Irwin & Rippe\'s manual of Intensive Care Medicine

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Editors

Richard S. Irwin,

MD

Professor of Medicine and Nursing University of Massachusetts and Graduate School of Nursing Chair, Critical Care Operations UMass Memorial Medical Center Worcester, Massachusetts

Craig M. Lilly,

MD

Vice Chair, Critical Care Operations Director, elCU Program UMass Memorial Medical Center Professor of Medicine, Anesthesia, and Surgery Departments of Medicine and Surgery University of Massachusetts Medical School Worcester, Massachusetts

James M. Rippe,

MD

Professor of Biomedical Sciences University of Central Florida Orlando, Florida Founder and Director Rippe Lifestyle Institute Shrewsbury, Massachusetts/Orlando, Florida Founder and Director Rippe Health Orlando, Florida

T h i s e d i t i o n is based on Irwin and Rippe's Intensive Care Medicine, seve nth ed i t i o n , ed ited by R i c h a rd S. I rw i n a n d Ja mes M . R i ppe.

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Wolters Kluwer Lippincott Williams & Wilkins Health

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Two Commerce Square 200 I Market Street Philadelphia, PA 19103

All rights reserved. This book is protected by copyright. No part of chis book may be reproduced or trans­ mitted in any form or by any means, including as photocopies or scanned-in or other electronic copies, or utilized by any information storage and retrieval system without written permission from the copyright owner, except for brief quotations embodied in critical articles and reviews. Materials appearing in this book prepared by individuals as part of their official duties as U.S. government employees are not covered by the

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Library of Congress Cataloging-in-Publication Data I [edited by] Richard S. Irwin, Craig M. Lilly and James M. Rippe. - Sixth

Manual of intensive care medicine edition. p. ; cm.

Preceded by Manual of intensive care medicine

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edited by Richard S. Irwin, James M. Rippe.

5th ed. c2010. Abridgement of: Irwin and Rippe's intensive care medicine

I

editors, Richard S. Irwin, James

M. Rippe. 7ch ed. c2012. Includes bibliographical references and index. ISBN 978-1-4511-8500-3

I. Irwin, Richard S., editor of compilation. II. Rippe, James M., editor.

[DNLM: 1. Intensive Care-Handbooks. 2. Intensive Care Units-Handbooks. WX 39]

RC86.7

616.02'8-dc23 2013019315 DISCLAIMER Care has been taken to confirm the accuracy of the information present and to describe generally accepted practices. However, the authors, editors, and publisher are not responsible for errors or omissions or for any consequences from application of the information in chis book and make no warranty, expressed or implied, with respect to the currency, completeness, or accuracy of the contents of the publication. Application of chis information in a particular situation remains the professional responsibility of the practitioner; the clinical treatments described and recommended may not be considered absolute and universal recommendations. The authors, editors, and publisher have exerted every effort to ensure char drug selection and dosage sec forth in chis text are in accordance with the current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of informa­ tion relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any change in indications and dosage and for added warnings and precautions. This is particularly impor­ tant when the recommended agent is a new or infrequently employed drug. Some drugs and medical devices presented in chis publication have U.S. Food and Drug Administration (FDA) clearance for limited use in restricted research settings. le is the responsibility of the health care provid­ ers to ascertain the FDA status of each drug or device planned for use in their clinical practice. To purchase additional copies of chis book, call our customer service department at (800) 638-3030 or orders to (301) 223-2320. Internacional customers should call (301) 223-2300.

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To Our Families Diane, Rachel, Sara, Jamie, Rebecca, Andrew K, Andrew M, and Adam; Leslie, Jonathan, Catherine, Stephanie, Hart, Jaelin, Devon, and Jamie

C o ntributors KonstantinAbramov, MD

Joshua M. Ammerman, MD

Assistant Professor ofInternal Medicine Division ofRenal Medicine University ofMassachusetts Medical School Worcester, Massachusetts

Clinical Assistant Professor ofNeurosurgery Department ofNeurological Surgery George Washington University School of Medicine Washington, District of Columbia

Christopher D. Adams, PharmD,

BCPS

Gustavo G. Angaramo, MD

Clinical Pharmacy Specialist Department ofPharmacy Services Brigham and Womens Hospital Boston, Massachusetts

Assistant Professor Department ofAnesthesiology and Critical Care Former Instructor in Surgery and Cardiothoracic Surgery Department ofSurgery University ofMassachusetts Medical School Worcester, Massachusetts

DeepAdhikari, MD

Renal Division University ofMassachusetts Medical School Worcester, Massachusetts SrinathAdusumalli, MD

Resident Physician Department ofInternal Medicine Massachusetts General Hospital Boston, Massachusetts Sumera R. Ahmad, MD

Department ofPulmonary and Critical Care Medicine University ofMassachusetts Medical School Worcester, Massachusetts David H. Ahrenholz, MD, FACS

Associate Professor ofSurgery University ofMinnesota Medical School Minneapolis, Minnesota Burns Program Director Regions Burn Center Regions Hospital St. Paul, Minnesota SewitAmde, MD

Medical Fellow Department ofSurgery University ofMinnesota Minneapolis, Minnesota

Kevin E. Anger, PharmD, BCPS

Clinical Pharmacist Specialist Department ofPharmacy Services Brigham and Womens Hospital Boston, Massachusetts AntonioAponte-Feliciano, MD

Assistant Professor ofAnesthesiology, Surgery, and Critical Care Medicine Department ofAnesthesiology University ofMassachusetts Medical School Worcester, Massachusetts NeilAronin, MD

Professor and Chief Division ofEndocrinology and Metabolism Department ofMedicine University ofMassachusetts Medical School Worcester, Massachusetts Seth M. Arum, MD, FACE

Assistant Professor ofMedicine Division of Endocrinology and Metabolism University ofMassachusetts Medical School Worcester, Massachusetts

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Contr i b utors

Gerard P. Aurigemma, MD

Isabelita R. Bella, MD

Professor ofMedicine and Radiology University ofMassachusetts Medical School Director, Noninvasive Cardiology UMass Memorial Medical Center Worcester, Massachusetts

Associate Professor ofNeurology Department ofNeurology University ofMassachusetts Medical School Worcester, Massachusetts

RiadAzar, MD

Consultant Cardiologist Department of Cardiology Imperial College Healthcare NHS Trust Hammersmith Hospital London, United Kingdom

Associate Professor ofMedicine Washington University School ofMedicine Division of Gastroenterology Department ofInternal Medicine Barnes-Jewish Hospital - North Campus St. Louis, Missouri

Michael F. Bellamy, MD, MRCP

David Cachia, MD

Director, Leukemia Program Massachusetts General Hospital Boston, Massachusetts

ChiefResident Department ofNeurology University ofMassachusetts Medical School Worcester, Massachusetts

Gisela I. Banauch, MD, MS

Jason P. Caplan, MD

Karen K. Ballen, MD

Assistant Professor ofMedicine Division ofPulmonary, Allergy, Critical Care, and Sleep Medicine University ofMassachusetts Medical School Worcester, Massachusetts Daniel T. Baran, MD

Adjunct Professor ofMedicine and Orthopedics University ofMassachusetts Medical School Worcester, Massachusetts Director, Medical Affairs Merck & Co., Inc. Upper Gwynedd, Pennsylvania Michael L. Barretti, DO

Fellow, Pulmonary and Critical Care Medicine Division ofPulmonary, Allergy, and Critical Care Medicine University ofMassachusetts Medical School Worcester, Massachusetts David M. Bebinger, MD

Assistant Professor ofMedicine Division ofInfectious Diseases and Immunology University ofMassachusetts Medical School Worcester, Massachusetts

Associate Professor ofPsychiatry ChiefofPsychiatry Creighton University School ofMedicine at St. Joseph's Hospital and Medical Center Phoenix, Arizona RaphaelA. Carandang, MD

Assistant Professor ofNeurology and Surgical Critical Care Department ofNeurology University ofMassachusetts Medical School Worcester, Massachusetts Stewart R. Carter, MD

Resident Department of Surgery Loyola University Health System Maywood, Illinois DavidA. Chad, MD

Associate Professor ofNeurology Harvard Medical School Massachusetts General Hospital EMC Laboratory Neuromuscular Diagnostic Center Boston, Massachusetts

Cont r i b utors

Dinesh Chandokt, MD, FACC,

Adam Cuker, MD, MS

FSCAI

Assistant Professor ofMedicine Division of Cardiology University ofMassachusetts Medical School Worcester, Massachusetts

Assistant Professor ofMedicine and Pathology and Laboratory Medicine Perelman School ofMedicine University ofPennsylvania Philadelphia, Pennsylvania

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Nikolaos Chandolias, MD

Adam D. Currier, MD

Fellow Department ofSurgery University ofMinnesota Minneapolis, Minnesota

Assistant Professor Department ofAnesthesiology University ofMassachusetts Medical School Worcester, Massachusetts

Sonia N. Chimienti, MD

Jennifer S. Daly, MD

Medical Director, Solid Organ Transplant Program Division ofInfectious Diseases UMass Memorial Medical Center Worcester, Massachusetts Felicia C. Chu, MD

Assistant Professor Department ofNeurology University ofMassachusetts Medical School Worcester, Massachusetts Ana Cojocaru, MD

Fellow Division ofPulmonary and Critical Care University ofMassachusetts Medical School Worcester, Massachusetts Elifce 0. Cosar, MD

Clinical Associate Professor Co-Director of Thoracic Anesthesia University ofMassachusetts Medical School Worcester, Massachusetts Eric Cucchi, PA-C

Adjunct Professor, Massachusetts College of Pharmacy Physician Assistant Lecturer at Bay Path College University ofMassachusetts Medical School Worcester, Massachusetts

Professor ofMedicine, Microbiology, and Physiological Sciences Clinical Chief, Infectious Diseases and Immunology University ofMassachusetts Medical School Worcester, Massachusetts Raul Davaro, MD

Associate Clinical Professor Department ofMedicine University ofMassachusetts Medical School Worcester, Massachusetts LauraA. Davis, MB, BCh, BAO

Resident Department of Cardiac Surgery Yale University School ofMedicine Yale University Surgical Director Yale-New Haven Hospital - Heart & Vascular Center New Haven, Connecticut

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Contr i b utors

JamesA. de Lemos, MD

Gina R. Dorlac, MD

Professor ofMedicine University of Texas Southwestern Medical Center Cardiology Service Chief Parkland Memorial Hospital Kern Wildenthal, MD, PhD, Distinguished Chair in Cardiology University of Texas Southwestern Medical Center Dallas, Texas

Colonel, US Air Force Director, Critical Care Air Transport Advanced Course Associate Professor Division of Trauma/Critical Care University of Cincinnati Cincinnati, Ohio

G. William Dec, MD

Chief Division of Cardiology Massachusetts General Hospital Boston, Massachusetts Paul F. Dellaripa, MD

Assistant Professor ofMedicine Harvard Medical School Division ofRheumatology and Immunology Brigham and Womens Hospital Boston, Massachusetts Thomas G. DeLoughery, MD, FACP,

FAWM

Professor ofMedicine, Pathology, and Pediatrics Divisions ofHematology/Medical Oncology and Laboratory Medicine Oregon Health and Sciences University Portland, Oregon Akshay S. Desai, MD, MPH

Instructor in Medicine, Harvard Medical School Associate Physician, Advanced Heart Disease Section Cardiovascular Division Brigham and Womens Hospital Boston, Massachusetts Leslie J. Domalik, MD

Assistant Professor Department ofMedicine Division ofDiabetes University ofMassachusetts Medical School Worcester, Massachusetts

DavidA. Drachman, MD

Professor ofNeurology, Chairman Emeritus University ofMassachusetts Medical School Worcester, Massachusetts Ty B. Dunn, MD, MS, FACS

Assistant Professor Division of Transplantation Department of Surgery University ofMinnesota Minneapolis, Minnesota Kevin M. Dushay, MD, FCCP

Assistant Professor ofMedicine Alpert Medical School ofBrown University Pulmonary, Critical Care & Sleep Medicine Rhode Island Hospital Providence, Rhode Island Kevin M. Dwyer, MD, FACS

Director of Trauma Vice-Chair ofSurgery Stamford Hospital Stamford, Connecticut James M. Ecklund, MD, FACS

Chairman, Department ofNeurosciences !nova Faiifax Hospital Professor ofNeurosurgery George Washington University Professor ofSurgery Uniformed Services University Falls Church, Virginia Richard T. Ellison III, MD

Professor ofMedicine, Microbiology, and Physiological Systems Division ofInfectious Diseases Department ofMedicine University ofMassachusetts Medical School Worcester, Massachusetts

Cont r i b utors

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Ashkan Emadi, MD, PhD

John Fanikos, RPh, MBA

Associate Professor ofMedicine University ofMaryland Greenebaum Cancer Center Baltimore, Maryland

Director ofPharmacy Business Department ofPharmacy Services Brigham and Womens Hospital Boston, Massachusetts

TimothyA. Emhoff, MD, FACS

Khaldoun Faris, MD

Chief, Trauma and Surgical Critical Care Department ofSurgery Division of Trauma University ofMassachusetts Medical School Worcester, Massachusetts

Clinical Associate Professor ofAnesthesiology and Surgery University ofMassachusetts Medical School Worcester, Massachusetts

Maurice Enriquez-Sarano, MD,

FACC, FAHA

Professor ofMedicine Mayo Medical School Director, Valvular Heart Disease Clinic Consultant, Cardiovascular Diseases and Internal Medicine Division of Cardiovascular Mayo Clinic Rochester, Minnesota Laurence M. Epstein, MD

Chief, Arrhythmia Service Cardiovascular Division Brigham and Womens Hospital Associate Professor ofMedicine Harvard Medical School Boston, Massachusetts Suzana K. Everett Makowski, MD,

MMM

Assistant Professor ofMedicine Co-ChiefofPalliative Medicine University ofMassachusetts Medical School Worcester, Massachusetts Pang-Yen Fan, MD

Associate Professor of Clinical Medicine Division ofRenal Medicine University ofMassachusetts Medical School Worcester, Massachusetts

Alan P. Farwell, MD

Associate Professor ofMedicine Interim Chief, Section ofEndocrinology, Diabetes, and Nutrition Boston University School ofMedicine Boston Medical Center Boston, Massachusetts Adam S. Fein, MD

Fellow Cardiac Electrophysiology Department ofMedicine Division of Cardiology Beth Israel Deaconess Medical Center Harvard Medical School Boston, Massachusetts Philip Fidler, MD, FACS

Associate Professor of Surgery Georgetown School ofMedicine Co-Director The Burn Center at MedStar Washington Hospital Center Washington, District of Columbia KimberlyA. Fisher, MD

Assistant Professor ofMedicine Division ofPulmonary/Critical Care Medicine University ofMassachusetts Medical School Worcester, Massachusetts Patrick F. Fogarty

Assistant Professor ofMedicine Director Penn Comprehensive Hemophilia and Thrombosis Center Hospital ofthe University ofPennsylvania Philadelphia, Pennsylvania

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Cont r i b utors

Nancy M. Fontneau, MD

Terry B. Gernsheimer, MD

Associate Professor of Clinical Neurology Department ofNeurology University ofMassachusetts Medical School Worcester, Massachusetts

Professor ofMedicine Division ofHematology University of Washington School of Medicine Seattle, Washington

Joseph J. Frassica, MD, FAAP, FCCP

Mitra Ghasemi, MD, FCCP

Vice President and ChiefMedical Informatics Officer/Chief Technology Officer Philips Healthcare-Patient Care and Clinical Informatics Andover, Massachusetts Senior Consultant Massachusetts General Hospital Boston, Massachusetts Research Affiliate Massachusetts Institute of Technology Cambridge, Massachusetts

Assistant Professor ofMedicine Department ofMedicine Division ofPulmonary, Allergy, and Critical Care Medicine University ofMassachusetts Medical School Worcester, Massachusetts

Julia M. Gallagher, MD

Palliative Care Physician Division ofPalliative Care University ofMassachusetts Medical School UMass Memorial Medical Center Worcester, Massachusetts Brian J. Gallay, MD, PhD

Associate Professor ofMedicine Department ofMedicine UC Davis School ofMedicine University of California, Davis Medical Center Sacramento, California Neeta Garg, MD

Clinical Associate Professor ofNeurology Multiple Sclerosis Center University ofMassachusetts Medical Center Worcester, Massachusetts Eli V. Gelfand, MD, FACC

Assistant Professor ofMedicine Harvard Medical School Director ofAmbulatory Cardiology Cardiovascular Division Beth Israel Deaconess Medical Center Boston, Massachusetts

John G. Gianopoulos, MD

The Mary Isabelle Caestecker Professor and Chair Department of Obstetrics and Gynecology Loyola University Stritch School ofMedicine Loyola University Health System Maywood, Illinois Michael M. Givertz, MD

Medical Director Heart Transplant and Circulatory Assist Associate Professor ofMedicine Harvard Medical School Cardiovascular Division Brigham and Womens Hospital Boston, Massachusetts Richard H. Glew, MD

Professor ofMedicine, Microbiology, and Physiological Systems Vice Chair ofMedicine, Undergraduate Medical Education and Faculty Affairs University ofMassachusetts Medical School Worcester, Massachusetts Richard P. Goddeau Jr, DO

Assistant Professor ofNeurology Department ofNeurology University ofMassachusetts Medical School Worcester, Massachusetts

Contr i b utors

Michael R. Gold, MD, PhD

David M. Harlan, MD

Chiefof Cardiology Michael E. Assry Professor ofMedicine Division of Cardiology Medical University of South Carolina Charleston, South Carolina

Professor Division ofDiabetes Department ofMedicine University ofMassachusetts Medical School Worcester, Massachusetts

Darrell M. Gray II, MD

Clinical Fellow Division of Gastroenterology Washington University School of Medicine St. Louis, Missouri BarthA. Green, MD, FACS

Professor and Chairman Department ofNeurosurgery University ofMiami Lois Pope LIFE Center Miami, Florida Bonnie C. Greenwood, PharmD,

BCPS

Clinical Pharmacy Practice Manager Department ofPharmacy Services Brigham and Womens Hospital Boston, Massachusetts C. Prakash Gyawali, MD, MRCP

Professor ofMedicine Division of Gastroenterology Washington University in St. Louis St. Louis, Missouri Wiley Hall, MD

Director ofNeurocritical Care Department ofNeurology UMass Memorial Medical Center Worcester, Massachusetts TarekAbou Hamdan, MD

Gastroenterology and Interventional Endoscopy Consultant Division of Gastroenterology Clemenceau Medical Center Affiliated with johns Hopkins International Beirut, Lebanon

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Lawrence J. Hayward, MD, PhD

Professor ofNeurology Department ofNeurology University ofMassachusetts Medical School Worcester, Massachusetts Stephen 0. Heard, MD

Professor ofAnesthesiology and Surgery Chair ofAnesthesiology Department ofAnesthesiology University ofMassachusetts Medical School Worcester, Massachusetts Nils Henninger, MD

Assistant Professor ofNeurology Department ofNeurology University ofMassachusetts Medical School Worcester, Massachusetts Helen M. Hollingsworth, MD

Associate Professor ofMedicine Pulmonary Center Boston University Medical Center Boston, Massachusetts Dorrough G. Howard, MD

Consultant Rheumatologist Department ofRheumatology St. jamess Hospital Dublin, Ireland Vanessa Humphreville, MD

General Surgery Staff Transplant Surgery Fellow Department of Transplant Surgery University ofMinnesota Minneapolis, Minnesota

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Contr i b u tors

Eric Iida, MD

Deirdre L. Kathman, DO

Assistant Professor ofMedicine Division ofRenal Medicine University ofMassachusetts Medical School Worcester, Massachusetts

Fellow Division ofPulmonary, Allergy, and Critical Care Medicine UMass Memorial Medical Center Worcester, Massachusetts

Richard S. Irwin, MD

Adam W. Katz, MPAS, PA-C

Professor ofMedicine and Nursing University ofMassachusetts Medical School and Graduate School ofNursing Chair, Critical Care Operations UMass Memorial Medical Center Worcester, Massachusetts Heba N. Iskandar, MD

Fellow in Gastroenterology Department ofMedicine Washington University in St. Louis St. Louis, Missouri Saef Izzy, MD

Neurology Resident UMass Memorial Medical Center Worcester, Massachusetts Mayur Jayarao, MD, MSc

Resident Physician Division ofNeurosurgery University ofMissouri - Columbia School ofMedicine Columbia, Missouri James C. Jeng, MD

Associate Director The Burn Center Washington Hospital Center Washington, District of Columbia JayA. Johannigman, MD, FACS

Professor of Surgery Division of Trauma, Critical Care, and Acute Care Surgery University of Cincinnati - College of Medicine Cincinnati, Ohio

StaffPhysician Assistant Department of Critical Care UMass Memorial Medical Center Worcester, Massachusetts Jaudat Khan, MD

Fellow Division ofRenal Medicine UMass Memorial Medical Center Worcester, Massachusetts Muhib Khan, MD

Vascular Neurology Fellow UMass Memorial Medical Center Worcester, Massachusetts DanielA. Kim, MD

Resident Department ofMedicine Johns Hopkins Bayview Medical Center Baltimore, Maryland IreneA. Kim, MD

EN T Resident Department ofHead and Neck Surgery University of California, Los Angeles Los Angeles, California Nam Heui Kim, MD

Assistant Professor Department ofSurgery Division of Trauma Services University ofMassachusetts Medical School Worcester, Massachusetts Dagmar Klinger, MD

Assistant Professor ofMedicine Division ofRenal Medicine University ofMassachusetts Medical School Worcester, Massachusetts

Contr i b utors

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Scott E. Kopec, MD

N. Scott Litofsky, MD, FACS

Assistant Professor ofMedicine Director, Pulmonary and Critical Care Fellowship University ofMassachusetts Medical School Worcester, Massachusetts

Professor and Chief Director, Radiosurgery and Neuro-Oncology Division ofNeurosurgery University ofMissouri - Columbia School ofMedicine Columbia, Missouri

BruceA. Koplan, MD, MPH

Instructor, Harvard Medical School Cardiovascular Division Brigham and Womens Hospital Boston, Massachusetts Kevin M. Korenblat, MD

Associate Professor ofMedicine Division of Gastroenterology Washington University School ofMedicine St. Louis, Missouri Stephen J. Krinzman, MD

Clinical Associate Professor ofMedicine Division ofPulmonary, Allergy, and Critical Care Medicine University ofMassachusetts Medical School Worcester, Massachusetts Jason Kurland, MD

Assistant Professor ofMedicine Division ofRenal Medicine University ofMassachusetts Medical School Worcester, Massachusetts Howard B. Levene, MD, PhD

Neurological Surgery Spine Fellow University ofMiami Miller School ofMedicine Department ofNeurological Surgery Lois Pope LIFE Center Miami, Florida Craig M. Lilly, MD

Vice Chair, Critical Care Operations Director, eIC U Program UMass Memorial Medical Center Professor ofMedicine, Anesthesia, and Surgery Departments ofMedicine and Surgery University ofMassachusetts Medical School Worcester, Massachusetts

Andrea Loiselle, MD, MPH

Instructor ofMedicine Division ofPulmonary and Critical Care Medicine Washington University School ofMedicine Barnes-Jewish Hospital St. Louis, Missouri Randall R. Long, MD, PhD

Medical Specialties/Neurology Dartmouth-Hitchcock Keene Keene, New Hampshire FredA. Luchette, MD, MSc

The Ambrose and Gladys Bowyer Professor ofSurgery Department ofSurgery Loyola University Medical Center Maywood, Illinois J. Mark Madison, MD

Professor ofMedicine and Microbiology and Physiological System Chief, Division ofPulmonary, Allergy, and Critical Care Medicine University ofMassachusetts Medical School Worcester, Massachusetts Samir Malkani, MD

Associate Professor of Clinical Medicine Diabetes Center ofExcellence University ofMassachusetts Medical School Worcester, Massachusetts Michael D. Mancenido, DO, AAHNS

StaffPhysician AIDS Care Rochester, New York

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Contr i b u tors

Sunil Mankad, MD, FACC, FCCP,

FaizA. Mirza, MD

PASE

Senior Fellow Division of Gastroenterology Washington University School ofMedicine St. Louis, Missouri

Associate Professor ofMedicine Mayo Clinic College ofMedicine Director, Transesophageal Echocardiography Associate Director, Cardiology Fellowship Mayo Clinic Rochester, Minnesota Theofilos P. Matheos, MD

Assistant Professor ofAnesthesiology and Surgery Department ofAnesthesiology Division of Critical Care Medicine University ofMassachusetts Medical School Worcester, Massachusetts Rairnis Matulionis, MD

Assistant Professor ofAnesthesiology and Surgery Department ofAnesthesiology University ofMassachusetts Medical School Worcester, Massachusetts

Ann L. Mitchell, MD

Associate Professor of Clinical Neurology Department ofNeurology University ofMassachusetts Medical School Worcester, Massachusetts Jahan Montague, MD

Assistant Professor ofMedicine Division ofRenal Medicine University ofMassachusetts Medical School Worcester, Massachusetts Majaz Moonis, MD, MRCPI(I),

DM, FAAN

Pulmonary and Critical Care Fellow Division ofPulmonary, Allergy, and Critical Care Medicine UMass Memorial Medical Center Worcester, Massachusetts

Professor ofNeurology Director, Stroke Services and Vascular Fellowship Program University ofMassachusetts Medical School Worcester, Massachusetts Director, Sleep Center Day Kimball Hospital Putnam, Connecticut

Robert M. Mentzer Jr, MD

John P. Mordes, MD

Professor ofSurgery and Physiology Wayne State University School ofMedicine Detroit, Michigan

Professor ofMedicine and Endocrinology Division ofEndocrinology and Metabolism University ofMassachusetts Medical School Worcester, Massachusetts

Avani T. Mehta, MD

Christopher P. Michetti, MD

Medical Director, Trauma Intensive Care Unit !nova Faiifax Hospital Trauma Services Falls Church, Virginia Marco Mielcarek, MD

Associate Professor Fred Hutchinson Cancer Research Center Associate Professor ofMedicine Department ofMedical Oncology University of Washington Seattle, Washington

Susanne Muehlschlegel, MD, MPH

Assistant Professor ofNeurology, Anesthesia/ Critical Care, and Surgery Division ofNeurocritical Care University ofMassachusetts Medical School Worcester, Massachusetts Marie Mullen, MD

Clinical Associate Professor ofEmergency Medicine Department ofEmergency Medicine University ofMassachusetts Medical School Worcester, Massachusetts

Contr i b utors

SaoriA. Murakami, MD

Sean O'Reilly, MD

Attending Psychiatrist Massachusetts General Hospital Assistant Medical Director Child and Adolescent Psychiatry Inpatient Unit McLean Hospital Brighton, Massachusetts

Assistant Professor ofMedicine University ofMassachusetts Medical School UMass Memorial Sleep Disorders Center Worcester, Massachusetts

Ashok Nambiar, MD

Alan Orquiola, MD

Associate Clinical Professor Department ofLaboratory Medicine Director Division of Transfasion Medicine University of California, San Francisco Medical Center San Francisco, California Shashidhara Nanjundaswamy, MD,

MBBS, MRCP, DM

Assistant Professor Department ofNeurology University ofMassachusetts Medical School Worcester, Massachusetts Ian J. Neeland, MD

Fellow in Cardiovascular Medicine Division of Cardiology University of Texas Southwestern Medical Center Dallas, Texas Dominic J. Nompleggi, MD, PhD

Chief Gastroenterology Division Associate Professor ofMedicine and Surgery University ofMassachusetts Medical School Worcester, Massachusetts Paulo J. Oliveira, MD, FCCP

Assistant Professor ofMedicine Director, Advanced Bronchoscopic and Pleural Procedures Medical Director, Respiratory Care Department Division ofPulmonary, Allergy, and Critical Care Medicine University ofMassachusetts Medical School Worcester, Massachusetts

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Assistant Professor Department ofAnesthesiology University ofMassachusetts Medical School Worcester, Massachusetts Suchitra Pandey, MD

Assistant Professor Department ofLaboratory Medicine Assistant Medical Director Transfasion Service and Blood Center University of California, San Francisco Medical Center San Francisco, California NereidaA. Parada, MD

Clinical Associate Professor ofMedicine Section ofPulmonary Diseases, Critical Care, and Environmental Medicine Tulane University School ofMedicine New Orleans, Louisiana Rupal Patel, MD

General Surgery Resident UMass Memorial Medical Center Worcester, Massachusetts Marie T. Pavini, MD, FCCP

Assistant Professor, Department of Medicine University of Vermont School ofMedicine Assistant Director, Department of Critical Care Rutland Regional Medical Center Rutland, Vermont David Paydarfar, MD

Professor Department ofNeurology University ofMassachusetts Medical School Worcester, Massachusetts

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Cont r i b utors

Crescens Pellecchia, DO, MD

Paula D. Ravin, MD

Assistant Professor Department ofMedicine Division ofPulmonary, Allergy and Critical Care Medicine University ofMassachusetts Medical School Worcester, Massachusetts

Clinical Associate Professor ofNeurology Department ofNeurology University ofMassachusetts Medical School Worcester, Massachusetts

CatherineA. Phillips, MD

Fellow Department ofInternal Medicine Division of Gastroenterology Barnes Jewish Hospital Washington University in St. Louis St. Louis, Missouri

Clinical Associate Professor ofNeurology Department ofNeurology University ofMassachusetts Medical School Worcester, Massachusetts Jennifer K. Plichta, MD, MS

Resident Department ofSurgery Loyola University Medical Center Maywood, Illinois Yuri B. Pride, MD

Clinical Fellow in Medicine Harvard Medical School Beth Israel Deaconess Medical Center Boston, Massachusetts John Querques, MD

Assistant Professor ofPsychiatry Harvard Medical School Associate Director Psychosomatic Medicine/Consultation Psychiatry Fellowship Program Department ofPsychiatry Massachusetts General Hospital Boston, Massachusetts Sunil Rajan, MD

Full partner Pulmonary Associates ofRichmond, Inc. Vice ChiefofStaff Bon Secours St. Francis Medical Center Midlothian, Virginia Anil Rajendra, MD

Cardiology Fellow Division of Cardiology Medical University ofSouth Carolina Charleston, South Carolina

KaraA. Regan, MD

Harvey S. Reich, MD, FACP, FCCP

Director, Critical Care Medicine Rutland Regional Medical Center Clinical Associate Professor ofMedicine University of Vermont College of Medicine Rutland, Vermont Jennifer Reidy, MS, MD

Palliative Care Physician Division ofPalliative Care Assistant Professor University ofMassachusetts Medical School UMass Memorial Medical Center Worcester, Massachusetts Peter E. Rice, MD

Assistant Professor ofSurgery University ofMedicine and Dentistry of New Jersey University Hospital New Jersey Medical Center New York, New York Noah B. Rindos, MD

Resident Department of Obstetrics & Gynecology Boston Medical Center Boston, Massachusetts

Contri b utors

James M. Rippe, MD

John L. Sapp Jr, MD, FRCPC

Professor ofBiomedical Sciences University of Central Florida Orlando, Florida Founder and Director Rippe Lifestyle Institute Shrewsbury, Massachusetts/Orlando, Florida Founder and Director Rippe Health Orlando, Florida

Director, Heart Rhythm QE II Health Science Centre Professor ofMedicine Dalhousie University Halifax, Nova Scotia, Canada

Peter N. Riskind, MD, PhD

Clinical Professor Department ofNeurology University ofMassachusetts Medical School Worcester, Massachusetts Anna G. Rudnicki, MD

Assistant Professor ofMedicine Department ofMedicine Division ofPulmonary, Allergy, and Critical Care Medicine University ofMassachusetts Medical School Worcester, Massachusetts Johnny S. Salameh, MD

Assistant Professor ofNeurology Director ofNeuromuscular Division and EMG Laboratory University ofMassachusetts Medical School Worcester, Massachusetts Wayra Salazar-Moreno, MD

Infectious Disease Fellow Division ofInfectious Disease UMass Memorial Medical Center Worcester, Massachusetts Frantisek Sandor, MD, PhD

Pulmonary and Critical Care Fellowship Internal Medicine - Pulmonary and Critical Care University ofMassachusetts Medical School Worcester, Massachusetts Pulmonary and Critical Care Physician Penobscot Respiratory - Pulmonary and Critical Care Penobscot Respiratory - Eastern Maine Medical Center Bangor, Maine

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Diane M. F. Savarese, MD

Clinical Instructor ofMedicine Harvard Medical School Attending Physician Division ofHematology Oncology Beth Israel Deaconess Medical Center Boston, Massachusetts Senior Deputy Editor Up ToDate Waltham, Massachusetts Gregory S. Sayuk, MD, MPH

Assistant Professor Department ofMedicine and Psychiatry Associate Program Director, GI Fellowship Program Washington University School ofMedicine Saint Louis, Missouri Oren P. Schaefer, MD

Clinical Associate Professor ofMedicine University ofMassachusetts Medical School Mass Lung & Allergy, P. C. Worcester, Massachusetts Vanessa Schroder, MD

Surgical Critical Care Fellow Department ofSurgery Duke University Medical Center Durham, North Carolina Benjamin M. Scirica, MD, MPH

Investigator, TIMI Study Group Levine Cardiac Intensive Care Unit Assistant Professor ofMedicine Harvard Medical School Associate Physician Cardiovascular Division Brigham and Womens Hospital Boston, Massachusetts

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Contr i b utors

Gail Scully, MD

NathanaelA. Slater, DO

Assistant Professor Division ofInfectious Disease and Immunology Department ofMedicine University ofMassachusetts Medical School Worcester, Massachusetts

Assistant Professor ofAnesthesiology and Surgery Department ofAnesthesiology/Critical Care Medicine University ofMassachusetts Medical School Worcester, Massachusetts

Raghu R. Seethala, MD

Instructor in Medicine Harvard Medical School Department ofEmergency Medicine Department ofSurgery Division of Trauma, Burn, and Surgical Care Brigham and Womens Hospital Boston, Massachusetts Hani Seoudi, MD, FACS

Associate Professor of Surgery Department ofSurgery Virginia Commonwealth University School ofMedicine Falls Church, Virginia Mark L. Shapiro, MD, FACS

Associate Professor of Surgery Chief, Acute Care Surgery Associate Director, Trauma Duke University Medical Center Durham, North Carolina

Heidi L. Smith, MD, PhD Assistant Professor ofMedicine Mass Biologics Boston, Massachusetts NicholasA. Smyrnios, MD, FACP,

FCCP

Associate Chief, Division ofPulmonary, Allergy, and Critical Care Medicine Director, Medical Intensive Care Units Professor ofMedicine University ofMassachusetts Medical School Worcester, Massachusetts Piotr Sobieszczyk, MD, RVT

Associate Director Cardiac Catheterization Laboratory Cardiovascular Division Brigham and Womens Hospital Boston, Massachusetts Suman L. Sood, MD

Resident Department of General Surgery Loyola University Medical Center Maywood, Illinois

Assistant Professor ofMedicine Department ofInternal Medicine Division ofHematology/Oncology University ofMichigan School ofMedicine Ann Arbor, Michigan

Bruce J. Simon, MD

Andres F. Sosa, MD

Michael Sigman, MD

Associate Professor Department ofSurgery Division of Trauma Services University ofMassachusetts Medical School Worcester, Massachusetts Nathan William Skelley, MD

Resident Physician Washington University in St. Louis School ofMedicine Barnes-Jewish Hospital Saint Louis, Missouri

Assistant Professor Interventional Pulmonary Division ofPulmonary, Allergy and Critical Care Medicine University ofMassachusetts Medical School Worcester, Massachusetts David D. Spragg, MD

Assistant Professor ofMedicine Division of Cardiology Johns Hopkins Bayview Medical Center Baltimore, Maryland

Contri b utors

Aruna Sree, MD

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Karen E. Thomas, MD

Infectious Disease Consultant Department ofInfectious Disease/Internal Medicine Somerset Medical Centre Somerville, New Jersey JFK Medical Centre Edison, New Jersey

Clinical Instructor Department ofMedicine Cardiovascular Division Beth Israel Deaconess Medical Center Harvard Medical School Boston, Massachusetts

TheodoreA. Stern, MD

Professor ofMedicine Division of Cardiology University ofMassachusetts Medical School Worcester, Massachusetts

Chief Avery D. Weisman Psychiatry Consultation Service Director, Office for Clinical Careers Massachusetts General Hospital Ned H. Cassem Professor ofPsychiatry in the field ofPsychosomatic Medicine/Consultation Harvard Medical School Massachusetts General Hospital Boston, Massachusetts Donald S. Stevens, MD

Director Center for Pain Management Marlborough Hospital Marlborough, Massachusetts William G. Stevenson, MD

Professor ofMedicine Harvard Medical School Director, Cardiac Electrophysiology Program Brigham and Womens Hospital Boston, Massachusetts Michael B. Streiff, MD, FACP

Associate Professor ofMedicine and Pathology Johns Hopkins University School ofMedicine Baltimore, Maryland Thejas N. Swamy, MD

Renal Fellow Division ofRenal Medicine University ofMassachusetts Medical School Worcester, Massachusetts Mya Sanda Thein, MD

Post-Doctoral Fellow Department ofHematology/Medical Oncology University ofMaryland Greenebaum Cancer Center Baltimore, Maryland

DennisA. Tighe, MD, FACC, FASE

Ulises Torres, MD, FACS

Assistant Professor of Surgery Department ofSurgery Director, Trauma Education and Outreach Associate Program Director General Surgery Residency University ofMassachusetts Medical School Worcester, Massachusetts Christoph Troppmann, MD, FACS

Professor Division of Transplantation Department ofSurgery University of California, Davis Medical Center Sacramento, California Susan Hongha T. Vu, MD

Gastroenterology Fellow Washington University in St. Louis St. Louis, Missouri J. Matthias Walz, MD, FCCP

Associate Professor ofAnesthesiology and Surgery Department ofAnesthesiology Division of Critical Care Medicine University ofMassachusetts Medical School Worcester, Massachusetts Michael Y. Wang, MD, FACS

Professor Department ofNeurosurgery and Rehabilitation Medicine University ofMiami School ofMedicine Lois Pope LIFE Center Miami, Florida

xxi i

J

Cont r i b utors

John P. Weaver, MD

Jorge D. Yarzebski, BA, NREMT-P

Associate Professor Department ofNeurosurgery University ofMassachusetts Medical School Worcester, Massachusetts

Faculty, Interprofessional Center for Experiential Learning and Stimulation Manager Office of Continuing Medical Simulation Center University ofMassachusetts Medical School Worcester, Massachusetts

Cynthia E. Weber, MD

Resident Department of General Surgery Loyola University Medical Center Maywood, Illinois Mark M. Wilson, MD

Associate Professor ofMedicine Associate Director ofMedical Intensive Care Unit Division ofPulmonary, Allergy, and Critical Care Medicine University ofMassachusetts Medical School Worcester, Massachusetts Joshua J. Wind, MD

Resident Department ofNeurological Surgery George Washington University Medical Center Washington, District of Columbia Dietmar H. Wittmann, MD, PhD,

FACS

Professor Emeritus Medical College of Wisconsin Milwaukee, Wisconsin Mary M. Wolfe, MD

Assistant Clinical Professor of Surgery UCSF-Fresno Medical Education Program Community Regional Medical Center Fresno, California Yee Wong, MD

Resident Department ofSurgery Loyola University Medical Center Maywood, Illinois

Robert W. Yeh, MD, MSc

Instructor in Medicine Harvard Medical School Massachusetts General Hospital Boston, Massachusetts Luke Yip, MD

Department of Veterans Affairs National Center for Patient Safety Ann Arbor, Michigan David D. Yuh, MD

Professor and Chief, Section of Cardiac Surgery Yale University School ofMedicine Surgical Director Yale-New Haven Hospital - Heart & Vascular Center New Haven, Connecticut Jiaying Zhang, MD

Vascular Neurology Fellow Department ofNeurology University ofMassachusetts Medical School Worcester, Massachusetts Iva Zivna, MD

Assistant Professor ofInfectious Disease and Immunology Division ofInfectious Diseases and Immunology University ofMassachusetts Medical School Worcester, Massachusetts

Preface We are delighted to present the sixth edition of the Manual ofIntensive Care Medicine. Previous editions have established this Manual as a leading source of information in the ever-evolving, diverse, and complicated field of critical care and intensive care medicine. The practical format and user-friendly, portable size of the Manual have made it a particularly valuable aid in the bedside practice of intensive care and a valu­ able reference for students, interns, residents, fellows, nurse practitioners and physi­ cian assistants, nurses, and respiratory care practitioners practicing in the critical care medicine environment. As in the previous edition of this work, the sixth edition of the Manual is intended to parallel our major textbook Irwin and Rippe's Intensive Care Medicine. This latter, hardcover book is now in its seventh edition and continues to be a leading source of intensive care knowledge both in the United States and throughout the world. We are pleased to announce that the sixth edition of the Manual will be avail­ able not only in print but also online and as an app for e-readers. Choice of format allows busy bedside providers access to the information they need the way they like to receive it. These resources allow immediate access to the information that allows busy professionals to optimally manage the complicated issues encountered in the care of critically ill adults. As in previous editions, we have challenged the section editors and authors to not only update all the content contained within the Manual, such as the important role that bedside ultrasonography plays in caring for the critically ill, but also emphasize salient concepts and focus on key, clinically relevant points. Annotated references are provided at the close of each chapter to guide the interested reader through key articles in the relevant literature. Each chapter reflects the best available evidence with a focus on patient safety, and, where appropriate, videos have been added to exemplify points and findings. The Manual of Intensive Care Medicine opens with an extensive section on Pro­ cedures and Techniques. The remaining 1 5 sections are divided among organ system problems and other common and important issues, such as palliative care and ethical issues, and transplantation. In each chapter within these sections, discussions of key conditions that present in the intensive care unit environments are presented together with targeted discussions focusing on treatment. We are delighted to welcome new section editors in the following areas: Dr. Gail Scully in Infectious Disease Problems; Dr. Samir Malkani in Endocrine Problems; Dr. Timothy A. Emhoff in Shock and Trauma; Dr. Sonia Chimienti, who joined Dr. Christoph Troppmann as a co-section editor in the Transplantation section; and Dr. Jennifer Reidy, who is the section editor of a new section in the book on Palliative Care and Ethical Issues in the Intensive Care Unit. As in the previous edition, the management of overdoses and poisonings is cov­ ered so comprehensively in the Pharmacology, Overdoses, and Poisonings section that the section mimics a textbook unto itself. For this, we have special thanks to the section editor Luke Yip, who created the easy-to-use tabular format of this section. We are also indebted to our other section editors who have continued to contribute in an extraordinary way by updating their sections: Dr. Stephen 0. Heard, who has overseen the Procedures and Techniques and Minimally Invasive Monitoring sec­ tion; Dr. Akshay S. Desai, Cardiovascular Problems and Coronary Care; Dr. J. Mark Madison, Pulmonary Problems; Dr. Pang-Yen Fan, Renal Problems; Dr. Dominic ]. Nompleggi, Gastrointestinal and Hepatobiliary Problems; Dr. Patrick F. Fogarty, x xii i

x x iv

I

Preface

Hematologic Problems; Dr. Fred A. Luchette, Surgical Problems; Drs. David Pay­ darfar and David A. Drachman, Neurologic Problems; Dr. Paul F. Dellaripa, Rheu­ matologic and Immunologic Problems; Dr. John Querques, Psychiatric Issues; and Dr. Joseph Frassica, Appendix. We wish ro acknowledge that many of the chapter authors for the current Manual have also made major contributors to our larger-format textbook, Irwin and Rippe 's Intensive Care Medicine. Although the Manual of Intensive Care Medicine has been edited and revised with the expert guidance of many section editors, many of the chapters were developed based on the expert knowledge of the original textbook con­ tributors, reorganized, and rewritten in a style necessary for the scope of this portable text. We also wish to once again acknowledge and thank a number of individuals with­ out whose assistance the sixth edition of this Manual would not have been possible. First and foremost, Dr. Rippe's Editorial Director, Elizabeth Grady, who continues to do a superb job in organizing and expediting all aspects of the manuscript preparation for this book and many others. Without Beth's superb editorial skills, projects such as this would not be possible. Gina Giangregorio and Linda Doherty, Dr. Irwin's and Dr. Lilly's administrative assistants, and Cynthia French, Dr. Irwin's clinical coordina­ tor, also have provided important assistance in managing their complex clinical and academic endeavors. Carol Moreau, executive assistant to Dr. Rippe, expertly juggles the diverse aspects of his clinical, research, and travel calendar to carve out time for projects of this magnitude. Debra Adamonis, office assistant to Beth Grady and Carol Moreau provides wonderful daily logistical support. A special word of thanks to the editorial team members at Lippincott Williams & Wilkins, who support all of our medical editing projects and have supported the process every step of the way. We wish to particularly thank our Senior Acquisitions Editor, Brian Brown, for his support throughout the process of writing this book. Nicole Dernoski, Senior Product Manager, also provided logistical support and exper­ tise throughout the editorial process on this and previous editions of the Manual. Finally, we wish to thank our families: Diane Irwin; Rachel, Andrew, Truman, and Bailey Koh; Sara, Benjamin, Jacob, and Isaac Diiorio; Jamie, Andrew, Emmett, and Asher Mcintosh; Rebecca and Adam Slater; Stephanie, Hart, Jaelin, Devon, and Jamie Rippe; and Leslie, Jonathan, and Catherine Lilly, who continue to love and sup­ port us in all of our efforts, both personal and academic, and make it all worthwhile.

Richard S. Irwin, MD Craig M. Lilly, MD James M. Rippe, MD

C o ntents S e cti o n 1 • Pro c e d u res a n d Tec h n i q u es a n d M i n i ma l ly I nvasive M o n ito r i ng i n t h e I C U Section Ed itor - Ste p h e n 0 . H e a rd

• A i rway M a nage m e nt a n d E n d otra c h e a l I ntu bati o n

1

El ifce 0 . Cosa r a n d Ad a m D . C u rrier

• C e ntra l Ve nous Cath ete rs

9

Anto n i o Apo nte- Fe l i c i a n o , A l a n O rq u io l a , T h eofi los P. M atheos, and Ste p h e n 0 . H e a rd

• Arte r i a l L i n e P l a c e m ent a n d Ca re • P u l m o n a ry Arte ry Cath ete rs 25 • Card i ove rs i o n a n d D efi b r i l l ati o n 33 • Pericard i o c e ntes is 39 • C h est Tu be I nserti o n a n d Care 45 • B ro n c h oscopy 53 • Thora c e ntes is 58

17

Kha l d o u n Fa ris

Kha l d o u n Fa ris

Ava n i T. M e hta a n d Pa u l o J . O l ive i ra

D i nesh C h a n d o k a n d D e n n i s A . lighe

G ustavo G . Anga ra m o

Ste p h e n J . Krinzm a n , P a u l o J . O l ive i ra , a n d R i c h a rd S . I rw i n

M i c h a e l L . B a r rett i , M a r k M . W i l so n , a n d R i c h a rd S . I rw i n

x xv

x xv i

I

• Tra c h e osto my Contents

63

M a r k L. S h a p i ro a n d Va nessa Sch rod e r

• D i agnost i c Perito n e a l Lavage a n d Para c e ntes is

70

M a r k L. S h a p i ro a n d Va nessa Sch rod e r

• Gastro esop hagea l Ba l l o o n Ta m po n a d e fo r Ac ute Va ricea l H e m o rrhage

78

M a rie T. Pavi n i

• P l a c e m e nt o f Feed i ng Tu bes 86 • Cerebrosp i n a l F l u i d Asp i rati o n 93 • N e u ro l og i c a n d l ntra c ra n i a l Press u re U l ises To rres a n d R u pa l Patel

R a i m is Matu l io n i s

M o n itori ng

98

R a i m is Matu l io n i s

• Perc uta n eous S u p ra p u b i c Cystostomy Anto n i o A ponte-Fe l ic i a n o , J o rge D . Ya rze bs k i , a n d Kevi n M . D ushay

1 02

• Asp i rati o n of J o i nts 1 06 • An esth esia fo r B e d s i d e Pro c e d u res 1 1 2 • Rout i n e a n d Ca rd i o resp i rato ry M o n itori ng i n H a rvey S. R e i c h

Natha nael A . Slate r a n d J . M atth ias Wa lz

t h e I ntens ive C a re U n it G isela I . B a n a u c h a n d Eric C u cc h i

1 18

Contents

x xv i i

mm E c h o c a rd i ogra phy i n the I ntensive Care lllW u n it 1 25 Den n is A. Tighe, D i nesh C h a n d o k , a n d G e ra rd P. Au rige m m a

II Arte ri a l P u n cture fo r B l oo d Gas Ana lys i s

1 32

M a rie T. Pavi n i a n d R i c h a rd S . I rw i n

lml l nte rvent i o n a l U ltraso u n d i n the I C U liil G isela I . B a n a u c h a n d Ad a m W. Katz S e cti o n 2 in the I C U

•

1 37

Pa l l i ative Care a n d Eth i c a l Issues

Section Ed itor - J e n n ifer R e i dy

• I ntegrative a n d Pa l l i ative Ca re i n the I ntens ive Care U n it

1 43

J e n n ife r R e i dy, J u l ia M . G a l lagher, a n d S uza na K. Eve rett M a kows k i

S e cti o n 3 • Card i ovasc u l a r Pro b l e ms and Coronary Care Section Ed itor - Akshay S. Desai

ml M a nage m e nt of the Resusc itate d ... Post-C a rd i a c Arrest Pat i e nt 1 50 Ragh u R . Seet h a l a a n d B e nja m i n M . Sci rica

BJ!I M a nage m e nt of Hypote n s i o n a n d Card i oge n i c liil S h o c k 1 56 M i c h a e l M . G ivertz

II The Card i o myo path i es : D i agnosis a n d I C U M a nage m e nt

G . W i l l i a m Dec

1 69

x xv i i i

I

Contents

nl Va lvu l a r H e a rt D isease 1 80 ... Akshay S . Desa i , M i c h a e l F. B e l l a my, a n d M a u rice En riq u ez-Sa ra n o 11'!1 C riti ca l Ca re of Peri ca rd i a ! D isease llil A n d rea Loise l l e a n d S u n i l M a n ka d nt The Ac ute Aort i c Syn d ro m es liil P i otr Sobieszczyk

1 90

1 99

1111 Eva l uati o n a n d M a nage m e nt of Hyp e rte n s i o n - i n the l C U 208 Benja m i n M . Sci rica

II Syn c o p e

21 6

Ad a m S . Fe i n a n d Ka ren E. T h o m a s

1BJ1 M a nage m e nt of U nsta b l e Angi na a n d N o n-ST - E l evati o n Myoca rd i a l I nfa rct i o n

224

Yu ri B. Pride a n d E l i V. G e lfa n d

• ST-Segm e nt E l evat i o n Myocard i a l I nfa rct i o n

237

I a n J . N e e l a n d a n d J a m es A . d e Le mos

• C o m p l i cated Myocard i a l I nfa rcti o n • Ve ntri c u l a r Ta c hyca rd i a 258 S r i n ath Ad usu m a l l i a n d R o bert W. Ye h

B ruce A . Ka p l a n a n d W i l l i a m G . Steve nson

llftl S u p raventr i c u l a r Ta c hyca rd i a .. J o h n L. S a p p J r a n d La u re n ce M . E pste i n In.I Te m p o ra ry Card i a c Pa c i ng - David D . S p ragg a n d D a n i e l A. K i m

268

28 1

246

Conte nts

I

xxix

.n Perm a n e nt Pa cema kers a n d Antia rrhyth m i c - Devices

290

An i l Raj e n d ra a n d M ic h a e l R . G o l d

S e cti o n 4 Care U n it

•

P u l m o na ry Pro b l ems in the I ntensive

Section Ed itor - J. M a r k M a d i s o n

nt A Phys i o l og i ca l Approa c h to M a naging - Res p i rato ry Fa i l u re

297

M a rk M . Wi lson a n d R ic h a rd S . I rw i n

.m Ac ute Res p i rato ry D i stress Syn d r o m e 303 - Fra ntisek Sa n d o r, M a rk M . Wi l so n , a n d R i c h a rd S . I rwi n

II Asth ma Exa c e rbat i o ns

307

J . M a r k M a d ison a n d R ic h a rd S . I rw i n

.a C h ro n i c O bstru ctive P u l m o n a ry D isease - Sea n O ' R e i l ly a n d D e i rd re L. Kath m a n

II Extra p u l m o n a ry Ca uses of Res p i rato ry Fa i l u re

31 9

Ava n i T. M e hta a n d M a rk M . Wi lson

II Ac ute Res p i rato ry Fa i l u re i n Pregna n cy

322

M itra G hase m i a n d O re n P. Schaefe r

II M a nagi ng H e m o ptys is

330

Pa u l o J . O l ive i ra a n d R i c h a rd S . I rw i n

.,. Asp i rati o n a n d D rown i ng

- N i cholas A.

338

S m yrn ios a n d R i c h a rd S . I rw i n

31 2

xxx

I

II P u l m o na ry Hyp e rte n s i o n i n the I nte ns ive Contents

C a re U n it

345

Ana Cojoca ru a n d K i m berly A. Fisher

llr!I P l e u ra l D isease i n th e C riti ca l ly I l l .. Pati ent

353

A n d res F. Sosa , C resce ns Pel lecc h i a , a n d M a rk M . Wi lson

II M ec ha n i ca l Ve nti l ati o n : I nvasive and N o n i nvas ive

358

Scott E. Kopec, S u m era R . A h m a d , a n d R i c h a rd S . I rw i n

• M ec ha n i ca l Ve nti l ati o n : D isconti n uati o n

365

Scott E. Kopec a n d R i c h a rd S . I rw i n

• Res p i rato ry Adj u n ct Th e ra py a n d N o n i nvas ive Res p i rato ry M o n ito r i n g

37 1

Ava n i T. M e hta , Scott E. Ko pec, a n d J . M a rk M a d ison

• Ac ute l n h a l ati o n a l I nj u ry a n d C h e m i c a l a n d B i o l og i c a l Age nts o f M ass D estru ct i o n M i c h a e l L . Ba rretti a n d M a rk M . Wi lson

1!11 D isord e rs of Te m p e ratu re C o ntro l : - Hypoth erm i a 385 J iaying Z h a ng, S u sa n n e M u e h lsch lege l , a n d M a rk M . Wi lson

1!11 D isord e rs of Te m p e ratu re C o ntro l : - Hyp e rth erm ia

39 1

Saef I zzy, S u sa n n e M u e h l sc h l egel a n d M a rk M . Wi lson

• S evere U p p e r Ai rway I nfect io ns

397

Ste p h e n J . Krinzma n , S u n i l Raja n , and R ic h a rd S . I rw i n

378

Conte nts

11'11 Ac ute I nfecti ous P n e u m o n i a - A n n a G . R u d n i c k i a n d A n d res F. Sosa S e cti o n 5 Care U n it

•

xxxi

404

Rena l Pro b l e m s i n the I nte ns ive

Section Ed itor - Pang-Ye n Fa n

1!1.11 M eta bo l i c Ac i d osis a n d M eta bo l i c - Al ka l os i s

41 1

J a h a n M o ntague a n d J ason K u r l a n d

11!1 D isord e rs of P l asma S od i u m a n d - Potass i u m 4 1 7 J a u d at Kha n , Eric I i d a , a n d Pang-Ye n Fa n

IZI Acute Ki d n ey I nj u ry i n the I ntens ive - Care U n it

427

Kon sta nti n A b ra m ov a n d Thejas N. Swa my

• D i a lyt i c Thera py in th e I ntensive Care S etting

436

Deep Ad h i ka r i a n d Dagm a r K l i nger

S e cti o n 6 • I nfect io us D isease Pro b l ems i n the I ntensive C a re U n it

- G a i l S c u l ly

II Ap p roa c h to Feve r i n the I nte nsive Care U n it Section Ed itor

Pat i e nt

44 1

So n i a N . C h i m ienti a n d R i c h a rd H . G lew

• The Use of Anti m i c ro b i a l s i n the Treatm e nt of I nfe ct i o n i n the C riti ca l ly I l l Pati ent

Wayra Salaza r- M o re n o a n d David M . B e b i nger

45 1

xxxi i

I

• C e ntra l N e rvous Syste m I nfecti ons 459 • I nfective E n d oc a rd itis a n d Cath ete r­ Contents

H e i d i L . S m ith

464

Ass o c i ate d B l o od Stre a m I nfections Wayra Salaza r- M ore n o a n d G a i l Scu l ly

• U ri na ry Tra ct I nfect io ns 47 1 • Toxi n - M e d i ated I l l n esses (Toxi c S h o c k H e i d i L. S m ith

Syn d r o m e , Teta n us , a n d Botu l ism)

475

I va Zivna a n d R i c h a rd T. E l l ison I l l

• I nfecti ons i n l m m u n o c o m p ro m ised H osts

47 9

So n i a N . C h i m ienti

r1!1 H u ma n I m m u n o d efi c i e ncy Vi rus i n th e - I ntensive Care U n it

495

Aruna S ree and Ra u l Dava ro

• Tu b e rc u l os i s i n the I nte ns ive C a re U n it

504

M i c h a e l D. M a ncen i d o and J e n n ifer S . Daly

llJll S evere C o m m u n ity-Ac q u i red Resp i rato ry - Vi ra l I nfecti ons

51 0

I va Zivna a n d R i c h a rd T. E l l ison I l l

• M a l a ria a n d Oth e r Vector-Borne I l l n esses

51 5

I va Zivna a n d R i c h a rd T. E l l ison I l l

Conte nts

I

S e cti o n 7 • Gastro i ntest i n a l a n d H e pato b i l i a ry Pro b l em s i n the I ntens ive Ca re U n it Section Ed itor - Do m i n i c J. N o m p l eggi

SD Gastro i ntesti n a l B l e ed i ng: Pri n c i p les of .. D i agnosis a n d M a nage m e nt

52 1

Darre l l M . G ray 1 1 a n d C . Prakash Gyawa l i

• Stress U l c e r Syn d ro m e

527

Fa iz A . M i rza a n d C . P ra kash Gyawa l i

• Va ricea l B l e ed i ng

533

S u s a n H o ngha T . Vu a n d C . Prakash Gyawa l i

• Gastro i ntesti n a l M oti l ity Pro b l e ms i n th e Criti c a l Care S etti ng

54 1

G rego ry S . Say u k

• Fu l m i na nt C o l itis and Toxi c M ega co l o n

548

H e ba N . l s ka n d a r a n d C. P ra kash G yawa l i

• H e pati c Dysfu n cti o n

554

Kev i n M . Koren blat

• Eva l uati o n a n d M a nage m e nt of Liver Fa i l u re

559

Kev i n M . Koren blat

• D i a rrhea

568

Ka ra A . Rega n a n d C . P ra kash Gyawa l i

xxx i i i

x x x iv

I

Contents

1!!11 S evere a n d Co m p l i cated B i l i a ry Tra ct - D isease 575 Ta re k A b o u H a m d a n a n d R iad Aza r

• The Bas i c Pri n c i p l es of N utriti o n a l S u p p o rt i n the I ntens ive Care U n it

58 1

Dom i n i c J . N o m p leggi

S e cti o n 8 • E n d o c r i n e Pro b l e m s i n the I ntensive C a re U n it Section E d itor - S a m i r M a l ka n i

• M a nage m e nt of Hyp e rglyc e m i a in the C ritica l ly I l l Pat i e nts

585

Les l i e J . Doma l i k a n d David M . H a r l a n

11!11 D i a b etic Comas: Ketoa c i d os i s a n d lill Hyperos m o l a r Syn d ro m e 590 Sa m i r M a l ka n i a n d J o h n P . M o rd es

• Thyro i d D is ord e rs i n the I C U

600

A l a n P. Fa rwe l l

1!'11 Hypo a dre n a l Crisis a n d the Stress lill M a nage m e nt of th e Pat i e nt o n C h ro n i c Stero i d Th e ra py

61 7

N e i l Aro n i n

• D isord e rs of M i n e ra l M eta b o l ism Seth M . A r u m a n d D a n i e l T. B a ra n

� Hypoglyc e m i a

- John

628

P. M o rd es a n d Sa m i r M a l ka n i

622

Contents

I

x x xv

S e cti o n 9 • H e mato l og i c Pro b l e m s in th e I nte nsive Ca re U n it Section Ed itor - Patr i c k F. Foga rty

• D isord e rs of H e m ostasis

637

Ad a m C u ke r a n d S u m a n L . Sood

• Thro m bocyto p e n i a in the C riti ca l Care Pat i e nt

653

Te rry B . Gerns h e i m e r

nll Antith ro m boti c Thera py i n Criti ca l ly I l l - Pat i e nts

664

Kev i n E. Anger, B o n n i e C . G ree nwood , C h risto p h e r D . Ad a m s , a n d J o h n Fa n i kos

II Ve n o u s Thro m bosis a n d R e l ated D isord e rs i n Criti c a l Care Pat i e nts

690

Mya S a n d a T h e i n , As h ka n Emad i , a n d M ic h a e l B . Stre iff

• An e m i a i n th e C riti ca l Ca re Pati e nt

713

T h o m a s G . Deloughery

Bn Tra nsfu s i o n Thera py: B l oo d C o m p o n e nts - a n d Tra nsfus i o n Co m p l i cati o ns 7 24 S u c h itra P a n d ey a n d As h o k N a m b i a r

• The Le u ke m ias 732 • O n c o l og i c E m e rge n c i es Ka ren K. B a l l e n

D i a n e M . F. Sava rese

738

x x xv i

I

Contents

S e cti o n 1 0 • Pharm a c o l ogy, Ove rdoses, and P o i so n i ngs Sect ion E d itor - Luke Y i p

BR Tox i c o l ogy - L u ke Yi p S e cti o n 1 1 C a re U n it

•

749

S u rg i c a l Pro b l e m s in the I ntensive

Sect ion E d itor - Fred A. L u c h ette

Bii E p i staxi s 837 - Cynt h i a E. We ber, Sewit A m d e , a n d

F red A . Luchette

Im.I Esop hagea l Perfo rati o n a n d Ac ute - M e d i asti n itis

840

Cynt h i a E . We ber, F red A . Luchette , a n d R o bert M . M e ntzer J r

• D i agnosis a n d M a nage m e nt of I ntra-Ab d o m i n a l S e psis

844

Yee Wo ng, M a ry M . Wolfe , a n d F red A. Luch ette

• Ac ute Pa n c reatitis

850

J e n n ifer K . P l ic hta a n d Fred A . Luch ette

• M esente r i c lsch e m i a

857

Yee Wo ng a n d Pete r E . R ice

• C o m p a rtm e nt Syn d ro m e of the Ab d o m i n a l Cavity

86 1

M i c h a e l Sigm a n , D i etm a r H . Wittm a n n , a n d F red A . Luchette

I

Contents

xxxvi i

Im N e c roti z i ng Fas c i itis a n d Oth e r S oft Tissu e - I nfect i o ns

865

Stewa rt R . Ca rte r, D a v i d H . A h re n h o l z , a n d Fred A . Luchette

Ill Pressu re U l c e rs : Preventi o n a n d Treatm e nt

872

Stewa rt R . Ca rte r, Sewit A m d e , a n d Fred A . Luchette

111m Pa i n M a nage m e nt i n th e C ritica l ly I l l

- J e n n ife r K.

875

P l ichta , D o n a l d S . Steve n s , a n d Fred A. Luchette

Im M a nage m e nt of the O bstetri c a l Pat i e nt llill i n the I ntens ive Ca re S etting 884 M i c h a e l Sigma n , N o a h B . R i n dos, a n d J o h n G . G i a nopou los

S e cti o n 1 2

•

S h o c k a n d Tra u ma

Section Ed itor - Ti m othy A. E m h off

1r.1J S h o c k : An Ove rv i ew

1111 Kev i n

890

M . Dwye r a n d Ti m othy A. E m h off

Dim H e m o rrhag i c S h o c k a n d Resusc itat i o n lliliil C h risto p h e r P. M ic h etti a n d Ti m othy A. E m h off lr.m Tra u m a : An Ove rv i ew

... Ti m othy A.

91 0

E m h off

� Tra nsporti ng the Criti ca l ly I l l Pat i e nt

1111 G i na

900

91 5

R . Dorlac, J a y A. J o ha n n igma n , a n d N a m H e u i K i m

Ill H ea d Tra u m a

91 9

J o s h u a J . Wi n d , J o s h u a M . Am merma n , J a m es M . Eckl u n d , and Nam Heui Kim

x x xv i i i

I

• S p i na l C o rd Tra u m a Conte nts

924

H owa rd B. Leve n e , M i c h a e l Y. Wa ng, B a rth A . G ree n , a n d Ti m othy A . E m h off

nm Ab d o m i n a l Tra u m a 1111 U l ises To rres

Ill B u rns

933

942

P h i l i p F i d l e r a n d J a m es C. J e ng

1111 Thora c i c Tra u m a 95 1 1111 H a n i Seo u d i a n d B ru ce J . S i m o n

• C o m p a rtm e nt Syn d ro m es Assoc i ated with M uscu l oske l eta l Tra u m a

955

Ti m othy A . E m h off

• S e ps i s a n d M u lti o rga n Fa i l u re

959

M a rie M u l l e n

S e cti o n 1 3 Ca re U n it

•

N e u ro l og i c Pro b l e m s in the I nte ns ive

Sect ion E d itors - David A. D ra c h m a n a n d David Payd a rfar

11n An Approach to N e u ro l og i c Pro b l e ms lllil i n the I ntens ive Care U n it 973 David A . D ra c h m a n

• Altered C o nsc i o usn ess

97 9

Raphael A. Ca ra ndang, Lawrence J . Haywa rd , a n d David A . D rac h m a n

• M eta b o l i c E n c e p h a l o pathy Pa u l a D . Ra v i n

986

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xxx ix

Ill G e n e ra l ized Anoxia/lsc h e m i a of th e N e rvous Contents

Syste m

99 1

Shash i d h a ra N a nj u n daswa my, N i ls H e n n i nger, R ic h a rd P. Goddea u J r, a n d Majaz Moonis

Im Status E p i l e pt i c us 995 1111 Fe l i c i a C . C h u a n d Cath e r i n e A. P h i l l i ps nmt C e re b rovascu l a r D isease 1 00 1 llill M ajaz M o o n i s , R ic h a rd P. Goddea u J r, M u h i b Kha n , a n d J o h n P. Weaver

Ill S u ba ra c h n o i d H e m o rrhage

1 008

Wi ley H a l l , J o h n P . Weaver, a n d M ajaz M o o n i s

Im The G u i l la i n -Ba rre Syn d ro m e llill 1sabel ita R . B e l l a a n d David A. C h a d 1111 Myasth e n i a G ravis

lliil J o h n ny S . Sa l a m e h a n d

1 014

1 020

R a n d a l l R . Lo ng

lnJ Acq u i red Wea kn ess i n the I ntens ive Care ... U n it

1 024

David A . C h a d

nmt N e u ro-O n c o l og i ca l Pro b l e m s i n the I ntens ive llil ca re U n it

1 03 1

M a y u r J aya ra o a n d N . Scott Litofs ky

Im M isce l l a n eous I ntensive Care U n it llmiil N e u ro l og i c Pro b l e m s 1 038 David Ca c h i a , N a n cy M . Fontnea u , a n d A n n L . M itch e l l

In C N S I nfecti o us a n d I nfl a m m atory 11111 D isorders 1 044 N eeta G a rg a n d Pete r N . R is k i n d

xI

[

Contents

S e cti o n 1 4

•

Transp l a ntat i o n

• Criti ca l Ca re of O rga n Tra n s p l a nt Re c i p i e nts : Sect ion E d itors - S o n i a N . C h i m i e nt i a n d C h risto p h Tro p p m a n n

Ove rv i ew

1 052

C h risto p h Tro p p m a n n

• Criti ca l Care of the Deceased O rga n Donor

1 057

C h risto p h Tro p p m a n n

In Rejection, I nfection, and Mal ignancy i n Solid liill Organ Transplant Recipients 1 067 B ri a n J . G a l lay

In Criti ca l Ca re of K i d n ey Transp l a nt ._ Rec i p i e nts

1 073

B ri a n J . G a l lay

In Criti ca l Ca re of Pa n c reas Tra n s p l a nt liill Rec i p i e nts 1 077 C h risto p h Tro p p m a n n

• Criti ca l Care of Liver Transp l a nt Rec i p i e nts

1 085

N i ko l a os C h a n d o l ias, Va n essa H u m p h revi l l e , a n d Ty B . D u n n

• Criti ca l Ca re of H e a rt and H e a rt-Lung Tra nsp l a nt Rec i p i e nts

1 092

La u ra A . Davis, I re n e A . K i m , Natha n W i l l i a m Skel ley, a n d David D . Yu h

• Criti ca l Ca re of H e mato p o i et ic C e l l Tra nsp l a nt Rec i p i e nts M a rco M i elcarek

1 098

Contents

S e cti o n 1 5 • R h e u mato l og i c a n d I m m u n o l og i c Pro b l em s i n t h e I ntens ive C a re U n it Section Ed itor - P a u l F. D e l l a r i p a

In R h e u mato l og i c D isord e rs i n the I ntens ive - Care U n it

1 1 07

Donaugh G . H owa rd

mm Ana p hylaxis 1 1 1 9 llllil H e l e n M . H o l l i n gsworth a n d N e reida A.

P a ra d a

Ill Vasc u l itis in the I ntens ive Care U n it

1 1 27

Pa u l F. Del l a r i pa

S e cti o n 1 6 • Psyc h iatr i c Issues i n I nte nsive Ca re Section Ed itor - J o h n Querques

mm D iagnos is a n d Treatm e nt of Ag itat i o n � a n d D e l i ri u m i n t h e I nte ns ive Care U n it Pat i e nt 1 1 32 Jason P. Ca p l a n

Im S u i c i d e 1 1 37 llllil Saari A. M u ra ka m i

Ill D i agnosis a n d Treatm e nt o f D e p ress i o n i n t h e I ntens ive Ca re U n it Pat i e nt

J o h n Querq u es a n d Theodore A . Ste rn

1 1 41

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Contents

Ap p e n d ix Ca l c u lati ons C o m m o n ly Used i n Criti c a l C a re 1 1 47 J oseph J . Frassica I n d ex

1 1 53

SECTION

1

Proced u res a n d Tec h n i q u es a n d M i n i ma l ly I nvas ive M o n itori ng i n th e I C U Ste p h e n 0 . H ea rd

A i rway M a n a ge m e nt a n d E n d otra c h ea l I ntu bati o n El ifce 0 . Casa r a n d Ada m D . C u rrier

I . G E N E RAL P R I N C I PLES

A. Maintenance of adequate ventilation and pulmonary gas exchange is very important in critically ill patients. Airway management in intensive care patients differs significantly from routine surgical procedures in the operating room. B. Critical care physicians should be familiar with the equipment and the techniques to maintain and secure the airway. I I . ANATO MY. The airway is divided into the upper airway and lower airway.

A. Nose. The nose serves a number of functions: respiration, olfaction, humidifica­ tion, filtration, and phonation. B. Pharynx. The pharynx extends from the base of the skull to the level of the cricoid cartilage.

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C. Larynx. 1 . The larynx lies in the adult neck opposite the third through sixth cervical vertebrae. 2. The laryngeal skeleton consists of hyoid bone and nine cartilages. These are the unpaired thyroid, cricoid, and epiglottis and the paired aryte­ noid, corniculate, and cuneiform cartilages. The cricoid cartilage is the only structure that completely encircles the airway. 3. Two nerves that are branches of the vagus innervate the larynx. a. The external branch of superior laryngeal nerve supplies motor innervation to the cricothyroid muscle. All other motor supply to the laryngeal muscles is provided by the recurrent laryngeal nerve. b. The internal branch of the superior laryngeal nerve provides sensa­ tion above the cords. Sensory innervation below the cords is supplied by the recurrent laryngeal nerve. D. Trachea. 1 . The adult trachea begins at the cricoid cartilage. It is 1 0 to 20 cm long. 2. It divides into right and left main bronchi at the level of fourth and fifth thoracic vertebrae. The right main bronchus is wider and shorter and takes off at a less acute angle than the left, thus making right main bronchus intubation more likely. I l l . EVALUAT I O N OF T H E A I RWAY

A. Several clinical criteria can be assessed. 1. Mourh opening. 2. Mallampati classification (Fig. 1 - 1 ) . 3 . Head and neck movement. 4. Ability to prognath (i.e., to bring the lower incisors in front of the upper incisors) . 5. Thyromental distance. 6. Body weight. 7. Neck circumference. 8. Previous history of difficult intubation (single most reliable predictor of a difficult airway) . B. Difficult airway in some patients will remain undetected despite the most careful airway examination. C. Cervical collars, halo devices, trauma to the mandible or neck, morbid obe­ sity, pregnancy, acromegaly, burns, and obstructive sleep apnea may signal a difficult airway. D. Age > 5 5 , body mass index >26, snoring, presence of a beard, lack of teeth, Mallampati class III or IV, abnormal mandibular protrusion test, and male gender are independent clinical risk factors for difficult mask ventilation. IV. AIRWAY EQU I P M E NT

A. An oxygen source, face masks of different sizes, a bag-valve ventilation device, suction catheters, and suction source with canister and tubing. B. Oral and nasopharyngeal airways (Fig. 1 -2) .

3

C h a pter 1 • Ai rway M a nagement a n d E n d otrac heal I ntubation

A

B

Figure 1 - 1 . Mallampati classification: class I airway, faucial pillars, soft palate, and uvula can be visualized (A); class II airway, faucial pillars, and soft palate can be visualized but the uvula is masked by the base of the tongue; and class III airway, only the soft palate can be visualized. The patient (B) has a class III airway, which is one of the predictors of difficult orotracheal intubation. (From Mallampati SR, Gatt SP, Gugino LD, et al. A clinical sign to predict difficult tracheal intubation: a prospective study. Can Anaesth Soc ] 1 98 5 ;32:420, with permission.)

A

B

Figure 1 - 2 . A: The proper position of the oropharyngeal airway. B: The proper position of the nasopharyngeal airway. (Reprinted Dorsch JA, Dorsch SE. A practical approach to anesthesia equipment. Philadelphia: Lippincott Williams & Wilkins, 20 1 1 :254-259, with permission.)

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S ECT I O N 1 • p R 0 c E D u R E s A N D T E c H N I Q u E s

Miller blade

Maci ntosh blade

A

B

Figure 1 - 3 . The two basic types of laryngoscope blades-Macintosh (A) and Miller (B) . The Macintosh blade is curved. The blade tip is placed in the vallecula, and the handle of the laryngoscope is pulled forward at a 45-degree angle. This maneuver allows visualization of the epiglottis. The Miller blade is straight. The tip is placed posterior to the epiglottis, thereby pinning the epiglottis between the base of the tongue and the straight laryngoscope blade. The motion on the laryngoscope handle is the same as that used with the Macintosh.

C. Laryngoscope blades and handle. Two basic types of laryngoscope blades are available: the curved blade (Macintosh) and the straight blade (Miller) . The Miller blade is more useful in patients who have a cephalad and anterior laryngeal inlet (Fig. 1 -3) . D. Various sizes of endotracheal tubes with stylers. In adults, endotracheal tubes with internal diameter of 7.0 to 8.0 mm are commonly used for women, while tubes with internal diameter of 8.0 to 9.0 mm are used for men. E. A device to detect end-tidal carbon dioxide: capnograph. F. Endotracheal tubes used in children may be based on this formula: Tube size (mm) [ 1 6 + age (years)] /4. G. Laryngeal mask airways (LMAs) can be used to provide a temporary airway until a more definite airway can be achieved. The LMA is contraindicated in patients at risk of aspiration due to the presence of a full stomach (Fig. 1 -4) . =

V. AIRWAY OBSTRUCTI O N

A . The hallmark o f upper airway obstruction i s diminished o r absent airflow in the presence of continued respiratory effort. B. Airway obstruction can be complete or partial. Partial obstruction is recognized by noisy inspiratory sounds. Snoring is the sound of partial airway obstruction, which is most audible during expiration. Stridor sug­ gests glottic obstruction and is heard most often in inspiration. Complete obstruction is an emergency with inaudible breath sounds.

C h a pter 1 • Ai rway M a nagement a n d E n d otrac heal I ntubation

T>

I

5

I

)

Figure 1 -4 . Correct position of the LMA. (From Malcby JR, Loken RG, Watson NC, et al. The laryngeal mask airway: clinical appraisal in 250 patients. Can ] Anaesth 1 990;37:509, with permission.)

VI. TREAT M E N T

A. The head tilt is the simplest and first maneuver. The head is tilted back by placing one hand under the neck and pushing down on the forehead. This approach should not be used in patients with a fractured neck. B. The second maneuver (jaw thrust) displaces the jaw forward by applying anterior pressure on the angle of the mandible. This procedure should not be done in patients with a dislocated or fractured jaw. C. The triple airway maneuver (combination of head tilt, jaw thrust, and opening the mouth) is the most reliable manual method to establish airway patency. D. When airway maneuvers are inadequate to establish airway patency, airway aids such as an oral or nasopharyngeal airway should be used (see Fig. 1 -2) . E. Applying positive pressure that permits 20 cm H20 to the airway through­ out the respiratory cycle via the mask-bag-valve device can also be used to relieve the upper airway obstruction. V I I . O ROTRAC H EAL I NTU BAT I O N

A. Before we yield a patient unconscious, we have to ask the following four questions. 1 . Can I ventilate this patient using a mask? 2. Will I be able to place a supraglottic device if needed?

6

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S ECT I O N 1 • p R 0 c E D u R E s A N D T E c H N I Q u E s

B.

C. D.

E.

F. G.

H. I. J.

3. Will I be able to intubate this patient? 4. If the surgical airway is required, will there be access to the patient's trachea? Endotracheal intubation achieves four main goals: airway protection, pro­ viding upper airway patency, pulmonary hygiene, and allowing mechanical positive pressure ventilation. The optimal position is the "sniffing" position: the head should be resting on a pad, which flexes the neck on the chest with concomitant extension of the head on the neck. The laryngoscope handle is held in the left hand while the patient's mouth is opened as wide as possible. The laryngoscope blade is inserted into the right side of the mouth, the tongue is swept to the left, and the blade is advanced forward toward the base of the tongue. The curved blade is advanced into the vallecula, and upward force at a 45-degree angle is used to raise the epiglottis. The straight blade is advanced, the tip of the blade is positioned beneath the epiglottis, and upward force is applied in the same manner as with the curved blade. Once the glottic opening is visualized, the endotracheal tube is advanced through the vocal cords until the cuff just disappears. The cuff is inflated until moderate tension is felt in the pilot balloon cuff. Determine that the tube is in the trachea. Signs of tracheal intubation consist of presence of co2 in the exhaled breath, breath sounds over the chest, lack of breath sounds over the stomach, lack of gastric distention, and respiratory gas moisture in the endotracheal tube. Insertion of the tube to 23 cm at the incisors in males and 2 1 cm in females generally provides optimal endotracheal tube position. If the laryngoscopist's view is not optimal, optimal external laryngeal manipulation (OELM) can be used by pressing the thyroid or cricoids cartilage, or hyoid bone in the cephalad and posterior direction. In the unconscious patient who is considered to have a full stomach, cricoid pressure should be applied by using the thumb and forefinger together to push downward on the cricoid cartilage. This maneuver can prevent passive regurgitation of stomach contents into the trachea during intubation.

V I I I . NASOTRAC H EAL I NTU BAT I O N

A . The nasal approach generally provides the easier route for intubation. B. Topical vasoconstrictors such as phenylephrine or cocaine (4%) should be applied to the nares to minimize nasal bleeding. C. Nasotracheal intubation is contraindicated in basilar skull fractures and coagulopathies. IX. FLEX I B L E E N D O S C O PY AND ALTERNATIVE TE C H N I QU ES OF AI RWAY MANAG E M E N T

- ' ' A. Fiberoptic endoscopy i s useful in suspected spine injury, known or antici­ pated difficult airway, morbid obesity, and patients with high risk of aspira­ tion (see Video 1 - 1 ) .

C h a pter 1 • Ai rway M a nagement a n d E n d otrac heal I ntubation

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7

B. It may be used in both awake and anesthetized patients via oral or nasal route. C. It may be useful in critically ill patients to evaluate the endotracheal tube patency and position and to change endotracheal tubes in patients with difficult airways. D. Fiberoptic endoscopy can be used with other intubation or alternative airway management techniques to overcome many difficult airways. E. The LMA (see Fig. 1 -4) or its variants and new generation supraglottic ventilatory devices are other alternative devices to manage the patient with a difficult airway. Rigid videolaryngoscopes that provide a non-line-of-sight view of the glottis are also available. F. Needle cricothyrotomy and percutaneous dilatational tracheostomy can be done for emergent airway access.

X. C O M PLICATI O N S O F E N D OTRAC H EAL I NTU BAT I O N

A. During intubation. 1 . Laryngospasm. 2. Laceration. 3. Bruising of lips or tongue. 4. Damage to teeth. 5. Aspiration. 6. Endobronchial or esophageal intubation. 7. Perforation of oropharynx, trachea, or esophagus. 8. Epistaxis. B. Postextubation. 1 . Laryngospasm, sore throat, hoarseness, stridor, glottic or subglottic edema. 2. Long-term intubation may result in tracheal stenosis, tracheomalacia, and tracheal mucosal ulceration. XI. EXTUBAT I O N

A . Should b e done i n the patient who i s fully awake and can protect his airway. B. Oropharyngeal secretions should be suctioned, head of the bed should be elevated, and endotracheal tube should be removed after a cuff leak test. C. In patients with a known difficult airway, extubation using an airway exchange catheter should be considered. D. Supplemental oxygen should be provided, and the patient should be observed in a monitored setting. E. Emergency airway equipment should be available to manage postextuba­ tion problems. SUGG ESTED R EADI NGS

El-Orbany M. Difficult mask ventilation. Anesth Analg 2009; 1 09 (6) : 1 870-1 880.

Review article that discusses the definition, pathophsiology, incidence and the prediction ofdifficult mask ventilation.

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Finucane BT, et al. Principles ofairway management. New York: Springer, 20 1 1 .

Evaluation ofthe airway. Ganzouri E. Preoperative airway assessment: predictive value of a multivariate risk index. Anesth Analg 1 996;82: 1 1 97-1 204.

Good article about applying a multivariable composite airway risk index in predicting preoperative difficult airways. Hagberg CA. Benumofand Hagberg's airway management, 3rd ed. Philadelphia: Elsevier Saunders, 20 1 3 .

The classic textbook i n airway management. Rosenblatt WH . Preoperative planning of airway management in critical care patients. Crit Care Med 2004;32: (suppl) 1 86-1 92.

Article that defines the importance ofpreoperative evaluation in critically ill patients.

C e ntra l Ve n o u s Cath ete rs Anto n i o Apo nte- Fe l i c i a n o , A l a n O rq u i o l a , Theofi los P. Math eos , a n d Ste p h e n 0 . H e a rd

I . G E N E RAL P R I N C I PLES

A. Catheter types. 1. Single lumen. 2. Multilumen (double, triple, or quad) . 3. Introducer. 4. Double-lumen dialysis catheters. B. Site selection. 1. Major sites. a. Internal j ugular vein (IJV) . b. Subclavian vein (SCV) . c. External jugular vein (EJV) . d. Femoral vein. e. Antecubital vein (peripherally inserted central catheters) . 2. Depends on skill of operator: greater risk of pneumothorax with subcla­ vian approach. 3. Risk of infection: femoral > internal jugular > subclavian. 4. Avoid sites involving infection, burns, or other dermatologic processes. C. Methods to reduce risk of catheter infection. 1. Education program with safety checklist. 2. Empowering nursing to stop procedure if sterile technique is violated. 3. Dedicated catheter cart stocked with all necessary supplies. 4. Use chlorhexidine preparatory solution. 5. Use subclavian site preferably. 6. Use maximum barrier precautions: cap, mask, sterile gloves and gown, and sterile drape that entirely covers patient. 7. Remove catheters when no longer needed. 8. Avoid guidewire exchanges as possible. 9. Use antimicrobial impregnated catheters if infection rates remain high despite institution of infection control measures. 10. Avoid use of femoral site and move catheter from femoral site to another as soon as possible. D. Use of ultrasonographic guidance. 1. Certain patient characteristics that carry higher risk of complications when using the anatomic approach. a. Anatomy: morbid obesity; local scarring; radiation therapy; short, thick neck; transplant patients; edema. 9

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S ECT I O N 1 • p R 0 c E D u R E s A N D T E c H N I Q u E s

b. Comorbidities: coagulopathy, bullous emphysema, maximal ventila­ tor support. 2. Allows better visualization of the anatomy, skin to vessel distance. Color flow Doppler allows one to identify flow direction (red toward and blue away from ultrasound probe) and avoidance of preexisting thrombus. The vein should be compressible. 3. The center of the screen will match the center of the probe. A mark on one side of the screen will match a mark or light on the ultrasound probe; this will allow orientation. 4. Decreases failure rate, multiple attempts at cannulation, mechanical failure rates, and infection rates. 5. Disadvantages: steep learning curve. 6. There are two ways to cannulate a vessel with ultrasound guidance. a. Transverse view: provides complete visualization of the surroundings of the vessel. The needle should be inserted parallel to the probe; deviation could cause arterial puncture or structural damage. b. Longitudinal plane: allows visualization of the path of the vessel and the needle entrance point. Ensure probe is maintained over the vein; sliding the probe laterally or medially could lead to an arterial puncture. I I . I N D ICAT I O N S

A . Monitoring of fluid status. B. Administration of irritant medications or vasoactive substances. C. Total parenteral nutrition. D. Hemodialysis. E. Placement of a temporary transvenous pacing wire. F. Procurement ofvenous access when peripheral vein cannulation is not possible. G. Aspiration of air in surgical procedures considered high risk for venous air embolism (e.g., posterior fossa craniotomy with the patient in the sitting position) . H. Venous access during cardiopulmonary resuscitation. I l l . P R O C E D U RES

A. Universal protocol with a time-out must be followed. B. IJV approach. 1. Approaches to IJV cannulation are the anterior, central, and posterior (Fig. 2- 1 ) . 2 . Central (Fig. 2- l C) . a. The patient i s placed i n a 1 5-degree Trendelenburg position, and the head is turned to the contralateral side. b. Using maximal barrier precautions, after infiltration of local anes­ thetic, the operator punctures the skin with a 22-gauge "finder" needle with an attached syringe at the apex of the triangle formed by the sternal and clavicular heads of the sternocleidomastoid muscle (SCM) and the clavicle (base) . The internal carotid artery pulsation is usually felt 1 to 2 cm medial to this point.

C h a pter 2 • Centra l Ve nous Catheters

I

1 1

A

B

c

D

Figure 2- 1 . A: Surface anatomy. The !JV emerges from the base of the skull and enters the carotid sheath dorsally with the internal carotid artery, courses posterolaterally ro the artery beneath the sternocleidomasroid muscle (SCM), lies medial to the anterior portion of the SCM in its upper part and beneath the triangle formed by the two heads of the muscle in the lower part, and enters the superior vena cava near the medial border of the anterior scalene muscle and beneath the sternal border of the clavicle. B: Anterior approach. C: Central approach. D: Posterior approach. To pro­ vide greater clarity of the anatomic landmarks, the sterile drape has been omitted from the figure. c.

3.

The finder needle is directed at a 45-degree angle toward the ipsi­ lateral nipple, while the operator applies constant aspiration on the syringe. After successful venipuncture with the finder needle, the large-bore needle is introduced in the identical plane. Once cannula­ tion occurs, tubing (20 cm in length) can be attached to the needle to confirm a low-pressure system indicating an intravenous location. d. After cannulation, the guidewire is then inserted through the large needle. Depth of insertion is limited to 1 5 to 20 cm to avoid arrhythmias. e. A scalpel is used to make a larger skin incision (if needed) . The bevel of the scalpel is against the guidewire, and the blade is facing away from the vessel. A dilator is advanced over the guidewire to dilate the tract and then removed. Care must be taken to hold the guidewire in place during dilator insertion to reduce the risk of vessel perforation. The central venous catheter (CVC) is then threaded over the guidewire. Anterior approach (Fig. 2- l B) . Initial needle insertion is 0 . 5 to 1 cm lateral to the carotid artery pulsation at the midpoint of the sternal head of the SCM.

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S ECT I O N 1 • p R 0 c E D u R E s A N D T E c H N I Q u E s

Figure 2 - 2 . A: Transverse view of the !JV at the level of the cricothyroid membrane. SCM, sternocleidomastoid muscle; !JV, internal jugular vein; EJV, external jugular vein; !CA, inter­ nal carotid artery; ASM, anterior scalene muscle. Notice that the IJV is lateral to the !CA. B: Longitudinal view of the !JV.

4. Posterior approach (Fig. 2- l D) . a. The EJV i s the key landmark. b. The needle is inserted 1 cm dorsal to the point where the EJV crosses the posterior border of the SeM or 5 cm cephalad from the clavicle along the clavicular head of the SeM and is directed caudally and ventrally toward the suprasternal notch at an angle of 45 degrees from the sagittal plane and with a 1 5-degree upward angulation. 5. Ultrasound view (Fig. 2-2) . C. EJV approach. 1. The patient is positioned in a slight Trendelenburg position, with arms by the side and face turned to the contralateral side. 2. After sterile preparation, the venipuncture is performed with a 1 6-gauge catheter over the needle, using the operator's left index finger and thumb to distend and anchor the vein. 3. The needle is advanced in the axis of the vein at 20 degrees to the frontal plane. When free backflow of blood is established, the needle is advanced a few millimeters further, and the catheter is threaded into the vein over the needle. 4. A guidewire can be introduced through this catheter, and a eve can be advanced over the guidewire. 5. Abduction of the ipsilateral arm and anteroposterior pressure exerted on the clavicle may help the guidewire to negotiate the angle formed at the junction of the EJV with the SeV. 6. The EJV can be successfully cannulated in 80% of patients. D. Femoral vein approach. 1. The patient is positioned supine, the groin is prepared and draped, and the venipuncture is made 1 to 1 . 5 cm medial to the femoral arterial pulsation. 2. The femoral arterial pulsation is usually found at the junction of the medial and middle third of a line joining the anterior superior iliac spine and the pubic tubercle.

C h a pter 2 • Centra l Ve nous Catheters

I

1 3

Figure 2-3. Transverse ultrasound view of the femoral vein anatomy. Structures from lateral to medial: femoral nerve, femoral artery, and the femoral vein.

An 1 8-gauge thin-walled needle attached to a syringe is inserted at a 45-degree angle pointing cephalad and 2 to 3 cm inferior to the inguinal ligament to minimize the risk of a retro peritoneal hematoma in the event of an arterial puncture. 4. Once venous blood return is established, the syringe is depressed to skin level, and free aspiration of blood is reconfirmed. 5. A guidewire and subsequently a dilator are advanced, and the catheter is finally threaded over the guidewire after the dilator has been removed. 6. Ultrasound view: The femoral anatomy can be appreciated in Figure 2-3. E. SCV approach (Figs. 2-4 and 2-5) . 3.

1. The patient is positioned in a 1 5- to 30-degree Trendelenburg position, with a small bedroll berween the scapulae. 2. The patient's head is turned to the contralateral side, and arms are by the side. 3. Infraclavicular approach. a. Skin puncture is made with an 1 8-gauge thin-walled needle attached to a syringe, 2 to 3 cm caudal to the midpoint of the clavicle and directed toward the suprasternal notch until it abuts the clavicle. b. The needle is "walked" down the clavicle until the inferior edge is cleared. c. As the needle is advanced, it is kept as close to the inferior edge of the clavicle as possible to avoid puncturing the dome of the pleura.

14

S ECT I O N 1 • P R 0 C E D U R E S A N D T E C H N I Q U E S

I

·�

a

A

B

Figure 2-4. A: Patient positioning for subclavian cannulation. The SCV is a direct continu­ ation of the axillary vein, beginning at the lateral border of the first rib and extending 3 to 4 cm along the undersurface of the clavicle to join the ipsilateral internal j ugular vein behind the sternoclavicular articulation to become the brachiocephalic vein. The SCV is bordered by muscles anteriorly, the subclavian artery and brachia! plexus posteriorly, and the first rib infe­ riorly. B: Cannulation technique for the supraclavicular approach. To provide greater clarity of the anatomic landmarks, the sterile drape has been omitted from the figure.

d. When blood return is established, the needle bevel (initially facing upward) is turned 90 degrees toward the heart, the syringe is removed, the guidewire is inserted, the needle is removed, and a dilator is advanced over the guidewire and removed. e. The CVC is advanced over the guidewire to the appropriate depth. 4. Supraclavicular approach. a. The skin puncture is just superior to the clavicle and is lateral to the insertion of rhe clavicular head of the SCM. b. The needle is advanced coward the contralateral nipple, j ust under the clavicle, and it should enter the jugular subclavian at a depth of 1 to 4 cm. c. A 90% to 95% success rate can be achieved with rhis approach. 5. Ultrasound approach: Find the vessel lateral to the angle of rhe clavicle. Color Doppler can help with identification (see Fig. 2-5) . IV. POSTPRO C E D U R E C O N S I D E RATI O N S

A . A chest radiograph i s required t o confirm proper position o f the catheter and to ensure absence of a pneumothorax. 1. The tip of the catheter cannot be positioned in the right atrium or right ventricle because perforation of the cardiac wall may occur and cause tamponade. 2. Arrhythmias from mechanical irritation or vessel perforation may also result from catheter tip malposition. The caval atrial junction is

C h a pter 2 • Centra l Ve nous Catheters

1 5

Figure 2-5. Subclavian vein, transverse view.

B.

approximately 1 3 to 1 7 cm from the right-sided SeV or IJV insertion sites and 1 5 to 20 cm for left-sided insertions. 3. Application of a chlorhexidine-impregnated dressing will reduce the incidence of catheter-related bloodstream infection. Other complications. 1. In addition to pneumothorax, cardiac tamponade, arrhythmias, and infection, observe for a. Air and catheter embolism. h. Hematoma. c. Arterial puncture. d. Hemothorax or hydrothorax. e. Line-associated thrombosis and/or embolism.

C. When removing a eve, the patient should be positioned flat in the bed (i.e., head of the bed is not elevated) and an occlusive dressing applied to the insertion site after catheter removal to reduce the risk of venous air embolism.

1 6

S ECT I O N 1 • P R 0 C E D U R E S A N D T E C H N I Q U E S

S U G G ESTED R EAD I NGS

Celinski SA, Seneff MG. Central venous catheters. In: Irwin RS, Rippe JM, Lisbon A, et al. , eds. Procedures and techniques i n intensive care medicine, 5th ed. Philadelphia: Lippincott Williams & Wilkins, 2 0 1 2 : 1 6-35 .

More detailed description ofthe techniques used to insert central venous catheters. Graham AS, Ozment C, Tegtmeyer K, et al. Central venous catheterization. New Engl] Med 2007;3 56:e2 l . http://content.nejm.org/ cgi/ content/ short/3 5 6/2 1 / e2 l .

Useful video ofIf central venous catheterization. Karakitsos D, Labropoulos N, de Groot A, et al. Real-time ultrasound-guided catheteriza­ tion of the internal j ugular vein: a prospective comparison with the landmark technique in critical care patients. Crit Care 2006; 1 0 : R l 62. http://ccforum.com/ content/ l 0/6/Rl 62.

These authors demonstrated that the use of ultrasound during I] cannulation will reduce complications and infections.

Keenan SP. Use of ultrasound ro place central lines. ] Crit Care 2002 ; 1 7 : 1 26-1 37.

Review ofthe utility of ultrasound to insert central venous catheters. Walz JM, Memtsoudis SG, Heard SO. Prevention of central venous catheter bloodstream infections. ] Intensive Care Med 20 1 0;25 (3) : 1 3 1 - 1 3 8 .

Concise review ofthe infectious complications associated with central venous catheterization.

Arte r i a l L i n e P l a c e m e nt a n d C a re Kha l d o u n Fa ris

I . G E N E RAL P R I N C I PLES

A. Cannulation sites. 1. Radial artery. 2. Dorsalis pedis artery. 3. Brachia! artery. 4. Femoral artery. 5. Axillary artery. B. Anatomy. 1 . The radial artery is one of two final branches of the brachia! artery. It lies just lateral to the flexor carpi radialis at the wrist (Fig. 3 - 1 ) . The anasto­ moses between the radial and ulnar arteries provide excellent collateral flow to the hand. A competent superficial or deep arch must be present to ensure adequate collateral flow. 2. The dorsalis pedis artery runs from the level of the ankle to the great toe. It lies superficially and just lateral to the tendon of the extensor hallucis longus. 3. The brachia! artery lies in the antecubiral fossa, medial to the tendon of the biceps, and in close proximity to the median nerve. 4. The common femoral artery courses under the inguinal ligament near the junction of the ligament's medial and middle thirds (Fig. 3-2) . 5. The axillary artery begins at the lateral border of the first rib and ends at the inferior margin of the teres major muscle. The artery is mostly superficial and covered only by skin and fasciae. C. Site selection. 1. The ideal artery should have extensive collateral circulation that will maintain the viability of distal tissues if thrombosis occurs. 2. The site should be comfortable for the patient, accessible for nursing care, and close to the monitoring equipment. 3. Sires involved by infection or disruption of the epidermal barrier should be avoided. 4. Larger arteries and catheters report pressures that are closer to aortic pressures. Distal artery recordings yield higher systolic values than cen­ tral artery recordings, but the mean pressures are similar.

1 7

1 8

I

S ECT I O N 1 • p R 0 c E D u R E s A N D T E c H N I Q u E s

Figure 3- 1 . Anatomy of the radial artery. Note the collateral circulation to the ulnar artery through the deep volar arterial arch and dorsal arch.

I I . I N D I CAT I O N S

A . Hemodynamic monitoring. 1. Beat-to-beat changes. 2. Waveform inspection. 3. The effect of arrhythmia on perfusion. 4. Continuous cardiac output (CO) monitoring using arterial pulse contour analysis. 5. Assessment of systolic pressure variation (SPV) , pulse pressure variation (PPV) , or stroke volume variation (SVV) to predict fluid responsiveness in mechanically ventilated patients with large tidal volumes (>8 mL/kg) . B. Frequent arterial blood gas sampling (more than two measurements per day) . C. Arterial administration of drugs such as thrombolytics. D. Intra-aortic balloon pump use.

C h a pter 3 • Arte r ia l Line P l acement and Care

Femoral sheath

1 9

Mf..!.Tf-- Femoral artery •+--'H'- Femoral vei n

Figure 3-2. Anatomy of the right femoral artery and adjacent structures. The artery is can­ nulated below the inguinal ligament.

I l l . PRO C E D U R E

A. Equipment. 1. The equipment necessary to display and measure arterial waveform includes. a. An appropriate intravascular catheter. b. Fluid-filled noncompliant tubing with stopcocks. c. A transducer. d. A device for constantly flushing the line. e. Electronic monitoring equipment. 2. Using this equipment, intravascular pressure changes are transmitted through the hydraulic (fluid-filled) elements to the transducer, which converts mechanical displacement into a proportional electrical signal. The signal is amplified, processed, and displayed as a waveform by the monitor.

20

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S ECT I O N 1 • p R 0 c E D u R E s A N D T E c H N I Q u E s ,...---

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Figure 3-3. Fast-flush test. A; Overdamped system. B: Underdamped system. C: Optimal damping.

Sources of error. a. Improper zeroing of the system and zero drift are important sources of error. b. Calibration of the system is usually not necessary because of standardization of the disposable transducer. c. If the zero referencing and calibration are correct, a fast-flush test will assess the system's dynamic response. d. An optimal fast-flush test results in undershoot followed by small overshoot and then settles to the patient's waveform (Fig. 3-3) . e. Overdamped tracings are usually caused by air bubbles, kinks, clot formation, compliant tubing, loose connections, a deflated pressure bag, or anatomic factors. All these problems are usually correctable. f. Underdamped tracings are caused by long tubing or an increased inotropic or chronotropic state. Technique. 3.

B.

1 . A time-out and the universal protocol must be followed. Foaming in and out, skin disinfection, and draping should be carried out as described in Chapter 2. 2. Radial artery cannulation. a . Modified Allen test. i. The modified Allen test does not necessarily predict the presence of collateral circulation, and some centers have abandoned its use as a routine screening procedure. ii. To perform this test, the examiner compresses both radial and ulnar arteries and asks the patient to clench and unclench the fist repeatedly until pallor of the palm is produced. One artery is then released, and the time to blushing of the palm is noted. The procedure is repeated with the other artery. iii. Normal palmar blushing is complete before 7 seconds (positive test) , and a result of 1 5 or more seconds is abnormal (negative test) . b. Percutaneous insertion. i. The hand is placed in 30 to 60 degrees of dorsiflexion. The volar aspect of the wrist is prepared and draped using the sterile tech­ nique, and lidocaine is infiltrated through a 25-gauge needle.

C h a pter 3 • Arte r ia l L i n e P l acement a n d Care

21

Figure 3-4. Cannulation of the radial artery. A: A towel is placed behind the wrist, and the hand is immobilized with tape. B: The 20-gauge catheter-needle-guidewire apparatus is inserted into the skin at 30- to 60-degree angle. C: The apparatus is advanced into the artery, and once a pulsatile flow is obtained, the guidewire is advanced. D: The catheter is advanced over the guidewire into the artery.

3.

ii. A 20-gauge catheter-needle-guidewire apparatus is used (Fig. 3-4) . Entry is made at a 30- to 60-degree angle to the skin, approximately 3 cm proximal to the distal wrist crease. iii. The apparatus is advanced until arterial blood return is noted in the hub. The guidewire is passed through the needle into the artery to serve as a stent for subsequent catheter advancement. iv. The guidewire and needle are then removed, and placement is confirmed by pulsatile blood return. v. The cannula is attached to the transducer tubing and firmly secured, and the site is bandaged. vi. Video instruction for the insertion of a radial arterial line can be found at (http://www.nejm.org/doi/full/ 1 0 . 1 056/NEJMvcm0441 49). Dorsalis pedis artery cannulation. a . The patient's foot is placed in plantar flexion and prepared in the usual manner. b. Vessel entry is obtained approximately halfWay up the dorsum of the foot. c. Advancement is the same as with cannulation of the radial artery. d. Systolic pressure readings are usually 5 to 20 mm Hg higher with dorsalis pedis catheters than with radial artery catheters, but mean pressure values are generally unchanged.

22

S ECT I O N 1 • P R 0 C E D U R E S A N D T E C H N I Q U E S

4. Brachia! artery cannulation. a. Brachia! artery cannulation is infrequently performed because of concern regarding the lack of effective collateral circulation. b. The median nerve lies in close proximity to the brachia! artery in the antecubital fossa and may be punctured in 1 % to 2% of cases. c. Cannulation of the brachia! artery can be performed with the same apparatus as described for radial artery catheterization. 5. Femoral artery cannulation. a. The artery is cannulated using the Seldinger technique with one of several available prepackaged kits. b. The patient lies supine with the leg extended and slightly abducted. c. Skin puncture should be made a few centimeters caudal to the inguinal ligament to minimize the risk of retroperitoneal hematoma or bowel perforation. d. The needle is directed, bevel up, cephalad at a 45-degree angle. When arterial blood return is confirmed, the needle and syringe are brought down against the skin to facilitate guidewire passage. e. The guidewire is inserted, the needle is withdrawn, and a stab inci­ sion is made with a scalpel at the skin puncture site. f. The catheter is threaded over the guidewire to its hub, and the guide­ wire is withdrawn. g. The catheter is then connected to the transducer tubing and sutured securely to the skin. 6. Axillary artery cannulation. a. The patient's arm is abducted, externally rotated, and flexed at the elbow by having the patient place the hand under his or her head. b. The artery is palpated at the lower border of the pectoralis major muscle. c. The remainder of the catheterization proceeds as described for femoral artery cannulation. 7. Ultrasonographic-guided cannulation (see Chapter 22) : Ultrasonography is used with increased frequency to guide vessel cannulation and mini­ mize complications. Although it is mainly used in central venous can­ nulation, ultrasonography has been used to guide the cannulation of the femoral artery and less frequently the radial artery and other arteries. IV. POSTPRO C E D U R E C O N S I D E RATI O N S A.

Complications. The complications associated with arterial catheterization are listed in Table 3-1 . 1 . Thrombosis. a. Thrombosis is the single most common complication of intra-arterial catheters with an incidence of 5% to 25%. b. Symptomatic occlusion requiring surgical intervention occurs in 6 30/1 2-20 801>6 80-1 00/0--6 60/6--8

20-2 5/0--6 2 5/4- 1 0 50/ 1 2-1 5 25112-18 25112-18 30-4011 8-2 5 50-60/2 5 301 1 2 80/3 5 80-1 00/40 60/35

0-6 4-1 0 $12 1 2- 1 8 $18 >18 18-25 1 , 500 > 1 , 500

250 >450 $250 $250 >250 >250 >250 >400 >500 >250

0-4

8-1 2 1 2- 1 8 0-6 0-6 >6 1 2-20 >6 0-6 6

'Hemodyn a m i c profile seen in a p p roximately one-th i rd of patients in late septic shock. "Co nfirmed by a p p ropriate RA- PA oxygen sat u ration step- u p . RA, right atri u m ; RV, right ve ntri cle; PA, p u l monary a rtery; PAW P, p u l m o n a ry a rtery wedge pressure; AO, aortic; C l , cardiac i n d ex; SVR , systemic vasc u l a r resista nce; PVR , p u l monary vasc u l a r resista nce; A M I , acute myoca rd i a l i nfa rction; LVF , left ve ntric u l a r fa i l u re ; RVF, right ventric u l a r fa i l u re ; R V I , right ventric u l a r i nfarcti o n ; VS R , ventric u l a r se pta l r u ptu re. Ada pted from Gore J M , Albert J S , B e n otti J R , et a l . Handbook of hemodynamic monitoring. Boston : Little B rown , 1984.

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32

S ECT I O N 1 • P R 0 C E D U R E S A N D T E C H N I Q U E S

S U G G ESTED R EAD I NGS

Binanay C, Califf RM, Hasselblad V, er al. Evaluation study of congestive heart failure and pulmonary artery carhererizarion effectiveness: the ESCAPE trial. JAMA 2005;294: 1 625-1633.

A trialfailing to show benefit for managing CHF Friese RS, Shafi S, Gentilello LM. Pulmonary artery catheter use is associated with reduced mortality in severely injured patients: a National Trauma Dara Bank analysis of 53,3 1 2 patients. Grit Care Med 2006;34: 1 597-1 60 1 .

A study that associated PAC use with improved outcomes in elderly trauma patients. Harvey S, Harrison DA, Singer M, er al. Assessment of the clinical effectiveness of pulmo­ nary-artery catheters in management of patients in intensive care (PAC-Man) : a randomized controlled trial. Lancet 2005;366;472-477.

A multicenter study that failed to associate PA catheter use with improved care. Koo KKY, Sun JCJ, Zhou Q, er al. Pulmonary artery catheters: evolving rares and reasons for use. Grit Care Med 2 0 1 1 ;39: 1 6 1 3- 1 6 1 8.

A study that traces the usage ofPA catheters. Kumar A, Anel R, Bunnell E, er al. Pulmonary artery occlusion pressure and central venous pressure fail to predict ventricular filling volume, cardiac performance, or the response to volume infusion in normal subjects. Grit Care Med 2004;32:69 1 -699.

A study that did notfind PA catheter estimates ofleft atrial pressure to correlate with cardiac performance. Mark JB. Atlas ofcardiovascular monitoring. New York: Churchill Livingstone, 1 99 8 .

A resource with helpfol visual presentations and practical demomtrations ofuse, Reich HS. Pulmonary artery catheters. In: Irwin RS, Rippe JM, eds. Irwin and Rippe's intensive care medicine, 7th ed. Philadelphia: Lippincott Williams & Wilkins, 20 1 2 :45-63 .

Comprehensive chapter on the PA catheter. An outstanding comprehensive resource. Richard C, Warszawski J, Anguel N, et al. Early use of the pulmonary artery catheter and outcomes in patients with shock and acute respiratory distress syndrome. JAMA 2003;290:27 1 3-2720.

A study ofthe use ofPA catheters in ARDS. Sandham JD, Hull RD, Brant RF, er al. A randomized controlled trial of the use of pulmonary-artery catheters in high-risk surgical patients. N Engl J Med 2003; 348 :5-14.

A seminal study that failed to find benefit ofPA catheter usage in surgical patients. The American Thoracic Society. Pulmonary artery catheter primer. http://www.thoracic. org2 0 1 3 .

An online resource focused on practical and helpfol demonstrations. The National Heart, Lung and Blood Institute ARDS Clinical Trials Network. Pulmonary artery versus central venous catheter ro guide treatment of acute lung injury. N Engl J Med 2006;354:22 1 3-2224.

A study that failed to find benefit in ARDS patients.

C a rd i ove rs i o n a n d D efi b r i l l at i o n Ava n i T. M e hta a n d Pa u lo J . O l ive i ra

I . G E N E RAL P R I N C I PLES

A. Basic concepts. 1. Electric countershock. a. Delivering electrical energy to depolarize the myocardium to termi­ nate a tachyarrhythmia. b. Definitions. i. Cardioversion delivers a synchronized shock, coinciding with the QRS complex on the electrocardiogram (ECG) . (a) If countershocked during the "vulnerable" period, late ven­ tricular systole marked by T wave on the ECG, there is risk of inducing ventricular fibrillation (VF). (b) Primarily used for emergency and elective treatment of various tachyarrhythmias. ii. Defibrillation delivers an unsynchronized shock to terminate VF and pulseless ventricular tachycardia (VT) . (a) Because VF/pulseless VT is immediately life threatening and there is no well-defined QRS complex, an unsynchronized electrical countershock is delivered. (b) Defibrillation success is defined as termination of VF for at least 5 seconds following the shock, not by restoration of a perfusing rhythm. B. Physiology of arrhythmias requiring cardioversion or defibrillation. 1. Reentry. a. Arrhythmias involving reentrant circuits (electrical activation over a closed conduction pathway) can be terminated with electric counter­ shock. i. Examples include atrial fibrillation (AFib) , atrial flutter, atrioven­ tricular (AV) nodal reentrant tachycardia, and most VT and VF. b. Cardioversion and defibrillation disrupt reentry by depolarizing at least a threshold quantity of excitable tissue. 2. Increased automaticity. a. Arrhythmias involving increased impulse formation do not respond to electric countershock. b. Examples of unresponsive arrhythmias involving triggered activity are sinus tachycardia, focal atrial tachycardia, and some types of VT.

33

34

I

S ECT I O N l • P R O C E D U R E S A N D T E C H N I Q U E S

C. Mechanism of action. 1. Effective countershock silences an adequate portion of the myocardium through depolarization, while the remaining myocardium cannot per­ petuate the arrhythmia. 2. Factors affecting successful shock include energy level, type of shock waveform, transthoracic impedance, and myocardial refractory state. 3. Subthreshold shocks may extinguish fibrillatory wavefronts, but ofren new wavefronts will form causing perpetuation of the fibrillation. II. I N D ICAT I O N S

A . Urgent. 1 . Hemodynamic instability. 2. Acute respiratory distress, congestive heart failure, and angina. 3. Important to recognize sinus tachycardia from rhythms that benefit from cardioversion or defibrillation. B. Elective. 1. Absence of acute symptoms and signs. 2. Weigh risks and benefits. I l l . PRECAU T I O N S

A . Digitalis toxicity and electrolyte imbalance can increase the risk of inducing VT and VF. B. Severe conduction disease (i.e., sick sinus syndrome) increases the risk of developing significant bradyarrhythmia after cardioversion. C. Risk of thromboembolism in patients with AFib. IV. P R O C E D U R E

A. Technical considerations. 1. Waveform types. a. Monophasic. i. Unipolar, delivers current in one direction. ii. Standard in older defibrillators. iii. Requires higher energy levels to terminate arrhythmia. b. Biphasic. i. Bipolar, delivers current in two directions with polarity reversal during the return phase. ii. Standard on most defibrillators. iii. Fewer shocks and lower total energy to terminate, with equal (perhaps superior) efficacy and improved safety profile. 2. Electrodes. a. Handheld paddles. i. Larger paddle size decreases transthoracic resistance, increasing energy delivery. ii. Pressure applied to chest with paddles decreases impedance and potentially improves efficacy of countershock.

C h a pter 5 • Card i overs i o n a n d Defi bri l l a t i o n

I

35

iii. Current recommendations favor use of gel pads to decrease the risk of arcing and skin burns. b. Self-adhesive pads. i. More common as convenient and easy to use. ii. Advantages: equally effective, no gel required, and minimizes risk to staff as less contact with bed and patient during delivery of shock. 111. May allow for temporary external pacing depending on model. c. Anatomic placement. i. Minimize impedance by avoiding breast tissue and clipping excessive body hair. ii. Optimal placement (controversial) . (a) Anterior-lateral: anterior pad/paddle on right infraclavicular chest and lateral pad/paddle lateral to the left chest longitu­ dinally. (b) Anterior-posterior: anterior pad/paddle as above and poste­ rior pad/paddle at left lower scapula. (I) This position may be favored for atrial tachyarrhythmias and in patients with implanted devices. iii. Biphasic waveform devices are less position dependent. B. Patient preparation. 1. In unstable patients, perform countershock urgently. 2. If elective procedure, follow the below guidelines. a. NPO (nil per os, nothing by mouth) for 6 to 8 hours to decrease risk of aspiration. b. Obtain informed consent. c. Follow universal protocol. d. Constant heart rhythm monitoring and 1 2-lead ECG before and after countershock. e. Sedation medications with rapid onset of action and a short half-life: a benzodiazepine (midazolam) and/or a narcotic agent (fentanyl) . f. Monitoring including frequent blood pressure and pulse oximetry checks; supplemental oxygen usually provided through nasal cannula. C. Cardioversion procedure/using defibrillator. 1. If low-amplitude QRS, optimize detection by changing leads (essential in synchronized cardioversion) . 2. Select "synchronization" function if performing cardioversion. 3. Select initial energy depending on device (most manufacturers will pro­ vide recommended energy dose on device) and arrhythmia. a. VF, pulseless VT: monophasic-360 J; biphasic- 120 to 200 J. b. VT with pulse: monophasic- 1 00 J; biphasic-unknown. c. AFib: monophasic- 1 00 to 200 J; biphasic- 1 00 to 120 J. d. Atrial flutter: monophasic-50 to 1 00 J; biphasic-unknown. 4. Charge capacitor, clear the area, and then deliver shock. 5. Be aware that many devices default back to "unsynchronized" mode fol­ lowing delivery of shock. 6. If no change in rhythm, escalate energy as appropriate and consider consulting a cardiologist or electrophysiology specialist.

36

I

S ECT I O N 1 • p R 0 c E D u R E s A N D T E c H N I Q u E s

D. Management of specific arrhythmias. 1. VF and pulseless VT. a. Important changes in the advanced cardiac life support (ACLS) algorithm for VF/pulseless VT in the 2005 and 20 1 0 guidelines published by the American Heart Association. b. No longer recommend delivery of three "stacked" shocks; instead, deliver one shock followed by five cycles of cardiopulmonary resuscitation (CPR) before assessing rhythm. c. Vasopressors (epinephrine or vasopressin) may be given before or after second shock, and antiarrhythmic agents (amiodarone is first line, but if unavailable, can consider lidocaine) may be considered before or after third shock. d. Emphasis is placed on timely delivery of adequate, uninterrupted CPR between shocks. e. CPR delivered in this manner (5 cycles of 30 compressions and 2 breaths per cycle or 2 minutes total) has been associated with improved success of defibrillation and potentially improved neuro­ logic outcome. 2. AFib. a. General overview. i. Most common indication for cardioversion. ii. Cardioversion performed in either the hemodynamically unstable patient or under elective circumstances to attempt reversion to normal sinus rhythm. iii. Elective cardioversion for stable AFib may become less common. iv. Published data have demonstrated that overall outcome may be more dependent on rate control and anticoagulation than on rhythm normalization. b. Anticoagulation. i. AFib/flutter is associated with development of thrombus in left atrial appendage or cavity during or after cardioversion. ii. Risk of pericardioversion thromboembolism is 5.3% in patients not anticoagulated versus 0.8% in those who are anticoagulated. iii. AFib of 24- to 48-hour duration is unlikely to be associated with thromboembolism. iv. Two options in patients with atrial fibrillation of longer or inde­ terminate duration: (a) Transesophageal echocardiogram (TEE) . (I) If no thrombus is noted in left atrial appendage, cardio­ version may be safely performed. (2) Anticoagulation with warfarin (goal international nor­ malized ratio [INR] 2 to 3) should be provided for 4 weeks after cardioversion (time required for return of organized mechanical activity after cardioversion) . (b) Defer cardioversion until the patient has been anticoagulated at therapeutic range for 3 to 4 weeks. (1) Must, again, anticoagulate for a minimum of 4 weeks after cardioversion.

