professor Department of Anesthesiology The University of Tennessee Health Science Center Director of Obstetric Anesthesia Regional Medical Center at Memphis Memphis, Tennessee

Monica San Vicente, MD, FRCPC Associate Professor Department of Anesthesiology Perioperative Medicine and Pain Management University of Saskatchewan Saskatoon, Saskatchewan, Canada Barbara M. Scavone, MD Professor Department of Anesthesia and Critical Care Department of Obstetrics and Gynecology The University of Chicago Chief Division of Obstetric Anesthesia University of Chicago Medical Center Chicago, Illinois

Sivam Ramanathan, MD (deceased) Professor Emeritus University of Pittsburgh Director of OB Anesthesia Research Associate Director OB Anesthesia Fellowship Department of Anesthesiology Cedars-Sinai Medical Center Los Angeles, California J. Sudharma Ranasinghe, MD, FFARCSI Professor of Clinical Anesthesiology Department of Anesthesiology University of Miami Miller School of Medicine Chief of Obstetric Anesthesia Department of Anesthesiology Jackson Memorial Medical Center Miami, Florida

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José M. Rivers, MD Associate Professor Department of Anesthesiology Baylor College of Medicine Faculty Department of Anesthesia Ben Taub Hospital Houston, Texas

George R. Saade, MD Professor Department of Obstetrics and Gynecology The University of Texas Medical Branch Chief of Obstetrics and Maternal-Fetal Medicine Department of Obstetrics and Gynecology John Sealy Hospital Galveston, Texas

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Scott Segal, MD, MHCM Chair, Department of Anesthesiology Tufts University School of Medicine Anesthesiologist-in-Chief Tufts Medical Center Boston, Massachusetts

Sally Radelat Raty, MD, MHA Associate Professor Department of Anesthesiology Baylor College of Medicine Chief, Division of General and Trauma Anesthesia Department of Anesthesiology Ben Taub General Hospital Houston, Texas Elena Reitman-Ivashkov, MD Assistant Professor Anesthesiology Department Columbia University Staff Anesthesiology Department The Presbyterian Hospital New York, New York

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Baha Sibai, MD Professor Department of Obstetrics and Gynecology The University of Texas Medical School Lyndon Baines Johnson General Hospital Houston, Texas

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Michelle Simon, MD Assistant Professor Department of Anesthesiology Galveston, Texas Julie A. Sparlin, MD Clinical Instructor Department of Anesthesiology Creighton University School of Medicine Associate Medical Director Center for Comprehensive Pain Management Valley Pain Consultants at St. Joseph’s Hospital and Medical Center Phoenix, Arizona Margaret Srebrnjak, MD, FRCPC Assistant Professor Department of Anesthesia University of Toronto Toronto, Canada Staff Anesthesiologist Department of Anesthesia The Credit Valley Hospital Mississauga, Ontario, Canada John T. Sullivan, MD, MBA Residency Program Director Department of Anesthesiology Northwestern University Feinberg School of Medicine Chicago, Illinois

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Contributors

William J. Sullivan, QC, LLB, MCL Adjunct Professor Faculty of Medicine The University of British Columbia Partner Guild Yule, LLP Barristers and Solicitors Vancouver, British Columbia, Canada

Ashutosh Wali, MD, FFARCSI Associate Professor of Anesthesiology Associate Professor of Obstetrics and Gynecology Baylor College of Medicine Director, Obstetric and Gynecologic Anesthesiology Director, Advanced Airway Management Ben Taub General Hospital Houston, Texas

Maya S. Suresh, MD Professor and Chairman Department of Anesthesiology Baylor College of Medicine Division Chief Obstetrics and Gynecologic Anesthesiology Ben Taub General Hospital Houston, Texas

Jonathan H. Waters, MD Professor Departments of Anesthesiology and Bioengineering University of Pittsburgh Chief of Anesthesia Services Department of Anesthesiology Magee-Womens Hospital Pittsburgh, Pennsylvania

Roulhac D. Toledano, MD, PhD Assistant Clinical Professor Department of Anesthesiology SUNY–Downstate Medical Center Director of Obstetric Anesthesia Lutheran Medical Center Brooklyn, New York Daniel A. Tolpin, MD Assistant Professor Department of Anesthesia Baylor College of Medicine Attending Physician Department of Cardiovascular Anesthesia Texas Heart Institute Houston, Texas Ashley M. Tonidandel, MD Assistant Professor Department of Anesthesiology Wake Forest University School of Medicine Wake Forest University Baptist Medical Center Winston-Salem, North Carolina

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Connie Khanh Vu Lan Tran, MD Associate Professor Department of Anesthesiology Baylor College of Medicine Ben Taub General Hospital Houston, Texas

Rakesh B. Vadhera, MD, FRCA, FFARCSI Professor Department of Anesthesiology Galveston, Texas Manuel C. Vallejo, MD, DMD Professor Department of Anesthesiology University of Pittsburgh Director, Obstetric Anesthesia Department of Anesthesiology Magee-Womens Hospital of UPMC Pittsburgh, Pennsylvania

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Samantha J. Wilson, BSc, BMBCh, FRCA Specialist Registrar Department of Anaesthesia University College Hospital London, United Kingdom

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David Wlody, MD Medical Director and Vice President for Medical Affairs Chief of Service, Department of Anesthesiology State University of New York Downstate Medical Center University Hospital of Brooklyn at Long Island College Hospital Professor of Clinical Anesthesiology Vice Chair for Clinical Affairs Department of Anesthesiology State University of New York Downstate Medical Center Brooklyn, New York

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Nikolaos Marios Zacharias, MD, FACOG Assistant Professor Department of Obstetrics and Gynecology, Maternal–Fetal Medicine Division Baylor College of Medicine Medical Director, Prenatal Ultrasound Department of Obstetrics and Gynecology, Maternal–Fetal Medicine Division Ben Taub General Hospital Houston, Texas Mark I. Zakowski, MD Adjunct Associate Professor of Anesthesiology Charles R. Drew University of Medicine and Science Chief of Obstetric Anesthesia and Obstetric Anesthesiology Fellowship Director Department of Anesthesiology Cedars-Sinai Medical Center Los Angeles, California

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FOREWORD

It has been ten years since the publication of the last edition of Shnider and Levinson’s Anesthesia for Obstetrics. I am very pleased, as I am sure Dr. Shnider would be, that Dr. Suresh has undertaken the formidable task of updating and completely revising this textbook. Reviewing the contents of the book’s first edition, published in 1979, and each of the subsequent editions, provides an interesting review of the progress obstetric anesthesiologists have made in providing safe analgesia and anesthesia for women having babies. For example, when the book was first published, anesthesia was the third leading cause of maternal deaths, 45% of cesarean sections were performed under general anesthesia, less than 20% of women in the United States received epidural analgesia for labor, and epidural infusions and neuraxial opioids were not available. Currently the majority of women having babies in the United States receive epidural anesthesia and many institutions report labor epidural rates between 80 and 90% of vaginal deliveries. The current practice of administering continuous epidural infusions with dilute concentrations of local anesthetics and low-dose opioids has made for much safer anesthesia with significantly greater patient satisfaction. General anesthesia for cesarean section is now a rarity,

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in many hospitals less than 5% of all cesarean sections, and typically is limited to patients with one of a few uncommon medical conditions or those requiring extremely emergent delivery. Despite increasing maternal age, with the inevitable increase in pre-existing maternal disease, the marked increase in maternal obesity, and the increase in cesarean section rates, anesthetic-related maternal mortality has fallen dramatically and is no longer one of the major culprits. Anesthesia for Obstetrics was intended to be both a basic clinical guide and a reference source for students and practitioners. To accomplish this, great emphasis was placed on presenting in a lucid and concise fashion the various aspects of the pregnant women’s modified response to anesthetic drugs, the fetal effects of both maternal physiologic alterations and placental transfer of these drugs, as well as understanding the unique perinatal and obstetric issues. In the fifth edition, Dr. Suresh has continued this approach and has produced an authoritative and comprehensive textbook of obstetric anesthesia. Those who practice and those who receive obstetric anesthesia should benefit greatly.

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Gershon Levinson, MD San Francisco, California

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PREFACE

Shnider and Levinson’s Anesthesia for Obstetrics, Fifth Edition is the result of the contribution of several dedicated national and international experts in obstetric anesthesia, who have conceptualized the current evidence-based practice of modern obstetrical anesthesia in this textbook. Dr. Sol M. Shnider, the first editor of this book, was born in Yorktown, Saskatchewan, Canada. Dr. Shnider received his medical degree from the University of Manitoba and underwent his residency training at the Columbia University in New York. He was the founding member of the Society for Obstetric Anesthesia and Perinatology and the recipient of numerous awards and honors. Indeed, he was one of the pioneers of modern obstetrical anesthesia. The first three editions were edited by Dr. Sol M. Shnider and Dr. Gershon Levinson. The fourth edition, published in 2002, was edited by the late Dr. Samuel C. Hughes, Dr. Gershon Levinson, and Dr. Mark Rosen. I am grateful to both Dr. Levinson and Dr. Mark Rosen for giving us approval to proceed with the publication of the fifth edition. The fifth edition is unique due to the contributions of both national and international editors: Dr. Scott Segal (USA), Dr. Roanne Preston (Canada), Dr. Roshan Fernando (UK), and Dr. LaToya Mason (USA), who with their editing style have provided a global perspective to the practice of obstetric anesthesia. Since the first edition in 1979, this book has become the international standard in the field of obstetric anesthesia, with translations in Spanish, French, Portuguese, German, and Japanese; we hope to add other languages including Chinese translation and an electronic version. This textbook will continue, as in the past, to serve as a valuable guide and reference source for the present and next generation of anesthesia trainees, academic and private anesthesia practitioners, and other clinicians. The fifth edition is divided into eleven sections and comprises 50 chapters and 4 appendices. There are other textbooks on obstetric anesthesia that are complete and well written, whereas the focus and organization of the current Sol M. Shnider Anesthesia for Obstetrics fifth edition is in keeping with the vision of Dr. Sol M. Shnider; it reflects evidence-based, best practice approach and complete care of the obstetric patient. This book provides a comprehensive view of the role of the anesthesiologist as a physician responsible for sound judgment and for optimal and best outcomes for mother and baby, a view more in keeping with the approach to cutting-edge modern anesthesia practice. Maternal mortality has emerged as one of the most challenging healthcare issues in the last decade; in addition, incidence of obesity has reached epidemic proportions in the USA and globally increasing the challenges confronted by the practitioner caring for obstetrical patients. Obstetric anesthesia practice has had an important albeit positive influence on maternal mortality. The contributing authors have made a conscious effort to address new technologies such as ultrasound-guided approach to regional anesthesia, new airway devices, and technologies in advanced airway management. Since the last edition, significant changes and advances have occurred; therefore, almost all the chapters have been

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rewritten. There are new chapters that address the challenges confronting the anesthesia practitioner in the United States and globally. These chapters include: “Global Perspective on Obstetric Anesthesia,” “Near Misses and Mortality,” “Utilization of Crisis Resource Management in Maternal and Neonatal Safety,” “Jehovah’s Witness: Ethical and Anestheticrelated Issue,” “Anesthesia for Vaginal Birth after Cesarean Delivery,” “Difficult and Failed Intubation: Strategies, Prevention and Management of Airway-related Catastrophes,” and much more. The authors have also focused on postoperative pain management, “Postoperative Multimodal Acute Pain Management: Cesarean and Vaginal Delivery,” and “Chronic Pain Issues in the Postpartum Period.” Chapters on amniotic fluid embolism, thromboembolism, and hemorrhage have new information. The exciting field of in utero fetal surgery and EXIT procedure has been highlighted in this book. The authors and editors have attempted to present the information with key points at the end of every section in order to facilitate learning; it also makes it easy for the reader to understand, retain, and discuss the information cogently. The book also serves as a useful reference guide to the practicing anesthesiologists in academic centers, tertiary referral centers, and community hospitals. At the outset, a major investment was made by the publisher of the textbook who recognized that the computer savvy as well as the millennial reader is accustomed to creative graphs and figures in color and therefore opted for enhanced visual aesthetics by having full color figures and graphical presentations throughout the book. We also hope that this book with the color illustrations will not only make it interesting for the reader, but it will also help the reader use the reference and illustrations to prepare lectures, slides, and other creative illustrative media. We trust that this textbook will continue the tradition of high quality as in the previous editions. A comprehensive textbook of this depth and scope is not possible without the support and assistance of the family members, colleagues, friends, and support staff who have assisted the authors and editors in preparation of this textbook. I personally wish to thank all the authors and I am very grateful for their dedication and contribution to this illustrious textbook that bears the name of Sol M. Shnider, an Obstetric Anesthesiologist icon. I want to acknowledge our editors and express my utmost gratitude for their valuable time and dedication to the book; they have put in an enormous amount of time to enhance the quality of the contributions. I would like to acknowledge and thank Brian Brown for giving me the opportunity to be the lead senior editor. I also wish to acknowledge the masterful assistance of Tom Conville, Nicole Dernoski, and Ruchira Gupta for their skilled efficiency in organizing and managing the manuscripts, the illustrations, and obtaining permissions and trying to keep everyone on a tight timeline. Finally, I would like to express my sincere gratitude to my husband, my grandson, and my administrative secretary Annette Brieno for their continued support.

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Maya S. Suresh, MD

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CONTENTS

  

  

Cesarean Delivery

Progress in Labor and Outcomes

IV

Antenatal Fetal Assessment, Therapy, and Outcomes

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Christina M. Davidson

Intrapartum Fetal Monitoring: Old and New Concepts . . . . . . . . . . . . . . . . . .

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Michelle Simon • Rakesh B. Vadhera • George R. Saade

ANALGESIA AND ANESTHESIA FOR LABOR AND VAGINAL DELIVERY

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Alternative (Non-pharmacologic) Methods of Labor Analgesia . . . . . . . . . . . . . .

III

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Systemic and Inhalational Agents for Labor Analgesia

182

Rodolfo Gebhardt • Sarah L. Armstrong • Oscar A. de Leon-Casasola • Thomas Chai • Julie A. Sparlin • José M. Rivers • Roshan Fernando

14 Chronic Pain Issues After Cesarean Delivery

199

Ruth Landau

15 Anesthesia for Nondelivery Obstetric Procedures

220

Christopher R. Cambic • Feyce M. Peralta

V

81

Katherine W. Arendt • William Camann

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Management: Cesarean and Vaginal Delivery

NEONATAL WELL-BEING: OLD AND NEW CONCEPTS

16 Neonatal Resuscitation

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165

13 Postoperative Multimodal Acute Pain

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ASSESSMENT OF THE FETUS

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McCallum R. Hoyt

David C. Campbell • Monica San Vicente

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12 Anesthesia for Cesarean Delivery

Placental Transfer of Drugs and Perinatal Pharmacology . . . . . . . . . . . . . . . . .

3

. . . . . . . .

18

Mark I. Zakowski • Sivam Ramanathan

G R

ANESTHESIA FOR CESAREAN DELIVERY: MANAGEMENT OF POSTOPERATIVE AND POSTPARTUM ISSUES

Emily J. Baird • Richard C. Month • Valerie A. Arkoosh

17 Management of Neonatal Neurologic Injury: Evidence-based Outcomes

92

. . . . . . . .

Uteroplacental Circulation and Respiratory Gas Exchange . . . . . . . . . . . . . . .

2

155

Elena Reitman-Ivashkov • Pamela Flood • Mrinalini Balki

Physiologic Changes of Pregnancy . . . . . . . . . 1 Brenda A. Bucklin • Andrea J. Fuller

. . . . . . . . .

11 Effects of Anesthesia on Uterine Activity,

PHYSIOLOGY AND PHARMACOLOGY

. . . . . . . . . . . . . . . . . . . . . . . . . . .

1

144

C. LaToya Mason • Nikolaos Marios Zacharias

  

I

. . . . . . . . . . . . . . . . . . . . .

10 Anesthesia for Vaginal Birth After

Contributors v Foreword xi Preface xiii

258

Mihaela Podovei • Bhavani Shankar Kodali

Samantha J. Wilson • Roshan Fernando

Local Anesthetics in Obstetrics: Evidencebased Applications, Controversies, Toxicity, and Current Therapies 104

VI

ANESTHETIC CONSIDERATIONS AND MANAGEMENT OF OBSTETRIC COMPLICATIONS

. . . . . . . . . . . . . . . . .

8

Regional Analgesia/Anesthesia Techniques in Obstetrics 119 . . . . . . . . . . . . . . . . . . . . . . . . .

9

Manuel C. Vallejo

18 Abnormal Fetal Positions, Breech

Presentations, Shoulder Dystocia, and Multiple Gestation . . . . . . . . . . . . . . . . . . . .

Barbara M. Scavone

267

Thomas A. Gough • Paul Howell

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xvi

Contents

.

19 Preterm Labor and Delivery . . . . . . . . . . . . 278

31 Asthma in Pregnancy . . . . . . . . . . . . . . . . . . 524

Carlo Pancaro

Uma Munnur • Venkata D. P. Bandi

20 Intrapartum Fever, Infection,

32 Neurologic and Neuromuscular

Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . 537

.

and Sepsis . . . . . . . . . . . . . . . . . . . . . . . . . . . 303 Laura Goetzl

Stephanie R. Goodman • Suzanne Wattenmaker Mankowitz

21 Obstetric Hemorrhage, Novel

Pharmacologic Interventions, Blood Conservation Techniques, and Hemorrhage Protocols . . . . . . . . . . . . . . . . . 311

33 The Parturient with Intracranial

Ashutosh Wali • Jonathan H. Waters

34 New Thoughts on Bleeding and

.

and Spinal Pathology . . . . . . . . . . . . . . . . . . 551 Ellen M. Lockhart • Curtis L. Baysinger

Coagulation Disorders . . . . . . . . . . . . . . . . . 572

VII RISKS, STRATEGIES AND

Moeen K. Panni

MANAGEMENT OF ANESTHETIC COMPLICATIONS

G R

35 Morbid Obesity . . . . . . . . . . . . . . . . . . . . . . . 580 J. Sudharma Ranasinghe • Donald H. Penning

.

22 Amniotic Fluid Embolism . . . . . . . . . . . . . . 333 Quisqueya T. Palacios

36 Human Immunodeficiency Virus:

V d

Maternal and Fetal Considerations and Management . . . . . . . . . . . . . . . . . . . . . 595 .

23 Venous Thromboembolism in Pregnancy

and Guidelines for Neuraxial Anesthesia Following Anticoagulant and Antithrombotic Drugs . . . . . . . . . . . . . . . . . 349 Quisqueya T. Palacios

Roulhac D. Toledano • May C. M. Pian-Smith

ti e

37 Renal and Hepatic Disorders

in Pregnancy . . . . . . . . . . . . . . . . . . . . . . . . . 606 Michael Paech

24 Difficult and Failed Intubation: Strategies,

Prevention and Management of Airway-related Catastrophes in Obstetrical Patients . . . . . . 363

Maya S. Suresh • Ashutosh Wali • Edward T. Crosby

25 NPO Controversies—Pulmonary

9 ri 9 h ta

-

Aspiration: Risks and Management . . . . . . . 403 Geraldine O’Sullivan • Scott Segal

26 Neurologic Complications of Regional

n U

38 Anesthesia for the Pregnant Patient

with Immunologic Disorders . . . . . . . . . . . . 626 Stephen H. Halpern • Margaret Srebrnjak

39 Psychiatric Disorders . . . . . . . . . . . . . . . . . . 647 Julio B. Delgado • Michael Frölich

40 Parturient with Pre-existing Congenital

Anomalies . . . . . . . . . . . . . . . . . . . . . . . . . . . 662 David G. Mann

.

Anesthesia in Obstetrics . . . . . . . . . . . . . . . 412

Alice L. Oswald

VIII ANESTHETIC MANAGEMENT OF THE PARTURIENT WITH COEXISTING DISORDERS

28 Hypertensive Disorders

of Pregnancy . . . . . . . . . . . . . . . . . . . . . . . . . 437 Jaya Ramanathan • Ravpreet Singh Gill • Baha Sibai

29 Anesthesia for Pregnant Patients with .

Endocrine Disorders . . . . . . . . . . . . . . . . . . 462 Peter H. Pan • Ashley M. Tonidandel

30 Anesthetic Management of the Pregnant

Cardiac Patient . . . . . . . . . . . . . . . . . . . . . . . 484 Shobana Chandrasekhar • Daniel A. Tolpin • Dennis T. Mangano

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IX

ETHICAL, MEDICAL, AND SOCIAL CHALLENGES AND ISSUES

41 Informed Consent and Other Ethical

and Legal Issues in Obstetric Anesthesia . . . . . . . . . . . . . . . . . . . . . . . . . . . 675

William J. Sullivan • M. Joanne Douglas

42 Substance Abuse and the Drug-addicted

Mother . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 683 John T. Sullivan

43 Jehovah’s Witness: Ethical and

Anesthetic-related Issues . . . . . . . . . . . . . . . 699 Connie Khanh Vu Lan Tran

44 Trauma During Pregnancy: Maternal

Resuscitation, Rapid Response Team, and Protocols . . . . . . . . . . . . . . . . . . . . . . . . 711 .

27 Postdural Puncture Headache . . . . . . . . . . . 425

.

David Wlody

Sally Radelat Raty • Kenneth L. Mattox • Uma Munnur • Andrew D. Miller • Mihaela Podovei

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Contents

50 Non-obstetric Surgery during

MATERNAL SAFETY, MORBIDITY, AND MORTALITY

Pregnancy

804

. . . . . . . . . . . . . . . . . . . . . . . . . . .

X

xvii

Yaakov Beilin

45 Utilization of Crisis Resource

Management and Simulation in Maternal and Neonatal Safety . . . . . . . . . . .

723

Stephen D. Pratt

APPENDICES

A Guidelines for Neuraxial

Joy L. Hawkins

B

47 Global Perspective on

Practice Guidelines for Obstetric Anesthesia: An Updated Report by the American Society of Anesthesiologists Task Force on Obstetric Anesthesia

750

. . . . . . . . . . . . . . . . . . .

C Optimal Goals for Anesthesia Care in Obstetrics

ANESTHETIC CONSIDERATIONS FOR REPRODUCTIVE, IN-UTERO AND NON-OBSTETRIC PROCEDURES

48 In vitro Fertilization and Reproductive

Nomenclature, Interpretation, and General Management Principles 841

778

. . . . . . . . . . .

Intrapartum Therapy (EXIT)

Index

  

Roanne L. Preston • Katherine L. Cheesman

49 In Utero Fetal Surgery and Ex Utero David G. Mann • Olutoyin A. Olutoye

9 ri 9 h ta

-

839

D Intrapartum Fetal Heart Rate Monitoring:

765

. . . . . . . . . . . . . . . . . . . . . . . . .

Technologies

G R

819

V d

849

ti e

n U

. . . . . . . . . . . . . . . .

XI

. . . . . . .

Holly A. Muir • Medge D. Owen

. . . . . . . . . . . . . . . . . . . . . . . . .

Obstetric Anesthesia

817

. . . . . . . . . . . . . . . .

Anesthesia in Obstetrics

739

. . . . . .

46 Near Misses and Maternal Mortality

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S EC TIO N

I

Physiology and Pharma ology

CHAPTER

1

Physiologic Changes of Pregnancy  

c

c

C  ard ovas ular Changes of Pregnan y (Table 1-1) i

■■

lood olume V

B

The physiologic alterations of the cardiovascular system function to support fetal growth and metabolism, by significantly increasing uterine perfusion and also to prepare the parturient for blood loss at delivery.

Both the intravascular and extravascular fluid volumes increase substantially during pregnancy. Much of the average 12.5 kg weight gain during pregnancy is attributed to the increase in the intravascular and extravascular fluid volumes. Significant increases in maternal blood volume occur, with plasma volume increasing 55% from 40 mL/kg to 70 mL/ kg and red blood cell volume increasing approximately 17% from 25 mL/kg to 30 mL/kg (1,2) (Fig. 1-1). This increase in volume begins in the first few weeks of gestation, rises sharply in the second trimester, peaks early in the third trimester and decreases slightly by term (1). The rise in plasma volume is likely achieved by a decreased osmotic threshold for thirst and alterations in arginine vasopressin metabolism (3). A large portion of the increased blood volume perfuses the gravid uterus and 300 to 500 mL of blood may be forced back into the maternal circulation with contractions during labor (2,4). Blood volume returns to prepregnancy values at approximately 7 to 14 days postpartum (2). Increased red blood cell production is stimulated by a rise in erythropoietin by the second month of gestation (5). The disproportionate increase in plasma volume to red blood cell

volume results in the “physiologic anemia of pregnancy” and a normal hemoglobin concentration of 11.6 gm/dL (6). Maternal anemia is present when the hemoglobin and hematocrit fall to less than 11 g/dL or 33% respectively, the most likely cause of which is iron deficiency. The increase in blood volume during pregnancy prepares the parturient for normal blood loss at delivery. Blood loss is usually less than 500 mL for vaginal delivery and 1,000 mL for cesarean delivery. Hemodynamic changes due to blood loss are usually not observed until the blood loss is greater than 1,500 mL and transfusion is rarely required unless blood loss exceeds this amount. Blood volume decreases to 125% of prepregnancy levels in the first postpartum week and by the sixth to ninth postpartum week there is a more gradual decline in the blood volume to 110% of the prepregnancy level. The hemoglobin and hematocrit also decrease during the initial postpartum period and then gradually increase to prepregnancy levels by the sixth postpartum week.

Central

emodynamics ( ig. 1-2) F

Unique anatomic and physiologic modifications occur during pregnancy, labor, delivery, and the postpartum period. Every organ system undergoes changes—from the substantial increase in cardiac output observed throughout pregnancy and the peripartum period to the brain’s increased sensitivity to anesthetic agents during pregnancy. The increased production of hormones from the ovaries and placenta and release of endorphins further impacts the physiologic changes. A thorough understanding of the anatomical and physiologic changes is a requirement for an anesthesia practitioner caring for women during this period in order to ensure safe and optimal outcomes for mother and baby.

H

 

Brenda A. Bucklin • Andrea J. Fuller

Cardiac output begins to increase around 10 weeks’ gestation (7). Serial assessment of maternal cardiac output by impedance cardiography and echocardiography demonstrates that changes in cardiac output start early in gestation with an increase of 35% to 40% by the end of first trimester. The cardiac output continues to increase during pregnancy until 34 weeks when it reaches 50% above prepregnant values and remains stable until term (8,9) (Fig. 1-3). During this time, the percentage of cardiac output devoted to uterine blood flow increases from 5% to 11% (8). The increase in cardiac output is due to increases in heart rate and stroke volume. The initial increase in cardiac output is due to an increase in the heart rate which starts to occur as early as the fifth week of gestation. The heart rate rises steadily during pregnancy and is elevated approximately 10 to 20 bpm above baseline at term (Fig. 1-4). The hormonal changes and release of estrogens results in an early increase in stroke volume of approximately 20% as early as the fifth to eighth week of gestation. The stroke volume continues to increase by 25% to 30% from the first to third trimester of gestation. During parturition, further demands are placed on the heart. Additional increases in cardiac output occur during labor and delivery as a result of elevated heart rate and stroke volume

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section I  •  Physiology and Pharmacology

Table 1-1  Changes in Cardiovascular System Average Change

Blood volume

↑

+35–40%

Plasma volume

↑

+50%

Red blood cell volume

↑

+20%

Cardiac output

↑

+40–50%

Stroke volume

↑

+30%

Heart rate

↑

+15–20%

Femoral venous pressure

↑

+15 mm Hg

Total peripheral resistance

↓

−15 mm Hg

Mean arterial blood pressure

↓

−15 mm Hg

Systolic blood pressure

↓

−0–15 mm Hg

Diastolic blood pressure

↓

−10–20 mm Hg

Central venous pressure

None

No change

Adapted from: Ueland K. Maternal cardiovascular dynamics. VII. Intrapartum blood volume changes. Am J Obstet Gynecol 1976;126:671– 677; Pritchard J. Changes in blood volume during pregnancy and delivery. Anesthesiology 1965;26:393–399; Lindheimer M, Davison J. Osmoregulation, the secretion of arginine vasopressin and its metabolism during pregnancy. Eur J Endocrinol 1995;132:133–143; Hendricks C. Hemodynamics of a uterine contraction. Am J Obstet Gynecol 1958;76:968–982; Cotes P, Canning C, Lind T. Changes in serum immunoreactive erythropoietin during the menstrual cycle and normal pregnancy. Br J Obstet Gynaecol 1983;90:304–311; Clark S, Cotton D, Lee W. Central hemodynamic assessment of normal term pregnancy. Am J Obstet Gynecol 1989;161:1439–1442; Flo K, Wilsgaard T, Vartun A, et al. A longitudinal study of the relationship between maternal cardiac output measured by impedance cardiography and uterine artery blood flow in the second half of pregnancy. BJOG 2010;117:837–844; Mabie W, DiSessa T, Crocker L, et al. A longitudinal study of cardiac output in normal human pregnancy. Am J Obstet Gynecol 1994;174:1061–1064; Warner M, Fairhead A, Rawles J, et al. An investigation of the changes in aortic diameter and an evaluation of their effect on Doppler measurement of cardiac output in pregnancy. Int J Obstet Anesth 1996;5:73–78; Ueland K, Hansen J. Maternal cardiovascular dynamics. III. Labor and delivery under local and caudal analgesia. Am J Obstet Gynecol 1969;103:8–18; Ueland K, Hansen J. Maternal cardiovascular dynamics. II. Posture and uterine contractions. Am J Obstet Gynecol 1969;103:1–7; Seth R, Moss A, McNitt S, et al. Long QT syndrome and pregnancy. J Am Coll Cardiol 2007;49:1009–1018.

(10,11). Cardiac output further increases 15% during the latent phase of labor, 30% during the active phase, and 45% during the expulsive stage of labor compared to prelabor values (11). Every uterine contraction results in an increase in cardiac output by an additional 10% to 25% (12). Immediately following cesarean delivery, cardiac index increases by 40% and systemic vascular resistance index (SVRI) decreases by 39%. However, the mean arterial pressure is maintained. These changes persist for approximately 10 minutes but may be present for up to 30 minutes after delivery, and return to baseline values by 2 to 5 days postpartum (13). Hemodynamic changes at delivery are

LWBK1120-C01_p01-17.indd 2

6.0 Total blood volume 4.5 Volume (L)

Variable

Direction of Change

Plasma volume 3.0 Red blood cell volume 1.5

0.0

0

10

20

30

40

Gestation (weeks)

Figure 1-1  Changes in intravascular fluid volume (blood volume), plasma volume, and erythrocyte volume during progression of normal pregnancy. The disproportionate increase in plasma volume accounts for the relative anemia of pregnancy. Adapted from: Moir DD, Carty MJ. In: Moir DD, ed. Obstetric Anesthesia and Analgesia. Baltimore, MD: Williams & Wilkins; 1977. similar regardless of mode of delivery (13,14). While this substantial increase in cardiac work is well tolerated by most parturients, those with cardiac disease who are unable to increase cardiac output by meeting the large demands are often at highest risk for complications immediately postpartum. Systemic vascular resistance decreases from approximately 1,530 dyn s/cm5 to 1,210 dyn s/cm5 during pregnancy by several mechanisms (7). The production of prostacyclin, a potent vasodilator, is increased during pregnancy (15). Progesterone also has a vasodilator effect on vascular smooth muscle. The low resistance placental circulation is in parallel with the systemic circulation. The sum of two resistances in parallel is less than either alone, which serves to decrease the afterload. The physiologic anemia of pregnancy results in a change in rheology resulting in decreased blood viscosity and improved blood flow, which also decreases afterload (16). Pulmonary vascular resistance (PVR) is also reduced by approximately 30% during pregnancy, presumably by similar mechanisms (7,17). This may have important implications in a patient with a shunt due to a congenital cardiac lesion as the balance between SVR and PVR may be disrupted during pregnancy. The increase in cardiac output during gestation results in an overall increase in uteroplacental perfusion, renal perfusion, and lower y perfusion. Uterine blood flow increases gradually from 50 mL/min to 700 to 900 mL/min at term with over 90% of the blood flow going to the intervillous space. The remainder of the perfusion goes to the myometrium. At term, the skin blood flow increases by 3- to 4-fold thus resulting in an increase in the skin temperature.

Cardiac Evaluation During gestation, the diaphragm is shifted upward by the gravid uterus. The result is a leftward shift in the position of the heart that can produce an enlarged appearance of the cardiac silhouette on chest radiograph (Fig. 1-5) as well as axis changes on the ECG. Echocardiographic studies reveal

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CO

HR

Stroke V

LV dD/dt Myoc Thck (systole) (end diast)

left ventricular hypertrophy, demonstrated by increased enddiastolic chamber size and increased left ventricular wall thickness compared to nonpregnant women (18). The increase in cardiac mass is due to increased cardiac myocyte size rather than increased myocyte number (19). The left ventricular mass increases during gestation by 23% by the third trimester. Left ventricular end-diastolic volume also increases during gestation, with no change in the end-systolic volume thus resulting in a larger ejection fraction. When monitoring the hemodynamics, it should be noted that the central venous pressure, pulmonary artery diastolic pressure, and pulmonary capillary pressure are the same and comparable to the values in nonpregnant patients. Asymptomatic pericardial effusion has been reported in some parturients by echocardiographic studies (20). Normal ECG findings in pregnancy include shortened PR and uncorrected QT interval, a shift in the QRS axis in any direction, a small right QRS axis deviation in the first trimester, a small leftward QRS axis deviation in the third

SVR

78 ± 22 dyne/sec/cm-5

119 ± 47 dyne/sec/cm-5

4.86 cm

4.67 cm

9.3 cm/s

6.7 cm/s

88.3 ± 11 mL

73.4 ± 9 mL

83 ± 10 b/m

71 ± 10 b/m

6.2 ± 1 L/m

4.3 ± 0.9 L/m

0

43%

1210 ± 266 dyne/sec/cm-5

Percent 50

21%

1530 ± 520 dyne/sec/cm-5

4%

a

f

 

28% 18%

100

a

C

 

Figure 1-2 Hemodynamic changes of pregnancy from echocardiographic and pulmonary artery catheter monitoring in healthy women. CO, cardiac output; HR, heart rate; Stroke V, stroke volume; LV dD/dt (systole), left ventricle change (diameter/time); Myoc Thck (end diast), myocardial thickness; SVR, systemic vascular resistance; PVR, pulmonary vascular resistance. Data extracted from: Robson SC, Hunter S, Moore M, Dunlop W. Haemodynamic changes during the puerperium: A Doppler and M-mode echocardiographic study. Br J Obstet Gynaecol 1987;94:1028–1039; Clark SL, Cotton DB, Lee W, et al. Central hemodynamic assessment of normal term pregnancy. Am J Obstet Gynecol 1989;161:1439–1442.

Nonpregnant Pregnant

43%

17%

3

ter 1 • Physiologic h nges o Pregn ncy  

ap

C

150

h

PVR

trimester, and transient S–T segment changes. Women with long QT syndrome experience fewer cardiac events during pregnancy but are at increased risk for cardiac events ranging from syncope to sudden death in the 9 months following delivery (21). The most common benign dysrhythmias in pregnancy are premature ectopic atrial and ventricular contractions and sinus tachycardia (22). These normal findings must be differentiated from those indicating heart disease which include: (a) Systolic murmur greater than grade III; (b) any diastolic murmur; (c) severe arrhythmias; and (d) unequivocal cardiac enlargement on radiographic examination (21,22). Regurgitation of the pulmonary and tricuspid valves is observed in 94% of normal pregnant women at term, while regurgitation of the mitral valve is present in

Pregnant Nonpregnant 100 90

6

Lateral

60

Delivery 4

10

0

70

20

30

50

40

0

Weeks of pregnancy

 

Figure 1-3 Changes in cardiac output during pregnancy. Adapted from: Lees MM, Taylor SH, Scott DB, et al. A Study of cardiac output at rest throughout pregnancy. J Obstet Gynaecol Br Commonw 1967;74:319.

2

4

6

8

Lunar months of pregnancy

10

2

4

6

Days postpartum

Figure 1-4 Changes in maternal heart rate during pregnancy. Adapted from: Burwell CS and Metcalfe JA: Heart disease and Pregnancy: Physiology and Management. Boston: Little, Brown and Co.; 1958.  

5

80

Delivery

Supine Heart rate

Cardiac output (L/min)

7

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section I  •  Physiology and Pharmacology

Figure 1-5  Chest radiograph of a woman during pregnancy (left) and postpartum (right). Reprinted by permission from: Burwell CS, McAnulty JH, Ueland K, eds. Heart Disease in Pregnancy: Physiology and Management. Boston: Little, Brown and Co;1986:60–63.

The maternal blood pressure measurement is affected by position, gestational age, maternal age, and parity. The changes in systemic vascular resistance result in a decrease in the systolic, diastolic, and mean arterial pressure during midgestation followed by a return to baseline by the end of gestation. The decrease in diastolic pressure is more than the systolic pressure with maximum decrease of 20% toward the midgestation (Fig. 1-6). Blood pressure increases with maternal age. Measurement of blood pressure obtained in the dependent left arm in the left lateral position correlates closely with the supine or sitting blood pressure.

