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Description

Your awareness of uncommon diseases and possible complications is vital to successful anesthetic patient management. Anesthesia and Uncommon Diseases, 6th Edition, brings you up to date with new information on less commonly seen diseases and conditions, including the latest evidence and management guidelines. This unique medical reference book is essential for a complete understanding of today’s best options and potential difficulties in anesthesia.

  • Improve your ability to successfully manage every patient, including those with rare diseases or conditions.
  • Avoid complications with unique coverage of an important aspect of anesthetic management.
  • Stay current with all-new chapters on adult congenital heart disease, rheumatic diseases, and the cancer patient, plus many more revisions throughout.
  • Get outstanding visual guidance with hundreds of illustrations, now in full color.

Sujets

Ebooks
Savoirs
Medecine
Cardiac dysrhythmia
Parkinson's disease
Cirrhosis
Sickle-cell disease
Amyotrophic lateral sclerosis
Circulatory collapse
Hospital
Photocopier
Hematologic disease
Hepatitis B
Guillain?Barré syndrome
Bone disease
Nose
Endocrine disease
Acute care
Systemic disease
AIDS
Neurological examination
Complications of pregnancy
Visual impairment
Pregnancy
Pulmonary fibrosis
Family medicine
Myopathy
End stage renal disease
Megaloblastic anemia
Glomerulonephritis
Traumatic brain injury
Coarctation of the aorta
Tracheoesophageal fistula
Mental health
Duchenne muscular dystrophy
Fatty liver
Ventricular septal defect
Congenital heart defect
Trauma (medicine)
Eye disease
Ear
Skin grafting
Chronic kidney disease
Acute kidney injury
Pulmonary alveolar proteinosis
Hypoparathyroidism
Pulmonary hypertension
Anesthetic
Paget's disease of bone
Nephropathy
Stroke
Dilated cardiomyopathy
Hypertrophic cardiomyopathy
Iron deficiency anemia
Hemolytic anemia
Patent ductus arteriosus
Amyloidosis
Review
Hypercalcaemia
Hypocalcaemia
Nutrition disorder
Acute respiratory distress syndrome
Physician assistant
Polycythemia vera
Septic shock
Critical care
Weakness
Anesthesiologist
Wound
Echocardiography
Lesion
Congenital disorder
Exanthema subitum
Eclampsia
Renal failure
Health care
Heart failure
Tetralogy of Fallot
Complete blood count
Rhabdomyolysis
Dietary mineral
Comorbidity
Internal medicine
Dyspnea
General practitioner
Local anesthetic
Pleasure
Mitochondrial disease
Sepsis
Diabetes mellitus type 2
Bleeding
Atherosclerosis
Anemia
Hypertension
Electrocardiography
Hepatitis C
Jaundice
Hypothyroidism
Anesthesia
Obesity
Ophthalmology
Metabolic syndrome
Emergency medicine
Pneumonia
X-ray computed tomography
Multiple sclerosis
Cystic fibrosis
Philadelphia
Cardiomyopathy
Diabetes mellitus
Hepatitis
Infection
Sleep apnea
Data storage device
Rheumatoid arthritis
Psychiatrist
Oxidative phosphorylation
Osteoporosis
Nephrology
Neurologist
Neurology
Mechanics
Mental disorder
Myasthenia gravis
Muscular dystrophy
Infectious disease
Hyperthyroidism
Major depressive disorder
Bipolar disorder
Anxiety
Fractures
Hypertension artérielle
Divine Insanity
Plague
Gene
Burns
Lésion
Planning
Cortisone
Fatigue
Coenzyme Q10
Electronic
Maladie infectieuse
Philadelphie
Ostéoporose
Copyright
Derecho de autor
Lesión
Miastenia gravis
Genoma mitocondrial

Informations

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Date de parution 20 avril 2012
Nombre de lectures 0
EAN13 9781455737550
Langue English
Poids de l'ouvrage 7 Mo

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Exrait

Anesthesia and Uncommon Diseases
Sixth Edition

Lee A. Fleisher, MD
Robert D. Dripps Professor and Chair, Department of Anesthesiology and Critical Care
Professor of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
Saunders
Copyright

1600 John F. Kennedy Blvd.
Ste 1800
Philadelphia, PA 19103-2899
ANESTHESIA AND UNCOMMON DISEASES ISBN: 978-1-4377-2787-6
Copyright © 2012 by Saunders, an imprint of Elsevier Inc.
Copyright © 2008, 2004, 1999 by Mosby, Inc., an affiliate of Elsevier Inc.
No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions .
This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein).

Notices
Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary.
Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility.
With respect to any drug or pharmaceutical products identified, readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications. It is the responsibility of practitioners, relying on their own experience and knowledge of their patients, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions.
To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein.
International Standard Book Number
978-1-4377-2787-6
Content Strategy Director: William Schmitt
Content Development Manager: Lucia Gunzel
Publishing Services Manager: Patricia Tannian
Project Manager: Sarah Wunderly
Design Direction: Louis Forgione
Printed in the United States
Last digit is the print number: 9 8 7 6 5 4 3 2 1
Dedication
This book is dedicated to my wife, Renee, who is my true partner in life, an outstanding example to our children, and a sounding board.
To my many teachers over the years, from professors during my residency to faculty colleagues and the many residents and medical students who taught me through their questions.
I particularly want to acknowledge one teacher, Stanley Rosenbaum, an internist, anesthesiologist, and intensivist at Yale University. Stanley, who was one of my first attendings, taught me the art and science of caring for patients with complex medical comorbidities and became an important collaborator in my early research efforts.

Lee A. Fleisher
Preface
It was a pleasure to edit the sixth edition of Anesthesia and Uncommon Diseases, following the traditions of Drs. Katz, Benumof, and Kadis from previous publications. When I was a resident at Yale New Haven Hospital, the third edition of this book was always an important component of my planning for the next day’s anesthetic. In developing the sixth edition, I have asked the authors to include tables and key points that highlight significant management practices for the various diseases to complement the comprehensive reviews in the text. Given the quality of the chapters from the previous edition, I invited many of the same authors to contribute some new chapters and ensured that all chapters have been updated to reflect the newest information available on these complex diseases.
In putting together a multiauthor text, numerous people must be acknowledged. I would like to thank my executive assistant, Eileen O’Shaughnessy, for managing a diverse group of authors. I would also like to thank Natasha Andjelkovic and Executive Content Strategist William Schmitt, my publishers at Elsevier, for their patience and support, and Content Development Manager Lucia Gunzel, whose guidance was very valuable.

Lee A. Fleisher, MD
Editor
Foreword
What are uncommon diseases? The Oxford English Dictionary defines “uncommon” as not possessed in common, not commonly (to be) met with, not of ordinary occurrence, unusual, rare. “Rare” has various meanings, such as few in number and widely separated from each other (in space or time), though also including unusual and exceptional. Another synonym for uncommon is “infrequent,” the definition of which includes not occurring often, happening rarely, recurring at wide intervals of time. The chapter titled Respiratory Diseases in this edition aims to review “less common” pulmonary conditions, rather than “uncommon.” None of these definitions includes quantification.
Why do we need a separate text to help us conduct the anesthetics of illnesses that do not happen often, if that is indeed the case? The simplest answer, congruent with the present obsession with the wisdom of the market, might be that the need has been already proven by the fact that the anesthetic community has bought sufficient copies of the previous five editions of this book to warrant a sixth. Nevertheless, it seems an intriguing question. Are the readers of the book residents studying arcane facts in order to pass certification examinations? Are they investigators searching for relevant questions to research? Are they isolated clinicians faced with the necessity of managing patients with unusual conditions the clinicians encounter so infrequently that they do not recall (or never knew) the most relevant facts requisite for providing safe care? Do the many uncommon conditions, even though each might occur infrequently, happen sufficiently often in the aggregate that we would ignore them to the peril of our patients?
To begin to approach this question, we need to consider the practice of medicine and the fact that medicine is a profession. Professions are occupations in which groups of individuals are granted a monopoly by society to learn and apply advanced knowledge in some area for the benefit of that society. The profession has the obligation to transmit that knowledge to others who will join that profession, to develop new knowledge, and to maintain standards of practice by self-regulation. There is a moral covenant with society to behave altruistically—that is, for the professional to subsume her or his own personal interests for the benefit of the society. These characteristics translate into an obligation to provide competent care for all who entrust themselves into our hands, no matter how rare or esoteric their condition may be. In the practice of anesthesiology (and of all of medicine, for that matter), it is not possible for any one individual to know everything necessary to fulfill that responsibility. Thus, we are dependent on rapid access to gain sufficient knowledge to approach that duty.
In the preface to the first edition of Anesthesia and Uncommon Diseases (1973), editors Jordan Katz and Leslie B. Kadis stressed their intention to present disease entities whose underlying pathophysiologic processes might profoundly affect normal anesthetic management. They noted that, “In general, the information we wanted to present has never been published.” This resulted in “a compendium of what is and is not known about unusual diseases as they may or may not relate to anesthesia.” The authors expressed the hope that their work would stimulate others to publish their experiences.
The subsequent three decades have seen a remarkable growth and development of knowledge in biomedical science, including anesthesiology and its related disciplines. Many others have indeed published their experiences with conditions covered in editions of this book. This has resulted in understanding the physiology and safe anesthetic management of many of these diseases, so that recommendations for their management can be provided with confidence. It has also been accompanied by recognition of other, not previously recognized, illnesses that have joined the ranks of “uncommon diseases.” An example of the former is the present virtually complete understanding of succinylcholine-associated hyperkalemia in certain muscle diseases; an example of the latter is the entire field of mitochondrial diseases, which was added in the fifth edition.
Anesthesiology has been characterized as hours of boredom interspersed with moments of terror. I would argue strongly that this is an incomplete and misleading characterization, but will not expand on that here. However, as a recovering clinician who spent decades (unsuccessfully) attempting to make every anesthetic as “boring” as possible, I can vouch that terror is indeed an inevitable component of the specialty. Knowledge—technical, experiential, judgmental, didactic—is the most effective deterrent to these vexing episodes and the best tool to successfully confront them when they occur. This book is a single source of extremely useful and provocative knowledge for trainees, practitioners, and investigators alike. I suspect this is why the previous editions of this book have been so successful, why this updated and much changed edition, with new topics and new contributors, will also be a success, and why we will need further new editions in future.

Edward Lowenstein, MD
Henry Isaiah Dorr Distinguished Professor of Anaesthesia and Professor of Medical Ethics,Harvard Medical School
Provost, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts
Contributors

Shamsuddin Akhtar, MBBS
Associate Professor, Department of Anesthesiology, Yale University School of Medicine, New Haven, Connecticut
Chapter 13: Diseases of the Endocrine System

Dean B. Andropoulos, MD, MHCM
Chief of Anesthesiology, Texas Children’s Hospital
Professor, Anesthesiology and Pediatrics, Baylor College of Medicine, Houston, Texas
Chapter 3: Congenital Heart Disease

Amir Baluch, MD
Research Associate, Louisiana State University School of Medicine, New Orleans, Louisiana
Attending Anesthesiologist, Baylor Surgicare, Dallas, Texas
Chapter 15: Psychiatric and Behavioral Disorders
Chapter 16: Mineral, Vitamin, and Herbal Supplements

Dimitry Baranov, MD
Assistant Professor of Clinical Anesthesiology and Critical Care, Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
Chapter 8: Neurologic Diseases

Paul X. Benedetto, MD
Chief Resident, Department of Dermatology, Cleveland Clinic Foundation, Cleveland, Ohio
Chapter 10: Skin and Bone Disorders

Sanjay M. Bhananker, MD, FRCA
Associate Professor, Department of Anesthesiology and Pain Medicine, University of Washington School of Medicine, Seattle, Washington
Chapter 18: Burns

Rafael Cartagena, MD
Medical Director of the Operating Room, Henrico Doctor’s Hospital
President, Total Anesthesia, Richmond, Virginia
Chapter 4: Respiratory Diseases

Maurizio Cereda, MD
Assistant Professor, Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
Chapter 7: Renal Diseases

Franklyn P. Cladis, MD
Assistant Professor of Anesthesiology
Director of Pediatric Anesthesia Fellowship Program, University of Pittsburgh School of Medicine
Attending Anesthesiologist, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania
Chapter 21: The Pediatric Patient

Bruce F. Cullen, MD
Professor Emeritus, Department of Anesthesiology, University of Washington School of Medicine, Seattle, Washington
Chapter 18: Burns

Peter J. Davis, MD, FAAP
Professor of Anesthesiology and Pediatrics, University of Pittsburgh
Anesthesiologist-in-Chief, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania
Chapter 21: The Pediatric Patient

Anahat Dhillon, MD
Assistant Clinical Professor, Department of Anesthesiology, David Geffen School of Medicine at UCLA, Los Angeles, California
Chapter 5: Liver Diseases

Richard P. Dutton, MD, MBA
Clinical Associate, University of Chicago, Chicago, Illinois
Executive Director, Anesthesia Quality Institute, Park Ridge, Illinois
Chapter 17: Trauma and Acute Care

Gregory W. Fischer, MD
Associate Professor of Anesthesiology, Department of Anesthesiology
Associate Professor of Cardiothoracic Surgery, Mount Sinai School of Medicine, Mount Sinai Medical Center, New York, New York
Chapter 11: Hematologic Diseases

Lee A. Fleisher, MD
Robert D. Dripps Professor and Chair, Department of Anesthesiology and Critical Care
Professor of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

Charles Fox, MD
Vice Chairman of Academics, Department of Anesthesiology, Tulane University School of Medicine, New Orleans, Louisiana
Chapter 15: Psychiatric and Behavioral Disorders

Erin A. Gottlieb, MD
Attending Pediatric Cardiovascular Anesthesiologist, Texas Children’s Hospital
Assistant Professor of Anesthesiology and Pediatrics, Baylor College of Medicine, Houston, Texas
Chapter 3: Congenital Heart Disease

Thomas E. Grissom, MD, FCCM
Associate Professor, Department of Anesthesiology, University of Maryland School of Medicine, R Adams Cowley Shock Trauma Center, Baltimore, Maryland
Chapter 17: Trauma and Acute Care

David L. Hepner, MD
Associate Professor of Anesthesia, Harvard Medical School
Staff Anesthesiologist, Department of Anesthesiology, Perioperative and Pain Medicine
Associate Director, Weiner Center for Preoperative Evaluation, Brigham and Women’s Hospital, Boston, Massachusetts
Chapter 19: Pregnancy and Obstetric Complications

Caron M. Hong, MD, MSc
Assistant Professor, Department of Anesthesiology and Surgery, University of Maryland School of Medicine, Baltimore, Maryland
Chapter 4: Respiratory Diseases

Jiri Horak, MD
Assistant Professor, Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
Chapter 7: Renal Diseases

Joel A. Kaplan, MD
Professor of Anesthesiology, University of California, San Diego, San Diego, California
Chapter 2: Cardiac Diseases

Adam M. Kaye, PharmD, FASCP, FCPhA
Associate Clinical Professor, Department of Pharmacy Practice, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Stockton, California
Chapter 16: Mineral, Vitamin, and Herbal Supplements

Alan D. Kaye, MD, PhD
Professor and Chairman, Department of Anesthesiology
Professor, Department of Pharmacology, Louisiana State University School of Medicine
Director of Anesthesia, Director of Interventional Pain Services, Louisiana State University Interim Hospital
Chapter 15: Psychiatric and Behavioral Disorders
Chapter 16: Mineral, Vitamin, and Herbal Supplements

Bhavani Shankar Kodali, MD
Associate Professor and Vice Chair, Department of Anesthesiology, Perioperative, and Pain Medicine, Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts
Chapter 19: Pregnancy and Obstetric Complications

Corry J. Kucik, MD, DMCC, FCCP
Assistant Professor of Anesthesiology and Critical Care, University of Southern California
Anesthesiology Program Director, Navy Trauma Training Center, Los Angeles, California
Chapter 17: Trauma and Acute Care

Jonathan Leff, MD
Assistant Professor of Anesthesiology, Albert Einstein College of Medicine
Chief of Cardiothoracic Anesthesia
Director Cardiothoracic Anesthesia Fellowship, Montefiore Medical Center, Bronx, New York
Chapter 11: Hematologic Diseases

Richard J. Levy, MD
Associate Professor of Anesthesiology and Critical Care Medicine, Pediatrics, and Integrative Systems Biology, The George Washington University School of Medicine and Health Sciences
Director of Cardiac Anesthesia
Vice Chief of Anesthesiology and Pain Medicine, Children’s National Medical Center, Washington, DC
Chapter 14: Mitochondrial Disease

Henry Liu, MD
Associate Professor of Anesthesiology, Tulane University School of Medicine
Staff Anesthesiologist
Director of Cardiothoracic and Vascular Anesthesia, Tulane University Medical Center, New Orleans, Louisiana
Chapter 15: Psychiatric and Behavioral Disorders

Maureen McCunn, MD, MIPP, FCCM
Assistant Professor, Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
Chapter 17: Trauma and Acute Care

Kathryn E. McGoldrick, MD
Professor and Chair, Department of Anesthesiology, New York Medical College, Valhalla, New York
Chapter 1: Eye, Ear, Nose, and Throat Diseases

Alexander Mittnacht, MD
Associate Professor of Anesthesiology
Director of Pediatric Cardiac Anesthesia, Mount Sinai School of Medicine, New York, New York
Chapter 2: Cardiac Diseases

Patrick Neligan, MA, MD, FCAI
Honorary Senior Lecturer in Anaesthesia and Intensive Care, National University of Ireland
Consultant Anaesthetist in Intensive Care, Galway University Hospitals, Galway, Ireland
Chapter 7: Renal Diseases
Chapter 12: Infectious Diseases and Biologic Weapons

Anthony N. Passannante, MD
Professor of Anesthesiology, University of North Carolina at Chapel Hill
Professor and Vice-Chair for Clinical Operations, University of North Carolina Health System, Chapel Hill, North Carolina
Chapter 4: Respiratory Diseases

Srijaya K. Reddy, MD
Assistant Professor of Anesthesiology and Pediatrics, Division of Anesthesiology and Pain Medicine, Children’s National Medical Center, George Washington University School of Medicine and Health Sciences, Washington, DC
Chapter 14: Mitochondrial Disease

David L. Reich, MD
Horace W. Goldsmith Professor and Chair of Anesthesiology, Mount Sinai School of Medicine, New York, New York
Chapter 2: Cardiac Diseases

Amanda J. Rhee, MD
Assistant Professor of Anesthesiology, Mount Sinai School of Medicine, New York, New York
Chapter 2: Cardiac Diseases

Peter Rock, MD, MBA, FCCM
Martin Helrich Professor and Chair, Department of Anesthesiology
Professor of Anesthesiology, Medicine and Surgery, The University of Maryland School of Medicine, Baltimore, Maryland
Chapter 4: Respiratory Diseases

Steven J. Schwartz, MD
Assistant Professor, Anesthesiology and Adult Critical Care, Johns Hopkins Bayview Medical Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
Chapter 20: The Geriatric Patient

Benjamin K. Scott, MD
Assistant Professor, Department of Anesthesiology, University of Colorado, Denver, Colorado
Chapter 8: Neurologic Diseases

Scott Segal, MD, MHCM
Professor and Chair, Department of Anesthesiology, Tufts University School of Medicine, Tufts Medical Center, Boston, Massachusetts
Chapter 19: Pregnancy and Obstetric Complications

Michael G.S. Shashaty, MD, MSCE
Instructor, Division of Pulmonary, Allergy, and Critical Care
Faculty Fellow, Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
Chapter 7: Renal Diseases

Linda Shore-Lesserson, MD, FASE
Professor of Anesthesiology, Albert Einstein College of Medicine, Bronx, New York
Chapter 11: Hematologic Diseases

Frederick E. Sieber, MD
Professor and Director of Anesthesia, Johns Hopkins Bayview Medical Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
Chapter 20: The Geriatric Patient

Ashish C. Sinha, MBBS, MD, PhD, DABA
President, International Society for the Perioperative Care of the Obese Patient (ISPCOP)
Professor and Vice Chairman of Research
Director of Clinical Research, Anesthesiology and Perioperative Medicine, Drexel University College of Medicine, Hahnemann University Hospital, Philadelphia, Pennsylvania
Chapter 6: Obesity and Nutrition Disorders

Doreen Soliman, MD
Assistant Professor of Anesthesiology
Director of Pediatric Anesthesia Residency Program, University of Pittsburgh School of Medicine
Attending Anesthesiologist, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania
Chapter 21: The Pediatric Patient

Randolph H. Steadman, MD
Professor and Vice Chair
Chief, Anesthesia for Liver Transplant, Department of Anesthesiology, David Geffen School of Medicine at UCLA, Los Angeles, California
Chapter 5: Liver Diseases

Patricia B. Sutker, PhD
Professor, Department of Anesthesiology, Louisiana State University School of Medicine, New Orleans, Louisiana
Chapter 15: Psychiatric and Behavioral Disorders

John E. Tetzlaff, MD
Professor of Anesthesiology, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University
Staff, Department of General Anesthesia, Anesthesiology Institute, Cleveland Clinic, Cleveland, Ohio
Chapter 10: Skin and Bone Disorders

Joshua M. Tobin, MD
Assistant Professor, Division of Trauma Anesthesiology, University of Maryland School of Medicine, R Adams Cowley Shock Trauma Center, Baltimore, Maryland
Chapter 17: Trauma and Acute Care

Michael K. Urban, MD, PhD
Associate Professor of Clinical Anesthesiology, Weil Medical College of Cornell University, Medical Director PACU/SDU, Hospital for Special Surgery, New York, New York
Chapter 9: Muscle Diseases

Ian Yuan, MEng, MD
Resident, Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
Chapter 6: Obesity and Nutrition Disorders
Table of Contents
Cover
Copyright
Dedication
Preface
Foreword
Contributors
Chapter 1: Eye, Ear, Nose, and Throat Diseases
Chapter 2: Cardiac Diseases
Chapter 3: Congenital Heart Disease
Chapter 4: Respiratory Diseases
Chapter 5: Liver Diseases
Chapter 6: Obesity and Nutrition Disorders
Chapter 7: Renal Diseases
Chapter 8: Neurologic Diseases
Chapter 9: Muscle Diseases
Chapter 10: Skin and Bone Disorders
Chapter 11: Hematologic Diseases
Chapter 12: Infectious Diseases and Biologic Weapons
Chapter 13: Diseases of the Endocrine System
Chapter 14: Mitochondrial Disease
Chapter 15: Psychiatric and Behavioral Disorders
Chapter 16: Mineral, Vitamin, and Herbal Supplements
Chapter 17: Trauma and Acute Care
Chapter 18: Burns
Chapter 19: Pregnancy and Obstetric Complications
Chapter 20: The Geriatric Patient
Chapter 21: The Pediatric Patient
Index
Chapter 1 Eye, Ear, Nose, and Throat Diseases

Kathryn E. McGoldrick, MD

Eye Diseases: General Considerations
     Corneal Pathology and Systemic Disease
     Lens Pathology and Systemic Disease
     Glaucoma and Systemic Disease
     Retinal Complications of Systemic Disease
Eye Diseases: Specific Considerations
     Marfan’s Syndrome
     Graves’ Disease
     Homocystinuria
     Hemoglobinopathies: Sickle Cell Disease
     Acquired Immunodeficiency Syndrome (AIDS)
     Retinopathy of Prematurity
     Incontinentia Pigmenti
     Retinitis Pigmentosa
     Eye Trauma
Ear, Nose, and Throat Considerations
     Sleep Apnea
     Recurrent Respiratory Papillomatosis
     Cystic Hygroma
     Wegener’s Granulomatosis
     Acromegaly
     Ludwig’s Angina
Conclusion

Key points

During ophthalmic surgery, the anesthesiologist is often positioned away from the patient’s face, preventing immediate access to the airway, and during many laryngologic surgeries, must share the airway with the surgeon. These logistical exigencies can compromise patient safety.
Patients with eye conditions are often at the extremes of age and may have extensive associated systemic processes or metabolic diseases.
Patients requiring ENT surgery may have preoperative airway compromise from edema, infection, tumor, or trauma; effective anesthesiologist-surgeon communication is vital for optimal patient outcome. Contingency planning is critical for patient safety.
Few ocular/ENT conditions have isolated ophthalmic or otorhinolaryngologic pathology. Multisystem involvement is common, and the anesthesiologist needs to have a comprehensive understanding of the disease process, surgical requirements, and effects of anesthetic interventions on both patient and proposed surgery.
In Lowe’s (oculocerebrorenal) syndrome, cataract is often the presenting sign, with other abnormalities such as mental retardation, renal tubular dysfunction, and osteoporosis appearing later. Drugs excreted by the kidney should be given cautiously and nephrotoxins avoided. Meticulous attention must be paid to gentle intraoperative positioning.
The primary areas of concern for the anesthesiologist caring for a patient with Graves’ disease involve the consequences of chronic corticosteroid use, side effects of antithyroid drugs, possible perioperative thyroid storm, and a potentially difficult intubation owing to tracheal deviation associated with a large neck mass.
In determining whether a patient with obstructive sleep apnea (OSA) is a candidate for outpatient surgery, it is imperative to consider the patient’s BMI and neck circumference, severity of OSA, presence or absence of associated cardiopulmonary disease, nature of the surgery, anticipated postoperative analgesic requirement, and the resources of the ambulatory facility.
Wegener’s granulomatosis is a systemic disease of unknown etiology characterized by necrotizing granulomas and vasculitis that affect the upper and lower airways and the kidneys. The anesthesiologist must anticipate a host of potential problems including the side effects of chronic corticosteroid and aggressive immunosuppressive therapy as well as the presence of underlying pulmonary and renal disease. Midline necrotizing granulomas of the airway are often present, and subglottic or tracheal stenosis should also be expected.
Many patients presenting for relatively “simple” ophthalmic or otorhinolaryngologic procedures suffer from complex systemic diseases. Although the surgeon may have the luxury of being able to focus on one specific aspect of the patient’s condition, the anesthesiologist must be knowledgeable about the ramifications of the entire disease complex and the germane implications for anesthetic management. Issues of safety often are complicated by the logistic necessity for the anesthesiologist to be positioned at a considerable distance from the patient’s face, thus preventing immediate access to the airway for certain types of ophthalmic surgery. Additionally, during many laryngologic surgeries, the anesthesiologist must share the airway with the surgeon. Moreover, many of these patients with complex disease undergo surgical procedures that are routinely performed on an ambulatory basis, further challenging the anesthesiologist to provide a rapid, smooth, problem-free recovery.
This chapter focuses on several eye diseases as well as ear, nose, and throat (ENT) conditions, many of which are relatively rare. Nonetheless, the anesthesiologist needs to understand the complexities involved, because failure to do so may be associated with preventable morbidity and mortality.

Eye diseases: general considerations
Patients with eye conditions are often at the extremes of age, ranging from fragile infants with retinopathy of prematurity or congenital cataracts to nonagenarians with submacular hemorrhage. These patients also may have extensive associated systemic processes or metabolic diseases. 1 Moreover, the increased longevity in developed nations has produced a concomitant increase in the longitudinal prevalence of major eye diseases. A study of elderly Medicare beneficiaries in the United States followed for 9 years during the 1990s documented a dramatic increase in the prevalence of major chronic eye diseases associated with aging. 2 For example, the prevalence of diabetes mellitus increased from 14.5% at baseline in the study patients to 25.6% nine years later, with diabetic retinopathy among persons with diabetes mellitus increasing from 6.9% to 17.4% of the subset. Primary open-angle glaucoma increased from 4.6% to 13.8%, and glaucoma suspects increased from 1.5% to 6.5%. The prevalence of age-related macular degeneration increased from 5% to 27.1%. Overall, the proportion of subjects with at least one of these three chronic eye diseases increased significantly, from 13.4% to 45.4% of the elderly Medicare population.
Ophthalmic conditions typically involve the cornea, lens, vitreoretinal area, intraocular pressure–regulating apparatus, or eye muscles and adnexa. These patients may present for, respectively, corneal transplantation, cataract extraction, vitrectomy for vitreous hemorrhage, scleral buckling for retinal detachment, trabeculectomy and other glaucoma filtration procedures for glaucoma amelioration, or rectus muscle recession and resection for strabismus. Conversely, they may require surgery for a condition entirely unrelated to their ocular pathology. Nonetheless, their ocular disease may present issues for anesthetic management, or the eye pathology may be only one manifestation of a constellation of systemic conditions that constitute a syndrome with major anesthetic implications ( Box 1-1 ).

Box 1-1 Ophthalmic Conditions often Associated with Coexisting Disease

Aniridia Macular hypoplasia Cataracts Nystagmus Colobomata Optic nerve hypoplasia Corneal dystrophies Retinal detachment Ectopia lentis Retinopathy Glaucoma Strabismus
Other, less common eye defects frequently linked with coexisting diseases include aniridia, colobomas, and optic nerve hypoplasia. Aniridia, a developmental abnormality characterized by striking hypoplasia of the iris, is a misnomer because the iris is not totally absent. The term describes only one facet of a complex developmental disorder that features macular and optic nerve hypoplasia as well as associated cataracts, glaucoma, ectopia lentis, progressive opacification, and nystagmus. Type I aniridia involves autosomal dominant transmittance of a gene thought to be on chromosome 2. Type II aniridia usually appears sporadically and is associated with an interstitial deletion on the short arm of chromosome 11 (11p13), although rarely a balanced translocation of chromosome 11 may produce familial type II. In addition to the typical ocular lesions, children with type II aniridia frequently are mentally retarded and have genitourinary anomalies—the “ARG triad.” Individuals with the chromosome 11 defect and this triad may develop Wilms’ tumor 3 and should be followed with regular abdominal examinations and frequent renal ultrasonography at least until they are 4 years old. Chromosomal analysis is indicated in all infants with congenital aniridia.
Coloboma denotes an absence or defect of some ocular tissue, usually resulting from malclosure of the fetal intraocular fissure, or rarely from trauma or disease. The two major types are chorioretinal or fundus coloboma and isolated optic nerve coloboma. The typical fundus coloboma is caused by malclosure of the embryonic fissure, resulting in a gap in the retina, retinal pigment epithelium, and choroid. These defects may be unilateral or bilateral and usually produce a visual field defect corresponding to the chorioretinal defect. Although colobomas may occur independent of other abnormalities, they also may be associated with microphthalmos, cyclopia, anencephaly, or other major central nervous system aberrations. They frequently are linked with chromosomal abnormalities, especially the trisomy 13 and 18 syndromes. Colobomas may be seen with the CHARGE syndrome (congenital heart disease, choanal atresia, mental retardation, genital hypoplasia, and ear anomalies) or the VATER association (tracheoesophageal fistula, congenital heart disease, and renal anomalies). Rarely, isolated colobomas of the optic nerve occur. They may be familial and associated with other ocular pathology as well as systemic defects, including cardiac conditions.
Optic nerve hypoplasia is a developmental defect characterized by deficiency of optic nerve fibers. The anomaly may be unilateral or bilateral, mild to severe, and associated with a broad spectrum of ophthalmoscopic findings and clinical manifestations. Visual impairment may range from minimal reduction in acuity 4 to blindness. Strabismus or nystagmus secondary to visual impairment is common. Although optic nerve hypoplasia may occur as an isolated defect in otherwise normal children, the lesion can be associated with aniridia, microphthalmos, coloboma, anencephaly, hydrocephalus, hydranencephaly, and encephalocele. Optic nerve hypoplasia may occur in a syndrome termed septo-optic dysplasia or de Morsier’s syndrome. There may be coexisting hypothalamic conditions and extremely variable endocrine aberrations. 5, 6 An isolated deficiency of growth hormone is most common, but multiple hormonal imbalances, including diabetes insipidus, have been reported. The etiology of optic nerve hypoplasia remains unknown. However, it has been observed to occur with slightly increased frequency in infants of diabetic mothers, 4 and the prenatal use of drugs such as LSD (lysergic acid diethylamide), meperidine, phenytoin, and quinine has been implicated sporadically.

Corneal Pathology and Systemic Disease
A vast spectrum of conditions may be associated with corneal pathology 7 ( Box 1-2 ). Associated inflammatory diseases include rheumatoid arthritis, Reiter’s syndrome, Behçet’s syndrome, and sarcoidosis. Connective tissue disorders such as ankylosing spondylosis, scleroderma, Sjögren’s syndrome, and Wegener’s granulomatosis have been associated with corneal disturbances. Associated metabolic diseases include cystinosis, disorders of carbohydrate metabolism, gout, hyperlipidemia, and Wilson’s disease. Also, such conditions as Graves’ hyperthyroid disease, leprosy, chronic renal failure, and tuberculosis may have associated corneal disease. Even skin diseases such as erythema multiforme and pemphigus have corneal manifestations (see Chapter 10 ). Finally, mandibulo-oculofacial dyscephaly (Hallermann-Streiff syndrome) is of interest to anesthesiologists because of anticipated difficulty with intubation.

Box 1-2 Systemic Diseases Associated with Corneal Pathology

Connective Tissue Disorders

Ankylosing spondylosis
Scleroderma
Sjögren’s syndrome
Wegener’s granulomatosis

Inflammatory Diseases

Behçet’s syndrome
Reiter’s syndrome
Rheumatoid arthritis
Sarcoidosis

Metabolic Diseases

Carbohydrate metabolism disorders
Chronic renal failure
Cystinosis
Gout
Graves’ disease
Wilson’s disease

Skin Disorders

Erythema multiforme
Pemphigus

Lens Pathology and Systemic Disease
A cataract is defined as a clouding of the normally clear crystalline lens of the eye. The different types of cataracts include nuclear-sclerotic, cortical, posterior subcapsular, and mixed. Each type has its own location in the lens and risk factors for development, with nuclear-sclerotic cataracts being the most common type of age-related cataract. The leading cause of blindness worldwide, cataracts affect more than 6 million individuals annually. 8 Indeed, cataract surgery is the most frequently performed surgical procedure in the United States, with more than 1.5 million operations annually. 9 More than half the population older than 65 develop age-related cataracts with associated visual disability. 10 Despite extensive research into the pathogenesis and pharmacologic prevention of cataracts, however, there are no proven means to prevent age-related cataracts.
Although age-related cataracts are most frequently encountered, cataracts may be associated with dermatologic diseases such as incontinentia pigmenti, exogenous substances, genetic diseases, hematologic diseases, infections, and metabolic perturbations ( Box 1-3 ).

Box 1-3 Conditions Associated with Cataracts

Aging

Chromosomal Anomalies

Trisomy 13
Trisomy 18
Trisomy 21
Turner’s syndrome

Dermatologic Disease

Incontinentia pigmenti

Exogenous Substances

Alcohol
Ergot
Naphthalene
Parachlorobenzene
Phenothiazines

Metabolic Conditions

Diabetes mellitus
Fabry’s disease
Galactosemia
Hypoparathyroidism
Hypothyroidism
Lowe’s syndrome
Phenylketonuria
Refsum’s disease
Wilson’s disease
Xanthomatosis

Infectious Diseases

Herpes
Influenza
Mumps
Polio
Rubella
Toxoplasmosis
Vaccinia
Varicella-zoster
Exogenous substances that can trigger cataracts include corticosteroids, 11 - 13 phenothiazines, naphthalene, ergot, parachlorobenzene, and alcohol. 14 Metabolic conditions associated with cataracts include diabetes mellitus, Fabry’s disease, galactosemia, hepatolenticular degeneration (Wilson’s disease), hypoparathyroidism, hypothyroidism, phenylketonuria, Refsum’s disease, and xanthomatosis. Another metabolic disorder important in the differential diagnosis of congenital cataracts is Lowe’s (oculocerebrorenal) syndrome. In this X-linked disorder, cataract is frequently the presenting sign, with other abnormalities appearing later. These anomalies include mental and growth retardation, hypotonia, renal acidosis, aminoaciduria, proteinuria, and renal rickets, requiring calcium and vitamin D therapy. 15, 16 Other concomitants include osteoporosis and a distinctive facies (long with frontal bossing). Although lens changes may also be seen in heterozygous female children, affected male children usually have obvious, dense, bilateral cataracts at birth. They may also be afflicted with associated glaucoma. Interestingly, carrier females in their second decade of life have significantly higher numbers of lens opacities than age-related controls; however, absence of opacities is no guarantee that an individual is not a carrier. Anesthetic management includes careful attention to acid-base balance and to serum levels of calcium and electrolytes. Renal involvement of oculocerebrorenal syndrome of Lowe comprises tubular dysfunction characterized by proteinuria and generalized aminoaciduria progressing to the renal Fanconi’s syndrome. Bicarbonate wasting and hyperkaluria result from a proximal tubule transport defect, with later glomerular disease. 17 The administration of drugs excreted by the kidney should be observed carefully and nephrotoxins avoided. The patient with osteoporosis should be positioned on the operating table gently and carefully.
Infectious causes of cataracts include herpesvirus, influenza, mumps, polio, rubella, toxoplasmosis, vaccinia, and varicella-zoster virus. 18 Chromosomal anomalies associated with cataracts include trisomy 13 (Patau’s syndrome), trisomy 18 (Edward’s syndrome), and trisomy 21 (Down syndrome). In Patau’s and Edward’s syndromes, congenital cataracts frequently occur in conjunction with other ocular anomalies, such as coloboma and microphthalmia. Cataracts have also been reported with Turner’s syndrome (XO).
An additional type of lens abnormality that can be associated with major systemic disease is ectopia lentis ( Fig. 1-1 and Box 1-4 ). Displacement of the lens can be classified topographically as subluxation or luxation. Luxation denotes a lens that is dislocated either posteriorly into the vitreous cavity or, less often, anteriorly into the anterior chamber. In subluxation, some zonular attachments remain, and the lens stays in its plane posterior to the iris, but tilted. The most common cause of lens displacement is trauma, although ectopia lentis may also result from other ocular disease, such as intraocular tumor, congenital glaucoma, uveitis, aniridia, syphilis, or high myopia. Inherited defects and serious systemic diseases, such as Marfan’s syndrome, homocystinuria, Weill-Marchesani syndrome, hyperlysinemia, and sulfite oxidase deficiency, are also associated with ectopia lentis. Indeed, lens displacement occurs in approximately 80% of patients with Marfan’s syndrome (see later discussion).

Figure 1-1 Ectopia lentis.
Displaced lens of the eye is common in patients with Marfan’s syndrome.
(Courtesy American Academy of Ophthalmology, 2011, aao.org.)

Box 1-4 Conditions Associated with Ectopia Lentis

Ocular Conditions

Aniridia
Congenital glaucoma
High myopia
Intraocular tumor
Trauma
Uveitis

Systemic Diseases

Homocystinuria
Hyperlysinemia
Marfan’s syndrome
Sulfite oxidase deficiency
Weill-Marchesani syndrome

Glaucoma and Systemic Disease
Glaucoma is a condition characterized by elevated intraocular pressure (IOP), resulting in impairment of capillary blood flow to the optic nerve and eventual loss of optic nerve tissue and function. Two different anatomic types of glaucoma exist: open-angle (or chronic simple) glaucoma and closed-angle (or acute) glaucoma. (Other variations of these processes occur but are not especially germane to anesthetic management. Glaucoma is actually many diseases, not one.)
With open-angle glaucoma, the elevated IOP exists in conjunction with an anatomically patent anterior chamber angle. Sclerosis of trabecular tissue is thought to produce impaired aqueous filtration and drainage. Treatment consists of medication to produce miosis and trabecular stretching. Common eyedrops include epinephrine, echothiophate iodide, timolol, dipivefrin, and betaxolol. Carbonic anhydrase inhibitors such as acetazolamide can also be administered by various routes to reduce IOP by interfering with the production of aqueous humor. All these drugs are systemically absorbed and thus can have anticipated side effects.
It is important to appreciate that maintenance of IOP is determined primarily by the rate of aqueous formation and the rate of aqueous outflow. The most important influence on formation of aqueous humor is the difference in osmotic pressure between aqueous and plasma, as illustrated by the following equation:

where K = coefficient of outflow, OPaq = osmotic pressure of aqueous humor, OPpl = osmotic pressure of plasma, and CP = capillary pressure. Because a small change in solute concentration of plasma can dramatically affect the formation of aqueous humor and thus IOP, hypertonic solutions such as mannitol are administered to reduce IOP.
Fluctuations in aqueous outflow can also greatly change IOP. The primary factor controlling aqueous humor outflow is the diameter of Fontana’s spaces, as illustrated by the following equation:

where A = volume of aqueous outflow per unit of time, r = radius of Fontana’s spaces, Piop = IOP, Pv = venous pressure, η = viscosity, and L = length of Fontana’s spaces. When the pupil dilates, Fontana’s spaces narrow, resistance to outflow is increased, and IOP rises. Because mydriasis is undesirable in both closed-angle and open-angle glaucoma, miotics such as pilocarpine are applied to the conjunctiva in patients with glaucoma.
The previous equation describing the volume of aqueous outflow per unit of time clearly underscores that outflow is exquisitely sensitive to fluctuations in venous pressure. Because an elevation in venous pressure results in an increased volume of ocular blood as well as decreased aqueous outflow, IOP increases considerably with any maneuver that increases venous pressure. Therefore, in addition to preoperative instillation of miotics, other anesthetic objectives for the patient with glaucoma include perioperative avoidance of venous congestion and of overhydration. Furthermore, hypotensive episodes should be avoided because these patients are purportedly vulnerable to retinal vascular thrombosis.
Although glaucoma usually occurs as an isolated disease, it may also be associated with such conditions as Sturge-Weber syndrome and von Recklinghausen’s disease (neurofibromatosis) ( Box 1-5 ). Ocular trauma, corticosteroid therapy, sarcoidosis, some forms of arthritis with uveitis, and pseudoexfoliation syndrome can also be associated with secondary glaucoma.

Box 1-5 Conditions Associated with Glaucoma

Ocular Conditions

Aniridia
Anterior cleavage syndrome
Cataracts
Ectopia lentis
Hemorrhage
Mesodermal dysgenesis
Persistent hyperplastic primary vitreous
Retinopathy of prematurity
Spherophakia
Trauma
Tumor

Systemic Diseases

Chromosomal anomalies
Congenital infection syndromes (TORCH * )
Hurler’s syndrome
Marfan’s syndrome
Refsum’s disease
Sarcoidosis
Stickler’s syndrome
Sturge-Weber syndrome
Von Recklinghausen’s disease

* Toxoplasmosis, other agents, rubella, cytomegalovirus, herpes simplex.
Primary closed-angle glaucoma is characterized by a shallow anterior chamber and a narrow iridocorneal angle that impedes the egress of aqueous humor from the eye because the trabecular meshwork is covered by the iris ( Box 1-6 ). Relative pupillary block is common in many angle-closure episodes in which iris-lens apposition or synechiae impede the flow of aqueous from the posterior chamber. In the United States, angle-closure glaucoma (ACG) is one-tenth as common as open-angle glaucoma ( Table 1-1 ). In acute ACG, if the pressure is not reduced promptly, permanent visual loss can ensue as a result of optic nerve damage. Because irreversible optic nerve injury can occur within 24 to 48 hours, treatment should be instituted immediately after making the diagnosis of acute ACG. Signs and symptoms include ocular pain (often excruciating), red eye, corneal edema, blurred vision, and a fixed, mid-dilated pupil. Consultation with an ophthalmologist should be sought immediately. Topical pilocarpine 2% is administered to cause miosis and pull the iris taut and away from the trabecular meshwork. A topical beta-adrenergic blocker (β-blocker) also should be considered. If a prompt reduction in IOP does not ensue, systemic therapy with an agent such as mannitol should be considered, but its potentially adverse hemodynamic effects should be weighed in a patient with cardiovascular disease.

Box 1-6 Glaucoma Patients: Anesthetic Objectives

Perioperative instillation of miotics to enhance aqueous humor outflow
Avoidance of venous congestion/overhydration
Avoidance of greatly increased venous pressure (e.g., coughing, vomiting)
Avoidance of hypotension that may trigger retinal vascular thrombosis
Table 1-1 Comparison of Open-Angle and Closed-Angle Glaucoma * Open-Angle Glaucoma Closed-Angle Glaucoma Anatomically patent anterior chamber angle Shallow anterior chamber Trabecular sclerosis Narrow iridocorneal angle Ten times more common than closed-angle Iris covers trabecular meshwork Painless Painful Initially unaccompanied by visual symptoms Red eye with corneal edema Blurred vision; fixed, dilated pupil Can result in blindness if chronically untreated Can cause irreversible optic nerve injury within 24-48 hours Requires emergency treatment
* Also called angle-closure glaucoma (ACG).
If medical therapy is effective in reducing IOP to a safe level and the angle opens, an iridotomy/iridectomy can be performed immediately, or delayed until the corneal edema resolves and the iris becomes less hyperemic.

Retinal Complications of Systemic Disease
Retinal conditions such as vitreous hemorrhage and retinal detachment are most frequently associated with diabetes mellitus and hypertension ( Box 1-7 ), although patients with severe myopia (unaccompanied by any systemic disease) are vulnerable to retinal detachment. In addition, collagen disorders and connective tissue diseases, such as systemic lupus erythematosus, scleroderma, polyarteritis nodosa, Marfan’s syndrome, and Wagner-Stickler syndrome, are often associated with retinal pathology. Serious retinal complications have been reported with skin conditions (e.g., incontinentia pigmenti). Moreover, such conditions as sickle cell anemia, macroglobulinemia, Tay-Sachs disease, Niemann-Pick disease, and hyperlipidemia can result in vitreoretinal disorders. During the past three decades, cytomegalovirus retinitis has been reported in AIDS patients, sometimes causing retinal detachment.

Box 1-7 Conditions Associated with Vitreoretinal Pathology

Collagen/connective tissue disorders
     Marfan’s syndrome
     Polyarteritis nodosa
     Scleroderma
     Systemic lupus erythematosus
     Wagner-Stickler syndrome
Diabetes mellitus
Hypertension
Human immunodeficiency virus/acquired immunodeficiency syndrome
Hyperlipidemia
Incontinentia pigmenti
Macroglobulinemia
Niemann-Pick disease
Tay-Sachs disease

Eye diseases: specific considerations
This section shifts focus from systemic to specific disease entities associated with serious ocular pathology and the anesthetic management of these patients.

Marfan’s Syndrome
Marfan’s syndrome is a disorder of connective tissue, involving primarily the cardiovascular, skeletal, and ocular systems. However, the skin, fascia, lungs, skeletal muscle, and adipose tissue may also be affected. The etiology is a mutation in FBNI, the gene that encodes fibrillin-1, a major component of extracellular microfibrils, which are the major components of elastic fibers that anchor the dermis, epidermis, and ocular zonules. 19 Connective tissue in these patients has decreased tensile strength and elasticity. Marfan’s syndrome is inherited as an autosomal dominant trait with variable expression.
Ocular manifestations of Marfan’s syndrome include severe myopia, spontaneous retinal detachments, displaced lenses (see Fig. 1-1 ), and glaucoma. Cardiovascular manifestations include dilation of the ascending aorta and aortic insufficiency. The loss of elastic fibers in the media may also account for dilation of the pulmonary artery and mitral insufficiency resulting from extended chordae tendineae. Myocardial ischemia caused by medial necrosis of coronary arterioles as well as dysrhythmias and conduction disturbances have been well documented. Heart failure and dissecting aortic aneurysms or aortic rupture can occur.
Marfan’s patients are tall, with long, thin extremities and fingers (arachnodactyly). Joint ligaments are loose, resulting in frequent dislocations of the mandible and hip. Possible cervical spine laxity can also occur. Kyphoscoliosis and pectus excavatum can contribute to restrictive pulmonary disease. Lung cysts have also been described, increasing the risk of pneumothorax. A narrow, high-arched palate is typical.
The early manifestations of Marfan’s syndrome may be subtle, and therefore the patient presenting for initial surgery may be undiagnosed. The anesthesiologist, however, should have a high index of suspicion when a tall young patient with a heart murmur presents for repair of a spontaneously detached retina. These young patients should have a chest radiograph as well as an electrocardiogram (ECG) and echocardiogram before surgery. Antibiotics for subacute bacterial endocarditis prophylaxis should be considered, as well as β-blockers to mitigate increases in myocardial contractility and aortic wall tension (dP/dT).