C h a pter 5 • Card i overs i o n a n d Defi bri l l a t i o n

37

V. POSTPRO C E D U R E C O N S I D E RATI O N S

A. Complications. 1. Thermal burns to the chest-risk may be decreased with biphasic wave­ form devices (lower total energy required) . 2. Risk of thromboembolic events, particularly when cardioverting AFib or flutter. 3. Countershocks can induce tachyarrhythmias and bradyarrhythmias. 4. Defibrillation in asystole should always be avoided because excessive vagal response may suppress intrinsic nodal activity. a. Always consider the possibility that VF with small-amplitude waves ("fine VF") may mimic asystole. b. Check more than one lead and for pulses before assuming a diagnosis of asystole. 5. Depolarizing the myocardium may inhibit the recovery of ventricular escape beat and thereby lead to worsening intrinsic pacemaker failure in individuals with baseline conduction abnormalities. 6. Clinically significant myocardial damage from cardioversion or defibril­ lation is unlikely; minimize the risk further by delivering shocks at least 1 minute apart. 7. Applying countershocks to patients with digoxin toxicity may be proar­ rhythmogenic, so check digoxin level and correct electrolytes before a procedure to minimize this risk. B. Special circumstances. 1. Patients with implanted pacemakers and defibrillators. a. May undergo external cardioversion and defibrillation safely. b. External energy delivery may alter programming of internal device. c. Energy may also be conducted down an internal lead causing local myocardial injury or changing the devices functional thresh­ olds. d. Never place pads/paddles directly over the internal device. e. Perform interrogation of device immediately after electric counter­ shock delivery. 2. Cardioversion and defibrillation in pregnancy. a. Procedure has been performed in all trimesters without obvious fetal effects or induction of premature labor. b. Consider fetal heart rhythm monitoring during cardioversion. 3. Accidental hypothermia. a. Ventricular arrhythmias and asystole may be refractory to conven­ tional therapy until the patient has been rewarmed. b. Cardiac arrest in this situation should be managed with an initial attempt at defibrillation and use of appropriate pharmacologic therapy. c. If unsuccessful, aggressive rewarming should continue and further attempts at defibrillation held until the core temperature reaches 30°C to 32°C. d. Optimal antiarrhyrhmic agent has not been determined.

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S U G G ESTED R EAD I NGS

American Heart Association. 20 1 0 American Heart Association guidelines for cardiopulmo­ nary resuscitation and emergency cardiovascular care science. Circulation 20 1 0 ; 1 22: S639-S933.

A comprehensive presentation of the newly revised guidelines for CPR, published over numerous supplements. Botkin NF. Cardioversion and defibrillation. In: Irwin RS, Rippe JM, eds. Irwin and Rippe 's intensive care medicine, 7th ed. Philadelphia: Lippincott Williams & Wilkins, 20 1 1 : 7 1 -77.

A concise, up-to-date review on the topics ofcardioversion and defibrillation. Deakin C, Nolan JP, Sunde K, et al. European Resuscitation Council Guidelines for Resuscitation 20 1 0 Section 3 . Electrical therapies: automated external defibrillarors, defibrillation, cardioversion, and pacing. Resuscitation 2 0 1 0;8 1 : 1 293- 1 304.

A review on electrical therapies, in conjunction with the article listed below by the A CCI AHA/HRS on Device-Based Therapies. Epstein AE, DiMarco JP, Ellenbogen KA, et al. ACC/AHNHRS 2008 guidelines for device­ based therapy of cardiac rhythm abnormalities. Circulation 2008; 1 1 7:2820-2840.

A current review of implantable defibrillators. Fuster V, Ryden LE, Cannom OS, et al. ACC/AHA/ESC 2006 guidelines for the manage­ ment of patients with atrial fibrillation. Circulation 2006; 1 1 4(7) :e257-e354.

A revised, comprehensive guideline for management ofatrial fibrillation. Grewal GK, Klosterman TB, Shrestha K, et al. Indications for TEE before cardioversion for atrial fibrillation: implications for appropriateness criteria. JACC 20 1 2; 5 (6) :64 1-648.

A study evaluating the indications and appropriateness of TEE before cardioversion. Soar ], Perkins GD, Abbas G, et al. European Resuscitation Council Guidelines for Resuscitation 20 1 0 Section 8. Cardiac arrest in special circumstances: electrolyte abnormalities, poisoning, drowning, accidental hypothermia, hyperthermia, asthma, anaphylaxis, cardiac surgery, trauma, pregnancy, electrocution. Resuscitation 20 1 0;8 1 ( 1 0) : 1 400- 1 433.

Guidelines discussing the resuscitative management ofaccidental hypothermia and other special circumstances. Wann LS, Curtis AB, January CT, et al. 20 1 1 ACCF/AHA/HRS focused update on the man­ agement of patients with atrial fibrillation (updating the 2006 guideline) . Circulation 20 1 1 ; 1 23 : 1 04-1 23.

An updated review on the topic ofatrial fibrillation and its management.

P e r i c a rd i o c e ntes i s D i nesh C h a n d o k 1 a n d De n n is A . Tighe

I . G E N E RAL P R I N C I PLES

A. Pericardiocentesis is an important and potentially lifesaving procedure whereby a needle is inserted into the space berween the visceral and pari­ etal pericardium for the purpose of either sampling or draining pericardial contents (fluid, blood, pus, or gas) . B. Diagnostic versus therapeutic pericardiocentesis. 1. Diagnostic pericardiocentesis is performed to obtain small amounts of pericardia! fluid for culture, cytologic study, or other fluid analyses. 2. Therapeutic pericardiocentesis is intended to drain fluid from the peri­ cardia! space to relieve pressure that limits diastolic filling. 3. Diagnostic and therapeutic pericardiocenteses are best performed electively, under controlled circumstances, with echocardiographic or fluoroscopic support. 4. Management of a patient with severe hemodynamic compromise may require that pericardiocentesis be performed on an emergency basis without imaging support. C. Pericardia! anatomy. Normally, only 1 5 to 50 mL of clear fluid is present in the pericardial space, its composition similar to that of plasma ultrafil­ trate. 1. Visceral pericardium is composed of a single layer of mesothelial cells covering the myocardium and is loosely adherent to the underlying muscle by a nerwork of blood vessels, lymphatics, and connective tissue. 2. Parietal pericardium is composed of a thick layer of fibrous connective tissue surrounding another mesothelial monolayer. This fibrous capsule is relatively nondistensible. D. Diseases affecting the pericardium. 1. Several disease states may lead to inflammation of the pericardium or fluid accumulation including infections (viral, bacterial, fungal, para­ sitic) , malignancies, certain rheumatologic disorders, uremia, myocardial infarction, recent cardiac surgery, and myocardial rupture. 2. The composition of the fluid may become exudative, purulent, or frankly bloody depending on the underlying cause. E. Cardiac tamponade. Abrupt accumulation of fluid of 250 mL or less may lead to the clinical signs and symptoms of tamponade with equalization of pressures in all four cardiac chambers due to the relative noncompliance of the parietal pericardium. However, with slowly developing effusions, the !Deceased 39

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parietal pericardium is able to stretch, and significantly larger amounts of fluid (sometimes >2 L) may accumulate without hemodynamic compromise. Three other clinical conditions promote hemodynamic compromise, even in the absence of large pericardia! effusion: intravascular volume depletion, impaired ventricular systolic function, and ventricular hypertrophy with decreased elasticity of the myocardium (diastolic dysfunction) . II. PROCEDURE

A. General considerations. 1. In the patient with tamponade physiology, the treatment is drainage of the pericardia! fluid. While awaiting performance of pericardiocentesis, some authors recommend medical treatment with volume infusion and, if needed, use of inotropic agents and vasoactive drugs. Medical treatment should be viewed as only a temporizing measure. It should be cautioned that aggressive fluid resuscitation may actually worsen the hemodynamic picture by intensifying the ventricular interactions and likely proves beneficial only to those patients who are hypovolemic. Administration of diuretics is contraindicated. Mechanical ventilation should be avoided if possible as it may further impair cardiac filling and output. 2. If time allows, a coagulation profile should be checked and corrected. 3. The authors recommend performing right heart catheterization whenever possible to measure pressures before and after pericardiocentesis. 4. Traumatic pericardia! effusion, myocardial rupture, aortic dissection, and severe bleeding disorders are relative contraindications. No absolute contraindication to pericardiocentesis exists. B. Material preparation. 1 . Site preparation: 2% chlorhexidine gluconate and 70% isopropyl alcohol combination solution or equivalent ( 1 0% povidone-iodine solution is used only when there is a sensitivity to the chlorhexidine) , large sterile drape, sterile gowns and gloves, masks, and caps; 1 % lidocaine (without epinephrine) , atropine, and code cart to bedside. 2. Procedure: a pericardiocentesis kit or an 1 8-gauge, 8-cm thin-walled nee­ dle with blunt tip; number 1 1 blade; multiple syringes (20 to 60 mL) ; ECG; hemostat; sterile alligator clip; specimen collection tubes; and pericardia! drain if indicated. 3. Postprocedure: sterile gauze, dressings, and sutures. C. Patient preparation. 1. The universal protocol should be followed, and maximum barrier pre­ cautions should be utilized. 2. The patient should be placed in a comfortable supine position with the head of the bed elevated to approximately 45 degrees or more. 3. The fully upright position may be necessary for extremely dyspneic patients. This position allows free-flowing effusions to collect inferiorly and anteriorly where they are most accessible through a subxiphoid approach. D. Pericardiocentesis procedure. 1. Except under extreme emergency conditions, pericardiocentesis should be performed under imaging guidance. The primary imaging

C h a pter 6 • Pericard i ocentes i s

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modality used currently is bedside echocardiography to determine the location of the fluid, the presence of loculation, and the most acces­ sible entry site (apical, parasternal, subxiphoid) into the pericardia! space. 2. In general, the distance between the skin and the parietal pericardium using a subxiphoid approach is approximately 6.0 to 7.5 cm. This dis­ tance may be greater among obese patients or those with a protuberant abdomen. 3. The clinician should attach the needle to a 1 0-mL syringe, approxi­ mately half filled with 1 % lidocaine. This technique permits delivery of anesthesia to the subcutaneous tissues and pericardium during needle entry while allowing sufficient space in the syringe for withdrawal of pericardia! fluid. E. Needle entry site selection.

1. The pericardial space may be entered at various points along the anterior thorax as guided by echocardiography, generally choosing the shortest distance between the skin and the fluid in the pericardia! space. The subxiphoid approach is preferred in an emergency situation. 2. When considering the subxiphoid approach (the approach most com­ monly used by the authors) , inspect and palpate to locate the xiphoid process and the left costal margin. The needle entry site should be 0.5 cm lateral to the left border of the xiphoid process and 1 .0 cm infe­ rior to the costal margin. 3. When using the parasternal approach, the needle insertion site should be perpendicular to the chest wall just lateral to the sternum in the fifth intercostal space. 4. With an apical approach, the needle insertion site should be located in the intercostal space below and 1 cm lateral to the cardiac apex. F.

Site preparation. 1. Strict sterile technique should be followed at all times. A wide area of the skin in the xiphoid region is prepared with a 2% chlorhexidine gluconate in 70% isopropyl alcohol combination solution (or equivalent) , and the area is draped with a large fenesrrated sterile drape. 2. The skin is anesthetized with 1 % lidocaine without epinephrine. 3. A small skin incision is made at the entry site with a scalpel to facilitate the insertion of the blunt needle through the skin; the pericardiocentesis needle does not have a beveled edge to minimize the risk of myocardial puncture.

G. Needle insertion. 1. When passing through the skin from the subxiphoid approach, the angle of entry should be 45 degrees directing the needle superiorly aiming toward the patient's left shoulder. 2. Draw back on the plunger of the syringe while advancing the needle and before injecting the anesthetic agent. 3. The posterior edge of the bony thorax is usually only 1 .0 to 2 . 5 cm below the skin, but this distance may be greater in obese patients. If the bony thorax is contacted during needle entry, reposition the needle so that it may be advanced under the costal margin.

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4. Once the needle tip has passed beyond the posterior border of the bony thorax, the angle between the needle and the skin should be reduced to approximately 1 5 degrees. This angle of entry should be maintained while the needle is directed toward the left shoulder. 5. With the parasternal approach, the needle is guided by ultrasound toward the most prominent collection of fluid located closest to the chest wall. 6. When approaching from the apex, the needle should be aimed toward the patient's right shoulder. H. Needle advancement. 1. Move the needle only in a straight trajectory from front to back. Moving the needle side to side may injure epicardial blood vessels and lymphatics. 2. Aspirate while advancing the needle. Pause to inject the subcutaneous tissues with lidocaine at periodic intervals. 3. A "give" will be felt on entry into the pericardia) space and as fluid is aspirated. 4. Injection of agitated saline or perflutren lipid microspheres through the needle under echocardiographic guidance can ascertain if the needle tip is in the pericardia) space or another structure if uncertainty about loca­ tion exists. 5. A vasovagal response can occur when the pericardium is breached. Intravenous atropine or saline infusion may be required to reverse bra­ dycardia and hypotension. 6. Observe the surface ECG monitor while advancing. The occurrence of frequent premature ventricular contractions and/or ST-segment elevations may indicate myocardial contact. In this situation, the needle should be withdrawn slightly and redirected. I. Fluid evacuation. A large-volume pericardial effusion may be evacuated by attaching a 5 0-mL syringe to the pericardiocentesis needle with repeated aspirations. In general, we do not recommend this technique because manipulation of the needle during repeated attempts may cause trauma to the myocardium or frank rupture. The recommended approach is place­ ment of a pericardial drain. To accomplish this, a multilumen pigtail-type catheter is introduced over a guidewire, as in the Seldinger technique, into the pericardial space and connected to a drainage bag. J. Tamponade. If the procedure was performed to relieve tamponade, the patient's hemodynamic status should improve promptly. Such improve­ ment may be observed after the evacuation of as little as 50 to 1 00 mL of fluid. Clinical signs that indicate relief of tamponade include an increase in systemic blood pressure and cardiac output with a concomitant fall in right atrial pressure and resolution of pulsus paradoxus. I l l . POSTPRO C E D U R E C O N S I D E RATI O N S

A. Monitoring. After pericardiocentesis, close monitoring i s required t o gauge the rate of pericardia) effusion reaccumulation and the potential return of tamponade.

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B. Chest radiograph. All patients should have an end-expiratory chest radiograph immediately following the procedure to detect the presence or document the absence of a pneumothorax. C. A transthoracic echocardiogram should be obtained within several hours of rhe pericardiocentesis to confirm adequacy of pericardia! drainage and at periodic intervals thereafter as indicated clinically. D. Potential complications. Cardiac puncture with or without hemoperi­ cardium or myocardial infarction, pneumothorax, ventricular arrhyth­ mias, bradycardia, inj ury to adjacent abdominal organs, cardiac arrest, coronary artery laceration, infection, fistula formation, and pulmonary edema. E. Complications are most likely when the effusion is small ( 100 mL) : involves placement of a catheter into the pleural space, similar to above. Commercial kits are widely available, each with specific instructions. Operators should be thoroughly familiar with the recommended procedure and should receive appropriate supervision from an experienced operator before performing therapeutic thoracentesis on their own.

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10. Fill a heparinized blood gas syringe with pleural fluid from the side port of the three-way stopcock, express all air from the sample, cap it, and place it in a bag containing iced slush for immediate transport to the lab­ oratory. Fill the 50-mL syringe and transfer its contents into appropriate containers for planned analyses. Always maintain a closed system during the procedure to prevent room air from entering the pleural space. 1 1 . With thoracentesis completed, remove the needle (or catheter) from the patient's chest. Apply pressure to the wound for several minutes, and apply a sterile bandage. 12. Obtain a postprocedure upright end-expiratory CXR if a pneumothorax is suspected. Immediately after the procedure, draw venous blood for total protein and lactate dehydrogenase (LDH) determinations. These studies are necessary to interpret pleural fluid values. B. Technique for removal of freely moving pneumothorax. 1. Follow the same general protocol described earlier for catheter-over­ needle removal of freely flowing fluid but instead, position the patient supine with the head of the bed elevated 30 to 45 degrees. 2. Prepare the anterior second or third intercostal space in the midclavicular line (to avoid the more medial internal mammary artery) . 3. Have the bevel of the catheter-over-needle apparatus facing upward and direct the needle superiorly to guide the catheter into the superior aspect of the hemithorax. 4. Air may be actively withdrawn by syringe or pushed out when intrapleural pressure is supraatmospheric (e.g., during a cough), as long as the catheter is intermittently open to the atmosphere. Air can leave but not reenter the pleural space if a one-way (Heimlich) valve system is attached or if the catheter is put to underwater seal. 5. If a tension pneumothorax is known or suspected and a chest tube is not readily available, quickly insert a 1 4-gauge angiocatheter according to the foregoing technique. If a tension pneumothorax is present, air will escape under pressure. When the situation has been stabilized, replace the catheter with a sterile chest tube. IV. POSTPRO C E D U R E C O N S I D E RATI O N S

A . The overall complication rate from thoracentesis i s :'> 5 % when done by experienced intensivists but may reach 50% to 78% when performed by less experienced operators. B. Major, possibly life-threatening, complications may occur in 1 5% to 1 9% and include pneumothorax, hemorrhage, hypotension, reexpansion pulmo­ nary edema, and venous or cerebral air embolism (rare) . C. The risk of pneumothorax varies depending on baseline patient character­ istics (e.g., presence or absence of chronic obstructive pulmonary disease) , operator experience, and the method used to perform the procedure. D. Minor complications depend on the method used and occur in 1 6% to 63%, including dry tap, anxiety, dyspnea, cough, pain, and subcutaneous hematoma or seroma.

C h a pter 9 • Thoracentesi s

61

V. I NTERPRETAT I O N OF PLEU RAL FLU I D ANALYS I S

A. A transudate is biochemically defined by meeting all the following (Light) criteria: pleural fluid-to-serum ratio for total protein 200 mL) for detection when compared to DPL. 5. 63% to 1 00% sensitivity. 6. 93% to 97% specificity. C. Local wound exploration. D. Laparotomy or laparoscopy (especially in penetrating trauma as a less invasive initial method to evaluate for violation of the peritoneal cavity) . V I . PRO C E D U R E

A. D P L i s almost always done i n the setting o f trauma a t the conclusion of the primary and secondary surveys. Control of the often chaotic situation and environment is essential as well as is the maintenance of universal and maximum barrier precautions. B. Decompress hollow viscus. 1. The stomach is often distended from aggressive bag-valve-mask ventila­ tion, anxiety-related aerophagia, or esophageal intubation and should be decompressed with an oro- or nasogastric tube. 2. Foley catheter. C. Choice of incision location. 1 . Above the umbilicus. a. In patients with pelvic fractures, the incision should be made above the arcuate line. b. In pregnant females, there is a risk of uterine perforation and DPL should be used with care as above. 2. Below the umbilicus is the choice in most patients as it facilitates placement of the catheter in the appropriate anatomic space. D. Anesthetize the skin with 1 % lidocaine with epinephrine (to reduce skin bleeding, which may obstruct the view or confound the results) over the length of the 2-cm incision. E. Semiopen technique (most common) . 1. Make a 2-cm incision through the skin to expose the fascia. 2. The fascia is grasped and elevated with two penetrating towel clamps.

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F.

3. The elevated fascia is incised in the midline. 4. A peritoneal dialysis catheter is inserted into the abdomen at a 45- to 60-degree angle aiming toward the pelvis and feeling for two distinct "pops" followed by a loss of resistance as the catheter enters the perito­ neal cavity. 5. First an attempt is made at aspiration of free intraperitoneal blood. If 1 0 mL of blood is aspirated, the exam is considered positive and terminated. 6. If the diagnostic peritoneal aspirate is negative, the examiner proceeds with the DPL. One liter of crystalloid (or 25 mL/kg) is infused via two­ way IV tubing, and then the bag is placed on the floor to drain depend­ ently. 7. Interpretation should be deferred until at least 200 to 300 mL has been collected. At that time, 70 mL should be removed and sent to the lab for analysis and cell count. 8. The catheter may now be removed and the incision closed or left in place for a repeat lavage if the results are equivocal. Complications. 1. Infection. 2. Iatrogenic intraperitoneal injury. 3. False positives due to imperfect technique leading to nontherapeutic laparotomies.

V I I . G E N E RAL P RI N C I PLES OF PARAC ENTESIS

A. A simple procedure performed at the patient's bedside by any properly trained practitioner involving the insertion of a needle into the peritoneal cavity and the aspiration of ascitic fluid for diagnostic or therapeutic purposes. B. Prior to considering this intervention, the presence of a sufficient volume of ascites must be confirmed by a physical exam and/or imaging. V I I I . I N D ICAT I O N S

A . Diagnostic ( 1 0% of procedures performed) (Table 1 1 - 1 ) . 1 . I f a paracentesis i s done fo r diagnostic testing, only a small volume need be removed. 2. Fluid may be sent for examination and quantification as transuda­ tive (cirrhosis due to various etiologies, congestive heart failure, and nephrotic syndrome) or exudative (peritonitis, carcinomatosis, ischemic or obstructed bowel, or pancreaticobiliary inflammation) as well as to evaluate for infection. 3. Tests such as Gram stain, acid-fast bacilli smear, and culture and sensitiv­ ity; cytology; cell count, LDH, total protein, glucose, amylase, albumin, and triglyceride; and specific gravity may be ordered depending on the clinical situation.

C h a pter 1 1 • D i agnostic Peritoneal Lavage a n d Paracentes i s

TA B L E 1 1 - 1

S ponta n eous bacteria l periton itis Ci rrhosis Congestive h ea rt fa i l u re Neop lastic process

N e p h rosis

75

Common Laboratory Studies with F i n d i ngs in the Diagnostic Paracentes i s Gram sta i n

S/A (g/d L}

G l ucose (mg/d L}

+/-

1.1

1 . 0 1 6 if p u ru lent

< 1 .0

>1 . 1 >1.1

1 .016

30 minutes) are associated with high rates of mortality.

C h a pter 1 5 • N e u ro l ogic a n d l ntracra n i a l Pressu re Mon itori ng

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Near-infrared spectroscopy: determines the relative concentrations of oxygenated and deoxygenated hemoglobin in brain tissue. 4. Neurochemical monitoring: microdialysis technique-recovered dialy­ sate can be analyzed for neurotransmitters or metabolic intermediates. G. Electrophysiologic monitoring. 3.

1. Used to detect potentially damaging cerebral hypoperfusion, isolated seizures, and status epilepticus and to define the depth or type of coma. 2. Has limited value as a precise diagnostic tool. 3. Quantitative EEG monitoring used to identify delayed ischemic deficits after subarachnoid hemorrhage, occasionally before clinical deteriora­ tion. 4. Sensory EPs, which include somatosensory evoked potentials (SSEPs) , brainstem auditory evoked potentials (BAEPs) , and visual evoked poten­ tials (VEPs) , can be used as qualitative threshold monitors to detect severe neural ischemia by evaluating characteristic waveforms to specific stimuli. 5. Obliteration of EPs occurs only under conditions of profound cerebral ischemia or mechanical trauma. EP monitoring is one of the most specific ways in which to assess neurologic integrity. 6. EPs are insensitive to less severe deterioration of cerebral or spinal cord oxygen availability and are modified by sedatives, narcotics, and anesthetics. SUGG ESTED R EADI N GS

Brain Trauma Foundation. American Association of Neurological Surgeons, Congress of Neurological Surgeons. Guidelines for the management of severe traumatic brain injury. ] Neurotrauma 2007;24(Suppl l ) : S l-S l 06.

Very useful guidelines for the management ofsevere head injury. Narotam PK, Morrison JF, Nathoo N. Brain tissue oxygen monitoring in traumatic brain injury and major trauma: outcome analysis of a brain tissue oxygen-directed therapy. J Neurosurg 2009; 1 1 1 (4) :672-682.

The authors describe their 5-year experience with brain tissue oxygen (PbO,) monitoring in trauma and TB! Smith M. Monitoring Intracranial Pressure in Traumatic Brain Injury. Anesth Analg 2008; 1 0 6 ( 1 ) :240-248.

Good review of neuromonitoring in TB!

P e r c uta n e o u s S u p ra p u b i c Cystosto my Anto n i o A ponte-Fe l i c i a n o , J o rge D . Ya rze bs k i , a n d Kev i n M . Dushay

I . ANATO MY

A. The urinary bladder is anterior and inferior to the peritoneal cavity and posterior to the pubic symphysis. 1. The bladder dome rises above the pubic symphysis when distended (Fig. 1 6 - 1 ) . B. The anterior-superior midline o f the external surface o f the urinary bladder is generally free of major blood vessels as well as the anterior abdominal wall. 1. Major arterial supply to anterior-superior surface is from internal iliac branches entering lateral walls of the bladder. 2. Venous drainage flows inferiorly and laterally to reach the internal iliac vems. I I . ALTERNATIVES TO PERCUTA N E O U S S U P RAP U B I C CYSTOSTOMY

A. Urethral catheterization. I l l . I N D ICAT I O N S

A. Unsuccessful urethral catheterization in the setting of 1. Acute or chronic urinary retention. 2. Need for accurate urinary output monitoring. 3. Prostatic hyperplasia, cancer, or prior prostate surgery. 4. Loss of or threat to skin integrity due to urinary incontinence. B. Inability to tolerate urethral catheter. 1. Following prostate or pelvic surgery, urethral pain, excoriation, necrosis, dementia/delirium causing patient to repeatedly remove catheter. C. Urethral disruption from pelvic trauma/fracture. D. Bladder drainage in the presence of severe infection: urethral, prostatic, or epididymal. E. Neurogenic bladder. F. Spinal cord injury patients. 1. May be easier for patient or caregiver. 2. May reduce frequency of urinary tract infections.

1 02

C h a pter 1 6 • Percutaneous S u pra p u b i c Cystostomy

I

1 03

Figure 1 6 - 1 . Ultrasound view of a distended bladder above the symphysis pubis.

IV. C O NTRAI N D I CATI O N S

A. Nonpalpable bladder, bowel loops over the anterior bladder wall o n sonographic evaluation. B. Previous lower abdominal surgery. C. Bladder carcinoma. D. Coagulopathy, anticoagulant, or antiplatelet medication administration is a relative contraindication. E. Lower abdominal wall infection. V. PRO C E D U R E

A. Obtain informed consent from the patient, health care proxy, or legal guard­ ian and perform a time-our and follow the universal precautions protocol. B. Equipment. 1. Two main types of devices. a. Catheter over introducer needle or obturaror. b. Sheath over needle or introducer, through which catheter is inserted. - . , C. Technique (see Video 1 8- 1 ) . 1 . Common procedure. a. Localize the bladder by palpation and/or by ultrasound ro evaluate, locate, and decrease the risk of trauma to adjacent structures. b. Familiarize yourself with the supplies; the kit may not include prep, lidocaine, catheter, or collection system. c. Follow aseptic precautions (mask, cap, eyeshields, gown, sterile gloves, full body drapes) .

1 04

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SECT I O N l • P R O C E D U R E S A N D T E C H N I Q U E S

d. Clip hair from the suprapubic area (if necessary) ; position the patient in Trendelenburg position; chlorhexidine prep, drape, lay out equip­ ment, and check catheter and the balloon (if present) for integrity. e. Inject 1 % lidocaine and make a midline skin wheal 2 to 4 cm above pubic symphysis; anesthetize tract perpendicular to body axis or angled 20 degrees caudally through subcutaneous tissue and rectus abdominis fascia using finder/introducer needle until bladder entry confirmed by aspiration of urine; then use scalpel to make stab wound along axis of needle. 2. Catheter over trocar technique. a. Withdraw finder needle; holding device near skin surface, insert it along prepared path until urine aspirated. b. Advance the device slightly and slide catheter into bladder while fixing trocar in place. c. Then remove trocar and secure catheter in position. 3. Seldinger technique. a. Remove syringe. b. Pass guidewire through introducer needle to indicator mark. c. Withdraw needle and pass the dilator(s) over the guidewire holding the dilator close to the skin until the introducer with preloaded cath­ eter or sheath can be inserted into bladder. d. Pinch the sheath as the guidewire and introducer are withdrawn to avoid urine leakage. e. Pass catheter through sheath until urine is obtained, then deploy the anchor/ balloon, and then withdraw and peel sheath away keeping catheter in place; secure catheter. 4. Catheter with internal fixation device. a. Gently withdraw until resistance felt. b. Advance the assembly 2 cm before securing to avoid bladder spasms. V I . POSTPRO C E D U R E C O N S I D E RATI O N S

A . Complications. 1. Hematuria-most common. 2. Bladder spasms also common. a . Can use any antispasmodic. i. Stop antispasmodics before suprapubic tube removal to avoid urinary retention. 3. Hemorrhage. 4. Bowel, rectal, uterine, or vaginal injury. 5. Bladder perforation. 6. Ureteral catheterization. 7. Catheter dislodgement or kinking. 8. Infection (i.e., cellulitis, deep wound infection, cystitis, pyelonephritis, and bacteremia) . 9. Postobstructive diuresis. 10. Hypotension. 1 1 . Retained catheter or guidewire fragment.

C h a pter 1 6 • Percutaneous S u pra p u b i c Cystostomy

1 05

SUGG ESTED R EAD I N GS

Aguilera PA, Choi T, Durham BA. Ultrasound-guided suprapubic cyscoscomy catheter place­ ment in the emergency department. ] Emerg Med 2004;26:3 1 9-32 1 .

Prospective case series ofpatients undergoing ultrasound-guided percutaneous suprapubic cystostomy catheter insertion with summary ofoutcomes. Allaparrhi S, Balaji KC, Ayvazian PJ. Percutaneous suprapubic cyscostomy. In: Irwin RS, Rippe JM, eds. Intensive care medicine, 7th ed. Philadelphia: Lippincott Williams & Wilkins, 2 0 1 1 : 1 50-1 54.

Excellent review of this subject. Harrison SC, Lawrence WT, Morley R, et al. British Association of Urological Surgeons' suprapubic catheter practice guidelines. B]U Int 2 0 1 1 ; 1 07 ( 1 ) :77-8 5 .

Current review on suprapubic catheterization. Klimberg I, Wehle M. Percutaneous placement of suprapubic cyscoscomy tube. Urology 1 98 5 ;26: 1 78- 1 79 .

Early briefdescription of use ofSeldinger technique fo r placement ofa suprapubic cystostomy. Lawrentschuk N, Lee D, Marriott P, et al. Suprapubic stab cyscosromy: a safer technique. Urology 2003;62:932-934.

Additional recommendation for ultrasound guidance in performing this procedure.

As p i rati o n of J o i nts H a rvey S . R e i c h

I . G E N E RAL P RI N C I PLES

A. Overview. 1 . Arthrocentesis involves the introduction of a needle into a joint space to remove synovial fluid. 2. It is an essential diagnostic technique for the evaluation of arthritis of unknown cause. 3. The presentation of conditions such as septic arthritis and crystalline arthritis may be similar, yet treatment may be different. 4. Arthrocentesis and synovial fluid analysis are important for accurate diagnosis. 5. Arthritis can involve a single joint (monoarthritis) or multiple joints (oligoarthritis) . I I . I N D ICAT I O N S

A. Principles. 1. Arthrocentesis is performed for both diagnostic and therapeutic reasons. 2. In the intensive care unit, arthrocentesis is most commonly performed to rule out septic arthritis in a patient with acute monoarthritis or oligoarthritis. 3. Before performing arthrocentesis, one must be certain that true joint space inflammation with effusion is present rather than a periarticular inflammarory process, such as bursitis, tendinitis, or cellulitis. 4. In the knee, the presence of an effusion may be confirmed by the bulge test or patella tap. a. Bulge test: Milk fluid from the suprapatellar pouch into the joint, slide the hand down the lateral aspect of the joint line, and watch for a bulge medial to the joint. b. Patellar tap: Apply pressure to the suprapatellar pouch while tapping the patella against the femur to determine if the patella is ballottable, which indicates an effusion. 5. Arthrocentesis with ultrasound guidance for evaluation of the joint and surrounding soft tissues can be performed at the bedside to assess for joint fluid, bursal fluid, or other soft tissue fluid collections such as an abscess. This can allow evaluation of bursal or soft tissue collections that may go undetected by blind aspiration.

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6. Arthrocentesis may also be used therapeutically, as in the serial aspiration of a septic joint for drainage and monitoring of the response to treatment. 7. Arthrocentesis allows for therapeutic injection of corticosteroid prepara­ tions into the joint space for treatment of various forms of inflammatory and noninflammatory arthritis. B. Etiology of inflammatory arthritis. 1. Rheumatoid arthritis. 2. Spondyloarthropathies. a. Psoriatic arthritis. b. Seronegative spondyloarthropathy. c. Ankylosing spondylitis. d. Ulcerative colitis/regional enteritis. 3. Crystal-induced arthritis. a. Monosodium urate (gout) . b. Calcium pyrophosphate dehydrate (pseudogour) . c. Hydroxyapatite. 4. Infectious arthritis. a. Bacterial. b. Mycobacterial. c. Fungal. 5. Connective tissue diseases. a. Systemic lupus erythematosus. b. Vasculitis. c. Scleroderma. d. Polymyositis. 6. Hypersensitivity. a. Serum sickness. C. Etiology of noninflammatory arthritis. 1. Osteoarthritis. 2. Trauma/internal derangement. 3. Avascular necrosis. 4. Hemarthrosis. 5. Malignancy. 6. Benign tumors. a. Osteochondroma. b. Pigmented villonodular synovitis. D. Contraindications. 1. Absolute contraindications to arthrocentesis include infection of the overlying skin or periarticular structures and severe coagulopathy. 2. If septic arthritis is suspected in the presence of severe coagulopathy, efforts to correct the bleeding diathesis should be made before joint aspiration. 3. Although known bacteremia is a contraindication to arthrocente­ sis given the potential for joint space seeding, j oint aspiration is

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SECT I O N 1 • p R 0 c E D u R E s A N D T E c H N I Q u E s

nonetheless indicated if septic arthritis is the presumed source of the bacteremia. 4. Articular damage and instability constitute relative contraindications to arthrocentesis. I l l . PROC E D U R E

A . Arthrocentesis equipment. 1 . Skin preparation. a. Two percent chlorhexidine and seventy percent isopropyl combination antiseptic or equivalent (ten percent povidone-iodine solution should be used only if the patient has a sensitivity to chlorhexidine) . 2. Local anesthesia. a. 1 % Lidocaine; 25-gauge, 1 -in. needle; 22-gauge, 1 . 5-in. needle; and 5-mL syringe. b. Sterile sponge/ cloth. 3. Arthrocentesis. a. Sterile gloves. b. 1 0- to 60-mL syringe (depending on size of effusion) . c. 1 8- to 20-gauge, 1 . 5-in. needle. d. Sterile sponge/ cloth. e. Adhesive bandage (Band-Aid) . 4. Collection. a. Fifteen milliliters in an anticoagulated tube. b. Sterile tubes for routine Gram stain and cultures. c. Slide, cover slip. B. Technique. 1. Joint aspiration requires knowledge of the relevant joint and periarticular anatomy and strict adherence to aseptic technique. 2. Joints other than the knee should be aspirated by an appropriate specialist. 3. Aspiration of some joints, such as the hip or sacroiliac joints, may require fluoroscopic, ultrasound, or computed tomographic guidance. 4. Confirm the presence of an effusion with the patient supine and the knee extended. 5. The superior and inferior borders of the patella are landmarks for needle placement. 6. Entry should be halfway between these borders j ust inferior to the undersurface of the patella, from either a medial or lateral approach, the former being more commonly used and preferable with small effusions. 7. Cleanse the area with a chlorhexidine-isopropyl alcohol antiseptic solu­ tion. Allow the area to dry. 8. Perform a time-out confirming the correct side and follow the universal precautions protocol.

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9. Local anesthesia can be achieved with infiltration of local anesthetic solution (e.g. , 1 % lidocaine) into the subcutaneous and deeper tissues. 10. To enter the knee joint, use an 1 8- to 20-gauge, 1 . 5-in. needle with a sterile 20- to 60-mL syringe. 1 1 . Use a quick thrust through skin and capsule. 12. Avoid periosteal bone to minimize pain. 13. Aspirate fluid to fill the syringe. If the fluid appears purulent or hemorrhagic, try to tap the joint dry. 14. Drainage of large effusions may require additional syringes, which may be exchanged for the original one while leaving the needle in place. 15. When the fluid has been obtained, the needle is removed, and pressure is applied to the puncture site with sterile gauze. 16. Apply an adhesive bandage after cleaning the area with alcohol. Apply prolonged pressure if the patient has a bleeding diathesis of any type. 17. Document the amount, color, clarity, and viscosity of the fluid. Send the fluid for cell count with differential, Gram stain, and routine culture; cultures for gonococcus, mycobacteria, and fungi, if indicated; and polarized microscopic examination for crystal analysis. 18. Anticoagulated tubes are needed for accurate assessment of fluid for cell count and crystal analysis. 19. Other tests, including glucose and complement levels, are generally not helpful. C. Synovial fluid analysis (Table 1 7- 1 ) . 1 . Synovial fluid i s divided into noninflammatory versus inflammatory types based on the total nucleated cell count. 2. A white blood cell (WBC) count of2,000/mm3 defines an inflammatory fluid.

liJ:i!ifli

'

J o i nt F l u i d Characteristics

Normal

N o n i n f l a m m atory

I nflam matory

Septic

Color

Clear

Ye l low

Yel l ow or opalescent

Cla rity Viscos ity M uc i n clot W B C/m m 3

Tra n s pa re nt Ve ry h igh Firm 1 00 , 000 >75 U s u a l ly positive

1 1 0

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SECT I O N 1 • p R 0 c E D u R E s A N D T E c H N I Q u E s

D. Color. 1. Normal synovial fluid is colorless. 2. Noninflammatory and inflammatory joint fluid has a yellow hue. 3. Septic effusions often appear whitish to frankly purulent. 4. Hemorrhagic effusions appear red or brown. 5. A repeated aspiration from an alternate site may be required if there is a question of a traumatic tap. 6. The hematocrit in a hemorrhagic effusion is typically lower than that of a peripheral sample and is equal to it in the case of traumatic tap. E. Clarity. 1 . The clarity of the synovial fluid depends on the amount of cellular or particulate matter within it. 2. On the basis of how well, if at all, black print on a white background can be read through a glass tube filled with synovial fluid, the fluid is categorized as being transparent, translucent, or opaque. F.

Viscosity. 1 . The viscosity of synovial fluid is a measure of the hyaluronic acid content. 2. Degradative enzymes such as hyaluronidase are produced in inflamma­ tory conditions resulting in a rhinner, less viscous fluid. 3. The string sign is a bedside measure of viscosity. 4. Normal synovial fluid forms at least a 6-cm continuous string when a drop of fluid is allowed to fall from the needle or syringe. 5. Inflammatory fluid drips and will not form a string. 6. The mucin clot, another measure of viscosity, is a test performed by mixing several drops of synovial fluid in 5% acetic acid. 7. A good, tenacious mucin clot forms with normal, noninflammatory fluid but not with an inflammatory sample.

G. Cell count and differential. 1. The cell count should be obtained as soon as possible after arthrocentesis to avoid a falsely low WBC count caused by delayed analysis. 2. Viscous fluid with much debris may give erroneous results with automated counters, thereby making a manual count more accurate in these circumstances. 3. The total WBC count and polymorphonuclear (PMN) cell count increase with infection and inflammation. 4. Septic fluid typically has a differential of > 75% PMN cells. H.

Crystals. 1 . As with the cell count, crystal analysis should be performed as soon as possible after arthrocentesis for optimal diagnostic yield. 2. Fluid is examined for crystals using a compensated polarized light microscope. 3. The presence of intracellular monosodium urate or calcium pyrophos­ phate dihydrate (CPPD) crystals confirms the diagnosis of gout or pseudogout, respectively.

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4. Monosodium urate crystals are usually needle shaped, are nega­ tively birefringent, and appear yellow when oriented parallel to the compensator axis. 5. CPPD crystals typically are smaller and rhomboid, weakly positively birefringent, and appear blue when parallel to the plan of reference. 6. If the fluid cannot be examined immediately, it should be refrigerated to preserve the crystals. 7. Even when crystals are found in a sample, infection must be considered, because crystals can occur concomitantly with a septic joint. Gram stain and culture. 1. The Gram stain is performed as with other body fluids. 2. Synovial fluid should routinely be cultured for aerobic and anaer­ obic organisms. Additional cultures for fungi, mycobacteria, and disseminated gonorrhea should be sent if clinically indicated.

IV. POSTPRO C E D U R E C O N S I D E RATI O N S

A. Complications. 1. The major complications of arthrocentesis are bleeding and iatrogeni­ cally induced infection. 2. These complications are exceedingly rare with strict adherence to aseptic technique and with correction of significant coagulopathy before joint aspiration. 3. Direct cartilaginous damage by the needle is difficult to quantitate and likely is minimized by avoidance of excessive needle movement or com­ plete drainage of the joint, as well as avoiding advancement of the needle any deeper than needed to obtain fluid. SUGG ESTED R EAD I N GS

De Zordo T. Ultrasound-guided procedures. Ultrasound Clin 2 0 1 2;7(4) :537-5 50.

A comprehensive review ofthe use ofultrasound in joint aspiration andjoint injections. Firestein GS, Budd RC, Gabriel SE, et al. Kelley textbook of rheumarology, 9th ed. Philadelphia: WB Saunders, 20 1 2 .

A standard, comprehensive text of rheumatolagy. Hollander JL, Jessar RA, McCarty DJ. Synovianalysis: an aid in arthritis diagnosis. Bull Rheum Dis 1 96 1 ; 1 2:263.

Classic article on the categorization ofdifferent types ofarthritis. Horowitz DL, Katzap E, Horowitz S, et al. Approach to septic arthritis. Am Fam Physician 20 1 1 ;84(6) :653-660.

An up-to-date review of the diagnosis and management ofseptic arthritis.

An esth es i a fo r B e ds i d e P ro c e d u res Natha n a e l A . S later a n d J . Matt h i a s Wa lz

I . G E N E RAL P RI N C I PLES

A. Managing pain in critical illness. 1. Anesthesia for bedside procedures in the intensive care unit (ICU) 1s accomplished with total intravenous anesthesia (TIVA) . 2. Selecting the proper dose of an analgesic to administer is challenging because of a. Difficulty in assessing the effectiveness of pain relief (delirium, obrundation, endorracheal intubation) . b. Pharmacokinetic (PK) differences between critically ill and other patients. c. Physiologic changes associated with aging (decrease in lean body mass, increase in volume of distribution of lipid-soluble drugs, decrease in drug clearance rates, increased sensitivity to hypnotics and analgesics) . B. PK considerations. 1. PK behavior in critically ill patients is unlike that in normal subjects for the following reasons (see also Dershwitz 20 1 2 , in Suggested Readings, for more derail) . a. ICU patients frequently have renal and/or hepatic dysfunction; therefore, drug metabolism and elimination may be significantly impaired. b. Hypoalbuminemia, common in critical illness, can decrease protein binding and increase free (active) drug concentration. II. I N D ICAT I O N S

A. Selection of agent. 1 . Procedures performed in the ICU can be differentiated according to their associated levels of discomfort. a. Mild to moderately uncomfortable (esophagogasrroscopy, paracentesis) . b. Moderately to severely uncomfortable (endotracheal intubation, tho­ racostomy, flexible bronchoscopy) . c. Extremely painful (rigid bronchoscopy, orthopedic manipulations, tracheotomy) . 2. Specific disease states should be considered so that safety and effectiveness are maximized. a. Head trauma. 1 1 2

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i. Effective yet brief anesthesia is desirable so that the capacity to assess neurologic status is not lost for extended periods. ii. The technique should not adversely affect cerebral perfusion pressure. iii. If the effects of the medications dissipate too rapidly, undesirable episodes of agitation and increased intracranial pressure (ICP) may occur. b. Coronary artery disease: Sufficient analgesia is necessary during and after invasive procedures to minimize tachycardia (which is a major determinant of ischemia) and reduce plasma catecholamine and stress hormone levels. c. Renal or hepatic failure. i. The risk of an adverse drug reaction is at least three times higher in patients with azotemia compared to those with normal renal function. ii. Liver failure alters the volume of distribution of many drugs by impairing synthesis of albumin and Cl.1 -acid glycoprotein. iii. Reductions in hepatic blood flow and hepatic enzyme activity decrease drug clearance rates. I l l . PRO C E D U R E

A. Hypnotics: The characteristics o f commonly used hypnotics are listed in Table 1 8- 1 . 1 . Propofol. a. Propofol is an extremely popular hypnotic agent for the following reasons. i. It is readily titratable and has more rapid onset and offset kinetics than midazolam. ii. The rapid recovery of neurologic status makes propofol a good sedative in ICU patients, especially those with head trauma. iii. Spontaneously breathing patients anesthetized with propofol may maintain normal end-tidal carbon dioxide values during minor surgical procedures. b. Maintenance infusion rates of 1 00 to 200 µg/kg/min are adequate in younger subjects, which should be reduced by 20% to 50% in elderly individuals. c. Adverse effects of propofol administration include i. Hypotension from depressed ventricular systolic function and/or decreased afrerload. ii. In patients with coronary artery disease, propofol administra­ tion may be associated with a reduction in coronary perfusion pressure. iii. The emulsion used as the vehicle for propofol supports bacte­ rial growth; iatrogenic contamination leading to septic shock is possible. iv. Hyperlipidemia with prolonged infusions can occur, particularly in infants and small children.

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TA B L E 1 8 - 1

Characteristics of I ntravenous Hypnotic Age nts

Propofol B o l u s dose ( m g/kg) O nset D u ration Ca rd iovasc u l a r effects R es p i ratory effects A n a lgesia A m nesia

1-2

0.2--0. 3

Etomidate

Keta m i ne

Fast S h o rt

Fast S h ort

None

Fast I ntermed iate

.J, None M i ld

.J,

1-2

M i dazolam

Dexmedeto m i d i ne

Intermed iate

0 . 5-1 µg/kg over 10 m i n Intermed iate

t

I ntermed iate Minimal

S h o rt M o d e rate .J,

.J,

M i n imal

.J,

Minimal

None M i ld

Profound Profound

Profound

0 . 05-0 . 1

None

M i n imal

Profound

L, decrease; 1', i n c rease. The l i sted doses s h o u l d be red u ced 50% i n elderly patients. Entries i n bold type i n d i cate noteworthy d ifferences a mong the d rugs.

2. Etomidate. a. Etomidate has onset and offset PK characteristics similar to those of propofol and lacks significant effects on myocardial contracriliry (even in the setting of cardiomyopathy) . b. Etomidate depresses cerebral oxygen metabolism and blood flow in a dose-dependent manner without changing rhe intracranial volume­ pressure relationship. c. Etomidate is particularly useful in patients with i. Hypovolemia. ii. Multiple trauma victims with closed head injury. iii. Patients with low ejection fraction, severe aortic srenosis, left main coronary artery disease, or severe cerebrovascular disease. d. Adrenal suppression can occur. i. Prolonged infusion is nor recommended because of adrenocorti­ cal suppression. ii. A single induction dose of etomidare may increase mortaliry in patients with established or evolving septic shock. 3. Ketamine. a. Keramine is unique among the hypnotic agents in that it has analge­ sic, sedative, and amnesric effects. b. Keramine has a slower onset and offset as compared to propofol or eromidare following intravenous (IV) infusion, and stimulates the cardiovascular system (i.e., raises heart rate and blood pressure by direct srimularion of rhe central nervous system [CNS] ) . c . Keramine may b e safer than other hypnotics o r opioids i n nonin­ rubated patients because it depresses airway reflexes and respiratory drive to a lesser degree. d. In the usual dosage, ketamine decreases airway resistance.

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e. The administration of ketamine can be associated with disorien­ tation, sensory and perceptual illusions, and vivid dreams; these effects have been termed emergence phenomena. To avoid emer­ gence phenomena after ketamine administration, pretreatment or concurrent treatment with a benzodiazepine or propofol should be considered. f. The combination of ketamine with a benzodiazepines and/or an opioid is useful in patients with coronary artery disease to avoid myocardial ischemia (the use of ketamine alone increases myocardial oxygen consumption) . g. Ketamine is relatively contraindicated in patients with increased ICP. 4. Midazolam. a. Administration of midazolam produces anxiolysis, amnesia, and relaxation of skeletal muscle (ideally suited for brief, relatively pain­ less procedures as well as for prolonged sedation) . b. Midazolam is highly (95%) protein bound, and recovery is prolonged in obese and elderly patients and after continuous infusion because it accumulates significantly. c. In patients with renal failure, active conjugated metabolites of midazolam may accumulate and delay recovery. d. Midazolam (0. 1 5 mg/kg IV) causes respiratory depression and blunts the ventilatory response to hypoxia. e. Midazolam has a stable cardiovascular profile and causes dose-dependent reductions in cerebral metabolic rate and cerebral blood flow. B. Opioids. 1. Opioids blunt pain by a. Inhibiting pain processing by the neurons of the dorsal horn of the spinal cord. b. Decreasing transmission of pain by activating descending inhibitory pathways in the brainstem. c. Altering the emotional response to pain by actions on the limbic cortex. 2. Morphine. a. Morphine is an agonise at µ, K, and 8 receptors. b. Morphine causes significant histamine release after IV bolus injection. c. Adverse effects of morphine include i. Gastrointestinal. (a) Constipation, nausea, and/or vomiting. (b) Reduced gastric emptying and bowel motility. ii. Cardiovascular: hypotension, especially if it is given rapidly (i.e., 5 to 1 0 mg/min) . iii. Respiratory. (a) Morphine decreases the ventilatory response to C0 2 and hypoxia. (b) Exaggerated ventilatory depression in patients with renal fail­ ure is possible because of the active metabolite, morphine-6glucuronide.

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S E CT I O N 1 • p R 0 c E D u R E s A N D T E c H N I Q u E s

3. Fentanyl and related drugs. a. Fentanyl, alfentanil, sufentanil, and remifentanil enter and leave the CNS much more rapidly than morphine (much faster onset of effect after IV administration) . b. They are selective µ-opioid receptors agonists (the only significant difference among these agents is their PK behavior) . c. Fentanyl may be useful when given by intermittent bolus injection (50 to 1 00 µg) , but when given by infusion its duration becomes prolonged. d. Remifentanil owes its extremely short duration to rapid metabolism by tissue esterases (primarily in skeletal muscle) ; its PK behavior is unchanged in the presence of severe hepatic or renal failure. e. Sufentanil infusion for TIVA may be initiated with a 0 . 5 to 1 . 5 µg/kg bolus followed by an infusion at 0.0 1 to 0.03 µg/kg/min. f. Remifentanil infusion for TIVA may be initiated with a 0.5 to 1 µg/kg bolus followed by an infusion at 0.25 to 1 µg/kg/min. g. Adverse effects can include hypotension when administered as a bolus, increases in ICP and adverse effects on cerebral perfusion pressure (fen­ tanyl and sufentanil) , and chest wall rigidity with large doses (fentanyl) . C. Dexmedetomidine. 1. Dexmedetomidine is an a-2 agonist, which provides sedation and sym­ patholysis and can be used as an analgesic adjunct for invasive procedures in the ICU. The drug is FDA approved for short-term administration (96 hours) as a continuous infusion of 0.2 to 0.7 µg/kg/h. a. Dexmedetomidine is administered as follows. i. If a bolus dose is required, the dose range is 0 . 5 to 1 µg/kg given over 1 0 minutes, followed by an infusion of 0.2 to 0.7 µg/kg/h. ii. Higher (off-label) doses up to 1 .4 µg/kg/h (some up to 2 . 5 µg/ kg/h) have been reported in the literature to be associated with increased risk of adverse effects such as hypotension and brady­ cardia in the higher dose range. 2. Potential uses in the ICU include sedation for bronchoscopy, awake fiberoptic intubation, and ameliorating agitation due to alcohol with­ drawal or head injury. 3. Dexmedetomidine produces little respiratory depression but can cause bradycardia and hypotension. D. Neuromuscular blocking agents. 1. Succinylcholine. a. Succinylcholine 1 mg/kg IV will result in excellent intubating condi­ tions in less than a minute. It is the drug of choice when the airway must be secured quickly (full stomach or symptomatic gastroesopha­ geal reflux) unless there are contraindications. b. Succinylcholine may trigger malignant hyperthermia in genetically susceptible persons. c. Succinylcholine may cause a malignant rise in the extracellular potas­ sium concentration in patients with major acute burns, upper or lower motor neuron lesions, prolonged immobility, massive crush injuries, and various myopathies.

C h a pter 18 • Anesthesia for Beds i d e Proced u res 2.

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Nondepolarizing neuromuscular blocking (NMB) agents. a. Vecuronium (0. 1 mg/kg) , rocuronium (0.6 to 1 .2 mg/kg) , and cisatracurium (0 . 1 to 0 . 2 mg/kg) are used when succinylcholine is contraindicated and are essentially devoid of cardiovascular effects. b. NMB agents may cause muscle weakness persisting for months afterward: Risk factors include concomitant glucocorticoid therapy or prolonged NMB.

SUGG ESTED R EADI N GS

Bailey JM. Context-sensitive half-times: what are they and how valuable are they in anaesthe­ siology? Clin Pharmacokinet 2002;4 I ( 1 1 ) : 79 3-799.

A review of the context-sensitive halftime. Barr J, Egan TD, Sandoval NF, et al. Propofol dosing regimens for ICU sedation based upon an integrated pharmacokinetic-pharmacodynamic model. Anesthesiology 200 I ;95 (2) :324-333.

An excellent example of theory guiding practice in the use oflong-term infosions (weeks) ofpropofol in ICU patients.

Chan CM, Mitchell LA, Shorr FA, Etomidate is associated with mortality and adrenal insuf­ ficiency in sepsis: a meta-analysis. Grit Care Med 2 0 1 2;40:2945-2953.

A meta-analysis that assess the quality and conclusions of the available data on use of etomidate for rapid-sequence intubation in septic patients. Dershwitz M. Anesthesia for bedside procedures. In: Irwin RS, Rippe JM, eds. Irwin and Rippe's intensive care medicine, 7th ed. Philadelphia: Lippincott Williams & Wilkins, 2012.

Detailed pharmacokinetic considerations. Dershwitz M, Rosow CE. Remifentanil: an opioid metabolized by esterases. Exp Opin Invest Drugs 1 996;5: 1 36 ! .

A comprehensive review ofthe pharmacology of remifentanil. Shafer SL, Varvel JR. Pharmacokinetics, pharmacodynamics, and rational opioid selection. Anesthesiology 1 9 9 1 ;74:53.

Explains why PK half lives do not describe the overall kinetic behavior oflipophilic medications.

R o ut i n e a n d Ca rd i o re s p i rato ry M o n ito r i n g i n th e I nte n s ive C a re U n it G isela I . B a n a u c h a n d Eric C u cc h i I . T E M P E RATU R E

A . General principles. 1. Estimate core temperature that is independent of ambient fluctuations because of hypothalamic regulation. B. Indications. 1. Indications are extensive and include infection, temperature dysregulation syndromes (autonomic dysfunction, neuroleptic malignant syndrome, malignant hyperthermia, endocrine syndromes), certain toxidromes (anti­ cholinergic, serotonin syndrome), and environmental causes of tempera­ ture dysregulation. C. Procedure. 1. Measure at least every 4 hours, continuously when 39°C, or temperature-altering interventions (cooling blanket, active rewarming) are applied. Probes in the mouth, axilla, auditory canal, or on the skin overlying the temporal artery allow intermittent monitoring. Probes in the pulmo­ nary artery, rectum, esophagus, or bladder allow continuous monitoring. D. Postprocedure considerations. 1. Rectal site can transmit resistant enteral bacteria. Axillary temperature is considered 1 °F cooler than core temperature. I I . ARTE RIAL PRESS U R E

A. General principles. 1. Assure adequate perfusion pressure for sufficient substrate/oxygen deliv­ ery and metabolic waste/carbon dioxide (C0 2) removal. a. Arterial catheter. i. Allows continuous monitoring. A fluid column continuously transmits arterial pressure to a transducer, where it is converted into electrical signals through diaphragm deformation-induced resistance changes in a Wheatstone bridge. b. Automated oscillometric monitor. i. Allows intermittent monitoring. Analyzes magnitude/shape of arterial pressure oscillations with intermittent, controlled, slow blood pressure cuff inflation/ deflation. 1 1 8

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1 1 9

B. Indications. 1. Arterial catheter. a. Indications for continuous monitoring are patients who are on vasoactive medications or who require frequent blood gas analyses. 2. Automated oscillometric monitor. a. Indications for intermittent monitoring are patients at risk for hypo­ or hypertension, which includes all patients admitted to an intensive care unit. C. Procedure. 1. Arterial catheter. a. Seldinger technique is used for insertions at the radial, femoral, and axillary sites. Once the catheter is placed, it is connected to the fluid column that is in specialized pressure tubing. The system is zeroed at the level of the right atrium. 2. Automated oscillometric monitor. a. Cuff bladder width should equal 40%, and the length should equal/ exceed 60% of extremity circumference. The cuff bladder is inflated until the distal pulse is obliterated. Air is slowly released from the cuff. When systolic pressure is reached, blood flow begins and is detected by the monitor as arterial wall vibrations. Arterial vibrations stop when diastolic pressure is reached. D. Postprocedure considerations. 1. Arterial catheter. a. Complications include distal vessel occlusion, hemorrhage, and infection. b. Erroneously high pressures from small air bubbles/heart rates close to transducer system's resonant frequency (overshoot) . c. Erroneously low pressures from large air bubbles and catheter throm­ bus/heart rates above transducer system's resonant frequency (damping) . 2. Automated oscillometric monitor. a. Intermittent measurements do not reflect rapidly changing hemodynamics. b. Inadequately sized cuffs (width/length) overestimate. c. Poor correlation with intra-arterial values at pressure extremes. d. Complications include distal limb ischemia and venous stasis with prolonged/frequent cuff inflation or deflation failure; do not perform on limbs with compromised arterial/venous/lymphatic circulation. e. Mean arterial pressure is a more reliable indicator of tissue perfusion than systolic and diastolic pressures. I l l . ELECTROCA R D I O G RAPHY

A. General principles. 1. Monitor endogenous cardiac electrical impulses to detect malignant arrhythmias or changes in electrical morphology as a result of structural

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S E CT I O N 1 • P R 0 C E D U R E S A N D T E C H N I Q U E S

damage to the myocardial tissue. Computerized arrhythmia detection is based on heart rate variability, electrocardiogram (ECG) intervals/ segment durations, and ECG morphology. B. Indications. 1. All critically ill patients should have an ECG as a baseline upon admission. Other indications are a high likelihood of malignant arrhythmia and/or cardiac ischemia. C. Postprocedure considerations. 1. Artifacts arise from muscle activity or poor transmission (obesity, poor skin preparation, improperly positioned electrodes) . IV. RES P I RATORY M O N ITO R I N G

A. General principles. 1. Assure adequate gas exchange. 2. Impedance pneumography. a. Measures thoracic impedance changes due to respiration-induced alterations in thoracic geometry and thus quantifies respiratory rate. 3. Mechanical ventilator. a. Measures inhaled/exhaled airflow versus time; derives respiratory rates, tidal volumes, and minute ventilation. 4. Pulse oximetry. a. Uses photoplethysmography to measure the difference in light absorption spectra of oxygenated/deoxygenated hemoglobin across pulsatile tissue bed over time; calculates absorption ratio change over time, which estimates arterial oxygen saturation. B. Postprocedure considerations. 1. Impedance pneumography. a. Imprecise at respiratory rate extremes and with physical motion. 2. Mechanical ventilator. a. Moisture on pneumotachograph overestimates flow/volume. b. Circuit leaks over- or underestimate respiratory rate and flow/ volume. 3. Pulse oximetry. a. Erroneous measurements from poor tissue perfusion (low cardiac output [CO] , high systemic vascular resistance, hypothermia, vasoconstrictors, hypovolemia, hypotension) . b. Falsely low measurements from methylene blue and other intravascular dyes. c. Falsely elevated measurements from carboxy/methemoglobinemia. d. Falsely low measurements in severe tricuspid insufficiency (venous regurgitation into capillaries results in pulsatile venous flow) . e. Forehead probes less reliable because they may include venous signals; earlobe probes less prone to artifact.

C h a pter 1 9 • R o u t i n e a n d Card i oresp i ratory M o n itoring i n the I ntensive Care U n it

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V. CAP N O G RAPHY

A. General principles. 1. Measures and displays expired partial pressure of carbon dioxide (ETC0 2) by infrared absorbance or mass spectrometry. B. Indications. 1. Verification of artificial airway placement. 2. Detection of extubation. 3. Detection return of spontaneous circulation after cardiac arrest. C. Procedure. 1. Airway gases can be sampled by sidestream or mainstream techniques during mechanical ventilation. D. Postprocedure considerations. 1. Changes in dead space will affect end-tidal PC0 2 (last 20% of exhalation) . 2. Changes on the shape of the waveform can indicate resistance to airflow (e.g. , bronchospasm) , cardiogenic oscillations, or attempts at spontane­ ous breathing during controlled mechanical ventilation. V I . CARDIAC O UTPUT M EAS U R E M E N T

A. Thermodilurion (see Chapter 4) . B. Esophageal Doppler (Fig. 1 9 - 1 ) . 1 . General principles. a. Doppler probe placed in esophagus uses Doppler shift principle to measure velocity of blood in descending aorta. b. Multiplying the cross-sectional area of the aorta by the velocity will yield flow (stroke volume) . i. Algorithms exist for estimating cross-sectional aortic area. ii. Other probes have an ultrasound, which can be used to measure the area. c. Flow time corrected (FT ) correlates with preload. d. Peak velocity correlates with contractility. 2. Indications: monitoring of hemodynamic variables including CO m unstable patients. 3. Procedure. a. Insert probe either through mouth or nose and into the esophagus with the probe directed posteriorly toward the descending aorta. b. Position the probe to obtain the best waveform on the monitor (Fig. 1 9- 1 ) . 4 . Postprocedure considerations. a. Probe may be left in place for extended period of time. b. Probe will likely need to be repositioned or refocused between measurement to obtain optimal waveform.

1 22

I

S E CT I O N 1 • p R 0 c E D u R E s A N D T E c H N I Q u E s

+---+ Stroke distance (cm)

� Flow time (seconds)

M i n ute distance (stroke distance

x

heart rate )

Figure 1 9- 1 . Esophageal Doppler flow-velocity waveform. (Adapted from Marik PE. Pulmonary artery catheterization and esophageal Doppler monitoring in the ICU. Chest 1 999; 1 1 6: 1 085- 1 0 9 1 .)

C. Pulse contour analysis. 1. General principles. a. Uses an algorithm and invasively measured arterial blood pressure to derive a continuous CO. b. All but one system requires CO calibration with either a trans­ p ulmonary thermodilution technique or lithium dilution technique. c. Changes in arterial impedance will necessitate a repeat calibration. 2. Indications: monitoring of hemodynamic variables including CO in unstable patients. 3. Procedure. a. Insertion of radial or femoral arterial catheter (see Chapter 3) and central venous catheter (CVC, see Chapter 2) . b. The arterial catheter is attached to the proprietary monitoring equipment that will measure the CO. c. The CVC is required for transpulmonary CO measurement (which is needed for the calibration) . 4. Postprocedure considerations. a. Stroke volume variation can be used to assess fluid responsiveness in mechanically ventilated patients but only when tidal volumes of >8 ml/kg are used. b. Accuracy of systems that do not use CO calibration has been brought into question. c. Accuracy of all of these systems during large changes in blood pressure and use of vasoconstrictors is questionable.

C h a pter 1 9 • R o u t i n e a n d Card i oresp i ratory M o n itoring i n the I ntensive Care U n it

1 23

D. Partial carbon dioxide rebreathing method. 1. General principles. a. Use of a device that allows for partial rebreathing of exhaled gas. b. CO is calculated by changes in carbon dioxide excretion and values of end-tidal carbon dioxide during normal and partial rebreathing periods. 2. Indications: monitoring of CO in unstable patients. 3. Procedure. a. Requires intubated patient. b. Apparatus is attached to the endotracheal tube and airway circuit of the patient. 4. Postprocedure considerations. a. Accuracy affected by tidal volume. b. Unclear if it is safe to use in patients with hypercapnia or elevated intracranial pressure. E. Bioreactance. 1 . General principles. a. Measures bioreactance or phase shift in voltage across the thorax. b. Phase shifts occur due to pulsatile flow (mostly from the aorta) . c. Entirely noninvasive. 2. Indications: monitoring of CO in unstable patients. 3. Procedure. a. Four dual electrodes are placed on the chest-two on each side-and attached to monitor. b. Transmits high-frequency sine waves and measures voltage changes. 4. Postprocedure considerations. a. Electrocaurery interferes with the signal. b. Accurate with ventricular and atrial arrhythmias. c. Compares favorably with thermodilution determined CO. VII. U R I N E OUTPUT M O N ITO R I N G

A. General principles. 1. Reflects kidney perfusion and thus is often used as marker of global tissue perfusion. B. Indications. 1. Assess/monitor for decreased tissue perfusion and/or acute kidney injury in critically ill patients including those with severe burn injuries, shock states, or hemorrhage. C. Procedure. 1. Continuous monitoring requires bladder catheterization. 2. Intermittent monitoring requires urine collection. D. Postprocedure considerations. 1. Indwelling bladder catheters confer a significant risk of infection as well as of lower urinary tract trauma.

1 24

S E CT I O N 1 • P R 0 C E D U R E S A N D T E C H N I Q U E S

S U G G ESTED R EAD I NGS

Balaji S, Ellenby M, McNames J, et al. Update on intensive care ECG and cardiac event monitoring. Cardiac Electrophysiol Rev 2002;6: 1 90-1 95.

Concise review of recent developments in ECG monitoring, including computer-assisted measurements such as signal averaging and analysis of heart rate variability. Bendjelid K. The pulse oximecry plethysmographic curve revisited. Curr opin Crit Care

2008; l 4;348-353. An updated review ofinterpretation ofplethysmographic signals.

Lakhal K, Macq C, Ehrmann S, et al. Noninvasive monitoring of blood pressure in the critically ill: Reliability according co the cuff site (arm, thigh, or ankle) . Crit Care

Med 2 0 1 2;4: 1 207. A synopsis of blood pressure measurement in critically ill adults. Magder S . Bench-co-bedside review: An approach co hemodynamic monitoring-Guyton at the bedside. Crit Care 2 0 1 2 ; 1 6:236.

This review discusses the various physiologic processes that can lead to hypotension in the critically ill patient, and discusses how information from minimally invasive cardiac output measurements can be integrated into a pathophysiologic approach to therapy. Marik PE. Noninvasive cardiac output monitors: A state of the art review. J Cardiothorac Vase

Anesth 20 1 3;27: 1 2 1 - 1 34. Excellent, up-to-date review ofthe noninvasive cardiac output monitors with algorithms for fluid, inotropic, and vasopressor management. McMorrow RC, Mythen MG. Pulse oximecry. Curr Opin Crit Care 2006; 1 2:269-27 1 .

Review of both the basic principles underlying pulse oximetry, as well as recent developments in the field, and clinical applications for the ICU physician. Ornaco JP. Hemodynamic monitoring during CPR. Ann Emerg Med 1 993;23 :289.

Discusses how various noninvasive devices can provide information about the quality and success ofongoing CPR. Also reviews how end-tidal C02 measurements can guide therapy in ICU patients who are not experiencing cardiac arrest. Pinsky MR. Hemodynamic evaluation and monitoring in the ICU. Chest 2007; 1 32:2020-2029.

Excellent review of recently developed, monitoring-driven treatment protocols for septic shock.

E c h o c a rd i og ra p hy i n th e I nte n s ive C a re U n i t De n n is A. Tighe, D i n es h C h a n d o k 1 , a n d G e ra rd P . Au rige m ma

I . G E N E RAL P R I N C I PLES

A. Echocardiography is frequently performed in critically ill patients. The major advantages of this diagnostic technique are its portability, lack of patient exposure to ionizing radiation and iodinated contrast, ability to provide real-time structural and functional (hemodynamic) information, and suitability for serial performance. B. Structural and functional information is provided by transmmmg ultrasound (US) energy (2 to 10 MHz) from the echocardiograph and receiving signals returning from the cardiac structures to create real-time two- (2D) and three-dimensional (3D) images of the heart. C. Using the Doppler principle, reflected US energy is used to determine the velocity and direction of flowing blood in the heart and great vessels provid­ ing information about the hemodynamic effects of stenotic and regurgitant valve lesions. In addition, Doppler echocardiography provides information about filling pressures, stroke volumes, and pulmonary artery systolic pres­ sures. Peak instantaneous pressure gradients (P) are estimated by measuring the peak flow velocity (V) and application of the modified Bernoulli equa­ tion, P 4 V2 . Color-flow Doppler provides a spatial velocity map of abnor­ mal flow within the heart and great vessels; it is most useful to estimate the degree of valvular regurgitation and identifying turbulent blood flow. Tissue Doppler imaging adds to the ability to estimate left heart filling pressures. D. A complete examination includes information provided by the 2D, Doppler, color-flow, and M-mode modalities. 3D echocardiography may add important structural and spatial information in selected cases. E. Echocardiography methods. 1. Transducer placed directly on the patient's chest (transthoracic echocar­ diography [TTE] ) . 2 . Transducer mounted o n a gastroscope passed into the patient's esopha­ gus and stomach (transesophageal echocardiography [TEE] ) . =

I I . I N D I CATI O N S F O R E C H OCARD I O G RAPHY I N T H E I NTENS IVE CARE U N IT ( I C U ) A.

1Deceased

Evaluation ofleft ventricular (LY) and right ventricular structure and function. 1. Estimation of ejection fraction and assessment of parameters such as wall thickness, chamber sizes, regional wall motion abnormalities, and diastolic dysfunction. 1 25

1 26

I

B. C.

D.

E.

F.

G.

H.

S E CT I O N 1 • p R 0 c E D u R E s A N D T E c H N I Q u E s

2. Doppler echocardiography can provide an accurate assessment of LV filling pressures and stroke volumes. Evaluation of hypotension/shock (Tables 20- 1 and 20-2) . Evaluation of cardiac valves. 1. Assessment of valvular stenosis or regurgitation requires a comprehen­ sive echocardiographic examination utilizing the 2D, pulsed-wave and continuous-wave Doppler, and color-flow Doppler modalities. 2. Suspected infective endocarditis (IE) . a. TTE has a sensitivity of 44% to 80% to identify valvular vegetations. TTE is relatively insensitive to diagnose myocardial or aortic root abscesses and infection of prosthetic valves. b. TEE has a sensitivity approaching 1 00% for vegetations as small as 2 mm. TEE can detect complications of IE, such as fistulous tracts, perforation, and abscess formation, in 90% to 95% of cases. It is the modality of choice with suspected prosthetic valve endocarditis or with suspected IE with highly invasive organisms like Staphylococcus aureus. Evaluation of the aorta and great vessels. 1. Aortic dissection. a . Detection of a mobile intimal flap, aortic regurgitation, pericardial effusion, and aortic rupture. b. TEE has higher sensitivity and specificity than TTE and equivalent diagnostic accuracy compared to CT angiography or magnetic resonance 1magmg. 2. Intramural hematomas and penetrating ulcers and variants of aortic dissection, which can cause acute aortic syndromes. 3. Deceleration injury to aorta/aortic trauma/valvular injuries. Evaluation of hypoxemia. 1. Acute pulmonary embolism: Echocardiography is not a first-line test. It can be helpful for determining RV structure and function for purposes of risk stratification and for emergent evaluation when other testing is not practical. 2. Right-to-left shunting through a patent foramen ovale or via pulmonary arteriovenous malformations (bubble test) . 3. Congenital heart lesions. Evaluation of cardiac source of embolism. Evaluation of difficulty to wean from mechanical ventilation. Monitoring of therapeutic procedures (such as pericardiocentesis) .

I l l . E C H O CARD I O G RAPHY P RO C E D U R E

A . A standard TTE examination i s performed b y placing a n U S transducer on the chest and imaging from a variety of areas. 1. In approximately 30% of critically ill patients, the image quality of TTE may be inadequate to obtain necessary diagnostic information. Administration of a microbubble contrast agent may improve the diagnostic utility of bedside TTE in this situation. When image quality

Ec hocard i ogra p h ic Featu res of Various Ca uses of He modyna m i c Com p ro m i se Diagnosis

LV structure a n d function

R V s ize a n d function

I VC s i ze

Oth er f i n d ings

D istrib utive s h ock (e .g. , sepsis)

Size m ost often norm a l LVE F m ost often n o r m a l to i ncreased About 25%-30 % may have red u ced LVE F. LV d ia stol i c dysfu n ction may be p resent. Ofte n d i lated with red u ced LVE F. Focal wa l l motion a bnormal ities may be prese nt. Acute processes (such as acute seve re AR o r M R a nd VS R ) may be associated with normal or i n c reased LVE F and normal LV c h a m b e r d i mensions. S m a l l size , hyperdyn a m i c fu nction

M ost often norma l . R e d u ced RV systo I i c fu nction may be observed in a m i n ority of patients .

Ofte n normal o r s m a l l in s ize; may be d i lated with RV dysfu nction

Va lvu l a r vegetations a n d regu rgitation m a y b e seen with i nfective e n doca rd itis.

D i late d , hypo k i n etic

D i lated

Tra nsient a pica l bal loon i n g ( "Ta kots u b o " ) synd ro m e

Ca rd ioge n i c s h ock

Hem orrhagic shock

Aortic or p u l m on i c stenosis Dyna m i c LV outfl ow tract o bstruction

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Ec hocard i ogra p h ic Featu res of Various Ca uses of H e modyna m i c Com p ro m i se (Continued) Diagnosis

LV structure a n d function

R V s ize a n d function

I VC s i ze

Oth er fi n d i ngs

P u lmona ry e m bo l i s m

Normal to sma l l size

D i lated , hypo k i n etic; increased rati o of RV to LV a rea

D i lated

Se pta I flatte n i ng a nd e n h a nced LV/RV inte raction " M cCon n e l l s ign " l ntracav ita ry t h ro m b u s may be obse rved . Tri c us p id regu rgitation R ight-to-left s h u nting via PFO Col l a pse of the RA a nd possibly left h ea rt cha mbe rs Respiratory va riation in m itra l a nd tric u s p i d E-wave veloc ities H e m o perica rd i u m with m yoca rd i a l ru ptu re

Ca rd ia c ta m po n a d e

S m a l l size , hyperdyn a m i c fu nction

S m a l l , d ia sto l i c col­ la pse

D i lated

A R , aortic regu rgitatio n ; M R , m itra l regu rgitati o n ; LV, left ventricle; LVEF, left ventri c u l a r ej ecti on fractio n ; P FO, patent fora m e n ova le; RA, right atri u m ; RV, right ventricle; VS R , ve ntri c u l a r septa l ru ptu re .

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C h a pter 20 • Echocard i ogra phy i n t h e I ntensive Care U n i t

TA B L E 2 0 - 2 -

1 29

Est i mation o f R ight Atr i a l Pressure from Assessment of S i ze a n d Respi ratory Cha nge i n D i a m eter of the I nferior Ve na Cava

-

I VC s ize•

Respi ratory c h a nge w i t h s n iff

::; 2 . 1 ::; 2 . 1 > 2.1 > 2.1

Colla pse Colla pse Colla pse Colla pse

cm cm cm cm

RA pressu re ( m m H g)

>50% 50% 1 ,000 x 1 09/L. 4. Unintentional sampling of the vein will result in a report of a low arterial Po 2 • 3.

B. Site selection 1. It is best to select an artery chat has good collateral circulation so chat if

spasm or clotting occurs, the distal tissue is not malperfused. It is also best to select a superficial artery for ease of entry as well as to minimize pain. The radial artery is the preferred site for arterial puncture. The ulnar artery provides sufficient collateral blood flow in approximately 92% of normal adults. The Allen test (or its modification) is not rou­ tinely necessary (see Chapter 3) before puncture to determine superficial palmar arch collateral flow. 2. If radial artery sites are not accessible, dorsalis pedis, posterior tibial, superficial temporal (in infants) , and brachia! and femoral arteries are alternatives (see Chapter 3) . 3. Brachia! and femoral artery punctures are not advised in patients with coagulopachies because adequate vessel camponade may not be possible. 4. Any vessel that has been reconstructed surgically should not be punc­ tured (see Section III) .

C. Technique 1. Prepare a bag or cup of ice or slush. 2. Perform a time-out. 3.

4. 5. 6.

7. 8. 9. 10.

If radial artery is the target, supinate the arm, slighcly hyperflex the wrist, and palpate the artery. Secure the patient's hand (i.e., with cape) in chis position such chat it is rendered immobile. Cleanse the site with a chlorhexidine/alcohol solution or an alcohol swab. You may choose to inject with a 25-gauge needle enough 1 % lidocaine intradermally to raise a small wheal where the puncture will be made. Attach a 22-gauge or larger needle to a glass syringe chat can accept 5 mL of blood. Wee the needle and syringe with a sodium heparin solu­ tion ( 1 ,000 unics/mL) and express all excess solution or use a regulation ABG kit. With the needle, enter the artery at an angle of approximately 30 degrees to the long axis of the vessel to avoid painful scraping of che periosceum below the artery. As soon as the artery is entered, blood appears in the syringe. Obtain at least 3 mL passively in the glass syringe or the prescribed amount for the commercial ABG kit. Immediately after obtaining the specimen, expel any tiny air bubbles to ensure that the specimen will be anaerobic and chat results will be accurate. Remove the needle, cap the syringe, and place in the bag of ice. If using the glass syringe, have an assistant roll it between both palms for 5 to 1 5 seconds to mix the heparin with the blood.

C h a pter 2 1 • Arte r i a l P u n ct u re for B l ood Gas Ana lysis

I

1 35

1 1 . Apply pressure to puncture site for approximately 5 minutes (longer if

a coagulopathy is present) . If the brachial artery is used, compress the vessel so that the radial pulse cannot be palpated. 12. Immerse the capped sample in a bag of ice and water/slush. (Some kits do not require this step.) Immediately transport the sample to the blood gas analyzer. Many hospitals now utilize point of care testing where blood can be immediately analyzed. Ensure that the sample is labeled with time of draw and ventilator settings (FI02 if not on ventilator) as well as the temperature of the patient.

V. POSTPRO C E D U R E C O N S I D E RATI O N S

A. Complications 1. Using the conventional radial artery technique, complications are unusual.

These include a. Vasovagal episode (rare) b. Local pain with or without breath holding (rendering false results) c. Limited hematomas ( 90 mm Hg, dobutamine or dopamine should be used to increase RV output. 4. In contrast to left-sided HF, for isolated right-sided HF, venous vaso­ dilators such as nitrates (and to a lesser extent morphine) should be avoided. 5. If hemodynamically significant sinus bradycardia or AV block develops, temporary ventricular pacing may be necessary. V I . LEFT VENTR I C U LAR DYS F U N CTI O N ( P U M P FAI LU RE)

A. Background. 1. The most important determinant of prognosis after MI is the degree of LV dysfunction. 2. The following factors influence residual ventricular function. a. LV function before the acute MI. b. Infarct size. c. Infarct location. 3 . Cardiogenic shock occurs in approximately 7% of MI cases and is the most malignant end of the spectrum of HF. Such patients with systemic hypoperfusion and pulmonary congestion have the highest risk of death after MI (inhospital mortality approaches 50%). B. Pathophysiology. 1 . The clinical consequence of myocardial injury is HF. There may be systolic dysfunction, manifested by reduced systemic perfusion and evidence of pulmonary congestion, or diastolic dysfunction, manifested by increases in LV filling pressures and pulmonary congestion, but less evidence of reduced systemic perfusion. Shock typically results from massive MI or severe ischemia leading to a sudden and substantial decline in cardiac output. 2. Diastolic dysfunction occurs almost uniformly in patients with acute MI, although it becomes clinically significant in only one-fourth to one­ third of such patients. It is the most common cause of early mild HF in the setting of acute MI and can be responsible for acute pulmonary edema.

C h a pter 34 • Co m p l i cated Myocard i a l I nfarction

I

25 1

C. Treatment. 1 . The initial goals of treatment for MI complicated by HF are to a. Ensure adequate oxygenation with supplemental oxygen (and endotracheal intubation, if necessary) . b. Maintain systolic blood pressure at 90 mm Hg or greater (MAP >65 mm Hg) . c. Ensure adequate perfusion of vital organs. d. Administration of diuretics and/or nitrates diminishes pulmonary congestion and reduces ventricular filling pressures; caution must be taken to avoid excessive preload reduction, which may compromise systemic perfusion (target PCWP 1 5 to 20 mm Hg) . e . Management may b e aided by pulmonary artery catheterization in those patients with persistent, refractory hypotension and in those on inotropic and pressor support. 2. Caution with use of �-blockers for patients with acute decompensated HF and systolic dysfunction who may not tolerate the negative inotropic effects. 3. Inotropes or mechanical circulatory support may be needed to man­ age cardiogenic shock. Please see Chapter 25 for a detailed discussion. 4. Early reperfusion of the infarct-related artery is a high priority in patients with MI complicated by shock. Early, emergent angiography and revascularization should be considered, particularly for patients younger than 75 years. V I I . M E C H AN I CAL C O M P L I CATI O N S

- ,,

A. Background. 1. Mechanical complications after an MI include ventricular septa! rupture (VSR, see Fig. 34-3 and Video 34- 1 ) , rupture of the ventricular free wall (Fig. 34-4) , and rupture of the papillary muscle (Fig. 34-5 and Video 34-2) . The incidence of these complications has decreased significantly with the advent of PCI. When they occur, the time course for these complications has a bimodal peak, with one peak within 24 hours of MI and a second peak 3 to 5 days post-MI. Table 34-2 sum­ marizes the clinical profiles manifested in the various mechanical complications of MI. B. Prognosis: Mechanical complications, particularly LV free wall rupture, are associated with mortality rates exceeding 80%. Prompt surgical repair of free wall rupture can improve outcome. C. Diagnosis. 1. A high index of suspicion is required for patients with hypotension, severe HF, cardiogenic shock, or an unexplained change in clinical sta­ tus, especially if a new systolic murmur is present. 2. Transthoracic echocardiography is the diagnostic test of choice in patients with suspected ventricular rupture. VSR can be differentiated from papillary muscle rupture leading to MR on the basis of right heart oximetric data with a step-up in oxygen saturation between the right

Figure 34-3 . Subcosral four-chamber view of transthoracic two-dimensional echocardiogram in a 68-year-old woman who developed shock 2 weeks after extensive MI. A rupture of the ventricular septum is noted (arrow). LV, left ventricle; RV, right ventricle.

Figure 34-4. Apical two-chamber view of a transthoracic two-dimensional echocardiogram in a 5 5-year-old man who collapsed 6 months after inferior MI. The image shows a left ventricular free wall rupture resulting in pseudoaneurysm (PSA) communicating with the left ventricle (LV) . LA, Left atrium.

C h a pter 34 • Co m p l i cated Myocard i a l I nfarction

I

253

Figure 34-5. Two-dimensional transesophageal echocardiogram in a patient undergoing mitral valve replacement for a ruptured papillary muscle (arrow) . LV, left ventricle; LA, Left atrium.

atrium and right ventricle. A new systolic murmur is a clinical feature of VSD and MR. D. Treatment. 1. Pericardiocentesis is potentially lifesaving in patients with free wall rup­ ture but should not delay surgical repair. 2. Supportive measures, IABP placement, and prompt surgical interven­ tion are mainstays of treatment in patients with MR or VSR. VI I I . T H RO M B O E M B O L I S M

A. Background: LV mural thrombus formation is a well-recognized com­ plication of acute MI, occurring in up to 40% of patients in the pre­ reperfusion era and now occurring in 4% to 1 0% of patients treated with fibrinolysis or PCI, especially after a large anterior-apical MI. Both arterial and venous emboli can occur, with LV mural thrombi accounting fo r most arterial emboli and RV or deep venous thrombi leading to PE.

254

I

SECT I O N 3 • C A R D I O V A S C U L A R P R O B L E M S A N D C O R O N A R Y C A R E

TA B L E 3 4 - 2

C l i n i c a l Prof i l es o f M ec h a n ical Com p l ications i n Acute M l

Va riable

VSR

Free wa l l r u pt u re

Pa p i l l a ry m usc le ru ptu re

I n c i d ence

-1 %-3 % in pret h rom bolytic era ; 0 . 2 %-0 .34% i n re perfusion era , 3 . 9 % a m o n g th ose with ca rd ioge n i c shock Age , fem a l e , no prior M l , tota l occ l usion with m i n i ma l collatera ls

0.8%-6 . 2 % of M l ( z 0

Atro p i n e , a m i nophyl l i n e ; te m po ra ry pac i n g

Ada pted fro m Antman E M . , M o rrow DA . ST-segment elevation myoca rd i a l i nfa rction : ma nageme nt. I n : B ra u nwa l d E, Bonow R O . Braunwald's heart disease: A textbook of cardiovascular medicine, 9th e d . P h i l a d e l p h i a : Elsevi er Sa u n d ers , 20 1 2 : 196 1 , 56. http://n rs . h a rvard .ed u/urn-3 : h u l .ebook: M DCON_l l301957.

0 0 ;lJ 0 z )> ;lJ -< 0

l> ;lJ rn

C h a pter 34 • Co m p l i cated Myocard i a l I nfarction

TA B L E 3 4 - 4

ACLS I ntravenous Antiarrhyt h m ic Drug Dos i ng

Drug

Bolus

I nfusion

Lidoca i n e

1 . 0-1 . 5 mg/kg i n itial ly; a d d iti o n a l bo l u ses ( 0 . 5-0 . 7 5 mg/kg eve ry 5-1 0 m i n ) as n ecessa ry to contro l VTN F to maxi m u m tota l load 3 mg/kg 1 5- 1 8 mg/kg (maxi m u m 1 ,000 mg) over 25-30 m i n

1-4 mg/m i n

Proca i n a m i d e

A m i odarone

257

1 50 mg ove r 1 0 m i n for SVT, 300 mg for VTNF. Can repeat secon d d ose of 1 50 mg if needed

1-4 mg/m i n ( red uce d ose in the presence of seve re ca rd iac/re n a l i m pa i rme nt) 1 mg/m i n for 6 h, then 0 . 5 mg/m i n fo r 1 8 h , then tra ns ition to ora l dosing

A C K N O W L E DG M E N T S

The authors would like to thank Dr. Michael Picard, director of clinical echocar­ diography at the Massachusetts General Hospital (Boston, MA) , for providing them with the echocardiogram still images and video clips included in this chapter. SUGG ESTED R EADI N GS

D'ascenw F, Biondi-wccai G, Moretti C, et al. TIMI, GRACE and alternative risk scores in Acute Coronary Syndromes: a meta-analysis of 40 derivation studies on 2 1 6,552 patients and of 42 validation studies on 3 1 ,625 patients. Contemp Clin Trials 20 1 2;33 (3) :507-5 14.

A comprehensive look at the TIMI and GRACE risk scores. Puymirat E, Simon T, Steg PG, et al. Association of changes in clinical characteristics and management with improvement in survival among patients with ST-elevation myo­ cardial infarction. JAMA 2 0 1 2;30 8 ( 1 0):998-1006.

A recent observational study based on four French registries highlighting a 68 % decrease in STEM! mortality from 1995 to 201 0. Thiele H, Zeymer U, Neumann FJ, et al. lntraaortic Balloon Support for Myocardial Infarction with Cardiogenic Shock. N Engl] Med 2 0 1 2;367: 1 287-1 296.

A landmark trial that has the potential to change the way intraaortic balloon pumps are utilized in cardiogenic shock. Topalian S, Ginsberg F, Parrillo JE. Cardiogenic shock. Crit Care Med 2008;36(1 Suppl) :S66-S74.

A review ofthe pathophysiology ofand treatment ofpatients sufferingfrom cardiogenic shock. Van de werf F, Bax J, Betriu A, et al. Management of acute myocardial infarction in patients presenting with persistent ST-segment elevation: the Task Force on the Management of ST-Segment Elevation Acute Myocardial Infarction of the European Society of Cardiology. Eur Heart J 2008;29(23) :2909-2945.

A report on recent guidelines from the European Society of Cardiology on the manage­ ment ofSTEM!, including management ofselect complications ofmyocardial infarction.

35

Ve ntri c u l a r Ta c hyca rd i a B ruce A . Ko p l a n a n d W i l l i a m G . Steve nson

I . G E N E RAL P RI N C I PLES

A. Definitions. 1. Ventricular tachycardia (VT) . a. �3 beats at a rate � 1 00 bpm. b. QRS width �0. 1 2 seconds. c. Originates from the ventricle. 2. Nonsustained ventricular tachycardia (NSVf). a. Terminates spontaneously within 30 seconds without causing severe symptoms. B. Classification (Fig. 35- 1 ) . 1 . Monomorphic VT. Same configuration from beat to beat. a. Usually due to a circuit through a region of old myocardial infarction (MI) scar. b. Idiopathic VT (less common) : VT in the absence of an identifiable cause (e.g., structural heart disease/prior MI) . i. Right ventricular outflow tract (RVOT) tachycardia: most com­ mon idiopathic VT. Lefr bundle branch block morphology with inferior axis. 2. Polymorphic VT. Continually changing QRS morphology. a. Etiologies. i. Active cardiac ischemia (most common) . ii. Electrolyte disturbance. iii. Drug toxicity. iv. Familial. b. Torsade de pointes. i. Unique form of polymorphic VT. ii. Waxing and waning QRS amplitude during tachycardia associ­ ated with prolonged QT interval. iii. Secondary to QT-prolonging drugs, electrolyte abnormalities, or familial ion channel disorders (long QT syndrome) . 3. Sinusoidal VT. Sinusoidal appearance often associated with severe elec­ trolyte disturbance (e.g., hyperkalemia) . 4. Accelerated idioventricular rhythm (AIVR) . a. Wide complex, ventricular rhythm at 40 to 1 00 beats/min. b. Usually hemodynamically stable. c. Can occur in the first 12 hours after reperfusion of an acute MI or during periods of elevated sympathetic tone. 258

C h a pter 35 • Ventr i c u l a r Tachycard i a

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259

A

B

c

Figure 3 5- 1 . Three different wide QRS tachycardias are shown: monomorphic VT in (A) ; polymorphic VT in (B) ; and sinusoidal VT due to hyperkalemia in (C) .

d. Onset typically preceded by sinus slowing. e. Usually resolves without specific therapy. f. Antiarrhythmic drug (AAD) treatment rarely necessary. I I . DIAG N O S I S

A. Differentiating VT from supraventricular tachycardia (SVT) i n a patient with a wide complex tachycardia (WCT) . 1. Differential diagnosis ofWCT. a. VT. b. SVT with aberrancy (bundle branch block) . c. SVT conducting down an accessory pathway (Fig. 35-28) . 2. Assume VT until proven otherwise. 3. WCT with a hisrory of MI should be assumed ro be VT unless proven otherwise. 4. If the patient is hemodynamically stable, obtain a 1 2-lead electrocardio­ gram (ECG) . 5. ECG criteria that favor VT over SVT (Fig. 35-3A and B). a. AV dissociation (Figs. 35-2A and 35-4) . b. Initial R in avR. c. QRS concordance. Absence of an rS or Rs complex in any precor­ dial lead (V,-VJ d. Capture beats/fusion beats during tachycardia (Fig. 35-4).

260

SECT I O N 3 • C A R D I O V A S C U L A R P R O B L E M S A N D C O R O N A R Y C A R E

A

-

B

c

D

Figure 3 5 - 2 . WCTs . A: Transition from sinus rhythm to VT with AV dissociation (P waves identified by small arrows) . B: Short PR and delta wave during sinus rhythm on left, and atrial fibrillation with rapid, irregular, wide complex ventricular response due to conduction over the accessory pathway in a patient with the WPW syndrome. C: The polymorphic VT torsade de pointes (right side) in a patient with QT prolongation (left side) . D: Motion artifact mimick­ ing a WCT. Note that within the artifact, QRS complexes (large arrows) are present occurring at the same interval as before and after the onset of the artifact waveform. AV, atrioventricular; VT, ventricular tachycardia.

i. Occur when a supraventricular conducts to the ventricles, depo­ larizing the ventricle (completely-capture beat or partially­ fusion beat) in advance of the next tachycardia beat. ii. Morphologically identical (capture beat) or similar (fusion beat) to the QRS complex seen in sinus rhythm but occur in the midst of a wide QRS complex tachycardia. iii. Capture beats during WCT are pathognomonic for VT. 6. Additional principles. a. Hemodynamic instability is dependent on the rate and underlying ventricular function and does not differentiate VT from SVT. b. Electrocardiographic artifacts can mimic VT/ventricular fibrilla­ tion (VF) (Fig. 35-2D) . I l l . TREAT M E NT. First priority-Determine whether the patient is hemodynami­

cally stable. A. Management of hemodynamically unstable VTNF (see Algorithm, Fig. 35-5).

1 . CPR and rapid defibrillation are the most important measures to improve survival.

C h a pter 35 • Ventr i c u l a r Tachycard i a

I

26 1

VT ve rsus SVT

�o

AV d issociation

VT

Yes

�"�:

Yes

No rs or Rs in any of V1 to V6

v

A

Yes

'\o

VT

VT

Possible SVT, VT sti l l possible

Wide Complex Tachycard i a :

Additi onal ECG/c l i n ical f i n d i n g s su pporti ng V T v s . SVT Characteristic

+

Prior known M l or C M P

+

Favors SVT

I rreg ularly i rreg ular

+

History of WPW, prior delta wave in S R

+

Onset with a PAC or S V T with similar rate

+

Identical ORS d u ring SR in a patient with preexisting BBB

B

Favors VT

Capture beats or fusion beats

+

Figure 35-3. A: Electrocardiographic features to differentiate VT versus SVT in patients pre­ senting with wide QRS complex tachycardia. VT, ventricular rachycardia; SVT, supravenrricular tachycardia; AV, atriovenrricular; RBBB, right bundle branch block; LBBB, left bundle branch block. (Modified from Vereckei A, Duray G, Szenasi G, et al. New algorithm using only lead aVR for differential diagnosis of wide QRS complex tachycardia. Heart Rhythm 2008;5:89-98) . See text for details. B: Additional clinical and ECG findings to assist with differentiation berween ventricular tachycardia (VT) and supravenrricular tachycardia (SVT) in patients with WCT. See text for details. ECG, electrocardiogram; MI, myocardial infarction; CMP, cardio­ myopathy; PAC, premature arrial contraction; SR, sinus rhythm; IHD, ischemic heart disease; RBBB, right bundle branch block; LBBB, left bundle branch block.

2.

AADs-see 111.B. 1 in subsequent text. a. Used when cardioversion fails or VT/VF recurs. b. Amiodarone (often used as first-line therapy), Procainamide (alterna­ tive to amiodarone) , lidocaine (most appropriate during suspected acute myocardial ischemia) .

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SECT I O N 3 • C A R D I O V A S C U L A R P R O B L E M S A N D C O R O N A R Y C A R E

Figure 35-4. Ventricular tachycardia with AV dissociation (arrows showing p waves) and capture beats during ventricular tachycardia (asterisks) . See text for details.

Hemodynamically u n stab le WCTNF

+

Start C P R G ive oxygen Attach monitor/defibrillator

VFNT

"\.

S h ock CPR

2

IV/PO

7

�

Asysto le/P EA C P R 2 m i n utes

m i n utes

Epinephrine every 3-5min

access

R hyth m shockable

Yes

R h yth m shockable

+

-

R h yth m shockable

"\.

No

S h ock

C P R 2 m i n utes

C P R 2 m i n utes

Epinephrine every 3-5min R h yt h m sh ockable

Yes 1 + Shock� ' C P R 2 m i n utes Amiodarone

+

Treat reversible causes -

No

�

R hyth m shockable

No

+

C P R 2 m i n utes

Repeat algorithm as appropriate

Figure 35-5. Approach to unstable WCT/VF. This algorithm assumes that CPR is initiated after the three unsuccessful shocks and maintained until a pulse is achieved. VF, ventricular fibrillation; PMVT, polymorphic ventricular tachycardia; VT, ventricular tachycardia; Arnio, amiodarone; Epi, epinephrine; MVT, monomorphic ventricular tachycardia; CPR, cardiopul­ monary resuscitation.

C h a pter 35 • Ventr i c u l a r Tachycard i a

263

Stable WCT

i

� WCT (diagnosis uncertain)

/

P reserved card iac fu nction

""'

E F < 40% clin ical C H F

t

P rocainamide or am iodarone or card ioversion

Amiodarone o r card ioversion

H i story & 1 2-lead ECG

""" �(seefigure S) PMVT

Monomorphic VT

/

�

Preserved cardiac fu nction Procainamide or amiodarone o r card ioversion

EF

SVT with aberrancy

< 40%

clin ical C H F

see er) (chapt

SVT

Am iodarone or l idocaine or card ioversion

Figure 35-6. Approach to stable WCT. WCT, wide complex tachycardia; ECG, electrocardio­ gram; EF, ejection fraction; CHF, congestive heart failure; VT, ventricular tachycardia; PMVT, polymorphic ventricular tachycardia; SVT, supraventricular tachycardias. See text for details.

B. Management of hemodynamically stable WCT (see Algorithm, Fig. 35-6) . 1 . AADs. a. Amiodarone. b. Procainamide. c. Lidocaine. 2. Electrical cardioversion is also an appropriate initial therapy. 3. If Wolff-Parkinson-White (WPW) syndrome {see Chapter 38) is suspected (Fig. 3 5-2B) , intravenous procainamide or cardioversion are first-line therapies. C. Management of polymorphic VT/sinusoidal VT. 1 . Correct reversible causes a. Cardiac ischemia. b. Metabolic abnormalities. c. Drug toxicity including QT-prolonging drugs. 2. Lidocaine and amiodarone can be considered for recurrent episodes. 3. Treatment of torsade de pointes (polymorphic VT due to QT prolonga­ tion) . a. Intravenous magnesium sulfate ( 1 to 2 g) (can be repeated) . b. Correct electrolyte abnormalities (hypokalemia, hypomagnesemia, hypocalcemia) . c. Discontinue QT-prolonging medications. d. Increasing heart rate with pacing or isoproterenol can be highly effective. Transvenous temporary ventricular pacing is most reliable (target rate of 1 1 0 to 1 20 bpm) . Isoproterenol should not be used if congenital long QT syndrome is suspected.

264

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D. Implantable cardioverter-defibrillators (ICDs) . 1 . For some patients at high risk for VT/VF, !CDs should be considered for long-term protection after acute issues resolve provided that acceptable functional recovery and survival for more than 1 year is anticipated. a. !CDs for primary prevention of sudden death should be considered for patients who have not had spontaneous sustained VT/VF but have the following risks factors. i. Persistently reduced ejection fraction ::;35% due to either isch­ emic or nonischemic cardiomyopathy, genetic diseases associated with sudden death (e.g., some hypertrophic and familial cardio­ myopathies) . ii. ICDs for secondary prevention of sudden death after resuscita­ tion from VT/VF are recommended if the arrhythmia is not due to a correctable, reversible cause, such as acute MI or drug toxicity. E. Management of NSVT /ventricular ectopy: "first do no harm". 1. NSVT/premature ventricular contractions (PVCs) are common in the intensive care unit (ICU) . 2. Treatment. a. Correct possible aggravating factors (e.g. , ischemia, electrolyte distur­ bance, hypoxia, hypoventilation, beta-agonists) . b. �-Blocking agents (if not contraindicated) . c. In the absence of symptoms, administration of antiarrhythmic agents should be avoided and may increase mortality. F. Electrical storm: defined as three or more episodes of VT or VF in a 24-hour- period. 1. May be managed with AADs. 2. Catheter ablation can be an effective option with acceptable risk. IV. OVERVIEW OF D R U G S C O M M O N LY U S E D FOR T H E MANAG E M E N T O F VTNF I N T H E I C U

A . General principles. 1. Narrow toxic-therapeutic relationship and potential for proarrhythmia necessitates careful monitoring. 2. Titration to achieve the desired effect is often required. B. �-Blockers (Class II) . 1. Indications. a. Symptomatic ventricular ectopy. b. Recurrent sustained ventricular tachyarrhythmias. The frequency of VT/VF (electrical storm) is often aggravated by high sympathetic tone and may improve with �-adrenergic blockade. 2. Short-acting agents (e.g. , metoprolol tartrate) are preferable in the ICU setting. a. Metoprolol. i. Can be given orally or as a 5-mg slow intravenous push and repeated every 5 to 1 0 minutes up to a total of 20 mg IV. Can

C h a pter 35 • Ventr i c u l a r Tachycard i a

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repeat intravenous boluses every 4 to 6 hours or oral dosing every 4 to 8 hours. ii. Esmolol (useful when there is concern that a �-blocker may be poorly tolerated) (short half-life 2 to 9 minutes) . (a) 500 µg/kg IV bolus over 1 minute followed by a mainte­ nance dose of 50 µg/kg/min titrated for effect up to 300 µg/ kg/min. Adverse effects of �-blockers. a. Negative inotropy (avoid with decompensated heart failure) . b. Bradycardia. c. Aggravation of bronchospasm.

C. Amiodarone. 1. Indications. a. First-line AAD in advanced cardiac life support (ACLS) VF/pulseless VT algorithm. b. Hemodynamically stable VT that recurs after cardioversion or fails IV procainamide. 2. Dosing. a. A 1 50- to 300-mg IV bolus over 10 minures, followed by an infusion at 1 mg/min for 6 hours and then 0 . 5 mg/min. b. Additional 1 50-mg boluses can be given for breakthrough arrhythmia up to a total load of approximately 2 g/24 hours and 5 to 8 g total. c. Can also be loaded orally (800 to 1 ,600 mg daily for 2 to 3 weeks, with maintenance dose of 400 mg daily for ventricular arrhythmias) . 3. Adverse effects. a. Even though amiodarone causes QT prolongation, torsade de pointes and other proarrhythmic complications are rare. b. Hypotension during intravenous administration. c. Bradycardia. d. Exacerbation of congestive heart failure (negative inotropic effect) . e. Phlebitis (when administered through a peripheral intravenous line) . Continuous infusions should be administered through a central venous catheter. f. Other adverse effects include hepatitis, hyper- or hypothyroidism, pneumonitis, neuropathy, and tremor. D. Procainamide. 1. First-line agent for WCT (along with amiodarone) for the treatment of hemodynamically stable WCT and WCT due to WPW syndrome. 2. Alternative agent for hemodynamically unstable WCT and VF. 3. Dosing: 20 to 30 mg/min IV infusion loading dose up to a total initial dose of 10 to 17 mg/kg, followed by a maintenance infusion of 1 to 4 mg/min. 4. Adverse effects. a. Vasodilatation and negative inotropy. i. Avoid with depressed ventricular function (ejection fraction 24 hours. ii. QTc interval and QRS complex width should be monitored. (a) Discontinue if the QRS widens by >50% from baseline. c. Avoid in patients with significant renal dysfunction. i. NAPA is excreted entirely by the kidney. E. Lidocaine (IB) . 1. Indications. a. Acute management of life-threatening ventricular arrhythmias, especially when associated with myocardial ischemia. Amiodarone, procainamide, and �-blockers are preferable. 2. Dosing: 1 to 1 . 5 mg/kg IV bolus. Can repeat to a maximum bolus of 3 mg/kg, followed by an infusion of 1 to 4 mg/min. 3. Adverse effects. a. Minimal adverse hemodynamic side effects. b. Neurologic toxicity (seizures, tremors, and confusion) . 4. Class IC AADs (jlecainide, propafenone) are rarely used in the ICU for VT/VF due to proarrhythmia and negative inotropic risks. They increase long-term mortality in patients with coronary artery disease and depressed ventricular function. S U G G ESTED R EAD I NGS

20 1 0 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care science. Circulation 20 1 0 ; 1 22:S729-S767.

This citation isfrom the current guidelines on acute management ofpatients with cardiac arrest. Aliot EM, Stevenson WG, Almendral-Garrote JM. EHRA/HRS expert consensus on catheter ablation of ventricular arrhythmias. Heart Rhythm 2009;6:8 86-933.

This consensus statement reviews different types of VTand the role ofcatheter ablation. Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardiovercer-defibrillator for congestive heart failure. N Engl] Med 2005;352:225-237.

A usefol discussion of the options for protection from arrhythmias in the setting ofconges­ tive heart failure. Bourke T, Vaseghi M, Michowitz Y, et al. Neuraxial modulation for refractory ventricular arrhythmias: value of thoracic epidural anesthesia and surgical left cardiac sympa­ thetic denervation. Circulation 20 1 O; 1 2 1 :225 5-2262.

The use ofmeasures to reduce sympathetic tone achieves control of recurrent VT/VF in some patients and can be lifesaving. Carbucicchio C, Santamaria M, Trevisi N, et al. Catheter ablation for the treatment of electrical storm in patients with implantable cardiovercer-defibrillators: short- and long-term outcomes in a prospective single-center study. Circulation 2008; 1 1 7: 462-469.

Patients with "electrical storm " defined as 3 or more episodes in 24 hours, of monomor­ phic VT, can often be controlled by catheter ablation, with acceptable risk.

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Epstein AE, DiMarco JP, Ellenbogen KA, et al. ACC/AHA/HRS 2008 guidelines for device­ based therapy of cardiac rhythm abnormalities. Circulation 2008; 1 1 7:e350-408 .

Guideline update and review ofthe use of!CDs and pacingfo r control ofarrhythmias. Gao 0, Sapp JL. Electrical storm: definitions, clinical importance, and treatment. Curr Opin Cardiol 20 1 3;28:72-79.

Causes and therapy of "electrical storm " defined as 3 or more episodes in 24 hours, of sustained VT or VF, are reviewed. Gorgels AP, Vos MA, Letsch IS, et al. Usefulness of AIVR as a marker for myocardial necrosis and reperfusion during thrombolysis in acute MI. A m ] Cardiol 1 988;6 1 :23 1 .

The association between AIVR and myocardial reperfasion is described. Knecht S, Sacher F, Wright M, et al. Long-term follow-up of idiopathic ventricular fibrillation ablation: a multicenter study. J Am Coll Cardiol 2009;54:522-528.

Rare cases of recurrent VF that are triggered by PVCs can be controlled by catheter abla­ tion targeting the PVCfocus.

O'Gara PT, Kushner FG, Ascheim DD, et al. 20 1 3 ACCF/AHA guideline for the manage­ ment of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 20 1 2; DOI: 1 0. 1 1 6 1 /CIR.Ob0 1 3e3 1 82742c84.

Guideline for management ofacute myocardial infarction including ventricular arrhyth­ mias during the event. Tchou P, Young P, Mahmud R, et al. Useful clinical criteria for the diagnosis of ventricular tachycardia. Am ] Med 1 988;84:53-56.

The utility ofthe clinical history to assist with the differentiation of VTfrom SVT with aberrancy in patients with wide complex tachycardia is discussed. Tomlinson DR, Cherian P, Betts TR, et al. Intravenous amiodarone for the pharmacologi­ cal termination of haemodynamically-rolerated sustained ventricular tachycar­ dia: is bolus dose amiodarone an appropriate first-line treatment? Emerg MedJ 2008;25 : 1 5- 1 8 .

Intravenous amiodarone often fails to convert hemodynamically tolerated monomorphic VT, and cardioversion should be immediately available during its administration. Vereckei A, Ouray G, Szenasi G, et al. New algorithm using only lead aVR for differential diagnosis of wide QRS complex tachycardia. Heart Rhythm 2008;5: 89-9 8 .

Use electrocardiographic criteria to differentiate VTfrom SVT in patients with wide complex tachycardia is described. Zipes DP, Camm AJ, Borggrefe M, et al. ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Circulation 2006; 1 1 4:e385-e484.

Consensus approaches to ventricular arrhythmias.

S u p rave ntri c u l a r Ta c hyc a rd i a J o h n L. Sa p p J r a n d La u re n ce M . E pste i n

I . BACKG RO U N D

A. Definition: Supraventricular tachycardias are those arrhythmias that require involvement of the atrioventricular (AV) node or atria for their perpetua­ tion. They are usually described by mechanism or by their electrocardio­ graphic appearance (Figs. 36- 1 and 36-2) . I I . M E CHAN I S M S : There are two main mechanisms underlying supraven­

tricular tachycardias. A. Focal Arrhythmias: for example, inappropriate sinus tachycardia, ectopic atrial tachycardia, atrial premature beats, mu!tifocal atrial tachycardia. B. Reentry: for example, atrioventricular reentrant tachycardia (AVRT) , atrio­ ventricular nodal reentrant tachycardia (AVNRT) , atrial flutter. I l l . R E C O G N I T I O N A N D D I AG N OS I S (see Figs. 36- 1 and 36-2) .

It should be noted that rate or hemodynamic stability does not predict the tachycardia mechanism. Rapid, poorly tolerated rhythms can be SVT, and slower, well-tolerated rhythms can be ventricular tachycardia (VT) . A. QRS is > 1 20 ms (wide complex tachycardia) .

1. Supraventricular activation with aberrancy or preexcitation (over an accessory AV pathway) will result in a wide complex tachycardia. This must be distinguished from ventricular tachycardia. 2. The presence of a history of significant structural heart disease or a QRS morphology atypical for bundle branch block increases the likelihood of VT. Consultation should be sought. B. QRS duration < 1 20 ms in all surface leads: likely supraventricular. C. Irregularly irregular QRS complexes most commonly signify atrial fibril­ lation (multifocal atrial tachycardia is distinguished by the presence of P waves with at least three different morphologies) . D. Irregularly irregular rhythm with wide/varying QRS width may suggest atrial fibrillation with ventricular preexcitation over an accessory pathway (AP) (this is uncommon) .

268

C h a pter 36 • S u p raventri c u l a r Tachycard i a

269

Regular

Long R P tachycardia ( R P>50%RR) AVNRT AVRT Ectopic atrial tachycardia Junctional tachycardia

Sinus tachycardia Ectopic atrial tachycardia

Atrial fibrillation

Uncommon AVNRT

90% with a 6 hours of deterioration) are most common

(approximately 90%) .

2. Sudden-progression attacks ( 95% can be achieved with a 6-month regimen among patients with drug-susceptible organisms. Corticosteroids are indicated for all patients with tuberculous meningitis and tuberculous pericarditis. Antiretroviral therapy (ART) is strongly recommended for all HIV-infected patients with active TB infection. 1 . If the patient's CD4 count is 250 g/day. 1 . Diarrhea can result in significant nutrient, water, and electrolyte loss, and, importantly, can contribute to perinea! and sacral skin breakdown. 2. Review medications for those who may precipitate diarrhea (see Section 11.A.8). 3. Maintain high suspicion for antibiotic-associated diarrhea, especially with unexplained leukocytosis, and diagnose via detection of stool poly­ merase chain reaction (PCR) for C. difficile, which is rapidly replacing the toxin assay because of its superior sensiriviry, specificiry, and rapid turnover. 4. Perform rectal examination to exclude a distal impaction; abdominal radiographs are required to exclude more proximal impaction. 5. Sigmoidoscopy or colonoscopy with biopsy may be helpful when diarrhea remains unexplained.

544

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IV. TREAT M E NT

A. Gastric stasis (delayed gastric emptying, gastroparesis) . 1. Initial approach. a. Eliminate iatrogenic factors and exclude mechanical obstruction. b. Minimize or eliminate narcotics and other provoking medications. c. Improve feeding tolerance by positioning the feeding tube ports beyond the pylorus (e.g., jejuna! or gastrojejunal feeding tube) ; notably, this maneuver does not eliminate the risk of tracheobronchial aspiration. d. Prone positioning allows for larger enteral feeding volumes. e. Parenteral nutrition can be considered if enteral feeds are not toler­ ated; however, rates of infection and hyperglycemia are greater. 2. Medical/nonpharmacologic treatments. a. Metoclopramide is the only clinically approved prokinetic in the United States and is the agent of choice in the ICU. i. Accelerates gastric emptying, but does not prevent aspiration pneumonia. ii. Significant side effects include confusion, agitation, somnolence, and dystonic reactions. b. Intravenous (IV) erythromycin, a motilin agonist, accelerates gastric emptying and facilitates postpyloric tube placement. i. To improve gastric emptying, erythromycin is given at a dose of 1 to 3 mg/kg three to four times daily. ii. Side effects include nausea, vomiting, abdominal cramps, and diarrhea. iii. Tolerance to the prokinetic effect of erythromycin occurs rapidly with repeated use via motilin receptor down-regulation. iv. Erythromycin in combination with metocloprarnide may be more effective than either agent alone. B. Managing GERO as an outcome consequence of gastric stasis. 1 . Conservative measures may reduce GERO (e.g., 45-degree elevation to head of bed, avoidance of large-bolus tube feedings, postpyloric feeding tube placement) . 2. Pharmacologic treatment also is required. a. Proton pump inhibitors (PPis) are the most effective acid-suppressant agents, and may be given by mouth or by nasogastric tube. b. The IV route of PPI administration may be used when the enteral route is not feasible or absorption is in question; pantoprazole, lanso­ prazole, and esomeprazole are available parenrerally. C. Acute colonic pseudoobstruction (Ogilvie syndrome). 1. Initial approach. a. Recognition and correction of potentially reversible precipitants, such as electrolyte imbalances, infection, or medications that slow transit, are essential. b. Reduce narcotic medication use. c. Newer µ-opioid receptor antagonists (alvimopan and methylnaltrexone) may be helpful in opioid-induced intestinal dysfunction.

C h a pter 75 • G astro i ntest i n a l M ot i l i ty Pro b l e m s i n t h e C r i t i c a l Care Sett i n g

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d. Nothing by mouth and implement low, intermittent nasogastric suction. e. Exclude fecal impaction and place a rectal tube. f. Follow abdominal examination serially, and pursue abdominal radio­ graphs as dictated by changes in clinical exam. 2. Pharmacologic treatment. a. The acerylcholinesterase inhibitor neostigmine can be used (2 mg intravenously over 5 minutes) when the patient fails to improve with conservative measures and reversal of underlying factors. b. Neostigmine is effective in approximately 90% of cases, with a low recurrence rate. c. Close monitoring is indicated during neostigmine use; it is con­ traindicated in cases with bradycardia, active bronchospasm, or mechanical bowel obstruction. 3. Colonic decompression. a. Colonoscopy for decompression is considered when distension worsens or persists, and clinical condition of the patient appears compromised. b. Overall success of colonoscopic decompression is 88%, though mor­ tality with the procedure in the setting of colonic pseudoobstruction is as high as 2%. c . The general value of colonoscopic decompression in colonic pseu­ doobstruction remains controversial; the procedure should be used selectively. 4. Surgical or interventional radiologic decompression occasionally is required when progressive findings of peritoneal irritation are detected on exam, or if imaging indicates perforation. D. Diarrhea. 1. Initial approach. a. Decrease feeding rate in rube-fed patients to improve diarrhea until the gut acclimates to the delivery of an increased osmotic and volume load. b. Recognize and correct electrolyte and other relevant metabolic abnor­ malities. c. If possible, discontinue medications potentially responsible for diarrhea, including offending antibiotics in presence of C. difficile infection. d. Incontinence devices (e.g., rectal rube) will minimize skin complications. 2. Pharmacologic treatment. a. Antidiarrheal agents should be used cautiously in ICU patients; focus first on addressing infectious or other reversible etiologies. b. Metronidazole remains the drug of choice for C. difficile infection. i. When suspected, initiate therapy in the more severely ill ICU patient while the toxin assay results are pending, and continue treatment for at least 14 days in confirmed cases. ii. Response of diarrheal symptoms may take as long as 7 to 1 0 days.