Sympathetic Nervous System Decreased systemic vascular resistance results in part from the blood flow through the developing low resistance bed of the uterine intervillous space. Studies attribute the decrease in vascular tone to a- and b-receptor down-regulation and increased prostacyclin production (25–27), resulting in increased renal, uterine, and extremity blood flow. Despite a general decrease in vascular tone, there is greater maternal dependence on the sympathetic nervous system for maintenance of hemodynamic stability during pregnancy. Dependence increases progressively throughout pregnancy and peaks at term (28–30). The effects of decreased vascular tone are primarily observed on the venous capacitance system of the lower extremities. These effects counteract the untoward

LWBK1120-C01_p01-17.indd 4

Systolic blood pressure

120 100

Diastolic blood pressure 80 60 40

Delivery

Blood Pressure

effects of uterine compression of the inferior vena cava on venous return. Parasympathetic deactivation toward term is likely to contribute to increased heart rate and cardiac output at rest (31). Complex hormonal mediation results in depression of baroreflexes during pregnancy, making pregnant women even more susceptible to hypotension (32). In addition, some investigators suggest that an even greater decrease in vagal tone during pregnancy allows for relatively normal sympathetic function (33,34). This helps to explain why few women become severely bradycardic despite the high sympathectomy commonly seen at cesarean delivery. Although pharmacologic sympathectomy in term pregnant women can result in a marked decrease in blood pressure, there are minimal changes in blood pressure in nonpregnant women (28).

Blood pressure (mm Hg)

27% (23). Changes in heart sounds are not uncommon during pregnancy with an accentuation of the first heart sound and an exaggerated splitting of the mitral and tricuspid component. There are minimal changes in the second heart sound. In late pregnancy, a third heart sound may be heard as well (24). A murmur resulting from aortic regurgitation is not normally present in the pregnant patient (23), but grade I to II systolic heart murmurs caused by increased blood flow and tricuspid annulus dilation are commonly heard on auscultation of the heart (24).

Pregnant Nonpregnant

20 0 0

2

4

6

8

Lunar months of pregnancy

10

2

4

6

Days postpartum

Figure 1-6  Changes in blood pressure during pregnancy.

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ortocaval Compression

Upon assuming the supine position, up to 15% of pregnant patients near term experience signs of shock, including hypotension, pallor, sweating, nausea, vomiting, and mental status changes. This constellation of symptoms is due to decreased venous return to the right ventricle and has been dubbed “supine-hypotension syndrome” (35). Imaging studies demonstrate complete or nearly complete occlusion of the inferior vena cava by the gravid uterus in the supine position (36,37). Partial compensation is accomplished by blood bypassing the obstructed inferior vena cava and returning to the heart via the paravertebral (epidural) veins emptying into the azygos system. However, the net result of occlusion of the inferior vena cava is decreased cardiac output and decreased organ perfusion in the supine position. Shifting from the supine to the lateral position partially relieves the obstruction of the vena cava (37) (Fig. 1-7). The collateral circulation is adequate enough to maintain right ventricular filling pressures in the lateral position. Compression of the inferior vena cava is most common in late pregnancy before the fetal presenting part becomes fixed in the pelvis. The pooling of venous blood in the lower extremities results in a tendency toward phlebitis, venous varicosities, and lower extremity edema during pregnancy. Ankle edema, leg varicosities, and hemorrhoids indicate lower extremity venous engorgement. Blood flow to the uterus is proportional to perfusion pressure, i.e., uterine artery minus venous pressure. Compression of the inferior vena cava affects uteroplacental perfusion resulting in an

 

Figure 1-7 Lateral and cross-sectional views of uterine aortocaval compression in the supine position and its resolution by lateral positioning of the pregnant woman. Reprinted by permission from: Bonica JJ, ed. Obstetric Analgesia and Anesthesia. Amsterdam: World Federation of Societies of Anaesthesiologists;1980.

a

f

a

C

 

ter 1 • Physiologic h nges o Pregn ncy  

ap

C A

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overall decrease in perfusion. Increased uterine venous pressure further decreases uterine blood flow which can compromise fetal well-being. Even when maternal blood pressure is normal, uterine artery perfusion pressure decreases in the supine position because of increases in uterine venous pressure. While typically not associated with maternal symptoms, aortic compression results in increased maternal blood pressure measured in the upper extremity analogous to an aortic cross clamp. Partial occlusion of the aorta by the gravid uterus occurs in the supine position as well (38). At the same time, arterial hypotension is occurring in the lower extremities and uterine arteries. This results in decreased uterine blood flow to the fetus and fetal hypoxia (39). Therefore, even with normal upper extremity maternal blood pressure, uteroplacental perfusion may be decreased in the supine position. In fact, turning the term parturient from the supine to the left lateral position increases intervillous blood flow by 20% and increases fetal oxygen tension by 40% (40,41). Nonreassuring fetal heart rate patterns are more often observed in parturients in the supine position, particularly in the presence of neuraxial or general anesthesia (42). It is critical during anesthetic management to recognize the importance of aortocaval compression, the effects of which are observed as early as the 20th week of gestation. Drugs causing vasodilation, such as propofol and volatile anesthetics, or techniques resulting in sympathetic blockade, will further decrease venous return to the heart in the presence of vena cava obstruction. The presence of sympathetic blockade reduces or eliminates vasoconstriction in response to decreased venous return thus prevention of aortocaval compression is imperative. The vast majority of women avoid the supine position at night after 30 weeks (43). Therefore, it would do well to heed this natural instinct and avoid the supine position in a gravid patient. Maintaining the patient in lateral position with left uterine displacement (LUD) is essential to prevent aortocaval compression. This can be accomplished by manual displacement of the uterus, where the uterus is lifted and displaced to the left. Other alternatives include tilting the operating or delivery table 15 degrees or using sheets, a foam rubber wedge, or an inflatable bag to elevate the right buttock and back 10 to 15 cm. In the presence of conditions such as polyhydramnios or multiple gestations where the uterus is unusually large, more displacement (up to 30 degrees) may be required to relieve compression of the great vessels (44). Visual assessment of the position of the uterus is often invaluable—when the patient is in the supine position, the uterus should be visibly tilted away from the great vessels in the abdomen. Frequently, when maternal hypotension is present left uterine displacement is inadequate and repositioning the patient should be immediately considered. Occasionally, right uterine displacement or right lateral position may be at least as effective as left uterine displacement. Placement of the mother in LUD is imperative during cesarean delivery because neonates have less frequent and less severe depression of Apgar scores and are less likely to develop acidosis when LUD is employed (45). The Trendelenburg position without LUD is not an effective means to prevent or treat maternal hypotension and in fact, may worsen the maternal vital signs by shifting the uterus back further onto the vena cava and aorta. Maternal bearing down during the second stage of labor may also cause aortocaval compression and potentially decreased uterine perfusion (46). Any gravid patient near term with hypotension should be placed in LUD or the complete lateral position without delay as adequate venous return is essential to the success of any subsequent treatment. The anesthetic significance of the cardiovascular changes in pregnancy is summarized in Table 1-2.

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Table 1-2  Cardiovascular Changes: Anesthetic Significance A. Venodilation may increase the incidence of ­accidental epidural vein puncture. B. Healthy parturients will tolerate up to 1,500 mL blood loss; transfusion rarely required (hemorrhage at delivery remains an important risk). C. High hemoglobin levels (>14) indicate low-volume state caused by preeclampsia, hypertension, or inappropriate diuretics. D. Cardiac output remains high in first few hours ­postpartum; women with cardiac or pulmonary disease remain at risk after delivery. E. Epidural block reduces cardiac work during labor and may be beneficial in some cardiac disease states. F. Maternal blood pressure of G depletes alfentanil-induced analgesia and protects against respiratory depression in homozygous carriers. Pharmacogenet Genomics 2006;16:625–636. 162. Walter C, Lotsch J. Meta-analysis of the relevance of the OPRM1 118A>G genetic variant for pain treatment. Pain 2009;146:270–275. 163. Beyer A, Koch T, Schroder H, et al. Effect of the A118G polymorphism on binding affinity, potency and agonist-mediated endocytosis, desensitization,

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186. Tegeder I, Costigan M, Griffin RS, et al. GTP cyclohydrolase and tetrahydrobiopterin regulate pain sensitivity and persistence. Nat Med 2006;12:1269–1277. 187. Dabo F, Gronbladh A, Nyberg F, et al. Different SNP combinations in the GCH1 gene and use of labor analgesia. Mol Pain 2010;6:41. 188. Diatchenko L, Anderson AD, Slade GD, et al. Three major haplotypes of the beta2 adrenergic receptor define psychological profile, blood pressure, and the risk for development of a common musculoskeletal pain disorder. Am J Med Genet B Neuropsychiatr Genet 2006;141:449–462. 189. Hocking LJ, Smith BH, Jones GT, et al. Genetic variation in the beta2adrenergic receptor but not catecholamine-O-methyltransferase predisposes to chronic pain: results from the 1958 British Birth Cohort Study. Pain 2010;149:143–151. 190. Campa D, Gioia A, Tomei A, et al. Association of ABCB1/MDR1 and OPRM1 gene polymorphisms with morphine pain relief. Clin Pharmacol Ther 2008;83:559–566. 191. Zwisler ST, Enggaard TP, Noehr-Jensen L, et al. The antinociceptive effect and adverse drug reactions of oxycodone in human experimental pain in relation to genetic variations in the OPRM1 and ABCB1 genes. Fundam Clin Pharmacol 2010;24:517–524. 192. Delaney A, Keighren M, Fleetwood-Walker SM, et al. Involvement of the melanocortin-1 receptor in acute pain and pain of inflammatory but not neuropathic origin. PLoS One 2010;5:e12498. 193. Mogil JS, Ritchie J, Smith SB, et al. Melanocortin-1 receptor gene variants affect pain and mu-opioid analgesia in mice and humans. J Med Genet 2005;42:583–587. 194. Carroll L, Voisey J, van Daal A. Gene polymorphisms and their effects in the melanocortin system. Peptides 2005;26:1871–1885. 195. Beltramo M, Campanella M, Tarozzo G, et al. Gene expression profiling of melanocortin system in neuropathic rats supports a role in nociception. Brain Res Mol Brain Res 2003;118:111–118. 196. Mogil JS, Wilson SG, Chesler EJ, et al. The melanocortin-1 receptor gene mediates female-specific mechanisms of analgesia in mice and humans. Proc Natl Acad Sci U S A 2003;100:4867–4872. 197. Reimann F, Cox JJ, Belfer I, et al. Pain perception is altered by a nucleotide polymorphism in SCN9A. Proc Natl Acad Sci U S A 2010;107:5148–5153. 198. Estacion M, Harty TP, Choi JS, et al. A sodium channel gene SCN9A polymorphism that increases nociceptor excitability. Ann Neurol 2009;66:862–866. 199. Nilsen KB, Nicholas AK, Woods CG, et al. Two novel SCN9A mutations causing insensitivity to pain. Pain 2009;143:155–158. 200. Oertel B, Lotsch J. Genetic mutations that prevent pain: implications for future pain medication. Pharmacogenomics 2008;9:179–194. 201. Waxman SG. Nav1.7, its mutations, and the syndromes that they cause. Neurology 2007;69:505–507. 202. Ahmad S, Dahllund L, Eriksson AB, et al. A stop codon mutation in SCN9A causes lack of pain sensation. Hum Mol Genet 2007;16:2114–2121. 203. Goldberg YP, MacFarlane J, MacDonald ML, et al. Loss-of-function mutations in the Nav1.7 gene underlie congenital indifference to pain in multiple human populations. Clin Genet 2007;71:311–319. 204. Cox JJ, Reimann F, Nicholas AK, et al. An SCN9A channelopathy causes congenital inability to experience pain. Nature 2006;444:894–898. 205. Rush AM, Dib-Hajj SD, Liu S, et al. A single sodium channel mutation produces hyper- or hypoexcitability in different types of neurons. Proc Natl Acad Sci U S A 2006;103:8245–8250. 206. Kim H, Ramsay E, Lee H, et al. Genome-wide association study of acute post-surgical pain in humans. Pharmacogenomics 2009;10:171–179. 207. Nissenbaum J, Devor M, Seltzer Z, et al. Susceptibility to chronic pain following nerve injury is genetically affected by CACNG2. Genome Res 2010;20:1180–1190. 208. Dworkin RH, McDermott MP, Raja SN. Preventing chronic postsurgical pain: how much of a difference makes a difference? Anesthesiology 2010; 112:516–518. 209. Kehlet H, Rathmell JP. Persistent postsurgical pain: the path forward through better design of clinical studies. Anesthesiology 2010;112:514–515. 210. Scholz J, Yaksh TL. Preclinical research on persistent postsurgical pain: what we don’t know, but should start studying. Anesthesiology 2010;112:511–513. 211. Wicksell RK, Olsson GL. Predicting and preventing chronic postsurgical pain and disability. Anesthesiology 2010;113:1260–1261.











































































and resensitization of the human mu-opioid receptor. J Neurochem 2004; 89:553–560. 164. Bond C, LaForge KS, Tian M, et al. Single-nucleotide polymorphism in the human mu opioid receptor gene alters beta-endorphin binding and activity: possible implications for opiate addiction. Proc Natl Acad Sci U S A 1998;95:9608–9613. 165. Chong RY, Oswald L, Yang X, et al. The mu-opioid receptor polymorphism A118G predicts cortisol responses to naloxone and stress. Neuropsychopharmacology 2006;31:204–211. 166. Janicki PK, Schuler G, Francis D, et al. A genetic association study of the functional A118G polymorphism of the human mu-opioid receptor gene in patients with acute and chronic pain. Anesth Analg 2006;103:1011–1017. 167. Wand GS, McCaul M, Yang X, et al. The mu-opioid receptor gene polymorphism (A118G) alters HPA axis activation induced by opioid receptor blockade. Neuropsychopharmacology 2002;26:106–114. 168. Landau R, Kern C, Columb MO, et al. Genetic variability of the mu-opioid receptor influences intrathecal fentanyl analgesia requirements in laboring women. Pain 2008;139:5–14. 169. Mague SD, Blendy JA. OPRM1 SNP (A118G): involvement in disease development, treatment response, and animal models. Drug Alcohol Depend 2010;108:172–182. 170. Wong CA, McCarthy RJ, Blouin J, et al. Observational study of the effect of mu-opioid receptor genetic polymorphism on intrathecal opioid labor analgesia and post-cesarean delivery analgesia. Int J Obstet Anesth2010;19:246–253. 171. Andersen S, Skorpen F. Variation in the COMT gene: implications for pain perception and pain treatment. Pharmacogenomics 2009;10:669–684. 172. Dai F, Belfer I, Schwartz CE, et al. Association of catechol-O-methyltransferase genetic variants with outcome in patients undergoing surgical treatment for lumbar degenerative disc disease. Spine J 2010;10:949–957. 173. Diatchenko L, Nackley AG, Slade GD, et al. Catechol-O-methyltransferase gene polymorphisms are associated with multiple pain-evoking stimuli. Pain 2006;125:216–224. 174. Jensen KB, Lonsdorf TB, Schalling M, et al. Increased sensitivity to thermal pain following a single opiate dose is influenced by the COMT val(158)met polymorphism. PLoS One 2009;4:e6016. 175. Lee PJ, Delaney P, Keogh J, et al. Catecholamine-O-methyltransferase polymorphisms are associated with postoperative pain intensity. Clin J Pain 2011;27:93–101. 176. Rakvag TT, Klepstad P, Baar C, et al. The Val158Met polymorphism of the human catechol-O-methyltransferase (COMT) gene may influence morphine requirements in cancer pain patients. Pain 2005;116:73–78. 177. Reyes-Gibby CC, Shete S, Rakvag T, et al. Exploring joint effects of genes and the clinical efficacy of morphine for cancer pain: OPRM1 and COMT gene. Pain 2007;130:25–30. 178. Zubieta JK, Heitzeg MM, Smith YR, et al. COMT val158met genotype affects mu-opioid neurotransmitter responses to a pain stressor. Science 2003; 299:1240–1243. 179. Kolesnikov Y, Gabovits B, Levin A, et al. Combined catechol-O-methyltransferase and {micro}-opioid receptor gene polymorphisms affect morphine postoperative analgesia and central side effects. Anesth Analg 2011;112:448–453. 180. Doehring A, Antoniades C, Channon KM, et al. Clinical genetics of functionally mild non-coding GTP cyclohydrolase 1 (GCH1) polymorphisms modulating pain and cardiovascular risk. Mutat Res 2008;659:195–201. 181. Campbell CM, Edwards RR, Carmona C, et al. Polymorphisms in the GTP cyclohydrolase gene (GCH1) are associated with ratings of capsaicin pain. Pain 2009;141:114–118. 182. Kim DH, Dai F, Belfer I, et al. Polymorphic variation of the guanosine triphosphate cyclohydrolase 1 gene predicts outcome in patients undergoing surgical treatment for lumbar degenerative disc disease. Spine (Phila Pa 1976) 2010;35:1909–1914. 183. Lotsch J, Klepstad P, Doehring A, et al. A GTP cyclohydrolase 1 genetic variant delays cancer pain. Pain 2010;148:103–106. 184. Smith HS. The role of genomic oxidative–reductive balance as predictor of complex regional pain syndrome development: a novel theory. Pain Physician 2010;13:79–90. 185. Tegeder I, Adolph J, Schmidt H, et al. Reduced hyperalgesia in homozygous carriers of a GTP cyclohydrolase 1 haplotype. Eur J Pain 2008;12:1069–1077.

 

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15

Anesthesia for Nondelivery Obstetric Procedures Christopher R. Cambic  •  Feyce M. Peralta

Anesthesia providers occasionally provide care for women undergoing obstetric-related procedures not directly connected to labor and delivery. These procedures include cerclage for cervical insufficiency, external cephalic version (ECV) for nonvertex presentation, postpartum tubal sterilization, and assisted reproductive technologies, which is covered in Chapter 48. Despite each procedure presenting a unique set of anesthetic issues, the impact of pregnancyinduced physiologic changes on maternal and fetal wellbeing still remains a priority in the management of these patients. ■■

Cerclage

Cervical insufficiency is the inability to sustain a pregnancy to term due to dysfunction of the uterine cervix. It is characterized by painless dilation and/or shortening of the cervix during the second trimester of pregnancy, resulting in preterm delivery and recurring pregnancy loss. The incidence of cervical insufficiency is difficult to determine due to poorly defined clinical criteria for the diagnosis. Instead, the frequency of cervical cerclage is used as a surrogate to estimate the incidence of cervical insufficiency. Martin et al. reported that the rate of cervical cerclage is of 4.4/1,000 live births in the United States (1). Risk factors for the development of cervical insufficiency include familial inheritance (e.g., connective tissue disorders such as Ehlers–Danlos and Marfan syndromes), African-American race, intrauterine infections, hormonal abnormalities, congenital uterine abnormalities (e.g., in utero maternal exposure to diethylstilbestrol), and diagnostic or therapeutic surgical interventions (2–6). Structural damage to the uterine cervix from biopsies, cauterization, conization, and mechanical dilation and curettage are also associated with cervical insufficiency. Diagnosis of cervical insufficiency is one of exclusion, based on medical history and clinical assessment. History of previous pregnancy losses during the second trimester, cervical shortening, painless cervical dilation, and the presence of known risk factors should point toward this diagnosis. The patient may report vaginal pressure, caused by the protruding membranes, urinary frequency, and increased mucoid vaginal discharge. If left untreated, eventual rupture of fetal membrane may occur, which will likely proceed to the delivery of a premature and/or nonviable neonate (7). Ultrasound can aid in assessing cervical length, as the risk of spontaneous preterm labor/delivery is higher with shorter sonographic cervical length in the mid-second trimester (8). Since only a small fraction of all patients who will have a spontaneous preterm birth have a shortened cervix in the mid-second trimester, surveillance of the cervical length by ultrasound should only be considered in patients at high risk for cervical insufficiency (7,9).

Although controversial, management of cervical insufficiency is centered on cerclage placement. Current evidence suggests that the subgroups of patients that may benefit from cerclage placement are those with clinical presentation of acute cervical insufficiency, or those with a previous history of cervical insufficiency and progressive shortening of the cervix as demonstrated by ultrasound (7,10,11). Other therapies that have been used in combination with cervical cerclage for the management of cervical insufficiency include administration of progesterone, tocolytic drugs, and perioperative antibiotics (12–14). In a study published by the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network, the authors concluded that, when compared to placebo, weekly injections of progesterone resulted in a substantial reduction in the rate of recurrent preterm delivery in the at-risk patient (14). Information regarding other adjunct therapies is less well defined. Cerclage placement can be considered elective, urgent, or an emergency (15). Elective cerclage is typically performed between 13 and 16 weeks of gestation in asymptomatic patients with a history of cervical insufficiency or multiple risk factors. Urgent cerclage is performed after ultrasonographic findings of decreasing cervical length (2 cm), with or without bulging of the fetal membranes, in the absence of labor. Emergency cerclage is controversial since it carries a higher procedural risk of fetal membrane rupture. The timing for cervical cerclages in relation to neonatal outcome is also debated, as it has not been adequately studied in large, randomized trials. The optimal surgical technique for cerclage placement is unclear. In general, two approaches are used: transvaginal or transabdominal. The McDonald and the modified Shirodkar are the most common techniques for cerclage placement. Both of these surgical techniques are done by a transvaginal approach and have similar fetal outcomes (16). The McDonald cerclage is less invasive with a purse-string suture placed at the cervicovaginal junction, without bladder mobilization (Fig. 15-1). The Shirodkar cerclage differs from the McDonald in that the suture is placed following bladder mobilization, to allow for a higher insertion level (15,17). In addition, removal of a McDonald cerclage can usually be accomplished without the need for pain medication, whereas a Shirodkar cerclage is more invasive, and removal typically requires analgesia and possibly anesthesia. Transabdominal cerclage, which requires a laparotomy or laparoscopy, serves as an alternative for patients in whom placement of a transvaginal cerclage is exceedingly challenging (e.g., previous cervical surgery) or those who have had a failed transvaginal approach. A systematic review

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Figure 15-1 McDonald cerclage procedure. A: Suture is placed in four areas around the junction of the vaginal mucosa and cervix. B: Cross-sectional view of the cervix with cerclage in place. Reproduced with permission from: Rock J, Jones HW III. TeLinde’s Operative Gynecology. 10th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2008. comparing pregnancy outcomes after a transabdominal versus a transvaginal cerclage in patients with a failed transvaginal cerclage during a previous pregnancy concluded that the risk of perinatal death and delivery before 24 weeks was lower for women who received a transabdominal cerclage (6.0% vs. 12.5%, respectively) (18). However, transabdominal cerclage was also associated with a higher incidence of serious operative complications compared to the transvaginal approach (3.4% vs. 0%; 95% CI 0.01% to 6.8%). Cesarean delivery is typically the mode of delivery for patients with a transabdominal cerclage. The most frequent procedural risks associated with cervical cerclages include iatrogenic rupture of membranes, chorioamnionitis, hemorrhage, cervical stenosis, and cervical laceration. Cervical cerclages also increase the number of obstetrical interventions (e.g., administration of tocolytics, cesarean delivery, etc.) and the need for repeat cerclage in the future (19). Moreover, a meta-analysis of eight studies demonstrated that women who underwent cervical cerclage placement had a slightly higher rate of cesarean delivery compared to women who received other forms of treatment for cervical incompetency (relative risk [RR] 1.19; 95% CI 1.01 to 1.40) (20). Cervical cerclage should not be performed in the setting of maternal hemodynamic instability, rupture of fetal membranes, intra-amniotic or vaginal infection, abnormal placentation, active maternal or fetal bleeding, uterine contractions or preterm labor, intrauterine fetal demise, major fetal abnormality incompatible with life, and gestational age >28 weeks (19). The anesthetic management for cerclage placement will depend on the technical approach and timing of the procedure. Transvaginal cerclages are typically performed with spinal, epidural, or general anesthesia, while the transabdominal is more frequently done under general anesthesia. The procedure is usually performed in the outpatient setting,

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requires 30 to 45 minutes for completion, and a T10 to L1 and S2 to S4 sensory blockade is desired to provide coverage of the cervix, vagina, and perineum. Among the different neuraxial techniques, spinal anesthesia is the preferred choice as it provides a faster and denser block compared to epidural anesthesia. A hyperbaric solution of lidocaine 30 to 70 mg, hyperbaric bupivacaine 5.25 to 12 mg, or mepivacaine 45 to 60 mg are reasonable options for spinal anesthesia. Lee et al. observed that the spread of analgesic effects of spinally administered hyperbaric bupivacaine was enhanced in women in the second trimester compared to the nonpregnant state (21). Lipophilic opioids (e.g., fentanyl 10 to 20 mg) are often used to reduce local anesthetic requirements and duration (22,23). Although lidocaine may be a better option for cervical cerclage placement in terms of its duration, increased concern for transient neurologic syndrome (TNS) after intrathecal administration has dissuaded many providers from using hyperbaric lidocaine for cerclage placement. Indeed, the incidence of TNS in nonpregnant patients is higher with lidocaine than bupivacaine, and this risk of TNS is not decreased by decreasing the concentration (24,25). Although not completely exempt from the risk of TNS, parturients may be at decreased risk compared to nonpregnant patients. In a prospective study, Wong and Slavenas reported a 0% incidence (95% CI 0% to 4.5%) of TNS in 67 parturients who received hyperbaric 5% lidocaine for cerclage placement (26). Although no cases of TNS were detected, the 95% confidence interval is still less than the 10% to 37% incidence reported in the nonobstetric population (25). In another study, Aouad et al. randomized patients undergoing cesarean delivery to spinal anesthesia with hyperbaric 5% lidocaine or hyperbaric 0.75% bupivacaine, reporting a 0% incidence of TNS (95% CI 0% to 3%) (27). Finally, Philip et al. randomized patients to receive intrathecal hyperbaric 5% lidocaine versus hyperbaric 0.75% bupivacaine for postpartum tubal ligation (28). The authors reported no difference in the incidence of TNS with lidocaine versus bupivacaine (3% vs. 7%) in this patient population. Overall, the evidence suggests that the use of hyperbaric lidocaine intrathecally in pregnant women is likely safe in terms of TNS risk and that this risk is likely less than that in the nonpregnant population, and comparable to the intrathecal administration of other local anesthetics. Low-dose epidural anesthesia can also be used to provide surgical anesthesia for cervical cerclages (29). Lidocaine 2% with epinephrine 5 mg/mL, 10 to 15 mL, typically provides adequate sensory coverage; fentanyl 50 to 100 mg can be added through the epidural catheter to increase the density of the neuraxial block. Finally, paracervical block is another option for a McDonald cerclage, but it has fallen out of favor due to the potential for fetal bradycardia after local anesthesia injection, with a reported incidence of 2% to 10% (30–32). Regardless of the anesthetic technique, postoperative analgesic requirements are none to minimal after transvaginal placement of a cervical cerclage. General anesthesia is more likely to be used for emergency cerclage as the use of volatile anesthetics provides uterine relaxation, potentially reducing cervical protrusion of fetal membranes. In addition, this anesthetic technique does not require a sitting or lateral position for administration, positions which may not be possible if protruding fetal membranes are present. Mask anesthesia or a laryngeal mask airway (LMA) is an acceptable option for healthy, fasted patients before 18 to 20 weeks of gestation. However, women of 18 to 20 weeks of gestation and later are at increased risk of aspiration, and therefore should undergo endotracheal intubation. If intubation is performed, beware that coughing

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Figure 15-2  Types of breech presentations. A: Frank Breech— the lower extremities of the fetus are flexed at the hips and extended at the knees. B: Complete Breech—both the hips and knees of the fetus are flexed. C: Incomplete Breech— one or both of the lower extremities of the fetus are extended at the hips. Reproduced with permission from: Evans, AT. Manual of Obstetrics. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2007.

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and vomiting increase intra-abdominal and intrauterine pressures, precipitating or worsening protrusion of the fetal membranes, or even promoting membrane rupture. Steps should be taken to ensure these perianesthesia events are avoided. ■■

External Cephalic Version

The incidence of breech presentation for term, singleton pregnancies is estimated to be between 3% and 4% (33). Breech fetal presentation occurs when the fetal head is in the fundus of the uterus with the buttocks, legs, or feet presenting. There are three main types of breech presentations: frank, complete, and incomplete (Fig. 15-2). A frank breech occurs when the fetus’s lower extremities are flexed at the hips and extended at the knees so that the feet are against the face and the buttocks only are the presenting part. A complete breech occurs when the fetus’s hips and knees are flexed but the feet do not extend below the buttocks. An incomplete breech (also known as footling breech) occurs when one or both fetal lower extremities are extended and one or both feet present in the vagina. Although the causes of breech presentation are unclear, there are both fetal and maternal factors that increase this likelihood (Table 15-1). A relative increase in the uterine volume (e.g., prematurity, low birth weight) prevents the accommodation of the fetus to the shape of the uterine cavity leading to malpresentation. Multiparity, multiple gestation, and polyhydramnios are also associated with breech presentation due to increased uterine relaxation. Finally, limited uterine space (e.g., pelvic tumors, uterine anomalies, abnormal placentation, oligohydramnios) and fetal muscular disorders (e.g., muscular dystrophy) can result in fetal malpresentation. In all of these situations, cephalic rotation of the fetus may not occur prior to delivery (34–36). Multiple delivery options exist for fetuses in breech presentation, including cesarean delivery, trial of labor with vaginal delivery, or ECV, each with its respective benefits and risks. The Term Breech Trial (TBT) randomized more than 2,000 women with a singleton fetus in breech presentation to cesarean or vaginal delivery (37), and demonstrated better neonatal outcomes after a cesarean delivery than after vaginal delivery for breech-presenting fetuses, (1.6% vs. 5%, respectively); (RR 0.33; 95% CI 0.19 to

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0.56; P < 0.0001). Since this publication, the breech vaginal delivery rate has declined. In a retrospective study that assessed the vaginal delivery rate of breech term pregnancies in the 8 years before and after the TBT, the authors observed that the rate of vaginal delivery in nulliparous and multiparous women decreased from 15.3% to 7.2% in the former group, and from approximately 32.6% to 14.8% in the latter group (38). Since cesarean and vaginal breech deliveries increase maternal and perinatal morbidity and mortality compared to vaginal vertex deliveries. The American College of Obstetricians and Gynecologists (ACOG) recommends the use of ECV to rotate the fetus to a vertex presentation at term (37,39–41). ECV is an obstetrical procedure performed for the purpose of changing a nonvertex (typically breech) fetal presentation to vertex by external rotation through the maternal abdominal wall. According to a systematic review of randomized controlled trials, the overall success rate of ECV is 60%, with results ranging from 35% to 85% depending if tocolytics are used (42,43). If successful, ECV not only reduces the need for cesarean delivery, but also results in improved maternal and perinatal outcomes (44,45).

Table 15-1  Predisposing Factors for Breech Presentation Fetal

Maternal

Prematurity

Uterine relaxation (e.g., high parity, multiple fetuses, polyhydramnios)

Fetal neurologic impairments (e.g., muscular dystrophy)

Abnormal placentation

Fetal congenital anomalies Contracted maternal (e.g., hydrocephalus, pelvis anencephaly) Short umbilical cord

Mullerian duct anomalies

Oligohydramnios

Uterine anomalies Pelvic tumors Previous breech delivery

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afety

Despite the fact that ECV reduces the rate of noncephalic presentation at term, as well as maternal and neonatal morbidity associated with cesarean and vaginal breech deliveries, there is resistance by both physicians and women to attempt this procedure. Studies have reported that the number of women suitable for ECV who were not offered an attempted procedure ranges from 4% to 33% (46,48). Even when offered, rates of maternal refusal of ECV range from 18% to 76% (49,50). In addition, ECV may not always be beneficial to the mother and/or fetus. ECV is contraindicated whenever the procedure may pose significant harm to the fetus, if the likelihood of success after an attempt is very low, or when the indication for cesarean delivery is not limited to breech presentation (Table 15-2). Concerns about the safety of ECV are one issue that may dissuade obstetric providers and mothers. However, available evidence suggests that the overall rate of severe complications is relatively low. In a meta-analysis by Collaris et al. of 44 studies involving more than 7,000 women, the most frequently reported complication was transient fetal heart rate changes, occurring in 5.7% of ECV attempts (51). Persistent fetal heart rate changes, vaginal bleeding, and placental abruption occurred much less frequently (0.37%, 0.47%, and 0.12%, respectively). Similarly, the rate of emergent cesarean delivery and perinatal mortality were also low at 0.43% and 0.16%, respectively. However, there was also a 3% risk of

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spontaneous reversion to breech presentation after successful ECV at or beyond 36 weeks of gestation. Similar findings were also reported in a systematic review of 84 studies of 12,955 ECV-related complications for singleton breech pregnancies after 36 weeks of gestation. In this meta-analysis, the authors found a pooled complication rate of 6.1% (95% CI 4.7 to 7.8), with a risk of serious complications (e.g., placental abruption, fetal death) occurring in 1/417 ECV attempts, and emergent cesarean delivery occurring in 1/286 (52). Overall, the risk of complications from ECV was found to be no different between successful and failed attempts (OR 1.24; 95% CI 0.93 to 1.7) (Fig. 15-3).

The overall success rate of ECV can be predicted by the presence of several clinical and ultrasound factors. Known clinical factors associated with successful ECV include multiparity, low body mass index, a relaxed uterus, and a nonengaged fetal head (53). Interestingly, fundal height and gestational age have no impact on the outcome of ECV (54). Posterior placental location, complete breech presentation, and increased amniotic fluid index are ultrasound parameter predictors of successful ECV (55). Cluver et al. performed a meta-analysis of 25 studies involving more than 2,500 women, comparing several interventions used to increase the success of ECV (42). The interventions included the use of tocolytic drugs, regional anesthesia, vibroacoustic stimulation, amnioinfusion, and systemic opioids. Of these interventions the authors concluded that only tocolytics improved the success rate of ECV. In addition, the use of regional anesthesia with tocolytics was superior in increasing the ECV success rate than use of tocolytics alone. There was insufficient data to make recommendations on the use of vibroacoustic stimulation, amnioinfusion, and systemic opioids for ECV. Recently, Kok et al. developed a predictive model to calculate the chance of successful ECV. Although this model still requires external validation, it appears to discriminate between women with a poor chance of successful ECV (less than 20%) and women with a good chance of success (more than 60%) in breech pregnancies after 36 weeks of gestation age (56). T

S

Several studies have addressed the issue of appropriate timing for ECV procedures. A Cochrane systematic review demonstrated that ECV performed early in the third trimester (i.e., between 32 and 34 weeks of gestation) did not reduce the number of breech fetuses at term, nor did it reduce the number of cesarean deliveries (15). However, the authors were unable to make any definitive recommendations regarding the use of ECV at 34 to 36 weeks of gestation versus 37 weeks or later. Two randomized controlled trials, the ECV1 and early ECV2 trials, investigated this issue. The ECV1 trial randomized 232 patients with singleton breech fetus to undergo ECV between 34 and 36 weeks of gestation (early group) or between 37 and 38 weeks of gestation (delayed group) (46). Although the authors demonstrated that malpresentation at delivery was lower in the early group than in the delayed group (56.9% vs. 66.4%, respectively), the results were not statistically significant, likely due to the study being underpowered. As such, the authors performed the early ECV2 trial, in which more than 1,500 women with a singleton breech fetus were randomized to undergo ECV between 34 and 36 weeks of gestation or at or after 37 weeks (47). The authors demonstrated that fewer fetuses were in a noncephalic presentation at birth in the early ECV group (41%) versus (49%) in the late ECV group (RR 0.84; 95% CI 0.75 to 0.94; P = 0.002). Despite this difference, there was no difference in the rate of cesarean delivery between groups. Similarly, there were no differences in the rate of preterm birth or risk of maternal or neonatal morbidity between groups. The authors concluded that even though ECV at an early gestation increases the likelihood of cephalic presentation at birth, it does not result in decreased cesarean delivery rates. Currently, ACOG recommendations state that ECV should be offered to eligible patients at term, defined as after completion of 36 weeks of gestation, due to concerns regarding fetal size, spontaneous versions, spontaneous reversions, and well-being of the preterm fetus (39).

ondelive y

T ble 15-2 bsolute and elative Contraindication to xternal Cephalic Version a

iming of CV

f

 A

 

r

nesthesia o

E

T

p

Cha te 15 •

ocolysis

Various tocolytic agents have been used to provide uterine relaxation during ECV. When compared to control groups neither ritodrine, salbutamol, nor nitroglycerin have been found to increase the success rate of ECV after their administration

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0.1 0.2

0.5

More when failed

1

2

5

10

More when successful

Figure 15-3  Forest plot of odds ratios from individual studies reporting on all complications related to ECV in relation to the ECV outcome. OR, odds ratio; CI, confidence interval. Reproduced with permission from: Grootscholten K, Kok M, Oei SG, et al. External cephalic version-related risks: a meta-analysis. Obstet Gynecol 2008;112:1143–1151.

(57–59). In a prospective study by Fernandez et al., terbutaline was found to increase the success rate of ECV when compared to placebo (52% vs. 27%, respectively; RR of 1.9; 95% CI 1.3 to 6.5, P = 0.01) (60). In a systematic review, Wilcox et al. observed that patients that received nifedipine compared to terbutaline, had lower rates of successful ECV (pooled risk ratio = 0.67; 95% CI 0.48 to 0.93, P = 0.016) (61). Based on the available evidence, terbutaline is the tocolytic recommended for ECV procedures.

Analgesic Options Several studies have investigated the impact of intravenous analgesia, neuraxial analgesia, and neuraxial anesthesia on ECV success rates. Yoshida et al. assessed the ECV success rate as they changed their practice, from the time when they performed ECV without neuraxial anesthesia to when it was offered (62). The authors reported that not only did the overall ECV success rate increase from 56% to 79% after regional anesthesia was offered, but also the cesarean delivery rate in the term breech population decreased from 50% to 33%. Similarly, in a systematic review of six randomized controlled trials, Goetzinger et al. concluded that regional anesthesia was associated with a higher ECV success rate compared with intravenous or no analgesia (59.7% compared with 37.6%) (Fig. 15-4) (63).