Anesthetic management
If general anesthesia is elected in the Marfan’s patient, the anesthesiologist should be prepared for a potentially difficult intubation ( Box 1-8 ). Laryngoscopy should be carefully performed to circumvent tissue damage and especially to avoid hypertension with its attendant risk of aortic dissection. The patient should be carefully positioned to avoid cervical spine or other joint injuries, including dislocations. The dangers of hypertension in these patients are well known. Presence of significant aortic insufficiency clearly warrants that the blood pressure (BP, especially diastolic) should be high enough to provide adequate coronary blood flow, but not be so high as to risk dissection of the aorta. Maintenance of the patient’s normal BP is typically a good plan. No single intraoperative anesthetic agent or technique has demonstrated superiority. If pulmonary cysts are present, however, positive-pressure ventilation may lead to pneumothorax. 20 At extubation, clinicians should take care to avoid sudden increases in BP or heart rate. Adequate postoperative pain management is vitally important to avoid the detrimental effects of hypertension and tachycardia.

Box 1-8 Marfan’s Syndrome: Anesthetic Concerns

Difficult intubation
Lung cysts
Restrictive pulmonary disease
Dysrhythmias and/or conduction disturbances
Dilation of aorta and pulmonary artery; dissecting/ruptured aortic aneurysms
Aortic and/or mitral insufficiency
     Consider antibiotic prophylaxis for subacute bacterial endocarditis.
Myocardial ischemia; heart failure
     Consider beta blockade.
Propensity to mandibular/cervical/hip dislocation
In appropriate patients having ophthalmic surgery, regional anesthesia may be a viable option. Retrobulbar or peribulbar block may be inadvisable in these patients because of the ocular perforation risk in the presence of high myopia. However, a catheter-based, sub–Tenon’s capsule approach using 5 mL of a 50:50 mixture of 4% lidocaine and 0.75% bupivacaine has been as effective as retrobulbar block in controlling intraoperative pain during vitreoretinal surgery. 21

Graves’ Disease
Graves’ disease is the most common cause of both pediatric and adult hyperthyroidism. Graves’ disease encompasses hyperthyroidism, goiter, pretibial myxedema, and often but not inevitably, exophthalmos. The condition occurs in conjunction with the production of excess thyroid hormone and affects approximately 3 in 10,000 adults (usually women), typically age 25 to 50. Graves’ ophthalmopathy includes corneal ulcerations and exophthalmos that can be severe. Retro-orbital tissue and the extraocular muscles are infiltrated with lymphocytes, plasma cells, and mucopolysaccharides. The extraocular muscles often are swollen to 5 to 10 times their normal size. If proptosis secondary to infiltrative ophthalmopathy is severe and if muscle function or visual acuity deteriorates, corticosteroid therapy (usually prednisone, 20-40 mg/day for adults) is initiated, especially if retrobulbar neuritis develops. Patients who fail to respond to corticosteroid therapy require surgical intervention. Lateral (Krönlein’s) or supraorbital (Naffziger’s) decompression is performed.
Graves’ disease is thought to be autoimmune in origin, with thyroid-stimulating immunoglobulins directed against thyroid antigens that bind to thyroid-stimulating hormone (TSH, thyrotropin) receptors on the thyroid gland. Soft, multinodular, nonmalignant enlargement of the thyroid is typical. There is a strong hereditary component with Graves’ disease, and the condition is likely exacerbated by emotional stress. These patients may have other signs of autoimmune involvement, including myositis and occasionally myasthenia gravis. Symptoms include weakness, fatigue, weight loss, tremulousness, and increased tolerance to cold. Proptosis, diplopia or blurred vision, photophobia, conjunctival chemosis, and decreased visual acuity may be noted. Cardiac symptoms include a hyperdynamic precordium, tachycardia, and elevated systolic BP, decreased diastolic BP, and widened pulse pressure. Atrial fibrillation, palpitations, and dyspnea on exertion may also occur.
The differential diagnosis of Graves’ disease includes other causes of hyperthyroidism such as pregnancy that may be associated with the production of an ectopic TSH-like substance, autoimmune thyroiditis, thyroid adenoma, choriocarcinoma, a TSH-secreting pituitary adenoma, and surreptitious ingestion of tri-iodothyronine (T 3 ) or thyroxine (T 4 ). 22 The goals of drug therapy in the hyperthyroid patient are to control the major manifestations of the thyrotoxic state and to render the patient euthyroid. The most frequently used agents are the thiourea derivatives propylthiouracil (PTU) and methimazole, which act by inhibiting synthesis of thyroid hormone. (PTU may also inhibit the conversion of T 4 to T 3 .) Because of the large glandular storage of hormone, 4 to 8 weeks is usually required to render a patient euthyroid with these drugs. Therapy typically lasts several months, after which thyroid reserve and suppressive response to thyroid hormone are re-evaluated. The major complication of this therapy is hypothyroidism, and the dosage is usually adjusted to the lowest possible once a euthyroid state is attained. 23 Other side effects encountered in patients taking these antithyroid drugs include leukopenia, which may be therapy limiting, as well as agranulocytosis, hepatitis, rashes, and drug fever. Beta-receptor numbers are reportedly increased by hyperthyroidism, 24 and β-blockers are used to control the effects of catecholamine stimulation rapidly, such as tachycardia, tremor, and diaphoresis. 25

Anesthetic management
The main areas of concern for the anesthesiologist in the patient with Graves’ disease involve chronic corticosteroid use, possible perioperative thyroid storm, and a potentially difficult intubation because of tracheal deviation from a large neck mass 26 ( Box 1-9 ). When surgery is planned, it is imperative to determine if the Graves’ patient is euthyroid because the euthyroid state will diminish the risks of life-threatening thyroid storm and of perioperative cardiovascular complications by more than 90%. Achievement of the euthyroid state is assessed by clinical signs and symptoms, plasma hormone levels, and evidence of gland shrinkage. The patient should also be evaluated for associated autoimmune diseases. A chest radiograph, lateral neck films, and computed tomography (CT) of the neck and thorax will determine tracheal displacement or compression. If there is a question about the adequacy of the airway or tracheal deviation or compression, awake fiberoptic intubation is a prudent approach. An armored tube or its equivalent is also useful if any tracheal rings are weakened. Liberal hydration is advised if the patient’s cardiovascular status will permit this intervention. High-dose corticosteroid coverage is indicated, and continuous temperature monitoring is essential. The eyes must be meticulously protected.

Box 1-9 Graves’ Disease: Anesthetic Concerns

Difficult intubation secondary to tracheal deviation or compression
Side effects of antithyroid drugs, including leukopenia and hepatitis
Effects of chronic steroid consumption
Meticulous intraoperative eye protection and temperature monitoring
Perioperative thyroid storm
     Determine euthyroid state.
Associated autoimmune disease(s)
Weakened tracheal rings
No single anesthetic drug or technique has proved superior in the management of hyperthyroid patients. However, anticholinergic drugs are not recommended, and ketamine should be avoided, even in the patient who has been successfully rendered euthyroid. 27 Sudden thyroid storm secondary to stress or infection is always a possibility, and the clinician must be alert for even mild increases in the patient’s temperature or heart rate. Other early signs of thyroid storm include delirium, confusion, mania, or excitement. The differential diagnosis of these symptoms includes malignant hyperthermia, pheochromocytoma crisis, and neuroleptic malignant syndrome. Treatment of thyroid storm is supportive, including infusion of cooled saline solutions, β-blocker therapy, antithyroid drugs, and corticosteroids.

Homocystinuria
Although rare, homocystinuria is generally considered the second most common inborn error of amino acid metabolism (incidence ~1:200,000), 28 after phenylketonuria (~1:25,000). 29 An error of sulfur amino acid metabolism, homocystinuria is characterized by the excretion of a large amount of urinary homocystine, which can be detected by the cyanide-nitroprusside test. A host of assorted genetic aberrations may be linked with homocystinuria, but the most common is a deficiency of cystathionine β-synthase, with accumulation of methionine and homocystine. The disorder is autosomal recessive. Disease occurs in the homozygote, but the heterozygote is without risk of developing the potentially life-threatening complications of the condition. Although one third of homocystinuric patients have normal intelligence, most are mentally retarded.
Ectopia lentis occurs in at least 90% of persons with homocystinuria (see Fig. 1-1 ). Frequently there is subluxation of the lens into the anterior chamber, causing pupillary block glaucoma, necessitating surgical correction. Other ocular findings reported in homocystinuria include pale irides, retinoschisis, retinal detachment, optic atrophy, central retinal artery occlusion, and strabismus.
Because of abnormal connective tissue, the skeletal findings are similar to those of Marfan’s syndrome. Most homocystinuric patients have arachnodactyly, kyphoscoliosis, and sternal deformity. They also may have severe osteoporosis. Kyphoscoliosis and pectus excavatum may be associated with restrictive lung disease.
It is imperative to appreciate that patients with homocystinuria are extremely vulnerable to thrombotic complications associated with high mortality 30 ( Box 1-10 ). An untreated homocystinuric patient may have a perioperative mortality rate as high as 50%. Elevated concentrations of homocystine irritate the vascular intima, promoting thrombolic nidus formation and presumably increasing the adhesiveness of platelets. 31 Other possible causes of the thrombotic tendency include increased platelet aggregation, Hageman factor activation, and enhanced platelet consumption as a result of endothelial damage. Patients with homocystinuria are also at risk for hypoglycemic convulsions secondary to hyperinsulinemia, which is thought to be provoked by hypermethioninemia. 32

Box 1-10 Homocystinuria Patients: Perioperative Concerns

Restrictive lung disease
Positioning-induced fractures associated with osteoporosis
Thrombotic complications
Hypoglycemic convulsions
Preoperative measures include a low-methionine, high-cystine diet and vitamins B 6 and B 12 and folic acid to regulate homocystine levels, as well as acetylsalicylic acid (aspirin) and dipyridamole to prevent aberrant platelet function. Besides appropriate dietary and drug therapy, proper perioperative care involves prevention of hypoglycemia and maintenance of adequate circulation. Patients with osteoporosis must be carefully positioned on the operating table. Glucose levels should be monitored perioperatively. Low-flow, hypotensive states must be assiduously avoided. The patients must be kept well hydrated and well perfused. 33 Anesthetic agents selected should promote high peripheral flow by reducing vascular resistance, maintain cardiac output, and foster rapid recovery and early ambulation. Postoperative vascular support stockings that prevent stasis thrombi in leg veins are indicated.

Hemoglobinopathies: Sickle Cell Disease
Hemoglobinopathies are inherited disorders of hemoglobin synthesis. There may be structural derangements of globin polypeptides or, as in thalassemia, abnormal synthesis of globin chains. In hemoglobin (Hb) S, for example, a single amino acid (valine) is substituted for glutamic acid in the β chain. This substitution has no effect on oxygen (O 2 ) affinity or molecular stability. Nonetheless, in the setting of low O 2 tension, it causes an intermolecular reaction, producing insoluble structures within the erythrocytes that result in sickling. 34 These atypical red blood cells lodge in the microcirculation, causing painful vaso-occlusive crises, infarcts, and increased susceptibility to infection. Low O 2 tension and acidic environments are major triggers and determinants of the degree of sickling. Sickled cells are thought to produce a rightward shift (P 50 = 31 mm Hg) of the oxyhemoglobin dissociation curve to enhance O 2 delivery.
Although ophthalmic pathology such as proliferative retinopathy can occur in all sickling diseases, it is more common in adults with Hb SC or Hb S thalassemia than in those with Hb SS. Proliferative retinopathy usually appears in the third or fourth decades of life and is the result of vascular occlusion. This occlusion of retinal vessels eventually produces ischemia, neovascularization, vitreous hemorrhage, fibrosis, traction, and retinal detachment or atrophy. Prophylactic laser photocoagulation has helped reduce the incidence of these conditions.
The severity of the anemia depends on the amount of Hb S present. In homozygous SS disease, the Hb S content is 85% to 90%, the remainder being Hb F. Sickle cell thalassemia (Hb SF) is characterized by an Hb S content of 67% to 82% and causes somewhat less severe problems. Indeed, patients with Hb SC and Hb S thalassemia typically have a much more benign course than those individuals with Hb SS and usually have only mild anemia and splenomegaly. Heterozygous persons with Hb SA (sickle trait) rarely have serious clinical problems. However, some increased risk of stroke and pulmonary emboli or infection has been suggested, but not well quantitated, after the stress of hypothermic, low-flow cardiopulmonary bypass in patients with sickle trait. 35
Sickle cell disease (Hb SS) is an autosomal recessive condition that occurs most frequently in individuals of African ancestry, although the gene for Hb S also occurs in persons with ancestors from areas endemic for falciparum malaria. From 8% to 10% of American blacks are heterozygous carriers of Hb S; approximately 0.5% of blacks are homozygous for Hb S disease. Patients with homozygous sickle cell disease have chronic hemolytic anemia ( Box 1-11 ). Organ damage results from vaso-occlusive ischemia because sickled cells are unable to traverse narrow capillary beds. Also, sickled cells tend to adhere to the endothelium and cause release of vasoactive substances. Chronic pulmonary disease gradually progresses as a result of recurrent pulmonary infection and infarction. Eventually, these individuals develop pulmonary hypertension, cardiomegaly, and heart failure, as well as renal failure.

Box 1-11 Sickle Cell Disease Patients: Perioperative Concerns

Anemia
Chronic pulmonary disease
Pulmonary hypertension
Cardiomegaly and heart failure
Renal failure
Extreme vulnerability to dehydration, hypothermia, hypoxia, and acidosis
Hemolytic transfusion reaction resulting from alloimmunization
Multiple problems place these patients at high perioperative risk, including anemia, underlying cardiopulmonary disease, and extreme vulnerability to dehydration, hypothermia, hypoxia, and acidosis. Preoperative management should include correction of anemia. In the past, controversy surrounded whether patients with sickle cell disease should receive a preoperative exchange transfusion with Hb A. Data now suggest, however, that preoperative transfusion to an Hb level of 10 g/dL, independent of the Hb S percentage, is equally effective in preventing perioperative complications as transfusion designed to establish a level of 10 g/dL and an Hb S level below 30%. 36 Controversy also surrounds the issue of the relative risks of transfusion for simple, brief surgical procedures in patients who are minimally symptomatic and considered at low risk for intraoperative vaso-occlusive crises. Clearly, all blood transfusion in these patients carries a high risk of hemolytic transfusion reaction because of alloimmunization from previous exposure.

Anesthetic concerns
In providing intraoperative management, clinicians should appreciate that no difference in morbidity or mortality has been shown among assorted anesthetic agents or between regional and general anesthetic techniques. 37 Factors that precipitate sickle crises, such as dehydration, hypoxia, acidosis, infection, hypothermia, and circulatory stasis, should be meticulously prevented. Intraoperative normothermia should be maintained with fluid warmers, breathing-circuit humidification, warming blankets, forced-air warmers, and a well-heated operating room (OR). Adequate perioperative volume replacement is critical; aggressive hydration with crystalloid or colloid is indicated, except in the patient with congestive heart failure (CHF). Supplemental oxygen and mild hyperventilation are desirable to prevent hypoxemia and acidosis. Although possibly valid with Hb S, pulse oximetry is extremely unreliable in the presence of deoxygenated, polymerized Hb S because aggregation of sickled cells interferes with the light-emitting diode. After surgery, O 2 therapy, liberal hydration, and maintenance of normothermia should be continued for a minimum of 24 hours, because crises may occur suddenly postoperatively. Additionally, adequate analgesia, early ambulation, and pulmonary toilet, including incentive spirometry, are important in preventing serious complications. Postoperative pneumonia in the patient with hemoglobinopathy can be fatal.

Acquired Immunodeficiency Syndrome (AIDS)
First described in the United States in 1981, the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic is one of the most devastating to have afflicted humankind. Although ongoing research continues to improve the quality of life for the millions of people affected, there is still no cure. Thus, anesthesiologists must be prepared to manage the AIDS patient’s numerous and complex challenges.
Patients with AIDS frequently develop cytomegalovirus retinitis, 38 a condition treated by the insertion of a slow-release antiviral drug packet into the vitreous. Occasionally, the retinitis will produce a retinal detachment that requires surgical correction.
Many patients with AIDS are extremely ill with cachexia, anemia, and residual respiratory insufficiency from previous episodes of Pneumocystis jiroveci (formerly P. carinii ) pneumonia, tuberculosis, or aspergillosis ( Box 1-12 ). In addition to reduced pulmonary reserve, these patients often have limited myocardial reserve because of the debilitating effects of their underlying disease. AIDS is strongly associated with the development of cardiomyopathy, hypertension, right ventricular dysfunction, myocarditis, pericardial effusion, and coronary artery disease. 39 The preoperative assessment must reflect that AIDS is a complex, multiorgan disease requiring risk stratification. Disease severity may be staged by considering the peripheral blood CD4 counts and the clinical manifestations. CD4 cell counts range from relatively normal (>500/mm 3 ) to severe depletion (<200/mm 3 ). The clinical manifestations are typically placed in strata based on the level of immunologic dysfunction, ranging from “minimal” to “AIDS-defining” conditions. The presence of neurologic, pulmonary, cardiovascular, and hematologic abnormalities is of particular concern.

Box 1-12 Aids Patients: Perioperative Concerns

Anemia
Respiratory insufficiency
Hypertension
Cardiomyopathy, myocarditis, right ventricular dysfunction, and coronary artery disease
Pericardial effusion
Vulnerability to infection and pressure sores
Altered drug requirements secondary to hypoglobulinemia and cytochrome P450 inhibition
Transmission of HIV or other drug-resistant pathogens
AIDS, Acquired immunodeficiency syndrome; HIV, human immunodeficiency virus.
Although antiretroviral therapy has greatly prolonged the lives of AIDS patients, these drugs can have disturbing side effects and notable drug interactions. The antiretroviral drugs fall into four categories: nucleoside analog reverse-transcription inhibitors, nonnucleoside reverse-transcription inhibitors, protease inhibitors, and fusion inhibitors. Although extremely effective in managing AIDS, the protease inhibitors inhibit cytochrome P450 enzymes, with the greatest effect on drugs metabolized by the CYPA4 enzyme. A strong interaction between ritonavir and fentanyl metabolism suggests that the dose of fentanyl should be reduced in patients taking ritonavir. 40
Severely debilitated patients may require invasive monitoring, depending greatly on the type of surgical procedure being performed, and strict attention must be paid to aseptic technique. Hypoglobulinemia is extremely common in AIDS patients and will reduce drug requirements. Therefore, anesthetic medications must be carefully selected and titrated. Moreover, supplemental oxygen should be provided to prevent perioperative episodes of desaturation. Additionally, these cachectic patients require special precautions to prevent pressure sores. Pre-emptive pain management may offer protection against additional immune suppression. 41
It cannot be overemphasized that, because of the risk of infection, strict hygienic practices are critical with AIDS patients. Moreover, medical personnel must protect themselves against the hazard of transmission of HIV and other drug-resistant pathogens by scrupulous adherence to the Universal Precautions.

Retinopathy of Prematurity
Although Terry 42 first described the pathologic condition in 1942, the neologism “retrolental fibroplasia” was coined in 1944 by Harry Messenger (Boston ophthalmologist and Greek/Latin scholar). 43 However, the term retinopathy of prematurity now has gained widespread acceptance because it describes the late, cicatricial phase of the disease as well as the earlier acute changes.
Retinopathy of prematurity (ROP) is usually associated with extremely low-birth-weight (LBW) (1000-1500 g) preterm infants and “micropremies” (<750 g) who require O 2 therapy. Hyperoxia is thought to trigger blood vessel constriction in the developing retina, causing areas of peripheral ischemia, poor vascularization, and neovascularization (proliferation of network of abnormal retinal vessels), which produces fibrosis, scarring, and retinal detachment. Because advances in neonatology have led to greater than 85% survival rates for extremely LBW infants and to approximately 75% survival rates for extremely preterm babies (born at 24-27 weeks’ gestation), it is not surprising that the prevalence of ROP increased in recent decades. Moreover, the assumption that ROP is caused exclusively by excess oxygen in this population is incorrect, because ROP has a multifactorial origin. 44 - 46 The factors associated with the development of ROP are highly interrelated, but Flynn established that low birth weight was the most significant predictor of risk. 47 Common problems of prematurity include respiratory distress syndrome (traditionally managed with antenatal corticosteroids, postnatal surfactant therapy, and effective ventilation), apnea, bronchopulmonary dysplasia (BPD), persistent pulmonary hypertension, patent ductus arteriosus, necrotizing enterocolitis, gastroesophageal reflux, anemia, jaundice, hypoglycemia and hypocalcemia, intraventricular hemorrhage, and ROP ( Box 1-13 ).

Box 1-13 Common Problems with Prematurity

Anemia
Apnea
Bronchopulmonary dysplasia
Gastroesophageal reflux
Hypoglycemia/hypocalcemia
Intraventricular hemorrhage
Jaundice
Necrotizing enterocolitis
Patent ductus arteriosus
Persistent pulmonary hypertension
Respiratory distress syndrome
Retinopathy of prematurity
Recent trials have shown, however, that the less invasive strategy of nasal continuous positive airway pressure (CPAP) in extremely preterm babies, compared with immediate intubation followed by surfactant therapy, has important benefits and no serious side effects. 48, 49 Mortality and BPD rates were similar in both approaches. Predicting which babies would have an inadequate response to treatment with CPAP and who should therefore receive early intubation/ventilation and surfactant should be a future goal. 50 Targeting oxygen saturation levels is extremely challenging, and a recommended O 2 saturation that is effective yet safe remains elusive. Analysis of retrospective data from the 1960s found that the standard practice of limiting the fraction of inspired oxygen (Fi O 2 ) to less than 0.5 resulted in 16 excess deaths for every one case of blindness prevented. 51 The arbitrary limiting of Fi O 2 disappeared as a practice when the arrival of continuous pulse oximetry allowed neonatologists to deliver only the O 2 amount necessary to maintain a safe level of oxygenation. This advance, however, has forced the question of what defines a “safe” oxygenation level.
The Surfactant, Positive Pressure, and Oxygenation Randomized Trial (SUPPORT) showed that a lower target level of oxygenation (85%-89%), compared with a higher range (91%-95%), was associated with a substantial decrease in severe ROP in survivors, but at the cost of increased mortality. 49 However, analysis of the raw pulse oximetry data showed considerable overlap, and the target ranges achieved in terms of O 2 saturation were not those sought in the study design. Moreover, no data on neurodevelopmental problems are yet available, which will be important in the long term. Considering these limitations, no major change in clinical practice seems warranted based on the SUPPORT results. The lowest Fi O 2 that maintains O 2 saturation above 90% may be the best available compromise based on current data.

Anesthetic concerns
Postoperative apnea is the most common problem associated with anesthesia in premature infants. 52 Almost 20% of premature infants can be expected to develop this life-threatening complication, with the greatest risk for infants at 50 weeks’ postconceptual age (gestational age plus chronologic age) and earlier. 53 Apnea may result from prolonged effects of anesthetic agents, a shift of the carbon dioxide (CO 2 ) response curve, or fatigue of respiratory muscles. Recommendations for continuous cardiopulmonary monitoring in patients less than 46 weeks’ postconceptual age 54 were extended to include monitoring for infants less than 60 weeks’ postconceptual age for at least 12 apnea-free hours after surgery. 55 Although the incidence of postoperative apnea is inversely related to postconceptual age, even full-term infants occasionally have postoperative apnea. 53 In addition to prematurity as a risk factor, infants with a history of anemia, 56 neonatal apnea spells, respiratory distress syndrome, and pulmonary disease have approximately twice the risk of developing postoperative apnea.
Chronic lung disease, also known as BPD, remains the primary long-term pulmonary complication among premature infants, associated with pulmonary hypertension, abnormalities of postnatal alveolarization, and neovascularization. 57 Infants with BPD have impaired growth 58 and may have poor long-term cardiopulmonary function, an increased vulnerability to infection, 59 and a greatly increased risk of abnormal neurologic development. 60 A University of Chicago investigation, however, reported that administration of nitric oxide to premature infants with respiratory distress syndrome reduced the incidence of chronic lung disease and death. 61
Although lacking a widely accepted definition, many neonatologists define BPD as a condition requiring supplemental O 2 after 36 weeks’ postmenstrual age. 62 Conditions associated with BPD include prematurity, persistent ductus arteriosus, and prolonged ventilation with high inspiratory pressure and O 2 concentration. Affected patients have abnormalities in lung compliance and airway resistance that may persist for several years. They also have chronic hypercarbia and hypoxemia. Abnormal findings on chest radiograph include hyperexpanded lungs, small radiolucent cysts, increased interstitial markings, and peribronchial cuffing. Treatment of BPD patients typically is bronchodilators to reduce airway resistance and diuretics to decrease pulmonary edema. Air trapping during assisted ventilation may be minimized using a prolonged expiratory time.
When undergoing anesthesia and surgery, premature infants must be kept warm because they defend their core temperature at considerable metabolic cost ( Box 1-14 ). The brown fat cells begin to differentiate at 26 to 30 weeks’ gestation and thus are absent as a substrate buffer in extremely premature infants. 63 Also, infants have a greater surface area per volume compared with adults and therefore tend to lose body heat rapidly in a cold environment. Metabolic acidosis is produced by cold stress. The acidosis causes myocardial depression and hypoxia, exacerbating the metabolic acidosis. Warming the OR (86° F, or 30° C) and using warming units may help maintain the infant’s body temperature. Warming intravenous (IV) and irrigation fluids may also be beneficial. Standard monitoring equipment includes electrocardiograph, stethoscope, BP monitor, temperature probe, pulse oximeter, and capnograph. A pulse oximeter probe placed in a preductal position on the right hand to reflect the degree of oxygenation in blood flowing to the retina can be compared with one located in a postductal position on the left foot to determine the severity of ductal shunting. Although pulse oximetry findings can be used to diagnose hypoxemia, hyperoxia in this vulnerable population cannot be detected by pulse oximetry. Maintaining O 2 saturation intraoperatively at 93% to 95% (preductal) places most premature infants on the steep portion of the oxyhemoglobin dissociation curve and avoids severe hyperoxia. 64 Reported levels of expired CO 2 may not accurately reflect arterial pressure (Pa CO 2 ) if the infant has congenital heart disease or major intrapulmonary shunting. In infants, changes in BP, heart rate, and intensity of heart sounds are helpful indicators of cardiac function, intravascular volume status, and depth of anesthesia. Hepatic and renal function in premature infants is immature and suboptimal, and their anesthetic requirement is considerably less than that of more mature and robust infants.

Box 1-14 Premature Infants: Anesthetic Management

Normothermia critical
Reduced anesthetic requirement
Intraoperatively, maintain preductal oxygen saturation at 93% to 95%.
Prolonged expiratory time often helpful
Extubate only when infant is vigorous and fully awake.
Postoperative cardiopulmonary monitoring for 12 hours or longer
The combination of ventilatory depression from residual anesthetic drugs with immature development of respiratory control centers can cause postoperative hypoventilation and hypoxia as well as apnea. Therefore, these infants with ROP must be wide awake and vigorously responsive before they are extubated. When indicated by clinical circumstances, they should be carefully monitored postoperatively for at least 12 hours for signs of apnea, hypoxia, or bradycardia. The margin of safety for premature infants is narrow. They have minimal pulmonary reserve and rapidly become hypoxic.

Incontinentia Pigmenti
Bloch-Sulzberger syndrome, also known as incontinentia pigmenti, is a rare hereditary disease with dermatologic, neurologic, ocular, dental, and skeletal manifestations ( Box 1-15 ). Inherited as either an autosomal dominant gene or a sex-linked dominant gene, the condition is observed predominantly in female patients because it is usually lethal in males. Skin involvement is typically noted at birth. The dermatopathology begins with inflammatory linear vesicles or bullae that progress to verrucous papillomata and eventually to splashes of pigmentation ( Fig. 1-2 ). By adulthood, however, these lesions are replaced by atrophic, hypopigmented lesions. Patients are retarded, and spastic paralysis, 65 seizures, 66 microcephaly, hydrocephalus, and cortical atrophy have been reported.

Box 1-15 Incontinentia Pigmenti Patients: Anesthetic Management

Control seizures.
Careful airway manipulation because of pegged teeth
Avoid succinylcholine in patients with spastic paralysis.
Autonomic hyperreflexia possible with high spinal cord involvement

Figure 1-2 Incontinentia pigmenti.
This genetic disorder affects the skin, hair, teeth, nails, and central nervous system, often with cataracts and retinal vascular abnormalities. Excessive deposits of melanin discolor the skin of the trunk and extremities.
(Courtesy goldbamboo.com.)
Individuals with incontinentia pigmenti are often blind. In addition to cataracts and strabismus, they may have retinitis proliferans and other types of retinopathy, 67 - 69 chorioretinitis, uveitis, optic nerve atrophy, foveal hypoplasia, 70 and retinal tears or detachments. Partial anodontia and pegged or conical teeth are characteristic of the condition. Assorted skeletal anomalies are sometimes present.
The major anesthetic concerns involve the teeth and the central nervous system abnormalities. Because of the dental pathology, airway manipulation must be performed with care. Succinylcholine should be avoided in patients with spastic paralysis, and patients with a high level of spinal cord involvement theoretically could develop autonomic hyperreflexia. No particular anesthetic technique has been recommended for patients with incontinentia pigmenti.

Retinitis Pigmentosa
Retinitis pigmentosa consists of a group of diseases, frequently hereditary, marked by progressive loss of retinal response (as elicited by ERG). The diseases are characterized by retinal atrophy, attenuation of the retinal vessels, clumping of pigment, and contraction of the field of vision. Retinitis pigmentosa may be transmitted as a dominant, recessive, or X-linked trait and is sometimes associated with other genetic defects.
Electroretinography (ERG) is a stimulated reflex response study to evaluate a patient for retinitis pigmentosa. The test measures the electrical response of the retina to light stimulation; ERG should not be equated with visual evoked potential testing, which assesses polysynaptic cortical activity. In young children, the ophthalmologist may request general anesthesia to perform ERG. Although retinitis pigmentosa, absent other genetic abnormalities, presents no anesthetic challenges related to the patient’s medical condition, the conditions of the test and selection of anesthetic agent are noteworthy.
Dark adaptation is required before recording the electroretinogram to obtain accurate responses from the rod photoreceptors, so ERG is performed in total darkness. After induction of anesthesia, contact lens–like electrodes are placed on both corneas, with reference electrodes on the forehead and both earlobes. A dome-shaped photostimulator is lowered over the patient’s face, serving as a flashing light source. The anesthesiologist frequently must work in cramped quarters, without the usual OR accoutrements, including adequate lighting and readily accessible emergency equipment. Additionally, the young patient’s face is partially obscured by rather bulky ophthalmologic equipment, and access to the child’s airway is less than ideal. Anesthesia equipment must include a suction apparatus and an immediately available light source. Monitoring should incorporate an electrocardiograph, a pulse oximeter, and an end-tidal CO 2 monitor. The airway should be secured with an endotracheal tube (ETT) or a laryngeal mask airway (LMA).
An electroretinogram produces three distinct waveforms that measure electrical responses of different types of retinal cells. Electrical responses from the rod and cone photoreceptors produce an a wave. The b wave is the result of activity of the second-order rod and cone bipolar cells. The activity of amacrine cells is measured by oscillatory potentials. Both the amplitude and the time to peak (implicit time) can be measured for these waves.

Anesthetic concerns
The choice of anesthetic agents is somewhat traditional rather than truly evidence based. Although ERG is a simple rod-cone reflex response study, anesthetic agents may affect the amplitude and latency of the ERG responses, distorting the interpretation. Although known to cause nystagmus and enhanced electroencephalographic activity, ketamine purportedly does not modify ERG responses significantly in rabbits. 71 Information is sparse about the effects of anesthetic agents on ERG testing in humans. In pigs, however, propofol appears to preserve the photoreceptor response better than thiopental. 72 The effect of propofol on the electroretinogram was studied in 20 children having strabismus surgery, and under certain conditions, a decrease in the b-wave amplitude was noted. 73 Furthermore, in dogs, halothane and sevoflurane strongly depress the scotopic threshold response while moderately depressing the b wave and increasing oscillatory potential amplitudes. 74 In rats, photoreceptor and postreceptoral responses recorded under the barbiturate pentobarbital (Nembutal) and the dissociative agent zolazepam (Telazol) differ significantly. 75 Therefore, almost by default, ketamine became the agent of choice for ERG testing in children. Recently, however, isoflurane and sevoflurane have been used successfully in children having ERG, 76 as has propofol. 77
By way of contrast, a brief discussion of visual evoked potentials (VEPs) is indicated. The visual pathway includes the retina, optic nerve, optic chiasm, optic tracts, lateral geniculate nucleus in the thalamus, optic radiation, and occipital visual cortex. Retinal stimulation produces an evoked electrical response in the occipital cortex, which may be altered with impairment of the visual apparatus and associated neural pathways. VEPs are recorded from scalp electrodes positioned over the occipital, parietal, and central areas. They are cortical near-field potentials with long latencies. 78 More information is available about the effects of anesthetic agents on VEPs in humans than when ERG testing is involved. For example, generally all volatile anesthetics dramatically prolong VEP latency and decrease amplitude in a dose-dependent manner. 79, 80 With IV agents, induction doses of thiopental decrease the amplitude and prolong the latency of VEP waves, 81 whereas etomidate produces a small increase in latency with no alteration in amplitude. 82 Ketamine has negligible effect on latency but produces a 60% reduction in amplitude. 83 To date, the available data indicate that opioid and ketamine or propofol-based anesthetic techniques, as well as regimens using low-dose volatile anesthetics without nitrous oxide, allow satisfactory intraoperative recordings of VEPs, with the caveat that there may be a high incidence of false-positive or false-negative results. 84
In summary, because these potentials represent polysynaptic cortical activity, VEPs are exquisitely sensitive to the effects of anesthetic agents and physiologic factors. Furthermore, VEPs are extremely dependent on appropriate stimulation of the retina and may be adversely affected by narcotic-induced pupillary constriction. 85 In contrast, subcortical potentials, such as ERG responses, are probably less sensitive to anesthetic effects.

Eye Trauma
Eye trauma may be penetrating or blunt. Special anesthetic considerations apply in the patient with a penetrating eye injury. As in all cases of trauma, it is axiomatic that other injuries, such as intracranial trauma and possible thoracic or abdominal injury, must be excluded before surgically addressing the penetrating eye injury.
Open-eye injuries requiring surgical repair vary in severity from a small corneal leak to a totally disrupted globe with damage to the sclera, cornea, iris, and lens, accompanied by loss of vitreous, choroidal vessel hemorrhage, and retinal detachment. Frequently it is difficult to determine the extent of the injury until the patient has been anesthetized. However, retrobulbar or peribulbar blocks traditionally had not been recommended in patients with open globes or extensive ocular trauma; disrupting the eye further is a risk because of concerns about potential extrusion of intraocular contents from the pressure generated by local anesthetic administration, as well as other factors. Recently, however, there have been case reports of successful use of ophthalmic blocks in select patients. Scott et al. 86 at Bascom Palmer Eye Institute safely blocked patients with open-globe injuries. 86 Eyes selected for regional techniques typically involved less severe injuries resulting from either intraocular foreign bodies or dehiscence of cataract or corneal transplant incisions. The eyes tended to have more anterior, smaller wounds than those repaired under general anesthesia and were less likely to have a pupillary defect. Indeed, in some patients the wounds may have been self-sealing.

Anesthetic management
Once the decision has been made to administer general anesthesia, it is important to appreciate that any additional damage to the eye that transpires after the initial trauma is not necessarily the result of anesthetic drugs and manipulations. In many cases, for example, the patient may have been crying, coughing, vomiting, rubbing the eye, or squeezing the eyelids closed before anesthesia was induced. 87 These maneuvers are known to increase IOP dramatically. Even a normal blink increases IOP by 10 to 15 mm Hg; forced eyelid closure causes an increase in IOP of more than 70 mm Hg, an effect that may be ameliorated by performing a lid block to prevent lid spasm using the O’Brien technique. Increased IOP also results from other forms of external pressure, such as face mask application and from obstructed breathing or Valsalva maneuvers. Also, IOP is increased by succinylcholine and endotracheal intubation, especially if laryngoscopy is difficult or prolonged.
Ideal anesthesia for an eye trauma patient with a full stomach requires preoxygenation via a gently applied face mask, followed by a rapid-sequence induction with cricoid pressure and a smooth, gentle laryngoscopy and intubation, to ensure a stable IOP ( Box 1-16 ). Experts disagree, however, on the best way to accomplish these goals, particularly selection of a muscle relaxant to secure the airway most safely without causing extrusion of intraocular contents or pulmonary aspiration of gastric contents.

Box 1-16 Open Eye/Full Stomach Setting: Anesthetic Management

Avoid coughing, vomiting, and direct eye pressure.
Ensure adequate anesthetic depth before attempting laryngoscopy.
Administer appropriate adjuvants and neuromuscular blocker before laryngoscopy.
Perform gentle and brief laryngoscopy.
Maintain and monitor intraoperative paralysis.
Maintain stable venous and arterial pressures.
Prevent periextubation bucking and coughing.
Extubate only when patient is fully awake.
Nondepolarizing neuromuscular blocking agents relax the extraocular muscles and reduce IOP. In general, however, at least 3 minutes must pass before the usual doses of nondepolarizing drugs given in the traditional manner provide adequate paralysis for endotracheal intubation. During this interval, the unconscious patient’s airway is unprotected by a cuffed ETT, and aspiration could occur. Further, if paralysis is incomplete, the patient may cough or “buck” on the ETT, causing an increase in IOP of 40 mm Hg. In contrast, the depolarizing drug succinylcholine provides an opportunity for swift intubation, airway protection, and consistently excellent intubating conditions within 60 seconds. Succinylcholine is rapidly cleared, permitting the patient to return to spontaneous respiration, which is important if the patient has a difficult airway. Succinylcholine, however, increases IOP by approximately 8 mm Hg. This relatively small increase occurs 1 to 4 minutes after IV administration, and within 7 minutes IOP values return to baseline. Factors contributing to the ocular hypertensive effect of succinylcholine are incompletely understood.
Interventions advocated to prevent succinylcholine-induced increases in IOP include pretreatment with acetazolamide, propranolol, lidocaine, 88 narcotics, 89 clonidine, 90 and nondepolarizing relaxants. None of these interventions, however, consistently and completely blocks the ocular hypertensive response. 91, 92 The use of succinylcholine in patients with open globes has traditionally been considered controversial, although this philosophy may be based more on anecdote and “zero tolerance” for a potential anesthesia-related complication than on incontrovertible scientific evidence. 93
If the anesthesiologist elects to use a nondepolarizing agent instead of succinylcholine, the administration of high-dose (400 μg/kg) vecuronium 94 or enlisting the “priming” technique 95 may accelerate the onset of available nondepolarizing muscle relaxants. With priming, approximately one tenth of an intubating dose of muscle relaxant is followed 4 minutes later by an intubating dose. After an additional 90 seconds, intubation may be accomplished. However, the use of large doses of nondepolarizing agents and the priming technique have serious disadvantages, including the risk of aspiration during the interval when the airway is unsecured and the unpredictable onset of sufficient paralysis to permit intubation without coughing. If high doses of such agents as atracurium or mivacurium are used, histamine release can cause untoward side effects, including hemodynamic instability. Large doses (1.2 mg/kg) of rocuronium do not consistently afford conditions for intubation as excellent as provided by succinylcholine. Rapacuronium, the nondepolarizing agent with a rapid onset, showed promise in this setting, but the occurrence of intractable bronchospasm reported after its administration resulted in its removal from U.S. markets.
An acceptable option, unless contraindicated by such conditions as hyperkalemia or a susceptibility to malignant hyperthermia, is to administer succinylcholine after pretreatment with a defasciculating dose of a nondepolarizing relaxant and, if necessary, an appropriate drug to prevent significant BP increases associated with laryngoscopy. Cases appear in the literature attesting to the apparent safety of using succinylcholine in the open eye/full stomach setting 96, 97 (see Box 1-16 ).
After intubation is safely and smoothly accomplished, the depth of anesthesia and the extent of muscle relaxation must be adequate to ensure lack of movement and to prevent coughing while the eye is open. This is best determined and followed by assessing the effects of peripheral nerve stimulation with a twitch monitor. Moreover, BP should be carefully maintained within an acceptable range, because choroidal hemorrhage is more likely in open-eye situations when hypertension and increased venous pressure are also present. Prophylactic administration of antiemetics is recommended to prevent postoperative vomiting. When surgery has been completed and spontaneous respiration has returned and the patient is awake with intact reflexes to prevent aspiration, the ETT is removed. IV lidocaine (1.5 mg/kg) and a small dose of narcotic may be given before extubation to attenuate periextubation bucking and coughing.
In summary, the decision to administer or avoid succinylcholine involves assessing and balancing risks for the individual patient. The critical factors in this individual calculation are the airway assessment, extent of ocular damage, and any potential medical contraindication to a particular approach. 98 A patient with a medical contraindication to succinylcholine, such as malignant hyperthermia susceptibility, whose airway assessment is reassuring may be managed using sufficiently large doses of a nondepolarizing neuromuscular blocker to enable accelerated onset of paralysis and satisfactory intubating conditions. Maintenance could then be accomplished with a total IV anesthetic technique. When confronted with a patient whose airway evaluation suggests potential problems, the anesthesiologist should consult with the ophthalmologist about the likelihood of salvaging the injured eye. In patients with minor injury, general anesthesia may be avoided by proceeding under topical or regional anesthesia. If this approach is not feasible because of extensive ocular damage, awake fiberoptic intubation may be the safest choice, realizing that substantial increases in IOP may ensue from gagging, retching, and coughing. These risks, however, pale in significance when balanced against the consequences of a lost airway.

Ear, nose, and throat considerations
Difficulty in managing the airway is a major cause of anesthesia-related morbidity and mortality. When the proposed surgical procedure involves the airway, consummate skill in airway management is required, especially because of possible airway compromise preoperatively by edema, infection, tumor, or trauma. Moreover, the anesthesiologist and the surgeon often must share the patient’s airway, so effective communication is critical to effect an optimal patient outcome.

Sleep Apnea
Sleep patterns disturbed by snoring are thought to occur in approximately 25% of the population. 99 However, most patients who snore do not have apnea or associated episodes of significant hypoxemia. Nonetheless, obstructive sleep apnea (OSA) is a relatively common disorder among middle-aged adults, especially (obese) Americans. Obesity is a critical independent causative/risk factor. The majority of people who have OSA are obese, and the severity of the condition seems to correlate with the patient’s neck circumference 100 and abdominal girth. Not all obese patients have OSA, however, and not all patients with OSA are obese. In the nonobese minority of OSA patients, causative risk factors are craniofacial and orofacial bony abnormalities, nasal obstruction, and hypertrophied tonsils. Young et al. 100 reported that the prevalence of OSA associated with hypersomnolence was 2% in women and 4% in men 30 to 60 years old.
Nonetheless, a much higher proportion of patients may be at risk for OSA, and the vast majority of these patients are undiagnosed. Because the anesthetic ramifications are important, it is critical to take a careful history, including sleep patterns, and harbor a high index of suspicion for the condition.
Obstructive sleep apnea is defined as cessation of airflow for more than 10 seconds despite continuing ventilatory effort, five or more times per hour of sleep, and usually associated with a decrease in arterial oxygen saturation (Sa O 2 ) of more than 4%. Although this review focuses predominantly on OSA, the three types of sleep apnea are obstructive, central, and mixed. Unlike OSA, respiratory efforts temporarily stop in central sleep apnea. Diagnosis is established definitively during polysomnography.
It is generally accepted that many patients with OSA have resultant pathologic daytime sleepiness associated with performance decrements. Also, patients with severe apnea develop major health problems; whether patients with less severe apnea incur the same detrimental consequences remains controversial because of methodologic problems and failure to control for confounding factors in many relevant investigations. Clearly, the study design with the greatest methodologic rigor for the identification of long-term health consequences of OSA is the prospective, population-based, cohort study. 101 Most clinical research in OSA, however, has used less rigorous research designs, such as case-control, cross-sectional, or case studies, which are more susceptible to problems of bias and less able to establish causality between adverse health consequences and OSA. Thus, few absolute conclusions can be drawn at this time about the long-term consequences of mild to moderate OSA. However, findings from the Sleep Heart Health Study, 102 the Copenhagen City Heart Study, 103 and others 104 demonstrate a firm association between sleep apnea and systemic hypertension, even after accounting for other important patient characteristics, such as age, gender, race, consumption of alcohol, and use of tobacco products.
Few definitive data exist to guide perioperative management of patients with OSA ( Box 1-17 ). Not surprisingly, many anesthesiologists question whether OSA patients are appropriate candidates for ambulatory surgery. The risks of caring for these challenging patients in the ambulatory venue are further amplified by 80% to 95% of people with OSA being undiagnosed; 105 they have neither a presumptive clinical diagnosis nor a sleep study diagnosis of OSA. This is of concern because these patients may suffer perioperatively from life-threatening desaturation and postoperative airway obstruction. Moreover, serious comorbidities may be present because prolonged apnea results in hypoxemia and hypercarbia, which can lead to increased systemic and pulmonary artery pressures and dysrhythmias. Cor pulmonale, polycythemia, and CHF may develop.