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SECT I O N 7 • G A S T R O I N T E S T I N A L A N D H E P A T O B I L I A R Y P R 0 B L E M S

iii. The IV administration route is required in patients intolerant of oral metronidazole. iv. If broad-spectrum systemic antibiotics cannot be discontinued, maintain metronidazole until their treatment courses are com­ pleted. v. Relapse of C. difficile infection is common and typically requires retreatment. c. Oral vancomycin and fidaxomicin are reserved for patients intolerant of, or who fail to improve with, metronidazole. d. Adjunct approaches including use of colestipol or cholestyramine as a toxin binder and probiotics may be used; importantly, the sequestrant agents will bind oral vancomycin, and thus must not be administered at the same time. S U G G ESTED R EAD I NGS

Crooks NH, Snaith C, Webster D , et al. Clinical review: probiotics in critical care. Crit Care 20 1 2; 1 6:237.

A systematic review ofexisting randomized controlled trials using pre-, pro-, or symbiotics compared to enteral therapies alone in critically ill patients. Geller A, Petersen BT, Gosrout CJ. Endoscopic decompression for acute colonic pseudo­ obstruction. Gastrointest Endosc 1 996;44: 1 44- 1 50.

A retrospective review of endoscopic decompression for acute colonic pseudoobstruction. Jeejeebhoy KN. Parenteral nutrition in the intensive care unit. Nutr Rev 2 0 1 2;70 ( 1 l ) : 623-630.

A comprehensive review of the nutritional needs and use ofparenteral nutrition in the ICU setting. Kreymann KG, Berger MM, Deutz NE, et al. ESPEN guidelines on enteral nutrition: inten­ sive care. Clin Nutr 2006;2 5 : 2 1 0-223.

Expert guidelines on the implementation ofenteral nutrition, with consideration ofissues relevant to the critically ill patient. Luo RF, Banaaei N. Is repeat PCR needed for the diagnosis of Clostridium difficile infection? J Clin Microbiol 2 0 1 0;48:3738-374 1 .

Review of the use of C. difficile PCR in the diagnosis and treatment of C. difficile infection. MacLaren R, Kiser TH, Fish DN, et al. Erythromycin versus meroclopramide for facilitating gastric emptying and rolerance to intragastric nutrition in critically ill patients. ]PEN J Parenter Enteral Nutr 2008;32(4) :4 1 2---4 1 9 .

An evaluation ofthe effects oferythromycin and metoclopramide o n gastric physiology in the ICU setting. Ukleja A. Altered GI motility in critically Ill patients: current understanding of pathophysiol­ ogy, clinical impact, and diagnostic approach. Nutr Clin Pract 2 0 1 0;25: 1 6-25 .

A review ofthe diagnostic approach and management of GI motility abnormalities in critically ill patients. van der Spoel JI, Oudemans-van Straaten HM, Stoutenbeek CP, et al. Neostigmine resolves critical illness-related colonic ileus in intensive care patients with multiple organ failure-a prospective, double-blind, placebo-controlled trial. Intensive Care Med 200 1 ;27:822-827.

A prospective study demonstrating benefit ofcontinuous neostigmine infusion compared with placebo in resolving critical illness-related colonic ileus.

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Wiesen P, Van Gossum A, Preiser JC. Diarrhea in the critically ill. Curr Opin Crit Care 2006; 1 2 (2): 1 49- 1 54.

A summary ofetiologies ofdiarrhea in the ICU setting and clinical approaches to management. Zahar JR, Schwebel C, Adrie C, et al. Outcome of ICU patients with Clostridium difficile infection. Crit Care 20 1 2 ; 1 6(6) : R2 1 5 .

A large study of the development of C. difficile infections in the ICU setting; dem­ onstrated that early detection mitigates the negative effect of C. difficile on patient mortality.

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I . G E N E RAL P RI N C I PLES

A. Definitions. 1. Fulminant colitis. a. Fulminant colitis implies a serious progression of colonic mucosal inflammation, extending into the deeper layers of the colon. b. Patients typically manifest severe bloody diarrhea, abdominal tender­ ness, and systemic toxicity. 2. Toxic megacolon. a. In the face of fulminant colitis, colonic circular muscle paralysis can precipitate acute colonic dilatation or toxic megacolon, the term used to describe this entire sequence of events, which includes systemic toxicity. b. Toxic megacolon is most commonly seen as a complication of ulcerative colitis or Clostridium difficile infection colitis. It can also occur with other inflammatory conditions (Crohn colitis, Behcet disease, and collagenous colitis) and other colonic infections (bacte­ rial: Salmonella, Shigella, Campylobacter, Yersinia, Escherichia coli; parasitic: Entameba, Cryptosporidium; fungal: Aspergillosis; and viral: Cytomegalovirus [CMV] and rotavirus) ; ischemia, colonic lymphoma, obstructive colon cancer, volvulus, diverticulitis, Kaposi sarcoma, chemotherapy, and idiopathic colitis are other causes. c. Factors associated with increased mortality include age older than 40 years, the presence of colonic perforation, and delay of surgery. d. Early recognition and treatment of toxic megacolon can substantially lower mortality from as high as 50% (with colonic perforation) to < 1 5%. e. Other conditions that can cause colonic dilation without systemic toxicity include Hirschprung disease, chronic constipation, and intes­ tinal pseudoobsrruction. II. DIAG N O S I S

A. Clinical presentation. 1. History. a. Inflammatory colitis. i. Toxic megacolon usually occurs in the background of extensive colitis associated with chronic inflammatory bowel disease, espe­ cially ulcerative colitis, and, less commonly, Crohn disease. 548

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ii. Toxic megacolon typically occurs during a relapse of established ulcerative colitis; however, 25% to 40% of cases present during an initial attack. Perianal disease and extraintestinal manifesta­ tions (joint, eye, skin, and liver) can be clues to a new inflamma­ tory bowel disease diagnosis. iii. Progressive bloody diarrhea and crampy abdominal pain are typical symptoms. A paradoxical decrease in stool frequency with passage of bloody "membranes" is an ominous sign. iv. Manipulation of the inflamed bowel with diagnostic exami­ nations such as barium enema or colonoscopy, medications (including vigorous laxatives, antidiarrheals, anticholinergics) , electrolyte imbalances, and pH disturbances can contribute to the development of the condition. v. Corticosteroids can suppress signs of perforation and peritonitis, bur whether these drugs can precipitate toxic megacolon is con­ troversial. b. Infectious colitis. i. C. difficile infections have been the cause of increasing hospitaliza­ tions over the last decade, due to increased use of broad-spectrum antibiotics and development of more virulent C. difficile strains. ii. Patients age 65 and older are at increased risk of C. difficile infection and a severe course, including toxic megacolon. Other risk factors for megacolon in C. difficile colitis are malignancy, chronic obstructive pulmonary disease, renal failure, antiperistal­ tic medications, and antibiotics, especially clindamycin. iii. A history of antibiotic use, antidiarrheals, anticholinergics, opiates, health facility contact, or immunosuppression (human immuno­ deficiency virus [HN] , chemotherapy) should be noted. iv. Travel to endemic areas may suggest Entameba infection. v. Exposure to others with gastrointestinal infectious symptoms should be elicited. 2. Physical examination. a. Systemic toxicity is heralded by fever and tachycardia and can prog­ ress to hypotension, confusion, agitation, or apathy. b. Abdominal tenderness and distension, with decreased bowel sounds on auscultation, are common. Constipation and obstipation may be present. c. Peritoneal signs indicate transmural inflammation or perforation, but they may be minimal or absent in elderly patients or in patients receiving corticosteroids. B. Diagnostic tests. 1. Laboratory studies. a. Laboratory tests should assess the degree of systemic toxicity, fluid and electrolyte deficits, pH disturbances, and the need for blood transfusion. b. Leukocytosis with a significant left shift is common. c. Elevated C-reactive protein and erythrocyte sedimentation rate is expected.

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2.

d. Anemia, hypokalemia, and hypoalbuminemia also commonly occur. e. Stool should be sent for C. difficile polymerase chain reaction (PCR) toxin and other pathogens. f. In HIV-positive patients, consideration should be given to CMV and Cryptosporidium. g. Blood cultures to assess for bacterial translocation are helpful. h. Most patients develop hypoalbuminemia. Radiologic studies. a. Abdominal imaging (plain x-ray, computed tomography) may reveal loss of colonic haustration, segmental or total colonic dilatation (to >6 cm) with mucosal thumbprinting, colonic wall thickening, stranding, air-fluid levels, abscess, intraperitoneal air, ascending pyelophlebitis, or pneumatosis cystoides coli in severe transmural disease. b. Small bowel ileus may accompany toxic megacolon and is a poor prognostic sign for conservative medical management. c. Discrepancies may exist between physical and radiographic findings.

Endoscopy. a. A limited proctoscopic examination may show extensive ulceration with friable, bleeding mucosa, or pseudomembranes. Biopsies may be obtained for histology if the etiology of the colitis is uncertain. b. More extensive endoscopic examination is contraindicated due to the risk of perforation. 4. The most commonly used diagnostic criteria require all components below: a. A dilated colon on imaging. b. At least three of the following: fever >38 degrees, tachycardia > 1 20, leucocytosis > 1 0 . 5 thousand with left shift, and/or anemia. c. At least one of the following: dehydration, altered mental status, electrolyte abnormalities, and/ or low blood pressure. 3.

I l l . TREAT M E NT

A. General measures. 1. Vigorous fluid, electrolyte, and blood replacement must be instituted early in the resuscitative effort, because hemodynamic instability is typical. Intensive-care-unit-level monitoring is recommended. a. Hypoalbuminemia, persistently elevated acute-phase reactants, small bowel ileus, and deep colonic ulcers are poor prognostic factors for successful medical therapy. b. Total body potassium depletion is common and needs urgent reple­ tion; phosphate, magnesium, and calcium deficiency also should be corrected parenterally. 2. Oral intake is discontinued, and nasogastric suction is employed for small bowel ileus. 3. Anticholinergic and narcotic agents should be stopped immediately.

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4. Serial abdominal exams should be done to assess for signs of deteriora­ tion or improvement. Serial abdominal x-rays may also be of value in some cases. 5. Stress ulcer prophylaxis and prophylaxis against deep venous thrombosis should be considered. B. Treatment of inflammatory bowel disease. 1. When inflammatory bowel disease is diagnosed or suspected, use of parenteral corticosteroids is essential. a. Augmented doses (hydrocortisone, 1 00 mg every 6 hours, or methylprednisolone, 6 to 1 5 mg every 6 hours) should be adminis­ tered. A continuous infusion can help maintain steady plasma levels. b. Aminosalicylates (e.g., mesalamine, sulfasalazine) have no role in the treatment of fulminant colitis or toxic megacolon and should be withheld until the patient has recovered and has resumed eating. c. Adrenocorticotropic hormone may be used in patients who have not had corticosteroid therapy in the last month; however, this is used rarely. 2. Intravenous cyclosporine (2 to 4 mg/kg/24 h in a continuous infusion) can be used when there is no improvement of severe ulcerative colitis after 7 to 1 0 days of intensive intravenous steroid therapy. The role of cyclosporine in toxic megacolon is controversial. 3. The role of infliximab in severe-to-fulminant ulcerative colitis continues to evolve. Most clinicians would consider infliximab infusion in steroid­ refractory severe colitis, but it is important not to delay definitive surgery when toxic megacolon is suspected. C. Antibiotics. 1. Broad-spectrum antibiotics are administered intravenously once toxic megacolon or transmural inflammation is suspected and are contin­ ued until the patient stabilizes over several days to a week. Antibiotics may reduce septic complications and provide coverage in the event of perforation. 2. Broad-spectrum antibiotics should be followed by pathogen-specific therapy in infectious colitis. 3. Intravenous metronidazole (500 mg every 8 hours) or oral/nasogastric vancomycin (500 mg four times daily) should be used if C. difficile infec­ tion is considered likely from the clinical presentation or proctoscopic findings. This should be accompanied by discontinuing any unnecessary antibiotics. D. Surgical indications. 1. Surgery is indicated if clinical deterioration or no significant improve­ ment occurs despite 1 2 to 24 hours of intensive medical management. Delay of operative therapy may promote higher mortality. 2. In ulcerative colitis, failure to respond to parenteral steroids or intrave­ nous cyclosporine after 7 days of therapy is an indication for surgery. 3. Evidence of colonic perforation, uncontrollable bleeding, and progres­ sive dilation are unequivocal indications for emergency surgery.

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4. Other indications for emergency surgery include signs of septic shock and imminent transverse colon rupture (the most dilated region in most cases of toxic megacolon) , especially if the diameter is > 12 cm. a. The absence of acute colonic dilatation may permit delay of surgical intervention for 5 to 7 days. b. The potential for prolonged intensive medical management and complications must be balanced against early surgical intervention to reduce mortality and morbidity. 5. Surgical options. a. The type of surgery performed for the treatment of fulminant colitis or toxic megacolon depends on the clinical status of the patient and the experience of the surgeon. b. Most surgeons prefer a limited abdominal colectomy with ileos­ tomy, leaving the rectosigmoid as a mucous fistula, or oversewing the rectum using a Hartmann procedure. This leads to a decreased morbidity and perioperative morality in ill patients, while leaving the option for a subsequent sphincter-saving ileoanal anastomosis. c. In less acutely ill patients, a one-stage resection with ileostomy may be appropriate. SUGGESTED READI NGS

Autenrieth DM, Baumgart, DC. Toxic megacolon. lnflamm Bowel Dis 2 0 1 1 ; 1 8 : 5 84-59 1 .

Comprehensive review of epidemiology, causes, pathogenesis, and therapy. Berman L, Carling T, Fitzgerald TN, et al. Defining surgical therapy for pseudomembranous colitis with toxic megacolon. J Clin Gastroenterol 2008;42:476-480.

Systematic review ofthe outcomes of 17 Clostridium. difficile cases complicated by toxic megacolon underscoring the importance ofearly diagnosis and treatment. Caprilli R, Vernia P, Colaneir 0, et al. Risk factors in toxic megacolon. Dig Dis Sci 1 980;25 : 8 1 7.

The severity ofelectrolyte imbalance and of metabolic derangement appears to be impor­ tant in the progression ofsevere colitis to toxic megacolon. Caprilli R, Vernia P, Latella G, et al. Early recognition of toxic megacolon. J Clin Gastroenterol 1 987;9: 1 60.

Persistent small bowel gaseous distension and severe metabolic alkalosis may predict the development oftoxic megacolon in severe ulcerative colitis. Cheung 0, Regueiro MD. Inflammatory bowel disease emergencies. Gastroenterol Clin North Am 2003;32 : 1 269- 1 28 8 .

Complications of inflammatory bowel disease, including folminant colitis and toxic megacolon, are comprehensively reviewed. Chew CN, Noland DJ, Jewell DP. Small bowel gas in severe ulcerative colitis. Gut 1 9 9 1 ;32: 1 53 5 .

Presence ofsmall bowel distension in severe ulcerative colitis predicts poor response to medical therapy. Gan SI, Beck PL. A new look at toxic megacolon: an update and review of incidence, etiology, pathogenesis, and management. Am J Gastroenterol 2003; 1 98 :2363-237 1 .

A discussion ofthe pathogenesis, diagnosis, investigation, and current management of toxic megacolon.

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Gore RM, Ghahremani GG. Radiologic investigation of acute inflammatory and infectious bowel disease. Gastroenterol Clin North Am 1 995;24:353.

Plain abdominal radiographs, barium studies, and cross-sectional imaging are comple­ mentary to endoscopic evaluation in acute enterocolitis. Imbriaco M, Balthazar EJ. Toxic megacolon: role of CT in evaluation and detection of com­ plications. Clin Imaging 200 1 ;25 : 349-354.

The use of CT scanning in the detection and management of toxic megacolon. Jalan KN, Sircus W, Card WI, et al. An experience of ulcerative colitis. Toxic dilation in 55 cases. Gastroenterology 1 969;57:68.

The most commonly used diagnostic criteria for toxic megacolon. Khanna S, Pardi DS. The growing incidence and severity of Clostridium difficile infection in inpatient and outpatient settings. Expert Rev Gastroenterol Hepatol 2 0 1 0;4:409-4 1 6.

Review ofincreased occurrence, morbidity, and mortality of C. difficile with associated virulent strains and increased antibiotic use. Lichtiger S, Present DH, Kornbluth A, et al. Cyclosporine in severe ulcerative colitis refractory to steroid therapy. N Engl] Med 1 994;330: 1 84 1 .

Intravenous cyclosporine is rapidly effective in some patients with severe, corticosteroid­ resistant ulcerative colitis.

H e p ati c Dysfu n ct i o n Kev i n M . Ko re n blat

I . G E N E RAL P RI N C I PLES

A. Hepatic dysfunction in the intensive care unit (ICU) setting can present as one of the following: 1. Abnormalities of liver chemistries or synthetic function. 2. Signs and symptoms of liver disease (e.g., jaundice, synthetic dysfunc­ tion, and complications of portal hypertension) . B. Hepatic metabolic processes are commonly disturbed in the setting of critical illness. These processes and their normal physiology include the following: 1. Bilirubin metabolism. a . Bilirubin is the end product of the catabolism of heme, the prosthetic moiety of hemoglobin, myoglobin, and other hemoproteins. b. Heme from senescent erythrocytes is the source of 80% of bilirubin. c. Unconjugated bilirubin is transported bound to albumin to the liver. d. Bilirubin is made soluble by conjugation with glucuronic acid within the hepatocytes. e. Conj ugated bilirubin is transported into the bile canaliculus and from the bile duct into the intestine. 2. Drug metabolism. a. The liver is frequently a site of first-pass metabolism of medications and other xenobiotics. b. Metabolic processes can be categorized as phase I or phase II reactions. i. Oxioreductases and hydrolases catalyze phase I reactions that increase water solubility of substances and potentially generate toxic metabolites. ii. Transferases catalyze phase II reactions that produce biologically less active metabolites. 3. Hemostasis. a. The liver is the site of production of many of the vitamin K-depen­ dent coagulation factors and the anticoagulants protein C and protein S . I I . ETI O LOGY

A. Clinical disorders commonly encountered in the critical care setting that result in hepatic dysfunction include the following: 1. lschemic hepatitis (Table 77- 1 ) . 554

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Causes of l s c h e m i c Hepatitis

Hypovo l e m i c shock B u rns He m orrhage Ca rd ioge n i c shock Hypoxe m ia Sepsis Sickle cell crisis H e patic a rte ry occ l u s i o n ; espec i a l l y post l iver tra n s pla ntation H eat stroke

a.

2.

3.

Develops in the setting of reduced liver blood flow, persistent hypo­ tension, or severe hypoxemia. b. A clearly defined period of hypotension may not be identifiable. c. A variable degree of central vein (zone 3) necrosis and collapse are present on liver histology. Congestive hepatopathy. a. Any process that increases hepatic vein pressures (e.g., right heart fail­ ure, pericardial disease, or pulmonary hypertension) can cause hepatic congestion. b. Mild elevations in serum aminotransferases, alkaline phosphatase, and bilirubin may be present. c. Long-standing hepatic venous congestion may result in cirrhosis (cardiac cirrhosis) . d. Alternate diagnoses that may resemble the presentation of congestive hepatopathy include the following: i. Budd-Chiari syndrome (hepatic vein thrombosis) . ii. Sinusoidal obstruction syndrome (venoocclusive disease) . iii. Inferior vena cava thrombosis at its hepatic portion (obliterative hepatocavopathy) . Total parenteral nutrition (TPN)-related liver injury. a. Hepatic steatosis and steatohepatitis are the most common hepatic complications in adults. b. Asymptomatic elevations in serum chemistries are a common presen­ tation of hepatic steatosis and steatohepatitis. i. Deficiencies of essential fatty acids (linoleic acid) or choline may contribute to the development of steatosis. c. Cholestasis is the predominant clinical finding in infants. i. Conditions associated with the development of cholestasis include large doses of lipid emulsion (> l g/kg/d) , short gut syn­ drome, and bacterial overgrowth. ii. Elevations in serum bilirubin may be mild to severe. iii. Cholestasis, particularly in infants, may result in progression to cirrhosis and liver failure. d. Biliary sludging.

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i. Biliary sludging may develop in up to 50% of patients managed with 6 weeks ofTPN. ii. Clinical manifestations of sludging may vary from asymptomatic to cholecystitis. 4. Sepsis. a. Hepatic dysfunction is common in sepsis and is a consequence of alterations in hepatic blood flow, activation of reticuloendothelial cells, and release of inflammatory cytokines. b. Elevations in serum aminotransferases two to three times the upper limits of the reference range may occur 2 to 3 days after the onset of bacteremia. c. Jaundice with elevations in serum levels of alkaline phosphatase may also occur and is known as sepsis-induced cholestasis. These elevations may become very high, particularly in human immunode­ ficiency virus (HIV)- !-infected patients. 5. Drug hepatotoxicity. a. There are a myriad of patterns associated with drug-induced liver injury. The pattern observed may depend on the dose and duration of drug exposure and host susceptibility factors. b. Idiosyncratic reactions (e.g., isoniazid, phenytoin) : The damage is dose independent and unpredictable. c. Intrinsic hepatotoxicity is dose dependent, as is seen with acetamino­ phen and methotrexate. I l l . DIAG N O S I S

A . History. 1 . Pertinent historical features include episodes of symptomatic hypoten­ sion, a history of right or biventricular heart failure, and new medica­ tions associated with liver injury. 2. Concurrent symptoms of abdominal or right upper quadrant abdominal pain may suggest mechanical biliary obstruction. 3. The history should be scrutinized for the use of nonprescription medica­ tions, including complementary and alternative medicines. B. Physical examination. 1. Physical findings associated with congestive hepatopathy include jaun­ dice, tender hepatomegaly, j ugular venous distension, edema, and, m severe cases, ascites. C. Laboratory studies. 1. In ischemic hepatitis, serum aminotransferases tend to rise rapidly to levels 1 0 to 40 times the upper limits of the reference range. Increases in alkaline phosphatase and bilirubin may rise as transaminase elevations decrease.

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Hyperbilirubinemia should be further investigated by measuring both direct-reacting (conjugated) bilirubin and indirect-reacting (unconju­ gated) bilirubin. The latter is calculated by subtracting the direct fraction from the total bilirubin. a. Indirect hyperbilirubinemia may result from hemolysis, decreased hepatic clearance due to impairment of bilirubin conjugation, or circumstances in which both processes occur simultaneously. i. Gilbert syndrome and Crigler-Najjar syndrome types I and II are inherited disorders resulting in decreased bilirubin conjugation. ii. Gilbert syndrome affects 8% of the general population and is characterized by a mild, unconjugated hyperbilirubinemia to levels that rarely exceed 4 mg/dL and normal liver function. b. Mixed direct and indirect hyperbilirubinemia or pure direct hyper­ bilirubinemia can be the result of heritable disorders of bilirubin canalicular excretion, liver disease, or biliary obstruction. D. Radiographic studies. 1. Sonography (with Doppler studies) of the right upper quadrant can provide information about liver architecture; diameter of intrahepatic and extrahepatic bile ducts; and flow in hepatic veins, portal vein, and hepatic artery. 2. Combined right heart and transjugular portal pressure measurements can differentiate ascites development from chronic passive congestion from hepatic cirrhosis. 2.

IV. TREAT M E N T

A. Treatment of ischemic hepatitis and congestive hepatopathy is supportive in nature; emphasis should be placed on maintaining organ perfusion and improving venous return. B. The cholestasis of sepsis is best managed by treatment of the underlying infectious process, correction of fluid and electrolyte imbalances, and intro­ duction of enteral feeding as soon as the clinical condition permits. C. TPN steatosis may be amenable to decreasing the carbohydrate load, decreas­ ing total calories (25 to 40 kcal/kg/d), and cycling the infusion schedule. D. Ursodeoxycholic acid ( 1 0 to 45 mg/kg/d) orally has been of variable success in the management of TPN-related cholestasis. E. Immediate cessation of the medication responsible for liver injury is the treatment of drug-induced liver injury. 1 . The development of jaundice in drug-induced liver injury is associated with a 1 0% to 50% case fatality rate and should prompt consideration for liver transplantation in the appropriate candidate for organ trans­ plantation. F. Treatment with corticosteroids can be considered in drug hypersensitivity syndromes (drug rash with eosinophilia and systemic symptoms [DRESS]) or drug-induced autoimmune reactions (e.g. , minocycline) .

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S U G G ESTED R EAD I NGS

Chalasani N, Fontana RJ, Bonkovsky HL, et al. Causes, clinical features and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology 2008; 1 3 5 (6) : 1 924- 1 934.

A prospective study ofdrug-induced liver injury (DILI) in the United States. Antimicrobial and medications for central nervous system disorders accounted for 60% of all cases ofDILI. Chand N, Sanyal AK. Sepsis-induced cholestasis. Hepatology 2007;45 ( 1 ) :230-24 1 .

A comprehensive review of the mechanisms, causes, and treatment ofsepsis-induced cholestasis. Guglielmi FW, Regano N, Mazzuoli S, et al. Cholestasis induced by total parenteral nutrition. Clin Liver Dis 2008; 1 2 ( 1 ) :97- 1 1 0.

Overview ofhepatic dysfonction associated with TPN Korenblat KM, Berk PD. Approach to the patient with jaundice or abnormal liver tests. In: Goldman L, Ausiello D, eds. Cecil's textbook of medicine, 23rd ed. Philadelphia: Elsevier Science, 2008.

A comprehensive review of bilirubin metabolism and approach to the investigation of hyperbilirubinemia and abnormal liver tests.

Eva l uati o n a n d M a n a ge m e nt of L i ve r Fa i l u re Kev i n M . Kore n b lat

I. G E N E RAL P R I N C I PLES A.

Acute liver failure (ALF), also known as fulminam hepatic failure, is a rare con­ dition defined as the development of coagulation disturbance and encephalopa­ thy in individuals without cirrhosis and with an illness of 30-degree elevation may improve cerebral venous drainage. c. Placement of an ICP monitor is appropriate for the identification and treatment of cerebral edema in subjects who are candidates for liver transplantation (LT) and progress beyond grade 2 encephalopathy. i. The cerebral perfusion pressure (CPP) is the difference between mean arterial pressure (MAP) and ICP; the goal of ICP monitor­ ing is to maintain the CPP > 50 mm Hg and ICP < 1 5 mm Hg. ii. Risks of ICP monitoring include epidural and intracranial bleed­ ing and infection. d. Treatment options for increased ICP include the following: i. Permissive hypernatremia. ii. Hypertonic saline to raise serum sodium to 145 to 1 5 5 mmol/L. iii. Intravenous (IV) mannitol (0. 5 to 1 g/kg) . iv. Hypothermia to a core body temperature of 32°C. v. Hyperventilation to maintain an arterial carbon dioxide partial pressure 25 to 30 mm Hg; the effects are short-lived. vi. The use of lactulose in the encephalopathy of ALF is controver­ sial. No clear benefits to severity of encephalopathy or outcome have been shown with its use. 5. Metabolic disorders. a. Hemodialysis may be required. Continuous modes of hemodialysis are preferable to prevent hemodynamic instability. b. Prevention of hypoglycemia is essential for preservation of neurologic function; frequent glucose monitoring and infusions of 1 0% to 50% dextrose solutions may be required. 6. Acetaminophen toxicity. The administration of N-acetylcysteine (NAC) is an effective, lifesaving antidote to acetaminophen toxicity. a. The decision to use NAC is based on reference to a standardized treatment nomogram and requires knowledge of serum acetamino­ phen level and time of ingestion.

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b. NAC is most effective when given within the first 24 hours after ingestion; NAC may still be useful even when treatment is delayed >24 hours or when signs and symptoms of ALF have developed. c. The oral dose of NAC is 140 mg/kg loading dose, followed by 1 7 doses o f 7 0 mg/kg every 4 hours. d. NAC can be given as a continuous IV infusion, and various dosing regiments are available. One dosing schedule is 1 50 mg/kg IV given over 1 5 minutes, followed by 50 mg/kg N given over 4 hours, and then 1 00 mg/kg IV given over 20 hours. e. Electrolyte imbalances, particularly hypophosphatemia, are common with acetaminophen-induced liver failure and correction of electro­ lyte disorders is essential. 7. Role of NAC in nonacetaminophen ALF. a. In a randomized, controlled trial, administration of NAC to subjects with nonacetaminophen ALF appeared to improve spontaneous sur­ vival when given during the early stages of encephalopathy. 8. LT: Patients with ALF without contraindications to LT should be man­ aged at LT center. a. The King's College criteria (Table 78-2) can be useful to identify poor prognostic factors that identify individuals who require LT for survival. These criteria are subdivided into acetaminophen and nona­ cetaminophen causes of ALF. i . Currently available scoring systems d o not adequately predict out­ come and should not be exclusively relied upon to determine need for LT. TA B L E 7 8 - 2

K i ng's College Criteria for Liver Tra n s p l a ntation for Acute Liver Fa i l ure (ALF)

Nonaceta m i n o p h e n ca uses of ALF I N R > 7 . 7 ( i r res pective of grade of encephalopathy) o r a ny t h ree of the fo l lowi ng: Age 40 U nfavo ra ble cause N o n -A, non-B h e patitis Drug reacti on Wi lson d i sease Period of ja u n d ice to encephalopathy >7 days I N R > 3.85 Seru m b i l i r u b i n > 1 7 mg/d L Aceta m i n ophen -related A L F p H < 7 . 3 ( i rrespective o f grade o f encepha l o pathy) or a l l th ree o f the fo l lowi ng G rade I l l-IV encephalopathy I N R > 7.7 Seru m c reati n i n e > 3.4 mg/d L I N R , i nternational normal ized ratio .

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lf;i:i!fi:fl

Ca uses of C h ro n i c Liver Fa i l u re

H e patitis B H e patitis C Autoi m m u n e h e patitis Hered ita ry h e m oc h rom atos is a 1 -Antitryps i n d efic iency Wi lson d isease N o n a lcoholic fatty l iver d isease Pri m a ry b i l i a ry ci rrhosis Pri m a ry sclerosing chola ngitis Alcohol-re lated l iver d isease

I l l . C H R O N I C LIVER FAI L U R E

A . Etiology. 1 . Chronic liver failure is the consequence of long-standing hepatic injury from multiple different causes (Table 78-3) . B. Pathophysiology. 1 . Cirrhosis also results in endothelial dysfunction and increased resis­ tance ro flow within the hepatic sinusoids. Sinusoidal hypertension and endothelial dysfunction produce portal hypertension and its cardinal features. a. Increased resistance ro mesenteric vascular flow. b. Activation of the compensatory systems to maintain effective arterial volume resulting in sodium and water retention and increased intra­ vascular volume. 2. Portal hypertension is responsible for many complications of chronic liver disease: a. Gastrointestinal bleeding. b. Ascites. c. Portosystemic encephalopathy. d. HRS . e . Pulmonary disease. i. Hepatopulmonary syndrome. ii. Portopulmonary hypertension. C. Diagnosis. 1. History. a. Common symptoms include fatigue, increased abdominal girth, emotional !ability, day-night sleep reversal, and poor mental concen­ tration. 2. Physical examination. a. Common physical findings include jaundice, temporal wasting, abdominal ascites, splenomegaly, asterixis, spider angiomata, and male gynecomastia.

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Blood tests. a. Varying degrees of thrombocytopenia and leucopenia may be present as a consequence of hypersplenism. b. Anemia associated with liver disease is rypically macrocytic. In advanced liver disease, a spur cell (acanthocytes) hemolytic anemia may develop. c. Elevations in serum rransaminases and alkaline phosphatase are vari­ able; hypoalbuminemia and prolongation of INR are common with cirrhosis and indicate synthetic dysfunction. d. A mixed direct- and indirect-reacting hyperbilirubinemia is common, particularly in cholestatic liver diseases. e. Elevations in serum ammonia are commonly seen with encephalopa­ thy; however, there is modest correlation with rhe magnitude of the elevation and the severiry of the encephalopathy. 4. Ascites studies. a. Ascites from portal hypertension is characterized by a difference > 1 . 1 g/dL between serum albumin and ascites albumin; this difference is known as the serum-ascites albumin gradient (SAAG) . b. Spontaneous bacterial peritonitis (SBP) is diagnosed when the neu­ trophil count in ascites fluid is >250/mL or when bacteria can be cultured from ascites. c. The ascites fluid should be inoculated directly into blood culture bottles to increase the potential for identification of bacteria. d. Peritonitis from either abdominal perforation or nonperforation abdominal abscess should be considered when multiple organisms are cultured from the ascites or the neutrophil count is high. i. The ascites in these conditions should fulfill two of the following criteria: (a) Total protein > l g/dL. (b) Glucose < 50 mg/dL. (c) LDH greater rhan upper limit of the reference range. 5. Urine studies. a. A random urine sodium 3 cardiac cycles) passage into the left heart of injected agitated saline bubbles. iii. Supplemental oxygen administration, exclusion of other causes of shunt, and LT are treatments. b. Portopulmonary hypertension. i. A disorder characterized by liver disease causing portal hyperten­ sion, mean pulmonary arterial pressure (PAP) > 25 mm Hg (at rest) , mean pulmonary capillary wedge pressure < 1 5 mm Hg, and pulmonary vascular resistance >3 Woods units. ii. Right heart catheterization with measurement of pulmonary artery pressure is the "gold standard" for diagnosis. iii. LT is contraindicated in subjects with severe pulmonary hyper­ tension (mean PAP > 50 mm Hg) but can be considered in those who respond to treatment with oral or IV vasodilator therapy. 7. Liver transplantation. a. LT in appropriately selected subjects can effectively treat all the com­ plications of end-stage liver disease.

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b. In the United States, prioritization for LT is determined by calcula­ tion of the model for end-stage liver disease (MELD) score. A MELD calculator is available at URL: http://www. unos.org/resources/ meld­ PeldCalculator.asp. SUGG ESTED R EAD I NGS

European Association for the Study of the Liver. EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis and hepatorenal syndrome in cirrhosis. } Hepatol 2 0 1 0;53(3):397-4 1 7.

Evidence-basedpractice guidelines on the management ofascites and its complications in cirrhosis. Lee WM, Hynan LS, Rossaro L, et al. Intravenous N-acetylcysteine improves transplant­ free survival in early stage non-acetaminophen acute liver failure. Gastroenterology 2009; 1 37:856-864.

A randomized, controlled clinical trial peiformed by the United States ALF Study group on the role ofNAC for nonacetaminophen ALF. Lee WM, Stravitz RT, Larson AM. Introduction to the revised American Association for the Study of Liver Diseases position paper on acute liver failure 2 0 1 1 . Hepatology 2 0 1 2 ; 5 5 (3):965-967.

Comprehensive evidence-based guidelines from the American Association for the Study of Liver Diseases on the management ofALF.

D i a rrh e a Ka ra A . R ega n a n d C . Prakash Gyawa l i

I . G E N E RAL P RI N C I PLES

A. Definition. 1. Diarrhea is traditionally defined as increase in frequency of stool or decrease in consistency, based upon the individual's baseline. 2. Other definitions include three or more loose or watery stools per day and stool weight > 200 g/day. B. Classification. 1. Acute diarrhea consists of diarrhea lasting � 1 4 days. 2. Chronic diarrhea is defined as diarrhea continuing for >30 days. Diarrhea lasting > 14 days but 60 years) can be as high as 8 5 % . I I . ETI O LOGY

A. Infectious causes. 1. Typical etiologies in the community may also apply to the patient in intensive care. The most commonly reported cause of acute gastroen­ teritis in the community is norovirus (Norwalk) ; other viral etiologies include rotavirus, enteric adenovirus types 40 and 4 1 , and astrovirus. Salmonella and Campylobacter are common bacterial causes. Bloody diarrhea can typically result from Shigella and Escherichia coli 0 1 57:H7 infections. Amebiasis can also cause bloody diarrhea and dysentery. 568

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Fungal and mycobacterial diarrhea are rare. Brainerd diarrhea is a chronic or persistent cause of diarrhea of rather acute onset but unclear etiology, first reported in Brainerd, Minnesota. 2. Clostridium difficile toxin-induced colitis is implicated in 1 5% to 20% of cases. Clindamycin, penicillin, and broad-spectrum cephalosporins are commonly associated with the diagnosis. 3. In the immunosuppressed and the elderly, cytomegalovirus (CMV) or herpes simplex virus (HSY) may be implicated. B. Iatrogenic causes.

1. Medications. a. Antibiotics, especially erythromycin, ampicillin, clindamycin, cepha­ losporins, and azithromycin, cause iatrogenic diarrhea in 3% to 29% of patients. Alterations in intestinal flora, breakdown of dietary car­ bohydrate products, and prokinetic effects (e.g., from erythromycin) are all postulated mechanisms for antibiotic-related diarrhea. b. Other medications implicated in the development of diarrhea include antacids (magnesium containing) , magnesium and phosphorus supplements, lactulose, colchicine, digitalis, quinidine, theophylline, levothyroxine, aspirin, nonsteroidal anti-inflammatory agents, cimeti­ dine, misoprostol, diuretics, �-blocking agents, chemotherapeutic agents, proton-pump inhibitors, and antiretroviral medications such as nelfinavir. These medications rarely cause severe diarrhea. 2. Enteral feeding. a. Diarrhea frequently occurs in enterally fed patients and is usually associated with concurrent antibiotic use. b. Osmolarity of the enteral solution can play a role in some instances, as can bolus feeding distal to the pylorus. c. Enteral formulas high in lactose or fat content may precipitate diar­ rhea in susceptible patients. C. Diarrhea as a primary manifestation of disease. 1. Inflammatory bowel disease (IBD) : The rwo named IBDs are Crohn's disease, which can affect any part of the luminal gut; and ulcerative colitis, which only affects the colon within the luminal gut. Less com­ mon patterns of inflammatory mucosa! disease include lymphocytic colitis, collagenous colitis, autoimmune enteritis, celiac disease, sarcoid, graft-versus-host disease (GVHD) , and other idiopathic processes. Fulminant colitis is addressed elsewhere (see Chapter 76) . 2. Malignancy: Certain types of adenocarcinoma can cause diarrhea, especially those with villous patterns. Lymphoma, carcinoid, gastrinoma, VIPoma, and somatostatinoma can also present as diarrhea. 3. Anatomical causes: Short gut syndrome, where 38. 5°C ( 1 0 1 .3°F), severe abdominal pain, older age, immunocompromised state, or pregnancy. a. Skin rashes or mucosa! ulcerations may suggest GVHD, IBD, or vasculitis; other extraintestinal manifestations of diseases associated with diarrhea should be noted. b. Postural hypotension suggests severe volume loss, adrenal insuffi­ ciency, or autonomic neuropathy. c. Fever suggests possible infection, vasculitis, adrenal insufficiency, or hyperthyroidism. d. Abdominal tenderness may suggest infection, ischemia, or vasculitis. e. An abnormal rectal examination may be the only sign of a partially obstructing fecal impaction. B. Laboratory studies. 1. Hyperchloremic metabolic acidosis, hypokalemia, prerenal azotemia, and other serious electrolyte imbalances may occur with severe diarrhea. Hyperkalemia may be present with adrenal insufficiency or uremia. 2. Leukocytosis may suggest infection or ischemia, neutropenia, an immunosuppressed state, or sepsis. A falling hematocrit may suggest GI bleeding.

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Additional tests can include TSH, celiac serology, urine 5-HIAA and serum chromogranin (carcinoid) , serum vasoactive intestinal peptide (VIPoma) , serum gastrin (gastrinoma) , somatostatin (somatostatinoma) , serum calcitonin, stool magnesium and laxative screen (laxative abuse) , and antienterocyte antibody (autoimmune enteropathy) . C. Stool studies. 3.

1. Fresh stool specimens should be sent for C. difficile toxin assay and cul­ ture for enteric pathogens. Stool PCR for C. difficile is rapidly replacing the toxin assay because of its superior sensitivity, specificity, and rapid turnover. Repeat tests are unnecessary; however, the test may remain positive for an indeterminate amount of time. 2. Immunosuppressed patients may need more extensive stool tests, including ova and parasite evaluation and concentration for isolation of Cryptosporidium, Microsporidium, or Isospora be/Ii. 3. The stool osmolar gap, that is, the difference between the expected stool osmolarity (290 mOsm/kg) and the calculated stool osmolarity { ( [stool Na•] + [stool K•] ) x 2}, may help distinguish between osmotic and secre­ tory causes when diarrhea is severe or protracted and no diagnosis is apparent; an elevated stool osmolar gap (>70 mOsm/L) suggests osmotic causes. 4. High-volume stool output that persists with fasting supports a secretory ongm. 5. A Sudan stain for fecal fat or stool pH occasionally is helpful (pH < 5 . 6 may indicate carbohydrate malabsorption) . D. Imaging studies. 1. Plain abdominal radiographs can detect partial obstruction, perforation, or changes associated with enteritis or colitis and are recommended in the presence of pain or an abnormal abdominal examination. 2. Contrast studies, including computed tomography (CT) and intestinal radiographs, may be required in difficult or protracted cases, when pos­ sible. CT imaging can help identify bowel wall thickening, tumors, and obstruction. MREnterography/CTEnterography can assist with better examination of the small bowel for abnormality and IBD. Small bowel follow-through can help better define the anatomy of the small bowel, and examine for evidence of small bowel abnormality or fistula. E. Endoscopy. 1 . Flexible sigmoidoscopy is useful in diagnosing pseudomembranous colitis, ischemic colitis, CMV colitis, herpetic proctocolitis, or GVHD and is usually considered in the presence of bright red rectal bleeding or other indicators of distal colitis. 2. Mucosa! biopsies are helpful on occasion when endoscopic findings are nonspecific or absent. Colonoscopy is most useful in chronic diarrhea for the identification of IBD, microscopic inflammatory disorders, and neoplasia. Upper endoscopy with small bowel biopsies may be of value to evaluate in diagnosing celiac disease, giardiasis, Crohn disease, Whipple disease, amyloid, and eosinophilic gastroenteritis. Duodenal aspirate could have value in diagnosing Giardia or small intestinal bacterial overgrowth.

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IV. TREAT M E NT

A. General measures. 1 . Correction of fluid and electrolyte imbalance needs immediate attention. 2. Central venous access and monitoring may be necessary in patients with severe fluid loss. 3. Proper patient hygiene and skin care should be maintained, and patient isolation with enteric precautions should be instituted when indicated. 4. Iatrogenic causes of diarrhea are corrected by withdrawal of the offending medications. 5. Enteral feedings suspected of causing diarrhea should be reduced in volume or temporarily discontinued. Some suggest an advantage of con­ tinuous infusion over bolus infusions. There is also evidence to suggest that the addition of fiber to continuous infusions decreases the incidence of diarrhea in tube-fed patients. 6. A change in formula to an elemental diet may be indicated in patients with short bowel syndrome, pancreatic insufficiency, radiation enteritis, fistula, or IBD. 7. In severe cases, total parenteral nutrition may be necessary as a tempo­ rary measure. B. Specific treatment. 1. Specific or pathogen-related treatment should be administered whenever possible in both immunocompromised and immunocompetent hosts. 2. Clostridium difficile colitis. a. If C. difficile related diarrhea is suspected, the offending antibiotic should be discontinued when possible; spontaneous improvement often results from this measure alone; 1 5% to 23% of patients have symptom resolution within 48 to 72 hours of stopping the offending agent. Unfortunately, this option is often not possible in the intensive care setting, as it is not possible to predict which patients will respond with spontaneous resolution with simple cessation of the antibiotic, and delaying therapy increases the period of contagion. b. Earlier studies indicated that oral metronidazole (250 to 500 mg three times daily) was as effective as oral vancomycin ( 1 25 to 500 mg four times daily), yet was less expensive and did not contribute to selection for vancomycin-resistant bacteria. In moderate to severe cases of C. difficile colitis, however, more recent studies have sug­ gested that oral metronidazole may be inferior to vancomycin. c. Vancomycin is typically reserved for treatment failures and severe cases. However, in toxic megacolon, intravenous metronidazole should be administered. d. Response is expected within 24 to 48 hours with improvement in diarrhea, pain, fever, and leukocytosis. Treatment should be contin­ ued for 7 to 14 days. e. As many as 24% patients have a relapse and, in these situations, longer and multiple courses of treatment are often required. -

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f. Anion-exchange resins such as cholestyramine or colestipol are reportedly useful as adjunctive measures in mild cases or in relapses. These agents can bind vancomycin, making their use less desirable. g. Antimotility agents should not be used, because they may lengthen the course of the illness. C. Symptomatic measures. 1. When a cause of diarrhea is not found, palliative treatment lessens fluid losses, patient discomfort, and morbidity. 2. Antimotility agents may decrease the frequency and severity of diarrhea, but monitoring for complications is required (e.g., central nervous sys­ tem side effects, gut hypomotility) . a. These drugs include loperamide (4 mg initially, and up to 1 6 mg/day) , diphenoxylate with atropine (20 mg of diphenoxylate four times daily initially, then decrease and titrate to symptoms) , and deodorized tincture of opium (6 to 1 2 gtt two to four times daily) . b. Octreotide can be used for palliation of diarrhea in patients with acquired immunodeficiency syndrome, GVHD, hormone-producing tumors, and other causes of secretory diarrhea. SUGG ESTED R EAD I NGS

Bartlett JG. Clinical practice. Antibiotic-associated diarrhea. N Engl] Med 2002;346:334-339.

A comprehensive discussion ofantibiotic-associated diarrhea. Bresee J, Marcus R, Venezia R, et al. The etiology of severe acute gastroenteritis among adults visiting the emergency departments in the United States. ] Infect Dis 2 0 1 2;20 5 : 1 374- 1 3 8 1 .

A discussion ofcauses ofacute gastroenteritis and the yield of initial stool investigation. Brown E, Talbot GH, Axelrod P, et al. Risk factors for Clostridium difficile toxin-associated diarrhea. Infect Control Hosp Epidemiol 1 990; 1 1 :283.

Age > 65 years, ICU admission, GI procedures, and administration ofantibiotics for more 1 0 days were associated with C. difficile-associated diarrhea. Cataldi-Betcher EL, Seltzer MH, Slocum BA, et al. Complications occurring during enteral nutritional support: a prospective study. ] Parenter Enteral Nutr 1 983;7:546.

Tube feedings are safely tolerated in most patients, but complications must be recognized and treated promptly. Cremonini F, Di Caro S, Nista EC, et al. Meta-analysis: the effect of probiotic administration on antibiotic-associated diarrhoea. Aliment Pharmacol Ther 2002; 1 6 : 1 4 6 1 - 1 467.

Probiotics may benefit patients with antibiotic-associated diarrhea. Dark DS, Pingleton SK. Nonhemorrhagic gastrointestinal complications in acute respiratory failure. Grit Care Med 1 989; 1 7:755.

Diarrhea is the most common nonhemorrhagic GI complication in the ICU, occurring more frequently in critically ill patients who are administered antacids. Fekety R. Guidelines for the diagnosis and management of Clostridium difficile-associated diarrhea in colitis. Am ] Gastroenterol 1 997;92:739.

Practical guidelines for the management of C. difficile diarrhea. Guenter PA, Settle RG, Perlmutter S. et al. Tube feeding-related diarrhea in acutely ill patients. ]PENJ Parenter Enteral Nutr 1 9 9 1 ; 1 5 : 277.

Antibiotic usage was the factor most strongly associated with diarrhea in acutely ill patients administered tubefeedings.

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Kelly TWJ, Patrick MR, Hillman KM et al. Study of diarrhea in critically ill patients. Crit Care Med 1 983; 1 1 :7. ,

Notes the significant incidence ofdiarrhea in critically illpatients, especially in associa­ tion with nasogastric feeding. Kuipers EJ, Surawicz CM. Clostridium difficile infection. Lancet 2008;37 1 : 1 486- 1 48 8 .

Review of C. difficile epidemiology, pathogenesis, presentation, diagnosis, and management. Luo RF, Banaaei N. Is Repeat PCR needed for the diagnosis of Clostridium difficile infection? j Clin Microbiol 2 0 1 0;48:3738-374 1 .

Review ofthe use of C. difficile PCR in the diagnosis and treatment of C. difficile infection. Musher DM, Aslam S. Treatment of Clostridium difficile colitis in the critical care setting. Crit Care Clin 2008;24:279-29 1 .

Reviews treatment of C. difficile colitis in the intensive care setting. Sakai L, Keltner R, Kaminski D. Spontaneous and shock-associated ischemic colitis. Am j Surg 1 980; 1 40:755.

Ischemic colitis carries a high mortality when it is associated with full-thickness necrosis; radiologic findings correlated well with clinical and pathologic evidence offull-thickness necrosis. Shimoni Z, Averbuch Y, Shir E, et al. The addition of fiber and the use of continuous infusion decrease the incidence of diarrhea in elderly rube-fed patients in medical wards of a general regional hospital: a controlled clinical trial. j Clin Gastroenterol 2007; 4 1 ( 1 0) : 9 0 1 -905.

Methods to decrease diarrhea in tube-fed elderly patients. Teasley DG, Gerding DN, Olson M, et al. Prospective randomized trial of metronidazole versus vancomycin for Clostridium difficile associated diarrhea and colitis. Lancet 1 983;2: 1 043. -

Metronidazole and vancomycin have equivalent efficacy and tolerance in treating C. difficile-associated diarrhea, but metronidazole is more economical. Thielman NM, Guerrant RL. Clinical practice. Acute infectious diarrhea. N Englj Med 2004;350:38--47.

A review ofthe etiology and management ofacute infectious diarrhea. Wiesen P, Van Gossum A, Preiser JC. Diarrhoea in the critically ill. Curr Opin Crit Care 2006; 1 2 (2): 1 49-1 54.

A discussion ofcauses and management ofdiarrhea in critically illpatients. Yassin SF, Young-Fadok TM, Zein NN, et al. Clostridium difficile-associated diarrhea and colitis. Mayo Clin Proc 200 1 ;76:725-730.

Clinical presentation, diagnosis, and management ofpseudomembranous colitis associated with C. difficile are reviewed. Zar FA, Bakkanagari SR, Moorthi KM et al. A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile associated diarrhea, stratified by disease severity. Clin Infect Dis 2007;45:302-307. ,

-

Vancomycin may be superior to metronidazole in severe C. difficile colitis.

S eve re a n d C o m p l i c ate d B i l i a ry Tra ct D i s e a s e Ta re k Abou H a m d a n a n d R iad Aza r

I . G E N E RAL P R I N C I PLES

A. Timely diagnosis and therapy of the different biliary disorders commonly encountered in the intensive care unit (ICU) reduce the significant mortal­ ity and morbidity from unrecognized disease. B. A practical approach to evaluate and treat biliary disorders using a wide array of noninvasive and invasive diagnostic and therapeutic aids is of para­ mount importance. I I . ETIOLOGY

A. Cholangitis. 1. Cholangitis occurs in patients with bile duct obstruction from stones, strictures, or recent manipulation of the biliary tree promoting bacterial translocation. 2. The clinical manifestations include fever, right upper quadrant (RUQ) abdominal pain, and jaundice (Charcot triad) . In severe cases, mental status changes and hypotension can be present (Reynold pentad) . 3. Laboratory abnormalities include elevated bilirubin, alkaline phospha­ tase, and white cell count. 4. Blood cultures are often positive for gram-negative bacteria and anaerobes. B. Biliary obstruction without cholangitis. 1. Common causes include stone disease, benign strictures, and tumors; other causes are listed in Table 80- 1 . 2 . When the obstruction i s painless, the most likely diagnosis is a neoplasm. C. Bile leak. 1. Bile leak can result from cholecystectomy, hepatic resection, liver trans­ plantation, trauma, or percutaneous biliary manipulations. 2. The resultant bile peritonitis produces abdominal pain, ascites, leukocy­ tosis, and fever. D. Acalculous cholecystitis. 1. Acalculous cholecystitis is typically seen in critically ill patients and can result in significant morbidity and mortality. 2. High degree of suspicion is needed because symptoms may be masked by the underlying clinical situation. 575

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lt'=i!j:l.11

Causes of B i l i a ry Obstruction

I ntrinsic lesions G a l lsto nes Chola ngioca rc i n o m a Ben ign strictu re Scleros i n g chola ngitis Peria rteritis nod osa A m p u l la ry ste nosis Pa ras ites Extri nsic lesions Pancreatic ca rc i n o m a M etastatic ca rc i n o m a Pancreatitis Pancreatic pse ud ocyst Viscera l a rte ry a n e u rysm Lym phadenopathy Choledoc h a l cyst H e patic cyst or cysts Duodenal d ive rticu l u m I atroge n i c lesions Posto perative strictu re

E. Gallstone pancreatitis. 1 . Evidence suggests that stone passage or impaction in the ampulla leads to pancreatitis. 2. The severity of pancreatitis can be graded based on prognostic scales that include the Ranson criteria, the Glasgow criteria, and computed tomography (CT) identifying those at risk for a complicated hospital course. I l l . DIAG N O S I S

A . Physical examination. 1. Physical examination may reveal icterus, ascites, or focal RUQ tenderness. 2. Findings range from acute abdomen to fever. B. Laboratory evaluation. 1. Bilirubin elevation may indicate an obstructive process, but can result from sepsis, drugs, or hemolysis in acutely ill patients. 2. Alkaline phosphatase elevation is not specific for biliary disease; concomi­ tant elevation of y-glutamyl transferase helps confirm hepatobiliary origin. 3. Elevation of transaminases can be seen with bile duct obstruction and may precede bilirubin and alkaline phosphatase elevation in the acute setting. 4. Occasionally, lab values can be normal as in cholecystitis.

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C. Plain abdominal radiograph. 1. Usually shows nonspecific findings. 2. Air in rhe biliary tree can result from a prior sphincterotomy, biliary­ enteric fistula or surgical anastomosis, or infection with gas-producing orgamsms. D. Ultrasonography. 1 . The initial procedure of choice and can be performed at the bedside. 2. Sensitive for determining biliary ductal dilatation, acute cholecystitis, and >95% accuracy in detecting cholelithiasis. 3. Limited accuracy in detecting choledocholithiasis, as gas in the duode­ num can obscure visualization of the distal bile duct. E. Radionuclide scanning. 1. 99mTechnetium (99mTc) hepatic iminodiacetic acid (HIDA) scans yield physiologic and structural information regarding the biliary tract. 2. Filling of rhe gallbladder confirms patency of the cystic duct virtually excluding acute cholecystitis. 3. Can be false positive in patients on long-term total parenteral nutrition (TPN) or afrer prolonged fasting. 4. Limited role in patients with poor hepatocellular function, complete biliary obstruction, and cholangitis, each of which prevents adequate uptake or excretion of the radiopharmaceutical into the biliary tree. 5. Evidence of radiotracer in the abdominal cavity is diagnostic of bile leaks. F. CT and magnetic resonance imaging (MRI). 1. Highly accurate for the detection of level and cause of biliary obstruction. 2. CT allows detailed visualization of the pancreas for grading the severity of pancreatitis and assessing its complications. 3. CT may reveal a biloma or free fluid in the abdominal cavity. 4. MRJ rhat incorporates cholangiopancreatography (MRCP) provides high­ resolution images of rhe pancreatobiliary system with very high sensitivity and specificity for diagnosis of choledocholithiasis, strictures, and tumors. 5. These studies are impractical in many ICU patients who are too sick for transport. G. Endoscopic ultrasound (EUS) . 1. The entire biliary tree and pancreas can be imaged without intestinal gas interference. 2. More sensitive than transabdominal ultrasonography in detecting cho­ ledocholithiasis. 3. EUS is an elective procedure and uncommonly used in the ICU. 4. Useful to identify patients who would benefit from endoscopic stone extraction by endoscopic retrograde cholangiopancreatography (ERCP) . IV. TREAT M E N T

A. Cholangitis and biliary obstruction. 1. If cholangitis is suspected, extended-spectrum antibiotics should be started promptly along with aggressive supportive measures.

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Emergent ERCP with sphincterotomy and biliary scenting to achieve biliary decompression. B. Bile leaks. 2.

1. ERCP for biliary decompression and scent placement should be performed immediately to allow the leak site to heal. 2. Broad-spectrum antibiotics protect against sepsis. C. Acute cholecystitis. 1. IV fluids, antibiotics, and nasogastric suction are the initial therapies. 2. Percutaneous cholecystostomy is an alternative in patients who are too unstable for operative cholecystectomy. D. Acute gallstone pancreatitis. 1. Majority will improve with conservative therapy. 2. Early ERCP indicated for severe pancreatitis, persistant jaundice, or cholangitis to remove retained common bile duct stones. 3. Definitive therapy with elective cholecystectomy or endoscopic sphinc­ terotomy with stone extraction in nonoperative candidates during initial hospital admission after pancreatitis has subsided to prevent recurrences. V. C O M PLICATI O N S

A . Cholangitis and biliary obstruction. 1. If ERCP is unsuccessful, percutaneous transhepatic cholangiography (PTC) should be performed. B. Bile leaks. 1. Bilomas usually require percutaneous drainage m addition to an ERCP. C. Cholecystitis. 1 . Complications of acute cholecystitis include gall bladder perforation and emphysematous cholecystitis. 2. The cholecystostomy drainage catheter is left in place until acute symp­ toms resolve. 3. In patients with severe comorbid illnesses, the tube may simply be removed with or without percutaneous stone extraction. D. Acute gallstone pancreatitis. 1. Tube feedings or TPN is required if symptoms do not resolve within 7 days. 2. Pseudocysts develop in 1 5% of patients, and bacterial colonization can lead to abscess formation mandating endoscopic, surgical, or percutane­ ous drainage. S U G G ESTED R EAD I NGS

Attasaranya S, Fogel EL, Lehman GA. Choledocholithiasis, ascending cholangitis, and gall­ stone pancreatitis. Med Clin N Am 2008;92:925-960.

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A well-referenced excellent article giving a comprehensive review about different biliary diseases with very helpfulflow charts. Barie PS, Eachempati SR. Acute acalculous cholecystitis. Gastroenterol Clin N Am 2 0 1 0;39:343-357.

A comprehensive review detailing the clinical patterns, pathogenesis, in-depth explanation ofthe different diagnostic radiologic studies, therapy, and complications ofacalculous cholecystitis. Borroff GA, Chen MY, Ott DJ, et al. Gallbladder stones: imaging and intervention. Radiographies 2000;20(3) :75 1-766.

A review of the role ofabdominal ultrasound, ERCP, and MRCP in the diagnosis of gallbladder stones in addition to the therapeutic role ofinterventional radiology. Elwood DR. Cholecystitis. Surg Clin N Am 2008;88: 1 24 1 - 1 252.

Addresses the clinical management ofacute calculous and acalculous cholecystitis. Fogel EL, McHenry L, Sherman S, et al. Therapeutic biliary endoscopy. Endoscopy 2005;37(2): 1 39- 1 4 5 .

A concise review of the role ofendoscopic therapy i n the management of bile leaks, biliary stones, and gallstone pancreatitis. Hungness ES, Soper NJ. Management of common bile duct stones. J Gastrointest Surg 2006; 1 0 (4) : 6 1 2-6 1 7.

A detailed explanation ofa proposed algorithm for the diagnosis and successful manage­ ment of CBD stones. Lee JG. Diagnosis and management of acute cholangitis. Nat Rev Gastroenterol Hepatol 2009;6:533-54 1 .

A n excellent review discusses current recommendations for the diagnosis ofacute cholangitis and addresses the advantages and disadvantages ofdiffe rent modalities of treatment. Massoumi H, Kiyici N, Herran H. Bile leak after laparoscopic cholecystectomy. J Clin Gastroenterol 2007;4 l :3 0 1 -305.

A concise review about the diagnosis and the different treatment modalities available for bile leak postcholecystectomy. Qureshi WA. Approach to the patient who has suspected acute bacterial cholangitis. Gastroenterol Clin North Am 2006;35 (2) :409-423.

An early clinical suspicion ofacute bacterial cholangitis should lead to both a prompt initiation ofantibiotics and an emergent ERCP. Robinson O'Neill DE, Saunders MD. Endoscopic ulrrasonography in diseases of the gallblad­ der. Gastroenterol Clin N Am 2 0 1 0;39:289-305 .

Reviews the use ofEUS i n different biliary diseases i n comparison to other modalities. Tse F, Yuan Y. Early routine endoscopic retrograde cholangiopancreatography strategy versus early conservative management strategy in acute gallstone pancreatitis. Cochrane Database Syst Rev 2 0 1 2;(5) :CD009779.

In acute gallstone pancreatitis, early routine ERCP did not significantly decrease mortal­ ity or complications and, however, should be considered in patients with coexisting cholangitis or biliary obstruction. Van Geenen EJM, Van der Peet DL, Bhagirath P, et al. Etiology and diagnosis of acute biliary pancreatitis. Nat Rev Gastroenterol Hepatol 2 0 1 0;7:495-502.

Discusses the pathogenesis of biliary pancreatitis and the clinical techniques used to establish its biliary origin. Increased AL T level (> 1. 0 µkat!l) is associated with a high probability ofgallstone pancreatitis.

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Wilson CT, de Moya MA. Cholecystectomy for acute gallstone pancreatitis: early vs delayed approach. ScandJ Surg 20 I 0;99 : 8 1 -8 5 .

Cholecystectomy recommended i n gallstone pancreatitis during index admission for mild disease and, at a later time, for severe cases, depending on the clinical circumstances. Yusoff IF, Barkun JS, Barkun AN. Diagnosis and management of cholecystitis and cholangitis. Gastroenterol Clin N Am 2003;32(4) : 1 145- 1 1 6 8 .

An excellent review ofthe diagnosis and management of biliary diseases and complications.

T h e Bas i c P r i n c i p l es of N utriti o n a l S u p p o rt i n th e I nte n s i ve Ca re U n it Do m i n ic J . N o m p leggi

I. G E N E RAL P R I N C I PLES

A. Severe protein-calorie malnutrition, unfortunately, is common in critically ill patients. B. In all patients with serious illness, appropriate measures to avoid substrate deficiency and to replete nutrient deficiency are best recognized promptly, and appropriate therapy is instituted without delay. I I . PAT H O G E N E S I S

A . Malnutrition can be present on admission or develop a s a result o f the metabolic response to injury. B. Changes in metabolic response are difficult to assess. C. Assessment includes evaluation of clinical, anthropometric, chemical, and immunologic parameters reflecting altered body composition. I l l . DIAG N O S I S

A . General assessment. 1. The purpose of nutritional assessment is to identify the type and degree of malnutrition in order to devise a rational approach to treatment. 2. Percentage weight loss in the last 6 months, serum albumin level, and total lymphocyte count are the commonly used measures to assess nutri­ tional status. 3. Weight loss of20% to 30% suggests moderate caloric malnutrition, while 30% or greater indicates severe protein-calorie malnutrition; loss of 1 0% or more over a short period of time is also considered clinically important. 4. The general appearance of the patient, with emphasis on evidence of temporal, upper body, and upper extremity wasting of skeletal muscle mass, provides a quick, inexpensive, and clinically useful measure of nutritional status. B. Laboratory assessment. 1. Serum albumin measures visceral protein stores; it is a useful and readily available indicator of kwashiorkor (protein malnutrition) . 2. Serum albumin is not a sensitive indicator of malnutrition in ICU patients because its synthesis is influenced by numerous factors other 581

582

SECT I O N 7 • G A S T R O I N T E S T I N A L A N D H E P A T O B I L I A R Y P R 0 B L E M S

than nutritional status (e.g. , protein-losing states, hepatic function, and acute infection or inflammation) . 3. Malnutrition is closely correlated with alterations in immune response as measured by skin test reactivity and total lymphocyte count. 4. A total lymphocyte count < l ,OOO/mm3 is indicative of altered immune function and is associated with decreased skin test reactivity. 5. Loss of skin test reactivity is a measure of impaired cellular immunity, which consistently has been found to be associated with malnutrition. C. Subjective global assessment.

1. Subjective global assessment (SGA) evaluates nutritional status using clinical parameters such as history, physical findings, and symptoms. 2. The SGA determines whether a. nutritional assimilation has been restricted because of decreased food intake, maldigestion, or malabsorption; b. any effects of malnutrition on organ function and body composition have occurred; and c. the patient's disease process influences nutrient requirements. 3. In hospitalized patients, SGA has been shown to provide reliable and reproducible results with more than 80% agreement when blinded observers assessed the same patient. IV. TREAT M E NT

A. Critical depletion of lean tissue can occur after 1 4 days of starvation in severely catabolic patients. B. Nutrition support should be instituted in patients who are not expected to resume oral feeding for 7 to 1 0 days. C. Enteral feeding. 1 . Enteral feeding reduces infection and preserves gut integrity, barrier, and immune function. 2. It is the preferred route of nutrient administration. 3. Current recommendations support initiation of enteral nutrition as soon as possible after resuscitation. 4. The only contraindication is a nonfunctioning gut. 5. Enteral feeding technique. a. Initiation of enteral feeding distal to the pylorus does not require active bowel sounds or the passage of flatus or stool. b. Small bowel feedings can be given in the presence of mild or resolving pancreatitis and low-output enterocutaneous fistulas (200 mg/dL. B. Treatment is recommended for blood glucose persistently above 140 to 1 80 mg/dL. C. Assess severity. 1 . Is ketoacidosis present? a. Based upon hisrory, physical findings, and laborarory results (anion gap acidosis and ketonuria or ketonemia) . b. For management, see Chapter 83. 2. Is hyperosmolarity present? a. Based upon extreme hyperglycemia and hyperosmolarity with severe dehydration and obtundation. b. For management, see Chapter 83. 3. Is the patient absolutely insulin dependent? Patients with T l D , surgical pancreatectomy, and certain other pancreatic diseases require continuous insulin treatment to avoid ketoacidosis.

C h a pter 82 • M a nagement of Hyperglycem i a i n t h e Critica l l y I l l Patients

587

D. Evaluation of the ICU patient with preexisting diabetes. 1. Assess cardiac function and peripheral circulation. 2. Look for the following: a. Occult infections (e.g., osteomyelitis, cellulitis, cholecystitis, gingivitis, sinusitis, cystitis, or pyelonephritis) . b. Hypertriglyceridemia as it may cause pancreatitis. c. Diabetic eye disease: though it does not contraindicate anticoagulation, its severity should be documented before instituting anticoagulation. d. Autonomic neuropathy may predispose to orthostasis, tachyarrhyth­ mias, and intestinal dysmotility; should be suspected based upon the EKG (absence of R-R interval changes) . 3. Kidney function assessment should include testing for proteinuria. 4. Poorly controlled diabetes may imply poor nurrition or thiamine deficiency. E. Bedside blood glucose monitoring. 1. Can be influenced by hematocrit, serum creatinine, and arterial Po2 • 2. Less accurate at blood glucose extremes, so should be verified with a sample sent to the laboratory. 3. Do not delay therapy awaiting confirmatory laboratory results. IV. TREAT M E N T

A. Target blood glucose concentration. 1. While there is a general agreement that excessive hyperglycemia in the ICU should be controlled, specific glycemia control targets remain controversial. 2. One center's early surgical ICU studies suggested that intensive insulin therapy with a target plasma glucose concentration :s; 1 1 0 mg/dL reduced in-hospital mortality and morbidity, but several subsequent random­ ized controlled trials in various ICU settings have not documented comparable benefit. 3. NICE-SUGAR, the largest trial to date, demonstrated that the intensive treatment group targeting blood glucose levels berween 8 1 and 1 08 mg/ dL had significantly more hypoglycemia and increased mortality. 4. A 2009 consensus statement from the American Association of Clinical Endocrinologists and American Diabetes Association endorsed good blood glucose control, targeting ICU blood glucose levels berween 1 40 and 1 8 0 mg/dL. The Society of Critical Care Medicine recom­ mends a target range of 1 00 to 1 50 mg/dL. 5. We suggest the following guidelines for ICU hyperglycemia management: a. All critically ill or surgical patients with a plasma glucose concentra­ tion :2: 1 80 mg/dL be treated to lower that concentration. b. Maintain plasma glucose as close to the normal range as is safely pos­ sible, targeting 1 00 to 1 80 mg/ dL. c. Certain patient groups may benefit from tighter control, and this needs to be individualized. d. Initial management should be with intravenous insulin infusion therapy. e. Avoid glucose concentrations :s;80 mg/dL because they pose the hazard of hypoglycemia and may contribute to mortality.

588

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SECT I O N 8 • E N D 0 c R I N E p R 0 B L E M s I N T H E I c u

B. Initiating intravenous insulin infusion. 1. Begin insulin infusion if two consecutive glucose values are > 1 40 to 1 80 mg/dL, based on institutional protocols or published intravenous insulin protocols. 2. Insulin requirements may be influenced by the primary illness, its treatment, and the patient's body mass index. C. Adjusting the insulin infusion rate. 1. Institutions are advised to implement an algorithm to achieve target blood glucose concentrations of 1 0 0 to 1 80 mg/dL. Various institutions have published protocols that can be accessed via the Internet. 2. The regular insulin infusion is based on both the glucose concentration absolute value and its rate of change. 3. Glucose concentrations are checked hourly until in the target range for two consecutive readings and every 2 hours thereafter. 4. Special considerations. a. Decrease exogenous carbohydrate loads prior to increasing insulin above 20 units/hour. b. Hepatic failure, renal failure, or adrenal insufficiency can lead to a decreased insulin requirement. c. A continuous glucose source is strongly recommended for all patients when glucose is 38. 5°C) , tachy­ cardia out of proportion to the fever, and mental status changes. 600

C h a pter 84 • Thyro i d D i sorders i n the I C U

liJ:iij:jli

601

C l i n ic a l Featu res of Thyro i d Storm

Feve r (as h igh as 105 .8°F) Tac hyca rd ia/tac hya rrhyth m ias Deleri u m/agitation M e nta l status c h a n ges Congestive heart fa i l u re Tremor N a u sea a n d vo m iting Dia rrhea Sweating Vasod i latation De hyd ration H e patomegly S p l e n o megly J a u nd ice

c.

2.

3.

Tachyarrhythmias, especially atrial fibrillation in the elderly, are common, as are nausea, vomiting, diarrhea, agitation, and delirium. d. Coma and death may ensue in up to 20% of patients, frequently due to cardiac arrhythmias, congestive heart failure (CHF) , hyperther­ mia, or the precipitating illness. Signs. a. Most patients display the classic signs of Graves disease, including ophthalmopathy and a diffusely enlarged goiter, although thyroid storm has been associated with toxic nodular goiters. b. In the elderly, severe myopathy, profound weight loss, apathy, and a minimally enlarged goiter may be observed. c. There are no distinct laboratory abnormalities, and thyroid hormone levels are similar to those found in uncomplicated thyrotoxicosis; there is little correlation between the degree of elevation of thyroid hormones and the presentation of thyroid storm.

Differential diagnosis. a. The differential diagnosis of thyroid storm includes sepsis, neurolep­ tic malignant syndrome, malignant hyperthermia, and acute mania with lethal catatonia, all of which can precipitate thyroid storm in the appropriate setting. b. Clues to the diagnosis of thyroid storm are a history of thyroid disease, history of iodine ingestion, and the presence of a goiter or stigmata of Graves disease. c. Burch and Wartofsky have published a scoring system for the diag­ nosis of thyroid storm (Table 84-2) . The diagnosis of thyroid storm was possible with a score of 25 to 45 and is likely with a score >45. Thyroid storm is unlikely with a score 1 04

5 10 15 20 25 30

C N S effects

Absent M i ld agitation Moderate Severe

0 10 20 30

Prec i p itant h i story

None P resent

0 10

G I-hepatic

Absent Moderate Severe (J a u nd ice)

0 10 20

P u l se

90-09 1 1 0-1 1 9 1 20-1 29 1 30-1 39 > 1 40

5 10 15 20 25

CHF

Absent M i ld Moderate Severe

0 5 10 15

AFib

Absent P resent

0 10

d. A recent study suggested new criteria fo r the rapid diagnosis of thyroid storm. i. Patients who had specific CNS manifestations (restlessness, delirium, psychosis/mental aberrations, somnolence/lethargy, convulsions) needed to have only one of four additional conditions: temperature

C h a pter 84 • Thyro i d D i sorders i n the I C U

I

603

of 38°C or higher; tachycardia of 1 30 beats per minute or higher; class IV CHF; or gastrointestinal/hepatic manifestations (diar­ rhea, nausea/vomiting, or a bilirubin above 3 mg/dL) . ii. Those without CNS mainfestations needed three out of four conditions: temperature of 38°C or higher; tachycardia of 1 30 beats per minute or higher; class IV CHF; or gastrointestinal (GI)/ hepatic manifestations (diarrhea, nausea/vomiting, or a bilirubin above 3 mg/dL) . e. In any event, the physician must have a high clinical index of sus­ picion for thyroid storm, as therapy must be instituted before the return of thyroid function tests in most cases. E. Treatment.

1. Thyroid storm is a major medical emergency that must be treated in an ICU (Table 84-3) . 2. Treatment includes supportive measures such as intravenous fluids, anti­ pyretics, cooling blankets, and sedation. 3. �-Adrenergic blockers or calcium channel blockers are given to control tachyarrhythmias. 4. Antithyroid drugs are given in large doses, with propylthiouracil (PTU) being preferred over methimazole due to its additional advantage of impairing peripheral conversion of T4 to T3. 5. PTU and methimazole can be administered by nasogastric tube or rec­ tally if necessary; neither of these preparations is available for parenteral administration. 6. Iodides, orally or intravenously, may be used only after antithyroid drugs have been administered, although the useful radiographic contrast dye iopanoic acid is no longer available in the United States. 7. High-dose dexamethasone is recommended as supportive therapy, as an inhibitor of T4-to-T3 conversion and as management of possible inter­ current adrenal insufficiency. 8. Orally administered ion-exchange resins (colestipol or cholestyramine) can trap hormone in the intestine and prevent recirculation, and plas­ mapheresis has also been used in severe cases. 9. Treatment of the underlying precipitating illness is essential to survival in thyroid storm. 10. Once stabilized, the antithyroid treatment should be continued until euthyroidism is achieved, at which point a final decision regarding anti­ thyroid drugs, surgery, or 1 31 Iodine ( 1 311) therapy can be made. F. Complications. 1. The mortality rate of thyroid srorm has been reported to be 1 0% to 20%. 2. Complications of thyroid storm other than mortality are the same as complications from the underlying etiology of the thyrotoxicosis (i.e., opthalmopathy in Graves disease) . 3. After definitive therapy for hyperthyroidism (surgery or radioactive iodine) , hypothyroidism is the most common, and desired, result.

604

I

SECT I O N 8 • E N D O C R I N E P R O B L E M S I N T H E I C U

lf;i:i!j:jfi

Treatment of Thyro i d Storm

S u p p o rtive therapy

Treatment of u n d erlying i l l nesses I ntravenous fl u id s Coo l i n g blan ket a nd/or a nti pyretics 13-Ad renergic blocking d rugs

Propra n o lol-1 mg I V/m i n to a tota l d ose of 10 mg, then 40-80 mg PO q 6 h , or Es molo l-500 mg/kg/m i n IV, then 50- 1 00 mg/kg/m i n , or M eto p rolol-1 00--400 mg PO q l 2 h , or Ate nolol-50-100 mg PO d a i ly Antithyro i d d rugs I n h i bition of thyro i d h o r m o n e synth esis

PTU-800 mg PO fi rst d ose, then 200-300 mg PO q 8 h, or M eth imazole-80 mg PO fi rst dose, then 40-80 mg PO q l 2 h

B l o c k release of thyro i d h o r m o n es from the g l a n d

SSK l-5 d rops PO q 8 h, or Lugol solution- 1 0 d rops PO q8 h, or Lith i u m-800-1 , 200 mg PO qd-a c h i eve seru m l ith i u m levels 0 . 5-1 . 5 m Eq/L

Block T4-to-T3 convers i o n

Corticoste roid s-dexa methasone 1-2 mg PO q 6 h M ost �-blockers-propra nolol 40-80 mg PO q6 h P ro pylth i o u ra c i l Te l a pa q u e ( i o p a n o i c a c i d )-no longer ava i la b le i n the U n ited States Remove thyro i d h o r m o n e s from the c i rc u lation

Plasma ph e resis, or Peritonea I d i a lysis, or Cholestyra m i ne-4 g PO q 6 h, or Colesti pol-20-30 mg PO q d

SS K I , satu rated sol ution o f potass i u m iod i d e .

II. MYX E D E M A C O M A

A. General principles. 1. Myxedema coma is a rare syndrome that represents the extreme expression of severe, long-standing hypothyroidism. 2. Even with early diagnosis and treatment, the mortality can be as high as 60%. 3. Myxedema coma occurs most often in the elderly and during the late fall and winter months. 4. Myxedema coma is primarily a clinical diagnosis, as there are no absolute levels of decreased thyroid hormones that are diagnostic. 5. Myxedema coma is a medical emergency that should be managed in the ICU.

C h a pter 84 • Thyro i d D i sorders i n the I C U

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605

B. Etiology. 1. Hypothyroidism by any cause can be the underlying cause of myxedema coma. 2. Most episoides of myxedema coma are caused by a precipitating factor in the setting of severe hypothyroidism. 3. Common precipitating factors include pulmonary infections, cerebro­ vascular accidents, trauma, surgery, and CHE 4. The clinical course of lethargy proceeding to stupor and then coma is often hastened by drugs, especially sedatives, narcotics, antidepressants, and tranquilizers, especially in the undiagnosed hypothyroid patient who has been hospitalized for other medical problems. C. Pathophysiology. 1. Myxedma coma is the most severe manifestation of hypothyroidsm. 2. Decreased levels ofT4 and T3 and increases in thyroid-stimulating hor­ mone (TSH) are necessary, but there is no absolute level upon which the diagnosis is clear. D. Diagnosis. 1. Symptoms. a. Cardinal features of myxedema coma are hypothermia, respiratory depression, hypotension, and unconsciousness (Table 84-4) . b. Most patients have the physical features of severe hypothyroid­ ism, including bradycardia; macroglossia; delayed reflexes; and dry, rough skin and myxedematous facies, which result from the periorbital edema, pallor, hypercarotinemia, periorbital edema, and patchy hair loss. c. Hypotonia of the gastrointestinal tract is common and often so severe as to suggest an obstructive lesion. d. Urinary retention due to a hypotonic bladder is related but less frequent.

TA B L E 8 4 - 4

C l i n ic a l Featu res o f M yxedema Coma

M e nta l o btu ndation Hypothermia B radyca rd ia Hypotension Coa rse , d ry skin Myxed ema facies Hypoglyce m i a Ato n i c G I tract Ato n i c bladder P l e u ra l , perica rd ia ! , a n d perito n ea l effusions G I , gastroi ntesti n a l .

606

SECT I O N 8 • E N D 0 C R I N E P R 0 B L E M S I N T H E I C U

Signs. a. Pleural, pericardial, and peritoneal effusions may be present. b. The thyroid hormone abnormalities are similar to those in uncompli­ cated hypothyroidism, with >95% of cases due to primary hypothy­ roidism. c. Dilutional hyponatremia is common and may be severe. d. Elevated creatine kinase concentrations, sometimes markedly so, are encountered frequently, suggesting cardiac ischemia; however, in most cases the myocardial band (MB) fraction is normal, and an electrocardiogram (ECG) often shows the low voltage and loss of T waves that are characteristic of severe hypothyroidism. e. Elevated lactate dehydrogenase concentrations, acidosis, and anemia are common findings. f. Lumbar puncture reveals increased opening pressure and high protein content. 3. Differential diagnosis. a. The diagnosis of myxedema coma is based on the presence of the characteristic clinical syndrome in a patient with hypothyroidism. b. Clues to the diagnosis include symptoms related by family and friends, an ourdated container of L-T4 discovered with the patient's belongings, previous treatment with radioactive iodine, or there may be a thyroidectomy scar present. c. Differential diagnosis includes protein-calorie malnurrition, sepsis, hypoglycemia, exposure to certain drugs and toxins, and cold exposure. d. What distinguishes myxedema coma from other disorders is the com­ bination of laboratory evidence of hypothyroidism, the characteristic myxedema facies with periorbital puffiness, the skin changes, obtunda­ tion, and other physical signs characteristic of severe hypothyroidism. e. The physician must have a high clinical index of suspicion for myxedema coma, as therapy must be instituted before the return of thyroid function tests in most cases. E. Treatment. 1. Myxedema is a medical emergency and must be managed in an ICU setting (Table 84-5) . 2 . The mainstays o f therapy are supportive care, with ventilatory and hemodynamic support, rewarming, correction of hyponatremia and hypoglycemia, and treatment of the precipitating incident and adminis­ tration of thyroid hormone. 3. Active heating in myxedema coma should be avoided as it increases oxy­ gen consumption and promotes peripheral vasodilation and circulatory collapse. a. An exception is at core temperatures below 28°C, when ventricular fibrillation is a major threat to life-in this case, the rate of rewarm­ ing should not exceed 0.5°C/hour until the core temperature is raised to approximately 3 1 °C. b. In general, patients should be kept in a warm room and covered with blankets. 2.

C h a pter 84 • Thyro i d D i sorders i n the I C U

liJ:iij:jJj

607

Treatment of Myxedema Coma

Ass isted ve nti lation for hypoventi lation H e m odyna m i c s u p port for hypotension I ntrave n ou s glucose for hy poglyce m ia Wate r restri cti on or hyperto n i c sa l i n e fo r severe hyponatrem ia Passive rewa rm i ng fo r hypotherm ia Ad m i n iste r thyroid hormone i ntravenously L-T4-200-300 µg load i ng dose, u p to 500 µg i n the fi rst 24 h ' a n d/or L-T3- 1 2 . 5 µg q6 h u ntil awa ke• Ad m i n iste r hyd rocortisone I V ( 1 00 mg q 8 h ) • Treat u nd e rlying i nfection a n d oth er i l l n esses, if prese nt Avo id all sedatives , hypnotics, and na rcotics 'N ote that dosage m u st be i n d ivid u a l ized (see text) .

F.

4. Sedatives, hypnotics, narcotics, and anesthetics must be minimized or avoided altogether due to their extended duration of action and exacer­ bation of obtundation in the hypothyroid patient. 5. Because of a 5% to 1 0% incidence of coexisting adrenal insufficiency in patients with myxedema coma, intravenous steroids are indicated before initiating T4 therapy. 6. Parenteral administration of thyroid hormone is necessary due to uncer­ tain absorption through the gut. a. A reasonable approach is an initial intravenous loading dose of 200 to 300 µg L-T4, with another dose of L-T4 given in 6 to 12 hours to bring the total dose during the first 24 hours to 0.5 mg, followed by 50 to 1 00 µg intravenously every 24 hours until the patient is stabilized. b. In the most severe cases, some clinicians recommend using L-T3 at a dosage of 1 2 . 5 ro 25 µg intravenously every 6 hours until the patient is stable and conscious, followed by a switch to L-T4. 7. Although myxedema coma is associated with substantial mortaliry risk, many patients can be saved by judicious therapy aimed at correcting the secondary metabolic disturbances and reversing the hypothyroid state in a sustained but gradual fashion, since an effort to correct hypothyroid­ ism too rapidly may completely negate the beneficial effects of the initial treatment. Complications. 1. Despite optimal treatment, the mortaliry of myxedema coma can be as high as 60%. 2. Hypotonia of the gastrointestinal tract is often so severe as to suggest an obstructive lesion. 3. Urinary retention due to a hypotonic bladder can also be seen.

608

I

SECT I O N 8 • E N D 0 c R I N E p R 0 B L E M s I N T H E I c u

I l l . S I C K E UTHYRO I D SYN D R O M E I N T H E I NTENS IVE CARE U N IT

A. General principles. 1. Critical illness causes multiple nonspecific alterations in thyroid hor­ mone concentrations in patients who have no previously diagnosed intrinsic thyroid disease that relates to the severity of the illness. 2. There is an ongoing debate whether such alterations are a physiologic adaptation or a pathologic perturbation. Because to the complexity of many patients with the sick euthyroid syndrome, it is likely that both physiologic and pathologic effects play a role. 3. Despite abnormalities in serum thyroid hormone parameters, there is little evidence that critically ill patients have clinically significant thyroid dysfunction. While some investigators have proposed otherwise, there is no current evidence to support thyroid hormone therapy in the manage­ ment of the sick euthyroid syndrome. 4. While a wide variety of illnesses tend to result in the same changes in serum thyroid hormones, these changes are rarely isolated and often are associated with alterations in other endocrine systems, such as reductions in serum gonadotropin and sex hormone concentrations and increases in serum adrenocorticotropic hormone (ACTH) and cortisol. 5. The sick euthyroid syndrome should not be viewed as an isolated patho­ logic event bur as part of a coordinated systemic reaction to illness that involves both the immune and endocrine systems. B. Etiology. 1. While the cause of the alterations in thyroid hormone economy in criti­ cal illness is largely unknown, cytokines, such as rumor necrosis factor alpha, interleukin 1 , and interleukin 6, have been shown to reproduce many of the features of the sick eurhyroid syndrome in both animal and human studies when administered in pharmacologic doses. 2. Whether the sick eurhyroid syndrome results from activation of the cyrokine nerwork or simply represents an endocrine response to systemic illness resulting from the same mediators that trigger the cytokine cas­ cade remains to be determined. C. Pathophysiology. 1 . Alterations in peripheral metabolic pathways. a. The major pathway of metabolism of thyroxine (T4) is by sequential monodeiodination by type 1 (D l ) or type 2 deiodinase (02) to gen­ erate triiodothyronine (T3) (activating pathway) or type 3 deiodinase (03) to generate rT3 (inactivating pathway) . h. One of the first alterations in thyroid hormone metabolism in acute illness is inhibition of D 1 in peripheral tissues, which is affected by a wide variety of factors (Table 84-6) and subsequent impairment in T4-to-T3 conversion. c. Because >80% ofT3 is derived from deiodination ofT4 in peripheral tissues, T3 levels fall soon after the onset of acute illness. D 1 also deiodinates rT3, so degradation is impaired, and levels of this inactive hormone rise in proportion to the fall in T3 levels.

C h a pter 84 • Thyro i d D i sorders i n the I C U

TA B L E 8 4 - 6

609

Factors that I n h i b it Thyrox i n e (T4) to Tri i odothyro n i ne (T3) Convers i o n in Periphera l Tissues

Acute a n d c h ro n i c i l l ness Caloric d e privation M a l n utrition GI u cocorticoids �-Ad re nergic bloc k i n g d rugs (e.g . , pro p ra n a l o l ) O ra l cholecystogra p h i c agents (e.g. , i o p a n o i c a c i d •, sod i u m i pod ate•) Am iodarone P ro pylth i o u ra c i l Fatty a c i d s Feta l/neonata l period Sele n i u m deficiency Cytoki nes ( 1 1- 1 , 1 1-6) •Cu rrently unava i la ble or l i m ited ava i l a b i l ity. I I , i nterle u k i n .

2.

3.

d. In general, D3 is unaffected by acute illness, so inner ring deiodination of T4 to produce rT3 is unchanged. However, recent studies have suggested that D 3 may be increased in certain tissues, leading to increased T3 disposal within those tissues. e. D2, a deiodinase abundant in the brain, has also been found to be abundant in skeletal muscle in humans, and levels may be increased in critical illness. The significance of these findings is uncertain at present. Alterations in the pituitary-thyroid axis. a. Synthesis and secretion of thyroid hormone are under the control of the anterior pituitary hormone, thyrotropin (TSH) , in a classic nega­ tive feedback system. b. While serum TSH levels are usually normal early in acute illness, lev­ els often fall as the illness progresses due to the effects of a variety of inhibitory factors that are common in the treatment of the critically ill patient (Table 84-7) . c. The use of dopamine, increased levels of glucocorticoids, either endogenous or exogenous, and inhibitory signals from higher cortical centers also may play a role in decreasing TSH secretion, as well as certain thyroid hormone metabolites that are increased in nonthyroi­ dal illness. Alterations in serum-binding proteins. a. Both T4 (99.97% bound) and T3 (99.7% bound) circulate in the serum bound primarily to thyroxine-binding protein (TBG) , and the binding of thyroid hormones to TBG is affected by a variety of factors in acute illness (Table 84-8) . b. Since only the unbound hormone has any metabolic activity (free hormone concept) , changes in the concentrations of, or binding to,

61 0

I

SECT I O N 8 • E N D 0 c R I N E p R 0 B L E M s I N T H E I c u

if;i=i!j:jQ

Factors that A l ter TS H Secretion

I nc rease

Dec rease

C h lorpromazine C i m etid i n e Dom perid i n e Dopa m i n e a ntago n i sts Ha loperidol I od i d e Lith i u m M etoc lopra m id e S u lfa pyrid i n e X-ray-contrast agents

Ac ute a n d c h ro n ic i l l n ess Adrenergic ago n i sts Ca loric restriction Ca rba maza p i n e Clofi brate Cypro h e pta d i n e Dopa m i n e a n d d o pa m i n e ago n i sts Endogenous d e p ress ion G l u cocorticoids I G F- 1 M etergo l i n e M ethylsergide O p i ates P h e nyto i n P h e ntola m i n e P i mozide Som atostati n Seroto n i n S u rgica l stress Thyroid hormone m eta bol ites

I G F - 1 , i n s u l i n - l i ke growth factor-1 .

TBG would have major effects on the total serum hormone levels but minimal changes in the free hormone concentrations, and, thus, overall thyroid function, are actually seen. 4. Stages of the sick euthyroid syndrome. a. Low T3 state. i. Common to all of the abnormalities in thyroid hormone concen­ trations seen in critically ill patients is a substantial depression of serum T3 levels, which can occur as early as 24 hours after the onset of illness and affects over half of the patients admitted to the medical service. ii. The decrease in serum T3 levels can be explained solely by inhibi­ tion of D l and subsequent impairment of peripheral T4-to-T3 convers10n. iii. Clinically, these patients appear euthyroid, although mild pro­ longation in Achilles reflex time is found in some patients. iv. This stage is common in patients with CHF and with acute car­ diac injury. In patients with cardiac disease, serum T3 concentra­ tions are a negative prognostic factor and inversely proportional to mortality.

C h a pter 84 • Thyro i d D i sorders i n the I C U

TA B L E 8 4 - 8

61 1

Factors t h a t Alter B i n d i ng o f Thyrox i n e (T4) to Thyroxi ne-B i n d i ng Prote i n I nc rease b i n d i n g

Dec rease b i n d i ng

Estroge ns M ethadone Clofi brate 5-Fl uoro u ra c i l H e ro i n Ta moxifen

G l u cocorticoids And roge n s 1 -asparagi nase Sa l icylates M efe n a m i c acid Antise i z u re med ications ( ph e nyto i n , tegretol ) Fu rose m i d e H e pa ri n Anabolic steroids

Drugs

R a l oxife n e

Syste m ic factors Liver d i sease Porphyria H I V i nfection I n herited

I n herited Acute i l l n ess N o n este rified free fatty acids

H IV, h u m a n i m m u nodeficiency virus.

b. High T4 state. i. Serum T4 levels may be elevated early in acute illness due to either the acure inhibition of T4-to-T3 conversion or increased TBG levels. ii. Increased serum T4 levels are seen most often in the elderly and in patients with psychiatric disorders. iii. As the duration of illness increases, nondeiodinative pathways of T4 degradation increase and return serum T4 levels to the normal range. c. Low T4 state. i. As the severity and the duration of the illness increase, serum total T4 levels may decrease into the subnormal range as a result of a decrease in the binding of T4 to TBG, a decrease in serum TSH levels leading to decreased production ofT4, and an increase in nondeiodinative pathways of T4 metabolism. ii. The decline in serum T4 levels correlates with prognosis in noncardiac ICU patients, with mortality increasing as serum T4 levels drop below 4 µg/dL and approaching 80% in patients with serum T4 levels

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ACS, acute coronary synd ro mes; LD, loa d i n g dose; P C I , percuta neous coro n a ry i ntervention; C B C , c o m plete blood cou nt; LFT, l ive r function tests; M l , myoca rd i a l i nfarcti on; U A , u n sta ble a ngina; T I A , tra nsient isc h e m i c attack; A N C , a bsol ute n e utroph i l count.

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I nd i cati ons

Abcixi m a b ( R eo p ro l

Treatment of LD: 0.25 mg/kg IV bol u s ACS +/­ (over 5 m i n) , fol lowed b y 0 . 1 25 PCI µg/kg/m i n (maxi m u m 10 µg!m i n ) IV i nfusion for 1 2 h i n com b i n ation with fibri nolytic treatment or after PC I , u n less com plications Treatment of LD: 180 µg!kg I V bo l u s based on ABW ( maxi m u m 22.6 mg) as ACS +/­ PCI soon as poss i b l e , fol l owed by 2 µg/kg ABW/m i n ( m a xi m u m 1 5 mg/h ) i nfusion u nti l d isc harge or CABG s u rge ry, u p to 72 h If undergoing PCI , ad m i n ister a second 1 80 µg/kg IV bolus 10 m i n after t h e first a n d conti n u e the i nfusion up to d ischarge, or for u p t o 18-24 h after proced u re , which­ ever com es fi rst, a l lowi ng for up to 96 h of thera py R e n a l i m pa i rment: CrCI 35,000 units/day) , to achieve a therapeutic-activated partial thromboplastin time (aPTT) , and is attributable to anti­ thrombin deficiency, increased heparin clearance, excess heparin­ binding proteins, factor VIII, and fibrinogen (Table 90-6) . e. Heparin dosing protocols are more effective in achieving goal antico­ agulation than an ad hoc approach. 2. Mechanism of action. a. Combines with antithrombin to block activated factors II, IX, X, XI, and XII. B. Low molecular weight heparin (LMWH) (Table 90-7) . 1. General principles. a. Produced from UFH, with more predictable dose response. b. SC administration results in onset of action of20 to 60 minutes with a t 1 12 of 3 to 6 hours. c. Eliminated via the kidneys. d. Dosing for obese patients 1s based upon adjusted body weight (AjBW) . AjBW = LBW + CF x (TBW - LBW) CF = correction factor = 0.4 LBW = (height - 1 5 0 cm) x 0.9 + 45 kg (female) o r LBW = (height - 1 50 cm) x 0.9 + 50 kg (male) where LBW lean body weight; TBW total body weight; cm centi­ meters. e. Discontinuation should be considered 12 to 24 hours before proce­ dure or surgery. =

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•t!1:11•::a:I•&-. U nfracti onated Heparin Drug

I nd ications

Dos i n g, t i m i ng, d u rati o n

Unfraction ated heparin

VT E treatment

LD: 80 u n its/kg bolus 1 8 u n its/kg/h infusion adj u sted per local hepa r i n n omogra m

ACS treatment

B r i d ge th era py for atrial fi bri l l atio n , c a rd i overs i o n

P ro p hylaxis o f VT E i n the m ed ic a l ly ill or s u rgical po p u l ation P ro phylaxis of VTE i n pregna ncy (with prior VTE)

LD: 6 0 u n its/kg ( m a x 4 , 000 u n its) 12 u n its/kg/h ( m a x i n itia l dosing 1 , 000 u n its/ h ) +!- fi bri n s pec ific adj u sted to m a i nta i n a PTT 1.5 to 2 t i m es control or per local hepa r i n n omogra m I V i n fusi o n : 60-80 u n its/kg b o l u s Target a P TT, 60s (ra n ge 50-70 s) 5 , 000 u n its S C q8 h

7 , 500- 1 5 , 000 u n its SC q l2 h

Mon itori n g

• • •

•

•

Precautions a n d co ntra i n d i cations

Precautions S igns of b leed i ng • A l l e rgic or hype rse ns itivity-type reactions CBC • Conge n ita l or acqu i red b leed i n g d i so rd e rs a PTT: at least 4 h • I n d we l l i ng e p i d u ra l cathete r afte r i n itiati o n , then • G I u l ceration a n d ongo i n g tu be d ra i n a ge of at l east o nce d a i ly the s m a l l i n test i n e or sto m a c h Anti-Xa l evel s (a lte r­ • H e patic d isease w i t h i m pa i red h e mosta s i s native if a va i la ble, co nsider i n patients • H e red ita ry a ntith ro m bi n I l l d efic i e n cy a n d concu rrent u s e o f a ntith rom b i n with h e pa ri n res ist­ • N eo n ates a nd i nfa nts weigh i ng < 1 0 kg a n c e or a nti p hos­ • P re m atu re i n fa nts weig h i n g < l kg phol i p i d a n t i body • R i s k of d e l ayed o nset of H I T a nd H I TT syn d ro m es) H I T a nti body testing Contraindications ( n ot wa rra n ted in • Uncontro l la ble active bleed i ng, except when the a bsence of d ue to d isse m i n ated intravasc u l a r coagu lation t h ro m bocyto pe• Insta nces in w h i c h b lood coagu lation tests n i a , t h rom bosis, c a n not be performed at n ecessa ry i n terva ls h e pa r i n - i n d uced • Severe throm bocyto pe n i a skin lesions, or oth e r • Pos itive test f o r i m m u ne-med iated H IT s i g n s pointi n g t o a • Patients with i n a rem ote h istory of H I T potentia I d iagnosis (> 1 00 d ays) cou l d be co nsidered for of i m m u n e­ a rech a l le nge with h e p a r i n provided a med iated H I T negat ive a n ti body test

VTE, ve nous throm boe m bolism; LD, l oa d i n g d ose; C BC, co m plete blood cou nt; a PPT, activated parti a l throm bo plasti n ti m e; ACS, a c ute coro n a ry synd romes; H I T , hepa ri n - i n d uced throm bocytopen ia; H I TT, h e pari n - i n d uced th rom bocyto penia w i t h throm bosis.

C h a pter 90 • Antith rombotic Therapy i n C r i t i ca l ly I l l Patients

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Heparin Dose Adj ustment Nomogram

Va riab les

Adjustment

I n itial d ose a PTT < 3 5 s a PTT 35-45 s a PTT 46-70 s a PTT 7 1-90 s a PTT > 90 s

80 u n its/kg bo l u s, 80 u n its/kg bo l u s, 40 u n its/kg bo l u s , No c h a nge Decrease i nfusion Hold i nfusion 1 h ,

then 18 u n its/kg/h then i n crease 4 u n its/kg/h then i n crease 2 u n its/kg/h rate by 2 u n its/kg/h then decrease i nfusion rate by 3 u n its/kg/h

a PTT, a ctivated pa rti a l t h rom boplasti n time. Ada pted from Rasch ke R , Gol l i h a re B , Peirce J. The effectiveness of i m plementing the weight- based heparin nomogra m as a practice g u i d e l i n e . Arch Intern Med 1996; 1 56 : 1 645- 1 649 .

2. Mechanism of action. a. Inhibits both factor Xa (predominately) and factor Ha activity. C. Factor Xa inhibitors (Table 90-8) . 1. General principles. a. Indirect (fondaparinux) and direct (rivaroxaban and apixaban) factor Xa inhibitors. b. Clearance reduced in patients with renal impairment. 2. Mechanism of action. a. Neutralizes factor Xa, inhibiting thrombin activation and thrombus development. D. Direct thrombin inhibitors (Table 90-9) . 1. General principles. a. Exhibit wide variability in pharmacokinetic parameters. 2. Mechanism of action. a. Direct binding to thrombin, leading to inhibition of thrombin-cata­ lyzed reactions including fibrin formation and platelet aggregation. E. Vitamin K antagonists (VKAs) (Table 90- 1 0) . 1 . General principles. a. Well absorbed from the GI tract and 99% bound to plasma albumin. b. Hepatically metabolized by cytochrome P450 (CYP) enzymes (mostly 2C9) . c. Average half-life is approximately 40 hours but is extremely variable (range: 20 to 60 hours) . d. Wide range of dosing required to maintain a therapeutic interna­ tional normalized ratio (INR) . e. CYP2C9 and VKORC l genetic variation influences patient response to initial and maintenance therapy and impacts bleeding risk. f. Lower doses required for elderly and patients with comorbidities. g. Both dietary and drug interactions can influence dosing; frequent monitoring of INR may be required.

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I nd i cations

Dos i ng, ti m i ng , d u ration

Mon itoring

Precautions a n d contra i nd i cations

Da lte pa r i n ( F ragm i n )

Treatment of VTE

99 k g : 1 8 , 000 i nternati o n a l u n its SC d a i l y 1 2 0 i nternational u n its/kg SC q l 2 h ( M ax 1 0 , 000 i n ternationa l u n its/ dose) 5, 000 i nternati o n a l u n its SC q 24 h

• Signs of bleed i ng • Anti-Xa levels in patients with sign ifica nt rena I i m pai rment, those experiencing bleed i ng or a bnorma l coagu lation parameters, pregna nt patients, obese or low-weight patients, and children • CBC • Seru m c reati n i ne • H I T a nti body testing ( n ot wa rranted i n the a bsence of th ram bocytopen i a , th rom bos is, hepa ri n - i n d uced ski n lesions, or oth er signs poi nting to a pote ntia l d iagnosis of H IT)

Precautions

Treatment of ACS Prophylaxis of VT E after h i p or other maj o r s u rgery (fi rst month) Prophylaxis of VT E in the med ica lly ill o r s u rgica l po pu lation

5, 000 i nternati o n a l u n its SC q 24 h

• I n dwel l i ng epid u ra l cath eter • Recent s p i n a l or ophtha l m o l ogic s u rgery • H i story of recent major bleed ( G I , i n tracra n ia l , etc . ) • Congen ita l or acq u i red bleed ing d isord ers • Bacteria l e nd oca rd itis • H i story of h e pa r i n - i n d u ced t h rom bocyto pe n i a • Liver d isease • Renal i m pa i rment (CrCI < 30 m Um i n ) , con sider U FH • Conco m ita nt use of a ntit h rom botic d rugs • Dia betic reti n o pathy • U n control led hyperte nsion

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Drug

I nd ications

Dosi ng, ti m i ng, d u ration

En oxa pa ri n ( Love n ox)

Treatment of VTE

1 mg/kg SC q l 2 h OR 1 . 5 mg/kg SC q 24 h CrCI < 30 m Um i n : 1 mg/kg SC q 24 h ST EM I : 30 mg bo l u s I V fo l l owed by 1 m g/kg SC q l 2 h + fi bri n o lytic NSTEM l/UA: 1 mg/kg SC q l 2 h CrCI < 30 m Um i n : not reco m m en d ed 1 mg/kg SC q l 2 h OR 1 . 5 mg/kg SC q 24 h CrCI < 30 m Um i n : 1 m g/kg SC q 24 h 40 m g S C q24 h R e n a l i m pa i rment: CrCI < 30 m Um i n : 30 m g SC q 24 h 30 mg SC q l 2 h OR 40 m g S C q24 h R e n a l i m pa i rment: CrCI < 30 m Um i n : 30 m g SC q 24 h 1 7 5 i nternational u n its a nti -Xa/kg SC d a i l y

Treatment o f ACS

Prophy laxis/bridge thera py for atria I fibri llation/ ca rd ioversion Prophylaxis o f VT E i n the med ica lly i l l o r s u rgica l po pu lation Prophylaxis of VT E i n tra u m a patie nts

Ti nza pari n ( l n nohep)

Treatment of DVT

Mon itoring

Precautions and contra i n d i cations

Contraindications

• Seve re a ctive bleed i ng • Hyperse ns itivity to e n oxapa ri n , d a lte pa r i n , t i n za pa ri n , heparin , or pork p rod u cts, su lfites (ti nzapa r i n ) , or fo rm u lation exci pients • Positive test fo r i m m u n e- m ed iated H IT • Patients with i n a re m ote h i story of H I T ( > 1 00 d ) co u l d be considered fo r a rec h a l l enge with h e pa r i n provided a negative anti body test

VTE, ve nous throm boe m bolism; S C , s u b c uta neous; ACS, acute coronary syn d ro m es; CBC, complete blood count; CrCI, creati n i n e c lea ra nce; H I T, hepa ri n - i n d uced thro m bocytope n i a ; U F H , u n fracti oned hepa r i n ; STEM I , ST-segment myoca rd i a l i nfa rction; NST E M I , non ST-segment myoca rd ia l i nfa rction; UA, u n sta ble a ng i n a ; DVT, deep vein th rom bosis.

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I nd ications

Dos i ng , t i m i ng , d u ration

M o n itoring

Precautions a n d contra i n d ications

Ap ixa ban ( E l iq u is)

DVT prophylaxis i n patients u nd ergoing knee or h i p re placement s u rgery P ro phylaxis of stroke a nd syste m ic e m bol ism i n no n-va l v u l a r atrial f i b r i l lation

2 . 5 mg o ra l ly twice d a i ly I n itial d ose 1 2-24 h after su rgery fo r 1 0-1 4 d ( k nee) 32-38 d ( h i p ) 5 mg o ra l ly twice d a i ly Dose a dj u stme nts : Any two of the fol lowi ng (>80 y, weight < 60 kg, or seru m c reati n i ne > 1 . 5 mg/dU : 2 . 5 mg ora l ly twice daily R e n a l i m pa i rment: CrCI 1 5-29 m Um i n 2 . 5 m g ora l ly twice d a i ly CrCI < 1 5 m Um i n or u n d ergo i n g d i a lysis: avoid use 1 00 kg : 1 0 m g SC d a i ly R e n a l i m pa i rment: co nsider e m p i ri c d osage red uction CrCI 50-80 m Um i n : 2 5 % red uction i n tota l c l ea ra nce CrCI 30-50 m Um i n : 40 % red uction i n tota l clea ra nce CrCI < 30 mUm i n : contra i ndicated

• Signs of bl eed i n g • CBC • Seru m c reati n i ne • Anti-Xa l evels in patients with sign ifica nt rena l/hepatic i m pa i rment, those experiencing bleed ing o r a bnorma l coagu lation pa ra m eters, pregnant pati ents, obese or low-weight pati ents, and c h i l d ren (agent-specific assay cali bration req u i red)

Precautions

Fo nda pa ri n u x Treatment o f VTE (A rixtra)

• I n dwe l l i ng e p i d u ra l cathete r • Recent s p i n a l or ophth a l m ologic su rgery • H i story of recent major b leed • Conge n ita l o r acq u i red b l eed i n g d i so rd ers • H e patic dysfu ncti o n (a pixa ban a n d riva roxa ba n ) • Conco m ita nt use with strong CYP3A4 a n d P-glyco protei n i n h i bitors and i n d u cers ( a p ixa ban a n d riva roxa ba n ) Contraindications

• Severe active bleed i ng • Bacterial e n d oca rd itis • Body weight

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SECT I O N 9 • H E M AT 0 L 0 G I C P R 0 B L E M S I N T H E I C U

2. Mechanism of action. a. Inhibits the synthesis of all vitamin K-dependent clotting factors (II, VII, IX, X, and protein C and S) . I l l . F I B R I N O LYTICS (Table 90- 1 1 )

A. General principles. 1. Methods of administration. a . Intravenous. b. Intravascular (i.e., catheter directed) . B. Mechanism of action. 1 . Enhances the conversion of plasminogen to plasmin, initiating degrada­ tion of fibrin and subsequent clot lysis. IV. REVERSAL

A. Antiplatelet agents (Table 90- 1 3) . 1 . Interruption o f therapy may warrant consultation o f specialist i n select patient care scenarios (i.e., recent placement of drug-eluting stent) . 2. Administration of desmopressin IV and platelet transfusion may be required. B. Unfractionated heparin (Table 90- 1 2) . 1 . Protamine. a. Dose required decreases rapidly as time from heparin administration elapses. i. Immediately recent UFH administration: give 1 mg prot­ amine/ 1 00 units of heparin administered. ii. Thirty to sixty minutes since UFH administration: 0 . 5 to 0.75 mg protamine for every 1 00 units of heparin. b. Administer slowly with no more than 50 mg in a 1 0-minute period. c. Perform postinfusion aPTT to verify response to reversal. C. Low molecular weight heparins (Table 90- 1 2) . 1. Protamine. a. Provides partial reversal of LMWH products. b. Protamine 1 mg neutralizes 1 00 anti-Xa units or 1 mg protamine neutralizes 1 mg of LMWH (e.g., enoxparin) administered. D. Indirect factor Xa inhibitor fondaparinux (Table 90- 1 3) . 1. Hold agent; duration o f effect i s dependent upon renal function/clear­ ance. 2. No pharmacologic reversal agent available; limited data to support rever­ sal strategies may be effective. E. Direct factor Xa inhibitors (Table 90- 1 3) . 1 . Hold agent: duration o f effect i s dependent upon renal function/clear­ ance and hepatic function.

F i br i n olytics •t!l:i•=-:111• 11 Drug

I nd ications

Dos i ng, t i m i ng, d u ration

A lte p l a se (Activase a n d CathfloActivase)

Ac ute ST e l evation M I

>67 kg LD: 15 mg IV bo l u s , fo l ­ lowed b y 50 mg infusion over 30 m i n , then 3 5 mg i nf u s i o n ove r 60 m i n (tota l = 1 00 mg) 22) (ische m i c stroke)

(continued)

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•t!1:1•:ama1• F i brinolytics (continued) Exc l u s i o n s : Age >80 y : evid ence of ta king oral a nticoagu lant thera py, base l i n e N I HSS score >25; h istory of stroke a n d d i a betes P e r i p h e ra l a rter i a l o r ven o u s throm bos is

Ve n o u s catheter occl usion

R ete p l a se ( R etavase)

Te necte plase (TN Kase)

Acute ST e l evation M I Ve n o u s catheter occl usiona Acute ST elevation M I

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Patients with m a j o r e a r l y i n fa rct signs o n co m p uterized cra n ia l tom ogra phy (isch e m i c stroke)

Contraindications •

C ath eter-d i rected ad m i n i strat ion : 1 . 5 mg/h by tra n scatheter i ntra -arte r i a l i nfusion u nti l lysis of t h ro m b u s Weight >30 kg 2 mg/2 m l Patient weight > 1 0 kg but 1 1 g/dL (and provide no additional benefit) ; a rapid rise in hemoglobin (> 1 g/dL over 2 weeks) may also contribute to these risks . . . [t] o decrease . . . risk of cardio- and thrombovascular events, use the lowest dose needed to avoid red blood cell transfusions." G. Antipsychotics. 1 . Atypical antipsychotics (clozapine, quetiapine, olanzapine, risperidone) associated with a twofold increased risk of VTE. 2. Low-potency antipsychotics (e.g., chlorpromazine) associated with a higher risk than high-potency antipsychotics (e.g., haloperidol) . 3. Further increase in VTE risk in the initial 3 months of treatment with use of > 1 anti psychotic and with supratherapeutic serum drug concentrations.

C h a pter 9 1 • Venous Thrombosis a n d R e l ated D i sorders i n C r i t i c a l Care Patie nts

I

709

4. Mechanism may involve drug-induced sedation, obesity, hyperleptinemia, antiphospholipid antibodies, or activation of platelets or coagulation proteins. 5. Weigh risks and benefits carefully in patients who have suffered VTE. H. Thrombopoietin receptor agonists-Eltrombopag and Romiplostim. 1 . Therapeutic goal: platelet count 2: 5 0 x 1 09 IL. 2. Thrombosis risk may be higher with platelet count > 200 x 1 09/L. 3. Need to reduce dose of Romiplosrim by 1 mcg/kg, and reduce daily dose of Eltrombopag by 25 mg if platelet count > 200 x 1 09/L. 4. Withhold dose and follow platelet count weekly if platelet count > 400 x 1 09/L. V I . MAJ O R TRAU MA-ASSOC IATED T H R O M B O S I S

A. General principles. 1. Very-high risk for VTE in patients with major trauma with an injury severity score (ISS) 2:9 in the absence of prophylaxis (venographic DVT 58%). 2. Patients receiving enoxaparin prophylaxis have an incidence of DVT as high as 3 1 % . 3 . Risk factors fo r VTE i n the major trauma patient (see Table 9 1 - 1 6) . B . Mechanism. 1. Virchow triad. a. Stasis (accumulation of activated coagulation factors, damage to endothelial cells due to decreased oxygen and nutrient delivery) . b. Vessel wall damage/dysfunction (exposes subendothelial TF, collagen leading to activation of platelets and coagulation) . c. Hypercoagulability (increased coagulation factor levels, increased TNF, increased leukocyte production) . 2. Shock/serious injury diminishes anti-thrombin-III (AT-III) levels in the trauma and ICU patients. 3. Elevated plasminogen activator inhibitor 1 (PAI- 1 ) levels, which inhibit tPA and decrease the production of plasmin, suppress fibrinolysis.

TA B L E 9 1 - 1 6

R i s k Factors for VTE i n Patients with Major Tra u m a

Pelvic and o r lower extre m ity fractu res S p i n a l cord i nj u ry I nj u ries req u i ring s u rgica l i nte rve ntion Fe mora l ve nous cath eters Major ve nous i nj u ries Age > 40 Prolo nged i m m o b i l ity Delayed i nstitution of th rom boprophylaxis

7 1 0

I

SECT I O N 9 • H E M AT 0 L 0 G I c p R 0 B L E M s I N T H E I c u

C. Diagnosis: depends on the anatomic site. 1 . Lower or upper extremities: duplex ultraso un_d. . 2. Lung (pulmonary emboli) : helical CT or V/Q scan. 3. Brain: MRV or computed tomography venogram (CTV) . 4. Venogram is useful in all locations but rarely available and not infallible. D. Prophylaxis. 1. Moderate-risk trauma patients (i.e., no major VTE risk factors) without contraindications: enoxaparin 30 mg subcutaneously q12 hours; signifi­ cantly more effective than 5 ,000 units UFH subcutaneously twice daily with an estimated decrease in risk of DVT from baseline, 47%, com­ pared with UFH (only 30% decrease) . 2. High-risk trauma patients: enoxaparin at above dose plus mechanical prophylaxis (sequential compression devices and GCS) . 3. Patients with contraindications to pharmacologic VTE prophylaxis (intracranial bleeding, active bleeding, spinal hematoma) : mechanical prophylaxis until contraindication is no longer present. 4. Vena cava filters or surveillance duplex ultrasonography: insufficient data to recommend use. E. Initial treatment. 1 . UFH or LMWH in therapeutic doses. Rivaroxaban less attractive if the patient at high risk for bleeding given that there is no antidote currently available. 2. If high risk of bleeding, UFH without bolus is preferable to LMWH or rivaroxaban. 3. If contraindication to anticoagulation, strongly consider a vena cava filter for proximal DVT or PE. 4. Give UFH/LMWH for at least 5 to 7 days; continue until an INR of 2 or more is achieved with warfarin. 5. Thrombolysis: reserve for trauma patients without contraindications and life- or limb-threatening thrombosis. F. Long-term treatment. 1 . Usually warfarin is used. Rivaroxaban is also a possibiliry if low risk for bleeding, adequate renal and hepatic function. 2. Duration of therapy: 3 months (DVT) to 6 months (PE) . 3. Vena cava filters. a. Transient contraindication to anticoagulation: consider retrievable vena cava filter. b. Long-term contraindications to anticoagulation: consider permanent vena cava filter. SUGGESTED READI NGS

Bennett CL, Silver SM, Djulbegovic B, et al. Venous thromboembolism and mortality associated with recombinant erythropoietin and darbepoetin administration for the treatment of cancer-associated anemia. JAMA 2008;299(8) : 9 1 4-924. Comprehensive review of erythropoietic stimulatory agents and adverse effects in cancer patients.