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Neuraxial Techniques Compared to no or intravenous analgesia, neuraxial techniques provide several benefits for patients undergoing ECV. First, they allow for relaxation of the maternal abdominal wall, prevention of involuntary abdominal tensing, and improvement of maternal tolerance to the procedure, potentially increasing the success rate of ECV. In addition, maternal pain scores are significantly lower in patients that received neuraxial blockade compared to control groups in several randomized controlled studies (64–66). Sullivan et al. demonstrated that patient satisfaction scores were significantly higher in patients who received a combined spinal–epidural technique versus those who received intravenous (IV) fentanyl (10 vs. 7, P < 0.005) (66). Maternal discomfort in control groups can also lead to ECV discontinuation in some cases (65,67). The ability to rapidly extend epidural analgesia to a surgical level of anesthesia for emergent cesarean delivery is particularly beneficial, as it circumvents the need for general anesthesia and its inherent risks. Finally, in patients who undergo a trial of labor after ECV, the presence of a functioning epidural catheter allows for the provision of labor analgesia without the need for a second anesthetic technique. Several studies have attempted to elucidate the impact of neuraxial anesthesia on ECV success rates. However, the heterogeneity of these studies has led to conflicting results not

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0.1

1

r

c

r

c

bstet i P o edu es r

O

ondelive y r

N

r

nesthesia o f

 A

 

r

p

Cha te 15 •

225

5

 

Figure 15-4 Meta-analysis of the outcome of successful ECV comparing neuraxial anesthesia with intravenous or no anesthesia. The pooled risk ratio (RR) is 1.58 (95% confidence interval [CI] 1.29–1.93), I2 = 14.9%. Reproduced with permission from: Goetzinger KR, Harper LM, Tuuli MG, et al. Effect of regional anesthesia on the success rate of external cephalic version: a systematic review and meta-analysis. Obstet Gynecol 2011;118:1137–1144.

euraxial echniques T

ow-dose

N

L

only on the impact of analgesic and anesthetic techniques on ECV success rates, but also on its impact on maternal and fetal safety. Factors where studies differ include parity, timing of ECV in relation to gestational age, type and route of administration of tocolytics, local anesthetics used, and dose variations of neuraxially administered medications.

euraxial echniques T

ntermediate-dose

N

I

Low-dose intrathecal bupivacaine (i.e., 2.5 mg) with opioid have been shown not to improve the success of ECV. Dugoff et al. compared the success rate of ECV in patients who randomized to spinal anesthesia (0.5% bupivacaine 2.5 mg and sufentanil 10 mg) or no analgesia, and demonstrated no difference in overall ECV success rate between groups (44% spinal vs. 42% no spinal, P = 0.86) (67). Similarly, Sullivan et al. randomized patients to CSE technique (0.5% bupivacaine 2.5 mg and fentanyl 15 mg) versus intravenous fentanyl 50 mg before the procedure (66). The authors reported an ECV success rate of 47% with CSE compared to 31% in the intravenous group, although this result was not statistically significant.

euraxial echniques T

igh-dose

N

H

Weiniger et al. investigated the effect of a higher dose of intrathecal bupivacaine (7.5 mg) on ECV success rates in two separate studies that controlled for parity. The first study randomized term, nulliparous women to spinal dosage of bupivacaine 7.5 mg or no analgesia (65). The success rate of ECV was 67% in the spinal group compared to 34% in the control group, (P = 0.004). The follow-up study also randomized term, multiparous patients to spinal analgesia (bupivacaine 7.5 mg) or no analgesia, resulting in similar success rates of 87% in the spinal group compared to 57% in the control group, (P = 0.009) (64).

Schorr et al. randomized term parturients scheduled for ECV to receive an epidural or no epidural anesthesia (68). Lidocaine 2% with 1:200,000 epinephrine was administered through the epidural catheter with the goal of achieving a T6 level. The success rate was higher for the epidural group,

with 69% compared with 32% in the control group (P = 0.01). Mancuso et al. performed a similar study with epidural anesthesia, obtaining comparable results (69). A systematic review and meta-analysis of randomized trials by Goetzinger et al. suggest that neuraxial blockade is associated with an increased success rate of ECV (60% compared with 38%; RR 1.58; 95% CI [1.29 to 1.93]) but the risk of cesarean delivery was not significantly different for parturients that received neuraxial blockade compared to those that received intravenous or no analgesia (48% compared with 59%; RR 0.8; 95% CI 0.55 to 1.17) (63). Similar results were reported in a 2012 Cochrane Collaboration regarding interventions that improved the success rate of ECV. The authors concluded that regional analgesia, in addition to tocolytics, increased the success rate of ECV. Cephalic presentation in labor or cesarean delivery rate, however, was not different (42). Results regarding the ideal neuraxial technique to improve the success rate of ECV are inconclusive. In Goetzinger’s study the association between regional anesthesia and higher ECV success rate prevailed when the data was further divided into spinal and epidural groups, with epidural technique associated with a higher chance of ECV success (RR 1.91, 95% CI 1.29 to 1.93) than a spinal or CSE technique (RR 1.46, 95% CI 1.14 to 1.87), although this difference may be explained by the higher doses of local anesthetic used in the epidural groups (63). Lavoie and Guay performed a meta-analysis that compared randomized controlled trials on ECV success rates after neuraxial blockade with analgesic versus anesthetic doses, and concluded that the success rate for ECV is only increased by a neuraxial blockade in anesthetic doses (Fig. 15-5) (70). There are several limitations to many of these studies. Neuraxial blockade is poorly defined, as the terms analgesia and anesthesia are used arbitrarily. Different tocolytics have been used at different doses and routes of administration. While b-mimetics increase the success rate of ECV, information regarding the effectiveness of other tocolytics (e.g., calcium channel blockers and nitric acid donor) is limited (42). Multiparity increases the success rate of ECV and by not controlling for parity the success rate may not achieve the same positive effect. Although most of the current studies seem to indicate that anesthetic doses can improve the success rate of ECV, the authors’ opinion is that the risk-to-benefit ratio to both

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0.1 0.2 0.5 1

2

5 10

Favours control favours CNB Mixed effects models

Figure 15-5  Meta-analysis investigating the effect of neuraxial anesthetic technique on the success rate of ECV. I2 = 30.25% for the overall analysis and 0% for each subgroup. The two subgroups are significantly different from each other (P = 0.007). Reproduced with permission from: Lavoie A, Guay J. Anesthetic dose neuraxial blockade increases the success rate of external fetal version: a meta-analysis. Can J Anaesth 2010;57:408–414.

the mother and the fetus as well as the costs engaged after the administration of an anesthetic dose should all be considered before final recommendations are made. Overall, the available evidence is inconclusive to recommend a specific neuraxial technique or dosage of local anesthetic which increases the success of ECV. Well-designed randomized controlled trials that specifically address the effect of neuraxial techniques on ECV outcomes and control for confounding factors are needed before any firm recommendations can be made. Nevertheless, the majority of studies suggest a strong association between higher neuraxial doses of local anesthetic and improved ECV success rates. Moreover, a CSE technique seems to be a better alternative to a spinal or epidural technique, in that it offers the benefit of a spinal anesthetic (e.g., rapid onset, dense and reliable block, lower doses of local anesthetic needed) with the versatility of an epidural catheter (e.g., ability to quickly augment block to surgical level of anesthesia, ability to be used for labor analgesia). ■■

Cost-effectiveness

Tan et al. studied the cost-effectiveness, from society’s perspective, of ECV compared to schedule cesarean delivery for term breech presentation. Cost-effectiveness, defined by a certain quality-adjusted life year, was less for ECV compared to scheduled cesarean deliveries for breech presentation. However, this only held true if the probability of successful ECV was >32% (71). Moreover, Bolaji and colleague demonstrated that even if the use of a neuraxial technique would increase the number of successful ECV by 15%, this would result in more than $33,000 in savings due to the decreased rates of cesarean delivery and its complications (72). ■■

Logistics

ECV should be attempted in the operating room or in the labor and delivery unit with an operating room available in case an emergent cesarean delivery becomes necessary.

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However, considering the cost of utilizing an operating room, it may be cost effective to perform this procedure in the labor and delivery unit. In addition, both mother and fetus should be monitored throughout the procedure. Blood pressure and pulse oximetry should be used for the mother, while fetal monitoring should be performed before and after each ECV attempt. Moreover, left uterine displacement should be ensured whenever the patient is supine, and providers should have the ability to rapidly treat hypotension if it develops. Finally, ECV should be performed at times that do not detract from the care of the rest of the patients in the labor and delivery unit (Table 15-3).

Table 15-3  General Recommendations for External Cephalic Version • Fetal presentation should be reassessed before preparing the patient for ECV. • Verify nil per os (NPO) status of the patient. • Discuss with the obstetrician the delivery plan for each scenario, if the ECV is successful or not. • Consider placing an epidural catheter if the plan is to deliver the fetus after the ECV, regardless of success of the procedure, to provide either labor analgesia for induction of labor, or anesthesia for a cesarean delivery. • Perform ECV in the labor and delivery room, preoperative holding area or postoperative unit, after confirming that there is an operating room available for emergent cesarean delivery. • Plan for routine noninvasive monitoring of the mother, especially when neuraxial blockade is performed. • Maintain left uterine displacement throughout the procedure. • Fetal heart rate monitoring before and after each ECV attempt is recommended.

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S

b

ostpartum u al terilization T

P

■■

S

Tubal sterilization is a highly effective form of female birth control, with a failure rate of 30 kg/m2 (Fig. 35-1). In the United States obesity rates has reached epidemic proportions with extreme obesity (BMI >40 kg/m2) showing the greatest increase, particularly among women (3). According to the latest data from the National Health and Nutrition Examination Survey (NHANES) in 2007 to 2008, the prevalence of obesity was 32.2% among adult men and 35.5% among adult women in the United States (4) and certain ethnic groups are affected more than others (5). The dramatically increasing rate of obesity in the general population also extends to women of reproductive age. Obesity increases the risk for cesarean delivery significantly and thus also the need for anesthesia. Anesthesiologists are thus increasingly faced with the care for morbidly obese parturients. Overweight and obesity are major risk factors for a number of chronic diseases, including diabetes, ischemic heart disease, stroke, hypertension, hypercoagulability, osteoarthritis, gall bladder disease, and several types of cancer. There is evidence that risk of chronic disease increases progressively from a BMI of 21 kg/m2. Obesity caused by poor diet and physical inactivity is now the second leading cause of death in the United States (3). In pregnant women, obesity is associated with serious consequences on birth outcome (6). ■■

DEFINITIONS

Body mass index (BMI) is a simple, clinically relevant measure of overweight and obesity in adult population. It can be easily computed and well correlated with the risk of mortality. It is defined as the total body weight (TBW) in kilograms divided by the square of the height in meters (kg/m2). The World Health Organization (WHO) defines “overweight” as a BMI ≥25, obesity as a BMI ≥30. Obesity is further categorized by BMI into Class I (30 to 34.9); Class II (35 to 39.9) and Class III obesity (>40). Morbid obesity is BMI ≥40 kg/m2 and super obesity is classified as a BMI ≥50 kg/m2 (7). Although there are no pregnancy-specific definitions of obesity, the American College of Obstetricians and Gynecologists (ACOG) recommends using height and weight ­measured at the first prenatal visit to calculate the BMI. Pregnant women are considered obese when the BMI is ≥30 kg/m2, and morbidly obese when the BMI is ≥40 kg/m2. The maternal body weight is expected to increase during

­ regnancy due to increase in blood volume, fetus, placenta, p amniotic fluid, and deposition of new fat and protein. The normal mean maternal weight increase during pregnancy is 17% of the pre-pregnancy weight or about 12 kg (8). However, it is important to recognize that the allowable weight gain during pregnancy varies by pre-pregnancy BMI (8) (Table 35-1). Obesity is an increasing problem in women of child-bearing age. According to the data from the NHANES survey, at least 60% of women of child-bearing age are overweight or obese (3). There are several subgroups of obese individuals. A. Simple obesity B. Obesity hypoventilation syndrome (OHS) also referred to as “Pickwickian syndrome” comprises 5% to 10% of obese individuals. Fortunately, patients with OHS are usually not seen in labor and delivery due to two reasons: (1) This syndrome usually develops later in life and (2) patients with OHS are unlikely to get pregnant. C. Obesity-related metabolic syndrome: Increasing incidence of obesity worldwide has led to the recognition of this obesity-related metabolic syndrome also referred to as syndrome X, which is characterized by “truncal” obesity, insulin resistance or glucose intolerance (hyperglycemia), altered lipid levels, low HDL cholesterol, and high LDL cholesterol—that foster plaque buildup in arteries prothrombotic state, high fibrinogen or plasminogen activator inhibitor-1 in the blood; proinflammatory state (e.g., elevated serum C-reactive protein), and hypertension (9). Obesity-related metabolic syndrome carries a different risk profile than obesity alone. These patients are at a greater risk for coronary artery disease (CAD), obstructive sleep apnea (OSA), hypercoagulability with predisposition to deep vein thrombosis (DVT), and pulmonary dysfunction. ■■

PHYSIOLOGIC DISTURBANCES

Both obesity and pregnancy are associated with significant physiologic changes in multiple organ systems. Many of the physiologic effects of pregnancy and obesity are additive and can lead to considerable functional impairment and decreased physiologic reserves. Therefore, obstetric- and anesthetic-related complications are more frequent in obese parturients. A report of anesthesia-related maternal deaths in Michigan (1985 to 2003) confirms that obesity is an important risk factor for anesthesia-related maternal mortality (10). In the 2003–2005 Confidential Enquiries into Maternal and Child Health (CEMACH) report from the UK, there were six women who died from problems directly related to anesthesia, and obesity was a factor in four of them (11).

580

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CHAPTER 35  •  Morbid Obesity

70

581

USA

Population percentage with BMI ? 30kg/m2

65 Australia

60

England

55

Mauritius

50 45 40 35

Brazil

30 25 20 15 10 5 0

1960

1965

1970

1975

1980

1985

1990

1995

Years

Respiratory Changes Lung Volumes and Pulmonary Function Tests (PFTs)

Pregnancy is associated with significant anatomical and functional changes in the respiratory system. Similar to pregnancy, obesity reduces the expiratory reserve volume (ERV), residual volume (RV), and functional residual capacity (FRC). One would speculate that when an obese woman gets pregnant these changes in lung volumes will be markedly accentuated. However, according to a study by Eng et al. (12), such is not the case. They found that in obese women with reduced prepregnancy FRC, further reduction in pregnancy is ­limited.

TABLE 35-1  The National Institute of Medicine’s Guidelines for Weight Gain in Pregnancy Pre-pregnancy BMI

Recommended Weight Gain in kg/(lb)

29 (obese)

7–11.5 (15–25) ≤6 (≤15)

Adapted with permission from: Stotland NE. Obesity and pregnancy. BMJ 2009;338:107–110.

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2000

2005

2015 2010

2025 2020

2030

FIGURE 35-1  Projected prevalence of obesity in adults by 2025. The Global Challenge of Obesity and the International Obesity Task Force. http://www.iuns.org/

The reason for this finding is not clear. In some respects, pregnancy may reduce some of the negative effects of obesity on respiratory system. Progesterone is a direct respiratory stimulant and increases the sensitivity of brainstem to carbon dioxide. The relaxing effect of progesterone on smooth muscle decreases airway resistance. Oxygenation and ventilation of obese pregnant women in the upright position seem to be intermediate between normal-weight–term pregnant women and obese, nonpregnant women (13) (Table 35-2). During the third trimester of pregnancy, gravid uterus pushes the diaphragm in a cephalad direction. It has been shown that the closing volume (CV) does begin to impinge on FRC as pregnancy advances. This is most likely from a reduction in RV and ERV (14). However, in contrast to obese parturients, this change does not worsen in normal-weight parturients upon taking the supine position (14). When the mass loading effect of obesity reduces FRC, it may fall at or below closing capacity leading to airway closure during tidal ventilation, especially in the dependent regions causing intrapulmonary shunting (15,16). Assumption of supine, lithotomy, or Trendelenburg position, use of abdominal straps to retract the panniculus cephalad, and induction of general anesthesia results in further reduction in FRC in the obese parturient (Fig. 35-2). Shunt fractions of 10% to 25% of cardiac output have been reported in obesity (15). Therefore, unlike in normal-weight pregnancy, in obese parturients there is mismatching of ventilation–perfusion ratio with concomitant increase in

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TABLE 35-2  Blood Gas Measurements by Pregnancy and Obesity Status PaO2 (SD) mm Hg Normal-weight–term pregnant

101.8 (1.0)

PaCO2 (SD) mm Hg

pH (SD)

Mean BMI (n)

30.4 (0.06)

7.43 (0.006)

23.6 (20)

Obese term pregnant

85 (5.0)

29.7 (2.8)

7.44 (0.04)

43.5 (12)

Obese postpartum

86 (10)

35.5 (3)

7.44 (0.04)

41.4 (12)

Obese nonpregnant

76.7 (16.1)

41.3 (5.7)

Not available

39.5 (62)

Obese nonpregnant with sleep apnea

70.9 (11.7)

42.8 (5.0)

Not available

39.6 (40)

Reprinted with permission from: Mhyre JM. Anesthetic management for the morbidly obese pregnant woman. Int Anesthesiol Clin 2007;45: 51–70.

alveolar to arterial oxygen tension difference, especially in the supine position. Oxygen saturation measured in the sitting and supine position during normal ventilation may provide evidence of airway closure and the degree of pulmonary reserve. Holley et al. (17) reported that in obese subjects with ERV less than 0.4 L (21% predicted), the distribution of a normal tidal breath was predominantly to the upper zones. This distribution pattern is similar to what is found in normal weight subjects at low lung volumes, i.e., upper lungs are predominantly ventilated at low lung volumes and opposite occurs at high lung volumes. Distribution of perfusion, on the other hand, remains gravity dependent and perfusion index increases approximately linearly with vertical distance down the lungs similar to normal-weight subjects (18). Thus, in obese subjects there is an abnormally low V/Q ratio in lower lung zones, which depends more on the amount of ERV reduction than to the degree of obesity. Even a very large increase in weight is not necessarily associated with severe decrease in ERV due to the fact that the increase in body mass may occur in lower half of the body, which would not interfere with the ERV (17). However, if the fat deposition occurs in the abdominal wall, this would cause an increase in abdominal pressure, and cause a considerable decrease

Effect of position on lung volumes

FRC CC

Nonobese

Obese upright

Obese supine

Obese Trendelenburg

FIGURE 35-2  Effect of position change on lung volumes in nonobese compared with markedly obese subjects. FRC, functional residual capacity; RV, residual volume; CC, closing capacity. Adapted with permission from: Vaughan RW. Pulmonary and cardiovascular derangements in the obese patient. In: Brown BR Jr, ed. Anesthesia and the Obese Patient. Philadelphia, PA: Davis. 1982:26.

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in ERV. The value of ERV may be taken as an approximate indicator as to whether a defect in ventilation distribution is likely in the parturient. Classically, spirometric values other than maximum voluntary ventilation (MVV) are not affected in obesity. Therefore, an abnormal pulmonary function test (PFT) value should be considered as an indication of intrinsic lung disease and not caused by obesity, unless in extreme obesity where a significant reduction in vital capacity (VC) and total lung capacity (TLC) can be seen (19). The pulmonary diffusion capacity remains unchanged during pregnancy and is well preserved in obesity as well. The lung parenchyma in obese subjects is essentially normal and the above-mentioned changes in pulmonary values reflect changes due to chest wall mechanics and low lung volumes. Obesity alters the relationship between the lungs, the chest wall, and the diaphragm (Table 35-3).

Work of Breathing

Early in pregnancy, the alveolar ventilation is increased, which is attributed to the respiratory stimulant effect of progesterone rather than a response to increased metabolism. In obesity, hyperventilation at rest occurs due to increased oxygen requirement and CO2 production by the excess fat that is deposited in the body. Dempsey et al. (20) demonstrated that excess body weight increases oxygen consumption and CO2 production in a linear fashion. Achieving this augmented ventilation imposes an additional physiologic burden, and work of breathing is increased tremendously in obesity. In patients with simple obesity, the total work of breathing may be increased up to twice normal. In patients with OHS, it is increased about 3 times above that of normal individual (21). The oxygen consumption in obesity is increased even more than the mechanical work of breathing, ranging 4 to 12 times normal thus reducing the efficiency of respiratory muscles in obesity (22). Compared to normal pregnancy, the most significant pulmonary mechanics change in obesity, is that the chest compliance is reduced to a much greater extent. This change is due to the increased weight of the chest and abdominal wall from accumulation of fat in and around the ribs, the diaphragm, and the abdomen. It has been estimated that 33% of the increased work of breathing in obese subject is due to elastic work done on the chest wall (22). Sharp et al. (21) showed that in obesity the total respiratory compliance is reduced to one-third of normal. Naimark et al. (23) reported further significant reduction in respiratory compliance in obese subjects when assuming supine position as compared to normal-weight patients. Another factor that may contribute to increased work of breathing in obesity is due to an increase in total airway resistance, secondary to the lower lung v­ olumes (24).

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TABLE 35-3  Resting Respiratory Changes in Pregnancy, Obesity, and Pregnancy and Obesity Combined Parameter

Pregnancy

Obesity

Combined

Tidal volume

↑

↓

↑

Respiratory rate

↑

↑

↑

Minute volume

↑

↓ or ↔

↑

Inspiratory reserve volume

↑

↓

↑

Expiratory reserve volume

↓

↓↓

↓

↓

↓ or ↔

↓

Functional residual capacity

↓↓

↓↓↓

↓↓

Vital capacity

↔

↔ or ↓

↔ or ↓

FEV1

↔

↓ or ↔

↔

FEV1/VC

↔

↔

↔

Total lung capacity

↓

↓↓

↓

Compliance

↔

↓↓

↓

Work of breathing

↑

↑↑

↑

Airway resistance

↓

↑

↓

V/Q mismatch

↑

↑

↑↑

DLCO

↔

↔

↔

PaO2

↑

↓↓

↓

PaCO2

↓

↑

↓

A–a gradient

↔

↑

↑↑

Residual volume

↑, increase; ↓, decrease; ↔, no change (multiple arrows represent the degree of intensity). CO2, carbon ­dioxide; FEV1, forced expiratory volume in 1 s; V/Q, ratio of ventilation to perfusion; DLCO, diffusion capacity of lung for carbon monoxide; PaO2, partial pressure of oxygen; PaCO2, = partial pressure of carbon dioxide. Modified with permission from: Sarvanakumar et al. Obesity and obstetric anaesthesia. Anesthesia 2006;61: 36–48, from Blackwell Publishing.

During pregnancy, resting minute ventilation increases primarily due to increase in tidal volume. In contrast, obese individuals with increased chest wall mass show a tendency to rapid shallow breathing pattern. This particular breathing pattern optimizes the work of breathing thus avoiding diaphragmatic muscle fatigue (25). However, in obesity, with increasing ventilation when breathing frequency and dead space increases, rapid breathing may become uneconomical leading to ventilatory failure (26). The adverse changes in the respiratory system illustrate that the obese parturient has minimal or absent pulmonary reserve and can develop hypoxemia rapidly.

Obstructive Sleep Apnea

Obesity is linked to many respiratory conditions which include asthma, OSA, OHS, pulmonary embolism, and aspiration pneumonia. With increased prevalence, obesity is now considered an emerging cause of chronic respiratory failure (27). The prevalence of OSA in pregnancy is unknown and in many cases may be undiagnosed. It has been suggested that pregnancy may precipitate or exacerbate this condition (28). During normal pregnancy it is not uncommon to have upper airway congestion and edema; which in the obese parturient at risk can precipitate OSA. OSA is characterized by periodic apnea during sleep that produces hypoxia and sleep disruption. Obesity in pregnancy complicated by OSA can have adverse effects on the mother and the fetus. Repetitive ­significant

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hypoxemia episodes concurrent with apneic episodes results in maternal hemodynamic consequences, such as elevation of maternal systemic and pulmonary artery pressures, rightsided heart failure and cardiac arrhythmias. Pulmonary vasoconstriction secondary to hypoxia and hypercapnia is believed to be the pathophysiology of this process. Pulmonary hypertension when superimposed by the physiologic changes of pregnancy and labor produces a lethal condition (29). Maternal oxygen desaturation during apnea can result in fetal hypoxia as demonstrated by resultant fetal heart rate abnormalities. Episodic fetal hypoxia may result in intrauterine fetal growth retardation (30). Careful history taking and prompt diagnosis by polysomnography would allow early treatment of OSA. Since daytime fatigue is very common in normal pregnancy, OSA is easily missed in this patient population. A recent systemic review and meta-analysis of clinical screening tests for OSA reported that the STOP questionnaire (S = Snoring, T = Tiredness, O = Observed apnea, P = Elevated blood pressure) is an excellent screening test for moderate-to-severe OSA (31) and must be ascertained preoperatively in the morbidly obese parturients. Patients who present with combination of high screening score, recurrent apneic episodes, and/or desaturations during immediate postoperative period were shown to be at increased risk of recurrent postoperative respiratory events (odds ratio = 21) (32). Therefore, these patients require close surveillance and postoperative monitoring to prevent adverse catastrophic respiratory events.

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Nasal CPAP is the mainstay of therapy for OSA. Diagnosis of OSA early in the prenatal period allows initiation of CPAP therapy. CPAP has been used successfully with improved perinatal outcome, with no adverse effects during pregnancy (33).

NORMAL

OBESE

Non pregnant

Late gestation

Late gestation

N Vascular resistance

Vascular resistance

Vascular resistance

Cardiovascular Changes The blood volume and cardiac output increases during pregnancy beginning early first trimester. Obesity, on the other hand, independently increases blood volume and cardiac output to double that of pregnancy. The increased cardiac output is required to meet high metabolic demands related to increased fat and increased work of breathing. Cardiac output increases by 30 to 35 mL/min for every 100 g of fat tissue (34). During normal pregnancy there is additional elevation of cardiac output during labor, and immediate postpartum period (125% increased from pre-pregnancy values). Obese parturients with reduced functional reserves may not be able to tolerate this dramatic increase in cardiac demand and is therefore at much higher risk during the peripartum period. In addition, obesity is a risk factor for peripartum cardiomyopathy, a potentially lethal disease (35). The systemic vascular resistance decreases during normal pregnancy, and is about 20% below pre-pregnancy value at term (36). In an obese or morbidly obese parturient, due to generalized atherosclerosis, the arterial walls can be less compliant, thus the normal pregnancy–associated afterload reduction, may not occur to the same extent (37). The combination of higher afterload and increased cardiac output contributes to the significant left ventricular hypertrophy that is found in obese parturients (37). In normal pregnancy, there is an increase in left ventricular diameter (38). However, this increase occurs without a corresponding enlargement in wall thickness. In contrast, cardiac adaptation to obesity results in left ventricular dilatation as well as ventricular hypertrophy (eccentric hypertrophy). Veille et al. (37) demonstrated significantly greater left ventricular posterior wall thickness and interventricular septal thickness with smaller radius-to-wall thickness in obese pregnant patients. This adaptation seems to be important to maintain normal systolic function in obese pregnant patients (Fig. 35-3). In spite of hypertrophy, left ventricular size and function are shown to be normal in otherwise healthy obese pregnant women during the third trimester of pregnancy (37). Up to about 15% of pregnant women at term experience a significant drop in blood pressure and bradycardia when they assume the supine position, the so-called supine hypotensive syndrome. This phenomenon is more pronounced in obese parturients since the fat pannus further contributes to pressure on the inferior vena cava in the supine position. Although left uterine decubitus (LUD) position is usually an effective measure to improve venous return, it may be very hard to achieve the LUD position in obese women due to the extra weight. Tamoda et al. (39) studied the effects of obesity on maternal hemodynamic changes. They concluded that obesity during pregnancy is clearly a risk factor for hypertension, hemoconcentration, and poor cardiac function. Obese parturients secrete excess insulin from the pancreas since adipose tissue is resistant to insulin. This hyperinsulinemia is considered to be the main cause of hypertension (40). During pregnancy, hyperinsulinemia will be more severe due to the fat deposition and enhanced insulin secretion due to estrogen (41). The possible mechanism for hemoconcentration is also thought to be due to sympathetic nervous activity caused by

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LEFT VENTRICLE

r/h

Wall stress r  X pressure h

h

h

h 2.7

r

r

r

3.5 ± 0.6

2.36 ± 0.5

Radius (r ) is increased wall thickness (h) stays the same r is h

FIGURE 35-3  Cardiovascular effects of pregnancy. Illustration of radius-to-wall thickness ratio (r/h) in nonpregnant, pregnant, and obese pregnant patients. The ratio in obese pregnant patient was significantly smaller than in pregnant patients but similar to that of nonpregnant patients. Modified with permission from: Veille JC, Hanson R. Obesity, pregnancy, and left ventricular functioning during the third trimester. Am J Obstet Gynecol 1994;171:980–983.

hyperinsulinemia. Pre-pregnancy obesity is a significant risk factor for preeclampsia (42). The hypertrophied myocardium that is found in morbidly obese population is vulnerable to serious arrhythmias. Drenick et al. (43) demonstrated that malignant arrhythmias can arise even with minor Q-Tc prolongations in morbidly obese patients undergoing stressful period (upper limit for a normal Q-T interval ranges from 0.425 to 0.44 seconds). Therefore, physiologic stresses should be minimized by appropriate measures in these patients. Screening and perioperative monitoring for Q-T interval prolongation, prophylactic beta-blockade during the stressful period, and avoidance of medications known to enhance sympathetic tone or to prolong the Q-T interval is recommended in this subset of morbidly obese patients (43). There have been reports of sudden cardiac arrest with positional change in morbidly obese surgical patients (44). The mechanism of cardiovascular collapse was believed to be three-fold: (1) Further decrease in lung volume and vital capacity secondary to high intra-abdominal pressure in the supine position while there was an increase in the ventilation requirement; (2) inability to increase ventilation due to respiratory center dysfunction; (3) inability of the already failing hypoxic myocardium to handle the shift of blood to the central circulation on assuming the supine position.

Gastrointestinal Changes Aspiration of gastric contents, although rare in the current obstetric practice, is a serious risk of general anesthesia. Obesity is associated with several risk factors that increase the risk for aspiration. These include increased incidence of emergent operative delivery (45–47), difficult mask ventilation (48), difficult intubation (47,49) gastro-esophageal reflux disease (50), and co-morbidities such as diabetes (41).

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CHAPTER 35  •  Morbid Obesity

There are alterations in pharmacodynamic properties of drugs also due to the effect of obesity on cardiac and respiratory functions. Morbidly obese patients show increased sensitivity to medications with respiratory and myocardial depressant effects.

200 Total body weight

kg

150

Induction Agents

100 Lean body weight

50 Fat weight

0 20

30

40

585

50

60

70

BMI (kg m–2)

FIGURE 35-4  Relationship of TBW, fat weight, and LBW to BMI in a standard height male. LBW and fat weight were derived from the equations of Janmahasatian et al. Modified with permission from: Ingrande J, Lemmens HJM. Dose adjustment of anesthetics in the morbidly obese. BJA 2010;105:i16–i23.

Endocrine Changes

Thiopental and propofol are commonly used intravenous induction agents. Administration of these agents based on TBW may result in overdose and profound hemodynamic changes. When morbidly obese subjects were given propofol based on LBW, they required similar doses and had similar time to hypnosis as lean control subjects given propofol based on TBW (55).

Opioids

Morbidly obese patients show exaggerated respiratory depression with opioids and are more susceptible to obstruction of the upper airway and hypoxemia when administered in the perioperative period (56). Almost half of the adverse respiratory events secondary to opioids were reported in obese or morbidly obese patients. If opioids are required in this patient population, the dosing should be calculated according to LBW (53), titrate as needed. Serious consideration should be given to the need for continuous monitoring in a high dependency unit.

Gestational diabetes and type II diabetes are both more frequently associated with obesity (6,41). Optimum glucose control is of utmost importance in these patients for the best possible outcome in pregnancy. During labor, insulin therapy should be adjusted to achieve levels between 4 and 8 mmol/L to prevent neonatal hypoglycemia. Following delivery, further reduction in insulin dose is required to prevent maternal hypoglycemia (51).

Inhalational Agents

Dose Adjustment of Anesthetic Drugs

Succinylcholine The rapid onset and short duration of action makes succinylcholine the neuromuscular blocking agent of choice in morbidly obese patients. Two factors that determine the duration of action of succinylcholine, namely the pseudocholinesterase level and the amount of extracellular fluid, are increased in the morbidly obese patients (58). Therefore, a larger dose of succinylcholine based on TBW is recommended to achieve optimal intubating conditions (59). However, the longer time to 50% twitch recovery (which should allow adequate spontaneous ventilation) associated with the large dose based on TBW could be a disadvantage if problems were encountered during intubation and subsequent mask ventilation.

In morbidly obese patients there are changes in the cardiac output, extra cellular fluid volume, and body composition, which alter the pharmacokinetic properties of most drugs (52,53). Although fat mass accounts for most of the increase in TBW, it is poorly perfused and therefore its increase in obese patients will not show proportionate increase in the volume of distribution of lipophilic drugs as obesity increases (Fig. 35-4). Lean body weight (LBW) is significantly correlated to cardiac output (54). Drug clearance also increases proportionately with LBW (53). These data suggests that the drug administration in morbidly obese patients should be based on LBW. Administration of drugs based on TBW may result in overdose. Ideal body weight (IBW) is a term that describes the weight that people are expected to weigh based on age, sex, and height. There are numerous equations to calculate the IBW. Before the introduction of BMI, IBW was used to define obesity. A person weighing greater than 120% of IBW was considered obese, and greater than 200% as pathologic obese. Administration of drugs based on IBW may result in underdosing in the morbidly obese patient because it does not account for the associated changes in body composition in obesity (52). The LBW is estimated as 20% to 30% above the IBW (55). Although LBW is the most appropriate for scaling drug doses, most equations to calculate LBW have limitations at extremes of obesity (52). Recently, Janmahasatian et al. (54) derived LBW equations for patients weighing between 40 and 220 kg. These data can be used to easily approximate LBW (Fig. 35-5).

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Newer, less lipophilic, less soluble agents such as sevoflurane and desflurane show no difference in time to awakening in morbidly obese subjects when compared with lean subjects (57). Although isoflurane is more lipophilic than sevoflurane and desflurane, the effect of BMI on uptake is clinically insignificant for procedures lasting less than 2 to 4 hours.

Neuromuscular Blockers

Nondepolarizing Muscle Relaxants

Intermediate acting drugs such as vecuronium, rocuronium, cisatracurium, or atracurium are commonly used in the current clinical practice. The dosing based on IBW is recommended to avoid prolonged recovery in obese (53) (Table 35-4). ■■

 REGNANCY-RELATED PROBLEMS P AND PERINATAL OUTCOME

Obesity complicates obstetric management because of the associated co-morbidities. Obesity increases the risk of emergency cesarean delivery in majority of the cohort studies (60,61). Obesity is shown to be a major predictor of maternal mortality and major complications (6). Maternal pregnancy– related complications such as gestational diabetes, gestational hypertension, preeclampsia, induction/augmentation of labor and cesarean section are significantly increased in

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MALES 120 HT (cm)

Lean body weight (kg)

220 100 175 80 150 60

40 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200 210 220 Total body weight (kg)

A

FEMALES 100 HT (cm) 220

FIGURE 35-5  Estimated lean body weight for men and women with weights between 60 and 220 kg and heights between 150 and 200 cm. Estimates are derived from the equation of Janmahasatian et al. Modified with permission from: Lemmens JM. Perioperative pharmacology in morbid obesity. Curr Opin Anesthesiol 2010;23:85–91).

Lean body weight (kg)

90 80

175

70 150

60 50 40

60 70 80 90 100 110 120 130 140 150 160 170 180 190 200 210 220 B

TABLE 35-4  Weight-Based Dosing Scalar Recommendation for Commonly Used IV Anesthetic Drugs Drug

Dosing Scalar

Thiopental

Induction: LBW Maintenance: TBW

Propofol

Induction: LBW Maintenance: TBW

Fentanyl

LBW

Remifentanil

LBW

Succinylcholine

TBW

Vecuronium

IBW

Rocuronium

IBW

Atracurium

IBW

Cisatracurium

IBW

IBW, ideal body weight; LBW, lean body weight; TBW, total body weight. Adapted from: Ingrande J, Lemmens HJM. Dose adjustment of anesthetics in the morbidly obese. BJA 2010;105:i16–i23.

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Total body weight (kg)

obese women (6). Barau et al. in a study involving more than 17,000 singleton live births demonstrated a significant linear association between maternal pre-pregnancy BMI and risk of caesarean section in term deliveries (45). Slow progress in labor has been observed before 7 cm of cervical dilation in overweight and obese parturients compared to normal-weight parturients (62). The monitoring of uterine contractions to ensure adequate labor also could be a challenging task in an obese parturient. Obesity seems to be an independent risk factor for fetal macrosomia. The morbidly obese patient, with or without diabetes, and with or without excessive weight gain during pregnancy is at increased risk of ­having a macrosomic fetus (45,62). Fetal macrosomia (>4,000 g) may result in shoulder dystocia and birth trauma. Obesity, especially when combined with diabetes, may be associated with increase in birth defects such as neural tube defects and abdominal wall defects (63). In obese parturients, the in utero diagnosis of fetal defects are often delayed or missed because of difficult ultrasound imaging. The less than optimal imaging of anatomical structures of the fetal heart, spine, kidneys, diaphragm, and umbilical cord are associated with increasing BMI (64).