Box 1-17 Sleep Apnea Patients: Anesthetic Management

Have high index of suspicion with obesity.
Identify and quantify comorbid disease(s).
Perform meticulous airway assessment.
Have low threshold for awake intubation.
Administer sedative-hypnotics and narcotics sparingly.
Use short-acting anesthetic drugs.
Administer multimodal analgesics.
Extubate only when patient is fully awake.
Recover in sitting position
Be able to administer continuous positive airway pressure.
Admit to telemetry ward when indicated.
Sleep apnea occurs when the negative airway pressure that develops during inspiration is greater than the muscular distending pressure, thereby causing airway collapse. Isono 106 emphasizes that patients with OSA have narrower, more collapsible airways than age-matched and body mass index (BMI)–matched, non-OSA patients. Obstruction can occur throughout the upper airway, above, below, or at the level of the uvula. 107, 108 Because of the inverse relationship between obesity and pharyngeal area, the smaller size of the upper airway in the obese patient causes a more negative pressure to develop for the same inspiratory flow. 108, 109 Also, a neurologic basis has been postulated for OSA, in that the neural drive to the airway dilator muscles is insufficient or is not coordinated appropriately with the drive to the diaphragm. 108 Indeed, it has been hypothesized that OSA is associated with complicated neuroanatomic interactions. During wakefulness, OSA patients have augmented basal genioglossus activity to compensate for their narrower, more collapsible airway. However, neural compensation for anatomic abnormalities that are operative during wakefulness is abolished during sleep. 110 Pharyngeal wall collapsibility is exacerbated by the reduced lung volumes associated with obesity. 106 The caudal tracheal traction that occurs during inspiration is reduced in obese, supine adults. This traction is thought to enhance longitudinal tension of the pharyngeal airway wall, thereby stiffening the airway. 111 Thus, it is important to maintain lung volume in patients with OSA, which is facilitated by the sitting or semisitting position.
Obstruction can occur during any sleep state but is often noted during rapid eye movement (REM) sleep. Nasal continuous positive airway pressure (CPAP) can ameliorate the situation by keeping the pressure in the upper airway positive, thus acting as a “splint” to maintain airway patency. The site(s) of obstruction can be determined preoperatively by magnetic resonance imaging (MRI), CT, and intraluminal pressure measurements during sleep. 112 Some studies suggest that the major site of obstruction in most patients is at the oropharynx, but obstruction can also occur at the nasopharynx, hypopharynx, and epiglottis. 113 If the surgery is designed to relieve obstruction at one area but a pathologic process extends to other sites, 114 postoperative obstruction is not only possible but probable, especially when one allows for the edema associated with airway instrumentation. Technologic advances have made CPAP devices more tolerable to patients. Weight loss may improve OSA as well.
French investigators observed that some patients who received a pacemaker with atrial overdrive pacing to reduce the incidence of atrial dysrhythmias reported a reduction in breathing disorders after pacemaker implantation. These cardiologists therefore initiated a study to investigate the efficacy of atrial overdrive pacing in the treatment of sleep apnea symptoms in consecutive patients who required a pacemaker for conventional indications. They found that atrial pacing at 15 beats per minute faster than the mean nocturnal heart rate resulted in a significant reduction in the number of episodes of both central sleep apnea and OSA. 115 Postulating that enhanced vagal tone may be associated with (central) sleep apnea, the investigators acknowledged, however, that the mechanism of the amelioration of OSA by atrial overdrive pacing is unclear. Moreover, whether these unexpected findings are germane to the sleep apnea patient with normal cardiac function is uncertain. Gottlieb 116 suggests that a central mechanism affecting both respiratory rhythm and pharyngeal motor neuron activity would offer the most plausible explanation for the reported equivalence in the improvement of central sleep apnea and OSA during atrial overdrive pacing. Do cardiac vagal afferents also inhibit respiration? Identification of specific neural pathways might also advance efforts to develop a pharmacologic treatment for sleep apnea.
Surgical approaches to treat sleep-related airway obstruction include classic procedures such as tonsillectomy that directly enlarge the upper airway. More specialized procedures to accomplish the same objective include uvulopalatopharyngoplasty (UPPP), uvulopalatal flap (UPF), uvulopalatopharyngoglossoplasty (UPPGP), laser midline glossectomy (LMG), linguoplasty (LP), inferior sagittal mandibular osteotomy and genioglossal advancement (MOGA), hyoid myotomy (HM) and suspension, and maxillomandibular osteotomy and advancement (MMO). Another approach is to bypass the pharyngeal part of the airway with a tracheotomy.
Although physicians and surgeons have been treating OSA for more than 25 years, few long-term, standardized results on the efficacy of different therapies are available. One report, however, suggests that at least 50% of patients with sleep apnea syndrome can be managed effectively with a single therapy or combination of therapies. Nasal CPAP, tracheotomy, MMO, and tonsillectomy typically receive high marks for efficacy; 117 UPPP showed positive results maintained for at least 1 year. 118 Another study, combining UPPP with genioglossus and hyoid advancement, reported encouraging results in patients with mild and moderate OSA and multilevel obstruction. 119 However, the long-term results of laser-assisted uvulopalatoplasty (LAUP) for management of OSA have been a concern. 120 The favorable, subjective, short-term results of LAUP apparently deteriorated over time. Postoperative polysomnography revealed that LAUP might lead to deterioration of existing apnea. These findings are probably related to velopharyngeal narrowing and progressive palatal fibrosis caused by the laser beam.
The debate about whether OSA patients should undergo surgery as outpatients is ongoing, with no “one size fits all” solution. 105 Any management strategy must consider the patient’s BMI and neck circumference, severity of OSA, presence or absence of associated cardiopulmonary disease, nature of the surgery, and anticipated postoperative opioid requirement. The degree of fat accumulation in the intra-abdominal region is associated with the metabolic syndrome and secretion of hormones and proinflammatory cytokines that may influence breathing in obese OSA patients. 121 Screening tests for OSA include the Berlin questionnaire, STOP-Bang instrument, American Society of Anesthesiologists (ASA) checklist, and Kushida morphometric index; these are highly accurate for identifying only severe OSA and have high false-negative rates for detecting mild OSA. 122 The “gold standard” for identifying and quantifying the presence and severity of OSA is polysomnography, but it is expensive, cumbersome to perform, and not universally available.
It seems reasonable to expect that OSA patients without multiple risk factors who are having relatively noninvasive procedures (e.g., carpal tunnel repair, breast biopsy, knee arthroscopy) typically associated with minimal postoperative pain may be candidates for ambulatory status. However, those individuals with multiple risk factors, or those OSA patients having airway surgery, most probably will benefit from a more conservative approach that includes postoperative admission and careful monitoring. Indeed, the 2006 ASA guidelines specifically state that adult airway surgery, tonsillectomy in children younger than 3 years, and laparoscopic surgery involving the upper abdomen are inadvisable outpatient procedures for OSA patients. 123 It is imperative to appreciate that these patients are exquisitely sensitive to the respiratory depressant effects of opioids. Moreover, the risk of prolonged apnea is increased for as long as 1 week postoperatively. A recent national (U.S.) study of inpatients having noncardiac surgery reported that sleep apnea is an independent risk factor for perioperative pulmonary complications, including aspiration pneumonia, adult respiratory distress syndrome, and the need for postoperative intubation or mechanical ventilation. 124

Anesthetic management
Is perioperative risk related to the type of anesthesia (general, regional, or monitored care) administered to sleep apnea patients? The limited evidence suggests that type of surgery probably supersedes selection of anesthetic technique. Certainly, the use of regional anesthesia, although strongly recommended by the ASA, may not necessarily obviate the need for securing the airway and may even require emergency airway intervention if excessive amounts of sedative-hypnotics or opioids are administered. Regardless of the type of anesthesia selected, sedation should be administered judiciously. CPAP or noninvasive positive-pressure ventilation (NIPPV) should be applied as soon as possible after surgery to patients who were receiving it preoperatively. The supine position should be avoided, if feasible, during recovery. The sitting position fosters improved lung volumes, which tend to minimize pharyngeal collapsibility. In addition, the ASA guidelines state that OSA patients should be monitored postoperatively for 3 hours longer than usual, and for 7 hours after the last episode of obstruction or room-air hypoxemia. 123 Patients should be awake and alert, have O 2 saturation within 2% of baseline, and have minimal pain and postoperative nausea/vomiting at discharge.
When confronted with an especially challenging OSA patient requiring general anesthesia, a judicious approach may include awake fiberoptic intubation; administering very-low-dose short-acting narcotics, short-acting muscle relaxants, and a low-solubility inhalational agent; and infiltrating the surgical site with a long-acting local anesthetic. Extubation should be performed only when the patient is without residual neuromuscular blockade and is fully awake, using a tube changer or catheter, and CPAP should be administered postoperatively. These high-risk patients should then be admitted to a telemetry ward or intensive care unit, because the challenge of maintaining the airway will extend well into the postoperative period, and OSA is an independent risk factor for perioperative pulmonary complications. 124 Respiratory events after surgery in OSA patients may occur at any time.
Anesthetic care of the OSA patient is especially challenging, and few definitive data are available to guide perioperative management, with recommendations based more on expert opinion than on evidence. The anesthesiologist should begin by having a high index of suspicion for the diagnosis and then seek to identify and quantify associated comorbidities. The major focus of the anesthesiologist must be establishing and maintaining the airway, a challenge that continues postoperatively, especially if surgery involves the oropharyngeal or hypopharyngeal area. Depending on the type of surgery, the anticipated amount of narcotic required postoperatively to manage pain, and the patient’s condition, outpatient surgery may not be prudent. The resources of the facility must also be considered when deciding whether to accept an OSA patient. Certain OSA patients might be appropriate for a hospital-based ambulatory surgery unit, but not for a freestanding facility or an office. The importance of effective communication, monitoring, vigilance, judgment, and contingency planning cannot be overemphasized.

Recurrent Respiratory Papillomatosis
Recurrent respiratory papillomatosis (RRP) is a disease of viral origin caused by human papillomavirus types 6 and 11 (HPV-6 and HPV-11) and associated with exophytic lesions of the airway that are friable and bleed easily ( Fig. 1-3 ). Although a benign disease, RRP may have devastating consequences because of the airway involvement, unpredictable clinical course, and risk of malignant conversion in chronic invasive papillomatosis.

Figure 1-3 Laryngeal papillomatosis.
Severe stridor and airway obstruction can occur.
(Courtesy goldbamboo.com.)
In children, RRP is both the most common benign neoplasm of the larynx and the second most frequent cause of hoarseness. 125 The disease is frustrating and often resistant to treatment because it tends to recur and spread throughout the respiratory tract. Although RRP most frequently affects the larynx, the condition can involve the entire aerodigestive tract.
The course of RRP is highly variable; some patients undergo spontaneous remission, whereas others experience aggressive papillomatous growth, necessitating multiple surgeries over many years. The differential diagnosis of the persistent or progressive stridor and dysphonia associated with RRP in infants includes laryngomalacia, subglottic stenosis, vocal cord paralysis, or a vascular ring ( Box 1-18 ).

Box 1-18 Differential Diagnosis of Infantile Progressive Stridor/Dysphonia

Laryngomalacia
Recurrent respiratory papillomatosis
Subglottic stenosis
Vocal cord paralysis
Vascular ring
In most pediatric series, RRP is typically diagnosed between 2 and 4 years of age, with a delay in correct diagnosis from time of symptom onset of about 1 year. 126 The incidence among U.S. children is estimated at 4.3 per 100,000, translating into more than 15,000 surgical interventions at a total cost exceeding $100 million annually. 127
Two distinct forms of RRP are recognized: a juvenile or aggressive form and an adult or less aggressive form. Adult-onset RRP may reflect either activation of virus present from birth or an infection acquired in adolescence or adulthood. HPV-6 and HPV-11, the same types that cause genital warts, are the most common types of HPV identified in the airway. Specific viral subtypes may be correlated with disease severity and clinical course. Children infected with HPV-11, for example, appear to develop more severe airway obstruction at a younger age and have a higher incidence of tracheotomy. 128 Numerous studies have linked childhood-onset RRP to mothers with genital HPV infections. Nevertheless, few children exposed to genital warts at birth develop clinical symptoms. 129 Other factors must be operative, such as duration and volume of virus exposure, behavior of the virus, presence of local trauma, and patient immunity.
Presenting symptoms of RRP include a change in voice, ranging from hoarseness to stridor to aphonia. The stridor can be either inspiratory or biphasic. The history may include chronic cough and frequent respiratory infections. Children are frequently misdiagnosed initially as having croup, chronic bronchitis, or asthma. Lesions usually are found in the larynx but may also occur on the epiglottis, pharynx, or trachea. The preoperative diagnosis is best made with an extremely small-diameter, flexible fiberoptic nasopharyngoscope to establish more fully the extent of airway encroachment.
No single modality has consistently been shown to eradicate RRP. The primary treatment is surgical removal, with a goal of complete obliteration of papillomas and preservation of normal structures. However, in patients with anterior or posterior commissure disease or extremely virulent lesions, the objective may be revised to subtotal removal with clearing of the airway. It is advisable to “debulk” as much disease as possible, while preventing the complications of subglottic and glottic stenosis, web formation, and diminished airway patency. Whenever possible, tracheostomy is avoided to prevent seeding of papillomas into the distal trachea.
The CO 2 laser has been the favored instrument in the eradication of RRP involving the larynx, pharynx, upper trachea, and nasal and oral cavities. However, large, bulky accumulations of papillomas may require sharp dissection. Adjuvant treatments may include interferon alfa-N1, 130 indole-3-carbinol, acyclovir, ribavirin, 131 retinoic acid, and photodynamic therapy. 132 Clearly, the objective of all interventions is to remove as much disease as feasible without causing potentially scarring permanent damage to underlying mucosa in critical areas. Although the CO 2 laser is the most common laser for laryngeal RRP, the KTP (potassium titanyl phosphate) or argon laser can also be used. Papillomas that extend down the tracheobronchial tree often require the KTP laser coupled to a ventilating bronchoscope for removal. Moreover, the endoscopic microdebrider may cause less laryngeal scarring than the CO 2 laser. 133

Anesthetic management
The anesthetic management of patients with RRP is often challenging and depends on the site of the lesions, degree of airway obstruction, and age of the patient 134 ( Table 1-2 ). The issues are further complicated by use of a laser and the anesthesiologist sharing the airway with the surgeon. Several approaches should be considered, each with advantages and disadvantages. A thoughtful risk/benefit analysis is essential. Teamwork and effective communication are critical to optimal outcome; video monitors allow the entire OR staff to view the surgery. The anesthesiologist and surgeon must communicate throughout the procedure, focusing on the patient’s current ventilatory status, amount of bleeding, vocal cord motion, O 2 concentration administered, and timing of laser use with respiration.
Table 1-2 Anesthetic Options for Recurrent Respiratory Papillomatosis Intubation Techniques Nonintubation Techniques Surgeon gowned and gloved before induction Same pretreatment and precautions as with intubation Preoperative dexamethasone   Slow, gentle inhalation induction with continuous positive airway pressure Insufflation of volatile agents with spontaneous ventilation Intubate with smaller-than-usual, laser-safe endotracheal tube Total intravenous anesthesia with spontaneous ventilation Eye protection for patient and staff Jet ventilation with muscle paralysis Fi O 2 <0.3 *   Awake extubation  
* Fraction of inspired oxygen concentration.
The available anesthetic options may be broadly separated into intubation and nonintubation techniques. When the lesions are assumed to be partially obstructing the airway, the best approach is a careful, gentle, smooth induction with sevoflurane, preferably with an IV line in place before induction is initiated. Preoperative IV dexamethasone, 0.5 mg/kg, is routinely given. The surgeon should be present in the OR, and all the requisite equipment to deal with total airway obstruction should be immediately available. Often a jaw thrust combined with positive pressure in the anesthesia circuit will maintain airway patency. Should complete airway obstruction occur, the anesthesiologist may elect to give an appropriate dose of propofol, if indicated, and attempt intubation with a smaller-than-usual ETT. If this attempt fails, the surgeon should use the rigid bronchoscope; as a last resort, a transtracheal needle should be placed or tracheotomy performed. The anesthesiologist may then choose among several techniques.
An intubation technique has the advantage of allowing the anesthesiologist to maintain control of the airway and ventilation. However, the ETT increases the risk of airway fire and may impede surgical exposure and access. The smallest possible laser-safe ETT tube should be used that permits adequate ventilation. If a cuffed tube is deemed necessary, the cuff should be filled with methylene blue–colorized saline to provide an additional warning if the cuff is perforated. 135 After the airway has been secured with a laser-safe ETT, the anesthesiologist has the option to administer muscle relaxants. The child’s eyes are protected with moist, saline-soaked gauze eye pads placed over the lids. Additionally, all OR personnel must wear safety glasses and special laser masks with extremely small pores to minimize exposure to the laser plume. The Fi O 2 delivered to the patient should be as close to a room air mixture as possible (0.26-0.3). During resection, the surgeon must exercise great care to avoid injuring the anterior commissure, and at least 1 mm of untreated mucosa should be left so that a web does not develop. If the surgeon detects disease in the posterior part of the glottis or in the subglottic region, the ETT obstructs exposure of these areas to the operative field, and an alternative means of anesthesia is selected. Often the surgeon will prefer an apneic technique in which the ETT is removed intermittently and surgery performed while the patient’s O 2 saturation is monitored. The ETT is periodically reinserted as needed. Typically, the lungs are reoxygenated for the same period that they were apneic before proceeding with the next “cycle.”
Alternatively, a nonintubation technique uses spontaneous ventilation with volatile anesthetic agents. 136, 137 The patient is induced as previously detailed, and maintenance of anesthesia is continued with sevoflurane, insufflated into the oropharynx by attaching the fresh gas flow hose to a side port on the suspension laryngoscope. The larynx is anesthetized with topical lidocaine (not to exceed 4-5 mg/kg) before proceeding with further surgical intervention. This is not an ideal (or easy) anesthetic technique because the anesthesiologist must deftly balance the anesthetic depth somewhere between too light (triggering laryngospasm) and too deep (causing apnea). Additionally, the OR environment becomes contaminated, but a vacuum hose is helpful in extracting exhaled gases and virus particles. Total IV anesthesia with an infusion of propofol and remifentanil is also appropriate with this nonintubated, spontaneous ventilation technique. 134 The surgeon, however, may complain of too much laryngeal movement with total IV anesthesia because patients anesthetized with these agents breathe slowly but very deeply.
Another anesthetic alternative is the use of jet ventilation, which eliminates the potential for ETT fire and allows good visualization of the vocal cords and distal areas. However, jet ventilation carries the risk of barotrauma and may allow transmission of HPV particles into the distal airway. The jet cannula can be positioned above or below the vocal cords; placement of the cannula proximal to the end of the laryngoscope decreases the risk of possible pneumothorax or pneumomediastinum. With large laryngeal lesions, narrowed airways, and ball-valve lesions, considerable outflow obstruction may develop, leading to increased intrathoracic pressure and pneumothorax. The anesthesiologist must carefully observe chest excursion and ensure unimpeded exhalation. Muscle relaxants are administered to prevent vocal cord motion. Constant anesthesiologist-surgeon communication is required on timing of ventilation in relation to surgical manipulation. Excessive mucosal drying and gastric distention are other disadvantages of jet ventilation. At the end of the procedure, the trachea is intubated with a standard ETT.
The trachea is extubated only when the child is fully awake. High humidity and, occasionally, racemic epinephrine are administered postoperatively. The patient is closely monitored for several hours before discharge, and often an overnight stay is advisable, especially if the disease was extensive and the airway was significantly compromised. Continuous pulse oximetry is mandatory and postoperative steroid administration may be helpful.

Summary
The scientific community is aggressively working to improve knowledge of RRP. A national registry of patients with RRP has been formed through the cooperation of the American Society of Pediatric Otolaryngology and the Centers for Disease Control and Prevention. 138 This registry identifies patients who are suitable for enrollment in multi-institutional studies of adjuvant therapies and better defines the risk factors for transmission of HPV and the cofactors that determine the virulence of RRP. Future projects will refine surgical techniques to minimize laryngeal scarring.

Cystic Hygroma
Cystic hygroma is a rare, multilocular, benign lymphatic malformation, usually involving the deep fascia of the neck, oral cavity, and tongue, although the axilla may also be affected ( Fig. 1-4 ). A cystic hygroma in a developing fetus can progress to hydrops and eventually fetal death. Some cases of congenital cystic hygroma resolve, leading to webbed neck, edema, and a lymphangioma. In other cases the hygroma can progress in size to become larger than the fetus. Cystic hygromas can occur as an isolated finding or in association with other birth defects and result from environmental, genetic, and unknown factors.

Figure 1-4 Cystic hygroma.
This histologically benign, lymphatic malformation can produce severe airway encroachment.
(Courtesy valuemd.com.)
When a cystic hygroma is diagnosed prenatally, the risk for a chromosomal abnormality approaches 50%. Cystic hygromas that develop in the third trimester or in the postnatal period, however, are usually not associated with abnormalities. These lesions are capable of massive growth and can be quite disfiguring. Almost all known cases of cystic hygroma have presented by 5 years of age, with most being observed in the neonatal period. 139 In fact, there are cases of antenatal diagnosis of cystic hygroma, with fetal airway encroachment detected by screening ultrasound. The few infants who survived to delivery were intubated immediately after the head was delivered, with the placenta functioning as an extracorporeal source of oxygenation until the airway was secured. 140, 141
As the tumor grows, it often encroaches on surrounding structures such as the pharynx, tongue, or trachea. Dysphagia and various degrees of airway obstruction can occur. Cystic hygromas are not responsive to radiation therapy, and multiple surgical resections are often necessary. Because the tumors are not encapsulated, hygromas easily envelop and grow into surrounding structures, preventing complete excision. The ability of cystic hygromas to elude complete extirpation has led to recrudescence, with injection of sclerosing agents intralesionally as primary or adjunctive therapy. 142 This approach had been abandoned, but the availability of newer, improved agents has led to better results.
Although sudden enlargement of the tumor can cause a true airway emergency, most often the children present for elective resection. Because of mechanical complications, the young child may be malnourished or dehydrated and may also have sleep apnea. Stridor is an ominous sign, suggesting imminent airway decompensation. A chest radiograph should be reviewed for tracheal deviation or mediastinal extension. Although CT or MRI will provide more complete information about the full extent of the lesion, the sedation necessary to obtain such studies may cause airway obstruction—an example of “perfection being the enemy of good.”

Anesthetic management
The patient with cystic hygroma is given an antisialagogue before anesthesia is administered to minimize secretions that might complicate anesthetic management ( Box 1-19 ). The surgeon is present in the OR, gowned and gloved, and ready to perform a tracheostomy if necessary. The anesthesiologist must carefully prepare a variety of difficult airway equipment in the event of an airway emergency. Clearly, the safest approach in these children is awake intubation, because a marginally adequate airway while the patient is awake may become totally obstructed during induction when the upper airway muscles relax and the tumor fills the airway.

Box 1-19 Cystic Hygroma Patients: Anesthetic Management

Evaluate preoperatively for stridor, tracheal deviation, or mediastinal extension.
Determine optimally tolerated position.
Administer preoperative antisialagogue.
Have surgeon gowned and gloved before induction/intubation.
Apply topical vasoconstrictor to nares.
Know that fiberoptic nasotracheal intubation is often necessary.
Perform extubation with caution.
However, because many, if not most, pediatric patients will not tolerate an awake intubation, children with cystic hygroma often undergo a slow, meticulous, titrated inhalation induction of anesthesia, with preservation of spontaneous ventilation and application of CPAP. When anesthetic depth is adequate, fiberoptic intubation is performed. A large, protruding tongue often makes oral intubation impossible, so the nasal route is chosen after administration of an appropriate vasoconstrictor to the nostrils. (If an unsuccessful direct laryngoscopy or an attempt at blind nasal intubation is performed initially, these approaches may trigger bleeding that could hamper subsequent attempts at fiberoptic intubation.) When the surgery is completed, it is helpful to perform direct laryngoscopy because the view may have improved significantly after the resection. 134 This information will prove useful in the event that reintubation is required postoperatively.
If attempts at fiberoptic intubation are unsuccessful, other options include passing a retrograde wire after asking the surgeon to aspirate fluid from the mass (which the surgeon may decline to perform because of concern about recurrence from an incompletely resected, ruptured sac), using a light wand or Bullard laryngoscope, attempting tactile intraoral tube placement, or trying a blind nasal intubation. In the event that these attempts fail and mask ventilation becomes inadequate, an LMA should be inserted. If this fails to open the airway, an emergency surgical airway should be attempted. In the event the surgeon is unable to expose the trachea, the only remaining option to save the child may be femoral cardiopulmonary bypass. 134

Wegener’s Granulomatosis
Wegener’s granulomatosis (WG) is a systemic disease of unknown etiology characterized by necrotizing granulomas and vasculitis that classically affects the upper and lower airways and the kidneys ( Fig. 1-5 ). Although the etiology is still not established, Staphylococcus aureus may play a role in the pathophysiology. 143 WG patients can have a myriad of head and neck manifestations, including mucosal ulceration of the nose, palate, larynx, and orbit, as well as deafness and subglottic 144 or tracheal stenosis. Ocular disease occurs in 50% to 60% of adults with WG 145 and may include such conditions as necrotizing scleritis with peripheral keratopathy, 146 orbital pseudotumor, 145 and ocular myositis, 145 as well as uveitis, vitreous hemorrhage, and central retinal artery occlusion. 147

Figure 1-5 Wegener’s granulomatosis.
This sometimes fatal vasculitis can cause saddle-nose deformity (perforated nasal septum, mucosal ulcerations, and underlying bone destruction of oral cavity) and necrotizing granulomas of the airway.
(From Aries P, Ullrich S, Gross W: A case of destructive Wegener’s granulomatosis complicated by cytomegalovirus infection, Nat Clin Pract Rheumatol 2:511-515, 2006.)
Wegener’s granulomatosis often starts with severe rhinorrhea, cough, hemoptysis, pleuritic pain, and deafness. However, WG is a truly systemic disease and varies widely in presentation. Some disease presentations are more subtle and indolent than the more typical, fulminant presentation. Indeed, the protean manifestations of WG often produce diagnostic delay. Diagnosis is supported by histopathologic studies showing a vasculitis, parenchymal necrosis, and multinucleate giant cells, but tissue biopsy alone is insufficient to establish the diagnosis of WG. The most specific test is a positive antineutrophil cytoplasmic autoantibody test (c-ANCA). 148 However, approximately 10% of patients with clinical phenotypes identical to those of ANCA-positive patients may be ANCA negative and may also respond to all anti-inflammatory or immunosuppressive therapies shown to be effective for seropositive patients. 149
Wegener’s granulomatosis was once fatal. With the advent of long-term corticosteroid and immunosuppressive therapy, however, WG patients survive longer, with a broader spectrum of disease observed in recent years. The incidence of subglottic stenosis in WG ranges from 8.5% to 23%. 150 It is a major cause of morbidity and mortality and typically is unresponsive to systemic chemotherapy. Other treatments have included mechanical subglottic dilation (with or without intratracheal steroid injection) and laser therapy, with variable success. Subglottic stenosis has been treated with endoscopic insertion of nitinol stents after dilation of the stenotic segment with bougie dilators. 144 Nitinol is a nickel-titanium alloy that has excellent properties, including biocompatibility, kink resistance, and elasticity, thus resembling the tracheobronchial tree. These metal stents are expandable, serving as an intraluminal support to establish and maintain airway patency. They are usually permanent but can be removed if necessary. For the intervention to be successful, however, the diseased segment must begin at least 1 cm below the vocal cords.

Anesthetic concerns
Patients with WG often present for ocular, nasal, or laryngeal surgery. The anesthesiologist must anticipate a host of potential problems ( Box 1-20 ). These challenges include addressing the side effects of chronic corticosteroid and aggressive immunosuppressive therapy as well as the presence of underlying pulmonary and renal disease. Although several years ago cyclophosphamide was credited with prolonging life in patients with WG, current thinking is that chronic long-term cyclophosphamide therapy is no longer justified. Remission maintenance therapies with methotrexate or azathioprine are as effective as prolonged cyclophosphamide and are much safer. 151 Additionally, midline necrotizing granulomas of the airway may cause obstruction or bleeding at intubation. Some degree of subglottic or tracheal stenosis should also be expected. Chest radiography, CT, or MRI of the airway; arterial blood gas analysis; pulmonary function tests; and blood urea nitrogen (BUN)/creatinine levels are helpful guides to optimal anesthetic management. (See also Chapter 4 .)

Box 1-20 Wegener’s Granulomatosis: Anesthetic Concerns

Side effects of steroids and immunosuppressive agents
Bleeding induced by airway manipulation
Subglottic stenosis
Tracheal stenosis
Reduced pulmonary reserve
Impaired renal function

Acromegaly
Acromegaly is a rare chronic disease of midlife caused by excess secretion of adenohypophyseal growth hormone (GH). Hypersecretion of GH before epiphyseal closure produces gigantism in younger individuals. GH acts on a wide variety of tissues, both directly and through insulin-like growth factor I (IGF-I), which is released mainly from the liver in response to GH. In addition to stimulating bone and cartilage growth, GH and IGF-I promote protein synthesis and lipolysis while reducing insulin sensitivity and causing sodium retention. Therefore, acromegaly is characterized by enlargement of the jaw, hands, feet, and soft tissues, as well as by diabetes mellitus and hypertension. Severe, chronic hypertension may result in cardiomegaly, left ventricular dysfunction, CHF, and dysrhythmias. Airway soft tissue overgrowth may produce macroglossia with glossoptosis, vocal cord thickening with hoarseness, and subglottic narrowing. Vocal cord paralysis has also been reported occasionally. Approximately 25% of acromegalic patients have an enlarged thyroid, which may produce tracheal compression or deviation. Diagnosis is confirmed by elevated 24-hour GH levels in conjunction with increased serum IGF-I levels.
Most pituitary tumors originate in the anterior part of the gland, and the overwhelming majority are benign adenomas. Proposed etiologic mechanisms include malfunction of normal growth-regulating genes, abnormal tumor suppressor genes, and changes in genes that control programmed cell death. 152 The prevalence of pituitary tumors is approximately 200 per 1 million population, 153 but random autopsy results indicate an incidence as high as 27%, 154 suggesting that the majority of pituitary adenomas are asymptomatic. The most common type of pituitary adenoma causes hyperprolactinemia. Adenomas producing acromegaly and Cushing’s disease are more unusual. The annual incidence of acromegaly, for example, is said to be 3 to 8 cases per 1 million.
The primary treatment of acromegaly is surgery, with or without subsequent radiotherapy. However, in the relatively few patients who respond to treatment with dopamine agonists such as bromocriptine, surgery can be avoided. Somatostatin also inhibits GH release, and long-acting analogs of somatostatin, such as octreotide, may be tried in those who fail to respond to dopamine agonists. 155

Surgery and anesthetic concerns
Acromegaly is widely recognized as one of many causes of difficult airway management 156, 157 ( Box 1-21 ). Careful preoperative airway assessment is therefore indicated, paying special attention to possible sleep apnea by questioning the patient about any history of loud snoring, frequent nocturnal awakening, and daytime hypersomnolence. It is imperative to appreciate that the risk of death from respiratory failure is threefold greater in patients with acromegaly. 158 Hypertension is common in acromegalic patients but usually responds to antihypertensive therapy. Myocardial hypertrophy and interstitial fibrosis are also common and may be associated with left ventricular dysfunction. Thus, indicated preoperative studies often include a chest radiograph, ECG, and echocardiogram, in addition to lateral neck radiographs and CT of the neck.

Box 1-21 Acromegaly Patients: Perioperative Concerns

Difficult airway management; suspect sleep apnea
Subglottic narrowing
Tracheal compression or deviation associated with thyroid enlargement
Hypertension
     Cardiomegaly
     Dysrhythmias
     Left ventricular dysfunction
     Congestive heart failure
Diabetes mellitus
Venous air embolism
Postoperative anterior pituitary insufficiency and diabetes insipidus
Postoperative cerebrospinal fluid rhinorrhea, meningitis, sinusitis, and cranial nerve palsy
The pituitary fossa can be approached using the transsphenoidal, transethmoidal, or transcranial route. For all but the largest tumors, the transsphenoidal route is preferred because of a lower incidence of associated complications. Otolaryngologists often assist neurosurgeons in performing transsphenoidal hypophysectomy, gaining access to the pituitary fossa using a sublabial or endonasal approach. Hormone replacement, including 100 mg of hydrocortisone, is administered intravenously at induction, and prophylactic antibiotics are given. An appropriate vasoconstrictor is applied to the nostrils, and care must be taken to prevent hypertension or dysrhythmias. Large face masks and long-bladed laryngoscopes should be prepared and a fiberoptic laryngoscope available. Depending on the airway assessment, awake fiberoptic intubation may be the preferred approach to securing the airway. The intubating LMA has also been used successfully in patients with acromegaly. Equipment for tracheostomy should be immediately available if airway involvement is extensive.
After intubation, the mouth and pharynx should be packed before surgery commences to prevent intraoperative bleeding into the laryngeal area, which may cause postextubation laryngospasm, and into the stomach, which may trigger postoperative nausea and vomiting.
Some surgeons request that a lumbar drain be inserted in patients with major suprasellar tumor extension. The intention is to produce prolapse of the suprasellar part of the tumor into the operative field by injecting 10-mL aliquots of normal saline as needed. Additionally, if the dura is perforated intraoperatively, the lumbar catheter can be left in situ postoperatively to control any leakage of cerebrospinal fluid (CSF). 159
Transsphenoidal surgery is conducted with the patient supine with a moderate degree of head-up tilt. Careful monitoring for venous air embolism is indicated if the head is elevated more than 15 degrees. Other monitoring should include direct arterial BP, ECG, O 2 saturation, and end-tidal CO 2 determination. VEPs have limited usefulness because they are very sensitive to anesthetic effects.
Any anesthetic approach that is compatible with the exigencies of intracranial surgery is acceptable. Regardless of whether an inhalational agent or total IV anesthesia is selected, short-acting agents are administered to allow rapid recovery at the end of surgery. Drugs such as propofol, sevoflurane, and remifentanil are excellent agents to accomplish this objective.
At the completion of surgery, pharyngeal packs should be removed. When the patient is awake with reflexes intact, extubation should be conducted, taking care not to dislodge nasal packs or stents. Patients with acromegaly should be carefully observed postoperatively for airway patency. Those with sleep apnea should be carefully followed in a monitored unit, because treatment options such as nasal CPAP cannot be applied after transsphenoidal surgery. Narcotics should be administered with special caution to patients with sleep apnea. Hormone replacement with tapered cortisol therapy is critical postoperatively. In addition to anterior pituitary insufficiency, diabetes insipidus may also develop postoperatively, but most borderline cases resolve spontaneously in a few days as posterior lobe function recovers. 159 Other potential complications include CSF rhinorrhea, meningitis, sinusitis, and cranial nerve palsy.

Ludwig’s Angina
Ludwig’s angina is a potentially lethal, rapidly expanding cellulitis of the floor of the mouth characterized by brawny induration of the upper neck ( Fig. 1-6 ). Odontogenic infections account for the majority of cases. Spread of the infection along the deep cervical fascia can result in mediastinitis, mediastinal abscess, jugular vein thrombosis, innominate artery rupture, empyema, pneumothorax, pleural and pericardial effusion, subphrenic abscess, necrotizing fasciitis, and mandibular or cervical osteomyelitis. The inflammation is typically caused by cellulitis, but gangrenous myositis may also be a component. 160

Figure 1-6 Ludwig’s angina.
This rapidly expanding cellulitis of the floor of the mouth can be fatal if not managed appropriately.
(From Dachs R, Tun Y: Painful oral ulcerations in a 51-year-old woman, Am Fam Physician 80:875-876, 2009.)
Although the symptoms appear in writings dating back to Hippocrates, Ludwig’s angina was best described initially in 1836 by its namesake, Karl Friedrich Wilhelm von Ludwig. He described this disease as a rapidly progressive, gangrenous cellulitis originating in the region of the submandibular gland that extends by continuity rather than lymphatic spread. During the late 19th and early 20th centuries, Ludwig’s angina was usually considered a complication of local anesthetics administered to facilitate extraction of mandibular teeth. 161 The actual pathogenesis was not elucidated until later.
In 1943, Tschiassny 162 clarified the unique role that the floor of the mouth played in the development of Ludwig’s angina. He described how periapical dental abscesses of the second and third mandibular molars penetrate the thin, inner cortex of the mandible. Because these roots extend inferior to the mandibular insertion of the mylohyoid muscle, infection of the submandibular space ensues. Because of communication around the posterior margin of the mylohyoid muscle, rapid involvement of the sublingual space occurs, followed quickly by involvement of the contralateral spaces. The unyielding presence of the mandible, hyoid, and superficial layer of the deep cervical fascia limits tissue expansion as edema develops and progresses. This resistance leads to superior and posterior displacement of the floor of the mouth and the base of the tongue. These patients therefore have an open-mouth appearance, with a protruding or elevated tongue, and exhibit marked neck swelling. Soft tissue swelling in the suprahyoid region, combined with lingual displacement and concomitant laryngeal edema, can occlude the airway and abruptly asphyxiate the patient.
Although the overwhelming preponderance of cases of Ludwig’s angina have an odontogenic origin, other risks include sublingual lacerations, tongue piercing, IV drug abuse, penetrating injuries to floor of mouth, sialadenitis, compound mandibular fractures, osteomyelitis of mandible, otitis media, infected malignancy, and abscesses located under the thyrohyoid membrane. 163 Patients typically present with fever, as well as edema of the tongue, neck, and submandibular region. These symptoms can progress to include dysphagia, inability to handle secretions, dysphonia, trismus, and difficulty breathing. Polymicrobial infections are common; usual organisms include streptococci, staphylococci, and Bacteroides.
In the preantibiotic era, Ludwig’s angina was associated with mortality rates exceeding 50%. Originally, the extremely sudden manner of death was ascribed to overwhelming sepsis. The lethal role of mechanical respiratory obstruction leading to asphyxia was not understood until later. 164 In 1942, Taffel and Harvey 165 succeeded in reducing mortality to less than 2% by emphasizing early diagnosis and advocating aggressive treatment with wide surgical decompression of the submandibular and sublingual spaces with the patient under local anesthesia. This intervention allowed the elevated base of the tongue to assume an anteroinferior position, thereby preserving the patency of the oropharyngeal airway.
The increasing availability of antibiotics in the 1940s reduced the incidence of and mortality from Ludwig’s angina. Currently, aggressive antibiotic therapy in the early stages of the disease has reduced the need for surgical decompression and airway intervention ( Box 1-22 ). Patterson et al., 166 for example, reported a series of 20 patients at their institution in whom only 35% required airway control through tracheotomy or endotracheal intubation. The anticipated need for airway control may differ among groups, with older patients who have more comorbidities apparently at greater risk for airway obstruction. 167, 168 Additionally, patients who are in poorer condition at presentation may well be in danger of imminent airway closure. Stridor, anxiety, cyanosis, and difficulty managing secretions clearly are late signs of impending obstruction and should indicate the need for immediate airway intervention.

Box 1-22 Ludwig’s Angina Patients: Anesthetic Concerns

Early, aggressive antibiotic therapy may obviate need for airway intervention/surgical decompression.
IV dexamethasone and nebulized epinephrine may alleviate airway obstruction.
Older, sicker patients purportedly at increased risk for airway obstruction.
Anticipate difficult airway management.
     Favor awake fiberoptic intubation with an armored tube or tracheostomy—under local anesthesia.

Anesthetic concerns
Airway management may be extremely difficult in patients with Ludwig’s angina, and intervention should occur early in the course of the disease. IV dexamethasone and nebulized epinephrine may help alleviate airway obstruction. Often, preliminary tracheostomy using local anesthesia may be the safest option. Depending on the patient’s condition, including the presence or absence of trismus and the ability of the patient to cooperate, other options include awake fiberoptic intubation, or inhalation induction if the case is mild and has not progressed, preserving spontaneous respiration, followed by intubation with direct laryngoscopy or fiberoptic assistance. If the oropharynx cannot be visualized by CT, a fiberoptic nasotracheal approach is advised. A surgeon should be present and a tracheotomy kit immediately available when the nonsurgical route to establish the airway is selected. Because of the potential for continued airway swelling after ETT placement, it seems prudent to insert an armored tube to protect the airway better.

Conclusion
Treatment of many complex ophthalmic and otolaryngologic conditions has undergone extraordinary progress during the past three decades. These patients often have complicated anesthetic issues and are presenting for many diagnostic and surgical procedures that did not exist a generation ago. The anesthesiologist must appreciate that few of the conditions presented here have isolated ophthalmic or ENT pathology, but rather are frequently associated with multisystem diseases. The anesthetic plan must reflect this reality. Typically, it is inappropriate to insist dogmatically that one anesthetic approach is unequivocally superior to all others in the management of any specific condition, especially the complex entities discussed here. The key to optimal anesthetic management and outcome resides in a comprehensive understanding of the disease process, the surgical requirements, and the effects of anesthetic agents and techniques on both the individual patient and the proposed surgery.

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136 Benjamin B., Lines V. Endoscopy and anesthesia in non-infective airway obstruction in children. Anaesthesia . 1972;27:22-29.
137 Kennedy M.G., Chinyanga H.M., Steward D.J. Anaesthetic experience using a standard technique for laryngeal surgery in infants and children. Can Anaesth Soc J . 1981;28:561.
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Chapter 2 Cardiac Diseases

Alexander Mittnacht, MD , David L. Reich, MD , Amanda J. Rhee, MD , Joel A. Kaplan, MD

Cardiomyopathies
     General Classification
     Hypertrophic Cardiomyopathy
     Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia
     Left Ventricular Noncompaction
     Conduction System Disease
     Ion Channelopathies
     Dilated Cardiomyopathy
     Restrictive Cardiomyopathies
     Human Immunodeficiency Virus and the Heart
     Miscellaneous Cardiomyopathies
     Secondary Cardiomyopathies
Cardiac Tumors
     Benign Cardiac Tumors
     Malignant Cardiac Tumors
     Metastatic Cardiac Tumors
     Cardiac Manifestations of Extracardiac Tumors
     Anesthetic Considerations
Ischemic Heart Disease
     Physiology of Coronary Artery Disease and Modification by Uncommon Disease
     Uncommon Causes of Ischemic Heart Disease
     Anesthetic Considerations
Pulmonary Hypertension and Cor Pulmonale
     Pathophysiology
     Cor Pulmonale
     Anesthetic Considerations
Pericarditis, Effusion, and Tamponade
     Constrictive Pericarditis
     Pericardial Effusion and Cardiac Tamponade
Uncommon Causes of Valvular Lesions
     Stenotic Valvular Lesions
     Regurgitant Valvular Lesions
     Anesthetic Considerations
Patients with Transplanted Heart
     The Denervated Heart
     Immunosuppressive Therapy
     Anesthetic Considerations
Conclusion

Key points

Even the most uncommon cardiac diseases are characterized by common and classifiable patterns of cardiac physiology and pathophysiology.
Knowledge of disease effects on determinants of cardiac function allows the practitioner to select appropriate anesthetic drugs and techniques based on the common patterns of cardiac pathophysiology.
Appropriate hemodynamic monitoring guides treatment options and allows for early intervention should hemodynamic instability occur. Intra-arterial blood pressure monitoring and transesophageal echocardiography are frequently helpful in addition to standard monitors.
Central venous catheters are often indicated for the administration of vasoactive drugs. Central venous pressure monitoring may be useful in assessing loading conditions.
Pulmonary artery catheters may be helpful in guiding treatment options, especially in patients with pulmonary hypertension, but have not been shown to improve patient outcome.
In ischemic heart disease, regardless of the underlying etiology, the key to optimizing myocardial perfusion is increasing myocardial oxygen supply and decreasing demand.
Pulmonary hypertension has many etiologies and can be present with or without right ventricular dysfunction and cor pulmonale. Pulmonary vasodilators such as inhaled nitric oxide may need to be continued or started in the perioperative period.
Constrictive pericarditis, pericardial effusion, and cardiac tamponade can lead to diminished ventricular filling and cardiac output; compensatory mechanisms ameliorate symptom severity in chronic disease. The effects of anesthetic induction may lead to hemodynamic collapse in patients with cardiac tamponade.
Valvular lesions can be regurgitant, stenotic, or both in uncommon cardiac diseases. Hemodynamic goals for stenotic lesions are to maintain preload and afterload for adequate perfusion pressure with fixed, low cardiac output; regurgitant lesions require high preload and relatively low afterload.
The newly transplanted heart is denervated, and the effect of common drugs such as atropine may be altered or abolished; direct-acting sympathomimetics result in more predictable responses.
The major cardiovascular diseases most often encountered are atherosclerotic coronary artery disease, degenerative valvular disease, and essential hypertension. Experience with these common diseases helps the anesthesiologist become familiar with both the pathophysiology and the anesthetic management of patients with cardiac disease. Although less common, the diseases discussed in this chapter are usually analogous to common patterns of physiology and pathophysiology. The anesthetic management of patients with uncommon cardiovascular disease is fundamentally no different from the management of the more familiar problems. The same principles of management apply, including (1) an understanding of the disease process and its manifestations; (2) thorough knowledge of anesthetic and adjuvant drugs, especially cardiovascular effects; (3) proper use of monitoring; and (4) an understanding of the requirements of the surgical procedure.
Because the diseases discussed here are infrequently or rarely seen, extensive knowledge of their pathophysiology, particularly in the anesthetic and surgical setting, is largely lacking. The use of hemodynamic monitoring provides the best guide to intraoperative and postoperative treatment of patients with uncommon cardiovascular diseases. Monitoring is no substitute for understanding physiology and pharmacology or for clinical judgment, but rather provides information that facilitates clinical decisions. Understanding the requirements of the surgical procedure and ensuring good communication between the anesthesiologist and surgeon are also necessary to anticipate intraoperative problems and thus formulate an anesthetic plan.
This chapter does not provide an exhaustive list or consideration of all the uncommon diseases that affect the cardiovascular system, although it covers a wide range. No matter how bizarre, a disease entity can only affect the cardiovascular system in a limited number of ways. It can affect the myocardium, coronary arteries, conduction system, pulmonary circulation, and valvular function, or it can impair cardiac filling or emptying. Subsections in this chapter follow this basic discussion approach.

Cardiomyopathies

General Classification
Cardiomyopathies are defined as diseases of the myocardium that are associated with cardiac dysfunction. Classified in various ways, cardiomyopathies are usually viewed, on an etiologic basis, as primary myocardial diseases, in which the disease locus is the myocardium itself, or secondary myocardial diseases, in which the myocardial pathology is associated with a systemic disorder. On a pathophysiologic basis, myocardial disease can be divided into three general categories: dilated (congestive), hypertrophic, and restrictive (obstructive) cardiomyopathies ( Fig. 2-1 ).

Figure 2-1 Fifty-degree left anterior oblique views of the heart in various cardiomyopathies at end systole and end diastole.
(From Goldman MR, Boucher CA: Value of radionuclide imaging techniques in assessing cardiomyopathy, Am J Cardiol 46:1232, 1980.)
Over the past decade, advances in understanding myocardial etiology and diagnosis and the identification of new diseases have led to updated classifications, notably the 2006 American Heart Association (AHA) contemporary definitions and classification of cardiomyopathies 1 ( Box 2-1 ). The AHA expert consensus panel defines the cardiomyopathies as “a heterogeneous group of diseases of the myocardium associated with mechanical and/or electrical dysfunction that usually (but not invariably) exhibit inappropriate ventricular hypertrophy or dilation and are due to a variety of causes that frequently are genetic. Cardiomyopathies either are confined to the heart or are part of generalized systemic disorders, often leading to cardiovascular death or progressive heart failure–related disability.” This classification scheme divides cardiomyopathies into two major categories : primary and secondary. When discussing the anesthetic management of patients with cardiomyopathies, the pathophysiologic changes often are more relevant than their etiology. This discussion refers to the most recent AHA recommended classification of cardiomyopathies, although the anesthetic management is discussed on the basis of the pathophysiologic changes that result from their underlying etiology.

Box 2-1 Classification of Cardiomyopathies (Primary Cardiomyopathies)

Genetic

Hypertrophic cardiomyopathy
Arrhythmogenic right ventricular cardiomyopathy/dysplasia
Left ventricular noncompaction
Glycogen storage cardiomyopathy
Conduction defects
Mitochondrial myopathies
Ion channel disorders

Mixed

Dilated cardiomyopathy
Restricted cardiomyopathy

Acquired

Inflammatory disorders
Stress-provoked conditions
Peripartum disorders
Tachycardia-induced conditions
Infants of insulin-dependent diabetic mothers
Modified from Maron BJ, et al: Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement, Circulation 113:1807-1816, 2006.