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Brodsky RA. How I treat paroxysmal nocturnal hemoglobinuria. Blood 2009; 1 1 3 (26): 6522-6527. Comprehensive review of on treatment ofPNH by a world's expert. Carobbio A, Thiele J, Passamonti F, et al. Risk factors for arterial and venous thrombosis in WHO-defined essential thrombocythemia: an international study of 8 9 1 patients. Blood 20 1 1 ; 1 17 (22) : 5 8 57-5859. Report from international collaborative study provides valuable information on risk factors far arterial and venous thrombosis in ET Cervera R, Espinosa G . Update on the catastrophic antiphospholipid syndrome and the "CAPS Registry." Semin Thromb Hemost 2 0 1 2;3 8 (4):333-338. Excellent recent update on CAP. Falanga A, Marchetti M. Thrombotic disease in the myeloproliferative neoplasms. Hematology Am Soc Hematol Educ Program 2 0 1 2;20 1 2: 5 7 1 -5 8 1 . Excellent review of thrombosis in myeloproliferative disorders by American Society of Hematology. Giannakopoulos B, Passam F, Ioannou Y, et al. How we diagnose the antiphospholipid syndrome. Blood 2009; 1 1 3 (5):985-994. Systematic approach on diagnosis and risk stratification ofpatients with APS. Hultcrantz M, Kristinsson SY, Andersson TM, et al. Patterns of survival among patients with proliferative neoplasms diagnosed in Sweden from 1 973 to 2008: a population-based study. J Clin Oncol 20 l 2;30(24) :2995-300 I . Large observational study indicating reduced life expectancy in MPN patients compared with the general population. Kahn SR, Lim W, Dunn AS, et al. Prevention of VTE in nonsurgical patients: Anti thrombotic Therapy and Prevention of Thrombosis, 9th ed. American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 20 1 2; 1 4 1 (2 Suppl) :el95S-e226S. The latest ACCP guideline on prevention of VTE in medical patients. Kearon C, Aki EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease: Anti thrombotic Therapy and Prevention of Thrombosis, 9th ed. American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 20 1 2; 1 4 1 (2 Suppl) :e4 1 9S-494S. The latest version of the authoritative A CCP Guideline on management of VTE. Khorana AA, Kuderer NM, Culakova E, et al. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood 2008; 1 1 1 ( I 0):4902-4907. Khorana and colleagues have developed a validated model that can identify cancer patients at increased risk of VTE during chemotherapy treatment. Kucher N. Clinical practice. Deep-vein thrombosis of the upper extremities. N Engl J Med 20 1 1 ;364(9) : 8 6 1 -869. An excellent overview ofthe pathogenesis and management ofupper extremity D VT Lidegaard 0, Milsom I, Geirsson RT, et al. Hormonal contraception and venous thromboem­ bolism. Acta Obstet Gynecol Scand 2 0 1 2 ; 9 1 (7) :769-778 . Recent review ofthe risks of VTE associated with hormonal therapy. Lussana F, Caberlon S, Pagani C, et al. Association ofV6 1 7F Jak2 mutation with the risk of thrombosis among patients with essential thrombocythaemia or idiopathic myelofi­ brosis: a systematic review. Thromb Res 2009; 1 24(4):409-4 1 7. Systematic review on the association ofV617FJAK-2 mutation and risk ofthrombosis in ET Marchioli R, Finazzi G, Specchia G, et al. ; CYTO-PV Collaborative Group. Cardiovascular events and intensity of treatment in polycythemia vera. N Engl J Med 20 l 3;368 ( 1 ) :22-33.

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A well-designed well-conducted clinical trial underscoring the clinical importance oftight hematocrit control in patients with PV Tefferi A. Polycythemia vera and essential thrombocythemia: 20 1 2 update on diagnosis, risk stratification, and management. Am J Hematol 20 l 2;87(3) :28 5-293. Recent review and update ofPV and ET by a world-recognized authority. Verstovsek S, Mesa RA, Gotlib J, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl] Med 201 2;366(9):799-807. Clinical trial showing clinical benefit ofRuxolitinib in myelofibrosis. White RH.The epidemiology of venous thromboembolism. Circulation 2003; 1 07 (23 Suppl 1 ) :14-18. A succinct review ofthe epidemiology of VTE by one of the leading authorities on the subject.

An e m i a i n th e C r i t i c a l C a re Pati e nt T h o m a s G . D e lo u g h e ry

I . E P I D E M I O LOGY O F A N E M I A I N CRITI CALLY I LL PAT I E NTS

A. Ninety-five percent of patients admitted to intensive care settings become anemic. B. Half of the patients in the intensive care unit (ICU) will receive red cell transfusion. C. Most common etiologies. 1. Inflammation (i.e., anemia of chronic disease) . 2. Blood loss. 3. Hemolysis. I I . C LAS S I FICAT I O N O F AN E M IA

A. Indices-classifies anemia by size of red cells (measured in femtoliters, fl) . 1. Microcytic ( 1 00 mg/L rules out iron deficiency) . 4. Therapy: oral or (refractory cases) IV iron. B. Folate. 1. Clinical features: macrocytic anemia, hypersegmented neutrophils, pancytopenia if severe. 2. Risk factors: poor nutrition, alcohol use. 3. Diagnostic test: high homocystiene level. 4. Therapy: oral folate (1 mg/day) . C. Vitamin B 1 2 • 1. Hematologic picture: macrocytic anemia, hypersegmented neutrophils, pancytopenia if severe. 2. Risk factors: pernicious anemia, gastric or bowel surgery (including gastric bypass) . 3. Diagnostic testing. a. Low vitamin B 1 2 level. b. Elevated methylmalonic acid level. 4. Therapy. a. Oral vitamin B 1 2 : 1 to 2 mg/day, or. b. Parenteral (intramuscular [IM]) B 1 2 : 1 mg daily for 1 week, followed by weekly for 1 month, followed by monthly thereafter.

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D. Copper. 1. Features: anemia and severe neutropenia; thrombocytopenia very rare. 2. Risk factors: gastric surgery, malnutrition, tube feedings. 3. Diagnostic testing. a. Low copper level. 4. Therapy: copper orally, 2 mg/day. V I I I . D I S O RD E RS O F D E C REAS ED R E D CELL P R O D U CTI O N

A. Anemia o f inflammation (i.e., anemia o f chronic disease) . 1. Hematologic features: mild-to-moderate anemia; microcytic m one­ third of cases. 2. Risk factors: may be secondary to infections, cancer, autoimmune dis­ ease, trauma, other entities. 3. Diagnostic testing. a. Low serum iron, low transferrin, normal or elevated ferritin. b. Inappropriately low erythropoietin for degree of anemia. 4. Therapy: therapy of underlying disease, transfusions; erythropoietin (see subsequent text) . B. Anemia of renal insufficiency. 1 . Clinical presentation: anemia in the setting of renal disease. 2. Risk factors: renal disease-can be subtle in older patients. 3. Diagnostic testing: low erythropoietin, glomerular filtration rate (GFR) 20% blasts. F. Molecular diagnostic studies. 1. BCR-ABL mutation diagnostic of CML. 2. PML-RAR-a diagnostic of APML. 3. FLT3 mutation is a negative prognostic feature for AML. V. TREAT M E N T

A. Acute lymphoblastic leukemia. 1. Induction chemotherapy with four to five chemotherapy drugs: a. Asparaginase, prednisone, vincristine, doxorubicin. b. CNS prophylaxis with intrathecal chemotherapy. c. Intensification and maintenance chemotherapy over 1 8 to 24 months (outpatient) . d. Philadelphia chromosome-positive patients also receive tyrosine kinase inhibitor such as imatinib or dasatinib. e. Allogeneic transplantation in first remission for high-risk or young patients. f. Cure rate 90% for children, 50% for young adults, 1 5% over age 50. B. Acute myelogenous leukemia. 1. Elderly patients have poor prognosis-consider supportive care with hydroxyurea, or outpatient treatment with 5-azacytidine or decitabine. 2. Induction chemotherapy with idarubicin and cytosine arabinoside (ARA-C) . 3. Allogeneic stem cell transplantation for patients at high risk of relapse, often based on cytogenetics. 4. Cure rate 70% with favorable subtypes, 30% with higher risk, 1 0% over age 60. C. Acute promyelocytic leukemia. 1. Cure rate of >90%. 2. Over 5% of patients die of bleeding before diagnosis can be made. 3. Prompt diagnosis and treatment are essential.

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4. All-trans-retinoic acid (ATRA) plus chemotherapy. 5. Consolidation with ATRA, daunorubicin, and arsenic. D. Chronic lymphocytic leukemia. 1. Observation until disease progression, often many years. 2. Fludarabine- or bendamustine-based therapy. 3. Alemtuzumab or allogeneic stem cell transplantation for refractory patients. 4. Long natural history, but transplant only known curative therapy. E. Chronic myelogenous leukemia. 1. Oral ryrosine kinase inhibitor-imatinib, dasatinib, or nilotinib. 2. Long natural history with tyrosine kinase inhibitors, not clear if patients cured. V I . C O M PLICATI O N S

A . Leukostasis. 1. Most likely when the blast count > 50,000/mm3 . 2. Can occur even with lower WBCs. 3. Most common in AML because blasts are large. 4. Hypoxia, pulmonary infiltrates, visual changes, mental status changes, CNS bleeding. 5. Treatment for leukostasis. a. Intravenous fluids. b. Prompt initiation of chemotherapy. c. Hydroxyurea 1 to 2 g PO rwice daily to lower WBCs. d. Leukapheresis. e. Avoid red blood cell (RBC) transfusions, which increase viscosity. B. Bleeding. 1. Thrombocytopenia. a. Increased risk CNS bleed when platelet count < 1 0,000/mm3 . b. Platelet transfusion when platelet count < 1 0,000/mm3 or bleeding. c. Irradiated, filtered blood products only. d. Human leukocyte antigen (HLA)-matched platelets if alloimmunized. e. No family member donations if patient a transplant candidate. 2. Disseminated intravascular coagulation. a. Common with APML, but can also be seen in AML/ALL. b. Life-threatening bleeding, stroke, CNS bleed. c. Treat with fresh frozen plasma, platelets, and cryoprecipitate for fibrinogen < 1 00. d. If APML or suspected APML, start ATRA promptly. C. Infections. 1 . General principles. a. WBCs may be high, but abnormal WBC function-patient func­ tionally neutropenic. b. Chemotherapy suppresses the immune system. c. Imaging procedures such as computed tomographic (CT) scans may help guide coverage; consider bronchoscopy for pulmonary infiltrates.

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Bacterial infections. a. Gram-positive infections related to indwelling catheters. b. Gram-negative infections related to a damaged intestinal tract.

3. Fungal infections. a. Increased with neutropenia, antibiotics, indwelling catheters, parenteral nutrition, and steroids. b. Candida (skin, liver, esophagus) . c. Aspergillus (lung, sinuses). 4. Viral infections. a. Herpes simplex virus, herpes zoster. b. Influenza, respiratory syncyrial virus serious infections in leukemia patients. 5. Other infections. a. Pneumocystis pneumonia (PCP) seen m ALL patients receiving steroids. 6. Treatment of infections. a. Treat fever immediately as presumptive infection. b. Coverage for gram-negative infections, including Pseudomonas.

if.j;l!ijii

S i d e Effects of Common Chemothera py Drugs

Drug

Cytos i n e a ra b i noside (ARA-CJ l d a r u b ic i n , d a u noru b i c i n Eto poside A l l trans retinoic acid (ATRA) Cyclophos p h a m ide (Cytoxa n ) P red n isone V i ncrist i n e Aspa rgi nase

A l opecia N a u sea/ Bone ma rrow Other vom iting s u ppress ion

+

+

++

++

++

++

+

+

+

+

++

++

+ +

l m ati n i b ( G l eevec) F l u d a ra b i n e

+

+, m i l d toxicity; ++, moderate-to-severe toxicity; -, A T R A toxicity.

Feve r, re n a l fa i l u re , cere be l l a r toxic ity Card iac, m u cositis, ves icant Hy potension I nc reased W B Cs Lung i nfi ltrates H e m orrhagic cystitis M uscle wea kness, ed e m a , glucose i nto lera nce N e u ropathy Pancreatitis, coag u l o pathy Elevated l iver tests , ras h I nc reased risk late i nfection

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SECT I O N 9 • H E M AT 0 L 0 G I C P R 0 B L E M S I N T H E I C U c. Persistent fever, coverage for gram-positive infections and fungus. d. Preventative regimens include gram-negative coverage (quinolone) , antifungal coverage (fluconazole) , and PCP coverage (in ALL patients) . 7. Tumor lysis syndrome. a. Rapid destruction of tumor cells. b. High uric acid, low calcium, high potassium. c. Can progress to acute renal failure with fatal hyperkalemia. d. Prevention of tumor lysis syndrome. i. Hydration before chemotherapy. ii. Allopurinol or rasburicase. D. Pulmonary toxicity. 1. Acute lung toxicity from fludarabine, cytarabine, bortezomib, rituximab, all-trans-retinoic acid < 5 % . 2 . Late lung toxicity (pulmonary fibrosis) from busulfan, bleomycin, BCNU, melphalan < 5 % . 3. Acute leukemia itself can present with pulmonary infiltrates-often respond to steroids. 4. Chemotherapy toxicity-see Table 94- 1 .

SUGGESTED READI NGS

Bassan R, Hoelzer D . Modern therapy of acute lymphoblastic leukemia. J Clin Oncol 20 1 1 ;29:532-543. Review of newer treatment strategies for adult with ALL, including pediatric inspired regimens, hematopoietic stem cell transplantation, and new targeted agents. Cortes J, Kim DW, Raffoux E, et al. Efficacy and safety of dasatinib in imatinib-resistant or-intolerant patients with chronic myeloid leukemia in blast phase. Leukemia 2008;22:21 76-2 1 83. Use ofalternative tyrosine kinase inhibitor, dasatinib, in patients with CML in blast crisis who are resistant to imatinib. Farag SS, Maharry K, Zhang M, et al. Comparison of reduced-intensity hematopoietic cell transplantation with chemotherapy in patients age 60-70 years with acute myeloge­ nous leukemia in first remission. Biol Blood Marrow Transplant 2 0 1 1 ; 1 7: 1 796-1 803. This study compares allogeneic stem cell transplant with conventional chemotherapy for older patients with AML. The transplant patients had improved leukemia-free survival (32% vs. 15%), although the nonrelapse mortality was higher (36% vs. 4%) for the transplant patients. Goldstone AH, Richards SM, Lazarus HM, et al. In adults with standard-risk acute lympho­ blastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial. Blood 2008; 1 l l : 1 827- 1 833. Large international study showing benefit to allogeneic transplant in young patients with standard risk disease. Kantarjian H, Ravandi F, O'Brien S, et al. Intensive chemotherapy does not benefit most older patients (age 70 years or older) with acute myeloid leukemia. Blood 20 1 0; 1 1 6:4422-4429. Review ofliterature indicating a high mortality rate for AML patients treated with intensive chemotherapy.

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Kantarjian HM, Shah NP, Cortes JE, et al. Dasatinib or imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: 2-year follow-up from a randomized Phase 3 trial. Blood 20 1 2; 1 1 9 : 1 1 23-1 129. In a randomized study, dasatinib produced a higher major molecular response and reduction ofbcr-abl than imatinib. Park JH, Qiao B, Panageas KS. Early death rate in acute promyelocyric leukemia remains high despite all-trans retinoic acid. Blood 2 0 1 1 ; 1 1 8 : 1 248-1 254. Large retrospective study of 1400 patients with APML, with early death rate of 17%. The death rate was higher in patients over age 55. Saglio G, Kim OW, Issaragrisil S, et al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl] Med 2 0 1 0;362:225 1-2259. Randomized study showing improvement in complete cytogenetic response and major molecular response for nilotinib over imatinib for treatment of newly diagnosed chronic myeloid leukemia. Schlenk RF, Dohner K, Kramer J, et al. Mutations and treatment outcome in cyrogenetically normal acute myeloid leukemia. N Engl] Med 2008;3 5 8 : 1 909-1 9 1 8. Importance of molecular diagnostic testjlt-3 and nucleophosmin in determination of prognosis for acute myeloid leukemia. Slichter SJ, Kaufman RM, Assmann SF, et al. Dose of prophylactic platelet transfusions and prevention of hemorrhage. N Engl J Med 201 0;362:600-6 12. Large study of 1,272 patients indicating that a low dose ofinfosed platelets in thrombocytopenic patients did not increase the risk of bleeding.

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O n c o l og i c E m e rge n c i es D i a n e M . F. Sava rese

I. S U P E R I O R VENA CAVA (SVC) SYN DRO M E

A. Etiology. 1 . SVC syndrome results from obstruction of venous return. a. Invasion of tumor into SVC or intravascular thrombus. b. External compression of the SVC. 2. Sixty-five percent to eighty percent of cases due to malignancy. a. Predominantly lung cancer and lymphoma. 3. Other causes. a. Thrombosis (usually with an indwelling intravascular device) . b. Mediastinal fibrosis. B. Clinical features and diagnosis. 1. Symptoms and signs of SVC syndrome (Table 95- 1 ) are related to the following: a. Poor venous return. b. Increased intravenous (IV) pressure. c. Collateral vessel engorgement. 2.

Radiographic studies are usually diagnostic. a. Chest radiograph abnormal in >80%: mediastinal widening, pleural effusion. b. Contrast-enhanced chest computed tomography (CT) the preferred diagnostic study. i. Identifies the site of venous obstruction. ii. Suggests etiology and identifies impending complications. c. Upper extremity venography. i. Gold standard for defining the level and extent of SVC obstruc­ tion. ii. Cannot identify etiology unless thrombosis is the sole cause.

3. Tissue diagnosis: Routine diagnostic procedures carry little excess risk. a. Pursue the least invasive option. i. Sputum or pleural fluid cytology. ii. Biopsy of an enlarged peripheral lymph node. iii. Transthoracic CT-guided biopsy. iv. Bronchoscopy with biopsy. b. Pursue more invasive procedure if necessary to establish diagnosis. i. Mediastinoscopy. ii. Video-assisted thoracoscopy. iii. Thoracotomy. 738

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Com mon Sym ptoms a n d Signs of S u perior Ve na Cava Syn d rome

Symptom or sign

H e m odyna m ic Fac i a l edema Arm edema D istended neck ve i n s D istended c hest ve i n s Fac i a l plethora Visual sym ptom s Respi ratory Dyspnea Cough H oa rse ness Strid or N e u rologic Syncope Headache D izzi ness Confu sion O bt u n dation/cerebrovasc u l a r eve nt

Percentage of all patie nts ( range)

82 46 63 53 20 2

(60- 1 00) ( 1 4-75) (27-86) (38-67) ( 1 3-23)

54 (23-74) 54 (38-70) 17 4 10 (8- 1 3 ) 9 (6--1 1 ) 6 (2-10) 4 2

Data from Armstrong BA, Perez CA, S i m pson J R , et a l . Role of i rrad iation in the ma nagement of s u perior vena cava syn d rome. Int J Radial Oneal Biol Phys 1987 ; 1 3 : 53 1-539 ; Yel l i n A, R osen A, Reichert N , e t a l . S u perior vena cava syn d ro m e : t h e myth - t h e facts. A m Rev Respir Dis 1990; 1 4 1 : 1 1 14-1 1 1 8; Schra ufnagel DE, H i l l R, Leech JA, et a l . S u perior vena cava l o bstruction-is it a medical emergen cy? Am J Med 1 98 1 ; 70: 1 1 69-1 1 74; C h e n J C , Bonga rd F, Klein S R , et a l . A contem porary pers pective on s u perior vena cava syn d ro m e . Am J Surg 1990; 1 60 : 207-2 1 1 ; R ice TW, Rod riguez R M , Barnette R, et a l . Preva lence a n d c h a racteris­ tics of pleural effusion i n su perior ve n a l cava l syn d rome. Respirology 2006; 1 1 : 299-305; a n d U rruticoechea A, M esia R , Dominguez J , e t a l . Treatment o f m a l ignant s u perior v e n a cava synd rome by e n d ovascular stent i nsertio n . Experience on 52 patients with l u ng cancer. Lung Cancer 2004;43 :209-2 14.

Emergent treatment before pursuing histologic diagnosis required if the following are present: i. Stridor. ii. Confusion, obtundation. iii. Hemodynamic compromise. C. Treatment. c.

1. Goals: Alleviate symptoms; treat underlying cause. a. Urgency of treatment depends on severity of SVC syndrome (Yu, 2008) . In the presence of the following severe life-threatening symptoms, perform immediate venogram and urgent endovascular stenting for rapid relief of symptoms; direct thrombolysis if thrombus present: i. Stridor. ii. Confusion, obtundation. iii. Hemodynamic compromise.

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b. After urgent management of severe or life-threatening symptoms, and for all others, establish the histologic diagnosis and tumor stage to select appropriate therapy for malignancy-associated SVC syndrome. 2. Definitive therapy depends upon underlying etiology. a. Malignant cause: Histology and tumor stage dictate initial antitumor treatment. i. Surgery for selected cases (nonmetastatic thymoma, residual germ cell cancer) . ii. For nonsurgically managed malignancy, chemotherapy is pre­ ferred for chemosensitive tumors (lymphoma, mediastinal germ cell tumor, small cell lung cancer) . iii. lntraluminal scenting. (a) Useful for extrinsic tumor compression. (b) Provides more rapid relief of symptoms in more patients than radiation therapy (RT) . (c) Does not compromise ability to establish a histologic diagnosis. iv. Radiation therapy. (a) Relieves symptoms, though not as quickly as scenting. b. Nonmalignant causes. i. lntravascular device associated. (a) Remove device, if possible. (b) Consider thrombolysis if thrombus ::;5 days old. ii. Mediastinal fibrosis. (a) Benefits of scenting are generally short lived. (b) Surgical bypass may be required. 3. Supportive care. a. Bed rest with head elevated to reduce central venous pressures. b. Diuretics (avoid depletion of intravascular volume) , decreased salt intake. c. Oxygen. 4. Glucocorticoids. a. Most useful in lymphoma and thymoma (cytolytic effect) . b. Short course of high-dose glucocorticoids may be recommended with emergent RT for impending airway obstruction. i. Minimizes edema. ii. Reduces the risk of central airway obstruction. I I . T U M O R LYS I S SYNDRO M E (TLS)

A. Pathophysiology. 1 . Massive cytolysis of malignant cells releases large amounts of potassium, phosphate, and uric acid with secondary hypocalcemia. 2. Acute renal failure from precipitation of uric acid and/or calcium phos­ phate in the renal tubules.

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B. Etiology. 1. Most commonly encountered after initial chemotherapy for the following: a. Clinically aggressive non-Hodgkin lymphomas (NHL, particularly the Burkitt and lymphoblastic subrypes) . b. Acute lymphoblastic leukemia (ALL) . 2. May also occur spontaneously in high-grade NHL or ALL. 3. May occur in other tumor rypes with a high proliferative rate, large tumor burden, or high sensitiviry ro cyrotoxic therapy. C. Diagnosis. 1. Cairo-Bishop definition (Table 95-2) . D. Prevention and treatment. 1. Best management is prophylaxis. Risk stratification guidelines are avail­ able (Cairo et al. , 20 1 0) . 2 . Prevention. a. Aggressive IV hydration (2 to 3 L/m 2/d) with diuresis to enhance washout of uric acid crystals. b. Limit phosphate and potassium intake during initial therapy. c. Administration of hypouricemic agent(s) . i . Allopurinol for low- and intermediate-risk disease (Cairo e t al., 20 1 0) . ii. Rasburicase (recombinant urate oxidase) for high-risk disease. (a) Burkitt or lymphoblastic lymphoma, Burkitt-ALL, or other ALL with a white blood cell (WBC) count � 1 0 0 x 1 0 9/L, and other high-risk lymphomas with a high lactate dehydro­ genase (LDH) or advanced stage, or other patients if uric acid �8 mg/dL (Cairo et al. , 20 1 0) . (b) Rasburicase contraindicated i n G6PD deficiency. TA B L E 9 5 - 2

Ca i ro- B ishop Defi n ition of Tu mor Lys i s Synd rome

Laboratory TLS

Abnorma l ities in two or more of the fol lowi n g serum va l u es, p resent with i n 3 days before, o r 7 d ays afte r i nstituting c h e m othera py: U ric acid � 8 mg/d l (476 µmol/L) or 25% i n c rease fro m base l i n e Potass i u m � 6.0 m m o l/L or 2 5 % i n c rease from base l i n e , Phosp hate � 6 . 5 m g/d l (2 . 1 m m ol/L) i n c h i ld re n , o r �4 . 5 m g/d l ( 1 .45 m m ol/L) i n a d u lts, or 2 5 % i n c rease from base l i n e Calci u m :::; 7 m g/d l ( 1 .75 m m ol/U or 2 5 % decrease fro m base l i n e C l i n ical TLS

La boratory T LS p l u s one o r more of the fo l lowi ng: I nc reased seru m creati n i n e conce ntration (�1 . 5 t i m es the u p per l i m it of n o r m a l [ U LN ] ) Ca rd iac a rrhyth m ia/s u d d e n death Seiz u re Ca i ro M S , Bishop M . T u m o u r lysis syn d ro m e : new thera peutic strategies a n d c lassification. Br J Haematol 2004; 127:3.

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d. Urinary alkalinization. i. Generally not recommended. ii. Benefit unproven; potential harms especially with hyperphospha­ temia. e. Monitoring during therapy. i. Closely monitor urine output, fluid balance, and serial assays of electrolytes, LDH, and serum uric acid. 3. Treatment of established TLS. a. Aggressive hydration and diuresis, continuous cardiac monitoring, and measurement of electrolytes, creatinine, and uric cid every 4 to 6 hours. b. Rasburicase if not given initially. c. Treat specific electrolyte abnormalities, especially hyperkalemia. d. Indications for renal replacement therapy. i. Severe oliguria or anuria. ii. Persistent hyperuricemia (rare with use of rasburicase) . iii. Persistent hyperkalemia. iv. Hyperphosphatemia-induced symptomatic hypocalcemia. I l l . E P I D U RAL S P I NAL CORD C O M PRESS I O N (ESCC)

A. Pathophysiology. 1 . Neoplastic mass in the epidural space with extrinsic compressesion of spinal cord. a. Direct invasion from any of the following: i. Enlarging vertebral body metastases. ii. Retroperitoneal lymphadenopathy extending through the para­ vertebral neural foramina. iii. Intradural metastases. 2. Increased intradural pressure and vascular compromise lead to spinal cord infarction and rapid, irreversible loss of function. B. Etiology. 1 . Most common tumor types are lung, breast, prostate, kidney cancer, lymphoma, and myeloma. C. Clinical presentation. 1. Back pain. a. Initial symptom in >90% of patients. b. Consider in any patient with known cancer (or symptoms suggesting the presence of undiagnosed cancer) and unexplained back pain. 2. Symmetric lower extremity weakness and hyperreflexia below the level of compression. a. Lesions below the conus medullaris (cauda equina lesion) have weak­ ness and depressed deep tendon reflexes in the legs. b. Motor weakness occasionally progresses to paraplegia within hours. c. Sensory deficits are rare initially, but usually develop at some point. i. The spinal sensory level, if present, is typically one to five levels below the level of compression.

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ii. Saddle sensory loss is common with cauda equina lesions; higher lesions usually spare the sacral dermatomes. 3. Loss of bowel or bladder control is a late and poor prognostic sign. D. Diagnosis. 1. Early diagnosis is essential; patients who begin treatment when paraple­ gic almost never regain ambulation. 2. Perform a thorough neurologic examination. 3. Obtain plain spine radiographs for evidence of the following: a. Pedicle loss. b. Vertebral compression fractures. c. Osteoblastic/ osteolytic bone lesions. d. Major vertebral body collapse or pedicle erosion with a matching radiculopathy predicts a 75% to 83% chance of ESCC. 4. If either examination or x-rays are abnormal, a magnetic resonance imaging (MRl) or myelogram is necessary to exclude ESCC. a. MRl of the entire spine is preferred to assess location and extent of ESCC. b. CT myelography if timely MRl is unavailable or contraindicated. 5. Assess spine stability. a. Pain from an unstable spine will not be relieved with RT. An unstable spine must be stabilized either by surgical fixation or by percutaneous vertebral repair. b. A classification system for spinal stability based upon clinical and radiographic findings has been proposed (Fisher et al. , 20 1 0) . F. Treatment. 1. Pain management. a. Glucocorticoids: relieve pain within hours in most cases. i. Suggested regimen: dexamethasone 10 to 24 mg IV bolus fol­ lowed by 16 to 24 mg orally daily in divided doses. ii. Higher initial doses (e.g. , dexamethasone 1 00 mg) may enhance analgesia, but associated with more serious compications and no better neurologic outcomes. b. Opiates: most patients also require opiates to tolerate diagnostic studies. 2. Initial decompressive surgery. a. Consider for patients who are candidates for a surgical intervention, have a limited disease burden who have symptomatic progression during or following RT, need for spinal stabilization, or have a stable spine with high-grade ESCC and a relatively radioresistant neoplasm (e.g. , melanoma, renal cell cancer) . 3. Radiation therapy. a. Required following decompressive surgery. b. Treatment of choice: if aggressive radical resection is not feasible. c. External beam RT alone a reasonable alternative ro surgery for patients with metastatic ESCC and a stable spine and radiosensitive neoplasm (breast cancer, lymphoma, myeloma) , particularly if high disease burden and relatively poor prognosis.

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d. Stereotactic radiosurgery should be considered for patients with a stable spine and a relatively resistant neoplasm (melanoma, renal cell cancer) who have no high-grade ESCC. 4. Chemotherapy. a. Is recommended for selected chemoresponsive malignancies (e.g., small cell lung cancer, lymphoma) . IV. HYPE RCALC E M IA O F MALIGNANCY

A. General principles. 1. Major metabolic abnormality in patients with cancer. a. Occurs in 1 0% of patients. 2. Most common in breast, lung cancer; multiple myeloma. B. Etiology and pathophysiology. 1 . Develops through three mechanisms, all of which lead to increased osteoclast activation. a. Osteolytic metastases. b. Ectopic tumor production of parathyroid hormone-related protein (PTHrP) . i. Lung (squamous cell) . c. Direct bone invasion or local production of humoral factors (e.g., osteoclast-activating factor) . i. Multiple myeloma. 2. Consider coincident primary hyperparathyroidism. a . Measure parathyroid hormone (PTH) in all hypercalcemic patients. b. If serum PTHrP and PTH concentrations are both high, coexisting primary hyperparathyroidism probably present. C. Clinical manifestations. 1 . Symptoms and signs are most apparent when the rate of rise of serum calcium is rapid. 2. Change in mental status. a. Can be subtle (e.g., lethargy or depression) . b. In the extreme, may include psychotic behavior, obtundation, and coma. 3. Cardiac arrhythmias. a. Electrocardiographic (ECG) changes: prolonged PR and shortened QT interval. b. Digitalis-toxic arrhythmias may develop more easily in hypercalcemic patients. 4. Renal consequences. a. Polyuria followed by dehydration and prerenal azotemia. b. Tubular damage from nephrocalcinosis (acidosis, glycosuria, hypo­ magnesemia, and aminoaciduria) . 5. Gastrointestinal symptoms. a . Anorexia. b. Nausea and vomiting.

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I

745

c. Constipation. d. Abdominal pain. D. Laboratory characteristics of hypercalcemia. 1. "Total serum calcium" not equivalent to "ionized calcium" (which rep­ resents biologically active calcium) . 2. Approximately 40% of total serum calcium bound to protein (primarily albumin) . a. Correct measured serum calcium in patients with hypoalbuminemia or hyperalbuminemia. i. One gram of albumin binds 0 . 8 mg of calcium; to calculate cor­ rected total serum calcium value, add 0 . 8 mg/dL to the measured total serum calcium for each 1 g/dL decrease in serum albumin below 4.0 g/dL. b. In multiple myeloma, total serum calcium may be spuriously elevated, because hyperglobulinemia leads to increased binding of calcium; in such cases, ionized calcium should be measured. 3. Severity of hypercalcemia based on corrected total serum calcium level: a. Mild = 1 1 to 12 mg/dL (2. 8 to 3 mmol/L) . b. Moderate = 1 2 to 1 4 mg/dL (3 to 3.5 mmol/L) . c. Severe = > 1 4 mg/dL (>3 . 5 mmol/L) . E. Diagnosis. 1 . Laboratory confirmation of hypercalcemia (see preceding text) . 2. Many potential causes can be eliminated by the patient's history (Table 95-3).

Differential Diagnosis o f Hyperca lcemia

Cancer With bone m etastasis (so l i d tu m or) Without bone m etastasis (so l i d t u m o r) H e m ato logic (e.g. , m u lt i p l e mye l o m a , l e u k e m i a , lym phoma with bone i nvolve m e nt) P r i m a ry toxic hyperpa rathyroidism Th iazides M i l k-a l ka l i syn d ro m e Vita m i n D or A toxic ity Endocri ne Thyrotoxicosis Ad re n a l i nsufficiency P h eoc h rom ocyto ma ( u s u a l ly i n association with p r i m a ry hyperpa rathyro i d i s m ) G ra n u lomato us d isease Tu berc u losis Sa rco idosis ( p a rti c u l a rly i m m o b i l ized patients with u n d e rlying bone d i sease) Artifactual Hypera l b u m i n e m ia or hyper-ga m ma-globu l i ne m ia Ve nous stasis ( p rolo nged to u r n i q u et a p p l icati o n )

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SECT I O N 9 • H E M A T O L O G I C P R O B L E M S I N T H E I C U

F. Treatment. 1. Best treatment: specific therapy of the underlying malignancy. 2. Avoid thiazide diuretics, which promote renal tubular resorption of calcium. 3. Asymptomatic or mildly symptomatic (e.g. , constipation) hypercalcemia (serum calcium � 14 mg/dL) does not require immediate treatment. An acute rise to levels > 1 2 mg/ dL may cause marked changes in sensorium, requiring treatment. Patients with a serum calcium > 14 mg/dL require treatment, regardless of symptoms. 4. Fluid replacement with normal saline. a. Most hypercalcemia patients are volume depleted. b. Initial rate of infusion: 1 5 0 to 300 mL/hour. c. Benefit usually temporary and insufficient to normalize the calcium level in most patients. 5. For euvolemic patients: a. Avoid further volume depletion. b. Furosemide: No clear evidence of benefit, and may cause harm by promoting diuresis and aggravating preexisting dehydration. c. Closely monitor total intake and output, weight, serum electrolytes, and urine electrolytes (at least within the first 1 2 hours) . 6. Parenteral zoledronic acid. a. Treatment of choice. b. Dose 4 mg over 1 5 minutes. c. Onset of action is within 24 hours. 7. Calcitonin. a. Consider if urgent need to decrease serum calcium (e.g., obtunda­ tion, ECG changes) . b. Relatively weak effect; lowers serum calcium by a maximum of 1 to 2 mg/dL (0.3 to 0 . 5 mmol/L) . c. Dose is 4 international units/kg IV administered subcutaneously or intramuscularly; onset of action is 4 to 6 hours; nasal calciro­ nin is ineffective. i. Doses can be increased up to 6 to 8 units/kg every 6 hours. ii. If a hypocalcemic response is seen in several hours, the frequency of dosing can be lengthened to every 6 to 1 2 hours. d. Tachyphylaxis limits efficacy to the first 48 hours, even with repeated doses. 7. Corticosteroids may be useful for patients with hematologic malignan­ cies or breast cancer. 8. Gallium nitrate (200 mg/m 2 IV daily for 5 days) may be considered for refractory patients. 9. Hemodialysis. a. Treatment of last resort for severe hypercalcemia (serum calcium 1 8 to 20 mg/dL [4. 5 to 5 mmol/L] ) . b . May b e required i n patients with renal failure. 10. In the absence of effective antineoplastic treatment, hypercalcemia typi­ cally recurs, and retreatment is required every 3 to 4 weeks. =

C h a pter 95 • Oncologic Emerge n c i es

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V. MALIG NANT P E R I CARDIAL EFFU S I O N

A. Indicates a poor prognosis. B. The most common primary rumor involving the pericardium is lung can­ cer; others include breast and esophageal cancer, melanoma, lymphoma, and leukemia. C. Treatment (see Chapters 2 and 28). 1 . Initial treatment is pericardiocentesis performed under echocardio­ graphic guidance. a. After pericardiocentesis alone, fluid reaccumulates in as many as 60% of cases. 2. Measures to prevent reaccumulation. a. Prolonged drainage through intrapericardial catheter with or without intrapericardial instillation of sclerosing agents (e.g., bleomycin 30 to 60 units) . b. Surgical management (e.g., pericardia! window) . 3. Systemic antirumor treatment for chemotherapy-responsive cancers (e.g., breast cancer, lymphoma) . 4. RT is useful in a few selected cases. SUGG ESTED R EA D I NGS

Cairo MS, Bishop M. Tumour lysis syndrome: new therapeutic strategies and classification. Br j Haematol 2004; 1 27:3. The authors delineate a system for classifjiing and grading the severity ofclinical and laboratory TLS. Cairo MS, Coiffier B, Reiter A, et al. Recommendations for the evaluation of risk and prophylaxis of tumour lysis syndrome (TLS) in adults and children with malignant disease: an expert TLS panel consensus. Br j Haematol 20 1 O ; 1 49:578. Evidence-based guidelines for risk assessment, prevention, and treatment of TLS. Cole JS, Patchell RA. Metastatic epidural spinal cord compression. Lancet Neurol 2008;7:459. This is an excellent summary ofpathophysiology, presentation, and diagnostic approach to and treatment ofESCC. Fisher CG, DePaola CP, Ryken TC, et al. A novel classification system for spinal instability in neoplastic disease: an evidence-based approach and expert consensus from the Spine Oncology Study Group. Spine 20 1 0;35:E l 22 1 . The authors propose a novel classification system fo r spinal instability in neoplastic disease that is based upon location, clinial aspects ofpain relief with position change, lesion quality (lytic, blastic, mixed), presence or absence of vertebral body collapse, radiographic spine alignment, and the posterolateral involvement ofspical elements. A spinal instabil­ ity neoplastic score (SINS) is generated by adding together the indivicual scores; scores indicating indeterminant or unstable spines (1 or higher) warrant surgical consultation. George R, Jeba ], Ramkumar G, et al. Interventions for the treatment of metastatic epidural spinal cord compression in adults. Cochrane Database Syst Rev 2008;CD0067 1 6 . A systematic review ofrandomized controlled trials ofsurgery, radiotherapy, and cortico­ steroids for the management ofESCC in adults. Howard SC, Jones DP, Pui CH. The tumor lysis syndrome. N Engl j Med 20 1 1 ;364: 1 84. A contemporary excellent review ofthe pathophysiology, etiology, risk assessment, manage­ ment, and prevention of TLS.

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LeGrand SB, Leskuski D, Zama I. Narrative review: furosemide for hypercalcemia: an unproven yet common practice. Ann Intern Med 2008; 1 49:259. The use offarosemide in the management ofhypercalcemia of malignancy is supported only by older case reports published before the introduction of bisphosphonates. It should not be considered a standard approach. Patchell RA, Tibbs PA, Regine WF, et al. Direct decompressive surgical resection in the treat­ ment of spinal cord compression caused by metastatic cancer: a randomised trial. Lancet 2005;366:643. This randomized trial demonstrated the superiority ofinitial aggressive surgical resection and postoperative RT compared to RT and salvage surgery, in patients initially present­ ing with ESCC that was not due to lymphoma or an intraspinal tumor. Wilson LO, Detterbeck FC, Yahalom J. Clinical practice. Superior vena cava syndrome with malignant causes. N Engl] Med 2007;3 5 6 : 1 862. The authors provide a succinct review of management strategy for patients with malignancy-associated SVC syndrome. Yu JB, Wilson LO, Detterbeck FC. Superior vena cava syndrome- a proposed classification system and algorithm for management. J Thorac Oncol 2008;3 :8 l I . The authors provide a proposed classification system for the severity ofSVC syndrome and a management algorithm based upon severity and the results of biopsy/tumor staging.

Tox i c o l ogy Lu ke Y i p

I N T R O D U CT I O N

This section focuses on the aspects of acute poisoning that are potentially life threat­ ening or may lead to permanent organ damage and hence require immediate, usually intensive, medical care. This has been organized into a table to facilitate rapid access to concise toxicology information guiding management of acutely poisoned patients. The table is divided into four columns. The first column is alphabetically organized into either a specific agent (e.g., acetaminophen) or a class of agent (e.g., alcohol) with specific toxins (e.g., ethylene glycol, isopropanol, and methanol) ; individual agents appear alphabetically in the index. This is followed by a list of organ systems that can be targeted by the agent or its systemic effects. The second column focuses on action alerts, critical laboratory values, guidelines for clinical intervention, and the dosing of therapeutic drugs, antidotes, or antivenom. The third column lists adjunct therapy and extracorporeal treatments. The fourth column highlights caveats and potential complications. The content of this section is not a substitute for reference textbooks in intensive care medicine or medical toxicology, and does not address envenomations that usually occur outside of the United States. The interested reader is referred to the current edition of Irwin and Rippe 's Intensive Care Medicine textbook and toxicology textbooks (e.g. , Gold.frank s Toxicologic Emergencies and Medical Toxicology) for more detailed information on a given subject.

749

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•t!l:J•::S:I:t!I• Agent Target Orga n Syste m i c Effect Ac eta m i n o p he n

Action A lert Critical Laboratory Va l u e C l i n ical I nte rvention

Adj u nct Thera py

Caveat

Extracorporeal S u pport

Com p l i cation

Se rum A PA P co n ce ntration a b ove "treatment" l i ne on aceta m i no p h e n toxic ity ( R u m ack­ M atthew) n o m ogra m ( Fig. 96- 1 ) : NAC • Ora l : 140 mg/kg followed by 70 mg/kg every 4 h (dil ute 3: 1 with carbonated/fruit beverage for pa lata bil ity) ; ad m i n ister IV a ntiemetic (e.g. , onda nsetron 8 mg; Peds: 0.2 mg/kg, max 8 mg) a n d repeat the sa me oral dose if vom iting occu rs with i n 1 h . OR • IV: 1 50 mg/kg i n 200 m l D5W ove r 1 h fol l owed by 50 mg/ kg i n 500 m l D5W over 4 h fo l l owed by 1 00 m g/kg i n 1 L D5W over 1 6 h (6.25 mg/kg/h ) .

Consider o ra l activated cha rcoa l 1-2 g/kg in a cooperative patient presenting with i n 4 h of ove r­ d ose .

The aceta m i nophen toxicity n o m ogra m is va l i d fol lowi ng an acute si ngle ove rd ose of n o n m o d ified re l ease A PA P occu rring between 4 a n d 2 4 h ; p lots a bove " proba ble" a n d " h igh-risk" l i nes i n d i cate 60% and 90% h e patotoxic ity risk, res pectively.

(APA P l

Acute: GI • H e patotoxi city • FH F N e u rologic • Encep h a l o pathy • Coma and m eta bo l ic acidosis with seru m APAP > 800 µg/m l (5,292 µmol/U 4-1 2 h posti ngestion . GU • O l iguric ren a l fa i l u re 24-48 h with protei n u ri a , m icroscopic hematuria and bac k pa i n ; u s u a l l y p roceeded by h e pa­ totoxic ity ; non-ol igu ric ren a l fa i l u re i s ra re .

NAC thera py may b e ter m i n ated if the patient rem a i n s asym pto­ matic, serum APAP conce ntration below "treatm ent" l i n e , and AST/ ALT rem a i ns i n the la boratory

When to con s i d e r hemodia lysis: Patient who present soon afte r a n ac ute overdose , w h e n N A C not ava i la b le , no other options a re ava i la b le a nd h e m o d i a lysis ca n be exped itiously i n itiate d ; coma and m eta bo l i c acidosis with se r u m APAP >800 µg/m l ( 5 , 292 µmol/U ; te rm i nate when serum A PA P 1 00 s/>6.5, C r >3 . 3 mg/d L (300 µmol/L) , and e n ce p h a l o pathy gra d e �I l l with i n a 24-h period a n d norma l a rteria l pH. U n re l i a b l e t i m e o f i n gestion • Patient with signs a n d sym ptoms consistent with h e patotoxicity : NAC treatment sa m e as a bove; conti n ue NAC treatment (ora l : every 4 h ; IV 6.25 mg/kg/h) u nt i l clear c l i n i­ cal a n d l a bo rato ry evid ence of i m p rove m ent i n patient's cond itio n . If d eteri oration i n c l i n ical a n d la bo rato ry status, consider pa ra m ete rs for refe r­ ra l to l iver u n it/I C U o r O LT. • Asym ptomatic patient with serum APA P concentration 96 h . • >40 mg/L ( 1 70 µmol/U i n c reased risk for coma, se izures, res p i ratory fa i l u re , ca rd iac cond uction d efects .

(continued)

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•t!l:J•::S:I:t!I• (continued) Agent Target Orga n Syste m i c Effect

Action Alert Critical Laboratory Va l u e C l i n ical I nte rvention

p rogressive C N S d e p ression , coma ; res pi rato ry de press io n . • C V : Dysrhyth m ias; hypo­ te nsion ; h ea rt fa i l u re ; res pi ratory arrest; asystol e from propylene glycol toxic ity d u ri ng ra pid IV p h e nytoi n a d m i n istration (e.g. , >50 m g/ min). Va l proic acid (VPA) • N e u rologic: D rows i n ess, leth a rgy; confus i o n , d isori­ e ntatio n ; seiz u res; encepha­ l o pathy; cere b ra l ed ema ; o bt u n dation , coma; res p i ra­ to ry fa i l u re . • C V : Ta chyca rd i a ; hypotension . • G I : Pa n c reatiti s ; h e patotoxic ity. • M eta b o l i c : A n i o n ga p m eta b o l i c acidosis; hypera m ­ m o ne m ia ; hypernatre m i a ; hypoca l ce m i a .

Adju nct Thera py

Caveat

Extracorporeal S u pport

Com p l i cation

conce ntration >40 µg/m l, mod e r­ ate neu rologic toxicity, or rising seru m phenyto i n levels fol l owing i n iti a l activated charcoa l d ose, but not i n patients with d e c reased bowe l so u n d s/i l e u s ; d i scon­ ti n u e before d rug leve ls rea ch thera peutic ra nge i n pati e nts on phenyto i n thera py. Com a , sym pto matic hypera m ­ mone m i a , sym ptomatic he pato­ toxicity, or ris i n g seru m a m mon ia leve ls: I V L-ca rn iti n e 1 00 mg/kg ( m a x 6 g) over 30 m i n fol l owed by 15 mg/kg eve ry 4 h over 1 0-30 m i n u nt i l c l i n ical i m p rove­ m e nt; consider treatment fo r patients with seru m V PA >450 µg/m l. Acute V PA ove rd ose with out h e patic enzyme a bnorma l ities o r hypera m m o n e m i a : Consider o ra l

G I deconta m i nation consi deration (afte r patient sta b i l ized and p re­ ca utiona ry m easu res to m i n i m ize a spiratio n ) : Gastric lavage ( See Box 96- 1 ) in ac ute ly sick patients fol l owed by activated cha rcoa l (ora l/n asogastric) 1 -2 g/kg; W B I (See B ox 96-2) fo r la rge i ngestion of mod ified re lease for m u lation; proced u ra l rem ova l of bezoa r/concretio n . Consider h e m o d i a lysis when coma, hemodyna m ic insta b i l ity,

R i s k stratification based on

peak serum VPA conce ntration :

• De layed pea k conce ntration may be >10 h postingestio n . • >450 µg/m l m od erate-to­ maj o r outcom e . • >850 µg/m l hypotensio n , com a , respi ratory depress ion , aspirati o n , m eta bo l ic acidosis.

H e m od ia lysis and CAVH/CWH a re n ot e q u iva lent, a n d th ey a re

• H e m atologic: T h rom bocytope n i a ; le u ko pe n i a .

L-carnitine 100 m g/kg/d ( max 3 g ) d ivided eve ry 6 h .

ra pid d eteriorati o n , h epatic dysfu n ction , m eta b o l i c acidosis u n responsive to fl u i ds, seru m VPA > l ,000 µg/m l; ter m i nate when ser u m VPA is i n the therapeutic ra nge .

not m utu a l l y exclus ive; CAVH/ CVVH may be the o n ly o ption i n hypote n s ive patie nts u nt i l hemod ia lysis can be tolerated .

ECG ( m ax i m a l l i m b- lead ) Q R S 1 20 m s : See B B . Hypodyna m i c myoca rd i u m • See B B . • I V calci u m gl u conate ( 1 0 % ) 0 . 6 m Ukg bolus (0.2 m l/kg 1 0% ca lci u m c h loride) over 5-1 0 m i n fo l lowed by cont i n u ­ ous ca lci u m g l u conate i nfusion

Ac i d e m i a worsens myoca rd ia l dysfu nction .

Extraord i na ry measu res : See B B . Ca lci u m treatment: M ixed c l i n i­ cal experience (d isa p pointing at times) , p ri ma r i ly i n otropic effect; gluconate safest .

at 0 .6-1 . 5 m l/kg/h (0.2-0 . 5 m Ukg/h 1 0 % ca lcium ch loride); titrate i n fusion to affect i m p roved b l ood pressu re/con­ tracti l ity ; fol l ow ion ized calci u m l eve ls eve ry 3 0 m i n i n itia l ly a n d t h e n every 2 h m a i nta i n i ng ion­ ized calci u m twice norma l .

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C a r d i oactive ste ro i d (e.g . , d igoxi n , d igitoxi n , olea nd er, a n d b ufo tox i n ) D igox i n • G e n e ra l : N a usea, vo m iting; fatigue. • CV: Va riety of dysrhyt h m ias; atri a l tachyca rd ia with va ri a b l e atrioventri c u l a r (AV) block ( pa roxys m a l atria l tachyca rdia 2 : 1 b lock) , accelerated j u nction a l rhyth m ( regularized atri a l fi bri l latio n ) , and fasc i c u la r tachyca rd ia h ig h ly suggestive and bid i rectiona l ventricu l a r tachyca rd ia ( i . e . , narrow-co m p l ex tachycard i a with right b u n d le b ranch morphology) h i g h ly s pecific for d igita lis toxicity.

Sym ptomatic patie nts, ca rd iac dysrhyth m ias that th reaten o r res u lt i n h e m odyna m i c com­ prom ise, se r u m pota ss i u m >5.0 m mol/L, serum d igoxi n con­ centration > 1 0 . 0 ng/m l ( 1 2 . 8 n m ol/U 6 h afte r ove rd ose o r > 1 5 ng/m l ( 1 9 . 2 n m o l/L) a t a ny ti m e : IV d igoxi n-specific a nti body fragments ( e . g . , D igi b i n d ® or Digi Fa b® ) : • F r o m d ose i n gested : O n e via l (40 m g ) b i n d s 0.6 mg of d igox i n ; for exa m pl e : I n gestion of 3 mg of d igoxi n ( bioava i l ­ a bi l ity 8 0 % (0.8]) req u i res fou r vials. • From serum d igoxi n concen­ tratio n , See B ox 96-3 .

G I deconta m i nation consid­ erations (afte r patient sta b i l ized a n d preca utionary m easu res to m i n i m ize a spiration ) : Activated c h a rcoa l ( o ra l/nasogastric) 1-2 g/ kg fo l lowed by hou rly, every 2 h , or every 4 h at a dose e q u iva lent to 12.5 g/h ( Peds: 1 0-2 5 g) for 1 2-24 h; n ot in patie nts with decrea sed bowel sou nds/ileus.

Ch ron ic d igoxi n toxi city: S i m i la r t o acute toxic ity and ha l l uci na­ tions, visu a l d i stu r ba nces such as cloudy or b l u rred vision, loss of visio n , a n d yel low-green ha los o r eve ryt h i ng a p pearing wa shed i n yel low (xa nthopsia); normo- o r hypo ka l e m i a is more co m mo n in patients with h ea rt d i sease. P red isposition to toxicity: H y poka l e m ia , hypomagne­ sem i a , a n d hyperca l c e m i a , re n a l d ysfu nction . Seru m d igox i n l eve ls m ost re l i­ a b ly correlate with toxic ity when obta i ned �6 h after d igox i n ad m i n istratio n . (continued)

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•t!l:J•::S:I:t!I• (continued) Agent Target Orga n Syste m i c Effect

Action Alert Critical Laboratory Va l u e C l i n ical I nte rvention

• C N S : Headache; wea kness; d izz i n ess; confusi o n ; syn­ cope; co m a .

• B y titratio n : Ad m i n iste r fou r to six vials a nd repeat d e pe n d i ng on c l i n ica l effect. If digoxin-specific an tibody frag­ ments una vailable, tem pora ry tra n svenous card iac pac i ng; IV magnes i u m su lfate 2.5 g ( 1 0 m mol) ove r 5 m i n fo r ventric u l a r ta chydysrhyt h m ias, repeat a s need e d . Acute a 1 lergic reactio n t o d igoxi n­ specific a nti body fragm e nts: Stop i nfus i o n ; treat accord i ng to c u rrent g u i d e l i nes.

Adju nct Thera py

Caveat

Extracorporeal S u pport

Com p l i cation

N atu ra l ly occ u rring card ioac­ tive ste roids fro m p l a nts a n d a n i ma l s ca n cross-react with the d igox i n assay; d egree of c ross-reactivity is u n known a n d no good correlation between ser u m l eve ls a n d toxicity. A fa lse- positive d igoxin assay ( 7 % H F; m i n i ma l ly sym ptomatic pati ents may ra pid ly progress to CV co l l a pse .

Ora l ca lc i u m - o r magnesi u m ­ conta i n i ng a nta cids 30--60 m l. H istory suggestive of a su bsta n­ tive exposu re that may lead to system ic toxic ity : • IV calc i u m ch loride 1 g over 30 m i n ; patients with norm a l

Resuscitation from card iac arrest fo l l owing system ic fluoride tox ic ity is ra re; focu s o n early i ntervention t o p revent ca r­ d iac dysrhyth m ias a n d arrest.

A l l patie nts shou l d be a d m itted to an I C U fol l owing a d e l i be rate H F i ngestion .

vita l signs and rem a i n sta ble should be m o n itored with seru m ca l c i u m levels every 30 m i n for t h e fi rst 2-3 h ; IV calci u m ch loride 1 g bol uses to m a i nta i n ser u m ca lci u m con centration in the h igh normal l a boratory reference ra nge; re peat as n eed ed ; a fa l l i n seru m ca lci u m concentration below the normal ra nge, dysrhyth m ias, or a fa l l in b lood pressu re is treated with IV ca l c i u m c h loride 2-3 g boluses every 15 m i n . OR • I V magnesi u m su lfate 2-6 g over 30 m i n fo l lowed by a n i nfu­ sion 1-4 g/h ; a d d itional mag­ n esi u m boluses as ind icated by ca refu l c l i n ical assess ments a n d la boratory investigations.

..... co "'

lsoniazid ( I N H ) • D izzi ness, s l u rred speec h , blu rred vis io n , a n d visua l h a l l u c i n ations (e.g . , bright colors, spots, stra nge designs); stu por and coma ca n ra pid ly d evelop, fol l owed by i ntra cta ble ton i c-clon ic

Fi rst sign of neu rotoxicity: I V d iazepa m or eq u ivalent a n d pyri­ d ox i n e in m i l l igra m d oses eq u a l t o t h e a m o u nt o f I N H i ngested o r 5 g i n ca ses o f u n known a m o u nt of i n gestion ad m i n istered over 30-60 m i n .

G I deconta m i nation consi deration (afte r patient sta b i l ized and p re­ ca utiona ry m easu res to m i n i m ize aspi ratio n ) : Gastric lavage ( See Box 96- 1 ) fo r acute ly i l l patients fol l owed by activated cha rcoa l (continued)

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�

''ilUflf1

(continued)

Agent Target Orga n Syste m i c Effect

Action Alert Critical Laboratory Va l u e C l i n ical I nte rvention

Adju nct Thera py

Caveat

Extracorporeal S u pport

Com p l i cation

genera l ized or loca l ized seizu res, hyperreflexia, or a refl exia; CV and res pi ratory colla pse . • M eta b o l i c : Severe m eta bol ic a c i d osis, hyperglyce m i a , keto n u ri a , and hyperka l e m ia . • Triad : M eta bo l i c acidosis refractory to sod i u m bicar­ bon ate thera py, seizu res refractory to a nticonvu lsa nts a nd coma .

Se izing patie nts: IV d iazepam or eq u iva lent and pyridox i n e ( m i l ­ ligra m d oses eq u a l to the a m o u n t o f I N H i ngested or 5 g i n cases of u n known a m o u nt of i n gestio n ) at 500 m g/m i n u nt i l seizu res te rm i n ate a n d re m a i nd e r of d ose infused over n ext few h o u rs; re peat pyridox i n e d ose if seizu res pers ist or rec u r.

{ 1 -2 g/kg) ; o ra l activated cha r­ coa l fo r asym pto matic patie nts.

Seizu res refra cto ry to d iazepam and pyri doxi ne: I nd u ce th iopenta l com a .

Local a n esth et i c

B u p ivaca i n e • C V : Red uctions i n card iac output wh i l e b lood press u re is m a i nta i n e d ; b radyc a rd ia , atria- a nd i ntraven ­ tric u l a r b locks, ventric u l a r dysrhyt h m ias; CV col la pse often refractory to treatment.

C l i n ical bu piva ca i n e toxicity: • C u rrent ACLS g u i d e l i nes. AN D • IV l i pi d e m u lsion (e.g. , l ntra l i pid ®, Liposyn 1 1 1 ® 2 0 % ) 1 m Ukg over 1 m i n ; repeat twice more at 3-5-m i n i nter­ va ls; then (or sooner if sta b i l ity is resto red ) convert to a n

La boratory data and accu­ m u lati ng c l i n ical expe rience with l i p id e m u lsion th era py i n b u p iva ca i n e , levo b u p ivaca i n e , m e pivaca i n e , p ri l oca i n e , a n d rop ivaca i n e toxicity su ggest early Ii pid thera py to atten uate progression of l oca l a nesthetic toxic syn d ro m e .

i nfu sion at a rate of 0.25 m U kg/m i n u n ti l hemodyna m i c recovery ( > 8 m Ukg is u n l i kely to be usefu l ) . OR • I V l i pid e m u lsion (e .g. , l ntra l i pid® 20% ) 1 00 m l followed by a n i nfusion 0 . 5 m Ukg/m i n .

B u p iva ca i ne: M o re ca rd i otoxic than m ost oth er loca l a nesthet­ ics (e.g. , l i d oca i ne, ropivaca i ne, levo b u pivac a i n e ) ; ea r l i est signs of card iac toxicity a re prolonged Q RS/QTc .

R efracto ry card iac a rrest : Card io p u l m o n a ry bypass .

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Lidoca i n e • N e u rologi c : N u m b ness o f t h e to ngue, l ight h eaded ness , visual/a u d itory d i stu rba nces, m us c u l a r twitc h i ng , u n con­ sc iousness, seizu res, coma , res p i rato ry d e p ression/ a p nea. • CV: Hy pertension a nd tachy­ card ia ( m i ld i ntoxicati o n ) progressi ng t o b ra dycard i a , hypotension , s i n us a rrest, hea rt blocks, i ntrave ntri c u l a r con d u ction defects (e.g. , p ro­ lo nged QRS), ventric u l a r dys­ rhyth m ias (e . g . , ventricu la r fi b r i l latio n ) , circulato ry col l a pse , asystole .

C l i n ical l oca l a n esthetic toxic ity : C u rre nt ACLS g u i d el i nes a nd consider IV l i p id e m u lsion thera py (See B u pivaca i n e) a nd card i o p u l m o na ry bypass fo r refractory ca rd iac a r rest.

Lid oca i n e toxic ity : Dose relate d ; neu rotox ic ma n ifestations before potentia l l y card iotox ic levels a re reached . A m i d e l oca l a n esth etics may act as oxid izing agents a n d lead to m eth emoglo b i n e m ia in toxi c doses.

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M eta ls

Arse n i c (As) • Respi ratory: P u l m o n a ry ed e m a . • C V : Prolo nged QTc a n d po lymorphic ventri c u l a r ta chycard ias (e.g. , torsad es de poi ntes ) . • G I : Abdom i n a l pa i n , p rofuse watery stoo ls, h e m o rrhagic gastroenteritis ( hypovo l e m ia shock). • N e u ro logi c : Confusi o n , d e l i r i u m , co nvu lsions, e n ce p h a l o pathy, a n d co m a ; po lyneu ropathy (e .g. , severe pa infu l bu rn i ng sensation i n soles of feet, asce n d i n g wea k n ess a n d pa ra lysis with n e u ro m u sc u l a r res p i rato ry fa i l u re ) . • H e m ato l ogic: Reve rs i b l e bo ne marrow de pression with pa ncyto pe n ia ( pa rtic u larly

Dys rhyt h m ias: C u rrent ACLS g u i d e l i nes a nd avoid c lass IA/I C a n tidysrhyth m ics; l i m ited success with lidoca i n e , m agnes i u m , a n d iso p roterenol i n m a n agement of a rse n ic- i n d uced torsa des d e po intes; tra n svenous pace m a ker fo r overd rive pacing. Sus pected acute sym pto m atic As poiso n i ng: IM B A L 3-5 m g! kg eve ry 4 h , gra d u a l ly ta peri n g to every 1 2 h ove r seve ra l days; switch ed to D M SA 10 mg/ kg eve ry 8 h for 5 d , red u ced to eve ry 12 h for a noth er 2 wk; a d d iti onal cou rse of treatment may be co nsidered based on posttreatment resu lts : 24-h u r i n a ry. As exc retion is fo l lowed befo re , d u ri ng, a n d after chela­ tion with conti n u ed c helation thera py u nt i l the u r i n a ry As excretion 1 00 µg/m l.

Sinus tachycard ia, supraventric u lar ta chya rrhyth m ias, ve ntricu la r i rrita b i l ity: IV propranolol 1-3 mg a n d then 1 mg every 5-1 0 m i n (Peds: 0 .02 mg/kg, not t o exceed ad u lt dose) u nti l dysrhyt h m ias correcte d ; potentia I haza rd is bronchospasm ; I V es molol 500 µg/kg ove r 1 m i n fol l owed by 25-200 µg/kg/m i n i nfusion; con­ sider I V adenosi n e 6 mg, esca late

GI deconta m i nation consi deration (afte r patient sta b i l ized a n d pre­ ca utiona ry m easu res to m i n i m ize aspi ratio n ) : • W B I (See Box 96-2 ) fo r l a rge i ngestion of mod ified release fo r m u lation . • Proced u ra l rem ova l of bezoa r/ co n c retion . • Activated charcoa l 1-2 g! kg followed by hou rly, eve ry 2 h , or every 4 h at a d ose eq u iva lent to 12.5 g/h ( Peds: 1 0-25 g) u ntil seru m theophyl­ l i n e < 1 5 µg/m l; a lternatively,

Life-th reate n i ng events assoc i­ ated with serum concentrations > 1 00 µg/m l; se izu res have occu rred at 50 µg!m l; d eath has been re ported at 80 µg/m l; 385 µg/m l has been assoc iated with su rviva l .

Alteration i n theophyl l i n e clea r­ a n c e : CY P 1 A2 a n d CYP 3A4 i n h i b ito rs (e.g. , eryth romyc i n , cla rith romyc i n , c i p rofl oxa c i n , c i m etid i n e ) , heart fa i l u re, l iver d i sease decrease c l ea ra n ce; ba r bitu rates, ca rba maze p i n e a n d po lya romatic hyd rocarbons of ciga rette s m o ke, hyperthy­ roi d i s m , cystic fi brosis i ncrease clearance. R is k stratification • Acute toxicity: Seru m theophyl l i n e 20-40 µg!m l: (continued)

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Action Alert Critical Laboratory Va l u e C l i n ical I nte rvention

• M eta b o l i c : m eta bo l i c acido­ sis; hypoka l e m i a , hypergly­ cem ia , hypo phosphate m ia , hypomagnese m ia , hyperca l­ cem ia .

to 12 mg ( Ped s: 50- 1 00 m g/kg a n d i n crease by 40 mg/kg i n cre­ ments, not to exceed a d u lt d ose) if needed . Ve ntri c u l a r i rrita b i l ity with he modyna m ic com p ro m ise: IV l i d oca i n e 1 . 5 m g/kg at 50 mg/ m i n fo l l owed by infusion 2-4 m g/ m i n ( Peds: 1 m g/kg over 2 m i n fo l l owed b y i nfusion 1 5-50 µg/kg/ m i n ) ; pu lseless ventri c u l a r tachy­ ca rd ia o r fibri l lati o n : IV a m iod a r­ o n e 5 m g/kg ove r 5 m i n . Hypotension with a wide pu lse pressu re : IV crysta lloid bol us, propra nol ol , va so p ressor ( e . g . , phenyle ph ri n e , n orepi neph ri ne ) . Se iz u res: I V B Z D , progress to th iopental or pento barbita l , a n d n e u ro m us c u l a r blockade a n d general a n esthes ia .

Adju nct Thera py

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Extracorporeal S u pport

Com p l i cation

0.25-0.5 g/kg/h via contin uous nasogastric i nfusi o n ; not i n patients w i t h decreased bowel sou nds/i leus. H e m od ia lysis consideration : • Befo re the o nset of l ife-th reat­ e n i n g events, h e m od yn a m i c i nsta bi l ity or re peated seizu res. • Acute i ntoxication and se ru m theophyl l i n e >80 µg/m l. • Patients 60 y with c h ro n ic overmed ication a n d seru m theo phyl l i n e >30 µg/ml. • Patient with m od erate toxicity a n d u nable to tolerate activated c h a rcoa l thera py. Exc h a nge tra nsfu sion u sed suc­ cessfu l ly i n n eonates with severe toxic ity.

na usea, vom iting, tachyca rd ia ; 40-70 µg/m l: pre matu re ventricular contractions, agitatio n , tre m ors; >80 µg/ ml: card iac dysrhyth m ias, i ntracta ble seizures. • C h ro n i c overmed ication : Neonates or e l d e rly patie nts (e.g. , >75 y) with u n d e rlyi ng ca rd iac d i sease a n d/or ta ke med ications that i n h i bit theophyl l i n e m eta b o l i s m ; no correlation betwee n se r u m theo phyl l i ne con­ ce ntration a n d a p pea ra nce of l ife-th reate n i ng eve nts (e.g. , severe i n toxication at steady-state seru m theophyl­ l i n e concentrations as l ow as 20-30 µg/m l a n d seizu res as Iow as 17 µg/ml ). • Ac ute-on-thera pe utic theophyl l i n e toxicity : Seru m

theophyl l i n e concentrations >60 µg!m L: l ife-th reate n i ng events . H y poka l e m ia p red o m i n a ntly res u lts as i ntrace l l u la r pota s­ s i u m s h ift with m i n i ma l tota l body potassi u m loss. H e m od ia lysis and CAVH/CVVH a re n ot e q u iva lent, a n d t h ey a re not m utu a l ly exc l u s ive; CAVH/ CVVT may be the o n ly opti o n i n hypote n s ive patie nts u nt i l he m od ia lysis can be tolerated . NSAID

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As pirin (acetylsal icyl ic ac i d , ASA) • M eta b o l i c : R es p i rato ry a l ka losis ( hyperpn ea/tac hyp­ nea), res p i rato ry a l ka losis/ m eta bol ic acid osis/acid u ria , m eta bol ic acid osis/res pi ratory acid os is/acid u ri a ; a n io n ga p m eta bolic acidosis; hypoka­ l e m i a ; hyperth e r m i a . • Res pi ratory: Respi ratory i n sufficiency/fa i l u re; acute l u ng i nj u ry/n oncard iogenic p u l m o nary edem a .

Signs a n d sym ptoms consistent with sa l i cy late toxicity, seru m ASA >30 m g/d l (2 . 1 7 m m o l/L) afte r acute overd ose: • F l u i d resusc itation . AN D • U ri n e a l ka l i n ization : I V sod i u m bicarbonate 2 m m ol/kg bol u s fol l owed b y conti n uous i nfusion of sod i u m bicarbonate 1 50 m m ol m ixed i n 1 , 000 m l D5W sta rti ng at 1 . 5-2 .0 times the m a i ntena nce rate , titrate to

Maxi m ize G F R : IV NS ta rget u r i n e output 2-4 m Ukg/h; I V fl u i d s shou ld conta i n a t least 5 0 g/L ( 5 % ) g l u cose , m i n i m u m 1 00 g/L ( 1 0% ) g l u cose when hypoglyce­ m ia/C N S sym pto m s a re evident . G I deconta m ination consideration (after patient stabil ized and pre­ cautiona ry m easu res to m i n i m ize aspiration ) : Gastric lavage (See Box 96- 1 ) fol lowed by oral activated charcoal 0-2 g/kg) fol lowi ng

Done nomogra m not u sefu l ; ca r bo n i c a n hyd rase i n h i bitors (e.g. , acetazo l a m ide) contra i n ­ d i cate d ; delayed onset a n d progressio n o f toxicity with enteri c-coated/su sta i ned-release ta blets; nonacute/c h ronic i ntoxi­ cation masq uerad e as S I RS, ac ute a bd o m e n , ACS/A M I , ence pha lopathy/e nee pha I it is, a l cohol intoxication/withd rawa l , orga n i c psychosis, sepsis, dementia or d e l i r i u m , O KA . (continued)

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• N e u rologic: Agitati o n ; s l u r red speec h ; a lte red menta l status; h a l l u c i nations; encepha lopathy; seizures; coma .

m a i nta i n u r i n a ry p H 8.0 a n d a rte ria l p H < 7 .55; assess c l i n i­ cal status/la bo ratory pa ra m eters (e.g . , electro lytes, acid-base, u rine p H ) hourly; te rm inate when clear c l i n i ca l-bioc h e m i ­ cal recovery a n d seria l decl i n e i n seru m A S A conce ntration towa rd thera peutic ra nge. AN D • Potassi u m re p lacement/su pplement.

serious overd ose; otherwise , ora l activated cha rcoa l ; W B I (See B ox 96-2) for large ingestion of m od ified release form ulation ; endosco pic rem oval of bezoar/con cretion.

U ri n e a l ka l i n ization : N ot a s u bstitute for hemodia lysis; success i n patients treated early i n the cou rse of poison i n g a n d n o t severe ly toxic/acidotic ; contra i n d icatio n : severe ASA toxicity, re na l/heart fa i l u re, cerebral/p u l m o n a ry edema, a rterial pH >7. 55; co m pl ication : hypoka le m ia , hypoca lcem i a , fl u i d/sod i u m overload , pu l mo­ n a ry ed e m a , teta ny.

Respi ratory i n sufficiency/fa i l u re : Adj ust venti lator m i n ute vo l u me to ma i nta i n PC0 2 to at least patient's prei ntu bation PC0 2 a nd a rra n ge for u rgent h e m od ia lys i s . P u l mona ry ede m a : M a n age ment same as ac ute l u ng i nj u ry/A R DS , a n d a rrange for u rgent h e m od i ­ a lysis. Hype rtherm i a : Exte r n a l coo l ing.

Consider h e m o d i a lysis when se r u m sa l i cy late >90 m g/d l ( 6 . 52 m m ol/U , n eed fo r e n d otrac heal i nt u batio n , c h ro n i c sa l i cy l is m , pe rs i stent acid u ri a , c l i n ical dete­ riorati o n , a lte red menta l status, patie nts with com orbid ities (e.g . , heart fa i l u re, chronic o bstru ctio n pu l mona ry d isease) , p u l m o nary ed e m a , pe rsistent acide m i a , pe rs i stent hy pote n s io n , coagu­ l opathy, rena l/h epatic dysfu n c­ tio n , extremes of age , seizu res; urgent hemodialysis i n patients need i n g endotrach ea l i ntu bati o n , with c h ro n i c sa l i cylate toxicity, a ltered m e nta l status, persiste nt a c i d e m i a , co morbid ities, e l d e rly patients.

H e m od ia lysis a n d CAVH/CWH a re n ot e q u iva lent, a n d th ey a re not m utu a l ly exclus ive; CAVH/ CVVH may be the o n ly o ption i n hypote n s ive patie nts u nt i l h e m od ia lysis can be tolerated .

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Oth e r N SA I D I bu p rofe n • M eta b o l i c acidosis, A R DS, re nal fa i l u re , com a , se izures, GI b l eed ing, c h o l estasis, he patotoxicity, t h rom bocyto­ pe n i a , hypotherm i a , shock; m e n i n goencephal itis (aseptic m e n i n gitis) with th era peutic dosi ng.

S u p po rtive care.

M efe n a m i c acid • M uscle twitch i ng, ton ic-clonic seiz u res, a pnea , coma , ca r­ d iac a rrest .

S u p po rtive care.

P h enyl b utazone • G I : Predominately latent he patotoxicity ( 1 2-24 h ) , a n d m a y be o n ly m a n ifestation of severe toxicity. • G U : R ed u ri n e ( py razo lone m eta bol ite : ru bazo n i c acid ) may be observed . • C N S : Progress ive i m pa i rment of consciousness with co ma a n d seizu res . • S u d d e n respi ratory a rrest fol ­ lowed b y card iac a rrest.

S u p po rtive care.

Adj u nct h e m operfusion with u n coated a m berl ite XAD-4 res i n i n cases with a poo r prognosis.

P h e n y l b utazone was with d rawn fro m the U . S. market 1970s, sti l l ava i la b le from vete ri n a ry sou rces a n d oth e r cou ntries.

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Opioid

Genera l : Coma, m i osis, res p i ra ­ to ry d e p ress i o n , decreased G I m otil ity. • Dextrom eth orph a n : Se roto n i n syn d ro m e from M A O I i nter­ actio n ; long-te rm use may res ult i n b ro m ide toxicity. • D i phe noxylate : Recu rrent res pi ratory/C N S d e p ress io n . • Fenta ny l : R a p i d IV a d m i n­ istration may resu lt i n ac ute myoclonic trunca l/chest wa l l rigid ity i m pa i ring res p i rati o n . • H eroi n : N o n cardioge n i c p u l m o n a ry ed ema , card iac con d uction a b normal ities/ dys r hyt h m ias; i n h a lation of h eated hero i n va pars ( i . e . , "chasi ng the d rago n " ) assoc iated with progress ive spongiform leu koencepha­ lo pathy.

Res p i ratory d e p ress io n/fa i l u re: IV naloxone 0 . 04-0 . 1 mg if opioid dependent, othe rwise 2 mg; 1 0-20 mg may be req u i red fo r h igh- poten cy opioids ( e . g . , methad o n e , pentazoc i n e , propoxy p h e n e , d i ph e n oxylate ) ; repeat I V na loxo n e bol uses m a y be req u i red every 20-60 m i n . Thera peutic I V n a l oxo ne infus i o n : M u lti ply t h e effective n a l oxo n e bo l u s dose b y 6 . 6 , a d d i n g that q ua ntity to 1 , 000 m l N S , i nfuse so l ution at 1 00 m Uh , titrated to m a i nta i n adeq uate s po n ta neous ve nti lation without prec i p itating opioid withd rawa l ; e m p i ri ca l ly conti n ued for 1 2-24 h a n d ca refu l ly observed fo r 2-4 h fo r rec u rrent resp i rato ry d e p ression after d isconti n u i ng n a l oxone

N a loxo n e : Goal is to reesta b l i s h a deq uate s ponta neous ve ntila­ tion; intra l i ngua l/e n dotracheal/ i ntraosseous ad m i n istration acce pta b l e if no i m med iate IV access ; I M/SC l ess des i ra ble in u rgent situation . D i ph e n oxylate : For m u lated with atro p i n e ( Lomoti l®) ; dec reased G I m otil ity and d ife nox i n ( m eta bol ite) acc u m u lati o n , a potent o p i o i d with a long ha If- l ife . Heroin may be "cut" with a m pheta m i ne, coca ine ( "speed ba l l " ) , sco pola m i n e, a n d naloxone thera py m a y " u n mask" sym pathom i m etic or anticholin­ ergic toxicity. P ropoxy p h e n e : Ava i l a b le a l o n e or in com b i n ation with

• M eperid i n e : Seizu res from normeperi d i n e ( m eta bol ite) acc u m u lation (e . g . , re n a l i m pa i rment) ; acute pa rkinson ism fo l lowi ng con­ ta m i nated ana l og M P P P use; fata l i nte ra ction with MAOI (seroton i n syn d rom e ) . • M etha done: Exceptiona l ly prolonged d u ration of action (ave rage ha lf- l ife 2 5 h , may be 52 h d u ri ng long-term thera py) ; aa ssoc iation between h igh d a i ly metha­ done d ose ( mea n 397 ± 283 mg) a n d torsades de poi ntes ( m e a n QTc 6 1 5 ± 7 7 ms) . • Propoxy p h e n e : R a pid ly progress ive ca rd iac dys rhyth m ias, c i rc u l atory col l a pse, seizu res, respi ratory a r rest. • Tra m a d o l : Seizu res; se roto n i n syn d ro m e .

i nfusi o n ; a l low n a l oxo n e to a bate in acute iatroge n i c o p i oi d withd rawa l . Spongiform leu koence p h a l opa­ thy: S u p portive; coenzym e Q 30 mg q i d , vita m i n E 2 , 000 mg every d, a nd vita m i n C 2 , 000 m g every d have been advocated .

aceta m i n ophen or ASA; withd rawn fro m the US m a rket at the req u est of the US Food a n d Drug Ad m i n istration ( 1 9 N ove m ber 20 1 0) . Co m p l ications i nc l u d e rhab­ domyo lys is, hyperka l e m i a , myoglo bi n u ri a , re n a l fa i l u re .

Seizu res : C u rrent g u i d e l i nes; adj u nct na loxo n e thera py may be effective i n propoxy p h e n e , but n o t meperi d i ne o r tra madol se iz u res; reported i m med iate ly fo l l owing n a l oxone a d m i n istration fo r tra madol ove rd ose. Seroto n i n synd ro m e : See Antid e­ pressa nts .

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Action Alert Critical Laboratory Va l u e C l i n ic a l I nte rvention

Adj u nct Thera py

Caveat

Extracorporeal S u pport

Com p l i cation

S u p portive care.

Preve nt seco n d a ry conta m i nation and poison i n g with a pp ro priate preca ution a ry measu res.

A stron g suspicion of a l u m i n u m p h os p h i d e poison i n g when vom itus has typica I rotten fish odor. Si lver n itrate test o n stoma ch co nte nts ( 5 m l) m ixed with 15 ml water p laced in a flask, rou nd stri p of fi lte r pa pe r i m pregnated with s i lver n itrate (0. 1 N) is p laced on the m o uth of flask and is heated to 50°C for 1 5-20 m i n , fi lte r paper stri p is then d ried ; p h os p h i ne's presen ce blackens s i lver n itrate pa pe r.

Pesti c i d e s

Al u m i n u m phosp h i d e I ngestion • G I : Retrosternal b u rn i ng, epigastric d iscomfort; recu r­ rent profuse vom iting; watery d ia rrhea ; G I bleed ; jaund ice with a bnormal l iver fu nction tests . • CV: Hypotension with clear menta l status; shoc k (heart rate ina ppropriately slow for degree shock); myoca rd ia l i nj u ry; dysrhythm ias, i ntraven­ tric u l a r con d u ction d i stur­ bances; global left ventricular a nd i nterventricu l a r septum hypokinesia with decreased ejection fractio n ; perica rd itis ( ra re). • Respi ratory: Tac hypnea; A R DS. • M eta b o l i c : M eta bo l ic acidosis; hypomagnese m i a ; hyperka l e m i a .

I V hyd rocortisone 400 mg every 4-6 h o r I V d exa methaso n e 4 mg eve ry 4 h, IV H 2 rece pto r antago­ n i st (e .g. , ra n iti d i n e ) , I V p roto n pu m p i n h i bitor (e.g. , o m e p razole) have been advocated . Ca rd iac dysrhyth m ias or hypomagnesem i a : I V magnesi u m 1-6 g over 30 m i n fo l lowed by i nfusion 0. 5-2 g/h has bee n ad vocated .

GI d econta m i nation considera­ tion (after patient sta b i l ized a n d preca utiona ry measures to m i n i m ize as p i rati o n ) : Gastric lavage (See B ox 96- 1 ) with a solution of 1 : 5 ,000 pota ss i u m perma nga nate ( re m ove a n d ox id ize u n a bsorbed a l u m i n u m p h os p h i d e ) ; nasa l gastric 2 % bica rbonate solution ( m i n i m ize p h os p h i n e release ) .

I ns uffic ient c l i n ical ev idence to m a n date ste roid a n d magne­ si u m thera py. Toxic ity ca n occ u r as a res u lt of i n ha lation of phosp h i ne gas rel ea sed when p h os p h i d e contacts water.

Anti coag u l a nt (e.g. , wa rfa r i n , su pe rwa rfa ri n ) • Cuta neous bleed i ng, soft tiss u e ecchymosis; gi ngiva l bleed i ng; e p i staxis; h e matu ria; men orrhagia ; h e m o ptysis; G I , perito n ea l , d iffuse a lveola r, I C H .

Patie nts with or s u spected major a nticoag u l a nt-rel ated hemorrhage or I N R >20 • IV p roth ro m b i n com p lex conce ntrate ( PCC) 50 U/kg or IV fresh froze n plasma ( F FP) 1 0-20 m Ukg o r I V reco m b i na n t activated fa ctor V I I ( r FV l l a ) 1 5-90 µg/kg . AN D • IV vita m i n K1 1 0 mg ( d i l uted with 5% d extrose, 0 . 9 % sod i u m c h loride, o r 5 % d extrose i n 0.9% sod i u m c h l o ri d e ; ad m i n istered at ::;1 mg/m i n ; be p re pa re to treat a na phylaxis) or oral/nasogastric vita m i n K1 7 mg/kg/d d ivided every 6 h .

G I deconta m i nation consi deration (afte r patient sta b i l ized a n d p re­ ca utiona ry m easu res to m i n i m ize aspi ratio n ) : Activated c h a rcoa l 1-2 g/kg .

PCC: Contra i n d icated i n d is­ sem i nated i ntravasc u l a r coagu­ lation and u n co m pen sated l iver d i sease; ad verse d rug events i nc l u d e t h rom bos is, d isse m i ­ nated i ntravasc u l a r coagu lation , blood-borne path ogens tra n s­ m iss i o n , a l l ergic reactions. r FVI la: U n l i ke l i hood of blood­ borne pathogen tra n s m ission , obviates vo l u me constra i nts of F F P ad m i n istrati o n , red u ces time fo r ad m i n istration a n d ach ieving a deq uate h e m ostasis.

D isconti n u e Vita m i n K1 thera py at an arbitra ry t i m e , o bta i n seria l I N R/PT a n d resta rt vita m i n K1 when I N R/PT is e l evated or m o n i ­ to r ser u m fa ctor VI I concentration a n d resta rt vita m i n K1 when a progress ive decrease i n fa ctor VI I leve ls to 30% of normal or serum brod ifacou m con centration < 1 0 ng/m l o r when serum vita m i n K co 0 U1

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Anti coag u l a nt (e.g. , warfa ri n , s u pe rwa rfa r i n ) (con tinued )

2,3-epoxid e co nce ntration begins to fa l l . Patient on wa rfa ri n with excess ive I N R a nd without bleed i ng • I N R 20 .0: I V vita m i n K 1 1 0 mg a n d PCC o r F F P or r FV l l a and re peat vita m i n K 1 d oses every 12 h as need e d .

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M ethyl b ro m id e • N e u ro logic : Vom iting; heada che, ga it d istu rba n ce , ve rtigo, visual d i stu rba nce ( p re m o n itory stage ) ; "Jerki­ ness, " i ntentio nal tre m ors, action m yoc l o n u s, seizu res, d e l i r i u m , ac ute m a n ia (cere b ra l i rritation stage) ; h a l ­ l u c i nations, a pathy, a m nesia, a p hasia, i n coo rd i n ation ( recovery stage, may last yea rs) . • Respiratory: Dyspnea ; bronchi­ tis; pu l m onary ed ema; pneu­ mon itis; respi ratory fa i l u re. • G U : P rote i n u ri a ; h ematuri a ; re nal fa i l u re . • Live r: J a u nd ice; l iver fu nction test a b n o r m a l ities. • S k i n : B u rn s ( u n d e rl i e c loth es a n d gloves where m ethyl bro m i d e gas is tra pped ) .

S u p portive care.

N-3-Pyridyl m ethyl- N' -p­ n itro phenylu rea ( P N U ; Va cor Rat- Ki l le r) • N a usea , vo m iting, abd o m i n a l pa i n , perforation (corrosive

Known or suspected P N U ex pos u re : I V o r I M n iaci n a m ide ( n icoti na m id e) 500 mg fol l owed by 1 00-200 mg every 4 h fo r u p to 48 h , i n c reased to every

R e m ove a l l c loth i ng, was h s k i n with soa p a n d wate r t o el i m i­ nate pote nti a l methyl bro m ide resid ues. Ea rly hemodia lysis assoc iated with i m p rovi ng m o rta l ity.

Seru m brom ide con centration : • Poor s u r rogate fo r m ethyl bro m i d e . • M ay confirm , but d oes not correlate with seve rity of exposu re . • Sign ifica ntly elevated con­ centrations may be seen as a n e l evated c h loride leve l . S pectro photo m etric m eth od may be m o re u sefu l in d etect­ i ng m ethyl brom ide in bio logic flu id matrix.

G I d econta m i nation co nsideration (after patient sta b i l ized , assess i ng G I tract i ntegrity, a n d p recau­ tionary m easu res to m i n i m ize as p i rati o n ) : Gastric lavage ( See

Ad m i n ister n ia c i n as a s u bstitute when n ia c i n a m id e ( n i coti n a m ide) is u nava i l a b le; vasod i latory effects may exacerbate hypote n sive effects (continued)

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effects) ; hypoglyce m i a fo l­ l owed by hype rglycem ia a n d ketoa c i d osis acco m pa n ied by severe postu ra I hypo­ te nsion a nd sensori moto r pe r i p h e ra l a n d a u tono m i c n e u ro path ies.

N, N- D i ethyl - m -to l u a m ide (d i ethyltol u a m ide o r D E ET) • N e u ro logi c : Anxiety; behav­ iora l c h a nges; tre m o rs ; leth a rgy; ataxia; co nfusio n ; seizu res ; co m a . • S ki n : I rritation , contact derma­ titis, u rtica ria; skin necrosis. • I m m u no logic : Ana phylactic reactions with cuta neous a p p l ication .

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2 h if signs of toxic ity d eve l o p , maxi m u m tota l d ose 3 g/d fo r ad u lt ( Ped s: one-h a lf of ad u l t dose) ; when patient a b le t o ta ke ora l m ed i cations 1 00 mg th ree to five ti mes d a i ly for 2 wk.

Box 96- 1 ) i n pati ents presenting soon after a serious i n gestion fol lowed by o ra l/na sogastric acti­ vated c h a rcoa l 1 -2 g/kg pro vided

of P N U , ca uses and exacer­ bates g l u cose i ntolera nce, l ess effective th a n n i aci na m ide; n i a c i na m i d e i n ca psu l e fo rm may be fou nd at n utritio na l s u p p lemen t o utlets .

no clinical evidence of serious caustic effect on the GI tract.

Mon itor seru m glucose closely and treat hypoglycemia with gl ucose su pplementation; man­ age m ent of s u bseq uent hypergly­ cem ia and ketoacidosis sa me as d iabetes mellitus and O KA.

Postural hypotension : Li m ited response to ora l fl ud roco rtisone 0.3 mg/d and elastic stoc k i ngs .

S u p po rtive care. Se iz u res: I V B Z D , progress to ba rbitu rate .

Deconta m i nation considera tio n : Remove a l l cloth ing, and m etic u lously was h s k i n with soa p a n d wate r.

Orga n oc h lorine [e.g. , d ic h l o­ rod i ph e nyl tric h l oroet h ane ( D DT) a n d related agents , hexa c h l o rocyc lohexa nes, the cycl od ienes (e .g. , c h lorda n e , h e pta c h l or, e n d r i n , a l d r i n , a n d d i e l d ri n ) , a nd toxa p h e n esl • G I : Na usea , vom it i n g, a n d d iarrhea , espec i a l l y if petrole u m d i sti l l ate a d d itives/ ve h i cles. • Respi ratory: As piration resu lt­ ing in ta chypnea, res p i ratory d istress, p u l mo n a ry ed e m a ; hypersensitivity p n e u m on itis fo llowing i n ha lation of orga noch lori ne m i xed with pyreth rins. • N e u ro logic: Psyc h om oto r agitation , C N S d e p ress i o n , op isth otonos, s l u rred s peec h , m uscle tre mors, wea k ness; se izu res w ith or with out a prod ro m e a n d may be de layed fo l l owi ng i ngestion or d e rm a l a bsorption . • CV: Ca rd iac d ysrhyt h m ias. co 0 "'

Seizu res : IV BZD, progress to ba rbiturate, neu rom uscu la r pa ra lysis, a n d general a n esthe­ sia; phe nyto i n not effective a n d m a y exa cerbate sei z u res . B ro n c hospasm : H u m id ified oxyge n and n e b u l ized broncho­ d i lators; parente ra l a d renergic a m i nes may potentiate myoca r­ d i a l irrita b i l ity.

Deconta m i nation con siderati o n : • Preca utiona ry m ea s u res to preve nt seconda ry conta m i ­ nation ; com p lete ly d isrobe, re m ove all jewel ry/accesso ries, m eticulously wash entire body with soa p and wate r i n cl u d i ng h a i r a n d finger n a i l s ; d iscard a l l wash water i n a sec u re fas h i o n ; p l a c e cloth i n g a n d leather goods i n a plastic bag labeled " b iohaza rd " fo r d i s posa l . • C h l o rd eco n e : Oral/nasga stric c h o l esty ra m i ne 4 g eve ry 6 h .

Syste m ic toxicity by i ngestion , d e rma l a bsorptio n , or i n hala­ tio n . Ch lori n ated h yd rocarbons a re rad iopa q u e , a n d d i rectly re lated to the n u m be r of c h lori ne ato m s per molecu le.

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Seizu res : I V atro p i n e and B Z D (e.g., d iazepam 0 . 2-0.4 mg! kg or l orazepa m 0.05 mg/kg) or p h e n o ba r b ita l 1 8 mg/kg.

Deconta m i nation : P reca ution a ry m easu res to prevent seconda ry conta m i n ation ; co m p l etely d is ro be ; re m ove a l l jewel ry/ accessories; m eticu lously wash entire body with soa p and water, i n c l u d i ng h a i r a n d finge rna i ls ; d isca rd a l l was h wate r i n a secu re fa s h i o n ; p lace c l ot h i ng a n d l eath er goods i n a plastic bag labeled " biohaza rd " for d i sposa l .

Chol i n e rgic poiso n i ng is a clinical diagnosis based on a h i sto ry of expos u re, p rese nce of a c h o l i n e rgic toxi d ro m e , a n d c l i n ical i m prove m e nt afte r a ppro p riate a ntidota l thera py; plasma ( pseudoc h o l i nesterase) a n d red b lood ce l l c hol i nester­ ase activity to confi r m c l i n ical d iagnosis.

• Acute DDT exposures presents with tremors, na usea , vom iting, muscle wea kness, and confu­ sion, progressing to seizures. Orga n o p hosphate (cho l i n ergic agents) • H EE N T: M iosis, lacri matio n , rh i n orrhea , sa l ivation . • Respi ratory: B ro n c h i a l m uscle spas m , p u l m ona ry ed e m a , res p i ratory fa i l u re. • CV: Hypertension/hypote n ­ sion ; dysrhyth m ias. • G I : Dia rrhea , vom iting; a bdom i n a l pa i n ; pa n c reatitis . • N e u ro logi c : Seizu res , coma, d e l i ri u m , C h eynes-Stokes res p i ration . • M uscu loskeleta l : Fasc i c u latio ns, dysto n i a s , choreoathetoid move m ents , pa ra lysis. • S k i n : D i a p h o resis.

C h o l i n ergic crisis: • R es p i rato ry su ppo rt. AND • I V atro p i n e 1-4 mg ( Ped s: 0 . 05 mg/kg) , d o u b le t h e d ose eve ry 5-1 0 m i n as n eeded u nt i l p u l mona ry secretions a re contro lled (tachyca rd ia is not a co ntra i n d ication to atro p i n e ) ; once sta b i l ized , sta rt atro p i n e i n fusion ( 1 0 %-20% o f tota l d ose for sta b i l ization per h o u r) a nd then titrated bac k the i nfu ­ sion ; resta rt atro p i n e at the fi rst signs of c h o l i n ergic excess .

Atro p i n e has no effect o n m u scle wea k ness o r pa ra lysis and wi l l not affect a cetylcho­ l i nesterase regeneration rate; pra l i d oxi m e regene rates ace­ tylch o l i nesterase and is m ost effective when i n itiated ea rly; res pi ratory m uscles a re the last to recove r.

• M eta bo l i c : Hyperglycem ia/ hypoglyce m ia . • I ntermed iate syn d rome: Asso­ ciated with severe orga no­ phosphate toxicity; conscious patient without fascicu lation or other cho l i nergic signs (a pparent recovery from acute chol i nergic crisis) d eveloping ma rked wea kness of neck flexion and va rying d egree of m otor cra n ia l nerve, p roxi m a l l i m b m uscle ( e . g . , shoulder a bd uction , hip flexion), and respi ratory m u scle wea kness 24-96 h after poison i ng, last­ i ng 5-1 8 d .

AN D • IV p ra l i d oxi m e 30 mg/kg ove r 30 m i n fo l lowed by a con­ ti n u ous i n fusion 8-1 0 mg/kg/h with e m p i ric d ose adj u stment based o n c l i n ica l res pon se ; conti n ue u ntil atro p i n e has n ot bee n req u i red fo r 24-48 h a nd patient extu bate d ; resta rt p ra l idox i m e if recu rrent signs/ sym ptoms. Agitati o n : Review atro p i n e dos i ng; I V B Z D . Review res p i rato ry function freq uently afte r atropi n e/pra l ­ idoxi m e/extu bation : I ntu bate/ve n­ ti late if tidal vo l u m e 60 % . I ntermed iate syn d ro m e : R egu­ larly assess flexor n eck stre ngth by asking patie nt to l ift thei r h ea d off the b e d a n d hold it w h i le p res­ s u re is a p p l ied to their fore h ead ; a ny wea k n ess s u ggests at risk

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S u cc i nylch o l i n e u se may result i n prolonged ( h o u rs to days) pa ra lysis. Ca rba mates a n d oth e r reve rs­ i ble c h o l i nesterase i n h i bitors: Signs/sy m ptoms s h o u l d resolve with i n 24 h ; atro p i n e a n d pra l idoxi m e have been used to treat ac utely i l l patients with ca rba mate toxicity u n less ca r ba ryl (Sev i n ) is known to be i nvolve d , then j ust atro p i n e a nd s u p portive ca re . Latent-on set toxic ity fol l owing fenth i o n , parat h i o n , d i ch l ofe n ­ thion , le pto p h os poison i n g; rec u rre nce of c h o l i n e rgic cri ses ( re l ease of fat-so l u bl e o rgano­ phosphorus fro m fat stores) days to weeks after i n gesti o n wi l l n eed retreatment with atro p i n e and pra l idox i m e .

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Orga n o p hos p h ate (cho l i n ergic agents) ( continued )

of deve l o p i n g res p i rato ry fa i l u re; assess res p i rato ry fu nction at least eve ry 4 h, a nd i ntu bate/ve n­ ti late if tidal vo l u m e 20 mg/d l. Gastroscopy co nsid eratio n : S u spected bezoa r (e.g. , relapsing conscious l eve l , prolo nged/erratic d rug a bsorption , pe rs istently elevated se ru m d rug leve l s ) ; gastrotomy as i n d icated .

Sympath o m i metic

A m p h eta m i n e • S a m e as coca ine; i n pa rtic ular a nxious, (para noid) psychosis, vo lati l e , aggressive , l ife­ th reate n i n g agitati on , vis u a l/ ta ct i l e h a l l u c i nations.

Agitation/d e l i r i u m/ha l l u c i nations: IV B Z D (e.g. , d iazepam 5- 1 0 mg) ra pidl y titrated to effect; la rge c u m u lative d oses may be need ed (e .g. , d iazepam > 1 00 mg) . Seiz u res, hyperth erm i a , hype rten­ sion, hypotension : See Coca i n e .

A m p heta m i n e c o m p l ications: See Coca i n e . P MA : Ta chyca rd i a , hyperth er­ m i a , co m a , seizu res, dysrhyth­ m ias, I VC D , hypoglycem i a , hype rka l e m i a .

Coca i n e • Sym pathetic hyperactivity with C N S excitation a n d pe riph era l sym pathetic sti m u lation (e.g. , mydriasis, hyperte n s i o n , tachycard i a , ta chypnea , pyrexia , d i a pho­ resis, heada che, a nxious, psych o m oto r agitatio n , confusi o n , psyc h osis, tre m o r, hyperreflexi a , se izures, visua l/ta cti le h a l l uc i n a tions); p rete r m i n a l eve nts: bradyca rd i a , hypote n s i o n , CV col l a pse . • M eta b o l i c : M eta bo l i c acido­ sis; hypoka l e m i a , hypergly­ cem ia .

Anxi ety/psyc homotor agitati o n : IV BZD (e.g. , d iaze pa m 5-10 mg) ra pidl y titrated to effect; la rge c u m u lative d oses may be need ed (e .g. , d iazepam > 1 00 mg) . Seizu res : IV B Z D , propofo l , o r barbitu rate . S i n u s ta chycard i a : IV B Z D (e .g. , d iazepa m 5- 1 0 mg or eq u iva l ent) titrated to effect. SVT: Ca rd iove rsion if h e m od y­ n a m ica l ly u n sta b l e ; IV B Z D ( e . g . , d i azepa m 5- 1 0 m g o r eq u iva­ le nt) ; IV d i ltiazem 20 mg or IV ve ra pa m i l 5-1 0 mg; IV ade nos i n e 6 mg or 1 2 m g . Ve ntri c u l a r d ysrhyt h m ias: D efi­ brillate if h e m odyn a m ica lly u nsta ­ ble; IV sod i u m b i carbonate 1 -2 m mol/kg; IV lidoca i n e 1 . 5 mg/ kg bolus fol l owed by 2 m g/m i n i nfu sio n ; I V B Z D ( e . g . , d iazepam 5- 1 0 m g o r eq u i va lent) .

Coca ine com p l ications (acute, hours, days after use ) : ACS, A M I , IVC D , dysrhyth m i as; CVA, SAH , i ntracere bra l hem orrhage; orga n ischem ia/i nfa rction , aortic d issection, vasc u l itis; acute l u ng i nj u ry/p u l m onary ede ma/AR DS, pneu mon itis ( "crack l u ng"), pneu mothorax, pneumome­ d iasti n u m ; rhabdomyolysis; infections (e.g. , endoca rd itis, hepatitis, p n e u m o n i a , epid u ra l a bscess); p lacentae a b ru ptio; BADS: decreased level of con­ sciousness, profound letha rgy, s i m i l a r to a prolonged posticta l period , normal thought content, normal slee p postures, ca n be a roused to orientatio n .

ACS : C u rrent g u i d e l i nes, IV B Z D (e .g. , d iazepa m 5- 1 0 mg o r eq u iva lent). co "'

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Coca i n e ( con tin ued )

Hyperte n s io n : R a p i d control of psych o m oto r agitation with IV B Z D ; I V phe ntola m i n e 1 mg, re peat in 5 m i n ; IV nitroglyce ri n or n itro p russide infusion titrated to effect. Hyperth e r m i a : R a pid control of psych o m oto r agitation with I V B Z D ; external coo l i ng. P u l m o na ry edema: I V n itro­ glycer i n i nfu sion titrated to blood pressu re ; IV fu rose m id e 20-40 m g ; I V morph i n e su lfate 2 mg every 5 m i n titrated to pa i n re l ief or res p i ratory status. Hy pote n s i o n : I V nore p i n e p h r i n e or e p i n e p h r i n e (avoid d o pa ­ m i ne).

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Syst e m i c asp hyx i a nt

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Ca rbo n mo noxide (CO) • Headache, d izzi ness; na usea a n d vom iti ng; progress ive i m pa i r m ent of conscious­ ness; hyperventi latio n ; hypotension ; i n c reased m uscle to n e , hype rrefl exia , c l o n u s , B a b i nski pos itive ; s k i n b l iste ri n g over p ress u re a reas; m eta bo l i c acidosis with normal oxyge n tension a n d red uced oxyge n sat u ra ­ tion ; d elayed n e u ro psych iat­ ric seq u elae .

Known or suspected CO toxic ity, severe a n d u n ex p l a i ned a n io n ga p m eta bol ic a c i d osis: • Ve ntilate a n d oxyge nate patient with 1 00% oxygen . • H B O consid erations: U n co n ­ s c i o u s a ny t i m e afte r CO expo­ s u re, n e u rologic o r psyc h iatric featu res ( e . g . , com a , seizu res, foca l d eficits, GCS < 1 5) , p regn a n cy, cardiac isc h e m ia , carboxy h e m ogl o b i n (COHgb) >20% ) .

Cya noge ns e . g . , cya n id e (C N ) • Anxiety, d izzi ness, pa l p ita­ tions, hea d a c h e , wea k ness; p u l m o nary edem a , res p i ra ­ to ry fa i l u re ; dysrhyth m ias, CV co l la pse; CNS dysfu n c­ tion , l oss of consciou sness, se iz u res, co m a ; m eta b o l i c acidosis. • N itropruss i d e- i n d u ced CN toxicity: Tac hyca rd i a , need fo r esca lating n itro prusside

Known or suspected C N toxic­ ity (e.g. , occu patio n , fi re i n a n e n c l osed space) , seve re a n d u nexpla i n a b l e a n io n ga p meta­ bol i c acidosis: • Ve ntilate a n d oxyge nate patient with 1 00% oxygen . • I V d icobalt ed etate 300 mg ( Peds: 1 0 mg/kg) over 1 -5 m i n if certa i n of the d i agnosis, partic u la rly when pati e nt is u nconscious with deteriorating

P u lse oxi m etry read i n g ove resti mates oxyh emoglobi n . C O H g b : Dete r m i nation of venous b lood sa m p le by co­ ox i m eter; h igh levels confi rm CO exposu re; levels n ot neces­ sarily p re d i ctive of sy m ptom s or outco m e ; levels can be with i n a la boratory reference range i f oxygen treatm e nt before obta i n ­ i ng b lood test.

GI deconta m i n ation consi deration (afte r patient sta b i l ized a n d p re­ ca utiona ry m easu res to m i n i m ize a spiratio n ) : Gastric lavage ( See Box 96- ll soon after i n gestion fol l owed by activated c h a rcoa l 1-2 g/kg . H B O considerations: CN toxicity co m pl i cated by coi n c id enta l CO poiso n i ng.

C N toxicity is a clinical diagnosis; plasma lactate "?.72 mg/d l (8 m m ol/U sensi­ tive s u r rogate for whole-b lood C N "?. 1 .0 µg/m l (39 µmol/U and sign ifica nt toxic ity; death "?.3 .0 µg/m l ( 1 1 7 µmol/U ; whole-blood CN concentra­ tion for confi r m ation of c l i n ical d iagnosis. An a bn o r m a l percent satu ra­ tion ga p (d ifference between (continued)

""

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''ilUflf1

(continued)

Agent Target Orga n Syste m i c Effect

doses to m a i nta i n bl ood pressure control (tachyphy­ laxis ) , m eta bo l ic acidosis with i n crease in seru m la ctate conce ntratio n , a narrowi ng of d iffe re nce i n oxyge n content of a rterial and ve nous bl ood , a n d ac ute u nexpla i n ed C N S dysfu nctio n .

Action Alert Critical Laboratory Va l u e C l i n ical I nte rvention

vita l signs, re peat 1-2 d ose base on c l i n ical response; adverse eve nts i nc l u d e hypo­ te nsio n , card iac dys rhyt h m ias, a ngioed ema . OR • I V hyd roxocoba l a m i n 5 g ove r 1 5 m i n , re peat 1-2 d oses base o n c l i n ica l res ponse; tra ns i ent p i n k d isco loration of m ucous m e m bra n es , s k i n , u ri n e ; may i nte rfe re with colorimetric d ete r m i nati o n s of seru m i ron , b i l i r u b i n , Cr con ce ntratio n . OR • I V sod i u m n itrite 300 mg ( 1 0 m l of a 3 % so lution a t 2 . 5-5 m Um i n ) ( Peds: 0 . 2 m Ukg of a 3% so l u tion [6 m g/kg or 6-8 m Um 2 B SA] at 2 . 5-5 m Um i n , max 1 0 m l [300 mg] ) and I V

Adju nct Thera py

Caveat

Extracorporeal S u pport

Com p l i cation

pe rcent oxyh e m oglo b i n re po rted by co-oxi m ete r a n d pe rcent satu ration ca lcu lated by b l ood gas a na lysis) d oes n ot suggest CN poison ing. Cya noge n expos u re : T h e rm a l decom position of polyu rethane foa m s i n furn itu re, contri b uto r to m o rta l ity i n smoke i n ha la­ tion ; latent on set ( > 1 2 h ) of toxicity fol lowi ng a ceto n itr i l e ( e .g . , a rtifi c i a l n a i l rem overs) i n gestion ; p rolo nged or excessive thera pe utic use of n itropruss i d e ; i n gestion of the cya nogen ic glycos ide a myg­ da l i n (vita m i n B 1 7) fo u n d i n kernels o f fru its (e.g . , a l m o n d s , a pples, a p ricots , ch erries, peaches, p l u m s ) .

sod i u m th iosu lfate 1 2 . 5 g (50 m l of a 25% sol ution i m med iately fol lowing sod i u m n itrite) ( Ped s: 1 m Ukg [250 m g/kg o r 30-40 m U m 2 BSA] , max 1 2 . 5 g [50 m l] ) ; red uce sod i u m n itrite dosage pro por­ tionate ly to Hgb concentration i n patients with known anem ia ; re peat treat m e nt using o n e­ h a lf orig i n a l d ose of sod i u m n itrite and sod i u m th iosu lfate if signs of poiso n i ng rea p pea r. OR • C N a n tidote kit: A m y l n itrite ( b ro ke n i n ga u ze a nd held c l ose to t h e nose a nd mouth of s po nta neously breat h i n g patients , o r ca n be placed i n to t h e face m ask l i p or inside t h e resusc itation bag) s h o u l d be i n h a led f o r 30 s of each m i n with a fresh pea rl used every 3-4 min and I V sod i u m n itrite 300 m g ( 1 0 m l of a 3 % solution) over 5-20 m i n (Peds: based o n h e m oglo b i n [ Hgb] conce ntratio n ; See Caveat) co "' U1

Pediatric IV sodium nitrite dosing

Hgb (g/d l) 7.0 8.0 9.0 10.0 1 1 .0 1 2 .0 13.0 14.0

3 % Sod i u m n itrite ( m Ukg) 0. 19 0.22 0.25 0.27 0.30 0.33 0.36 0.39

Excessive m ethemogl o b i n e m i a res u lting from n itrite or 4- D M A P : I V m ethylene blue 1 mg/kg (onset of action :::;3 0 m i n ) ; re peat d oses based o n c l i n ica l res ponse .

(continued)

"" "' en

•t!l:J•::S:I:t!I• (continued) Agent Target Orga n Syste m i c Effect

Cya nogens e . g . , cya n id e (C N ) ( contin ued )

Action Alert Critical Laboratory Va l u e C l i n ical I nte rvention

and IV sod i u m th iosu lfate 1 2 . 5

g (50 m l o f a 2 5 % sol ution) ( Peds: 0 . 4 1 m g/kg [ 1 . 65 m l of 2 5 % sol ution/kg ] , max 1 2 . 5 g (50 m LJ ) over 10 m i n ; re peat 1 -2 d oses of sod i u m n itrite and th iosu lfate base on c l i n ical respo nse. OR • I V 4-d i m ethyla m i n o p h e n o l (4- D M A P) 3 - 5 mg/kg; precise exte nt of i nd uced methe­ m ogl o b i n e m i a may not be p red icta ble. When d iagnosis is u n certa i n and patient is conscious, ad m i n iste r I V sod i u m th iosu lfate . Preve ntive n itroprusside toxicity: Add 1 g ( 1 0 ml of 1 0 % ) sod i u m th iosu lfate to each 1 00 m g bag of sod i u m n itro p ru ss i d e ( i . e . , 1 0 : 1 ratio) .

Adju nct Thera py

Caveat

Extracorporeal S u pport

Com p l i cation

Hyd roge n s u lfide ( H S) • Alte red menta l status; res­ pi ratory d i stress ; p u l m o n a ry ed e m a ; cya nosis; se izu res; com a ; d e layed n e u ro psyc h i­ atric seq uelae; blacken i n g o f copper a n d si lve r co i n s i n patient's pocket o r da rken i ng of jewel ry.

Known or suspected HS toxic ity (e .g. , ra pidly loses conscious ness " k nockd own , " rotten egg odor, resc ue fro m sewer or m a n u re pit, m u lt i p l e vict i m s with sudden death syn d ro m e , card iac a rrest in previously h ea lthy worke r at wo rk site) , severe and u nex pla i n a b le a n i o n ga p m eta bo l i c a c i d osis: • Ve ntilate a n d oxyge nate the patient with 100% oxyge n . • I V sod i u m n itrite : See Cya n o­ gens, Cya n id e a ntidote kit, sod i u m n itrite com ponent. • Consider H B O .

Withdrawa l syn d rome

Baclofen • Ora l : S i m i la r to etha nol (sed a­ tive hypnotic) withd rawa l .

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• l ntratheca l : Latent onset 1-3 d ; ta chyca rd i a , hypotension/ labile b l ood pressu re , hyper­ therm i a , a lte red/d e p ressed conscious ness, ha l l u ci na ­ t i o n s , m uscu l a r spasticity/ rigid ity, seizu res, pria pism .

Ora l : I V B Z D a n d titrate t o desi red effects ; ad m i n ister o ra l/e ntera l bac l ofe n ( patie nt's presc ri bed dos i ng p rior to w ithd rawa l ) .

Baclofen : M u sc u l a r rigid ity may progress to fata l rha bdomyoly­ sis; o ra l dosing not re l i a b le as sole treatment.

l ntrath eca l : Ad m i n ister baclofe n (ora l or ente ra l ) � 1 2 0 mg/d i n 6-8 d ivided doses (safety not esta b l ished < 1 2 yea rs of age) early in c l i n ica l c o u rse; resto re i n tratheca l bac lofe n ( I T B ) thera py via progra m med bolus t h ro ugh (continued)

"" "' ""

•t!l:J•::S:I:t!I• (continued) Agent Target Orga n Syste m i c Effect

Action Alert Critical Laboratory Va l u e C l i n ical I nte rvention

Baclofen ( continued )

cath eter access port, by l u m ba r pu nct u re , o r t h ro ugh exte r n a l ­ ized intratheca l cathete r; IV B Z D i nfusion titrated to effect u nti l ITB thera py is restored .

Adju nct Thera py

Caveat

Extracorporeal S u pport

Com p l i cation

Consult physici a n experienced i n ITB ma nageme nt; i nterrogate pu m p status using m a n ufac­ tu rer's progra m m ing device , perform bi plane or CT i magi ng of the p u m p/catheter system to identify problems (e.g. , catheter lea k , brea k, ki nk, d i slodge me nt); depen d i ng on resu lts, experi­ enced physic ian should e m pty pu m p reservoi r, refi l l with baclofen sol ution at proper concentration , a n d exped itiously perform system trou bleshooti ng to d ete r m i n e cause o f ITB thera py i nterru ptio n . G a m m a hyd roxybutyrate (G H B ) , 1 ,4-buta n ed io l , ga m m a­ butyro l actone

I V B Z D titrated t o sedatio n , norm a l ization of vita l signs a n d sensori u m .

Pentoba rbita l may be more effective th a n B Z Ds at control­ l i ng d e l i r i u m i n patients with

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• Withd rawa l syn d ro m e may progresses over 2-3 d; i nsom ­ n ia , tremor, vom iting, tachy­ card i a , hypertensio n , tremor, d ia p h o resis, a u d ito ry/visua l hall uci nations, a nxiety, confu­ sion , d isorientation, d e l i ri u m , agitati o n , ra pid fl uctuations i n sensori u m , seiz u res.

Severe withd rawa l ( d e l i r i u m or a utonom ic insta b i l ity) or h igh-dose BZD (e.g. , c u m u lative loraze pa m d ose 0.4-1 mg/kg d u ri ng a 6- h period ) d oes not control agitation a n d tac hyca rd i a : IV pentobarbita l 1-2 mg/kg every 30-60 m i n titrated t o sedatio n , normal ization of v ita l signs and sensori u m .

a bnorma l vita l signs, pa ra noid d e l usions, a n d h a l l u c i nations; pre matu re pentoba rbita l ta per­ i ng may resu lt i n recrudes­ cence of d e l i ri u m .

O p io id • Myd rias is, lacrim atio n , r h i n orrhea , d i a phoresis, yawn i ng, p i loerecti on , a n xi­ ety, restl essness; ta chyca rd ia , hyperte n s i o n , mya lgias, vo m iting, d i a rrhea , a n o rexia , a bdom i n a l pa i n , dehyd rati o n ; i ntense d rug c ravi ng; n ot l ife th reate n i n g ( i . e . , do not h ave a lte red m e nta l statu s , hyper­ therm i a , seizu res) except neonata l withd rawa l a n d may i n volve seizu res.

C l i n ical opioid with d rawa l : I M m eth adone 1 0 m g , re peat i n 1 h i f no s ign ifica nt re l i ef o r o ra l clon id i n e 0. 1-0 . 2 m g eve ry 4-6 h x 5-1 0 d a n d slowly ta pered by 0.2 mg/d .

I M m ethad o n e 1 0-20 m g wi l l b l o c k most physiologic m a n ifes­ tations of withd rawa l ; 20-40 mg da i ly or d ivided eve ry 1 2 h may be req u i red to avoid psyc ho­ logic withd rawa l ; afte r acute med ical i l l n ess is sta b i l ized , heroin-depe n d e nt patie nts may be ta pered with m eth adone over 1 wk; m etha done-depend­ ent patients req u i re �4 wk of gra d ua l ly d ec reas i n g dosages . C l o n i d i n e : Hy pote nsion es pe­ c ia l ly with fi rst d ose ; tachyp hy­ laxis to a ntiwith d rawa l effects may deve l o p by 1 0- 1 4 d . Co m p l ications: Dehyd ration, electro lyte d istu rbances, (continued)

"" "" 0

•t!l:J•::S:I:t!I• (continued) Agent Target Orga n Syste m i c Effect

Action Alert Critical Laboratory Va l u e C l i n ical I nte rvention

O p io id ( continued )

Sedative hypnotics (e.g. , ethanol, BZD, barbitu rate, non-BZD non­ ba rbitu rate sedative hypnotic) • Tre mors, vo m iti ng, a norex i a , a n xiety, a nd i nsom n i a , se izu res (status e p i l e pticus ra re ) , d e l i r i u m tre m e ns ( i.e . , a lte red se nsori u m with path ologic auto n o m i c a n d C N S hype ractivity; e.g. , ta chycard i a , hypertensio n , hyperpy rexia, d i a p h o resis, myd rias is, d isorientati o n , global confusion , h a l l u c i n a ­ t i o n s , d e l u s i o n s , m u m bl i ng speec h , psychomoto r agitation ) .

Adju nct Thera py

Caveat

Extracorporeal S u pport

Com p l i cation

hyperth erm i a , rha bd omyolysis, seiz u res, a s p i ration ) ; withd rawa l treatm e nt (e.g. , C N S/respi rato ry d e p ression , aspi rati o n ) ; u n d er­ lying i l l n ess (e.g. , infection, n u tritional d efic iencies, tra u m a ) . Determ i n e need for sedation using the C I WA sca le (a n u m bered grad ing system based on menta l status e.g., re ported a nxiety, hal­ luci nations, d isorientation); goa l is to control agitatio n : I V d iazepa m every 5-1 0 m i n u ntil patient q u ietly sleepi ng, yet easily awaken, start with 5 mg ( 2 . 5 mg/m i n ) ; if not effective , re peat d ose; if sec­ ond dose not effective, ad m i n ister 10 m g for the t h i rd and fou rth doses; if not effective, a d m i n ister 20 mg for the fifth and su bseq uent doses u ntil sedation is ach ieved ; ad m i n ister 5-20 mg every hour as needed to mai nta i n l ight som nolence; may req u i re > l g in

Antici pate/recogn ize ea rly with­ d rawa l to a l low ti mely treatm ent and prevent serious m a n ifesta­ tions (e . g . , se iz u res, hype rther­ m i a , d e l i ri u m ) ; lo ng-acting B Z D with a ctive m eta bol ites (e.g. , d iazepa m , c h lord iazepoxide) offe r prolo nged thera peutic effect with out need for freq uent d os i ng; risk of res p i ratory d e p ression with ba rbitu rates ; phenoth iazines (e.g. , proch lor­ perazine, ch lorpromazine) a n d butyropheno nes (e.g. , ha lop­ eridol) l ower seiz u re t h reshold , i n d uce hypotension, i m pa i r therm oreg u lati o n ; ta per d rug

24 h or IV lorazepa m 1-4 mg every 5-1 5 m i n or I M lorazepa m , 1-40 mg every 30--60 m i n u ntil ca l m , a nd then every h o u r a s needed to mai nta i n l ight som n o lence.

d ose over 2-4 wk by 1 0 %-20% eve ry 3 d .

If u n responsive to BZD, IV pro pofol 1-2 . 5 mg/kg stat a n d then 3-1 2 mg/kg/h or pe nto ba rbita l 1-2 mg/ kg every 30-60 m i n . N e u ro l e ptic agents may b e consid ered in conjunction with BZD w h e n agitat i o n , percept u a l d istu rbances, o r d istu rbed th i n k­ i ng not adeq uate ly contro l l e d ; I V/ I M h a loperidol 0 . 5-5 m g every 30-60 m i n or oral ha loperidol 0 . 5-5 mg every 4 h as needed for severe agitation .