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Obesity is the most prevalent risk factor for unexplained still birth (65). The mechanisms suggested include decreased ability to perceive changes in fetal movement, atherosclerosis affecting placental blood flow, and desaturation secondary to OSA (66). External fetal monitoring is difficult in the presence of maternal obesity; therefore, internal fetal monitoring may be more effective. Occasionally, the morbidly obese woman may be unaware of pregnancy until full term (67). The perioperative complication rate is also increased (61,68) in obese women and include (1) increased intraoperative blood loss of >1,000 mL, (2) increased operative time, (3) increased postoperative wound infection and endometritis (even with elective cesarean delivery and antibiotic prophylaxis), and (4) need for vertical incision, which has a wound complication rate of 12%. When planning for cesarean delivery, the care team should be aware of the longer time required to prepare and commence surgery in obese patients. Therefore, when an emergent or urgent cesarean delivery is required, the decision to delivery interval may be longer in obese parturients. Thomas et al. (69) demonstrated that prolonged decision to delivery intervals of more than 75 minutes may result in poor maternal and fetal outcomes, and therefore proper planning is required and all emergency caesarean deliveries should occur within this time. Currently, there are no studies that adequately address decision to delivery interval in obese patients.

Pregnancy Following Bariatric Surgery Initial reports indicate that following bariatric surgery and adequate weight loss, many of the obesity-related detrimental effects on fertility and pregnancy are reversed (70). The American College of Obstetricians and Gynecology recommends that women should avoid pregnancy for 18 months after bariatric surgery, which is the rapid weight loss period (71). According to recent case reports, significant maternal and fetal problems can occur post-bariatric surgery (71–74) including mechanical obstructive problems or herniation due to the growing uterus. Vitamin B12, folate, and vitamin K deficiency may be present in up to 70% of post-bariatric surgery patients. These patients may present with peripheral neuropathy secondary to nutritional deficiency (72) or rapid weight loss (73). A thorough history and physical examination is mandatory before a neuraxial block is performed in these patients with neuropathy. Adverse neonatal outcome due to vitamin K deficiency following pre-pregnancy bariatric surgery also has been reported (74). These include increased incidence of congenital abnormalities, small for gestational age, and intrauterine growth retardation. ■■

ANESTHETIC MANAGEMENT

Transport and positioning: Standard operating room tables have a maximum weight limit of approximately 200 kg. Operating tables (Herculean tables) that will support up to 455 kg with extra width are available. Particular care should be taken to prevent pressure-related injuries. Patient should be properly secured on the operating table with strapping so as to achieve adequate LUD. Sufficient number of personnel should be available for safe transfer of patient to the operating room and table. Vascular access: Peripheral venous access can be difficult and extravasations may not be immediately apparent. The use of ultrasound guided peripheral venous access, which is becoming increasingly popular, can be very helpful. Ultrasound guided central venous access may be necessary if the peripheral access is inadequate or unobtainable.

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587

Monitoring: Noninvasive blood pressure measurement requires appropriately sized cuff; if the cuff is too small both systolic and diastolic readings will be overestimated. The forearm may be used if the upper arm is too large or conical shape. Invasive arterial pressure monitoring is necessary in some cases to accurately monitor the blood pressure.

Evaluation of the Airway In obese patients, use of a single test such as Mallampati score alone, in predicting potential difficult airway in the obese parturient seems to have a lesser value when compared to lean patients. A study involving more than 100 morbidly obese patients, more than 50% of the difficult laryngoscopies were not detected by the Mallampati assessment alone. In contrast, the multivariate simplified airway risk (SAR) index, which combines several airway risk factors, resulted in a much greater ability to predict actual occurrence of grade 3–4 laryngeal views (49). Therefore, a complete airway evaluation including Mallampati score, mouth opening, evaluation of the dentition, ability to protrude the lower teeth beyond the upper teeth, thyromental distance, range of motion of the neck, and a measure of neck circumference should be performed just before any anesthetic procedure in obese parturients (see Chapter 22).

Aspiration Prophylaxis Effective prophylactic measures increase gastric pH, reduce gastric volume, and therefore, decrease the risk of pneumonitis should aspiration occur. Prophylactic measures include: 1. Antacid: All parturients should receive 30 mL of a nonparticulate acid, such as 0.3 molar sodium citrate, immediately before or within 20 minutes before induction of anesthesia. 2. For elective cesarean delivery, an H2-receptor antagonist (ranitidine 150 mg or famotidine 20 mg) or a proton pump inhibitor (omeprazole 40 mg) should be administered orally the night before and again 60 to 90 minutes before the induction of anesthesia. Administration of metoclopramide 10 mg orally 60 minutes before or intravenously 30 minutes before induction of anesthesia increases the lower esophageal sphincter tone and accelerates gastric emptying (75), which is particularly beneficial in obese parturients. 3. For emergency cesarean delivery, metoclopramide 10 mg should be administered intravenously. In addition, ranitidine 50 mg or omeprazole 40 mg also should be given intravenously. Although ranitidine may not have an effect at the time of induction of anesthesia, there will be a decrease risk of aspiration pneumonitis at the time of extubation. Although H2-receptor antagonists begin to work within 30 minutes of administration, the peak effect occurs in 60 to 90 minutes. The duration of action of the drug is long enough to cover emergence from anesthesia during cesarean delivery (76). Some obstetric units administer H2-receptor antagonists orally every 6 hours to morbidly obese parturients in labor.

Antibiotic Prophylaxis Because of the increased postoperative wound infection and endometritis in obese parturients (47,68), timely administration of antibiotic prophylaxis during cesarean delivery is important. According to the new ACOG guidelines (77) antibiotic prophylaxis should be administered within 60 minutes of the start of the cesarean delivery.

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Thromboprophylaxis The risk of thromboprophylaxis is increased in obese parturients. The incidence of thromboembolism was shown to be 2.5% in obese parturients and only 0.6% in the normalweight parturient (6). Early ambulation and graduated compression stockings are recommended for obese parturients in the postpartum period (71). Thromboprophylaxis with postpartum low molecular weight heparin should be considered in obese parturients at high risk for venous thromboembolism (VTE), especially those on bed rest or having surgery (71).

Neuraxial Anesthesia and Analgesia Techniques for Labor and Delivery Epidural for Labor Analgesia Advantages Neuraxial labor analgesia has been widely accepted as the most effective, safe and the least depressive form of intrapartum analgesia currently available. Effective pain control during labor can significantly improve maternal respiratory function, reduce oxygen consumption, and attenuate sympathetically mediated cardiovascular stress response (78,79). A functional epidural catheter in situ helps avoid the implementation and associated risks of general anesthesia and tracheal intubation should any urgent operative delivery be required. According to a prospective study by Hood et al. (47), 48% of laboring morbidly obese parturients required emergency cesarean section, compared with 9% of control laboring patients. Potential Difficulties Locating the epidural space and obtaining adequate neuraxial block may present unique challenges in this patient population: (1) Proper positioning of the patient and palpation of the midline may be difficult; (2) there is a high incidence of false loss of resistance when this technique is used to locate the epidural space due to the presence of fat pockets (47); (3) a high incidence of accidental dural puncture (47) and epidural venous puncture (80) also has been reported. Initial failure rate for epidural catheter placement in obese parturients can be as high as 42% and multiple attempts at catheter placement are common (47). Early placement of epidural catheter should be encouraged to allow ample time for this potentially difficult procedure. Sitting position is preferable and landmarks may be easier to identify compared to the lateral position. In recent years, prior to placement of regional blocks, ultrasound has been used to identify the landmarks so as to facilitate proper epidural placement. Ultrasound (US) imaging in the transverse plane can reliably determine the skin puncture site, predict the depth to the epidural space, and thereby facilitate epidural catheter placement in obese parturients (81). A 5.0 MHz curved US array probe provides accurate measurements. Clinkscales et al. (82) presented a mathematical formula that can be used to calculate the depth of skin to epidural space in centimeters relative to BMI and age: Depth = 3.0 + (0.11 × BMI) − (0.01 × age) in centimeters One may use this formula to decide whether it is necessary to use an extra long epidural needle to locate the epidural space, in the absence of ultrasound equipment. Multiple studies (81,83), however, have reported that only a small percentage of obese patients have epidural space deeper than 8 cm. Therefore, in most cases a standard epidural needle is of adequate length and a longer needle should only be used when necessary. The long needles may bend more easily and are more difficult to steer in the intended direction and thus have greater potential for injury.

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Frequent evaluation of the quality of the labor epidural block in these patients is vital because several investigators (47,84) have demonstrated high risk of epidural failure in obese patients. Any questionable catheters should be replaced promptly. One should be aware that opioid containing solutions can mask a malpositioned epidural catheter because of the pain relief caused by the absorption of opioids. The epidural catheter may move as much as 2 cm out of the epidural space when an obese patient stretches her back with the catheter already secured to the skin (85). Therefore, it is recommended that the obese parturient should straighten the back in the upright sitting position or lateral position before securing the catheter (86).

Combined Spinal-epidural (CSE) for Labor Analgesia The CSE technique offers the advantage of combining rapid onset of subarachnoid analgesia with the flexibility of continuous epidural analgesia. However, the function of the epidural catheter inserted under CSE technique is uncertain until after the duration of spinal analgesia wears off. Possible delayed recognition of nonfunctional catheter therefore is a concern in this high risk obese parturient with a possible difficult airway.

Continuous Spinal for Labor Analgesia Continuous spinal technique is one of the most reliable regional techniques available for providing both analgesia and anesthesia in the morbidly obese parturient. However, its acceptance and usage is currently minimal due to limitations on the proper size needles and catheters. Currently, what are available for continuous spinal techniques in the United States include epidural kits with 17 or 18 G Tuohy-type epidural needle and 20 G epidural catheters or the Wiley Spinal continuous catheters. Because of the high incidence of post-dural puncture headache (PDPH) rate that accompany the use of the epidural needle and catheter, continuous spinal anesthesia is considered a less favorable routine option in obstetric patients. However, the incidence of PDPH appears to be lower in morbidly obese parturients compared to ­normal-weight parturients (87). Morbid obesity increases the cesarean delivery rate. The need for emergent or urgent cesarean delivery during labor is also higher. The rate of epidural failure is shown to be higher in morbidly obese parturients (47). Therefore, a continuous spinal catheter can provide reliable rapid onset of surgical anesthesia with low dose local anesthetics. It is important that the continuous spinal catheter is clearly labeled and strict sterility is maintained. Communication with all personnel involved in her care is crucial so as to avoid accidental administration of epidural doses of medications.

Anesthesia for Cesarean Delivery Patient Positioning During Cesarean Delivery

Optimal positioning before the induction of anesthesia as shown in Figure 35-6B is critical prior to induction of general anesthesia in the morbidly obese parturient. In this ramped position, the shoulders are elevated with blankets or the ramp/Troop elevation pillow under the patient’s thorax and head allowing the breasts and soft tissues to fall away from the chin and to open up the neck area. Sniffing position is obtained by flexing the neck on the chest with blankets or pillows under the occiput and extending the head on the neck (atlanto-occipital extension) by tilting the head

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CHAPTER 35  •  Morbid Obesity

A

589

B

FIGURE 35-6  A: Morbidly obese parturient in the supine position. B: The same patient correctly positioned for laryngoscopy in the ramped position. backwards. When morbidly obese patient is correctly positioned for laryngoscopy in the ramped position, an imaginary horizontal line can be drawn from the sternal notch to the external auditory meatus (88). Even when counting on a neuraxial block for surgical anesthesia, patients should be positioned optimally on the operating room table in the ramped position, and devices to establish an airway should be immediately available. In morbidly obese parturients the panniculus needs to be retracted to permit adequate surgical exposure. The panniculus can be retracted caudad, cephalad, or vertically depending on the surgical incision (Fig. 35-7). A panniculus may weigh over 70 kg in some patients. When a heavy panniculus is retracted cephalad, as commonly done to enable a Pfannenstiel incision, it can cause aortocaval compression, maternal hypotension, respiratory distress, nonreassuring fetal heart tones, and even fetal death (89).

Anesthetic Technique The anesthetic options for cesarean delivery include neuraxial anesthesia and general anesthesia. Neuraxial techniques include epidural, single shot spinal, continuous spinal, and CSE.

Neuraxial Techniques Epidural Anesthesia

Epidural anesthesia using a catheter technique offers the advantage of the ability to prolong the block and respiratory plus hemodynamic stability with titrated dosing. Epidural is the preferred technique if a functional catheter is already in place. The height of an epidural block for a given volume of local anesthetic is shown to be proportional to BMI and maternal weight, not height (83). Therefore, epidural local

Panniculus Panniculus

Bladder A

Vertical skin incision

Public bone

Abdominal muscles

Panniculus

Transverse skin incision

Bladder B

Transverse skin incision

Public bone

Abdominal muscles

Bladder

Public bone

Abdominal muscles

C

FIGURE 35-7  The panniculus is shown (A) retracted caudad to permit a vertical incision above; (B) retracted cephalad to permit a transverse Pfannenstiel incision; and (C) retracted vertically. Direction of retraction is shown by arrows. Modified with permission from: Hodgkins R, Husain FJ. Cesarean section associated with gross obesity. Br J Anaesth 1980;52:919–923.

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anesthetics should be gradually titrated to avoid high block and its consequences.

Single Shot Spinal

Although spinal anesthesia provides quick onset, reliable, and dense surgical anesthesia for cesarean delivery, there are many concerns of using single shot spinal anesthesia in morbidly obese parturients. These include hemodynamic compromise due to sudden onset of high thoracic block and inability to prolong the block. In obese patients, the block can be often exaggerated. Large buttocks place the vertebral column in the Trendelenburg position; cerebral spinal fluid volume also shown to be decreased in obese patients (90). In most cases, surgery can exceed 2 hours (61).

Combined Spinal-epidural (CSE) Anesthesia

The CSE technique is the most common technique that is currently used in obese parturients undergoing cesarean delivery. The advantages with the CSE technique include: (1) It allows the spinal dose reduction; (2) reducing the dose helps to minimize hemodynamic effect of the block; (3) the quality of the sensory block and surgical anesthesia is superior to an epidural anesthesia; (4) the epidural catheter allows the option to extend the block with the indwelling epidural catheter.

Continuous Spinal Anesthesia

This technique offers the advantages of spinal anesthesia with the ability to prolong the block, and hemodynamic stability due to the possibility of incremental dosing.

General Anesthesia General anesthesia is hazardous in the morbidly obese parturient. As reviewed earlier, there are a number of features of morbidly obese parturients that increase the risk of hypoxia during rapid sequence induction of anesthesia. However, general anesthesia may be required in emergency cesarean delivery or when regional anesthesia is contraindicated or technically difficult. Endotracheal intubation is an essential component of general anesthesia for cesarean delivery. Pregnancy alone increases the frequency of failed intubation rate by eight- to ten-fold when compared to nonpregnant population (91). Endotracheal intubation via direct laryngoscopy may be difficult or impossible in morbidly obese patients due to several reasons. These include increased amount of soft tissues of the upper airways, increased tongue size, large breasts, short neck with increased circumference, and difficult neck extension due to the presence of large posterior fat pad. One-third of the tracheal intubations are shown to be difficult in morbidly obese parturients, with a failure rate of 6% (47). Mask ventilation is also difficult or impossible in obese patients. BMI of 30 kg/m2 or greater has been identified as one of the independent predictors for difficult mask ventilation grade 3, which is defined as inadequate mask ventilation or requiring two providers (48). Isono et al. demonstrated that in obese patients mandibular advancement (a helpful maneuver to relieve airway obstruction) does not improve retropalatal airway, as it may in nonobese persons (92). After induction of anesthesia there is reduced compliance and increased resistance of the lungs also due to a sharp decrease in lung volumes. Therefore, pregnancy and obesity each independently increases the risk of failed or difficult intubation and ventilation. Both conditions also increase the oxygen consumption, reduce the FRC, and shorten the time before hypoxemia develops.

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Airway Management

Prior to induction of general anesthesia of a morbidly obese parturient, anesthesiologist should ensure presence of additional experienced personnel and availability of difficult intubation equipment. The equipment should include videolaryngoscope, laryngeal mask airway (LMA size 3 and 4), FastrachTM LMA, CombitubeTM and percutaneous cricothyrotomy kit, connected to high pressure jet ventilator to maintain oxygenation and ventilation should attempts at intubation fail (93). The short-handled laryngoscope and small diameter endotracheal tube (6.5 or 7.0) should be prepared for intubation. An assortment of laryngoscope blades and various sizes of endotracheal tubes should be immediately available. Anesthesiologists should be familiar with the American Society of Anesthesiologists Practice Parameter on the Difficult Airway (93). If difficulty with the airway is anticipated prior to induction of anesthesia, and it is not an emergency situation, the parturient should be prepared for awake fiberoptic intubation through oral route with adequate topicalization of the airway. If time permits, topicalization of the upper airway and “one quick look” with a laryngoscope to evaluate the upper airway in an awake patient can be performed before induction of anesthesia. The videolaryngoscopy represents a recent addition to airway management. Videolaryngoscopy has been shown to provide a better view of the larynx and improvement in the intubation technique. It does not require alignment of oral– pharyngeal–tracheal axis which may be difficult to achieve in some cases. Its design makes it potentially useful for emergency situations. Marrel et al. (94) in a randomized study involving 80 morbidly obese patients found that the grade of laryngoscopy was significantly lower (at least one or two points on the Cormack–Lehane scale) with the videolaryngoscope compared with the direct vision laryngoscopy (P < 0.001). It could possibly reduce the timing for intubation and the number of intubation attempts. Refer to Chapter 22 for details on management of the difficult airway. However, a parturient requiring an emergent cesarean delivery may not be a candidate for awake fiberoptic intubation. In this situation, anesthesiologist should call for an experienced surgeon capable of performing emergency surgical airway in case intubation fails. Alternative methods of intubation should be readily available in case conventional laryngoscopy fails. The alternative methods include: 1. Videolaryngoscope 2. Intubating LMA (FastrachTM LMA). The FastrachTM intubating LMA is shown to be associated with high success rate (96.3%) of tracheal intubation (95) in morbidly obese patients. It allows “blind” or fiberscope guided endotracheal tube placement through the LMA. Fortunately, in recent years many airway devices/techniques have been introduced to facilitate intubation in difficult or failed airway situations. Various supraglottic devices are available to establish an artificial airway, if intubation fails. Currently, there are many other supraglottic and extraglottic devices to ensure airway control, The supraglottic devices are often effective and permit ventilation and oxygenation in “cannot intubate, cannot ventilate” situations. The LMA, first described by Archie Brain in 1983, can be considered as the device that paved the way for the supraglottic airway approach. The ProSeal LMA (PLMA) is especially helpful in parturients since it provides a separate channel opening into the upper esophagus for insertion of a standard gastric tube to prevent accidental gastric insufflation, and permits drainage of gastric fluid. Anesthesiologists should ensure that all these

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CHAPTER 35  •  Morbid Obesity

equipment are immediately available in the OB suite to be used in an emergency situation.

Anesthetic Induction, Maintenance, and Recovery Preoxygenation

The aim of preoxygenation for 3 minutes with 100% oxygen with a tightly fitting mask utilizing tidal volume ventilation before induction of anesthesia is to optimize oxygen reserves and thereby increase the period of apnea without hypoxia. In urgent situations, 8 deep breaths of 100% oxygen over 60 seconds appear to be as effective as the 3-minute tidal volume method (96). However, it requires patient cooperation and high fresh gas flow at 10 L/min (See Figure 35.8). McClelland et al. using a computational simulation found that labor and obesity both considerably accelerate preoxygenation and, more importantly, also decrease the time to arterial desaturation (97). They found that the safe period of apnea in obesity, particularly during labor, after induction of anesthesia and paralysis is as short as 40 seconds. This means after waiting for the onset of succinylcholine action there is probably time only for one attempt at tracheal intubation before a critical reduction in arterial oxygen saturation occurs with that in mind the first attempt should be the best attempt at intubation with adequate positioning, adequate maneuvers, and airway devices. In an attempt to prolong safe apnea time, a number of preoxygenation methods have been studied. In morbidly obese patients, 30-degree reverse Trendelenburg position has been shown to prolong safe apnea time by at least 30% (98) as compared with the supine. However, head-up position has the risk of hypotension and increased difficulty with tracheal intubation. Gander et al. (99) demonstrated that application of positive end-expiratory pressure (PEEP) during induction of general anesthesia (100% oxygen through a CPAP device set at 10 cm H2O for 5 minutes) increases

100 90 80

SaO2(%)

nonhypoxic apnea duration by 50% or 1 minute in morbidly obese patients. PEEP increases FRC, decreases atelectasis, and shunt. However, the studies performed on nonpregnant women may not fully translate to pregnancy because of the effects of gravid uterus and physiologic changes of pregnancy; the effects on the uterine blood flow and the fetus are also not known.

Induction of Anesthesia

In hemodynamically stable patients with a favorable airway, rapid sequence induction may be performed with propofol. Etomidate is preferred for patients with cardiac dysfunction and ketamine may be the drug of choice for patients with significant blood loss. Succinylcholine is the drug of choice to achieve optimal laryngoscopic conditions in morbidly obese patient. Cricoid pressure should be applied concurrently by a skilled assistant. Proper placement of the endotracheal tube should be confirmed with capnography and bilateral auscultation prior to skin incision. Exaggerated catecholamine response to laryngoscopy and intubation in hypertensive, obese parturients can be hazardous. A short acting vasodilator or antihypertensive agent should be prepared depending on the presence or absence of invasive monitoring such as an arterial line. Intravenous nicardipine or labetalol can be titrated in the absence of invasive monitoring. Additional muscle relaxation with intermediate duration nondepolarizing muscle relaxants may be required if surgery is technically difficult or prolonged in morbidly obese patients. Anesthesia can be maintained with 50% nitrous oxide/oxygen and 0.5 MAC isoflurane, sevoflurane, or desflurane. Some patients may require more than 50% oxygen to maintain satisfactory oxygen saturation. In those cases, additional hypnotic/amnestic agents should be considered. In obese patients, intraoperative ventilation strategies to reduce atelectasis and improve oxygenation include recruitment maneuvers (35 to 55 cm H2O for 6 seconds followed by the application of PEEP of 10 cm H2O) and reverse Trendelenburg position. However, these maneuvers should be performed only when the patient is normovolemic and hemodynamic stabilization is reached after induction of anesthesia. The effect of these maneuvers on uterine blood flow and fetal well-being also should be taken into consideration.

Extubation

70 A

60

B

50 40 30 20 10 0

591

0

1

2

3

4 5 Time (min)

6

7

8

FIGURE 35-8  Time course of SaO2 during apnea after 99% denitrogenation. The heavy dashed line represents the average pregnant subjects. Line AB transects subjects in the following order, left to right: BMI 50 and labor; BMI 35 and labor; labor; sepsis; BMI 35; twins; hypovolemia; average pregnant; anemia; preeclampsia. Modified with permission from: McClelland SH, Bogod DG, Hardman JG. Pre-oxygenation and apnoea in pregnancy: changes during labour and with obstetric morbidity in a computational simulation. Anaesthesia 2009;64:371–377.

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A recent report of pregnancy-associated deaths highlights the importance of continued vigilance during emergence from general anesthesia, especially in obese women. According to the report, anesthesia-related deaths occurred not during induction of general anesthesia but during emergence and recovery from airway obstruction or hypoventilation (10). Spontaneous ventilation against an obstructed airway may also lead to rapid development of negative pressure pulmonary edema requiring reintubation. Therefore, an obese parturient with a difficult airway should be extubated fully awake. This means that the patient should be rational, oriented, and following commands in a clear manner. Full recovery of neuromuscular blockade should be proven by a monitor as well as by clinical criteria. Extubation in the semirecumbent position minimizes compression of the diaphragm by intra-abdominal contents, improves breathing, and reduces atelectasis. If the patient was on CPAP preoperatively, postoperative CPAP should be started immediately upon arrival in the PACU. If doubt exists about the adequacy of breathing, patient should remain intubated and should be transferred to an intensive care setting.

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Postoperative Care Following Cesarean Delivery In the postoperative period, beach chair position, noninvasive respiratory support, aggressive physiotherapy, careful fluid management, adequate pain relief, and recovery in a high-dependency unit with O2 saturation and end tidal CO2 monitoring is essential to reduce pulmonary complications (9). Postoperative ambulation should be initiated early to reduce the risk of DVT, and formation of decubitus ulcers. Because of the exaggerated respiratory depression with sedatives and opioids, postoperative pain management may be challenging in these patients. Neuraxial morphine is used commonly for postoperative pain relief following cesarean delivery. However, respiratory arrest has been reported after neuraxial morphine administration in high risk patients, such as patients with sleep apnea (100). Multimodal techniques that have been shown to improve postoperative analgesia and patient satisfaction while limiting opioid usage should be utilized more frequently in these patients. These techniques include neuraxial analgesia with low concentration local anesthetics, peripheral nerve blocks such as transverse abdominis plane (TAP) blocks (101), ilioinguinal block (102), or continuous incisional infusion of local anesthetic (103). Addition of acetaminophen and nonsteroidal anti-inflammatory drugs improve pain relief and helps to further reduce the opioid usage (101). Effective respiratory monitoring is also critical to patient safety in clinical situations where hypoventilation, respiratory obstruction, and respiratory depression and arrest are not only a potential complication, but also a common theme in preventable deaths particularly in morbidly obese parturients. Although oximetry provides an excellent measure of oxygenation, it does not reflect adequacy in monitoring ventilation. During apnea, oxygen desaturation may not occur for several minutes, especially in patients receiving supplemental oxygen. The new technology Microstream® Capnography with Integrated Pulmonary Index technology may provide a better assessment of the patient’s respiratory status which includes: (1) Accurate physiologic respiratory rate, (2) adequacy of ventilation represented by a numeric value for end tidal CO2, (3) a breadth-to-breadth waveform that indicates any respiratory conditions such as hypoventilation, apnea, or airway obstruction whereas respiratory rate monitoring alone by itself does not provide complete factual information. As O2 cannula is already part of patient care in the PACU, the Microstream® capnography integrates oxygen delivery and CO2 sampling into a single line, and prevents the additional points of attachment to the patient. In the near future, capnography will become a standard of care for monitoring ventilation in high risk patients who are susceptible to hypoventilation and adverse respiratory events.

KEY POINTS ■■

Many of the effects of pregnancy and obesity on major organs are additive and can lead to decreased physiologic reserve and thus significant functional impairment. The obese parturient is at increased risk for diabetes, ischemic heart disease, stroke, hypertension, hypercoagulability, osteoarthritis, and gall bladder disease and pregnancy-associated complications. General anesthesia and anesthesiarelated complications are much higher in the morbidly obese parturient. There are a number of features that increase the risk of hypoxia, morbidity and mortality during induction of anesthesia, intrapartum, emergence and postpartum period in these patients.

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Early placement of a neuraxial catheter during labor should be encouraged to allow ample time for this potentially difficult procedure. A functional epidural during labor avoids the risks of general anesthesia and tracheal intubation should any urgent operative intervention be required. ■■ Frequent evaluation of the quality of the labor epidural block in these patients is vital because of the high risk of epidural failure in obese patients. Any nonfunctioning catheters should be replaced promptly. ■■ A continuous spinal technique is a reliable regional technique available for providing both analgesia and anesthesia in the morbidly obese parturient. Strict sterility should be maintained to avoid infectious complications. ■■ When planning for cesarean delivery, the care team should be aware of the longer time required to prepare and commence surgery in obese patients. ■■ Even with a functioning neuraxial blockade for surgical anesthesia, the patient should be positioned optimally on the OR table in the ramped position, with immediate access to a difficult airway cart to establish an airway if necessary. ■■ Adequate preoperative assessment and preparation prior to induction of general anesthesia in a morbidly obese parturient is critical. ■■ A recent report of pregnancy-associated deaths highlights the importance of continued vigilance during emergence from general anesthesia, especially in obese women. ■■ Because of the exaggerated respiratory depression with sedatives, and opioids, implementation of multimodal analgesic techniques to improve postoperative analgesia and patient satisfaction, limiting opioid usage, and monitoring of oxygenation and ventilation is crucial to avoid postoperative adverse respiratory outcomes. ■■

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95. Frappier J, Guenoun T, Journois D, et al. Airway management using the intubating laryngeal mask airway for the morbidly obese patient. Anesth Analg 2003; 96:1510–1515. 96. Chiron B, Laffon M, Ferrandiere M, et al. Standard preoxygenation technique versus two rapid techniques in pregnant patients. Int J Obstet Anesth 2004;13:11–14. 97. McClelland SH, Bogod DG, Hardman JG. Pre-oxygenation and apnoea in pregnancy: changes during labour and with obstetric morbidity in a computational simulation. Anaesthesia 2009;64:371–377. 98. Dixon BJ, Carden JR, Burn AJ, et al. Preoxygenation is more effective in the 25 degrees head-up position than in the supine position in severely obese patients: a randomized controlled study. Anesthesiology 2005;102:1110–1115. 99. Gander S, Frascarolo P, Suter M, et al. Positive end-expiratory pressure during induction of general anesthesia increases duration of nonhypoxic apnea in morbidly obese patients. Anesth Analg 2005;100:580–584. 100. Lamarche Y, Martin R, Reiher J, et al. The sleep apnoea syndrome and epidural morphine. Can Anaesth Soc J 1986;33:231–233. 101. Belavy D, Cowlishaw PJ, Howes M, et al. Ultrasound-guided transversus abdominis plane block for analgesia after Caesarean delivery. Br J Anaesth 2009;103:726–730. 102. Gucev G, Yasui GM, Chang TY, et al. Bilateral ultrasound-guided continuous ilioinguinal-iliohypogastric block for pain relief after cesarean delivery. Anesth Analg 2008;106:1220–1222. 103. Liu SS, Richman JM, Thirlby RC, et al. Efficacy of continuous wound catheters delivering local anesthetic for postoperative analgesia: a quantitative and qualitative systematic review of randomized controlled trials. J Am Coll Surg 2006; 203:914–932.

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36

Human Immunodeficiency Virus: Maternal and Fetal Considerations and Management Roulhac D. Toledano  •  May C. M. Pian-Smith

The human immunodeficiency virus (HIV-1) was identified in 1983, and is now estimated to infect over 40 million people worldwide. Women of childbearing age comprise a growing proportion of those infected, with racial minorities in the United States affected disproportionately. An estimated 25% of infants born to these women, if untreated, will become infected with HIV. This chapter reviews the medical management of HIV-1-infected women, including early detection of infection in parturients, peripartum treatment options, and anesthetic considerations, with emphasis also on the pathogenesis of HIV and the multiorgan nature of the disease. ■■

 PIDEMIOLOGY AND SCOPE  E OF THE DISEASE

While data most likely underestimate the true incidence of HIV-1 infection, roughly half of the 40 million individuals living with HIV worldwide are women (1). Of the industrialized countries, the United States is the most heavily affected, with an estimated 56,000 new cases annually (2). In 2006, more than 1.2 million individuals were living with HIV in the United States (3), and women comprised an estimated one-third of those infected. Of note, approximately onequarter of these infected individuals are unaware of their HIV-­positive status (4). Both African American and Hispanic men, as well as women of ethnic and racial minority groups, are affected disproportionately in the U.S. epidemic. Indeed, the rate of new HIV and acquired immunodeficiency syndrome (AIDS) diagnoses in 2005 was 21 times higher among African American women than among white women (5). More recent statistics estimate that Blacks/African Americans account for 52% of all diagnoses of HIV infection in the United States and 44% of all persons living with an AIDS diagnosis (2). The rate of infection among Hispanics is roughly 3 times higher than that of the white population. From 2007 to 2010, males accounted for 79% of all diagnoses of infection among adults and adolescents, while the rate of HIV infection among women decreased slightly to 8/100,000 (6). Unprotected heterosexual intercourse and, secondarily, intravenous (IV) drug use with contaminated needles are the two main sources of HIV infection among female minority subgroups. Among all women, heterosexual intercourse is the primary source of infection. In Western Europe, HIV infection is also becoming endemic, with both heterosexual transmission and cases imported from Africa accounting for a large proportion of new infections. In Eastern Europe and Asia the incidence of HIV infection is burgeoning, in large part due to IV drug use, the sex-trade industry, and subsequent secondary transmission to stable partners. In the Russian Federation and the Ukraine, women accounted for roughly 40% of the new infections in 2005, most likely acquired during heterosexual intercourse.

Sub-Saharan Africa, however, carries the greatest burden of HIV infection worldwide, with 70% of HIV-infected individuals; 68% of new infections; and more than 90% of the world’s HIV-infected children and AIDS orphans (7). Statistics from the late 1990s indicate that more than 80% of the women infected with HIV worldwide were African. HIV infection rates among pregnant women in some urban centers in southern and eastern Africa reach an astounding 25% (8). ■■

PATHOGENESIS OF HIV

HIV-1 is a single-stranded RNA virus that is related genetically, morphologically, and biologically to the lentivirus subfamily of retroviruses. Like other lentiviruses, HIV-1 has a complex viral genome and characteristically causes indolent infections with extensive central nervous system (CNS) involvement and long periods of clinical latency. HIV-1 infection begins when glycoproteins on the HIV lipid envelope interact with CD4 receptors and a variety of co-­receptors, such as CCR5 and CXCR4, on host cells. The CD4 antigen complex was first detected on helper T cells, and was subsequently identified on B cells, macrophages, and monocytes. It is also located on placental cells, thereby providing a route for vertical transmission to the fetus in early pregnancy. Once the virus enters the cell it is copied by a reverse transcriptase enzyme into a double-stranded DNA, which can be inserted into the infected host’s cells. Mutations during the process and the rapid rate of viral replication contribute to viral resistance and complicate drug therapy. The human immunodeficiency virus type 2 (HIV-2) is similar to HIV-1, but is more commonly encountered in West Africa and has a longer asymptomatic stage, lower transmission rate, and less pathogenic course than HIV-1 (9). The most common mode of HIV-1 infection is via sexual transmission through the genital mucosa, although transmission also occurs by exposure to infected blood or blood products and by perinatal transfer from mother to child. In the United States, high-risk heterosexual transmission of HIV comprises the principal source of infection of women of all races and ethnicities, and accounts for at least 80% of new infections among women (10). Perinatal transmission can occur in utero, during labor and delivery, and postnatally from breastfeeding, although the majority occurs in the intrapartum period (11). Regardless of the mode of transmission, within 2 days the virus can be detected in peripheral lymphoid tissues and it can be cultured from the plasma within a week. Thereafter there is a rapid rise in plasma viremia, as the virus spreads to lymphoid organs and to the brain. CD4+ T cells are infected early in the course of the disease, and play a key role in propagating the infection. The number of CD4+ cells declines sharply during initial infection and slowly rebounds as the immune system combats viral replication. An

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asymptomatic period marked by a balance between CD4+ cell production and destruction ensues, ending once viral replication outpaces the immune system’s defenses. In general, the decline in CD4+ cells marks HIV progression from the initial infection and accounts for the profound immunodeficiency of advanced AIDS (12). Plasma viral load also serves as a marker for disease progression, and is extremely high during the acute infection and subsides during the latent stage. Patients tend to be highly infectious during the early stages of infection as a result of the high viral load. Acute infection manifests with transient flu-like symptoms of fever, fatigue, rash, headache, lymphadenopathy, pharyngitis, myalgia, arthralgia, and nausea, vomiting, and diarrhea. ■■

 CREENING AND DIAGNOSTIC S TESTS FOR HIV INFECTION DURING PREGNANCY

Since the mid-1990s, diagnosed cases of perinatally acquired HIV infection have declined by an estimated 90% in the United States (13). This sharp decline is attributed in part to routine HIV screening during pregnancy and the widespread availability of therapeutic drugs that prevent transmission. Preconceptual counseling for known carriers of HIV or early detection of HIV infection during pregnancy in patients whose HIV status is unknown, with subsequent counseling, are cornerstones of the prevention of mother-to-child transmission of HIV. Currently, the Centers for Disease Control and Prevention (CDC), U.S. Public Health Service (USPHS), and the ­American College of Obstetricians and Gynecologists (ACOG) recommend HIV screening for all pregnant women. The so-called “opt-out” approach to prenatal HIV testing encourages health care providers to test routinely for HIV infection unless the woman specifically refuses. Under universal opt-out screening, all parturients are notified that they will receive an HIV test as part of the routine prenatal tests unless they decline. Additional written documentation of informed consent beyond that required for routine tests is not necessary. The HIV test should be performed early in pregnancy and should be repeated in the third trimester in particular “at-risk” populations, such as IV drug users, women whose partners are infected, women who themselves or whose partners have more than one sexual partner during pregnancy, women who exchange sex for money or drugs, or women who receive healthcare in areas with an elevated incidence of HIV/AIDS (14). A repeat test in the third trimester for all pregnant women, regardless of risk factors, is also considered cost-effective. If testing has not been performed prior to term gestation or if the HIV status remains unknown at the onset of labor, rapid HIV testing is recommended at the time of presentation to the labor and delivery unit, unless the patient declines. If maternal HIV status is still unknown postpartum, a rapid test is recommended. Newborns whose maternal HIV status is unknown should be tested as soon as possible after birth. Several diagnostic tests, with varying degrees of sensitivity and specificity, are available to determine HIV status. The enzyme-linked immunosorbent assay (ELISA) detects antibodies to HIV in the patient’s serum and is often the initial screening test for HIV. Rapid enzyme-linked immunoassay (EIA) blood and oral secretion tests are also available and are recommended during labor and delivery for women of unknown HIV status. Obstetrician–gynecologists may also choose to use rapid testing as their standard outpatient test (15). Currently, four rapid HIV antibody tests are available in the United States, two of which are approved for point-ofcare. Results are interpreted visually; when HIV antibodies in

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a positive specimen bind to HIV antigens affixed to the test strip, a color change occurs. Positive EIA tests are confirmed by a more specific test, such as a Western blot, immunofluorescence assay (IFA), or HIV RNA polymerase chain reaction (HIV RNA-PCR). In the event that a parturient of previous unknown HIV status presents in labor and has a positive rapid HIV test by the opt-out approach, delaying treatment for confirmatory tests is not feasible. The expectant mother should be counseled that her preliminary test is positive and that the newborn may be exposed to HIV. Immediate initiation of antiretroviral (ARV) prophylaxis should be recommended. Antiretroviral therapy (ART) for both the mother and child will be discontinued if the confirmatory test result is negative (16). False-positive and false-negative results, as well as indeterminate confirmatory testing, occasionally occur. Both the EIA test and the Western blot test rely on the detection of antibodies to HIV antigens, yet there may be a period after initial infection during which adequate antibody levels have not yet formed or remain undetectable. During this “window period,” a patient may be highly contagious despite negative test results. Immunosuppressive therapy may also account for false-negative results. False-positive EIA tests can be caused by autoimmune disease, hepatitis B immunization, and high parity, among other things. Indeterminate test results occur when a positive EIA test is followed by a Western blot result that is insufficient to make a definitive diagnosis. Causes of indeterminate results include partial seroconversion, organ transplantation, autoimmune disease, blood transfusions, and advanced AIDS. Repeat testing can be delayed if indeterminate test results occur early in pregnancy, as initiation of ARV prophylaxis in the absence of maternal indications is suggested after the first trimester (but no later than 28 weeks’ gestation). For patients with confirmed HIV disease, preconception counseling is highly advised. Counseling provides the opportunity to discuss modes of mother-to-child transmission, methods to avoid transmission, safe sex practices during pregnancy, means of optimizing maternal health and nutrition, when to initiate ART, and concerns about potential adverse effects of ARV therapy for both mother and fetus. Birth control options to prevent future pregnancies, smoking cessation initiatives, referrals for drug counseling, delivery options, and alternatives to breastfeeding might also be discussed. For women whose HIV-positive status is discovered during prenatal testing, similar subjects should be broached during that or subsequent prenatal visits. ■■

 IV DISEASE: CLINICAL H MANIFESTATIONS

It is estimated that up to 25% of HIV-1-infected people will require surgery at some stage during the course of their illness (17). Further, given the rising rate of infection among women of childbearing years, anesthesiologists will encounter infected patients in the labor and delivery suites with increasing frequency. HIV infection affects multiple organs, and the provision of care may be further complicated by opportunistic infections, substance abuse, social and domestic issues, therapeutic drugs, tumors, and the risk of viral transmission to the health care worker. The following sections review the multiple organ systems affected by HIV.