Hypertrophic Cardiomyopathy
Hypertrophic cardiomyopathy (HCM) is an autosomal dominant genetic disease and the most common genetic cardiovascular disease, with a prevalence of approximately 1 in 500 young adults in the United States. 2 HCM is the most common cause of sudden cardiac death in young U.S. athletes and an important cause of heart failure at any age. Morphologically, it is defined by a hypertrophied, nondilated left ventricle in the absence of another causative disease for hypertrophy, such as chronic hypertension or aortic stenosis. The variety of genetic defects that results in HCM explains the heterogeneity of its phenotypic presentation. 3
Hypertrophic cardiomyopathy usually results from asymmetric hypertrophy of the basal ventricular septum and occurs in either an obstructive or a nonobstructive form ( Table 2-1 ). A dynamic pressure gradient in the left ventricular outflow tract (LVOT) is present in the obstructive forms. 4 - 7 other conditions also present the picture of an obstructive cardiomyopathy, such as massive infiltration of the ventricular wall, as occurs in Pompe’s disease, where an accumulation of cardiac glycogen in the ventricular wall produces LVOT obstruction. This is caused by genetic mutations interfering with cardiac metabolism.
Table 2-1 Treatment Principles of Dilated Cardiomyopathies Clinical Problem Treatment Relatively Contraindicated ↓ Preload Volume replacement Positional change Nodal rhythm High spinal anesthesia ↓ Heart rate Atropine Pacemaker Verapamil ↓ Contractility Positive inotropes Digoxin Volatile anesthetics ↑ Afterload Vasodilators Phenylephrine Light anesthesia
Obstructive HCM, also referred to as hypertrophic obstructive cardiomyopathy (HOCM), asymmetric septal hypertrophy (ASH), or idiopathic hypertrophic subaortic stenosis (IHSS), has the salient anatomic feature of basal septal hypertrophy. 8 Obstruction of the LVOT is caused by the hypertrophic muscle mass and systolic anterior motion (SAM) of the anterior leaflet of the mitral valve. Hypotheses for the mechanism of SAM include a Venturi effect of rapidly flowing blood in the LVOT. 9 Other theories include alteration in the position of the leaflet coaptation point in relation to the interventricular septum, and blood flow changes caused by the bulging septum that cause parts of the anterior mitral valve tissue and subvalvular apparatus to protrude or to be “pushed” into the LVOT during systole. 10, 11 Various degrees of mitral regurgitation are typically associated with SAM. The outflow tract obstruction can result in hypertrophy of the remainder of the ventricular muscle, secondary to increased pressures in the ventricular chamber.
The current therapeutic options for patients with hypertrophied cardiomyopathy are based on pharmacologic therapy, surgical interventions, percutaneous transluminal septal myocardial ablation, and dual-chamber pacing. 12 - 16 An automated implantable cardioverter-defibrillator (AICD) is frequently implanted to treat arrhythmias so as to prevent sudden cardiac death. 17, 18 The pharmacologic therapy of obstructive HCM has been based on beta-adrenergic blockade, although it is still unclear whether this prolongs life expectancy. Patients who do not tolerate β-blockers instead receive verapamil, with beneficial effects likely resulting from depressed systolic function and improved diastolic filling and relaxation. Patients whose symptoms are inadequately controlled with β-blockers or verapamil receive disopyramide, a type IA antiarrhythmic agent with negative inotropic and peripheral vasoconstrictive effects. Amiodarone is administered for the control of supraventricular and ventricular arrhythmias. 19
Data are minimal or lacking to support the use of combination therapy for HOCM. 20 Most patients with obstructive HCM are treated only with medical therapy. Nevertheless, 5% to 30% of patients are surgical candidates. The surgery is septal myotomy/myectomy, mitral valve repair/replacement or valvuloplasty, or a combination of the two. 21 The potential complications of surgical correction of the LVOT obstruction include complete heart block and late formation of a ventricular septal defect from septal infarction.
Percutaneous transluminal alcohol septal ablation is performed in the catheterization laboratory but requires special expertise that is limited to experienced centers. 22 Although this may be efficacious for subsets of patients with obstructive HCM, the procedural complication rate may exceed that of surgical myectomy. 23 Ablation is also associated with the risk of serious adverse events, such as alcohol toxicity and malignant tachyarrhythmias. 24 A relatively new alternative to induce septal ablation involves percutaneous transluminal septal coil embolization, which avoids the problem of alcohol toxicity. Further experience and outcome data are required before this new technique is considered a standard treatment modality for HCM. 25 Although still controversial, evidence suggests that atrioventricular sequential (DDD) pacing is beneficial for patients with obstructive HCM. 26, 27

Anesthetic considerations
The determinants of the functional severity of the ventricular obstruction in obstructive HCM are (1) the systolic volume of the ventricle, (2) the force of ventricular contraction, and (3) the transmural pressure distending the LVOT.
Large systolic volumes in the ventricle distend the LVOT and reduce the obstruction, whereas small systolic volumes narrow the LVOT and increase the obstruction. When ventricular contractility is high, the LVOT is narrowed, increasing the obstruction. When aortic pressure is high, the increased transmural pressure distends the LVOT. During periods of decreased afterload and hypotension, however, the LVOT is narrowed, resulting in greatly impaired cardiac output often associated with significant mitral regurgitation. As the ventricle hypertrophies, ventricular compliance decreases, and passive filling of the ventricle during diastole is impaired. The ventricle becomes increasingly dependent on the presence of atrial contraction to maintain an adequate ventricular end-diastolic volume. Monitoring should be established that allows continuous assessment of these parameters, particularly in patients in whom the obstruction is severe.
In patients with symptomatic obstructive HCM presenting for surgery, an indwelling arterial catheter for beat-to-beat observation of ventricular ejection and continuous blood pressure (BP) monitoring should be placed before anesthesia induction. Transesophageal echocardiography (TEE) provides useful data on ventricular function and filling, the severity of LVOT obstruction, and the occurrence of SAM and mitral regurgitation. A pulmonary artery catheter (PAC), once more widely used, has not shown to improve outcome. Its use may be helpful in guiding treatment options, especially in patients with obstructive HCM undergoing major surgery with large fluid shifts.
Special consideration should be given to those features of the surgical procedure and anesthetic drugs that can produce changes in intravascular volume, ventricular contractility, and transmural distending pressure of the outflow tract. Decreased preload, for example, can result from blood loss, sympathectomy secondary to spinal or epidural anesthesia, use of potent volatile anesthetics and nitroglycerin, or postural changes. Ventricular contractility can be increased by hemodynamic responses to tracheal intubation or surgical stimulation. Transmural distending pressure can be decreased by hypotension secondary to anesthetic drugs, hypovolemia, or positive-pressure ventilation. Additionally, patients with obstructive HCM do not tolerate increases in heart rate. Tachycardia decreases end-diastolic ventricular volume, resulting in a narrowed LVOT. As noted earlier, the atrial contraction is extremely important to the hypertrophied ventricle. Nodal rhythms should be aggressively treated, using atrial pacing if necessary.
Halothane, now a historical drug and no longer available in the United States, had major hemodynamic advantages for the anesthetic management of patients with obstructive HCM. Its advantages were to decrease heart rate and myocardial contractility. Of the inhalational anesthetics, halothane had the least effect on systemic vascular resistance (SVR), which tended to minimize the severity of the obstruction when volume replacement was adequate. Sevoflurane decreases SVR to a lesser extent than isoflurane or enflurane and thus may be preferable. Agents that release histamine, such as morphine, thiopental, and atracurium, are not recommended because of the resulting venodilation. Agents with sympathomimetic side effects (ketamine, desflurane) are not recommended because of the possible tachycardia. High-dose opioid anesthesia causes minimal cardiovascular side effects along with bradycardia and thus may be useful in these patients. Preoperative β-blocker and calcium channel blocker therapy should be continued. Intravenous (IV) propranolol, esmolol, or verapamil may be administered intraoperatively to improve hemodynamic performance. Table 2-2 summarizes the anesthetic and circulatory management of obstructive HCM. 28
Table 2-2 Treatment Principles of Hypertrophic Obstructive Cardiomyopathy Clinical Problem Treatment Relatively Contraindicated ↓ Preload Volume Phenylephrine Vasodilators Spinal/epidural anesthesia ↑ Heart Rate β-Adrenergic blockers Verapamil Ketamine β-Adrenergic agonists ↑ Contractility Halothane Sevoflurane β-Blockers Disopyramide Positive inotropes Light anesthesia ↓ Afterload Phenylephrine Isoflurane Spinal/epidural anesthesia
Anesthesia for management of labor and delivery in the parturient with obstructive HCM is quite complex. “Bearing down” (Valsalva maneuver) during delivery may worsen LVOT obstruction. Beta-blocker therapy may have been discontinued during pregnancy because of the association with fetal bradycardia and intrauterine growth retardation. Oxytocin must be used carefully because of its vasodilating properties and compensatory tachycardia. Pulmonary edema has been observed in parturients with HCM, emphasizing the need for careful fluid management. 29 Spinal anesthesia is relatively contraindicated because of the associated vasodilation, but epidural anesthesia has been used successfully. 30 General anesthesia is preferred by many practitioners. If hypotension occurs during anesthesia, the use of beta-agonists such as ephedrine may result in worsening outflow tract obstruction, and alpha-agonists such as phenylephrine, once thought to result in uterine vasoconstriction, are now preferred. 31, 32 However, careful titration of anesthetic agents and adequate volume loading (most often guided by invasive monitoring) is essential to safely conducted anesthesia in this clinical setting.

Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia
Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is an uncommon (estimated 1:5000 young adults), newly described, autosomal dominant disease with incomplete penetrance. ARVC/D is frequently associated with myocarditis but is not considered a primary inflammatory cardiomyopathy. It involves predominantly the right ventricle initially, progressing to affect the left ventricle in later stages. There is a progressive loss of myocytes, with replacement by fatty or fibrofatty tissue, which leads to regional (segmental) or global pathology. It is three times more common in women.
The clinical presentation of ARVC/D usually includes ventricular tachyarrhythmias, such as monomorphic ventricular tachycardia, syncope, or cardiac arrest, with global or segmental chamber dilation and regional wall motion abnormalities. It has been recognized as an important cause of sudden death in young athletes. 33 Diagnosis involves assessment of multiple facets of cardiac physiology, including electrical, functional, and anatomic pathology.

Anesthetic considerations
The main therapeutic options are similar to those for other arrhythmia-prone or heart failure patients. Patients often present with AICDs, and antiarrhythmic agents such as β-blockers or amiodarone may be helpful should arrhythmias occur. 34 Catheter ablation of diseased areas of myocardium (acting as arrhythmogenic foci) can be useful in cases of refractory medical therapy. Cardiac transplantation is also an option as a final alternative.
As a rarer heart disease, minimal evidence exists for the optimal anesthetic management of patients with ARVC/D. It is one of the main causes of sudden, unexpected perioperative death, which can occur in low-risk surgical candidates, even in patients with a history of successful anesthesia. 35, 36 The uncommon nature of the disease makes it difficult to make specific recommendations for anesthetic management. If the condition is known, invasive continuous arterial BP monitoring is prudent intraoperatively. A PAC should probably be avoided, given the tendency toward arrhythmias. Propofol and etomidate appear to be safe induction agents. 34 Neuromuscular blocking agents such as vecuronium, cisatracurium, and rocuronium are probably safe as well. AICDs should be managed according to the guidelines published and referred to throughout this text, 37 regardless of the presence of ARVC/D. 38

Left Ventricular Noncompaction
Left ventricular (LV) noncompaction of ventricular myocardium is a genetic disorder with familial and nonfamilial types. LV noncompaction has a distinctive “spongy” appearance to the LV myocardium, with deep intertrabecular recesses (sinusoids) that communicate with the LV cavity. LV noncompaction results in LV systolic dysfunction, heart failure, thromboemboli, arrhythmias, sudden death, and ventricular remodeling. 1

Anesthetic considerations
Anesthetic management in patients with LV noncompaction depends on the severity of ventricular dysfunction, which should be evaluated preoperatively. In patients with impaired cardiac function, management should be directed toward preserving contractility and baseline levels of preload and afterload. Up to 80% of patients with LV noncompaction have a neuromuscular disorder, such as Duchenne’s or Becker’s muscular dystrophy or myotonic dystrophy. 39 Thus, depolarizing neuromuscular junction blockers should be avoided or used with caution. 40 Patients may be receiving anticoagulation for thromboembolic prophylaxis and may therefore have contraindications for using neuraxial techniques. AICDs are often inserted for indications such as arrhythmias or heart failure, and patients should be managed accordingly. 41, 42
Data are limited regarding anesthetic management in patients with LV noncompaction syndrome. In a retrospective study on 60 patients with noncompaction undergoing 220 procedures, only patients undergoing general anesthesia experienced complications, compared to regional anesthesia or sedation/analgesia. 43 Because the nature of the surgery often dictates the need for general anesthesia, patients with noncompaction syndrome requiring general anesthetics warrant vigilant monitoring in the perioperative period.

Conduction System Disease

Lenègre’s disease
Progressive cardiac conduction defect, also known as Lenègre’s disease, has an autosomal dominant pattern of inheritance resulting in ion channelopathies, which manifest as conduction abnormalities. Lenègre’s disease involves primary progressive development of cardiac conduction defects in the His-Purkinje system. This leads to widening QRS complexes, long pauses, and bradycardia. 1, 44

Wolff-parkinson-white syndrome
Wolff-Parkinson-White (WPW) is a rare pre-excitation syndrome that presents often as paroxysmal supraventricular tachycardia episodes. The presence of accessory anatomic bypass tracts enables the atrial impulse to activate the His bundle more rapidly than through the normal atrioventricular (A-V) nodal pathway. If the refractoriness in one of the pathways increases, a re-entrant tachycardia can be initiated. The electrocardiogram (ECG) in WPW syndrome demonstrates a short PR interval (< 0.12 msec), a delta wave (slurred transition between PR interval and R-wave upstroke), and a widened QRS complex. 45 - 47 The incidence of sudden cardiac death in patients with WPW syndrome is estimated at 0.15% to 0.39% over 3 to 10 years of follow-up, and in WPW patients with a history of cardiac arrest, it is the presenting symptom in approximately 50%. 48
Medications that produce more refractoriness in one of the pathways can create a window of functional unidirectional block. This initiates a circle of electrical impulse propagation that results in a rapid ventricular rate. These patients are usually treated with drugs that increase the refractory period of the accessory pathway, such as procainamide, propafenone, flecainide, disopyramide, ibutilide, and amiodarone. 49 - 51 However, individual patient response will vary depending on the window of unidirectional block, as well as the different effects the same drug has on both pathways. For example, verapamil and digoxin may perpetuate the arrhythmias, especially when WPW syndrome is associated with atrial fibrillation. 48, 52 A nonpharmacologic approach in the treatment of patients with pre-excitation syndromes is catheter ablation of the accessory pathways, 53, 54 with initial success of approximately 95% in most series. 55

Anesthetic considerations
The current treatment of choice for WPW is ablation of the accessory pathway, which is usually performed in electrophysiology laboratories. 56, 57 The procedures often involve periods of programmed electrical stimulation in attempts to provoke the arrhythmias before and after the ablation of the accessory pathway. Antiarrhythmic medications are usually discontinued before the procedure. Thus, these patients present for an anesthetic in a relatively unprotected state. Premedication is indicated to prevent anxiety, which could increase catecholamine levels and precipitate arrhythmias. Electrocardiographic (ECG) monitoring should be optimal for the diagnosis of atrial arrhythmias (leads II and V1).
If arrhythmias occur in WPW patients, A-V nodal blocking agents such as adenosine, β-blockers, diltiazem, and verapamil, as well as lidocaine, should be used with caution. These A-V blockers must be avoided if atrial fibrillation is suspected, because these drugs can promote conductance through the accessory pathway with rapid ventricular response. Digoxin is contraindicated in WPW patients. Amiodarone, sotalol, ibutilide, flecainide, or procainamide is preferable in such cases. 48
If general anesthesia is needed, it is reported that opioid-benzodiazepine or opioid-propofol anesthetic regimens show no effect on electrophysiologic parameters of the accessory conduction pathways. 58, 59 Volatile anesthetics theoretically increase refractoriness within the accessory and A-V pathways; however, modern volatile anesthetic agents are widely used in patients undergoing ablation procedures under general anesthesia. 60, 61 Dexmedetomidine is frequently used for radiofrequency ablation procedures performed under sedation, because it is unlikely to exacerbate tachycardias and more likely to cause bradycardia. 62

Ion Channelopathies
There are a variety of ion channelopathies of genetic origin in which defective ion channel proteins lead to arrhythmias that can cause sudden death. Diagnosis requires identification of the pathology on a 12-lead ECG.

Long QT syndrome
Long QT syndrome, the most common of the ion channelopathies, is characterized by prolongation of ventricular repolarization and the QT interval (QTc > 440 msec). It increases the risk of developing polymorphic ventricular tachycardia (torsade des pointes). This can lead to syncope and sudden cardiac death. The more common pattern of inheritance is autosomal dominant, referred to as Romano-Ward syndrome. The rare, autosomal recessive inheritance pattern is associated with deafness, called Jervell and Lange-Nielsen syndrome. 63 - 65 In untreated patients, mortality approaches 5% per year, quite remarkable for a population with median age in the 20s. The severity of the disease is judged by the frequency of syncopal attacks. These attacks may be caused by ventricular arrhythmias or sinus node dysfunction. The development of torsade de pointes is especially ominous and may be the terminal event for these patients. 66
Torsade de pointes is a malignant variety of ventricular tachycardia with a rotating QRS axis that is resistant to cardioversion. 67, 68 The pathogenesis of this syndrome is theorized to be an imbalance of sympathetic innervation. Left stellate ganglion stimulation lowers the threshold for ventricular arrhythmias, while right stellate ganglion stimulation is protective against ventricular arrhythmias. Patients receiving β-blockers and those with high left thoracic sympathectomy had relief of syncope and decreased mortality. 69

Brugada’s syndrome
Patients with Brugada’s syndrome have characteristic ECG findings of right bundle branch block and ST-segment elevation in the anterior precordial leads (V 1 -V 3 ). It is inherited in an autosomal dominant pattern. Brugada’s syndrome may present as sudden nocturnal death from ventricular fibrillation or tachycardia, especially in Southeast Asian males. 1, 63, 70

Catecholaminergic polymorphic ventricular tachycardia
Catecholaminergic polymorphic ventricular tachycardia (CPVT) has two patterns of inheritance that lead to ventricular tachycardia triggered by vigorous physical exertion or acute emotion, usually in children and adolescents. This can lead to syncope and sudden death. The resting ECG is unremarkable, with the exception of sinus bradycardia and prominent U waves in some cases. The most common arrhythmia seen in CPVT is a bidirectional ventricular tachycardia with an alternating QRS axis. 1, 63, 71

Short QT syndrome
Short QT syndrome is characterized by a short QT interval (QTc < 330 msec) and ECG appearance of tall, peaked T waves. It is associated with polymorphic ventricular tachycardia and ventricular fibrillation. 1, 72, 73

Idiopathic ventricular fibrillation
The literature describes a group of cardiomyopathies designated as idiopathic ventricular fibrillation. Data are insufficient, however, to establish this as a distinct cardiomyopathy. It is likely the summation of multiple etiologies that lead to arrhythmias, probably caused by ion channel mutations. 1, 74

Anesthetic considerations
Patients with ion channelopathies may present intraoperatively or in the postanesthesia care unit with sudden arrhythmias that warrant vigilant ECG monitoring. Continuous invasive intra-arterial BP monitoring should be considered in patients with a history of frequent arrhythmias. Patients should be treated as any patient prone to arrhythmias; this includes avoiding arrhythmogenic medications and immediate availability of a cardioverter-defibrillator device. Few data are available on anesthetic recommendations for these cardiomyopathies. Patients with long QT syndrome will occasionally present for high left thoracic sympathectomy and left stellate ganglionectomy, although most patients with these ion channelopathies will most likely present for surgery unrelated to their primary disorder.
Patients with long QT syndrome seem to be at increased risk of arrhythmia during periods of enhanced sympathetic activity, particularly during emergence from general anesthesia with use of potent volatile agents, and when neuromuscular blocker reversal drugs were given with ondansetron in children. 75 Beta blockade has been described as the most successful medical management of patients with congenital long QT syndrome types I and II, which affect potassium channels. Beta blockade is contraindicated in type III, which involves sodium channels. 76 In patients who receive β-blockers, it is reasonable to continue beta blockade perioperatively. Intraoperatively and particularly during long procedures, supplemental IV doses of a β-blocker or a continuous infusion of esmolol should be considered.
The anesthetic technique should be tailored to minimize sympathetic stimulation. A balanced anesthetic technique with adequate opioid administration is appropriate for this purpose, and is effective at suppressing catecholamine elevations in response to stimuli. Nitrous oxide (N 2 O) causes mild sympathetic stimulation and thus should be avoided. Medications that can further prolong the QT interval should probably be avoided, including isoflurane, sevoflurane, 77 thiopental, succinylcholine, neostigmine, atropine, glycopyrrolate, metoclopramide, 5HT3 receptor antagonists, and droperidol. 78 Ketamine is generally not recommended as an induction agent in patients with congenital long QT syndrome. Despite the QT-prolonging effect, thiopental has been used without adverse consequences. Propofol has no effect on or may actually shorten the QT interval and is theoretically a good choice of induction agent. 79 Anxiolysis with midazolam has been used successfully. 80
In patients with Brugada’s syndrome, sodium channel blockers such as procainamide and flecainide are contraindicated, and medications such as neostigmine, class 1A antiarrhythmic drugs, and selective α-adrenoreceptor agonists may increase ST segment elevation and should also be avoided. Thiopental, isoflurane, sevoflurane, N 2 O, morphine, fentanyl, ketamine, and succinylcholine have been used successfully. 81 - 83 Some report arrhythmias related to propofol administration. In contrast to patients with long QT syndrome, propofol should be used with caution in patients with Brugada’s syndrome. 84, 85

Dilated Cardiomyopathy
Dilated cardiomyopathy (DCM) has both genetically derived and acquired components, as well as inflammatory and noninflammatory forms. 86 It is a relatively common cause of heart failure, with a prevalence of 36 per 100,000 people, 87 and is a common indication for heart transplantation. DCM is characterized by ventricular chamber enlargement and systolic dysfunction with normal left ventricular wall thickness. From 20% to 35% of DCM is familial, with predominantly autosomal dominant inheritance, but also X-linked autosomal recessive and mitochondrial patterns. 88 The main features of DCM are left ventricular dilation, systolic dysfunction, myocyte death, and myocardial fibrosis. 89 Evidence indicates genetic similarities between hypertrophic and dilated cardiomyopathy. 90 Nonfamilial causes for DCM include infectious agents, particularly viruses that lead to inflammatory myocarditis, and toxic, degenerative, and infiltrative myocardial processes. 91, 92 Although there are different systems for classifying DCM, this section discusses inflammatory and noninflammatory forms.

Inflammatory cardiomyopathy (myocarditis)
There are a wide variety of toxins and drugs that cause inflammatory myocarditis ( Table 2-3 ). Infectious myocarditis typically evolves through several stages of active infection, through healing, and may ultimately culminate in DCM.

Table 2-3 Inflammatory Cardiomyopathies (Dilated)


Myocarditis presents with the clinical picture of fatigue, dyspnea, and palpitations, usually in the first weeks of the infection, progressing to overt congestive heart failure (CHF) with cardiac dilation, tachycardia, pulsus alternans, and pulmonary edema. Between 10% and 33% of patients with infectious heart diseases will have ECG evidence of myocardial involvement. Mural thrombi often form in the ventricular cavity and may result in systemic or pulmonary emboli. Supraventricular and ventricular arrhythmias are common. Fortunately, patients usually have complete recovery from infectious myocarditis, although exceptions include myocarditis associated with diphtheria or Chagas’ disease. Occasionally, acute myocarditis may even progress to a recurrent or chronic form of myocarditis, resulting ultimately in a restrictive type of cardiomyopathy caused by fibrous replacement of the myocardium. 93, 94
In the bacterial varieties of myocarditis, isolated ECG changes or pericarditis are common and usually benign, whereas CHF is unusual. Diphtheritic myocarditis is generally the worst form of bacterial myocardial involvement; in addition to inflammatory changes, its endotoxin is a competitive analog of cytochrome B and can produce severe myocardial dysfunction. 95, 96 The conduction system is especially affected in diphtheria, producing either right or left bundle branch block, which is associated with 50% mortality. When complete heart block supervenes, mortality approaches 80% to 100%. Syphilis, leptospirosis, and Lyme disease represent three examples of myocardial infection by spirochetes. 97 Tertiary syphilis is associated with multiple problems, including arrhythmias, conduction disturbances, and CHF. Lyme disease myocarditis usually presents with conduction abnormalities, such as bradycardia and A-V nodal block. 98
Viral infections manifest primarily with ECG abnormalities, including PR prolongation, QT prolongation, ST-segment and T-wave abnormalities, and arrhythmias. However, each viral disease produces slightly different ECG changes, with complete heart block being the most significant. Most of the viral diseases have the potential to progress to CHF if the viral infection is severe. 99 Recent advances in molecular biologic techniques have allowed for more accurate identification of viruses. Previously, coxsackievirus B was the most common virus identified as producing severe viral heart disease. Currently, the most prevalent viral genomes detected are enterovirus, adenovirus, and parvovirus B19. 100 - 102 Although the pathogenic role of enterovirus in myocarditis and chronic DCM is well established, whether parvovirus B19 is incidental or pathogenic in viral myocarditis is still unclear. Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6) have also been implicated in viral myocarditis. The presence of parvovirus B19, EBV, and HHV-6 is associated with a decline in cardiac function within 6 months.
Subsequently, there may be an autoimmune phase in which the degree of the cardiac inflammatory response correlates with a worse prognosis, which may culminate in DCM. 103 The 2009 H1N1 pandemic influenza strain was associated with myocarditis as well. In one study, patients with H1N1 influenza associated with myocarditis were predominantly female, young (mean age 33.2 years), and had morbidity/mortality of 27%. 104, 105
Mycotic myocarditis has protean manifestations that depend on the extent of mycotic infiltration of the myocardium and may present as CHF, pericarditis, ECG abnormalities, or valvular obstruction.
Of the protozoal forms of myocarditis, Chagas’ disease, or trypanosomiasis, is the most significant, and the most common cause of chronic CHF in South America. ECG changes of right bundle branch block and arrhythmias occur in 80% of patients. In addition to the typical inflammatory changes in the myocardium that produce chronic CHF, a direct neurotoxin from the infecting organism, Trypanosoma cruzi, produces degeneration of the conduction system, often causing severe ventricular arrhythmias and heart block with syncope. The onset of atrial fibrillation in these patients is often an ominous prognostic sign. 106, 107
Helminthic myocardial involvement may produce CHF, but more frequently symptoms are secondary to infestation and obstruction of the coronary or pulmonary arteries by egg, larval, or adult forms of the worm. Trichinosis, for example, produces a myocarditis secondary to an inflammatory response to larvae in the myocardium, even though the larvae themselves disappear from the myocardium after the second week of infestation.

Noninflammatory dilated cardiomyopathy
The noninflammatory variety of dilated cardiomyopathy also presents as myocardial failure, but in this case caused by idiopathic, toxic, degenerative, or infiltrative processes in the myocardium 108, 109 ( Table 2-4 ).

Table 2-4 Noninflammatory Cardiomyopathies (Dilated)



As an example of the toxic cardiomyopathy type, alcoholic cardiomyopathy is a typical hypokinetic noninflammatory cardiomyopathy associated with tachycardia and premature ventricular contractions that progress to left ventricular failure with incompetent mitral and tricuspid valves. This cardiomyopathy probably results from a direct toxic effect of ethanol or its metabolite acetaldehyde, which releases and depletes cardiac norepinephrine. 110 Alcohol may also affect excitation-contraction coupling at the subcellular level. 111 In chronic alcoholic patients, acute ingestion of ethanol produces decreases in contractility, elevations in ventricular end-diastolic pressure, increases in SVR and systemic hypertension. 112 - 115
Alcoholic cardiomyopathy is classified into three hemodynamic stages. In stage I, cardiac output, ventricular pressures, and left ventricular end-diastolic volume (LVEDV) are normal, but the ejection fraction (EF) is decreased. In stage II, cardiac output is normal, although filling pressures and LVEDV are increased, and EF is decreased. In stage III, cardiac output is decreased, filling pressures and LVEDV are increased, and EF is severely depressed. Most noninflammatory forms of DCM undergo a similar progression.
Doxorubicin (Adriamycin) is an antibiotic with broad-spectrum antineoplastic activities. Its clinical effectiveness, however, is limited by its cardiotoxicity. Doxorubicin produces dose-related DCM. Doxorubicin may disrupt myocardial mitochondrial calcium homeostasis. Patients treated with this drug must undergo serial evaluations of left ventricular systolic function. 116, 117 Dexrazoxane, a free-radical scavenger, may protect the heart from doxorubicin-associated damage. 118

Pathophysiology
The key hemodynamic features of the DCMs are elevated filling pressures, failure of myocardial contractile strength, and a marked inverse relationship between afterload and stroke volume. Both the inherited and the nonfamilial forms of inflammatory and noninflammatory DCMs present a picture identical to that of CHF produced by severe coronary artery disease (CAD). In some conditions the process that has produced the cardiomyopathy also involves the coronary arteries. The pathophysiologic considerations are familiar. As the ventricular muscle weakens, the ventricle dilates to take advantage of the increased force of contraction that results from increasing myocardial fiber length. As the ventricular radius increases, however, ventricular wall tension rises, increasing both the oxygen consumption of the myocardium and the total internal work of the muscle. As the myocardium deteriorates further, the cardiac output falls, with a compensatory increase in sympathetic activity to maintain organ perfusion and cardiac output. One feature of the failing myocardium is the loss of its ability to maintain stroke volume in the face of increased afterload. Figure 2-2 shows that in the failing ventricle, stroke volume falls almost linearly with increases in afterload. The increased sympathetic outflow that accompanies left ventricular failure initiates a vicious cycle of increased resistance to forward flow, decreased stroke volume and cardiac output, and further sympathetic stimulation in an effort to maintain circulatory homeostasis.

Figure 2-2 Stroke volume (SV) as a function of afterload for normal left ventricle, for left ventricle with moderate dysfunction, and for failing left ventricle.
Mitral regurgitation is common in severe DCM due to stretching of the mitral annulus (Carpentier Type I) and distortion of the geometry of the chordae tendineae, resulting in restriction of leaflet apposition (Carpentier Type IIIb). 119 The forward stroke volume improves with afterload reduction, even with no increase in EF. This suggests that reduction of mitral regurgitation is the mechanism of the improvement. Afterload reduction also decreases left ventricular filling pressure, which relieves pulmonary congestion and should preserve coronary perfusion pressure. 120
The clinical picture of the DCM falls into the two familiar categories of forward and backward failure. The features of “forward” failure, such as fatigue, hypotension, and oliguria, are caused by decreases in cardiac output with reduced organ perfusion. Reduced perfusion of the kidneys results in activation of the renin-angiotensin-aldosterone system, which increases the effective circulating blood volume through sodium and water retention. “Backward” failure is related to the elevated filling pressures required by the failing ventricles. As the left ventricle dilates, end-diastolic pressure rises, and mitral regurgitation worsens. The manifestations of left-sided failure include orthopnea, paroxysmal nocturnal dyspnea, and pulmonary edema. The manifestations of right-sided failure include hepatomegaly, jugular venous distention, and peripheral edema.

Anesthetic considerations
Electrocardiographic monitoring is essential in the management of patients with DCMs, particularly in those with myocarditis. Ventricular arrhythmias are common, and complete heart block, which can occur from these conditions, requires rapid diagnosis and treatment. The ECG is also useful in monitoring ischemic changes when CAD is associated with the cardiomyopathy, as in amyloidosis.
Direct invasive intra-arterial BP monitoring during surgery provides continuous information and a convenient route for obtaining arterial blood gases (ABGs). Any DCM patient with a severely compromised myocardium who requires anesthesia and surgery should have central venous access for monitoring and vasoactive drug administration. The use of a PAC is much more controversial. The American Society of Anesthesiologists (ASA) Task Force on Pulmonary Artery Catheterization has published practice guidelines. 121, 122 The indication for PAC placement depends on a combination of patient-, surgery-, and practice setting–related factors. Patients with severely decreased cardiac function from DCM have significant cardiovascular disease and are considered at increased or high risk. With no evidenced-based medicine to support outcome differences, recommendations for PAC monitoring were based on expert opinion at that time. Patients with DCM presenting for surgery who have an overall increased or high-risk score should probably have hemodynamic parameters monitored with a PAC. In addition to measuring right- and left-sided filling pressures, a thermodilution PAC may be used to obtain cardiac output and calculate SVR and pulmonary vascular resistance (PVR), which allow for serial evaluation of the patient’s hemodynamic status. PACs with fiberoptic oximetry, rapid-response thermistor catheters that calculate right ventricular EF, and pacing PAC are available. Pacing PAC and external pacemakers provide distinct advantages in managing the patient with myocarditis and associated heart block. Recent evidence seems to provide further support for clinicians who choose not to use PAC monitoring on the basis of no outcome differences between high-risk surgical patients who were cared for with and without PAC monitoring and goal-directed therapy. 123 - 125
Transesophageal echocardiography provides useful data on ventricular filling, ventricular function, severity of mitral regurgitation, and response of the impaired ventricle to anesthetic and surgical manipulations. Recent guidelines indicate that hemodynamic decompensation is a class I indication for TEE monitoring. 126 - 128 With the increased availability of equipment and trained anesthesiologists, TEE will become increasingly important in the perioperative management of patients with cardiomyopathies.
The avoidance of myocardial depression still remains the goal of anesthetic management for patients with DCM, although, paradoxically, beta-adrenergic blockade has been associated with improved hemodynamics and improved survival in patients with DCM. 129 - 133 (This may result from an antiarrhythmic effect.) All the potent volatile anesthetic agents are myocardial depressants, and therefore high concentrations of these agents are probably best avoided in these patients. Low doses are usually well tolerated, however, and frequently used as part of a balanced anesthetic.
For the patient with severely compromised myocardial function, the synthetic piperidine narcotics (fentanyl, sufentanil, remifentanil) are useful because myocardial contractility is not depressed. Bradycardia associated with high-dose narcotic anesthesia may be prevented by the use of pancuronium for muscle relaxation, anticholinergic drugs, or pacing. Pancuronium, however, should be avoided in patients with impaired renal function, a common problem in cardiomyopathy patients. For peripheral or lower abdominal surgical procedures, a regional anesthetic technique is a reasonable alternative, provided filling pressures are carefully controlled and the hemodynamic effects of the anesthetic are monitored. A recent study suggests that thoracic epidural used as a therapeutic strategy in addition to medical therapy in patients with DCM may improve cardiac function and reduce hospital readmission and mortality. 134 One problem is that regional anesthesia is frequently contraindicated because patients with cardiomyopathies are frequently treated with anticoagulant and antiplatelet drugs to prevent embolization of mural thrombi that develop on hypokinetic ventricular wall segments.
In planning anesthetic management for the patient with DCM, associated cardiovascular conditions, such as the presence of CAD, valvular abnormalities, LVOT obstruction, and constrictive pericarditis should also be considered. Patients with CHF often require circulatory support intraoperatively and postoperatively. Inotropic drugs such as dopamine and dobutamine are effective in low output states and produce modest changes in SVR at lower dosages. In severe ventricular failure, more potent drugs such as epinephrine may be required. Phosphodiesterase-III inhibitors, such as milrinone, with inotropic and vasodilating properties, may improve hemodynamic performance. As previously noted, stroke volume is inversely related to afterload in the failing ventricle, and reduction of left ventricular afterload with vasodilating drugs such as nicardipine, nitroprusside, and nesiritide are also effective in increasing cardiac output.
In patients with myocarditis, especially of the viral variety, transvenous or external pacing may be required should heart block occur. Intra-aortic balloon counterpulsation, left ventricular assist devices, and cardiac transplantation are further options to be considered in the case of the severely compromised ventricle. Incidence of supraventricular and ventricular arrhythmias increases in myocarditis and DCM. 135, 136 These arrhythmias often require extensive electrophysiologic workup and may be unresponsive to maximal medical therapy. Frequently, patients with DCM present for AICD implantation or ventricular arrhythmia ablation procedures. 137

Restrictive Cardiomyopathies
Primary restrictive nonhypertrophied cardiomyopathy is a rare form of heart muscle disease and heart failure characterized by biatrial enlargement, normal or decreased volume of both ventricles, normal left ventricular wall thickness and A-V valves, and impaired ventricular filling with restrictive pathophysiology. Restrictive (or restrictive/obliterative) cardiomyopathies are usually the end stage of myocarditis or an infiltrative myocardial process (amyloidosis, hemochromatosis, scleroderma, eosinophilic heart disease) or the result of radiation treatment 138 ( Table 2-5 ). New evidence suggests that restrictive cardiomyopathy is genetic in origin, with mutations in sarcomeric contractile protein genes. 139, 140

Table 2-5 Restrictive/Obliterative Cardiomyopathies (Including Restrictive Endocarditis)
Restrictive cardiomyopathy may share characteristics with constrictive pericarditis. Cardiac output is maintained in the early stages by elevated filling pressures and an increased heart rate. However, in contrast to constrictive pericarditis, an increase in myocardial contractility to maintain cardiac output is usually not possible. 141 Thromboembolic complications are common and may be the initial presentation. Advanced states can lead to elevated jugular venous pressure, peripheral edema, liver enlargement, ascites, and pulmonary congestion. Also, whereas constrictive pericarditis is usually curable surgically, restrictive cardiomyopathy requires medical therapy and in some patients, valvular repair or cardiac transplantation. Imaging techniques such as echocardiographic evaluation with speckle-track imaging, velocity vector imaging combined with computed tomography (CT), and cardiac magnetic resonance imaging (MRI) can help differentiate constrictive and restrictive types of cardiomyopathy. 138, 142

Anesthetic considerations
Anesthetic and monitoring considerations in patients with restrictive cardiomyopathies are similar to those of constrictive pericarditis and cardiac tamponade, with the additional feature of poor ventricular function in later stages of the disease. (See Constrictive Pericarditis later for the physiology and management of restrictive ventricular filling and earlier Dilated Cardiomyopathy for the management of impaired ventricular function.) Anesthetic management depends on whether restrictive physiology or heart failure is predominant.
Despite normal ventricular function, diastolic dysfunction in patients with restrictive cardiomyopathy leads to a low cardiac output state. Monitoring should include at a minimum invasive intra-arterial BP monitoring, and central venous access should be established in patients with advanced disease. A PAC offers the advantage of cardiac output measurement and the assessment of loading conditions, both of which may be helpful in guiding anesthetic management, even though outcome data has not been established for this particular group of patients.
When inducing anesthesia, it may be prudent to avoid medications that produce bradycardia, decreased venous return, and myocardial depression. Etomidate can be used for anesthesia induction with little impact on hemodynamics and myocardial function. 143 Ketamine, even though intrinsic cardiodepressive properties have been described, maintains SVR and is frequently used in these patients. Anesthesia can typically be maintained with a balanced anesthesia technique using lower doses of inhaled potent volatile anesthetics, supplemented with an opioid such as fentanyl or sufentanil. 144, 145 A high-dose opioid technique, as recommended in the past, is usually reserved for patients with advanced disease who may not tolerate inhalational anesthetic agents.

Human Immunodeficiency Virus and the Heart
According to the U.S. Centers for Disease Control and Prevention (CDC), at the end of 2010, more than 1 million people in the United States and more than 34 million worldwide may be infected with the human immunodeficiency virus (HIV). 146, 147 HIV affects all organ systems, including the cardiovascular system. The heart can be affected by the virus directly, by opportunistic infections related to the immunocompromised state, by malignancies common to the disease, and by drug therapy.
Left ventricular diastolic function is affected early in the course of HIV infection. Echocardiographic evaluation of 51 HIV-positive patients compared with data from age-matched and gender-matched controls found that HIV-positive patients, regardless of the presence of symptomatic disease, had impaired LV diastolic function. 148 The mechanism of dysfunction is unclear but may be secondary to viral myocarditis; the clinical significance remains to be determined. Systolic dysfunction has been reported later in the disease course. Signs and symptoms of LV failure may also be masked by concurrent pulmonary disease. Pulmonary hypertension also has been described in patients with HIV infection. 149
Systolic dysfunction in HIV-positive patients may be a side effect of antiviral medications, especially the reverse-transcriptase inhibitor zidovudine (AZT). 150 Electron microscopy studies show that AZT disrupts the mitochondrial apparatus of cardiac muscle. 151, 152 Children infected with HIV who were treated with AZT had a significant decrease in LV ejection fraction compared with those not receiving AZT; Domanski et al. 150 recommended serial evaluation of LV function. Starc et al. 153 found that 18% to 39% of children diagnosed with acquired immunodeficiency syndrome (AIDS) developed cardiac dysfunction within 5 years of follow-up, and that cardiac dysfunction was associated with an increased risk of death. The effects of the newer antiviral agents on the heart have not yet been established.
Heart involvement was found in 45% of patients with AIDS in an autopsy study. 154 Pericardial effusion, DCM, aortic root dilation and regurgitation, and valvular vegetations were the more frequent findings. 155, 156 The pericardium is sometimes affected by opportunistic infections (e.g., cytomegalovirus) and tumors (e.g., Kaposi’s sarcoma, non-Hodgkin’s lymphoma). Additionally, an autonomic neuropathy associated with HIV infection can cause QT prolongation, which may predispose these patients to ventricular arrhythmias. 157

Anesthetic considerations
General anesthesia is considered safe in HIV/AIDS patients, but drug interactions and their impact on various organ systems and the patient’s overall physical status should be considered preoperatively. Rarely, patients with advanced disease may also have pericardial involvement with pericardial effusion and tamponade. An echocardiographic evaluation may provide useful information in this setting. A preoperative chest radiograph should be available in all symptomatic patients undergoing surgery under general anesthesia to rule out tuberculosis and acute pulmonary infections. Although general anesthesia may suppress the immune system, no adverse effects on patients with HIV/AIDS have been found. 158 Regional anesthesia is often the technique of choice, and early concerns regarding neuraxial anesthesia and the potential spread of infectious material intrathecally could not be confirmed. 159 - 164
Drug interactions between antiviral medications and drugs used during anesthesia induction and maintenance have been described, 165 - 167 but serious side effects are rare. Antiviral medications should be continued perioperatively in patients scheduled for surgery. 168, 169

Miscellaneous Cardiomyopathies

Stress (Takotsubo) Cardiomyopathy
Stress cardiomyopathy is a relatively recently described clinical entity, also known by its Japanese name, Takotsubo, (“octopus trap”). It is typically characterized by reversible apical left ventricular systolic dysfunction in the absence of atherosclerotic CAD that is triggered by profound psychological stress. 170, 171 Although traditionally the disease is described as “apical ballooning” (resembling an octopus trap), Takotsubo cardiomyopathy may manifest as midventricular and basal ventricular dysfunction. 172 The ventricular pathology overall is the result of myocardial stunning, leading to transient periods of ischemia, possibly from coronary artery vasospasm. 173 Other proposed mechanisms include catecholamine-induced damage, microvascular endothelial dysfunction, and neurogenically mediated myocardial stunning. 174 On ECG, this disease mimics ST-elevation myocardial infarction. 175, 176
Treatment includes providing mechanical ventilatory support, vasopressors to support systemic blood pressure, and diuretics as needed. 177 - 179 Fortunately, stress cardiomyopathy is usually transient and resolves with supportive care.
There is no current consensus on how to best deliver anesthesia to patients with a history of Takotsubo cardiomyopathy. Most case reports describe that adverse events occurred mostly during general anesthesia, and surgery performed under regional anesthesia was well tolerated. Such reports are so few, however, that recommendations on anesthesia technique cannot be made at this time. 180 - 186 It seems prudent to make attempts to prevent emotional stress or sympathetic surges, which frequently occur in the perioperative period. Adequate sedation and anxiolysis should therefore be provided preoperatively.

Peripartum cardiomyopathy
Peripartum cardiomyopathy typically develops during the third trimester of pregnancy or within 5 months after delivery. 187, 188 It is a distinct form of cardiomyopathy and unrelated to any other cause of heart failure. Symptoms are those of systolic heart failure, including sudden cardiac arrest, and develop in the majority of patients within 4 months after delivery. 189 Perioperative cardiomyopathy (HCM) carries a significant risk for high morbidity and mortality, but full recovery is possible. 190 Treatment and anesthetic management of patients with peripartum cardiomyopathy depend on the severity of presenting symptoms. The most common form of clinical presentation for anesthesiologists is significantly decreased systolic cardiac function, including cardiogenic shock, and should be treated accordingly. The underlying pathophysiology is similar to that of a dilated cardiomyopathy, as discussed earlier.

Secondary Cardiomyopathies
Many disease processes lead to myocardial pathology, and the presentation varies with secondary cardiomyopathies. Each patient should receive individualized treatment based on the manifestations of their specific disease. Typically the underlying etiology will result in a cardiac manifestation affecting the myocardium or valvular function, and perioperative care should be managed accordingly.

Cardiac tumors
Primary tumors of the heart are unusual. However, the likelihood of encountering a cardiac tumor increases when metastatic tumors of the heart and pericardium are considered. For example, breast cancer and lung cancer metastasize frequently to the heart. 191 Primary cardiac tumors may occur in any chamber or in the pericardium and may arise from any cardiac tissue. Of the benign cardiac tumors, myxoma is the most common, followed by lipoma, papillary fibroelastoma, rhabdomyoma, fibroma, and hemangioma 192 - 194 ( Table 2-6 ). The generally favorable prognosis for patients with benign cardiac tumors is in sharp contrast to the prognosis for those with malignant cardiac tumors. The diagnosis of a malignant primary cardiac tumor is seldom made before extensive local involvement and metastases have occurred, making curative surgical resection an unlikely event.
Table 2-6 Primary Neoplasms of the Heart and Pericardium Type No. Cases Percentage BENIGN Myxoma 130 29.3 Lipoma 45 10.1 Papillary fibroelastoma 42 9.5 Rhabdomyoma 36 8.1 Fibroma 17 3.8 Hemangioma 15 3.4 Teratoma 14 3.2 Mesothelioma of A-V node 12 2.7 Granular cell tumor 3 0.7 Neurofibroma 3 0.7 Lymphangioma 2 0.5 Subtotal 319 72.0 MALIGNANT Angiosarcoma 39 8.8 Rhabdomyosarcoma 26 5.8 Mesothelioma 19 4.2 Fibrosarcoma 14 3.2 Malignant lymphoma 7 1.6 Extraskeletal osteosarcoma 5 1.1 Neurogenic sarcoma 4 0.9 Malignant teratoma 4 0.9 Thymoma 4 0.9 Leiomyosarcoma 1 0.2 Liposarcoma 1 0.2 Synovial sarcoma 1 0.2 Subtotal 125 28 TOTAL 444 100

Benign Cardiac Tumors
Myxomas are most frequently benign tumors. They typically originate from the region adjacent to the fossa ovalis and project into the left atrium. They are usually pedunculated masses that resemble organized clot on microscopy and may be gelatinous or firm. A left atrial myxoma may prolapse into the mitral valve during diastole. This often results in a ball-valve obstruction to left ventricular inflow that mimics mitral stenosis; it may also cause valvular damage by a “wrecking-ball” effect. More friable tumors result in systemic or pulmonary embolization, depending on the location and the presence of any intracardiac shunts. Pulmonary hypertension may result from mitral valve obstruction or regurgitation caused by a left atrial myxoma, or pulmonary embolization in the case of a right atrial myxoma. Atrial fibrillation may be caused by atrial volume overload. Surgical therapy requires careful manipulation of the heart before institution of cardiopulmonary bypass, to avoid embolization, and resection of the base of the tumor to prevent recurrence, with overall very good early and long-term outcomes. 195 - 197
Other benign cardiac tumors occur less frequently. In general, intracavitary tumors result in valvular dysfunction or obstruction to flow, and tumors localized in the myocardium cause conduction abnormalities and arrhythmias. Papilloma (papillary fibroelastoma) is usually a single, villous connective tissue tumor that results in valvular incompetence or coronary ostial obstruction. Cardiac lipoma is an encapsulated collection of mature fat cells. Lipomatous hypertrophy of the interatrial septum is a related disorder that may result in right atrial obstruction. Rhabdomyoma is a tumor of cardiac muscle that occurs in childhood and is associated with tuberous sclerosis. Fibroma is another childhood cardiac tumor. 198

Malignant Cardiac Tumors
Of the 10% to 25% of primary cardiac tumors that are malignant, almost all are sarcomas. 199, 200 The curative therapy of sarcomas is based on wide local excision that is not possible in the heart. Also, the propensity toward early metastasis contributes to the dismal prognosis. Rhabdomyosarcoma may occur in neonates, but most cardiac sarcomas occur in adults. Sarcomas may originate from vascular tissue, cardiac or smooth muscle, and any other cardiac tissue. Palliative surgery may be indicated to relieve symptoms caused by mass effects. 201 Patients with these tumors respond poorly to radiotherapy and chemotherapy. 202

Metastatic Cardiac Tumors
Breast cancer, lung cancer, lymphomas, and leukemia may all result in cardiac metastases. About one fifth of patients who die of cancer have cardiac metastases. Thus, metastatic cardiac tumors are much more common than primary ones. Myocardial involvement results in CHF and may be classified as a restrictive cardiomyopathy. Pericardial involvement results in cardiac compression from tumor mass or tamponade caused by effusion. Melanoma is particularly prone to cardiac metastasis. 203

Cardiac Manifestations of Extracardiac Tumors
Carcinoid is a tumor of neural crest origin that secretes serotonin, bradykinin, and other vasoactive substances. 204 Hepatic carcinoid metastases result in right-sided valvular lesions, presumably from a secretory product that is metabolized in the pulmonary circulation. Recently, serotonin itself has been implicated in the pathogenesis of tricuspid valve dysfunction. 205 - 207 The end result is thickened valve leaflets that may be stenotic or incompetent, although regurgitation is more common.
Pheochromocytoma is a catecholamine-secreting tumor also of neural crest origin. Chronic catecholamine excess has toxic effects on the myocardium that may result in a dilated cardiomyopathy. 208

Anesthetic Considerations
The presence of a cardiac tumor requires a careful preoperative assessment of cardiac morphology and function. Transthoracic and transesophageal echocardiography, CT, and MRI are all used for diagnosis and assessment of treatment options. For the anesthesiologist planning for the appropriate technique, these imaging results are essential. A right-sided tumor, for example, is a relative contraindication to PAC insertion because of the risk of embolization. Functional mitral stenosis caused by a large left atrial myxoma may require hemodynamic management similar to that of fixed mitral stenosis should the patient become hemodynamically unstable. Adequate preload to maximize ventricular filling in the presence of an obstructing tumor, slow heart rate, and high afterload to maintain perfusion pressure in the setting of a fixed low cardiac output, are all goals when planning an appropriate anesthetic technique. The use of intraoperative TEE can be invaluable in the management of patients with cardiac tumors ( Fig. 2-3 ). In the 2010 practice guideline update, use of TEE is recommended for all open-heart surgery, including removal of intracardiac tumors. 126

Figure 2-3 A, Transesophageal echocardiogram of mass on right cusp of aortic valve. B, Photograph of resected aortic valve from same patient, with the tumor attached to right cusp.
Carcinoid tumors demand more challenging management strategies because the hypotension that can result from their manipulation may not be responsive to, and may even be provoked by, certain vasoactive drugs, including epinephrine, norepinephrine, and dopamine. Castillo et al. 209 review the management of patients undergoing surgery for carcinoid heart disease. Usually, general anesthetic management includes administration of a preoperative loading dose of the somatostatin analog octreotide, followed by a continuous infusion. Episodes of hypotension and hypertension are treated with additional octreotide boluses and vasoactive drugs. Epinephrine should probably be avoided and has been associated with higher mortality in a recent study. Weingarten et al. 210 acknowledge, however, that patients receiving epinephrine had worse preoperative New York Heart Association (NYHA) functional class symptoms, which could partly explain this finding. The use of vasopressin in the hypotensive patient with carcinoid is generally considered safe. Most inotropic and vasoactive drugs have been administered in these patients in true emergencies and during significant hemodynamic compromise when unresponsive to octreotide alone. The perioperative administration of octreotide probably decreases the triggering effect of these drugs. Histamine-releasing medications (e.g., morphine, meperidine, atracurium) should be avoided. Induction medications (e.g., etomidate, propofol) and benzodiazepines (e.g., midazolam) have all been used successfully in patients with carcinoid disease.