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4 M P , 4-methyl pyrazole (fomepizole); ACLS, Adva n ce Cardiac Life S u p port; ACS, acute coronary synd rome; AM I , acute myocard i a l i nfarctio n ; APL, acute promye locytic leukemia; A R DS , a d u lt respi ratory d istress syndrome; AST/ALT, aspa rtate a m i n otra nsferase or a l a n i n e a m i n otra nsferase ; BADS, biogenic a m i nes depletion syn d rome; BAL, d i mercaprol, 2,3-d i merca pto- l - propanol, British anti-Lewisite; BSA, body su rface a rea ; B Z D , benzodiazepine; C, Celsi us; Ca EDTA, calc i u m d i sod i u m edetate; CAV H , conti n uous a rteriovenous hemodiafi ltratio n ; C I WA, Cli nical I n stitute Withd rawa l Assessm ent; C N S, centra l nervo us system ; C P R , cardiopulmonary resuscitatio n ; C r, c reati n i ne; C T , com puted to mogra phy; C V , ca rd iovascular; CVA, cerebrovascu la r accident; CWH , conti n uous venovenous hemodiafi ltratio n ; d , day; D M SA, 2,3-d i m erca ptosuccinic acid ; D5W, dextrose 5 % water; D KA, d ia betic ketoacidosis; ECG , electrocard iogra m ; EEG, electro­ encephalogra m ; F H F, fu l m i n a nt hepatic fa i l ure; GCS, Glasgow Coma Sca le; G F R , glom erular filtration rate; G I , gastrointesti na l ; G U , gen itourinary; h, hours; H BO , hyperba ric oxygen ; H EE N T, h ea d , ears, eyes, nose, th roat; I C H , i ntracra n i a l hem orrhage; I C U , intensive ca re u n it; J M , i ntra m uscular; I N R , i nternati onal normal ized ratio; IV, i ntravenous; max, maxi m u m ; IVCD, intrave ntricu l a r cond ucti on delay; M P PP, methyl-phenyl-propionoxypi perid ine; ms, m i l l iseconds; N AC , N-acetylcysteine; N D I , nephrogenic d ia betes insipidus; NS, norma l sa l i n e ; NSAI Ds, non-steroidal anti-inflam matory d rugs; O LT, orthotopic l iver tra n spla nt; Peds, Ped iatrics; PEG , polyethylene glycol (soluti o n ) ; PMA, para m eth oxya m ph eta m i ne; PT, prothro m b i n time; QTc, corrected QT interva l ; RaVR, term i n a l R wave i n lead aVR; R/SaVR , R-wave/S-wave ratio in lead aVR; SAH, subara c h noid hemorrhage; SC, s u bc uta neous; S I A D H , synd rome of ina ppropriate anti d i u reti c hormone; S I R S , system i c i nfla m m atory res ponse synd rome; SVR , system ic vascular resista nce; SVT, s u p raventric u l a r tac hyca rdia; W B I , whole bowe l irrigation; wk, wee ks.

Box 96- 1 . G astric lavage

Endotrac hea l or nasotrachea l i nt u bation s h o u l d p recede gastric lavage in th e comatose patient; p lace o ra l a i rway betwee n teet h ; place patient i n l eft latera l/head d own pos ition (20-degree ti lt); measure a n d mark le ngth o f t u be ( m outh t o sto m a c h ) with ro u nded e n d that is sufficiently firm to be passed i nto the stoma ch via the mouth, yet flexi ble enough n ot to cause m u cosa ! d a mage (a d u lt: at least 36-40 French [exte r n a l d ia m ete r 1 2-1 3 . 3 m m ] , P ed s : at least 24-28 F re n c h ga uge [externa l d i a m eter 7 . 8-9 .3 m m ] ) ; l u bricate tu be with a hyd roxyethylce l l u lose j e l ly and pass the tube without excessive force; c heck tu be place m e n t either by air i nsufflation w h i le l iste n i ng over th e sto mach a nd/o r, by as p i ration with pH testing of the a spirate; lavage is carried out usi n g 200-300-m l a l i q u ots of wa rm fl u id (e.g. , norma l sa l i n e , ta p water), P ed s : wa rm normal sa l i n e 1 0 m Ukg; vol u m e o f lavage fl u i d retu rned sho u l d a p p roxi m ate a m o u nt a d m i n iste red ; conti n ue lavage u n ti l recovered lavage so lution is clea r o f particulate matte r.

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A negative or poor lavage return d oes not ru le out a sign ificant i n gestio n .

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Box 9 6 - 2 . Whole bowel irrigation

I nsert nasogastric/ora l t u be and a d m i n ister P EG solution at 2 Uh fo r 5 h, and clear recta l effluent is evident (sma l l c h i l d re n : 500 m l/h ) ; d o u btfu l patients wou ld be coope rative or to lerate oral P EG .

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Box 96- 3 . D igox i n -s pec ific anti body fragm ents dosing c a l c u lator

. D i g o x i n b o d y b u r d e n t o b e n e utralize d in ng I ml ( n m o l / L x 1.28) x We i g ht (kg) x V o l u m e o f d i st ri b ut i o n (Vd ) N u m be r of vi a ls = ----------------------------------� 1 , 000 x 0.6 mg I vial

Vd : A d u lts 8 Ukg, c h i l d re n 2- 1 0 y 13 Ukg, i nfa nts 2-24 m o 1 6 L/kg, neonates 10 Ukg

)> z

0 "1J 0 (/J 0 z z Gl (/J

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C h a pter 96 • Toxicology (SI U n its) µM/L 6000 5000 4000 3000

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2000 1 300 1 000 900 800 700 600 500 400

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" 24 hours. Be aware of the risk of pressure necrosis. 2.

B. In cases of severe or uncontrolled epistaxis: 1. ABCs-airway, breathing, circulation. a. Intubation may be necessary. b. Insure adequate venous access for fluid resuscitation. 2. Monitor vital signs, check blood count, type/screen, and coagulation studies. 3. Consider gastric decompression to minimize aspiration of blood. 4. Obtain consultation from an otolaryngologist. C. If epistaxis is recurrent or refractory to packing, open or endoscopic arterial ligation or selective angiographic embolization may be necessary. 1. Anterior nasal bleeding is abated by ligation of the anterior ethmoid artery. 2. Posterior bleeding is controlled by ligation of the sphenopalatine artery. D. Other methods that might work-cold water irrigation, have patient suck on ice cube, cold towel to forehead. E. For patient in the intensive care setting, prevention is important. 1. Rotate and inspect nasal tubes regularly. 2. Use lubricating agents when inserting tubes. 3. Humidified oxygen is essential to prevent mucosal drying and desiccation. 4. Hypertension and coagulopathies should be treated immediately. SUGG ESTED R EA D I NGS

Asanua A, Timoshenko AP, Vercherine P, et al. Sphenopalatine and anterior ethmoidal artery ligation for severe epistaxis. Ann Otol Rhino! Laryngol 2009; 1 1 8 (9):639-644. This study discusses endoscopic arterial ligation. Barnes ML, Spielmann PM, White PS. Epistaxis: a contemporary evidence based approach. Otolaryngol Clin North Am 201 2;45 : 1 005- 1 0 1 7. This review discusses all options for treatment ofepistaxis and recommends early ligation instead ofprolonged packing. Kucik CJ, Clenney T. Management of epistaxis. Am Fam Physician 2005;71 (2) :305-3 1 1 . This review provides guidelines for primary care practitioners and has good anatomical diagrams.

Eso p h a gea l P e rfo rat i o n a n d Ac ute M e d i a st i n it i s Cynt h i a E . We ber, F red A . L u c h ette , a n d R o b e rt M . M e ntzer J r

I . ESOP HAG EAL PE RFORAT I O N

A. Definitions. Esophageal perforation can be a result of multiple patho­ physiologic etiologies. 1 . "Spontaneous" perforation due to increased wall tension. 2. Penetrating injuries. a. Due to intraluminal pathology. b. Result of extraluminal causes. B. Etiology. 1. Spontaneous (barogenic) perforation. a . Rapid increase in intraluminal pressure (violent vomiting-Boerhaave syndrome, blunt trauma) . b. Necrosis of the esophageal wall from esophageal cancer. c. Inflammatory esophageal lesions: tuberculosis, Barrett esophagus, idiopathic eosinophilic esophagitis. 2. Extraluminal perforation. a. Penetrating trauma from stab or gunshot wounds. b. Esophageal surgery: resection or esophagomyotomy. c. Adjacent surgical procedures: cervical procedures, truncal vagotomy, pneumonectomy, laparoscopic Nissen fundoplication, aortic sur­ gery, atrial fibrillation procedures through surgical or percutaneous approach, hiatal hernia repair, thoracic aneurysm repair, tracheos­ tomy, and tube thoracostomy. 3. Intraluminal perforation. a. Instrumentation. i. More common with rigid than flexible endoscopy. ii. More common during interventions such as balloon dilation of a stricture. iii. Leading edge of a stricture is the point most likely to rupture. b. Esophageal stent placement, especially in the setting of prior radia­ tion or chemotherapy. c. Congenital anomalies (esophageal atresia) or from nasogastric (NG) tube placement. d. Transesophageal echocardiography-very rare. e. Endotracheal intubation. f. Ingested foreign bodies. 840

C h a pter 98 • Esophagea l Perfora ti o n a n d Acute Med i ast i n i t i s

I

84 1

Chemical burns from alkali or strong acids, resulting in mucosal damage and stricture. h. Reflux esophagitis with ulceration. i. Endoscopic sclerotherapy, laser therapy, phocodynamic therapy. g.

C. Clinical presentation. 1. Tachycardia-earliest sign of mediastinitis. 2. Tachypnea. 3. Subcutaneous emphysema of the face and chest. 4. Pain: precordial, substernal, epigastric, or scapular due to diaphragmatic irritation. 5. Fever. 6. Dysphagia and odynophagia. 7. Hoarseness and cervical tenderness in cervical esophageal perforations. D. Diagnosis. 1. Chest radiography (OCR) : mediastinal air, hydropneumothorax, pleural effusion, subcutaneous emphysema. 2. Contrast esophagram-most sensitive diagnostic test; water-soluble contrast preferred; can confirm with barium if needed. 3. Computed tomography (CT) scan: extraluminal air, periesophageal fluid, wall thickening, extraluminal contrast. 4. Possible role for endoscopy to aid in diagnosis. E. Treatment. 1. Early (24 hours or extensive inflammation) . a. Esophageal diversion. b. Generous drainage. c. Broad-spectrum antibiotics. d. If small, closure over T-tube. 3. Contained perforation with no signs of sepsis: antibiotics, NG drainage, total parenteral nutrition (TPN) . 4. Persistent esophagomediastinal fistula: control with esophageal scents or fibrin glue. 5. Endoscopic management-clipping, transesophageal drainage, scents alone or in combination with open or laparoscopic repair. 6. Endoluminal scenting effective for malignant perforations, especially in nonoperative esophageal cancer. I l l . ACUTE M E D IAST I N ITIS

A. Etiology. 1. Primary mediastinitis-rare, alone or in conjunction with pharyngitis, epiglottitis, pneumonia, pericarditis, bronchitis. 2. Secondary mediastinitis-most commonly associated with sternotomy and intrathoracic or endoscopic procedures.

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Predisposing factors for mediastinitis following cardiac surgery include advanced age, obesity, smoking, emergency surgery, lower preoperative ejective fraction, prolonged cardiopulmonary bypass time, postoperative bleeding and need for reoperation, diabetes mellitus, use of bilateral internal mammary artery grafts, immunosuppression as seen in heart transplant recipients, and use of blood transfusions. 4. Other less common causes of secondary mediastinitis: a. Cervical or thoracic esophageal perforation. b. Complications from central lines. c. Ludwig angina or retropharyngeal abscesses. d. Periodontal infections. e. Descending necrotizing infections. f. Extracorporeal membrane oxygenation (ECMO). B. Clinical presentation. 3.

1. Fever. Pain localized to the chest or radiating to the neck. 3. Tachycardia. 4. Subcutaneous emphysema. 5. Leukocytosis. 6. Postoperative infection. a. Occurs 3 days to 4 weeks after surgery. b. Associated with sternal drainage and sternal instability. C. Diagnosis. 1. CXR: air tracking in the mediastinum, retrosternally, or between the leaves of the sternum. 2. CT scan: localized mediastinal fluid, pneumomediastinum, pleural effusion, sternal changes; however, they may be difficult to distinguish postoperative changes from surgical dissection. D. Treatment. 1. True acute mediastinitis is a surgical emergency. 2. Obtain blood and mediastinal fluid cultures. 3. Broad-spectrum antibiotics and source control. 4. Resuscitate to maintain adequate cardiac output and oxygen delivery. 5. Drain or debride fluid collections or necrotic tissue. 6. Open-window thoracotomy for bronchopleural or esophagopleural fistulas. 7. Irrigation and sternal debridement with rewiring for early exploration. 8. Irrigation catheter in cases of gross purulence. 9. Unilateral or bilateral pectoralis major, omental, or rectus abdominal muscle flap closure after radical sternal debridement for postoperative infections. 10. Vacuum-assisted closure (VAC) therapy for drainage, closure, and increased blood supply to the area. E. Complications. 1. Late failure of internal mammary artery bypass grafts in postoperative mediastinitis. 2. Free right ventricular wall rupture with sternal mobilization during delayed closure or upon spontaneous cough or movement. 2.

C h a pter 98 • Esophagea l Perfora ti o n a n d Acute Med i ast i n i t i s

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SUGG ESTED R EAD I N GS

Abboud CS, Wey SB, Baltar VT. Risk factors for mediastinitis after cardiac surgery. Ann Thorac Surg 2004;77:676-683. This study identifies obesity and smoking as two independent preoperative risk factors for mediastinitis after open heart surgery. Ang LB, Veloria EN, Evanina EY. Mediastinitis and blood transfusion in cardiac surgery: a systematic review. Heart Lung 201 2;41 (3):25 5-263. This review concludes that blood transfosion during cardiac surgery increases the risk of postoperative mediastinitis. Banazadeh M, Eshraghi M, Rahim MB, et al. Successful management of acute necrotizing mediastinitis with trans-cervical drainage. Ann Thorac Cardiovasc Surg 2 0 1 1 ; 1 7 (5) :298-500. This article describes good results from transcervical drainage of mediastinitis. Chang EI, Festekjian JH, Miller TA, et al. Chest wall reconstruction for sternal dehiscence after open heart surgery. Ann Plast Surg 20 1 3;7 1 ( 1 ) :84-87. The authors found that radical sternectomy, including resection of the costal cartilages, lowers morbidity. Kimberley KL, Ganesh R, Anton CK. Laparoscopic repair of esophageal perforation due to Boerhaave syndrome. Surg Laparosc Endosc Percutan Tech 20 1 1 ; 2 1 (4) :e203-e205. This article proposes that laparoscopic repair ofa spontaneous esophageal perforation is safe in patients presenting early and without signs ofsepsis. Koivukangas V, Biancar F, Merliainen S, et al. Esophageal stenting for spontaneous esophageal perforation. } Trauma Acute Care Surg 2 0 1 2;73(4) : 1 0 1 1-1 0 1 3. The authors stented 14 comecutive patients who presented with spontaneous esophageal perforation and report their results as effective treatment. Kuppusamy MK, Felisky C, Kozarek RA, et al. Impact of endoscopic assessment and treatment on operative and non-operative management of acute oesophageal perforation. Br j Surg 201 1;98(6) :8 1 8-824. This article discusses the role of endoscopy in both the diagnosis and treatment of esopha­ geal perforations. Ridder GJ, Maier W, Kinzer S, et al. Descending necrotizing mediastinitis: contemporary trends in etiology, diagnosis, management, and outcome. Ann Surg 20 1 0;25 1 :528-534. Retrospective review of41 patients with descending necrotizing mediastinitis. Risnes I, Abdelnoor M, Veel T, et al. Mediastinitis after coronary artery bypass grafting: the effect of vacuum-assisted closure versus traditional closed drainage on survival and reinfection rate. Int Wound} 20 1 2 . doi: I O. l l l l /j . 1 742-48 1 . Retrospective review of 130 patients with mediastinitis treated with either VAC therapy or closed drainage. Sepesi B, Raymon DP, Peters JH. Esophageal perforation: surgical, endoscopic, and medical management strategies. Curr Opin Gastroenterol 20 1 0;26(4):379-383. This article discusses the paradigm shift from aggressive operative management to more judicial nonoperative management in carefully selected patients with esophageal perfora­ tions. Wu JT, Mattox KL, Wall MJ Jr. Esophageal perforation: new perspectives and treatment paradigms. j Trauma 2007;63(5): 1 7 1 3-1 784. Excellent discussion of the causes, diagnosis, and treatment options for esophageal perforatiom.

D i ag n o s i s a n d M a n a ge m e nt of I ntra -Abd o m i n a l S e ps i s Yee Wo n g , M a ry M . Wo lfe , a n d Fred A . L u c h ette

I. G E N E RAL P R I N C I PLES

A. Intra-abdominal infections are commonly encountered in the intensive care unit (ICU) . B. The presentation and causes are varied. 1. Many of these patients have undergone abdominal surgery or a procedure, and there is a suspicion for an intra-abdominal abscess. 2. Some patients will present with clinical manifestations suggestive of sepsis, but an infectious source may not be immediately evident. Radiologic imaging is helpful in these cases. a. Causes of sepsis may be unrelated to the initial surgical procedure. b. It may be seen in bowel ischemia, necrotizing pancreatitis, cholecys­ titis, or in diverticulitis. I I . ETIOLOGY

A. Pathogenesis may be secondary ro spontaneous causes or to contamination of the perironeal cavity after a perforated viscus that causes breakdown of peritoneal defense mechanisms. B. Perironeal defense mechanisms provide a system for effective clearance of foreign particulates and organisms from the intraperironeal space. 1. Resident perironeal macrophages, neurrophils, and monocytes ingest microorganisms and secrete proinflammarory cytokines. 2. Lymphatic channels provide drainage of perironeal fluid with bacteria and proinflammarory mediarors into the venous system. 3. Inspiration, especially during positive-pressure ventilation, causes a pres­ sure gradient favoring fluid movement out of the abdomen. 4. Entry of proinflammarory cyrokines into the vascular space leads ro systemic sepsis and subsequent hemodynamic and respirarory changes. C. Pathogens include mixed flora-aerobic, anaerobic, and facultative gram-negative organisms are common pathogens. 1. Facultative and aerobic gram-negative organisms release endoroxin and endoroxin-associated proteins-most notably lipopolysaccharide from their outer membrane, which triggers an intense inflammatory response. 844

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Cytokines and leukocyte-derived inflammatory mediators give rise to systemic responses that can include tachycardia, fever, peripheral vasodi­ latation, hypotension, and decreased cardiac output. 3. Host immune defenses can be suppressed by bacterial synergy that inhibits complement activation and leukocyte migration.

2.

I l l . DIAG N O S I S

A. The initial therapeutic goal should focus o n resuscitation, diagnosis, and source control of the infection. B. History, physical examination, and imaging studies are crucial to the diag­ nosis of intra-abdominal sepsis in the critically ill patient. 1. Systemic inflammatory response syndrome (SIRS) is defined as having two or more of the following: a. Temperature >38°C or 90 beats per minute. c. Respiratory rate >20 per minute or pco 1 2,000 cells/mm 3 or fewer than 4,000 cells/mm3 , or with more than 1 0% immature (bands) forms. 2. Sepsis is defined as SIRS with an identifiable or suspected infectious source. 3. Signs and symptoms of intra-abdominal sepsis include fever, tachycardia, localized or diffuse abdominal tenderness, peritonitis, tachypnea, and delirium. 4. Laboratory findings often show leukocytosis, electrolyte abnormalities, hyperglycemia, increased liver enzymes, and elevated lactic acid. C. Radiology. 1 . Plain radiographs may reveal the following findings for intra-abdominal sepsis, but are often nonspecific. a. Perforation/pneumoperitoneum. b. Bowel obstruction. c. Pneumatosis intestinalis and portal venous gas from ischemic bowel. d. Pneumonia. e. Pleural effusion. 2. Ultrasound (US) may be diagnostic if an intra-abdominal abscess and cholecystitis (or nephrolithiasis) are suspected. a. It is noninvasive and can be done at bedside to localize extraluminal fluid collection. b. It can allow guided drainage of an intra-abdominal collection and biliary or ureteral drainage. c. Results are highly operator dependent and limited by body habitus, bowel gas, and location of abscess. 3. Computed tomography (CT) is often the most utilized diagnostic tool for intra-abdominal infection. a. It provides noninvasive identification of pathology not identified on physical examination, plain radiographs, or US. b. It may also be used for guided drainage of fluid collection. c . It is also helpful in diagnosing pancreatitis, colitis, and ischemic bowel.

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IV. TREAT M E NT

A. Initial resuscitation. 1 . Aggressive fluid resuscitation to counter vasodilation should be initiated before surgical or radiologic intervention in order to maintain end-organ perfusion. 2. Appropriate monitoring should be utilized, including arterial cath­ eterization for continuous blood pressure assessment, central venous pressure, and urine output to guide the adequacy of fluid resuscitation. 3. Metabolic acidosis and coagulopathy should be corrected as expedi­ tiously as possible. 4. Vasopressors, such as dopamine, phenylephrine, norepinephrine, and vasopressin, can also be used to increase cardiac output or reverse vaso­ dilation. However, vasopressors should not replace volume resuscitation to maintain blood pressure and organ perfusion. B. Administration of empiric antibiotics should be instituted as soon as intra-abdominal sepsis is suspected (Table 99- 1 ) . 1 . Appropriate coverage must anticipate pathogens most likely to be encountered at the site of infection. Initial empiric antibiotics should cover enteric gram-negative facultative and obligate anaerobic bacilli or Clostridium difficile. 2. Proximal small bowel has gram-positive aerobic and gram-negative anaerobic organisms that are generally susceptible to �-lactam antibiotics. 3. Distal small bowel and colon perforations cause contamination with gram-negative facultative organisms and obligate anaerobes that should be covered with broad-spectrum antibiotics, such as carbapenems, cephalosporins, or penicillins plus �-lactamase inhibitors. 4. Once culture results return, empiric antibiotics should be narrowed down to target specific organisms.

TA B L E 9 9 - 1

Bacteria Com mo n l y Encou ntered in I ntra-Abdom i n a l I nfections

Fac u ltative gra m - n egative bac i l l i

O b l igate anaerobes

Facu ltative gra m -positive cocc i

Escherichia coli Klebsiella s pecies Proteus species Morganella morganii

Bacteroides fragilis Bacteroides species Fusobacterium s pecies Clostridium s pecies Peptococcus s pecies

Enterococci

Other e nteric gra m - n egative bac i l l i Aerobic gra m - n egative baci l l i Pseudomonas aeruginosa

Peptostreptococcus

species

Lactobacil/us species

Staphylococcus s pecies Streptococcus species

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C. Percutaneous drainage can be performed when fluid collection is identified and when there are no signs of peritonitis. It is preferred over open surgical intervention, which is associated with increased morbidity and mortality. If the abscess is accessible by US or CT, a drain should be emergently placed and left until the abscess has resolved. D. Surgery is indicated for evidence of intestinal perforation and diffuse peri­ tonitis. Primary goal of surgical intervention is to control the source of contamination. 1 . Bowel resections should be performed in cases of ischemic bowel, with end ostomy if necessary. When the patient is hemodynamically unstable, the bowel should be left in discontinuity (damage control) and a second­ look laparotomy planned. 2. Primary closure of the wound is controversial and must take into consid­ eration the abdominal wall edema and aggressiveness of the volume resus­ citation required, in order to avoid abdominal compartment syndrome. a. A temporary abdominal closure device, such as vacuum-assisted abdominal dressing, has been gaining popularity in recent years. It allows for rapid application and easy reentry into the peritoneal cav­ ity, and avoids abdominal compartment syndrome. b. Temporary closure also shortens the time when the patient is under anesthesia. Resuscitation and correction of acidosis and coagulopathy can then be completed in the ICU until the patient is hemodynami­ cally stable before definitive closure of the abdomen. c. Second-look laparotomy may also be necessary to achieve complete control of infection. V. S P E C I F I C I N FECT I O N S

A. Acute pancreatitis. 1 . Infections superimposed on acute pancreatitis are among the most dif­ ficult intra-abdominal infections to manage. 2. See Chapter 100. B. Biliary infections. 1. Ascending cholangitis is often caused by biliary obstruction with second­ ary bacterial infection of the bile, and patients can present with Charcot triad; right upper quadrant (RUQ) abdominal pain, fever, and jaundice. With severe disease and development of sepsis, patients may also have mental status changes and hypotension in addition to the triad, also known as the Reynold pentad. a. US or CT may show biliary ductal dilatation with gallstones or with inflammatory changes when acalculous cholecystitis is present. b. Laboratory findings include hyperbilirubinemia, leukocytosis, and elevated liver enzymes. c. Treatment includes resuscitation, broad-spectrum antibiotics, and supportive care. If there is no clinical improvement in 24 to 48 hours, one should proceed with drainage of the common bile duct with endoscopic retrograde cholangiopancreatography/percuraneous or

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transhepatic cholangiography (ERCP/PTC) . ERCP or PTC should not be delayed for imaging if cholangitis has been diagnosed based on clinical presentation and laboratory findings. d. Initial antibiotic therapy should be monotherapy with a �-lactam/ �-lactamase inhibitor or metronidazole with third-generation cephalosporin or a fluoroquinolone. 2.

Acute cholecystitis. a. Acalculous cholecystitis is most common in ICU secondary to micro­ vascular and mucosa! dysfunction and presents as occult sepsis with or without RUQ tenderness. b. US/CT may show gallbladder wall thickening, pericholecystic fluid, and sludge. c. Treatment includes antibiotics and percutaneous cholecystostomy tube for high-risk patients who are not a surgical candidate for cholecystectomy and do not respond to antibiotic therapy. d. Initial antibiotic therapy is the same as the treatment for ascending cholangitis.

C. Mesenteric ischemia (see Chapter 1 0 1 ) . 1 . Arterial o r venous occlusion o r low flow states are causative factors. Thromboembolic events should be considered in the setting of atrial fibrillation or arrhythmia. 2. Plain radiographs can be used to evaluate for pneumatosis intestinalis and portal venous gas in cases of severe ischemia, but are often inconclusive. 3. Angiography is considered the gold standard for diagnosing mesenteric ischemia; however, it is invasive and should be delayed if patient presents with peritonitis. 4. CT is useful to evaluate stable patients with less specific symptomatol­ ogy. Early changes such as bowel dilatation and transmural thickening with inflammatory changes in the perienteric fat can sometimes be seen. D. Postoperative intra-abdominal infections. 1. It must be considered in patients with signs of sepsis who have undergone gastrointestinal (GI) anastomosis or those who present with peritonitis. 2. Patients with anastomotic leak will often develop fever, tachycardia, and leukocytosis during the early postoperative period. Management usually involves relaparotomy with abdominal washout, resection of the anasto­ mosis, and creation of an end ostomy. a. Percutaneous drainage can be considered if an abscess adjacent to an anastomosis is small and easily accessible by CT, and the patient is clinically stable. b. Antibiotic therapy should target specific enteric pathogens and then be tailored to final sensitivities. E. Enteric fistulas. 1. About 1 5% to 25% of mortality associated with enteric fistulas is secondary to sepsis and multiorgan system failure. 2. Small intestine is the most common source, followed by the colon, stomach, duodenum, biliary tract, and pancreas.

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3. Multiple risk factors inhibit the spontaneous closure of fistulas, includ­ ing foreign bodies, radiation, inflammatory bowel diseases or infection, epithelialization or fistula tract 5 5 years; WBC > 1 6,000/mm 3; glucose > 200 mg/dL; lactate dehydrogenase (LOH) > 350 international units/L; glutamic­ oxaloacetic transaminase (GOT) > 250 units/dL.

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During initial 48 hours: HCT decrease > 1 0%; BUN rise >5 mg/dL; serum calcium 4 mEq/L; and fluid sequestration >6 L. 3. Less than three criteria: mild pancreatitis- 1 % mortality. 4. Seven or eight criteria: severe pancreatitis-90% mortality. D. APACHE-IV-a method for more precisely determining mortality risk. E. Peripancreatic fluid collections on CT scan. 1. Two or more fluid collections-6 1 % incidence of late pancreatic abscess. 2. One fluid collection- 1 2% to 1 7% incidence of pancreatic abscess. 3. Pancreatic enlargement only-zero incidence of pancreatic abscess. 2.

VI. TREAT M E N T O F ACUTE PAN C R EATITIS

A. The main goal of initial management is to maintain adequate organ perfu­ sion that typically consists of adequate isotonic volume administration, analgesia, antiemetics, and continual reassessment of clinical parameters. B. Analgesia: hydromorphone may be preferred over morphine, as morphine stimulates the sphincter of Oddi to contract. C. Fluid and electrolyte replacement (isotonic crystalloid preferred over colloid) . 1. Initially, hypochloremic alkalosis due to vomiting and decreased fluid intake. 2. Subsequently, metabolic acidosis due to hypovolemia, poor tissue perfu­ sion, and management with chloride-containing fluids. 3. Hypomagnesemia and hypoalbuminemia due to preexisting malnutri­ tion in chronic alcoholism. 4. Untreated hypocalcemia may lead to tetany and carpopedal spasm. 5. Hemodynamic alterations of severe attacks resemble septic shock: increased heart rate, cardiac output, cardiac index, arterial-venous oxygen difference and decreased pulmonary vascular resistance and hypoxemia. D. Other treatments. 1. Unclear value of nasogastric suction and agents that reduce pancreatic function, inhibit inflammatory or cytotoxic responses, or inhibit diges­ tive enzymes. 2. Use of early enteral nutrition (initiated within 36 hours of symptom onset) has shown benefit over parenteral nutrition in terms of duration of hospital stay, infectious morbidity, and need for surgery. 3. Consider foley catheter and/ or central venous catheter. E. Role of surgery and endoscopy for gallstone pancreatitis. 1. Mild pancreatitis-no indication for early surgical or endoscopic inter­ vention. 2. Severe gallstone pancreatitis-early surgical or endoscopic intervention should be considered to either remove the source of the gallstones (i.e., cholecystectomy) or to relieve a possible obstruction from choledocholi­ thiasis (i.e., ERCP with sphincterotomy and possible stent placement) . 3. Recurrent attacks of gallstone pancreatitis may be prevented by cholecys­ tectomy combined with surgical or endoscopic duct clearance.

854

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V I I . PREVENTI O N A N D TREAT M E N T O F SYSTE M I C C O M PLICATI O N S

A . Aggressive fluid and electrolyte therapy may be the most effective method of preventing pulmonary and renal failure. B. Pulmonary toilet and monitoring of pulmonary function with arterial blood gas measurements should be considered. C. Prophylaxis with antacids, H 2 -blockers, or proton-pump inhibitors (PPis) may prevent stress-induced bleeding of gastroduodenal lesions, although this remains controversial. D. For most patients with acute pancreatitis, antibiotic prophylaxis does not reduce the risk of infectious complications and is associated with an increased risk of death. 1. Intravenous imipenem or meropenem for 1 4 days may be of benefit in patients with infected pancreatitis by reducing mortality and morbidity. 2. Fluconazole decreases the emergence of resistant fungi. E. All patients are at increased risk for thrombotic complications and require venous thromboembolism prophylaxis. V I I I . LOCAL C O M PLICATI O N S OF PAN C REATITIS

A. Definitions. 1. Acute pancreatic and peripancreatic fluid collections-pancreatic inflam­ mation results in fluid collections (lacking walls) and often occur early, in or near the pancreas. 2. Pancreatic necrosis-either sterile or infected area of nonviable pancre­ atic tissue, diffuse or focal, associated with peripancreatic fat necrosis. 3. Pancreatic pseudocyst. a. Occurs 4 to 6 weeks after the acute episode, nonepithelialized wall of fibrous or granulation tissue enclosing a collection of pancreatic juice rich in digestive enzymes. b. Leakage into peritoneal cavity or chest leads to pancreatic ascites or pancreatic-pleural fistula, respectively. 4. Pancreatic abscess-circumscribed intra-abdominal collection of puru­ lence with gas close to the pancreas with or without necrosis. B. Diagnosis. 1. Contrast-enhanced CT-identifies and quantitates areas of pancreatic necrosis or abscess based on extraintestinal gas, poor enhancement, or Gram stain of CT-guided fine-needle aspirate. 2. ERCP-determines communication of fluid collections with the main pancreatic duct and/or localizes the point of duct rupture. C. Management. 1. Acute fluid collections--resolve spontaneously and rarely require treatment. 2. Sterile pancreatic necrosis-typically nonoperative management, unless clinically deteriorates despite aggressive nonoperative treatment. 3. Infected pancreatic necrosis-surgery is considered the gold standard, although current guidelines suggest waiting until the 3rd or 4th week after the onset of symptoms in the stable patient.

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4. Pancreatic abscess-percutaneous or surgical drainage is recommended. 5. A step-up approach using percutaneous drainage followed by minimally invasive video-assisted retroperitoneal debridement (VARD) and peroral endoscopic necrosectomy have been shown to be superior to traditional open necrosectomy. 6. Pseudocysts-treat only if symptomatic, regardless of size, with internal surgical drainage (cystogastrostomy, cystoduodenostomy, and Roux-en-Y cystojejunostomy) , endoscopic drainage (cystogastrostomy and cystodu­ odenostomy) , or percutaneous drainage with or without administration of somatostacin. 7. Pancreatic ascites or pancreatic-pleural fistula-bowel rest, nutrition, somatostatin; most require ERCP for identification of ductal disruption with subsequent distal pancreatectomy, Roux-en-Y pancreatojejunos­ tomy, or endoscopic scent placement. SUGG ESTED R EA D I NGS

Al-Omran M, et al. Enteral versus parenteral nutrition for acute pancrearitis. Cochrane Database Syst Rev 20 1 0 ; ( l ) :CD002837. A systematic review of randomized controlled trials demonstrated a benefit to EN over TPN in patients with acute pancreatitis requiring nutritional support. Anand N, Park JH, Wu BU. Modern management of acute pancreatitis. Gastroenterol Clin N Am 20 12;4 1 ( 1 ) : 1-8. A review of current management principles for acute pancreatitis, including prognostic scoring systems, resuscitation, imaging, antibiotics, nutrition, and interventional options. Bakker OJ, et al. Endoscopic transgastric vs surgical necrosectomy for infected necrotizing pancreatitis: a randomized trial. JAMA 2 0 1 2;307( 1 0) : 1 053-1 06 1 . Randomized trial of22 patients demonstrating that endoscopic necrosectomy reduces the proinjlammatory response, the number ofpancreatic fistulas, and the onset ofnew organ failure. Bharwani N, et al. Acute pancreatiris: the role of imaging in diagnosis and management. Clin Radiol 2 0 1 1 ;66(2) : 1 64- 1 7 5 . Summary ofthe natural course ofacute severe pancreatitis, nomenclature, staging, and complications, as they relate to the potential role ofinterventional radiology. Elmunzer BJ, et al. A randomized trial of rectal indomethacin to prevent post-ERCP pancre­ atitis. N Engl] Med 20 1 2;366( 1 5) : 1 4 1 4-1 422. Randomized trial of 602 patients demonstrated significant reduction in the incidence of post-ERCP pancreatitis with the administration ofrectal indomethacin. Fisher JM, Gardner TB. The "golden hours" of management in acute pancreatitis. Am J Gastroenterol 20 1 2; 1 07(8) : 1 1 46- 1 1 50. A review ofprognostic tools, end points for fluid resuscitation, prophylactic antibiotics, and early ERCP in acute pancreatitis. Freeman ML, et al. Interventions for necrotizing pancreariris: summary of a multidisciplinary consensus conference. Pancreas 20 1 2;4 1 (8) : 1 1 76-1 1 94. Recommendations for the management ofnecrotizing pancreatitis, incorporating many of the recent developments in minimally invasive techniques for necrosectomy. Frossand MJL, et al. Acute pancreatitis. Lancet 2008;37 1 : 1 43- 1 52. Comprehensive overview ofepidemiology, pathophysiology, diagnosis, and treatment of acute pancreatitis.

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Jiang K, et al. Present and future of prophylactic antibiotics for severe acute pancreatitis. World] Gastroenterol 20 1 2; 1 8 (3):279-284. A meta-analysis of randomized controlled trialsfound no significant benefit to adminis­ tration ofprophylactic antibiotics to patients with severe acute pancreatitis. Kelly TR, Wagner OS. Gallstone pancreatitis: a prospective randomized trial of the timing of surgery. Surgery 1 988; 1 04:600. An excellent randomized study of 165 patients and their outcomes based on early versus delayed surgical intervention for gallstone pancreatitis. Papachrisrou GI, et al. Comparison of BISAP, Ranson's, APACHE-II, and CTSI scores in predicting organ failure, complications, and mortality in acute pancreatitis. Am ] Gastroenterol 20 1 0 ; 1 0 5 (2) :435--44 1 . Comparison ofprognostic scoring systems for patients at risk for developing severe disease early in the course ofacute pancreatitis. Skipworth JR, Shankar A, Pereira SP. Managing acute and chronic pancreatitis. Practitioner 2 0 1 0;254 ( 1 733) :23-27. Review ofacute and chronic pancreatitis, including etiology, clinical presentation, diag­ nosis, scoring systems, and imaging. Tonsi AF, et al. Acute pancreatitis at the beginning of the 2 1 st century: the state of the art. World] Gastroenterol 2009; 1 5 (24) :2945-2959. Review ofthe pathophysiology, etiology, and management strategies for acute pancreatitis. Van Baal MC, et al. Systematic review of percutaneous catheter drainage as primary treatment for necrotizing pancreatitis. Br] Surg 20 1 1 ;9 8 ( 1 ) : 1 8-27. Percutaneous catheter drainage may provide adequate treatment for some patients with necrotizing pancreatitis and avoid the needfor surgical necrosectomy. Villatoro E, Mulla M, Larvin M. Antibiotic therapy for prophylaxis against infec­ tion of pancreatic necrosis in acute pancreatitis. Cochrane Database Syst Rev 2 0 1 0;(5) :CD00294 l . Review of randomized controlled trials comparing antibiotics versus placebo in acute pancreatitis demonstrated no benefit to antibiotics in preventing mortality or infection of pancreatic necrosis (except for imipenem}.

M es e nte r i c lschem ia Yee Wo n g a n d P ete r E . R i ce

I . G E N E RAL P R I N C I PLES

A. Defined as a compromise of intestinal arterial or venous perfusion that may occur acutely or over the course of several months in the setting of chronic ischemia. B. Decreased blood flow and oxygen to the bowel leads to ischemia, acidosis, leu­ kocytosis, and the eventual development of sepsis and multiple-organ failure. C. Mortality is in excess of 60% to 80% for acute arterial occlusion, usually due to a delay in diagnosis and the rapid progression of intestinal ischemia to tissue necrosis. D. Risk factors include advanced age, atrial arrhythmias, history of congestive heart failure or recent myocardial infarct, valvular heart disease, previous cardiac or vascular surgeries, and atherosclerotic disease. E. Early diagnosis and prompt revascularization are the key factors to a favor­ able outcome. I I . ETI OLOGY

A. Acute mesenteric ischemia is usually divided into three categories, with occlusive disease or thromboembolism accounting for 80% of all cases. 1. Mesenteric arterial occlusion from embolism, thrombosis, dissection, vasculitis, or stent placement. 2. Mesenteric venous occlusion secondary to bowel obstruction, thrombo­ sis, or phlebitis. 3. Nonocclusive ischemia as a result of cardiopulmonary bypass, various shock states, and vasoconstrictive medications (i.e., a-adrenergic, digi­ talis, or vasopressin) . B. Mesenteric arterial embolism or thrombosis involves the superior mesen­ teric artery (SMA) in 8 5 % of cases. Most individuals have preocclusive atherosclerotic disease in other locations, including the visceral vessels. C. Emboli from a cardiac source typically lodge at the first branch point of the SMA, the inferior pancreatoduodenal artery. Arterioarterial emboli tend to be smaller and lodge in the more distal mesenteric circulation. D. Thrombosis usually develops at or near the origin of vessels or areas of concurrent atherosclerotic stenoses. In contrast with embolic occlusion, acute ischemia from thrombosis is usually a late complication of athero­ sclerotic disease and develops after two of the three mesenteric arteries are completely occluded. 857

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E. Mesenteric venous thrombosis (MVT) is a rare disorder resulting from a variety of acquired and inherited hypercoagulable states. MVT usually involves the superior mesenteric and splenic veins and, less commonly, the inferior mesenteric and portal veins. I l l . PAT H O P HYS I O LOGY

Acute arterial obstruction will rarely present with acute mesenteric ischemia at normotensive pressures due to the excellent collateral circulation of the gut. B. Ischemic times as short as 3 hours can produce significant irreversible dam­ age to the intestinal mucosa. C. Reduction of blood flow initiates a cascade of events, including an acute inflammatory response with the release of cytokines and platelet-activating factor, resulting in the breakdown of the mucosal barrier with bacterial translocation and the ultimate progression of sepsis, multisystem-organ failure, and death. D. Nonocclusive ischemia is the result of mesenteric vasospasm, usually in the distribution of the SMA. A.

1. Homeostatic mechanisms attempt to maintain cardiac and cerebral per­ fusion at the expense of visceral and peripheral organs. IV. D IAG N O S I S

A . Clinical presentation. 1 . One hallmark of acute mesenteric ischemic is pain out of proportion to the physical examination. 2. Onset of pain may be accompanied by gut emptying (e.g., vomiting, bowel movement, or diarrhea) . 3. Bloody bowel movements and tachycardia are also common late signs of intestinal ischemia. 4. Physical examination may reveal diffuse abdominal tenderness, hypoac­ tive to absent bowel sounds, and peritoneal findings with progression of disease to bowel infarction and perforation. 5. A high index of suspicion in patients with preexisting cardiac disease and critically ill patients with a shock state from trauma, burns, and sepsis. 6. Patients with acute ischemia from thrombosis may have a history of chronic postprandial abdominal pain associated with significant weight loss. B. Laboratory findings. 1 . Elevation of serum amylase concentration. 2. Elevation of serum lactate often implies severe ischemia or bowel infarc­ tion. 3. Most common laboratory abnormality is a persistent and profound leukocytosis; in excess of 1 5,000 cells/mm 3 . 4. Electrolyte derangements from dehydration and acidosis with pH < 7.2 and base deficit of 7 to 8 are seen in the advanced stages of intestinal infarction.

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C. Imaging. 1. Plain radiographs typically demonstrate no abnormalities until late in the clinical course. Late findings include distended bowel loops with air-fluid levels, bowel wall thickening, intestinal pneumatosis, which is very specific for bowel necrosis, portal venous gas, and free air from perforation. 2. Duplex ultrasonography is highly specific; however, the result is highly operator dependent and can be limited by distended bowel loops or in obese patients. 3. Computed tomography (CT) is also highly specific and is usually the imaging study of choice for rapid diagnosis. Computed tomographic angiography has a sensitivity of 96% and specificity of 94% in diagnos­ ing acute mesenteric ischemia. It is usually preferred over conventional angiography for its noninvasiveness and ability to evaluate for other abdominal pathologies. Findings for ischemia include bowel wall thick­ ening and/or distention, mesenteric fat stranding, pneumatosis, and portal venous gas. 4. Angiography remains the "gold standard" for imaging of mesenteric occlusion and can even be diagnostic for nonocclusive disease. It can also offer therapeutic interventions; however, it is invasive and is limited to patients without peritoneal signs. V. TREAT M E N T

A. Acute mesenteric ischemia i s a vascular emergency, and immediate surgical intervention improves outcome. Emergent laparotomy is usually indicated when patients present with signs of peritonitis. B. Aggressive resuscitation is essential as patients will likely develop systemic inflammatory response with progression of ischemia. C. SMA embolism. 1. Arteriotomy with embolectomy should be performed as soon as possible. Closure of arteriotomy can be achieved primarily or with patch angio­ plasty. 2. Bowel resection should be performed after revascularization when frank bowel necrosis is present. Second-look laparotomy within 48 hours is warranted when reperfusion injury is suspected. 3. Endovascular approaches with thrombolysis, angioplasty, and stenting are alternative options for high-risk patients without signs of bowel infarction or in the setting of chronic mesenteric ischemia. D. SMA thrombosis. 1. In patients with extensive stenosis, an antegrade or retrograde bypass with prosthetic or autologous venous grafts is required. Antegrade aortomesenteric bypass has been the procedure of choice historically. However, retrograde iliomesenteric bypass has also been described, although there is no convincing evidence that one approach is superior to the other. Venous graft is usually preferred in patients with bowel infarction.

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Endovascular scenting with or without chrombolysis may be beneficial for chronic mesenteric ischemia with extensive collateral circulation; however, it is limited co patients without signs of bowel compromise.

E. Nonocclusive ischemia. 1. Expedient management of cardiac events and shock states is essential. Systemic vasoconscrictors should be avoided and replaced by vasodilacors that diminish cardiac preload and afcerload when possible. 2. Pharmacologic treatment may involve selective intra-arterial infusion of papaverine into the SMA. 3. If peritoneal signs develop or abdominal pain persists despite papaverine infusion, emergent exploratory laparocomy is indicated. F. Mesenteric venous thrombosis. 1. Conservative management with bowel rest and systemic anticoagulation (heparin followed by warfarin) . 2. Percutaneous endovascular intervention with direct thrombolysis into the superior mesenteric vein (SMV) or portal vein may be indicated if systemic anticoagulation is ineffective. 3. Laparocomy is usually reserved for complications, such as bowel infarc­ tion. Management involves bowel resection and venous chrombectomy if thrombosis is localized co SMV or portal vein. SUGGESTED READI NGS

Aschoff AJ, et al. Evaluation of acute mesenteric ischemia: accuracy of biphasic mesenteric multi-detector CT angiography. Abdom Imaging 2009;34(3) :345-357. Discussion of CT angiography in diagnosing acute mesenteric ischemia. Herbert GS. Acute and chronic mesenteric ischemia. Surg Clin North Am 2007;87(5): 1 1 1 5- 1 1 34. A comprehensive review of the topic. Johnson JO. Diagnosis of acute gastrointestinal hemorrhage and acute mesenteric ischemia in the era of multi-detector row CT. Radio! Clin North Am 2 0 1 2 ; 5 0 ( 1 ) : 1 73-1 82. A comprehensive review ofacute mesenteric ischemia and discusses radiologic findings. Kougias P. Management of chronic mesenteric ischemia. The role of endovascular therapy. ] Endovasc Ther 2007; 1 4 (3):395-405 . A comprehensive review of the available series o n the endovascular treatment of chronic mesenteric ischemia. Renner P, et al. Intestinal ischemia: current treatment concepts. Langenbecks Arch Surg 20 1 1 ;396 ( 1 ) :3-1 1 . A recent comprehensive review. Wain RA. Surgical management of mesenteric occlusive disease: a contemporary review. Cardiol Rev 2008; 1 6(2) :69-75. An overview ofthe clinical and radiologic diagnosis ofacute and chronic mesenteric ischemia and their management.

C o m p a rtm e nt Syn d ro m e of th e Abd o m i n a l C a v i ty M i c h a e l S i g m a n , D i etm a r H . W ittm a n n , a n d F red A . L u c h ette

I . G E N E RAL P R I N C I PLES

A. Overview. 1. The abdominal cavity is considered as single compartment enclosed by an aponeurotic envelope with limited compliance. 2. First coined by Kron et al. in 1 984 when they described the pathophysi­ ologic changes following a ruptured abdominal aortic aneurysm. 3. Elevated intra-abdominal pressure (IAP) can impair blood flow and organ function. 4. Once critical threshold volume is reached, small increments in tissue volume lead to exponential increases in intraperitoneal pressure. Elevated IAP may result in multiorgan failure and death if not reversed promptly. B. Definitions. 1. Compartment syndrome: increased pressure in a confined anatomic space that adversely affects function and viability of tissue within the compartment. 2. Abdominal compartment syndrome (ACS) : acutely increased and sus­ tained pressure within the abdominal wall, pelvis, diaphragm, and retro­ peritoneum, adversely affecting function of organs and tissue within and adjacent to the abdominal cavity. Usually requires operative decompres­ sion of the peritoneal cavity. 3. Intra-abdominal hypertension (IAH): sustained (>6 hours) increase in IAP that may or may not require operative decompression. 4. On the basis of the consensus statement of the World Society of the Abdominal Compartment Syndrome, IAH was defined as IAP 2'. 1 2 mm Hg and ACS as a sustained IAP 2'. 20 (measured at the level of the mid-axillary line) , which is associated with new organ dysfunc­ tion or failure. Note that there is no definitive IAP at which ACS occurs. a. Normal abdominal pressure: 1 0 mm Hg. b. Grade I: 12 to 1 5 mm Hg. c. Grade II: 16 to 20 mm Hg. d. Grade III: 21 to 25 mm Hg. e. Grade IV: >25 mm Hg.

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lf;i:i!ll1fIi

Causes of Abdom i n a l Hyperte n s i o n

Periton itis, tra u m a , bu rns Fluid ove rload : h e m o rrh age or septic shock Bowel ed e m a , re perfusion i nj u ry, ac ute pa ncreatitis I ntra-a bd o m i n a l mass Ascites, i ntra-a bdom i n a l fl u i d col lection

Retroperitoneal hematoma Perito n ea l operative tra u ma l i eus, bowe l o bstruction Abdo m i na l clos u re u n d e r te nsion La pa rosco pic a bd o m i n a l i n sufflation Weight l ifti ng up to >200 mm Hg ( p hysiologic abd. hypertension)

II. PAT H O P HYS I O LOGY

A. Causes: Most IAH is caused by peritoneal, mesenteric, or retroperitoneal edema impinging on the fascia! envelope of the abdominal compartment. 1. Total surface area of peritoneum is about 1 . 8 m 2 , which is approximately equal to the entire surface area of skin. Theoretically, 1 mL of peritoneal thickening may contain 1 5 to 1 8 L of fluid. 2. Expanding edema can quickly exceed compensatory elasticity of abdom­ inal fascia and diaphragm and can lead to organ function compromise. 3. Increased venous outflow resistance results in reduction in effective per­ fusion of the capillary beds, leading to tissue ischemia and inflammatory mediator activation. B. Table 1 02- 1 lists many of the causes of IAP. I l l . D IAG N O S I S

A . Clinical presentation. 1 . The key to diagnosis includes identifying patients at risk, recognizing salient clinical features, and remaining proactive in carrying out diag­ nostic measures to confirm the diagnosis. 2. Patients typically present with a tense abdominal wall, shallow respira­ tions, low urinary output, and increased central venous pressure. 3. Physiological impairments in all systems observed. a. Cardiac: Output initially rises as a result of increased venous return from intra-abdominal veins but diminishes as pressure rises above 1 0 mm Hg. i. Decreased preload, result of pooling in lower extremities and functional narrowing of the vena cava. ii. Afterload increased and ventricular function decreased as filling pressures were negatively affected by increased IAP. b. Pulmonary: Decrease in diaphragmatic excursion resulting in atel­ ectasis, and ventilation-perfusion mismatch. Positive end-expiratory ventilation to maintain alveolar patency worsens intrathoracic pres­ sure and cardiac output.

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Renal: Impaired as a result of decreased cardiac output, compression of both renal inflow and outflow, and direct compression of kidney parenchyma; development of "renal compartment syndrome." d. Hepatic: Reduction in blood flow affecting production of acute-phase proteins, immunoglobulin, and factors of the other host defense system. e. Gastrointestinal (GI) : Splanchnic hypoperfusion possibly affecting mucosa! pH, bacterial translocation, and bowel motility. c.

B. Measurement of IAP. 1. Direct method: Inrraperitoneal catheter is connected to a pressure trans­ ducer to take direct measurements. This is the preferred method for most experimental studies. 2. Indirect method: Less invasive; relies on pressure transduction to the inferior vena cava, stomach, or, most commonly, the bladder. Transvesical technique: bladder behaves as passive diaphragm when volume is low; abdominal pressure can be measured transvesically. a. Instill no more than 25 mL of sterile saline into the empty bladder through Foley catheter. Tubing drain clamped and 1 8-gauge needle advanced through aspiration port and connected to pressure trans­ ducer or manometer. b. Recordings correlated with direct measurements in range of 5 to 70 mm Hg. IV. TREAT M E N T

A. Conservative and nonsurgical measures. 1. The best treatment for ACS is prevention. 2. Early recognition of patients at increased risk prompts the institu­ tion of early corrective/preventative measures before full-blown ACS develops. 3. Nonsurgical treatment options include the following: a. Gastric and rectal decompression. b. Sedation and neuromuscular blockade. c. Body positioning. d. Diuretics, venovenous hemofilrration/ultrafiltration. e. Paracentesis. B. Decompression. 1. Nonoperative decompression reserved for distension caused by ascites. 2. Operative decompression: Opening abdominal cavity in the operating room or intensive care unit once intravascular fluid deficits, temperature, and coagulation abnormalities are corrected. a. Postdecompression compensation has been reported: Systemic vascu­ lar resistance falls markedly after decompression, with cardiac output increases that are usually not sufficient to maintain the preinterven­ tion blood pressure. b. Careful monitoring, volume resuscitation before decompression, and judicious use of vasoconstrictors postoperatively are recommended.

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C. Closure. 1. The abdomen can be reapproximated by a variety of methods. 2. Type of closure dependent on degree of decompression; the abdomen can be reclosed when fascia can be reapproximated without undue tension. a. Vacuum-assisted closure (VAC) techniques such as the commercial Wound VAC (Kinetic Concepts, San Antonio, Texas) are now widely used. b. Synthetic fascial materials that are sutured to the fascial edges, which can be approximated slowly, offer another reliable option (Artificial Burr, Wittmann Patch) ; all meshes help to decompress the abdomen, fascial reapproximation, and final closure; however, they can be difficult. SUGGESTED READI NGS

Balogh Z, McKinley BA, Holcomb JB, et al. Both primary and secondary abdominal com­ partment syndrome can be predicted early and are harbingers of multiple organ failure. J Trauma 2003;54(5):848-859; discussion 8 5 9-86 1 . A good study that characterizes diagnosis and outcomes for compartment syndromes. Cheatham ML, Malbrain ML, Kirkpatrick A, et al. Results from the international conference on the experts on intra-abdominal hypertension and abdominal compartment syndrome: II. Recommendations. Intensive Care Med 2007;33:95 1-962. Consensus statement relating to the definition, diagnosis, and treatment ofA CS. Fabian TC. Damage control in trauma: laparotomy wound management acute to chronic. Surg Clinic North Am 2007;87:73-93. Excellent review ofissues related to management ofthe open abdomen. Garner GB, Ware DN, Cocanour CS, et al. Vacuum-assisted wound closure provides early fascia! reapproximation in trauma patients with open abdomens. Am J Surg 200 1 ; 1 82 (6):630-638 . One ofthe earliest studies to examine efficacy ofvacuum-assisted closure of the open abdomen. Luckianow GM, Ellis M, Governale D, et al. Abdominal compartment syndrome: risk factors, diagnosis, and current therapy. Crit Care Res Pract 2 0 1 2;20 1 2:908 1 69 . A current review of the latest i n epidemiology, diagnosis, and therapy ofA CS. Wittmann DH. Staged abdominal repair: development and current practice of an advanced operative technique for diffuse suppurative perironitis. Eur Surg 2000;32: 1 7 1 - 1 78 . A retrospective study showing the development ofand improved morbidity and mortality with staged laparotomy. Wittmann DH, Aprahamian C, Bergstein JM. A burr-like device ro facilitate temporary abdominal closure in planned multiple laparotomies. Eur J Surg 1 993;1 59:75. A practical technique for temporary closure ofthe abdominal wound.

N e c roti z i ng Fasc i itis and Oth e r S oft Tiss u e I nfe cti o ns Stewa rt R . Ca rte r, D a v i d H . A h re n h o l z , a n d F red A . L u c h ette

I . OVERVIEW

A. General principles. 1. Our skin functions as a barrier to infection; therefore, any break in the skin can allow bacteria to invade. 2. Risk factors for infection include trauma, edema, hematoma, ischemia, and foreign body. 3. Virulent infections are associated with impaired host defenses (i.e., diabetes, cancer, malnutrition, immunosuppression, advanced age, and major trauma) . B. Pathophysiology. 1. Group A, �-hemolytic Streptococcus pyogenes: highly virulent; cellulitis; erysipelas with demarcated borders; ecthyma contagiosum; streptococcal lymphangitis; seen in necrotizing fasciitis; exotoxins result in lymphocyte activation causing shock (toxic shock syndrome [TSS]) (see Sections II and III) . 2. Staphylococcus aureus: most common cause of skin infection; purulence; folliculitis (dermis) ; superficial abscess (soft tissue) ; carbuncle (burrow­ ing infection) ; pyomyositis (hematogenous spread to intramuscular hematoma) ; also associated with necrotizing fasciitis. Also produces TSS (see Sections II and IV) . A growing number of skin and soft tissue infec­ tions (SSTis) are the result of methicillin-resistant Staphylococcus aureus (MRSA) infection. 3. Clostridium perfringens, Clostridium novyi, Clostridium septicum, and Clostridium tertium: most common in ischemic muscle; exotoxins cause myonecrosis and sepsis (see Section V) . 4. Eikenella corrodens: human bite wounds; sensitive to cephalosporins and penicillin. 5. Pasteurella multocida: animal bites or scratches; treat with cephalosporins, penicillin, tetracycline, trimethoprim-sulfamethoxazole + clindamycin. 6. Vibrio vulnificus: aggressive disease; more common in alcoholics; due to immunologic defects; marine-related organisms; aggressive debridement and treat with doxycycline plus intravenous ceftazidime. Ciprofloxacin is alternative (see Section III) .

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7. Escherichia coli, Klebsiella: abscess of perinea! area; usually arising from infected pilonidal cyst or laceration of rectal mucosa causing a perirectal abscess; can occur in other areas; initially treat with drainage and fluoro­ quinolones when indicated. 8. Cryptococcus neoformans and other fungi can mimic cellulitis due to group A Streptococcus (see Section II) . 9. Bartone/la: Gram-negative bacteria previously classified as rickettsiae; cause several uncommon diseases: cat-scratch disease, an acute febrile anemia, a chronic cutaneous eruption, and disseminated disease in immu­ nocompromised hosts; treat with gentamicin and a second antibiotic depending on the Bartone/la species and severity of the disease process. 10. Actinomycosis: chronic localized or hematogenous infection due to Actinomyces israelii; local abscess with multiple draining sinuses; seen more commonly in adult males as cervicofacial (lumpy jaw) abscess, portal of entry is decayed teeth; treat with surgical excision followed by cephalosporins. I I . C E LLU LITIS A N D S U B C UTA N E O U S I N FECTI O N S

A . Etiology. 1 . Most common organisms: S. aureus and group A streptococci causing a diffuse curaneous infection; nonpyogenic; starts with a minor break in skin, such as an insect bite, puncture limited to skin, and subcutaneous tissues; infections spread through tissue facilitated by toxins and enzymes. 2. In the extremity: presents with lymphadenitis or lymphangitis involving dermal lymphatics. 3. High-risk cellulitis when infection involves the face or extremities of immunocompromised patients. 4. Folliculitis: nontoxic pyodermas centered in hair follicles. 5. Subcutaneous abscess (complicated cellulitis) : most common soft tissue infection. 6. Hidradenitis suppurativa: chronic burrowing infection of groin or axilla involving infected hair follicles; more commonly seen in diabetic or very obese patients. 7. Community-acquired MRSA: because of increasing cases of MRSA soft tissue infections, the distinction between community-acquired, and health care-associated MRSA is becoming less useful in guiding therapy. B. Diagnosis. 1. Presents with progressive erythema and edema; may cause tenderness over the involved area. 2. Varying diagnostic yield on cultures of tissue or aspirate; due to the emergence of MRSA, routine culture is important for guiding antimi­ crobial susceptibility. C. Treatment. 1. Uncomplicated cellulitis: treatment with antibiotics and elevation; sur­ gery not indicated unless joints or tendon sheath are involved. 2. P-lactams (penicillins, nafcillin, cephalosporins, carbapenams) , or if concern for MRSA; clindamycin, trimethoprim-sulfamethoxazole, doxycycline, minocycline, or linezolid.

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3. Abscess, furuncle, or carbuncle all require incision and drainage. 4. Complicated SSTI in hospitalized patients should be treated with intra­ venous antibiotics with empiric coverage for MRSA pending culture results; vancomycin, linezolid, telavancin, or clindamycin. D. Complications. 1. Symptoms refractory to medical management may indicate missed abscess or fluid collection; imaging can be helpful in determining depth of involvement. 2. Recurrent cellulitis of the upper extremities is most commonly seen after a modified radical mastectomy or axillary lymph node dissection; it is seen in the lower extremities after saphenous vein harvesting for coronary artery bypass grafting surgery; it is best treated with long-term antibiotics targeting group A Streptococcus. I l l . N E C ROTI Z I N G FAS C l lTIS

A. Definition. 1. A severe, progressive, and rapidly spreading infection along fascia planes with minimal cutaneous signs. 2. Typically occurs after trauma or surgery in immunocompromised patients (i.e., those with peripheral vascular disease, diabetes, or malignancy) . 3. Fournier gangrene: a rapidly spreading infection of the scrotal skin. 4. Meleney gangrene: streptococcal dermal gangrene anywhere on the body. 5. Requires prompt surgical debridement and parenteral antibiotics; if not treated aggressively, necrotizing fasciitis can result in death. B. Etiology. 1. Predisposing factors include diabetes mellitus, immune suppression, end-stage renal failure, liver cirrhosis, pulmonary diseases, malignancy, and use of injection drugs. 2. Necrotizing fasciitis (NF) has been reported after treating cellulitis with �-lactams secondary to rapid release of exotoxins. 3. Associated with hematogenous seeding of contusion after blunt trauma. 4. Infection in children is rare and is usually in the setting of Varicella zoster infection complicated by streptococcal skin infections. 5. Classified into three major types: a. Type I (80% of cases)-polymicrobial, often caused by a synergistic mixture of anaerobes, and facultative anaerobes (E. coli, Pseudomonas spp., and Bacteroides spp.); easily recognized clinically; associated with better prognosis. b. Type II (47%, highest in immunocompromised.

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C. Diagnosis. 1 . Pain out proportion to physical findings, edema, fever, and leukocytosis with a left shift. 2. Blistering, erythema, skin crepitus, and dermal necrosis are rare, but suggestive findings. 3. Streptococcal necrotizing fasciitis develops rapidly within 24 to 48 hours with typical symptoms plus tachycardia, localized erythema, edema, and watery drainage; positive blood cultures; blistering of skin, which turns dusky after cutaneous vascular thrombosis. 4. Diagnosis is made at time of surgical exploration. Plain radiographs or computed tomography scan may show gas fluid but often only show tissue edema. Magnetic resonance imaging with gadolinium can differ­ entiate necrosis from inflammatory changes. If NF is suspected, surgical exploration is mandatory and should not be delayed by imaging. D. Treatment. 1 . Immediate surgical referral improves survival; surgical debridement after fluid resuscitation; preoperative antibiotics to cover for polymicrobial infection. 2. Empiric broad-spectrum antibiotic coverage with multidrug regimens, including high-dose penicillin for group A Streptococcus, high dose clindamycin for limiting exotoxin production, and a fluoroquinolone or aminoglycoside for gram-negative coverage. Vibrio spp. are treated with doxycycline plus ceftazidime or alternatively with ciprofloxacin. 3. Due to the emergence of penicillin-resistant staphylococci, a fourth­ generation antistaphylococcal cephalosporin, with an aminoglycoside and metronidazole should be considered when MRSA is not a concern. 4. Modifications to the antibiotic regimen should be based on intraopera­ tive Gram stain and wound cultures. 5. Serial debridement with daily dressing changes; vacuum-assisted closure on clean tissue to promote wound granulation. 6. Wound can then heal by secondary intention or can be skin grafted. 7. Amputation of the extremity is sometimes necessary to control the spread of infection. 8. Intravenous (IV) immunoglobulin administration can be helpful for TSS. 9. Diverting colostomy reduces perinea! soiling but is not mandatory for Fournier gangrene. 10. Aggressive nutritional support: treatment is similar to burned patient ( 1 . 5 x basal metabolic expenditure) . 1 1 . Postsurgery hyperbaric oxygen (HBO) increases subcutaneous tissue oxygen tension and is generally accepted, although there is no definitive clinical data to support its use; HBO use should not delay debridement or amputation. E. Complications. 1 . Delayed diagnosis or incomplete debridement can result in profound sepsis and death. 2. Intra-abdominal sepsis can follow postoperative treatment of necrotizing fasciitis.

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3. Mortality ranges from 25% to 30% with worse prognosis associated with increasing age, female gender, delay of surgical intervention, elevated serum lactate, and multisystem organ failure. IV. N O N C LOSTRID IAL MYONECROSIS

A. Etiology. Same as necrotizing fasciitis; rarely Aeromonas hydrophilia or Bacillus cereus. B. Diagnosis. Similar signs and symptoms of necrotizing fasciitis; radio­ graphs show gas outlining muscles; debridement reveals muscle and fascia necrosis; differs from clostridial myonecrosis as there are mixed organisms on Gram stain and fewer systemic effects. C. Treatment. Excision of all necrotic tissue including muscle, fascia, and skin. D. Complications. Overall mortality is 76% . V. C LOSTRI D IAL MYO N E C ROS I S

A. Definition. 1. Necrotizing muscle infection often with C. perfringens exotoxins; requires debridement and sometimes amputation. 2. Gas gangrene: term describing clostridial myonecrosis; gas is seen in both clostridial abscess and nonclostridial myonecrosis. 3. Gram stain shows large number of gram-positive rods, few polymor­ phonuclear leukocytes (PMNs) are found in the exudates, and free fat globules are demonstrated with Sudan stain. B. Etiology. 1 . Can be traumatic or spontaneous in origin. 2. Traumatic clostridial myonecrosis is associated with war inj uries, farm machinery accidents, or deep tissue wounds exposed to soil organisms. Other causes include surgical manipulation, irrigation with pressure devices, injection and air, and disruption of the esophagus or trachea. 3. Can occur when a wound is inadequately debrided; contamination from gastrointestinal or biliary tract surgery with leakage of contents into soft tissue; C. perfringens is the most common toxin-producing organism. 4. Spontaneous gangrene occurs in the absence of obvious bacterial entry or contamination. Presents as a primary infection of the perineum, scrotum, or extremity. Associated with C. septicum and C. tertium. Associated with colonic lesions (e.g., neoplasms) and subsequent translocation of gut flora. C. Diagnosis. 1. Sudden onset of excruciating pain at infectious site. Rapid development of a foul-smelling wound with serosanguinous discharge and air bubbles. Woody or brawny edema gives way to cutaneous blisters with maroon-colored fluid. Necrotic tissue can advance several inches per hour with delayed treatment. 2. Severe systemic toxicities; delirium and septic shock. 3. Muscle changes from a lusterless pink to deep red then gray-green/ mottled purple; muscle does not contract on stimulation.

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4. Other causes of dermal necrosis: ischemic dermal necrosis (dry gangrene) ; ulcerating skin lesions (Meleney cutaneous gangrene) ; also seen in disseminated intravascular coagulation after septicemia (purpura fulminans) , streptococcal necrotizing fasciitis. D. Treatment. 1 . Surgical emergency: wide debridement of nonviable fascia and muscle. 2. Wound is packed open. 3. Penicillin G 12 to 20 million units/day plus clindamycin or tetracycline. Clostridium tertium is highly resistant to penicillins and clindamycin and should be treated with a tetracycline, vancomycin, or metronidazole. 4. HBO therapy may be helpful particularly in extremities, as a supplement to antibiotics and surgical exploration and excision of necrotic tissue but should not delay surgical debridement. 5. Amputation of infected limb remains the single best life-saving measure. E. Complications. Worse prognosis if hemaruria is present. V I . TOXIC S H O C K SYN D R O M E

A . Etiology. 1 . Usually exotoxin-producing strains of S. aureus and S. pyogenes. 2. Disease progression stems from a superantigen toxin that allows the nonspecific binding of major histocompatibility complex (MHC) II with T-cell receptors, resulting in polyclonal T-cell activation. 3. Staphylococcus aureus commonly colonizes skin and mucous membranes in humans. 4. Associated with use of tampons in women and complications of skin abscesses or surgery. B. Diagnosis. 1. Characterized by sudden onset of fever, chills, vomiting, diarrhea, muscle aches, and rash. 2. Diagnosis ofTSS is probable with five out of six clinical criteria present and confirmed with all six; Criteria are as follows: a. Fever �38 .9°C. b. Diffuse, macular erythrodermic rash. c. Desquamation, particularly on the palms and soles, can occur several weeks after onset of the illness. d. Hypotension. e. Mu!tisystem involvement of three or more of the following: i. Gastrointestinal-diarrhea and emesis early in illness. ii. Thrombocytopenia (platelet count :o; 1 00,000/mm 3) . iii. Central nervous system (CNS) involvement. iv. Renal failure (serum creatinine greater than two times normal) . v. Hepatic-serum total bilirubin twice the upper limit of normal. vi. Hyperemia of mucous membranes (oropharyngeal, vaginal or conjunctiva!) . f. Negative blood culture, cerebrospinal fluid (CSF) , or throat swab (blood may be positive for S. aureus) as well as a rise in titer to Rocky Mountain Spotted Fever, leptospirosis, or measles.

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3. Diagnosis of streptococcal toxic shock-like syndrome (STSS) requires isolation of group A Streptococcus from a normally sterile site (e.g., blood) , hypotension and two or more of the following: a. Renal failure (serum creatinine greater than two times normal) . b. Hepatic inflammation (alanine aminotransferase [ALT] and aspartate aminotransferase [AST] greater than two times normal) . c. Thrombocytopenia (platelet count < 1 00,000/mm 3 ) . d. Desquamation, particularly o n the palms and soles, can occur several weeks after onset of the illness. e. Soft tissue necrosis (NF, myonecrosis, or gangrene) . C. Treatment 1 . Aggressive IV fluid resuscitation, targeted antibiotics, and immuno­ modulatory therapy with Intravenous immunoglobulin (IVIG) ( 1 ,000 mg/kg day 1 and 500 mg/kg days 2 and 3). 2. Methicillin-sensitive S. aureus can be treated with nafcillin, cloxacillin, or flucloxacillin, plus clindamycin; MRSA requires vancomycin, line­ zolid, or teicoplanin, plus clindamycin. 3. STSS treatment consists of penicillin in conjunction with clindamycin. 4. With proper treatment, patients usually recover in 2 to 3 weeks. The condition can be fatal within hours. SUGG ESTED R EAD I NGS

Bryant AE, Stevens DL. Clostridial myonecrosis: new insights in pathogenesis and manage­ ment. Curr infect Dis Rep 20 1 O ; 1 2:383-3 9 1 . A review of clostridial myonecrosis. Eke N. Fournier's gangrene: a review of 1 726 cases. Br J Surg 2000;87: 7 1 8 . A review of necrotizingfasciitis ofthe perineum. Lancerotto L, Tocco I, Salmao R, et al. Necrotizing fasciitis: classification, diagnosis, and management. ] Trauma 2012;72(3) :560-566. Detailed review ofnecrotizingfasciitis, with current classification and management strategies. Miller LG. Necrotizing fasciitis caused by community associated methicillin-resistant Staphylococcus aureus in Los Angeles. N Engl J Med 2005;352: 1445-1453. A single institutions experience with community-associated MRSA causing necrotizing fosciitis. Sabitha R. Skin and soft-tissue infection: classifying and treating a spectrum. CC]M 20 1 2;79 ( 1 ) : 57-66. A review of current management ofskin and soft tissue infections, with focus on the emergence ofMRSA infection. Silversides JA, Lappin E, Ferguson AJ. Staphylococcal toxic shock syndrome: mechanisms and management. Curr Infect Dis Rep 20 1 0 ; 1 2:392-400. Diagnosis and management ofstaphylococcal toxic shock.

P ress u re U l c e rs : P reve nti o n a n d Tre atm e nt Stewa rt R . Ca rte r, Sewit A m d e , a n d Fred A . L u c h ette

I. E P I D E M I O LOGY

A. In an acute care setting, the incidence of pressure sores ranges from 7% to 9% with an associated prevalence between 1 4% and 1 7% . B. Residents i n chronic care facilities, such a s those with spinal cord injuries and patients in the intensive care units (ICUs) , are at the highest risk for the development of pressure sores. C. The development of pressure ulcers in the ICU results in increases in length of stay, morbidity, mortality, and associated health care costs. I I . PATH O P H YS I O LOGY

A. Pressure sores form as the end result of unrelieved pressure exerted on tissue overlying bony prominences; approximately 80% develop over the sacrum, coccyx, femoral trochanters, ischial tuberosities, lateral malleoli, and heels. B. Normal arterial capillary blood pressure is critically low when external pres­ sures are >32 mm Hg. Tissues overlying bony prominences are subject to this critical pressure while a patient is in the supine position. C. Prolonged exposure to ischemia results in tissue necrosis; differing tissues exhibit different sensitivities to ischemia. 1. Muscle has much poorer tolerance to pressure than does skin or subcu­ taneous tissue. 2. Muscle and subcutaneous tissue infarction without skin necrosis is the "rip of the iceberg" phenomenon. 3. Studies have shown that ischemic necrosis can be prevented with inter­ mittent restoration of blood flow. D. Risk factors associated with pressure ulcer formation in ICU patients include tissue hypoxia, hyporension, excessive moisture or perspiration, hyper-/hypothermia, malnutrition, impaired mobility and sensation, the presence of positioning devices such as restraints, braces, vests, or fixation devices, and fecal or urinary incontinence. Unrelieved pressure associated with naso- and orogastric tubes and endotracheal tubes is also a risk factor. I l l . PREVENTI O N

A. Prevention o f pressure sores begins with education and dedicated care. 872

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1. Institutions should have structured risk assessment policies and practice to identify vulnerable patient populations; risk assessment should be con­ ducted on admission and repeated as necessary, particularly when acuity increases. 2. Skin assessment and routine care should be performed to identify early signs of pressure damage; avoid massaging, friction, and turning onto body surfaces with erythema from previous episodes of pressure loading. 3. Offer high-protein mixed oral nutritional supplements and/or tube feeds in addition to an appropriate diet in individuals with malnutrition and risk for pressure ulcers. 4. Repositioning should be considered in all at-risk individuals and must take into consideration the condition of the patient and support surface in use. 5. Support surfaces used for pressure redistribution; foam mattress, air mat­ tress, low air loss beds, air-fluidized beds, and oscillating support surfaces. 6. Patients with acute traumatic injuries and a decreased level of conscious­ ness should be removed from backboards and cervical collars as soon as safely possible; careful pressure redistribution in all surgical patients, specifically during positioning prior to, during, and afrer surgery. IV. WO U N D C LASS I F I CATI O N

A. Stage I : Nonblanchable erythema of the skin with the lesion being limited to the epidermis and dermis; may be difficult to detect in individuals with dark skin tones. B. Stage II: Partial-thickness ulceration with loss of dermis; shallow open ulcer with a viable wound bed without slough; may also present as an intact or open/ruptured blister. C. Stage III: Full-thickness ulceration extending to the subcutaneous fat; may include undermining or tunneling. D. Stage IV: Full-thickness tissue loss with exposed muscle, tendon, or bone; can extend into supporting structures, making osteomyelitis or osteitis likely. V. WO U N D MANAG E M E N T

A. Management strategies entail identification, debridement, wound dress­ ings, pressure dispersion, and maximization of overall health status. 1. Most stage I and II ulcers respond well to these measures. 2. Stage III and IV ulcers may require sharp or enzymatic debridement; moist dressings are recommended to provide an optimal wound environ­ ment for healing exposed tissue. 3. Data concerning the use of negative-pressure wound therapy in the management of pressure ulcers are inconclusive, although some studies have documented success. 4. An occlusive hydrocolloid dressing can be used as an alternative in a well-debrided wound with minimal dead space. 5. Deeper ulcers also respond to the use of air-fluidized pressure dispersion mattresses. 6. Optimize nutrition; supplementation of vitamin C and fish oils both have shown benefit in healing pressure ulcers.

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B. With appropriate care, up to 80% of pressure sores heal without surgery. C. Operative treatment is reserved for patients with wounds showing poor healing despite maximal conservative therapy. 1. Surgery is less frequently required in the ambulatory patient. 2. Spasticiry must be medically addressed as part of treatment for pressure ulcer in spinal cord-injured patients. 3. Devitalized tissue is removed, and, if necessary, bony prominences are partially reduced. 4. A variery of musculocutaneous or fasciocutaneous advancement flaps are used to achieve closure, depending on the wound location. 5. Care is taken to avoid hematoma formation and tension on the closure. 6. Complications of flap creation include infection, wound dehiscence, skin necrosis, hematoma, seroma, and bursa formation. D. Postoperatively, it is critical to avoid compression on the flap vascular pedicle and minimize tension or shearing forces. 1. A special air or fluid mattress is important for the first 3 weeks. 2. Gradually, a program of weight bearing is used for the following 6 to 8 weeks. 3. The greatest challenge is to minimize future risks of pressure sore devel­ opment. SUGGESTED READI NGS

Levine SM, Sinno S, Levine JP, et al. An evidence-based approach ro the surgical management of pressure ulcers. Ann Plast Surg 20 1 2;69(4):482-484. An evidence-based approach at examining current techniques in the management of pressure ulcers. National Pressure Ulcer Advisory Panel and European Pressure Ulcer Advisory Panel. Pressure ulcer treatment: technical report. Washingron, DC: National Pressure Ulcer Advisory Panel; 2009. Available at www.npuap.org. Accessed Ocrober 22, 2 012. The government's approach to pressure ulcer management with usefal statistics. Reilly EF, Karkousis GC, Schrag SP, et al. Pressure ulcers in the intensive care unit: the "forgotten" enemy. OPUS 12 Scientist 200 7 ; l (2) : l 7-30. Comprehensive review ofpressure ulcers in the critical care setting. Rubayi S, Chandrasekhar BS. Trunk, abdomen, and pressure sore reconstruction. PRS] 20 1 1 1 2 8 (3):20 l e-2 1 5e. Detailed description ofoperative management ofpressure ulcers, including preoperative and postoperative care. Theilla M, Schwartz B, Cohen ], et al. Impact of a nutritional formula enriched in fish oil and micronutrients on pressure ulcers in critical care patients. Am J Crit Care 20 1 2; 2 1 (4) :el 02-e l 09. Prospective randomized controlled study showing that supplementation with fish oil-enrichedformula may slow progression ofpressure ulcers in critical care patients. Ubbink D, Westerbos S. Topical negative pressure for treating chronic wounds. Cochrane Database Syst Rev 20 1 1 ;3:CD00 1 898. Examines the role of negative pressure therapy in the setting of chronic nonhealing wounds.

Pa i n M a n a ge m e nt i n th e C r it i c a l ly I l l J e n n ife r K . P l i c h ta , D o n a l d S . Steve n s , a n d F red A . L u c h ette

I . OVERVIEW

A. Pain, discomfort, restlessness, and agitation are major problems for critically ill patients. B. The ideal strategy aims to manage patient pain and discomfort first, before providing sedative therapy, often resulting in improved patient outcomes. C. Pain may be under-treated, as a result of avoiding depressing spontaneous ventilation, inducing opioid dependence, and precipitating cardiovascular instability. D. Appropriate pain resolution facilitates recovery. E . Pain and anxiety are difficult ro measure, because they constitute subjective phenomena. The clinician should not judge the appropriateness of pain, but rather concentrate on managing it appropriately. I I . G E N E RAL P R I N C I PLES

A. Identify the etiology of pain. B. Determine a baseline before starting treatment, and assess the degree of pain in an objective manner with the help of validated scales and instruments. C. Understand other potential contributing factors such as anxiety, ethnocul­ tural facrors, situational meaning, and prior experience. D. Establish and maintain drug levels for appropriate analgesia and anxiolysis, and determine the end point of treatment. E. Understand that therapy is an iterative process in which measurements are made, therapeutic actions are taken, effectiveness is reevaluated, and action is repeated until the desired clinical outcome is reached. I l l . D E F I N ITI O N S A N D PATH O G E N E S I S

A. Pain i s a n unpleasant sensory and emotional experience that can b e associ­ ated with actual or potential tissue damage. B. Pain-related behavior is the only manifestation that can make the observer conclude that pain is being experienced. C. Acute pain has an identifiable temporal and causal relationship to an injury, in contrast to chronic pain that persists beyond the healing process and may not have an identifiable cause. D. Nociception is the detection and signaling of the presence of a noxious stimulus. 875

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E. Pathophysiology of pain. 1. Acute pain begins with damage to the skin or other innervated tissues. 2. Locally produced and released mediators (prostaglandins, small pep­ tides) sensitize or stimulate peripheral nociceptors, whose fibers propa­ gate the signal into the dorsal horn of the spinal cord or the sensory nuclei in the brainstem. 3. Before reaching pain-specific areas in deep brain structures or the cortex, the signal is modulated (amplified or attenuated) that can increase or decrease the response to painful stimuli. IV. D IAG N O S I S

A . Location: I t should be determined whether the location i s consistent with the type of injury sustained or the surgery performed, or whether it is entirely different. 1. Look for unrecognized sources of pain, such as missed or new injuries. 2. Pain can be chronic, neuropathic, or a result of malpositioning during surgery. 3. Medication selection and dosages may be influenced by a history of chronic pain, medication usage, sleep disturbance, fatigue, arthritis, alcohol or other substance abuse, and psychiatric illness. B. Intensity: Visual or verbal analog scales aid in quantifying a patient's pain, thereby providing a baseline for the evaluation of the response to treatment. 1. The most widely used scale is the visual analog scale (VAS) , where a spec­ trum of pain from "no pain" to "the worst pain I've ever had" is depicted as a scale from 0 to 1 0. 2. In patients who are unable to communicate (e.g., intubated) , markers of sympathetic activity such as restlessness, sweating, tachycardia, lacrima­ tion, pupillary dilation, and hypertension can be graded as signs of pain intensity. 3. It is important to identify reliable and valid tools for evaluating pain in the noncommunicative patient in the ICU. Parameters such as facial expression, upper limb movement, compliance with mechanical ventila­ tion, among others, may be important factors that can help determine if the patient is experiencing pain. C. Quality of sensation: Pain can be sharp if it is due to direct nociception (e.g., incision) , dull or aching if it arises from deeper structures, or pulling or tugging in nature if it is related to the presence of sutures or visceral stimulation. 1 . Pain manifested as tingling, stinging, or buzzing sensations is usually related to abnormal neural function, secondary to either recovery from regional anesthesia or reestablishment of neural function after neural compression. 2. Painful dysesthesias may occur in conjunction with peripheral neuropathy.

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D. Confounder: Delirium. 1 . A transient disorder of attention and cognition resulting in intermittent agitation, hallucinations, disruptive behavior. 2. Common in critically ill patients. 3. Identify the type and potential cause (e.g., induced by sedative or anal­ gesic medications) . E. Assessment and reassessment. 1. Patient-focused sedation and analgesia stress the importance of indi­ vidual assessment of patients and periodic reevaluation. 2. Identify all therapeutic interventions and measures that may be causing or contributing to pain-related distress (e.g., suctioning, intubation, nasogastric tubes, phlebotomy, or placement of invasive lines) . F. Monitoring the degree of sedation. 1 . Successful sedation protocols. a. Frequently assess pain, anxiety, and agitation using a reproducible scale. b. Utilize combination therapies coupling opioids and sedatives. c. Encourage careful communication between team members. 2. Two broad categories of sedation protocols: a. Patient-targeted sedation protocols rely on structured assessments to carefully guide drug titrations. b. Daily interruptions of continuous sedative infusions may be employed to focus care providers on the goal of achieving a period of awakening in the earliest phases of critical illness possible. 3. Several numerical scales have been developed to help guide the appropriate dosage of analgesic/sedative medication based on the depth of sedation. a. The most popular is the 6-point Ramsay Scale (RS)-based on motor responsiveness, ranging from 1 anxious or restless or both, to 6 no response to stimulus; demonstrates excellent interrater reliability. b. Other scales include the Sedation-Agitation Scale (SAS), Richmond Agitation-Sedation Scale (RASS), Glasgow Coma Scale (GCS) , and the Motor Activity Assessment Scale. 4. More sophisticated monitoring techniques currently being used in the operating room, like the bispectral index (BIS) , provide objective data based on cortical and subcortical interactions, are still being investigated. =

=

V. TREAT M E N T

A. Peripheral analgesia: nonsteroidal anti-inflammatory drugs (NSAIDs) , local anesthetic infiltration, and peripheral nerve blockade. 1. NSAIDs-achieve analgesia through nonselective, competitive inhibi­ tion of cyclooxygenase (COX) , thereby interfering with the production of prostaglandins and other mediators of the inflammatory cascade. 2. Ketorolac-shown to provide additional analgesia when used in con­ junction with opioid analgesics without compromising respiratory drive. a. Adverse effects: nausea, peptic ulceration, and inhibition of platelet function.

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b. Severe bronchospasm can occur in patients with asthma, nasal polyposis, or an allergy to NSAIDs. c . Contraindicated in acute or chronic renal failure and in the presence of hypovolemia; should not be given for >5 days; renal function should always be monitored. 3. Local infiltration with anesthetics. a. Useful in the management of postoperative pain. b. Analgesic effect persists for at least 48 hours. c. Prolonged effect is termed preemptive analgesia, and was shown to be superior to spinal or general anesthesia in the control of postoperative pain after hernia repair. 4. Repeated intermittent intercostal nerve blocks have been used to provide analgesia for thoracic injuries and surgery. a. Nerve blocks provide analgesia without sedation or respiratory depression. b. The need for repeated injections, the risk for pneumothorax, and the risk for systemic toxicity are disadvantages of this procedure. 5. Paravertebral nerve blockade provides analgesia over several dermatomes by bathing multiple intercostal nerves with an anesthetic via a single injection or continuous infusion through a catheter. 6. lntrapleural analgesia with bupivacaine is useful for analgesia in the thorax and upper abdomen. a. Unfortunately, this technique loses effectiveness in the presence of a thoracostomy tube (anesthetic is drained out of the pleural space) or if the pain is bilateral (increased absorption and toxicity, and bilateral sympathetic blockade) . b. Contraindications to this technique include fibrosis of the pleura, inflammation/infection with or without blood or fluid in the pleural space, and anticoagulation or infection at the site of injection. 7. Other regional blocks include brachia! plexus blocks and femoral nerve or lumbar plexus blocks for the upper and lower extremities. B. Spinal cord analgesia: transcutaneous electrical nerve stimulation (TENS) and epidural and intrathecal infusions of local anesthetics or opioids. 1. TENS utilizes high frequency (80 to 1 00 Hz) , low-intensity stimulation through sterile skin electrodes, in combination with other methods of analgesia. a. Down-modulates the afferent nociceptive signal at the spinal cord and brainstem levels, thereby controlling postoperative (peri-incisional) pain. b. Associated with reduced rates of complications (nausea, vomiting, atelectasis, ileus) . 2. Afferent conduction can be blocked at the nerve root or spinal cord level with local anesthetics; nociceptive signals can be centrally down­ modulated by intraspinal opioids acting on specific opioid receptors in the dorsal horn. 3. Regional analgesic techniques include subarachnoid and epidural administration of local anesthetics, opioids, or mixtures thereof, with intermittent dosing or continuous infusion.

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Continuous subarachnoid analgesia with local anesthetics can be used to manage postoperative pain. It requires continuous bedside moni­ toring because of the potential for profound sympathectomy and hemodynamic instability. It has been associated with central nervous system infection, but current techniques are safe for at least 48 hours. b. Continuous epidural infusion of local anesthetics allows for prolonged analgesia, although frequently associated with hypotension due to sym­ pathetic blockade. This side effect can usually be managed with intra­ vascular volume expansion or small doses of an a-adrenergic agent. c. The opioid most commonly used for epidural blockade is morphine, which, because of its low lipid solubility, tends to stay dissolved in the cerebrospinal fluid. Systemic absorption and rostral spread may be responsible for adverse effects such as nausea, prurirus, urinary retention, and respiratory depression (usually preceded by progres­ sive sedation rather than decreased respiratory rate) . Naloxone can be used to treat significant respiratory depression. Epidural catheters usually remain in place for at least 2 to 3 days; may remain in place indefinitely, as long as there are no signs of infection or inflamma­ tion. Combinations of local anesthetics with opioids for continuous epidural infusion often result in fewer side effects and increased effectiveness in postoperative pain management. a.

C. Inhalational anesthetic agents have a limited role in critically ill patients. 1. Useful during short, painful procedures such as dressing changes in burn patients. 2. Complications may result from prolonged exposure, such as toxicity and bone marrow suppression. D. Sedatives (such as benzodiazepines, barbiturates, phenothiazines, and butyro­ phenones) are given in conjunction with opioids and are used for anxiolysis, sedation, and production of amnesia. 1. Potential for depressing consciousness and respiratory effort. 2. Useful in patients who need prolonged mechanical ventilation or require sedation for the first 24 to 48 hours postoperatively. V I . DOS I N G

A. Systemic opioid analgesia. 1. Limited use in ICU patients due to extreme delay in attaining therapeutic levels. 2. Typically given as IV, IM, or SC injections; small IV doses are most effective. 3. An alternative is the use of a transdermal fentanyl patch. a. They have various rates of delivery and have a delayed onset of action of 1 2 to 1 6 hours. b. Potential complications arise from choosing the wrong dose, particu­ larly in opioid-nai:ve patients. c. Side effects may gradually worsen and persist longer than expected, depending on skin blood flow.

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B. Continuous IV infusion of opioids is a relatively simple technique, as long as the loading dose and the rate of infusion are calculated correctly to main­ tain therapeutic levels. 1. Most opioids have a half-life of 3 hours. 2. The dose required to maintain a level of analgesia is one-half the loading dose used to achieve analgesia in the first place. 3. This maintenance dose is divided by 3 to calculate the hourly requirements. 4. When patients experience breakthrough pain, it must be addressed as new-onset pain and the new infusion rate titrated to effect. C. Patient-controlled analgesia (PCA) administers small doses of an opioid IV on a demand basis. 1. When establishing the upper limit for PCA ( 1 - to 4-hour dosage limit) , a temporary fivefold increase in need during the early postoperative period must be considered, from what was originally calculated for an hourly requirement. 2. Maintenance doses should generally not exceed 0.02 mg of morphine per kg, or 1 . 5 mg per dose in most adults. 3. The lockout interval (5 to 1 0 minutes) accounts for the time required for an adequate concentration of the opioid to be established at the active site before another dose is given. 4. PCA is useful for maintaining established analgesia but not for establish­ ing it in the first place. 5. Most patients actually choose not to eliminate pain entirely. 6. Overdose with PCA is rare because patients tend to titrate themselves into the therapeutic range. Overdose is a significant risk if a basal infu­ sion rate is administered. 7. Accumulation tends to occur if the rate is set too high. 8. Basal rates should not exceed half the estimated hourly requirement. 9. Lack of adequate analgesia results from inadequate dosing secondary to the patient failing to understand the technique, equipment malfunction, or programming errors. 10. An unusual problem is parent- or spouse-controlled PCA. 1 1 . PCA requires that patients are awake and cooperative. 12. PCA has also been used to give epidural medications (patient-controlled epidural analgesia [PCEA] ) with considerable safety and efficacy. V I I . S E LECTION O F D R U G S

A. Analgesics. 1. Morphine. a. First-line opioid recommended for use in the ICU. b. Hydrophilic, delayed peak affect; causes histamine release, venodila­ tion, and a decrease in heart rate. c. Significant dosing variability related to tolerance and metabolic and excretory ability. d. Adverse effects include respiratory depression, nausea, ileus/ constipa­ tion, spasm, pruritus, and contraction of the sphincter of Oddi.

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Renal impairment may cause accumulation of morphine-6glucuronide (a potent analgesic with 20 to 40 times the activity of morphine) , making it a suboptimal analgesic in critically ill patients.

2. Fentanyl. a. Good choice for patients with hemodynamic instability or in patients with morphine allergy. b. 80 to 1 0 0 times more potent than morphine and has a short duration of action when administered in small doses. c. Fat-soluble, synthetic opioid undergoes hepatic metabolism. d. Continuous infusions may lead to accumulation and prolonged drug effects. 3. Remifentanil. a. Fat-soluble, short-acting opioid. b. Metabolized by nonspecific blood and tissue esterases and undergoes rapid metabolism; independent of the duration of infusion or any organ insufficiency. c. Can be used for analgesia and sedation in all kinds of adult ICU patients. d. Results in rapid and predictable offset of effect, with subsequent reduction in weaning and extubation times. 4. Hydromorphone. a. Approximately 5 to 10 times more potent than morphine. b. Minimal hemodynamic effects. 5. Methadone. a. Synthetic opioid that can be given enterally or parenterally. b. Drug of choice in patients who have prolonged mechanical ventila­ tion requirements and recovery times. c. Also used to wean patients off infusions of other opioid analgesics. 6. Ketamine is a short-acting phencyclidine compound that can be used for short, painful procedures, such as dressing changes in the burn ICU. B. Sedatives. 1 . Lorazepam is the preferred agent for the prolonged treatment of anxiety in the critically ill adult. a. Effects are similar to diazepam bur is 5 to 1 0 times more potent. b. Onset of action is relatively slow, but it is longer acting. c. Administered with propylene glycol, which makes it precipitate in IV lines and can cause metabolic acidosis and acute tubular necrosis. 2. Midazolam is a short-acting benzodiazepine that has a short duration of action. a. Frequently combined with propofol and used for short-term treatment of anxiety in the critically ill adult. b. Also used for patients requiring prolonged ventilatory support in the ICU. c. Can cause hypotension and respiratory depression. 3. Diazepam is a weaker alternative that can be used in patients with prolonged hospital courses and recovery times.

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4. Propofol is a lipid-soluble alkylphenol that is prepared as a lipid infusion and has excellent sedative and hypnotic effects. a. Does not provide analgesia. b. Mechanism of action not completely understood. c. Rapid levels of sedation can be quickly achieved and controlled. d. Discontinuation leads to rapid recovery, which makes it a popular choice for general anesthesia induction and maintenance. 5. Haloperidol is used to treat delirium in the ICU. a . Potential for causing arrhythmias, lowering seizure thresholds, and causing extrapyramidal reactions. V I I I . C O M PLICATI O N S

A . Under-treated pain and anxiety can lead t o complications secondary to physiologic responses. B. Constant stimulation of the autonomic nervous system and the release of humoral factors as a part of the stress response to injury, infection/sepsis, or surgery can lead to hemodynamic instability and increased demands on the heart, with ensuing myocardial ischemia or even infarction. C. The stress response also causes insulin resistance, increased metabolic rate and protein catabolism, together with immunosuppression. D. Adequate pain management can curb these once-considered physiologic responses and accelerate recovery after surgery or trauma. SUGGESTED READI NGS

Devabhakthuni S, Armahizer MJ, Dasta JK, et al. Analgosedation: a paradigm shift in intensive care unit sedation practice. Ann Pharmacother 20 1 2;46(4) :530-540. A review of randomized controls trials examining ICU sedation in criticallJ ill mechanicallJ ventilatedpatients Gommers D, Bakker J. Medications for analgesia and sedation in the intensive care unit: an overview. Crit Care 2008 ; 1 2 (Suppl 3):S4. An overview and discussion ofprotocols and agents usedfor analgesia and sedation in criticallJ ill patients. Jacobi J, Fraser G, Coursin D, et al. Clinical practice guidelines for the sustained use of seda­ tives and analgesics in the critically ill adult. Crit Care Med 2002;30: 1 1 9- 1 4 1 . This article provides guidelines for drug selection and use ofsedative and analgesic drips in the criticallJ ill patient. Liu L, Gropper M. Postoperative analgesia and sedation in the adult intensive care unit: a guide to drug selection. Drugs 2003;63:755-767. This article provides a comprehensive set ofguidelines on postoperative pain management. Schweickert WD, Kress JP. Strategies to optimize analgesia and sedation. Crit Care 2008; 1 2 (Suppl 3):S6. A comparison ofpatient-targeted sedation protocols, dairy interruptions ofcontinuous sedative infosion protocols, and intermittent drug administration protocols. Sessler CN, Grap MJ, Ramsay MA. Evaluating and monitoring analgesia and sedation in the intensive care unit. Crit Care 2008; 1 2 (Suppl 3):S2. Reviews ofanalgesia and sedation evaluation schemes.

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Sessler C, Varney K. Patient-focused sedation and analgesia in the ICU. Chest 2008 ; 1 33: 5 52-565. A review ofstrategies for optimizing analgesia and sedation in ICU patients, including an interdisciplinary approach, appropriate medication selection, frequent monitoring, and the use ofvalidated tools and protocols. Wilhelm W, Kreuer S. The place for short-acting opioids: special emphasis on remifentanil. Crit Care 2008 ; 1 2 (Suppl 3):S5. These articles provide a focused approach on pain management in critically ill patients.

M a n a ge m e nt of th e Obstet r i c a l Pat i e nt i n th e I nte n s ive C a re S ett i n g M i c h a e l S i g m a n , N oa h B . R i n d os , a n d J o h n G . G i a n o po u los

I . OVERV I EW

A. General principles. 1. Maternal physiologic adaptation to pregnancy. a. Cardiovascular. i. Increased: cardiac output, blood volume. ii. Decreased: peripheral vascular resistance. b. Respiratory. i. Increased: tidal volume and respiratory rare. ii. Decreased: total lung capacity and functional residual capacity. iii. No change: pulmonary artery pressure. c. Hematologic. i. Increased: blood volume, pH, coagulability. ii. Decreased: hemarocrir. d. Renal. i. Increased: renal artery perfusion, glomerular filrrarion rare (GFR) , creatinine clearance, renal clearance of medications, and risk of urinary tract infection (UTI) . ii. Decreased: blood urea nitrogen (BUN) , serum creatinine, and serum uric acid. e. Gasrroinresinal. i. Increased: gastroesophageal reflux and risk of aspiration with intubation ii. Decreased: motility and LES pressure. 2. Diagnostic radiation exposure. a. Ultrasound and MRI are preferred to imaging that involves ionizing radiation. b. There is a small risk of carcinogenesis in ionizing radiation at all gestational ages. c. After the first 14 days, radiation exposure over 0.5 Gy may be asso­ ciated with an increased risk of congenital malformations, growth restriction, and intellectual disability. d. Abdominal/pelvic shielding should be used when possible. e. Single-exposure films minimize radiation/risk to rhe fetus.

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f. Computed tomography (CT) delivers radiation that is likely too low in dose to cause significant teratogenesis, however, should be avoided due to increased risk of carcinogenesis. 3. Medications and pregnancy. a. Analgesics. i. Short courses of opiates are tolerated. ii. Codeine is teratogenic in the first 1 2 weeks. b. Nonsteroidal antiinflammatory drugs (NSAIDs) : are generally avoided due to possible premature closure of the ductus arteriosus. Short courses can be given in the second trimester to treat pain but are contraindicated in the third trimester. c. Antibiotics. i. No known fetal effect: penicillins, cephalosporins, erythromycin, clindamycin, and vancomycin. ii. Streptomycin and kanamycin: fetal ototoxicity. iii. Gentamicin can be used if necessary; monitor levels closely. iv. Sulfonamides should be avoided in third trimester-associated with kernicterus. v. Tetracycline is teratogenic. vi. Fluoroquinolones are contraindicated throughout pregnancy due to effects on cartilage development. d. Anticoagulants. i. Coumadin: teratogenic in first trimester, later it carries risk of fetal bleeding. ii. Heparin: does not cross placenta and is the anticoagulant of choice. iii. Low molecular weight heparin: safe, change to unfractionated in third trimester-low molecular weight heparin associated with epidural hematoma with regional anesthesia. e. Antihypertensives. i. Avoid angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers-associated with fetal renal dys­ function and oligohydramnios. ii. Sodium nitroprusside can lead to fetal thiocyanide poisoning. iii. Hydralazine and labetalol are the first line IV medications in pregnancy. iv. Any patient with elevated blood pressure should be evaluated for preeclampsia by sending a 24-hour urine collection, checking platelets ALT and AST (see section II below) . f. Pressors. i. Because ephedrine, which has alpha- and beta-stimulating effects, tends to preserve uterine blood flow while reversing systemic hypo­ tension, it may be the preferred pressor to try first. Phenylephrine has been used alone and in combination with ephedrine to reverse maternal hypotension with epidural anesthesia. ii. Be aware that predominantly alpha-adrenergic agents improve maternal blood pressure but decrease uterine blood flow due to uterine artery vasoconstriction.

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g.

Tocolytics. i. Multiple classes: �-adrenergic, NSAID, calcium channel blockers, magnesium sulfate. ii. Limited efficacy, only used to gain 48 hours of additional preg­ nancy for the administration of betamethasone for fetal pulmo­ nary development. iii. All have been associated with maternal pulmonary edema-use continuous pulse oximetry, avoid multiple agents as these increase the risk, treat with diuretics and supplemental oxygen, intubation or noninvasive ventilation.

I I . HYPERTE N S IVE D I S O RD E RS O F PREG NANCY CPREECLA M PS IA)

A. General principles: 8% to 1 0% of pregnancies. Leading cause of obstetric morbidity/mortality. B. Classification: chronic, gestational, preeclampsia/eclampsia, chronic with superimposed preeclampsia. C. Etiology: unknown. D. Pathophysiology: arteriolar vasospasm with intravascular volume depletion is the primary pathophysiologic alteration in preeclampsia. 1. Peripheral vascular resistance increases -7 hypertension (HTN) -7 proteinuria. 2. Decreased albumin in blood -7 decreased oncotic pressure. E. Diagnosis. 1. Mild: sustained blood pressure > 1 40 mm Hg systolic and/or 90 mm Hg diastolic developing after 20 weeks' gestation and proteinuria (>300 mg in a 24-hour collection) . 2. Severe: one or more of the following: blood pressure > 1 60 mm Hg systolic and/or 1 00 mm Hg diastolic (twice/6 hours apart) ; > 5 g protein­ uria; 500 mL (vaginal delivery) or 1 ,000 mL (cesarean section) , palpate for uterine tone, explore for retained placenra, examine for laceration, lab studies for clotting time. E. Treatment. 1. Previa: bed rest, blood replacemenr, hospitalization near term and cesar­ ean section. 2. Abruption: IV fluid and blood products, Kleihaur-Berke (a test for fetal hemoglobin in the maternal circulation) to assess for fetal maternal hemorrhage, delivery at term, expectant managemenr and steroids if stable and remote from term. 3. Postpartum: uterine massage, urerotonics (pitocin, methergine [conrra­ indicated with HTN] , prosraglandins) , uterine curettage, and repair of any lacerations. 4. Rhogam given to Rh negative, anribody negative women within 48 hours of delivery if they deliver an Rh-positive baby. Rhogam should be given to all women who have Rh-negative blood with any vaginal bleeding and also at 28 weeks. F. Complications: feral loss, placenral accreta (growth inro the myomerrium) , hysterectomy, and maternal hypotension with cerebral ischemia. IV. AM N I OT I C FLU I D E M B O L I S M

A. General principles: sudden and acute cardiovascular and respiratory collapse at or around the rime of delivery. B. Etiology: enrry of amniotic fluid inro maternal circulation. C. Pathogenesis: unknown. D. Diagnosis: primarily clinical diagnosis of exclusion. Feral squamous cells may be presenr in the maternal blood. E. Treatmenr: early intubation and ventilation, inotropic and vasoconsrrictive agenrs, invasive right-sided cardiac monitoring. F. Complications: maternal death (>50%), disseminated inrravascular coagu­ lation (DIC) .

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V. HEMOLYTIC UREMIC SYN DROM E/TH ROM BOTIC THRO M BOCYTOPENIC P U R P U RA

A. General principles: rare in pregnancy, can be mistaken for preeclampsia. B. Diagnosis. 1. Hemolytic uremic syndrome (HUS) : renal failure, thrombocytopenia, and hemolysis. 2. Thrombotic thrombocytopenic purpura (TTP) : renal failure, thrombo­ cytopenia, hemolysis, fever, and neurologic changes usually associated with lack of function of the enzyme ADAMTS 1 3 . C . Treatment: high-dose I V steroids, plasmapheresis. D. Complications: bleeding and maternal mortality. V I . B U R N I NJ U R I ES

A. General principles: pregnancy does not alter the acute management of the burn victim. Fetal loss rate is correlated with severity of burn and develop­ ment of complications. B. Treatment: if remote from term-steroids for fetal lung maturity. If preterm labor and 50%, then loss approaches 1 00%. VII. TRA U M A

General principles: most common cause o f maternal and fetal death i n preg­ nancy. Maternal physiology may delay the manifestations of shock. Uterus is particularly susceptible to blunt and penetrating trauma in the third trimester. Fetal compromise may occur early after trauma. When evaluating hypotension, place the pregnant patient in lefi: lateral decubitus position to optimize blood return from the lower extremities and minimize uterine compression of the NC. B. Treatment.

A.

1. Blunt trauma: fetal assessment using ultrasound and continuous fetal monitoring (4-hour minimum, longer if abdominal pain, vaginal bleeding, or contractions) . Kleihaur-Betke (fetal maternal hemorrhage) . Rh immu­ noglobulin for Rh-negative mothers. Treat maternal injuries appropriately. 2. Penetrating trauma: uterus protects other maternal abdominal organs. Fetal injury is common in abdominal penetrating injury (66%) with high fetal mortality (40% to 70%) . Management is controversial. Most advocate surgical exploration, but conservative management (imaging/ observation) may be considered. C. Complications: abruption, fetal compromise or demise, and fetal injury. D. Any woman who is at 24 weeks or greater gestation should have a prompt evaluation by the obstetrical team. Women who are pregnant should receive the same level of care that a nonpregnant woman would receive­ remember that the fetus poorly tolerates maternal death.

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See Chapter 44 for other causes of acute respiratory failure in pregnancy and Chapter 89 for discussion of the HELLP syndrome. SUGG ESTED R EA D I NGS

American College of Obstetrics and Gynecology Committee.

http ://www. acog.org/

Resources_And_Publicarions/Committee_Opinions/Committee_on_Obstetric_ Practice/Guidelines_for_Diagnostic_lmaging_During_Pregnancy

This is the official ACOG Committee opinion on the guidelines for diagnostic imaging in pregnancy. It was last reaffirmed in 2009. Briggs GG, Freeman RK, Yaffe SJ, et al. Drugs in pregnancy and lactation: a reference guide to fetal and neonatal risk. Baltimore: Lippincott Williams & Wilkins, 2005 . Excellent reference for medication use in pregnancy. Condous GS, Arulkumaran S. Medical and conservative surgical management of postpartum hemorrhage. J Obstet Gynaecol Can 2003;25 ( 1 1 ) :9 3 1 -936. Review ofthe diagnosis and management ofpostpartum hemorrhage. Foley MR, Strong TH Jr, Garite TJ. Obstetric intensive care manual. New York: McGraw-Hill, 2004. Excellent quick reference for critically ill obstetric patients. Gilmore DA, Wakins J, Secrest J, et al. Anaphylactoid syndrome of pregnancy: a review of the literature with latest management and outcome data. AANA J 2003;7 l : 1 20. This is a comprehensive review of the current understanding ofamniotic fluid embolism. Guo SS, Greenspoon JS, Kahn AM. Management of burn injuries during pregnancy. Burns 200 1 ;27(4) :394-397. Excellent overview of management of burn injury with respect to pregnancy. The Magpie Trial Collaborative Group. Do women with preeclampsia, and their babies, benefit from magnesium sulfate? The Magpie Trial: a randomized placebo controlled trial. Lancet 2002;3 5 9 : 1 877. This is the article that definitively established magnesium sulfate as the therapy ofchoice for preventing and treating seizures in preeclampsialeclampsia. Pearlman M, Tintinalli J, Lorenz R. A prospective controlled study of outcome after trauma during pregnancy. Am ] Obstet Gynecol 1 990; 1 62 : 1 502. Good prospective study on the effect of trauma on pregnancy outcomes.

S h o c k: An Ove rv i ew Kev i n M . Dwye r a n d Ti m othy

A . E m h off

I . G E N E RAL P R I N C I PLES

A. Definition. 1. Shock is a defined as inadequate end-organ perfusion that, left to itself, will result in anaerobic metabolism and ultimately end-organ failure and death. 2. A momentary pause in the act ofdeath. R Adams Cowley. B. Description. 1. Perfusion may be decreased systemically with obvious signs such as hypotension and tachycardia. 2. Perfusion may be decreased because of maldistribution as in septic shock, where systemic perfusion may appear elevated but ineffective. 3. Malperfusion may be isolated, leading to single-system failure such as in thrombotic or occlusive disease of the gastrointestinal (GI) tract or extremity. 4. Prognosis is determined by age, degree of shock, duration of shock, number of organs affected, previous organ dysfunction, precipitating factors, and genetic predisposition. II. ETIOLOGY C LAS S I F I CAT I O N O F S H O CK

A. Hypovolemic shock. 1 . Initial loss of circulating intravascular volume results in decrease in car­ diac preload, increase in afterload (vasoconstriction) . 890

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Classification of Hypovo l e m i c Shock Hypovo l e m i c shock (based o n a 70-kg patie nt)

Class I

C l ass I I

Class I l l

Class I V

B l ood loss ( m l) B l ood vo l u m e ( % ) P u lse rate BP Ca p i l l a ry refi l l Res p i rato ry rate U ri n a ry output ( m Uh ) M e nta l status F l u i d re placement

U p to 750 U p to 15 < 1 00 Normal Normal Normal >30 M i ld a nxiety C rysta l loid

750- 1 , 500 1 5-30 > 1 00 Normal Decreased 20-30 20-30 Anxiety Crysta l loid

1 , 500-2 , 000 30-40 > 1 20 Decreased Decreased 30-40 5-1 5 Confu sed C rysta l loid + blood

>2,000 >40 > 1 40 Decreased Decreased Distress 1 0 units packed red blood cells [PRBCs] in 24 hours) , transfusing fresh frozen plasma (FFP) and blood in a 1 : 1 ratio while minimizing the use of crystalloids has been shown to have a clear survival benefit in trauma. Concomitant hemorrhage control is key to a successful resuscitation. Colloid infusion (albumin) has no value in the initial resuscitation of hypovolemic shock. B. Obstructive shock. 1. Caused by a mechanical obstruction to normal cardiac output (CO) with a decrease in systemic perfusion. 2. Frequent causes: cardiac tamponade and tension pneumothorax. a. Clinical signs. i. Jugular venous distension. ii. Tachycardia. iii. Hypotension.

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b. Ultrasound exam can quickly confirm pericardial fluid (tamponade) or pneumothorax (tension pneumothorax) . 3. Other causes are massive venous thromboembolism and air embolism. 4. Treatment is maximizing preload (isotonic crystalloids) and relief of the obstruction. C. Cardiogenic shock. 1. Caused by myocardial (pump) failure. 2. Most common cause is extensive myocardial infarction. 3. Other causes are reduced contractiliry (cardiomyopathy, sepsis induced) , aortic stenosis, mitral stenosis, atrial myxoma, acute valvular failure, and cardiac dysrhythmias. 4. Treatment is maximizing preload, cardiac performance, and reducing afterload. D. Distributive shock. 1. Caused by systemic vasodilatation from an inciting cause (infection, anaphylaxis, neurologic injury) resulting in systemic hypotension, and increased or decreased CO. 2. Sepsis is the most common precipitant of distributive shock. The endo­ thelial toxiciry and diffuse vasodilation are enhanced by messengers of the inflammatory response such as tissue necrosis factor-a (TNF-a) and interleukins 1 and 6. 3. Septic shock is associated with a brisk and often extensive inflammatory response. Despite a high CO, there is cellular hypoxia likely associated with disruption of mitochondrial function manifest as poor oxygen extraction/utilization. 4. In addition to sepsis, other causes of the systemic inflammatory response syndrome (SIRS) include posttraumatic shock and pancreatitis. 5. Treatment of septic shock is with massive volume to supplement pre­ load, augmentation of blood pressure (BP) with vasoconstrictors as necessary, and treatment of the underlying cause. 6. Other causes of distributive shock are anaphylaxis, severe liver dysfunc­ tion, and neurogenic shock. 7. Neurogenic shock is due to cervical spinal cord injury with loss of sym­ pathetic vascular tone. There is little inflammatory response. The patient has hypotension, bradycardia, and warm extremities. Treatment is with judicious volume expansion and a vasoconstrictor (low-dose dopamine or phenylephrine) . E. Endocrine shock. 1 . Caused by hypothyroidism, hyperthyroidism with cardiac collapse, or adrenal insufficiency. Treatment is focused on the underlying disease. 2. Adrenal insufficiency may be a contributor to shock in critically ill patients. Patients unresponsive to treatment should be tested for adrenal insufficiency. I l l . PAT H O P HYS I O LOGY

A. The result of shock is tissue anaerobic metabolism, systemic acidosis with elevated lactate.

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B. Cellular hypoxia leads to cellular ischemia. Ischemic cells are primed by alterations of calcium and adenosine 3',5'-cyclic monophosphate (cAMP) and creation of superoxide radicals. C. Endothelial cells under hypoxic conditions will have enhanced vascular permeability and less control over membrane transport functions. D. Reperfusion can result in release of oxygen radicals that may cause further cell damage. E. These processes activate neutrophils and the release of enzymes, oxidants, and proinflammatory cytokines. F. The inflammarory response results in further cellular damage, third spac­ ing, and activation of the coagulation system, leading to microcirculatory thrombosis, collapse, and further ischemia. G. Microcirculatory collapse leads to multiple organ failure. IV. DIAG N O S I S

A. Vital signs. Heart rate (HR) , BP, temperature, urine output, and pulse oximetry are traditional measures to identify shock and judge the response to treatment, and most clinicians still rely on these. However, 50% to 8 5 % of patients with normal or near-normal vital signs are still in shock as evidenced by ongoing systemic acidosis and declining end-organ function. 1 . HR. a . Tachycardia is an early sign of significant volume loss in shock. b. The HR in young, elderly, or patients on �-blockers HR may not mcrease. c. Bradycardia after prolonged hypotension may be a prelude to cardio­ vascular collapse. 2. BP. a. Hypotension and narrowed pulse pressure are a sign of severe volume loss and shock. b. Hypotension in the elderly may be significant for systolic BP < 1 1 0 mm Hg. c. Mean arterial pressure (MAP) is a better guide to therapy than sys­ tolic BP. 3. Temperature. a. Hyperthermia, normothermia, or hypothermia may be present in shock. b. Hypothermia is a sign of severe hypovolemic and septic shock; more common in the elderly and immunocompromised patients. B. Urine output. 1. A urine flow of 40% as massive soft tissue edema can occur during resuscita­ tion. B. Burn shock. 1. Ideal resuscitation perfuses the partial-thickness injury and optimizes organ function. 2. Underperfusion deprives the wound of nutrient delivery and gas exchange, leading to full-thickness conversion. 3. Excessive resuscitation leads to tissue edema, pulmonary edema, abdominal compartment syndrome, and extremity compartment syn­ drome. 4. Central venous access is generally necessary and preferably placed through uninvolved tissue. 5. Resuscitative regimens. a. TBSA burned and weight-guide fluid management. b. No evidence-based level-one data for resuscitative fluids use.

C h a pter 1 1 4 • B u rn s "Rule of N i n es"

945

Lund-Browder

Head and _,... neck 9% __

a

Genital ia

A

Relative percentage of body s u rface areas (% BSA) affected by growth

a- 112 of head b- 112 of 1 thigh c- Y2 of 1 lower leg

O yr

1 yr

5 yr

1 0 yr

9112 2% 2112

8112 3% 2112

6112 4 2%

5112 41/.i 3

1 5 yr

-������

Figure 1 1 4- 1 . A: Rule of Nines. B: Lund-Browder scale.

i. Lactated Ringer's most commonly used. Normal saline in large volumes causes hyperchloremic acidosis and should be avoided (Table 1 1 4- 1 ) . c. Colloid use remains controversial and serves a s adjunct t o crystalloid. 6. End points of resuscitation. a. Urine output. i. Primary end point for majority of burn centers. ii. Goals: adult 0 . 5 mL/kg/h, children 1 mL/kg/h. iii. Adjust fluid administration hour to hour based on urine output. b. Other end points of resuscitation-base deficit, lactate, and stroke volume variability. C. Metabolism and nutrition. 1 . Metabolism. a. Insensible fluid and protein losses from burn wounds are extreme and may result in hyperrhermia initially. b. As vasomotor autoregulation diminishes, significant evaporative heat loss occurs. c. Keep the patients' room temperature >90°F. d. Increased muscle proteolysis, lipolysis, and gluconeogenesis occur. e. Hyperglycemia is common and may exacerbate muscle wasting. f. Glucose control is essential with insulin drip.