Neurologic Effects Neurologic involvement occurs early in the course of HIV infection, but may manifest at any stage during the disease (Table 36-1). According to some sources, an estimated 80%

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CHAPTER 36  •  HUMAN IMMUNODEFICIENCY VIRUS

TABLE 36-1  Neurologic Manifestations of HIV Infection Early (initial infection and latent phase)

Headache Retro-orbital pain Depression Irritability Peripheral neuropathies Visual disturbances

Late (AIDS)

Encephalopathy (AIDS dementia complex) Infectious/opportunistic ­meningitis Intracranial masses (TB, ­lymphoma, KS) Myopathy (including vacuolar myelopathy, chronic distal symmetric polyneuropathy) Autonomic dysfunction

of AIDS patients demonstrate neurologic abnormalities at autopsy, and roughly half suffer from overt signs and symptoms of CNS dysfunction (18). However, the frequency of HIV-1-related CNS disease has been reduced by a variety of highly effective ARV agents with improved brain penetration (19). Like other lentiviruses, HIV-1 invades the CNS very soon after the initial systemic infection (20). During the earliest stage of primary infection, the HIV-1 virus can be isolated from the cerebrospinal fluid (CSF). Neurologic disturbances such as headache, retro-orbital pain, depression, irritability, peripheral neuropathies, and visual disturbances are not uncommon during this period of primary infection (21). An acute inflammatory demyelinating polyneuropathy similar to Guillain–Barre syndrome, cauda equina syndrome, and acute aseptic encephalitis have also been reported. In severe immunocompromised states or as the disease progresses to clinical AIDS, patients are more susceptible to diffuse encephalopathy (a.k.a., the AIDS dementia complex), infectious/­opportunistic meningitis (e.g., cryptococcal or syphilitic), and focal intracranial masses, such as tuberculosis (TB), lymphomas, or, less commonly, Kaposi’s sarcoma (KS). Cerebrovascular complications, such as hemorrhage and vasculitis, may develop within cerebral tumors. In addition, CNS tumors can cause cerebral edema, elevated intracranial pressure, changes in cerebral hemodynamics, or overt cognitive dysfunction that renders the patient unable to consent to and cooperate for procedures. Myopathy and segmental or diffuse myelopathy also manifest in the late stages of infection. Vacuolar myelopathy, which affects the lateral and posterior columns of the thoracic cord, affects up to 20% of the AIDS population (22). While peripheral neuropathies may be seen during all stages of the HIV infection, patients with advanced HIV or AIDS frequently develop a chronic distal symmetric polyneuropathy, with clinical features of numbness, dysesthesias, paresthesias, weakness, and decreased deep tendon reflexes. Autonomic dysfunction, including diarrhea, syncope, and orthostatic hypotension, also can present in the later stages of HIV progression.

Pulmonary Manifestations Pulmonary complications of HIV affect an estimated 70% of infected individuals at least once during the course of the disease (23). Causes include a variety of bacterial, viral, fungal, and parasitic opportunistic infections, as well as several noninfectious conditions. Upper respiratory tract infections, acute

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bronchitis, and acute sinusitis most often involve Streptococcus pneumoniae, Haemophilus influenza, and Pseudomonas aeruginosa. The clinical course of each of these conditions is similar in individuals with and without HIV, but HIV-infected individuals are prone to more frequent recurrences. Further, there is some evidence that bronchitis in HIV-positive patients progresses more frequently to bronchiectasis, and, in conjunction with cigarette smoking, can progress to emphysema earlier than in the non-HIV population. Bacterial pneumonia also occurs more frequently in HIV-infected individuals than in the general population. Common causative organisms include S. pneumonia and H. influenza, while Staphylococcus aureus and P. aeruginosa, as well as other gram-negative organisms, are implicated in patients with advanced disease. Abscesses, empyemas, and intrapulmonary cavitations are not uncommon complications of bacterial pneumonia in the HIV population. Viruses, too, can cause a clinical pneumonia and may play a critical role in producing other pulmonary and extrapulmonary complications of HIV, including neoplasms. The outbreak of Pneumocystis jiroveci pneumonia (formerly Pneumocystis carinii pneumonia, PCP) among four homosexual men heralded the HIV/AIDS epidemic in the early 1980s. Despite the current widespread use of both highly active antiretroviral therapy (HAART) and prophylaxis against opportunistic infections, PCP still accounts for a large proportion of respiratory events in HIV-infected individuals. Patients susceptible to PCP generally have CD4+ counts of 40 mmol/L indicates severe disease with poorer prognosis (70,95). Resolution begins within 24 hours of delivery and is usually complete in 2 to 6 weeks (93), although recurrence in subsequent pregnancy is likely (94) and in rare familial forms, fibrosis may occur (70). The fetus is not at risk from very mild disease but risks rise in proportion to maternal bile salt concentration (in contrast, bilirubin does not cross the placenta significantly). Preterm labor is common (30% to 40%), neonatal respiratory distress may be a consequence of the disease as well as preterm birth,

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and there are higher rates of meconium aspiration and late stillbirth clustered around 38 weeks’ gestation, with perinatal mortality approximately 3% (93,95). Induction of labor at 37 weeks is controversial but commonplace, because complications of prematurity and cesarean rates are high (95). Fetal distress in labor is also common, mandating close intrapartum monitoring. The neonate should receive vitamin K therapy to prevent intracranial bleeding. Despite inadequate levels of evidence, pruritus and abnormal liver function appears to be improved by use of ursodeoxycholic acid 15 mg/kg/day in 2 divided doses. This hydrophilic bile acid stimulates biliary secretion of bile salt export pump, reduces bile salt and sulfated progesterone metabolite concentrations (70), and displaces toxic bile acids (cholic acid and chenodeoxycholic acid, products of cholesterol metabolism) from hepatic membranes (92–95). Pruritus is relieved and the drug well tolerated. The anesthesiologist should assess the severity of liver dysfunction and check for rare cases of coagulation disturbance. Prophylactic oral vitamin K is sometimes given empirically against fat-soluble ­vitamin deficiency and consequent maternal postpartum hemorrhage.

Acute Fatty Liver of Pregnancy

AFLP is a rare, potentially fatal metabolic disorder with an estimated population incidence of 1 in 20,000 (96) and referral hospital based incidence of 1 in 1 to 15,000 pregnancies (69,70,72,75,90) (Table 37-10). It usually presents in the third trimester, often close to term, and infrequently after delivery, with prodromal malaise and vomiting for several days to 2 weeks, then more severe abdominal pain, polydipsia, headache, or infrequently encephalopathy. Jaundice is mild and complications include renal failure, acute respiratory distress, diabetes insipidus, and pancreatitis (96,97) (Table 37-10). More severe jaundice suggests preeclampsia, viral hepatitis, cholestasis, or bile duct obstruction. Pruritus is uncommon (incidence 5% to 30%) and the liver size is normal. The diagnosis of AFLP is clinical, supported by early laboratory coagulation abnormalities (although elevated fibrin degradation products and low fibrinogen are less common), later liver dysfunction (aminotransferases moderately elevated between 100 and 1,000 U/L), low blood glucose, and renal dysfunction (early elevation of serum creatinine and ammonia and metabolic acidosis from high serum lactate levels) (Table 37-10). Profound hypoglycemia is ­common, due to ­depression

of glucose-6-phosphatase activity, and indicative of more severe disease. Cholesterol, triglycerides and ­antithrombin are low. Marked neutrophil leukocytosis to 30,000/mm3 with left shift, microangiopathic hemolytic anemia and thrombocytopenia, are very common. Some patients also have preeclampsia with hemolysis, elevated liver enzymes, low platelets (HELLP), the main distinguishing features of AFLP being hypoglycemia, hyperammonemia, more severe coagulopathy, less severe thrombocytopenia, and less right upper quadrant pain or hypertension (98) (Table 37-11). Abdominal ultrasound may show ascites or a bright liver (96) and excludes gallstones, while diagnostic liver biopsy is almost always precluded by the bleeding risk. This disease affects women of all ages, races, and ethnicities and may appear after several normal pregnancies, but is more common in nulliparous women, multiple pregnancy, and preeclampsia (69,96). Metabolic, synthetic and excretory functions of the liver are abnormal due to fat infiltration and inflammation (72). AFLP occurs in 30% to 80% of women heterozygous for long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency, one of four enzymes that are part of a mitochondrial trifunctional protein complex responsible for long-chain fatty acid oxidation in the liver. If the fetus is homozygous (even heterozygous) and unable to oxidize 3-hydroxy fatty acids sufficiently it may present in infancy or after extended fasting with a hypoglycemic, Reyelike syndrome. Preceding this, excess fetal fatty acids transfer to the mother where they impair mitochondrial function and accumulate as microvesicles in hepatocytes. AFLP is also associated with deficiencies in carnitine palmitoyltransferase I and medium- and short-chain ­acyl-CoA dehydrogenase. Supportive therapy in an intensive care unit is required. Invasive monitoring and dextrose infusions to correct hypoglycemia, hemodialysis for renal failure, desmopressin for diabetes insipidus, and blood products for correction of coagulopathy, are often needed. About 50% of cases have coagulopathic bleeding, requiring blood product transfusion. Coagulopathy may worsen postpartum, when antithrombin levels fall further. Mortality is due to gastrointestinal hemorrhage and sepsis. In women with preeclampsia, adjustment of magnesium doses is necessary if renal impairment is present. Patients who develop encephalopathy need lactulose and may require intubation and ventilation, mandating general anesthesia for cesarean delivery.

TABLE 37-10  Diagnostic Features of Acute Fatty Liver of Pregnancy Feature

Frequency Outside Normal Range

Typical Range of Values

Low blood glucose

Very common

1–8  mmol/L

High bilirubin

Almost always

15–650 mmol/L

Coagulopathy

Extremely common

APTT 20–100 s

High serum urate

Extremely common

50–850 mmol

High serum creatinine

Common

60–400 mmol/L

High transaminases

Almost always

AST 40–3,000 IU/L ALT 20–1,100 IU/L

Low platelet count

Very common

15–450 × 109/L

High ammonia

Common

15–70 mmol

Six or more of: Vomiting, abdominal pain, polyuria/polydipsia, encephalopathy, elevated bilirubin, urate, transaminases or ammonia, hypoglycemia, leukocytosis, ascites, renal impairment, coagulopathy, micro­ vesicular steatosis on liver biopsy. APTT, activated partial thromboplastin time; AST, aspartate aminotransferase; ALT, alanine aminotransferase.

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619

TABLE 37-11  Differences Between Severe Preeclampsia with HELLP Syndrome and Acute Fatty Liver of Pregnancy Symptom or Feature Incidence

Severe Preeclampsia (HELLP) 0.2–0.6%

AFLP 0.005%

Parity

Nulliparous, multiple pregnancy

Multiparous, older age

Vomiting

Possible

Common

Epigastric pain

Common

Possible

Hypertension

Common

Possible

Proteinuria

Common

Possible

Hyperuricemia

Common

Very common

Elevated creatinine

Possible

Common

Transaminases

Mild to 20-fold elevation

Variable but to 500-fold elevation

APTT

Normal

Prolonged

Glucose

Normal

Low

Ammonia

Normal

High

Platelet count

Low or very low

Low–normal

Fibrinogen

Normal or high

Low

Encephalopathy

No

Sometimes

Maternal mortality

1–10%

5–20%

HELLP, hemolysis, elevated liver enzymes, low platelets.

After resuscitation and stabilization, usually within 24 hours of presentation, expedited delivery is mandated. Most women who enter spontaneous labor show evidence of fetal compromise, so about 75% of women with AFLP undergo cesarean delivery (96). Common neonatal problems arise due to prematurity, growth retardation, intrapartum hypoxia, and hypoglycemia. Although intensive care is needed for several days because of the risk of maternal hypoglycemia and hemorrhage, recovery is rapid over a few days, with resolution of disseminated intravascular coagulopathy and restoration of normal liver function within 4 weeks. Recurrence is unusual but genetic counseling should be offered. Greater awareness of the disease, intensive therapy and prompt delivery of the fetus have resulted in a significant fall in maternal mortality over the past 25 years, such that reported maternal case fatality rates of 7% to 18% probably exceed current rates (96). Unfortunately, perinatal mortality (usually stillbirth) is 10-fold normal (96), at 10% or more. Neonates with LCHAD deficiency can experience failure to thrive, hepatic failure, cardiomyopathy, and hypoglycemia. The anesthesiologist should assist with multidisciplinary optimization of medical care, and initiate intensive monitoring of maternal physiology and neurologic status. Blood pressure, blood glucose, fluid and electrolytes, coagulation, and acid–base status need regular assessment. Arterial cannulation is invaluable and good venous access via a central venous or peripherally inserted central catheter assists with infusion of dextrose-containing fluids, maintenance of adequate urinary output, treatment of hypertension, and replacement of electrolytes. Prophylactic H2-receptor antagonists are prescribed and coagulation defects corrected using IV vitamin K and blood products if clinical bleeding occurs. Successful urgent liver transplant has been used in cases with raised intracranial pressure or deteriorating neurologic function. Anesthesia is tailored to the situation (88,96), with regional anesthesia more likely to preserve hepatic blood flow provided blood pressure is maintained (99), but contraindicated in at least half the cases by fetal compromise or coagulation

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abnormalities and hematoma risk (96). General anesthesia may worsen encephalopathy but is often the method of choice for cesarean delivery (84,100,101). Strategies to reduce rises in intracranial pressure (obtunding the responses to intubation and extubation, avoiding coughing or venous obstruction in the head and neck, avoiding hypercarbia) are warranted if encephalopathy is present. Care with laryngoscopy to minimize airway trauma and avoidance of intramuscular injections, acetylsalicylic acid and NSAIDs are also recommended.

Hepatitis

Autoimmune hepatitis is a chronic disease of uncertain origin affecting women of child-bearing age. It reduces fertility because of associated hypothalamic–pituitary dysfunction, making it rare in pregnancy. Severity varies and concurrent autoimmune diseases may confound the diagnosis. Immunotolerance in pregnancy usually has a positive effect on disease progression, but disease flares occur in 20% to 35% and in 10% to 50% postpartum (102). Fetal outcomes are highly variable. Treatment with immunosuppressive therapy is usually continued, but the cytokine shift from a T-helper type 1 cytotoxic profile to a T-helper type 2 anti-inflammatory profile, mediated by high estrogen levels, allows a reduction in drug dose or even temporary elimination (103). Both prednisolone and azathioprine are safe to continue and if ceased, should be resumed post-delivery. The major fetal risk is premature delivery, leading to fetal mortality of 20% and perinatal or maternal mortality of 3% to 4% (102). Peliosis hepatitis is a rare infective disease, sometimes noted in immunodeficient patients, caused by the gram-negative bacteria genus Bartonella, which also causes “cat scratch disease.” Opportunistic infections present with angiomatosis, liver and spleen vasculitis, and endocarditis. Patients may be asymptomatic or develop portal hypertension, liver failure, or intraperitoneal hemorrhage. Therapies include antibiotics and hepatic artery embolization (103). Drug-induced hepatitis, from amoxicillin–­clavulanic acid or methyldopa, for example, is usually transient.

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Viral hepatitis is the most common cause of hepatitis, hepatic dysfunction, and jaundice during pregnancy. Acute hepatitis can usually be distinguished from other causes of acute liver disease by the high liver transaminase concentrations (often 10-fold normal). A number of other viruses cause acute hepatitis during the systemic infection phase, especially among immunosuppressed patients. In addition to hepatitis A and E, these include the herpes simplex virus (HSV), which is more likely to cause fulminant hepatitis than in non-pregnancy, cytomegalovirus, Epstein–Barr virus and, in Africa, Crimean-Congo hemorrhagic fever. In HSV there may be fever, oropharyngeal or genital lesions, coagulopathy and very high serum AST and ALT, but near normal bilirubin levels. Treatment with antiviral drugs is indicated but prognosis is poor and maternal mortality 40% to 75% (70,104). Hepatitis A, B, C, D and E virus may present as acute or chronic disease, with hepatitis B (HBV) and C (HCV) the most important for chronic liver disease. Only hepatitis E (HEV) appears to be more severe in pregnancy, but an impact on maternal obstetric and fetal outcomes is likely if disease is fulminant. The risk of vertical intrapartum transmission varies with each virus, being greatest with HBV and HEV. Hepatitis A virus (HAV) varies in prevalence geographically, but is endemic in Africa, Asia, and Central America. It shows fecal–oral transmission and affects approximately 1 in 1,000 pregnant women in the United States, with most infections asymptomatic or subclinical. Symptoms are similar to non-pregnancy, although pruritus is more common because of high estrogen levels and disease more severe with advancing age (70). Serum AST and ALT levels are significantly elevated and IgM anti-HAV is present in acute infection, followed by development of acquired immunity (anti-HAV IgG-positive serostatus) over a few weeks. Both inactivated vaccine for high-risk women and post-exposure immunoglobulin prophylaxis are safe during pregnancy. Although vertical transmission to the fetus or neonate is very rare, perinatal transmission may occur, so immunoglobulin can be given to the neonate and close household contacts. Breastfeeding should be encouraged. Hepatitis B virus (HBV) is a highly infectious doublestranded enveloped virus transmitted by cutaneous (especially needle sharing) or mucosal (especially sexual) exposure, and vertically from mother to fetus. It is one of the most common infections in the world, with over 350 million chronic carriers worldwide and prevalence of 1% to 3%. Most acute infections (incidence 1 in 500 to 1,000 pregnancies in the United States) present 6 weeks to 6 months after exposure and are sub-clinical, although nausea, vomiting, abdominal pain, and jaundice occur with similar severity to non-pregnancy. The diagnosis is made by detection of HBV surface antigen in the serum or other secretions, and is confirmed by detection of IgM antibodies to HBV core antigen. After the acute phase hepatitis e (envelope) antigen antibody develops (antiHBe) and patient infectivity decreases, but remains if HBsAg is present. About 5% of immunocompetent adult patients become carriers (105). Chronic infection in pregnancy has a prevalence of 0.1% to 6% depending on ethnicity, and these women usually do well (106), although poorer perinatal outcome may result from preterm labor and low birth weight. All pregnant women should be tested for HBsAg toward the end of the first trimester and vaccination during pregnancy is considered safe. Post-delivery flares, with or without HBeAg seroconversion, may be triggered by rapidly falling cortisol levels. Since most women have mild disease and the antiviral drugs have limited safety data in pregnancy, antiviral treatment is usually deferred until after delivery and those on treatment have it ceased, unless they are at high risk of a

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flare. Transplacental transmission of HBV occasionally occurs in early pregnancy (rate: 10%), but is common in later pregnancy, rising to 90% in the third trimester for HBeAgpositive women. The neonates of women with high viral loads may benefit from third trimester maternal treatment. The best safety data are for lamivudine, with tenofovir or telbivudine alternatives (70,105), although no antiviral drug has confirmed safety during lactation (105,106). Passive immunization with HBIg (immune globulin) within 12 hours of birth, and active immunization starting within 7 days of birth and continuing over the first 6 months of neonatal life, is highly effective in preventing neonatal disease, but 5% to 10% of children of HBeAg-positive women still become chronically infected. Hepatitis C virus (HCV) is a blood borne virus endemic in Asia, the eastern Mediterranean region and Africa in particular, but also prevalent now (2% to 3% worldwide) among patients with a history of intravenous drug use, blood transfusion prior to the introduction of screening, tattooing, body piercing, and organ transplantation. HCV causes up to 20% of acute viral hepatitis, although the 6 to 9 week illness is often subclinical or mild. Approximately 70% of those infected progress to chronic asymptomatic infection, and later cirrhosis (incidence 20% by 40 years post-viral acquisition), liver failure or hepatocellular carcinoma (1.5% to 4% of those with cirrhosis) can ensue (107). LFTs are usually normal among carriers of HCV but a number of obstetric complications (maternal cholestasis, congenital malformation, preterm delivery, low birth weight, and higher perinatal mortality) (108) are increased. Treatment with interferon and ribavirin often fails to clear the infection and should only be instituted after pregnancy due to teratogenicity and serious adverse effects. The risk of sexual transmission is very low, but vertical transmission from mother to fetus occurs in approximately 6% of women who are HCV polymerase chain reaction (PCR) positive. Quantitative HCV-RNA testing is a marker of the risk of vertical transmission, and is more likely to be positive in the presence of co-infection with human immunodeficiency virus (HIV) and certain HCV genotypes (70). Transmission is most likely at the time of delivery through contact with contaminated vaginal secretions, but the role of elective cesarean delivery in reducing transmission has not been determined. Both HBV and HCV are detectable in human milk but breast-feeding is considered safe (70). Neonatal surveillance is with HCV antibody screening at about 12 months (maternal antibody is detectable for up to 18 months) or HCV-RNA by PCR within the first few months of life. Hepatitis D virus (HDV) is a single-stranded RNA virus that requires the presence of HBV to replicate. HDV causes more severe disease and higher rates of chronicity and cirrhosis than hepatitis B. Infection appears rare in pregnant women and children, suggesting that vertical transmission is uncommon. Hepatitis E virus (HEV) is a single-stranded RNA virus endemic to developing countries that commonly causes acute hepatitis via fecal–oral spread. Disease during pregnancy, especially in the late second or third trimesters, is more severe and may be fulminant, leading to very high mortality (up to 50%) (109). Depending on the viral load, vertical intrapartum transmission to the newborn occurs in 33% to 50%, with neonatal hepatic failure (107) and chronic infection both reported (110). Hepatitis G virus is detected by reverse-transcriptase PCR. It has similar epidemiology to HIV and transmission similar to HCV, but significant liver disease is unlikely. Vertical transmission appears very common but free of adverse effect on the infant.

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CHAPTER 37  •  Renal and Hepatic Disorders in Pregnancy

Cirrhosis, Portal Hypertension and Budd–Chiari Syndrome

Cirrhosis is caused by a number of conditions, especially chronic hepatitis B, C, D, and E or alcoholism, but due to hormonal derangements that cause anovulation, is rare in women of child-bearing age (rate 1 in 2,500) and even rarer in pregnancy (1 in 6,000) (111). Improvements in care have resulted in higher conception rates and better obstetric outcomes among women with well-compensated cirrhosis (111), although 25% experience deterioration in liver function and maternal mortality is 10% (70). Elevation of portal venous pressure predisposes to esophageal varices, which bleed in 15% to 25% of pregnant women with cirrhosis and 50% of those with known portal hypertension. Screening is advised in the second trimester and b-blockers can be commenced if indicated (70,90). Diversion of blood through the azygous venous system and reflux esophagitis further predispose to variceal bleeding, ascites and portal hypertensive encephalopathy. Hematemesis, especially during later pregnancy, is associated with mortality of 20% to 50% (112). Screening for splenic artery aneurysms is also warranted, and these considered for surgical or interventional radiologic therapy, because the incidence of rupture is up to 2.5% (69). Portal hypertension may also be present without cirrhosis, secondary to portal vein thrombosis or congenital hepatic fibrosis. Non-cirrhotic portal hypertension is much more common in Asian countries, but is associated with better outcomes (113). Essential thrombocythemia may cause recurrent abortion, placental infarction, or intra-abdominal mesenteric, portal, and hepatic venous thromboses, leading to portal hypertension. Therapy includes albumin, diuretics, ultrasound-guided paracentesis for ascites, and non-selective b-blockers such as propranolol to lower portal pressure, despite their association with fetal growth restriction, neonatal hypoglycemia or bradycardia. Endoscopic band ligation is used in preference to chemical sclerotherapy for acute variceal hemorrhage (111). Octreotide is not of established safety but has been used for acute bleeding, as has transjugular intrahepatic portosystemic shunt (TIPS) placement. Surgical splenorenal or portocaval shunts or liver transplantation are a last resort after life-threatening hemorrhage (114), but those patients with existing shunts are at lower risk of hematemesis and the outcome of pregnancy is usually good (111). Fifty percent of patients with cirrhosis and significant portal hypertension develop either acute variceal bleeding, severe anemia (as a result of chronic illness or bleeding varices), thrombocytopenia (as a result of hypersplenism), or rupture of a splenic artery aneurysm (incidence approximately 2% and associated with very high maternal and fetal mortality). Hepatic function may deteriorate because of bleeding, sepsis, hypotension, or drugs. Drugs with anti-platelet activity potentiate the bleeding risk; impaired acetaminophen (paracetamol) and morphine-3- and -6-glucuronide metabolism result in hepatotoxicity or central nervous system depression respectively, making opioids without active metabolites (e.g., fentanyl) preferable. Intra-abdominal surgery on patients with advanced cirrhosis is associated with very high 30-day mortality (60% or more), especially if urgent or associated with concurrent ­coagulopathy (115). Spontaneous abortion and preterm birth rates are doubled and neonatal mortality is increased. When vaginal delivery is planned, provided both coagulation tests and the platelet count are adequate, regional analgesia is useful in preventing straining during delivery (116). If general anesthesia is required, the principles of anesthesia that pertain to severe liver disease are applicable.

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Budd–Chiari syndrome occurs in women of child-bearing age and is characterized by thrombotic obstruction of hepatic veins or the inferior vena cava, leading to liver ischemia and portal hypertension. Presentation during pregnancy is exceptionally rare, although some cases present postpartum, usually between the fourth day and third week after delivery (117). The etiology is uncertain, but anti-cardiolipin antibodies may be present and the condition is associated with several pro-thrombotic conditions, such as polycythemia rubra vera, paroxysmal nocturnal hemoglobinuria, inherited thrombophilias (e.g., antithrombin, protein C or S deficiency, factor V Leiden) and malignancy. The hypercoagulable state of pregnancy is a concern for those women with the condition who contemplate falling pregnant. Liver biopsy shows congestion and centrilobular liver necrosis (118) and the clinical presentation with hepatomegaly, ascites, and liver failure may be insidious over months or acute. The diagnosis is made with ultrasound Doppler flow studies, venography, or magnetic resonance imaging. Initial presentation during pregnancy carries high maternal mortality (119). Known cases that are well treated before pregnancy have very high rates of early fetal loss, especially in those with factor II gene mutation (120), but show good maternal and fetal outcome after 20 weeks’ gestation. Vaginal delivery is encouraged because of the risks of difficult surgery (large pelvic collateral veins), bleeding, and thrombosis associated with cesarean delivery. Management is antenatal anticoagulation with heparin and postpartum warfarin, but the obstruction may prove resistant to anticoagulation, thrombolytic therapy, and other attempts at revascularization (118). The TIPS procedure is technically more difficult in late pregnancy, so surgical shunts or liver transplantation may be necessary.

Liver Tumors

Pregnancy complicated by hepatocellular carcinoma, cholangiocarcinoma, hepatic adenoma, hemangioma, or focal nodular hyperplasia (a vascular benign tumor) is very rare and many such tumors are found incidentally. Hepatocellular carcinoma is either a very rare primary malignancy or more often, secondary to chronic HBV or HCV infection. Maternal mortality is high, possibly influenced by estrogenstimulated acceleration. Benign hepatic adenomas are almost exclusive to women and stimulation of tumor growth during pregnancy results in a 25% incidence of hemorrhagic rupture into the abdominal cavity (69). Hemangioma is the most common benign tumor of the liver and spontaneous rupture is rare, but potentially fatal. Termination of pregnancy may be recommended and surgical resection of symptomatic or >5 cm hepatic tumors is recommended. Successful surgical options are partial hepatectomy in the second trimester or preoperative arterial embolization prior to surgery for acute rupture. Cirrhosis and metastatic disease need consideration during assessment and planning for anesthesia. Intraoperative fetal monitoring is warranted if the fetus is viable. If resection is attempted, massive hemorrhage should be expected and full preparations are mandatory, including consideration of cell salvage.

Hepatolenticular Degeneration (Wilson Disease)

Hepatolenticular degeneration (Wilson disease) is a rare (prevalence 1 in 20 to 30,000) (121) autosomal recessive disorder involving multiple gene mutations of ATP7B which codes for a copper-transporting ATPase. This reduces copper excretion into bile and inhibits the plasma copper binding transport protein ceruloplasmin, leading to copper damage to the liver, brain, and other organs, although renal function is usually maintained.

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As well as liver disease, up to 50% of patients have movement abnormalities similar to Parkinson’s disease, recurrent miscarriage or golden deposits of copper in Descemet’s membrane of the cornea (Kayser–Fleischer rings). Treatment is with chelators such as penicillamine or trientine, but in pregnancy the safest chelating agent is zinc (122). Copper chelation restores fertility and in asymptomatic patients without significant liver disease or portal hypertension, the fetus is unlikely to suffer liver toxicity and outcomes are good. Estrogen induces a rise in plasma ceruloplasmin, so clinical improvement or remission may occur. Pregnancy is rarely reported and descriptions of obstetric anesthesia are also rare (123). Anesthetic assessment should be that of hepatic dysfunction, thrombocytopenia, coagulopathy, and bulbar neurologic involvement. Skin problems may warrant care with pressure from face masks or at intravascular sites. For patients on penicillamine, neuromuscular blocking drugs should be monitored because of an associated myasthenic syndrome (123). Regional techniques are valuable if not contraindicated, although cranial nerve involvement may mandate general anesthesia.

Hemochromatosis

Hemochromatosis is one of the most common genetic diseases, with estimated prevalence 1 in 300, autosomal recessive inheritance and over-representation in men. Women with juvenile idiopathic hemochromatosis and iron overload may have multiple endocrine dysfunction, heart failure, and hypopituitarism. There is little information about pregnancy, other than a successful case after regular phlebotomy to restore serum ferritin and iron levels and conception through assisted reproductive technology (124).

Hepatic Porphyrias

There are a number of acute and non-acute hepatic porphyrias, arising from defects in the heme biosynthesis pathways, with AIP the most severe. The prevalence of AIP, an autosomal dominant disease with incomplete penetrance, is 1 to 10 per 100,000. Although up to one-third of women present for the first time in pregnancy or the postpartum period (69), case series involving pregnancy are rare. In AIP, porphobilinogen deaminase activity is markedly reduced and disease is triggered by drugs and hormones that stimulate aminolevulinic acid synthetase in the liver. Pregnancy is associated with increased excretion of porphobilinogens and coproporphyrins but not to the extent of porphyric attacks, which cause abdominal pain, gastrointestinal symptoms, autonomic disturbance, neuropathies, and mental changes (125). Attacks are prevented by administration of oral or parenteral glucose and hematin. The effect of pregnancy on the disease is unpredictable, but fasting, vomiting, or hormonal changes are triggers that make flares more common. Pregnancy outcomes are variable but generally satisfactory, with fetal loss 10% or more. Crises are most frequently triggered by drugs and maternal mortality in hospitalized patients is less than 10% (69,91). The anesthesiologist should assess mental status, peripheral neuropathy, and bulbar dysfunction. Regional anesthesia may be suitable in the absence of an acute crisis (126). General anesthesia should be induced with propofol (127), while volatile anesthetics, opioids, and neuromuscular blocking drugs are safe (128,129).

Hydatid Disease

Hydatid disease (cystic echinococcosis) is a parasitic disease found worldwide, but is most prevalent in the Mediterranean, Middle and Far East, Australasia, Africa, and South America, where the incidence reaches 200 per 100,000. In the United

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States and Europe the incidence is much lower (approximately 0.5 per 100,000), but probably increasing because of immigration. Primarily a disease of sheep and cattle, humans are accidental hosts, with the adult worm containing eggs transmitted in canine feces. Larvae develop in the intestine, penetrate into the portal circulation and invade the liver, spleen, mesentery, and pelvis, although not placenta, so the neonate is not exposed (130). Cysts are often asymptomatic, being diagnosed on ultrasound, with infection confirmed by an indirect hemagglutination test. Larger cysts (>5 cm) may rupture, causing life-threatening anaphylaxis and peritoneal infection (131). Although reduced cellular immunity favors echinococcosis growth, the disease is rare during pregnancy, with a rate of less than 1 in 20 to 30,000 in endemic areas (132) and few published reports. Drug treatment is with anti-helmintics, such as praziquantel, albendazole, and mebendazole, which do not reduce cyst size but inhibit the polymerization of tubulin to microtubules, blocking glucose absorption, causing glycogen depletion and cellular autolysis. Albendazole shows teratogenicity and embryotoxicity in rat but not sheep models and appears safe after the first trimester (131,132). Drug therapy is usually reserved for recurrent disease or when surgery is impossible, although the World Health Organization does not recommend surgery during pregnancy because of the risk of intra-abdominal dissemination or anaphylaxis from spill of cyst content. Nevertheless, urgent surgery including partial hepatectomy, may be mandated by cyst torsion, rupture, or obstruction to labor (130).

Acute Cholecystitis

Cholelithiasis during pregnancy occurs most commonly during the second and third trimesters and early postpartum period as serum lipid concentrations peak, bile acid excretion is reduced, and intestinal motility slows. Increased biliary cholesterol forms monohydrate crystals that agglomerate to produce gallstones, detectable in 10% of the pregnant population and associated with higher parity (133,134). Despite gallstones, acute cholecystitis is uncommon, having a prevalence of 0.01% to 0.1% and associations with maternal obesity and elevated serum leptin (134). The clinical presentation is similar to non-pregnancy, features being right upper quadrant pain, tenderness, fever, and leukocytosis. The course of cholecystitis is unchanged by pregnancy and ultrasound imaging is indicated to identify gallstones or ­biliary sludge, followed by magnetic resonance cholangiopancreatography (75). Endoscopic retrograde cholangiopancreatography (ERCP) to detect common bile duct stones is also safe provided the uterus is shielded with lead to minimize fetal exposure to radiation. Most women respond to conservative management with analgesia, antibiotics, intravenous fluid, and fasting, but the relapse rate is over a third, so surgery is often required. Cholecystectomy (rate: 1 to 8 per 10,000 pregnancies) is the second most common non-gynecologic operation performed during pregnancy and is best deferred until the second trimester. Laparoscopic and even open cholecystectomy is associated with good maternal and fetal outcomes, even if disease is severe (135). Treatment delays may lead to pancreatitis, which confers a poorer fetal prognosis, and surgery in the third trimester is less safe (134). Anesthetic management follows the usual principles of anesthesia during pregnancy (136,137).

Primary Biliary Cirrhosis

Primary biliary cirrhosis is a rare disease, primarily of women aged 30 to 60 years, with an estimated prevalence 1 in 13,000 (138,139) and an association with other autoimmune

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CHAPTER 37  •  Renal and Hepatic Disorders in Pregnancy

­ isorders. The diagnosis is made by detection of IgG autod antibodies to mitochondrial pyruvate dehydrogenase or by liver biopsy, demonstrating slowly progressive destruction of intrahepatic bile ducts, portal inflammation, and scarring. The clinical spectrum and natural history varies, with most patients asymptomatic but some having pruritus, jaundice, and fatigue. The serum ALP and GGT are raised, as may be aminotransferases and bilirubin. Infertility is common and pregnancy rare, with maternal health and fetal outcomes unclear but probably poor (75,111,138). Management is with ursodeoxycholic acid before pregnancy and again after the first trimester (140). Methotrexate is teratogenic, so must be avoided, and liver transplantation is the only definitive therapy for advanced disease.