Ischemic heart disease
The most important aspects of coronary artery disease remain the same regardless of the etiology of the obstruction in the coronary arteries. As with that produced by arteriosclerosis, the CAD produced by an uncommon disease retains the key clinical features. Physiologic considerations remain essentially the same, as do treatment and anesthetic management.
The preoperative assessment should determine the symptoms produced by the CAD. Symptoms in the patient history are angina, exercise limitations, and those of myocardial failure, such as orthopnea or paroxysmal nocturnal dyspnea. The physical examination retains its importance, especially when quantitative data regarding cardiac involvement are not available. Physical findings such as S3 and S4 heart sounds are important, as are auscultatory signs of uncommon conditions such as cardiac bruits, which might occur in a coronary arteriovenous fistula. If catheterization, echocardiography, and other imaging data are available, the specifics of coronary artery anatomy and ventricular function, such as end-diastolic pressure, ejection fraction, and presence of wall motion abnormalities, are all useful in guiding management. 211, 212
After ascertaining the extent of CAD, the clinician should consider special aspects of the disease entity producing the coronary insufficiency. In ankylosing spondylitis, for example, coronary insufficiency is produced by ostial stenosis, yet valvular problems often coexist and even overshadow the CAD. 213 In rheumatoid arthritis, however, airway problems may be the most significant part of the anesthetic challenge. Hypertension, which frequently coexists with arteriosclerotic CAD, is also a feature of the CAD produced by Fabry’s disease. Other features to consider are metabolic disturbances, as when systemic lupus erythematosus produces both CAD and renal failure. 214

Physiology of Coronary Artery Disease and Modification by Uncommon Disease
The key to the physiology of CAD is the balance of myocardial oxygen (O 2 ) supply and demand ( Fig. 2-4 ). Myocardial O 2 supply depends on many factors, including the heart rate, patency of the coronary arteries, hemoglobin concentration, Pa O 2 , and coronary perfusion pressure. The same factors determine supply in uncommon diseases, but the specific manner in which an uncommon disease modifies these factors should be sought. A thorough knowledge of the anatomy of the coronary circulation and how the disease process can affect arterial patency is a useful starting point; this information is usually derived from coronary angiography. In assessing the adequacy of coronary perfusion, the viscosity of the blood should be considered because flow is a function both of the dimensions of the conduit and the nature of the fluid in the system. In disease processes such as thrombotic thrombocytopenic purpura, sickle cell disease, or polycythemia vera, the altered blood viscosity can assume critical importance. 215 - 218

Figure 2-4 Myocardial oxygen supply and demand balance.
Oxygen carrying capacity must also be considered in certain uncommon disease states. Hemoglobin concentration is usually not a limiting factor in the O 2 supply to the myocardium. However, in diseases such as leukemia, anemia may be a prominent feature, and the myocardial O 2 supply may be reduced accordingly. Another example is myocardial ischemia in carbon monoxide poisoning, where the hemoglobin, although quantitatively sufficient, cannot carry oxygen. Similarly, the partial pressure of oxygen in arterial blood (Pa O 2 ) is usually not a limiting factor. However, in conditions where CAD coexists with cor pulmonale, as in schistosomiasis or sickle cell disease, the inability to maintain adequate oxygenation may limit the myocardial O 2 supply. In sickle cell disease it may be the key feature; failure to maintain an adequate Pa O 2 , secondary to repeated pulmonary infarctions, further increases the tendency of cells containing hemoglobin S to sickle, compromising myocardial O 2 delivery through “sludging” in the coronary microcirculation. 219
The major factors determining myocardial O 2 demand include heart rate, ventricular wall tension, and myocardial contractility. Tachycardia and hypertension after tracheal intubation, skin incision, or other noxious stimuli are common causes of increased myocardial O 2 demand during surgery. Additionally, complicating factors of an unusual disease may also produce increases in demand. Increases in rate may occur as a result of tachyarrhythmias secondary to sinoatrial (SA) or A-V nodal involvement in amyloidosis or in Friedreich’s ataxia. Increases in wall tension may occur in severe hypertension associated with systemic lupus erythematosus (SLE), periarteritis nodosa, or Fabry’s disease. Outflow tract obstruction with increased ventricular work can occur in primary xanthomatosis or tertiary syphilis; and diastolic ventricular radius can also increase, with greater wall tension, as in aortic regurgitation associated with ankylosing spondylitis.
Modern cardiac anesthesia practice should tailor the anesthetic management to the problems posed by the peculiarities of the coronary anatomy. For example, knowledge of the presence of a lesion in the left main coronary artery dictates great care during anesthesia to avoid even modest hypotension or tachycardia. Lesions of the right coronary artery are known to be associated with an increased incidence of atrial arrhythmias and heart block, and steps must be taken either to treat these or to compensate for their cardiovascular effects.
In diseases such as primary xanthomatosis or Hurler’s syndrome, the infiltrative process that produces CAD usually involves the coronary arteries diffusely, but some diseases may have features that can mimic either isolated left main CAD or right CAD. Bland-White-Garland syndrome, which is anomalous origin of the left coronary artery from the pulmonary artery, and coronary ostial stenosis produced by aortic valve prosthesis both behave as left main CAD. A similar syndrome could be produced by bacterial overgrowth of the coronary ostia, ankylosing spondylitis, a dissecting aneurysm of the aorta, or Takayasu’s arteritis. Right CAD could be mimicked by the syndrome of the anomalous origin of the right coronary artery from the pulmonary artery, or infiltration of the SA or A-V nodes in amyloidosis or Friedreich’s ataxia. In small-artery arteritis, which occurs in periarteritis nodosa or SLE, the small arteries supplying the SA or A-V nodes may be involved in the pathologic process, producing ischemia of the conduction system.
The uncommon diseases that produce CAD can be divided into those that produce CAD associated with good (normal) left ventricular function and those associated with poor LV function ( Box 2-2 ). In any of these diseases, ventricular function can regress from good to poor. In some conditions the CAD progression and ventricular deterioration occur at the same rate, and LV function is eventually severely depressed. In other situations, coronary insufficiency is primary, and LV dysfunction eventually occurs after repeated episodes of ischemia and thrombosis. Ventricular function must be evaluated by clinical signs and symptoms, echocardiography, nuclear imaging, MRI, or cardiac catheterization. The converse is severe arterial disease coupled with relatively good LV function. This is the picture of a cardiomyopathy associated with almost incidental CAD, as occurs in Hurler’s syndrome, amyloidosis, or SLE. Most anatomic lesions, such as Kawasaki’s disease, coronary AV fistula, and trauma-induced coronary insufficiency, are usually associated with good LV function. There is a clinical “gray zone” where CAD and poor LV function coexist, with neither process predominating, such as with tuberculosis and syphilis. These diseases can only be characterized by investigating the extent of involvement of the coronary arteries and the myocardium in the disease process. The following discussion focuses on select disease states that affect the coronary arteries.

Box 2-2 Uncommon causes of coronary artery disease

Coronary Artery Disease Associated with Cardiomyopathy (Poor Left Ventricular Function)

A. Pathologic basis: infiltration of coronary arteries with luminal narrowing
     1. Amyloidosis: valvular stenosis, restrictive cardiomyopathy
     2. Fabry’s disease: hypertension
     3. Hurler’s syndrome: often associated with valvular malfunction
     4. Hunter’s syndrome: often associated with valvular malfunction
     5. Primary xanthomatosis: aortic stenosis
     6. Leukemia: anemia
     7. Pseudoxanthoma elasticum: valve abnormalities
B. Inflammation of coronary arteries
     1. Rheumatic fever: in acute phase
     2. Rheumatoid arthritis: aortic and mitral regurgitation, constrictive pericarditis
     3. Periarteritis nodosa: hypertension
     4. Systemic lupus erythematosus: hypertension, renal failure, mitral valve malfunction
C. Embolic or thromboembolic occlusion of coronary arteries
     1. Schistosomiasis
     2. Sickle cell anemia: cor pulmonale depending on length and extent of involvement
D. Fibrous and hyaline degeneration of coronary arteries
     1. Post transplantation
     2. Radiation
     3. Duchenne’s muscular dystrophy
     4. Friedreich’s ataxia: possibly associated with hypertrophic obstructive cardiomyopathy
     5. Roussy-Lévy syndrome: hereditary polyneuropathy
E. Anatomic abnormalities of coronary arteries
     1. Bland-White-Garland syndrome (left coronary artery arising from pulmonary artery): endocardial fibroelastosis, mitral regurgitation
     2. Ostial stenosis secondary to ankylosing spondylitis: aortic regurgitation

Coronary Artery Disease Usually Associated with Normal Ventricular Function

A. Anatomic abnormalities of coronary arteries
     1. Right coronary arising from pulmonary artery
     2. Coronary arteriovenous fistula
     3. Coronary sinus aneurysm
     4. Dissecting aneurysm
     5. Ostial stenosis: bacterial overgrowth syphilitic aortic
     6. Coronary artery trauma: penetrating or nonpenetrating
     7. Spontaneous coronary artery rupture
     8. Kawasaki’s disease: coronary artery aneurysm
B. Embolic or thrombotic occlusion
     1. Coronary emboli
     2. Malaria and/or malarial infested red blood cells
     3. Thrombotic thrombocytopenic purpura
     4. Polycythemia vera
C. Infections
     1. Miliary tuberculosis: intimal involvement of coronary arteries
     2. Arteritis secondary to salmonella or endemic typhus (associated with active myocarditis)
D. Infiltration of coronary arteries
     1. Gout: conduction abnormalities, possible valve problems
     2. Homocystinuria
E. Coronary artery spasm
F. Cocaine
G. Miscellaneous
     1. Thromboangiitis obliterans (Buerger’s disease)
     2. Takayasu’s arteritis

Uncommon Causes of Ischemic Heart Disease

Coronary artery spasm
The luminal narrowing of the coronary arteries secondary to spasm has been associated with angina and myocardial infarction (MI). 220 The mechanism of coronary artery spasm remains unclear. The smooth muscle cells of the coronary artery walls may contract in response to various stimuli. 221 There may be abnormal responses to various vasoactive substances, 222, 223 and, in addition, there may be increased alpha-adrenergic tone. 224 Another theory is that vessels with eccentric atherosclerotic plaques have a segment of disease-free wall that may be a site for vasospasm, which can convert an insignificant obstruction into a critical lesion. Patients with coronary artery vasospasm may respond to nitroglycerin and calcium channel blockers.

Cocaine abuse
Cocaine can affect the heart in several ways, and cocaine use can result in myocardial ischemia, MI, and sudden death. 225 - 228 Cocaine exerts its effects on the heart mainly by its ability to block (1) sodium channels, resulting in a local anesthetic or membrane-stabilizing property, and (2) reuptake of norepinephrine, resulting in increased sympathetic activity. Not surprisingly, therefore, cocaine administered acutely can have a biphasic effect on LV function, with transient depression followed by a sustained increase in contractility. 229 Cocaine also induces coronary vasospasm and reduced coronary blood flow while increasing heart rate and blood pressure. These effects decrease myocardial O 2 supply and increase O 2 demand. Cocaine and its metabolites can also induce platelet aggregation and release platelet-derived growth factor, which can promote fibrointimal proliferation and accelerated atherosclerosis. 230, 231 Chronic users of cocaine also have an exaggerated response to sympathetic stimuli, which may contribute to the LV hypertrophy frequently observed.

Coronary artery dissection
When there is separation of the intimal layer from the medial layer of the coronary artery, there may be obstruction of the true coronary artery lumen with subsequent distal myocardial ischemia. Coronary artery dissection may be primary or secondary. Primary coronary artery dissection may occur during coronary artery catheterization or angioplasty and in trauma to the heart. Primary coronary artery dissection may also occur spontaneously. Spontaneous dissection is usually associated with coronary arterial wall eosinophilia, and can also be seen in the postpartum period 232 and with cocaine abuse. 233 Secondary coronary artery dissection is more common and is usually caused by a dissection in the ascending aorta.

Inflammatory causes

Infectious
Infectious coronary artery arteritis may be secondary to hematogenous spread or direct extension from infectious processes of adjacent tissue. The infectious process results in thrombosis of the involved artery with myocardial ischemia. Syphilis is one of the most common infections to affect the coronary arteries. Up to 25% of patients with tertiary syphilis have ostial stenosis of the coronary arteries. 234, 235 HIV infection has also been associated with CAD. 236

Noninfectious

Polyarteritis Nodosa
This systemic necrotizing vasculitis involves medium-sized and small vessels. Epicardial coronary arteries are involved in the majority of cases of polyarteritis nodosa. After the initial inflammatory response, the coronary artery may dilate to form small, berrylike aneurysms that may rupture, producing fatal pericardial tamponade. 237, 238

Systemic Lupus Erythematosus
The pericardium and myocardium are usually affected in SLE. Patients with SLE, however, may suffer acute MI in the absence of atherosclerotic CAD. 239, 240 The hypercoagulable state of SLE together with a predisposition to premature coronary atherosclerosis has been implicated. In addition, glucocorticoids used for the treatment of SLE may also predispose these patients to accelerated atherosclerosis.

Kawasaki’s Disease (Mucocutaneous Lymph Node Syndrome)
In this disease of childhood, a vasculitis of the coronary vasa vasorum leads to weakened walls of the vessels with subsequent coronary artery aneurysm formation. 241 Thrombosis and myocardial ischemia can also occur. Patients with Kawasaki’s disease are prone to sudden death from ventricular arrhythmias and occasionally from rupture of a coronary artery aneurysm. Thrombus in the aneurysm may also embolize, causing myocardial ischemia. 242

Takayasu’s Disease
This disease leads to fibrosis and luminal narrowing of the aorta and its branches. The coronary ostia may be involved in this process. 243

Metabolic causes

Homocystinuria
An increased incidence of atherosclerotic disease is reported in patients with high levels of homocysteine. 244, 245 This process may involve intimal proliferation of small coronary vessels and an increased risk of MI. Nevertheless, meta-analysis and prospective studies have not consistently confirmed these findings. 246, 247

Congenital abnormalities of coronary arterial circulation

Left Coronary Artery Arising from Pulmonary Artery
In Bland-White-Garland syndrome the right coronary artery arises from the aorta, but the left coronary arises from the pulmonary artery. Flow in the left coronary arterial system is retrograde, with severe LV hypoperfusion as well as myocardial ischemia and infarction. As such, most patients with this defect present in infancy with evidence of heart failure. Untreated patients usually die during infancy. Patients who survive childhood may present with mitral regurgitation from annular dilation. The goals of medical therapy are to treat CHF and arrhythmias. The defect can be corrected surgically by primary anastomosis of the left coronary artery to the aorta. 248, 249 In older children, a vein graft or the left internal mammary artery may be used to establish anterograde flow in the left coronary arterial system. Postoperative improvement in LV function can be expected if this surgery is performed early. 250, 251

Coronary Arteriovenous Fistula
There is an anatomic communication between a coronary artery and a right-sided structure, such as the right atrium, right ventricle, or coronary sinus. The right coronary artery is more frequently affected and is usually connected to the coronary sinus. Most patients are asymptomatic. These patients are at risk for endocarditis, myocardial ischemia, and rupture of the fistulous connection. 252 These fistulas should be corrected surgically. 253

Anesthetic Considerations
The anesthetic employed in patients with ischemic heart disease or CAD should be tailored to the degree of myocardial dysfunction. 254 In patients with pure coronary insufficiency with good LV function, anesthetic management is aimed at decreasing O 2 demand by decreasing myocardial contractility while preserving O 2 supply. Continuous monitoring of hemodynamic parameters extending into the postoperative period is probably more important for patient outcome than choice of anesthetic technique. In patients with poor ventricular function, the anesthetic technique should maintain hemodynamic stability by avoiding drugs that produce significant degrees of myocardial depression. A regional technique, if applicable, may be the preferred anesthetic technique for smaller procedures. A neuraxial technique is not contraindicated as long as the patient’s coagulation status, including potent antiplatelet medications, is considered, and may actually provide superior pain control and reduce the stress response to surgery. However, caution must be exercised to prevent a sudden drop in blood pressure, and thus a spinal technique is relatively contraindicated. For major surgery, most practitioners employ a balanced general anesthetic technique.
When coronary vasospasm is considered, it is important to maintain a relatively high coronary perfusion pressure. Pharmacologic agents, such as nitroglycerin and calcium channel blockers, may also be used. Patients who are chronic users of cocaine should be considered at high risk for ischemic heart disease and arrhythmias. These patients may respond unpredictably to anesthetic agents and other drugs used in the perioperative period. Ephedrine and other indirect sympathomimetic drugs should be avoided in cocaine users.
In periarteritis nodosa or Fabry’s disease, hypertension is often associated with poor LV function. In such patients a vasodilator such as nicardipine, sodium nitroprusside, or nitroglycerin can be used to control hypertension, rather than a volatile anesthetic. Milrinone and nesiritide are also options. The principles for the management of intraoperative arrhythmias remain the same as for the treatment of arrhythmias in the patient with atherosclerotic CAD.
The degree of functional impairment of the myocardium and coronary circulation dictates the extent and type of monitoring. The selection of ECG leads to monitor depends on the coronary anatomy involved. Diseases involving left CAD are best monitored using precordial leads, such as the V 5 lead. In patients with right CAD, ECG leads used to assess the inferior surface of the heart (leads II, III, or aV F ), or the posterior surface (esophageal lead), are preferable. 255 - 257
Arterial blood pressure should be monitored by indwelling catheter in patients with known coronary insufficiency undergoing major procedures. The clinician should be cautious when using peripheral arterial monitoring in patients with generalized arteritis and carefully evaluate the adequacy of collateral blood flow before cannulation of the peripheral artery. In occlusive diseases (e.g., Raynaud’s, Takayasu’s arteritis, Buerger’s) or in cases of sludging in the microcirculation (e.g., sickle cell disease), the area distal to the cannulated artery should be checked frequently for signs of arterial insufficiency. A more central and larger vessel, such as the axillary artery, should be chosen for arterial catheterization. The use of a PAC, once routinely deployed in patients with impaired ventricular function and CAD, has not been shown to improve outcome. In the absence of convincing evidence of outcome benefits associated with pulmonary artery catheterization, decisions regarding this type of monitoring should be made on a case-by-case basis. Central venous access should be considered for administration of vasoactive medications in patients with significant CAD undergoing major procedures.

Pulmonary hypertension and cor pulmonale
Pulmonary hypertension (PHT) has been defined as mean pulmonary artery pressure (PAP) greater than 25 mm Hg at rest or greater than 30 mm Hg during exercise, or pulmonary vascular resistance (PVR) of 3 Wood units or greater, with a pulmonary artery occlusion pressure of 15 mm Hg or less. 258 More recently, it has been suggested to simplify the definition of PHT as a mean PAP greater than 25 mm Hg at rest, without taking exercise or PVR into consideration. 259 The 2008 revised nomenclature on PHT (Dana Point Classification) lists five main categories: (1) pulmonary arterial hypertension, (2) PHT caused by left-sided heart disease, (3) PHT caused by lung disease and/or hypoxia, (4) chronic thromboembolic PHT, and (5) PHT with unclear multifactorial mechanisms 1, 260 ( Box 2-3 ).

Box 2-3 Diagnostic classification of pulmonary hypertension

1. Pulmonary arterial hypertension (PAH)
     1.1 Idiopathic PAH
     1.2 Heritable PAH
     1.3 Drug- and toxin-induced
     1.4 PAH associated with
     1.5 Persistent PAH of the newborn
     1.6 Pulmonary veno-occlusive disease
2. Pulmonary hypertension caused by left-sided heart disease
     2.1 Systolic dysfunction
     2.2 Diastolic dysfunction
     2.3 Valvular disease
3. Pulmonary hypertension caused by lung disease and/or hypoxia
     3.1 Chronic obstructive pulmonary disease
     3.2 Interstitial lung disease
     3.3 Other pulmonary diseases
     3.4 Sleep-disordered breathing
     3.5 Alveolar hypoventilation disorders
     3.6 Chronic exposure to altitude
     3.7 Developmental abnormalities
4. Chronic thromboembolic pulmonary hypertension
5. Pulmonary hypertension with unclear multifactorial mechanisms
     5.1 Hematologic disorders
     5.2 Systemic disorders (e.g., sarcoidosis)
     5.3 Metabolic disorders
Modified from Simonneau G, et al: Updated clinical classification of pulmonary hypertension, J Am Coll Cardiol 54:S43-S54, 2009.

Pathophysiology
The normal pulmonary vasculature changes from a high-resistance circuit in utero to a lower-resistance circuit in the newborn secondary to several concomitant changes: (1) the relief of hypoxic vasoconstriction that occurs with breathing air; (2) the stenting effect of air-filled lungs on the pulmonary vessels, which increases their caliber and decreases their resistance; and (3) the functional closure of the ductus arteriosus, secondary to an increase in the Pa O 2 . The muscular medial layer of the fetal pulmonary arterioles normally involutes in postnatal life, and PAP assumes normal adult values by 2 to 3 months of age. Assuming there is no active vasoconstriction, PAP remains low even when blood flow across the pulmonary vascular bed is increased, because of the numerous parallel vascular channels that distend and lower their resistance when blood flow is increased. General pathologic conditions, which are the basis of the PHT classification, will convert this normally low-resistance circuit into a high-resistance circuit. A decrease in pulmonary arterial cross-sectional area results in increased PVR, as dictated by Poiseuille’s law, which states that resistance to flow is inversely proportional to the fourth power of the radius of the vessels.
There are a number of rarer causes of decreased pulmonary arterial cross-sectional area. For example, filarial worms, the eggs of Schistosoma mansoni, or multiple small thrombotic emboli are typical embolic causes of PHT. Primary deposition of fibrin in the pulmonary arterioles and capillaries caused by altered hemostasis with prothrombotic mechanisms, especially increased platelet activation, also decreases cross-sectional area. Pulmonary arterial medial hypertrophy can occur if there is increased flow or pressure in the pulmonary circulation early in life. In this situation the muscular media of the pulmonary arterioles undergo hypertrophy rather than the normal postnatal involution. 261 As the muscle hypertrophies, reflex contraction increases in response to PAP elevation. This raises the PAP even higher by further reducing cross-sectional area. Long-standing PAP elevation results in intimal damage to the pulmonary arterioles, followed by fibrosis, thrombosis, and sclerosis, with an irreversible decrease in cross-sectional area of the arterial bed, as often occurs in long-standing mitral valve disease or emphysema.
Primary vasoconstrictors, such as the seeds of Crotalaria plants, or hypoxia associated with high altitude or pulmonary parenchymal disease can also cause PHT. 262 PHT resulting from increases in pulmonary arterial flow is usually associated with various congenital cardiac lesions, such as atrial septal defect, ventricular septal defect (VSD), patent ductus arteriosus, or in adult life, VSD occurring after a septal MI. Hypoxemia will aggravate this situation; an increased incidence of PHT is seen in infants with congenital left-to-right shunting who are born at high altitudes compared with similar infants born at sea level. Long-standing increases in flow with intimal damage may result in fibrosis and sclerosis, as previously noted. An increase in PAP in these patients ultimately may result in Eisenmenger’s syndrome, in which irreversibly increased PAP results in a conversion of left-to-right shunting to right-to-left shunting, with the development of tardive cyanosis.
As with systemic arterial hypertension, PHT is characterized by a prolonged asymptomatic period. As pulmonary vascular changes occur, an irreversible decrease in pulmonary cross-sectional area develops, and stroke volume becomes fixed as a result of the fixed resistance to flow. As such, cardiac output becomes heart rate dependent, resulting in the symptoms of dyspnea, fatigue, syncope, and chest pain. Right ventricular (RV) hypertrophy often occurs in response to PHT, which may progress to RV dilation and failure. 263

Cor Pulmonale
Cor pulmonale (also known as pulmonary heart disease ) is usually defined as an alteration in the structure and function of the right ventricle, such as RV hypertrophy, dilation, and right-sided heart failure secondary to increased resistance or pressure in the lungs. Therefore this excludes RV failure, which occurs after increases in PAP secondary to increases in pulmonary blood flow, pulmonary capillary pressure, or venous pressure. Both increases in pulmonary blood flow and passive increases in pulmonary venous and capillary pressure can produce RV failure, but strictly speaking, do not produce cor pulmonale. The physiologic considerations in cor pulmonale and in RV failure from other causes are similar. The many causes of cor pulmonale include pulmonary parenchymal disease, pulmonary embolism, chronic hypoxia, obstructive sleep apnea, and primary pulmonary artery disease. 264

Types
Cor pulmonale is divided into two types: acute and chronic. Acute cor pulmonale is usually secondary to a massive pulmonary embolus, resulting in a 60% to 70% decrease in the pulmonary cross-sectional area, associated with cyanosis and acute respiratory distress. With acute cor pulmonale, there is a rapid increase in RV systolic pressure, which slowly returns toward normal secondary to displacement of the embolus peripherally, lysis of the embolus, and increases in collateral blood flow. Massive emboli may be associated with acute RV dilation and failure, elevated central venous pressure, and cardiogenic shock. Another feature of massive pulmonary embolization is the intense pulmonary vasoconstrictive response. 265, 266
Chronic cor pulmonale presents with a different picture, associated with RV hypertrophy and dilation and a change in the normal crescentic shape of the right ventricle to a more ellipsoid shape. This configuration is consistent with a change from volume work that the right ventricle normally performs, to the pressure work required by a high afterload. LV dysfunction may occur in association with RV hypertrophy. This dysfunction cannot be related to any obvious changes in the loading conditions of the left ventricle and is probably caused by displacement of the interventricular septum. Chronic cor pulmonale is usually superimposed on long-standing pulmonary arterial hypertension associated with chronic respiratory disease. 267

Bronchitis
Chronic bronchitis is probably the most common cause of cor pulmonale in adults, and its pathophysiology can serve as a guide to understanding and managing cor pulmonale from all causes. Initially, the PVR in chronic bronchitis is normal or slightly increased because cardiac output increases. Later, there is a further increase in PVR or an inappropriately elevated PVR for the amount of pulmonary blood flow. Recall that normally there is a slight decrease in PVR when pulmonary blood flow is increased that is probably secondary to an increase in pulmonary vascular diameter and flow through collateral channels. In chronic bronchitis the absolute resistance of the pulmonary circulation may not change, because of the inability of the resistance vessels to dilate. A progressive loss of pulmonary parenchyma occurs and, because of dilation of the terminal bronchioles, an increase in pulmonary dead space causes progressively more severe mismatching of pulmonary ventilation and perfusion. In response to the ventilation/perfusion mismatch, the pulmonary circulation attempts to compensate by decreasing blood flow to the areas of the lung that have hypoxic alveoli. This occurs at the cost of decreased pulmonary arteriole cross-sectional area and increased PAP. 268
Long-standing chronic bronchitis results in elevations in PAP, with resulting alterations in the structure and function of the right ventricle, such as RV hypertrophy. In any form of respiratory embarrassment, whether infection or progression of the primary disease, further increases in PVR elevate PAP, and RV failure supervenes. With the onset of respiratory problems in the patient with chronic bronchitis, several changes can make PHT more severe and can precipitate RV failure. A respiratory infection produces further ABG abnormalities, with declines in Pa O 2 and elevations in Pa CO 2 . Generally, PAP is directly proportional to Pa CO 2 , although the pulmonary circulation also vasoconstricts in response to hypoxemia. With a decrease in Pa O 2 , there is usually an increase in cardiac output in an effort to maintain O 2 delivery to tissues. This increased blood flow through the lungs may result in further PAP elevations because of the fixed, decreased cross-sectional area of the pulmonary vascular bed. In addition, patients with chronic bronchitis and long-standing hypoxemia often have compensatory polycythemia. The polycythemic blood of the chronic bronchitis produces an increased resistance to flow through the pulmonary circuit because of its increased viscosity.
The patient with chronic bronchitis normally has increased airway resistance that worsens during acute respiratory infection because of secretions and edema that further decrease the caliber of the small airways. These patients also have a loss of structural support from degenerative changes in the airways and from a loss of the stenting effect of the pulmonary parenchyma. For these reasons, the patient’s small airways tend to collapse during exhalation, and airway pressure increases because of this “dynamic compression” phenomenon. In chronic bronchitis and emphysema, the decrease in cross-sectional area of the pulmonary vessels does not result from fibrotic obliteration of pulmonary capillaries or arterioles, but rather from hypertrophy of the muscular tunica media of the pulmonary arterioles. The vessels become compressible but not distensible, so that with exhalation and an increase in intrathoracic pressure, airway compression results in a further increase in PVR and an increase in PAP. The hypertrophied muscular tunica media vasorum prevents the resulting PAP increase from distending the pulmonary vessels and maintaining a normal pressure. With the onset of respiratory embarrassment in the patient with chronic bronchitis, there are increases in PAP, afterload, and RV work requirement that may result in RV failure.
A similar pattern may be observed in other forms of pulmonary disease, because the compensatory mechanisms are much the same as in chronic bronchitis. Chronic bronchitis, however, is somewhat more amenable to therapy because the acute pulmonary changes are often reversible. Relief of hypoxemia, for example, may be expected to ameliorate the PHT. In PHT and cor pulmonale secondary to pulmonary fibrosis, relief of hypoxia probably has little to offer the pulmonary circulation; the PVR increase is not caused by vasoconstriction of muscular pulmonary arterioles, but rather by a fibrous obliteration of the pulmonary vascular bed.

Anesthetic Considerations
Monitoring for patients with significant PHT, and in patients with right-sided heart failure, should provide a continuous assessment of PAP, RV filling pressure, RV myocardial O 2 supply/demand balance, and some measure of pulmonary function. The ECG allows for the monitoring of arrhythmias. In the setting of RV hypertrophy, with an increased risk of coronary insufficiency, ECG monitoring allows observation of the development of ischemia or acute strain of the right ventricle, seen in the inferior or right precordial leads. PAP monitoring provides an estimate of the severity of PHT, and in patients with right-sided heart failure, an indication of the workload imposed on the right ventricle. The PAC permits monitoring of PAP as well as central venous pressure, as an indication of RV filling pressure. Most anesthesiologists would choose PAP monitoring in patients with significant PHT, as well as in those with right-sided heart failure undergoing major surgical procedures associated with major fluid shifts, even without documented benefits in patient outcome. The PAC can also help distinguish between LV failure and respiratory failure. In LV failure, elevated PAP occurs with elevated pulmonary capillary wedge pressure (PCWP), whereas in respiratory failure, PAP is often elevated with a normal PCWP. The PAC also allows for the determination of cardiac output and PVR. It is important to follow the PAP in these patients; an increase in PAP is often the cause of acute cor pulmonale, and serial measurements of PAP and PVR allow evaluation of the effects of therapeutic interventions. Perioperative TEE is increasingly useful in this patient population because of the increasing numbers of trained individuals and equipment. Two-dimensional imaging of biventricular function and noninvasive estimates of RV systolic pressure (using tricuspid regurgitant jet and modified Bernoulli equation), as well as the severity and mechanism of tricuspid regurgitation, which is often seen with RV failure, are examples of applications of TEE monitoring for patients with PHT.
Pulse oximetry and ABG sampling are simple ways of assessing pulmonary function. Capnography is not an accurate method of assessing Pa CO 2 when significant “dead space” ventilation is present. The use of an indwelling arterial catheter facilitates arterial blood sampling and continuous arterial BP monitoring. Calculation of intrapulmonary venous admixture by using mixed venous blood samples obtained from the pulmonary artery, however, is a more sensitive indicator of pulmonary dysfunction than Pa O 2 values alone.
In the anesthetic management of patients with PHT or cor pulmonale, special consideration must be given to the degree of PHT and the functional state of the right ventricle. Possible scenarios include isolated PHT with or without right-sided heart failure and acute or chronic cor pulmonale with or without right-sided heart failure. The anesthetic management may differ accordingly, ranging from vigilant monitoring to acute cardiopulmonary resuscitation (CPR). Some general principles apply. Hypoxia, hypercarbia, acidosis, and hypothermia should be avoided because they increase PVR. 258 The use of a high inspired fraction of oxygen (Fi O 2 ) is often advised, but pulmonary vascular reactivity and the underlying etiology will often determine if a patient benefits from pulmonary vasodilator (including O 2 ) administration. For example, if PHT is coexistent with hypoxia in a patient with chronic bronchitis, O 2 administration may afford significant relief of the PHT. If the PHT is secondary to massive pulmonary fibrotic changes or acute mechanical obstruction from thromboembolism, however, little relief of PHT would be expected with O 2 administration.
The type of anesthetic and anesthesia technique is probably less important to patient outcome than the severity of PHT, associated right-sided heart failure, and surgery with expected hemodynamic instability. In 156 children with PHT undergoing 256 procedures, the incidence of complications increased with the severity of PHT, and complications were not associated with the type of anesthetic or airway management. 269 This was confirmed in another retrospective analysis of children with PHT undergoing general anesthesia. 270 The type of agents used for induction or maintenance of anesthesia was not associated with periprocedural complications. Major surgery, however, was a predictor of adverse events. Traditionally, it has been taught that nitrous oxide might increase PAP and should be used cautiously in this setting, even though scant data support this. 271
When PHT coexists with cor pulmonale, the anesthetic technique should attempt to preserve RV function. The primary concern is the maintenance of RV function in the face of an elevated RV afterload. In this setting, a balanced anesthesia technique employing opioids, such as fentanyl or sufentanil, in combination with sedative-hypnotic drugs, such as propofol or midazolam, or low doses of a potent inhalational agent will usually provide cardiovascular stability. 272 Inotropic support is often required in the patient with RV failure with chronic cor pulmonale. An inotropic agent should be selected only after considering its pulmonary effects, and the effects of the inotropic intervention should be monitored. As in LV failure, where the reduced LV afterload can increase stroke volume and cardiac output, in RV failure the reduction in RV afterload can produce similar effects.
Dobutamine or milrinone tend to reduce PAP and PVR and probably are the inotropic drugs of choice in RV failure without systemic hypotension. If RV perfusion pressures need to be maintained, or when RV contractility is severely impaired, norepinephrine or epinephrine is the preferred catecholamine, even in patients with PHT. 273, 274 Furthermore, vasopressin is particularly effective for systemic hypotension in patients with RV failure. 275 Vasodilators found effective in reducing RV afterload include sodium nitroprusside, nitroglycerin, milrinone, adenosine, nifedipine, amlodipine, and prostaglandin E 1 . 276, 277 Inhaled nitric oxide (NO) selectively dilates the pulmonary vasculature and has been used to treat PHT in various clinical settings. 278 - 280
Prostacyclin acts via specific prostaglandin receptors and has also been shown to reduce PHT. 281 However, the vasodilation is not selective for the pulmonary vasculature, and systemic hypotension may ensue. Prostacyclin analogs, such as epoprostenol, are given for chronic PHT and may also be useful for intraoperative use. One caveat is that inadvertent discontinuation of chronic IV epoprostenol therapy may lead to a fatal pulmonary hypertensive crisis. The administration of prostacyclin, nitroglycerin, and milrinone by inhalation is one strategy to reduce systemic side effects. 282, 283 Inhaled prostaglandins are replacing inhaled NO in some institutions because of cost considerations. Selective phosphodiesterase-5 inhibitors (e.g., sildenafil) are becoming the mainstay of chronic PHT therapy. Preoperative optimization of patients with severe PHT using sildenafil has been described. 284, 285
Endothelin receptor (ET-1)–A antagonists (e.g., bosentan, sitaxsentan, ambrisentan) are newer drugs that have been approved by the U.S. Food and Drug Administration (FDA) for the use in patients with PHT. 286, 287 Table 2-7 summarizes the hemodynamic effect on the systemic as well as pulmonary circulation of some of the more common drugs used in the anesthesia setting. Furthermore, medications used for treatment of chronic PHT should not be discontinued perioperatively because of the expected acute exacerbation of PHT. Since systemic hypotension is a side effect of some of these drugs, appropriate monitoring as previously outlined should be established before anesthesia induction. An anesthetic technique associated with a sudden drop in arterial blood pressure, such as a spinal anesthetic, is relatively contraindicated, except with careful preparation and monitoring. A balanced general anesthesia or epidural technique is preferred.

Table 2-7 Select Pulmonary Vascular Pharmacopeia

Pericarditis, effusion, and tamponade

Constrictive Pericarditis
The pericardium is not essential to life, as demonstrated by the benign effects of pericardiectomy. Nevertheless, the pericardium has several important functions. The intrapericardial pressure reflects intrapleural pressure and is a determinant of ventricular transmural filling pressure. During spontaneous ventilation, the pericardium serves to transmit negative pleural pressure, which maintains venous return to the heart. 288
Constrictive pericarditis results from fibrous adhesion of the pericardium to the epicardial surface of the heart. Table 2-8 lists conditions associated with constrictive pericarditis. With the key feature of increased resistance to normal ventricular filling, constrictive pericarditis is a chronic condition usually well tolerated by the patient until well advanced. Constrictive pericarditis often resembles a restrictive cardiomyopathy and occasionally presents a diagnostic dilemma. 289 - 292 Unlike restrictive cardiomyopathy, however, ventricular relaxation is usually preserved in patients with constrictive pericarditis. It restricts ventricular diastolic filling, so normal ventricular end-diastolic volumes are not obtained, and stroke volume is decreased. Compensatory mechanisms include an increase in heart rate and contractility, usually secondary to an increase in endogenous catecholamine release. This maintains cardiac output in the face of the restricted stroke volume until the decrease in ventricular diastolic volume is quite severe. As cardiac output falls, there is decreased renal perfusion, resulting in increased levels of aldosterone and thus increased extracellular volume. The greater extracellular volume increases RV filling pressure, which eventually becomes essential for maintaining ventricular diastolic volume in the presence of severe pericardial constriction.
Table 2-8 Conditions Causing Pericarditis and Cardiac Tamponade Pericarditis/Tamponade Associated Conditions CONSTRICTIVE PERICARDITIS   Idiopathic causes   Infectious causes   Can be sequela of most acute bacterial infections that produce pericarditis Myocarditis Cardiomyopathy Tularemia Valve malfunction Tuberculosis   Viral: especially arbovirus, coxsackievirus B Valvular obstruction Mycotic: histoplasmosis, coccidioidomycosis   Neoplasia   Primary mesothelioma of pericardium   Secondary to metastases: especially malignant melanoma   Physical causes   Radiation Cardiomyopathy Posttraumatic CAD Postsurgical   Systemic syndromes   Systemic lupus erythematosus Cardiomyopathy, CAD Rheumatoid arthritis Cardiomyopathy, CAD Aortic stenosis Uremia Cardiomyopathy Cardiac tamponade CARDIAC TAMPONADE   Infectious causes   Viral (most) Myocarditis Cardiomyopathy Valve malfunction Bacterial: especially tuberculosis   Protozoal: amebiasis, toxoplasmosis   Mycotic infection Valvular obstruction Systemic/metabolic causes   Systemic lupus erythematosus Cardiomyopathy, CAD Constrictive pericarditis Acute rheumatic fever   Rheumatoid arthritis Cardiomyopathy, CAD Aortic stenosis Pericarditis/Tamponade Associated Conditions Collagen disease   Uremia   Myxedema Low cardiac output Hemorrhagic diatheses   Genetic coagulation defects; anticoagulants   Drugs   Hydralazine, procainamide (Pronestyl), phenytoin (Dilantin)   Physical causes   Radiation Cardiomyopathy, CAD Constrictive pericarditis Trauma (perforation): surgical manipulation, intracardiac catheters, pacing wires   Neoplasia   Primary: mesothelioma, juvenile xanthogranuloma   Metastatic disease   Miscellaneous   Postmyocardial infarction: ventricular rupture   Pancreatitis   Reiter’s syndrome Aortic regurgitation Behçet’s syndrome   Löffler’s syndrome: endocardial fibroelastosis with eosinophilia Restrictive cardiomyopathy Long-standing congestive heart failure  
CAD, Coronary artery disease.
A number of characteristic hemodynamic features accompany constrictive pericarditis as well as pericardial tamponade. Rather than the slight respiratory variation in blood pressure seen in normal patients, dramatic respiratory variations in BP (pulsus paradoxus) are present. Kussmaul’s sign (jugular venous distention during inspiration) may also be seen. With adequate blood volume, right atrial pressure in constrictive pericarditis is usually 15 mm Hg or greater and usually equals left atrial pressure. Both constrictive pericarditis and cardiac tamponade demonstrate a diastolic “pressure plateau” or “equalization of pressures,” in which the right atrial pressure equals the right ventricular end-diastolic pressure, pulmonary artery diastolic pressure, and left atrial pressure.

Anesthetic considerations
Monitoring should assess the compensatory mechanisms in constrictive pericarditis. The ECG should be observed for heart rate and ischemic changes, because the myocardial O 2 supply/demand ratio can be altered by the pathologic process and therapeutic interventions. An indwelling arterial catheter for continuous BP monitoring should be established before anesthesia induction. A central venous pressure catheter is often indicated for venous access in patients with constrictive pericarditis undergoing more than minor procedures. The use of a PAC is controversial, however, and has not been shown to improve outcome. In patients with advanced disease, use of a PAC may provide useful information about cardiac function, loading conditions, and cardiac output, particularly in the postoperative period when echocardiography is often not readily available. The intraoperative use of TEE can be helpful in patients with constrictive pericarditis undergoing noncardiac surgery, when hemodynamic compromise can be expected based on the planned surgery, or when circulatory instability persists despite attempted therapy. 126
The main anesthetic goals are to minimize any effects of anesthetic techniques and drugs on the compensatory mechanisms that maintain hemodynamic stability in patients with constrictive pericarditis. Accordingly, bradycardia and myocardial depression must be avoided, and preload and afterload need to be maintained in the face of a fixed, low cardiac output. It is reasonable to induce general anesthesia using IV ketamine or etomidate titrated to effect. Propofol is relatively contraindicated because it may produce hypotension. Thiopental is best avoided because of venodilation and cardiac depression. A high-dose opioid anesthesia will not depress myocardial contractility, but the associated bradycardia may not be tolerated. In patients who rely on sympathetic tone for compensation, even the use of high-dose opioids may cause sudden hemodynamic compromise during anesthetic induction and must be immediately treated, preferably with epinephrine and norepinephrine. The use of a spinal/epidural technique is not recommended in symptomatic patients with constrictive pericarditis because of the sympathectomy.

Pericardial Effusion and Cardiac Tamponade
As with constrictive pericarditis, pericardial effusion and cardiac tamponade also restrict ventricular diastolic filling, although from extrinsic compression of the ventricular wall by fluid in the pericardium. Symptoms seen with pericardial effusion depend on the rate and volume of fluid accumulation. 292 Chronic pericardial effusion may be well tolerated for some time. In contrast, acute cardiac tamponade is a syndrome with a rapid and dramatic onset of symptoms. 293 - 296 With a more gradual accumulation of fluid, the pericardium stretches, and larger pericardial volumes are tolerated before symptoms occur. Once symptoms begin, however, they proceed rapidly because of the sigmoidal relationship between pressure and volume in the pericardial sac. As the limit of pericardial distensibility is reached, small increases in volume produce dramatic increases in intrapericardial pressure. As such, the removal of small volumes of pericardial fluid in a situation of severe cardiac tamponade can produce dramatic relief of symptoms as a result of a rapid fall in intrapericardial pressure. 297
The clinical features of cardiac tamponade result from restriction of diastolic ventricular filling and increased pericardial pressure. The increased pericardial pressure is transmitted to the ventricular chamber. This decreases the atrioventricular pressure gradient during diastole and impedes ventricular filling. Thus, despite an increase in diastolic ventricular pressure, there is a decrease in the end-diastolic ventricular volume and stroke volume. Similar to advanced constrictive pericarditis, equilibration of right atrial pressure, right ventricular end-diastolic pressure, pulmonary artery diastolic pressure, and left atrial pressure can be seen. Pulsus paradoxus is another nonspecific sign, also seen in patients with constrictive pericarditis. It consists of a decline in systolic pressure during inspiration of more than 12 mm Hg. Additionally, increased diastolic ventricular pressure decreases coronary perfusion pressure and results in early closure of the mitral and tricuspid valves, limiting diastolic flow and reducing ventricular volume ( Fig. 2-5 ).

Figure 2-5 Physiology of tamponade.
The compensatory mechanisms in cardiac tamponade are similar to those in constrictive pericarditis. A decrease in cardiac output results in an increase in endogenous catecholamines. The consequent increases in heart rate and contractility help maintain cardiac output in the face of a decreased stroke volume. Increased contractility increases the ejection fraction, allowing more complete ventricular emptying.

Anesthetic considerations
Monitoring in patients with pericardial effusion is similar to patients with constrictive pericarditis and depends on the acuteness of the case. At a minimum, an indwelling arterial catheter for continuous BP monitoring should be established before anesthetic induction. The first step in the anesthetic management of patients with pericardial effusion or cardiac tamponade is to assess its severity. The anesthesiologist must decide whether induction of anesthesia can be tolerated. If the patient is tachycardic, hypotensive, and unable to assume a supine position, with distended jugular veins indicative of high filling pressures, then pericardiocentesis or a small pericardial window performed under local anesthesia should be considered before induction of general anesthesia. Any patient with a significant pericardial effusion, however, should be expected to deteriorate suddenly at any time. In the presence of restricted ventricular diastolic filling, the initiation of positive-pressure ventilation (PPV) may severely decrease venous return and cause sudden hemodynamic collapse. If time permits, placement of a central venous catheter in an awake, spontaneously breathing patient may be indicated before anesthesia induction for central administration of vasoactive drugs. Many institutions require the surgical team to be present in the room prior to anesthesia induction. Hemodynamically unstable patients should be prepped and draped with a surgeon ready to perform pericardial drainage immediately after the patient has been induced.
Similar to patients with constrictive pericarditis, bradycardia and myocardial depression must be avoided, and preload and afterload need to be maintained in the face of a fixed, low cardiac output. IV ketamine or etomidate titrated to effect are good choices. The onset of PPV may decrease venous return and cardiac output further, resulting in sudden cardiovascular collapse. Thiopental and propofol are relatively contraindicated because of possible hypotension; thiopental is known to cause venodilation and cardiac depression. Again, high-dose opioid may not be well tolerated in patients who rely on sympathetic activation as a compensatory mechanism. Hypotension during anesthetic induction must be treated immediately, preferably with epinephrine and norepinephrine. The use of a spinal/epidural technique is best avoided in symptomatic patients with pericardial effusion or tamponade. 298 - 300

Uncommon causes of valvular lesions
This section considers the pathophysiology of uncommon causes of valvular lesions and how these diseases affect cardiac compensatory mechanisms. Anesthetic management of valvular lesions is directed at preserving the compensatory mechanisms, so it is essential to understand how these diseases interfere with compensation and how anesthetic manipulations interact with them.

Stenotic Valvular Lesions

Valvular aortic stenosis
Aortic stenosis results from narrowing of the aortic valve orifice, resulting in a pressure gradient across the aortic valve. The obstruction to flow is proportional to the decrease in cross-sectional area of the obstructed outlet. The left ventricle compensates by increasing the transvalvular pressure to maintain flow. The ventricle undergoes concentric hypertrophy in order to force blood across the stenotic valve, but compliance decreases resulting in increased LV filling pressure that is required to maintain adequate preload and cardiac output. As a result of hypertrophy, ventricular wall tension per unit area is partially decreased toward a more normal range, but total ventricular O 2 demand is increased because of an increase in LV mass. As ventricular compliance falls, passive filling of the ventricle during diastole is decreased, and the ventricle becomes increasingly dependent on atrial augmentation of ventricular diastolic volume. In this setting the atrial “kick” may contribute as much as 30% to 50% to the LV end-diastolic volume. Diastolic subendocardial blood flow is also decreased as a result of an increase in LV diastolic pressure. Aortic diastolic pressure must remain high to maintain adequate myocardial blood flow. 301, 302
Uncommon disease processes can affect compensatory mechanisms to the progressively narrowing of the aortic valve orifice or LVOT by several mechanisms. First, a disease could potentially interfere with the compensatory mechanism of concentric hypertrophy and increased ventricular contractility. In Pompe’s disease, LV hypertrophy occurs but is only secondary to massive myocardial glycogen accumulation. Ventricular strength is not increased to compensate for the typical outflow tract obstruction that occurs in Pompe’s disease. In amyloidosis, aortic stenosis is coupled with a restrictive cardiomyopathy; as in Pompe’s disease, the heart is unable to increase ventricular muscle mass or contractility. A disease process may also interfere with the critical atrial augmentation of LV end-diastolic volume, as in sarcoidosis or Paget’s disease. Diseases of this type infiltrate the cardiac conduction system, resulting in arrhythmias or heart block, with the loss of synchronous atrial contraction. The requirement for elevated ventricular diastolic filling pressure may be compromised in methysergide toxicity, which can produce mitral stenosis coupled with aortic stenosis. This reduces both passive ventricular filling and ventricular filling resulting from atrial contraction. Table 2-9 lists causes of aortic stenosis and key features of their pathophysiology that can adversely affect cardiac compensatory mechanisms.