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TA B L E 1 1 4 - 1

Pa rkland form u la Mod ified B rooke form u l a

Pa rkland a n d Mod ified B rooke Form u las

Tota l fl u i d s fo r 2 4 h R i nger lactate Tota l fl u i d s fo r 24 h R i nger lactate Plasma D5W

=

4 ml

x

kg

x

% BSA

=

1 . 5 ml x kg 0.5 ml x kg 2 , 000 m l

x x

% BSA % BSA

Exa m ple: A 70-kg m a n with a 50% TBSA b u rn wou l d therefore have a tota l deficit of 1 4 L (4 ml x 70 kg x 50% BSA = 14,000) in 24 h. H a lf the 24-h d eficit s h o u l d be repleted in the fi rst 8 h, due to the h igh risk of hypovo l e m i c shock early i n the cou rse. In this exa m ple, that is 7 L with i n the fi rst 8 h or a rate of 875 m Uh for the fi rst 8 h. It is i m porta nt to note that this recom mendation starts at the estimated time of i n j u ry, not s i m ply the time care is rendered . The rate wou l d su bseq u ently be decreased to 438 mUh for the n ext 16 h . BSA, body s u rface a rea ; D5W, d extrose 5% i n water.

g.

Hypermetabolic response that occurs after a thermal injury is greater than that observed after any other form of trauma or sepsis. i. Protein catabolism is compounded by insensible losses through the wound bed and leaking into the interstitium, resulting in severe hypoproteinemia.

2. Nutrition. a. Ideally, enteral nutrition should be started the day of the injury and can serve to provide volume and calories. b. Caloric need is equal to two to three times normal basal energy expenditure and requires minimum of 2 g/kg protein per day. c. Enteral nutrition is preferred, and total parenteral nutrition (TPN) is used only for patients who do not tolerate enteral feedings. d. Anabolic enhancement. i. Recombinant human growth hormone. (a) Caution: may cause hyperglycemia. ii. Oxandrolone: given enterally 1 0 mg bid. iii. Propanolol: titrate to reduce heart rate by 20%. C. Infection. 1 . Multiple defects in burn patients' immune system predispose them to an increased risk of infection. 2. Burn wound sepsis. a. Prevention of i. Topical antimicrobials (e.g., silver sulfadiazine or mafenide acetate) . (a) Mafenide acetate penetrates eschar and is most effective against gram-negative organisms bur can cause metabolic acidosis because it is a carbonic anhydrase inhibitor. ii. Local wound care. b. Treatment. i. Urgent surgical excision and tissue coverage with autograft, skin substitute, or topical antibiotics when burn wound sepsis is sus­ pected.

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D. Inhalation/respiratory injury. 1. Restrictive respiratory failure secondary to burn eschar involving the torso requires urgent escharotomy. 2. Inhalation injury. a. Airway management as always is paramount. i. Observe for signs of upper airway obstruction, secondary to edema, which develops hours after the initial injury. ii. Stridor is an indication for urgent placement of an endotracheal (ET) tube of sufficient caliber to permit bronchoscopy in this setting. iii. Immediate life-threatening exposures. (a) Carbon monoxide. (I) Lethal level >60% CO Hgb. (2) FI0 2 1 00% until normal level. (b) Hydrogen cyanide (CN-) . (1) Lethal level i n serum � l µg/mL. (2) Inhibits cytochrome oxidase. (3) Consider sodium thiosulfate. b. Inhalation of toxic combustants can cause a severe inflammatory response in the bronchial pulmonary tree and systemically. i. Endobronchial and interstitial edema. ii. Mucociliary dysfunction. iii. Alveolar disruption. iv. Functional pulmonary shunting. v. Decreased lung compliance. vi. Endobronchial sloughing. (a) Combines with exudates + fibrin casts with increased bacte­ rial growth and obstruction of airways. vii. Neutrophils invade in alveolar spaces through the pulmonary vasculature release enzymes and likely contribute to 0 2 free radi­ cal production, promoting the inflammatory cascade and local injury. viii. Mortality is greatly increased when matched to burn injuries of like size without inhalational injury. ix. Upper airway assessment should be carried out before extubation by deflating cuff and noting an air leak. It may not be safe to extubate if no air leak is audible! c. Shock state can be more severe in the presence of inhalational injury, often requiring up to 50% more fluid to meet the urine output end points of resuscitation. E. Chemical injury. 1 . Acids. a. Burn by coagulation necrosis creating an eschar that limits deeper penetration. b. Hydrofluoric acid burns carry the unique concern of calcium and magnesium chelation and risk cardiac arrest secondary to severe hypocalcemia and hypomagnesemia. i. Intra-arterial infusion of calcium gluconate has been met with some success and may limit digital ischemia. =

948

SECT I O N 1 2 • S H O C K A N D T R A U M A

ii. Calcium gluconate slurry may be massaged into the exposed area to potentiate systemic absorption. iii. Carefully monitor electrocardiogram (ECG) . 2. Alkali. a. Burn by causing liquefaction necrosis in the subcutaneous fat, creat­ ing vascular thrombosis and subsequent dermal ischemia. F. Electrical injury. 1. Life-threatening problems include dysrhythmias. 2. Spinal cord injury. a. Direct nerve/cord damage. b. Tetany resulting in spinal column fracture and cord injury. c. May result in impaired respiratory function depending on the level of injury. 3. Cutaneous lesions. a. May be subtle, and efforts should be made to find entrance and exit lesions, as these will direct the practitioner to focus on the intervening tissues. 4. Compartment syndromes. a. Myonecrosis is common, particularly in the upper extremities. b. Myonecrosis puts the kidneys at risk for myoglobinuric renal failure. i. Elevations of creatinine phosphokinase (CPK) into the tens of thousands are often present, and maintaining a urine output of 1 00 mL/hour or greater in adults reduces the risk of renal failure. ii. Mannitol may be added once resuscitation is well under way. iii. Alkalinizing the urine is advocated by some. iv. Maintain urine output at 1 00 mL/hour in adults. v. Consider monitoring the CPK for several days to assess the amount of muscle damage and recovery; with continued eleva­ tions suggesting need for further debridement. c. Fasciotomy for elevated compartment pressures. d. Debridement of nonviable or necrotic muscle and/or other tissue. 5. Fluid resuscitation must be initiated quickly, with higher volumes than anticipated due to underlying tissue injury. G. Pain. 1 . Rationale. a. On a scale of 1 - 1 0 , most burns are rated at a 1 0 . b . Pain control leads to i. Patient comfort. ii. Decreased catabolism, cardiovascular stress. iii. Reduced risk of posttraumatic stress disorder. 2. Management. a. Simultaneous drips of narcotic and benzodiazepines. b. Anticipate higher doses than are usual for other clinical settings. c. It is not prudent to reduce these medications for frequent neurologic assessment.

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949

d. Once the patient's burn wounds have been managed adequately, a stepwise weaning of these agents is done to permit ventilator weaning and to avoid withdrawal. VI I I . C O M P LI CAT I O N S

A. Eschar formation. 1 . Escharotomy. a. Particularly for circumferential chest eschar to optimize oxygenation/ ventilation. b. For limbs to prevent compartment syndromes. 2. Burn wound sepsis. a. Early excision. i. Reduced risk of this complication. ii. Nonetheless, loss of skin barrier and immune suppression may still not totally prevent burn wound sepsis. b. Signs. i. Diffuse or focal discoloration of the burn. ii. Purulent fluid from the wound. iii. Early eschar separation. iv. Confirm by biopsy of wound. c. Treatment. i. Immediate treatment or systemic sepsis will occur. ii. Total excision of the infected wound. iii. Systemic antibiotics covering the infective microbes. 3. Abdominal compartment syndrome. a. Leads to renal failure, respiratory failure, and bowel ischemia. b. Urinary bladder pressure measurement protocol. c. Provides an indirect measure of abdominal pressure. d. Levels 2::2 0 cm H 2 0 pressure suggest abdominal hypertension, and 2:: 3 0 cm H20 is generally accepted as requiring operative intervention, celiotomy, and leaving the abdominal compartment open. 4. Pneumonia. a. Increased risk because of immune compromise, immobility, and impaired secretion clearance. b. More frequent with inhalational injury. c. Incidence increases with the burn area. d. Prevention. i. Good pulmonary toilet. ii. Limit aspiration by keeping head of bed at 30 degrees. iii. If on ventilator, lung-protective ventilator management. iv. Frequent surveillance. v. Prophylactic antibiotics are not recommended. e. Treatment. i. Initial empiric therapy based on local biograms followed by culture-directed therapy based on the sensitivities of the isolated orgamsms.

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SUGGESTED READI NGS

Cancio LC, Lundy JB, Sheridan RL. Evolving changes in the management of burns and environmental injuries. Surg Clin N Am 201 2;92:959-986. An excellent and detailed review. Greenhalgh DG. Burn resuscitation: the results of the ISBI/ABA survey. Burns 201 0;36(2) : 1 76- 1 82. Informative survey ofhow burn care practiced. Rai J, Jeschke M, Barrow RE, et al. Electrical injuries: a 30-year review. j Trauma 1 999;46(5): 933-936. An excellent historical review. Ryan CM, Schoenfeld DA, Cassem EH, et al. Estimates of the probability of death from burn injuries. N Engl] Med 1 998;338(25) : 1 848- 1 8 5 0 . A paper detailing the relation ofadvances i n burn care and mortality. Sheridan RL, Tompkins RG. What's new in burns and metabolism. } Am Coll Surg 2004; 1 9 8 (2): 243-263. A review oftherapies focused on metabolism. Tricklebank S. Modern trends in fluid therapy for burns. Burns 2009;35:757-767. A helpfol reference to guide resuscitation. Williams FN, Branski, LK, Jeschke MG, et al. What, how and how much should burns be fed. Surg Clin N Am 20 1 1 ; 9 1 :609-629. A source ofinformation regarding nutritional support.

1 15

Th o ra c i c Tra u m a H a n i S eo u d i a n d B ruce J . S i m o n

I . G E N E RAL P R I N C I PLES Chest injuries cause one of every four trauma deaths in North America. Multiple life-threatening injuries can result from thoracic trauma and there­ fore should be sought during the primary trauma survey. I I . ETI OLOGY Motor vehicle crashes, falls, and penetrating wounds are the principal causes. I l l . DIAG N O S I S

A. Tension pneumothorax. Air enters the pleural space b u r does not leave because of a flap valve effect in the injured lung or from an open (sucking) chest wound. As a result, positive intrapleural pressure occurs, the ipsilateral lung collapses, and the mediastinum is pushed toward the contralateral lung. This results in hypotension and tachycardia due to impaired venous return. B. Massive hemothorax. This represents rapid accumulation of > 1 , 5 00 mL of blood within the pleural space and manifests as hemorrhagic hypovole­ mia in addition to respiratory compromise. C. Flail chest. This indicates that a segment of chest wall has lost bony con­ tinuity with the remainder of the chest due to fracture of three or more adjacent ribs in more than one location unilaterally or bilaterally. This results in paradoxical movement of the flail segment during respiration. The morbidity of this condition is primarily due to the pain and associated severe pulmonary contusion. D. Cardiac tamponade. This may result from either blunt or penetrating trauma. Acute accumulation of relatively small amounts of blood can result in tamponade pathophysiology. Clinical findings include hypoten­ sion, tachycardia, muffled heart sounds, distended neck veins, and pulsus paradoxus. Detection is by trauma ultrasound exam ("extended FAST exam" ) . E . Major airway injury. This injury i s characterized b y stridor and subcuta­ neous emphysema. Endotracheal intubation can be very difficult, and failed attempts at intubation can further compromise airway function. It is rec­ ommended that an emergency tracheostomy rather than cricothyroidotomy be performed. Urgent operative repair is needed. F. Penetrating chest injury. Penetrating injuries in addition to the stated problems may also result in bronchovenous fistula, whereby air flows from the injured bronchus into one of the pulmonary veins, resulting in massive 951

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air embolism. This condition can have a delayed presentation and appear when positive pressure ventilation is initiated. The condition is rapidly fatal and requires immediate thoracotomy. IV. I M M E D IATE LI FESAV I N G I NTERVE N T I O N S

A. Endotracheal intubation. Intubation is indicated when the airway is compromised by direct trauma, aspiration of blood/gastric contents, or a depressed level of consciousness. Orotracheal intubation is the preferred method. B. Cricothyroidotomy. Dividing the cricothyroid membrane provides a much quicker surgical access to the airway compared to tracheostomy. Tracheostomy is usually not performed in a lifesaving situation. C. Needle decompression or tube thoracostomy. Immediately on iden­ tification of a tension pneumothorax, a needle thoracostomy should be performed. This should be followed by a tube thoracostomy as quickly as possible. D. Thoracotomy. It is recommended that a thoracotomy be performed if the initial drainage from the tube thoracostomy is 1 ,500 mL or greater or when the hourly ourpur is >250 mL for several hours. Resuscitative thoracotomy, also known as emergency department thoracotomy, is performed on pulseless victims of penetrating trauma who have other signs of life. Generally, a resuscitative thoracotomy is not performed on blunt trauma victims who are without vital signs. The overall success rate of this procedure is low. V. DIAGNOSTIC S T U D I E S

A. Chest radiograph is the first imaging study performed for the trauma patient after the primary survey. However, in many centers extended FAST (eFAST) ultrasound of the chest is immediately performed on patient arrival to the trauma bay to assess for pneumothorax. B. eFAST exam is done of the pericardium to rule out hemopericardium. C. Computed tomography (CT) . High-speed helical CT scanners permit rapid evaluation of chest injuries and are accurate for diagnosing lung con­ tusions and occult hemopneumothorax. Modern CT scanners are highly accurate in diagnosing blunt aortic injury. D. Angiography. Aortography remains the gold standard for making the diag­ nosis of blunt aortic injury but is gradually being supplanted by thin-slice CT angiography. V I . TREAT M E NT

A. Chest wall and pleural cavity injury. 1 . Rib fractures: Rib fractures need only be treated symptomatically. Pain control can be challenging depending on the number and extent of the fractures. A thoracic epidural catheter or unilateral paravertebral catheter is useful for pain control in older individuals and those with multiple rib fractures.

C h a pter 1 1 5 • Thorac i c Tra u m a

B.

C.

D.

E.

F.

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2. Flail chest: This injury is particularly challenging because patients frequently go into respiratory failure due to the severe pain and hypoxia due to the underlying pulmonary contusion. Mechanical ventilation is usually necessary. Repair is sometimes done, but the benefit remains controversial. 3. Sternal fracture. Symptomatic treatment for this injury is appropriate. 4. Pneumothorax. a. Pneumothorax is generally treated with tube thoracostomy. A very small pneumothorax may be observed if the patient is not symptom­ atic. Open pneumothorax: the initial management includes imme­ diately applying an occlusive dressing over the wound and insertion of a chest tube; operative intervention is urgently needed when the assessment for other life-threatening injuries has been completed. Lung. 1 . Pulmonary contusion. Treatment is supportive with supplemental oxy­ gen. Mechanical ventilation is necessary if there is severe hypoxia. 2. Acute respiratory distress syndrome (ARDS). ARDS is a syndrome of diffuse inflammatory reaction in the lung as part of a systemic inflamma­ tory response. It may occur following multiple traumas, sepsis, massive blood transfusions, and many other causes (see Chapter 40 for more details) . Trachea and major bronchial injuries. After securing an airway, these injuries require immediate operative intervention. When patients are otherwise unstable, repair can often be deferred if respiratory function is acceptable and the air leak is not excessive. Heart and great vessels. 1. Blunt cardiac injury. This term encompasses a variety of inj uries, includ­ ing myocardial contusion, rupture of a cardiac chamber or septum, and valve disruption. a. Treatment for myocardial contusion requires cardiac monitoring and supportive care. b. Treatment of chamber, septal, or valve injury often requires urgent surgical repair. 2. Blunt aortic injury. Most patients with this injury die before reaching the hospital. Approximately half of those who reach the hospital will have a free rupture within the first 24 hours. Therefore, urgent surgical repair is indicated. Nonoperative management: treatment principles are similar to nonoperative management of aortic dissection, that is, �-blockade and antihypertensives; endovascular stent grafts are now being used much more frequently, particularly for the poor-risk or elderly patient. Traumatic asphyxia. When a trauma patient is diagnosed with this prob­ lem, treatment is supportive after establishing an airway and ventilation. Elevated intracranial pressure should be ruled out by CT scan if mental status is altered. Esophageal rupture. Surgical treatment is indicated to avert mediastinal and/ or pleural sepsis.

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SUGGESTED READI NGS

American College of Surgeons. Advanced trauma life support for doctors, 9th ed. Chicago: American College of Surgeons Committee on Trauma, 2 0 1 2 . Sets the standardfo r initial evaluation and management of the trauma patient by Emergency Medicine physicians and Trauma Surgeons. Bastos R, Baisden C, Harker L. Penetrating thoracic trauma. Semin Thorac Cardiovasc Surg 2008;20 ( 1 ) : 1 9-25 . An overview ofthe etiology, evaluation, and treatment ofpenetrating thoracic injury. Clancy K, Velopulos C, Bilaniuk J. Screening for blunt cardiac injury. ] Trauma Acute Care Surg 20 1 2;73(5):S30 1-S306. Reviews in difficulties in diagnosing this entity. Moreno C, Moore E, Majure J, et al. Pericardia! tamponade: a critical determinant for survival following penetrating cardiac wounds. J Trauma Acute Care Surg 201 1 ;71 (6): 82 1-825 . Reviews the etiology, treatment, and outcome oftraumatic tamponade. Neschis D, Scalea T, Flinn W. Blunt aortic injury. N Engl J Med 2008;359: 1 708- 1 7 1 6. Reviews etiology, detection, and treatment ofthis injury. Richardson J. Outcome of ttacheobronchial injuries: a long-term perspective. J Trauma Acute Care Surg 2004; 5 6 ( 1 ) :30-36 Discusses principles oftreatment and determinants of outcome. Simon B, Ebert J, Bokhari F, et al. Management of pulmonary contusion-flail chest; An EAST Practice Management Guideline. J Trauma Acute Care Surg 201 2;73(5 Suppl 4): S35 1 -S36 1 . A n evidence-based review ofthe evaluation and treatment ofthis major component of blunt chest trauma. Wong E, Knight S. Tracheobronchial injuries from blunt trauma. ANZ] Surg 2006;76(5): 4 1 4-4 1 5 . Discusses etiology and management ofairway system injuries.

C o m p a rtm e nt Syn d ro m es Ass o c i ate d w ith M us c u l os ke l eta l Tra u m a Ti m othy A . E m h off

I . TRAUMAT I C C O M PART M E N T SYN DROM ES

A. General principles. 1. Any anatomic structure or external device that limits the abiliry of tissues to swell can cause compartment syndrome. 2. Compartment syndromes due to trauma are rypically described in extremities (leg, arm, thigh) , abdomen (see Chapter 1 02) , face (eye) , and head (see Chapter 1 1 1 ) . 3. Anatomically, extremiry compartments are formed b y fascia! layers surrounding muscle groups. 4. As compartment pressure increases, nerves, followed by muscles, lose function (if treatment is delayed) . 5. Extremiry compartment syndrome can occur in the calf, thigh, buttock, forearm, arm, hand, or foot. The most frequent compartment affected is the anterior compartment of the calf. 6. With trauma to the face, retrobulbar hemorrhage or edema may jeopardize the optic nerve. 7. In closed head injury, unrelieved elevated intracranial pressures may be amenable to decompressive craniectomy before permanent brain damage occurs. B. Etiology. 1. Extremiry compartment syndrome: crush, ischemia, arterial injury, vascular ligation (including vena cava, common iliac, common femoral, or popliteal veins) , fracture (open or closed) , direct blunt trauma (with hematoma or edema) , prolonged external pressure, electrical injury, or contrast injection/ extravasation. 2. Secondary extremiry/ocular compartment syndrome: hypotension and/ or massive volume resuscitation leads to whole-body tissue edema, including the muscles of the various compartments. This may be the result of massive burns or other large physiologic insults, and is part of the postresuscitation systemic inflammatory response syndrome (SIRS).

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C. Pathophysiology. 1 . Injury and/or resuscitation causes a hematoma and/or edema of the muscles. 2. In the face of a fixed compartment volume, pressure increase follows muscle edema. 3. At some point, pressure in the compartment exceeds capillary perfusion pressure (approximately 30 mm Hg), and the capillaries collapse. 4. Tissue ischemia results in nerve (initial) and muscle damage (late) . D. Diagnosis. 1. High index of suspicion is the key, especially in the neurologically com­ promised patient. 2. Lower extremity clinical examination. a. Four compartments: i. Anterior: peroneal nerve: dorsiflex foot and toes. ii. Posterior: plantar flex the foot. iii. Lateral: plantar flex the foot. iv. Deep posterior: inverts foot, flexes toes. b. Tense or tight compartments to touch (compare right to left) . c. Pain disproportionate to associated injury. i. Critical mistake is to treat with more pain medication. d. Increased pain with passive muscle stretch (classically for anterior calf compartment: dorsiflexion of the great toe) . e. Hypesthesia and/or muscle weakness: test for all compartments. f. Pallor: sluggish capillary refill in the skin/nail bed. g. Distal pulses remain intact unless a proximal arterial injury is the reason for the compartment syndrome. i. Critical mistake is to think that diagnosis of compartment syn­ drome is dependent on pulse loss. h. Direct measurement. i. Arterial line setup and 1 6-gauge needle. ii. Commercial device with direct readout (Stryker Orthopedics: www. stryker.com) . iii. Less than 20 mm Hg is usually not problematic; 20 to 30 requires expert interpretation of the clinical picture; >30 is clearly abnor­ mal and requires fasciotomy. 3. Upper extremity clinical exam. a. Three compartments: i. Volar: (includes carpal tunnel) : median, ulnar, and anterior inter­ osseous nerves (flexor muscles) . ii. Dorsal: posterior interosseous nerve (extensor muscles) . iii. Mobile wad: radial nerve. 4. Ocular clinical exam. a. Proptosis. b. Computed tomography: blood, fluid, bone forcing eye forward, stretching optic nerve ("balloon-on-a-string"). c . Physical exam (PE) : firm globe to touch. (Note: measured intraocular pressure may NOT reflect increased pressure behind the globe, which threatens the optic nerve and retinal perfusion.)

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d. Sluggish papillary response (direct and indirect) . e. "Pale" optic nerve on funduscopic exam. f. Awake patient: blurred vision (progressive) . g. Direct measurement: not done. E. Treatment. 1. Extremity compartment syndrome. a. The first step is always to remove constnctmg wraps or dressings and to remove or bivalve any cast as these devices may cause or hide compartment syndrome. b. Fasciotomy: within 6 hours of onset; 3 to 4 hours if high compart­ ment pressures are associated with severe blood loss, hypoperfusion, and systemic/limb hypotension. c. Prophylactic, if high enough index of suspicion or with prolonged ischemia or ligated major vein, especially in the face of a proximal arterial injury, repair and reperfusion to the limb. d. Mandatory for high compartment pressure with possible viability. e. Surgical fasciotomy. i. Lower extremity: a four-compartment fasciotomy through two incisions, one lateral and one medial (with large fascial incisions, approximately 25-cm long in each compartment) . ii. Upper extremity. (a) Volar incision: crossing curvilinear across the wrist in to the hand (thenar) and curvilinear across antecubital fossa into the upper arm. (b) Dorsal: longitudinal. (c) Mobile wad: longitudinal (may have already been decom­ pressed with volar incision) . f. Skin left open. g. May require a late skin graft to cover the resulting defect if unable to reapproximate over 5 to 7 days. 2. Ocular compartment syndrome. a. Emergent lateral canthotomy: optic nerve/retinal ischemia can occur within 60 minutes of unrelieved pressure; permanent loss of vision in 1.5 to 2 hours. F. Complications. 1. Extremity. a. Rhabdomyolysis. b. Ischemic neuropathy. c. Myonecrosis and fibrosis. d. Renal failure from myoglobinemia. e. Reperfusion syndrome: resulting in further swelling, higher compart­ ment pressures. f. Limb loss. g. Fasciotomy in fractured extremities. i. Prolonged bony healing. ii. Increased incidence of nonunion. 2. Ocular: loss of vision.

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SUGGESTED READI NGS

Guiliani SC, er al. The effect of ischemia reperfusion injury on skeletal muscle. Injury 2 0 1 2;43(6):670-675 . Review ofthe pathophysiolof!Y ofischemic-reperfosion injury i n muscle and its consequences. Khan FY. Rhabdomyolysis: a review of the literature. Neth J Med 2009;67(9) :272-283. Excellent review ofthe etiologies, diagnosis, and treatment of rhabdomyolysis. Fully referenced. Leversedge FJ, er al. Compartment syndrome of the upper extremity. J Hand Surg 20 1 1 ;36A:544-559. Detailed review ofupper extremity compartment syndrome: anatomy, physiolof!Y, diagnosis, and treatment. Murdoch M. Compartment syndrome: a review of the literature. Clin Podiatr Med Surg 2 0 1 2;29(2) : 3 0 1-3 1 0 . Concise review ofcompartment syndrome: diagnosis and management. Ojike NI, er al. Compartment syndrome of the thigh: a systematic review. Injury 20 1 0;4 1 : 1 33- 1 36. Analysis of the current literature on the diagnosis, treatment, and complications of this relatively rare compartment syndrome. Perry M. Acute proprosis in trauma: rerrobulbar hemorrhage or orbital compartment syndrome-does it really matter? J Oral Maxillofoc Surg 2008;66: 1 9 1 3-1 920. Review ofthe etiolof!Y, diagnosis, and treatment of ocular compartment syndrome. Rush RM , er al. Management of complex injuries: rourniquers, compartment syndrome detection, fascioromy and amputation care. Surg Clin N Am 201 2;92(4) :987- 1 007. Up-to-date review of complex limb injuries, including compartment syndrome.

S e ps i s a n d M u l t i o rga n Fa i l u re M a rie M u l l e n

"Hectic fever (sepsis) at its inception is difficult to recognize but easy to treat. Left untended, it becomes easy to recognize but difficult to treat.

"

- Niccolo Machiavelli ( 1 498)

I . G E N E RAL P R I N C I PLES

A. Definitions. 1. Systemic inflammatory response syndrome (SIRS). a . Clinical response to nonspecific injury, including trauma, burns, infection, pancreatitis, or alternative inflammatory insult. b. Clinical components of SIRS (two elements required to define) . i. Temperature �38°C or �36°C. ii. Heart rate �90 per minute. iii. Respirations �20 per minute. iv. Leukocyte count > 1 2,000 or 1 0% bands. v. Paco2 < 32 mm Hg. 2. Sepsis. a. Documented or suspected infection and evidence of clinical inflam­ matory response. b. 1 992 criteria-Two or more SIRS criteria with associated infection define sepsis. c. 200 1 criteria-Documented or suspected infection with some mark­ ers of inflammation (Table 1 1 7- 1 ) . 3 . Severe sepsis. a. Sepsis with associated organ dysfunction or tissue hypoperfusion (Table 1 1 7-2) . 4. Septic shock. a. Sepsis with refractory hypotension after appropriate fluid resuscita­ tion. b. Suggested appropriate resuscitation of at least 30 mL/kg crystalloid minimum to be considered refractory. 5. Multiple-organ dysfunction syndrome (MODS) .

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lf;i:l!fffii

Diagnostic Criteria Sepsis

Infection', documented or suspected, and some of the following:b,c

G e n e ra l va ria bles Feve r (core tem peratu re >38.3°C) Hy poth e r m i a (core tem peratu re 90 m i n- 1 o r >2 SD a bove the norma l va l u e fo r age Ta chypnea Altered m e nta I status Sign ifica nt edema or positive fl u i d ba l a n ce (>20 m Ukg ove r 24 h) Hyperglyce m ia ( p lasma g l u cose > 1 20 m g/d l or 7.7 m m o l/L) in the a bsence of d i a betes I nfla m matory va ria b l es Le u kocytosis (WBC cou nt > 1 2 ,000 µL- 1 ) Le ucopenia (WBC count 1 0 % i m mature forms Plasma C- reactive protei n >2 S D a bove the normal va l u e P l a s m a p roca lcito n i n >2 S D a bove t h e n o r m a l va l u e H e m odyna m i c va riables Arteria l hy potension b ( S B P 3 . 5 L· m i n- 1 - M-23 O rga n dysfu nction va ria b les Arteria l hypoxe m ia ( Pa O / F I O < 300) Acute ol igu ria ( u ri n e output 0 . 5 m g/d l Coagu lation a b norm a l ities ( I N R > 1 . 5 or a PTT >60 s) l ieus (a bsent bowe l sounds) T h ro m bocyto pen ia ( p late let cou nt < 1 00,000 µL- 1 ) Hyperbi l i ru bi n e m i a ( p lasma tota l b i l i r u b i n >4 m g/d l or 70 m m o l/U 1issue perfusion va ria b les Hyperlactate m ia (> 1 m m o l/L) Decreased ca p i l l a ry refi l l o r m ottl i ng 'I nfection d efi ned as a pathologic process i n d uced by a m i c roorga n is m . "Sv0 saturation >70% is n o r m a l i n c h i l d re n (normal ly, 75%-80 % ) , a n d C l 3 . 5-5. 5 is norma l 2 in c h i l d re n ; therefore, N EI T H E R s h o u l d be used as signs of sepsis in n ewborns or c h i l d ren . 'Diagnostic criteria for sepsis in the ped iatric popu lation a re signs a n d sym ptoms of i nfla m m a ­ t i o n plus i n fection with hyper- or hypothermia ( recta l tem peratu re >38.5°C or 2 h , desp ite adeq uate fl u i d resusc itation ALI with Pa0/F l 0 2 2 m g/d l (34 . 2 mol/U P late let count < 1 00,000 Coagu lopathy ( I N R > 1 . 5) D e l l i nger R P , Levy M , R hodes A e t a l . , S u rviving Sepsis Ca m pa ign : I nternational g u i d e l i nes for m a n agement of severe sepsis a n d septic shock. 2012 Grit Care Med 2013;4 1 ( 2 ) : 580-637 .

a. Disease spectrum in which one or more organ systems are unable to maintain homeostasis without support in an acutely ill patient. b. MODS has many potential sources. Sepsis is one of the most common (Table 1 1 7-3) . B. Epidemiology. 1. Severe sepsis represents 20% of all ICU admissions in the United States (US) . 2. Severe sepsis is the number one cause of death in the non-coronary care ICU and the 1 0th leading cause of death in the US. 3. Severe sepsis has an estimated 28% ro 50% mortality rate. 4. Septic shock has an estimated mortality of 60%. 5. MODS is a leading cause of death in the ICU. Depending on the num­ ber of organ systems involved, MODS can carry an 80% mortality rate. I I . PAT H O P H I S I O LOGY

A. Infection. 1. Sepsis is an overwhelming and complicated proinflammatory response to infection. 2. Inciting organisms have changed with time. Change is connected to drug resistance. 3. Gram-negative and gram-positive organisms are each separately linked to 25% of sepsis-related infections. 4. Mixed gram-negative and gram-positive infections account for about 1 5% of causative infections. 5. Fungi associated with 5% to 1 0% of infections. B. Pathogen induction. 1. Inflammatory response starts with recognition of pathogen molecular components by receptors on cells of the innate immune system.

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lf;Mliffii

R i s k Factors for M O DS

Infect i o n

Periton itis a n d i ntra-a bdom i n a l i nfection P n e u m o n ia N ec rotizing soft tissue i nfections Tropical i nfecti ons (e.g. , fa/ciparum m a l a r i a , typhoid feve r, dengue feve r) Inflammation

Pa ncreatitis lschemia

R u ptu red aortic a n e u rysm H e m orrhagic shock M esenteric isc h e m ia I m m u n e react i o n s

Autoi m m u n e d i sease Reactive h e m o phagocytic synd ro m e Anti phos p h o l i p i d a nti body syn d ro m e Tra nsplant rejection G raft versus host d i sease Iatrog e n i c causes

Delayed or m i ssed i nj u ry B lood tra nsfusion I nj u rious mecha n ica l ve ntilation Treatme nt-associated i n c reased i ntra-a bdom i n a l p ress u re Intoxication

Drug reactions (a nticonvu lsa nts , carboplati n , a nti retrov i ra l s , co l c h i c i nes, p ro pofo l , a m iodarone, monoclonal a nti bod ies) Arse n i c D r u g i ntoxicatio n (ecstasy, coca i n e , sa l i cylates , aceta m i no p h e n ) Endocrine

Ad re n a l crisis P h eochrom ocytoma Thyroid sto rm Myxed ema coma R eprod uced from M izock BA . The m u ltiple orga n dysfu n ction synd ro m e . Dis Mon 2009;55:476-526.

2. Innate immune cell members consist of neutrophils, macrophages, monocytes, basophils, eosinophils, natural killer cells, mast cells, den­ dritic cells, and platelets. 3. Pathogen-inducing components capable of triggering an immune response are numerous and include lipopolysaccharide (LPS) from gram-negative bacteria; lipoteichoic acid from gram-positive bacteria, and flagellin. C. Toll-like receptors (TLRs). 1. TLRs are cell membrane proteins that exist to specifically recognize a variety of pathogen- and tissue damage-associated components.

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2. TLRs are a key element to initiating the immune response. TLRs along with other proteins comprise a cadre known as pattern recognition receptors (PRRs) . 3. Activation ofTLRs leads to initiation of the inflammatory cascade. This includes activation of the critical transcription factor NF-KB . Ongoing response is variable and host dependent. 4. Key TLRs include TLR-2 and TLR-4. D. Mediators of sepsis. 1. Activation of the inflammatory cascade precipitates the release and inter­ action of myriad important mediators. 2. These mediators encompass cycokines, including interleukin- ! (IL- 1), inter­ leukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-a(TNF-a) . 3. High mobility group box- 1 (HMGB- 1 ) is a unique cytokine that can provoke a lethal proinflammatory response. 4. Additional mediators include platelet-activating factor (PAF) , bradykinin, nitric oxide, and elements of the complement system. E. End-organ consequences. 1. Sepsis-associated mediators contribute to end-organ damage. Damage elements include vasodilatation and altered perfusion, microvascular permeability and thrombosis, myocardial depression, mitochondrial dys­ function, maladaptive use of cellular nutrients, and cellular apoptosis. I l l . DIAG N O S I S

A. Clinical features o f sepsis. 1. Early sepsis consists of suspected or confirmed infection and evidence of inflammation (Table 1 1 7- 1 ) . Early signs include SIRS criteria (tachycar­ dia, tachypnea, etc.) and hyperglycemia. 2. Progression to severe sepsis leads to evidence of organ dysfunction, including oliguria, renal insufficiency, altered mental status, coagulopa­ thy, and significantly elevated lactic acid levels. 3. Late sepsis deteriorates to present with fluid refractory hypotension (septic shock) and acute respiratory distress syndrome (ARDS). MODS will likely manifest in the late stages of sepsis as well. B. Inflammatory source identification. 1. Early inflammatory source identification and treatment are critical actions. Missed source control prolongs the inflammatory response and attenuates resuscitation efforts. 2. Most common sources of infection include the respiratory tract and the urinary tract. Other potential sources can be found in Table 1 1 7-4. 3. Primary organisms involved are gram-positive or gram-negative organ­ isms separately or in a mixed infection. Fungi or anaerobes account for 1 0% of sepsis-related infections. 4. Concerted effort to identify the cause is paramount. Evaluation should include blood and urine cultures. Cerebrospinal fluid (CSF) , body fluid, and stool cultures should be considered as appropriate. Radiologic imag­ ing needs to be initiated as indicated.

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SECT I O N 1 2 • S H O C K A N D T R A U M A Com mon S i tes a n d D i seases Assoc iated with Sepsis/S I RS

Orga n syste m

Locat ion

D i sease

Respi rato ry

U p per res p i rato ry tract

S i n usitis Mastoid itis P n e u m o n ia Lung a bscess Em pye ma Eso phagea l ru ptu re/pe rforation H e patic a bscess Chola ngitis Chol ecystitis I ntest i n a l i nfa rction/perforation pa ncreatitis I ntra-a bdom i na l/d ivertic u l a r a bscess Posto pe rative m ed iasti n itis Endocarditis

Lowe r res p i ratory tract Gastrointesti n a l

M ed iasti n u m H e pato b i l i a ry I ntra-a bd o m i n a l

Ca rd iovasc u l a r G e n ito u r i n a ry

M ed iasti n u m N ative or p rosthetic ca rd iac va lve K i d n ey, u reter, a n d bladder

N e u rologic

B ra i n a n d m e n i nges

Dermatologic

Tra u m atic wo u n d , s u rgica l wou n d , or bu rn site

Prosthetic

Central/perip h e ra l ve nous catheter Arterial cathete r Ve ntri c u l o perito n ea I s h u nt Dia lysis catheter Arti c u l a r prosthetic d evice Dia lysis graft/s h u nt Va sc u l a r syste m

Other

Peri n e p h ric a bscess Pye l o n e p h ritis Cystitis M e n i ngitis l ntracra n i a l a bscess Soft tissue a bscess Necrotizing fasc i itis I nfected d e c u b itus u lcer F u l l - and pa rtia l -th ickness bu rn Cathete r i nfection

I nfected p rosth esis Septic t h ro m bophle bitis

C. Predisposition, Infection, Response, and Organ dysfunction (PIRO) sepsis­ staging system. 1. Scoring system for sepsis that attempts to better describe prognosis and response to therapy. Based on the cancer TMN scale. 2. Stratifies patients based on four criteria (PIRO) . a. P-Predisposition to develop and respond to sepsis. Includes age, comorbidities, and genetic factors that impact occurrence and pro­ gression of sepsis.

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b. I-Infection elements. Evaluates infection site, severity, type, and organism susceptibility. c. R-Response to infection. Measures host reaction to infection using clinical and laboratory values, including vital signs, white blood cell count, and lactate levels. d. 0-0rgan dysfunction presence. Considers number of organ dys­ function markers. 3. PIRO is a relatively new and developing concept. Future use may enable individualization of prognosis and treatment. IV. M O D S

A. Background. 1. Up to 1 5% of all medical and surgical patients will develop MODS. 2. Often the consequence of initial successful resuscitation. 3. A more refined definition describes MODS as the manifestation of potentially reversible physiologic dysfunction in two or more organ systems not originally associated with the initial disease and developing as a consequence of a serious life-threatening insult. 4. Number of organs involved and duration of failure directly impact mor­ tality. 5. Single-organ failure carries a 20% mortality rate; two-organ involvement invokes a 40% mortality rate; injury involving three organs predicts an 80% mortality estimate. 6. Sepsis patients tend to have a predominance of lung involvement (68%) followed by abdominal injury (22%) . B. Scoring systems. 1. MODS mortality is linked directly to severity of organ dysfunction. 2. Multiple scoring systems exist to stratify mortality and initial disease severity. 3. Scoring changes showing improvement or deterioration serve as useful quality indicators in the ICU. 4. Two frequently used scales include the sequential organ failure assess­ ment (SOFA) and the multiple-organ dysfunction score (Table 1 1 7-5). C. Pathophysiology. 1. MODS evolution is not completely understood. Research efforts have been made to better understand its method of action and injury. 2. One of the better understood pathologic mechanisms is the disordered immune response (Fig. 1 1 7- 1 ) . a. Innate immune system involving TLR i s activated. This i s followed by release of inflammatory cytokines (IL- 1 , IL-6, TNF-a) . b. Inflammatory response potentiates and activates the complement and coagulation system. Cytokines prime neutrophils, leading to the release of superoxides and other mediators. c. In MODS, this immune response progresses unchecked. Organ dam­ age ensues, including capillary leak, edema, microcoagulation, tissue hypoxia, and subsequent mitochondrial injury.

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TA B L E 1 1 7 - 5

Pa ra m eter

Respi ratory Coagu lation H e patic Ca rd iac CNS Renal Aggregate score

i n i cal Measu rement Systems t o Assess Orga n ysfunction

S O FA

Pa0/ Fi0 2 venti lation P late l et n u m ber Cell n u m be r Bilirubin B lood pressu re Vaso p ressor use

Score

M O DS

Score

0-4 0-4

Pa0/F I 0 2 P late let n u m be r

0-4 0-4

0-4 0-4

Bilirubin B lood pressu re H ea rt rate CV P G lasgow coma sca le Creati n i n e u r i n e output Add worst d a i ly score

0-4 0-4

0-4 G lasgow c o m a sca le Creati n i n e u r i n e output 0-4 0-24 Add worst d a i ly score

0-4 0-4 0-24

SOFA, sepsis-related orga n fa i l u re assessm e nt; M O D S , m u lti ple-orga n dysfu nction score; CNS, centra l n e rvous system .

3. The intestine i s thought t o contribute t o MODS (gut hypothesis) . a. Intestinal injury creates increased permeability. Mucosal disruption cre­ ates a cytokine-generating entity that potentiates the immune response. b. Tissue injury decreases the protective effect of gut-associated lym­ phoid tissue (GALT) . Lack of nutrition further attenuates GALT potency. c. Tissue damage triggers virulence genes in commensal gut flora and potentiates damage to the intestine. 4. Elements of MODS are thought to further develop through an immune priming mechanism (the "Two Hit" hypothesis) . a. The initial severe injury occurs followed by a more minor insult (second hit) . The second lesser injury then generates an exaggerated immune response. 5. There is currently no unifying mechanism to explain MODS. It remains a concert involving the inflammatory cascade, the coagulation system, and tissue hypoperfusion leading to clinical organ dysfunction (Fig. 1 1 7-2) . V. TREAT M E NT

A. Timing is everything. 1 . Severe sepsis, septic shock, and MODS are time-dependent disease pro­ cesses. They are as time dependent as an acute myocardial infarction or acute ischemic stroke. 2. MODS management overlaps many of the principles used to approach severe sepsis and septic shock. This includes early source control, early resuscitation, and appropriate organ support using the most up-to-date literature.

Cha pter 1 1 7 • Sepsis and M u lt i orga n Fa i l u re

I

967

I N F ECTION I N J U RY

Coag u l ation

Monocyte

activation

Macrophage activation

Persistent

I ncreased

stl m u l atlon

expression

-Gut inflam -Bio trauma -Transfusion -ACS

of adhesion molecules

Neutroph i l

Cytokine

sequestration

production

_._.�Microvascular

Autonomic dysfunction

I ncreased

i nj u ry

oxidant production

M itochond rial damage

Organ dysfunction

Fai l u re of

Successful

biogenesis

biogenesis

DEATH

R ECOVERY

Figure 1 1 7- 1 . Overview of cellular and molecular mechanisms leading to MODS. TLR, Toll-like receptor; ACS, abdominal compartment syndrome. (Reused from Mizock BA. The multiple organ dysfunction syndrome. Dis Mon 2009;55 :476-526.)

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I nsult

I nfect i o u s o r N o n i nfect i o u s

Syste m i c i n f l a m m atory response

M i c rova s c u l a r

H e m o dy n a m i c

02 hypoxia

Vaso d i l at i o n

E n doth e l i a l function

Myocard i a l d e p ression

M i croe m b o l i

Cell

R e d i stri bution/s h u nt i n g

G u t m u cosal isch e m i a

M itoc h o n d r i a l

�

Organ

!�./

�

C e l l u l a r d a m a g e/apopto s i s

H epatic

CNS CVS

MODS

Renal

P u l m o n a ry H e m at o l o g i c

Figure 1 1 7- 2 . Multiple organ dysfunction syndrome (MODS) etiologic facrors. CNS, central

nervous system; CVS, cardiovascular system.

3. Initial severe sepsis treatment can be divided into care bundles. The Surviving Sepsis Campaign endorses a 3-hour and 6-hour bundle (Table 1 1 7-6) . These bundles are then augmented with recommended supportive care measures. B. Early goal-directed therapy (EGDT) . 1. Patients with sepsis and a lactic acid level � 4 mmol/L or sepsis and hypotension after initial fluid resuscitation merit EGDT. 2. Identification of global tissue hypoxia in the normotensive septic patient is crucial. An initial lactic acid level should be part of any labs ordered for a patient with suspected sepsis. If a patient is ill enough to require blood cultures, he is ill enough to order a lactic acid test. 3. EGDT requires placement of a central venous catheter (CVC) and the achievement of the following goals within 6 hours of resuscitation: a. Central venous pressure (CVP) 8 to 12 mm Hg ( 1 2 to 1 5 mm Hg for mechanical ventilation) . b. Mean arterial pressure (MAP) � 65 mm Hg.

Cha pter 1 1 7 • Sepsis a n d M u lt i orga n Fa i l u re

liJ:l!jipj

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S u rviving Sepsis Campaign B u n d les

TO B E C O M PLETED WITH I N 3 H O U R S :

1) 2) 3) 4)

Meas u re lactate leve l O bta i n blood c u ltu res prior to a d m i n istration of a ntibiotics Ad m i n iste r b road-s pectru m a n t i b i otics Ad m i n iste r 30 m Ukg c rysta l l o i d for hypotension or lactate 4 m m o l/L

TO B E C O M PLETED WITH I N 6 H O U R S :

5) A p p ly vaso pressors (for hypotension that d oes not res pond to i n itial fl u i d res usc itatio n ) t o m a i nta i n a M A P 6 5 m m H g 6) I n the eve nt o f persiste nt a rterial hypotension desp ite vol u m e resu sc itation (septic shock) or i n itia l lactate 4 m m ol/L (36 mg/d U M ea s u re CVP• M ea s u re centra l venous oxyge n satu ration (Scv0 2 )• 7) R e m eas u re lactate if i n itia l la ctate was e levated • • •

'Targets for q u a ntitative resuscitation i n c l uded in the g u i d e l i nes a re CVP of 8 mm Hg, Scvo, of 70% , a n d normal ization of lactate.

c. Urine output ;::: 0 . 5 mL/kg/h. d. Central venous oxygen saturation (Scv02) ;::: 70% or mixed venous (Sv0 2) ;::: 65%. 4. Crystalloid resuscitation is the preferred and ongoing modality of fluid administration. Colloid, particularly albumin, may be added as an adjunct. Hetastarches and hydroxyethyl starches are not recommended for use. Recommended initial resuscitation is 30 mL/kg fluid as part of the 3-hour bundle. 5. CVP has limitations in volume assessment. Some authors recommend using such adjuncts as CVP variability, pulse pressure variation (PPV) , stroke volume variation (SVV) , passive leg raise (PLR) , and ultrasound­ guided vena cava variability to augment guided fluid resuscitation. 6. Vasopressor and inotrope use for refractory MAP and cardiac dysfunction. a. Norepinephrine is the preferred initial vasopressor agent in septic shock (0.05 to 1 . 5 µg/kg/min) . b. Epinephrine recommended when an additional agent needed for hypotension (0.05 to 0 . 5 µg/kg/min) . Epinephrine may be added or substituted in a refractory situation. c. Dopamine suggested in only selected low cardiac output or low heart rate states with low arrhythmia risk (5 to 20 µg/kg/min) . d. May consider adding vasopressin 0.03 units/minute for refractory shock to augment MAP or decrease vasopressor requirement. e. Dobutamine is recommended for myocardial dysfunction in sepsis (2. 5 to 20 µg/kg/min) . f. Low-dose dopamine for renal protection has no clinical benefit and is not recommended.

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g. Arterial catheter monitoring is recommended with vasopressor use. h. Pulmonary artery catheter (PAC) use has not shown a benefit in comparison to the use of a CVC. Risks and complication of PAC insertion need to be considered prior to use. 7. Low Scv0 2 after fluid resuscitation may be addressed with several modalities. Consider transfusion for low Scv0 2 and a hematocrit (Hct) level 45 minutes.) 7. Reassessment encouraged for de-escalation as soon as possible. 8. Frequent reevaluation considered for toxicity. 9. Source identification and control. a. Cultures in addition to blood as appropriate-urine, CSF, body fluid, wound, stool. b. Appropriate radiologic evaluations. c. Emergency source control within 12 hours recommended. Measures may include abscess drainage, tissue debridement, or removal of indwelling devices. d. Failure to appropriately cover an infecting organism or to obtain source control may create an ongoing infective insult that attenuates resuscitative measures. D. Sepsis care adjuncts. 1. Corticosteroid use. a. Critical illness-related corticosteroid insufficiency is a known phe­ nomenon. Routine corticosteroid use is not recommended. b. May consider low-dose hydrocortisone in cases of fluid- and vasopressor-refractory shock. c. Consider 200 mg intravenous hydrocortisone per day if unable to restore hemodynamic stability with fluid resuscitation and vasopressors. 2. Glycemic control. a. Hyperglycemia of critical illness is a recognized entity and linked to mortality.

Cha pter 1 1 7 • Sepsis a n d M u lt i orga n Fa i l u re

3.

4.

5. 6.

7. 8.

I

97 1

b. Protocolized insulin (other than tight glycemic control) and nutrient management recommended. c. Hypoglycemia may be missed with bedside glucose monitoring. Exercise caution in use of point-of-care glucose testing, as levels may be overestimated. Lung-protective strategies. a. Sepsis accounts for a significant number of cases of acute lung injury (ALI) and ARDS. b. Low tidal volume mechanical ventilation is a key component to ALI/ ARDS care. c. Recommend setting a goal tidal volume of 6 mL/kg ideal body weight for mechanically ventilated sepsis ALI/ARDS patients. d. Limit plateau pressure to �30 cm H 2 0 . Prophylaxis. a. Deep venous thrombosis (DVT) prophylaxis should be administered to all patients unless contraindicated. b. Stress ulcer prophylaxis indicated for all patients unless contraindicated. Renal replacement therapy should be initiated for MODS and kidney failure. For MODS, some literature supports the use of antimicrobial agents to decontaminate the oropharynx and digestive tract to reduce the risk of ventilator pneumonia and eliminate harmful intestinal bacteria. These practices remain controversial in the US due to antimicrobial stewardship issues and concerns for higher levels of antibiotic resistance in the US. Early enteral nutrition is supported in the management of MODS. Comfort-only care. a. Communication with the patient and family is an important element of care. Early discussions regarding expected outcome should be initi­ ated. Aggressive care needs to be balanced with patient wishes.

S UGG ESTED R EAD I NGS

Annane D, Aegerter P, Jars-Guincestre MC, et al. Current epidemiology of septic shock: the CUB-Rea Network. Am ] Respir Crit Care Med 2003; 1 68 : 1 65- 1 72. Serves as a review ofsepsis epidemiology. Artinian V, Krayem H, DiGiovine B. Effects of early enteral feeding on the outcome of criti­ cally ill mechanically ventilated medical patients. Chest 2006; 1 29:960-967. Important study illustrating the impact on early enteral nutrition in reducing mortality in critically ill patients. Cine! I, Opal SM. Molecular biology of inflammation and sepsis: a primer. Crit Care Med 2009;37:29 1-304. Comprehensive review ofmolecular mechanisms involved in the sepsis inflammatory cascade. Dellinger RP, Levy MM, Rhodes A, et al. International Surviving Sepsis Campaign Guidelines Committee. Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 20 1 2 . Crit Care Med 20 1 3 ;4 1 :5 80-637. Most recent consensus guidelines on severe sepsis and septic shock management. de Smet AM, Kluytmans JA, Cooper BS, et al. Decontamination of the digestive tract and oropharynx in ICU patients. N Engl] Med 2009;360:20-3 1 .

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Study presenting reduced mortality with selective oropharyngeal and digestive tract decon­ tamination. Kumar A, Roberts D, Woods K, et al. Duration of hypotension before initiation of effective Antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 2006;34: 1 5 89-1 596. Original article illustrating the critical time dependence ofantibiotic delivery in hypoten­ sive sepsis patients. Levy MM, Fink MP, Marshall JC, et al. 200 1 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 2003;3 I : 1 250- 1 256. Most recent consensus definitions for sepsis, severe sepsis, and septic shock. Marshall JC, Cook DJ, Christou NV, et al. Multiple organ dysfunction score: a reliable descriptor of a complex clinical outcome. Crit Care Med 1 99 5 ;23 : 1 638-1 652. Original article describing development and validation ofthe multiple-organ dysfanction score. Marcin GS, Mannino DM, Eaton S, et al. The epidemiology of sepsis in the United States from 1 979 through 2000. N Engl] Med 2003;348 : 1 546- 1 5 54. A 20-year review ofsepsis epidemiology trends. Mizock BA: The multiple organ dysfunction syndrome. Dis Mon 2009;55 :476-526. Comprehensive and educational review ofMODS. Nice-Sugar Investigators, Intensive versus Conventional Glucose Control in Critically Ill Patients. N Engl] Med 2009;360 : 1 283-1 297. Large randomized trial used by Surviving Sepsis Campaign 2012 to make most recent glucose management recommendations. Otero, RM, Nguyen, B, Huang, DT, et al. Early goal-directed therapy in severe sepsis and septic shock revisited. Chest 2006; 1 3 0 : 1 579- 1 5 9 5 . In-depth review of the controversies surrounding EGD T Ranieri VM, Thompson BT, Barie PS, et al. Drotrecogin alfa (activated) in adults with septic shock. N Engl J Med 20 1 2;366:205 5-2064. Repeat randomized trial showing no difference in mortality in sepsis patients receiving activated protein C. Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of Severe sepsis and septic shock. N Engl]Med 200 1 ;345 : 1 368-1 377. Original landmark EGD T trial. Rivers E. Point: adherence to early goal-directed therapy: does it really matter? Yes. After a decade, the scientific proof speaks for itself. Chest 20 1 0 ; 1 3 8 :476-480. Thorough review ofthe evidence supporting EGD T in practice. Sprung C, Brezis M, Goodman S, et al. Corticosteroid therapy for patients in septic shock: Some progress in a difficult decision. Crit Care Med 20 1 1 ;39:571-574. Educational literature review ofpast andpresent steroid use in sepsis with current recommendations. The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 2000;342: 1 3 0 1 - 1 308. Original ARDS network trial illustrating the importance oflow tidal volume mechanical ventilation. Vincent JL, Moreno R, Takala J, et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related problems of the European Society of Intensive Care Medicine. Intensive Care Med 1 996;22:707-7 1 0 . Explanation ofthe SOFA score.

An Ap p roa c h to N e u ro l og i c P robl e m s i n th e I nte ns ive Ca re U n it D a v i d A. D ra c h m a n

I . G E N E RAL P R I N C I PLES

A. Patients with neurologic problems present in the intensive care unit (ICU) as primary neurologic problems or as neurologic complications secondary to medical or surgical disorders. Only a few common neurologic situations occur in the ICU, although they can be caused by many diseases. 1 . Depressed state of consciousness, coma. 2. Altered mental function. 3. Required support of respirations or other vital functions. 4. Monitoring: increased intracranial pressure (ICP) , respirations, consc10usness. 5. Determination of brain death. 6. Prevention of further damage to the central nervous system (CNS). 7. Management of seizures or status epilepticus. 8. Evaluation of a neurologic change occurring as a result of known medical disease. 9. Management of medical disease developing during neurologic illness. 10. Acquired weakness during an ICU stay.

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B. Primary neurologic problems in the ICU include the following: 1. Stroke. 2. Guillain-Barre syndrome. 3. Status epilepticus. 4. Myasthenia gravis. 5. Head or spinal cord trauma. C. Neurologic complications of medical disease are far more common than primary neurologic problems. They include: 1. Impaired consciousness following cardiac arrest and cardiopulmonary resuscitation. 2. Altered mental status from metabolic disorders. 3. Development of delirium. 4. Critical care neuromyopathy. 5. Focal neurologic deficits, or impaired consciousness, in a patient with multisystem disease. D. Indications for neurologic consultation in the ICU. 1. Depressed state of consciousness. Depressed consciousness ranges from lethargy to coma and raises many questions: a. Is there a focal brainstem lesion or diffuse cerebral involvement? b. Is there an anatomic lesion or a metabolic disorder? c. Have vital brainstem functions been impaired? d. Is ICP increased? 2. The most common primary neurologic causes of depressed consciousness include: a. Head trauma. b. Intracranial hemorrhage. c. Nonconvulsive seizures. 3. The secondary conditions seen most often are a. Metabolic-anoxic disorders. b. Drug intoxications. c. Diabetic ketoacidosis. 4. It is crucial to establish whether depressed consciousness is the result of a. Intrinsic brainstem damage. b. Increased I CP. c. Toxic substances. d. Widespread anoxia/ischemia. e. Other, less common causes. I I . D IAG N O S I S

A . In the patient with depressed consciousness, i t i s particularly important to identify as rapidly as possible the component(s) that may be treatable! 1. Neurologic examination of patients with stupor or coma. Examination of the patient with depressed consciousness includes evaluation of (a) mental status, (b) cranial nerve functions, (c) motor functions and coordination, (d) reflexes, (e) sensation, and (f) vascular integrity; supplemented by appropriate laboratory studies.

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a. Mental status. i. Detailed evaluation of memory and cognitive function is rarely possible in lethargic patients and is impossible when stupor or coma is present. ii. Estimate the responsiveness of the patient, including vital func­ tions, respiratory pattern, eye opening, response to painful stimuli, and speech. b. Cranial nerve evaluations: Vision (e.g. , blink to threat) , pupils (size and response) , corneal reflexes, "doll's eyes" responses, and, if absent, ice water caloric response, cough, facial movements to pain, and gag reflex are tested. c. Motor function: Evaluate by observing all limbs for spontaneous movement, symmetry, and adventitious movements. Pinch or other noxious stimulus may help evaluate purposeful defensive movements. i. Decerebrate (four-limb extensor) or decorticate (upper limbs flexor, lower limbs extensor) rigidity is observed. ii. Tone is assessed for spasticity or rigidity. d. Reflexes: Deep tendon reflexes, grasp, suck, snout, and plantar reflexes are evaluated. e. Sensation: Pain is often the only testable sensation; withdrawal from pinprick in the feet must be distinguished from an extensor plantar response. f. Vascular status: Listen for bruits over the carotid, subclavian, and vertebral arteries. 2. Laboratory studies. a. Imaging studies: Magnetic resonance imaging (MRI) or computed tomography (CT) can reveal evidence of stroke, hemorrhage, trauma, tumor, and so forth, despite the difficulty of obtaining these studies. b. Electroencephalography (EEG) : This reveals seizure activity, func­ tional state, symmetry, certain toxic-metabolic conditions. Can be performed at the bedside. c. Metabolic studies: Electrolytes, ammonia, pH, 0 2 saturation, renal function, hepatic function, toxic substances, and others. 3. Interpretation. This examination reveals the patient's state of con­ sciousness, the integrity of brainstem reflexes, the presence of focal versus diffuse neurologic deficits, and provides information on specific metabolic disorders. B. Management of patients with depressed consciousness depends on deter­ mining the cause and applying the appropriate techniques for eliminating toxins, reducing ICP, and maintaining vital functions. 1 . Altered mental function: In the awake patient, disorders that affect mental function can produce patterns of confusion, delirium, aphasia, dementia, or isolated memory impairment. Ask the following questions: a. Is the abnormal mentation a recent change or long-standing? b. Did the change develop abruptly after surgery, cardiac arrest, or other event? c. Is the mental change improving, worsening, or stable?

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Confusion and delirium: often result from metabolic or toxic disorders; they are commonly reversible. 3. Persistent aphasia and isolated memory impairment: suggest focal anatomic damage to the brain. Neurologic examination for localization and imaging studies are useful. 4. Dementia/cognitive impairment: can be assessed only in patients with a clear sensorium; it cannot be evaluated in patients with depressed consciousness, confusion, or delirium. Cognitive impairment can indi­ cate either reversible (drug-induced, depression-related) conditions or irreversible damage (diffuse anoxia, ischemia, strokes, or a degenerative dementia) . 5. Recent change of mental status in the ICU requires evaluation by an experienced neurologist as early as possible! 2.

C. Support of respiration and other vital functions. 1. Respiratory support is needed for neurologic patients with a. Loss of brainstem control of respiration. b. Impairment of effective transmission of neural impulses to respira­ tory muscles. c. Brainstem lesions produce characteristic respiratory patterns, depend­ ing on the site of damage (e.g., central neurogenic hyperventilation, Cheyne-Stokes or periodic breathing, apnea) . Transmission of respira­ tory impulses can be impaired at the cervical spinal cord, anterior horn cells, peripheral nerves, neuromuscular junctions, or muscles of respi­ ration. Traumatic cervical cord injuries, amyotrophic lateral sclerosis, the Guillain-Barre syndrome, myasthenia gravis, and muscular dystro­ phy interfere with breathing at these different levels. Some conditions are transitory (Guillain-Barre syndrome) or treatable (myasthenia gravis), with complete recovery if respiration is successfully maintained. D. Monitoring ICP and state of consciousness. Head trauma, subarachnoid hemorrhage, tumor, and stroke may require neural monitoring. 1. Lethargic patients should be observed for increased ICP caused by cere­ bral edema, intracranial (subdural, epidural, inrracerebral) hemorrhage, or both. 2. Once uncal or tonsillar herniation with brainstem compression occurs, the secondary brain injury may far outweigh the initial damage (meth­ ods for monitoring ICP and assessing consciousness with the Glasgow coma scale are described in Chapter 1 5 and the Appendix of this manual) . E. Determination of brain death. 1. Death of the brain and brainstem is equivalent to death of the patient. a. Brain death is specifically a determination that the brain and the brainstem are already dead-not a prediction of unlikely useful recovery. b. The mnemonic CADRE is useful to remember the criteria for brain death: coma, apnea, dilated fixed pupils, reflex (brainstem) absence, and EEG silence.

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F. Preventing further damage to the CNS. 1. In stroke, thrombolytic treatment or mechanical clot removal can reverse the ischemic process, and neuroprotective agents may prevent further damage. 2. Spinal cord compression by tumor requires decompression and/or radia­ tion therapy to avoid cord transection. 3. Cerebral ischemia, anoxia, hemorrhage, increased ICP, spinal cord compression, and other acute neurologic disorders require prompt institution of treatment. G. Managing status epilepticus. Status epilepticus threatens lasting deficits or death if not controlled. 1. Patients with continuous or recurrent seizures that cannot be promptly arrested must be treated in the ICU. 2. Therapy ranging up to general anesthesia and support including mechanical ventilation may be required. H. Evaluating secondary neurologic disease in severe medical illness. Patients in the ICU with myocardial infarctions, subacute bacterial endo­ carditis, cardiac arrhythmias, pneumonia, renal disease, and other diseases that impact neurologic function may develop neurologic changes during treatment for the medical problem. These neurologic findings may result from the underlying disease or be coincidental; a neurologist should evalu­ ate such patients. I. Managing secondary severe medical disease in neurologic illness. Patients with chronic neurologic disorders often develop unrelated medical illness: for example, myocardial infarction that occurs in a demented patient or septicemia in a patient with multiple sclerosis. Early recognition of a change in the neurologic patient's condition is often critical to a suc­ cessful outcome. I l l . PROGN OSTIC AND ETH I CAL C O N S I D E RATI O N S

A. When severe damage involves the brain, physicians and their families often seek guidance regarding the probable outcome. Three critical questions should be addressed: 1. Will the patient survive? 2. Has irreversible brain damage occurred? 3. What is the likely degree of residual disability? B. The most important consideration is whether irreversible damage has affected crucial brain areas, rather than the level of consciousness. The probability of neurologic recovery declines with age, size, and location of the lesion and duration of the deficit. Discontinuing sedation is critical in evaluating the patient's functional state. When prognosis is unclear, waiting and watching for an extra day is often of value. (Some reported statistical guidelines are of value in estimating recovery; see, e.g., Levy D, Caronna J, Singer B, et al. in Suggested Readings.).

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SUGGESTED READI NGS

Levy D, Caronna J, Singer B, et al. Predicting outcome from hypoxic-ischemic coma. JAMA 1 9 8 5;253: 1 420. An excellent summary ofthe features that predict survival andfonction following hypoxic-ischemic coma. Posner JB, Saper CB, Schiff ND, et al. Plum and Posner's diagnosis ofstupor and coma, 4th ed. New York: Oxford University Press, 2007. A classic review ofthe neurologic aspects ofimpaired consciousness, updated. Ropper A. Neurological and neurosurgical intensive care, 4th ed. Philadelphia: Lippincott Williams & Wilkins, 2003. A multiauthor book with detailed discussions ofmany aspects ofneurologic intensive care. Wanzer S, Federman D, Adelstein S, et al. The physician's responsibility toward hopelessly ill patients: a second look. N Engl] Med 1 989;320: 844. A thoughtful approach to end-oflife issues in patients with terminal illness. Wijdicks E, Hijdra A, Young G, et al. Practice parameter: prediction of outcome in comatose survivors after cardiopulmonary resuscitation (an evidence-based review) . Neurology 2006;67:203-2 1 0 . Guidelines fo r assessment ofprognosis i n post-CPR coma. Zandbergen E, deHaan R, Reitsma J, et al. Survival and recovery of consciousness in anoxic-ischemic coma after cardiopulmonary resuscitation. Intensive Care Med 2003;29: 1 9 1 1- 1 9 1 5 . A review of recovery following anoxic-ischemic coma. Zandbergen E, Hijdra A, Koelman J, et al. Prediction of poor outcome within the first 3 days of postanoxic coma. Neurology 2006;66:62-68 . Somatosensory evoked potentials and neuron-specific enolase predict poor outcome following cardiopulmonary arrest.

A l te re d C o ns c i o u s n ess R a p h a e l A . C a ra n d a ng , Lawre n c e J . H a ywa rd , a n d D a v i d A . D ra c h m a n

I . OVERVIEW

A. Introduction. Many diseases lead t o acute impairment o f consciousness, including some that are potentially life threatening but treatable if recognized early, and require a systematic and complete evaluation: 1. Rapid determination of the type of mental status change. 2. Administration of emergent treatment and life support measures when needed. 3. Obtaining a detailed history, physical and neurologic examinations, and ancillary studies. 4. Initiation of definitive treatment based on this assessment. B. Pathophysiology. 1. Altered sensorium (state of consciousness) results from damage or dys­ function of the reticular activating system (RAS) in the brainstem and diencephalon, and/or their projections ro both cerebral hemispheres. 2. Many structural/physiologic disorders can affect the RAS or both hemi­ spheres diffusely and impair consciousness (Table 1 1 9- 1 ) . C . Prognosis. Depends o n the cause o f coma and any secondary complications. D. Diagnosis. The clinician must distinguish among potential causes, includ­ ing normal sleep, coma, status epilepticus, akinetic mutism, locked-in state, and aphasia. E. Treatment. Depends on the underlying cause and the presence or absence of cerebral edema. I I . T H E PAT I E NT W H O APPEARS U N C O N S C I O U S

A. General principles. Some patients appear r o be unconscious when this is not the case. The differential diagnosis includes the following: 1. Normal sleep (can be aroused to complete wakefulness by verbal or physical stimulation) . 2. Psychogenic coma (demonstrate clinical and electroencephalographic [EEG] evidence of wakefulness) . 3. Locked-in state (awake and can communicate by vertical eye movements) . 4. Nonconvulsive status epilepticus (impaired consciousness with EEG evidence of continuous seizures) . 5. Stupor/coma (sustained arousal by stimuli cannot be obtained) . 6. Brain death (absence of brain activity clinically and by ancillary testing) . 979

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TA B L E 1 1 9 - 1

fferential Diagnosis of I m pa i red o r Altered onscious ness

I. I m pa i red consciousness with foc a l or latera l izing signs of bra i n d isease:

A. Neop lastic or i nfla m matory mass lesions: b ra i n t u m o r, b ra i n a bscess B. Vasc u l a r d isease: cere b ra l h e m orrhage, throm bosis, e m bolism C . Tra u m atic bra i n i nj u ry: contu s i o n , s u bd u ra l , or e p i d u ra l hemato ma I I . I m pa i red consciousness with signs o f men i ngea l i rritat i o n :

A. Se ptic•: i n fectious m e n i ngitis ( bacteria l , mycobacteria l , v i ra l , fu nga l , parasitic) B. Vasc u lar: s u ba ra c h n o i d hem orrhage C . Neoplastic : lepto m e n i ngea l ca rc i nomatos is or lym phoma D . R h e u m atologic cond itio n s : m e n i ngea l gra n u lomatou s d i sorders (e.g . , sa rcoid , polya ngiitis gra n u l omatosis p reviously referred to as Wege ner gra n u lomatos is) I l l . I m pa i red consc iousness without foca l , latera l izi ng, or m e n i ngea l signs:

A. Toxic encephalopathy: a lcoho l , ba rbitu rate, o p iates, carbon mo noxide poison i ng, se roto n i n syn d ro m e , n e u ro l e ptic m a l ignant syn d ro m e , tricy­ c l i c a ntidepressa nts, a m p h eta m i n es, a ntic h o l i n e rgic agents, sedatives, carbon monoxide, and h eavy m eta l toxins B . M eta bo l i c b : a n oxia/hypoxe m i a , hype rca p n i a , hyponatre m i a , hypoglycem i a , hyperglyce m i a , u re m i a , h e patic fa i l u re, hypertherm i a , hypoth e r m i a , hype rca l ce m i a , t h ia m i n e , or coba l a m i n deficiency C. Septic : i nfectious encephal itis, bacterial a n d vira l e n ce p h a l itis, se pticem ia , p n e u m o n i a , rheu matic feve r, a n d connective tissue d i seases D. Va sc u la r : hyperte nsive encephalopathy E. Ac ute hyd roce p h a l u s : o bstructive F. Tra u matic: concussio n , d iffuse axona l i nj u ry G . Electrica l : nonconvu lsive status e p i l e pticus, seizu res H . Situati o n a l psych oses : i nte ns ive ca re u n it, puerpera l , posto perative , or posttra u matic psyc hoses; severe sleep d e p rivation ca n be com pl icat­ ing fa ctor I . Neoplastic/i nfla m matory: pa ra n eo p lastic syn d romes, vasc u l itis, a n d l u pus cerebritis 'M e n i ngismus is often a bsent i n deeply comatose patients with m e n i ngea l i nfla mmati o n . 'Meta bolic derangements can prod uce foca l signs, for exa m ple, ocu l a r moti l ity d istu rbance d u e t o t h ia m i n e deficiency a n d foca l deficits with hypoglycem i a . Ada pted from A d a m s R D, Victor M . Principles o f neurology. 4th ed . N ew York: M c G raw- H i l l , 1989 .

B. Prognosis. 1. Depressed consciousness: Prognosis depends on the underlying cause, degree of reversibility, and presence of secondary brain damage from effects of raised intracranial pressure (ICP) or tissue shifts. 2. Locked-in state: Patients usually have permanent paralysis but can com­ municate through blinks. Acute locked-in state can sometimes be reversible with treatment of the underlying cause (i.e., thrombolytic therapy for a basilar artery stroke) .

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3. Status epilepticus: Usually reversible with antiepileptic drugs but may sustain permanent damage after prolonged seizure activity. When seen in anoxic coma, indicates a poor prognosis for recovery. 4. Stupor/coma: Prognosis depends on anatomic damage, physiologic, or biochemical etiology. C. Diagnosis. 1. Rapid evaluation for the presence of neck rigidity on flexion (meningitis or subarachnoid hemorrhage) , needle marks (drug overdose) , hypogly­ cemia, or asymmetric dilated pupils (impending herniation) should be a priority before a more detailed examination. 2. Detailed history of onset, preceding events, past medical history, and the medication/drug history is crucial to establishing the correct diagnosis. 3. In mild brain dysfunction (drowsiness, hypersomnolence), mild sensory stimulation results in orientation and appropriate responses are made. In more severe brain dysfunction (stupor) , more severe and sustained sensory stimuli are required to achieve transient arousal. Patients may have purpose­ ful movements when aroused but lack normal content of consciousness. 4. Apparently comatose patients demonstrating active resistance, rapid closure of the eyelids, pupillary constriction to visual threat, fast phase of nystagmus on oculovestibular or optokinetic testing, and avoidance of self-injury may have psychogenic coma. 5. If spontaneous blinking is present in a paralyzed patient, appropriate responses may be elicited to questions, indicating normal cortical func­ tion (locked-in syndrome) . 6. Severe brain dysfunction results in coma, from which patients cannot be aroused. 7. Nonfocal neurologic examination is suggestive of a toxic-metabolic coma, with some exceptions (meningoencephalitis, subarachnoid hem­ orrhage, bilateral subdural hematomas, or thrombosis of the superior sagittal sinus) (Table 1 1 9- 1 ) . 8 . Presence o f focal neurologic signs (cranial nerves o r motor system) sug­ gests a structural lesion as the underlying cause of coma. 9. Brain death is the irreversible destruction of the brain (total absence of all cortical and brainstem function) , although spinal cord reflexes may remam. a. Pupils are in midposition, are round, and do not respond to light. b. The Apnea test. No inspiratory effort (i.e., central apnea) even when arterial carbon dioxide tension (PCO ,) is raised to levels that should stimulate respiration. Sedating medications, drug intoxications, metabolic disturbances, hypothermia, and shock should be excluded as complicating conditions in determining brain death. D. Ancillary tests. 1. Imaging. a. Computed tomographic (CT) or magnetic resonance imaging (MRI) scan without contrast demonstrate intracranial hemorrhage and hydrocephalus. b. Contrast enhancement is indicated for the detection of infections or neoplastic masses.

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c. MRI demonstrates ischemia within minutes after stroke onset. d. CT and MR angiography or conventional angiography may be indi­ cated if vascular causes are suspected. 2. Comprehensive metabolic profile, blood gases, and toxic screen must be performed, especially if CT and MRI fail to demonstrate a structural lesion. 3. The cerebrospinal fluid must be examined if meningoencephalitis or subarachnoid hemorrhage is suspected. 4. EEG is most useful in suspected seizures, as a confirmatory test for brain death, in suspected infections (herpes encephalitis, Creutzfeldt-Jakob disease) , and to demonstrate normal rhythm and reactivity in locked-in syndrome and psychogenic coma. E. Treatment. 1 . Definitive treatment of altered consciousness depends on the underlying cause. 2. Reversal of depressed consciousness with intravenous thiamine, glucose, or naloxone often provides rapid diagnostic clues about unsuspected thiamine deficiency, hypoglycemia, or opioid overdose, respectively. 3. In cases of suspected clinical herniation, emergent administration of osmotherapy with mannitol or hypertonic saline, and emergent neuro­ surgical consultation, may be needed. 4. In suspected cases of acute cerebral ischemia, emergent stroke neurologic evaluation is indicated for consideration of tPA, clot retrieval, or a neu­ rointerventional procedure. 5. Fluid replacement, oxygenation, suctioning, positioning, nutrition, cor­ neal protection, and bowel and bladder care are essential. NB: Sedating drugs confound the accurate diagnosis and monitor­ ing of the patient's neurologic condition and should be avoided or minimized whenever possible.

6. In patients with ischemia/hypoxia in the setting of cardiac arrest­ induced hypothermia, may limit neurologic damage and improve out­ come (see Chapter 24) . I l l . T H E PAT I E N T APPEARS AWAKE B U T IS C O N FU S E D O R N O N C O M M U N I CATIVE

A. General principles. Patients with this clinical presentation may have acute confusional state, delirium, nonconvulsive seizures, receptive aphasia, or akinetic mutism. 1. Acute confusional state: Easily distracted, poor attention span with resultant poor recall, and short-term memory. 2. Delirium (see chapter 1 42 that deals with this in the Psychiatry section) . a. Behavior that suggests an acute confusional state. b. Hypervigilance with delusions and often visual hallucinations. c. Autonomic hyperactivity. d. Psychomotor retardation in "quiet delirium."

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3. Nonconvulsive status epilepticus. Signs that are suggestive of this diagnosis are episodic staring, eye deviation or nystagmoid jerks, facial or hand myo­ clonic activity, or automatisms. 4. Receptive aphasia. a. Unable to respond to or repeat commands. b. Fluent but jargon speech with paraphasias (word substitution) .

5. Akinetic mutism. a. Brainstem function is intact, and sleep-wake cycles may be present. b. Little evidence is seen of cognitive function. Patient may open eyes to auditory stimulation or track moving objects, but only a paucity of spontaneous movement occurs. 6. Persistent vegetative state. a. Similar to akinetic mutism, more severe and usually follows pro­ longed coma. b. Complex subcortical responses are absent, but decorticate or decer­ ebrate posturing and rudimentary subcortical responses (e.g., yawn, cough) are seen. 7. Minimally conscious state. a. Similar to persistent vegetative state but shows some evidence of self and environmental awareness, visual tracking, follows simple com­ mands, gives gestural yes or no responses, purposeful behaviors. b. Transitional phase of recovery from coma or afrer vegetative state. B. Diagnosis. 1. The history is critical in determining the cause of the patient's condition, and efforts to locate family members, witnesses, and medication lists are almost always fruitful. a. Knowledge of preexisting cerebral dysfunction (e.g., dementia, multiple sclerosis, mental retardation) is important in determining the degree of depressed consciousness or confusion expected for a specific systemic derangement (e.g. , hyponatremia, sepsis, drug intoxication) . b. A reliable account of the tempo of loss of consciousness is important. For example, rapid-onset coma in a healthy person suggests intracra­ nial hemorrhage, brainstem ischemic stroke, meningoencephalitis, an unwitnessed seizure, or drug intoxication. 2. Focal neurologic signs suggest a structural cause of altered consciousness, although focal weakness or partial motor seizures sometimes occur in metabolic encephalopathies (e.g. , hypoglycemia) . Other falsely local­ izing signs include sixth nerve palsies caused by transmitted increased ICP, and visual field cuts caused by compression of the posterior cerebral artery. Conversely, a nonfocal examination does not invariably indicate toxic-metabolic encephalopathy, although it often will cause symmetric neurologic dysfunction (Table 1 1 9-2) . 3. Treatment. Refer above to treatment of impaired consciousness.

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TA B L E 1 1 9 - 2

assification o f Causes o f Altered Consc iousness ased o n M ost Com mon C l i n ical Presentation

1.

Depressed conscious ness or ac ute confusional state without foca l or late ra l iz i n g n e u rologic signs a n d without signs of m e n i ngea l irritat i o n . • • M eta bolic d isord ers: h e patic fa i l u re , u re m i a , hyperca p n i a , hypoxi a , hypoglyce m ia , d i a betic hyperos m o l a r state , hyperca lcem i a , th i a m i n e or coba l a m i n d eficie ncy, hypotension • Drug i ntoxications o r poison i n g : o piates, a lcohol, barbitu rates, tricyc l i c a ntidepressa nts, a m pheta m i nes, a nticholi nergic agents, oth er sedatives, carbon monoxide, h eavy m eta l toxins • I nfectious a n d oth er fe brile i l l n esses: septice m i a , p n e u m o n i a , r h e u m atic feve r, conn ective tissue d iseases • Nonconvulsive status e p i lepticus o r postconvu ls ive letha rgy • Situational psyc hoses: i ntensive ca re u n it, puerpera l , postoperative, o r posttra u matic psyc h oses; severe s l e e p d e p rivation ca n be co m p l icati ng facto r • Abstinence states ( i . e . , withd rawa l states) : a lcohol (del i ri u m tre m e n s ) , barbitu rates, benzod iaze p i nes • S pace-occ u pying lesions: b i l atera l s u bd u ra l hemato m a , m i d l i ne cere b ra l t u m o rs (e.g. , lym p h o m a , g l i o m a ) , a bscess • Hyd rocep h a l u s

2.

Alte red consciousness with signs o f m e n i ngea l i rritation • I nfectious d isord e rs : m e n i ngoence p h a l itis ( bacteria l , v i ra l , funga l , parasitic) • S u ba ra c h n o i d h emorrhage: bra i n contusion , ru ptu red a n e u rysm , or oth e r vasc u l a r ma lformation • R h e u m atologic conditions: m e n i ngea l gra n u l omato u s d i so rd e rs (e.g. , sa rco i d , Wege ner gra n u lomatosis)

3.

Alte red consciousness with focal or lateralizing neurologic signsb • S pace-occ u pying lesi o n : neoplas m , hem orrhage, i nfla m matory p rocess (e.g. , a bscess, a u to i m m u ne encephal itis) • Cere b ra l isc h e m ia o r i nfa rction : stroke, hyperte nsive encephalopathy

' M e n i ngismus is often a bsent i n deeply comatose patients with m e n i ngea l infl a m mati o n . 'Meta bolic dera ngements ca n prod uce foca l signs, for exa m ple, ocu l a r moti l ity d istu rba n ce d u e t o t h ia m i n e deficiency a n d foca l deficits with hypoglycem i a .

SUGGESTED READI NGS

Carandang RA, Hayward LJ, Drachman DA. Evaluating the patient with altered conscious­ ness in the intensive care unit. In: Irwin RS, Rippe JM, eds. Intensive care medicine, 7th ed. Philadelphia: Lippincott Williams & Wilkins, 2 0 1 2 . The foll-length version (Chapter 1 69) ofthis chapter. Posner JB, Saper CB, Schiff N, et al. Plum and Posner's diagnosis ofstupor and coma, 4th ed. New York: Oxford University Press, 2007. Classic monograph, with original investigations on stupor and coma, recently expanded and updated.

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Ropper AH, Brown RH. Adams and Victor's principles of neurology, 8th ed. New York: McGraw-Hill, 2005. A lucid and comprehensive review ofdisorders ofcomciousness (Chapter 1 7) and acute confusional states (Chapter 20). Wijdicks EFM. The practice ofemergency and critical care neurology. Oxford, UK: Oxford University Press, 20 1 0 . A detailed, updated approach to the comatose patient (Chapter 1 2 "Comatose "), including algorithms for diagnosis and treatment.

M etabo l i c E n c e p h a l o p athy Pa u l a D . R a v i n

I . BACKG RO U N D

A. Metabolic encephalopathy i s defined as global brain dysfunction caused by a biochemical derangement. B. There is often a fluctuating level of consciousness with nonfocal signs. Patients can present with the following: 1. Delirium (confusion, inattentiveness, sleeplessness, hallucinosis) . 2. Depressed level of consciousness (drowsiness, stupor, coma) . 3. Seizures, behavioral disturbances, visual impairment. C. Metabolic encephalopathy is common in illnesses that cause multiorgan failure (see Table 1 20- 1 for typical patient profiles) . D. The following increase the risk of developing metabolic encephalopathy: 1. Age older than 60 years. 2. Systemic infection. 3. Temperature dysregulation. 4. Chronic disease of the central nervous system (CNS). 5. Organ failure. 6. Endocrine disorders. 7. Multiple CNS-acting drugs. 8. Nutritional deficiency. 9. Alcoholism. 10. Hisrory of perinatal injury. 1 1 . Sleep deprivation, sensory deprivation. E. In cases of a correctible metabolic disorder, prompt treatment may result in reversal of encephalopathy. F. Progression ro stupor or coma may lead ro prolonged encephalopathy and complications, with a poor neurologic outcome. I I . ETIOLOGY

A. B. C. D.

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Drugs and toxins (50%). Hepatic, renal, or pulmonary failure ( 1 2%). Endocrine or electrolyte disturbances (8%) . Other causes: thiamine deficiency (exacerbated by glucose loading) , pro­ longed hypoglycemia, hypoperfusion during cardiac bypass, hyperthermia (> 1 05°F), hyperammonemia, and severe hypertension.

C h a pter 1 2 0 • Metabo l i c E n c e p h a l opathy

TA B L E 1 2 0 - 1

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atient Prof i l e i n M eta bo l i c Encepha lopathy

• • • • •

G ra d u a l onset over h o u rs P rogressive if u ntreated Waxi ng a n d wa n i ng leve l of consciousness Patient treated with m u lt i pl e C N S-acting d ru gs Patient with o rga n fa i l u re , posto perative state, e lectrolyte or e n d ocri ne i m ba l a nce • N o evidence of CVA, bra i n tu mor: n onfoca l exa m i nation • Ca n be heralded by foca l o r gen e ra l ized seizu res • I nc reased s ponta neous m otor activity

C N S , centra l nervous system ; CVA, cerebrovascu l a r accident.

I l l . PAT H O G E N E S I S

A. Altered substrate (glucose/oxygen) for neurotransmitter function. B. CNS-depressant drug accumulation due to abnormal volume of distribution (decreased protein, high lipophilicity) . C. Impaired cerebral blood flow. D. Abnormal cerebrospinal fluid (CSF) dynamics. E. Altered neuronal function due to temperature and/or ionic changes. IV. DIAG N O S I S . Metabolic encephalopathy should be considered when a patient exhibits altered cognition or alertness. The clinical examination should include the following:

A. General physical examination. 1 . Vital signs, breathing pattern, and pulse oximetry. 2. Funduscopy, to evaluate for papilledema (increased intracranial pres­ sure) , septic emboli. a. Cardiovascular examination: Global cerebral hypoperfusion may result from congestive heart failure. 3. Bowel sounds: Obstruction/perforation may cause agitation and changes in mental status. 4. Bladder distention: Retention can lead to agitation. B. Neurologic examination. 1 . Behavioral changes: inattention, diminished speech, disorientation, impaired short-term memory, indifference, blunted affect, waxing and waning consciousness, and visual hallucinations. 2. Abnormal extraocular eye movements should raise suspicion of brain­ stem stroke or thiamine deficiency; pupils are usually small and reactive, although they may be dilated in some toxic encephalopathies related to adrenergic excess (e.g., thyroid storm, cocaine overdose) . 3. Respiratory pattern can be deranged in a variety of ways, includ­ ing hyperventilation (e.g., acidosis) , Cheyne-Stokes respiration,

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hypoventilation, gasping, apneic episodes (central or obstructive) , and hiccoughing. 4. Abnormal motor activity: tremors, myoclonus, asterixis, restlessness, chorea, muscle spasms, rigidity, and rigors. 5. Hyperreflexia and Babinski signs may be present. 6. Dysautonomia with widely fluctuating blood pressure and core tempera­ ture should raise suspicion of sepsis.

C. Metabolic encephalopathy should be distinguished from the following: 1. Brainstem stroke (see Chapter 1 23). 2. Increased intracranial pressure from an expanding mass lesion in the brain. 3. Meningoencephalitis (e.g., herpes) . 4. Occult head trauma. 5. Nonconvulsive status epilepticus. D. Metabolic encephalopathy due to thiamine deficiency (Wernicke-Korsakoff syndrome) should be suspected in all encephalopathic patients who are malnourished and/or have a history of alcohol abuse. Patients with the syn­ drome can present with oculomotor paresis, nystagmus, or pupillary abnor­ malities. Administration of glucose without parenteral thiamine can lead to an acute exacerbation of encephalopathy with permanent CNS injury. E. PRES (Posterior Reversible Encephalopathy Syndrome) may occur in patients with abrupt hypertension, renal impairment, autoimmune disorders, trans­ plantation, and treatment with immunosuppressive drugs. It is characterized by blindness, headache, confusion, seizures, and altered consciousness. The magnetic resonance imaging (MRI) shows characteristic white matter hyper­ intensities, typically (but not always) in the posterior parietal and occipital regions. It is a reversible syndrome; and removal of the trigger factors-chemo­ therapy, hypertension control, and treatment of other systemic disease--ofi:en results in recovery within a week, with slower resolution of the MRI changes. V. LAB O RATORY STU D I ES

A. Body fluids. 1. Toxicology screen, especially in patients with history of major depres­ sion, substance abuse. Include salicylates, barbiturates, opioids, amphet­ amines, alcohol, benzodiazepines, caffeine, and theophyllines. 2. Drug levels: digoxin, anticonvulsants, lithium. 3. Metabolic panel: blood urea nitrogen (BUN) , creatinine, electrolytes, complete blood count (CBC) , platelet count, thyroid-stimulating hor­ mone (TSH), calcium, phosphate, arterial ammonia, blood gases, serum and urine osmolality, and blood glucose. 4. When indicated, CSF analysis for infection, inflammation, subarach­ noid blood. 5. Urinalysis, urine culture, and blood cultures. B. Electroencephalogram (EEG) : Background slow wave activity or frontal triphasic waves are seen in metabolic encephalopathy. Epileptiform activity raises possibility of nonconvulsive status epilepticus.

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C. Imaging studies. 1. Computed tomography (CT) or preferably MRI scan of the brain, to evaluate for an acute structural lesion. 2. Chest radiographic films, to evaluate for occult pneumonia. 3. Abdominal radiographic films, to evaluate for bowel obstruction. VI. TREAT M E N T

A. Correction o f the underlying metabolic disturbance. Acute encephalopathy due to thiamine deficiency is a medical emergency. If suspected, give thia­ mine 1 00 mg intravenously daily for at least 3 days; the oral route is not as effective for rapidly repleting thiamine. B. Improvement in cognition and arousal may lag behind the improvement in metabolic parameters by days to weeks in some cases. 1. With underlying neurodegenerative disease, patients may not recover to their baseline level despite stabilized metabolic values. 2. Avoid adding CNS-acting drugs such as stimulants and sedatives (especially benzodiazepines) that can worsen the behavioral changes of metabolic encephalopathy, and focus on addressing the inherent causes. Treatment with an antipsychotic such as haloperidol, Zyprexa, or Seroquel can be helpful for the management of agitated delirium. VII. CONCLUS IONS

A. Metabolic encephalopathy i s a common cause o f altered neurologic function in the intensive care unit (ICU) setting. B. It should be suspected when there is a fluctuating or impaired mental status, bouts of restlessness, and a nonfocal examination. C. The causes are varied, but vigilant correction of metabolic disorders, reduction in CNS-acting drugs, and general supportive measures improve the outcome in most patients. D. Patients in the ICU commonly have poor nutritional status and global encephalopathy. These patients should be treated empirically for acute thiamine deficiency. SUGG ESTED R EA D I NGS

Barias I, et al. Neurologic complications in intensive care. Curr Opin Crit Care 2001 ;7:68-73 . This article helps narrow your focus on the most common metabolic encephalopathy syndromes in the ICU. Fenves A, Boland CR, Lepe R, et al. Fatal hyperammonemic encephalopathy after gastric bypass surgery. Am J Med 2008 ; 1 2 1 ( l ) : e l -e2. These encephalopathic complications are more common as bariatric surgery evolves. Hung SC, et al. Thiamine deficiency and unexplained encephalopathy in peritoneal dialysis patients. Am } Kidney Dis 200 1 ;38:94 1 -947. This is helpfol in recognizing the spectrum ofthiamine-induced metabolic encephalopathies.

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JanKarakoc E, Erdem S, Sokmensuer C, et al. Encephalopathy due to carnitine deficiency in an adult patient with gluten enteropathy. Clin Neurol Neurosurg 2006; 1 08(8): 794-797. This article reminds you to look for systemic complications ofgastrointestinal (GI) diseases in general. Kunze K. Metabolic encephalopathies. j Neurol 2002;249: 1 1 50-1 1 59. This article includes good tables and charts on metabolic encephalopathy. Lewis M, Howdle PD. The neurology of liver failure. QJM 2003;96:623-633 . Information pertinent to understanding encephalopathic mechanisms in liver failure. Li Y, Gor D, Walicki D, et al. Spectrum and potential pathogenesis of reversible posterior leukoencephalopathy syndrome. j Stroke Cerebrovasc Dis 2 0 1 2;2 l (8) :873-882. A useful discussion of the typical clinical picture ofPRES andputative pathophysiology. Marmatton BV. Sepsis associated encephalopathy. Neurol Res 2006;29 (7) :794-797. This covers the pathophysiology of metabolic encephalopathy in the context ofsepsis. Ropper AH, Brown RH. The acquired metabolic disorders of the nervous system. In: Adams and Victors principles of neurology, 8th ed. New York: McGraw Hill, 2005 :959-982. A superb overview of metabolic encephalopathies. Roth C, Ferbert A. The posterior reversible encephalopathy syndrome: what's certain, what's new? Pract Neurol 2 0 1 1 ; 1 1 : 1 36-144. A brief review of this syndrome, including typical MRI images and discussion ofthe etiology. Victor M. Neurologic disorders due ro alcoholism and malnutrition. In: Baker AB, Baker LH, eds. Clinical neurology, 2nd ed. Philadelphia: Harper & Row, 1 983. A classic, ifnot recent, chapter that covers the wide spectrum of nutritional metabolic encephalopathies.

G e n e ra l i z e d An oxi a/ls c h e m i a of th e N e rvo us Syste m S h a s h i d h a ra N a nj u n d a swa m y, N i ls H e n n i n g e r, R i c h a rd P. G o d d ea u J r, a n d M aj a z M oo n i s

I . G E N E RAL P R I N C I PLES

A. Failure o f blood flow (cardiac arrest) or reduced oxygenation t o the brain (respiratory failure, carbon monoxide, or cyanide poisoning) for 4 to 5 minutes' duration results in brain damage. B. Anoxia resulting from isolated respiratory arrest is better tolerated than when the primary event is a cardiac arrest. I I . PROG N O S I S . Many factors determine the prognosis after anoxic brain insult. These include the cause of the anoxic/ischemic insult, effective time to reestab­ lish circulation (arrest time [AT] , cardiopulmonary resuscitation [CPR] time) , level of consciousness, age of patient, and neurologic signs present at 24 to 72 hours.

A. Favorable prognostic indicators include the following: 1. Retained consciousness during the anoxic/ischemic insult. 2. Primary respiratory failure carries a better prognosis than primary car­ diac arrest. 3. Recovery of multiple brainstem responses within 48 hours of arrest (pupillary, corneal, and oculovestibular) . 4. Return of purposeful motor movements within 24 hours (localization of pain) . 5. Younger age (children may do well even beyond this time period) . 6. Hypothermia (e.g., cold water drowning) . B. Poor prognostic indicators in patients with persistent coma after 72 hours include the following: 1. The absence of pupillary responses at 24 hours or loss of pupillary reflexes at 72 hours. 2. No motor response or extensor-only response to pain at 72 hours. 3. Presence of diffuse cerebral edema on computed tomography (CT) scan with loss of gray-white differentiation. 4. Certain abnormal electroencephalogram (EEG) patterns, including burst suppression, a-coma, and low-voltage unreactive delta activity. Myoclonic status epilepticus has a very poor prognosis even with treatment.

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5. Absence of bilateral N20 somatosensory response within 1 to 3 days after CPR. 6. Elevated levels of serum neuron specific enolase >33 µg/L at days one to three days post-CPR. I l l . ETIOLOGY

A. Cardiac arrest from any cause. B. Respiratory failure from any cause. C. Poisoning (carbon monoxide, cyanide, others) . IV. PAT H O P H Y S I O LOGY. Following these injuries, excess glutamate release results in activation of the excitotoxic cascade, calcium influx into neurons, and cell death. V. D IAG N O S I S

A . History. 1 . Cardiac arrest. 2. Respiratory failure. 3. Drowning. 4. Toxic drug exposure/intoxication. B. Examination: Patients are comatose usually withour focal neurologic defi­ cits. Rarely soft neurologic signs have been documented. C. Imaging and laboratory studies. 1. CT or MRI scans to rule out structural lesions and brain herniation and demonstrate evidence of ischemic encephalopathy (cortical ribbon on diffusion MRI and loss of gray-white differentiation on CT) . 2. Blood glucose and liver function tests, including ammonia, blood urea nitrogen, and creatinine, should be obtained to rule out metabolic encephalopathy. Toxicologic screen should be obtained when the cause of coma is unknown. An immediate EEG if nonconvulsive status epilep­ ticus is suspected. V I . TREAT M E NT

A. Adequate oxygenation (Pao 2 at or over 1 00 mm Hg) and mean arterial blood pressure (90 to 1 1 0 mm Hg) should be maintained. B. Head of the bed should be elevated to 30 degrees. C. Underlying causes such as toxins or drug ingestion should be treated. D. Cardiac arrhythmias should be controlled. E. A diligent search for infections should be conducted and treated appropriately. F. Patients should not be allowed to become hyperthermic. G. All other toxic, metabolic, or structural causes of comas should be ruled out.

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H. Vital signs, hematocrit, electrolytes, blood sugar, and serum osmolarity should be maintained within the normal range. I. Seizures (25%) : Fosphenyroin at 20 mg phenytoin equivalents/kg intrave­ nously (IV) or intramuscularly (low risk of inducing hypotension and can be given intramuscularly if there is no IV access) . Alternatively, phenytoin in the same doses can be given with careful blood pressure and cardiac monitoring. If serious acute underlying cardiac arrhythmias exist, IV phe­ nobarbital is preferred. Intravenous valproate or intravenous levetiracetam is an alternate option, levetiracetam especially in cases where there is signifi­ cant liver dysfunction. J. EEG monitoring. 1. If seizures are controlled, a delayed EEG is done after 48 hours. 2. Continuous EEG monitoring is required for status epilepticus. K. Controlling brain edema. 1. There is no role for the use of steroids or high-dose barbiturates, and hyperosmolar agents are seldom helpful in anoxic or hypoxic coma. 2. Controlled hyperventilation with a Pco 2 of 25 to 28 mm may be effec­ tive in the short term to avoid impending herniation. L. Hypothermia: In two prospective randomized and controlled trials, induced hypothermia (IH) with rapid cooling to 33°C for 12 to 24 hours resulted in significant improvement in outcome after coma due to cardiac arrest compared with patients allowed to maintain normothermia. This is further supported by a meta-analysis of 5 randomized trials of 48 1 patients demonstrating improved outcome with IH. Increased vascular resistance, lactic acidosis, and decreased cardiac output were important complications. However, the incidence of cardiac arrhythmia was similar in the hypothermic and normothermic groups. Given these data, IH is currently considered the standard of care. Based on the published evidence to date, the International Liaison Committee on Resuscitation (ILCOR) Advanced Life Support (ALS) Task Force has made the following recom­ mendations: Unconscious adult patients with spontaneous circulation after out-of-hospital cardiac arrest should be cooled to 32°C to 34°C for 12 to 24 hours when the initial rhythm was ventricular fibrillation (VF). Such cooling may also be beneficial for other rhythms or in-hospital cardiac arrest. M. Mobilization: Once coma begins to lighten, early mobilization should be the goal to prevent other complications. V I I . C O M P LI CAT I O N S

A. Delayed brain damage: Seen rarely, 3 to 30 days after the initial recovery, especially following carbon monoxide poisoning, a late functional decline occurs with irritability, lethargy, and increased muscle tone. Pathologically, widespread demyelination is found. Most patients survive this second insult. B. Intention myoclonus is another delayed consequence. This can be distin­ guished from seizures by the absence of corresponding EEG changes.

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C. Persistent vegetative state: No cortical function, although the patient appears awake and retains many bodily functions (feeding, sleep-wake cycle) . D. Brain death: The clinical criteria of brain death are defined in Chapters 1 5 , 1 1 8 and 1 32. Total absence o f electrocerebral activity, not associated with sedative hypnotic drugs or hypothermia, is helpful in confirming brain death in difficult cases. Similarly, a brain scan showing absence of blood flow is strongly suggestive of brain death. SUGGESTED READI NGS

Abramson NS, Safar P, Detre KM . Neurological recovery after cardiac arrest. Effect of dura­ tion of ischemia. Crit Care Med 1 9 8 5 ; 1 4:930. A useful article that reviews the relationship between the duration ofcerebral ischemia and clinical outcome in anoxic encephalopathy. Ajisaka H . Early electroencephalographic findings in patients with anoxic encephalopathy after cardiopulmonary arrest and successful resuscitation. ] Clin Neurosci 2004; 1 1 :6 1 6-6 1 8 . A small study suggesting that EEG may b e more useful than C T scans in predicting prognosis following anoxic coma. Arrich J, Holzer M, Havel C, et al. Hypothermia for neuroprotection in adults after cardio­ pulmonary resuscitation. Cochrane Database Syst Rev 20 l 2;9:CD004 l 28. A systematic review of the evidence for induced hypothermia therapy. Bernard SA, Gray T'W, Buist MD, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 2002;346:5 57-563. This landmark prospective trial demonstrated that IH improves outcome after out-ofhospital cardiac arrest and anoxic coma. Chatrian GE. Coma, other states of altered responsiveness and brain death. In: Daly DD, Pedley AT, eds. Current practice of clinical electroencephalography, 2nd ed. Philadelphia: J.B. Lippincott, 1 997:42 5 . Electroencephalogram patterns and their prognostic significance in coma. Levy DE, Bates D, Caronna JJ, et al. Prognosis in non-traumatic coma. Ann Intern Med 1 9 8 1 ;94:293. A landmark article on the prognosis in nontraumatic coma. Nolan JP, Morley PT, Vanden Hoek TL, et al. Therapeutic hypothermia after cardiac arrest: an advisory statement by the Advanced Life Support Task Force of the International Liaison Committee on Resuscitation. Circulation 2003; 1 0 8 : 1 1 8 . A systemic review ofhypothermia trials and task force recommendations. Posner JB, Saper CB, Schiff ND, et al. Plum and Posner's diagnosis ofstupor and coma, 4th ed. New York: Oxford University Press, 2007. A classic review ofthe neurologic aspects ofimpaired consciousness, recently updated. Young GB. Neurologic prognosis after cardiac arrest. N Engl J Med 2009;36 1 :607-6 1 1 . Assesses the different prognostic indicators, including electrodiagnostic activity. Zandbergen EGJ, de Haan RJ, Stoutenbeek CP, et al. Systemic review of early prediction of poor outcome in anoxic-ischemic coma. Lancet 1 998;352: 1 808. A summary of the literature concerning reliable indicators ofdeath or a vegetative state following acute anoxia.

1 22

Status E p i l e pt i c u s F e l i c i a C. C h u a n d Cat h e r i n e A. P h i l l i ps

I . D E F I N IT I O N S

A. Status epilepticus i s defined as 1. One or more epileptic seizures lasting 30 minures or longer withour recovery between attacks (formal definition) ; or 2. Seizure activity lasting 5 minutes or longer (operational definition) with­ out recovery between attacks. B. Myoclonic status is repetitive, asynchronous myoclonic jerks typically in the setting of severe encephalopathy such as cerebral anoxia. C. Simple partial status is continuous or repetitive focal seizures withour loss of consciousness, such as focal motor seizures in epilepsia partialis continua. D. Nonconvulsive status is a confusional state of 30 minutes or more. 1. Absence status: may have subtle myoclonic facial movements and autom­ atisms of face and hands. 2. Complex partial status: either a series of complex partial seizures, sepa­ rated by a confusional state, or a prolonged state of partial responsiveness and semipurposeful automatisms. I I . ETI OLOGY

A. Symptomatic status-status caused by a neurologic or metabolic insult-is more common than idiopathic status. B. Status can be caused by stroke, anoxic brain injury, electrolyte disturbances (e.g., hyponatremia, hypomagnesemia, hypoglycemia, hyperglycemia, ure­ mia, sepsis) , drug or other toxicity, alcohol or other drug withdrawal, and decreasing antiepileptic medication. C. Viral encephalitis from Epstein-Barr syndrome or herpes simplex virus can have an abrupt onset heralded by status epilepticus. I l l . PRO G N O S I S AND S E Q U E LAE

A. Overall, mortality rate is 7% to 25%. Advanced age, generalized tonic­ clonic status epilepticus, depth of coma on presentation, and prolonged status (typically >24 hours) are poor prognostic factors. B. Status caused by anoxia has the highest mortality rate followed by hemor­ rhage, tumor, metabolic disorders, and systemic infection. Status caused by alcohol withdrawal and antiepileptic drug discontinuation, and idiopathic status have lower mortality rates. 995

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C. Long-term sequelae may include permanent focal neurologic deficits and chronic epilepsy. Aspiration pneumonia is a common complication of status. IV. I N ITIAL ASSESS M E NT, MANAG E M E NT, A N D M E D I CAL STA B I L I ZATI O N

A . Initial assessment and treatment should begin within 5 minutes o f onset of seizure activity (Table 1 22- 1 ) . B . History and exam: check fo r preexisting chronic seizure disorder, antiepi­ leptic drug use, illicit drug use and trauma. Examine for focal neurologic abnormalities. C. Status-induced hyperthermia will worsen neuronal injury and is essential to treat. D. Metabolic acidosis often develops early in status and resolves spontaneously once seizures stop without treatment with bicarbonate. E. When a metabolic disorder causes status, pharmacologic intervention alone is not effective. F. Exclude systemic and central nervous system (CNS) infections; lumbar puncture (LP) is often necessary; leukocytosis, fever, and cerebrospinal fluid pleocycosis may be caused by status itself. G. Only short-acting paralytic agents should be used; ongoing electroencepha­ logram (EEG) monitoring may be necessary for more continuous use. H. Contrast-enhanced head computed tomography (CT) scan can be done after the patient has been stabilized and the seizures controlled. Magnetic resonance imaging (MRI) is preferred but often not practical in the emer­ gent setting. V. P H A R M AC O L O G I C E P I LE PT I C U S

MANAG E M E N T

OF

G E N E RA L I Z E D

S TAT U S

A . Goals: stop seizures early; prevent recurrence; try t o determine the cause. Generalized convulsive status is a medical emergency. B. A benzodiazepine drug is the initial therapy for status. Both diazepam and lorazepam have essentially the same cardiac (hypotension) , respiratory (respiratory depression and apnea) , and CNS-depressant side effects. 1. Lorazepam IV: 0 . 1 mg/kg at 2 mg/minute; a 2- to 4-mg dose may be given initially up to 0.2 mg/kg. The dose of diazepam is 0. 1 5 mg/kg, additional 0 . 1 mg/kg if necessary. 2. Rectal diazepam is an alternative. For adults, 7.5 to 1 0 mg of the IV preparation or 0.2 mg/kg of the rectal gel preparation is administered per rectum (PR) . The incidence of significant respiratory depression is lower with PR compared to IV administration. 3. Intramuscular (IM) absorption of these agents is delayed and incom­ plete; this route is unsuitable for treating status. 4. Midazolam IM can be effective if there is no IV access. For adults, 5 to 10 mg can be administered intramuscularly or rectally. C. Phenytoin IV: 20 mg/kg IV load, 50 mg/minute. Give additional 5 mg/kg boluses of phenytoin to a maximum of 30 mg/kg, as needed. Do not give IM.

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M a nagement Protoco l for General ized Status Epi lepticus

Minutes: 0-1 0; first-line agents (benzodiazepines)

If d iagnosis is u ncerta i n , observe rec u rre nce of ge nera l ized seizu res without s u bseq uent recovery of consciousness. 2. S i m u lta neously, assess ca rd iopul monary status; esta b l ish a i rway; a d m i n ister 0 2 ; i n itiate ca rd iac mon itoring. 3 . Sta rt an I V l i n e for a d m i n istration of normal sa l i n e (avoid d extrose solution with p h e nyto i n ) . 4 . D raw b lood fo r com p l ete blood c o u n t a n d d iffe re ntia l , g l u cose , b l ood u rea n itroge n , creati n i n e , e l ectro lytes, ca l c i u m , l iver fu n ction tests , a nti e p i l e ptic d ru g leve l s , toxicology scree n ; perform bed s i d e g l u cose d ete rm i natio n . 5 . G ive g l u cose ( 050) 5 0 m l a n d th ia m i n e 1 00 m g I V i f hypoglyce m ia ( B G < 80) is prese nt. 6 . M o n itor res p i rations, blood press u re , ECG , oxi metry, a n d , if poss i b l e , EEG . 7. G ive loraze pa m (0. 1 m g/kg) IV bolus, 48 hours at doses > 5 mg/kg/h) resulting in car­ diocirculatory collapse with lactic acidosis, hypertriglyceridemia, and rhabdomyolysis. Close monitoring of serum triglycerides and serum lactate is mandatory. 9. The following drugs have been used in treatment of refractory status epilepticus with reported efficacy: a. Topiramate NG/PO 300 to 1 ,600 mg/day, divided two to four times daily. b. Lacosamide IV 200 to 400 mg, 200 mg IV over 1 5 minutes. c. Lyrica NG/PO 375 mg/day, divided two to three times daily. 10. Ketogenic diet is an emerging nonpharmacologic treatment of refractory status. The high-fat and low-protein/carbohydrate diet is administered via nasogastric tube and subsequently induces a metabolic shift toward acidosis, resulting in ketonuria, which can be present within a few days of initiation of the diet. Successful treatment of refractory status with the ketogenic diet has been described. V I . P H A R M AC O L O G I C MANAG E M E N T OF S TAT U S E P I L E PT I C U S

PART IAL A N D A BS E N C E

A. I n nonconvulsive or focal motor status, the diagnosis requires 30 minutes of continuous clinical (or electrical) seizure activity. When status epilepticus presents with a change in mental status only, an EEG is required for confir­ mation. B. Absence status is not associated with the severe adverse sequelae of convul­ sive status, but should be treated promptly, using the same protocol as for generalized status but with longer time allotments for each phase of the protocol, particularly before the induction of generalized anesthesia.

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SUGGESTED READI NGS

Brophy GM, Bell R, Clasassen J, et al. Guidelines for the evaluation and management of status epilepticus. Neurocrit Care 20 1 2 ; 1 7 ( 1 ) :3-23. Status epileptic treatment recommendations presented by the Neurocritical Care Society. A Status Epilepticus Guideline Writing Committee was established in 2008 to develop evidence-based expert consensus guidelines for diagnosing and managing status epilepticus. Knake S, Gruener J, Hattemer K, et al. Intravenous levetiracetam in the treatment of benzodi­ azepine refractory status epilepticus. ] Neurol Neurosurg Psychiatry 2008;79 :588-5 89. Presents data showing efficacy ofintravenous levetiracetam in the treatment ofstatus epilepticus. Neligan A, Shocvon SD. Prognostic factors, morbidity and mortality in tonic-clonic status epilepticus: a review. Epilepsy Res 20 1 1 ;93 ( 1 ) : 1 - 1 0 . Evaluates factors impacting prognosis ofconvulsive status epilepticus independent ofetiol­ ogy. In addition to analysis of mortality, morbidity is measured in terms offonctional decline, cognitive/intellectual decline, and risk ofdevelopment ofepilepsy. Rossetti AO, Lowenstein DH. Management of refractory status epilepticus in adults: still more questions than answers. Lancet Neurol 20 1 1 ; 1 0 ( 1 0) :922-930. Reviews risks and benefits of various treatments for refractory status epilepticus. Shorvon S. The emergency treatment of epilepsy. In: Shorvon S. Handbook ofepilepsy treat­ ment, 3rd ed. West Sussex: Wiley-Blackwell, 2 0 1 0:287-3 1 3 . Reviews the current concepts in the definition, clinicalfeatures, pathophysiology, and management ofstatus epilepticus. Wusthoff CJ, Kranick SM, Morley JF, et al. The ketogenic diet in treatment of two adults with prolonged nonconvulsive status epilepticus. Epilepsia 2 0 1 0;5 1 (6) 1 083- 1 0 8 5 . Case reports ofsuccessfol use ofthe ketogenic diet i n two adult patients with refractory nonconvulsive status epilepticus.

C e rebrova s c u l a r D isease M aj a z M o o n i s , R i c h a rd P. G o d d e a u J r, M u h i b K h a n , a n d J o h n P. Weaver

I . G E N E RAL P R I N C I PLES

A. Cerebrovascular disease includes the following: 1. Stroke caused by arterial thrombotic or embolic ischemia (IS) . 2. Intracerebral hemorrhage (ICH) and extracerebral hemorrhage (EH) into the subarachnoid, subdural, and epidural spaces. B. Admission to the intensive care unit (ICU) is often warranted because of the severiry of the disease or institution of newer therapies. C. This chapter focuses on ischemic cerebrovascular disease (ICVD) and ICH. I I . I CVD

A. Prognosis. 1. Altered sensorium (state of consciousness) , conjugate gaze paresis, and early radiologic signs of large infarction predict a poor outcome. 2. Lacunar stroke has a better prognosis (70% to 80% recovery) . 3. Transient ischemic attack (TIA) patients have a 5 . 5 % chance of stroke within 48 hours and 1 0% risk of stroke within 30 days. B. Etiology. 1. ICVD results from restriction of blood flow to the brain, usually because of arterial occlusion. 2. Cardioembolic stroke is due to ischemic/valvular heart disease, atrial fibrillation, or cardiomyopathy. 3. Atherothrombotic stroke is caused by occlusion of a large intra-/extra­ cranial portion of the carotid/vertebrobasilar system from progressive stenosis and occlusion. 4. Lacunar stroke is due to small blood vessel occlusion. 5. Watershed territory strokes result from systemic hypotension, with resulting border zone infarction (areas between anterior and middle cerebral artery [MCA] , or middle and posterior cerebral artery distribu­ tions) . C. Diagnosis. 1. History-helps to determine the rype of stroke. a. Cardioembolic more common during the day with acute onset. b. Atherothrombotic more often during sleep.

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Intracranial hemorrhage often starts with a headache, and deficit may progress for a considerable time. d. TIA is defined as a neurologic/ retinal deficit due to IS, followed by full recovery and lack of infarction on imaging studies. c.

2. Examination. a. Aphasia, hemiparesis or hemiparesthesia, and monocular visual loss suggest carotid system IS. b. Vertigo, cerebellar ataxia, and crossed deficits (ipsilateral cranial nerve and contralateral hemiparesis or hemianesthesia) suggest involvement of the vertebrobasilar system. c. Pure motor hemiparesis, pure sensory stroke, ataxic hemiparesis, and dysarthria-clumsy hand syndrome-suggest the diagnosis of lacu­ nar stroke. 3. Laboratory and radiologic evaluation. a. Neuroimaging-. An essential procedure! i. To exclude ICH or subarachnoid hemorrhage. ii. To select patients for acute thrombolytic therapy. iii. Noncontrast head computed tomography (CT) usually does not demonstrate the region of infarction in the acute period (within 1 2 hours of onset) . Diffusion-weighted magnetic resonance imaging (DW-MRI) can demonstrate ischemic lesions within minutes of onset, whereas perfusion imaging (PI) demonstrates the area at risk of eventual infarction. A diffusion-weighted per­ fusion imaging (DW-PI) mismatch demonstrates the penumbra (salvageable tissue) . Perfusion computed tomography (CTP) and CT angiography (CTA) are accurate, faster, and, therefore, more practical when thrombolytic therapy is anticipated. b. An electrocardiogram (ECG) and telemetry in all patients with IS: A 30-day cardiac event monitor/implantable long-term cardiac moni­ tor at discharge in cryptogenic stroke, to look for atrial fibrillation. c. Echocardiography, transesophageal echocardiogram in selected cases. d. Carotid ultrasound and transcranial Doppler ultrasound are used in patients with contraindications to CTA or magnetic resonance angi­ ography (MRA) . e. Blood studies, at a minimum, should include the following: a com­ plete blood count (CBC) , fasting lipids, blood glucose, and sCRP. Hypercoagulable workup and anticardiolipin antibodies may be obtained in younger patients or those with prior venous thrombo­ sis, recurrent abortions, thrombocytopenia, and migraine (lupus antiphospholipid antibody anticoagulant syndrome) . D. Treatment. 1. Identify patients who are candidates for thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA) (Table 1 2 3- 1 ) . Thrombolysis: 33% greater probability o f being free o f any disability; at 3 months, 1 0-fold relative increased risk of intracranial bleeding. a. Patients presenting within 4 . 5 hours of onset of ischemic stroke should have an urgent CT scan to rule out hemorrhage and large

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ntravenous Thrombo lytic Therapy for Acute l s c h e m i c Stroke

A . I nc l u s i o n c riteria

1 . Age older than 18 y

2.