Primary Sclerosing Cholangitis

Primary sclerosing cholangitis is a rare chronic inflammatory, fibrotic disease of bile ducts that leads to cirrhosis and the need for liver transplantation. The etiology is unclear and no medical therapy is effective, although ursodeoxycholic acid may improve liver biochemistry. Complications include metabolic bone disease, cholangitis, and cholangiocarcinoma (141). Most cases occur in men with inflammatory bowel disease, so few pregnancies have been reported. Pruritus is prominent, the course of the disease appears unaltered, and neonatal ­outcome appears good (142).

Choledochal Cysts

Choledochal cysts are very rare, having a prevalence of 1 in 100,000. They present with abdominal pain, jaundice and a mass, although the latter can be obscured by the uterus during pregnancy, delaying the diagnosis (made using ultrasound, magnetic resonance imaging, or if need be cholangiography) until complications arise (143). Cyst growth, obstruction and compression during labor increase the risk of rupture (144), so elective cesarean delivery is often recommended. Definitive surgery is delayed until after delivery if possible (69,143,145). The anesthesiologist is likely to encounter these patients at emergency explorative laparotomy for bile drainage or at elective excision, with reconstructive hepaticoenterostomy (145).

Pancreatitis

Acute pancreatitis is rare in pregnancy (prevalence up to 1 in 1,000) and mostly associated with gallstones or less frequently excess alcohol intake or viral illness. Patients present most commonly in the third trimester, possibly due to the lithogenic effect of estrogen, and complications occur in less than 5% (146). With early recognition (the diagnosis being made on the basis of abnormal serum amylase and lipase tests, although LFTs may be normal) and better care, including the safe performance of ERCP, mortality is very much lower than in the past (146).

KEY POINTS Renal disease in pregnancy is uncommon (approximate incidence 1 in 1,000) and results from renal disease prior to pregnancy, multisystem or organ-specific diseases, obstetric disorders involving the kidney, or complications of pregnancy or childbirth. ■■ The obstetric outcomes of women with severe renal disease appear to have improved significantly in recent years, largely because of the use of erythropoietin for anemia, better ■■

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management of hypertension, high-flux dialysis for endstage or acute renal failure, and progress in neonatal care. ■■ The anesthetic management of women with renal disease follows the principles that apply to the non-pregnant patient, with a variety of modifications because of the physiologic differences and pharmacologic considerations that pertain during pregnancy. Neuraxial techniques are frequently appropriate. ■■ Abnormalities of LFTs and jaundice are uncommon, but approximately 1 in 500 women develop serious hepatic disease. ■■ Various congenital and acquired liver diseases present during pregnancy, the most common being viral hepatitis, but diseases unique to pregnancy (e.g., IHCP and AFLP) are frequent causes of fetal mortality and rarely, maternal mortality. Women with cirrhosis, portal hypertension, acute liver failure, or hepatic rupture pose major anesthetic ­challenges. ■■ The anesthesiologist may be required to manage critically ill women with acute hepatic failure; or those requiring cesarean delivery or urgent liver transplantation. Serious issues to address include coagulopathy and encephalopathy and general aims are maintenance of liver and renal blood flow, avoidance of hepatotoxicity and cross-infection, and management of risks such as thromboembolism and postpartum hemorrhage. ■■ There are a number of anesthetic options for women with liver disease, with neuraxial anesthesia sometimes contraindicated by coagulopathy, obtundation, or surgical needs.

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116. Heriot JA, Steven CM, Sattin RS. Elective forceps delivery and extradural anaesthesia in a primigravida with portal hypertension and oesophageal varices. Br J Anaesth 1996;76:325–327. 117. Khuroo MS, Datta DV. Budd-Chiari syndrome following pregnancy. Report of 16 cases with roentgenologic, hemodynamic and histologic studies of the hepatic outflow tract. Am J Med 1980;8:113–121. 118. Lee WM. Pregnancy in patients with chronic liver disease. Gastroenterol Clin North Am 1992;21:889–903. 119. Dilawari JB, Bambery P, Chawla Y, et al. Hepatic outflow obstruction (BuddChiari syndrome). Experience with 177 patients and a review of the literature. Medicine (Baltimore) 1994;73:21–36. 120. Rautou PE, Angermayr B, Garcia-Pagan JC, et al. Pregnancy in women with known and treated Budd-Chiari syndrome: maternal and fetal outcomes. J Hepatol 2009;51:47–54. 121. Bihl J. The effect of pregnancy on hepatolenticular degeneration. Am J Obstet Gynecol 1973;78:1182–1183. 122. Brewer GJ. Novel therapeutic approaches to the treatment of Wilson’s disease. Expert Opin Pharmacother 2006;7:317–324. 123. El Dawlatly AA, Bakhamees H, Seraj MA. Anesthetic management for cesarean section in a patient with Wilson’s disease. Middle East J Anesthesiol 1992;11:391–397. 124. Farina G, Pedrotti C, Cerani P, et al. Successful pregnancy following gonadotropin therapy in a young female with juvenile idiopathic hemochromatosis and secondary hypogonadotrophic hypogonadism. Haematologica 1995;80:335–337. 125. Kanaan C, Veille JC, Lakin M. Pregnancy and acute intermittent porphyria. Obstet Gynecol Surv 1989;44:244–249. 126. McNeill MJ, Bennet A. Use of regional anaesthesia in a patient with acute porphyria. Br J Anaesth 1990;64:371–373. 127. Kantor G, Rolbin SH. Acute intermittent porphyria and caesarean delivery. Can J Anaesth 1992;39:282–285. 128. Jensen NF, Fiddler DS, Striepe V. Anesthestic considerations in porphyrias. Anesth Analg 1995;80:591–599. 129. Harrison GG, Meissner PN, Hift RJ. Anaesthesia for the porphyric patient. Anaesthesia 1993;48:417–421. 130. Manterola C, Espinoza R, Munoz S, et al. Abdominal echinococcosis during pregnancy: clinical aspects and management of a series of cases in Chile. Trop Doct 2004;34:171–173. 131. van Vliet W, Scheele F, Sibinga-Mulder L, et al. Echinococcosis of the liver during pregnancy. Int J Gynecol Obstet 1995;49:323–324. 132. Montes H, Soetkino R, Carr-Locke DL. Hydatid disease in pregnancy. Am J Gastroenterol 2002;97:1553–1555. 133. Ko CW, Beresford SA, Schulte SJ, et al. Incidence, natural history, and risk factors for biliary sludge and stones during pregnancy. Hepatology 2005;41:359–365. 134. Mendez-Sanchez N, Chavez-Tapia NC, Uribe M. Pregnancy and gall bladder disease. Ann Hepatol 2006;5:227–230. 135. Lu EJ, Curet MJ, El-Sayed MD, et al. Medical versus surgical management of biliary tract disease in pregnancy. Am J Surg 2004;188:755–759. 136. Graham G, Baxi L, Tharakan T. Laparoscopic cholecystectomy during pregnancy: a case series and review of the literature. Obstet Gynecol Surv 1998; 53:566–574. 137. Steinbrook RA, Bhavani-Shankar K. Hemodynamics during laparoscopic surgery in pregnancy. Anesth Analg 2003;93:1570–1571. 138. Goh SK, Gull SE, Alexander GJ. Pregnancy in primary biliary cirrhosis complicated by portal hypertension: report of a case and review of the literature. BJOG 2001;108:760–762. 139. Rinella ME. Primary biliary cirrhosis. Ann Hepatol 2006;5:198–200. 140. Poupon R, Chretien Y, Chazouilleres O, et al. Pregnancy in women with ursodeoxycholic acid-treated primary biliary cirrhosis. J Hepatol 2005;42:418–419. 141. Silveira MG, Lindor KD. Clinical features and management of primary sclerosing cholangitis. World J Gastroenterol 2008;14:3338–3349. 142. Janczewska I, Olsson R, Hultcrantz R, et al. Pregnancy in patients with primary sclerosing cholangitis. Liver 1996;16:326–330. 143. Hewitt PM, Krige JE, Bornman PC, et al. Choledochal cyst in pregnancy: a therapeutic dilemma. J Am Coll Surg 1995;181:237–240. 144. Benchellal ZA, Simon E, d’Alteroche L, et al. Choledochal cyst rupture during pregnancy. Gastroenterol Clin Biol 2009;33:390–391. 145. Singham J, Yoshida EM, Scudamore CH. Choledochal cysts. Part 3 of 3: Management. Can J Surg 2010;53:51–56. 146. Tang SJ, Rodriguez-Frias E, Singh S, et al. Acute pancreatitis during pregnancy. Clin Gastroenterol Hepatol 2010;8:85–90.

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CHAPTER

38

Anesthesia for the Pregnant Patient with Immunologic Disorders Stephen H. Halpern  •  Margaret Srebrnjak

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INTRODUCTION

The role of the immune system is to rid the body of foreign material such as bacteria, viruses, and other foreign matter. However, in predisposed individuals, an overreaction to foreign antigens can occur, resulting in a wide variety of pathologic states and syndromes. Some immunologically mediated disorders are acute and life-threatening, such as anaphylaxis, while others are chronic, such as rheumatoid disease and allograft rejection. None of these preclude pregnancy. Immunologic responses are divided into two major divisions, the innate immune response and the adaptive immune response. The innate immune system is a non-specific and immediate reaction to a foreign allergen and does not change regardless of how many times an infectious agent is encountered. It includes physical barriers, such as the epidermis and mucous, as well as elements of the immune system such as natural killer cells, phagocytes, cytokines, and complement. Complement factors are a group of serum and cell surface proteins, which cause an amplifying series of enzymatic reactions when activated; they can cause direct cell lysis, facilitate phagocytosis of the foreign cell, or cause the release of mediators (1). Higher organisms have also developed an antigen-specific immunologic reaction called adaptive immunity that works in concert with innate immunity. Specifically, an individual will respond, more rapidly and robustly, to specific antigens on subsequent exposure, using T and B cells. It is a reaction with “memory,” since it relies on an initial exposure (2). When an antigen is presented and recognized by antigenspecific T cells and B cells, priming, activation, and differentiation occur. B cells proliferate and differentiate into antigen-specific memory cells and plasma cells. Plasma cells secrete antibodies, such as immunoglobulin (Ig) A, G, or E, whose role is to neutralize toxins, activate complement, and facilitate phagocytosis of foreign cells. Only IgG crosses the placenta (1). T cells also proliferate and differentiate into memory cells as well as effector T cells. There are four classic hypersensitivity reactions that lead to tissue injury. Similar mechanisms also cause autoimmune diseases. For the purpose of this chapter, the classification works well for both (Table 38-1). Recently, several subcategories under Type IV hypersensitivity have been included as our understanding of immune reactions has expanded (2).

Type I Hypersensitivity (IgE-mediated Reactions) Immediate hypersensitivity or anaphylaxis is a reaction that requires the recognition of antigens by membrane-bound IgE on mast cells in the tissues and basophils in blood. A single cell may be armed with specific IgE molecules for many

different antigens. When an allergen is re-encountered, a change in the shape of the cell membrane occurs resulting in degranulation and the release of vasoactive peptides and chemotactic factors. The immediate reaction is mostly carried out by mast cells with basophils being activated and recruited a few hours later (2). Inhalation of antigens and subsequent mediator release leads to bronchoconstriction and mucous secretion; ingestion of antigens causes diarrhea and vomiting; and subcutaneous antigens produce urticaria and angioedema. With intravascular antigen exposure, systemic activation occurs, causing increased capillary permeability, hypotension, tissue swelling, and smooth muscle contraction (Fig. 38-1) (2).

Anaphylaxis Terminology

Defining anaphylaxis is a challenge. Some interpret it as a broad term describing a severe, life-threatening, generalized hypersensitivity reaction, while others define it as a specific IgE-mediated reaction (3,4). Recently, National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network proposed clinical criteria for the diagnosis (Table 38-2). Anaphylactoid reactions appear similar to IgE-mediated hypersensitivity, but do not involve antibodies or a previous exposure. Mechanisms include, non-specific complement activation and direct histamine release. For example, most muscle relaxants and opioids release histamine directly from mast cells. Unlike anaphylaxis, many anaphylactoid reactions can be attenuated with antihistamines, corticosteroids, and the slow administration of drugs. Most drugs can cause both types of reactions (5).

Type II Hypersensitivity (Antibody-mediated Cytotoxic Reactions) The antibody-mediated cytotoxic immune response is initiated by the binding of circulating IgM or IgG antibodies with cell surface or tissue-matrix antigens, which have been modified to make the antigen foreign. The antigens may be normal red blood cell antigens like those in autoimmune hemolytic anemia or they may be altered such as when penicillin attaches to red blood cells and initiates a drug-induced hemolytic anemia (1,2). Once antibodies bind to the cells, the complement cascade is initiated. Activated complements C3 and C5, also known as anaphylatoxins, work directly to cause mast cell degranulation. Some complement factors enhance phagocytosis of the targeted cell by macrophages, neutrophils, and eosinophils; others form a membrane-attack complex that perforates the cell membrane causing cell lysis and death. This mechanism is responsible for disorders such as erythroblastosis fetalis, immune thrombocytopenia, and myasthenia gravis (1,2).

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TABLE 38-1  Major Types of Immune-mediated Hypersensitivity Reactions Mechanism

Antigen

Effector Mechanism

Examples

Type I Hypersensitivity (Immediate)

Soluble allergen

Mast cell–bound IgE •• Histamine, tryptase, carboxypeptidase, serotonin, PAF

Anaphylactic shock Allergic rhinitis Angioedema Urticaria

Cell-surface Ag Tissue-matrix Ag

IgG or IgM •• Phagocytes, NK cells •• Complement

Hemolytic transfusion reactions Erythroblastosis fetalis ITP Graves’ disease

Type III Immune complex mediated

Soluble Ag

IgG •• Phagocytes, NK cells •• Complement

SLE SBE

Type IV Delayed-type hypersensitivity

Soluble Ag

TH 1 cell •• Release cytokines to attract macrophages TH 2 cell •• Release cytokines to attract eosinophils and stimulate B cells TC cell

Tuberculin test Contact dermatitis RA (in part) Multiple sclerosis Chronic rhinitis Chronic asthma Allograft rejection (in part)

Type II Hypersensitivity (Cytotoxic)

Soluble Ag

Cell-associated Ag

Ag, antigen; IgE, immunoglobulin E; IgG, immunoglobulin G; IgM, immunoglobulin M; PAF, platelet activating factor; ITP, immune thrombocytopenic purpura; SLE, systemic lupus erythromatosus; SBE subacute bacterial endocarditis; TH 1, Type I helper T cell; TH 2, Type II helper T cell; TC, cytotoxic T cell; RA, rheumatoid arthritis Adapted from: Salmon JE. Mechanisms of immune-mediated tissue injury. In: Goldman L, Ausiello D, eds. Cecil Medicine. 23rd ed. Philadelphia, PA: Saunders Elsevier; 2008:266–270.

Antigen B cell

Plasma cell

Mast cell IgE

Subsequent exposure

Skin

Flushing Angioedema Urticaria Tachycardia Hypotension Dysrhythmias

Signs and Symptoms

Heart Bronchospasm Mucous plugging

Lung Nausea Vomiting Diarrhea Abdominal cramps

Mediators: Histamine, tryptase, carboxypeptidase, platelet-activating factor, cytokines

Gastrointestinal System

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FIGURE 38-1  Mechanisms of IgE-mediated reactions.

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SECTION VIII  •  ANESTHETIC MANAGEMENT OF THE PARTURIENT WITH COEXISTING DISORDERS

TABLE 38-2  Clinical Criteria for Diagnosing Anaphylaxis Anaphylaxis is highly likely when any one of the following three criteria are fulfilled: 1. Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, or both (e.g., generalized hives, pruritus or flushing, swollen lips–tongue–uvula) AND AT LEAST ONE OF THE FOLLOWING a.  Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced PEF, hypoxemia) b.  ↓BP or associated symptoms of end-organ dysfunction (e.g., hypotonia [collapse], syncope, incontinence) 2. TWO OR MORE OF THE FOLLOWING that occur rapidly after exposure to a likely allergen for that patient (minutes to several hours): a. Involvement of the skin–mucosal tissue (e.g., generalized hives, itch-flush, swollen lips–tongue–uvula) b.  Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced PEF, hypoxemia) c.  ↓ BP or associated symptoms (e.g., hypotonia [collapse], syncope, incontinence) d.  Persistent gastrointestinal symptoms (e.g., crampy abdominal pain, vomiting) 3. ↓ BP after exposure to known allergen for that patient (minutes to several hours) •• Systolic BP of less than 90 mm Hg or greater than 30% decrease from that person‘s baseline PEF, Peak expiratory flow; BP, blood pressure Data from: Sampson HA, Munoz-Furlong A, Campbell RL, et al. Second symposium on the definition and management of anaphylaxis: summary report-Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J Allergy Clin Immunol 2006;117:391–397.

Type III Hypersensitivity (Immune Complex Diseases) Immune complex diseases occur when small, soluble antigen– antibody complexes deposit in vascular beds, glomerular and pulmonary basement membranes, and serous cavities. Complement is activated and inflammation occurs. The prototypical Type III autoimmune disease is systemic lupus erythematosus (SLE). Patients with SLE develop circulating IgG against native cellular elements such as DNA (2).

Type IV Hypersensitivity (Delayed-type Reactions) Delayed hypersensitivity is mediated by antigen-specific effector T cells that require 1 to 3 days to respond. These T cells include antigen-specific T helper cells and cytotoxic T cells. Cytotoxic T cells directly attack foreign cells while antigen-specific T helper cells release cytokines. In the tuberculin test or contact dermatitis, Type I T helper cells release cytokines to signal macrophages to the site of reaction. Rheumatoid arthritis and multiple sclerosis are thought to be caused in part by a Type I T helper cell–mediated reaction. With chronic asthma and chronic allergic rhinitis, Type II T helper cells use cytokines to facilitate antibody production from B cells and to attract eosinophils to carry out tissue inflammation. Chronic allograft rejection is largely due to cytotoxic T cell function (2).

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 YPE I HYPERSENSITIVITY T (IgE-MEDIATED REACTIONS)

Allergy to Anesthetic and Non-anesthetic Agents Epidemiology

The incidence of perioperative immediate hypersensitivity is poorly defined because of variations in reporting accuracy and completeness. However, the incidence of all immediate hypersensitivity reactions associated with anesthesia is about 1:5,000, while the incidence of allergic anaphylaxis is about 1:10,000. The associated mortality is between 3% and 9% (6). Neuromuscular blockers are most frequently implicated

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as a cause of perioperative anaphylaxis, followed by latex, and antibiotics (Fig. 38-2). There are no specific risk factors for allergy to medications. However, patients who have had a previous, uninvestigated severe reaction during anesthesia are at increased risk of recurrence (7). It is unrelated to atopy, a history of multiple allergies, genetics, allergy to non-anesthetic drugs, or a history of multiple chemical sensitivities (8). Although asthma does not increase the incidence of anaphylaxis during anesthesia, it is a risk factor for severe respiratory symptoms (7).

Presentation

In general, agents that have been used for long, continuous periods before the onset of an acute reaction are less likely a cause of hypersensitivity than agents recently introduced (9). Intravenously administered medications cause symptoms rapidly. Drugs given rectally elicit symptoms over 15 to 30 minutes and chlorhexidine allergy often takes 10 minutes or longer to manifest depending on the route of administration (10).

Opioids 2.4% Othersa 7% Antibiotics 14.7% Neuromuscular blockers 54% Latex 22.3%

a

Others include Colloids 2.8% Hypnotics 0.8%

Data from reference 25

FIGURE 38-2  Causes of anesthetic-related anaphylaxis.

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CHAPTER 38  •  Anesthesia for the Pregnant Patient with Immunologic Disorders

Cutaneous signs • Generalized erythema • Urticaria, angioedema • Mild fever

Grade I

Grade II

Grade III

Severity of Clinical Signs in Immediate Reactions

Measurable, not life-threatening • Cutaneous signs • Hypotension, tachycardia • Bronchospasm, wheezing

Life-threatening • Shock • Severe bronchospasm • Bradycardia, arrhythmias

Cardiac arrest Respiratory arrest

Grade IV

Data from reference 13

FIGURE 38-3  Grading of the severity of the clinical signs of immediate hypersensitivity. Presentation of anaphylaxis is variable but if symptoms occur rapidly, it is more likely the reaction will be severe and life-threatening (11). In addition, anaphylaxis produces more severe symptoms than anaphylactoid reactions (12). A fourpoint grading scale may be useful to describe the severity of the reaction (Fig. 38-3) (13). The awake patient may complain of pruritus around the lips, tongue, ear canal, eyes, palms, and genitalia. They also complain of a metallic taste in the mouth, headache, and a feeling of impending doom. Gastrointestinal symptoms include nausea, vomiting, and abdominal cramps. With progressive angioedema, they may have hoarseness, dysphonia, shortness of breath, chest pain, and eventual cardiovascular collapse. Female patients may also complain of uterine cramps (11). During general anesthesia, common initial features include pulselessness, desaturation, and difficulty with ventilation (7). Low oxygen saturation can occur as a result of mucus plugging, bronchospasm, or impaired circulation. Skin manifestations are less helpful since draping can obscure urticaria and angioedema, and in severe cases, cardiovascular collapse may occur before skin signs appear. Overall, cutaneous symptoms can be absent in 33% of patients (14) but some of these appear after blood pressure is restored. Cardiovascular symptoms typically include tachycardia and hypotension but in 10% of cases, bradycardia is a prominent feature due to profound hypovolemia (4,7). In very severe cases, the patient may also develop disseminated intravascular coagulation (DIC) (11).

Management

Management of the parturient should include: (1) Remove or discontinue the offending agent, (2) administer 100% oxygen and maintain an open airway, (3) call for help and administer epinephrine for Grade III and IV reactions, and (4) maintain venous return by displacing the uterus to the left or positioning

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the patient in the full left lateral position. Pharmacologic treatment is discussed in Table 38-3. It is important to administer intravenous epinephrine and maintain intravascular volume. While epinephrine is not used for Grade I reactions, it is indicated for Grade III or IV reactions. Electrocardiographic monitoring is needed since epinephrine can provoke ventricular arrhythmias. Patients on β blockers can have a blunted response to epinephrine, often requiring large volumes of fluid, high doses of epinephrine, and glucagon. Other resuscitative drugs should be considered in epinephrine-resistant anaphylaxis, such as dopamine, norepinephrine, or vasopressin. In Grade IV cases, as much as 35% to 50% of the intravascular fluid can transfer to the extravascular space within 10 minutes; large volumes of colloid or crystalloid may be required and therapy should be initiated early (7). Histamine receptor blocking drugs and corticosteroids may be useful adjuncts. Antihistamines are particularly effective for angioedema and urticaria but the value of corticosteroids for reducing the risk of a recurrence has not been proven. Corticosteroids decrease late swelling of the pharynx and larynx. Salbutamol or albuterol are indicated for bronchoconstriction, but should not replace epinephrine in instances of severe bronchospasm and cardiovascular collapse (7). Patients have also been given tranexamic acid when anaphylaxis has been associated with DIC (11). Anaphylaxis usually resolves in 2 to 8 hours in the absence of secondary pathology (4), but continued vigilance is mandatory since reactions may recur 1 to 72 hours after onset, in up to 23% of patients (11).

Specific Considerations in the Pregnant Patient

During anaphylaxis, the fetus is not exposed to maternal toxic inflammatory mediators such as histamine, as they are metabolized by the placenta. Since maternal IgE does not cross the placenta, an immune reaction should not occur in the fetus. However, the fetus is vulnerable to inadequate placental perfusion secondary to maternal hypotension. While epinephrine may cause uterine artery vasoconstriction, it should be used in effective doses to terminate the anaphylactic reaction. The use of ephedrine is controversial (15), as it may not effectively correct maternal hypotension. Left uterine displacement should be used after 20 weeks’ gestation to avoid aortocaval compression. The American Heart Association advocates that critically ill parturients who are at risk for cardiac arrest should be placed in the full lateral position to maintain venous return, blood pressure, cardiac output, and fetal oxygenation (16). For an urgent or emergency cesarean delivery, regional anesthesia can be considered if the patient is hemodynamically stable and the fetus is not in distress. If the patient experienced oropharyngeal or laryngeal edema, immediate airway management may be indicated. Observation for airway obstruction should continue for several hours in case relapse occurs (11).

Specific Allergies Local Anesthetic Agents

Many patients experience adverse reactions to local anesthetics (LAs) but only less than 1% are due to immune hypersensitivity reactions (17). When patients are referred for LA allergy testing, other allergens such as chlorhexidine or latex are found much more frequently to be responsible for the reaction (18). Both Type I and Type IV hypersensitivity reactions occur, with delayed-type hypersensitivity being more common (17). Immediate hypersensitivity caused by LAs, presents with the typical symptoms of anaphylaxis within minutes of injection. Delayed-type hypersensitivity manifests as contact

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TABLE 38-3  Pharmacologic Management of Anaphylaxis in the Parturient Ephedrine

Grade II reactions (moderate): •• BOLUS: 10 mg IV every 1–2 min Switch to epinephrine if there is no response or severity increases

Epinephrine

Grade II reactions (moderate): •• BOLUS: 10–20 mg IV •• Sc/im 200–500 mg (lateral thigh) every 5 min until IV obtained Grade III reactions (severe): •• BOLUS: 100–200 mg IV every 1–2 min •• INFUSION: 1–4 mg/min Grade IV reactions/Cardiac Arrest: •• BOLUS: 1–3 mg IV over 3 min (3–5 mg over next 3 min) INFUSION: 4–10 mg/min

Fluid

IV crystalloid 5–10 mL/kg over 5 min •• 1,000–2,000 mL, after 30 mL/kg switch to colloids

Diphenhydramine

25–50 mg IV (Grade II–IV reactions require epinephrine first)

Ranitidine

50 mg IV (Grade II–IV reactions require epinephrine first)

Salbutamol or Albuterol

Inhalation: 2.5–5 mg in 3 mL saline nebulized BOLUS: Salbutamol 100–200 mg INFUSION: Salbutamol 5–25 mg/min

Glucocorticoids

Hydrocortisone hemisuccinate 200 mg IV every 6 h (Grade II–IV reactions require epinephrine first)

Other vasopressors: 1. Dopamine: 2–20 mg/kg/min 2. Glucagon: 1–5 mg IV over 5 min, then 5–15 mg/min •• Consider early with patient on β blockers 3. Norepinephrine: 5–10 mg/kg/min 4. Vasopressin: Bolus: 2–10 IU IV until response IV, intravenous; mg, micrograms; sc, subcutaneous; im, intramuscular.

dermatitis from topical preparations or localized edema from dental injections. Type IV reactions appear within 1 to 3 days but some occur as soon as 2 hours, causing difficulty in differentiating them from a Type I immediate reaction (17). Local anesthetics are divided into two groups, based on their chemical structure. The benzoic acid or ester LAs (Group I) includes drugs such as benzocaine, chloroprocaine, and tetracaine. Allergy in Group I is much more common due to the metabolite, para-aminobenzoic acid, or preservatives such as methylparaben or metabisulfites (19). The amide group (Group II) includes bupivacaine, lidocaine, and ropivacaine, and reports of true hypersensitivity allergy are rare. Cross-reactivity among ester LAs is common, but not with amides. There is little evidence that ester LAs crossreact with amide LAs (7). Ideally, the pregnant patient who has experienced an adverse response to LAs should be seen prior to pregnancy for testing. However, pregnant patients can undergo skin testing for LAs, after informed consent if clinically indicated. After a comprehensive history, a common protocol for diagnosing LA allergy includes the administration of skin tests followed by a provocative challenge (12); a summary appears in Table 38-4. If the offending agent is unknown, the challenge should consist of LAs likely to be used in labor and delivery such as preservative-free bupivacaine and lidocaine. If the offending LA is known, it is best to use an LA with the other chemical structure. However, since substantial crossreactivity among amides has not been well documented, another amide can also be considered if the suspicion of LA allergy is low (20).

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TABLE 38-4  Approach to the Parturient with a History of Adverse Reactions to Local Anesthetics 1.  History a. Determine nature of reaction and LA implicated b. If the history is suggestive of immediate LA allergy •• Consultation from allergist if possible •• Identify if LA is ester or amide •• Weigh risks and benefits of skin and challenge testing •• Obtain informed consent if testing is considered c. Perform test near term or when patient presents for delivery 2. Which LA agent? If LA is known: Test with LA with other structure, or another amide If LA is unknown: Test with LA to be used for labor and delivery 3. Perform challenge tests a. Perform test in area with resuscitative facilities and monitoring b. Intravenous catheter should be placed and the patient fasted c. Notify obstetrical and neonatal team

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CHAPTER 38  •  Anesthesia for the Pregnant Patient with Immunologic Disorders

General Anesthetic Agents Induction Agents Propofol is currently mixed with a solution vehicle including soy and egg lecithins (extracted from egg yolks). There had been concern that patients allergic to soy or eggs may have reactions to propofol administered intravenously. However, in a small study of 25 egg-allergic patients, all propofol skin tests were negative (19). More commonly, propofol causes direct mast cell activation especially with higher doses (11,21). The estimated incidence of anaphylaxis with propofol is 1 in 60,000 (19). The incidence of thiopental allergy is estimated at 1 in 30,000 administrations. Etomidate, ketamine, and benzodiazepines are exceedingly rare causes for IgE-mediated anaphylaxis (19). There are no reported cases of anaphylaxis to inhalational anesthetics (4). Neuromuscular Blockers Neuromuscular blocking agents are among the most common agents to cause perioperative anaphylaxis and may cause a reaction on first exposure. This may be due to the structural similarity between neuromuscular blocking agents and certain chemicals found in toothpastes, detergents, cough medicines, and shampoos. Succinylcholine is the most common neuromuscular blocker implicated (4). The incidence of cross-reactivity among muscle relaxants lies between 60% and 70% (7). Opioids Most reactions to opioids such as morphine, codeine, and meperidine are secondary to direct mast cell mediator release from skin mast cells rather than IgE mechanisms. As a result, skin tests are invariably positive, even in normal control subjects. However, fentanyl, sufentanil, and remifentanil do not directly stimulate skin mast cells, so skin tests may be helpful. The incidence of cross-reactivity is unknown, although cases have been described in which meperidine, and methadone have cross-reacted with morphine antibodies, despite having different chemical structures (21).

Non-anesthetic Drugs Oxytocin Synthetic oxytocin has rarely been implicated in severe anaphylactic reactions (22). The test itself must be interpreted cautiously, since oxytocin can be irritating to the skin (23). Latex allergy should always be considered when symptoms of anaphylaxis occur soon after the administration of oxytocin since oxytocin may facilitate the development of symptoms in latex-allergic patients (24). Antibiotics Penicillins and cephalosporins elicit approximately 70% of the allergic reactions to antibiotics (7). With the recent Group B streptococcus infection prevention guidelines, it has become a more pressing issue in the parturient. Early cephalosporins were known to contain trace amounts of penicillin and cross-reactivity was often demonstrated. However, current drug preparations have a low level of cross-reactivity (11). A cross-sensitivity rate of 8% to 10% is often quoted; however, many of these reactions are related to skin rashes that are not immunologic in origin (19). First generation cephalosporins are more likely to cross-react with penicillin than third generation agents (7). Non-steroidal Anti-inflammatory Drugs (NSAIDs) NSAIDs are increasingly recognized as a cause of anaphylactoid reactions due to the inhibition of cyclooxygenase and the generation of excessive leukotrienes. The onset is usually 10 minutes after intravenous administration, 30 minutes after rectal dosing and up to 1 hour after oral administration (10).

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Since aspirin and NSAIDs do not initiate specific IgE antibodies, allergy can only be established by an oral challenge (21). Cross-reactions occur between aspirin and most of the NSAIDs (5). Chlorhexidine Chlorhexidine is increasingly recognized as a cause for both Type I and Type IV hypersensitivity reactions. It is often overlooked as a cause of anaphylaxis, since reactions are delayed up to 10 minutes. Reactions can be triggered by cutaneous, mucosal, or parenteral application (21). Synthetic Colloids Synthetic colloids, such as hydroxyethyl starch, gelatins, and dextran-containing colloids cause 3% of all perioperative hypersensitivity reactions (25). The vast majority of reactions occur after 30 minutes and are non-allergic in nature (10). Gelatins and dextrans cause more reactions than hetastarch (25) with estimates of IgE-mediated anaphylaxis, ranging from 0.06% to 0.35% (7).

Allergy to Latex Epidemiology The introduction of universal precautions in the 1980s increased the use of latex-containing gloves and medical equipment, with a subsequent increase in the incidence of latex allergy and sensitivity to 1.4% and 7%, respectively (25). More recently, latex avoidance in the workplace and the restriction of powdered latex gloves may be reducing the incidence of allergy (26,27). Latex sensitivity is defined as the presence of positive skin tests or positive in vitro tests to latex; patients are frequently asymptomatic until a threshold of exposure triggers an allergic reaction. Latex allergy is defined as the presence of allergic symptoms when there is contact with latex in a latex-sensitive person (9). The most dramatic presentation for latex allergy is the IgE-mediated reaction, although Type IV allergic contact dermatitis is four times more common (28). Three high-risk groups for latex allergy have been identified— health care workers, workers with occupational exposure, and children with spina bifida and genitourinary abnormalities (11). Among health care workers, the prevalence of latex sensitivity ranges from 12.5% to 15.8% with the majority being asymptomatic (29). Exposure is most often from latexcontaminated aerosolized cornstarch powder that is added to latex gloves to make them easier to put on. Latex proteins from the gloves attach to the cornstarch during processing and storage, and eventually disperse with manipulation (30). Latex allergy and sensitivity may affect over half of the patients with spina bifida. Interestingly, studies show they are allergic to different latex proteins than hospital workers probably as a result of parenteral and mucous membranes exposure rather than through inhalation (30). There are other risk factors for latex allergy including specific food allergies and atopy. Fruits such as chestnuts, bananas, kiwis, and avocados may have peptides that crossreact with latex (25,30). Atopic patients are also at high risk for latex sensitivity if they have occupational exposure (27). Presentation The clinical manifestations of latex anaphylaxis can differ depending on whether exposure is outside or inside the hospital setting. Typical histories outside the surgical suite include oral itching, facial redness, or swelling to latex toy balloons or during dental examinations (30). Vaginal symptoms occur with the use of condoms. Contact urticaria on the hands is commonly described when wearing latex gloves, and bronchospasm and rhinoconjunctivitis typically occurs

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with exposure to latex glove powder (9). Severe reactions may result in cardiovascular collapse (11). In the hospital, symptoms of vaginal pruritus and swelling have been described at the time of examination, delivery, or immediately peripartum. Airborne exposure can lead to rhinitis, conjunctivitis, and bronchospasm, rarely leading to cardiovascular collapse and fetal distress (31). The signs and symptoms of anaphylaxis due to latex may occur from 20 minutes to an hour after exposure, making it difficult to differentiate from intravenously administered agents (11). Pregnancy itself may be associated with higher rates of latex sensitivity (24). During cesarean delivery, symptoms of latex anaphylaxis may follow the intravenous injection of oxytocin, leading to misdiagnosis. It is possible that latex proteins released from surgical gloves during the skin and uterine incision enter the circulation after the administration of oxytocin. The contracting placental site provides the portal of entry causing symptoms. Alternatively, the reaction may occur because oxytocin has structural similarity to latex, or oxytocin may form part of the epitope of the latex antigen. Management Many hospitals have formulated policies and procedures for detection and management of patients with latex allergy or sensitivity. They have also taken the initiative to decrease the risk of latex sensitivity among their staff. Suggestions regarding the management of latex allergy patients appear in Table 38-5. Testing for latex allergy can be difficult because numerous different latex proteins have been implicated in IgE-mediated immunologic reactions. In addition, skin test extracts are not commercially available. “Home-made” preparations have been produced, however due to the wide variability of glove protein content; latex skin tests have a limited sensitivity and

specificity. Serologic tests that identify latex IgE are available but not sufficiently sensitive for screening purposes (11). Elective procedures on known latex-sensitive individuals should be carried out in a “latex-free” environment and should be performed at the start of the day (9). Airborne latex may persist in significant quantities, particularly on scrub suits (32). Synthetic gloves should be used when preparing equipment for the medical procedure in a latex-sensitive patient (4). Ideally, all latex products should be avoided but in reality, certain latex devices are more apt to cause a reaction than others, depending on the method of manufacture. Dry natural rubber, such as that used for syringe plungers and vial stoppers contain much less protein than surgical gloves made from latex concentrate and are less likely to cause reactions (30). Since it is not mandatory to identify the latex content of vial stoppers, guidelines advocate removal of the stopper or restrict use to a single puncture (33). Hand Dermatitis Hand dermatitis, both allergic contact dermatitis and common irritant dermatitis, are known risk factors for IgE-mediated latex reactions. The abraded skin may provide a portal of entry into the bloodstream for a variety of latex allergens (27). Allergic contact dermatitis (Type IV hypersensitivity) is caused by a hypersensitivity to the various chemicals added to the latex mixture during manufacture, rather than the latex proteins themselves. The reactions appear 24 to 48 hours after a repeated exposure. Signs and symptoms include erythematous or scaling patches with blistering (30). Irritant dermatitis is caused by moisture under the gloves, other workplace chemicals, and repeated hand washing. It is a non–immune-mediated reaction, characterized by pruritus, irritation, scaling, and cracking at the site of contact. It appears minutes to hours after exposure (9).