Table 2-9 Uncommon Causes of Valvular Lesions: Aortic Stenosis

Mitral stenosis
The primary defect in mitral stenosis is restriction of normal LV filling across the mitral valve. As in other stenotic lesions, the area of the valve orifice is the key to flow, and as the orifice becomes smaller, turbulence across the valve increases, and total resistance to flow increases. The compensatory mechanisms in mitral stenosis include (1) dilation and hypertrophy of the left atrium, (2) increases in atrial filling pressures, and (3) a slow heart rate to allow sufficient time for diastolic flow with minimal turbulence. 303 Decompensation in rheumatic mitral stenosis usually occurs when there is atrial fibrillation with a rapid ventricular rate. This causes a loss of the atrial contraction and decreased time for ventricular filling, which results in pulmonary vascular engorgement. Thus, altered LV function is almost never the limiting factor in the ability of the heart to compensate for mitral stenosis. 304
As in other valvular lesions produced by uncommon diseases, coexistent cardiovascular problems that interfere with compensatory mechanisms are very important. Diseases such as sarcoidosis or amyloidosis can infiltrate ventricular muscle, preventing LV filling by decreasing compliance. Amyloidosis, gout, and sarcoidosis can also affect the conduction system of the heart, resulting in heart block, tachyarrhythmias, or atrial fibrillation ( Table 2-10 ).

Table 2-10 Uncommon Causes of Valvular Lesions: Mitral Stenosis

Tricuspid stenosis
Isolated tricuspid stenosis is rare, and the etiology is either carcinoid or congenital ( Table 2-11 ). The problems in tricuspid stenosis are similar to those in mitral stenosis. There is a large, right atrial–right ventricular diastolic gradient, and flow across the stenotic tricuspid valve is related to valve area. 305, 306 The compensatory mechanisms in tricuspid stenosis are also similar to those in mitral stenosis. An increase in right atrial pressure maintains flow across the stenotic valve and is associated with hepatomegaly, jugular venous distention, and peripheral edema. The implications of slow heart rate in tricuspid stenosis are the same as in mitral stenosis. Right ventricular contractility is usually well maintained. The onset of atrial fibrillation in tricuspid stenosis may produce symptoms such as increased peripheral edema, whereas in mitral stenosis it results in signs of left-sided failure. 307

Table 2-11 Uncommon Causes of Valvular Lesions: Tricuspid Stenosis
Diseases can interfere with cardiac compensation for tricuspid stenosis in much the same way as for mitral stenosis. Further restriction of RV filling may occur in conditions such as malignant carcinoid syndrome that produce endocardial fibrosis, reducing RV compliance. Tricuspid stenosis frequently coexists with pulmonic stenosis in patients with carcinoid syndrome, resulting in severely restricted cardiac output. 308

Pulmonic stenosis
As in aortic stenosis, the valve area is the critical determinant of transvalvular blood flow. Pulmonic stenosis produces symptoms that are similar to the classic clinical features of aortic stenosis: fatigue, dyspnea, syncope, and angina. The compensatory mechanisms in pulmonic stenosis are similar to those in aortic stenosis, including RV hypertrophy, and RV dilation, with a change from a crescent-shaped chamber best suited to handle volume loads to an ellipsoid chamber best suited to handle pressure loads. The hypertrophied and dilated right ventricle also interferes with LV function, and LV failure may supervene. Angina occurs occasionally in pulmonic stenosis and should be especially noted. Normally, the right ventricle is a thin-walled chamber with low intraventricular pressures, resulting in a high transmural perfusion pressure and good subendocardial blood flow that limits development of RV ischemia. Concentric hypertrophy increases both RV mass and RV pressures, increasing the potential for ischemia of the right ventricle, since RV O 2 requirements are increased and coronary perfusion may be decreased. Cyanosis can occur with severe pulmonic stenosis accompanied by a fixed, low cardiac output. When RV pressure rises, a patent foramen ovale may produce right-to-left interatrial shunting. Usually, isolated pulmonic stenosis is well tolerated for long periods until compensatory mechanisms fail. When a second valvular lesion coexists with pulmonic stenosis, the potential effects of this lesion on compensatory mechanisms should be considered. 309
Compensatory mechanisms in pulmonic stenosis can be altered in much the same way as in aortic stenosis. Decreases in RV contractility occur in infiltrative diseases of the myocardium, such as Pompe’s disease and sarcoidosis. The loss of the atrial “kick” and the development of tachyarrhythmias have the same implications for cardiac function in pulmonic stenosis as in aortic stenosis. In subacute bacterial endocarditis, or with geometric changes resulting in tricuspid annular dilation, tricuspid insufficiency may coexist with pulmonic stenosis, impairing pressure development in the right ventricle, especially when RV failure supervenes. With the increase in RV mass and the increased requirement for O 2 delivery to the right ventricle, RV O 2 supply may be compromised, as in the coronary artery pathology of Pompe’s disease ( Table 2-12 ).

Table 2-12 Uncommon Causes of Valvular Lesions: Pulmonic Stenosis
Many patients with pulmonic stenosis are candidates for balloon valvuloplasty of the pulmonic valve. A balloon catheter is placed percutaneously and the tip guided across the pulmonic valve. The balloon is inflated, tearing the fused leaflets apart. 310 Various degrees of pulmonic regurgitation are invariably produced, but this is typically well tolerated for a long time.

Regurgitant Valvular Lesions

Aortic insufficiency
The primary problem in aortic insufficiency is a decrease in net forward blood flow from the left ventricle caused by diastolic regurgitation of blood back into the LV chamber. Acute aortic insufficiency is poorly tolerated and represents an acute volume overload of the LV chamber, resulting in increased wall tension, end-diastolic pressure, acute mitral regurgitation, pulmonary edema, and cardiogenic shock. In chronic aortic insufficiency, however, a number of compensatory changes apply, and depending on the severity of aortic regurgitation, patients may be asymptomatic for years. The LV chamber size increases, causing an eccentric hypertrophy. The LV compliance is increased, able to accommodate large diastolic volumes at relatively low filling pressures. The increase in ventricular volume allows full use of the Frank-Starling mechanism, whereby the strength of ventricular contraction is increased with increasing fiber length. Ejection fraction is maintained, because both stroke volume and ventricular end-diastolic volume increase together. Despite these compensatory mechanisms, however, studies have shown that ventricular contractility is not normal, and eventually symptoms of heart failure develop. 311 Nevertheless, the onset of clinical symptoms of aortic insufficiency does not necessarily correlate with ventricular function status. 312
The increase in chamber size and eccentric hypertrophy, which help maintain cardiac function in aortic insufficiency, can be compromised in such conditions as ankylosing spondylitis in which myocardial fibrosis limits the increase in chamber size to the degree that this disease produces a restrictive picture. Cogan’s syndrome produces a generalized cardiomyopathy with CAD and can alter the compensatory mechanism by decreasing both the ability of the left ventricle to hypertrophy and the ability of the coronary arteries to deliver oxygen to the ventricle. Increases in LV compliance could be prevented in situations such as aortic insufficiency caused by methysergide, which produces an endocardial fibrosis and thus decreased ventricular compliance. The usual ability of the left ventricle to maintain the ejection fraction in aortic insufficiency could be compromised by the cardiomyopathy of amyloidosis. The aortic insufficiency produced by acute bacterial endocarditis is occasionally associated with complete heart block, resulting in a slow heart rate with ventricular overdistention and a decrease in cardiac output. Aortic insufficiency caused by conditions (e.g., SLE) associated with increased PVR can increase the regurgitant fraction in the face of the incompetent aortic valve. 313, 314 Table 2-13 lists causes of aortic insufficiency and key features of their pathophysiology that can adversely affect cardiac compensatory mechanisms.

Table 2-13 Uncommon Causes of Valvular Lesions: Aortic Insufficiency



Mitral regurgitation
As with aortic regurgitation, mitral regurgitation results from failure of the affected valve to maintain competence during the cardiac cycle. Mitral regurgitation occurs by one of three basic mechanisms: (1) damage to the valve apparatus itself, (2) inadequacy of the chordae tendineae-papillary muscle support of the valvular apparatus, or (3) left ventricular dilation and stretching of the mitral valve annulus with loss of the structural geometry required for valvular closure. 315 Mitral regurgitation represents a volume overload of both the left atrium and the left ventricle. In mitral regurgitation, ventricular ejection appears to be well preserved because of the parallel unloading circuit through the open mitral valve, which allows a rapid reduction of wall tension and change in volume during systole. However, the chronic volume overload results in an irreversible decrease in contractility, which is often apparent only after the mitral valve function has been restored, by repairing or replacing the mitral valve. 316, 317
Compensatory mechanisms in mitral regurgitation include ventricular dilation, elevations in ventricular filling pressure, and the maintenance of low PVR. As in aortic insufficiency, ventricular dilation allows maximum advantage to be gained from the Frank-Starling mechanism. A low PVR maintains forward flow, whereas increases in PVR increase the degree of regurgitant flow through the mitral valve. In mitral regurgitation, the heart benefits from a relatively rapid heart rate; a slow rate is associated with an increased ventricular diastolic diameter, which may distort the mitral valve apparatus even further and result in increased regurgitation.
A number of diseases can be cited that interfere with the compensatory mechanisms in mitral regurgitation. When mitral regurgitation is secondary to amyloid infiltration of the mitral valve, ventricular dilation is compromised by coincident amyloid infiltration of the ventricular myocardium, which restricts ventricular diastolic filling. 318 Amyloid infiltration of the conduction system can cause heart block and bradycardia, resulting in increased mitral regurgitation for reasons previously noted ( Table 2-14 ).

Table 2-14 Uncommon Causes of Valvular Lesions: Mitral Regurgitation

Tricuspid insufficiency
Tricuspid insufficiency is mechanically similar to mitral insufficiency. The most common cause of tricuspid insufficiency is right ventricular failure. 319 Carcinoid disease can cause deformation and insufficiency of the tricuspid valve, 320 and endocarditis affecting the tricuspid valve can be seen in IV drug users. Tricuspid insufficiency represents a volume overload of both the right ventricle and the right atrium. Isolated tricuspid regurgitation is often well tolerated, unless RV dysfunction develops or coexists. In this situation the loss of integrity of the RV chamber from the incompetent tricuspid valve increases regurgitant flow at the expense of forward flow through the pulmonary circulation, decreasing the volume delivered to the left ventricle, with a resulting decrease in cardiac output ( Table 2-15 ).

Table 2-15 Uncommon Causes of Valvular Lesions: Tricuspid Regurgitation

Pulmonic insufficiency
Pulmonic insufficiency usually occurs in the setting of PHT or cor pulmonale but may exist as an isolated lesion, as in acute bacterial endocarditis in IV drug users. Pulmonic insufficiency may also be iatrogenic, frequently a sequela of pulmonary valvuloplasty procedures or tetralogy of Fallot repair involving a transannular patch. It is well tolerated for long periods. As with aortic insufficiency, pulmonic insufficiency represents a volume overload on the ventricular chamber, but the crescentic RV geometry is such that volume loading is easily handled. The right ventricle is normally a highly compliant chamber, and with its steep filling pressure–stroke volume curve, it functions well in the presence of volume increases.
Disease states can interfere with the compensatory mechanisms of the right ventricle in several ways. Diseases that produce pulmonic insufficiency, such as the malignant carcinoid syndrome, also produce an endocardial fibrosis that decreases the ability of the RV chamber to dilate in response to volume loading. Increases in RV afterload increase the regurgitant fraction. This is especially true when pulmonic insufficiency is secondary to PHT. Hypoxemia can increase PVR, as occurs with the hypoxemia that results from pulmonary vascular dysfunction in carcinoid syndrome. It is unusual for a cardiomyopathy to coexist with isolated pulmonic insufficiency; thus the potential for eccentric hypertrophy usually remains intact. However, syphilis could allow a cardiomyopathy to coexist with pulmonic insufficiency, although this would depend on the extent of syphilitic involvement of the myocardium ( Table 2-16 ).

Table 2-16 Uncommon Causes of Valvular Lesions: Pulmonic Insufficiency

Anesthetic Considerations
Perioperative problems will arise from valvular lesions when compensatory mechanisms acutely fail. Monitoring should be selected to give a continuing assessment of the status of these compensatory mechanisms. Standard monitoring that includes an ECG is essential for monitoring cardiac rhythm and ischemic changes. 321 In moderate or severe valvular lesions, blood pressure is best monitored continuously with an indwelling arterial catheter, which also allows for the monitoring of ABGs. TEE is useful for assessing the changes in preload and contractility that result from anesthetic and surgical manipulations. Pulsed-wave Doppler and color flow mapping are useful for determining the flow characteristics of valvular lesions and their response to pharmacologic or surgical manipulations. 322 The insertion of a central venous catheter for vasoactive drug administration, as well as for monitoring right-sided filling pressures, is indicated in patients with moderate to severe valvular disease. The value of a PAC is controversial; it may be contraindicated in patients with tricuspid stenosis and difficult to deploy in patients with severe tricuspid regurgitation. In patients with significant left-sided valvular disease, accurate assessment of loading conditions can be difficult or misleading because of the underlying valvular disease. Cardiac output determination using a PAC can be inaccurate in patients with severe tricuspid regurgitation. The decision to employ a PAC in patients with valvular disease should be made on an individual basis, considering surgery-related factors and practitioner experience as well.
The anesthetic management in patients with valvular lesions varies significantly, depending on the severity of the valvular disease, the underlying etiology, and the planned procedure. In patients with uncommon diseases, these are the primary considerations in the choice of anesthetic drugs and techniques. With increasing severity of the valvular lesion, patient management depends on the type of valvular lesion rather than underlying disease, particularly in stenotic valvular disease. In patients with fixed, low cardiac output from a stenotic valvular lesion, afterload should be maintained at all times to allow adequate perfusion of vital organs, including coronary perfusion. Therefore, an intrathecal technique is often contraindicated in patients with significant stenotic valvular lesions. If a neuraxial technique is chosen, an epidural technique is preferred, with careful monitoring and intervention to maintain sympathetic tone. Many practitioners, however, choose a balanced general anesthetic technique with invasive hemodynamic monitoring in patients with significant valvular disease. For anesthesia induction, etomidate is well tolerated by patients with valvular lesions, 323 whereas thiopental and propofol must be administered slowly and titrated to effect. 324 Neuromuscular blocking agents should be selected according to their autonomic properties. In stenotic lesions, cisatracurium, rocuronium, and vecuronium will not result in significant increases in heart rate and are preferred over pancuronium. 325, 326 In the past, a high-dose opioid technique was often used to maintain anesthesia in patients with significant valvular heart disease, providing stable hemodynamics. Consequently, prolonged mechanical ventilation was frequently required. In current practice, a balanced anesthesia technique using low doses of a potent inhalational volatile anesthetic supplemented with shorter-acting opioids is preferred by most practitioners aiming to achieve immediate or early extubation after surgery.

Patients with transplanted heart
The first human heart transplantation was performed in the late 1960s, but this practice was limited by early experiences with organ rejection and opportunistic infections. Since 1980, with the introduction of more effective immunosuppression and improved survival, the procedure has emerged as a widely acceptable treatment modality for end-stage heart disease. 327 These recipients of heart transplants may present for noncardiac surgery, and therefore the physiology of the denervated heart and the side effects of the immunosuppressive agents must be considered.

The Denervated Heart
The recipient atrium (which may remain after transplantation) maintains its innervation, but this has no effect on the transplanted heart. Therefore, the transplanted heart is commonly referred to as being “denervated.” The efferent (to the heart) and afferent (away from the heart) limbs of the parasympathetic and sympathetic nervous systems are disrupted during cardiac transplantation. This has significant impact on the physiology of the transplanted heart and the response to common pharmacologic agents in the perioperative period. Some degree of sympathetic reinnervation of the transplanted heart has been documented, although this reinnervation is delayed and incomplete. 328, 329

Immunosuppressive Therapy
The main agents used for chronic immunosuppression are calcineurin inhibitors, azathioprine, rapamycins (everolimus/sirolimus), tacrolimus, mycophenolate mofetil, corticosteroids, and azathioprine. 330, 331 These drugs may interact with anesthetic agents and have side effects with anesthetic implications. Cyclosporine is nephrotoxic and hepatotoxic. Another important side effect associated with the use of cyclosporine is hypertension. Cyclosporine can also lower the seizure threshold. Tacrolimus is nephrotoxic and can lead to diabetes and high blood pressure. Chronic corticosteroid therapy is associated with glucose intolerance and osteoporosis, and azathioprine is toxic to the bone marrow. The immunosuppressive agents should be considered in the anesthetic plan, and organ systems that could be affected must be evaluated preoperatively. 332, 333

Anesthetic Considerations
The physiology and response to pharmacologic agents are different in the denervated heart. The vagal innervation of the heart is disrupted, and there is a lack of heart rate variability with respiration, vagal maneuvers, and exercise. Cholinesterase inhibitors, such as neostigmine and edrophonium, do not usually produce bradycardia, although case reports have linked cardiac arrest and bradycardia to neostigmine administration, even in the transplanted heart. 334, 335 However, the effects on other organ systems (e.g., salivary glands) remain, and these drugs must still be used in combination with anticholinergic agents. 336 Similarly, anticholinergic agents, such as atropine, do not increase the heart rate, so that bradycardia is treated with direct acting agents, such as isoproterenol, or with pacing. A paradoxical response with the development of A-V block or sinus arrest was reported after administration of atropine in patients with transplanted hearts. 337 Drugs with vagolytic side effects, such as pancuronium, do not produce tachycardia. The denervated sinus and A-V nodes have been shown to be supersensitive to adenosine and theophylline. 338
Sympathetic stimulation can originate from two sources: neuronal or humoral. In the denervated heart the neuronal input is initially disrupted and only partially restored, but increases in circulating catecholamines will increase heart rate. Because of the denervation, indirect-acting cardiovascular agents have unpredictable effects. The response of the coronary circulation may also be affected. 339, 340
The normal, innervated heart responds to an increase in aerobic demand mainly by an increase in heart rate. However, the initial response of the denervated heart to an increased demand is through the Frank-Starling mechanism: increasing stroke volume through preload augmentation. The increase in heart rate by the humoral pathway or circulating catecholamines is delayed. Overall, the response of the denervated heart to exercise or increased metabolic demand is subnormal. 341 - 343
Sensory fibers in the heart play an important role in maintaining systemic vascular resistance. With rapid changes in SVR, the denervated heart may not respond appropriately, and these patients tolerate hypovolemia poorly. Sensory fibers in the heart are also important in the manifestations of myocardial ischemia. As such, the patient with a denervated heart may not experience angina, although there are reports to the contrary.
Another factor that must be considered in the anesthetic management of these patients is that the transplanted heart is also predisposed to accelerated coronary artery disease. Fibrous proliferation of the intima of epicardial vessels may result from a chronic rejection process, and within 5 years of transplantation, many patients have developed significant occlusion of the coronary arteries. 344, 345 Therefore, these patients must be evaluated for CAD.

Conclusion
Although the main focus of these discussions is the cardiovascular pathology encountered in uncommon cardiac diseases, the clinician should remember that these diseases seldom have isolated cardiovascular pathology. Many of the diseases discussed are severe multisystem diseases, and an anesthetic plan must also consider the needs of monitoring dictated by other systemic pathology (e.g., measurements of blood sugar in diabetes secondary to hemochromatosis) and the potential untoward effects of drugs in unusual metabolic disturbances (e.g., use of drugs with histamine-releasing properties, such as thiopental or morphine, in malignant carcinoid syndrome).
One anesthetic technique never is absolutely superior to all others in the management of any particular lesion, particularly those caused by uncommon cardiac conditions. The key to the proper anesthetic management of any uncommon disease lies in an understanding of the disease process, particularly the compensatory mechanisms involved in maintaining cardiovascular homeostasis, the cardiovascular effects of anesthetic drugs, and appropriate monitoring of the effects of anesthetic and therapeutic interventions.

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335 Bjerke R.J., Mangione M.P. Asystole after intravenous neostigmine in a heart transplant recipient. Can J Anaesth . 2001;48:305-307.
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Chapter 3 Congenital Heart Disease

Dean B. Andropoulos, MD, MHCM , Erin A. Gottlieb, MD

General Principles
     Classification
     Pathophysiology
     Hemodynamic Management
     Ventilatory Management
Anesthetic Agents and Hemodynamic Effects
     Volatile Anesthetics
     Opioids and Benzodiazepines
     Propofol
     Ketamine
     Etomidate
     Dexmedetomidine
     Pharmacokinetics and Intracardiac Shunts
Preanesthetic Assessment and Planning
     History and Physical Examination
     Premedication and Monitoring
     Airway and Ventilation Management
     Anesthetic Techniques
     Postoperative Care Plan and Disposition
     Infective Endocarditis Prophylaxis
     Patients at Greatest Anesthetic Risk
Specific Cardiac Lesions
     Left-to-Right Shunt Lesions
     Patent Ductus Arteriosus
     Aortopulmonary Window
     Atrial Septal Defect
     Ventricular Septal Defect
     Atrioventricular Canal
     Double-Outlet Right Ventricle
     Truncus Arteriosus
     Anomalous Pulmonary Venous Return
     Left-Sided Obstructive Lesions
     Right-Sided Obstructive Lesions
     Single Ventricle
     Coronary Artery Anomalies
     Regurgitant Valvar Lesions
     Vascular Rings
Other Cardiac Disease
     Pulmonary Hypertension
     Dilated Cardiomyopathy and Myocarditis
     Pericardial Effusion and Tamponade
Pacemakers and Defibrillators
The Post–Cardiac Transplant Patient
Conclusion

Key points

Congenital heart disease (CHD) is the most common birth defect requiring invasive treatment.
With improved medical, surgical, and perioperative care, about 1 million children and 1 million adults now live with CHD.
Although relatively uncommon in the general population, anesthesiologists must understand which CHD patients are at higher anesthetic risk and plan perioperative care accordingly.
The patient with CHD is classified by anatomic lesion, state of cardiac surgical repair, and residual defects.
Anesthesiologists determine the pathophysiologic effects of the patient’s lesion, set hemodynamic goals for anesthetic care, and then plan drug administration and the ventilation and preload/afterload strategies to achieve these goals.
Outcome studies of noncardiac and cardiac anesthetics show that the highest-risk patients have left-sided obstructive lesions, pulmonary hypertension, single functional ventricle, or dilated cardiomyopathy.
For individual CHD lesions, see key points listed in the chapter boxes.
Congenital heart disease (CHD) occurs in 8 to 9 per 1000 live births, making it the most common birth defect requiring invasive treatment. Surgical mortality is now less than 5% in high-quality centers, and as a result of improvements in medical, surgical, and perioperative care, the number of children and adults with CHD is increasing. In the United States, about 1 million children and 1 million adults are living with CHD. 1 About 55% of these patients have simple lesions, 30% have moderately complex lesions, and 15% have complex CHD. An increasing number of patients with complex CHD survive in the modern era, and these children will present for anesthetic care for noncardiac procedures more frequently than in the past. More adult patients with simple and complex congenital heart defects will present for surgery and procedures that require anesthetic care. Thus, although CHD is a relatively uncommon disease in the general population, it is essential that the anesthesiologist understand which patients are at higher anesthetic risk and plan their perioperative care accordingly.
Pediatric and adult patients with CHD may present for surgery or a diagnostic procedure at a pediatric, adult, maternity, or community hospital or outpatient center. The anesthesiologist caring for the pediatric or adult patient with CHD needs to understand the cardiac lesion and physiology, stage of repair or palliation, the patient’s current physiologic state, and effects of CHD on anesthetic care. In addition, the anesthesiologist needs to assess the appropriateness of caring for these often-complicated patients at a proposed venue. This chapter discusses the preoperative assessment and planning, general principles of intraoperative care, and postoperative care for the patient with CHD undergoing anesthesia. Key CHD lesions are reviewed, with prevalence, anatomy, corrective approaches, pathophysiology, and anesthetic considerations discussed for each lesion.

General principles

Classification
The myriad of classification and nomenclature schemes for CHD make consensus difficult regarding the best methods to organize these lesions. The following classification scheme for the anesthesiologist to categorize CHD, as well as some acquired forms of pediatric heart disease, is useful:

Left-to-right shunt lesions: two ventricles
Right-to-left shunt lesions: two ventricles
Complete-mixing two-ventricle lesions
Complete-mixing single-ventricle lesions
Obstructive lesions without shunting
Regurgitant lesions without shunting
Cardiomyopathies
Another useful approach to CHD involves the stage of repair: unrepaired, palliated, completely repaired with residual defects, or completely repaired with no residual defects. 2 Table 3-1 summarizes the major lesions in these categories. The anatomy, pathophysiology, and approach to anesthesia are detailed in the sections addressing the individual lesions.
Table 3-1 Classification of Congenital Heart Disease (CHD) for Anesthesiologists * Category Examples Characteristics Left-to-right shunt lesions: two ventricles VSD, ASD, PDA; aortopulmonary window; partial atrioventricular canal; partial anomalous pulmonary venous return Acyanotic Right-to-left shunt lesions: two ventricles Tetralogy of Fallot; pulmonary atresia with VSD, pulmonary atresia with intact ventricular septum; double-outlet right ventricle; Ebstein’s anomaly Cyanotic Complete-mixing two-ventricle lesions Dextrotransposition of the great arteries; total anomalous pulmonary venous return; truncus arteriosus; complete atrioventricular canal Cyanotic; level of cyanosis depends on communications at atrial, ventricular, and great vessel levels Complete-mixing single-ventricle lesions HLHS, tricuspid atresia, other forms of univentricular heart Cyanotic; complete mixing of pulmonary and systemic venous return; level of cyanosis depends on systemic/pulmonary blood flow ratio and degree of mixing Obstructive lesions without shunting Aortic stenosis, mitral stenosis, pulmonic stenosis; coarctation of aorta; interrupted aortic arch; cor triatriatum; hypertrophic cardiomyopathy   Regurgitant lesions without shunting Aortic insufficiency, mitral insufficiency, pulmonic insufficiency, tricuspid insufficiency   Cardiomyopathy Dilated cardiomyopathy, myocarditis, anomalous origin of left coronary artery from pulmonary artery; post–cardiac transplant coronary artery vasculopathy Anatomically “normal” with decreased ventricular function
ASD, Atrial septal defect; PDA, patent ductus arteriosus; HLHS, hypoplastic left heart syndrome; VSD, ventricular septal defect.
* Some lesions may fall into more than one category depending on exact anatomy. For example, double-outlet right ventricle without pulmonary stenosis is a left-to-right shunt lesion; most have some pulmonary stenosis and are right-to-left shunts. Ebstein’s anomaly often has an ASD with right-to-left shunting; with no ASD, this is a two-ventricle regurgitant lesion without shunting.

Pathophysiology
When approaching the patient with congenital heart disease, after classification into the scheme previously noted, the anesthesiologist should determine the pathophysiologic consequences of the patient’s lesion, then construct a set of hemodynamic goals for the anesthetic care of that patient. After these goals are decided, the anesthesiologist can plan anesthetic and vasoactive drug administration, ventilation strategies, and strategies for preload and afterload management to achieve these goals ( Fig. 3-1 ).

Figure 3-1 General approach to pathophysiology in patients with congenital heart disease (CHD).
A, Hemodynamic consequences and goals for intracardiac and extracardiac shunting lesions. Hypoxic gas mixtures are used infrequently, and risk/benefit should be assessed carefully. LV, Left ventricular; PVR, pulmonary vascular resistance; SVR, systemic vascular resistance; Fi O 2 , fraction of inspired oxygen. B, Obstructive lesions. RV, Right ventricular; L → R, left-to-right; R → L, right-to-left. C, Regurgitant lesions. CVP, central venous pressure; RAP, right atrial pressure; LAP, left atrial pressure; PCWP, pulmonary capillary wedge pressure. D, Mixing lesions. Qp/Qs, pulmonary/systemic blood flow ratio; paco 2 , arterial carbon dioxide partial pressure.
(Data from Andropoulos DB: Hemodynamic management. In Andropoulos DB, et al, editors: Anesthesia for congenital heart disease, ed 2, Oxford, UK, 2010, Wiley-Blackwell.)
When considering patients with two ventricles without obstructive or shunting lesions, the four major determinants of cardiac output are preload, afterload, heart rate, and contractility. The patient with CHD has additional dimensions for consideration. Because of the frequent presence of mixing lesions resulting in arterial desaturation, additional parameters are addressed to optimize cardiac output and oxygen (O 2 ) delivery, including hemoglobin (Hb) concentration. Many cyanotic patients depend on increased Hb levels for O 2 -carrying capacity (14-17 g/dL). A “normal” Hb level for an infant or young child of 11 g/dL is often too low for these patients. Also, the mixed venous oxygen saturation (Sv O 2 ) is important because, of necessity, Sv O 2 is lower in patients with arterial desaturation with the same O 2 extraction. Therefore, raising Sv O 2 is a way to increase arterial oxygen saturation (Sa O 2 , Sp O 2 ) in the patient with right-to-left (R-L) shunting or mixing lesions. Besides increasing Hb, decreasing O 2 consumption by using deeper anesthetic levels, lowering temperature, or lowering myocardial O 2 consumption are also important to increase Sv O 2 ( Fig. 3-2 ).

Figure 3-2 Determinants of cardiac output and oxygen delivery in congenital heart disease.
(Data from Andropoulos DB: Hemodynamic management. In Andropoulos DB, et al, editors: Anesthesia for congenital heart disease, ed 2, Oxford, UK, 2010, Wiley-Blackwell.)
Avoiding any introduction or entrainment of air bubbles into the venous circulation is an important consideration in all patients with CHD, particularly those with obligatory R-L shunting or complete intracardiac mixing. In these patients, even a small amount of air may rapidly pass into the arterial circulation and lodge in a coronary artery, causing myocardial ischemia and possibly ventricular fibrillation, or into the cerebral circulation, causing cerebral ischemia. However, even in patients with predominantly left-to-right (L-R) shunting, Valsalva maneuvers and other conditions can cause paradoxical air embolus. Techniques for infusion of intravenous (IV) fluids and injection of drugs must meticulously avoid this problem.

Hemodynamic Management
Patients with congenital heart disease undergoing an anesthetic procedure may require inotropic, lusitropic (improving diastolic ventricular function), and vasodilator or vasoconstrictor support to achieve the optimal hemodynamic state. Tables 3-2 and 3-3 list currently available agents and their dosages. 2 With many choices but few data, the anesthesiologist often is unable to choose one drug over another from similar classes. Therefore it is often preferable to become familiar with a limited number of agents to use for hemodynamic management.

Table 3-2 Inotropic Drugs

Table 3-3 Vasoactive Drugs
Two of the most common drugs in modern practice for inotropic support are milrinone and epinephrine. Milrinone is a phosphodiesterase-III inhibitor that prolongs the actions of cyclic adenosine monophosphate (cAMP), and has inotropic, lusitropic, and mild pulmonary and systemic vasodilator properties. Therefore, milrinone is particularly useful in patients with normal or high systemic vascular resistance (SVR) and failing ventricles with a degree of pulmonary hypertension. Single-ventricle patients in need of such hemodynamic support are particularly responsive to milrinone. A loading dose of 50 to 75 μg/kg, given over 30 minutes, rapidly achieves therapeutic plasma levels; this can be problematic because of milrinone’s vasodilating properties. For this reason, the infusion is often initiated without a loading dose. Infusion rates of 0.375 to 0.75 μg/kg/min are effective. Risk of tachycardia or atrial and ventricular arrhythmias is minimal for milrinone.
For patients in need of significant inotropic support, epinephrine, at low dose of 0.02 to 0.04 μg/kg/min, moderate dose of 0.05-0.09 μg/kg/min, or high dose of 0.1-0.2 μg/kg/min is effective. Patients requiring high-dose epinephrine for longer than several hours are candidates for mechanical support of the circulation. For hypotension, vasopressin at 0.02 to 0.04 units/kg/hr is effective in increasing SVR; again, patients requiring vasopressin for more than several hours should be evaluated for other means of circulatory support.

Arrhythmias
Maintaining normal sinus rhythm, or at least atrioventricular synchrony to allow for complete ventricular filling and optimize stroke volume, is an important goal for every patient with CHD receiving anesthesia. Generally, the incidence of arrhythmias increases with increasing age, and the potential severity and hemodynamic effect of the arrhythmia (i.e., ventricular arrhythmias or significant atrial arrhythmias) are observed more often in older patients.
The anesthesiologist must understand the patient’s underlying cardiac rhythm, any drug or other therapy, symptoms of the arrhythmia, and recent data (e.g., 24 hour Holter monitoring, electrophysiologic studies) to plan the anesthetic procedure. In the operating room (OR), adequate electrocardiographic (ECG) monitoring, preferably a five-lead system (right/left arms/legs, V lead) capable of displaying up to eight leads simultaneously and recording episodes of arrhythmia, is important for any patient with the potential for hemodynamically significant arrhythmia. Pharmacologic, pacing, and cardioversion-defibrillation therapy must be available for CHD patients ( Tables 3-4 and 3-5 ). 3

Table 3-4 Pharmacologic Therapy for CHD Patients with Acute, Hemodynamically Significant Arrhythmias

Table 3-5 Pacing, Cardioversion, and Defibrillation for CHD Patients with Acute, Hemodynamically Significant Arrhythmias

Ventilatory Management
Management of ventilation in patients with congenital heart disease often has exaggerated effects on cardiac function, pulmonary vascular resistance (PVR), and cardiopulmonary interaction not seen in patients with normal hearts. Appropriate ventilatory management during anesthesia can help achieve hemodynamic goals, or if used inappropriately, can be harmful to the patient with CHD. 4 Therefore, planning ventilation strategy is as important as the anesthetic or vasoactive agents when attempting to achieve a set of hemodynamic goals.
For example, the neonate’s pulmonary vasculature is exquisitely sensitive to fraction of inspired oxygen concentration (Fio 2 ), arterial carbon dioxide partial pressure (Pa CO 2 ), and pH; maintenance of these parameters is the cornerstone of achieving the goals for PVR. Many neonates will need a higher PVR to shunt blood away from the lungs, toward the systemic circulation through a patent ductus arteriosus (PDA) before surgical repair, to lower pulmonary/systemic blood flow ratio (Qp/Qs). Low Fi O 2 , often 0.21, along with lowering minute ventilation to elevate Pa CO 2 , is often used to achieve this goal. Conversely, in the infant with elevated PVR causing R-L shunting or poor cardiac output, high Fi O 2 and hyperventilation to produce mild to moderate hypocarbia is effective at lowering PVR.
Positive-pressure ventilation (PPV) often has detrimental effects on single-ventricle patients who have undergone the Fontan operation. The absence of a right ventricular pumping chamber means that flow through the Fontan circuit depends significantly on negative intrathoracic pressure from spontaneous respiration creating a pressure gradient from the extrathoracic veins; positive pressure decreases this gradient and reduces flow. In contrast, PPV may actually improve ventricular function in patients with a failing left or systemic ventricle. The intrathoracic positive pressure is transmitted to the pericardial space, which reduces the transmural wall tension across the ventricle, compared to spontaneous ventilation with negative intrathoracic pressure. This decreased wall tension reduces the work of the ventricle, resulting in more efficient contraction. These examples illustrate the importance of careful planning of ventilatory strategy in patients with CHD.

Anesthetic agents and hemodynamic effects
Anesthetic agents can have profound effects on hemodynamics in patients with congenital heart disease, much more than in patients with normal hearts. The usual doses of typical agents (e.g., induction dose of propofol) are well tolerated in patients with normal hearts and vascular systems but may lead to severe hemodynamic compromise in some patients with CHD ( Box 3-1 ).

Box 3-1 Anesthetic Management Principles in Congential Heart Disease

Understand hemodynamic consequences of patient’s lesion and state of repair.
Construct a set of hemodynamic goals for each patient.
Plan anesthetic agents and techniques, ventilatory management, and inotropic/vasoactive drug support based on these goals.
Although no anesthetic agent or technique is contraindicated, avoid agents or doses counter to hemodynamic goals, and use agents that promote these goals.

Volatile Anesthetics
Although halothane is no longer available in the United States because of its profound myocardial depressant effects, it is useful to review studies in CHD patients comparing new agents to halothane. A study using transthoracic echocardiography comparing halothane, isoflurane, and sevoflurane in 54 children with two-ventricle CHD reported that halothane at 1 and 1.5 minimum alveolar concentration (MAC) caused significant myocardial depression, resulting in a decline in mean arterial pressure (MAP decline of 22% and 35%), ejection fraction (EF decline of 15% and 20%), and cardiac output (CO decline of 17% and 21%), respectively, in patients age 1 month to 13 years undergoing cardiac surgery ( Fig. 3-3 ). 5 Sevoflurane maintained both CO and heart rate (HR) and had less profound hypotensive effects (MAP decrease 13% and 20% at 1 and 1.5 MAC) and negative inotropic effects (EF preserved at 1 MAC, 11% decrease at 1.5 MAC) compared with halothane. Isoflurane, in concentrations as high as 1.5 MAC, preserved CO and EF, had less suppression of MAP (22% and 25%) than halothane, increased HR (17% and 20%), and decreased SVR (20% and 22%).

Figure 3-3 Hemodynamic changes assessed by echocardiography.
In 54 patients with CHD with two ventricles: A, ejection fraction; B, cardiac output. H, Halothane; S, sevoflurane; I, isoflurane; F/M, fentanyl/midazolam; MAC, minimal alveolar concentration. See text for details.
(Data from Rivenes SM, et al: Anesthesiology 94:223-229, 2001.)
The effects of volatile anesthetics on pulmonary (Qp) and systemic (Qs) blood flow in 30 biventricular patients and in L-R shunts has also been assessed. Halothane, isoflurane, and sevoflurane did not change Qp/Qs as measured by echocardiography. 6 Russell et al. 7 compared halothane with sevoflurane in the prebypass period in 180 children with a variety of cardiac diagnoses, including 14 with single-ventricle physiology and 40 with tetralogy of Fallot. The incidence of significant hypotension, bradycardia, and arrhythmia requiring drug treatment with atropine, phenylephrine, epinephrine, or ephedrine was higher with halothane (two events per patient vs. one). Serum lactate also increased slightly with halothane.
Patients with a single functional ventricle constitute an increasing proportion of patients undergoing anesthesia for both cardiac and noncardiac surgery, and studies of hemodynamic effects of anesthetic agents are limited. Ikemba et al. 8 studied 30 infants with a single functional ventricle immediately before their bidirectional cavopulmonary connection, randomized to receive sevoflurane at 1 and 1.5 MAC, or fentanyl/midazolam at equivalent doses. Myocardial performance index (MPI), a transthoracic echocardiographic measurement of ventricular function that can be applied to single-ventricle patients, was unchanged with any of these regimens compared with baseline, indicating that either sevoflurane or fentanyl/midazolam can be used in this population to maintain hemodynamic stability.
In normal children, desflurane usually produces tachycardia and hypertension during the induction phase, followed by a slight reduction in HR and systolic blood pressure (BP) during steady state at 1 MAC anesthetic level. 9, 10 There are no reports of its hemodynamic profile in patients with congenital heart disease.
In summary, isoflurane and sevoflurane have had some study in the CHD population, and both maintain normal cardiac output at anesthetic concentrations in patients with normal, or only slightly compromised, ventricular function. There have been no published studies of these agents in patients specifically with significantly depressed myocardial function; these volatile anesthetics should be used with caution in these patients.

Opioids and Benzodiazepines
Midazolam is often used with fentanyl anesthesia to provide sedation and amnesia, as a substitute for low-dose volatile anesthetics, particularly in hemodynamically unstable patients and young infants, in whom the myocardial depressant effects of volatile agents are more pronounced. Fentanyl and midazolam combinations have been studied in two different clinical dose regimens to simulate 1 and 1.5 MAC of volatile agents: fentanyl , 8- to 18-μg bolus followed by 1.7 to 4.3 μg/kg/hr infusion, then repeat bolus at 50% of original doses followed by 50% increase in infusion, depending on age; and midazolam, 0.29-mg/kg bolus followed by 139 μg/kg/hr infusion, then repeat bolus at 50% of original dose, followed by 50% increase in infusion, for all ages; for induction and the prebypass period in congenital heart surgery in biventricular patients (see Fig. 3-3 ). 5 Vecuronium was used for muscle relaxation to isolate the effects of the other two agents on hemodynamics. Measurements of cardiac output and contractility were made by echocardiography. Fentanyl/midazolam caused a significant decrease (22%) in CO despite preservation of contractility, predominantly from a decrease in HR.

Propofol
Williams et al. 11 measured the hemodynamic effects of propofol (50-200 μg/kg/min) in 31 patients age 3 months to 12 years undergoing cardiac catheterization. Propofol significantly decreased MAP and SVR; however systemic CO, HR, and mean pulmonary artery pressure (PAP), as well as PVR, did not change. In patients with cardiac shunts, the net result was a significant increase in the R-L shunt, a decrease in the L-R shunt, and decreased Qp/Qs, resulting in a significant decrease in Pa O 2 and Sa O 2 , as well as reversal of the shunt from L-R to R-L in two patients. Another study of cardiac catheterization showed that patients could experience a 20% decrease in HR or MAP. 12 These effects of propofol, causing venodilation and vasodilation, decreased HR, and possibly decreased contractility with significant induction doses, mandate caution with this agent in patients who are preload and afterload dependent. Such patients include those with dilated cardiomyopathy and coronary artery lesions requiring higher coronary perfusion pressures.

Ketamine
Despite the potential adverse effects of dysphoria, hallucinations, excessive salivation, tachycardia, and hypertension, ketamine has been a mainstay in the induction of general anesthesia in patients with congenital heart disease. 13, 14 Administered intravenously (IV) or intramuscularly (IM), ketamine will reliably maintain HR, BP, and systemic CO at an induction dose of 1 to 2 mg/kg IV or 5 to 10 mg/kg IM, with a maintenance dose of 1 to 5 mg/kg/hr in patients with a variety of congenital diseases, including tetralogy of Fallot. 15, 16
Several studies addressed exacerbation of pulmonary hypertension (PH). Morray et al. 17 demonstrated that in cardiac catheterization patients, 2 mg/kg of ketamine caused a minimal (< 10%) increase in mean PAP, and pulmonary/systemic vascular resistance ratio (Rp/Rs), with no change in direction of shunting or Qp/Qs. Hickey et al. 18 studied postoperative cardiac surgery patients with normal Pa CO 2 and found that ketamine at 2 mg/kg had no effect on PAP or calculated PVR, in patients with normal or with elevated baseline PVR. Ketamine, 2-mg/kg load followed by 10 μg/kg/min infusion, did not change PVR in 15 children with severe PH, when breathing spontaneously with a baseline of 0.5 MAC sevoflurane. 19 Recent reports indicate that ketamine is effective and safe for patients with CHD and with PH receiving noncardiac anesthetics, as long as the airway is managed properly to avoid significant hypercarbia or hypoxemia. 19, 20

Etomidate
Etomidate is an imidazole derivative and sedative-hypnotic induction agent thought to be devoid of cardiovascular effects, thus achieving widespread use in patients with limited cardiovascular reserve. Few reports address the hemodynamic effects of etomidate in children with congenital heart disease. In 20 patients with a variety of congenital defects studied in the cardiac catheterization laboratory (CCL), etomidate (0.3-mg/kg bolus followed by 26 μg/kg/min infusion) had similar effects as ketamine (4 mg/kg followed by 83 μg/kg/min infusion): a slight increase in HR but no change in MAP during induction or the 60-minute infusion. 21 Sarkhar et al. 22 studied etomidate (0.3-mg/kg bolus) in 12 children undergoing cardiac catheterization for device closure of atrial septal defect (ASD) or radiofrequency ablation of atrial arrhythmias. There were no significant changes in any hemodynamic parameter (HR, MAP, filling pressures, SVR or PVR, Qp/Qs, Sv O 2 ). A case report of stable hemodynamics with etomidate induction in a pediatric patient with end-stage cardiomyopathy receiving a second anesthetic 4 weeks after cardiovascular collapse with ketamine induction demonstrates the utility of this drug in this population. 23 Etomidate has been used for induction of anesthesia in adults with congenital cardiac conditions such as ruptured aneurysm of the sinus of Valsalva, as well as for cesarean section in a patient with uncorrected coronary artery–to–pulmonary artery fistula, with no cardiovascular effects in these patients. 24, 25
Thus, etomidate seems best utilized in patients with the most limited cardiac reserve. It appears particularly useful in teenagers or adults with poorly compensated, palliated CHD presenting for cardiac transplantation or revision of previous surgeries. Temporary adrenal suppression will occur with even one induction dose of etomidate.

Dexmedetomidine
Dexmedetomidine has been studied as an adjunct agent in general anesthesia for pediatric cardiac surgery. Dexmedetomidine, 0.5-μg/kg load followed by 0.5 μg/kg/hr infusion, with an isoflurane-fentanyl-midazolam anesthetic, significantly reduced HR, MAP, and cortisol, blood glucose, and serum catecholamine response in children age 1 to 6 years undergoing cardiac surgery with bypass, compared with the baseline anesthetic. 26 Chrysostomu et al. 27 studied 38 pediatric patients (average age 8 years) after biventricular repair with cardiopulmonary bypass; 33 were extubated. Dexmedetomidine infusion rate varied from 0.1 to 0.75 μg/kg/hr (mean 0.3), and desired sedation was achieved in 93% and analgesia in 83% of patients. There was no respiratory depression, but hypotension was observed in 15% of patients. 27

Pharmacokinetics and Intracardiac Shunts
The presence of a right-to-left intracardiac shunt decreases the rate of rise of the concentration of inhaled anesthetic in the arterial blood, as a portion of the systemic cardiac output bypasses the lungs and then dilutes the anesthetic concentration in the systemic arterial blood. The anesthetic concentration in the blood thus never equals the exhaled concentration. Inhaled induction is noticeably slower in cyanotic CHD patients. Huntington et al. 28 studied six children with R-L shunts from a fenestrated Fontan operation whose average Qp/Qs was 0.58. These patients achieved an arterial anesthetic concentration (Fa) of only 55% of inspired halothane concentration (Fi) after 15 minutes during wash-in of 0.8% halothane. After closure of R-L shunt (occlusion of Fontan fenestration in CCL), the Fa of halothane equaled the Fi. This difference between Fa and Fi is greater during induction or washout and greater with less soluble drugs (sevoflurane, desflurane, nitrous oxide) than with more soluble drugs (halothane).
In the face of significant R-L intracardiac shunting, IV agents given by bolus may pass directly into the left side of the heart with less dilution by systemic venous blood and passage through the pulmonary vascular system. This may result in transiently high arterial, brain, and cardiac concentrations of drugs such as lidocaine. 29 IV induction agents and muscle relaxants may also achieve sufficient arterial and brain concentrations more rapidly with R-L intracardiac shunts. 30
Left-to-right intracardiac shunts have minimal effect on the speed of induction with inhaled anesthetic agents. 31 The recirculation of blood through the lungs results in increased uptake of anesthetic and in a higher blood anesthetic concentration in the pulmonary capillaries, reducing anesthetic uptake. The two effects cancel each other. Only in severe congestive heart failure from L-R shunt, with significant interstitial and alveolar edema, would L-R intracardiac shunting be expected to slow inhalation induction, from the combined effects of diffusion limitation and ventilation/perfusion mismatch, resulting in alveolar dead space ventilation with no uptake of any new anesthetic agent.