Ti m e fro m stroke onset 35 s 2. Cu rrent use of ora l a nticoag u l a n ts ( e . g . , wa rfa ri n sod i u m ) or recent use with an I N R > 1 . 6 or c u rre nt use of new a nticoagu la nts ( D a bigatra n , Apixa ba n , R iva roxi ba n ) . F u l l-dose e noxa pa ri n with i n 2 4 h 3. With i n 3 m o , a n y sign ifica nt i ntracra n i a l su rgery, serious head tra u m a , o r previous stroke 4. C l i n ical presentation suggestive of s u ba ra c h n oid h e m orrhage, eve n with normal CT 5. Systo l i c a rte rial pressu re > 185 mm Hg or d iastolic a rte ria l p ressu re > 1 1 0 m m Hg refractory to a ntihyperte ns ive thera py 6 . Known cerebra l AV M , or a n e u rysm 7. Recent major i ntracra n i a l h e morrhage 8 . O n ly m i n or o r ra pid ly i m proving stroke sym ptom s 9 . M a j o r s u rgery or s e r i o u s tra u m a , exc l u d i ng h ea d tra u m a , i n the previous 14 d 1 0 . H isto ry of gastroi n test i n a l or u r i n a ry tract h e m o rrhage with i n 2 1 d 1 1 . Recent a rterial p u n ctu re at a noncom p ress i b l e site or recent l u m ba r pu n ctu re 1 2 . Abnormal blood gl u cose (400 mg/d U , with reversa l of d efic its with d extrose 1 3 . Postmyoca rd i a l i nfa rction perica rd itis 1 4. Se i z u re at the ti m e of onset of stroke ( perform CT a ngiogra m : if cerebra l a rterial occl usion is fou n d , proceed to t h ro m bolysis) 1 5 . For rt- PA beyo nd 3 h, N I HSS > 24, p revious stroke, and d ia betes , as we l l a s a nticoag u l a nts, a re relative contra i n d ications. Consent i s p refera ble i n a l l cases, b u t req u i red beyond 3 h .

CT, com puted tomogra phy; a PTT, a ctivated partia l thromboplasti n ti m e ; I N R , i nternational norm a l ized ratio; N I H S S , N ational I nstitutes of Hea lth Stroke Sca le; rt-PA, reco m b i n a nt tissue plasmi nogen a ctivator.

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2.

3.

4. 5. 6.

7.

infarcts (greater than one-third of the MCA territory) . CTA should be considered to evaluate for large vessel occlusion amenable to endovascular thrombectomy. CTP or MRI (DW-PI) may be helpful to define extent of ischemic penumbra. b. In the absence of a large infarct, if CTP or DW-PI demonstrates a mismatch, there may be grounds to consider thrombolysis, later than 4 . 5 hours after onset of ischemic stroke. The DIFFUSE-2 trial dem­ onstrated that intra-arterial interventions up to 12 hours in patients with a DWI-PI mismatch led to favorable 1- and 3-month outcomes compared to patients withour a mismatch. c. In patients with IS due to occlusion of the internal carotid, basilar, or proximal MCA, suggested by a high National Institutes of Health Stroke Scale (NIHSS) score and confirmed by CTA, intravenous thrombolysis can be initiated at community hospitals; however, rapid transfer to a tertiary hospital should be considered for possible intra­ arterial endovascular rhrombolysis or thrombectomy, which may be considered as a primary measure when it can be instituted without delay. d. Written informed consent is desirable bur not necessary in the first 3 hours as thrombolysis within the first 3 hours is considered standard of care (Table 1 23- 1 ) . Blood pressure should b e lowered to < 1 85/ 1 1 0 m m H g before throm­ bolyric rherapy is initiated. For other patients, blood pressure can be observed in the absence of malignant hypertension; it should not be excessively lowered unless it exceeds 220/ 1 20 mm Hg or end-organ fail­ ure (congestive heart failure [CHF] , renal) is present. If blood pressure has to be lowered acutely, the goal should be a 1 5% to 20% reduction. Patients with limb paresis are at high risk of deep vein thrombosis, which can be prevented with pneumatic compression boots, subcutaneous heparin, or enoxaparin. In patients receiving rt-PA, initiation of prophy­ lactic anticoagulant should be delayed for 24 hours. Elevated temperature and hyperglycemia should be aggressively treated. Oral feedings should be delayed until swallowing is deemed to be safe. Cardioembolic stroke due to atrial fibrillation can be prevented with long-term anticoagulation using warfarin. Alternate drugs include thrombin inhibitors, factor Xa inhibitors, including dabigatran, apixa­ ban, and rivaroxaban. Dabigatran using a dose of 1 50 mg twice daily is superior to warfarin with lower risk of spontaneous ICH. These newer anticoagulant drugs require no monitoring or dietary restrictions. The major disadvantage is lack of a reversal agent except with dialysis. There is no clear role for the use of full intravenous heparin or heparinoids in secondary stroke prevention or to improve outcome. Antiplatelet therapy should be considered in patients who do not have a clear embolic source. Extended-release dipyridamole and aspirin (ERDP/ASA; Aggrenox) is FDA approved and is 23% more effective in reducing recurrent stroke compared with aspirin. The results for a recently completed international trial (PROFESS) suggests that clopido­ grel may be as effective as ERDP/ASA) .

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High-dose statins may be beneficial within the first 48 hours due to pleiotropic effects. In the long term, statins should be administered to reduce low-density lipoprotein (LDL) cholesterol to 50% absolute risk reduction in mortality, and >25% more patients achieve a better functional outcome. 8.

Ill. ICH

A. General principles. I C H often requires management i n the ICU. The leading cause is hypertensive ICH. Other causes are rupture of saccular aneurysms or arteriovenous malformations (AVMs) , and cerebral amyloid angiopathy. B. Prognosis. The prognosis for ICH is worse for larger lesions. Pontine ICH has the highest mortality, followed by cerebellar and then basal ganglia ICH. Lobar ICH carries the most favorable outlook for survival and func­ tional recovery. C. Etiology. 1 . Hypertensive ICH results from rupture of arterial branch-point­ acquired microaneurysm (Charcot-Bouchard aneurysms) . Surrounding edema exerts a mass effect, and blood may block ventricles, causing hydrocephalus. 2. Nonhypertensive hemorrhage. a. Amyloid angiopathy. b. Rupture of AVM/aneurysm. c. Bleeding or coagulation disorders causing thrombocytopenia, loss of factors involved in coagulation (leukemia, idiopathic thrombocy­ topenia, severe liver disease, disseminated intravascular coagulation [DIC]) , and other rare disorders of coagulation. Angiitis of the cen­ tral nervous system and reversible cerebral vasoconstriction syndrome (RCVS) as well as venous thrombosis and dural fistulas are rare causes to consider. d. Anticoagulation and antiplatelet use. D. Diagnosis. 1. History: The presentation of ICH is abrupt and often associated with headache and progressive neurologic deficits over minutes to hours. 2. Examination. a . Helpful clinical hints to suggest ICH include deficits that extend beyond the distribution of a single artery and presence of altered sensonum.

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b. Localization. i. Putamen (hemiparesis, hemiesthesia) . ii. Pons (hyperthermia, coma, pinpoint pupils) . iii. Thalamus (hemihypesthesia, disconjugate vertical gaze) . iv. Cerebellum (ataxia, nystagmus, head tilt, vomiting) . v. Cerebral cortex (if cortical signs are present in a nonhypertensive ICH, suspect cerebral amyloid angiopathy) . 3. Radiologic and laboratory tests. a. CT scan demonstrates the site and size of the hematoma with great accuracy. b. MRI is as sensitive to detect blood and may demonstrate underlying pathology such as a vascular malformation or tumor. c. Angiography should be considered if an underlying vascular malfor­ mation is suspected. d. Lumbar puncture is contraindicated in most cases of ICH because of the risk of transtentorial herniation. e. Coagulation profile and platelet count to exclude underlying bleed­ ing disorder. E. Treatment. 1 . Correct any predisposing systemic hemorrhagic factors to prevent fur­ ther clinical deterioration. Reverse warfarin-related bleeds with recombi­ nant factor VII or prothrombin complex concentrate. Vitamin K 10 mg IV should always be given. Fresh frozen plasma is less useful because of the slow speed of reversal. 2. Lower systolic blood pressure in the acute phase of ICH to between 1 1 0 and 1 60 mm Hg. �-Blockers are the agents of choice. Intravenous nica­ rdipine is a safe alternative. Vasodilators (e.g., nitroprusside [Nipride] ) should be avoided, because they can promote cerebral edema and elevate ICP. 3. Acute increases in ICP may require hyperosmolar agents, such as manni­ tol. Treatment ofICH with steroids can be detrimental. Hyperventilation reduces ICP, but severe hypocapnia can result in diffuse cerebral vaso­ constriction. 4. Elevation of ICP from hydrocephalus is treated with ventriculostomy. 5. Surgery may be indicated for large superficial lobar ICH and cerebellar ICHs. Early surgical intervention is indicated for lesions >2.5 cm associ­ ated with changes in mental status. Decompressive hemicraniectomy may be lifesaving, but the quality of life will depend on rhe extent of brain damage and potential for reversibility. Prophylactic anticonvul­ sants are not routinely used in ICH. 6. Four-vessel angiography is the procedure of choice to evaluate for under­ lying vascular malformation or aneurysm.

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SUGG ESTED R EAD I N GS

Adams HP Jr, Alberts M, Brass M, et al. Guidelines for the early management of adulcs with ischemic stroke: a scientific statement from the Stroke Council of the American Stroke Association. Stroke 2007;38: 1 6 5 5- 1 7 1 1 . Guidelines for acute stroke treatment offered by the stroke council ofthe American Stroke Association. Albers GW, Amarenco P, Easron DJ, et al. Antithrombotic and thrombolytic therapy for ischemic stroke. Chest 2004; l 26:483S. Practice guidelines for acute stroke management. Broderick JP, Adams HP, Barsan W, et al. American Heart Association Guidelines for the man­ agement of spontaneous intracerebral hemorrhage. A statement for healthcare profes­ sionals. From a Special Writing Group of the Stroke Council. Stroke 1 999;30:905. Evidence-based recommendations for management ofintracerebral hemorrhage. Current practice recommendations in primary and secondary stroke prevention. Furie K, Kasner SE, Adams RJ, et al. Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack: a guideline for healch care professionals from the American Heart Association/American Stroke Association. Stroke 201 1;42:227-276. A comprehensive recent update on stroke prevention, incorporating results ofthe most recent trials. Lansberg MG, Straka M, Kemp S, et al. MRI profile and response to endovascular reper­ fusion after stroke (DIFFUSE 2) : a prospective cohort study. Lancet Neurol 20 1 2; 1 1 ( 1 0) :860-867. Discusses the importance ofthe penumbra in outcomes ofischemic stroke beyond the traditional window. Those with a penumbra and endovascular treatment within 12 hours ofstroke omet had a better outcome with an adjusted odds ratio of8. 8 versus those without a mismatch-adjusted odd ratio 0.2. Moonis M, Fisher M. Antiplatelet treatment for secondary prevention of acute ischemic stroke and transient ischemic attacks: mechanisms, choices and possible emerging patterns of use. Expert Rev Cardiovasc Ther 2003; 1 (4):6 1 1-6 1 5 . This is a useful article that puts into perspective antiplatelet agent use in primary and secondary stroke prevention. Moonis M, Fisher M. Considering the role of heparin and low-molecular-weight heparins in acute ischemic stroke. Stroke 2002;33 (7) : 1 927-1 933. This article offers a balanced view ofthe current role offull-dose intravenous heparin in acute ischemic stroke. National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue PA for acute ischemic stroke. N Engl] Med 1 99 5 ;333: 1 5 8 1 . The seminal work o n tissue-type plasminogen activator in the treatment ofacute stroke. Vahedi K, Hofmeijer J, Juetcler E, et al. Early decompressive surgery in malignant infarction of the middle cerebral artery: a pooled analysis of three randomised controlled trials. Lancet Neurol 2007;6(3) : 2 1 5-222. Discusses the criteria that should be used for decompressive hemicraniectomy derivedftom a pooled prospective analysis ofthree trials.

S uba ra c h n o i d H e m o rrhage W i l ey H a l l , J o h n P. Weaver, a n d M aj a z M o o n i s

I . G E N E RAL P R I N C I PLES

A. Frequency and morbidiry of subarachnoid hemorrhage (SAH). 1 . Aneurysmal SAH accounts for 8 5 % of nontraumatic SAH. 2. Perimesencephalic and other mechanisms of nontraumatic SAH account for the remaining 1 5% of cases and have lower incidences of morbidiry and mortaliry from rebleeding and delayed ischemic deficits. 3. lntracranial hemorrhage secondary to the rupture of saccular aneurysms accounts for 2% to 5% of all new strokes and accounts for over 30,000 new cases in the United States annually. B. Management of SAH caused by a ruptured aneurysm includes: 1. Early aneurysm repair to limit rebleeding. 2. Nimodipine to ameliorate cerebral injury secondary to vasospasm. 3. Hemodynamic and endovascular intervention to treat and overcome vasospasm. I I . PROG N O S I S . Prognostic indicators:

A. Unruptured aneurysms > 1 0 mm in size and smaller aneurysms at the basilar tip are more likely to rupture as compared with smaller aneurysms in other locations. B. Decerebration or coma at onset (Hunt and Hess grades 4 and 5) are associ­ ated with worse outcome. C. Up to 5 1 % of patients with SAH die, many before reaching medical care and most of the remainder in the first 2 weeks of care. Up to 33% of survi­ vors need long-term care, and up to 46% of survivors suffer some form of long-term cognitive dysfunction. I l l . PAT H O G E N E S I S

A. Saccular (berry) aneurysms are distinguished from other rypes of intrace­ rebral aneurysms caused by trauma, vascular dissection, or mycotic lesions and those related to tumors. B. Of saccular aneurysms, 8 5 % are located in the anterior circulation and 1 5% in the posterior circulation. Multiple aneurysms can occur in families or with systemic diseases such as polycystic kidney, Marfan syndrome, Ehlers­ Danlos syndrome, pseudoxanthoma elasticum, fibromuscular dysplasia, and coarctation of the aorta. 1 008

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C. Risk factors include tobacco use, heavy alcohol use, cocaine abuse, hyper­ tension, and history of intracranial aneurysm in a first-degree relative. IV. DIAG N O S I S

A. History. 1 . Severe headache that is usually described as the worst ever and maximum intensity at onset. Reversible vasoconstriction syndrome and benign exertional headaches can mimic SAH. 2. Sudden loss of consciousness, nausea, vomiting. 3. Facial pain, pupillary dilation and ptosis (from oculomotor nerve compres­ sion) , and visual field defects (from optic nerve or chiasm compression) . 4. A warning leak, or sentinel hemorrhage affects 1 5% to 37% of patients. Physicians should have a high index of suspicion for aneurysmal expan­ sion or warning leak when patients present with sudden, maximal head­ ache because such events precede major hemorrhage. B. Examination. 1. Neck stiffness. 2. Altered sensorium. 3. Focal signs (hemiparesis, oculomotor palsy, visual loss, paraparesis) . C. Laboratory studies. 1. A noncontrast head computed tomography (CT) is used to identify, localize, and quantify the hemorrhage. Modern CT is over 98% sensitive for SAH on the first day of hemorrhage. 2. Lumbar puncture (LP) is indicated if CT is nondiagnostic in a case with strong clinical suspicion. 3. When CT and LP are negative, in some cases escalation to computed tomography angiography (CTA) or conventional catheter angiography may be performed. 4. If surgery is emergent, CT angiography is the preferred study. 5. Four-vessel cerebral angiography is the most precise imaging study to localize the aneurysm(s) , define the vascular anatomy, and assess vaso­ spasm. Magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) or CTA can be performed to reveal aneurysms larger than 4 mm. a. Imaging the upper cervical spine with angiography and MRI is important when cerebral angiography fails to reveal the source of hemorrhage. b. If the initial angiogram fails to demonstrate rhe source of SAH, angi­ ography may be repeated in 1 to 2 weeks. If clinically stable, patients may be discharged home after the second negative angiogram. In some cases, a third angiogram may be performed in several months' time. V. PREVE NTI O N . Prevention of SAH is possible by screening for aneurysm in high-risk populations (e.g., polycystic kidney disease) and reducing risk factors (e.g., smoking) . Early surgery may be considered in some patients with asymp­ tomatic aneurysms at high risk of rupture, which depends on size and location.

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V I . TREAT M E NT

A. Management. 1. Preoperative medical management includes bed rest, head elevation to improve cerebral venous return, pulmonary toilet, thrombophlebitis prophylaxis, antiemetics, blood pressure control, and pain control. 2. Transfer to a center with neurosurgical expertise, preferably where a minimum of 60 SAH patients are treated annually, should be arranged rapidly as rebleeding and early hydrocephalus are important causes of morbidity. 3. Rebleeding is a serious complication of SAH, postulated to be caused by breakdown of the perianeurysmal clot. The peak incidence of rebleed­ ing occurs during the first day after SAH, and one-half to two-thirds of patients who rebleed die. Key preventative measures include early repair of the aneurysm and blood pressure control. 4. Before aneurysm repair, systolic blood pressure is maintained below 1 60 mm Hg with /}-blocking agents that also reduce the risks of cardiac arrhythmias. Nicardipine may be used when bradycardia exists. Nitrates are avoided due to their potential to raise intracranial pressure (ICP) . No consensus exists on upper limits for blood pressure after aneurysm repair when vasospasm dominates morbidity; 200 to 220 mm Hg is a common limit. Some authors suggest treating hydrocephalus before significantly lowering blood pressure in case ICP is elevated so as not to compromise CPP. 5. Hypothalamic damage can cause cardiac dysrhythmias from excessive sympathetic stimulation. Myocardial ischemia may occur from increased sympathetic tone, as can global myocardial depression. 6. Hydrocephalus can develop within the first 24 hours after SAH because of impaired cerebrospinal fluid (CSP) resorption by the arachnoid granulations or intraventricular blood obstruction of CSP outflow. Ventricular drainage may be emergently indicated. 7. Anticonvulsant prophylaxis with phenytoin or levetiracetam is com­ mon. There is controversy over the necessary duration of therapy, and some data suggest worse cognitive outcomes for patients on long-term prophylaxis. 8. Steroids are frequently administered to limit inflammation at the arach­ noid granulations and treat perioperative edema. 9. Hyponatremia can develop from hypothalamic dysfunction, causing a salt-wasting syndrome. This is commonly confused with syndrome of inappropriate antidiuretic hormone (SIADH); the two are distinguished by urine output and electrolyte levels. Hyponatremia is treated with iso­ tonic or hypertonic saline. Fluid restriction is not indicated. Euvolemia is maintained throughout the hospital course. B. Repair of ruptured aneurysm. 1. Surgical management is craniotomy with clip occlusion of the aneurysm neck, usually within 48 hours of rupture in most noncomatose patients. a. Unique problems that dictate the use of specialized techniques included vertebral-basilar system aneurysms, giant aneurysms (>25 mm) , and multiple aneurysms.

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b. Follow-up angiography is performed to evaluate occlusion of the aneurysm and patency of the surrounding vessels. 2. Endovascular repair includes coil embolization of appropriately shaped aneurysms. a. Some lesions require balloon or stent-assisted techniques due to aneu­ rysm morphology. b. In cases where embolization and surgical clipping are not possible, balloon or coil occlusion of the parent artery may be considered. 3. Surgical clipping is definitive, but a higher percentage of patients may develop epilepsy post repair. Endovascular repair is less invasive, but patients may require multiple coilings due to aneurysm recanalization and patients have been reported to have higher incidence of vasospasm, possibly due to lack of drainage of blood during craniotomy or due to a selection bias. C. Neurologic complications. 1. Cerebral vasospasm is a major cause of morbidity and mortality. Noted angiographically in 70% of patients, vasospasm causes symptoms because of cerebral ischemia in only 36% of cases. Vasospasm occurs progressively, with a peak berween days 4 and 1 2 . It occurs more fre­ quently in patients with a poor clinical condition, thick focal blood clots, or a diffused layer of blood in the subarachnoid space. Neurologic deficits may be focal, correlated with the areas of cerebral ischemia; more global, cognitive deficits may signal distal microvascular ischemia. Vasospasm is diagnosed by angiography or noninvasively by Transcranial Doppler (TCD) that detects spasm in up to 50% of patients. a. Calcium antagonists. The calcium antagonist nimodipine reduces delayed neurologic deficits caused by vasospasm. Nimodipine exerts a beneficial effect by decreasing postinjury intracellular calcium; dilating leptomeningeal vessels; improving collateral circulation to ischemic areas; improving erythrocyte deformability; or exerting an antiplatelet aggregating effect. Nimodipine (60 mg) is given orally every 4 hours for 2 1 days from the onset of SAH. If hypotension occurs, the dose is divided in half and administered every 2 hours. b. HMG-CoA reductase inhibitors may decrease the incidence and severity of vasospasm. Simvastatin 80 mg daily has been shown to be safe and effective. A large multicenter trial is under way to quantify the benefit better. c. Hyperdynamic therapy. The current mainstay of medical therapy for symptomatic vasospasm is hypertensive, hypervolemic therapy (HHT) to augment cerebral blood flow (CBF) . Elevation of arterial pressure increases CBF; volume augmentation provides hemodilu­ tion, decreases viscosity, and improves cerebral microcirculation. i. Criteria to initiate treatment include increased TCD blood flow velocity, focal neurologic deficits, or impaired consciousness without hydrocephalus. ii. Vasopressors are used to keep systolic blood pressures elevated, and plasma volume is maintained with fluids and occasionally albumin.

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iii. Hematocrit is often maintained at approximately 30, though controversy exists regarding the risk/benefit of transfusion ro this goal. iv. Risks of therapy include myocardial infarction, congestive heart failure, dysrhythmias, hemorrhagic infarcts, rebleeding, hypona­ tremia, and hemothorax. d. Endovascular treatments for vasospasm may be employed when HHT fails. Options include intra-arterial injection of vasodilators such as nicardipine, verapamil, or milrinone. For proximal vessel vasospasm, balloon angioplasty may be performed. e. Emerging technologies such as brain tissue oximetry, microdialysis, and CBF monitoring may in the future permit earlier detection and more targeted treatment of vasospasm. 2. Treatment of intracranial hypertension may require an ICP monitor and/or CSF drainage. Mannitol and hypertonic saline may be used, but strict attention to euvolemia is required. 3. Unresponsive patients should undergo electroencephalography (EEG) monitoring. Subclinical seizures have been reported in up to 20% of such cases. SUGG ESTED R EAD I N G

Allen GS, Ahn HS, Preziosi TJ, et al. Cerebral arterial spasm-a controlled trial of nimodip­ ine in patients with subarachnoid hemorrhage. N Engl] Med 1 983;308 ( 1 1 ) : 1 1 . Sentinel paper o n nimodipine 's benefit in SAH. Bederson JB, Connolly ES, Batjer HH, et al. Guidelines for the management of aneurysmal subarachnoid hemorrhage. A Statement for healthcare providers from a special writing group of the Stroke Council, American Heart Association. Stroke 2009;40:994- 1 02 5 . A detailed consensus committee summary ofdiagnosis and management ofsubarachnoid hemorrhage due to ruptured cerebral aneurysms. Brisman JL, Eskridge JM, Newell DW Neurointerventional treatment of vasospasm. Neurol Res 2007;28 (7) :769-776. Review ofendovascular treatments for vasospasm. Chason JM, Hindman WM. Berry aneurysms of the circle of Willis. Neurology 1 9 5 8;8:4 1-44. Sentinel paper on aneurysm localization. Chou SH-Y, Smith EE, Badjatia N. A randomized, double-blind, placebo-controlled pilot study of simvastatin in aneurismal subarachnoid hemorrhage. Stroke 2008;39:289 1-2893. The seminal article regarding the role ofHMG-CoA reductase inhibitors for the treat­ ment ofvasospasm. Claassen J, Mayer SA, Kowalski RG, et al. Detection of electrographic seizures with continu­ ous EEG monitoring in critically ill patients. Neurology 2004;62: 1 743- 1 748. Incidence ofsubclinical seizures in SAH patients. Diringer MN. Management of aneurysmal subarachnoid hemorrhage. Crit Care Med 2009;37:432. Excellent review ofSAH and management. Guglielmi G, Vinuela F, Dion J, et al. Electrothrombosis of saccular aneurysms via endovascu­ lar approach. J Neurosurg 1 9 9 1 ;75:8. Sentinel paper on endovascular repair ofintracranial aneurysms.

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International study of unruptured intracranial aneurysms investigators. N Engl] Med 1 998;339: 1 725-1 733. Largest study on risk of rupture of incidentally discovered unruptured aneurysms. Jakobsson KE, Saveland H, Hillman J, et al. Warning leak and management outcome in aneurysmal subarachnoid hemorrhage. J Neurosurg 1 996;85:995. Article documenting the frequency of missed SAH. Jost SC, Diringer MN, Zazulia AR, et al. Effect of normal saline bolus on cerebral blood flow in regions with low baseline flow in patients with vasospasm following subarachnoid hemorrhage. J Neurosurg 2005; 1 03:25-30. Effect offluid management on vasospasm. Sarrafzadeh AS, Sakowitz OW, Kiening KL, et al. Bedside microdialysis: a tool to monitor cerebral metabolism in subarachnoid hemorrhage patients? Crit Care Med 2002;30(5): 1 062-1 070. An experimental method of monitoring impending brain metabolic changes due to spasm following SAH. Subarachnoid hemorrhage. In: Ropper AH, Gress DR, Diringer MN, et al., eds. Neurological and neurosurgical intensive care. Philadelphia: Lippincott Williams & Wilkins, 2004. Un ruptured aneurysms-risk of rupture and risks ofsurgical intervention. Overall Review.

T h e G u i l l a i n - B a rre Syn d ro m e I s a b e l ita R . B e l l a a n d D a v i d A . C h a d

I . G E N E RAL P R I N C I PLES

A. Guillain-Barre syndrome (GBS) encompasses a group of acute immune­ mediated polyneuropathies that present with rapidly progressive weakness, areflexia, and elevated cerebrospinal fluid (CSF) protein without pleocytosis. B. Acute inflammatory demyelinating polyradiculoneuropathy (AIDP) is the most common subrype in North America and Europe, occurring at all ages and producing multifocal demyelination of nerve roots and cranial and peripheral nerves. C. Axonal forms of GBS include acute motor axonal neuropathy (AMAN) and acute motor-sensory axonal neuropathy (AMSAN) . AMAN is seen in children and young adults in northern China, Mexico, and Japan, is commonly pre­ ceded by Campylobacter jejuni infection, and generally has a good prognosis. D. GBS is the most common cause of rapidly progressive sporadic weakness; 60% of patients recover fully, but 1 5% have major residual deficits and up to 5% succumb to respiratory, autonomic, and other complications of the illness. I I . D IAG N O S I S

A. Clinical features of AIDP. 1. The major clinical features of AIDP are rapidly evolving weakness (usually over days) and areflexia, heralded by dysesthesias of the feet or hands, or both. a. Weakness classically ascends from legs to arms but may begin with weakness of cranial nerve-supplied muscles or of upper limb muscles and descend to the legs. b. Proximal muscle involvement is often seen early in the course of the disease. c. In severe cases, respiratory and bulbar muscles are affected. 2. Patients may become quadriparetic and respirator dependent within a few days, or they might have only mild nonprogressive weakness of the face and limbs throughout the course of the illness. 3. Weakness rypically does not progress beyond 4 weeks. a. Progression beyond 2 months is designated "chronic inflammatory demyelinating polyradiculoneuropathy" (CIDP) , a disorder with a natural history different from GBS. b. A small percentage (2% to 5%) of patients will have recurrent-two or more episodes-of GBS. 1014

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4. Approximately two-thirds of patients have an antecedent infectious event 1 to 3 weeks before the onset of GBS. a. Often there is a prodromal flu-like or diarrheal illness caused by a variety of infectious agents, including cytomegalovirus, Epstein-Barr and herpes simplex viruses, Mycoplasma, Chlamydia, and C. jejuni. b. GBS has also been associated with human immunodeficiency virus (HIV) infection, Hodgkin disease, systemic lupus erythematosus, immunization, general surgery, and renal transplantation. Lyme disease can mimic GBS. B. Physical examination. 1. There is symmetric weakness in both proximal and distal muscle groups associated with attenuation or loss of deep tendon reflexes. 2. Objective sensory loss is usually mild. 3. Between 1 0% and 2 5 % of patients require ventilator assistance within 1 8 days after onset. Patients must be followed carefully with serial vital capacity (VC) measurements until weakness has stopped progressing. 4. Mild-to-moderate bilateral facial weakness often occurs in addition to bulbar difficulties. 5. Ophthalmoparesis is unusual unless seen in the Miller Fisher variant (characterized by ophthalmoplegia, ataxia, and areflexia, with little limb weakness) . 6. Autonomic nervous system disturbances are seen in more than 50% of patients and include cardiac arrhythmias, orthostatic hypotension, hyper­ tension, transient bladder paralysis, increased or decreased sweating, and paralytic ileus. C. Clinical features in axonal forms. 1. Patients with axonal forms (AMAN and AMSAN) present similarly to AIDP with rapidly progressive weakness, areflexia, and albuminocyto­ logic dissociation, but they differ in the following ways: a. AMAN patients lack sensory abnormalities, and this form is more commonly found in northern China, Japan, and Mexico during summer months among children and young adults, is very commonly associated with prior C. jejuni infection, and has a good prognosis for recovery. b. AMSAN is generally associated with more pronounced deficits and longer time to recovery. D. Laboratory studies. 1. Cerebrospinal fluid. a. An elevated CSP protein without an elevation in cells (albuminocy­ tologic dissociation) is characteristic of G BS. b. CSP protein may be normal within the first 48 hours, but often is elevated within 1 week of onset; rarely, it remains normal several weeks after the onset of GBS. c. The cell count rarely exceeds 10 cells/cm 3 and is mononuclear in nature.

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d. When GBS occurs as a manifestation of HIV infection or Lyme disease, the CSF white cell count is generally increased (25 to 50 cells) . e. The CSF glucose is always normal. 2. Electrodiagnostic studies in AIDP. a . Typically disclose slowing ( 3 0 % of VC, M I P, or M E P i n 2 4 hours. 5. Tracheostomy should not be performed at the outset of the disease because patients can improve rapidly. B. Because of potential autonomic dysfunction, careful monitoring of blood pressure, fluid status, and cardiac rhythm is essential in managing patients with GBS. Hypertension can be managed with short-acting agents such as labetolol or nitroprusside, hypotension with fluids, and bradyarrhythmias with atropine.

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C. Immunotherapy with plasmapheresis (PE) or intravenous immune globulin (IVIG) is recommended for those patients who are nonambulatory and present within 4 weeks of symptom onset. PE or IVIG is also suggested for those patients who are ambulatory bur not recovered within 4 weeks of symptom onset. For those patients who have only mild symptoms and are already recovering, immunorherapy is nor recommended. 1. Although both PE and IVIG are equally efficacious, IVIG is more com­ monly used as the initial treatment because it is easier to administer. 2. Plasmapheresis: a. GBS study group recommends exchanging 200 to 250 mL/kg in three to five sessions over 7 to 14 days. b. Requires good venous access and can induce hypotension; requires caution in patients with cardiovascular disease. 3. IVIG: a . Dose administered is 400 mg/kg/d for 5 consecutive days. b. Easier to administer bur can produce side effects such as flu-like symptoms, headache, and malaise. c . Should be avoided in patients with immunoglobulin A (IgA) defi­ ciency and renal insufficiency. 4. Corticosteroids have no role in the treatment of GBS. 5. Treatment with PE followed by IVIG has nor been found to be superior to either treatment used alone. V. OUTCOMES

A. Most patients recover over weeks to months. B. Ar 1 year, approximately 60% recover full motor strength, while 1 4% have severe motor problems. About 5% to 1 0% have a protracted course, are ventilator dependent for several months, and do not fully recover. C. Poor prognostic factors include those with electrodiagnosric evidence of axon loss, a higher disability grade at nadir, older age, and rapid onset of disease. D. Despite close monitoring in rhe ICU, approximately 5% of patients die. E. Causes of fatal outcomes include dysauronomia, sepsis, acute respiratory distress syndrome, and pulmonary emboli. SUGGESTED READI NGS

Asbury AK, Cornblath DR. Assessment of current diagnostic criteria for Guillain-Barre syndrome. Ann Neurol 1 990;27(Suppl) :S2 1 -S24. This article describes the clinical, laboratory, and electrodiagnostic criteria of Guillain­ Barre syndrome. Griffin JW, Li CY, Ho TW, et al. Pathology of the motor-sensory axonal Guillain-Barre syndrome. Ann Neurol 1 996;39: 1 7-28. An excellent article that enlightens the pathophysiology ofthe various forms of Guillain­ Barre syndrome. Hughes RAC, Cornblath DR. Guillain-Barre syndrome. Lancet 2005;366: 1 653-1 666. An excellent review of Gui/lain-Barre syndrome and its various subtypes.

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Hughes RAC, Wijdicks EFM, Barohn R, et al. Practice parameter-immunotherapy for Guillain-Barre syndrome: report of the Quality Standards. Neurology 2003;61 (6) :6. This practice parameter provides evidence-based recommendations on the management ofGBS. Lewis RA. Chronic inflammatory demyelinating polyneuropathy. Neurol Clin 2007;25:71-87. A nice review of the clinical, laboratory, and therapeutic modalities in CIDP. Lo YL. Clinical and immunological spectrum of the Miller Fisher syndrome. Muscle Nerve 2007;36:6 1 5-627. This article describes the Miller Fisher variant of Guillain-Barri syndrome. McKhann GM, Cornblath DR, Griffin JW, et al. Acute motor axonal neuropathy: a frequent cause of acute flaccid paralysis in China. Neurology l 993;33:333-342. This article describes a pure motor form of Gui/lain-Barri syndrome. Plasma Exchange/Sandoglobulin Guillain-Barre Syndrome Trial Group. Randomised trial of plasma exchange, intravenous immunoglobulin, and combined treatments in Guillain-Barre syndrome. Lancet 1 997;349:22 5-230. A prospective trial comparing efficacy of certain treatment options in 383 patients. Rajabally YA, Uncini A. Outcome and its predictors in Guillain-Barre syndrome. ] Neurol Neurosurg Psychiatry 20 1 2;83:7 1 1-7 1 8 . This article discusses prognostic factors and outcome in GBS. Ropper AH. The Guillain-Barre syndrome. N Engl] Med 1 992;326: 1 1 30-1 1 36. An excellent review of Gui/lain-Barre syndrome. Ropper AH, Kehne SM. Guillain-Barre syndrome: management of respiratory failure. Neurology 1 985;35: 1 662- 1 665. This article suggests criteria for intubation. Sekiguchi Y, Uncini A, Yuki N, et al. Antiganglioside antibodies are associated with axonal Guillain-Barre syndrome: a Japanese-Italian collaborative study. ] Neurol Neurosurg Psychiatry 20 1 2;83:23-28. An article describing the significance ofantiganglioside antibodies in GBS. The Guillain-Barre Syndrome Study Group. Plasmapheresis and acute Guillain-Barre syndrome. Neurology 1 985;35 : 1 096- 1 1 04. This classic paper presents the benefits ofPE as seen in a large randomized trial. van der Meche FGA, Schmitz PIM, Dutch Guillain-Barre Study Group. A randomized trial comparing intravenous immune globulin and plasma exchange in Guillain-Barre syndrome. N Engl] Med 1 992;326: 1 1 23-1 129. First large randomized trial showing comparative efficacy of intravenous immunoglobulin to plasma exchange. Vucic S, Kiernan MC, Cornblath DR. Guillain-Barre syndrome: an update. ] Clin Neurosci 2009; 16 :733-74 1 . A nice general review of GBS, particularly the pathogenesis of GBS. Yuki N. Ganglioside mimicry and peripheral nerve disease. Muscle Nerve 2007;35:69 1-7 1 1 . A n excellent review describing the role of molecular mimicry in Gui/lain-Barre syn­ drome. Yuki N, Hartung HP. Guillain-Barre Syndrome. N Engl] Med 2 0 1 2;366:2294-2304. An excellent review ofthe immunologic pathogenesis of GBS along with its diagnosis and management.

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M ya sth e n i a G ra v i s J o h n ny S . Sa l a m e h a n d R a n d a l l R . L o n g

I . G E N E RAL P R I N C I PLES

A. Myasthenia gravis (MG) is an autoimmune disorder characterized by muscle weakness and exaggerated muscle fatigue. B. Prevalence is between 1 0 and 20 per 1 00,000 with a 3:2 female-to-male predominance. C. Incidence in women peaks in the third decade and in men in the fifth to sixth decades. D. Oculomotor and bulbar muscles are most commonly affected; proximal muscles are usually more affected than distal muscles; variability over time in both severity and distribution of weakness is common. E. About 20% of patients with generalized MG experience myasthenic crisis, which reflects severe bulbar and respiratory muscle weakness, constituting a medical emergency and requiring intensive care. F. Facrors commonly associated with myasthenic crisis include systemic infec­ tion, electrolyte imbalance, anesthesia, and drugs that impair neuromuscular transmission (Tables 1 26- 1 and 1 26-2) . I I . PAT H O P HYS I O LOGY

A. Circulating autoantibodies bind with acetylcholine receptors in postsynap­ tic muscle membrane. B. Receptors may be blocked, and receptor density decreases due to accelerated degradation and turnover. C. Miniature end-plate potentials are normal in number (indicating normal quantal release of acetylcholine) but decreased in amplitude. I l l . PROG N O S I S

A . Available therapies offer effective treatment for the vast majority of patients. B. Aggressive airway management and respiratory support during myasthenic crisis minimize morbidity and mortality with current mortality rate < 5 % . C . Elective thymectomy favorably alters the natural history of the disease. IV. D IAG N O S I S

A. Clinical presentation. 1. MG should be considered in any patient with unexplained weakness, especially when weakness fluctuates or involves bulbar muscles. 1 020

C h a pter 1 26 • Myast h e n i a Gravis

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Conditions That May Contribute to Myasthe n i c Crisis

l nterc u rrent syste m i c i n fection Electro lyte i m ba l a nce (Na, K, Ca , P, Mg) Thyrotoxicosis o r hypothyroid ism Anesthesia Med ication effects (Ta b le 1 26-2) C h o l i n e rgic crisis (disconti n u e c h o l i n esterase i n h i b itors)

2. Normal sensation, tendon reflexes, pupillary reflexes, and mental status distinguish MG from most other acute and subacute paralytic illnesses. B. Antiacetylcholine receptor antibodies. 1. Eighty percent of patients have serum antibodies to acetylcholine recep­ tors. 2. Among "seronegative" patients, about 40% will have anti-muscle­ specific tyrosine kinase (MuSK) antibodies. Med i cations That May Accentuate Myasth e n i c Wea kness Antibiotics

A m i ka c i n C l i n da myc i n Colistin F luo roq u i nolones Genta m i c i n Neomyc i n Polymyx i n Streptomyc i n Tobramyc i n Tetra cyc l i n es Tri m ethopri m/s u lfa m ethoxazole Antia rrhyth m ics and anti hyperte n s ives

Lidoca i n e Quinidine P roca i n a m ide ,l}- B l ockers Ca lci u m c h a n n e l blocke rs Anti psychotics

Lith i u m P h e nothiazi nes Tricyc l ics

N e u ro m u sc u lar blockers a n d m u sc l e relaxants

Anecti ne (succinylc h o l i ne) N o rc u ron (vec u ron i u m ) Pavu lon ( pa n c u ro n i u m ) Tacri u m (atrac u r i u m ) Benzod iaze p i n es C u ra re Dantri u m (da ntrolene) Flexe r i l (cyclobenza p rine) Lioresa l ( baclofe n ) R o baxi n ( m eth oca rba m o l ) S o m a (ca risoprod o l ) Q u i n i n e su lfate Antirheu matics

C h l o roq u i n e o-pe n i c i l la m i ne Others

O piate a n a lgesics O ra l contra ce ptives Anti h ista m i n es Anticho l i n e rgics

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C. Edrophonium (Enlon) test. 1. Useful in patients with objective findings on physical examination. 2. May be performed at bedside; monitor for bradyarrhythmia. 3. Not as sensitive or specific as the serological and electrodiagnostic studies. D. Electrodiagnostic studies. 1. Decrement (2'. 1 0%) in compound muscle action potential amplitude with 2 to 3 Hz repetitive supramaximal stimulation. 2. Increased "jitter" on single-fiber electromyography (EMG) . 3. Electrodiagnostic studies may support-but never exclude-the diagnosis of MG. E. Chest imaging: All patients with MG should be screened for thymic hyper­ plasia or thymoma. V. TREAT M E NT. lmmunosuppressive therapy is indicated for most patients with MG, but benefits are often delayed. Plasmapheresis and intravenous immune globulin (IVIG) offer a more rapid, but transitory, benefit (Table 1 26-3) . Cholinesterase inhibition is a useful adjunctive therapy.

A. Plasmapheresis. 1. Exchange 5 0 mL/kg/d for 3 to 7 days. 2. Response within 48 to 72 hours. B. IVIG. 1 . 400 mg/kg/d for 5 days. 2. Response within 7 to 1 0 days. C. Corticosteroids. 1. Response rate >80%. 2. 20 mg/day (single dose) , increasing by 5 mg/day every 3rd day to 60 to 80 mg/day. 3. Beware of increased weakness at the outset of steroid treatment. 4. After maximal response (2 to 3 months) , gradually shift to equivalent alternate day dose; then taper slowly by decreasing alternate day dose by 5 mg each month to 20 mg every other day target.

lf.j;l!itJjl

M a nagement of Myasth e n i c Crisis

Ai rway assista n ce and ventilation Disconti n u e a ntic h o l i n esterases and offe n d i n g m ed i cation I d e ntify and treat i nfection Ca rd iac m o n itor Sta rt s pecific treatment (see below) Plasmapheresis: excha nge 50 m Ukg/d for 3 to 7 d I VI G : 400 mg/kg/d fo r 5 d Corticoste roids: 20 mg/d (single d ose) , i n c reas i n g by 5 m g/d eve ry 3 rd d to 60 to 80 mg/d

C h a pter 1 26 • Myast h e n i a Gravis

I

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5. Complete discontinuation, with maintained response, is rare; avoid stop­ ping prednisone! 6. Azathioprine, cyclosporine, methotrexate, mycophenolate mofetil, and other immunosuppressants can be considered in patients who are steroid intolerant or unresponsive. D. Cholinesterase inhibition. 1 . Pyridostigmine (Mestinon) and neostigmine (Prostigmine) are useful adjuncts. 2. Conversion of PO pyridostigmine: IV pyridostigmine is 30: 1 (may be useful following surgery) . 3. Cholinergic crisis is increased weakness due to excess cholinergic stimu­ lation; fasciculation, diaphoresis, and diarrhea are concomitants. E. Supportive care in the intensive care unit (ICU) and recovery room. 1 . Avoid incentive spirometry and magnesium boluses. 2. Maximal inspiratory pressure (MIP) , maximal expiratory pressure (MEP) , and forced vital capacity (FVC) are the best indicators of respira­ tory muscle function; 0 2 saturation is a poor indicator. 3. Early intubation is prudent in the event of declining respiratory muscle function; consider mechanical ventilation when the FVC declines to 1 5 mL/kg. 4. Cholinesterase inhibition (pyridostigmine) will increase oral and airway secretions. F. Thymectomy: Elective thymectomy through median sternotomy is indi­ cated for all but the most elderly, frail myasthenic patients. Results are best when done within 5 years of onset. SUGG ESTED R EAD I NGS

Chaudhuri A, Behan PO. Myasthenic crisis. QJM 2009 ; 1 02:97- 1 07. An excellent review of myasthenia crisis. Drachman DB, Jones RJ, Brodsky RA. Treatment of refractory myasthenia gravis: "rebooting" with high-dose cyclophosphamide. Ann Neurol 2003;53:29. A novel approach to treatment of refractory MG. Hughes BW, Moro De Casillas ML, Kaminski HJ. Pathophysiology of myasthenia gravis. Semin Neurol 2004;24:2 I . A review of the pathogenesis ofMG. Jani-Acsadi A, Lisak RP. Myasthenic crisis: guidelines for prevention and treatment. J Neurol Sci 2007;26 1 : 1 27- 1 33 . A review of myasthenia crisis etiology and treatment options. Keesey JC. Clinical evaluation and management of myasthenia gravis. Muscle Nerve 2004;29:484. An excellent overview ofdiagnosis and treatment. Kumar V, Kaminski HJ. Treatment of myasthenia gravis. Curr Neurol Neurosci Rep 20 1 1 ; 1 1 ( 1 ) : 89-96. An overview ofall treatment modalities in MG.

Ac q u i re d Wea k n ess i n th e I nte n s ive C a re U n it D a v i d A. C h a d

I . G E N E RAL P R I N C I PLES

A. A large prospective cohort study found the incidence of severe acquired weakness in the intensive care unit (ICU) to be 25%. B. Although preexisting neuromuscular disorders may cause weakness in ICU patients, two of the most common causes of newly acquired weakness arising in the ICU setting are critical illness myopathy (CIM) and critical illness polyneuropathy (CIP) . C. Both disorders may cause severe generalized weakness-a syndrome of flaccid, generalized weakness (quadriplegia) with failure to wean from mechanical ventilation. The two disorders are known to occur separately or in combination. The most common form of weakness acquired in the ICU is CIM. D. A major risk factor for the development of CIM is exposure to intrave­ nous corticosteroids (CSs) and neuromuscular blocking agents (NMBAs) ; CIM develops in one-third of patients treated for status asthmaticus in the ICU. E. CIM also develops in patients who have not received CS and NMBAs, but who have had severe systemic illness with multiorgan failure and sepsis; in fact, CIM accounts for 42% of patients with weakness in the surgical and medical ICU setting. F. The major risk factors for CIP are sepsis and multiorgan failure; of patients admitted to the ICU for at least 2 weeks, 50% show at least EMG evidence of an axon loss polyneuropathy. I I . D IAG N O S I S O F CRITICAL ILLN ESS MYOPATHY

A. Clinical features. 1 . Weakness is typically widespread and nonfocal. 2. Weakness affects all limb muscles and neck flexors-a flaccid quadripa­ resis that has a proximal > distal distribution. 3. Weakness may involve facial muscles, but exrraocular muscles are rarely involved. 4. Tendon reflexes are often depressed or absent. 5. Weakness typically affects the diaphragm, causing failure to wean from ventilator. 1 024

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B. Laboratory studies. 1. Serum creatine kinase (CK) is elevated in 50% of patients; the rise tends to occur early in the course of the illness. 2. Electromyography. a. Nerve conduction studies reveal low-amplitude, long-duration (broad) responses, or absent motor responses; sensory responses are relatively preserved (sensory responses may be reduced) . b. The needle electrode examination discloses fibrillation potential activity in weak muscles in some, but not all, patients. c. Voluntary muscle contraction reveals early recruitment of motor unit potentials (MUPs) that may be short in duration, low in amplitude, and polyphasic in form. d. MUP analysis is difficult owing to severe weakness or encephalopa­ thy, or both (no motor units may be available for analysis) . e. Stimulation of the phrenic nerves with diaphragm recording evokes absent or very low motor responses. f. Direct stimulation of a weak limb muscle may demonstrate electrical inexcitability of the muscle membrane. g. Direct stimulation of muscle and direct nerve stimulation yield com­ parably reduced muscle responses (in contrast to the results found in CIP [vide infra] ) . 3 . Muscle biopsy. a. Reveals a characteristic finding of selective loss of myosin, which is revealed as a central area of pallor or lack of histochemical reactivity to myosin ATPase. b. Muscle fiber atrophy (especially type II fibers) . c. Mild-to-moderate degree of muscle fiber necrosis m some patients. C. Pathogenesis. 1. Loss of myosin thick filaments, with multifactorial causation, includ­ ing an increase in muscle apoptosis, up-regulation of calpain, and up-regulation of the transforming growth factor (TGF)-�/mitogen­ activated protein kinase pathway. 2. Muscle is noted to be inexcitable in CIM. This may result from improper regulation of the sodium channels with increased inactivation of sodium channels at the resting membrane potential. D. Treatment. 1. Treatment is essentially symptomatic. 2. Strive to prevent the development of this disorder by using CSs or NMBAs, or both as sparingly as possible. 3. Intensive insulin therapy (with target blood glucose concentrations of 80 to 1 1 0 mg/dL) may lower the incidence of CIM (and CIP) . E. Outcome. 1. Most patients recover over weeks to months, although patients may be left with residual weakness depending upon the initial severity and dura­ tion of weakness.

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I l l . D IAG N O S I S O F CRITICAL ILLN ESS POLYN E U RO PATHY

A. Clinical features. 1. Distal more than proximal symmetrical weakness and sensory loss. 2. Deep tendon reflexes are attenuated or lost. 3. Cranial nerve-innervated muscles are typically spared. 4. There is often a concomitant encephalopathy (the encephalopathy of sepsis). B. Laboratory studies. 1. Serum CK levels are typically normal. 2. CSF studies are normal (normal protein and normal cell count) . 3. Electromyography. a. Nerve conduction studies reveal reduced or absent sensory and motor responses and reduced or absent phrenic motor responses. b. Nerve conduction velocities are within the range of normal or are mildly reduced (the pattern considered classical for polyneuropathies that are primarily axon loss in character) . There is typically no evi­ dence for partial conduction block or prolonged F-wave latencies. c. After 2 to 3 weeks of the illness, needle electrode examination may reveal abnormal insertional activity in the form of fibrillation poten­ tials and positive sharp waves; and these are more likely to be found in distal rather than proximal muscles; in the first 2 to 3 weeks of the illness, fibrillation potentials may be absent. d. Voluntary activation may reveal reduced recruitment ofMUPs; in the first few weeks of the illness, MUPs may have a normal appearance, but after several months, as is typical of resolving polyneuropathies characterized by axonal regeneration, collateral sprouting, and muscle reinnervation, MUPs typically become complex or polyphasic in form, and increased in size. e. Direct needle stimulation of muscle elicits a relatively higher ampli­ tude response compared to the response recorded from muscle after nerve stimulation. 4. Muscle biopsy. a. Neurogenic atrophy. C. Pathogenesis. 1. Inadequate perfusion of peripheral nerves as a result of the systemic inflammatory response that causes injury to the microcirculation of distal nerves and resultant nerve ischemia and axon loss. 2. As in CIM, there is evidence for dysregulation of sodium channel gating in peripheral nerve that could lead to nerve inexcitability and contribute to generalized weakness. D. Treatment. 1. Attempt to stabilize and treat the underlying critical illness; especially vigorous treatment of sepsis. 2. Intensive insulin therapy (with target blood glucose concentrations of 80 to 1 1 0 mg/dL) may lower the incidence of CIP.

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E. Outcomes. 1. Recovery of sensory and motor function occurs over weeks to months depending on the severity of the underlying polyneuropathy. IV. D I FFERE NTIAL DIAG N O S I S OF ACQU I R E D WEAKNESS I N T H E I C U

A. Guillain-Barre syndrome (see Chapter 1 25). B. Acute intermittent porphyric neuropathy. 1 . Generalized weakness (symmetrical or asymmetrical) in the context of abdominal pain, psychiatric disorder, and prominent dysautonomia. 2. Triggered by drugs that induce the hepatic cytochrome P-450 system (e.g., barbiturates) . 3. May be associated with respiratory failure. 4. EMG: Marked motor axon loss-type polyneuropathy without conduc­ tion block. 5. Diagnosis suggested by the presence of urinary porphyrin precursors, notably 8-aminolevulinic acid. 6. Responds to oral or parenteral carbohydrate loading and to IV hematin therapy. C. Prolonged neuromuscular blockade by muscle relaxants. 1. Associated with renal or hepatic failure. 2. Elevated levels of vecuronium metabolite m some instances (3-desacetyl vecuronium) . 3. No sensory deficits and normal reflexes. 4. Normal sensory and motor nerve conduction studies. 5. On EMG, decremental response at slow rates of stimulation (3 Hz) . 6. Transient improvement after infusion of acetylcholinesterase inhibitors. D. Myasthenia gravis (see Chapter 1 26) . E. Lambert-Eaton myasthenic syndrome. 1. Generalized weakness with autonomic symptoms and signs. 2. Strength typically improves after repetitive contractions of an initially weak muscle. 3. About 50% of patients have an underlying neoplasm (typically small cell lung cancer) . 4. Presence of antibody to voltage-gated calcium channels in 80% of patients. 5. EMG: very low amplitude motor responses that increase after a short burst ( 1 0 seconds) of isometric exercise; sensory studies are normal. F. Botulism. 1. Diffuse, symmetrical weakness; proximal greater than distal muscle involvement. 2. Cranial nerve involvement. 3. Dysarthria and dysphagia. 4. Ptosis and ophthalmoparesis. 5. Autonomic involvement. 6. Dilated pupils.

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S ECT I O N 1 3 • N E U R 0 L 0 G I C P R 0 B L E M S I N T H E I C U

Bradyarrhythmias. Hypotension. Urinary retention. 10. Management is supportive care and trivalent (ABE) antitoxin. 7.

8. 9.

G. Motor neuron disease (amyotrophic lateral sclerosis) . 1 . Scenario: an ICU patient admitted for pneumonia and ventilator support who fails to wean. 2. The examination classically reveals a combination of lower and upper motor neuron signs (atrophy/fasciculations and hyperreflexia/spasticity/ Babinski signs, respectively) in bulbar (especially tongue and palate) and limb muscles (often asymmetric, distal and proximal) , with a normal sensory examination. H. Muscular dystrophies: uncommon scenario, but patients with certain muscular dystrophies are prone to respiratory muscle involvement and pneumonia. These include the following: 1. Myotonic dystrophy. a. Percussion and grip myotonia. b. Frontal balding/temporalis muscle atrophy. c. Distal muscle weakness and wasting. d. Cardiac conduction defects, especially atrial arrhythmias with risk of complete heart block. e. Central hypoventilation. 2. Duchenne and Becker dystrophy (X-linked dystrophy-30 degrees. 2. Fluid restriction (slight) . 3. Hyperosmolar therapy (hold if serum osmolaliry >320 mOsm/kg) . a. Agents. i. Mannitol 1 to 1 . 5 g/kg IV bolus initially, then 0.25 to 0 . 5 g/kg every 4 to 6 hours. ii. Thirry to fifty milliliters 23.4% NaCl bolus, then 30-mL bolus every 4 to 6 hours. iii. Three percent hypertonic saline at 30 to 1 00 mL/h, titrated to a serum sodium goal of approximately 1 5 5 mEq/dL. b. Caveats. i. Use only one agent at a time. ii. Close monitoring of renal function and electrolytes. 4. Furosemide 1 mg/kg IV single dose or as 1 0 to 20 mg adjunct with mannitol. 5. Dexamethasone 1 0 to 20 mg IV initially, then 4 mg every 6 hours. 6. ICP monitoring (external ventricular drain [ventriculostomy] preferred) . 7. Hyperventilation (for short periods only) to achieve Paco 2 25 to 32 mm Hg. I l l . HYDRO C E P HALUS

A. Background: Increased ventricular size due to increased CSF volume and pressure. B. Patbophysiology/etiology. 1 . Subarachnoid tumor. a. Leptomeningeal tumor infiltration in subarachnoid space can prevent normal absorption of CSF by arachnoid granulations. 2. Cerebellopontine angle tumors: compress brainstem and fo urth ventricle. 3. Intraventricular tumors: obstruct outflow foramen. 4. Intraparenchymal tumors. a. Basal ganglia and thalamic tumors: compress foramen of Monro. b. Pineal region tumors: compress third ventricle or cerebral aqueduct. c. Brainstem or cerebellar tumors: compress fourth ventricle or cerebral aqueduct. C. Diagnosis. 1. Clinical presentation: Increased ICP (see Section II) . 2. Radiologic studies: CT more readily available while MRJ demon­ strates better detail.

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D. Treatment. 1. Dexamethasone 1 0 to 20 mg IV initially, then 4 mg every 6 hours. 2. External ventricular drain. 3. Tumor resection. 4. CSP diversion either internally (third ventriculostomy) or externally (shunt) . IV. S E IZU R E S

A. Background: May precipitate rapid deterioration when ICP is elevated. B. Pathophysiology/etiology. 1 . Tumor presence or progression. 2. Hemorrhage. 3. Hypoxia. 4. Hyponatremia. 5. Hypoglycemia. 6. Subtherapeutic anticonvulsant levels. C. Diagnosis. 1. Clinical presentation. a. Variable: generalized, tonic-clonic, partial, focal or transient dysfunction. 2. Radiologic studies: CT scan. 3. Laboratory studies: a. Anticonvulsant levels (when applicable) . b. Serum electrolytes. c. Arterial blood gas. D. Treatment. 1. Airway management. a. If mechanically ventilated: maintain normocarbia. 2. Acute anticonvulsants. a. Lorazepam: 2 mg every 5 minutes IV (8 mg maximum for status epilepticus) . b. Phenytoin. i. Loading dose: 1 5 ro 20 mg/kg IV. ii. Maintenance: 1 00 mg IV/PO every 8 hours (serum goal 1 0 to 20 µg/mL) . c. Fosphenytoin. i. Loading dose: 1 5 to 20 mg/kg IV. ii. Maintenance: 5 mg/kg/d (serum goal 1 0 to 20 µg/mL) . iii. Phenobarbital: 1 5 mg/kg IV. 3. Prophylactic anticonvulsants. a. Levetiracetam. b. Phenytoin. c. Fosphenytoin. d. Carbamazepine. e. Phenobarbital.

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V. POSTO PERATIVE C O M P L I CATI O N S

A . Diagnosis. 1. Clinical presentation. a. Headache. b. Neurologic deficit. c. Fever. d. Polyuria/polydipsia. 2. Etiology. a. Intracranial hemorrhage. i. Risk factors: coagulopathy, hypertension. b. Cerebral edema. c. Cerebral infarction. d. Endocrinopathies. i. Diabetes insipidus (DI) . (a) May be transient, permanent, or triphasic. (b) Usually 1 8 to 36 hours postoperatively. (c) Greater than 250 mL/hour urine output for 2 consecutive hours. (d) Urine specific gravity < 1 .005 and urine osmolality < 200 mOsm/kg. (e) Urine sodium > 1 4 5 mEq/L and serum osmolality > 290 mOsm/kg. ii. Hypocortisolemia. iii. Hypothyroidism. iv. Hyponatremia. (a) Usually from syndrome of inappropriate secretion of antidi­ uretic hormone (SIADH) . (b) Cerebral salt wasting (CSW) uncommon with neoplastic processes. v. Central nervous system infection. (a) Meningitis: usually 2 days to 2 weeks postoperatively. (b) Cerebral abscess: uncommon, presents weeks to months post­ operatively. (c) Bone flap infection: presents months postoperatively. 3. Radiologic studies: CT or MRI with and without contrast. 4. Laboratory studies. a. Serum electrolytes and osmolality. b. Complete blood count. c. Erythrocyte sedimentation rate, C-reactive protein. d. Hormone levels. e. Urine specific gravity, electrolytes, and osmolality. f. CSF chemistries, Gram stain, and culture. B. Treatment. 1. Intracranial hemorrhage. a. Correct coagulopathy (maintain INR ::; 1 .3, platelets 2': 1 00,000 mm 3) . b . Systolic blood pressure 1 1 0 t o 1 50 m m Hg.

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Cerebral edema. a. Hyperventilation. b. Dexamethasone. c. Hyperosmolar therapy. 3. Cerebral infarction. a. Maintain cerebral perfusion. b. Treat symptomatic edema.

2.

4. Endocrinopathies. a. Hydrocortisone (adrenal insufficiency) . b. Levothyroxine (hypothyroidism) . c. Desmopressin (DDAVP) for DI: i. IV or subcutaneous: 2 to 4 µg/day in two divided doses. ii. Intranasal ( 1 00 µg/mL solution) : 10 to 40 µg/day divided one to three times per day. iii. Fluid restriction. 5. Hyponatremia. a. Fluid restriction for SIADH or fluid replacement for CSW. b. Three percent hypertonic saline or 23.4% NaCl if symptomatic. c. Do not correct > 12 mEq/day due to risk of central pontine myelinolysis. 6. Central nervous system infection. a. Antibiotics. b. Drain infections, remove infected bone flap. V I . S P I NAL T U M O RS

A. Background: ICU care indicated if there are postoperative ventilator issues. B. Pathophysiology/etiology. 1 . Tumor compression. 2. Spinal cord ischemia and infarction. 3. Postoperative hemorrhage. 4. Autonomic dysfunction. C. Diagnosis. 1. Clinical presentation. a. Respiratory insufficiency. i. Paralysis of intercostal muscles (lesions C6 and below) . ii. Decreased diaphragmatic and accessory respiratory muscle func­ tion (lesions above C6) . b. Other. i. Ileus. ii. Urinary retention. iii. Hypotension. iv. Bradycardia. 2. Radiologic studies. MRI more specific than CT. 3. Tests/laboratory studies. a. Oxygen saturation with vital capacities every 6 hours. b. Frequent neurologic exams.

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S ECT I O N 13 • N E u R 0 L 0 G I c p R 0 B L E M s I N T H E I c u

D. Treatment. 1 . Indications for mechanical ventilation: a. Vital capacity < 10 to 1 5 mL/kg. b. Hypoxia (Spo 2 < 90%, Pao2 < 5 5 ) . c . Inability t o ventilate (rising PaCo 2, respiratory acidosis, mental status change) , patient unable to protect airway. 2. lieus: nasogastric or orogastric tube. 3. Urinary retention: urinary catheter. 4. Vasopressors to maintain systolic blood pressure >90 mm Hg. 5. Atropine versus pacing for symptomatic bradycardia. 6. Surgery to relieve cord compression. 7. Orthosis (bracing) may provide support during healing. 8. Radiation therapy: a. May be primary treatment of metastatic disease. b. Also for residual postoperative disease. V I I . SYSTE M I C C O M PLICAT I O N S S E C O N DARY TO B RA I N T U M ORS

A. Patbophysiology. 1 . Immobility. 2. Hypercoagulable state. 3. Local or systemic infection. B. Diagnosis. 1 . Clinical manifestations. a. Deep venous thrombosis (DVT) . b. Pulmonary embolus. c. Systemic infection. d. Urinary tract infection. e. Pneumonia. f. Line sepsis. g. Meningitis. 2. Radiologic studies. a. Chest radiograph for pneumonia. b. Venous duplex scan for deep vein thrombosis. c. Pulmonary embolus. i. CT pulmonary embolus protocol. ii. Ventilation perfusion scan. 3. Laboratory studies. a. Complete blood count. b. Complete metabolic profile. c. Urinalysis and culture. d. Sputum Gram stain and culture. e. Central line tip cul ture. f. Blood cultures. g. Lumbar puncture for CSP analysis.

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C. Treatment. 1. Antibiotics. 2. DVT prophylaxis. a. Thromboembolic deterrent (T.E.D.) hose. b. Leg sequential compression devices (SCDs) . c. Pharmacologic subcutaneous therapy (if no evidence of active bleeding) . i. Low-dose unfractionated heparin 5,000 units rwo ro three times per day. ii. Enoxaparin 30 mg rwice daily or 40 mg daily. d. Warfarin (Coumadin) is generally safe if patient is >2 weeks postop­ erative and is not actively bleeding. SUGG ESTED R EA D I NGS

Greenberg MS, ed. Handbook of neurosurgery, 7th ed. New York: Thieme, 20 1 0 . Comprehensive neurosurgical handbook covering a wide range of issues. Litofsky NS, Muzinich MC. Neuro-oncological problems in the intensive care unit. In: Irwin RS, Rippe JM, eds. Irwin and Rippe's intensive care medicine, 7th ed. Philadelphia: Lippincott Williams & Wilkins, 20 12: 1 787- 1 797. Detailed chapter discussing management of neurosurgical patients in the ICU Suarez JI, ed. Critical care neurology and neurosurgery, 2nd ed. New York: Springer Verlag, 20 1 0 . Authoritative review ofneuroscience critical care diagnostic, clinical, and management issues. Winn RH, ed. Youmans neurological surgery, 6th ed. Philadelphia: Saunders, 201 1 . Comprehensive, authoritative neurosurgical volumes covering the field of neurosurgery. 20 1 2 Online medical reference featuring articles written fo r clinicians by experts in the field including seizure, hypernatremia, hyponatremia, meningitis, sepsis, and pulmonary em bolus.

www. uptodate.com,

M isce l laneous I nte n s ive C a re U n it N e u ro l og i c P robl e m s D a v i d Cac h i a , N a n cy M . F o n t n ea u , a n d A n n L . M itc h e l l

I . OVERVIEW A variety of disorders affecting the nervous system, not easily categorized oth­ erwise, require management in the intensive care unit (ICU) . These include the following:

A. B. C. D. E. F. G.

Suicidal hanging. Electrical injuries. Carbon monoxide (CO) poisoning. Decompression syndrome ("the bends"). Cerebral fat embolism. Hiccups. Peripheral nerve disorders.

I I . S U I C I DAL HAN G I N G Second most common means of committing suicide among adolescents in the United States (US) .

A. Pathophysiology. 1 . Death is usually by slow strangulation with compression of the jugular veins or carotid arteries. 2. Interruption of blood flow for more than a few minutes results in hypoxic-ischemic injury with neuronal death, cytotoxic/vasogenic edema, and increased intracranial pressure (ICP) . B. Prognosis. 1. Poor prognostic signs. a. Evidence of cardiopulmonary arrest, low Glasgow Coma Scale score. b. Spontaneous respiratory rate of :::i Cl

"' ii> 3 3 ti> 8'

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0 +. U1

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S ECT I O N 1 3 • N E U R O L O G I C P R O B L E M S I N T H E I C U

iii. Central nervous system (CNS) vasculitis. iv. Sarcoidosis and other inflammatory disorders. I I . E N C E P HALITIS

A. Definition: Inflammation of brain parenchyma associated with clinical evidence of brain dysfunction, in most cases associated with inflammatory meningeal involvement as well, hence the term meningoencephalitis. B. Epidemiology. 1 . Incidence of encephalitis among adults in the US is 2.0 to 2 . 5 cases per 1 00,000 persons per year. 2. Causative agents. a. Most encephalitis cases are of viral etiology. C. Prognosis. 1. Mortality and morbidity depend on the specific pathogen and immuno­ logic status of the patient. 2. With HSY, mortality reaches up to 50% to 70% without treatment, but is high even with treatment; Japanese encephalitis also has high mortality. 3. Overall mortality is 50%, lower with eastern equine encephalitis (EEE) and St. Louis encephalitis. 4. Tends to be more severe among very young and very old. D. Etiology. The following viruses are implicated in causing encephalitis, with the most common agents indicated by asterisk: 1. HSY type i · and 2 (usually causes aseptic meningitis) . 2. Varicella zoster virus". 3. Epstein-Barr virus (EBY)'. 4. Enterovirus". 5. Measles". 6. Mumps". 7. Arbovirus (Eastern equine and Western equine, St. Louis, West Nile, Dengue, Japanese B encephalitis) . 8. Others: Poliovirus, influenza, lymphocytic choriomeningitis, rabies, CMV (seen in patients with HIV) , progressive multifocal leukoencepha­ lopathy (PML) (seen in immunocompromised patients) , HIV: E. Pathogenesis. 1 . Viral entry via bloodstream, except after head trauma or neurosurgery. 2. Innate immune responses to infectious components cause leukocyte infiltration, altered cerebral blood flow. 3. Symptoms and signs are related to meningeal irritation. 4. Altered neurologic function is due to metabolic and circulatory distur­ bances. F. Diagnosis. 1. History. a. The diagnosis should be suspected in a febrile patient with altered mental status.

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b. Other neurologic findings: seizures, focal neurologic disturbances (e.g., aphasia, hemiparesis, hemianopsia) , neuropsychiatric symptoms such as psychosis, agitation, personality and behavioral changes, and cognitive dysfunction. c. History of travel, contact with animals and sick persons, insect bite, immune status, and occupational history may be important. 2. Physical exam. a. General exam. i. May provide clues to etiology. Skin rash, paroriris (mumps) , signs of upper respiratory infection, cardiomyoparhy. ii. Other findings may indicate complications-autonomic dys­ function, diabetes insipidus, or syndrome of inappropriate antidiureric hormone secretion (SIADH) . b. Neurologic exam. i. Diffuse and focal cerebral dysfunction-altered consciousness may range from lethargy to coma; reflects the severity of encepha­ litis; focal neurologic deficits may be present. ii. Meningismus-due to associated meningitis. 3. Laboratory studies. a. Blood. i. Blood counr-lymphocyrosis commonly seen. ii. Blood culture, chest x-ray-general workup for febrile illness. iii. Virologic studies-antibodies to common viruses, including HSV- 1 and 2, VZV, HV-6 and 7, CMV, EBY, HIV, influenza A and B, and some enteroviruses: measured in the serum, and ratio in serum and cerebrospinal fluid (CSF) can be measured for inrrathecal antibody production. b. CSF analysis-an essential part of the diagnostic workup; should be performed promptly except when there is a suggestion of a mass lesion. i. Mild lymphocyric pleocytosis, 95%) if obtained within the first week of onset of symptoms, requires only small amount of CSF, and is available for HSV- 1 and 2, VZV, human herpes virus (HHV)-6 and 7, CMV, EBV, HIV, and enteroviruses viruses. c. Virus detection from other body sources such as blood, urine, stool, and throat secretions are less specific. d. Neuroimaging/radiologic studies. i. Cranial computed tomography (CT)-initial screening prior to magnetic resonance imaging (MRJ) . ii. MRJ of the brain. (a) More sensitive than CT scan-leptomeningeal enhancement may be present. (h) May show edema, mass effect, hemorrhage, and contrast enhancement in temporal lobes and insula in HSV encephalitis. (c) Initial changes may include high signal intensity on T2-weighted image (T2WI) and fluid attenuated inversion recovery (FLAIR) secondary to edema. (d) Involvement of the cingulate gyms and bilateral temporal lobes is typical of HSV encephalitis. (e) lschemic or hemorrhagic infarctions-can be seen with VZV encephalovasculitis. (f) Basal ganglia and thalamic involvement-Japanese and EBV encephalitis. d. EEG. i. Diffuse slowing of background rhythm in most cases. ii. In HSE, fo cal slowing or periodic lateralized epileptiform discharges (PLEDS) in bilateral temporal lobes.

G. Treatment. Suspected cases of viral encephalitis should be treated urgently. 1. Acyclovir should be started empirically as soon as possible while waiting for CSP results, using dose of 1 0 mg/kg every 8 hours intravenously for 1 0 days. Drug dosing should b e adjusted in patients with renal impairment. 2. Vidarabine 1 5 mg/kg/d is an alternative, less effective than acyclovir when used for HSV and VZV encephalitis. a. Acyclovir and vidarabine are of no benefit in nonherpetic encephalitis cases. 3. Corticosteroids. a. Limited role in patients with VZV encephalitis complicated by vasculitis. b. Occasionally also used for severe HSE with severe cerebral edema. 4. Supportive care. a. Seizure management with antiepileptic medications. I l l . ACUTE D I SS E M I NATED E N C E P HALOMYELITIS

A. Definition. A fulminant monophasic CNS autoimmune syndrome with inflammation and demyelination, typically following immunization (postvaccination, encephalomyelitis) or infection (postinfectious demyelination) .

C h a pter 1 3 0 • C N S I nfect ious a n d I nf l a m m atory D i sorders

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B. Epidemiology. 1 . More common in the younger population; may be related to high rate of infection and vaccination in this group. 2. Slight male predominance in the pediatric population; more prevalent in spring and winter. 3. About 1 0% to 1 5 % cases of acute encephalitis in the United States; overall incidence is 0.4 per 1 00,000 per year; incidence in adults unknown. C. Etiology. 1 . Believed related to preceding infection/immunization triggering a cell­ mediated and humoral autoimmune response resulting in inflammation and demyelination. 2. Measles virus, the most common antecedent infection prior to measles vaccine. Seen with mumps, rubella, VZV, EBV, CMV, HSV, coxsackie viruses as well. 3. Bacterial and parasitic infections-Mycoplasmapneumoniae, Streptococcus, malaria, Borrelia burgdorferi-are less frequently implicated. 4. Among vaccines, Semple Rabies and earlier strains of smallpox vaccine have the strongest correlation. D. Pathogenesis. 1. Possible "molecular mimicry and self sensitization"-induction of autoantibodies and/or T cells by epitopes of a virus, vaccine, or other antigens cross-reactive to the epitopes on CNS myelin or axonal glycoprotein. 2. Inflammatory response causes demyelination by activated macrophages, and oligodendrocyte damage by cross-reacting antibodies and comple­ ment fixation. 3. Pathologically-perivenular infiltrates of T cells and macrophages with associated perivenular demyelination. AHLE is a variant with inflamma­ tory damage to blood vessels. E. Clinical presentation. 1. Monophasic rapidly progressive encephalopathy syndrome (usually in young children or adults) with headache and altered sensorium (confu­ sion, stupor, or coma) , with or without meningismus and focal neuro­ logic deficits and seizures. 2. Prodromal history of vaccination or infection days to weeks previously. 3. Focal neurologic deficits may include hemiparesis, hemianopsia, cranial nerve deficits, ataxia, and myelopathy. 4. Absence of fever or mild fever at the onset. 5. In children with chickenpox-typical acute ataxia syndrome seen sec­ ondary to postinfectious meningocerebellitis. 6. AHLE-more rapidly progressive, fulminant course; mortality is high. F. Laboratory studies. 1. Routine blood studies. a. May show mild leukocytosis. b. Serologic studies for preceding infection are often negative.

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S ECT I O N 1 3 • N E U R 0 L 0 G I C P R 0 B L E M S I N T H E I C U

2. CSP-changes are usually nonspecific. a. Mild lymphocystic pleocytosis, < 5 0 cell/mm 3 , mildly elevated protein, and normal glucose in most cases. h. Oligoclonal bands usually absent. c. MRI-mainstay of diagnosis in the last decade. i. Classic findings include multifocal or diffuse subcortical lesions with high signal intensity on T2WI and FLAIR; can be asym­ metric. ii. Basal ganglia and thalamic involvement may be seen. G. Prognosis. 1. Usually good with gradual recovery over weeks to months in majority of cases. 2. Some patients may be left with residual neurologic deficits. 3. AHLE has a less favorable outcome. H. Treatment. 1 . No standardized treatment protocol; immunomodulatory drugs are the mainstay of treatment. 2. High-dose corticosteroids-500 to 1 ,000 mg (20 to 30 mg/kg) methyl­ prednisolone IV daily for 3 to 7 days or dexamethasone 1 00 to 200 mg (1 to 3 mg/kg) daily for 5 days; follow-up oral prednisone taper. 3. Intravenous immunoglobulin ( 1 to 2 g/kg given over 5 days) or plasma exchange is used in cases of steroid failure. SUGGESTED READI NGS http ://www. cdc.gov/ meningitis/bacterial.html

A link to the CDC's public information on meningitis. Chaudhuri A, Kennedy PG. Diagnosis and treatment of viral encephalitis. Postgrad Med J 2002;78 (924) :575-5 83. A review ofthe diagnosis, workup, and management ofacute encephalitis with specific focus on herpes simplex encephalitis. Strategies for arboviral and zoonotic encephalitides are also discussed. Dalmau J, Gleichman AJ, et al. Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol 2008;7 ( 1 2) : 1 0 9 1-1098. An excellent discussion of clinical and immunologic features ofencephalitis associated with antibodies to the NMDA receptor. Day GS, High SM, et al. Anti-NMDA-receptor encephalitis: case report and literature review of an under-recognized condition. J Gen Intern Med 20 l 1 ;26(7) : 8 1 1-8 1 6. The classic presentation ofanti-NMDA-receptor encephalitis is described, with review of differential diagnosis, treatment options, and the needfor increased awareness. Habek M, Adamec I, et al. Diagnostic approach of patients with longitudinally extensive trans­ verse myelitis. Acta Neurol Belg 20 1 2; 1 1 2 ( 1 ) :39-43. A review ofdiagnosis and therapy in patients with transverse myelitis. Harris MK, Maghzi AH, et al. Acute demyelinating disorders of the central nervous system. Curr Treat Options Neurol 2009 ; 1 l ( 1 ) : 5 5-63 . A review ofclinical manifestations and therapeutic options for CNS acute demyelinating disorders, including multiple sclerosis, neuromyelitis optica, acute disseminated encephalo­ myelitis, optic neuritis, and transverse myelitis.

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Huppatz C, Gawarikar Y, et al. Should there be a standardized approach ro the diagnostic workup of suspected adult encephalitis? a case series from Australia. BMC Infect Dis 20 1 0 ; 1 0:353-3 5 8 . Clinicalfeatures, laboratory data, neurodiagnostic studies, and outcomes i n acute encephalitis cases from Australia. Kirton A, Busche K, et al. Acute necrotizing encephalopathy in caucasian children: two cases and review of the literature. ] Child Neurol 2005;20 (6) :527-532. The clinical, neuroimaging, andpathologic findings in pediatric cases ofacute necrotiz­ ing encephalopathy. Krishnan C, Kaplin AI, et al. Demyelinating disorders: update on transverse myelitis. Curr Neurol Neurosci Rep 2006;6(3) :236-243 . A review of clinical manifestations, prognosis, therapeutic approach, and pathologic features oftransverse myelitis (TM). Leake JA, Albani S, et al. Acute disseminated encephalomyelitis in childhood: epidemiologic, clinical and laboratory features. Pediatr Infect Dis J 2004;23 (8):756-764. A review ofADEM in childhood. Sejvar JJ. Acute disseminated encephalomyelitis. Curr Infect Dis Rep 2008 ; 1 0 (4):307-3 14. This review article describes the clinicalfeatures, pathogenesis, and neuroimaging find­ ings ofADEM. Steiner I, Budka H, et al. Viral encephalitis: a review of diagnostic methods and guidelines for management. Eur J Neurol 2005; 1 2(5):33 1-343. The diagnosis of viral encephalitis based on clinical presentation, CSF analysis, and MRI is discussed in this paper. The limited role ofbrain biopsy and evidence for antiviral therapy for different types ofencephalitis are reviewed. Wingerchuk DM. Postinfectious encephalomyelitis. Curr NeurolNeurosci Rep 2003;3(3) :256-264. In this paper, the differences between childhood and adult ADEM, risks ofdevelopment of multiple sclerosis, and the nosology of CNS demyelinating syndromes are discussed.

C r i t i c a l Ca re of O rga n Tra ns p l a nt R e c i p i e nts : Ove rv i ew C h r i sto p h Tro p p m a n n

I . G E N E RAL P R I N C I PLES

A. The increased number of organ transplants (28,05 1 transplants in the United States in 20 1 2, compared with 1 2,623 in 1 988) has been paral­ leled by significant improvements in both patient and graft survival. These improvements can be attributed ro several facrors. 1. The availability of polyclonal and monoclonal antibody preparations (antithymocyte globulin, anti-CD 52-directed alemtuzumab, and anti-IL-2 receptor-directed basiliximab) to prevent and treat rejection episodes. 2. The introduction in the 1 980s of a powerful immunosuppressant agent, cyclosporine, followed a decade later by tacrolimus and mycophenolate mofetil. More recently, additional new drugs have become available (e.g., sirolimus, everolimus, belatacept) , augmenting the immunosuppressive armamentarium considerably and allowing for more individualized immunosuppression of organ recipients. 3. Improvements in organ preservation (e.g., introduction of the University of Wisconsin preservation solution in the late 1 9 80s) . 4. Thorough preoperative patient screening. 5. Increasing sophistication in postoperative intensive care, allowing also for transplantation in high-risk recipients with significant medical comorbidities. 1 052

C h a pter 1 3 1 • Critical Care of Orga n Tra n s p l a n t R ec i p i e nts: Overv i ew

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6. Availability of potent, yet nontoxic antibacterial, antifungal, and antiviral agents has allowed for more effective prevention and treatment of oppor­ tunistic infections. 7. Refinements in surgical techniques. B. Transplantation has therefore become the treatment of choice for many patients with end-stage failure of kidneys, liver, endocrine pancreas, heart, lungs, and small bowel. Criteria for potential recipients have been expanded to include infants, children, and individuals thought to be at higher risk for complications (e.g., patients with diabetes, elderly patients) . C. Current absolute contraindications to transplantation include malignancy (untreated, metastatic, or at high risk for recurrence) ; uncontrolled infec­ tion; and medical-surgical contraindications to undergo, or inability to recover from, a major surgery. D. The gap berween available organs and patients awaiting transplantation is widening. As a result, mortality on many transplant wait lists is increasing. I I . T H E O RGAN D O N O R S H O RTAG E : POTENTIAL S O L U T I O N S

A. Live donors. 1. Owing to the lack of deceased organ donors, and the development of a noninvasive (laparoscopic) nephrectomy technique, the number of live donor kidney transplantation has significantly increased. In 200 1 , for the first time, live kidney donors outnumbered deceased kidney donors in the United States. Current initiatives (e.g., wider implementation of paired kidney exchange for incompatible live donor-recipient pairs) aim at increasing live donor transplant rates even further. 2. Live donor liver, small bowel, and lung transplants are also performed but continue to represent only a very small proportion (

;;: · "' 0 OJ

5 0,000/mm3 . 4. The presence of crystals does not out rule the possibility of infection. C. Treatment. 1. Repeated daily aspirations or surgical washout is essential. 2. Empiric antibiotic therapy should be initiated following a stat Gram stain and antibiotics adjusted once cultures become available (Table 1 39-3) .

''"="'''''

Anti b i otics in Septic Arthritis

C l i n ic a l setting

Top th ree m ic roorga n i s m s

I n it i a l e m p i r i c a n t i b i otic choice

N o n i m m u nocomprom ised , not sexu a l ly active

1. Staphylococcus

Va ncomyc i n or th i rdgeneration cepha losporin depending on resu lts of G ra m sta i n G ra m sta i n negativeth i rd-generation cepha lospori n G ra m sta i n shows gra m - positive cocci i n c l u ste rs-va ncomyc i n pe n d i ng sensitivity If N. gonorrhoeae suspected ( G ra m - n egative d i p l ococc i ) , then ceftriaxone and azith romyc i n Va ncomyc i n and th i rd generation cepha losporin or ciprofloxacin u ntil G ra m sta i n a n d c u l tu res ava i la ble; consider add ition of a m i noglycoside if Pseudomonas suspected Va ncomycin and third generation cepha lospori n u ntil c u ltu res ava i la ble; seek I. D . i n put ea rly

N o n i m m u n ocom pro m ised , sexu a l ly active

a ure us 2. Streptococcus

3. G ra m -negative bac i l l i 1 . Neisseria gonorrhoeae

2. Staphylococcus a ure us

3. Stre ptococci

Prosthetic joi nts

1 . Staphylococcus epidermidis

2. Staphylococcus a u re us

3 . Ente ro bacteriaceae

l m m u nocom prom ised

Large variety of organ isms possible

C h a pter 1 3 9 • R he u matologic D i sorders in t h e I ntensive Care U n it

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3. The joint should be rested with physical therapy referral to prevent contractures. 4. Baseline radiographs should be obtained to follow progress. 5. Baseline C-reactive protein (CRP) may be helpful in monitoring longer term therapeutic response. 6. Fungal joint infection is rare, more indolent in presentation, and occurs usually in immunocompromised patients. 7. Fungal components are normally visible on Gram stain, allowing for early initiation of antifungal therapy. V. ANTI P H O S P H O L I P I D ANTI B O DY SYN D R O M E . Defined as recurrent arte­ rial or venous thrombosis often associated with fetal losses in the presence of anticardiolipin antibodies or lupus anticoagulant. It may be primary or may be associated with another connective tissue disease.

A. Diagnosis. Clinical features include the following. 1. One or more episodes of arterial or venous thrombosis or both. 2. Fetal death or recurrent spontaneous abortion. 3. Other features include thrombocytopenia, livedo reticularis, cardiac valvular lesions, migraine headaches, chorea, and leg ulcers. 4. Presence of either anticardiolipin antibody immunoglobulin M (IgM) or IgG in medium or high titer or lupus anticoagulant on two occasions, at least 6 weeks apart. B. Treatment. 1. Anticoagulation with heparin followed by lifelong warfarin is indicated. See recently published guidelines on managing long-term anticoagula­ tion (Antithrombotic and thrombolytic therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th edi­ tion) . Chest 2008 ; 1 33(6) : 1 60S- 1 98S). 2. The catastrophic antiphospholipid antibody defines a syndrome involv­ ing widespread thrombosis with life-threatening illness. Treatment may include corticosteroids, cyclophosphamide, plasmapheresis, anticoagula­ tion, and possibly rituximab. V I . I D I O PATH I C I N FLAM MATORY MYOS ITIS. Polymyositis and dermato­ myositis are inflammatory muscle diseases characterized by proximal muscle weakness, elevated muscle enzymes, and characteristic cutaneous features.

A. Diagnosis. Clinical features include the following. 1. Proximal girdle and shoulder weakness. 2. Skin involvement includes Gottron papules (an erythematous and often scaly eruption typically seen symmetrically over the extensor surfaces of the metacarpophalangeal [MCP] and to a lesser extent the interpha­ langeal joints and elbows) ; erythema of the neck, chest, and forehead; heliotrope rash; and periungual erythema. 3. Dysphagia and aspiration pneumonia. 4. ILD, especially in patients who are Jo- 1 antibody positive. 5. Cardiomyopathy, arrhythmias, and congestive heart failure.

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S ECT I O N 1 5 • R H E U M A T O L O G I C A N D I M M U N O L O G I C P R O B L E M S

B. Treatment. 1 . High-dose corticosteroids with consideration for an additional agent such as methotrexate. 2. In progressive ILD, high-dose steroids with cyclophosphamide are indicated. Other agents such as mycophenolate, tacrolimus, and azathio­ prine may be used. V I I . SYSTE M I C L U P U S E RYT H E MATOS U S

A. General principles. A n inflammatory disorder o f unknown etiology characterized by antibody production, immune complex deposition, and a wide variety of organ and system involvement. Diagnosis is based on the presence of characteristic clinical features and laboratory findings, includ­ ing decreased complement levels, cytopenias, and typical autoantibody profiles. B. Renal involvement. Occurs in 50% of patients. Treatment protocols exist, depending on the histologic classification on renal biopsy, with active nephritis requiring treatment with high-dose corticosteroids and cyclophos­ phamide or mycophenolate. C. Pulmonary involvement. 1. Pleuritis is the most common pulmonary manifestation of systemic lupus erythematosus (SLE) , affecting approximately 50% of SLE patients. 2. Pulmonary hemorrhage is a rare but serious complication of SLE. a. Patients, frequently young females, present with severe hypoxia, patchy infiltrates, and hemoptysis. b. Treatment is with high-dose corticosteroids and immunosuppressive agents with a potential role for plasmapheresis. c. Pulmonary hypertension is a rare but well recognized complication of SLE. D. Hematologic. 1. Autoimmune hemolytic anemias respond well to high-dose steroids; other immunosuppressants, rituximab, and splenectomy are options for unresponsive cases. 2. Idiopathic thrombocytopenic purpura (ITP) can also occur; treatment is with high-dose oral or IV steroids and if needed IV immunoglobulin. E. Neurologic. 1. Neuropsychiatric lupus is the name given to the large variety of neuro­ logic presentations seen in SLE. 2. These include seizure disorders, stroke disease, demyelinating disorders, psychosis, transverse myelopathy, peripheral neuropathy, and headache. V I I I . SCLERODERMA

A. General principles. Multisystem disease characterized by tissue inflamma­ tion and fibrosis with vascular involvement leading to episodic vasospasm and tissue ischemia.

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B. Interstitial lung disease. Frequent complication and the leading cause of death. 1. High-resolution CT findings range from ground glass opacities to hon­ eycombing. 2. BAL shows an elevated neutrophil and eosinophil count; pulmonary function tests show a restrictive pattern. 3. Treatment including cyclophosphamide combined with corticosteroids although newer therapies are emerging. C. Pulmonary hypertension. 1. Complication of typically long-standing limited scleroderma. 2. Diagnosis is suggested by echocardiography or an otherwise unexplained elevation of the B-type natriuretic peptide (BNP) and confirmed on right heart catheterization. 3. Treatment with IV and inhaled prostacyclins, phosphodiesterase inhibi­ tors, and endothelin antagonists. D. Scleroderma renal crisis. 1. Renal crisis is a syndrome of rapidly progressive hypertensive renal failure. 2. Accompanied by microvascular hemolysis. 3. The associated hyperreninemic state drives the process, and treatment is therefore with urgent administration of high-dose angiotensin-convert­ ing enzyme inhibitors. 4. Rarely, normotensive renal crisis can occur. 5. Occurs more commonly in those who are RNA polymerase III antibody positive. E. Gastrointestinal. 1. Constipation due to decreased peristalsis with pseudo-obstruction a possibility. 2. Diarrhea due to bacterial overgrowth. 3. Gastroesophageal reflux disease (GERD) is almost universal. 4. Emera! nutrition should be maintained when possible in the ICU setting. S U GG ESTED R EAD I NGS

Bayrakcar UD, Erkan D, Bucciarelli S, et al. The clinical spectrum of catastrophic antiphospholipid syndrome in the absence and presence of lupus. ] Rheumatol 2007;34(2) :346-352. Highlights the clinical presentations ofa rare, often overlooked diagnosis. Donahue KE, Garclehner G, et al. Systematic review: comparative effectiveness and harms of disease-modifying medications for rheumaroid arthritis. Ann Intern Med 2008; 14 8(2) : 1 24-1 34. An update on DMARD therapy in RA, including the new biologic agents. Grijalva CG, et al. Initiation of tumor necrosis factor-a antagonises and the risk of hospitalization for infection in patients with autoimmune diseases. JAMA 20 1 1 ;306(2 1 ) :233 1-2339. Johnson SR. Pulmonary hypertension in systemic sclerosis and systemic lupus erythematosus. Eur Respir Rev 2 0 1 1 ;20(1 22) :277-286. Thorough review on a rapidly moving topic.

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Leslie KO, Trahan S, Gruden J. Pulmonary pathology of the rheumatic diseases. Semin Respir Crit Care Med 2007;28 (4) :369-378. Excellent review on ILD in RA, SLE, scleroderma, Sjogren s, and myositis. Majithia V, Geraci SA. Rheumatoid arthritis: diagnosis and management. Am ] Med 2007; 120( 1 1 ) :936-939. With early intervention clearly improving outcome, the needfor early diagnosis has become ever more important. Margaretten ME, Kohlwes ], Moore 0, et al. Does this adult patient have septic arthritis? JAMA 2007;297( 1 3) : 1 478-1488. An important review for all intensivists. Rider TG, Jordan KM. The modern management of gout. Rheumatology 20 1 0;49 ( 1 ) :5-14. Compares the various available treatments for this commonly seen problem. Tan A, et al. Recent advances in the diagnosis and treatment of interstitial lung disease in systemic sclerosis (scleroderma): a review. Clin Exp Rheumatol 20 1 1 ;29(2 Suppl 65): S66-S74. A well-referenced review of the scleroderma-associated lung disease.

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A n a p hy l ax i s H e l e n M . H o l l i n gsworth a n d N e re i d a A . Pa ra d a

I . G E N E RAL P R I N C I PLES

A. Anaphylaxis is a severe and potentially fatal fo rm of immediate hypersensitivity (immunoglobulin E [IgE] -mediated antigen recognition) . An anaphylactoid reaction is caused by a mechanism other than IgE recogni­ tion of antigen. B. In this chapter, IgE-mediated and non-IgE-mediated reactions are referred to as anaphylactic reactions. I I . PAT H O P H YS I O LOGY

A. Binding of allergenic antigen (Table 140- 1 ) to adjacent IgE molecules on sensitized mast cells/basophils activates synthesis and secretion of mediators of anaphylaxis, such as histamine, leukotrienes (LTC4, LTD4, and LTE4) , and cytokines. B. Mast cell and basophil activation also occur through a variety of non­ IgE-mediated mechanisms (Table 1 40-2) . I l l . C LI N I CAL FEAT U R ES

A. The major clinical features of anaphylaxis are urticaria, angioedema, respiratory obstruction (stridor, wheezing, breathlessness) , and vascular collapse (dizziness, hypotension, loss of consciousness), with urticaria being the most common. B. Additional clinical manifestations include a sense of impending doom, rhinorrhea, generalized pruritus and swelling, dysphagia, vomiting, and abdominal pain. C. Physical examination of a patient with anaphylactic shock often reveals a rapid, weak, irregular, or unobtainable pulse; tachypnea, respiratory distress, cyanosis, hoarseness, or stridor, diminished breath sounds, wheez­ ing, and hyperinflated lungs; urticaria, angioedema, or conjunctiva! edema. Only a subset of these may occur in any given patient. D. Laboratory findings include elevation of blood histamine and mature �-tryptase, and total tryptase levels, low complement levels, and disseminated intravascular coagulation (DIC) . Documentation of an elevated serum or plasma total tryptase at the time of the reaction compared with baseline levels provides support for diagnosis of anaphylaxis. A normal tryptase level does not exclude anaphylaxis. E. Arrhythmias may occur.

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1 1 20

S ECT I O N 1 5 • R H E U M AT 0 L 0 G I C A N D I M M U N 0 L 0 G I C P R 0 B L E M S Causes of lgE-mediated Anaphylaxis

Type

Agent

Exa m p l e

Prote i n s

A l lerge n extracts Enzymes Food

Po l l e n , d ust m ite , mold , a n i m a l d a n d e r Chymopa pa i n , streptoki nase, L-asparagi nase Egg wh ite, leg u m es , m i l k , n uts , shel lfis h , wheat Teta n u s a ntitoxi n , a ntithym ocyte globu l i n , s n a ke a ntivenom I ns u l i n , ACTH , TS H , progesteron e , sa l m o n calcito n i n I nflue nza Hymenopte ra Hepari n , latex, t h i o ba rbitu rates, se m i na l fl u i d �- Lacta m s , eth a m buto l , s u lfona m ides, va ncomyc i n Ethylene oxi d e Benzoca i n e , tetraca i n e , xyloca i n e , m e p ivaca i n e Cisplati n , ca rbop lati n

H eterologous ser u m Hormo nes

H a pte n s

Vac c i n es Ve noms Oth ers Anti biotics D i s i n fecta nts Loca l a nesthetics• Others

'Precise mecha nism not esta blished. ACT H , a d renocorticotro pic hormone; TS H , thyroid-st i m u lating hormone.

TA B L E 1 4 0 - 2

a u ses o f N on-lgE-med i ated Anaphylaxis

C o m p l e m e n t activation B lood prod u ct tra nsfusion i n a n lgA-d eficient patient H e m od ia lysis• D i rect release of c h e m ica l m ed iato rs of a n a phylaxis Prota m i ne' RCM Keta m i n e A C E i n h i bitors• Loca l a n esthetics• Cod e i n e a n d othe r opiate na rcotics H igh ly c h a rged a n t i b i otics, i n c l u d i n g a m p h ote ricin B Nonstero i d a l a nti-infl a m m atory med ications ( N SA I Ds) b Anti neop lastic agents ( e . g . , pacl itaxe l•, eto posid e') S u lfiting agents Exercisec I d i o path i c rec u rrent a n a phylaxis 'Precise mecha nism n o t esta blished. May be d u e t o com bi nation o f factors . 'Som e N SA I Ds cause a n a phylaxis through an lgE-d ependent mecha n i s m . 'A costi m u l us such as a food , med icati o n , or c o l d exposu re is u s u a l l y i n volved .

Cha pter 1 4 0 • Anaphylaxis

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1 1 21

IV. DIAG N O S I S

A. The rapid onset and progression of typical symproms to a severe and sometimes fatal outcome after exposure to a typical antigen or inciting agent are characteristic of anaphylaxis. B. Mild systemic reactions often last for several hours, but rarely >24 hours. C. Severe manifestations (e.g. , laryngeal edema, bronchoconstriction, hypotension) , if not fatal, can persist or recur for several days, but some­ times resolve within minutes of treatment. V. TREATMENT: GENERAL CARDIOPULMO NARY S U PPORTIVE M EASU RES

A. Oxygen saturation, blood pressure, cardiac rate, and rhythm should be monitored closely, and supplemental oxygen administered. B. Intubation and assisted ventilation may be necessary for laryngeal edema or severe bronchoconstriction. C. Occasionally, cricothyroidotomy is necessary. D. One characteristic of patients with biphasic or protracted anaphylaxis is oral ingestion of the offending antigen. Oral administration of activated charcoal and sorbitol may reduce absorption and duration of exposure to the antigen. VI. TREAT M E NT: PHARMACOLOG I C

(Table 1 40-3) . A. Adrenergic agents.

1. Epinephrine should be given promptly to treat all initial manifesta­ tions of anaphylaxis; a delay in administration of epinephrine may be fatal. 2. In adults, the dose of epinephrine hydrochloride ( 1 mg/mL) is 0.3 to 0 . 5 mL intramuscularly (IM) in the mid-anterolateral thigh. This may be repeated in 5 to 1 5 minutes. In children, the dose is 0.0 1 mg/kg (maximum per dose 0 . 5 mg) IM in the mid-anterolateral thigh and may be repeated in 5 to 1 5 minutes. B. Antihistamines. 1. H 1 receptor-blocking antihistamines reverse histamine-induced vaso­ dilatation, tachycardia, and bronchoconstriction, as well as cutaneous manifestations, but are insufficient to treat anaphylaxis in the absence of epinephrine. 2. H2 receptor-blocking antihistamines are often prescribed, although evidence of benefit is limited. C. Glucocorticoids. 1. Systemic glucocorticoids increase tissue responses to �-adrenergic agonises and inhibit generation of LTC4, LTD4, and LTE4. 2. Glucocorticoids may prevent late recurrences of anaphylaxis, although biphasic anaphylaxis occurs in 20% of anaphylactic reactions despite glucocorticoid therapy.

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S ECT I O N 1 5 • R H E U M A T O L O G I C A N D I M M U N O L O G I C P R O B L E M S

TA B L E 1 4 0 - 3

reatment o f Anaphylaxis i n Adu lts

M a ndatory and i m med iate

G e n e ra l m easu res Ad m i n ister a q u eous e p i n e p h r i n e ( 1 mg/m l) , 0 . 3-0 . 5 m l I M in the m id -a nterolatera l th igh , up to 3 d oses at 1 - to 5-m i n i nte rva ls Apply a tou r n i q u et prox i m a l to the a ntigen i njecti on o r sti n g s ite Ad m i n ister s u p p l e m e nta l oxyge n For l a ryngea l o bstruction or res p i ratory arrest Esta blish a i rway u s i n g e n d otrachea l i n t u bati o n , cricothyroidotomy, or trach eoto my I n itiate mecha n ica l ve ntilation After c l i n ic a l apprais al

G e n e ra l m easu res D i phen hyd ra m i ne , 1 . 25 m g/kg to maxi m u m of 50 mg, IV or I M Aq ueous hyd rocortisone, 200 mg; d exa methasone, 1 0 mg; or m ethy l p red n iso lone, 1 2 5 mg; IV eve ry 6 h for 24-48 h C i m etid i n e , 300 mg, or ra n itid i n e 50 mg, IV over 3-5 m i n For hypotension Aq ueous e p i n e p h r i n e (1 m g/m l) , 1 ml i n 500 ml of sa l i ne at 1-5.0 m U m i n , o r 2 to 1 0 µg/m i n titrated to m a i nta i n a m ea n a rteria l press u re ( M AP) of 65 m m Hg, by a n i nfusion pu m p t h rough a ce ntra l venous l i n e . Vol u m e expa nsion w i t h normal sa l i n e . N o re p i n e p h ri n e 4 mg i n 1 , 000 m l o f D 5 W a t 2- 1 2 µg/m i n I V. G l u cagon (if patient is rece iving �-blocker thera py) 1 to 5 mg IV bo l u s or i nfusion or 1 m g/l of D5W at a rate of 5-1 5 m Um i n . For b ro nc h oconstriction S u pplementa l oxyge n A l b uterol (0. 5 % ) , 0 . 5 m l i n 2 . 5 m l of sa l i n e , by a n e b u l izer. If i ntu bated , use a l b utero l - m ete red d ose i n ha l e r ( M D I ) 1 0-20 puffs , e n d otracheal ly, every 20 m i n , as need ed .

V I I . PREVENTI O N O F ANAPHYLACTI C REACT I O N S

A. A careful history identifying possible precipitants of anaphylaxis at the time of presentation is crucial. B. Patients should be encouraged to wear a MedicAlert (MedicAlert Foundation, 2323 Colorado Ave. , Turlock, CA 95382 or www. medicalert. org) or a similar identifying bracelet. C. Patients should carry two epinephrine devices (e.g., EpiPen or EpiPen, Jr.) for intramuscular injection. D. �-Blocking medication may increase the risk of anaphylaxis and make it more refractory to treatment; therefore, �-blocking medication should be avoided, if possible, in patients at risk for recurrent anaphylaxis.

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VI I I . MANAG E M E NT OF ANAP HYLAXI S TO S PE C I F I C PREC I P ITANTS

A. For patients with a history of anaphylaxis to penicillin and related antibiotics who are admitted to the intensive care unit (ICU) and need antibiotic therapy: 1 . Approximately 1 0% of allergic reactions to �-lactams are life threaten­ ing: of these, 2% to 1 0% are fatal. 2. Skin testing that includes both major (PrePen) and minor (Penicillin G 1 0,000 units/mL) determinants can detect IgE-mediated sensitivity, but it does not evaluate other types of sensitivity, such as serum sickness reactions, morbilliform rashes, and interstitial nephritis. 3. IgE-mediated cross-reactivity between penicillins carbapenems is high, so desensitization is needed if administration of a carbapenem is necessary. 4. If skin testing for the major and minor penicillin determinants is negative, cephalosporins may be administered. The risk of a reaction is < 1 %. If pen­ icillin skin testing is positive, a graded challenge or desensitization to the indicated cephalosporin is necessary. If penicillin skin testing is not avail­ able, then desensitization to the indicated cephalosporin is performed. 5. Patients allergic to amoxicillin/ampicillin (but not penicillin) may have cross reactivity with certain cephalosporins, although not usually with ceftriaxone or ceftazidime. 6. Monobactams (e.g. , aztreonam) do not show cross-reactivity with penicillins, but may cross-react with the cephalosporins. 7. For less severe reactions and when no alternative agent is available, desensitization may be attempted in the ICU setting. Five to six 1 0-fold dilutions of the target concentration are administered in sequence, starting with the most dilute and progressing to the next stronger concentration every 1 5 to 20 minutes, as tolerated. B. Stinging insect venom anaphylaxis: 1 . After initial treatment, patients should be referred to an allergist for skin testing and possible desensitization. 2. Specific venom desensitization provides > 9 5 % protection against anaphylaxis on subsequent stings. C. Food anaphylaxis. 1. Eggs, milk, peanuts, soy, tree nuts, wheat, fish, and shellfish are the most commonly implicated foods. Sensitivity is confirmed by serum immu­ noassay. 2. Strict avoidance of implicated foods and careful education about prompt administration of epinephrine at the onset of a reaction are essential. D. Radiographic contrast medium anaphylaxis. 1. Radiographic contrast media (RCM) are classified based on osmolality, ionicity, and whether they are monomers or dimers. In patients with a history of a previous radiocontrast medium anaphylactic reaction, the repeat reaction rate is reported to be 3 5 % to 60%. 2. Patients with a general history of allergies (e.g., inhalant allergens, foods, medications) have an increased RCM reaction rate. However,

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pretreatment of such patients is not suggested for studies using a nonionic low osmolal agent, as long as the patient has not had a prior reaction to RCM. Asthma should be well controlled prior to the procedure. 3. For patients with a history of RCM anaphylaxis, use of low ionic con­ trast or alternative imaging studies (e.g., computed tomography with a gadolinium-based agent, magnetic resonance imaging, or ultrasound) should be considered. 4. Pretreatment with glucocorticoids (50 mg prednisone, 13 hours, 7 hours, and 1 hour before administration) and diphenhydramine (50 mg orally or IM 1 hour before administration) with or without ephedrine (25 mg orally 1 hour before administration) may reduce the reaction rate to RCM. 5. For an emergent procedure, hydrocortisone (200 mg) can be given intravenously (IV) immediately and repeated every 4 hours until the procedure in addition to diphenhydramine (50 mg IV) immediately before the procedure.

E. Latex-induced anaphylaxis. I . Latex is found in a broad spectrum of medical products. Health care workers and patients with spina bifida or a history of multiple medical procedures are at increased risk of latex-induced anaphylaxis. 2. Serum immunoassay (CAP-Pharmacia) to latex is helpful, but may have false-negative results (50% to 60% sensitivity) . 3. Standardized skin testing is not commercially available. 4. Patients with latex allergy should be cared for in latex-free operating rooms, ICUs, and hospital rooms. F. Angiotensin-converting enzyme (ACE) inhibitor anaphylaxis. I. Severe, potentially life-threatening facial and oropharyngeal angioedema can occur in individuals with sensitivity to ACE inhibitors and angio­ tensin receptor blockers (ARBs) . 2. Onset of angioedema usually starts within the first several hours or up to a week after beginning therapy, bur may be delayed for months to years. 3. Cross-reactivity does occur among the different ACE inhibitors, but usually not between ACE inhibitors and ARBs. 4. Epinephrine is not always helpful: endotracheal intubation or cricothy­ roidotomy may be necessary to maintain an airway. Angioedema may take 1 to 3 days to resolve. Antihistamines and systemic glucocorticoids are frequently administered, although evidence of benefit is limited. 5. The bradykinin antagonist icatibant or fresh frozen plasma (FFP) may be effective for severe or persistent cases. G. Hereditary angioedema (HAE) . I. Individuals with absent or inactive C l esterase inhibitor can develop life-threatening angioedema of the upper respiratory tract. 2. Urticaria is generally not present, but a history of recurrent abdominal pain from intestinal angioedema may be elicited. 3. Acutely, complement C2 and C4 levels are low; C l q is normal in the hereditary form and low in the acquired form. 4. Cl esterase inhibitor is either low or nonfunctional. 5. Angioedema is frequently refractory to epinephrine, necessitating intuba­ tion or cricothyroidotomy. Antihistamines and glucocorticoids are NOT effective.

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6. C l -inhibitor replacement protein (concentrate) can be administered IV for acute attacks. The dosing is 20 units/kg, infused over 1 0 minutes. 7. Ecallantide, the recombinant kallikrein inhibitor, is given for acute attacks of HAE. The adult dose is 30 mg administered in three separate 1 0-mg subcutaneous injections to the abdominal wall. It may cause allergic reactions and anaphylaxis. 8. Icatibant is a synthetic polypeptide that competitively antagonizes bradykinin. The dose in adults is 30 mg administered by subcutaneous injection/infusion in a location 5 to 1 0 cm below the umbilicus over a minimum of 30 seconds. 9. FFP is considered a second-line therapy to be used when the C l -inhibitor concentrate, icatibant, and ecallantide are not available. FFP may be given in 2 units every 2 to 4 hours until symptoms improve. SUGG ESTED R EAD I NGS

Bowen T, Cicardi M, Farkas H, et al. 20 I 0 International consensus algorithm for the diagnosis, therapy and management of hereditary angioedema. Allergy Asthma Clin Immunol 20 1 0;6:24. International guidelines for the diagnosis and treatment ofhereditary angioedema. Castells M. Rapid desensitization for hypersensitivity reactions to medications. Immunol Allergy Clin North Am 2009;29 (3) : 5 8 5-606. Outlines desensitization protocols for a variety ofdrugs. Golden DB. Insect sting anaphylaxis. Immunol Allergy Clin North Am 2007;27:26 1 . A comprehensive review ofvenom allergy and immunotherapy. Greenberger PA, Patterson R. The prevention of immediate generalized reactions to radio-contrast media in high-risk patients. ] Allergy Clin Immunol 1 9 9 1 ;87: 867-872. Details the preventive management ofcontrast medium use in emergent situations in patients with previous anaphylaxis reactions. Gruchalla RS . Drug allergy. ] Allergy Clin Immunol 2003 ; 1 l I :S548-S559. Excellent review ofpenicillin, cephalosporin, and sulfonamide allergy. Kemp SF, Lockey RF. Anaphylaxis: a review of causes and mechanisms. J Allergy Clin Immunol 2002; 1 1 0:341-348. A review article that includes mechanisms, epidemiology, clinicalfeatures, and approaches to anaphylaxis prevention and therapy. Litcle FF, Hollingsworth HM. Anaphylaxis. In: Irwin RS, Rippe JM, eds. Intensive care medicine, 7th ed. Philadelphia: Lippincott Williams & Wilkins, 20 1 2:203 1 . A n in-depth discussion of critical care management ofanaphylaxis. Neugut Al, Ghatak AT, Miller RL. Anaphylaxis in the United States: an investigation into its epidemiology. Arch Intern Med 200 1 ; 1 6 1 : 1 5-2 1 . Reviews relative frequency ofdifferent causes ofanaphylaxis in the United States. Roberts JR, Wuerz RC. Clinical characteristics of angiotensin-converting enzyme inhibitor-induced angioedema. Ann Emerg Med 1 9 9 1 ;20:555-558. Details the clinical allergic reactions to angiotensin-converting enzyme inhibitors. Salkind AR, Cuddy PG, Foxworth JW. Is this patient allergic to penicillin? An evidence-based analysis of the likelihood of penicillin allergy. JAMA 200 1 ;285 ( 1 9) :2498-2505. Describes the approach to the diagnosis of/3-lactam allergy. Sampson HA, Mendelson L, Rosen JP. Fatal and near-fatal anaphylactic reactions to food in children and adolescents. N Engl] Med 1 992;327:380-384. A review of common food allergens and clinical manifestations.

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Sampson HA, Munoz-Furlong A, Campbell RL, et al. Second symposium on the definition and management of anaphylaxis: summary report-Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. ] Allergy Clin Immunol 2006; 1 1 7:39 1-397. A comprehensive document that provides consensus summary statements for the treatment and management ofanaphylaxis. Thomas M, Crawford I. Best evidence topic report. Glucagon infusion in refractory anaphylactic shock in patients on beta-blockers. Emerg Med J 2005;22:272-273. Reviews evidence for use ofglucagon to treat anaphylaxis in patients taking {3-blocking medication. Toogood JH. Risk of anaphylaxis in patients receiving beta-blocker drugs. J Allergy Clin lmmunol 1 988;8 1 : 1-5. Describes the risks of{3-blocker use in patients undergoing anaphylaxis and treatment strategy. Wong S, Dykewicz MS, Patterson R. ldioparhic anaphylaxis. Arch Intern Med 1 990; 1 50: 1 323- 1 328. A retrospective evaluation of 1 75 patients with idiopathic anaphylaxis.

Vas c u l i t i s i n th e I nte ns ive Ca re U n it Pa u l F. D e l l a ri pa

I . OVERVI EW. A group of disorders in which inflammation and necrosis of blood vessels lead to organ dysfunction due to the development of thrombosis or hemorrhage. Mimics of vasculitis include subacure bacterial endocarditis, atrial myxoma, antiphospholipid syndrome, and cholesterol embolism. I I . G RAN U LO MATOS I S WITH POLYAN G l lTIS (G PA) (formerly refe rred to as Wege n e r gra n u l o matosis)

A. General principles. 1. Characterized by granulomatous inflammation of the upper and lower respiratory tract, segmental necrotizing glomerulonephritis, and small vessel inflammation of other organ systems. 2. Reasons for intensive care unit (ICU) admission for GPA and all of the vasculitides include respiratory failure due to alveolar hemorrhage, rapidly progressive renal failure, and infections, including those due to immunosuppressive treatment of disease. Stridor due to subglottic ste­ nosis can occur in GPA. B. Pathogenesis. 1. There is no known etiologic agent for GPA. 2. Antineutrophilic cytoplasmic antibodies (ANCA) are present in >90% of cases of GPA. C-ANCA (with specificity to PR3 antigen) seen in 90% and P-ANCA (with specificity to myeloperoxidase [MPO] ) seen in a minority of cases. C. Diagnosis. 1. Clinical presentation typically includes sinusitis, rhinitis, epistaxis, otitis media, and hearing loss. 2. Lower respiratory tract is involved frequently, with cough, dyspnea, hemoptysis, and progressive respiratory failure due to alveolar hemor­ rhage. Pulmonary infiltrates may be diffuse, patchy, nodular, or cavitary. Lung biopsy may be necessary to confirm diagnosis and eliminate the possibility of mycobacterial or fungal disease. 3. Renal involvement may be rapidly progressive leading to dialysis. Rarely, ANCA-associated vasculitis coexists with antiglomerular basement anti­ bodies (anti-glomerular basement membrane [GBM] ) . Diagnosis is confirmed based on clinical findings, presence of ANCA, and tissue biopsy

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of affected organs, including the kidney, lung, eye, nerve, or skin. In some cases, tissue biopsy may not be necessary when the clinical suspicion for dis­ ease is high, and the ANCA pattern unequivocally supports the diagnosis.

D. Treatment. 1. In the setting of severe disease (respirarory failure, alveolar hemorrhage, and progressive renal failure), therapy should include cyclophospha­ mide (CYC) or rituximab (375 mg/m2 weekly for 4 weeks or 1 g twice separated by 2 weeks) and high-dose corticosteroids. Intravenous (IV) methylprednisolone in doses of 1 ,000 mg/day for 3 days may be considered. 2. Oral dosing of CYC is 2 mg/kg but, in renal failure, it is as follows: 1 . 5 mg/kg/d if creatinine clearance (CrCl) is 50 ro 99; 1 .2 mg/kg/d if CrCl is 25 to 49; 1 .0 mg/kg/d if CrCl is 1 5 to 24; and 0 . 8 mg/kg/d if CrCl is < 1 5 or dialysis. 3. In the setting of critical illness and potential variability of gastrointes­ tinal (GI) absorption, IV CYC (0. 5 g/m2 to 1 g/m 2) may be indicated. Appropriate IV hydration pre- and post-CYC infusion and addition of MESNA are important. 4. Pneumocystis pneumonia (PCP) prophylaxis should be offered. 5. Plasmapheresis and IV immunoglobulin (lg) may be useful during preg­ nancy or in severe or refracrory GPA and severe alveolar hemorrhage with or without anti-GBM antibodies. 6. The presence of worsening pulmonary infiltrates in those treated with CYC and steroids raises the suspicion of fungal infections and PCP, warranting early bronchoscopy or biopsy and early consideration for antifungal and PCP therapy. 7. Other agents such as mycophenolate mofetil, azathioprine, or metho­ trexate may be used in less severe cases or in refracrory cases. I l l . M I C RO S C O P I C P O LYA N G l lTIS

A. General principles. 1. Small- and medium-vessel necrotizing vasculitis presenting with pauci­ immune segmental necrotizing glomerulonephritis and pulmonary capillaritis with alveolar hemorrhage. 2. ANCA (P-ANCA with MPO specificity) is positive in 70% of cases. 3. Clinical presentation can overlap with GPA, though pathologically there is lack of granulomas. B. Diagnosis. Biopsy of appropriate tissue, typically the kidney, lung, or nerve, in conjunction with ANCA positivity. C. Treatment. Treatment similar ro that for GPA. IV. E O S I N O P H I LI C G RAN U LO M AT O S I S WITH P O LYA N G l lT I S ( E G PA) PREVI O U S LY KNOWN AS C H U RG-STRAU S S SYN D R O M E (CSS)

A. General principles. 1. Characterized by eosinophilic infiltrates and granulomas in the respira­ rory tract in the setting of a hisrory of asthma and eosinophilia.

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2. Peripheral neuropathy, mesenteric ischemia, cardiac, and central nervous system (CNS) involvement may occur. Renal involvement and alveolar hemorrhage are rare. B. Diagnosis. ANCA is positive in 60% of patients, mostly MPO pattern. Biopsy of suspected organs shows granulomas and fibrinoid necrosis. C. Treatment. 1. Corticosteroids in milder presentation, with CYC or rituximab or other immunosuppressant agent in more severe disease. 2. Five-factor score (proteinuria > 1 g/day, azotemia, GI or CNS dysfunc­ tion, cardiomyopathy) may help to determine prognosis and level of treatment. V. POLYARTERITIS N O D OSA ( PAN)

A. General principles. Systemic necrotizing vasculitis involving small and medium muscular arteries. B. Etiology. The etiology of PAN is unknown, though, rarely, the presence of circulating hepatitis B surface antigen in vessel walls is noted. C. Diagnosis. 1. Presents with a prodrome of malaise, fatigue, fever, and weight loss. 2. Vasculitic lesions may result in mononeuritis multiplex, cutaneous lesions, intestinal ischemia, myocardial infarction, and congestive heart failure. 3. Laboratory findings include anemia and elevated sedimentation rate. ANCA is absent. 4. Diagnosis is confirmed by tissue biopsy or evidence of microaneurysms on mesenteric angiogram. D. Treatment. 1. High-dose corticosteroid therapy orally or intravenously with pulse methylprednisolone at 1 g/day for 3 days; CYC used in severe cases. 2. In cases associated with hepatitis B, antiviral therapy may be used in early conjunction with corticosteroids and plasmapheresis. V I . CRYO G LO B U L I N E M I C VAS C U LITIS

A. General principles. Cryoglobulins are Igs that prec1p1tate in the cold. There are three types, with types II and III closely, though not exclusively, associated with hepatitis C infection. B. Diagnosis. 1. Findings include palpable purpura, peripheral neuropathy, and infre­ quently life-threatening renal, GI, and pulmonary involvement, includ­ ing pulmonary hemorrhage. 2. Laboratory values include low complement levels (C4) , abnormal liver enzymes, and positive rheumatoid factor.