TABLE 38-5  Recommendations for the Management of Latex-sensitive and Latex-allergic Patients

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Identify and Prioritize

•• Identify the latex sensitive patient •• Arrange in vivo and in vitro testing if possible •• Notify the entire health care team •• Arrange list so patient is first of the day •• Place sign on operating/labor room door “Latex Allergy”

Patient Preparation

•• Antihistamines and corticosteroids not recommended •• Prepare all medication and equipment with non-latex gloves •• A latex-free cart with supplies should be available •• Cotton wrappings to protect skin from latex based blood pressure cuffs or tubing •• Avoid latex esmarchs, tapes, tourniquets, drains, and urinary catheters

Gloves

•• NO low protein latex gloves •• Use alternatives: Styrene, styrene-butadiene, neoprene, and polyvinylchloride

Syringes

•• Glass or non-natural latex syringes are preferred •• Regular syringes are acceptable providing that drugs are freshly drawn and administered (within 6 h)

Medications

•• Glass ampoules •• Remove rubber stopper from vial or one puncture through fresh vial

Intravenous sets

•• Tape over injection ports and use stopcocks. •• Avoid buretrols •• Regular intravenous bags or minibags may be used •• Add medications through port to be spiked

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CHAPTER 38  •  Anesthesia for the Pregnant Patient with Immunologic Disorders

Investigation of Anaphylaxis Acute Assessment

If anaphylaxis is suspected, patients should be referred to an allergist to confirm that anaphylaxis has occurred and to identify the offending agent. Blood for serum tryptase levels should be drawn immediately and within 2 hours of symptoms, and again at 24 hours. Histamine can be tested in the blood and urine. Since elevations in plasma histamine return to baseline within 60 minutes, samples must be drawn quickly (34). Similar to tryptase, it is elevated in both allergic and non-allergic mechanisms and its absence does not preclude an anaphylactic reaction (7). In addition, false negative values have been identified in pregnancy (12).

Allergy Testing

When allergy tests are performed after a reaction, many centers advocate waiting 4 to 6 weeks from the event before skin and in vitro tests are administered. It allows the levels of immunoglobulins and mediators to return to prereaction levels (7). Skin Testing Skin prick tests and intradermal testing involve exposing mast cells in the skin to specific antigens (in drugs or products). Both are performed on the upper back or the volar surface of the forearm. If specific IgE on the mast cells encounters the corresponding antigen, a skin reaction occurs, confirming a Type I reaction (5). It is more sensitive than in vitro testing and is the diagnostic procedure of choice for detecting IgEmediated allergies (11). Appropriate positive (histamine or codeine) and negative (saline) controls should be used. There is difficulty in studying some anesthetic agents, such as opioids and neuromuscular blockers, since standard solutions cause direct histamine release. Guidelines have been developed for the appropriate dilution of drugs for skin tests (12). Skin prick tests are performed using a hypodermic needle which is passed through a drop of testing reagent at a 45-degree angle to the skin. The skin is gently lifted, causing a small break in the epidermis and a minute amount of allergen penetrates and interacts with the mast cells. The site is compared to positive and negative controls after 15 minutes. The mean diameter of the wheal (calculated by adding the longest diameter to the diameter at 90 degrees divided by 2) should be at least 3 mm more than the negative control (35).

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Intradermal tests consist of injecting larger amounts of diluted allergen into the dermis at various volumes. Criteria for positive reactions are similar to those of skin prick tests (35). Experience in the interpretation of intradermal skin tests is necessary due to a relatively high incidence of reactions caused by direct histamine release. A true positive is more likely if a patient reacts to very dilute solutions (10). Skin prick tests are less likely to cause systemic reactions than intradermal skin tests (4). Case reports of true anaphylaxis during testing are rare, with rates of 0.1% and 0.3% for antibiotics and neuromuscular blockers, respectively (36). Fatalities are extremely uncommon. Local Anesthetic Skin Testing and Provocative Challenge in Pregnancy Pregnancy is not a contraindication to allergy testing (12). Anesthesiologists may need to perform allergy testing for local anesthetics in pregnant patients during labor and delivery in order to perform a regional block. This should be done at a time when the risks and benefits of the procedure can be explained to the patient. If the history suggests an immediate reaction, then skin tests and the performance of a provocative challenge by the anesthesiologist before epidural placement would follow. Fetal monitoring and appropriate resuscitative equipment should be available. Intradermal skin tests alone may give a high false positive rate because of injection trauma, skin distension, and localized histamine release. Provocative challenge testing is considered the gold standard for the diagnosis of LA allergy. It involves injecting a series of small aliquots of testing reagent into the subcutaneous tissue and observing for local or systemic reactions. Several large series testing hundreds of patients with a history suggestive of “local anesthetic allergy” have shown that provocative challenge testing is not only safe but clearly the test of choice (35). A suggested protocol appears in Table 38-6. In Vitro Testing Ideal tests in pregnancy include in vitro tests because they only require patient sera. Specific IgE antibody levels in the serum sample can be measured using radioimmunoassay. Significant levels are not proof that a particular drug is responsible, only that the patient is sensitized (7). The assays are limited by their low sensitivity. Tests such as the leukocyte histamine release test and the basophil activation test represent emerging tools for diagnosis. However, their role in confirming specific allergy has not yet been validated (25).

TABLE 38-6  Suggested Protocol for Skin Prick Tests and Progressive Challenge for Local Anesthetics Initial Test

Skin Prick Test: Undiluted LAa

Step

Route

Volume (mL)

Dilution

1

Subcutaneous

0.1

Undiluted LAa

2

Subcutaneous

0.5

Undiluted LA

3

Subcutaneous

1.0

Undiluted LA

4

Subcutaneous

2.0

Undiluted LA

a

15 min interval in between Positive challenge test: Presence of local wheal and erythema or systemic anaphylactic symptoms a

Consider dilutions of 1:100 or 1:1,000 with a history of severe reactions (Thyssen JP, Menne T, Elberling J, et al. Hypersensitivity to local anaesthetics-update and proposal of evaluation algorithm. Contact Derm 2008;59:69–78.) LA, local anesthetic.

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Preventing an Allergic Reaction

Skin testing is not recommended for preoperative screening if there is no prior history of an anesthetic reaction because many subjects screened for allergy to, for example, neuromuscular blockers have a positive test despite no previous exposure (19). When the offending agent is known, avoidance is the best management since no treatment can reliably prevent anaphylactic reactions. The use of corticosteroids and histamine receptor blocking drugs preoperatively is not recommended and may mask the early signs and symptoms of anaphylaxis (19). However, there is a role for these drugs in reducing the incidence of side-effects from contrast media and medications that cause direct histamine release (10). When the offending agent is unknown, regional anesthesia is prudent and products with latex or chlorhexidine should be avoided. When general anesthesia is chosen, inhalational agents are preferred and both neuromuscular blockers and histamine-releasing drugs should not be given.

Differential Diagnosis of Anaphylaxis Urticaria and Angioedema There is a broad differential diagnosis to anaphylaxis because of the numerous conditions that may present with urticaria and angioedema (see Fig. 38-4). They can occur together or in isolation. Urticaria is defined as superficial skin wheals of various sizes, with or without erythema. It is caused by histamine and other mediators released from mast cells and basophils. Patients may complain of pruritus or, occasionally, burning sensations. Acute urticaria typically lasts 1 to 24 hours, and can be associated with infection, medications, or certain foods (37). If urticaria occurs, continuously or intermittently for 6 weeks, it is considered chronic urticaria, of which 80% to 90% are idiopathic (38). Common triggers include pressure, heat cold, and exercise. Angioedema is a condition that involves swelling of the deep dermal and subcutaneous/submucosal tissues due to the mediator bradykinin (39). It is non-pruritic and non-pitting,

lasting up to 72 hours. It can be associated with pain instead of pruritus, and often involves the mucous membranes (37). The chronic forms of angioedema are not associated with urticaria and are not responsive to antihistamines (39). Mastocytosis Mastocytosis is a heterogeneous group of diseases characterized by an increase in mast cells in the skin, lymph nodes, liver, spleen, gastrointestinal tract, and bone marrow. There are several different variants including: Cutaneous mastocytosis, indolent systemic mastocytosis, aggressive systemic mastocytosis, and mast cell leukemia. Treatment depends on the type of mastocytosis, with the benign forms being managed with antihistamines and supportive therapy (40). Patients with cutaneous mastocytosis have fixed, pigmented, reddish brown macules, or papules over their body known as urticaria pigmentosa. It is estimated to occur with an incidence between 1 in 1,000 and 1 in 8,000 of individuals. Systemic mastocytosis is much less frequent occurring in 10% of those with urticaria pigmentosa (41). The clinical manifestations of mastocytosis are the symptoms of overwhelming mast cell degranulation resulting in elevated serum levels of tryptase, histamine, and other mediators. Skin features include hives, flushing, and pruritus. Systematic symptoms often include abdominal pain, nausea and vomiting, diarrhea, and gastroesophageal reflux. Profound hypotension and vascular collapse can be life-threatening; however, bronchospasm is not a prominent finding (42). Episodes can be triggered by trauma, extremes of temperature, spicy foods, alcohol, NSAIDs, and histamine-releasing drugs (41,42). In benign cutaneous or systemic mastocytosis, treatment includes antihistamines and occasionally corticosteroids, in both non-pregnant and pregnant patients (40,43). Lifethreatening hypotension is treated with epinephrine that also helps to stabilize the mast cell membrane (41). Prior to surgical procedures, pretreatment with antihistamines and corticosteroids has been advocated to prevent attacks but is not always effective (41).

nsion, tachycardia pote y H

Bronchospasm

Amniotic fluid embolus Pulmonary/Air embolus Drug effect Carcinoid Syndrome Sepsis Hypovolemia Vasovagal reaction (bradycardia) Pulmonary embolism High block Anaphylaxis Myocardial ischemia Anaphylactoid reaction IgA deficiency (with transfusion)

Asthma Pulmonary aspiration Pulmonary edema Pneumothorax Mechanical obstruction

C1-Esterase deficiency Mastocytosis Non-immune urticaria Drug-induced flushing

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ut ane

C

FIGURE 38-4  Differential diagnosis of anaphylaxis.

ous Sig

ns

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CHAPTER 38  •  Anesthesia for the Pregnant Patient with Immunologic Disorders

During pregnancy, particularly the first and second trimesters, and postpartum, half of the parturients may have a worsening of urticaria pigmentosa lesions, pruritus, flushing, and abdominal pain. Labor itself does not seem to exacerbate symptoms and labor pain can be treated with neuraxial analgesia, provided there are no local broken pustules that may be secondarily infected. Some clinicians use premedication with antihistamines during labor and delivery. Epinephrine is given if indicated (43). Medications for general anesthesia should include non–histamine-releasing drugs and active patient warming (42). Neonatal outcomes appear unaffected by maternal mastocytosis (43). C1-esterase Inhibitor Deficiency C1-esterase inhibitor (C1-INH) deficiency is a group of disorders characterized by deficient or dysfunctional levels of C1-INH. CI-INH is necessary to prevent unchecked activation of the complement cascade and parts of the fibrinolytic system. In hereditary angioedema, attacks usually occur in late childhood, while acquired forms of C1-INH deficiency have been associated with lymphoproliferative disorders and autoimmune diseases in adults. Clinically, C1-INH features intermittent subcutaneous or submucosal edema in any part of the skin, respiratory tract, and gastrointestinal tract. Symptoms include recurrent, nonpruritic edema and abdominal pain. The presence of urticaria should lead to a search for another diagnosis. Fifty to seventy-five percent of patients have life-threatening airway obstruction at some point due to angioedema of the pharyngeal and laryngeal structures; symptoms include voice change and dysphagia, and the mortality rate is 15% to 33% (44). Abdominal edema can lead to nausea, vomiting, diarrhea, or the symptoms of an acute abdomen (45). With severe angioedema, the patient is at risk for hypotension and shock, due to diarrhea and the re-distribution of intravascular fluid into swollen intestinal tissue (46). Typically, symptoms develop over several hours and subside over 2 to 5 days. However, abdominal pain may occur suddenly and airway obstruction can occur over 20 minutes (44). Common triggers include infection, dental work, minor trauma, snoring, anxiety, and emotional upset (45). Acute attacks are treated with appropriate doses of C1-INH concentrate, which can start alleviating symptoms within 30  minutes and reduce the duration of attacks to a mean of 15 hours. The effects of C1-INH concentrate can last up to 2 days. Hereditary angioedema is not treated with antihistamines, corticosteroids, or epinephrine (44,45). Long-term treatment includes anti-fibrinolytics and androgens to reduce the frequency and severity of attacks. Anti-fibrinolytics inhibit plasminogen activation and “spare”

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endogenous C1-INH. Tranexamic acid is not teratogenic and has been used during pregnancy in patients not at risk for thrombosis. Androgens are relatively contraindicated in parturients due to potential virilizing effects in female fetuses (44). Information from reported cases indicates that attacks decrease in the second and third trimester and most patients have an uncomplicated peripartum period (46). However, abdominal pain may be attributed to hereditary angioedema and obscure serious obstetric disorders. Perineal edema may cause urethral obstruction (44) or appear as the first sign of angioedema leading to irreversible shock (47). Regional analgesia is advised to lessen pain, anxiety, and the risk associated with airway manipulation (44). If general anesthesia is required, appropriate prophylaxis with C1-INH is required and common induction agents, muscle relaxants, and inhalational agents can be used (45). Prophylaxis during pregnancy may include tranexamic acid or regular doses of C1-INH replacement. C1-INH concentrate can be given prophylactically, for both vaginal and operative deliveries or on reserve in the event that the patient develops symptoms. If C1-INH concentrate is not available, two units fresh frozen plasma can be used (44). A comparison of systemic mastocytosis and hereditary angioedema appears in Table 38-7. IgA Deficiency IgA deficiency is a disorder characterized by low levels of immunoglobulin A in serum and mucous secretions. It occurs with a prevalence of 1 in 500 individuals. A significant proportion of affected individuals produce IgG antibodies to IgA. If the patient has high antibody titers, a severe transfusion reaction can occur with the administration of blood products. Overall, the risk of a severe hypersensitivity reaction is low. Under normal circumstances, patients may be asymptomatic or suffer from recurrent sinus, respiratory, or gastrointestinal infections. Systemic lupus erythematosus (SLE) and rheumatoid arthritis have been associated with the deficiency (48). ■■

 YPE II HYPERSENSITIVITY (ANTIBODYT MEDIATED CYTOTOXIC REACTION)

Erythroblastosis Fetalis Erythroblastosis fetalis or, hemolytic disease of the newborn (HDN), is a condition in which specific maternal IgG antibodies (which freely cross the placenta) attach to antigens on fetal red blood cells, leading to fetal anemia and extramedullary hematopoiesis. The red blood cell antigen commonly involved includes the rhesus D (RhD) antigen, although other blood groups such as the ABO and Kell systems can be

TABLE 38-7  Comparison of Systemic Mastocytosis and Hereditary Angioedema Systemic Mastocytosis

Hereditary Angioedema

Antihistamines Corticosteroids Epinephrine

C1-INH Anti-fibrinolytics

Pretreatment

Antihistamines Corticosteroids

C1-INH Fresh frozen plasma

Airway

Usual

Manipulations cause pharyngeal and laryngeal angioedema

Medications

Avoid histaminereleasing drugs

Common agents acceptable

Regional

Acceptable

Encouraged

Treatment

Anesthetic Implications

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responsible (49). With the routine use of anti-D (antibodies against RhD antigens) prophylaxis for RhD negative mothers, the incidence and severity of HDN has fallen dramatically (50). Pathophysiologically, an RhD negative mother produces antibodies when exposed to blood cells from a fetus that is RhD (paternally inherited) positive. The first pregnancy does not usually prompt maternal antibody production until delivery; therefore, it is the subsequent pregnancies which are affected (51). Prior to the detection and treatment of HDN, most fetuses were either miscarried, stillborn, or developed hydrops fetalis. The syndrome of hydrops fetalis is initiated by profound fetal anemia and extramedullary hematopoiesis. Anemia impairs oxygen delivery leading to endothelial damage and leaky capillary membranes. Extramedullary hematopoiesis results in impaired hepatic protein synthesis, hepatosplenomegaly, and elevated portal and umbilical venous pressures. Eventually, extravasation of fluid occurs, producing ascites, pleural effusions, pericardial effusions, scalp edema, subcutaneous edema, and polyhydramnios (50). During pregnancy, antibody titers are measured in the RhD antigen negative mother and the presence of the RhD antigens in the fetus are assayed (51). Until recently, the main investigation for fetal genotype-testing was amniocentesis. However, new and sophisticated tests have taken advantage of the normal presence of cell-free fetal DNA in maternal serum. From this, the fetal Rh genotype can be determined. An RhD antigen negative fetus does not require follow-up but an RhD antigen positive fetus requires close monitoring during the entire pregnancy (50). Follow-up includes serial maternal antibody titers and tests to estimate the degree of fetal anemia. When maternal antibody titers against RhD reach a critical level, the risk of fetal hydrops rises significantly and prompts further investigation. Fetal anemia can be estimated by sampling amniotic fluid for hyperbilirubinemia or by measuring the peak velocity of blood flow in the middle cerebral artery by Doppler ultrasound. Studies show Doppler ultrasound is superior in accuracy and safety, and may supplant amniocentesis (50). Many affected fetuses can be managed after delivery with phototherapy. However, when serial tests during pregnancy indicate progressive anemia, invasive fetal hemoglobin testing is performed. If anemia is significant, intraperitoneal or umbilical vein blood transfusions can temporarily reverse the complications until the fetus can be delivered. Fetal immobilization is required for both procedures, which can be accomplished indirectly with maternal sedation or, more commonly by injecting a neuromuscular blocking agent, directly into the umbilical vein. Vecuronium is commonly used (51). With proper prenatal monitoring, most parturients and newborns have a relatively uncomplicated course. However, if a fetus at risk is not treated, fetal organomegaly and ascites can lead to dystocia necessitating cesarean delivery. ■■

 YPE III HYPERSENSITIVITY REACTIONS T (IMMUNE COMPLEX MEDIATED)

Systemic Lupus Erythematosus SLE is a multisystem chronic inflammatory disease caused primarily by autoantibodies and immune complexes. The diagnostic criteria for the disease include a characteristic malar rash, non-erosive arthritis of peripheral joints, serositis, renal dysfunction, neurologic manifestations, hematologic disorders, and abnormal circulating antibodies including antinuclear antibody. The disease is nine times more common in women than in men and has an increased incidence

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in African Americans compared to Caucasians (52). While maternal mortality has greatly improved, patients with SLE continue to have a mortality rate 20 times higher than the pregnant woman without SLE (53).

Patient Considerations

The signs and symptoms associated with SLE may be mild and confined to one organ system or fulminating, leading rapidly to death. Fever, weight loss, and fatigue may be the first signs of the disease. The skin may be affected, causing the classic malar “butterfly rash.” Involvement of mucous membranes with painful ulcerations in the pharynx, mouth, or vagina may also occur (52). The heart may be affected in a number of ways. Pericarditis with chest pain occurs in over 50% of patients with SLE but progression to cardiac tamponade is uncommon. It may be caused by coronary arteritis, myocarditis, or focal necrosis and atrophy of the myocardium. Some patients develop cardiac valvular lesions (Libman–Sacks endocarditis) that are usually asymptomatic. The cardiovascular system is best evaluated by physical examination. An electrocardiogram (ECG) may be useful to assess rhythm abnormalities and ischemic changes. Polyserositis is relatively common, with pleurisy occurring in 50% of cases. If the patient is dyspneic, the respiratory system should be assessed to rule out pulmonary vasculitis, infarction, hemorrhage, pleural effusions, and pulmonary hypertension. Lupus nephritis is common and accounts for the majority of fatalities due to SLE. A urinalysis, blood urea nitrogen, serum creatinine, serum electrolytes, and blood sugar should be measured. Hypokalemia and glucose intolerance are common in patients receiving corticosteroids. Casts in the urine sediment indicate active nephritis. There may be several coagulation defects in patients with SLE. Patients may have thrombophilia, or thrombocytopenia due to antiplatelet antibodies and splenomegaly. In addition, specific circulating anticoagulants may be present with factor VIII inhibitors being the most common (54). Their presence contraindicates the use of regional block. The presence of high anti-phospholipid antibody titers and a history of recurrent venous or arterial clotting and fetal loss characterize the anti-phospholipid antibody syndrome. This antibody is often reported as the “lupus anticoagulant” because in the laboratory it causes an elevated activated thromboplastin time, although clinically, it causes thrombosis. While this syndrome is often treated with immunosuppressants such as corticosteroids, other therapy such as low molecular weight heparin and/or aspirin may also be used in an attempt to reduce the incidence of thrombosis. These therapies may contraindicate use of regional anesthesia (55). Many of the neurologic complications of SLE are due to vasculitis or complications related to steroid treatment. Patients can develop psychosis, transverse myelopathy, cranial nerve palsies, and peripheral neuropathy. Intracerebral bleeding or status epilepticus may lead to death. Findings of polyarthralgia or arthritis follow the same distribution as rheumatoid arthritis but are usually milder and not deforming. Avascular necrosis of the head of the femur may result from either chronic steroid therapy or vasculitis.

Obstetrical Considerations

Pregnancy increases the incidence of lupus flares in 30% to 60% of patients (56). Lupus flares can occur at any time and are more common in parturients with renal involvement, active urine sediment (casts and red cells), or falling complement levels. They consist of arthralgias, anemia, thrombocytopenia, worsening hypertension, proteinuria, renal ­dysfunction,

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encephalopathy, abdominal pain, and hepatic failure. As pregnancy advances, a lupus flare becomes very difficult to differentiate from preeclampsia, which is also more common in lupus patients (53). Treatment of a lupus flare includes high doses of corticosteroids and antihypertensive agents while preeclampsia is treated by delivery of the fetus. Approximately 10% of infants have neonatal lupus erythematosus as a result of transplacental passage of anti-SSA/ Ro or anti-SSB/La. Of these, approximately half have skin manifestations that resemble those seen in the adult. Cardiac manifestations include complete heart block, cardiomyopathy, and valvular lesions (57). Neonates are often premature and growth restricted (53).

Analgesia and Anesthesia for Labor and Delivery

Analgesia for vaginal delivery can include opioids, inhalational analgesia, and epidural analgesia. Before any neuraxial technique, there should be a detailed examination of the neurologic system and complete review of the coagulation status. Intrathecal or epidural opioids, with or without local anesthetic may be useful. Although a fixed neurologic deficit is not an absolute contraindication to regional block, it should be documented. If raised intracranial pressure is suspected, options other than regional blockade should be considered. Cesarean delivery is more common in patients with lupus. Provided the coagulation and neurologic status is normal, it can be performed safely under regional or general anesthesia. Cross-matching of blood products may be a problem due to irregular circulating antibodies, therefore blood should be available in advance. Hourly urine output using a Foley catheter should be measured. An arterial line may be placed to monitor blood pressure if hypertension is difficult to control. If severe renal disease is present, a central venous or pulmonary artery catheter may be required to assess and optimize fluid status and cardiac output. When general anesthesia is indicated, a rapid sequence induction may need to be modified for extremely ill patients. If myocardial function is poor, a reduced dose of induction agent combined with an opioid such as fentanyl may be required. Succinylcholine is still used as a muscle relaxant to facilitate endotracheal intubation. If there is a history of a recent stroke with paralysis, a non-depolarizing muscle relaxant such as rocuronium should be used, since succinylcholine can trigger massive hyperkalemia. Agents that require renal excretion to terminate their action should be avoided if renal failure is present. Finally, the delivery should take place in a facility that is prepared to take care of the infant should it be affected with neonatal SLE.

Progressive Systemic Sclerosis (Scleroderma) Scleroderma or progressive systemic sclerosis (PSS) is a generalized disorder, characterized by excessive deposits of connective tissue in the skin and viscera and is associated with microvascular and immunologic changes (58). The disease is five times more common in women than men with an average age of onset of 40 years. Fifty percent of patients with scleroderma may become pregnant, in part as a result of the trend toward delayed pregnancy (59). It is classified as an autoimmune disorder because autoimmune hemolytic anemia, hypergammaglobulinemia, rheumatoid factor, and numerous autoantibodies have been found in patients with this disease. However, the immunopathologic mechanism is still unknown.

Patient Considerations

The most striking findings of scleroderma are the cutaneous changes. The skin becomes sclerosed and thickened from the

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dermis to the subcutaneous tissue, starting with the digits and extending proximally to include the trunk. The fetus may be difficult to assess clinically if the tissue over the abdomen is severely affected. The skin of the face may become tightly adherent to underlying structures, limiting the patient’s ability to open her mouth, creating difficulties with intubation. Raynaud’s phenomenon is a hallmark feature of PSS. Its presence is associated with a decrease in renal blood flow in some patients. In addition, coronary vascular spasm may occur, causing arrhythmias and angina in patients with anatomically normal coronary arteries. The myocardium may show focal or generalized fibrosis leading to congestive heart failure (60). During pregnancy, aspirin and antihypertensive agents are prescribed to treat some of these complications. Pulmonary function is often impaired. Interstitial fibrosis may lead to pulmonary hypertension, a restrictive lung defect, and a decrease in diffusing capacity. In pregnancy, the gravid uterus and an increased metabolic rate may further aggravate hypoxemia. Hypoxia may increase pulmonary artery pressures further, leading to cor pulmonale. Arterial blood gasses and chest x-rays may be required. Almost 50% of patients with scleroderma have proteinuria, hypertension, and azotemia. Patients with diffuse, rapidly progressing skin thickening are more likely to suffer a renal crisis, which is characterized by progressive renal failure and malignant hypertension. These patients may present with severe headaches, hypertensive encephalopathy, retinopathy, seizures, and left ventricular failure. Renal crisis is a leading cause of mortality. While the condition may respond to a number of antihypertensive agents, angiotensin converting enzyme inhibitors appear to be most effective. This class of drugs is not generally recommended in pregnancy because of potential risks to the neonate such as refractory hypotension and oliguria, but it may be life saving for the mother. The entire gastrointestinal tract can be involved with PSS. Swallowing may be difficult due to tongue and palate pathology. Abnormalities of esophageal motility, lower esophageal sphincter competence, and peptic strictures increase the risk of aspiration. Malabsorption can result in malnutrition and an elevated prothrombin time due to lack of vitamin K. The small joints of the hands and feet are often arthritic exhibiting severe deformities, and positioning can be problematic.

Obstetric Considerations

Parturients with scleroderma are high-risk pregnancies. A recent American study compared 149 pregnant scleroderma patients to a cohort of unaffected parturients. Patients with PSS were more likely to have hypertensive disorders (odds ratio 4.0, 95% confidence interval 2.4 to 6.6) and intrauterine growth restriction (odds ratio 3.7, 95% confidence interval 1.5 to 9.0), presumably as a result of scleroderma-associated microvascular abnormalities associated with the disease (61).

Analgesia and Anesthesia for Labor and Delivery

The pregnant patient with severe PSS poses several difficult anesthetic management problems. Often there is a lack of suitable peripheral veins for intravenous therapy. Large veins in the forearm or a central vein should be cannulated, since Raynaud’s phenomena can lead to digit necrosis and gangrene if cool fluids are infused. Patients should be kept warm to limit vascular spasm. Blood pressure may be difficult to measure due to skin changes, but indwelling arterial catheters should be avoided if possible because these may provoke distal vasospasm and gangrene. Epidural analgesia is appropriate for the relief of labor pain or operative delivery, provided coagulation parameters are normal. Performance of the epidural block may be technically

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difficult due to skin changes or arthritis in the lumbar spine. Early case reports suggested that the action of local anesthetics were enhanced in patients with scleroderma, but the difference may not be clinically significant. Cesarean delivery has been performed successfully under spinal anesthesia (62). Vasopressors should be given judiciously to avoid severe hypertension and vasospasm. For the same reasons, ergot preparations should be used with caution. If general anesthesia is required, several precautions should be noted. In patients with impaired esophageal motility, an attempt should be made to empty the lower esophagus of secretions with an orogastric tube. A non-particulate antacid can be given but if there is esophageal pathology, oral antacids may not be adequate. An H2 antihistamine, such as ranitidine may be useful to reduce gastric acid secretion and metoclopramide may accelerate gastric emptying. Facial deformities may make tight placement of an anesthetic mask and preoxygenation problematic. If a difficult intubation is suspected because of restricted mouth opening, awake fiberoptic oral intubation under local anesthesia may be the safest way to secure the airway. If oral intubation fails, a tracheostomy may be required. Intraoperative monitoring is often difficult in patients with PSS, and the benefits of using each monitoring device must be weighed against the risks. Ideally non-invasive methods are preferred in stable patients. However, skin and subcutaneous tissue changes may make non-invasive blood pressure and oxygen saturation monitoring inaccurate (60). ■■

 YPE IV HYPERSENSITIVITY T (CELL-MEDIATED REACTIONS)

Rheumatoid Arthritis Rheumatoid arthritis (RA) is a chronic inflammatory disease of diarthrodial joints that is frequently combined with the dysfunction of other organ systems. It is more common in females and can occur in any age group. The etiologic factors of the disease, point in part, to a Type IV cell-mediated immune mechanism. Juvenile rheumatoid arthritis is a similar disease with an onset before age 16 years. This condition can result in crippling sequelae by childbearing age.

Patient Considerations

The patient with RA suffers from multisystem complications. The musculoskeletal changes of the airway are often the most challenging for the anesthesiologist. The severity of joint involvement ranges from mild inflammation and thickened synovium to articular cartilage destruction and ankylosis. The ankylosis can result in a significant restriction of joint movement. Tendons and ligaments may also be weakened, leading to instability and subluxation. The cervical spine is involved in up to 85% of patients with RA but most are asymptomatic. Atlanto-axial subluxation with cord or nerve root compression, presents with symptoms of headache, subjective upper extremity pain, or objective long track signs (63). X-rays of the cervical spine including anteroposterior, open mouth, and flexion/extension views may show odontoid erosions, subaxial subluxations, apophyseal joint erosions, and disk space narrowing. If these are not available, one should assume that the neck is unstable. Ankylosis of the temporomandibular joint, particularly in patients with juvenile rheumatoid arthritis, may make mouth opening so restricted that oral endotracheal intubation is difficult. Observing for at least a 4 cm opening when the parturient opens her mouth can test the temporomandibular joint. The patient should also be viewed from the side to note micrognathia.

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Cricoarytenoid arthritis is present in about 59% of patients with RA. Approximately 14% have constriction of the glottic opening leading to stridor and obstructive sleep apnea (64). Complaints of hoarseness, wheezing, sore throat, and dysphagia, suggest cricoarytenoiditis and recurrent aspiration pneumonitis from vocal cord dysfunction and gastroesophageal reflux disease. A full otolaryngologic examination using indirect or direct fiberoptic laryngoscopy can diagnose these problems. Visceral involvement may occur in patients with longstanding disease. Cardiac and respiratory reserve may be reduced with the progression of pregnancy as well as with labor and delivery. Cardiac function may be compromised due to pericardial effusions, conduction defects, valvular heart disease, and cardiomyopathies. Lung manifestations include restrictive lung disease secondary to pleural effusions, kyphosis, and (to a lesser extent) fixation of the ribs by arthritis (64). As the gravid uterus becomes larger, this restriction may become more severe because of impaired diaphragmatic excursion. Other skeletal abnormalities include deformities of the hips that limit flexion and abduction, a concern for positioning with vaginal delivery. Bony pelvic abnormalities increase the risk of cephalopelvic disproportion and cesarean delivery. Restricted movement of the lumbar vertebral column or deformities may complicate the performance of a neuraxial block. An ultrasound assessment may be helpful in demonstrating calcification in the midline ligaments. Medications are often continued during pregnancy. Corticosteroids and NSAIDs such as salicylates, indomethacin, naproxen, and diclofenac are not known to be teratogenic. Other, agents such as methotrexate, leflunomide, and other biologic therapies are contraindicated (65). Large doses of aspirin near the time of delivery predispose patients to delayed and prolonged labor and an increased risk of blood loss during delivery (66). Physiologic maternal anemia can be aggravated by iron deficiency secondary to gastrointestinal loss. NSAIDs may cause reversible premature closure of the ductus arteriosus in the third trimester. This effect is less prominent with COX-2 inhibitors (65). In addition, newborns exposed to high doses of aspirin in utero may have an increased incidence of central nervous system bleeding after delivery. Platelet function may be impaired for days after discontinuing the drug. The use of NSAIDs does not increase the risk of epidural hematoma after neuraxial blockade in these patients (55).

Analgesia and Anesthesia for Labor and Delivery

History, physical examination, and laboratory investigations should reflect the patient’s medical condition. For patients with mild disease, that is, those with no joint deformities and limited drug therapy, the methods for administering pain relief during labor and delivery are the same as those in normal pregnancy. All patients on NSAIDs should have large intravenous access and blood available for delivery because of the potential risk of postpartum hemorrhage (66). Anesthesia for vaginal delivery can be managed in the usual fashion with the following in mind. If the patient has severe airway abnormalities, early epidural should be encouraged if coagulation is normal. The use of opioids in these patients should be used with caution, as sedation may lead to the loss of muscle tone resulting in upper airway obstruction. Severe contractures and osteoporosis, secondary to steroid treatment or immobility, may be present. The range of motion (ROM) of each of the large joints should be determined before any neuraxial blockade so that over extension and dislocation do not occur under anesthesia. It is particularly important to test the hip joints by maximally abducting and

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CHAPTER 38  •  Anesthesia for the Pregnant Patient with Immunologic Disorders

flexing them before placing the patient in stirrups. The ROM and positioning should be done carefully to avoid pathologic fractures. Peripheral neuropathies should be assessed and documented, although it is not an absolute contraindication to regional anesthesia. Patients with long-standing, crippling RA are likely to require a cesarean delivery because of hip joint or pelvic bony involvement. For elective cesarean delivery, lumbar epidural, spinal, or general anesthesia can be used. If there are upper airway deformities or cervical spine abnormalities, conduction anesthesia is preferred if technically possible. If general anesthesia is used in patients with severe airway deformities, the airway must be secured while the patient is awake using fiberoptic intubation. This technique limits cervical spine manipulation before permanent neurologic damage occurs. Topical anesthesia of the upper airway is required and small doses of an opioid or benzodiazepine for anxiolysis may be useful. Glycopyrrolate, which has limited transplacental passage, will decrease airway secretions. A tracheostomy under local anesthesia may be necessary if other options fail. Several pillows can support the head if there is a preexisting severe flexion deformity of the neck. Otherwise the neutral position is ideal. The arms may have to be placed at the sides if there is restriction of shoulder movement. Patients with hip contractures may require pillows under the knees. If an emergency cesarean delivery is required in a patient with a severely deformed upper airway, the experience of the anesthesiologist and the operating team determines the conduct of anesthesia. Extension of an epidural, rapid spinal anesthesia, or awake intubation prior to general anesthesia are options. If the operating team has had experience using local anesthesia, an abdominal wall field block using chloroprocaine and supplemental sedation may be necessary. While chloroprocaine has a short duration of action, there is no need to worry about local anesthetic toxicity because of its rapid metabolism. Therefore sufficient volume can be used to ensure patient comfort. After the procedure, the patient must be fully awake with a return in full muscle function before extubation. If glottic narrowing is severe, she should be observed for several hours following extubation in an area where re-intubation or emergency tracheostomy can be performed.

Transplanted Organs and Pregnancy Overview

Transplantation allows women whose health and fertility have been restored by an organ transplant to conceive. Manipulation of the cell-mediated immune system allows successful organ transplantation. Although most parturients with a transplanted organ have healthy newborns and an intact functioning graft, they continue to be at high risk for complications (67). The anesthetic considerations for the parturient with an allograft are summarized in Figure 38-5. Pregnancy is usually considered after the first year, provided that allograft function is stable and there have been no episodes of rejection within that year. At that point immunosuppressant doses are low and viral prophylaxis has been completed (67). When formulating an anesthetic plan, the history, physical examination, and laboratory investigations should reflect the extent of the parturient’s systemic disease and obstetrical history. In some patients, the primary disease that led to the transplant may continue to require attention. In lung recipients, cystic fibrosis is associated with failure of the exocrine pancreas and obstructive biliary disease. In liver recipients, Wilson’s disease causes significant neurologic, renal, and cardiac complications. Similarly, long-standing diabetic changes may not improve following pancreatic allografts or continue to progress in renal transplant patients.

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Parturients on chronic immunosuppression have an increased the risk of opportunistic and reactivated infections. The risk of cytomegalovirus (CMV), in the mother and fetus, is particularly high immediately after transplantation due to higher levels of immunosuppression. Extra time may be needed to find CMV-free blood (68). The risk of urinary tract infections, regardless of the transplant allograft approaches 40% (69). Since infection is a major cause of morbidity and mortality, invasive procedures should only be used if the benefits outweigh the risks. Transplant patients have 100 times the risk of malignant disease. The mechanism may include chronic immunosuppression, loss of immune surveillance, and chronic antigenic stimulation (70). For example, 5 years after cardiac transplantation, 22% of recipients die from malignancy with skin cancers, the most common diagnosis (71). Hypertension, renal dysfunction, and diabetes are significant co-morbidities in all solid organ recipients, particularly with regimens that include cyclosporine and corticosteroids. Hypertension is most frequent among kidney and kidney– pancreas transplant patients and least frequent among liver recipients. Hyperglycemia is often a reflection of corticosteroid dosing, as seen in lung recipients who suffer a 27% incidence of diabetes (72). All transplant patients have a higher incidence of preeclampsia and hypertension. Unlike non-transplant patients, where serum uric acid levels help in diagnosis, transplant patients often have elevated uric acid levels secondary to immunosuppressant therapy (67). Neonatal support is imperative. Maternal complications such as preeclampsia and premature rupture of amniotic membranes (PROM) contribute to the 50% incidence of prematurity and low birth weight, especially in pancreas and lung recipients (72). This compares to rates in the general population of 5% to 15% (73). Pregnancy does not increase the risk of allograft rejection in any solid organ transplant (67). Good graft function is associated with successful maternal and fetal outcomes and poor graft function should alert the anesthesia care team of the potential for increased morbidity and mortality (72). In renal recipients, fever, graft tenderness, and graft swelling suggests rejection which may require higher doses of immunosuppression or additional monitoring (73). In addition, previous transplant surgery may make cesarean delivery more difficult (69,73). Most centers recommend stress-doses of corticosteroids for both vaginal and cesarean delivery. A discussion of the appropriate doses for corticosteroids and other immunosuppressants appear in the subsequent delivery on immunosuppressants.