Preanesthetic assessment and planning
Patients with congenital heart disease often have complicated histories, including operative and CCL reports, echocardiographic images, computed tomography (CT) and magnetic resonance imaging (MRI) studies, and extensive clinic visits. The modern electronic medical record has greatly facilitated the gathering of pertinent information in these complicated patients and should be used whenever possible. A common question is whether cardiology consultation is necessary before anesthesia. Any patient with poor cardiac compensation should have cardiology consultation before anesthesia, including patients with significant cyanosis, poor ventricular function, uncontrolled arrhythmias, and significant PH. Optimization of medical management and postponement of elective surgery may be necessary in some cases. Occasionally, a very ill patient with CHD surgery is cancelled permanently after a thorough assessment of operative risks and benefits along with anesthetic risks. Patients with good cardiac compensation but with complex disease should receive cardiology consultation and echocardiography within 6 months of anesthesia. Well-compensated patients with simple or moderately complex disease do not usually require cardiology consultation in this period.

History and Physical Examination
Preoperative assessment should include a detailed description of the patient’s cardiac anatomy, cardiac surgery history, and catheter-based interventions. Residual defects after surgery are important because many patients and parents assume these are completely repaired after complex surgery. All diagnostic echocardiographic and catheterization studies should be reviewed with careful attention to ventricular function, atrioventricular valve competency, and PVR measurement 32 ( Figs. 3-4 and 3-5 ). Cardiac MRI and CT angiographic images and data should also be reviewed, particularly in delineating extracardiac anatomy such as the aorta and its branches 33 ( Figs. 3-6 and 3-7 ). A history of thrombosis or occlusion of veins or arteries will help guide invasive catheter placement, and knowledge of previous interventions helps determine appropriate locations (e.g., avoidance of left radial arterial line in patients who had aortic coarctation repaired with left subclavian flap technique). The patient or caregiver should be questioned about the patient’s functional status, limitations on activity, and other cardiac symptomatology.

Figure 3-4 Preoperative echocardiographic findings in CHD.
A, Perimembranous ventricular septal defect (VSD). Color flow Doppler image depicts left-to-right shunting through defect in membranous septum (arrow). B, Complete atrioventricular canal, transesophageal view. Four-chamber view demonstrates ostium primum atrial septal defect (ASD; arrow ) and inlet VSD (arrow with asterisk). C, Cor triatriatum. Obstructive membrane in left atrium (LA) (arrowheads) divides cavity into proximal and distal portions. RA, right atrium. D, Dextrotransposition of the great arteries (d-TGA). Pulmonary artery (PA) arises from left ventricle (LV), and aorta (AO) arises from right ventricle (RV). Associated perimembranous VSD is seen (arrow).
(Modified from Russell IA, Miller-Hance WC: Transesophageal echocardiography in congenital heart disease. In Andropoulos DB, et al, editors: Anesthesia for congenital heart disease, ed 2, Oxford, UK, 2010, Wiley-Blackwell.)

Figure 3-5 Hypoplastic left heart syndrome (HLHS).
Catheterization diagram of infant with HLHS after stage I palliation and bidirectional cavopulmonary anastomosis (Glenn anastomosis). This one-page document summarizes history, anatomy, and physiology and contains a wealth of information necessary to plan anesthetic care. Numbers in circles are oxygen saturations, numbers without circles are pressures; arrows indicate catheter course; a, a-wave pressure; v, v-wave pressure; m, mean pressure; ABG, arterial blood gas; BSA, body surface area; LSVC, presence of left superior vena cava; Qp, pulmonary blood flow; Qs, systemic blood flow; PAR, pulmonary artery resistance; U, Wood units; Rp:Rs, pulmonary-to-systemic vascular resistance ratio; VO 2 , oxygen consumption.

Figure 3-6 Magnetic resonance angiograms of coarctation.
A, Severe coarctation (arrows) of the aorta in 15-year-old male patient, just distal to left subclavian artery. B, Large collateral arterial vessels are seen in posterosuperior aspect of thorax, and a large internal mammary artery is present (arrowheads).
(From Mossad EB, Joglar JJ: Preoperative evaluation and preparation. In Andropoulos DB, et al, editors: Anesthesia for congenital heart disease, ed 2, Oxford, UK, 2010, Wiley-Blackwell.)

Figure 3-7 Severe aortic coarctation.
This 19-year-old male patient was diagnosed with aortic coarctation using narrow-collimation contrast-enhanced multislice computed tomography (CT). Axial CT image shows severe aortic coarctation. The main pulmonary artery is seen branching into the right and left pulmonary arteries. The ascending aorta is imaged in cross-section alongside the pulmonary artery. In comparison, the black arrow indicates the severely narrowed proximal descending thoracic aorta. Enlarged internal mammary arteries (double white arrows) and numerous enlarged collateral vessels (arrowheads) are also present.
(From Mossad EB, Joglar JJ: Preoperative evaluation and preparation. In Andropoulos DB, et al, editors: Anesthesia for congenital heart disease, ed 2, Oxford, UK, 2010, Wiley-Blackwell.)
Chronic medication use should also be reviewed. Many patients with CHD are taking medications for afterload reduction (angiotensin-converting enzyme [ACE] inhibitors), diuresis (furosemide, other diuretics), pulmonary hypertension (endothelin receptor antagonists, prostacyclins, phosphodiesterase inhibitors), arrhythmias (β-blockers, amiodarone), and systemic anticoagulation (aspirin, low-molecular-weight heparin, warfarin). The anesthetic implications of all medications should be considered. In general, all cardiac medications should be continued up to and including the day of surgery, with the exception of anticoagulants. Aspirin use is common in infants with systemic-to-pulmonary artery and other shunts and is often safe to continue for peripheral surgery. Other agents (e.g., heparin, warfarin) must be addressed with the surgeon and cardiologist, depending on the indication and the procedure.
On physical examination, signs of poor cardiac output and long-standing cyanosis may include peripheral vasoconstriction and clubbing, respectively. Pulse oximetry readings on room air or baseline O 2 delivery should be noted. In addition, the volar aspect of the wrists should be examined for scars indicating previous arterial cutdown that may complicate arterial line placement. A careful airway examination is necessary because of the association of CHD with a number of craniofacial syndromes that may complicate airway management. Pulmonary examination to assess degree of respiratory distress is important. The major examination findings are discussed later for each lesion.
Depending on the severity of cardiovascular disease, comorbidities, and the proposed procedure, extensive preoperative testing may be warranted. Common laboratory tests include hemoglobin and hematocrit, platelet count, coagulation studies, and electrolytes. Exercise stress testing, electrocardiogram (ECG), and Holter study may also be indicated. Table 3-6 summarizes important preanesthetic considerations in the CHD population.
Table 3-6 Preanesthetic Considerations for CHD Patients Evaluation Findings Anesthetic Implications History Cardiac lesion: cyanotic or acyanotic, one or two ventricles Septated, or intra-atrial or ventricular communications Surgery or catheter interventions: Palliated or corrected Residual defects Source of pulmonary blood flow: PDA, shunt, native, collaterals Ventricular function Coronary anatomy Outflow tract obstruction Exercise tolerance, feeding, NYHA functional class Medical therapy Overall anesthetic planning Physical examination General appearance BP: normal, elevated, low for age Cyanosis, clubbing Tachypnea, retractions Peripheral perfusion and pulses Precordium, heart sounds, murmurs Hepatomegaly, jugular venous distention Diaphoresis Adequacy of peripheral veins and arterial pulses Degree of compensation and physiologic reserve to tolerate anesthesia and surgery Anesthetic drugs and doses Arterial and central venous catheterization Airway and ventilatory management Need for central venous access Chest radiography Heart size and configuration: normal or small heart; cardiomegaly Pulmonary vasculature: normal, increased, or decreased Pulmonary parenchymal disease Functional degree of left-to-right or right-to-left shunting Plan ventilatory management. Adequacy of medical therapy (e.g., diuretics) Electrocardiography; including 24-hour Holter monitoring Rhythm: normal sinus vs. atrial or ventricular arrhythmias; paced rhythm Rate ST segments Axis deviation Plan antiarrhythmic and pacemaker therapy. Degree of ventricular hypertrophy General condition of myocardium Hemoglobin Normal, low, or elevated for age and gender Relative degree and duration of cyanosis Need for blood transfusion Oxygen saturation (Sp O 2 ) Normal: 95%-100% Mild desaturation: 85%-95% Moderate cyanosis: 75%-85% Severe cyanosis: < 75% Establish normal ranges for patient Plan ventilatory, hemodynamic, and transfusion management Echocardiography Cardiac anatomy, residual defects, ventricular function Outflow tract obstruction Valvar regurgitation Atrial/ventricular communication Plan hemodynamic goals for anesthesia: BP/SVR (afterload-vasodilator) PVR/PAP (RV afterload) HR, contractility (inotropic support) Ventricular filling (preload) Diastolic function (lusitropy) Computed tomography (CT) angiography Anatomy of extracardiac structures: aorta, pulmonary arteries and veins Detailed anatomy of extracardiac structures: Aortic, PA, or pulmonary venous obstruction Cardiac magnetic resonance imaging (MRI) Anatomy of intracardiac/extracardiac structures, ventricular function, Qp/Qs Detailed anatomy Plan ventilatory management, inotropic/vasodilator support Cardiac catheterization Detailed anatomy Hemodynamics, including pressures in all vessels/chambers SVR/PVR and Qp/Qs, PVR reactivity Most detailed hemodynamic information; plan hemodynamic goals
PDA, Patent ductus arteriosus; NYHA, New York Heart Association; BP, blood pressure; SVR, systemic vascular resistance; PVR, pulmonary vascular resistance; PAP, pulmonary artery pressure; RV, right ventricular; PA, pulmonary artery; Qp/Qs, pulmonary/systemic blood flow ratio.

Premedication and Monitoring
Premedication plays a significant role in allaying anxiety in patients with congenital heart disease. Many patients, both pediatric and adult, have undergone multiple procedures, and providing a comfortable separation from family members and transfer to the OR can enhance the perioperative experience. Anxiolysis can also reduce myocardial O 2 consumption and sympathetic stimulation. However, excessive sedation can also be detrimental in the CHD patient. Hypoxemia and hypercarbia from hypoventilation can decrease pulmonary blood flow in patients with systemic-to-pulmonary arterial shunts or passive pulmonary blood flow (Fontan) and can cause cardiovascular collapse in patients with PH.
Common premedications in CHD children include oral or IV midazolam, ketamine, and pentobarbital. Common anxiolytics in adults include oral diazepam and IV diazepam, midazolam, and ketamine. Patients with CHD receiving premedication should be monitored closely for signs of respiratory depression and poor CO, with pulse oximetry and ECG monitoring.
The use of invasive monitoring depends on the patient’s physiology, the procedure, and the need for close BP control and frequent arterial blood gases (ABGs). Sites for arterial catheter placement depend on previous surgery. For example, patients with classic or modified Blalock-Taussig shunts will often have spuriously low BP when monitored on the ipsilateral upper extremity. In addition, patients with left subclavian flap repair of aortic coarctation will have unreliable BP measurements on the left upper extremity. Arterial cutdown for previous surgeries can also complicate percutaneous arterial catheter placement.
Central venous pressure (CVP) monitoring can also be helpful, but it is important to understand the patient’s venous anatomy before placement. Depending on the stage of palliation, the superior vena cava (SVC) may be connected to the pulmonary artery, and pressure measurement in the SVC reflects PAP, not true CVP. Measurement of CVP in the patient with a superior cavopulmonary connection requires a catheter in the inferior vena cava (IVC). After the Fontan operation, both the SVC and the IVC are connected to the pulmonary arteries, and pressure measured in these locations is not equivalent to atrial pressure. In addition, CVP catheter placement in the internal jugular vein of an infant with a planned single-ventricle palliation is discouraged because a stenosis or thrombosis of the SVC can preclude further palliation.
Cerebral oximetry monitoring using near-infrared spectroscopy (NIRS) is often considered routine during cardiac surgery, but it can also be used during noncardiac surgery to trend O 2 delivery and CO. Somatic oximetry with the same device, using a probe placed on the flank at the tenth thoracic–first lumbar vertebral (T10-L1) level, is an important monitor of systemic O 2 delivery in single-ventricle infants and may be considered for major noncardiac surgery in these patients. 34, 35
Transesophageal echocardiography (TEE) can be used to monitor function and filling intraoperatively and assist the anesthesiologist in adjusting pharmacologic therapy and fluid administration during major surgery in patients with complex CHD. 36

Airway and Ventilation Management
Depending on the type of procedure planned and patient selection, a natural airway, laryngeal mask airway (LMA), or endotracheal tube (ETT) can all be used safely. Knowledge of the patient’s cardiac lesion and function and the goals for ventilation and oxygenation are critical. Pulmonary hypertension is exacerbated by hypoxemia and hypercarbia, so airway and ventilation management should be planned accordingly. Left-to-right shunt lesions such as ventricular septal defects, truncus arteriosus, and systemic-to-pulmonary arterial shunts can become unstable with the administration of high concentrations of inspired O 2 and with hypocarbia.

Anesthetic Techniques
When delivered with care, any anesthetic drug can be used in the patient with congenital heart disease. Myocardial depressants should be avoided in patients with poor ventricular function and who would poorly tolerate a BP decrease. Regional anesthetic techniques are also used in many patients with CHD, but careful assessment, including knowledge of anticoagulant therapy, is important for planning these techniques. Plans for emergence and tracheal extubation should also be considered. Tracheal extubation with deep levels of anesthesia can avoid the increased PVR that can accompany light planes of anesthesia and straining against an ETT. However, use of tracheal extubation must be weighed against the potential for airway obstruction, which can be disastrous in patients with PH.

Postoperative Care Plan and Disposition
Before anesthetizing a CHD patient for a procedure, the clinician should have a postoperative care plan. Depending on the lesion, preoperative status, and procedure, it is often necessary to reserve a bed in an intensive care unit (ICU) or a patient floor. Patients with delicate physiology (e.g., systemic shunt-dependent pulmonary flow, poor ventricular function) are usually admitted to the ICU or cardiology ward after administration of most anesthetics. At a minimum, these patients need a period of observation (4-6 hours) to ensure that they are hemodynamically stable in their baseline cardiac rhythm, maintaining stable S O 2 without airway or pulmonary problems, and can take oral fluids before discharge home.
Although procedures can be performed in CHD patients at freestanding outpatient surgical facilities, careful preoperative evaluation must occur. If there is any potential for instability or need for hospital admission, the lack of proximity to skilled help, drugs, and equipment precludes safe anesthesia care in these facilities, and the procedure should be performed in a hospital setting with adequate backup provisions.

Infective Endocarditis Prophylaxis
Infective endocarditis (IE) is a serious cause of morbidity and mortality, and patients with congenital heart disease have an increased incidence of IE, 1.1 per 1000 patient-years, compared with the general population, 1.7 to 6.2 per 100,000 patient-years. 37
The American Heart Association (AHA) published new guidelines for IE prevention in 2007. 38 The committee found that very few cases of IE could be prevented by the administration of antimicrobial endocarditis prophylaxis. As a result, the indications were narrowed considerably over previous versions of the guidelines. Patients must first have a cardiac indication; these are now limited to the presence of a prosthetic valve, previous endocarditis, and some forms of CHD. The CHD indications include unrepaired cyanotic CHD, complete repair with a prosthetic patch or material but only in the first 6 months after the procedure, and those with residual defects near the site of a patch. Transplant patients with valvulopathy are also included. In addition, a procedural indication must exist for IE prophylaxis. These include dental work with disruption of gums or mucosa; airway procedures such as tonsillectomy; and gastrointestinal (GI), genitourinary (GU), or skin, soft tissue, and orthopedic procedures involving infected tissue. Simple GI, GU, or other procedures without infection are no longer indications for prophylaxis. Box 3-2 and Table 3-7 summarize the major recommendations involving dental procedures and antibiotic regimens. 38

Box 3-2 High-Risk Cardiac Conditions in Endocarditis Patients for Whom Dental Prophylaxis is Reasonable

Prosthetic cardiac valve or prosthetic material used for cardiac valve repair
Previous infective endocarditis (IE)
Congenital heart disease *
• Unrepaired cyanotic CHD, including palliative shunts and conduits
• Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure †
• Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibit endothelialization)
Cardiac transplantation recipients who develop cardiac valvulopathy
Data from Wilson W et al: Prevention of infective endocarditis, Circulation 116:1736-1754, 2007.

* Except for the conditions listed above, antibiotic prophylaxis is no longer recommended for any other form of CHD.
† Prophylaxis is reasonable because endothelialization of prosthetic material occurs within 6 months postoperatively.

Table 3-7 Endocarditis Prophylaxis: Dental Regimens for CHD Surgical Patients
The American College of Obstetrics and Gynecology (ACOG) and AHA do not recommend IE prophylaxis for uncomplicated vaginal or cesarean deliveries, regardless of the type of maternal cardiac disease. The maternal cardiac conditions associated with the highest risk of adverse outcome from IE are appropriate for antibiotic administration only if the patient has an established infection that could cause bacteremia. 39

Patients at Greatest Anesthetic Risk
Patients with congenital heart disease are known to be at much higher risk for perioperative cardiac arrest and death than those without cardiac disease. A Mayo Clinic study of 92,881 pediatric anesthetic procedures from 1988 to 2005 revealed that 88% of the 80 arrests involved patients with CHD. The rate of cardiac arrest was several hundred–fold higher for patients with CHD. 40 Recent data also show which CHD patients are at the highest risk for cardiac arrest and death during or shortly after anesthesia ( Box 3-3 ).

Box 3-3 Highest-Risk Chd Lesions for Patient Anesthesia

Left-sided obstructive lesions
Pulmonary hypertension (PH)
Single-ventricle (SV) lesions
Dilated cardiomyopathy (DCM)
The Pediatric Perioperative Cardiac Arrest Registry evaluated 393 pediatric patients (127 with heart disease) who had anesthetic-related cardiac arrest from 1994 to 2005. 41 About 59% of these patients were unrepaired, and 26% were palliated, so only 15% had undergone reparative surgery. Single-ventricle diagnosis was most common (19%), with hypoplastic left heart syndrome (HLHS) in the most patients. Mortality was only 25% after cardiac arrest in this group. Left-to-right shunt lesions were the next most common diagnosis, with 18%, but mortality was low (17%) after arrest. Left-sided obstructive lesions were seen in 16%, but with high mortality (45%). Aortic stenosis had the single highest mortality rate after cardiac arrest under anesthesia (62%). Data on anesthetic-related 24-hour and 30-day mortality for 101,885 pediatric anesthetic patients from 2003 to 2008 at Royal Children’s Hospital in Melbourne, Australia, revealed 10 anesthetic-related deaths, five in patients with PH with or without CHD; eight had complex CHD, PH, or both. 42

Specific cardiac lesions

Left-to-Right Shunt Lesions
Left-to-right shunt lesions are among the most common CHD lesions that the anesthesiologist will encounter. The level of shunting can occur at any location between intracardiac chambers (i.e., ventricular septal defect [VSD] or atrial septal defect [ASD]), or extracardiac structures (i.e. patent ductus arteriosus [PDA]). The pathophysiologic consequences of L-R shunt depend on several factors: the size of the defect, pressure gradient between chambers or arteries, the pulmonary/systemic vascular resistance (PVR/SVR) ratio, the relative compliance of right and left ventricles, and blood viscosity 43 ( Fig 3-8 ).

Figure 3-8 Pathophysiology of left-to-right shunting lesions.
Flow diagram depicts factors that affect left-to-right shunting at atrial, ventricular, and great artery level and pathophysiology produced by these shunts. A large shunt will result in left ventricular (LV) failure, right ventricular (RV) failure, and pulmonary edema. Increased pulmonary blood flow and pulmonary artery pressures lead to pulmonary hypertension and eventually Eisenmenger’s syndrome. These final common outcomes are highlighted in bold. PVR, Pulmonary vascular resistance; SVR, systemic vascular resistance; LA, left atrial; BP, blood pressure; RVEDV, right ventricular end-diastolic volume; RVEDP, right ventricular end-diastolic pressure; LVEDP, left ventricular end-diastolic pressure; LVEDV, left ventricular end-diastolic volume; R → L, right to left.
(Data from Walker SG: Anesthesia for left-to-right shunt lesions. In Andropoulos DB, et al, editors: Anesthesia for congenital heart disease, ed 2, Oxford, UK, 2010, Wiley-Blackwell.)
In general, atrial-level shunting produces the least degree of change, resulting in increased right ventricular (RV) filling and mild increases in RV end-diastolic volume and pressure. Symptoms are minimal, and these shunts may be tolerated for decades. Ventricular-level shunting is often more problematic, and if the defect is large and unrestrictive, RV pressure is close to left ventricular (LV) pressure, also elevating pulmonary artery (PA) pressure and flow significantly. Qp/Qs greater than 3:1 will produce significant increases in left atrial (LA) and LV blood flow, LV end-diastolic pressure (LVEDP) and volume (LVEDV), and can lead to pulmonary venous congestion, pulmonary edema, and respiratory distress. Smaller, restrictive ventricular defects, where RV pressure is significantly lower than LV pressure, produce lesser elevations in Qp/Qs, and pulmonary congestion is less severe.
Shunts at the great artery level, if large, are the most problematic. In young infants, these lesions can produce a “steal” of blood flow away from the aorta to the PA, lowering diastolic BP and causing coronary ischemia, heralded by global LV dysfunction and dilation, poor CO, and ST-segment changes on ECG. Any L-R shunt that is large enough, particularly at the ventricular or great artery levels, produces pulmonary hypertension, which, if left untreated over years, may become irreversible. This syndrome results from increased shear stress and circumferential stretch on the pulmonary arterioles causing endothelial dysfunction and vascular remodeling. Smooth muscle cells proliferate, extracellular matrix increases, and intravascular thrombosis occurs in the smaller arterioles. This increases PVR, and eventually the shunt inverts, resulting in cyanosis (Eisenmenger’s syndrome). 44 Although encountered less frequently in contemporary practice, patients with Eisenmenger’s syndrome are always at high risk under anesthesia and require careful assessment and planning (see later discussion).
Ventilatory management during general anesthesia will affect pathophysiology, especially with large L-R shunts in small infants, whose pulmonary vasculature will respond vigorously to changes in Fi O 2 and Pa CO 2 . Hyperoxygenation and hyperventilation usually lower PVR greatly and increase the L-R shunt, which may cause lower diastolic pressure, coronary steal, and large increases in both RV and LV volumes, leading to acute myocardial dysfunction. Generally, lower Fi O 2 and normocarbia are the goal during anesthesia in these infants, to limit increases in pulmonary blood flow. Positive end-expiratory pressure (PEEP) also limits increases in Qp/Qs. Any anesthetic regimen can be used in these patients; most agents are pulmonary vasodilators, and none, even ketamine, is a pulmonary vasoconstrictor ( Box 3-4 ; see also Pulmonary Hypertension).

Box 3-4 Large Left-to-Right (L-R) Shunts

Controlling pulmonary/systemic blood flow ratio (Qp/Qs) is an important goal.
Limiting Fi O 2 prevents large decreases in pulmonary vascular resistance.
Avoiding hyperventilation and adding PEEP help balance Qp/Qs.

Patent Ductus Arteriosus
The patent ductus arteriosus (PDA) is the connection between the pulmonary artery and lesser curve of the arch of the aorta, which during fetal life carries blood from the PA to the aorta, bypassing the lungs so that only 5% to 10% of the fetal cardiac output passes through the lungs 45, 46 ( Fig. 3-9 ). Normally, patency is maintained by low fetal oxygen tension (P O 2 ), low levels of circulating prostanoids produced by the placenta, and lack of prostanoid metabolism by the lungs. At birth, with onset of respiration and expansion of the lungs, oxygenation, and decreased levels of prostanoids, the PDA constricts, and normally is functionally closed by 48 to 72 hours of life, and anatomically closed by 2 weeks, producing the ligamentum arteriosum. However, some PDAs never close, and it is one of the most common, simple CHD lesions.

Figure 3-9 Patent ductus arteriosus with resultant left-to-right shunting.
Some of the blood from the aorta crosses ductus arteriosus and flows into pulmonary artery (arrows).
(Modified from Brickner ME, Hillis LD, Lange RA: N Engl J Med 342:256-263, 2000.)
Isolated PDA incidence is 1:2000 to 1:5000 live births and accounts for 3% to 7% of congenital heart disease. 1 PDA is more common in premature infants but may be encountered at any age, including adults. It is also a component of many more complex cardiac diseases, and early neonatal survival depends on the PDA for many lesions, including stenosis or atresia of the pulmonary or aortic valves (e.g., pulmonary atresia, HLHS). Maintaining ductal patency with prostaglandin E 1 (PGE 1 ) for such lesions is mandatory until surgical or catheter palliation or correction can be performed.
Flow through the PDA is normally left to right (i.e., aorta to PA). The amount of flow depends on the diameter, length, and tortuosity of the PDA and the relative pressure and resistances in the aorta and PA. Anatomic variations range from a tiny PDA with almost no flow to large, aneurysmal, calcified PDA in adults, with very high pressures from years of exposure to aortic pressure and flows. The pathophysiologic consequences of a PDA range from minimal through significant increases in Qp/Qs (> 2:1), causing increases in RV volume and pressure and possible increases in LA and LV flow to the point that LVEDV and LVEDP are elevated, which can increase pulmonary venous pressure and cause transudation of fluid through pulmonary capillaries into the interstitial and alveolar spaces. This is particularly common in premature infants, who may be ventilator dependent solely as a result of the PDA. In addition, patients with very large PDA may have a large steal of flow from the aorta to the PA, lowering diastolic BP and potentially causing coronary ischemia. Over time, patients with a large, long-standing PDA may develop irreversible elevations in PA pressure, leading to reversal of the shunt and Eisenmenger’s syndrome. Many patients with small PDA are asymptomatic, with increasing symptomatology according to the PDA size and Qp/Qs. Recurrent respiratory infections, difficulty feeding, diaphoresis, and impaired growth are seen in infants with large PDA. Occasionally, congestive heart failure (CHF) is seen.
Physical examination in isolated PDA usually reveals an acyanotic child, with Sp O 2 of 95% to 100% on room air. Peripheral pulses are easily palpable because of the increased pulse pressure resulting from lowered diastolic BP. Precordial examination yields a vigorous cardiac impulse, with the LV apex often displaced to the left. A compensatory tachycardia at rest is often present. With a small shunt, there may only be a soft grade I-II/VI systolic murmur over the left infraclavicular area. With increasing shunt, the murmur will become louder and longer, and with very large PDA there is a continuous, machinery-like murmur, loudest just after the second heart sound (S 2 ), which is often accentuated. Examination of the lungs may reveal tachypnea, retractions, and fine rales if there is significant pulmonary congestion.
Diagnostic testing in patients with PDA includes an ECG, which often reveals evidence of LA and LV enlargement and in more severe cases, RV enlargement as well. Rhythm is normally sinus, although adults may develop atrial fibrillation from long-standing atrial enlargement. Chest radiograph findings range from near-normal to cardiomegaly with increased pulmonary vascular markings in larger PDA. Transthoracic echocardiogram is the most useful diagnostic modality and is often sufficient to make an accurate diagnosis as to size, tortuosity, direction of shunting, and enlargement of cardiac chambers and any associated defects. Both two-dimensional and color Doppler images, as well as pulsed and continuous-wave Doppler studies, are obtained for a complete picture of anatomy and physiology. The PDA is often larger than the aorta and the branch PAs in premature infants. In PDA with complex or questionable anatomy, additional studies (e.g., CT angiography, MRI) are performed. These studies are particularly useful if a coarctation of the aorta is suspected, often present in the juxtaductal position. Cardiac catheterization is performed only in particularly difficult cases or when PDA is associated with device closure in the CCL.
Closure of the PDA is performed by one of three methods: thoracotomy with ligation or ligation/division, video-assisted thoracoscopy (VATS) with ligation, or endovascular closure with coils, plugs, or other devices in the CCL. 47 Robotic-assisted VATS has also been reported. 48 Choice of closure method depends on the size of the patient, anatomy of the PDA, and institutional practice, including surgeon and cardiologist preference. In general, premature and other small infants will have left thoracotomy with extrapleural dissection and closure of the PDA; larger infants can undergo thoracotomy or VATS repair. Surgical closure is used for large or tortuous PDAs or when coarctation of the aorta may be present. In the modern era, most small to moderate PDAs in larger infants and children are occluded in the CCL. Adult patients with large, aneurysmal PDAs may require cardiopulmonary bypass (CPB) or even deep hypothermic circulatory arrest (DHCA) through a thoractomy or sternotomy. 49
Anesthetic considerations in PDA patients include thorough preoperative evaluation with complete examination and assessment of all diagnostic studies, to assess the degree of L-R shunting and pathophysiologic severity. Packed red blood cells must be available in the OR or CCL, in case of tearing or rupture of the PDA, which although rare, can cause catastrophic bleeding. Standard monitors are applied before induction, and inhalational induction with sevoflurane or IV induction with various agents can be accomplished. An arterial line, preferably in the right radial artery, is indicated for small infants undergoing surgery, as well as other patients with significant pathophysiology. In the CCL the cardiologist will acquire femoral arterial access for monitoring and approach to the PDA. A central venous catheter is needed only for large PDAs accompanied by significant pathophysiology. For thoracotomy or VATS in small infants, single-lung ventilation (SLV) is usually unnecessary; the technical difficulty and time required often are significant. Insufflation of CO 2 with lung retraction for VATS, or simple retraction and packing for thoracotomy in small infants, is usually sufficient for surgical exposure. Alternately, the endotracheal tube may be advanced into the right main bronchus in a small infant; the problem with this approach is that the right upper-lobe bronchus is often close to the carina and is occluded by the ETT. In larger patients, SLV can be provided by bronchial blockers, or in larger patients (> 30 kg), a small, left-sided double-lumen ETT, and will assist with surgical exposure, particularly in VATS.
Any combination of inhaled or IV agents may be used for maintenance of anesthesia, keeping in mind the severity of pathophysiology. Severely ill neonates with large PDA will be intolerant of the myocardial depressant and hypotensive effects of significant concentrations of halogenated anesthetics. Nitrous oxide (N 2 O) should be avoided because of its potential to expand closed air spaces. In small infants with large L-R shunts, high Fi O 2 accompanied by hyperventilation to lower Pa CO 2 will often excessively lower PVR, resulting in large increases in Qp/Qs, more diastolic steal of systemic blood flow, and large increases in both LV and RV volumes, all of which may lead to acute myocardial failure. Inotropic support with dopamine or epinephrine may be needed in some patients, particularly the premature infant. Precise ventilation, with a microprocessor-controlled anesthesia ventilator capable of delivering small tidal volumes, or hand ventilation, may be required.
Premature infants often undergo thoracotomy at the bedside in the neonatal ICU, to avoid the stresses of transport to a distant OR. A complete anesthesia setup, with all necessary equipment and drugs, is brought to the bedside. Normally the infant’s NICU ventilator is used, and anesthesia is provided with fentanyl (30-50 μg/kg) and small doses of midazolam, along with neuromuscular blockade with vecuronium, pancuronium, or other nondepolarizing agent. This approach provides sufficient anesthesia to prevent hemodynamic response to surgery, while allowing hemodynamic stability in these fragile patients. 50 During PDA ligation, particularly in premature infants, the anesthesiologist must have a method to monitor lower-extremity perfusion, such as pulse oximeter probe on the toe or foot. The PDA is often larger than the descending thoracic aorta, and the aorta has been mistakenly ligated in some cases; disappearance of pulse oximeter signal on the lower extremity must immediately be noted, and the surgeon must ensure that the correct structure has been occluded. Ligation of the left PA is also possible in small infants. Method of occlusion can be with vascular clips; however, many surgeons believe the most secure method is ligation at both ends of the PDA with heavy silk sutures or oversewing, followed by ligation to ensure permanent occlusion. A thoracostomy tube is typically placed, although some surgeons do not place these tubes in premature infants. A postoperative chest radiograph is obtained in all patients.
In small infants with significant pathophysiology, the trachea is left intubated to allow recovery from both the cardiac and the pulmonary effects of a large PDA. In almost all other patients, the trachea can be extubated at the end of the procedure. Postoperative analgesia can include thoracic nerve blocks or wound infiltration by the surgeon, or possibly thoracic epidural analgesia (not usually used because recovery is typically rapid). Opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) are used for postoperative pain. Postoperative stay for uncomplicated PDA ligation is short, usually 24 to 48 hours; CCL closure is usually followed by discharge home the same day.
According to the latest AHA infective endocarditis guidelines, acyanotic patients with unrepaired or repaired PDA do not require prophylaxis. 38

Aortopulmonary Window
Aortopulmonary (AP) window is an abnormal connection between the intrapericardial components of the aorta and pulmonary artery. AP window is a rare lesion, only 0.1% to 0.6% of congenital heart defects. 51 About half of patients also have associated cardiac defects (e.g., PDA, VSD). The AP window can range from small, circular communication to total absence of the septum between the aorta and PA. Some AP window defects have a tubular communication. The pathophysiology of an AP window is similar to that of a large PDA and depends on size of the communication and relative SVR and PVR. AP window is usually diagnosed in early infancy, with the presence of a systolic or continuous murmur similar to that of a PDA, with pulmonary overcirculation, tachypnea, poor feeding and growth, and signs of CHF. Diastolic coronary steal may impair ventricular function. Diagnosis is by echocardiography. Repair is most often done in early infancy, almost always with CPB; the AP window is repaired by patching if large, or by direct suture ligation if small. Older children with suitable defects may have an AP window occluded in the CCL with various closure devices. Anesthetic management is the same as for the patient with a large PDA, with the same approach to pathophysiologic derangements. Approach to the infant undergoing repair with CPB is the same as for any complex case.

Atrial Septal Defect
Atrial septal defects (ASD) represent 5% to 10% of congenital heart defects and are classified as secundum (80% of defects), primum, sinus venosus, or coronary sinus ASDs 52 ( Fig. 3-10 ). The secundum ASD is in the middle of the atrial septum, in the fossa ovalis, and results from lack of proper formation of the secundum septum. A primum ASD is low in the atrial septum, just above the tricuspid valve, a result of abnormal formation of the septum primum. It is often associated with a cleft mitral valve or with partial or complete atrioventricular (A-V) canal defects. Sinus venosus ASDs are usually found just below the SVC orifice but may also be found just above the IVC orifice. This lesion is often associated with partial anomalous pulmonary venous return (PAPVR; see later). 1, 43, 53 A coronary sinus ASD, or “unroofed coronary sinus,” results from lack of a partition between the coronary sinus and left atrium, allowing LA blood to drain into the right atrium. This defect is usually associated with a persistent left SVC. Finally, a probe-patent foramen ovale (PFO) is present in up to one third of normal individuals, resulting from failure of fusion of the overlapping primum and secundum septae. As long as LA pressure is higher than right atrial (RA) pressure, ASD is asymptomatic; however, paradoxical embolus and stroke or transient ischemic attack may occur if RA exceeds LA pressure, as during a Valsalva maneuver.

Figure 3-10 Atrial septal defects.
A, Atrial septal anatomy. Schematic diagram shows the location of atrial septal defects, numbered in decreasing order of frequency: 1, secundum; 2, primum; 3, sinus venosus; 4, coronary sinus type. IVC, Inferior vena cava; PT, pulmonary trunk; RV, right ventricle; SVC, superior vena cava. B, Secundum atrial septal defect (ASD), right atrial view. SVC, Superior vena cava; RAA, right atrial appendage; CS, coronary sinus; TV, tricuspid valve; RV, right ventricle.
(Modified from Porter CJ, Feldt RH, Edwards WD, et al: Atrial septal defects. In Emmanouilides GC, Riemenschneider TA, Allen HD, Gutgesell HP, editors: Moss and Adams heart disease in infants, children, and adolescents: including the fetus and young adult, Baltimore, 1995, Williams & Wilkins.)
Flow through the ASD is left to right, and symptomatology depends on the size of the shunt. Because of the low pressure in the atria and small interatrial pressure gradients, the magnitude of the shunt is usually 2:1 or less. Ventricular compliance also affects degree of shunting; the relatively stiff right ventricle in the first few months of life prevents significant shunt. Symptoms are often minimal, and may go undetected for many years, even decades. Exercise intolerance is one of the usual symptoms; more severe symptoms (e.g., CHF, atrial flutter/fibrillation) are late signs and usually in patients over age 40. Pulmonary hypertension during childhood is rare but occurs in about 20% of patients age 20 to 40 and half of patients over 40. Rarely, fixed pulmonary pressures result in Eisenmenger’s syndrome. LV and RV sizes and function remain normal, but right atrium and right ventricle are enlarged with the added volume load. Systemic CO and Sa O 2 are normal ( Box 3-5 ).

Box 3-5 Atrial Septal Defect (ASD)

Three major types of ASD are secundum, primum, and sinus venosus.
Symptoms are usually mild.
Pulmonary vascular disease does not develop until the fourth or fifth decade of life.
Physical examination reveals an acyanotic child, usually in no distress. Patients with ASD often have no symptoms until later in life. Cardiac examination is usually abnormal, with a fixed, split S 2 the most consistent finding. This results from increased RV volume, delaying full ejection and keeping the pulmonary valve open later, and eliminating the respiratory variation. The murmurs are soft, I-II/VI, systolic, and at the left upper sternal border. A soft mid-diastolic murmur may be present with large shunts. In many ASD patients the physical examination findings are subtle, resulting in delayed diagnosis. ECG normally reveals sinus rhythm; biatrial enlargement, right-axis deviation, and first-degree A-V block may be seen in some patients. As noted, atrial fibrillation or flutter is a late sign usually seen only in unrepaired adults. Chest radiograph reveals cardiomegaly, increased PA size, and increased pulmonary vascular markings in patients with moderate to large L-R shunts.
Diagnostic modalities for ASD include transthoracic echocardiography, the most useful test, which typically is sufficient to make the diagnosis and plan treatment. Two-dimensional (2D) echocardiography defines the size, position, and morphology of the defect, ventricular size and function, and any associated intracardiac lesions (e.g., PAPVR). Color flow Doppler defines the direction of blood flow and its velocity, to assess the relative LA and RA pressures. Agitated saline contrast injection during a Valsalva maneuver can diagnose an R-L shunt through a PFO by the early appearance of microbubbles in the left atrium. Cardiac MRI and CT are not used for ASD diagnosis, except in cases of complex or uncertain anatomy, with associated defects not well defined by echocardiography. Cardiac catheterization is only used in conjunction with planned device closure of the ASD.
Most patients with an unrepaired ASD will tolerate anesthesia well without hemodynamic compromise. The usual techniques and drug doses used for patients without heart disease can be employed. Air bubbles must be avoided in any IV fluids; paradoxical embolization can occur during Valsalva-type maneuvers. Patients with CHF, atrial arrhythmias, or PH must be carefully evaluated and the anesthetic planned accordingly. Infective endocarditis prophylaxis for ASD patients is only indicated after patch repair in the first 6 months. 38
Secundum ASDs with adequate rims of tissue in all dimensions or PFOs are normally closed in the CCL, with various devices deployed by large sheaths introduced via the femoral vein. 54 For children, general anesthesia is normally employed, and the device is positioned with the aid of fluoroscopy and TEE necessitating a general anesthetic. In older patients, it is possible to use sedation without endotracheal intubation, if an intracardiac echo catheter technique is used. 55 These procedures usually are not accompanied by major hemodynamic instability or blood loss. Larger defects, or other types of ASDs (sinus venosus, primum, coronary sinus) are closed surgically with CPB; minimally invasive techniques with tiny sternotomy incisions can be used. Most patients have short CPB and aortic cross-clamp times, and repair is with autologous pericardial patch or direct suture closure. The majority of these patients can be extubated in the OR and do not experience much bleeding or hemodynamic instability. 56

Ventricular Septal Defect
Ventricular septal defect (VSD) is the most common form of congenital heart disease; up to 20% of patients have this lesion as an isolated defect. In addition, as many as 40% to 50% of all patients have a VSD as some component of their CHD. 1, 43, 57 VSD anatomy is highly variable, but four main types are encountered, as follows:

1. Perimembranous VSD is the most common form (75%-80% of VSDs) is found in the middle of the ventricular septum, underneath the septal leaflet of the tricuspid valve.
2. Subarterial or outlet VSD (5%-15%) is high in the outlet septum, underneath the aortic and pulmonary valves.
3. Muscular VSD (2%-7%) can be found anywhere in the muscular septum.
4. Inlet-type VSD (5%) is located in the inlet septum underneath the tricuspid valve.
Many other variations and combinations of VSD range from tiny muscular VSDs that close spontaneously to very large and multiple defects 58 ( Fig. 3-11 ).

Figure 3-11 Anatomic position of ventricular septal defects.
A, Subarterial or outlet defect; B, papillary muscle of the conus; C, perimembranous defect; D, marginal muscular defects; E, central muscular defects; F, inlet defect; G, apical muscular defects.
(Redrawn from Graham TP Jr, Gutgesell HP: Ventricular septal defects. In Emmanouilides GC, et al, editors: Moss and Adams heart disease in infants, children, and adolescents: including the fetus and young adult, Baltimore, 1995, Williams & Wilkins.)
Left-to-right shunt through the VSD depends on the size of the defect, the relative pressures in the right and left ventricles, and the relative ventricular compliances, as well as the PVR and SVR. If the VSD is small and restrictive, there is significant resistance to flow, the pressure drop across the VSD is large, and Qp/Qs is less than 2:1. As the VSD size increases, resistance is less and flow greater, until the defect is termed unrestrictive; LV and RV pressures are similar, Qp/Qs increases significantly to 3:1 or greater, and relative PVR/SVR ratio becomes the important determinant of flow. In clinical practice, Qp/Qs ranges from essentially 1:1 with a tiny VSD to extreme elevations of 5:1 or greater in infants with very large VSD and low PVR. Certainly, elevated PVR may develop with months or years of high pressure and flows into the pulmonary arteries. If left untreated, the increased PVR can become fixed and suprasystemic, and flow direction can reverse to produce an R-L shunt, cyanosis, and Eisenmenger’s syndrome. Although unusual before several years of life, Eisenmenger’s syndrome can occur as early as 1 to 2 years in patients with large VSDs ( Box 3-6 ).

Box 3-6 Ventricular Septal Defect (VSD)

Three major types of VSD are perimembranous, subarterial, and muscular.
The Qp/Qs ratio varies from near-normal to greater than 3:1.
The Qp/Qs depends on size of the defect, left/right ventricular pressures, and pulmonary vascular resistance.
Pulmonary vascular disease may develop early in life in patients with large VSD.
Physical examination findings range from asymptomatic patients to those with severe CHF. Infants with large VSD are normally acyanotic with Sp O 2 of 95% to 100%. Tachypnea is common, reflecting the pulmonary congestion, and a compensatory tachycardia to maintain systemic CO in the face of a large L-R shunt is often present. Feeding is often tiring for these infants, and growth is often poor, both from inadequate caloric intake and from a very high metabolic rate accompanying increased myocardial work. CHF is heralded by retractions, fine rales, hepatomegaly, jugular venous distention, and diaphoresis. Cardiac examination reveals an active precordium, displacement of the ventricular apex to the left, and a murmur, which is usually a grade II-III/VI pansystolic murmur between the second and third left intercostal spaces. Smaller, restrictive defects produce more turbulent flow and may be accompanied by a grade IV/VI murmur. Large VSD in young infants whose PVR has not yet experienced its physiologic fall may have minimal or no murmur, explaining why some of these patients are diagnosed late. Qp/Qs greater than 3:1 will also produce a mid-diastolic flow murmur at the cardiac apex. Heart sounds are normal unless PVR is significantly elevated. ECG findings are not specific for VSD, are usually sinus rhythm, and may exhibit right-axis deviation with significant shunts. Chest radiography normally reveals cardiomegaly and increased pulmonary vascular markings, in proportion to the size of the L-R shunt. Echocardiography is the mainstay of diagnosis, with 2D echocardiography revealing the size, position, and shape of the defect, ventricular size and function, and associated intracardiac defects (see Fig. 3-4 , A ). MRI, CT, and cardiac catheterization are required only for complicated VSD with associated defects or for hemodynamic catheterization if PVR is a concern.
Patients with an unrepaired small VSD are relatively asymptomatic and will tolerate any of the common anesthetic techniques and drugs. Again, no bubbles must be introduced into the venous circulation by drug injection or IV fluids; paradoxical R-L shunt can easily occur with elevated PVR or Valsalva-type maneuvers. Infants under age 1 year with a large VSD often have very labile PVR, and rapid increases can occur with hypercarbia, acidosis, or hypoxemia; these patients may experience periods where PVR is higher than SVR, leading to R-L shunt and further hypoxemia, which can be life threatening. Conversely, excessive decreases in PVR, which often accompany high Fi O 2 and hyperventilation, can greatly increase Qp/Qs, with adverse hemodynamic consequences, including acute RV and LV dilation and dysfunction, low diastolic BP resulting in coronary ischemia, and in some patients, cardiac arrest. Indeed, in 127 infants and children with CHD experiencing cardiac arrest under anesthesia, 18% had an L-R shunt lesion, with VSD the most common. 41 Thus, even relatively simple lesions have the potential for extreme pathophysiologic derangements. When anesthetizing an infant with an unrestrictive VSD, it is prudent to decrease the Fi O 2 to low levels (0.21-0.3) and to avoid hyperventilation, in order to prevent excessive increases in Qp/Qs.
VSD closure can sometimes be carried out in the CCL, with devices similar to those used for ASD closure, if the VSD is suitably accessible. However, this procedure may have significant hemodynamic instability and blood loss. 59 Complications, including complete A-V block, can be seen in up to 11% of patients, with mortality in 3%. 60 The vast majority of VSDs are closed surgically in the first 2 years of life, with CPB, and patching of the VSD with polyester fiber (Dacron) or the patient’s own pericardium using a transatrial approach. Contemporary surgical series from excellent centers report mortality of 0.5%, with no complete A-V block and no VSD recurrences or reoperations. 61 Many patients older than 6 to 12 months are candidates for early tracheal extubation and rapid ICU discharge. Infectious endocarditis prophylaxis is not indicated for unrepaired isolated VSD or repaired VSD after 6 months with no residual defects. 38

Atrioventricular Canal
Atrioventricular canal (AVC) results from failure of the endocardial cushion to form early in fetal development. This defect is present in 3% to 5% of patients with CHD and is particularly prevalent in trisomy 21 patients, 20% to 33% of whom have AVC. 1, 43, 62
The three major variants of AVC are partial, transitional or intermediate, and complete AVC. The unifying feature of all types is the presence of a common A-V junction, with either a single A-V valve, or if separated, both tricuspid and mitral valves at the same level in the heart, rather than complete septation, with tricuspid annulus inferior and mitral annulus superior. Partial AVC consists of an ostium primum ASD and a cleft in the anterior leaflet of the mitral valve. There is no VSD component in this lesion. Transitional AVC consists of the ostium primum ASD, common A-V valve, and a small inlet VSD component that may be covered by A-V valve tissue. There is some degree of A-V valve regurgitation in this lesion.
Complete AVC is characterized by the primum ASD, common A-V valve, and a large inlet VSD. Complete A-V canal is further subdivided according to the arrangement of the anterior bridging leaflet of the common A-V valve and the position of its chordal attachments. In Rastelli type A the bridging leaflet is mostly contained on the LV side, and the chordae are attached to the crest of the ventricular septum 63, 64 ( Fig. 3-12 ). In Rastelli type B the bridging leaflet is more on the RV side, and the papillary muscle of the leaflet is attached to the right side of the ventricular septum. Type B is rare. Rastelli type C is the most common, and the superior bridging leaflet is unattached to the ventricular septum. Other variants of complete AVC include RV or LV dominant, with discrepant ventricular size; tetralogy of Fallot with complete AVC; and complete AVC with LV outflow tract obstruction.