The Parturient with a Cardiac Allograft Common indications for cardiac transplantation include: Valvular and congenital heart disease, as well as, ischemic, viral, infiltrative, and idiopathic dilated cardiomyopathy. The 5-year patient and graft survival is 69% and 67%, respectively (69). Cardiac recipients with previous peripartum cardiomyopathy are not at risk of recurrence in subsequent pregnancies (74). One cause of the high morbidity and mortality is attributed to premature multi-vessel coronary artery stenosis, known as cardiac allograft vasculopathy (CAV). The incidence ranges between 30% and 60% after 5 years (69). In non-transplant patients, pregnancy increases blood volume by 40% and cardiac output (CO) by 30% (74). Labor increases CO 30% further, but it is the immediate postpartum period in which the most significant changes occur. Following the autotransfusion of 500 mL of blood, the CO

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Patient Considerations Obstetric Considerations 1. Primary disease 2. Residual complications from organ failure 3. Risk of infection 4. Risk of malignancy 5. Drug effects i) Calcineural inhibitors • Nephrotoxicity • Hypertension • Accelerated atherosclerosis ii) Glucocorticoids • Glucose intolerance • Hypertension • Osteopenia • “Pulse” dose steroids iii) Azathioprine • Thrombocytopenia • Anemia

1. Physiologic changes of pregnancy 2. Risk of preeclampsia i) Treatment(s) 3. Labor analgesia and Cesarean section anesthesia i) Monitioring ii) Neuraxial technique iii) Infection risk iv) Complicated surgery 4. Fetal Issues i) Teratogenesis ii) Prematurity iii) IUGR or low birth weight iv) Transplacental passage of immunosuppressants v) Long-term side-effects

Allograft Considerations 1. Current organ function 2. Physiology of allograft 3. Rejection i) Acute ii) Chronic

FIGURE 38-5  Anesthetic considerations in the parturient with an allograft.

reaches a peak of 60% above normal (75). Although the cardiac recipient can only reach a CO of 60% to 70% of normal due to chronotropic limitations and higher required filling pressures (76), they seem to compensate well with no evidence of adverse sequelae (69).

The Denervated Heart

After transplantation, when the heart is fully denervated, it beats at an intrinsic rate of 90 to 110 beats per minute (77). It has an impaired sympathetic response to exercise, hypovolemia, intubation, and the pain associated with labor and delivery (78). It also fails to produce a bradycardic parasympathetic response with carotid sinus massage and valsalva maneuvers. Heart rate and contractility increase as a result of circulating catecholamines in response to a particular stress. Catecholamines or cardiac pacing can be used to treat

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­ radycardia; β blockers can decrease the heart rate and block b the effects of circulating catecholamines (77). Drugs such as pancuronium and phenylephrine may not cause tachycardia or bradycardia respectively in the absence of an intact autonomic nervous system. Reversal of paralysis with neostigmine may cause bradycardia in some patients due to direct muscarinic receptor action (79). A muscarinic antagonist such as atropine or glycopyrrolate can be administered but direct chronotropic agents should be available to treat significant bradycardia (80). The transplanted heart is considered preload-dependent and sensitive to hypovolemia. It relies on fluid volume to increase cardiac output since autonomic input is required to produce reflex tachycardia (77). Hypotension should be treated with fluids and direct acting vasoconstrictors, such as phenylephrine. Ephedrine has both direct and indirect

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CHAPTER 38  •  Anesthesia for the Pregnant Patient with Immunologic Disorders

actions and may only result in a small increase in heart rate and blood pressure (80). Coronary autoregulation is intact and flow remains dependent on pH and arterial carbon dioxide tension (80). Over several years, re-innervation of the heart occurs with sympathetic nerve re-growth much more common than parasympathetic (81). This phenomenon explains how some cardiac recipients develop angina and rarely vasovagal responses.

Patient Assessment

Patients with a cardiac allograft must have a detailed assessment of exercise capabilities as well as the usual anesthetic history and physical examination performed. A thorough review of the laboratory investigations, ECG, echocardiogram, previous cardiac biopsies, and angiogram can help formulate anesthetic management. Some findings are typical and inconsequential while others necessitate further investigation. In cardiac recipients without evidence of re-innervation, myocardial ischemia is silent (80). Symptoms of paroxysmal dyspnea and a poor exercise tolerance may indicate ischemia. The ECG is distinctive, with two P waves and incomplete or complete right bundle branch block (77). Non-lethal ectopic ventricular beats that occur in all patients immediately after transplantation usually decrease over the subsequent months (80). Pacemakers are necessary in 5% of cardiac recipients and should be evaluated for functionality during pregnancy (68). If late bradyarrhythmias occur, ischemia of the allograft sinoatrial node and allograft rejection should be considered (82). Valvular lesions can include mitral regurgitation and moderate to severe tricuspid regurgitation. Left ventricular function is usually normal, although, diastolic dysfunction is common immediately after transplantation. Graft rejection can occur at any time and presents as fever, fatigue, atrial and ventricular dysrhythmias, silent myocardial ischemia, and congestive heart failure (80).

Analgesia and Anesthesia for Labor and Delivery

The mode of delivery is dependent on obstetrical indications. Cesarean delivery offers no specific advantage and does not prevent cardiac overload postpartum. With adequate prehydration, an epidural or a combined spinal–epidural can help minimize the hyperdynamic cardiovascular responses of labor and postoperative pain. Treatment of bradycardia and hypotension should be consistent with management of the denervated heart. Continuous electrocardiographic monitoring is recommended as a result of the high incidence of dysrhythmias and ischemia (83). Cesarean delivery can be safely managed with non-invasive monitoring if the parturient has a normal exercise tolerance. If invasive monitoring is indicated, strict asepsis is required. Cautious extension of a labor epidural is safe for cesarean delivery. The precipitous drop in preload associated with spinal anesthesia may not be tolerated (68). When general anesthesia is indicated, anesthetic requirements are similar to those in the non-transplant patient (77), although, judicious use of all agents is prudent (79). The American College of Obstetricians and Gynecologists guidelines for antibiotic prophylaxis for infective endocarditis do not recommend prophylaxis for vaginal or cesarean delivery regardless of the cardiac lesion. However, if there is an established infection such as chorioamnionitis or pyelonephritis, the underlying infection should be treated including treatment for endocarditis prophylaxis in high-risk patients (84). The American Heart Association guidelines consider patients with a cardiac transplant and cardiac valvulopathy as high risk for infective endocarditis and recommend prophylactic antibiotics (85).

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The Parturient with a Lung Allograft Lung transplantation is performed for a number of end-stage conditions such as chronic obstructive pulmonary disease, emphysema, cystic fibrosis, pulmonary fibrosis, and primary pulmonary hypertension. The reported 5-year patient and graft survival for all lung transplants is 47% and 46%, respectively (69). Declining lung function, fever, fatigue, and dyspnea is often attributed to obliterative bronchiolitis, a form of chronic graft rejection (78). The incidence is 60% to 70% after 5 years (79). The number of lung transplant recipients who become pregnant is extremely small and the incidences of rejection and poor obstetric outcome are much less favorable than patients with other solid organ transplants (86). During pregnancy there are many physiologic changes to the respiratory system decreasing the reserve. In the absence of rejection, lung recipients adapt well to the changes of pregnancy (83).

Donor Lung

Lung transplantation causes a number of changes to lung physiology. Lymphatic disruption requires meticulous fluid management particularly early after transplantation in order to avoid pulmonary edema (79). Evidence in the canine model indicates that lymphatic drainage can re-establish within 2 to 4 weeks (87). Double lung transplants can be performed en bloc with denervation of the carina, or sequentially without resection of the carina, which allows for the preservation of the cough reflex (79). However, any degree of decline in the cough reflex with impaired mucociliary transport and silent aspiration, leaves the recipient more prone to infection. Preliminary studies indicate that the transplanted lung may reinnervate over the site of the anastomosis with recovery of the cough reflex after the first year (88). Peak lung function occurs 6 months following transplantation with virtually normal lung function in those with double lung transplants. Pulmonary artery pressures, pulmonary vascular resistance, and pulmonary vasoconstriction in response to hypoxia, function immediately. Arterial blood gasses return to normal within a few weeks, but persistent hypercapnia can indicate diaphragmatic or allograft dysfunction. Bronchial hyper-responsiveness causing bronchoconstriction can occur and is responsive to β agonists. In patients with single lung transplants, 60% to 80% of pulmonary perfusion and ventilation is toward the transplanted lung (79).

Patient Assessment

Patients with a lung or heart–lung allograft must have a detailed assessment of exercise capabilities as well as the usual anesthetic history and physical examination performed. Particular attention should be given for signs and symptoms of infection or chronic rejection (obliterative bronchiolitis). Regular pulmonary function tests should be performed during pregnancy, and chest radiographs and invasive procedures should be performed if clinically indicated (83). Hypercapnia and a wide alveolar–arterial oxygen gradient on arterial blood gasses should trigger further investigation (79). Lung recipients have an incidence of diabetes of 27%, likely due to the higher levels of corticosteroids required for the control of rejection (72).

Analgesia and Anesthesia for Labor and Delivery

The mode of delivery is dependent on obstetrical indications (72). Regional analgesia for labor is acceptable but fluid boluses should be given judiciously (78). In the supine position, the vast majority of pulmonary blood flow travels to the transplanted lung (in single lung transplants). When placing

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the epidural in the lateral position, the transplanted lung should be non-dependent to prevent hypoxemia (79). Standard monitors for cesarean delivery are appropriate in stable patients (79). The incidence of gastroesophageal reflux is high in lung recipients and there is evidence linking it to chronic allograft rejection (89). Therefore aspiration prophylaxis should be considered. Continuous epidural anesthesia reduces the risk of airway manipulation and allows the patient to continue lung physiotherapy in pain-controlled circumstances postoperatively (79). Special care should be taken to prevent paralysis of the intercostal muscles that may lead to respiratory insufficiency. When general anesthesia is indicated, assessment of the airway should note the possibility of subglottic stenosis from a previous tracheostomy or prolonged ventilation (79). Strictures may also occur at the site of tracheal or bronchial anastomoses (79,89). Mechanical ventilation should incorporate low volume protective ventilation with airway pressures less than 35 mm Hg and PEEP at or below 5 mm Hg (89).

The Parturient with a Liver Allograft Liver transplantation dramatically improves fertility in patients with chronic liver disease. Most women of reproductive age resume normal menses within 8 weeks of transplantation. If pregnancy occurs within a year of transplantation there is a high risk of complications, possibly because of high circulating cytokinin levels. Registry data suggests that pregnancy results in about an overall 70% live birth rate but the incidence of hypertension, preeclampsia, and infection occurs in more than one-third of patients. Pregnancy does not seem to alter the incidence of graft failure (90). In non-transplant pregnancies alkaline phosphatase levels (ALP) rise due to placental ALP after the second trimester. Liver transaminases and other serum proteins remain normal (91). Any elevations in liver enzymes remote from the transplant surgery can indicate rejection and the need for additional immunosuppressants (69).

Patient Assessment

The cardiorespiratory changes associated with end-stage liver disease improve steadily in the months following transplantation (78). The liver’s ability to metabolize drugs or produce proteins is considered adequate if the INR or prothrombin time is normal (92). When biochemical abnormalities occur, preeclampsia and HELLP syndrome should be differentiated from acute rejection. Liver biopsies may be necessary for a clear diagnosis (90).

Analgesia and Anesthesia for Labor and Delivery

The mode of delivery is dependent on obstetrical indications and additional monitoring will depend on concurrent medical conditions. Regional analgesia and anesthesia has been used effectively in liver transplant patients when there is normal liver and coagulation function. If general anesthesia is employed for cesarean delivery, standard medications are acceptable in the absence of renal impairment. Isoflurane may be the vapor of choice, since it causes vasodilation of the hepatic circulation (92), although sevoflurane and desflurane are good alternatives. Liver transplantation during pregnancy may be required acutely if there is hepatic rupture secondary to HELLP syndrome or hepatic failure due to fulminant viral hepatic failure. Management of the fetus has included delivery, if the fetus is viable, or continuation of the pregnancy with successful neonatal outcomes (93).

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The Parturient with a Renal Allograft Long-standing insulin-dependent diabetes mellitus, hypertension, and collagen vascular disorders are common primary conditions that can lead to chronic renal failure. Despite transplantation these disorders continue to have a significant impact on anesthetic management. Patient survival after kidney transplantation at 5 years is 86%, with graft survival of 72% (69). In pregnant patients, the glomerular filtration rate (GFR) reaches a peak of 60% above normal at the end of the second trimester (94). Well-functioning renal allografts mirror these changes (70). However, with moderate or severe renal impairment the increase in GFR will be blunted or may not occur. Physiologic hydronephrosis occurs in all pregnancies and is caused by compression of the ureter by the enlarging uterus. It can lead to urinary reflux and an increased risk of pyelonephritis (94).

Patient Assessment

The assessment of a patient with a renal transplant involves a meticulous evaluation of the renal, cardiorespiratory, and neurologic systems. Patients with prepregnancy graft dysfunction have a greater risk of preeclampsia, graft rejection, and preterm delivery (72). Hypertension occurs in 60% to 80% of patients (94) while transient proteinuria occurs in 40% in the third trimester (73). These findings make the diagnosis of preeclampsia problematic, necessitating the need for a renal biopsy. Ultimately, 33% of patients are diagnosed with preeclampsia (67), which is four times higher than the general pregnant population (72). Common anti-hypertensive agents used in parturients include methyldopa, labetalol, nifedipine, and thiazide diuretics. The prevalence of coronary artery disease (CAD) can approach 92% in renal recipients who had renal failure from childhood. Although CAD does not improve following transplant surgery, uremic cardiomyopathy can resolve to a variable degree (95). Kidney transplantation can also improve uremic peripheral neuropathies but has little effect on autonomic neuropathic dysfunction (96). Signs and symptoms of autonomic neuropathy include: Silent myocardial ischemia, postural hypotension, diarrhea, delayed gastric emptying, and the loss of heart rate variability with deep breathing and Valsalva maneuvers.

Analgesia and Anesthesia for Labor and Delivery

Vaginal delivery is tolerated well in renal recipients. In rare instances, the allograft can cause labor dystocia or can be damaged with high vaginal or cervical lacerations (69). Regional techniques are good options for analgesia or anesthesia in the renal transplant patient providing that there is no evidence of coagulopathy. When there is underlying kidney dysfunction, fluid loading should be done cautiously. Cesarean delivery can be indicated for typical obstetrical reasons or for dystocia from pelvic osteodystrophy from the effects of chronic renal failure, dialysis, and prolonged steroid use (70). If gastroparesis is present, antacid prophylaxis should be considered. Positioning and intravenous access should take into account any preexisting arteriovenous fistulas. Surgery may be prolonged and difficult, secondary to the previous abdominal surgery. Reports of injury to the transplanted kidney and ureter have been reported. The transplanted ureter is often found superior to the uterine artery as it runs from the retroperitoneal pelvic kidney coursing over the lower uterine segment to the bladder (69). When general anesthesia is required, a rapid sequence induction is indicated. Precautions for a difficult intubation are needed in recipients with long-standing diabetes mellitus

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and stiffness at the atlanto-occipital joint (97). In the presence of myocardial dysfunction, reduced doses of induction agents, meticulous fluid management, and additional monitoring may be necessary. The choice of general anesthetic agents should be based on current renal function. Sevoflurane is metabolized in the liver to inorganic fluoride, which is nephrotoxic. Isoflurane and desflurane are not metabolized and therefore are better choices (95). The pharmacokinetics and pharmacodynamics of fentanyl, alfentanil, sufentanil, and remifentanil are not altered by kidney disease and can be used without modifying the dose. In the setting of renal dysfunction, active metabolites of meperidine and morphine can accumulate. High levels of normeperidine may cause seizures and metabolites of morphine may have a prolonged effect (95). NSAIDs are known to be nephrotoxic and are not recommended (79).

The Parturient with a Pancreas Allograft Pancreatic transplantation has allowed many insulin-dependent diabetics the freedom from insulin injections with improved glycemic control. Patient survival after isolated pancreas transplantation at 5 years is 80%, with graft survival of 49% (69). Almost 80% of those who receive a pancreatic transplant, simultaneously receive a kidney allograft (97). Morbidities are similar to those with kidney transplants except for a higher risk of infection, premature delivery, and lower mean newborn birth weights (94). Parturients with functioning pancreatic grafts produce adequate amounts of endogenous insulin to deal with the common problem of insulin resistance in the second and third trimesters (72).

Patient Considerations

Pancreatic allografts may not reverse the effects of diabetic complications but they may prevent further deterioration of nerve structure and function. Unfortunately, macrovascular complications such as CAD continue to progress (97). When euglycemia is not maintained during pregnancy, graft rejection should be suspected (72).

Analgesia and Anesthesia for Labor and Delivery

Management of analgesia and anesthesia is similar to those with kidney transplants. The location of the pelvic pancreatic allograft leaves it at risk for injury; therefore special care should be used during cesarean delivery. Postoperatively, extra emphasis on respiratory monitoring is required due to a diabetic-related impaired response to hypoxia (97).

Medications used in Autoimmune Diseases and Transplantation Immunosuppressants can be prescribed for a number of conditions including autoimmune diseases and transplantation. Reports of newer agents for the treatment of autoimmune disorders are limited with respect to pregnancy. However, agents used in transplant patients have a significantly longer history in the literature. See Table 38-8 for the FDA classification of drug safety in pregnancy. Tumor necrosis factor inhibitors such as infliximab, etanercept, and adalimumab have been introduced for the treatment of rheumatoid arthritis. They show no increase in miscarriage, prematurity or congenital structural malformations. Other drugs such as leflunomide, abatacept, and rituximab are not typically recommended during pregnancy because the teratogenic potential is unknown (98). Many patients with autoimmune diseases are also prescribed NSAIDs. Platelet function may be impaired for days after NSAIDs are discontinued, depending on the drugs. NSAIDs

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TABLE 38-8  FDA Classification of Drug Safety in Pregnancy •• Category A—tested and safe •• Category B—extensive experience in pregnancy and appear •• Category C—insufficient safety data and may cause problems for mother and fetus •• Category D—clear health risk to the fetus •• Category X—shown to cause birth defects and should not be given in pregnancy Drug

Category

Corticosteroids Prednisone Betamethasone Dexamethasone

C C C (D in the first trimester)

Non-steroidal Antiinflammatory drugs Aspirin Naproxen Diclofenac Indomethasone

B C (prescribe with caution in the last trimester) C (D after 30 wks) C (D after 30 wks)

Antimetabolites Methotrexate

X

Cyclo-oxygenase inhibitors Celecoxib

C

Tumor necrosis factor inhibitors infliximab etanercept adalimumab leflunomide abatacept rituximab

B B B X C C

Immunosuppresants azathioprine calcineurin inhibitors tacrolimus cyclosporine Others mycophenalate mofetil

D C C

D

and aspirin do not pose enough of a risk that would interfere in the performance of neuraxial blocks (55). After 20 weeks’ gestation, all NSAIDs can cause constriction of the ductus arteriosus and impair fetal renal function. NSAIDs should be withdrawn at week 32 gestation. High dose aspirin and indomethacin given close to delivery can cause bleeding tendencies and hemorrhage in the central nervous system in the newborn. COX-2 inhibitors can be used throughout gestation (99). Transplant patients are often on multiple medications, such as glucocorticoids, azathioprine, or calcineurin inhibitors such as tacrolimus or cyclosporine. It may be a single drug or the combination of medications that predispose to maternal hypertension, preeclampsia, prematurity, and IUGR. All of these immunosuppressants cross the placenta and with the exception of mycophenolate mofetil, none are proven teratogenic at therapeutic doses in humans (67). Common sideeffects are described in Table 38-9. There is significant experience in pregnant patients with the calcineurin inhibitors, cyclosporine, and tacrolimus. Cyclosporine can cause gingival hyperplasia which can be

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TABLE 38-9  Side-effects of Common Immunosuppressants Corticosteroids

Azathioprine

Tacrolimus

Cyclosporine

Cardiovascular

Hypertension

Dyspnea Palpitations

Hypertension

Neurologic

Psychosis Mood changes

Tremor Parasthesias Seizures Focal neurologic deficits

Tremor Palmer and plantar parasthesias Seizure Confusion

Gastrointestinal

Peptic ulcer disease

Hepatotoxicity Pancreatic dysfunction Nausea and vomiting

Nausea and vomiting

Nausea and vomiting Mild hepatic dysfunction

Hematologic Renal and metabolism

Glucose intolerance Salt and water retention Adrenal suppression

Myelosuppression Thrombocytopenia

Nephrotoxicity Hyperkalemia Glucose intolerance

Nephrotoxicity Hyperkalemia Hypomagnesemia Hyperuricemia Inhibition of insulin secretion

Musculoskeletal

Myopathy Osteoporosis Osteonecrosis

Arthralgias

Others

Weight gain Increased risk of infection Cataracts

Increased risk of neoplasia and infection

Increased risk of neoplasia

Increased risk of neoplasia and infection Gingival hyperplasia

Fetus/Newborn

IUGR Adrenal insufficiency

IUGR Neonatal bone marrow suppression (correlates with maternal suppression)

Mild reversible renal dysfunction

IUGR

problematic during airway manipulation (68). In addition, it is more likely than tacrolimus to produce renal artery vasoconstriction and nephrotoxicity (73) and in some cases can lead to renal failure (68). Cyclosporine and tacrolimus also lower the seizure threshold, so hyperventilation should be avoided under general anesthesia (68,80). In addition, they may prolong the effect of muscle relaxants due to druginduced changes in liver metabolism (80). Azathioprine is dose-limited due to myelosuppression and thrombocytopenia. In the pregnant patient, neonatal myelosuppression can also occur. It crosses the placenta readily but the fetus cannot convert it to its teratogenic metabolite. While sporadic cases of congenital malformations have occurred, azathioprine is commonly used (100). Corticosteroids have many complications that can affect pregnancy, including hypertension and hyperglycemia (99). They also increase the risk of PROM, prematurity, and IUGR. The mechanism for PROM could be due to abnormalities in the membrane itself or from alterations in maternal corticotrophin-releasing hormone (released centrally) making spontaneous labor more likely (100). Vaginal or cesarean delivery may be complicated by poor wound healing and limited options for patient positioning. Accelerated bone loss and osteonecrosis increases the risk of damage to joints, tendons, and ligaments with positioning for delivery. Neuraxial analgesia can increase the risk further since the patient is unable to determine her limits of flexion and extension. Maternal adrenal suppression is a concern at prednisone doses greater than 5 mg per day (94). However, doses less than this can cause suppression in some patients leading many centers to give stress dose steroids to all transplant recipients (94). Stress doses should consist of hydrocortisone 50 to

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100 mg intravenously at delivery and every 8 hours thereafter until oral steroids are tolerated (73). Fetal exposure to prednisone, cortisol, and methylprednisolone is minimal since the placenta metabolizes all but 10% of the active drug (99). However, both betamethasone and dexamethasone cross the placenta and reach high concentrations in the fetal circulation. ■■

SUMMARY

Immunologic disorders in the parturient may be manifest as acute, life-threatening events or chronic illnesses. Anaphylaxis to drugs or physical agents may occur unexpectedly and must be treated considering the special conditions associated with pregnancy. Parturients with conditions such as collagen vascular diseases or other chronic disorders may conceive, but their pregnancies are complicated by the primary disease process, end organ damage, and drug side-effects. Many of these considerations, along with organ rejection, also apply to parturients with organ transplants. A team approach to planning and care of these patients is needed.

KEY POINTS ■■

Acute hypersensitivity reactions to drugs and environmental agents can occur unexpectedly in the parturient. Treatment of reactions should take both mother and fetus into account. Physical maneuvers such as uterine tilt or rapid surgical removal of the fetus may be necessary to optimize the outcome.

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Chronic diseases with an immunologic basis do not preclude pregnancy. Management will depend on the severity of the disease, ongoing pharmacologic management, and interactions with obstetrical considerations. ■■ Parturients with transplanted organs require special care. Organ dysfunction and rejection may occur and may mimic obstetrical conditions such as preeclampsia. Management will depend on maternal underlying disease, the state of the transplant, ongoing drug therapy, and obstetrical requirements. ■■

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82. Allard R, Hatzakorzian R, Deschamps A, et al. Decreased heart rate and blood pressure in a recent cardiac transplant patient after spinal anesthesia. Can J Anesth 2004;51:829–833. 83. Wu DW, Wilt J, Restaino S. Pregnancy after thoracic organ transplantation. Semin Perinatol 2007;31:354–362. 84. American College of Obstetricians and Gynecologists Committee on Obstetric Practice. ACOG Committee Opinion No. 421, November 2008: antibiotic prophylaxis for infective endocarditis. Obstet Gynecol 2008;112:1193–1194. 85. Wilson W, Taubert KA. Gewitz M, et al. Prevention of infective endocarditis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation 2007;116:1736–1754. 86. McKay DB, Josephson MA. Pregnancy after kidney transplantation. Clin J Am Soc Neph 2008;3(Suppl 2):S117–S125. 87. Ruggiero R, Muz J, Fietsam R Jr, et al. Reestablishment of lymphatic drainage after canine lung transplantation. J Thorac Cardiovasc Surg 1993;106:167– 171. 88. Duarte AG, Terminella L, Smith JT, et al. Restoration of cough reflex in lung transplant recipients. Chest 2008;134:310–316. 89. Rosenberg AL, Rao M, Benedict PE. Anesthetic implications for lung transplantation. Anesthesiol Clin North America 2004;22:767–788. 90. Bonanno C, Dove L. Pregnancy after liver transplantation. Semin Perinatol 2007;31:348–353. 91. Degli Esposti S, Reinus J. Gastrointestinal and hepatic disorders in the pregnant patient. In: Feldman M, Friedman L, Brandt L, eds. Sleisenger and Fordtran’s Gastrointestinal and Liver disease. 9th ed. Philadelphia, PA: Saunders Elsevier; 2010:626. 92. Steadman RH. Anesthesia for liver transplant surgery. Anesthesiol Clin North America 2004;22:687–711. 93. Zarrinpar A, Farmer DG, Ghobrial RM, et al. Liver transplantation for HELLP syndrome. Am Surg 2007;73:1013–1016. 94. Fuchs KM, Wu D, Ebcioglu Z. Pregnancy in renal transplant recipients. Semin Perinatol 2007;31:339–347. 95. Lemmens HJ. Kidney transplantation: recent developments and recommendations for anesthetic management. Anesthesiol Clin North America 2004; 22:651–662. 96. Solders G, Persson A, Wilczek H. Autonomic system dysfunction and polyneuropathy in nondiabetic uremia. A one-year follow-up study after renal transplantation. Transplantation 1986;41:616–619. 97. Larson-Wadd K, Belani KG. Pancreas and islet cell transplantation. Anesthesiol Clin North America 2004;22:663–674. 98. Ostensen M, Lockshin M, Doria A, et al. Update on safety during pregnancy of biological agents and some immunosuppressive anti-rheumatic drugs. Rheumatology 2008;47(Suppl 3):28–31. 99. Ostensen M, Khamashta M, Lockshin M, et al. Anti-inflammatory and immunosuppressive drugs and reproduction. Arthritis Res Ther 2006;8:209. 100. Fuchs KM, Coustan DR. Immunosuppressant therapy in pregnant organ transplant recipients. Semin Perinatol 2007;31:363–371.

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CHAPTER

39

Psychiatric Disorders Julio B. Delgado  •  Michael Frölich

■■

INTRODUCTION

Diagnosis and treatment of psychiatric disorders during pregnancy and the postpartum period is a topic of significant relevance due to the high prevalence of these conditions and the multiple barriers to provide an appropriate diagnosis as well as effective and safe treatment. It is now more commonly acknowledged that new onset and exacerbation of psychiatric disorders during pregnancy and the postpartum period are frequent problems that may require a multidisciplinary approach to provide effective and timely diagnosis and treatment thereby minimizing the inherent risks secondary to treatment or lack of an early and effective intervention. Physicians who treat women during the childbearing years should be able to appropriately screen and provide guidance to effectively diagnose, refer, and treat patients who have a history of primary psychiatric disorders or exhibit symptoms which require a psychiatric evaluation. Empirical approaches to treatment are not ideal and consultation with psychiatry should be considered to provide safe and effective treatment minimizing morbidity to the mother and potential serious implications to the child. Pharmacologic treatment during pregnancy implies unique risks including neonatal exposure but untreated psychiatric illness can be more risky. The decision to treat includes many factors. A detailed history that addresses psychiatric issues and a careful assessment of the potential scenarios that affect the course of the specific condition during pregnancy and the postpartum period need to be carefully evaluated. In addition, consultation with psychiatry should be considered. In the absence of a thorough evaluation and planning, the consequences may be significant. The rationale to screen patients for psychiatric symptoms even before conception allows for better planning and better access to effective care.

Epidemiology In general, psychiatric diseases affect both genders and all socioeconomic and ethnic groups. It is interesting to note that mental disease often affects highly functional and creative individuals. The association between mental illness and art is reflected in the painting Broken Lines by the German artist G. Schetelig (Fig. 39-1). The specific incidence and prevalence of most psychiatric disorders during pregnancy and the postpartum period has been described by Bijl (1,2). Therefore, there now exists a good understanding of the potential implications of having a primary psychiatric disorder prior to conception, the potential risks of developing a new condition, and the changes in the course of these illnesses during pregnancy and the postpartum period. According to Bijl’s findings, roughly 40% of the adult population under 65 years of age has experienced at least one Diagnostic & Statistical Manual of Mental Disorders, Third Edition, Revised (DSM-III-R) disorder in their

lifetime. Among them, 23% have experienced a disorder within the preceding year. No gender differences were found in overall morbidity, but there was certainly a gender difference in the disease incidence as shown in Table 39-1. Depression, anxiety, and alcohol abuse and dependence were most prevalent; there was a high degree of comorbidity between them.

Diagnosis and Initial Evaluation during Pregnancy Psychiatric disorders are some of the most prevalent conditions in mankind and produce significant morbidity in the general population and in women during the reproductive years. Regardless of their high prevalence, they are frequently undiagnosed, untreated, or misdiagnosed. An appropriate evaluation and accurate diagnosis are critical components in the process of providing successful treatment. Many nonpsychiatric physicians feel uncomfortable approaching, diagnosing, and treating psychiatric disorders. The reasons are many including negative attitudes toward patients with psychiatric disease. Frequently, there is a basic lack of knowledge and understanding of the nature and relevance of diagnosing and treating primary disorders or psychiatric manifestations of other conditions. A systematic approach in the evaluation, diagnosis, and treatment is based on reliable evidence that allows a clear specific diagnosis and more effective treatments. The diagnostic criteria are based on the DSM-IV produced by the American Psychiatric Association (APA). This manual of mental disorders provides the basic parameters for diagnosing specific psychiatric syndromes and entities based on reliable evidence that allows a methodic approach to classifying and diagnosing specific conditions, which correlates well with specific therapeutic approaches. The DSM-IV should be consulted for the diagnostic parameters and classification of psychiatric disorders. This chapter will emphasize a diagnostic approach based on basic signs and symptoms to facilitate an efficient and practical way to assessing, diagnosing, and planning appropriate and timely interventions initiated and provided by the anesthesiologist. An accurate diagnosis is the main initial goal to provide effective treatment. The initial approach should facilitate the patient’s description of her symptoms and concerns after the physician formulates open-ended questions to elicit general information to evaluate the presence of a primary psychiatric syndrome, to explore personality features, or to recognize the presence of a personality disorder. Such information may not be easily obtained if a structured set of concrete questions is the initial interaction. It is important to keep an open-minded approach exploring groups of signs and symptoms before diagnosing specific entities. Regardless of this initial flexibility, the anesthesiologist remains in control of the interviewing process by providing the necessary structure to the evaluation and

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SECTION VIII  •  ANESTHETIC MANAGEMENT OF THE PARTURIENT WITH COEXISTING DISORDERS

FIGURE 39-1  Creativity and Madness: Many psychiatrists have been intrigued by the definite link between creativity and madness. This female painter illustrates this concept by using broken (disconnected) lines that embody the madness of a painting that is in perfect harmony with color and shape. (Broken Lines by Gesine Schetelig, reprinted with permission.) subsequently inquiring about the presence of specific symptoms but at the same time facilitating the description of the patient’s perceived problems to orient the diagnostic process and to make a preliminary impression. The rationale to consider obtaining a formal psychiatric consultation will depend on the patient’s history, severity of symptoms, and the patient’s and the physician’s preference. For patients who are actively suicidal, psychotic, manic, or where the diagnosis is completely unclear, a psychiatric consultation should be requested. When the emotions, behavior, or thought processes of a patient appear unconventional or generate concern, a formal assessment should be initiated to rule out the possibility of a psychiatric disorder, a medical condition with psychiatric manifestations, or the consequences of substance abuse.

Specific Syndromes with Anesthetic Implications Mood Disorders

Mood is the perception of the world through the patient’s eyes; it can be pathologically lowered, elevated, or it may excessively cycle between the two. True mood disorders are not the typical reactions to life stressors but prolonged and abnormal affective stages that require an appropriate evaluation.

Major Depression

As indicated above, the presence of depression during the childbearing years is 2 to 3 times more common in women (3,4) with the highest incidence in the age group from 25 to 44 and a lifetime risk of up to 25%. Depression is a recurrent disorder with a high risk of suicide and a progressively worsening course if it is not appropriately treated.

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The problems of mental illness (in general) and depression (in particular) have long been misjudged. One in six persons in the United States will, at some point, deal with major depression. Depression is also a leading cause of medical disability in women in the United States (5). Recent studies suggest that 10% of gravid women meet criteria for major depression (6,7) and up to 18% show depressive symptoms during gestation (8). Variable prevalence rates noted within the scientific literature reflect the variety of methods for screening subjects, whether subjects report symptoms themselves or whether trained researchers collected the data. Gender differences in the expression of affective disorders have been attributed to the impact of hormonal influence, socialization, and genetics. The negative influence of maternal depression on maternal and child health, psychological well-being and other possible outcomes are significant (9). Because women are more likely to experience first time depression beginning at puberty and because reproductive life transitions are associated with relapse and recurrent episodes, the urgency to treat depression as fully and as early as possible is of critical importance. The main clinical manifestations consistent with the presence of clinically significant depression are feelings of sadness, guilt, inadequacy, hopelessness or helplessness, irritability, difficulty concentrating, low energy level, insomnia or hypersomnia, anorexia, decreased libido, social isolation, anhedonia, decreased psychomotor activity, and suicidal thoughts. Patients who have five or more of the above symptoms for a time period greater than 2 weeks fulfill criteria for the diagnosis of major depression and require treatment. The precipitating causes are diverse and include genetic factors, environmental factors, or other medical conditions. It is important not to assume that the clinical syndrome is just a consequence of the specific stressors but instead it is a clinical condition that requires specific treatment. Appropriate treatment will allow the patient a much faster recovery and will improve her ability to deal effectively with the ongoing stressors that may have precipitated the episode. The magnitude of the symptoms and the presence of feelings of hopelessness, guilt, or suicidal ideation are significant parameters that clearly suggest the presence of major depression. The clinical course can be acute or chronic, but a major depressive episode without treatment can produce significant morbidity for several months or may precipitate suicide. Depression can be effectively treated with psychotherapy, electroconvulsive therapy (ECT), or pharmacologic interventions. Specific therapeutic approaches will be discussed later. One of the most significant components of the assessment in the patient with depression is evaluating the potential for suicide. Women attempt suicide more frequently than men. A detailed approach to evaluating the potential risk factors includes: The presence of a clinical syndrome consistent with major depression ■■ History of previous suicide attempts, impulsive behavior, substance abuse ■■ History of physical or sexual abuse or significant recent losses ■■ Family history of suicide ■■ A plan to commit suicide and access to the means to implement the plan ■■ History of a severe personality disorder ■■

A suicide risk assessment is an inherent component of every mental status examination and should be evaluated in more detail in patients with a history of previous suicide attempts, severe character pathology with impulsivity, and acts of selfdestructive behavior. Passive suicidal thoughts should be differentiated from the true intentions of self-inflicting lethal harm. If the above assessment is consistent with a high risk of suicide,

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CHAPTER 39  •  Psychiatric Disorders

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TABLE 39-1  Incidence Rate of Psychiatric Diseases by Gender and Incidence Rate Ratio Women

95% CI

Men

95% CI

IRR (f/m)

95% CI

Wald χ2

p-value

Mood disorders

3.25

(2.48–4.02)

1.34

(0.89–1.79)

2.39

(1.55–3.68)

28

2 mg/kg should theoretically be avoided. No study, however, has ever documented that any particular anesthetic agent or technique is associated with a greater or smaller incidence of abortion or preterm labor.

Laparoscopic Surgery Once considered an absolute contraindication during pregnancy, laparoscopic surgery is now routinely performed (97,98). Commonly performed laparoscopic procedures include appendectomy, cholecystectomy, and surgery for adnexal masses. Reedy et al. (99) in a survey study, compared five fetal outcome variables among pregnant women who had a laparotomy (n = 2,181) versus those who had laparoscopy (n = 1,522) between the fourth and twentieth weeks of gestation, and the general pregnant population who did not undergo surgery. The outcome variables studied were birth weight, gestational duration, intrauterine growth restriction, congenital malformation, and infant survival. They found that there was an increased risk of preterm delivery and low birth weight (