Figure 3-12 Atrioventricular septal defect.
A, Common form of complete atrioventricular septal defect (Rastelli type A), originally classified according to division of anterior bridging leaflet (A) and attachment to septum. Current interpretation has only the left-sided portion of anterior leaflet as anterior bridging leaflet, and the right-sided portion is “true” anterior tricuspid leaflet. P, Posterior bridging leaflet; L, two lateral leaflets corresponding to posterior mitral valve (MV) and tricuspid valve (TV) portions of leaflets; RA , right atrium; RV, right ventricle. B, Schematic four-chamber view of complete atrioventricular septal defect, showing common valve and atrial and ventricular communications.
( A redrawn from Porter CJ, et al: Atrioventricular septal defects. In Emmanouilides GC, Riemenschneider TA, Allen HD, Gutgesell HP, editors: Moss and Adams heart disease in infants, children, and adolescents: including the fetus and young adult, Baltimore, 1995, Williams & Wilkins; B from Castaneda AR, et al, editors: Atrioventricular canal defect. In Cardiac surgery of the neonate and infant, Philadelphia, 1994, Saunders.)
The L-R shunt in AVC may occur at the atrial or ventricular levels as well as through a ventriculoatrial shunt secondary to A-V valve regurgitation, which is normally an LV-to-RA shunt. The magnitude of the shunting depends on the total sizes of the defects, the relative pressures in the left and right cardiac chambers, and the ventricular compliance. As with a large VSD, complete AVC shunting also depends on the relative PVR and SVR. The magnitude of the L-R shunt ranges from less than 2:1 in partial AVC to 3:1 to 4:1 or greater in complete AVC in some young infants. Patients with unrepaired complete AVC have elevated PAP and can develop elevated PVR, which over time can become fixed, resulting in reversal of shunt and cyanosis (Eisenmenger’s syndrome). Patients with trisomy 21 are especially susceptible, developing elevated PVR sooner than patients with normal chromosomes, and thus must be repaired in the first year of life. Before the 1980s, surgery was often not offered to trisomy 21 patients, and a significant number of these patients who had developed Eisenmenger’s syndrome presented for noncardiac anesthetic procedures. The vast majority of these patients have since died, and it is now unusual to encounter a patient with unrepaired complete AVC. Other considerations after AVC repair include residual mitral (much more common) or tricuspid insufficiency. The technical difficulties of repairing malformed A-V valves result in many patients with this residual defect ( Box 3-7 ).

Box 3-7 Atrioventricular Canal (AVC)

Three major types of AVC are partial, intermediate (transitional), and complete.
Complete AVC is highly associated with trisomy 21.
Pulmonary vascular disease occurs in the first 2 years of life in trisomy 21 patients with unrepaired complete AVC.
Physical examination findings vary according to the size of the L-R shunt, from almost asymptomatic with partial AVC to severe CHF in complete AVC in an infant with a large L-R shunt. Patients are acyanotic with Sp O 2 of 95% to 100%. They are often tachypneic and tachycardic, with poor feeding and growth, and have frequent respiratory infections from pulmonary congestion. Patients with CHF are diaphoretic, with hepatomegaly and jugular venous distention. Patients with trisomy 21 have the physical characteristics associated with condition. The cardiac examination usually reveals an active precordium with the apex displaced to the left. A fixed, split S 2 is similar to that heard in ASD. A systolic murmur is heard at the left upper sternal border, ranging from grade II-IV/VI, depending on the degree of flow across the ASD and VSD, turbulence, and A-V valve regurgitation. Patients with Qp/Qs greater than 3:1 have a diastolic murmur at the left lower sternal border.
The ECG findings in AVC are distinctive; the PR interval is prolonged in about 90% of patients, and the QRS axis is deviated superiorly and to the right, the “northwest axis.” This results from the deficiency of the endocardial cushion. The QRS interval is also prolonged in the majority of patients. Chest radiography reveals cardiomegaly and increased pulmonary vascular markings in proportion to the degree of L-R shunt. Patients with complete AVC presenting late, after 6 months of life, may have smaller hearts and normal pulmonary vascular markings on radiography, indicating elevated PVR that has limited the degree of shunting. Diagnosis of AVC is by 2D and color Doppler echocardiography, which is sufficient to define ventricular anatomy, magnitude of the A-V valve regurgitation, any other associated defects, and the magnitude and direction of shunting (see Fig. 3-4 , B ). The relative pressures in the ventricles can also be defined. In recent years, three-dimensional echocardiography has further defined A-V valve morphology. MRI and CT are not indicated unless there are other complicating anatomic features. Cardiac catheterization is reserved to study pulmonary vascular resistance and reactivity in those patients presenting for late repair, whose PVR may be so elevated as to preclude complete septation of the heart.
The anesthetic considerations for unrepaired AVC are similar to those noted earlier for ASD and VSD. Partial or transitional AVC patients normally have small L-R shunts and will tolerate any common anesthetic technique. Again, air bubbles must be assiduously avoided in these patients. Infants with complete AVC are approached similar to those with a large VSD; excessive Fi O 2 or hyperventilation producing low Pa CO 2 for prolonged periods will result in a greatly increased Qp/Qs and hemodynamic compromise. The trisomy 21 infant, after age 6 months with unrepaired complete AVC, presents a significant challenge because of elevated and reactive PVR; periods of hypoxemia or hypercarbia may rapidly elevate PVR and lead to increased R-L shunting and cyanosis. These patients should be approached with caution and plans made to treat a pulmonary hypertensive crisis, (such as having inhaled nitric oxide [iNO] available). According to AHA infective endocarditis guidelines, an acyanotic patient with unrepaired AVC does not require prophylaxis. Prophylaxis is indicated in the first 6 months after repair or in patients with residual defects (e.g., significant A-V valve regurgitation). 38
Repair of AVC is always surgical using CPB; timing depends on the magnitude of L-R shunt, A-V valve regurgitation, and symptomatology. Partial or transitional AVC patients with minimal mitral regurgitation often have repair at 2 to 5 years of age. Infants with complete AVC are repaired before age 6 months, to prevent the sequelae of long-standing elevated PVR, particularly in trisomy 21 patients. A one-patch or two-patch technique is used to close the ASD and VSD, attach the common A-V valve to the patch and/or the ventricular septum, and repair the clefts in the A-V valves. 65 Complete AVC patients are at risk for pulmonary hypertensive crisis immediately after repair and thus are not extubated early in the postoperative period; precautions to prevent this complication are taken. 66 In the modern era of very early repair, severe pulmonary hypertensive crises are much less common. Even after repair, many AVC patients have residual A-V valve regurgitation, which is more important if the mitral valve is involved; this is an important factor when evaluating patients with repaired AVC for later anesthesia.

Double-Outlet Right Ventricle
Double-outlet right ventricle (DORV) refers to a heterogeneous spectrum of lesions characterized by a VSD, with both the aorta and the pulmonary artery arising either completely or partially from the right ventricle. DORV is present in 1% to 1.5% of patients with CHD. The most common variant is the subaortic-type defect, where the VSD is located beneath the aortic valve. This arrangement is present in about half of patients with DORV, and when pulmonary or subpulmonary stenosis is present, it is known as tetralogy of Fallot–type DORV. 43, 67 DORV with a subpulmonary VSD represents about 30% of these patients; if the aorta is positioned to the right of and parallel to the PA, this is known as Taussig-Bing–type DORV, and the physiology is similar to transposition of the great arteries. DORV with noncommitted VSD is present in 12% to 17% of patients; the VSD is remote from the great vessels, either in the inlet or the muscular septum, and may be associated with AVC defects. The DORV with doubly committed VSD represents 5% to 10% of patients; the VSD sits below both aortic and pulmonic valves, with varying degrees of override.
The pathophysiology of DORV is complex and depends on size and position of the VSD, presence of pulmonic stenosis, streaming of blood through the VSD to one or the other great vessel, PVR/SVR ratio, and relative RV/LV compliance. Without pulmonary or subpulmonary stenosis, DORV patients often have similar pathophysiology to the patient with a large VSD; Qp/Qs can be 2:1 or greater, and the patient can develop RV dilation, which can lead to CHF. Elevated PVR can develop over time. With obstruction to pulmonary blood flow, the shunting can vary from left to right with a Qp/Qs of just over 1:1, to significant obstruction to pulmonary blood flow and cyanosis, with pathophysiology very similar to tetralogy of Fallot. With transposition-type physiology, the patient will have cyanosis because most of the RV blood is directed to the aorta ( Box 3-8 ).

Box 3-8 Double-Outlet Right Ventricle (DORV)

Pathophysiology in the DORV patient depends on degree of right ventricular outflow tract (RVOT) obstruction.
Cyanosis and “tetralogy of Fallot” are associated with significant RVOT obstruction.
The acyanotic patient with VSD has no RVOT obstruction.
The physical findings in DORV also depend on the degree of L-R or R-L shunting, which in turn is influenced by the degree of pulmonary stenosis. Presentation ranges from acyanotic and relatively asymptomatic patients with Sp O 2 of 95% to 100%, to those in CHF from very large L-R shunts, to those with significant cyanosis (Sp O 2 70%-90%) from R-L shunting. It is important to categorize the DORV patient with (1) primarily left-to-right shunt, (2) primarily right-to-left shunting from pulmonary stenosis, or (3) cyanosis from transposition-type physiology and lack of mixing of systemic and pulmonary blood flows. Murmurs are normally grade II-IV/VI, along the left sternal border, and may be from flow across the VSD or turbulence caused by pulmonary stenosis. A diastolic flow murmur is heard in patients with large Qp/Qs (> 3:1).
The ECG shows no characteristic findings; sinus rhythm is the norm, and right-axis deviation is common. Chest radiography is variable and depends on degree of L-R shunting. Cardiomegaly and increased pulmonary vascular markings predominate in large L-R shunts. An essentially normal chest radiograph may be seen with balanced circulation. In R-L shunt patients, a normal or small heart with a paucity of pulmonary vascular markings is observed. Echocardiography is the mainstay of anatomic and physiologic diagnosis, to determine size and position of the VSD and its relationship to the great vessels, degree of pulmonary stenosis, and presence of associated anomalies. CT and MRI are not usually indicated. Cardiac catheterization is also not usually performed; the details of the exact cardiac anatomy and surgical approach are normally determined by the surgeon in the OR, with direct intracardiac examination after CPB and aortic cross-clamping are initiated.
Repair of DORV is undertaken when the patient is symptomatic and can vary from complete repair with complex VSD patch/tunnel, to palliation with systemic-to-pulmonary arterial shunting in the neonatal period, to an arterial switch operation. 68 CPB is typically used, and because of the complex intracardiac repair, residual defects such as subaortic or subpulmonary obstruction are seen. Approach to anesthesia for noncardiac surgery in the DORV patient considers basic anatomy and pathophysiology, previous repair, and any residual defects. Patients with a large L-R shunt are treated similar to those with a large VSD, as previously noted. Endocarditis prophylaxis is indicated if the patient is cyanotic or has residual defects, both of which are common in DORV.

Truncus Arteriosus
Truncus arteriosus is an uncommon defect, representing about 1% of all cases of CHD. Truncus arteriosus is defined by the presence of a single great artery arising from the base of the heart that provides all aortic and pulmonary blood flow. A large, subarterial VSD is present. Truncus arteriosus results from failure of septation of the ventricular outlets into the aorta and pulmonary artery, caused by failure of the sixth aortic arch to develop. A genetic cause is strongly suspected because up to one third of these patients have microdeletions in the chromosome 22q11 region, with associated DiGeorge or velocardiofacial syndromes. This syndrome is variable, but components include absent or hypoplastic thymus and parathyroid glands from abnormal development of the third and fourth pharyngeal pouches, resulting in T-cell deficiency and hypocalcemia. Other components include a high, arched palate, varying degrees of micrognathia, and neurodevelopmental delay. 43, 69
The most common classification system is that of Collett and Edwards. Type I truncus accounts for about 70% of cases, characterized by a short, main PA arising from the truncal artery and dividing into right and left PAs. Type II accounts for almost 30% of truncus arteriosus patients, characterized by no main PA but separated branch PAs arising directly from the truncal artery immediately adjacent to each other. Type III truncus is rare (~ 1%), characterized by widely separated branch PAs arising from the lateral aspect of the truncal artery. Other findings include an abnormal truncal valve, comprising two to six leaflets, with either truncal stenosis or regurgitation. Also, the aortic arch itself is hypoplastic or interrupted in 5% to 10% of truncus arteriosus patients. “Type IV” is actually tetralogy of Fallot with pulmonary atresia, with pulmonary blood flow supplied entirely by aortopulmonary collaterals from the descending thoracic aorta, and so is no longer classified as truncus arteriosus 70 ( Fig. 3-13 ).

Figure 3-13 Classification of truncus arteriosus.
A, Type I with a short main pulmonary artery segment arising from the leftward, posterior aspect of ascending aorta. B, Type II with separate origins of right and left pulmonary arteries arising close to each other on posterior aspect of ascending aorta. Note the left-sided aortic arch in A and B. C, Type III with separate origins of right and left pulmonary arteries arising far apart from posterolateral aspect of ascending aorta. D, Type IV, more appropriately described as pulmonary atresia and ventricular septal defect; separate origins of right and left pulmonary arteries arise from descending aorta. Note the right-sided aortic arch in C and D.
(Redrawn from Grifka RG: Pediatr Clin North Am 46:405-425, 1999.)
The pathophysiology of truncus arteriosus is unique and results from the aortic, pulmonary, and coronary circulations arising from a single artery. Because of this parallel circulation and presence of a large VSD, there is some degree of mixing of systemic and pulmonary circulations, producing a mild degree of cyanosis, with Sp O 2 normally 85% to 95%. Left-to-right shunting predominates, with PVR lower than SVR, and with the normal fall in PVR in early postnatal life, the lungs are progressively overcirculated, resulting in extremely large Qp/Qs (≥ 3:1-4:1). CHF thus often ensues. The unique anatomy of truncus also means that increasing pulmonary blood flow will steal flow from the arterial side, including the coronary arteries. This results in low diastolic BP, and myocardial ischemia is possible, with ST-segment changes, myocardial dysfunction, and cardiac arrest from ventricular fibrillation due to ischemia. In addition, the steal of systemic flow can lead to ischemia of the gut and kidneys, leading to necrotizing enterocolitis and renal dysfunction and failure in the neonatal period. Unrepaired patients who survive the neonatal period develop increased PVR in the first few months of life and may have a temporary reduction in CHF symptoms as the L-R shunt decreases. Eventually, reversal of shunt from fixed, elevated PVR can ensue, causing cyanosis. This severe pathophysiologic derangement and unsatisfactory result from palliative neonatal procedures (e.g., PA banding) led to complete repair of truncus arteriosus, one of the first such lesions in neonates so approached 71 ( Box 3-9 ).

Box 3-9 Truncus Arteriosus

Major types of truncus arteriosus (I, II, III) depend on degree of pulmonary artery branching.
Common arterial trunk leaves systemic, pulmonary, and coronary circulations in parallel.
Lowering PVR with excessive Fi O 2 and hyperventilation creates systemic/coronary steal and myocardial ischemia.
Physical examination of the patient with truncus arteriosus normally reveals an acyanotic or mildly cyanotic infant with Sp O 2 of 85% to 95%. The magnitude of L-R shunt is usually large, and tachypnea, tachycardia, pulmonary congestion, hepatomegaly, and diaphoresis with poor feeding and growth are common. Peripheral pulses are bounding because of the increased pulse pressure from diastolic runoff into the PAs. The precordium is active, with apex displaced to left. The heart sounds may be abnormal with a split S 2 , always a systolic murmur, and grade II-IV/VI at the left sternal border from both VSD flow and increased flow across the truncal valve. Significant stenosis of the truncal valve is accompanied by grade IV/VI murmur. A diastolic murmur may be heard at the left upper sternal border with truncal valve regurgitation, or at the left lower sternal border with increased diastolic flow from large Qp/Qs.
The ECG normally reveals sinus rhythm and signs of both LV and RV hypertrophy; ST-segment abnormalities may be present. The chest radiograph is often remarkable for extreme cardiomegaly and increased pulmonary vascular markings. As PVR increases, these findings are less extreme over time. Echocardiography is the mainstay of diagnosis and will define the truncal valve anatomy, stenosis, and regurgitation, as well as PA anatomy and size of the VSD. Echocardiography is also important to determine the degree of biventricular dilation and dysfunction. Other modalities, such as MRI, CT, or cardiac catheterization, are rarely indicated in the initial planning of truncus arteriosus repair.
Repair of truncus arteriosus is almost always in the neonatal period, with CPB; the VSD is closed, and an RV-to-PA conduit is placed after the PAs are separated from the truncal artery. The truncal valve may require repair. Importantly, even after repair, truncus patients often have residual aortic stenosis or regurgitation, and all patients will outgrow their RV-PA conduit and thus will return for repeat surgery. The anesthesiologist must thoroughly evaluate their anatomy and residual defects when these patients present for noncardiac surgical anesthesia.
The approach to anesthetic delivery in the unrepaired truncus patient requires detailed attention to the pathophysiologic derangements. In general, any agents can be used, but further myocardial depression from anesthetics and increase in Qp/Qs leading to coronary steal and further myocardial dysfunction must be avoided at all costs. This means that Fi O 2 must be reduced and hyperventilation avoided in the young infant with reduced PVR. PEEP of 5 to 10 cm H 2 O is also effective at shunting blood flow away from the lungs. Maintaining adequate diastolic BP, with vasoconstrictive agents if needed, is another important goal. Strict avoidance of intravenous injection of air is critical, as the bubbles can directly enter the systemic and coronary arteries. Invasive monitoring in the form of arterial and CVP catheters are indicated for major noncardiac surgery in unrepaired truncus arteriosus patients. Endocarditis prophylaxis is indicated in most of these patients because they have a cardiac indication.

Anomalous Pulmonary Venous Return
Anomalous pulmonary venous return refers to conditions where some or all of the pulmonary veins have their blood return to the right atrium, either directly or through the SVC or an abnormal, connecting venous structure. The two classifications are total anomalous pulmonary venous return (TAPVR), and partial anomalous pulmonary venous return (PAPVR). TAPVR is an uncommon lesion, accounting for about 1.5% to 2.5% of CHD cases. PAPVR is often asymptomatic and is present in about 0.5% of the population in autopsy studies; however, only a fraction of these patients present for surgical treatment. 43, 72
Total APVR has four main subtypes. The supracardiac type is seen is in 45% to 55% of TAPVR patients; the pulmonary venous confluence connects to a vertical vein that in turn connects to the innominate vein, thus draining all pulmonary venous blood into the SVC and right atrium 71 ( Fig. 3-14 ). The infracardiac type of TAPVR (13%-25%) consists of a pulmonary venous confluence connected to a draining vein that courses inferiorly, through the esophageal hiatus and below the diaphragm, and usually connects to the portal venous system; thus the blood flows through the liver to the hepatic vein and IVC. The cardiac type of TAPVR (25%-30%) consists of the pulmonary venous confluence draining into the coronary sinus or directly to the right atrium. Mixed types of TAPVR are rare and account for less than 5% of cases.

Figure 3-14 Classification of total anomalous pulmonary venous return.
A, Type I; four pulmonary veins drain into vertical vein that enters innominate vein. B, Type II; pulmonary veins drain into coronary sinus that enters right atrium. C, Type III; pulmonary veins join to form a descending vein that courses through diaphragm and drains into portal venous system. D, Type IV, mixed pulmonary venous return; two right pulmonary veins and left lower pulmonary vein drain to coronary sinus while left upper pulmonary vein drains into a vertical vein. Note that in all four types there is an atrial septal defect.
(Modified from Grifka RG: Pediatr Clin North Am 46:405-425, 1999.)
Partial APVR consists of one or two pulmonary veins draining into the SVC or right atrium in 75% of cases. In almost all patients, this lesion is associated with a sinus venosus ASD. In most of the remaining patients, the right pulmonary veins connect to the IVC; it is rare to have anomalous left pulmonary vein connections to the left innominate vein or coronary sinus.
The pathophysiology of PAPVR is usually mild, with Qp/Qs of less than 2:1, because some of the pulmonary venous blood returns to the right atrium, creating a left-to-right shunt. There also can be shunting across the ASD itself; but because of the low pressures in the atria and the relatively low pressure gradient between them, this shunting is limited. This explains why so many PAPVR patients are asymptomatic for many years; this pathophysiology is similar to that of a small to moderate-sized secundum ASD, where symptoms of dyspnea on exertion only occur during the second or third decades of life or later. PAPVR rarely is associated with anatomic obstruction to pulmonary venous flow.
Total APVR pathophysiology depends mostly on the degree of obstruction to pulmonary venous flow. Infracardiac TAPVR is more likely to be obstructed, with the tortuous course of pulmonary venous return though the liver a setup for this problem; indeed, almost all these patients have significant obstruction. Patients with supracardiac TAPVR are less likely to be obstructed; if the vertical vein passes directly between the left PA and left main bronchus, a “bronchopulmonary vise” is created, leading to obstruction. Cardiac TAPVR with connection to the coronary sinus is least likely to be obstructed. Obstruction leads to severe pulmonary venous congestion and decreased pulmonary blood flow. The result is severe cyanosis and respiratory distress from interstitial and pulmonary alveolar edema. In addition, further obstruction is encountered if the patient has only a small PFO or ASD; a large interatrial communication at least allows egress of blood out of the right atrium and may lessen the degree of functional obstruction. Infants with TAPVR who are not obstructed, and have adequate atrial septal defects may escape diagnosis in the neonatal period because of only mild symptoms. Later, as PVR decreases and pulmonary blood flow increases, the L-R shunt increases, and they will experience mild cyanosis from the R-L shunt at the atrial level. These patients will appear similar to infants with CHF from a large VSD, with the exception of the cyanosis ( Box 3-10 ).

Box 3-10 Anomalous Pulmonary Venous Return

Major types of anomalous pulmonary venous return are partial (PAPVR) and total (TAPVR).
PAPVR patients usually have mild symptoms of a small, left-to-right shunt.
TAPVR symptomatology depends on degree of obstruction to pulmonary venous return.
Infradiaphragmatic TAPVR patients are prone to severe pulmonary venous obstruction, hypoxia, and respiratory failure.
The physical examination of a patient with PAPVR usually reveals a near-normal-appearing acyanotic patient, with SpO 2 of 95% to 100%. Findings depend on the degree of L-R shunt, but with Qp/Qs typically less than 2:1, tachypnea and tachycardia are minimal. Cardiac examination is almost normal, except for the fixed, split S 2 , which is often present, and a soft, I-II/VI systolic murmur at the left sternal border. Chest radiography usually reveals mild cardiomegaly and mild increase in pulmonary vascular markings. Some PAPVR patients have scimitar syndrome, which is PAPVR to the IVC, pulmonary sequestration, and hypoplasia of the right lung. The chest radiograph reveals a curved shadow in the shape of a scimitar, the descending anomalous right pulmonary veins or vertical vein.
The ECG is usually normal but may show atrial arrhythmia later in life if RA enlargement is significant. Echocardiography usually makes the diagnosis, although CT, MRI, and cardiac catheterization may be needed if unusual pulmonary venous anatomy is suspected. TAPVR patients with obstructed pulmonary venous return usually are severely ill, with severe cyanosis and respiratory distress, and require emergency tracheal intubation and ventilation as well as inotropic support. Chest radiography reveals a small heart resulting from lack of pulmonary venous return to the left side of the heart. The severe pulmonary venous congestion has a ground-glass appearance. Indeed, these patients are sometimes mistaken for infants with severe persistent fetal circulation and are placed on extracorporeal membrane oxygenation (ECMO) before a diagnosis is made. 73
Older patients with supracardiac TAPVR that is not obstructed have a “figure of 8” or “snowman” configuration in which the engorged vertical vein on the left and the engorged innominate vein and SVC on the top and right form a globular shadow in the upper mediastinum. Urgent echocardiography is mandatory when the diagnosis of TAPVR is suspected; in severely ill patients this is sufficient to make the diagnosis of infracardiac or supracardiac TAPVR and to rule out associated cardiac anomalies. Echocardiography will reveal the site of obstruction, size of an atrial communication, and often a severely underfilled left ventricle, compressed by an overfilled, hypertensive right ventricle that is limiting both filling and output. In less ill patients, echocardiography is usually sufficient in straightforward TAPVR; in some cases (mixed TAPVR), however, it cannot provide precise images, and CT angiography, MRI, or cardiac catheterization is needed. During repair, the surgeon will also directly examine the pulmonary venous return to detect unsuspected variations.
Repair of PAPVR can be undertaken when the child is 2 to 4 years of age using standard CPB techniques; these patients usually have a straightforward intraoperative course and can be extubated in the OR. Partial APVR often presents late, so teenagers and adults are frequently put forward for this surgery. The sinus venosus ASD is repaired concomitantly using CPB, and often the ASD patch can be placed so that the anomalous pulmonary vein orifices are on the left side of the patch. If the pulmonary veins connect to the SVC, the Warden procedure may be needed; the SVC is translocated to the RA appendage, and an intracardiac baffle is placed, leading to a lower incidence of pulmonary venous obstruction. 74
Repair of TAPVR is often a surgical emergency in a critically ill neonate; these patients require institution of CPB as rapidly as possible to prevent cardiac arrest or severe hypoxemic end-organ damage, including neurologic injury. Repair is accomplished on CPB, usually with DHCA, and involves dividing and ligating the abnormally draining vein, anastomosing the pulmonary venous confluence to the back of the left atrium, and closing atrial communications. 75 These patients often have severe PH immediately after surgery and usually require iNO. Some TAPVR patients have recurrence of pulmonary vein obstruction, caused by either scarring at the anastomotic site or progressive pulmonary vein sclerosis from long-standing in utero obstruction. Even after repair, therefore, any residual obstruction must be monitored during evaluation for a noncardiac anesthetic procedure.
The anesthetic approach in patients with PAPVR can include any of the usual agents and techniques, because most patients have mild pathophysiology. For TAPVR patients with severe obstruction, attention is directed to supporting respiration and circulation and institution of CPB as quickly as possible. Although the anesthesiologist may want to use high Fi O 2 and even iNO preoperatively to increase pulmonary blood flow in the patient with severe PH, these maneuvers are often counterproductive because the increased pulmonary flow is met with a fixed anatomic obstruction, which may worsen ventilation and oxygenation. Older patients with unrepaired, unobstructed TAPVR have symptomatology similar to patients with a large VSD; excessive Fi O 2 and hyperventilation may make ventilation more difficult because of increased pulmonary blood flow; these parameters are adjusted to achieve the same baseline Sp O 2 and hemodynamic state that existed before the anesthetic. Endocarditis prophylaxis is indicated in unrepaired patients and those with residual defects.
Left-Sided Obstructive Lesions

Coarctation of the aorta
Coarctation of the aorta refers to a discrete narrowing, usually near the insertion of the ductus arteriosus. Coarctation is one of the most common congenital lesions, found in 8% to 11% of patients with CHD. 1 Turner syndrome has a strong association with coarctation of the aorta. Coarctation may be an isolated lesion, which is the case for older infants and children presenting with this disorder, or may have associated lesions, such as aortic or subaortic stenosis and VSD, which is often true for neonates presenting with coarctation.
Severity ranges from mild narrowing presenting later in life to severe obstruction and near-interruption presenting in the first days to weeks of life. With more severe cases of obstruction, blood flow beyond the coarctation depends on a patent ductus arteriosus. In addition, ductal tissue is often present in the wall of the aorta itself; thus constriction of the PDA results in severe obstruction, lack of flow to the lower body, and severe increase in afterload, leading to cardiovascular collapse in the neonate. 76 In this case, PGE 1 is started emergently to reopen the PDA, and resuscitation with inotropic support and mechanical ventilation are also instituted. Because end-organ injury (e.g., renal/hepatic failure, intestinal ischemia) often occurs in these situations, the patient is stabilized, end-organ function is allowed to recover, and repair is done semielectively several days later. 77 Infants with less severe obstruction often have signs of CHF as the PDA closes, with cardiomegaly and pulmonary interstitial edema, accompanied by tachypnea, diaphoresis, and poor feeding.
Older patients are often relatively asymptomatic, and the coarctation is discovered during routine physical examination when the patient is hypertensive in the upper extremities, particularly in the right arm. Weakened and delayed femoral pulses and a systolic BP gradient of 20 mm Hg or more are hallmarks of this disease. If present, a murmur is soft, grade I-II/VI systolic at the upper left sternal border, radiating to the axilla and back; this is often not appreciated early in life. Older patients also often develop collateral arterial circulation, from the right and left subclavian arteries, thyrocervical trunk, and intercostal and thoracic arteries above the area of coarctation 45 ( Fig. 3-15 ). This allows better circulation to the lower extremities and minimizes symptomatology during childhood. Continuous murmurs best heard at the back may be present from these collaterals. Occasionally, adults present with unrepaired coarctation; of necessity they have extensive collateralization, and they have been hypertensive for decades. These patients are prone to early hypertensive cardiovascular disease, including coronary artery disease (CAD) and cerebrovascular accident (CVA, stroke), often in their 30s and 40s.

Figure 3-15 Coarctation of the aorta.
Coarctation causes severe obstruction of blood flow in the descending thoracic aorta. The descending aorta and its branches are perfused by collateral channels from the axillary and internal thoracic arteries through the intercostal arteries (arrows).
(Modified from Brickner ME, Hillis LD, Lange RA: N Engl J Med 342:256-263, 2000.)
Diagnosis of coarctation is initially made by transthoracic echocardiography; the suprasternal notch views will delineate the aortic arch, ductus arteriosus, and descending thoracic aorta well. Echocardiography can show whether the ductus arteriosus is patent, as well as direction of flow in the PDA, exact location and degree of obstruction, and presence of diastolic runoff, which is a sign of severe obstruction. In addition, the position of the subclavian arteries and, importantly, the presence of associated intracardiac lesions are also delineated. ECG findings may demonstrate left-axis deviation as seen in LV hypertrophy but otherwise is nonspecific. Chest radiography may demonstrate cardiomegaly and interstitial edema in infants with heart failure. Later changes include normal or enlarged cardiac silhouette and signs of collateralization (e.g., rib notching) or pre- and post-stenotic dilation of the aorta (e.g., “figure 3” sign). Particularly in older children, the presence of collateral arterial circulation is important in planning the surgical approach, so most patients require MRI or CT angiography before repair (see Figs. 3-6 and 3-7 ). Because the risk of paraplegia from aortic cross-clamping is higher without adequate collateralization, these patients may require special techniques, such as partial left-sided bypass.
Repair of isolated coarctation of the aorta is undertaken as soon as the diagnosis is made, urgently in the neonate with ductus-dependent circulation and electively in less ill infants. Delaying surgery is thought to increase risk of chronic end-organ dysfunction from hypertension, including the left ventricle. Monitoring of arterial BP is done by arterial catheter in the right arm; left-arm or lower-extremity arterial monitoring will not yield accurate information. Also, 5% to 10% of these patients have an aberrant right subclavian artery originating distal to the coarctation; during cross-clamping, perfusion to the brain must be monitored by pulse oximeter on the ear, temporal artery pulse or arterial line, or NIRS. Repair is normally performed through a left thoracotomy, after dissection and isolation of the aorta, the coarctation, PDA or ligamentum arteriosum, subclavian arteries, and intercostal and collateral arteries in the field. After cross-clamping above and below the coarctation, the coarctation segment and any ductal tissue are excised, and the aorta is repaired using one of several methods. Most often the direct or extended end-to-end anastomosis is used, with excellent long-term results and low recurrence rate ( Fig. 3-16 ). Other techniques include the subclavian flap angioplasty, which uses the proximal subclavian artery to reconstruct the narrowed segment. Because some studies report a higher recurrence rate with this approach, many centers no longer use this technique. Patients with subclavian flap angioplasty will have diminished pulses, lower BP, and possibly poor growth of the left arm ( Box 3-11 ).

Figure 3-16 Technique of extended end-to-end repair of coarctation of aorta.
A, Left thoracotomy approach is used, a cross-clamp is applied proximal to coarctation to include left subclavian and left carotid arteries; a distal clamp is also used. B, Ductus arteriosus is ligated and coarctation segment excised. C, Extended anastomosis is created to produce a widely patent transverse and distal thoracic aorta.
(Modified from Hoschtitzky JA, Anderson RH, Elliott MJ: Aortic coarctation and interrupted aortic arch. In Anderson RH, et al, editors: Paediatric cardiology, ed 3, Philadelphia, 2010, Elsevier/Churchill Livingstone.)

Box 3-11 Coarctation of the Aorta

Coarctation is normally an isolated narrowing in the juxtaductal region.
Symptoms vary from cardiovascular collapse in a PDA-dependent neonate to late presentation with hypertension in the upper extremities.
Early surgery with extended end-to-end anastomosis is the preferred approach to coarctation.
Recurrent coarctation is often treated with dilation and stenting.
Blood pressure monitoring in the right upper extremity is important.
During thoracotomy, CPB typically is not used, and the period of aortic cross-clamping is 20 to 30 minutes. Cross-clamping often is well tolerated because patients with severe obstruction have minimal change in afterload. Patients with less severe obstruction have adequate LV function to tolerate the temporary increase in afterload and may be hypertensive during clamping. The risk of paraplegia from inadequate collateralization and clamping above the artery of Adamkiewicz (major arterial supply to spinal cord, normally at T9 but variable) is very low with this approach (1 in 1000). Nevertheless, body temperature is usually cooled to 34 ° C (93.3 ° F), and BP measured in the right radial artery is maintained at high-normal ranges to promote flow through collaterals. Generally, patients with hypertension during cross-clamping should not be treated with IV vasodilators, to avoid hypotension; adjusting volatile anesthetic concentrations is often effective. Anticipated cross-clamp periods longer than 30 minutes are usually approached with partial left-sided heart bypass to provide flow to the descending aorta. SLV techniques are normally not necessary in small infants. Many anesthesiologists avoid thoracic epidural analgesia for coarctation repair because of the paraplegia issue; epidural anesthesia will complicate the workup and management of this significant problem. Hypertension is common after coarctation repair and requires effective control with IV vasodilators and/or beta-adrenergic blocking agents in the early postoperative period. 78
Recurrent coarctation in an older child is often approached in the interventional CCL; balloon dilation and stenting is an effective treatment. Other approaches for severe lesions include median sternotomy with complete anatomic reconstruction by CPB. 79 Noncardiac surgery in the patient with coarctation of the aorta must be preceded by evaluation of the patient’s anatomy and pathophysiology. Unrepaired patients with cardiac failure may require invasive monitoring and inotropic support for major surgery. Repaired patients may have recurrent coarctation or hypertension that may affect anesthetic management.

Interrupted aortic arch
Complete interruption of the aortic arch (IAA) can be viewed as the most severe end of the spectrum of coarctation of the aorta. IAA is a relatively uncommon lesion, accounting for approximately 1% of patients with CHD. The most common classification divides IAA into type A, interruption at the aortic isthmus just distal to the left subclavian artery (25%-40% of cases); type B, interruption between the left subclavian and left carotid artery (50%-75%); or type C, proximal interruption between the innominate and left carotid artery (5%) ( Fig. 3-17 ). The majority of patients with type B interruption have DiGeorge syndrome, associated with chromosome 22q11.2 deletions, and velocardiofacial syndrome, hypocalcemia, and absent thymus with T-cell immune deficiency. 76, 78 Severe hypoplasia of the proximal transverse aortic arch is a variant of IAA and is approached in the same manner. Patients with IAA present in early infancy because a PDA needs to perfuse the lower body. Because of the complete interruption, closure of the PDA is associated with shock and cardiovascular collapse, with resuscitation as for the neonate with severe coarctation performed as previously noted. IAA is rarely an isolated lesion; almost all neonates will have a VSD and some form of aortic valve obstruction, most often subvalvar stenosis.

Figure 3-17 Classification of interrupted aortic arch.
The descending aorta is supplied by the patent ductus arteriosus.
(Modified from Hoschtitzky JA, Anderson RH, Elliott MJ: Aortic coarctation and interrupted aortic arch. In Anderson RH, et al, editors: Paediatric cardiology, ed 3, Philadelphia, 2010, Elsevier/Churchill Livingstone.)
Repair of IAA usually occurs in the neonatal period and is most often done with CPB, both for complete anatomic reconstruction of the aortic arch and to repair the associated intracardiac defects. Periods of DHCA or regional cerebral perfusion are often used. 80 Because IAA patients normally have two ventricles, recovery from surgery is usually uncomplicated. Noncardiac surgery after repair must account for the presence of residual lesions (e.g., recurrent aortic arch obstruction) or DiGeorge syndrome, potentially with difficult tracheal intubation.

Aortic stenosis
Congenital anomalies of the left ventricular outflow tract account for approximately 6% to 7% of patients with CHD. Congenital valvar aortic stenosis (AS) accounts for the majority, about 75% of patients with LVOT defects. Subvalvar AS represents about 25%. Supravalvar stenosis is uncommon but as noted later, is a very significant lesion for the anesthesiologist because most of these patients have Williams’ syndrome 81 ( Fig. 3-18 ).

Figure 3-18 Types of congenital aortic stenosis.
A, Fibromuscular or tunnel type of subaortic stenosis with obstruction to left ventricular emptying by muscular overgrowth of the entire outflow tract. B, Membranous subaortic stenosis; a membrane is present 1 to 2 cm below the aortic valve orifice obstructing ventricular outflow. C, Thickened, domed, fused leaflets of congenital valvar stenosis. D, “Hourglass” narrowing of the supravalvar aorta producing supravalvar stenosis.
(Redrawn from Rosen DA, Rosen KR: Anomalies of the aortic arch and valve. In Lake CL, editor: Pediatric cardiac anesthesia, Stamford, Conn, 1998, Appleton & Lange.)
Isolated bicuspid aortic valves are often not diagnosed during childhood, and the true incidence of AS is unknown; this may well be the most common CHD lesion of all, necessitating treatment at any stage of life, but particularly in older adults. 78, 82 Presentation of these lesions ranges from shock and cardiovascular collapse in the neonate with severe AS whose PDA has closed, to the asymptomatic patient with a murmur. Intermediate presentations may include chest pain and syncope with exertion in older patients with severe AS. Most patients have a harsh systolic murmur at the left upper sternal border, usually grade III-IV/VI. The murmur may radiate to the carotid arteries. Left ventricular hypertrophy and enlargement may displace the ventricular apex downward and to the left.
The ECG often reveals left-axis deviation and LV hypertrophy. Chest radiography in the neonate usually reveals cardiomegaly and interstitial pulmonary edema; in the older patient, increased LV size may be apparent. Echocardiography is the mainstay of diagnosis of all forms of AS; morphology of the valve and degree of subvalvar, valvar, or supravalvar stenosis are assessed using calculations of peak and mean Doppler gradients; area of aortic valve opening is also calculated. The presence of a PDA, direction of flow in the PDA, and direction of flow in the proximal aorta can also be delineated. Degree of LV hypertrophy and ventricular dysfunction can also be assessed. Other diagnostic modalities are rarely necessary; catheterization is usually reserved for intervention on the aortic valve itself.
Critical AS in the neonate is most often treated urgently in the CCL with balloon valvuloplasty. These patients are often critically ill; resuscitation drugs and equipment must be immediately available in case of cardiac arrest caused by ventricular fibrillation from coronary ischemia, as a result of interrupted aortic flow during balloon inflation. Surgical backup for emergency ECMO initiation may be planned. After balloon dilation relieves all or most of the obstruction, some aortic insufficiency may result; this is usually well tolerated until the infant recovers and grows, then has aortic valve repair or replacement. Other approaches include surgery to resect subvalvar fibrous or muscle tissue, repair or replacement of a stenotic valve, or patch repair of supravalvar AS. All these repairs must be done with CPB ( Box 3-12 ).

Box 3-12 Aortic Stenosis

Aortic stenosis may be subvalvar, valvar, or supravalvar.
Hemodynamic goals are to maintain afterload, normal to slow heart rate, and preload and to avoid increases in contractility.
Williams syndrome patients often have coronary artery involvement out of proportion to aortic stenosis.
After aortic stenosis repair, patients are often hypertensive.
Hemodynamic goals during anesthesia for AS patients serve to (1) minimize resistance to flow across the AS, (2) optimize stroke volume across the stenotic area, and (3) optimize LV oxygen demand/supply ratio in the often-hypertrophied ventricle. Whichever anesthetic regimen is used, decreases in SVR (BP) must be minimized because this will increase turbulence of flow and thus resistance across the stenotic area. This results in less systemic cardiac output. In addition, if the coronary arteries are involved, as in Williams syndrome, critical myocardial ischemia may result. Even if the coronary arteries are not directly involved, BP lowering will compromise coronary perfusion pressure. Therefore, maintaining normal or high-normal BP is an important goal. In addition, tachycardia is poorly tolerated because diastolic filling time and systolic ejection time across the obstruction are reduced, resulting in lower stroke volume and systemic CO. Also, myocardial O 2 demand will be significantly increased, resulting in risk for subendocardial ischemia and ventricular dysfunction. Excessive increases in contractility will also increase the functional gradient across the stenosis and increase myocardial O 2 demand. Patients poorly tolerate hypovolemia from prolonged fasting, unreplaced blood, or third-space fluid losses because LV filling must be maintained to optimize stroke volume across the obstruction.
The pathophysiology of left-sided obstruction was recently studied in 127 cardiac arrests under anesthesia in pediatric patients with cardiac disease. 41 Left-sided obstructive lesions accounted for 16% of the total; but 45% of these patients could not be resuscitated and died, making patients with these obstructive lesions extremely high-risk for anesthetic procedures.
Supravalvar AS associated with Williams syndrome deserves special consideration. 83 Williams syndrome is a defect in the elastin gene on chromosome 7, resulting in abnormal connective tissue, particularly affecting the ascending aorta, which narrows just above the sinotubular junction, and often affecting the orifices of the coronary arteries by partially obstructing them with a hood of abnormal tissue. The supravalvar gradient itself may not be severe, but the coronary circulation is tenuous, and any BP lowering will significantly affect coronary perfusion, which may result in coronary ischemia, ventricular fibrillation, and death with anesthesia. Case reports and series detail Williams syndrome patients in cardiac arrest during anesthesia for noncardiac surgery. 84, 85 A cardiologist’s consultation and recent echocardiographic results are particularly important before noncardiac surgery in these patients. Patients with significant supravalvar AS and coronary artery involvement should probably have cardiac surgery first, before elective surgery or anesthesia. In addition, the coronary arteries may not be well imaged on echocardiography, and CT angiography is often performed.
Intraoperative course, postoperative care, and provisions for backup assistance must be planned carefully in case of major instability or resuscitation. Adherence to hemodynamic goals (avoiding decreases in SVR, tachycardia, and hypovolemia) is crucial to achieving the best anesthetic outcomes. Williams syndrome patients with significant supravalvar AS and coronary disease also often have mild to moderate supravalvar pulmonic and branch PA stenosis, which usually diminishes over time with patient growth.

Mitral stenosis
Congenital mitral stenosis as an isolated lesion is rare, accounting for 0.2% to 0.4% of patients with congenital heart disease. 86 Mitral stenosis can result from malformation of the valve leaflets, a supravalvar mitral ring, or abnormal papillary muscles. In addition, mitral stenosis can result after repair of a left-sided A-V valve, as in complete atrioventricular canal. Rheumatic heart disease can also cause mitral stenosis. The presentation in isolated mitral stenosis usually involves symptoms of pulmonary congestion and frequent respiratory infections, even wheezing, resulting from LA hypertension causing pulmonary venous hypertension and interstitial edema. Infants have tachypnea, diaphoresis, poor feeding, and failure to thrive. PH may ensue in long-standing mitral stenosis.
Cardiac auscultation usually reveals a loud, low-pitched mid-diastolic murmur at the apex. Chest radiography often shows increased interstitial pulmonary vascular markings and increased LA size, with normal LV shadow. The ECG reveals LA enlargement, and patients with long-standing MS may have atrial fibrillation. Echocardiography is the most important diagnostic tool, revealing important anatomic information and calculating a peak and mean gradient across the valve with Doppler interrogation. In addition, the degree of PH can be assessed. Three-dimensional echocardiography is increasingly used for precise definition of the anatomic defect to plan surgical approaches. Cardiac catheterization is reserved for PH patients to assess risk of surgery.
Mitral stenosis is repaired surgically if the patient cannot be managed medically to achieve near-normal respiratory status and growth. Surgery usually involves repair of the valve in infants and children; valve replacement is avoided as much as possible in a growing child who would be obligated to future surgery. Also, anticoagulation management in active young children is often problematic. Occasionally, mitral stenosis can be addressed in the CCL with balloon valvuloplasty.
Anesthetic hemodynamic goals are similar to those for left-sided obstructive lesions noted earlier. Normal to slow heart rate will allow for increased diastolic filling time to improve stroke volume. Adequate intravascular volume status will achieve the same effect. Patients with PH must be approached with care; inadequate anesthesia, hypercarbia, or hypoxemia may cause a sudden increase in PVR, restricting LV filling and severely compromising systemic CO. On the other hand, excessively lowering PVR with high Fi O 2 , hyperventilation, or NO, may result in a significant increase in pulmonary blood flow without relief of the anatomic obstruction at the mitral valve, resulting in worsening ventilatory mechanics from increased interstitial edema. Therefore, these patients should be approached carefully with an anesthetic plan designed to achieve these goals ( Box 3-13 ).

Box 3-13 Mitral Stenosis

Isolated mitral stenosis is unusual in patients with CHD.
Left atrial hypertension may lead to pulmonary interstitial edema and pulmonary hypertension.
Hemodynamic goals are to maintain afterload, normal to slow heat rate, and normal preload.

Cor triatriatum
Cor triatriatum is an abnormal membrane, or division, present in the left atrium above the mitral valve, resulting in varying degrees of obstruction to flow into the left ventricle. It is a rare lesion, accounting for only 0.1% of CHD defects 87 (see Fig. 3-4 , C ). The pathophysiology is essentially identical to that of mitral stenosis, and only echocardiography often differentiates the two conditions. Surgical repair is undertaken when the diagnosis is made. Milder forms of cor triatriatum may be undetected for months and even years in patients whose only real symptoms are recurrent respiratory infections and wheezing.

Shone’s complex
Also known as Shone’s syndrome or anomaly, Shone’s complex consists of multiple levels of left-sided obstruction coexisting in the patient. Typically, at least three levels of obstruction must be present for the diagnosis, 78 usually including mitral stenosis with a supravalvar mitral ring and parachute mitral valve, subaortic stenosis with a fibromuscular membrane or tunnel, and coarctation of the aorta. Additional lesions include bicuspid aortic valve with aortic stenosis and a VSD. Severe forms of Shone’s complex form a continuum on the mild side of hypoplastic left heart syndrome (see later). Symptomatology depends on the severity of obstruction and the level of the most significant obstruction. Neonates with severe coarctation with Shone’s complex often present similar to those with isolated coarctation when the PDA closes. Mitral stenosis as the most significant level of obstruction is similar to isolated mitral stenosis discussed earlier.
The general approach in less severe obstruction is to manage the patient medically until large enough for surgery to address all levels of obstruction. In some patients the coarctation of the aorta is addressed in the neonatal period using left thoracotomy without bypass; this approach may merely shift the level of worst obstruction proximally to the subaortic area. Pulmonary hypertension often complicates the perioperative and hospital course of these patients. Careful individual evaluation, with echocardiography, cardiac catheterization to define the worst levels of obstruction, and medical management, including diuretics to minimize pulmonary edema, are necessary in these patients. Even after repair, the small size of the left ventricle in many of these patients leads to ongoing LA hypertension and low cardiac output.

Hypertrophic Cardiomyopathy
Hypertrophic cardiomyopathy (HCM) is defined as an increase in left ventricular muscle mass, in the absence of a condition that would produce abnormal loading of the left side of the heart, such as valvar aortic stenosis, hypertension, or coarctation of the aorta. The incidence of HCM is estimated at 0.3 to 0.5 per 100,000 children and 1 in 500 adults. 88 Familial or genetic causes include glycogen or lysosomal storage diseases, actin and myosin abnormalities, carnitine deficiency, and mitochondrial cytopathies. Nonfamilial etiology includes obesity, infants of diabetic mothers, HCM in trained athletes, and amyloid disease. Regardless of the cause, the pathophysiology is similar, and diastolic dysfunction is a major feature. Ventricular compliance is reduced, resulting in abnormal diastolic filling, in turn contributing to the reduced stroke volume. In addition, LV end-diastolic pressure is elevated, which may eventually result in LA hypertension, pulmonary interstitial edema, dyspnea, and exercise intolerance. LV systolic function is usually preserved early in the course of HCM and may even be hyperdynamic because of the increased muscle mass. LV outflow tract obstruction occurs in many patients because the thickened interventricular septum interacts with the mitral valve apparatus to narrow the subaortic region during systole. The thickened LV mass predisposes HCM patients to coronary ischemia and arrhythmias, which are often ventricular in origin and represent a significant risk for sudden death. The fibrosis from this ischemia and often-disordered arrangement of myocardial cells apparently give rise to this risk of ventricular tachycardia and fibrillation ( Box 3-14 ).

Box 3-14 Hypertrophic Cardiomyopathy (HCM)

Left ventricular outflow tract (LVOT) obstruction occurs from hypertrophied ventricular septum and systolic anterior motion of the mitral valve.

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