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C. Treatment. 1 . Treatment consists of high-dose corticosteroid and adding rituximab or CYC in cases of renal failure or mononeuritis multiplex, as well as treat­ ment for hepatitis C when present. 2. Plasmapheresis or cryofiltration may be beneficial in severe cases. V I I . P U L M O NARY CAPI LLARITIS

A. General principles. 1. Pathologically, pulmonary capillaritis is due to alveolar wall inflamma­ tion that leads to disruption of the integrity of the alveolar capillary base­ ment membrane, presenting clinically as diffuse alveolar hemorrhage (DAH) . a. It is most often associated with immune-mediated processes such as GPA, microscopic polyangiitis, the antiphospholipid antibody syndrome, systemic lupus erythematosus (SLE) , Henoch Schonlein purpura, IgA nephropathy, and drug-induced vasculitis such as pro­ pylthiouracil. 2. Clinically, pulmonary capillaritis may be an isolated phenomenon or can be seen in concert with other systemic manifestations, including glomerulonephritis, known as the so-called pulmonary renal syndrome. B. Diagnosis. 1. In patients with evidence of either isolated alveolar hemorrhage or pulmonary renal syndrome, assessment of ANCA, antinuclear antibody (ANA) , anti-GBM, and antiphospholipid antibodies is appropriate. 2. Biopsy of the lung or kidney may be useful, though may be difficult to accomplish in the setting of critical illness. C. Treatment. 1. Treatment consists of empiric high-dose steroids 1 g/day IV for 3 days, cytotoxic therapy, and consideration for plasmapheresis if respiratory or renal failure is severe. In established cases of vasculitis in patients already on immunosuppression, DAH should also raise suspicion for infections such as Aspergillus. V I I I . VAS C U LITIS OF T H E C E N TRAL N E RVO U S SYSTEM

A. General principles. Heterogeneous group of neurologic disorders divided into primary angiitis of the CNS (PACNS) and secondary forms related to rheumatic syndromes such as SLE, rheumatoid arthritis (RA) , sarcoidosis, Sjogren, and Behcet syndromes as well as various infections. A condition known as reversible cerebral vasoconstriction syndrome can present with features similar to PACNS, though symptoms are more abrupt in onset, of shorter duration, and with angiographic findings that resolve over a period of weeks. The focus of this section is on PACNS.

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B. Diagnosis. 1. PACNS : usually a slow, progressive process characterized by headache, focal deficits, and changes in higher cortical function. a. Lumbar puncture reveals mononuclear pleocytosis and elevated protein. b. Magnetic resonance imaging (MRI) shows abnormal multifocal vascular lesions and leptomeningeal enhancement. c. Angiography is nonspecific or normal in up to 60% of cases. d. Biopsy of the cortex and leptominges showing granulomas and giant cells is the diagnostic procedure of choice. C. Treatment. PACNS is treated with corticosteroids and CYC. SUGG ESTED R EA D I NGS

Baldini C, Talarico R, Della Rossa A, et al. Clinical manifestations and treatment of the Churg-Strauss syndrome. Rheum Dis Clin North Am 2 0 1 0;36(3) : 527-543. An excellent review on the unusualform ofvasculitis. DaVita S, Quartuccio L, Isola M, et al. A randomized controlled trial of rituximab for the treatment of severe cryoglobulinemic vasculitis. Arthritis Rheum 20 1 2;64(3) :843-8 53. An excellent study that showed a survival benefit and improvement in disease activity in the Rituxan group compared to conventional therapy (corticosteroids, azathioprine, or cyclophosphamide}. Guillevin L, Lhote F, Gayraud M, et al. Prognostic facrors in Polyarreritis nodosa and Churg-Strauss syndrome. Medicine (Baltimore} 1 996;75 ( 1 ) : 1 7-28 . Classic description ofkey clinical prognostic factors that define the 5-factor scoring system. Hajj-Ali RA, Calabrese LH . Primary vasculitis of the central nervous system. Autoimmun Rev 2 0 1 3 ; 1 2 (4) :463-466. Excellent review on this unusual clinical syndrome. Jones RB, Tervaert JW, Hauser T et al. Rituximab versus cyclophosphamide in ANCA associ­ ated renal vasculitis. N Engl] Med 2 0 1 0;363 (3) :2 1 1 -220. One of two randomized prospective trials using B-cell deletion in the treatment of ANCA-associated disease, which showed clinical equivalence in outcome between rituxan and CYC. Lee A, Specks U. Pulmonary capillaritis. Semin Respir Crit Care Med 2004;25(5): 547-5 5 5 . General review on diffese alveolar hemorrhage. Mahr A, Chaigne-Delalande S, De Menthon M. Therapeutic plasma exchange in sys­ temic vasculitis: an update on indications and results. Curr Opin Rheumatol 2 0 1 2:24(3) :26 1-266. Excellent review on the clinical indications ofplasma exchange in autoimmune diseases based on best available trials and case series. Stone JH, Merkel PA, Spiera R et al. Ricuxan versus cyclophosphamide for AN CA-associated vasculitis. N Engl J Med 2 0 1 0;363 (3) :22 1-232. Prospective trial utilizing B-cell-deleting therapy in the treatment ofsystemic manifesta­ tions ofANCA-associated vasculitis, which showed noninferiority of rituxan compared to cyclophosphamide.

D i ag n o s i s a n d Tre atm e nt of Ag itat i o n a n d D e l i r i u m i n th e I nte n s ive C a re U n it Pati e nt J a s o n P. Ca p l a n

I . G E N E RAL P R I N C I PLES

A. Definition. 1. Agitation is a frequent behavioral aberration in severely ill patients, which carries significant risks for the safety of the patient and staff. 2. Agitation may be a symptom of delirium (a neuropsychiatric manifesta­ tion of a systemic disturbance) , the most common cause of agitation in the intensive care unit (ICU) . Delirium is defined as alterations in attention and cognition that develop over hours to days and wax and wane. The hallmark of delirium is inattention that can be gauged by simple bedside testing (e.g., attention ro conversation, serial subtraction of 7 from 1 00, recitation of the months of the year backwards) .

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B. Epidemiology. 1 . Delirium occurs in >30% of all patients in the ICU and in >80% of patients in the ICU who are intubated. C. Risk factors. 1. Acute physiologic risk factors include metabolic disturbances, infec­ tion, shock, hypoxia, renal failure, hepatic failure, and intracranial processes. 2. Chronic physiologic risk factors include advanced age; malnutrition; alcohol or drug abuse; and prior diagnoses of depression, dementia, stroke, seizure, congestive heart failure, or human immunodeficiency virus infection. 3. Iatrogenic risk factors include medication side effects (most commonly those of anticholinergics, benzodiazepines, opioids, antihistamines, and steroids) and the presence of indwelling catheters. I I . ETIOLOGY A N D PAT H O G E N E S I S

A. The mnemonic "WWHHHHIMPS" aids recall of the life-threatening causes of delirium (Table 1 42- 1 ) . B . The current leading hypothesis o n the neural mechanism o f delirium impli­ cates hypocholinergic and hyperdopaminergic states. C. Acetylcholine is the primary neurotransmitter of the reticular activating system, a network vital to both alertness and attention. Therefore, a relative cholinergic deficit is likely to disrupt these functions. D. Impaired oxidative metabolism increases the release, and disrupts the reuptake and extracellular metabolism, of dopamine. Excess dopamine is associated with hallucinations, delusions, and other psychotic symptoms, and may facilitate the excitatory effects of glutamate, thereby producing agitation. TA B L E 1 4 2 - 1

W H H H H I M PS : A M ne m o n i c for the Life-th reate n i ng a u ses of De l i ri u m

Withd rawa l We rni c ke encephalopathy Hypoxia or hypoperfusion of the bra i n Hyperte nsive crisis Hypoglyce m ia Hyper- or hypotherm ia l ntracra n i a l mass or h e m o rrhage M e n i ngitis or e n ce p h a l itis Poisons ( i n c l u d i ng med ications) Status e p i l e pticus Ada pted from W i s e M G , Trze pacz P T . D e l i r i u m (confusional states) . I n : R u nd e l l J R , W i s e M D , eds. The A merican psychiatric press textbook of consultation-liaison psychiatry. Wash i ngto n , DC: American Psyc h iatric Press, 1996:258-274.

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I l l . D I FFERE NTIAL DIAG N O S I S

A . Two delirium screening scales have been validated for use b y nonpsychi­ atric personnel in the ICU: the Confusion Assessment Method for the ICU (CAM-ICU) and the Intensive Care Delirium Screening Checklist (ICDSC) . Both are available at www.icudelirium.org. B. Delirious patients may present with a hypoactive subtype that is com­ monly mistaken for depression. Hypoactive delirium is distressing to the patient, may progress to the agitated form, and requires appropriate treatment. C. Patients with dementia are at risk for agitation and delirium in the ICU as a result of being in unfamiliar surroundings. Behavioral measures should be employed to help these patients maintain orientation to their milieu. D. Patients with schizophrenia also may have difficulty adapting to ICU restric­ tions. Measures should be taken to make the ICU as familiar and comfort­ able as possible. Table 1 42-2 compares and contrasts the diagnostic features of these different causes of agitation. Differential Diagnosis of Causes of Agitation

O nset C o u rse Revers i b i l ity Leve l o f c o n s c i o us n ess Atte ntion/ m e m o ry

H a l l u c inations

Delusions

De l i r i u m

Dementia

Depress ion

Sch izophre n i a

Acute F l u ctuating U s ua l ly I m pa i red

I nsid ious• P rogress ive b N ot usua l l y Clea r u ntil late stages P o o r m em ory without m a rked i n atte ntion

Va ria ble Va riable U s u a l ly U n i m pa i red

Va ria ble Va ria ble No U n i m pa i redc

I nattenti o n , poor m e m ory

Atte ntion Poor attenti o n , m e m ory i ntact usua l ly i ntact, m em ory i ntact U s u a l ly a u d itory Usua l ly visua l ; C a n b e visual U s u a l ly a u d itory ca n be or a u d itory a u d ito ry, tacti l e , gustatory, olfactory Para n o i d , Com plex, Fleeti ng, Freq uent, often fixed fragmented , moodcom p lex, system atized , usua l ly congruent persecutory often pa ra no id

'Exce pt f o r dem entia d u e to stroke. 'Lewy body dementia often presents with a waxing a n d wa n i n g course i m posed on a n overa l l progressive decl i n e . 'Exce pt when complicated b y catato n i a . Ada pted from Trze pacz P T , M eagher DJ . D e l i ri u m . I n : Levenson J L, ed . The A merican Psychiatric Publishing textbook of psychosomatic medicine. Was h i ngto n , D C : American Psyc h iatric P u b l i s h i ng, 2005 :91-130.

C h a pter 1 4 2 • D i agnosis a n d Treatment of Agitation a n d Del i r i u m i n t h e I C U Pat i e n t

I

1 1 35

E. Alcohol or sedative-hypnotic withdrawal is a prominent cause of delirium in the ICU. This syndrome results from decreased activity of y-aminobutyric acid (GABA) and unopposed noradrenergic, glutamatergic, and dopami­ nergic activation when the intake of alcohol or sedative-hypnotic agents is ceased suddenly. Confusion, agitation, diaphoresis, tremor, and autonomic instability (collectively known as delirium tremens) may progress to seizure and death. F. Inadequately controlled pain, overwhelming anxiety, or hopelessness result­ ing from depression also may result in agitation. IV. TREAT M E N T

A. Definitive treatment of delirium requires identification and treatment of the underlying causes. B. Agitation and other symptoms of delirium may be managed adjunctively with neuroleptics due to their antagonism of the dopamine receptor. C. The "gold standard" of this adjunctive treatment is intravenous (IV) halo­ peridol. IV administration, although "off label," is the standard of care and is preferable to other routes due to better absorption, less discomfort, and reduced extrapyramidal side effects (EPS). 1 . Treatment with IV haloperidol is usually initiated with a dose ranging from 0.5 mg (in the elderly) to 1 0 mg (for severe agitation) . Subsequent doses can be doubled at 30-minute intervals until optimal tranquilization is achieved. 2. Complete absence of agitation should be the goal, afrer which a fraction of the cumulative dose ofhaloperidol required to control the agitation can be divided and given 2 or 3 times daily with additional doses provided as needed. 3. Over time, the total dose can be gradually decreased; it is usually wise to wean the evening dose last. D. Data on the efficacy and safety of the atypical or second-generation neuro­ leptic agents (e.g., risperidone, olanzapine, quetiapine, ziprasidone) in the delirious patient are limited, though single randomized, controlled trials have found both risperidone and olanzapine to be as effective as haloperidol. E. Quetiapine may have a niche role in the treatment of delirium in patients with Parkinson disease or Lewy body dementia, as it is less likely than halo­ peridol to exacerbate these disorders. F. Treatment of alcohol or sedative-hypnotic withdrawal typically requires administration of a benzodiazepine (e.g., lorazepam) . Great care should be taken in the diagnosis of alcohol or sedative-hypnotic withdrawal in the agitated patient, since the prescribed treatment (i.e., a benzodiazepine) is almost certain to exacerbate delirium due to another etiology. V. C O M P LI CAT I O N S

A. Delirium has been associated with prolonged hospital stay and increased morbidity and mortality. Fiscally, delirium predicts heightened costs in the ICU and in overall hospital care.

1 1 36

S ECT I O N 1 6 • P S Y C H I A T R I C I S S U E S I N

I NTENSIVE CAR E

B. Neuroleptic administration may contribute to progressive widening of the QT interval, resulting in an increased risk for torsades de pointes (TDP) and possible death. 1. Although the incidence of fatal TDP is relatively low, cardiac rhythm should be carefully monitored with close attention paid to serum levels of potassium, magnesium, and calcium. 2. Prolongation of the corrected QT interval (QTc) >25% from baseline or a QTc >500 ms may warrant telemetry, cardiologic consultation, and reduction or discontinuation of haloperidol. 3. Other potential QTc-prolonging agents (e.g., fluoroquinolone antibiotics, calcium channel blockers, methadone) may need to be discontinued. SUGGESTED READI NGS

Caplan JP, Cassem NH, Murray GB, et al. Delirious patients. In: Stern TA, Fricchione GL, et al., eds. Massachusetts general hospital handbook ofgeneral hospital psychiatry, 6th ed. Philadelphia: Saunders, 2 0 1 0:93- 1 04. A practical "hands on " guide to the workup and management ofdelirium. Fricchione GL, Nejad SH, Esses JA, et al. Postoperative delirium. Am J Psychiatry 2008 ; 1 65:803- 1 2 . A useful review of the pathophysiology and management ofdelirium i n the postoperative period. Gusmao-Flores D, Figueira Salluh JI, Chalhub RA, et al. The confusion assessment merhod for the intensive care unit (CAM-ICU) and intensive care delirium screening check­ list (ICDSC) for the diagnosis of delirium: a systematic review and meta-analysis of clinical studies. Grit Care 20 1 2 ; 1 6:Rl 1 5 . A meta-analysis comparing the sensitivity and specificity of the CAM-ICU and ICDSC for detection ofdelirium in the ICU setting. Martin BJ, Buth KJ, Arora RC, et al. Delirium: a cause for concern beyond the immediate postoperative period. Ann Thorac Surg 2 0 1 2;93: 1 1 1 4- 1 1 20. A prospective study of8,474 patients undergoing coronary artery bypass grafting showing delirium to be associated with a doubling ofpostoperative length ofstay and an indepen­ dentpredictor ofstroke and mortality. Repper-DeLisi J, Stern TA, Mitchell M, et al. Successful implementation of an alcohol-with­ drawal pathway in a general hospital. Psychosomatics 2008;49:292-299. An outline of the development and implementation ofa protocolfor the prophylaxis and management ofalcohol withdrawal delirium in the general hospital. Wenzel-Seifert K, Wittmann M, Haen E. QTc prolongation by psychotropic drugs and the risk of torsade de pointes. Dtsch Arztebl Int 20 1 1 ; 1 08:687-693 . A review ofthe multifoctorial nature of QTc prolongation in the setting ofpsychotropic administration.

1 43

Suicide S a o r i A . M u ra ka m i

I . G E N E RAL P R I N C I PLES

A. Description. 1. The treatment of a suicidal patient in the intensive care unit (ICU) includes evaluation, management, and safeguarding the patient. 2. Evaluation and management of the suicidal patient require an under­ standing of risk factors, protective factors, the interplay among these elements, and the relationship between the staff and the patient. 3. Psychiatric care is essential during and after the stabilization of medi­ cal problems. It is helpful to initiate psychiatric involvement from the beginning of the admission, even if the patient is intubated and heavily sedated. In these circumstances, the consulting psychiatrist can obtain collateral information, assess the severity and lethality of the attempt, establish the chronology of symptoms leading to the presentation, and conduct serial safety assessments. B. Risk and protective factors. 1. Suicide is the 1 0th leading cause of death in the United States (as of 2009, 7th in men, 1 4th in women) . 2. It is not possible to make absolute predictions of suicidal behavior. 3. Risk factors for suicide include sociodemographic factors, past and cur­ rent psychiatric and medical illnesses, family history, and psychosocial stressors (Table 1 43- 1 ) . 4 . Protective factors include the absence o f these risk factors and the pres­ ence of support from medical treaters, family, and community. 5. Assessment of risk and protective factors must be conducted on a case-by-case basis. I I . TREAT M E N T

A. Nonpharmacologic interventions. 1. Suicidal thinking can be expressed in various ways, including explicit declaration or implicit action (e.g., refusal to eat or to cooperate with care) . All forms of suicidal thinking require immediate attention. 2. Monitoring is essential and can be accomplished through 1: 1 observa­ tion or frequent checking on the patient. In some situations, physical restraints may be necessary. 3. The ICU staff should be aware of potential means by which the patient may harm himself or herself, including personal belongings and items brought in by visitors. 1 1 37

1 1 38

I

S ECT I O N 1 6 • P S Y C H I A T R I C I S S U E S I N I N T E N S I V E C A R E

liJ:l!i§fii

R i s k Factors for S u i c ide

Sociodemogra p h i c factors

• Age : late adolescence to yo u n g a d u lth ood , older than 65 y • G e n d e r : m e n a re more l i kely to co m p lete s u i c i d e , wo m e n m o re l i kely to atte m pt • Race: n o n - H ispa n ic wh ite, N ative America n , Alaska n native • Ma rita l statu s : d ivorced or wid owed > s i ngle > ma rried • Access to letha I agents Psyc h iatric h i story a n d present psyc h iatric i l l ness

• • • • •

Psyc h iatric d isord e rs S u bsta nce a b use H istory of s u i c i d e atte m pts H o pelessn ess or n egative expectations a bout the futu re Recent d ischarge fro m a psyc h iatric hospita l

M e d i c a l h i story a n d present med ical i l l ness

• • • • • • • • • •

N e u rologic d isord e rs H ead tra u m a Cogn itive deficits M a l igna n c ies H u ma n i m m u nodeficiency virus i nfection C h ro n i c pa i n syn d romes C h ro n i c i nfla m m atory d isease C h ro n i c ren a l fa i l u re Heart d i sease C h ro n i c p u l m o n a ry d isease

Fa m i ly h i story

• Psyc h iatric i l l n ess or s u bsta nce a b use • H istory of com p leted s u i c i d e Psyc hosoc i a l stressors

• • • • • • •

Fa m i ly l ife Work l ife Relations h i ps F i n a n ces Recent rea l or perce ived loss Few s u p ports Tu m u ltuous ea rly fa m i ly environ ment

Ada pted from B rendel R , W e i M , Lagomasino IT, e t a l . Ca re o f t h e s u i c i d a l patient. I n : Stern TA, Fricc h ione G L, Cassem N H , et a l . , eds. Massachusetts general hospital handbook of general hospital psychiatry, 6th ed . P h i la d e l p h i a : Sa u n d e rs, 2010:541-554.

4. Safety assessments should be made at least daily. 5. The primary team should identify and address negative feelings that may be induced by some suicidal patients, particularly those who have made multiple attempts or who clamor for the attention of the ICU staff.

C h a pter 1 43 • S u i c i d e

I

1 1 39

B. Medications. 1. Consideration should be given to discontinuing or decreasing the dose of medications that may heighten impulsivity or disinhibition (e.g., benzodiazepines and anticholinergic agents) . 2. Establishing an accurate psychiatric diagnosis will guide the decision to start or restart psychiatric medications following a suicide attempt. Outpatient medications should not be resumed reflexively. a. The patient's physical condition, sensorium, and risk for seizures and arrhythmias, as well as medication side effects, should be considered. 3. While treating the underlying psychiatric diagnosis with medications will assist in lowering overall suicide risk, psychotropic medications have not independently been associated with a decrease in suicide. C. Psychiatric consultation. 1. Psychiatric consultation is strongly recommended whenever there is a question regarding the potential for self-harm. a. This is particularly important in cases of implicit action or when there are overwhelming risk factors even without an explicit declaration. 2. The primary team should provide the consultant with as many details of the suicide attempt as possible. When an explicit declaration has been made, the team should inform the consultant of the exact words used and the context of rhe statement. 3. Clear documentation is important. 4. Consultation can also be helpful in understanding and processing the psychological dynamics between the patient and staff. D. Disposition. 1. The most common options for discharge are home or a psychiatric facility. 2. This decision is usually made with the help of the psychiatric consul­ tant, who will assist with placement, insurance authorization, and legal matters (e.g., involuntary commitment if the patient is unwilling to be hospitalized psychiatrically) . SUGG ESTED R EA D I NGS

American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 5th ed. Washington: American Psychiatric Association, 20 1 3 . The definitive reference fo r psychiatric diagnosis. Brendel R, Wei M, Lagomasino IT, et al. Care of the suicidal patient. In: Stern TA, Fricchione GL, Cassem NH, et al. , eds. Massachusetts general hospital handbook ofgeneral hospi­ talpsychiatry, 6th ed. Philadelphia: Saunders, 201 0:54 1-554. This comprehensive reference for the psychiatric management of medically ill, hospital­ ized patients summarizes the epidemiology, risk factors, evaluation, and management of suicidal thoughts and behavior. Centers for Disease Control and Prevention, National Center for Injury Prevention and Control. Web-based Injury Statistics Query and Reporting System (WISQARS) . 2009. Available at: www.cdc.gov/ncipc/wisqars This CDC Web site provides the most recent statistics on fatal and nonfatal suicidal thoughts and behavior.

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S ECT I O N 1 6 • P S Y C H I A T R I C I S S U E S I N I N T E N S I V E C A R E

National Institute of Mental Health. Suicide Prevention. Available at:

http://www.

Accessed September 1 , 2 0 1 2 . The NIMH provides a listing ofpublications with information about suicide risk factors, statistics, treatment, and prevention. nimh.nih.gov/health/publications/suicide-prevention-listing.shtml.

Sudak H. Suicide. In: Sadock BJ, Sadock VA, Ruiz P, eds. Kapl.an & Sadock 's comprehensive textbook ofpsychiatry. 9th ed. Philadelphia: Lippincott Williams & Wilkins, 2009: 271 7-273 1 . This chapter in one of the major textbooks ofpsychiatry provides a summary ofthe epide­ miology, risk factors, evaluation, and management ofsuicidal thoughts and behavior. United States Department of Veterans Affairs. Suicide Risk Assessment Guide. Available at: http ://www. mentalhealth.va.gov/docs/Suicide_Risk_Assessment_Guide.doc.

Accessed September 1 , 2 0 1 2 . This Web site provides a guided summary ofsuicide risk assessmentfor nonpsychiatric clinicians. The information is also avail.able as a pocket card.

D i a g n os i s a n d Tre atm e nt of D e p ress i o n i n th e I nte ns ive Ca re U n it Pat i e nt J o h n Q u e rq u es a n d T h eo d o re A. Ste r n

I . G E N E RAL P R I N C I PLES

A. Major depressive disorder is a psychiatric condition that affects mood and neurovegetative functions (e.g., sleep, appetite) . 1 . While experiencing a depressed mood transiently can be a normal and expected part of life, having the full constellation of symptoms meeting the criteria for major depressive disorder is never a normal or appropriate reaction to a stressful situation. 2. Left untreated, major depression increases rates of morbidity and mor­ tality, especially from cardiac conditions. B. Definition. 1. Major depressive disorder is a syndrome characterized by five or more of the symptoms listed in Table 1 44 - 1 for 2 weeks or more. 2. One of the five symptoms must be either depressed mood or anhedonia (i.e., an absence of pleasure) . 3. The mnemonic SIG: E CAPS (i.e., label: energy capsules) is a helpful guide to remember these defining criteria (Table 1 44- 1 ) . I I . DIAG N O S I S

A. Clinical features. The manifestations o f depression include affective, behav­ ioral, and cognitive abnormalities (i.e., the ABCs of depression) (Table 1 44-2) . Though a depressed patient may be psychomotorically slowed and have scant facial expression, his or her sensorium will be intact. This helps to distinguish depression from delirium, in which the patient will have a reduced level of wakefulness, alertness, and/or attentiveness. The hypo­ manic or manic patient will have an elevated, expansive, or irritable mood rather than a dysphoric one. B. Differential diagnosis. Depression in the intensive care unit (ICU) can occur as a primary affective disorder (e.g., major depressive disorder) , a mood disorder associated with a specific medical condition or its treatment, or a psychological reaction to an acute medical illness.

1 1 41

M ne m o n i c for the Diagnostic Criteria for a Depressive Episode-S I G : E CAPS

Depressed m ood Sleep ( i n c reased or decreased ) I nterest (decreased ) G u i lt ( p reoccu pation with fee l i n g g u i lty or worth less) Energy (decreased ) Concentration (d ecreased ) Ap petite d istu rbed ( i n c reased or decreased ) or we ight ga i n or loss Psyc h o m otor agitation o r reta rd ation S u icida l th i n k i n g or tho ughts of death Ada pted from American Psych iatric Associatio n . Diagnostic a n d statistical manual of mental disorders. 4th e d . Was h i ngto n , DC: America n Psych iatric Associati o n , 1994.

TA B L E 1 44-2

Affective , Behaviora l , a n d Cog n itive Features of Depress ion-the ABCs

Affective sympto m s

Depressed mood H o pelessness C ryi ng I rrita b i l ity Anger Decreased i nte rest Behaviora l sym pto ms

I nso m n ia Anorexia Apathy I nc reased sleep I nc reased a p petite Decreased energy Psyc h o m otor agitation Psyc h o m otor reta rd ation Noncom plia nce D e l i be rate self-harm l m p u lsivity Poor eye contact I nc reased o r i ntracta ble pa i n C ogn itive sym pto ms G u i lty ru m i nation Decreased concentration S u i c i d a l t h i n k i n g o r thoughts of d eath Confusion Dementia- l i ke sym pto ms Somatic preocc u pation Ada pted from Geri nger ES, Querq u es J , Kolodziej M S , e t a l . Diagnosis a n d treatment of depres­ sion in the i nte nsive ca re u n it patient. I n : I rw i n RS, R i ppe J M , eds. Intensive care medicine, 7th ed . P h i la d e l p h ia : L i p p i n cott W i l l ia m s & W i l k i n s , 2012: 2087-2099.

C h a pter 1 44 • D i agnosis a n d Treatment of Depress i o n i n the I ntensive Care U n it Pat i e n t TA B L E 1 44 - 3

I

1 1 43

Sel ected M e d i c a l C o n d i t i o n s Assoc iated with Depress ion

C a r d i ovasc u l a r

Congestive heart fa i l u re Hypertensive ence p h a l o pathy C o l lagen vasc u l a r

Syste m i c l u pus erythematos us Endocrine

Dia betes m e l l itus Hypo- a n d hypera d re n a l i s m Hypo- a n d hyperpa rathyro i d is m Hypo- a n d hyperthyroid ism I nfect i o u s

H e patitis H u ma n i m m u n od efic iency virus i nfection M o n o n ucleosis M eta b o l i c

Acid-base d i sorders Hypoka l e m ia Hypo- a n d hypernatre m ia R e n a l fa i l u re N e o p l asti c

Ca rc i noid syn d ro m e Pa n c reatic ca rc i n o m a Para n eoplastic syn d romes N e u ro l og i c

B ra i n tu m o r M u lt i p l e sc lerosis Parkinson d i sease Co m pl ex pa rtia l seizu res Stroke S u bcortica l d e m e ntia N utriti o n a l

Vita m i n B 1 2 d eficiency ( pern icious a n e m ia ) T h ia m i ne d eficie ncy (We r n i c ke encepha l o pathy) Ada pted from Geri nger ES, Querques J, Kolodziej MS, et al. Diagnosis a n d treatment of depres­ sion in the i ntensive ca re u n it patient. I n : I rw i n RS, R i ppe J M , eds. Intensive care medicine, 7th ed . P h i ladel p h i a : Lippincott W i l l i a m s & W i l k i n s , 201 2: 2087-2099.

1. Medical causes. Various medical conditions (Table 1 44-3) and medications (Table 1 44-4) can cause depression. Laboratory testing should be guided by results of a comprehensive history and physical examination. 2. Psychological reaction. Critical illness often threatens a patient's sense of physical integrity, autonomy, and control and can remind a patient of either a personal or family history of similar life-threatening circum­ stances.

1 1 44

I

S ECT I O N 1 6 • P S Y C H I A T R I C I S S U E S I N I N T E N S I V E C A R E

TA B L E 1 44-4

Selected Med i cations Assoc iated with Depress ion

Acyc l ovi r (espec i a l l y at h igh d oses) Anticonvulsa nts (at h igh d oses o r plasma leve l s ) : carba m aze p i n e , p h e nyto i n , pri m id o n e Antihyperte nsives: th iazides, clon i d i n e , n ifed i p i n e , prazos i n Baclofe n Ba rbitu rates Be nzod iaze p i n es �-B l oc ke rs B romocripti ne Contraceptives Corticosteroids Cyc loser ine Da psone Digita l is (at h igh d oses o r in elderly patie nts) D i ltiazem Disopyra m i d e Ha loth a n e ( posto peratively) H ista m i ne-2 rece ptor a ntago n ists I nte rferon-a lsoniazid Levod o pa (espec i a l ly i n eld erly patients) M efloq u i ne M etoc l o p ra m id e Na rcotics Nonstero i d a l a nti-i nfla m matory d rugs P h enyle p h ri n e P h enyl propa n ola m i n e (withd rawa l ) Proca i n e d erivatives: pe n ic i l l i n G proca i n e , l i doca i n e , p roca i n a m id e Thyroid hormone Tri m ethopri m -s u lfa m ethoxazole Ada pted from Geri nger ES, Querq u es J , Kolodziej M S , e t a l . Diagnosis a n d treatment of depression in the i ntensive ca re u n it patient. I n : I rwin R S , R i ppe J M , eds. Intensive care medicine, 7th e d . P h i l a d e l p h i a : Lippincott W i l l i a m s & W i l k i n s , 2012:2087-2099.

I l l . TREAT M E NT

A. Management of depression includes pharmacologic treatment, psychologi­ cal interventions, and/or electroconvulsive therapy (ECT) . B. Pharmacologic treatment. In the ICU, medications are used most fre­ quently (Table 1 44-5) . An antidepressant medication is selected based on its side effect profile and its rapidity of action. 1 . Psychostimulants. a. Dextroamphetamine and methylphenidate work within hours to days. b. Stimulants can cause or contribute to tachycardia, hypertension, arrhythmias, and coronary spasm, but rarely do so at the low doses (5 to 20 mg daily) usually used.

C h a pter 1 44 • D i agnosis a n d Treatment of Depress i o n i n t h e I ntensive Care U n it Pat i e n t

TA B L E 1 44 - 5

I

1 1 45

Usual Starting Doses o f Antidepressant Agents i n Critica lly I l l Patients U s u a l sta rting dose (mg/day)

Age nt SSRls

Cita lo p ra m Escita lopra m F l u oxetine Pa roxet i n e Sertra l i n e

5- 1 0 5- 1 0 5- 1 0 5- 1 0 25-50

S N Rls

D u loxetine Ve n lafaxi ne

30-60 3 7 . 5-75

Others

B u propion Dextroa m ph eta m i ne M ethyl phen idate M i rtaza p i n e

50- 1 00 2 . 5-5 5 7 . 5- 1 5

Bupropion and modafinil also can b e used for their stimulant-like effects; they usually have some effect within a few days to a week, certainly earlier than the selective serotonin reuptake inhibitors (SSRis) . 2. Selective serotonin reuptake inhibitors. a. SSRis exert their therapeutic effect within 4 weeks. b. SSRis can cause agitation, irritability, insomnia, tremulousness, diaphoresis, anorexia, nausea, vomiting, diarrhea, and sexual dysfunc­ tion. c. SSRis, when given in combination with other serotonergic drugs (rarely when used alone) , can cause serotonin syndrome, an uncom­ mon but potentially fatal condition of serotonergic hyperstimulation characterized by confusion, agitation, incoordination, tremor, myoc­ lonus, diaphoresis, shivering, diarrhea, hyperthermia, and hyper­ reflexia. Treatment of serotonin syndrome is largely supportive and includes discontinuation of the offending agents. d. SSRis have fewer cardiovascular effects than tricyclic antidepressants (TCAs) and do not commonly cause orthostatic hypotension. e. SSRis are extensively metabolized by the hepatic cytochrome P (CYP)-450 system. f. All SSRis, except citalopram and escitalopram, inhibit the CYP-450 pathway and raise serum levels of coadministered drugs (Table 1 44-5). c.

3. Serotonin-norepinephrine reuptake inhibitors (SNRis) . a. Venlafaxine. i. Venlafaxine exerts its therapeutic effect within 4 weeks, a time­ frame similar to that of SSRis.

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S ECT I O N 1 6 • P S Y C H I A T R I C I S S U E S I N I N T E N S I V E C A R E

ii. Venlafaxine can cause a dose-dependent increase in supine dia­ stolic blood pressure. iii. Venlafaxine does not inhibit the CYP-450 system. b. Duloxetine. i. Duloxetine exerts its therapeutic effect within 4 weeks, similar to the time course of SSRls. ii. Duloxetine is also U.S. Food and Drug Administration (FDA) approved for the treatment of diabetic neuropathy. 4. C:X2 -Adrenergic receptor antagonist. a. Mirtazapine. i. Mirtazapine enhances presynaptic release of norepinephrine and serotonin. ii. Mirtazapine improves sleep and appetite within a few days, while a full antidepressant effect usually develops within 4 weeks. iii. Mirtazapine is available in an orally disintegrating formulation that is useful in patients who cannot swallow pills. 5. TCAs. a. TCAs exert their therapeutic effect within 4 weeks. b. TCAs can cause sedation, confusion, blurred vision, dry mouth, constipation, orthostatic hypotension, and disturbances of cardiac conduction and rhythm. c. TCAs should be used with great caution in patients. i. With preexisting conduction delays. ii. With a corrected QT interval (QTc) of >440 ms. iii. Who are taking other drugs that also have type I antiarrhythmic effects. 6. Monoamine oxidase inhibitors (MAO Is) . a. MAOis exert their therapeutic effect within 4 weeks. b. Phenelzine and tranylcypromine are not recommended in the ICU because of the profound hypertensive crises that might result when these agents are combined with pressors. C. Psychological. Patients often benefit from information, clarification, reas­ surance, and support. Asking about a patient's family, work, hobbies, and interests helps to restore his or her sense of identity. D. ECT. ECT is reserved for patients with severe or delusional depression and for those who cannot tolerate, or have failed to respond to, pharmacologic and psychological therapies. SUGGESTED READI NGS

Cassano P, Cassem NH, Papakostas GI, et al. Mood-disordered patients. In: Stern TA, Fricchione GL, Cassem NH, et al., eds. Massachusetts general hospital handbook of general hospital psychiatry, 6th ed. Philadelphia: Saunders Elsevier, 20 1 0 :73-92. A comprehensive review of the characteristics ofdepressive disorders, their differential diagnosis, and their treatment in the context of comorbid medical illness. Fava M, Papakostas GI. Antidepressants. In: Stern TA, Rosenbaum JP, Fava M, et al., eds. Massachusetts general hospital comprehensive clinical psychiatry. Philadelphia: Mosby Elsevier, 2008 :595-6 1 9. A comprehensive review of the entire antidepressant armamentarium.

A p pe n d i x Ca l c u l at i o ns C o m m o n l y U s e d i n C riti ca l C a re J os e p h J . F rass i ca A . FA H R E N H E I T A N D C E L S I U S T E M P E R AT U R E CONVERSIONS

OF

oc

OF

1 13.0 1 1 1 .2 109.4 107.6 105. 8 1 04 . 0 102.2 100.4 98.6 98.2 96.8 95

34 33 32 31 30 29 28 27 26 25 24

93.2 9 1 .4 89 .6 87.8 86 84 . 2 82.4 80.6 78.8 77 75.2

oc

45 44 43 42 41 40 39 38 37 36.8 36 35 0c to ° F : ° F

° F to °C: °C

= =

(°C (°F

x -

9/5) + 32 32) x 5/9

B . ACT I O N S O F COM MO N

I N T R AV E N O U S VA S O A C T I V E

DRUGS

Dopa m i n e Dobuta m i n e N o re p i n e p h r i n e Epinephrine lsoprote re nol P h e nyl e p h r i n e Vasopress i n

1 0 µg/kg/m i n .

1 1 47

1 1 48

I

APPENDIX

C . H E M O D Y N A M I C C A L C U L AT I O N S

MEAN ARTERIAL BLOOD PRESSURE (mm Hg) = MAP = [systolic BP + (2 X diastolic BP) ] /3 = diastolic BP + 1 /3 (systolic BP - diastolic BP) Normal range: 8 5 to 95 mm Hg FICK EQUATION FOR CARDIAC INDEX (L/min/m2) = Cl = CO/BSA = oxygen. consumption/ (arterial 0 2 content - venous 0 2 content) = [ 1 0 x V0 2 (mL/min/m 2) ] / [Hgb (g/dL) x 1 .39 x (arterial % saturation - venous % saturation)] . Normal range: 2 . 5 to 4.2 L/min/m2 SYSTEMIC VASCULAR RESISTANCE (dyne/sec/cm5) = SVR = [80 x (MAP - right atrial mean BP)] /CO (LI min) Normal range: 770 to 1 ,500 dyne/sec/cm5 PULMONARY VASCULAR RESISTANCE (dyne/sec/cm5) = PVR = [80 x (pulmonary artery mean BP - pulmonary capillary wedge pressure)] /CO (LI min) Normal range: 20 to 1 2 0 dyne/sec/cm5 D . P U L M O N A R Y C A L C U L AT I O N S

ALVEOLAR GAS EQUATION (mm Hg) PAo 2 = Pl0 2 - (Paco/R) = [FI02 x (P,rm - P H2 0)] - (Paco/R) = 1 5 0 - (Paco/R) (on room air, at sea level) Normal value: 1 00 mm Hg (on room air, at sea level) �

ALVEOLAR-ARTERIAL OXYGEN TENSION GRADIENT (mm Hg) = A - a gradient = PAo2 - Pao 2 Normal values (upright) : 2 . 5 + (0.2 1 x age) ARTERIAL BLOOD OXYGEN CONTENT (mL/dL) = Cao 2 = oxygen dissolved in blood + oxygen carried by hemoglobin = [0.003 1 (mL o/dL) x Pao2 ] + [ 1 .39 x Hgb (g/dL) X % Hgb saturated with 0 2] Normal range: 1 7. 5 to 23.5 mL/dL COMPLIANCE (mL/cm Hp) = �Volume/�Pressure On Mechanical Ventilation: Static respiratory system compliance = C,, = Tidal volume/ (P plm•u - P,nd "'P) Dynamic effective compliance = Cdyn = Tidal volume/ (P P''"' - P,n& "'P )

Ca l c u l at i o n s Com m o n l y Used i n C r i t i c a l Care

I

1 1 49

E . E L E C T R O LY T E A N D R E N A L C A L C U L A T I O N S

ANION GAP (mEq/L) = [Na+] - ( [CJ-] + [HCo -] ) 3 Normal range: 9 to 1 3 mEq/L EXPECTED ANION GAP IN HYPOALBUMINEMIA = 3 x [albumin (g/dL)J CALCULATED SERUM OSMOLALITY (mOsm/kg) = (2 x [Na+] ) + ( [glucose] / 1 8) + ( [BUN) /2.8) Normal range: 275 to 290 mOsm/kg OSMOLAR GAP (mOsm/kg) = Measured serum osmolaliry - Calculated serum osmolaliry Normal range: 0 to 5 mOsm/kg Na+ CORRECTION FOR HYPERGLYCEMIA Increase [Na+] by 1 .6 mEq/L for each 1 00 mg/dL increase in [glucose) above 1 00 mg/dL Ca2+ CORRECTION FOR HYPOALBUMINEMIA Increase [Ca2+] by 0 . 8 mg/dL for each 1 .0 g/dL decrease in [albumin) from 4 g/dL WATER DEFICIT IN HYPERNATREMIA (L) = [0.6 X body weight (kg)] x {( [Na+J / 1 40) - 1 } Na+ DEFICIT I N HYPONATREMIA (mEq) = [0.6 x body weight (kg)) x (desired plasma [Na+] - 1 40) FRACTIONAL EXCRETION OF SODIUM (%) = FENa = {(excreted [Na+] )/(filtered [Na+] )} X 1 00 = {(urine [Na+J )/(serum [Na+] )}/{(urine [Crear] )/(serum [Crear] )} x 1 00 CREATININE CLEARANCE (mL/min) = (urine [Crear] ) X (urine volume over 24 h) = {(urine [Crear (g/dL)] ) X { [urine volume (mL/d) ) / 1 ,440 (min/day) ] }/serum [Crear) (mg/dL) Estimated for males = { ( 1 40 - age) x [lean body weight (kg))}/{serum [Crear) (mg/dL) x 72} Estimated for females = 0 . 8 5 x (estimate for males) Normal range: 74 to 1 60 mL/min F. A C I D - B A S E F O R M U L A S

HENDERSON EQUATION FOR [W) [W] (nm/L) = 24 x {Paco/ [HC0 -) } 3 Normal values: [H+J is 40 nm/L at pH of 7.40 and each 0.0 1 unit change in pH corresponds to an approximate opposite deviation of [H+J of 1 nm/L (over the pH range of ?. 1 0 to 7.50) METABOLIC ACIDOSIS Bicarbonate deficit (mEq/L) = (0.4 + [2.6/HC0 -] ) 3 x lean body weight (kg) X (24 - [HC0 -] ) 3

1 1 50

I

APPENDIX

Expected Paco 2 compensation = ( 1 . 5

x

[HC 03 ] ) + 8 -

±

2

RESPIRATORY ACIDOSIS Acute = L1[H+] /�Paco2 = 0.8 Chronic = L1[H+] /�Paco2 = 0.3 RESPIRATORY ALKALOSIS Acute = L1[H+] !�Paco2 = 0 . 8 Chronic = L1[H+] /�Paco2 = 0 . 1 7 G . N E U R O L O G I C C A L C U L AT I O N S

GLASGOW COMA SCALE = eye score ( 1 -4) + motor score ( 1 -6) + verbal score ( 1 -5) S p ec i f i c C o m p o n e n ts of t h e G l a sgow C o m a S c a l e : Component

Eye o pe n i n g S ponta n eous To speech To pa inful sti m u l i Eye o pe n i n g n ot o bserved M otor res ponse O beys co m ma n d s Loca l izes With d rawa l res ponse Abnormal flexion res ponse Abnorma l extension res ponse N o moto r res ponse Verba l response Orie nted Confused/conversa nt U ses i n a p p ro p riate words I ncom prehensi ble N o ve rba l res ponse N o r m a l tota l va l u e : 15 ( ra nge 3-1 5)

H . P H A R M A C O L O G I C C A L C U L AT I O N S

DRUG ELIMINATION CONSTANT = Ke = fractional elimination of drug per unit time = {In ( [peak] / [trough] )/(tpeak - tnough) } DRUG HALF-LIFE = t l/2 = 0.693/Ke

Score

4 3 2 1 6 5 4 3 2 1 5 4 3 2 1

1 1 51

Ca l c u l at i o n s Com m o n l y Used i n C r i t i c a l Care 200

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1 1 52

I

APPENDIX

VOLUME OF DISTRIBUTION (Llkg) = Vd = [(dose) x (fraction of active drug in circulation)] / [ (area under single dose curve) x Ke] DRUG CLEARANCE = Vd x Ke DRUG LOADING DOSE = Vd x [target peak] DRUG DOSING INTERVAL = {-Ke-1 X In ( [desired trough] / [desired peak] )} + infusion time (h) I . N U T R I T I O N A L C A L C U L AT I O N S

BODY MASS INDEX = BMI = weight (kg)/ [height (cm)] 2 RESPIRATORY QUOTIENT =R = co 2 production (mL/min) /0 2 consumption (mL/min) Normal value: 0 . 8 HARRIS-BENEDICT EQUATION OF RESTING ENERGY EXPENDITURE (kcal/day) Males = 66 + [ 1 3.7 x weight (kg)] + [5 x height (cm)] - (6.8 x age) Females = 6 5 5 + [9.6 x weight (kg)] + [ 1 .8 x height (cm)] - (4.7 x age) J . B O D Y S U R FA C E A R E A F O R M U L A A N D N O M O G R A M ( A D U LT )

BODY SURFACE AREA = BSA = (height [cm] )0 7 1 8 X (weight [kg] )0427 X 74.49 To use the adult nomogram (Fig. A- 1 ) , place a straightedge connecting the persons' weight in the right column with their height in the left column. The point where the straightedge crosses the center column denotes that persons' body surface area in square meters.

I n d ex Note: Page numbers followed by f indicate a figure; t following a page number indicates tabular material A

Abciximab, 230, 669t Abdominal aortic aneurysm (AAA) , 205-206 Abdominal compartmental syndromes (ACS), 86 1 , 908 Abdominal fat pad biopsy, 1 77 Abdominal trauma computed romography, 934 diagnosis, 933-935, 936f diaphragm injury, 938-939, 939f etiology, 933 facror responsible, 933 focused assessment with sonography for trauma (FAST), 934-935 kidney injury, 938 laparoscopy, 935 liver and porta hepatis, 935-936 nonoperative management (NOM), 935 patient history and physical examination, 933, 934f radiographs, 934 small intestine injury, 934f, 939-940 spleen injury, 936-938, 937f treatment, 935 Absolute neutrophil count (ANC) , 479, 485 Acalculous cholecystitis, 575 complications, 578 treatment, 577-578 Accelerated hypertension, 208 Accelerated idioventricular rhythm (AIVR) , 258-25 9 Accidental hypothermia, 37 Acclimatization, 3 9 1 Acetaminophen (APAP), 5 5 6, 559, 56 1 , 562, 750t-754t, 833f Acetazolamide, 4 1 6 Acid-base formulas, 1 1 49-1 1 50 Acid-fast staining bacillus (AFB), 497, 504-506 Acidosis, 542, 622 with an expanded AG, 4 1 1 with a normal AG, 4 1 2 Acinetobacter species, 456t, 943 Acquired disorders, 638 Acquired hemostasis disorders acquired hemophilia, 643-644 coagulopathy of liver disease, 64 1 disseminated intravascular coagulation (DIC) , 64 1-643

trauma-induced coagulopathy, 643 vitamin K deficiency, 640 Acquired weakness, in ICU diagnosis of critical illness myopathy, 1 024- 1 025 diagnosis of critical illness polyneuropathy, 1 026- 1 027 differential diagnosis of, 1 027-1 028 general principles, 1 024 Actinomycosis, 866 Activated partial thromboplastin time (aPTT) , 639t Acute aortic syndromes aortic dissection (AD) , 1 99-203 intramural hematoma (IMH), 204 penetrating atherosclerotic ulcer (PAU), 204-205 ruprured abdominal aortic aneurysm (AAA) , 205-206 Acute colonic pseudoobstruction, 543 Acute confusional state, 982 Acute coronary syndrome (ACS), 666t-669t, 672t Acute disseminated encephalomyelitis (ADEM), 1 044 clinical presentation, 1 049 definition, 1 048 epidemiology, 1 049 etiology, I 049 laboratory studies, I 049- 1 0 5 0 pathogenesis, 1 049 prognosis, 1 0 5 0 treatment, 1 050 Acute hemolytic transfusion reaction (AHTR), 727, 729 Acute infectious pneumonia, 443 Acute inhalation injury, 53 Acute intermittent porphyric neuropathy, 1 027 Acute kidney injury (AKI), in ICU blood tests, 431 classification, 427 complete blood count (CBC) , 43 1 complications, 43 1 , 432t definitions, 427 diagnosis, 430-43 1 epidemiology, 427 etiology, 427 intrinsic, 428, 430 1 1 53

1 1 54

I n dex

Acute kidney injury (AKI), in ICU (Continued) nonoliguric, 432 pathogenesis, 427, 433t postrenal, 430 prognosis and outcome, 432 radiologic studies, 43 1 renal biopsy, 43 1 serologic tests, 43 1 serum chemistry studies, 43 1 ST-segment elevation myocardial infarction, 244 treatment, 43 1 , 433t urinalysis, 430-43 1 Acute leukemia, 479, 48 1 Acute liver failure (ALF) causes, 560t complications, 5 6 1 definition, 5 6 1 etiology, 5 5 9-56 1 renal failure, 5 6 1 treatment, 56 1-563 Acute lymphoblastic leukemia, 733 Acute mediastinitis clinical presentation, 842 complications, 842 diagnosis, 842 etiology, 841-842 treatment, 842 Acute myelogenous leukemia, 733 Acute pancreatitis clinical presentation, 8 5 1 complications, 854-8 5 5 definitions, 850 diagnosis, 852 etiology, 850-8 5 1 prognosis, 852-853 Ranson's prognostic signs, 852-8 53 treatment, 853 Acute pericarditis, 1 9 1 - 1 92 Acute progressive disseminated hisroplasmosis, 5 0 1 Acute promyelocytic leukemia, 733-734 Acute pulmonary embolism, 345 Acute respiratory distress syndrome (ARDS), 26, 340, 345, 382, 495, 497, 505, 508, 5 1 0, 5 1 1 complications, 306 corticosteroids, 305-306 diagnosis, 304 etiology, 303-304 fluid management, 305 general principles, 303 mechanical ventilation, 305

pathophysiology, 304 patient positioning, 305 pharmacologic therapies, 306 treatment, 305-306 Acute tubular necrosis (ATN), 428 Acute venous thrombosis, 700 Acyclovir, 455t, 1 048, l 1 44t Addison's disease, 6 1 7, 623 Adenocorticotrophic hormone (ACTH), 6 1 7 Adenosine, 272t Adjunctive antithrombotic therapy, 242-243 Adrenal function tests, 6 1 9 Adrenal hemorrhage, 6 1 9 Adrenal steroids, 620 Adrenal suppression, 1 1 4 Adrenergic agents, 1 1 2 1 a-Adrenergic agonists, 393 P-Adrenergic agonists, 325 P-Adrenergic blocker (BB), 603 P-Adrenergic receptor blockers, 223 a 1 -adrenergic receptors, 1 57 P 1 -adrenergic receptors, 1 57 Adult enteric infectious botulism, 476 Advanced trauma life support (ATLS) , 9 1 1 Aerodynamic filtration, 338 Aerosol therapy medications and indications, 371-372 principles, 371 procedure, 372 Aerosolized antimicrobials, 37 1 Aerosolized N-acetylcysteine (Mucomyst), 3 7 1 Aerosols, 408 Agitation complications, 1 1 35-1 1 36 definition, 1 1 32 differential diagnosis, 1 1 34-1 1 3 5 , l 1 34t epidemiology, 1 1 33 etiology and pathogenesis, 1 1 33, l 1 33t risk factors, 1 1 33 treatment, 1 1 3 5 P-agonists, 175 Airway clearance, 373 Airway management airway obstruction, 4 anatomy, 1 -2 complications of endotracheal intubation, 7 equipment, 2, 3f-5f, 4 evaluation of airway, 2, 3f extubation, 7 flexible endoscopy and alternative techniques, 6-7 general principles, 1 of intensive care patients, 1 nasotracheal intubation, 6

I n dex

orotracheal intubation, 5-6 treatment, 5 Airway obstructing lesions, 54, 64 Airway pressure release ventilation (APRV) , 360 Akinetic mutism, 983 Albumin, 906 Alburerol, 309, 3 1 0 Alcohol ethylene glycol (EG) , 755t-756t isopropanol, 756t methanol (MeOH), 756t-757t Alcoholic ketoacidosis, 590, 632 clinical presentation, 598 diagnosis, 598 laboratory studies, 598 pathophysiology, 598 treatment, 598 Aldosterone antagonists, 171, 243 Alfentanil, 1 1 6 Alkalemia, 4 1 5 Alkalosis, 542, 622 Allen test, modified, 20 Allograft failure, I 095 Alteplase (Activase and Cathflo Activase), 683t Altered consciousness classification of causes of, Gt diagnosis, 979 pathophysiology, 979 patients awake but is confused/ noncommunicative, 982-984, 984t patients who appear to be unconscious, 979-982, 980t prognosis, 979 treatment, 979 Alveolar gas equation, 1 1 48 Alveolar-arterial oxygen gradient, 298, 1 1 00 Alveolar-arteriole oxygen tension gradient, 1 1 48 Amanita phalloides mushroom toxin, 632 Amantadine, 395 American Spinal Injury Association (ASIA) Grading Scale, 924, 925t Amikacin, 453t E-Aminocaproic acid, 650 Aminoglycoside, 473, 484 Aminosalicylates, 5 5 1 Amiodarone, 265, 273t, 274, 276 Amniotic fluid embolism, 327, 328t, 887 Amoxicillin, 5 1 9 Amphetamine, 820t Amphotericin B, 455t, 473, 485 Ampicillin, 454t Ampicillin-sulbactam, 453t

I

1 1 55

A'9"' technetium (99"' Tc)-labeled red blood cell scan, 524 Amyotrophic lateral sclerosis (ALS), 3 1 9, I 028 Analgesia, preemptive, 878 Analgesics, 885 Anaphylaxis, 64 angiotensin-converting enzyme inhibitor, 1 1 24 causes of non-IgE-mediated anaphylactiod reactions 1 1 20t clinical features, 1 1 1 9 diagnosis, 1 1 2 1 food, 1 1 23 general principles, 1 1 1 9 hereditary angioedema, 1 1 24- 1 1 2 5 I C U setting, 1 1 23 latex-induced, 1 1 24 management of anaphylaxis to specific precipitants, 1 1 23-1 1 2 5 pathophysiology, 1 1 1 9, 1 1 20t prevention of anaphylactic reactions, 1 1 22 radiographic contrast media, 1 1 23-1 1 24 stinging insect venom anaphylaxis, 1 1 23 treatment in adults, 4t cardiopulmonary supportive measures, 1 121 pharmacological, 1 1 2 1 , 1 1 22t Anaplasma phagocytophilum, 5 1 8 Anaplasmosis diagnosis, 5 1 8-5 1 9 general principles, 5 1 8 pathogenesis, 5 1 8 treatment, 5 1 9 Anesthesia, fo r bedside procedures indications, 1 1 2-1 1 3 pain management, 1 1 2 pharmacokinetic (PK) considerations, 1 1 2 procedure, 1 1 3-1 1 7 Angina-like chest pain, 1 74 Angiodysplasia, 522 Angiographic embolization, 839 Angiography, 524, 525, 952 Angiotensin-converting enzyme (ACE) inhibitors, 1 7 1 , 1 78, 229, 233, 243, 885, 1 1 24 Angiotensin-receptor blocker (ARB), 229 Anidulafungin, 455t Anion gap (AG) acidosis, 4 1 4, 5 9 1 , 1 1 49 Ankylosing spondylitis, I 07, 320 Anorectal disease, 522 Anoxia, 34 1 Antacids, 529, 542, 854

1 1 56

I n dex

Antecubital vein, 9 Anthracycline cardiomyopathy, 1 7 1 t Anthrax {Bacillus anthracis), 382-383 Antiarrhythmic agents, 278 Antiarrhythmic drugs (AAD) , 261 Antiarrhythmics versus Implantable Defibrillators (AVID), 293 Antibiotic-associated colitis, 443 Antibiotics, 328t, 408-409, 542, 5 5 1 , 885, 1 037 Antibody-dependent cell-mediated cytotoxicity (ADCC) , 480 Anticholinergic medications, 54 1 , 757t-76 l t Anticoagulation, 36, 46, 275, 276, 438 Antidepressants, 76 l t-763t, 1 1 45t Antidiabetic agents, 629 Antidiarrheal agents, 545 Antifungal therapy, 485 Antihistamines, 1 1 2 1 Antimalarial, 763t-765t Antimicrobial therapy differential diagnosis, 45 1 dose/duration of, 45 1-452 in the ICU setting, 452t-458t Antimotility agents, 573 Antineutrophilic cytoplasmic antibodies (ANCA) , 1 1 27-1 1 29 Anti-N-methyl-D-aspartate (NMDA), 1 044, 1 045t Antiphospholipid antibody syndrome, 1 1 1 5 Antiphospholipid syndrome catastrophic antiphospholipid syndrome (CAPS) diagnosis, 703, 706t general principles, 703, 704t pathophysiology, 703, 705t prognosis, 706-707 treatment, 703-706 Antiplatelets, 242 Antipsychotics, 708-709 Antiretroviral therapy (ART) , 502, 507-508 Antithrombotic therapy, 248 Anti-tumor necrosis facror (Anti-TNF) therapy diagnosis, 490-4 9 1 etiology, 490 general principles, 489-490 pathophysiology, 490 treatment, 49 1 Aortic dissection (AD) , 126 diagnosis, 1 9 9-200, 2 0 1 t epidemiology, 1 9 9 pathophysiology, 1 99, 200t prognosis, 1 9 9

Stanford classification system, 1 99 treatment, 202-203, 202f, 203t Aortic regurgitation (AR) clinical presentation, 1 82 etiology, 1 8 1 investigations, 1 82 management, 1 82-1 83 pathophysiology, 1 8 1 - 1 82 Aortic stenosis (AS) clinical natural history, 1 80 clinical presentation, 1 80 etiology, 1 80 investigations, 1 80- 1 8 1 management, 1 8 1 pathophysiology, 1 80 progression, 1 80 Aortoenteric fistula, 522, 524 Apnea test, 9 8 1 Argatroban, 678t Arrhythmias, 33, 255, 256t, 257t management of specific, 36 mechanism of action, 34 Arsenic (As) , 786t-787t, 787t Arterial aneurysmal dilation, 1 37 Arterial blood gases (ABGs) contraindications, 1 33 diagnostic indications, 1 32-1 33 equipment, 1 32 postprocedure considerations, 1 3 5 procedure, 1 33- 1 3 5 technical considerations, 1 32 Arterial blood oxygen content, 1 1 48 Arterial cannulation, 1 37 Arterial catheterization arterial anaromy, 1 7 cannulation sites, 1 7 indications, 1 8 postprocedure considerations, 22-24 procedure, 1 9-22 site selection, 1 7 Arterial hypercapnia, 320 Arterial pressure monitoring, in ICU, 1 1 8-1 1 9 Arteriovenous fistula (AVF) , 438 Arteriovenous graft (AVG) , 438 Arthritis, 1 07 Arthrocentesis, 1 06, 1 0 8 Ascites, 1 9 5 Aspergillus species, 456t, 483, 4 8 5 , 492, 1 070 Aspiration of air, 328t definition, 338 diagnosis, 339, 339t of joints complications, 1 1 1

I n dex

contraindications, 1 07- 1 0 8 indications, 1 06-1 0 8 principles, 1 06-1 07 procedure, 1 08-1 1 1 pathogenesis, 338-339 syndromes, 338, 339t treatment, 340 Aspirin, 233, 664, 665t, 670t, 70 1 , 707, 708 Asplenia, 486, 488 Asplenic patients diagnosis, 488-489 etiology, 487 general principles, 486-487 pathophysiology, 487-488 treatment, 489 Assist control (AC), 3 5 8-35 9 Asthma exacerbations, 6 4 , 327, 328t definitions, 307 differential diagnosis, 308 etiology, 307 history and physical examination, 308, 308t oxygenation assessment, 309 pathophysiology, 307 pulmonary function tests (PFTs), 308 treatment, 309-3 1 0 Asymptomatic ventricular arrhythmias, 1 73 Atelectasis, 53, 54 Atovaquone, 5 1 8 Atrial fibrillation (Afib), 33, 1 75-176, 27 1 , 273-276, 274f, 275f Atrial flutter, 276, 292 Atrioventricular nodal reentrant tachycardia (AVNRT), 276-277 Atrioventricular reentrant tachycardia (AVRT), 277 Atropine, 383 Automated oscillometric monitor, 1 1 9 Avascular necrosis, 1 07 Avian influenza virus A (H5N l ) diagnosis, 5 1 0-5 1 1 general principles, 5 1 0 pathogenesis, 5 1 0 treatment, 5 1 1 Axillary artery, 1 7, 22 Azithromycin, 327, 454t, 5 1 8 Azotemia, 442 Aztreonam, 453t, 484, 493 B

Babesia microti, 5 1 7 Babesiosis, 487 diagnosis, 5 1 8 general principles, 5 1 7-5 1 8

I

1 1 57

pathogenesis, 5 1 8 treatment, 5 1 8 Bacillus Calmette-Guerin (BCG) Baclofen, l l 44t Bacteremia, 1 04, 480, 48 1 , 484, 485, 487, 493 Bacterial cellulitis, 4 01 Bacterial colonization, 578 Bacterial infection, 735 Bacterial meningitis complications, 462 diagnosis, 460 etiology, 459 pathogenesis, 459-460 treatment, 461 Bacterial pneumonia, 340, 495 Bacterial tracheitis, 400 Bacteroides, 40 1 Balloon enteroscopy, 525 Balloon tamponade, 536 Band ligation, 78, 535 Barbiturates, 879, 1 1 44t Barium enema, 549 Bartone/la henselae, 1 044 Bartone/la species, 465, 487, 866 �-blockers (BB), 203, 233, 243, 277, 537-538, l 1 44t Benzodiazepines, 879, l 1 44t Bernard-Soulier, 650 Beta-adrenergic blocker (BB), 765t-767t Bicarbonate (HC0-3), 1 32 for hemorrhagic shock, 906 supplementation, 4 1 4 therapy, i n OKA, 593-594 Bile leak, 575 complications, 578 treatment, 578 Biliary obstruction, 575 Biliary sludging, 5 5 5-5 56 Biliary tract diseases, in ICU causes, 576t complications, 578 computed tomography (CT) and magnetic resonance imaging (MRI), 577 diagnosis, 576-577 etiology, 575-576 general principles, 575 physical examination, 576 radiographic studies, 577 radionuclide scanning, 577 treatment, 577-578 ultrasonography, 577

1 1 58

I n dex

Bioprosthesis, 1 87 Biphasic waveforms, 34-35 Bisphosphonates, 623 Bi-V pacing, 290 Bivalirudin, 23 1 , 678t Bladder carcinoma, 1 03 Bladder spasms, 1 04 Blastomycosis, 1 070 Bleeding disorders clinical presentation, 637-638 etiology, 637 laboratory studies, 638-640 pathway of coagulation, 639f personal and family bleeding history, 638 physical examination, 638 site of bleeding, 637 Blood-borne viral infection, 649 Blunt aortic injury, 953 Blunt cardiac injury, 953 Blunt chest trauma, 54 Blunt trauma, during pregnancy, 888 Body mass index, 1 1 52 Body packer, 767t-768t Body surface area formula and nomogram (ADULT), 1 1 5 l f, 1 1 52 Bordetella holmesii, 487 Borrelia a.foe/ii, 5 1 9 Borrelia burgdorferi, 5 1 9, 1 044, 1 049 Botulinum, 383 Botulism, 1 027- 1 028 diagnosis, 476 general principles, 476 pathogenesis, 476 treatment, 476-477 Bowel perforation, 1 04 Brachia! artery, 1 7 cannulation, 22 punctures, 1 34 Bradyarrhythmia, 34 Bradycardia, 264, 265, 28 1 , 282f, 1 0 3 1 , 1 035, 1 036, 1 094 Brain abscess, 397 Brain death, tests for, 98 1 Brain oxygenation monitoring, 1 00-1 0 I Brain tissue oxygen tension, 1 00 Brainstem auditory evoked potentials (BAEPs), 1 0 1 Bromocriptine, 395, 1 1 44t Bronchial arterial circuit, 33 1 Bronchoalveolar lavage (BAL) , 482, 483, 49 1 Bronchodilator therapy, 309, 372 Bronchopleural fistula, 54

Bronchoscopy, 407 complications, 54-5 5 contraindications, 5 5 diagnostic indications, 53-54 procedural considerations, 5 5-56 therapeutic indications, 54 Bronchus, 2 Bruce/la species, 465, 1 044 Bulge test, 1 06 Bullous lung disease, 46 Bumetanide, 2 1 2 Bupivacaine, 784t-785t Bupropion, 1 1 45 Burkholderia cepacia, 456t Burn wound sepsis, 949 Burns airway management, 944 burn shock, 944-945, 946t classification, 942 complications, 949 definition, 942 diagnosis, 944 epidemiology, 942-943 metabolism, 945-946 nutrition, 946 pathophysiology, 943 physical examination, 944, 945f resuscitation techniques, 945 treatment, 944-949 Butyrophenones, 879 Bypassing agents, 644t c

CADRE, mnemonic, 976 Calcitonin, 623 Calcium acetate, 626 Calcium channel antagonist (CCA), 175, 2 1 2, 27 1 , 603, 768t-769t Calcium disorders acid-base balance and, 622 hypercalcemia, 622-623 hypocalcemia, 623-624 pathophysiology, 622 Calcium gluconate, 624 Calcium pyrophosphate dihydrate (CPPD) crystals, 1 1 0 pseudogout, 1 07 Calibration, 20 Cameron lesions, 522 CAMP degradation, suppression of, 671 Campylobacter jejuni, 492 Canadian Implantable Defibrillator Study (CIDS), 293

I n dex

Cancer chemotherapy, 4 8 1 Candida species, 456t, 4 6 8 , 469, 47 1 , 473, 483, 485 Cannulation sites, for arterial cannulation, 1 7 Capnocytophaga canimorsus, 480, 487 Capnography, 377 Capsule endoscopy, 523 Captopril, 2 1 2 Carbamazepine, 1 033 Carbapenems, 846 Carbidopa, 395 Carbon monoxide (CO) poisoning, 1 039-1 040 Carboxyhemoglobin (COHgb), 376, 378 Cardiac amyloidosis, 178 Cardiac Arrest Study Hamburg (CASH), 293 Cardiac biomarkers, 238 Cardiac catheterization, 1 8 1 , 1 82, 1 84 Cardiac cirrhosis, 5 5 5 Cardiac enlargement, 1 69 Cardiac output monitoring, in ICU, 1 2 1-123 Cardiac pacing, temporary background, 28 1 , 282f complications, 287-288, 287t contraindications, 284-285 efficacy, 287 indications, 2 8 1 -285, 283t, 284t moniroring, 288 pacing options, 2 8 1 placement o f, 6 t procedure, 285-287, 286t troubleshooting, 287t Cardiac puncture, 43 Cardiac resynchronization therapy (CRT), 290 Cardiac tamponade, 39-40, 1 90, 9 5 1 Cardiac valves, evaluation o f, 126 Cardioactive steroid, 769t-770t Cardiogenic failure, 393 Cardiogenic shock management adrenergic receptor physiology, 1 57 cardinal manifestations, 1 5 6 mechanical circularory support extracorporeal membrane oxygenation, 1 66-1 67 intra-aortic balloon counterpulsation, 1 64-1 6 5 percutaneous ventricular assist device, 1 65-1 66 vasopressors and positive inotropes dobutamine (dobutrex) , 1 59-1 60 dopamine (intropin) , 1 5 8-1 59

I

1 1 59

ephedrine, 1 60 epinephrine, 1 57-1 5 8 norepinephrine (levophed), 1 58 phenylephrine (neo-synephrine), 1 60 vasopressin (pitressin), 1 60- 1 6 1 Cardiomyopathies, 1 69-1 78 classification, 1 69, 1 70t ischemic, 1 70 Cardiorespiratory complications, 5 6 1 Cardiovascular disease, 25 Cardioversion complications, 37 definition, 33 indications, 34 postprocedure considerations, 37 in pregnancy, 37 procedure, 34-36 Carotid sinus massage, 223 Carotid upstroke, 1 74 Cartilages, 2 Cartilaginous damage, 1 1 1 Caspofungin, 455t, 485 Catastrophic antiphospholipid syndrome (CAPS) diagnosis, 703, 706t general principles, 703, 704t pathophysiology, 703, 705t prognosis, 706-707 treatment, 703-706 Catecholamines, 175, 1 039 Catheter ablation, 275, 277 Catheter dislodgement, 1 04 Catheter over trocar, 1 04 Catheter-associated bloodstream infections (CA-BSI) diagnosis, 468 etiology, 468 general principles, 467 pathogenesis, 468 treatment, 468-469 Catheter-associated UTI (CAUTI), 443 Catheter-related bloodstream infections (CRBSis) , 442-443 Cavernous sinus thrombosis, 397 CBF monitoring, 99 CD0 2 components, 98 Cefazolin, 454t Cefepime, 484 Ceftaroline, 453t Ceftazidime, 439, 452t, 484, 493 Ceftriaxone, 453t, 5 1 9 Cefuroxim, 5 1 9 Cellulitis, 1 04, 866-867

1 1 60

I n dex

Centers for Disease Control and Prevention (CDC) , 5 1 1 Central nervous system (CNS) infections, 444, 489, 1 034, 1 035 acute disseminated encephalomyelitis, 1 048- 1 0 5 0 classification, 1 044, 1 045t, 1 046 complications, 462 diagnosis, 460-46 1 encephalitis, 1 046- 1 048 etiology, 459 general principles, 459 pathogenesis, 459-460 treatment, 46 1-462 Central venous catheter (CVC), 480-482, 484, 485, 690, 69 1 , 695 Central venous catheterization catheter types, 9 indications, 1 0 methods t o reduce risk o f catheter infection, 9 postprocedure considerations, 1 4- 1 5 procedure EJV approach, 1 2 femoral vein approach, 1 2- 1 3 IJV cannulation, 1 0- 1 2 SCV approach, 1 3-14, 14f, 1 5f site selection, 9 use of ultrasonographic guidance, 9-1 0 Cephalosporins, 327, 846, 8 8 5 Cerebellopontine angle tumors, 1 032 Cerebral computed tomography (CT) , 99 Cerebral edema, 5 6 1 , 597, 1 034, 1 035 Cerebral embolization, 23 Cerebral fat embolism syndrome, 1 04 1 Cerebral infarction, 1 034, 1 035 Cerebral ischemia, 98, 1 0 3 1 Cerebrospinal fluid ( CSF) , 1 00 analysis, 1 047- 1 048 aspiration for drug therapy, 9 5 fistulas, 9 5 general principles, 93 indications, 93-95 intracranial hypertension, 95 neurological disorders, 94 procedure, 9 5-97 shunt system failure, 94 cell count, 93 central nervous system infections, 460 glucose, 93 protein, 93 Cethrin, 93 1 Chemical asphyxiants, 378

Chemical injury, 947-948 Chemical pneumonitis, 340 Chemotherapy, 707 Chest pain, 1 92, 347 Chest physical therapy (CPT) , 373, 408 Chest radiograph (OCR) , 293 acute mediastinitis, 841-842 bilateral pulmonary infiltrates on, 304 cardiogenic pulmonary edema, 380 edema on, 325 esophageal perforation, 841 febrile neutropenia, 483 fecal radiation exposure, 325 hemoptysis, 332 signs of a PTX, 356 thoracic trauma, 952 tuberculosis, 505, 506 Chest cube insertion and care anatomy and physiology of pleural space, 45 chest cube management and care, 50-5 1 chest tube removal, 5 1 complications, 50 contraindications, 46 general principles, 45 indications empyema, 45 hemothorax, 45 pleural effusion, 45 pneumothorax, 45 postoperative considerations, 50-5 1 preparation, 46 procedure, 46-50 techniques, 46-50 Chest wall and pleural cavity injury, 952-953 Child class A cirrhosis, 537 Chlamydophila pneumoniae, 407 Chloramphenicol, 5 1 7-5 1 9 Chlorhexidine gluconate, 40, 4 1 Chloride-responsive alkalosis, 4 1 5 Chloride-to-bicarbonate ratio, 4 1 4 Cholangitis, 575 complications, 578 treatment, 578 Cholecystostomy, 578 Cholestasis, 5 5 5 Cholestyramine, 546, 573, 603 Cholinergic antagonists, 309 Chronic liver failure, 5 5 9 ascites studies, 5 6 5 blood tests, 5 6 5 causes, 564t diagnosis, 564-565

I n dex

etiology, 564 pathophysiology, 564 physical examination, 564 treatment, 565-567 urine studies, 565 Chronic lymphocytic leukemia (CLL) , 480, 734 Chronic myelogenous leukemia, 734 Chronic obstructive pulmonary disease (COPD), 64 and airflow obstruction, 3 1 2 chest computed tomography (CT) , 3 1 3 chest roentgenogram, 3 1 3 cigarette smoking and, 3 1 2 diagnosis, 3 1 2-3 1 4 etiology, 3 1 2 general principles, 3 1 2 homozygous a l -antitrypsin deficiency, 312 intubation and mechanical ventilation, 3 1 5-3 1 6 noninvasive positive-pressure ventilation (NIPPY) , 3 1 5 pathophysiology, 3 1 2 physical examination, 3 1 3 prevention of exacerbations, 3 1 6-3 1 7 treatment, 3 1 4-3 1 6 Churg-Strauss syndrome (CSS) , 1 1 28-1 1 2 9 Chvostek's sign, 623 Cilostazol (Pletal), 670t, 671 Ciprofloxacin, 452t Cirrhosis, 541 Cisatracurium, 1 1 7 Citrate, 438 Citrate accumulation, 438 Citrobacter species, 47 1 Clarity, of synovial fluid, 1 1 0 Clindamycin, 5 1 6, 5 1 8, 885 Clonidine, l 1 44t Clopidogrel (Plavix), 666t Clopidogrel, UNNSTEMI, 233 Clostridial myonecrosis, 374, 869-870 Clostridium botulinum, 383, 476 Clostridium difficile, 456t, 482, 492, 542, 545, 548, 550 colitis, 572 Clostridium difficile colitis, 443, 447, 1 070 Clostridium novyi, 865 Clostridium perfringens, 382, 482, 865 Clostridium septicum, 482, 865 Clostridium tetani, 477 CO poisoning, 374, 379 Coagulation tests, 643

I

1 1 61

Coagulopathies, 5 5 , 80, 1 03, 5 6 1 , 562, 637, 64 1 , 1 094 Cocaine, 6, 821 t-822t Coccidioides immitis, 492 Coccidioidomycosis, 325, 1 070 COCJ, , 379 Colestipol, 573, 603 Colistin, 453t Colitis, 522 Colonic mucosa! inflammation, 548 Colonoscopy, 523, 549 Color-flow Doppler, 126 Colostomy, 868 Combination antibiotic therapy, 5 1 8 Community-acquired pneumonia (CAP), 404 Compartmental syndromes of abdominal cavity causes of abdominal hypertension, 862t clinical presentation, 862 closure, 864 definitions, 8 6 1 diagnosis, 862-863 measurement of IAP, 863 nonoperative decompression, 863 pathophysiology, 862 treatment, 863-864 complications, 957 diagnosis, 956-957 etiology, 9 5 5 general principles, 9 5 5 pathophysiology, 956 treatment, 957 Competitive inhibition of cyclooxygenase (COX) , 877 Complete blood count (CBC) , 482, 491 Computed tomography (CT) , 72, 93, 200 abdominal trauma, 934 acute pancreatitis, 852 altered consciousness, 982 encephalitis, 1 048 febrile neutropenia, 483 gastrointestinal bleeding, 524 thoracic trauma, 952 toxoplasmic encephalitis, 499 traumatic brain injury (TBI), 920-921 traumatic compartment syndromes, 956 tuberculosis, 506 Concomitant skeletal myopathy, 1 69 Conduction block, predicting risk of, 282 Congenital deficiency, of a coagulation factor, 645 Congenital disorders, 638 Congenital qualitative platelet disorders, 650

1 1 62

I n dex

Congestive heart failure (CHF), 332 Connective tissue diseases, 1 07 Continuous cardiac output PAC, 25 Continuous mixed venous 02 PAC, 25 Continuous positive airway pressure ( CPAP) , 360-3 6 1 Continuous renal replacement therapy (CRRT), 436-439 Continuous subarachnoid analgesia, 879 Continuous venovenous hemodiafiltration (CVVHD), 436, 437 Contraceptives, l l 44t Contrast esophagogram, 84 1 Conventional endoscopy, 523 Cooling blankets, 392 Coronary artery disease, 1 1 3 Coronary revascularization, 1 53-1 54 Corrected calcium, 622 Corticosteroids, 309, 328t, 372, 549, 970, 1 1 44t Corcrosyn test, 620 Corynebacterium jeikeium, 48 5 Cosyntropin (Cortrosyn), 6 1 9 Coumadin, 8 8 5 Countershock, 3 3, 34 Coxiella burnetii, 465 C-reactive protein (CRP) , 447 Creatine kinase (CK), 1 025 Creatinine clearance (CrCl) , 1 1 28, 1 1 49 Cricoid cartilage, 2, 6, 64, 65 Cricoid pressure, 6 Cricothyroid membrane, 64 Cricothyroid muscle, 2 Cricothyroidotomy, 952 Crigler-Najjar syndrome types I and II, 557 Critical illness myopathy (CIM) , 1 024-1 027 Critical illness-related corticosteroid insufficiency, 6 1 9 Crohn's colitis, 548 Croup, 400 Cryoglobulinemic vasculitis, 1 1 29- 1 1 30 Cryoprecipitate, 64 1 Cryptococcosis diagnosis, 498 etiology, 498 general principles, 498 pathogenesis, 498 treatment, 498 Cryptococcus neoformans, 397, 480, 498, 500, 866, 1 070 Cryptosporidium, 492 Crystal analysis, 1 1 0 Crystal arthropathy, 1 1 1 2- 1 1 1 3, l l 1 3t Crystal-induced arthritis, 1 07

Cuff-leak test, 368 Curling ulcers, 528 Cushing triad, 1 0 3 1 Cushing ulcers, 528 Cushing's disease, 4 1 4 Cyanide exposure, 382 Cyclooxygenase-2 inhibitors, 325 Cyclophosphamide (CYC) , 644, 706, 1 1 28 Cycloserine, l l 44t Cyclospora species, 492 Cyclosporine, 372, 5 5 1 Cystitis, 1 04 Cytochrome P-450 isoenzymes, 1 1 45, l 145t Cytochrome P-450 system, 5 5 9 Cytomegalovirus (CMV) , 9 4 , 1 067, 1 068, 1 070, 1 07 1 , 1 094 D

Dacron-cuffed catheters, 438 Dalteparin (Fragmin) , 675t Dantrolene, 393 Dapsone, l 1 44t Daptomycin, 454t, 476 Decompression sickness, 1 040- 1 0 4 1 Deep space neck infections airway management, 402-403 anatomy, 401 antimicrobial therapy, 403 descending infections, 402 etiology, 4 0 1 lateral pharyngeal space infections, 401-402 RPS infections, 402 submandibular space infection, 40 1 Deep venous thrombosis (DVT), 690, 69 1 , 693, 693t, 695-697, 709, 7 1 0 Deep wound infection, 1 04 De-escalation strategy, 409 Defibrillation complications, 37 definition, 33 indications, 34 postprocedure considerations, 37 in pregnancy, 37 procedure, 34-36 Dehydration, 3 9 1 Delirium, 1 47, 9 8 2 complications, 1 1 35-1 1 36 definition, 1 1 32 differential diagnosis, 1 1 34-1 1 35, 1 1 34t epidemiology, 1 1 33 etiology and pathogenesis, 1 1 33, l 1 33t risk factors, 1 1 33 treatment, 1 1 3 5

I n dex

Depressed state of consciousness, 97 4 Depression affective, behavioral, and cognitive (ABC) features, l l 42t definition, 1 1 4 1 , l 1 42t diagnosis, 1 1 4 1 , l 1 42t-1 1 44t, 1 1 43 mnemonic for, 1 1 42t treatment, 1 1 44-1 1 46, l 145t Dermatomyositis, 1 1 1 5-1 1 1 6 Desamino-8-n-arginine vasopressin (DDAVP) , 649 Descending infections, 402 Device erosion, 292 Device malfunction, 292 Dexamethasone, 603, 1 032, 1 033, 1 035 Dextroamphetamine, 1 1 44 OFT testing, 295 1 ,3-�-D-glucan assays, 483 Diabetes insipidus (DI) , 1 034 Diabetes mellitus, 5 4 1 Diabetic ketoacidosis, 4 1 3 blood urea nitrogen (BUN) o f patients, 592 diagnosis, 5 9 1 -592 pathophysiology, 590-5 9 1 plasma ketone levels, 592 serum sodium concentration, 5 9 1 treatment, 5 92-594 Diagnostic peritoneal lavage (DPL) accuracy, 7 0-7 1 o f blunt trauma, 70 contraindications, 7 1 general principles of, 70 indications, 7 1 other modalities, 72-73, 72f in penetrating trauma, 70 procedure, 73-74 Dialysate solutions, 438 Dialytic therapy, in ICU background, 436 complications, 439 discontinuation, 440 indications, 437 principal mechanisms, 436 renal replacement therapy, 437 Dialyzed blood, 436 Diarrhea, 543, 548, 582 clinical presentation, 570 endoscopy, 571 enteral feedings, 5 72 hygiene and skin care, 572 iatrogenic causes, 569 imaging studies, 5 71 laboratory studies, 570-571

I

1 1 63

mucosal biopsies, 5 7 1 a s a primary manifestation of the disease, 569 secondary to underlying diseases, 570 stool studies, 571 treatment, 545-546, 572-573 Diastolic dysfunction, 40 Diazepam, 8 8 1 Dieulafoy lesions, 522 Difficult mask ventilation, 2 Diffuse alveolar hemorrhage (DAH), 1 1 30 Diffuse intrapulmonary hemorrhage, 330 Digitalis, 271 Digoxin, 1 7 1 , 273t Digoxin antibody dosing calculator, 832b Dihydropyridines, 2 1 2 Dilated cardiomyopathies (DCMs) background, 1 69, 1 7 1 t diagnosis, 1 70, l 72t pathophysiology, 1 69 prognosis, 1 73, l 73t treatment, 1 70-173 Diltiazem, 272t, l l 44t Diphenoxylate with atropine, 6 Dipyridamole, 664, 670t Direct thrombin inhibitors, 673, 678t-679t Directly observed therapy (DOT), 507 Disopyramide, l l 44t Disseminated intravascular coagulation (DIC) , 6, 324, 64 1-642 Distal artery, 1 7 Diuretics, 40, 1 7 5 , 2 1 2, 5 6 5 , 906 Diverticulosis, 522 Dobutamine, 1 72, 175, 969 Dofetilide, 273t Dopamine, 393, 969 Dopaminergic receptors, 15 7 Doppler interrogation, 1 74 Doppler principle, 1 2 5 Doripenem, 452t Dorsalis pedis artery, 1 7, 2 1 Double-lumen dialysis catheters, 9 Doxycycline, 5 1 7, 5 1 9 Drowning anoxia, 34 1 cardiac effects, 342 complications, 342 definitions, 340 diagnosis, 342-343 hematologic effects, 342 hypothermia, 34 1 musculoskeletal effects, 342 neurological effects, 342 pathogenesis, 34 1-342

1 1 64

I n dex

Drowning ( Continued) pulmonary effects, 341-342 renal effects, 342 risk factors, 34 1 serum electrolytes, 342 statistics, 341 treatment, 343-344 Drug clearance, 1 1 52 Drug dosing interval, 1 1 52 Drug elimination constant, 1 1 50 Drug half-life, 1 1 50 Drug hepatotoxiciry, 5 5 6 Drug loading dose, 1 1 52 Drug volume of distribution, 1 1 52 Drug-associated thrombosis antipsychotics, 708-709 chemotherapy, 707 eryrhropoietin, 708 hormone replacement therapy, 707 oral and transdermal contraceptives, 707 tamoxifen and raloxifene, 707 thalidomide and lenalidomide, 707-708 thrombopoietin receptor agonists, 709 Drug-induced hyperthermia, 395 Dual-lumen venous catheter, 437-438 Duchenne and Becker dystrophy, 1 028 Duloxetine, 1 1 46 Duodenal ulcers, 527 Dysequilibrium syndrome, 439 Dyspnea, 1 7 4, 1 92 Dysrhyrhmias, 393, 1 094 E

Early goal-directed therapy (EGDT), 968-970 Eastern equine encephalitis (EEE), 94, 1 046 Echinococcus, 1 044 Echocardiogram, 1 74 Echocardiography, 1 70, 1 94 general principles, 1 2 5 indications, 1 25-1 26 postprocedure considerations, 1 30 procedure, 1 26, 1 29-1 3 0 Ectopic atrial tachycardia, 278 Eculizumab, 702 Edema, 325, 943 Ehrlichia chajfeensis, 5 1 8 Ehrlichiosis diagnosis, 5 1 8-5 1 9 general principles, 5 1 8 pathogenesis, 5 1 8 treatment, 5 1 9 Eikenella corrodens, 865 Electrical injuries, 944, 948, 1 039

Electrocardiography (ECG), 33, 40, 1 20, 1 048 pulmonary hypertension, 348 ST-segment elevation myocardial infarction, 237-238 ventricular tachycardia (VT) , 259-260, 260f, 261 f, 262f Electroconvulsive therapy (ECT), 1 1 44, 1 1 46 Electrolyte and renal calculations, 1 1 49 Electromyography, 1 025, 1 026 Electrophysiologic monitoring, 1 0 1 Eltrombopag, 709 Embolism, 126 Emphysematous pyelonephritis, 474 Empyema, 45 Enalaprilat, 2 1 2 Encephalitis, 5 1 0, 1 044 complications, 462 definition, 1 046 diagnosis, 460, 46 1 , 1 046-1 048 epidemiology, 1 046 etiology, 459, 1 046 general principles, 459 pathogenesis, 459-460, 1 046 prognosis, 1 046 treatment, 462 Encephalopathy, 5 6 1 , 562, 566 Endocarditis, 444 Endocrinopathy, 1 034, 1 035 Endoluminal esophageal stents, 841 Endomyocardial biopsy, 1 77 Endoscopy, 80, 523, 525 Endotracheal intubation, 7, 54, 80, 3 8 1 , 536, 952 Endotracheal suctioning, 373 Endotracheal tubes, 4 Enoxaparin (Lovenox), 675t, 1 037 Enteral feeding, 542, 5 82-583 Enteral nutrition (EN) , 86 administration of, 86 contraindications, 87 postprocedure considerations, 87-88 procedure, 88-9 1 Enterobacter species, 456t, 468, 471 Enterococcus species, 457t Enteroviruses, 1 044 Envenomation, 77 1 t-777t Ephedrine, 326, 885 Epidural abscess, 397 Epidural devices, 1 00 Epidural spinal cord compression (ESCC) clinical presentation, 742-743 diagnosis, 743 etiology, 742

I n dex

pathophysiology, 742 treatment, 743-744 Epinephrine, 969 Epistaxis diagnosis, 838 etiology, 838 principles, 83 7-838 treatment, 838-839 Epstein-Barr virus (EBY) , 94 Eptifibatide, 230, 668t Ergocalciferol, 624 Erythromycin, 327, 885 Eryrhropoietin, 708 Eschar formation, 949 Escharoromy, 949 Escherichia coli, 456t, 468, 47 1 , 487, 490, 566, 866, 1 044 Esmolol, 2 1 2, 264, 272t Esophageal devascularization with gastroesophageal stapling, 78 Esophageal Doppler, 1 2 1 - 1 22 Esophageal Doppler moniroring (EDM), 894 Esophageal perforation clinical presentation, 841 definitions, 840 diagnosis, 84 1 etiology, 840-84 1 treatment, 841 Esophageal reconstruction, 64 Esophageal transection, 78 Esophageal variceal hemorrhage, 78, 80 Esophagitis, 522 Esophagogastroduodenoscopy (EGO), 523 Essential thrombocythemia (ET) bleeding, 699 clinical presentation, 699 diagnosis, 699-700, 700t incidence of, 699 treatment, 70 1 Ethambutol, 506, 507 Etomidate, 1 1 4 Evaporative cooling, 394 Ewald rube, 80 Exacerbations, of COPD, 3 1 4 Exertional dyspnea, 347 Exerrional heat stroke, 3 9 1 Exertional syncope, 347 Exogenous lipoid pneumonia, 340 Extensively drug-resistant tuberculosis (XOR-TB), 507 Extensor hallucis longus, 17 External j ugular vein (EJV), 9 Extracorporeal membrane oxygenation (ECMO), 1 66- 1 67, 5 1 1

1 1 65

Extraluminal perforation, 840 Extrapulmonary disorders, 3 1 9 Extremity compartment syndrome, secondary, 9 5 5 , 957 Exrubation, 7 F

Facial reconstruction, 64 Familial hypercalciuric hypercalcemia (FHH), 623 Family meetings, 1 44, 1 45t- 1 46t Fasciotomy, 948, 957 Fat embolism, 642 Fatigue, 347 Febrile neutropenia diagnosis, 48 1-483 etiology, 480 general principles, 479-480 pathophysiology, 480-48 1 treatment, 484-486 Febrile nonhemolytic transfusion reaction, 729 Feeding tube placement, see Enteral nutrition (EN) Femoral artery, 1 7 cannulation, 22 pulsation, 1 2 punctures, 1 34 Femoral vein, 9 Fenoldopam, 2 1 2 Fentanyl, 1 1 6, 8 8 1 Fever biologic markers, 447-448 blood cultures, 445 bronchoscopy, 54 definition, 44 1 description, 44 1-442 diagnosis, 445-448 epidemiology, 442 fluid collection cultures, 447 infectious causes, 442-444 intravascular catheter tip cultures, 446 laboratory studies, 445-448 lumbar puncture, 447 noninfectious causes, 444 pathophysiology, 444-445 patient history and physical examination, 445 radiologic studies, 448 sputum cultures, 446 stool studies, 447 treatment, 448-449 urine studies, 446-447

1 1 66

I n dex

Fever of unknown origin (FUO), 397 Fiberoptic bronchoscopy, 446 Fibrinogen, 64 1 Fibrinolytics, 1 86, 240, 24 1 t, 242, 243, 683t-684t, 688, 706 Fick equation for cardiac index, 1 1 48 Five-lumen catheter, 26 Flail chest, 320, 9 5 1 , 953 Flaviviridae, 5 1 6 Flecainide, 266, 272t Flexible endoscopy, 6-7 Flexible sigmoidoscopy, 5 7 1 Flexor carpi radialis, 1 7 Fluconazole, 473, 485, 854 Fludrocortisone, 223, 6 1 9 Fluoxetine, 223 Focal myocardial compression, 1 94 Focused assessment with sonography for trauma (FAST), 73, 934-935 Foley catheter, I 092 Folliculitis, 866 Fondaparinux, 232 Fondaparinux (Arixtra), 676t Foodborne botulism, 476 Foreign body aspiration, 340 Fosphenytoin, I 033 Fraction of inspired oxygen (Fio 2), 3 6 1 Fractional excretion of N a (FENa) , 4 1 7, 1 1 49 Francisella tularensis, 5 1 6 Fresh frozen plasma (FFP), 64 1 , 726 Fulminant colitis, 548 Fungal infections, 735 Furosemide, 2 1 2, 1 032 Furosemide (Lasix), 623 Fusarium species, 482, 483, 485 Fusobacterium, 40 I G

Gallstone pancreatitis, 576 complications, 578 treatment, 577-578 Ganciclovir, 455t Gastric alkalinization, 530 Gastric and esophageal balloon devices, 536 Gastric antral vascular ectasia, 522 Gastric aspiration, 324-325, 324t Gastric lavage, 832b Gastric stasis, 542, 544 Gastroesophageal balloon tamponade contraindications, 80 definitions, 78 indications, 78, 80

postprocedure considerations, 83-85 , 84f procedure, 80-83, 8 I f, 82f, 83f Gastroesophageal reflux disease (GERD), 340, 541-544, 544, 1 1 1 7 Gastrointestinal (GI) anastamosis, 848 Gastrointestinal bleeding (GIB) acute, 5 2 1 angiographic therapy, 5 2 5 clinical presentation, 523 diagnosis, 523-524 endoscopy, 525 etiology, 5 2 1 -522 lower, 522 nonsurgical management, 525 pharmacologic therapy, 525 resuscitation, 524 surgical consultation, 525 surgical therapy, 530 treatment, 524-525 upper, 5 2 1 -522 vagotomy and oversewing of ulcers, 530 Gastrointestinal infections, 443 Gastrointestinal (GI) motility diagnosis, 542-543 etiology, 5 4 1 -542 general principles, 5 4 1 treatment, 544-546 Gentamicin, 5 1 7, 885 Gilbert syndrome, 557 Glanzmann's thrombasthenia, 650 Glasgow Coma Scale (GCS) , 98-99t, 9 1 1 , 9 1 2, 1 1 50 Global Initiative for Chronic Obstructive Lung Disease (GOLD), 3 1 3 Glomerular injury, 430 G lottic opening, 6 Glucagon, 635 Glucagon deficiency, 632 Glucocorticoids, 6 1 8, 1 1 2 1 deficiency, 632 therapy, in stressed patients, 620-62 1 Gluconeogenesis, 586 a-glucosidase inhibitors, 629 Glycogenolysis, 586 Glycoprotein Ilb/IIIa inhibitors, 664, 668t Glycosaminoglycan, 671 Gout, 1 1 1 2, 1 1 1 3 t Graft pancreatitis, I 082 Graft-versus-host disease (GVHD), 483, 492 Gram stain, 1 1 1 Gram-negative enteric bacilli, 405 Granulomatosis with polyangiitis (GPA), 1 1 27- 1 128 Granulomatous disease, 623

I n dex

Graves' disease, 601 Guillain-Barre syndrome (GBS) , 3 1 9, 5 1 0, 974, 1 027 H

Haemophilus, Actinobacillus, Cardiobacterium, Eikenella and Kingella (HACEK), 464, 467 Haemophilus influenzae, 459, 46 1 , 480, 487, 5 1 0, 938, 1 044 Haloperidol (Haldol) , 882 Halothane, l l 44t Hand-held paddles, 34-3 5 Hantaviridae, 5 1 1 Hantavirus cardiopulmonary syndrome (HCPS) diagnosis, 5 1 1 general principles, 5 1 1 pathogenesis, 5 1 1 treatment, 5 1 1 -5 1 2 Harris-Benedict equation of resting energy expenditure, 1 1 52 H 2 -blockers, 854 HCPS, see Hantavirus cardiopulmonary syndrome (HCPS) Head tilt, 5 Head trauma, 1 1 2-1 1 3 , 974, see also Traumatic brain injury (TB!) Heart failure decompensation, 1 70 Heat stroke diagnosis, 392 etiology, 39 1 general principles, 3 9 1 pathophysiology, 39 1-392 treatment, 392-393 HELLP syndrome, 642 Hemarthrosis, 1 07 Hematemesis, 523 Hemarochezia, 523 Hematopoietic cell transplant (HCT) , 479, 483, 49 1 Hematuria, 1 04, 1 082 Hemobilia, 522, 524 Hemodialysis, 10, 425, 465, 562, 645 Hemodynamic calculations, 1 1 48 Hemodynamic monitoring, 1 8, 1 7 1 Hemodynamically stable WCT, management, 262, 263f Hemodynamically unstable VT/VF, management, 260-26 1 , 262f Hemodynamics, 80, 1 54, 1 092, 1 093 �-hemolytic Streptococcus pyogenes, 865 Hemolytic uremic syndrome (HUS), 888

I

1 1 67

Hemophilia, 647t, 838 Hemophilic arthropathy, 649 Hemoprysis, 53-54 angiography, 335 bronchoscopy, 333 definition, 330 diagnosis, 332-333 idiopathic, 330 laboratory studies, 332-333 massive, 330 medical history, 332 nonmassive, 330, 33 l t pathogenesis, 3 3 1 -332 physical examination, 332 treatment, 333-336 Hemorrhage, 82, 439, 1 03 1 , 1 074 Hemorrhagic shock (HS) abdominal compartment syndrome, 908 coagulopathy, 907 complications, 907-908 definition, 900 diagnosis, 9 0 1 -903 epidemiology, 900 factor dysfunction and deficiency, 907 multiple organ failure (MOF), 907 outcome, 900 pathophysiology, 900-901 platelet dysfunction and deficiency, 907 treatment, 903-907 Hemostasis disorders acquired, 640-645 bleeding disorders, 637-640 congenital, 645-645 1 Hemostatic therapy, 642-643 Hemosuccus pancreaticus, 522 Hemothorax, 45, 292, 9 5 1 Henderson-Hasselbalch equation, 299 Henderson's equation, 1 1 49 Heparin, 1 33, 438, 885 Heparin dose-adjustment nomogram, 673t Heparin resistance, 671 Hepatic dysfunction, 386 etiology, 5 54-5 56 general principles, 554 history, 5 5 6 laboratory studies, 556-557 physical examination, 556 radiographic studies, 557 treatment, 5 5 7 Hepatic failure, 1 1 3 Hepatic steatosis, 5 5 5 Hepatitis B virus (HBV) , 4 9 1 Hepatitis C virus (HCV), 49 1

1 1 68

I n dex

Heparomegaly, 1 9 5 Heparopulmonary syndrome, 566 Hepatorenal syndrome (HRS) , 5 6 1 Herbicide, 777t-78 l t Hereditary angioedema (HAE), 1 1 24-1 1 25 Hereditary hemorrhagic telangiectasia (HHT) , 522 Herpes simplex virus (HSY), 94, 459, 484 Herpes viruses, 492, 1 070 Hiccups, 1 04 1 - 1 042 Hidradenitis suppurativa, 866 Highly active antiretroviral therapy (HAART) , 502 High-riding innominate artery, 64 Histamine-2 receptor antagonists, l 1 44t Histamine-2-recepror antagonists, 529 Histoplasma capsulatum, 492, 5 0 1 Histoplasmosis, 1 070 diagnosis, 5 0 1 etiology, 5 0 1 general principles, 5 0 1 pathogenesis, 5 0 1 treatment, 5 0 1 Hormone replacement therapy (HRT), 707 Hotline, 5 1 5 Human immunodeficiency virus (HIV) infection, 495 mortality, in ICU, 502 testing, in ICU, 502 Hyaluronidase, 1 1 0 Hydralazine, 2 1 2, 885 Hydrocephalus, 1 03 1 , 1 032- 1 033 Hydrocortisone, 62 1 Hydrofluoric acid (HF) , 78 l t-783t Hydrogen cyanide (HCN) , 378 Hydromorphone, 8 8 1 Hydroxyapatite, 1 07 1 ,25-hydroxyvitamin D, 622 Hyoid bone, 2 Hyperalimentation, 589 Hyperbaric oxygen therapy, 374 Hyperbilirubinemia, 557 Hypercalcemia, 542, 622-623 clinical manifestations, 744-745 diagnosis, 745 , 745t etiology and pathophysiology, 744 general principles, 744 laboratory characteristics of, 745 treatment, 746 Hypercapnia, 298-299 Hypercarbia, 1 0 3 1 Hyperchloremic metabolic acidosis, 5 9 5 Hyperglycemia, 542, 1 1 49

Hyperglycemia, in ICU bedside blood glucose monitoring, 587 complications, 5 8 9 diagnosis, 5 86--5 87 general principles, 5 8 5 insulin therapy, 5 8 7 pathophysiology, 586 treatment, 587-5 88 Hyperglycemic hyperosmolar syndrome (HHS), 590 clinical presentation, 596 glomerular filtration rate (GFR) , 595 glucose concentrations in, 596 impairment of cerebral functions in, 596 ketones, 596 laboratory studies, 596 pathophysiology, 595-596 serum osmolality, 596 serum potassium concentration in, 596 serum sodium concentration in, 596 treatment, 596-597 Hyperkalemia, 4 1 3 Hypernatremia, 1 1 49 clinical presentation, 420 diagnosis, 420-42 1 history and physical examination, 420-42 1 pathophysiology, 420 treatment, 42 1-422 Hyperosmolar coma, 5 8 5 Hyperosmolar formulas, 542 Hyperosmolar therapy, 1 032 Hyperphosphatemia, 626 Hyperreflexia, 623, 626, 929 Hypersensitivity, 1 07 Hypertension approach to patient, 208, 2 1 0, 2 1 0t definitions, 208, 209t hypertensive emergencies, 2 1 1 pharmacologic agents, 2 1 2, 2 1 3t-2 1 4t treatment, 2 1 0-2 1 1 Hypertensive crisis, 208 Hypertensive disorders of pregnancy (preeclampsia), 886 Hypertensive emergencies and urgencies, 208, 209t Hyperthermia, 39 1-395 Hypemophic cardiomyopathies (HCMs) background, 17 4 diagnosis, 1 74

I n dex

pathophysiology, 1 74 prognosis, 17 6 treatment, 175 treatment algorithm, 175, l 76f Hyperventilation, 596, 1 032 Hypesthesia, 956 Hypoadrenal crisis cause of primary adrenal failure, 6 1 7 clinical manifestations, 6 1 8-6 1 9 diagnosis, 6 1 8-6 1 9 etiology, 6 1 7 general principles, 6 1 7 glucocorticoids, 6 1 8 treatment, 6 1 9-620 Hypoadrenalism, 6 1 9 Hypoalbuminemia, 550, 583, 1 1 49 Hypocalcemia, 623-624, 1 076 Hypocortisolemia, 1 034 Hypofibrinogenemia, 643 Hypoglycemia, 5 6 1 , 590 diagnosis, 632-634 general principles, 628 pathophysiology, 628-632 treatment, 634-636 Hypoglycemic agents, 629 Hypoglycemic coma, 599 Hypokalemia, 415, 542 Hypomagnesemia, 542 Hyponatremia, 1 033- 1 03 5 , 1 034 clinical presentation, 4 1 8 diagnosis, 4 1 8--4 1 9 etiology, 4 1 9 history and physical examination, 42 1 laboratory studies, 42 1 pathophysiology, 4 1 9--420 treatment, 42 1-422 water metabolism, 420 Hypophosphatemia, 439, 626 Hyposplenism, 486 Hypotension, 7 1 , 1 04, 265, 439, 475 adjunctive agents, 1 6 1 adrenergic receptor physiology, 1 57 cardinal manifestations, 1 56 end-organ perfusion, 1 5 6 first-line agents, 1 6 1- 1 62, 1 62t hemodynamic monitoring and complications, 1 62-1 64 mechanical circulatory support extracorporeal membrane oxygenation, 1 66- 1 67 intra-aortic balloon counterpulsation, 1 64- 1 6 5 percutaneous ventricular assist device, 1 65-166

I

1 1 69

therapy directed, 1 56 vasopressors and positive inotropes doburamine (doburrex), 1 5 9- 1 60 dopamine (intropin) , 1 5 8-1 59 ephedrine, 1 60 epinephrine, 1 57- 1 58 norepinephrine (levophed), 1 5 8 phenylephrine (neo-synephrine) , 1 60 vasopressin (pitressin) , 1 60- 1 6 1 Hypothermia, 34 1 , 44 1 , 442, 903, 907, 93 1 AHA recommendations, 1 52 contraindications for, 1 53 phases of, 1 53 therapeutic clinical application of, 388 general principles, 387 induction phase, 388 maintenance phase, 388 pathophysiology, 388 rewarming phase, 388 unintentional diagnosis, 386 etiology, 385 general principles, 385 pathogenesis, 385-386 treatment, 386-387 Hypothyroidism, 1 034 Hypoventilation, 298 Hypovolemia, 1 75 , 597 Hypoxemia, 1 26, 298, 439, 566 Hypoxia, 39 1

Ibutilide, 273t Iced saline lavage, 394 Idiopathic DCM, 1 73 Idiopathic inflammatory myositis, 1 1 1 5-1 1 1 6 Idiopathic pancreatitis, 8 5 1 Idiopathic restrictive disease, 178 Idiopathic thrombocytopenic purpura, 838 Idiosyncratic reactions, 556 Iloprost, 372 Imipenem, 484, 493 Imipenem-cilastatin, 452t Immune reconstitution inflammatory syndrome (IRIS), 508 Immune reconstitution syndrome (IRIS) diagnosis, 500 general principles, 499 pathogenesis, 500 treatment, 500 Immunocompromised patient, 94

1 1 70

I n dex

Immunoglobulin titers, 94 Immunosuppressive agents, 596, 1 079, 1 094- 10 9 5 Impaction, 8 5 Impaired ventricular systolic function, 4 0 Impedance pneumography, 120 Implantable cardioverter defibrillators (ICDs), 263-264 general principles, 29 3 indications, 293, 294t maintenance, 295 procedure, 294 programming, 294 syncope, 222, 222t Inappropriate sinus tachycardia, 268 Infant botulism, 476 Infarct-related artery (IRA), 237 Infection, 23-24, 946 Infectious arthritis, 1 07 Infective endocarditis (IE) catheter-associated bloodstream infections (CA-BSI), 467-469 classification, 464 definition, 464 diagnosis, 465-466 etiology, 464-465 pathogenesis, 465 treatment, 466-467 Inferior vena cava (IVC) , 1 29t, 5 5 5 Inflammatory arthritis, 1 07 Inflammatory bowel disease, 5 5 1 Inflation pressure limit, 3 6 1 Infliximab, 5 5 1 Influenza infections, 325 Influenza virus A (H5N l ) , 5 1 0 Inhalational botulism, 476 Inhalational injuries asphyxiants, 378-379 chemical and biologic agents of mass destruction, 382-383 general principles, 378 irritant gases, 379-380 smoke inhalation, 380-3 8 1 Inhalation/respiratory injury, 947 Injury Severity Score (!SS) , 9 1 2 Inspiratory flow rate (Vi) , 362 Inspiratory respiratory muscle fatigue, 365 Insulin overdose, 628-629 Insulin therapy, 594 Intensive care unit (ICU), monitoring in acquired weakness arterial pressure, 1 1 8-1 1 9 cardiac output, 1 2 1 - 1 23

diagnosis of critical illness myopathy, 1 024- 1 025 diagnosis of critical illness polyneuropathy, 1 026-1 027 differential diagnosis of, 1 027-1 028 electrocardiography, 1 1 9- 1 20 general principles, 1 024 nutritional support, 5 8 1-583 respiratory monitoring, 120 temperature, 1 1 8 acute kidney injury (AKI), 427-435 dialytic therapy, 436-440 enteral feedings, 542 gastrointestinal (GI) motility abnormalities, 5 4 1 hemodynamic goals for DCM management, 1 72 hypertension, see Hypertension integrative and palliative care effective communication and decision making strategy, 1 44, 1 45t- 1 46t existential/ spiritual suffering, 14 7 hospice nonpain symptoms, 1 43, l 44t loss of personhood, 147 nonpain symptoms, 1 43, 1 44t, 147 pain, 1 47 prognostication/goals of care, 1 43-1 44 symptom assessment and treatment, 1 46 transition of care, 1 48-149 withholding and withdrawing life­ sustaining treatments, 148 stress ulcer syndrome (SUS), 527-530 ultrasound-guided body cavity access general principles, 1 40 indications, 1 40 postprocedure considerations, 1 4 1 procedural pitfalls, 140- 1 4 1 procedure, 140 ultrasound-guided vascular access general principles, 1 37 indications, 1 37 local contraindications, 1 3 7 machine position, 1 37- 1 3 8 postprocedure considerations, 1 40 screen tilt, 1 3 8 Seldinger technique, 1 3 9 site selection, 1 37 site-specific considerations, 1 38-1 3 9 sterile equipment, 1 38 transducer marker, 1 3 8 vessel puncture, 1 3 8 Interferon-a, l l 44t Interferon-y release assays (IGRAs) , 504, 505

I n dex

Interleukin 1 (IL- I ) , 608 Interleukin 6 (IL-6), 608 Intermittent hemodialysis (!HD), 436, 437 Internal iliac veins, 1 02 Internal jugular vein (!JV), 9, 1 0 Intra-abdominal infections acute pancteatitis, 847 bacteria commonly encountered in, 846t biliary infections, 847-848 diagnosis, 845 enteric fistulas, 848-849 etiology, 844-845 intestinal ischemia, 848 percutaneous drainage for, 847 postoperative intra-abdominal infections, 848 principles, 844 resuscitation therapy, 845 treatment, 846-847 Intra-aortic balloon counterpulsation, 1 64-1 6 5 lntracranial hemorrhage, 1 034 lntracranial pressure (ICP), 64, 99- 1 00 Intractable pericarditis, 1 93 lntraluminal perforation, 840-841 Intramural hematoma (IMH), 1 26, 204 lntraparenchymal tumors, 1 032 lntratubular obstruction, 428 lntravascular hypovolemia, 1 37 Intravenous (IV) erythromycin, 544 Intravenous (IV) haloperidol, 1 1 3 5 Intravenous hypnotic agents, l l 4t Intravenous (IV) immunoglobulins, 868 Intravenous immunoglobulins (!VIG), 476, 705-706 Intravenous vasoactive drugs, 1 1 47 lntraventricular devices, 1 00 !ntraventricular tumors, 1 032 Intrinsic hepatotoxicity, 5 5 6 Intrinsic inhibitory neural overactivity, 542 Introducer, 9 Iodides, 603 Ipsilateral thoracic surgery, 46 Iron (Fe), 787t-790t Irritant gases, 379-380 Ischemic hepatitis, 5 5 5t, 5 5 6 lschemic neuropathy, 957 lsoniazid (!NH), 506, 507, 556, 783t-784t, 1 1 44t lsoproterenol, 263 Isospora species, 492 IV verapamil, 270 Ixodes scapularis, 5 1 8

I

1 1 7 1

J

]AK2 tyrosine kinase gene, 699 Jaundice, 557 Jaw thrust, 5 Jugular venous distension OVD), 1 69 Jugular venous saturation monitoring, 1 00 K

Kanamycin, 885 Kelly clamps, 46-47 Ketamine, 1 1 4- 1 1 5, 8 8 1 Ketogenesis, 586 Ketonemia, 632 Ketonuria, 632, 633 Kidney and sodium excess, 4 1 9 Kidney disease, 632 Kiesselbach plexus, 838 King's College criteria, for LT, 563-564t Kinking, 1 04 Klebsiella species, 456t, 468, 47 1 , 566, 866, 943 Kussmaul respirations, 4 1 3 Kyphoscoliosis, 320 L

Labetalol, 2 1 2 �-Lactam allergies, 473 �-Lactam/�-lactamase inhibitor, 848 �-Lactams, 866 Lactic acid production, 895 Lactic acidosis, 413, 561 diagnosis, 500-5 0 1 general principles, 500 pathogenesis, 500 treatment, 5 0 1 Lactulose, 542, 562 Lambert-Eaton myasthenic syndrome, 1 027 Laparotomy, 7 1 , 73 Laryngeal mask airway (LMA), 4, S f, 7 Laryngeal nerve, 2 Laryngeal skeleton, 2 Laryngoscope blades, 4, 4f Laryngoscope handle, 6 Larynx, 2 Lateral pharyngeal space infections, 401-402 Latex-induced anaphylaxis, 1 1 24 L-3,4-dihydroxyphenylalanine (L-DO PA), 395 Lead (Pb) , 790t-793t Left ventricular dysfunction (pump failure), 250-25 1

1 1 72

I n dex

Leg sequential compression devices, 1 037 Legionella pneumophila, 405 Legionella species, 457t, 1 093 Leishmania, 1 070 Lenalidomide, 707-708 Leptospira, 1 044 Leukemias, 838 bone marrow aspirate and biopsy, 733 complications, 734-736, 735t diagnosis, 733 etiology, 732 examination, 733 general principles, 732 hisrory, 733 laboratory studies, 733 molecular diagnostic studies, 733 pathophysiology, 732 peripheral blood smear, 733 treatment, 733-734 Leukocytosis, 549 Leukostasis, 734 Levetiracetarn, 1 033 Levodopa, l l 44t Levofloxacin, 452t Lidocaine, 20, 40, 4 1 , 47, 55, 263, 266, 785t, 1 1 44t Limb loss, 957 Linezolid, 409, 454t, 476 Linton tube, 8 1 Linton-Nachlas balloons, 536 Lipolysis, 586 Listeria monocytogenes, 457t, 459, 46 1 , 480, 490, 1 044, 1 070 Listeria species, 1 09 3 Listeriosis, 325 Lithium (Li) , 793t-795t Liver disease, 632, 838 Liver enlargement, 1 69 Liver transplantation (LT) , 562, 566-567 Lobar atelectasis, 54 Lobar bronchi, 63 Loop diuretics, 1 7 1 , 2 1 2 Loperamide, 573 Lorazeparn, 8 8 1 , 1 033 Low molecular weight heparin (LMWH), 327, 67 1 , 673, 674t, 692t, 694, 695t, 700, 708, 7 1 0 Lumbar puncture (LP) , 9 3 , 447 contraindications, 95 postdural puncture headache (PPH), 96-97 steps for, 96 Lumen, 9 Lund-Browder scale, 944, 945f

Lung abscess, 340 Lung allograft dysfunction, 1 097 Lung expansion techniques, 373 Lyme disease diagnosis, 5 1 9 general principles, 5 1 9 pathogenesis, 5 1 9 treatment, 5 1 9 Lymphocytic choriomeningitis, 1 044, 1 046 M

Macintosh blade, 4, 4f Macronutrients, 583 Magnesium disorders hypermagnesemia, 624-625 hypomagnesemia, 624-625 pathophysiology, 624 Magnesium oxide, 625 Magnetic resonance imaging (MRI) encephalitis, 1 048 toxoplasmic encephalitis, 499 Major trauma-associated thrombosis diagnosis, 7 1 0 general principles, 709, 709t mechanism, 709 prophylaxis, 7 1 0 treatment, 7 1 0 Malaria, 487 diagnosis, 5 1 5 general principles, 5 1 5 pathogenesis, 5 1 5 treatment, 5 1 5 Malignancy, 1 07, 444 Malignant hypertension, 208 Malignant hyperthermia diagnosis, 394 etiology, 393 general principles, 393 pathophysiology, 393 treatment, 394 Malignant pericardia! effusion, 747 Mallory-Weiss tears, 522 Mannitol, 562, 1 032 Mask-bag-valve device, 5 Mean arterial pressure (MAP), 2 1 0, 362, 1 1 48 Mechanical ventilation (MV) , 1 20, 3 1 0 cardiovascular failure, 365 continuous positive airway pressure (CPAP), 360-3 6 1 failed extubation, 368 general principles, 358-364, 365 indications, 366

I n dex

inspiratory respiratory muscle fatigue, 365 managing failure, 369-370 modes, 367 NIPPY, 363-364 pressure-limited, 359-360 procedure, 367-370 prorocols, 368-369 pump failure, from inspirarory respirarory muscle fatigue, 365 ventilator settings for invasive positive­ pressure, 36 1 -363 volume-cycled, 358-35 9 Meckel's diverciculum, 522 Medical gases, administration of, 374-375 Mefl o quine, 1 1 44t Meglitinides, 629 Melena, 523 Mendelson syndrome, 340 Meningitis, 397, 1 044 Mercury (Hg) , 795t-796t Meropenem, 452t Mesenteric arterial embolism, 857 Mesenteric ischemia diagnosis, 85 8-8 5 9 etiology, 857-85 8 general principles, 857 pathophysiology, 8 5 8 treatment, 859-860 Mesenteric venous thrombosis, treatment, 860 Metabolic acidosis, 39 1 , 1 1 49-1 1 50 background information, 4 1 1 classification, 4 1 1-4 1 2 clinical presentation, 4 1 3 definition, 4 1 1 diagnosis, 4 1 3-4 1 4 etiology, 4 1 2 laboratory studies, 4 1 3 multiple acid-base disturbances, 4 1 3-4 1 4 pathogenesis, 4 1 2-4 1 3 respiratory compensation, 4 1 3 Metabolic alkalosis clinical presentation, 4 1 5 definition, 4 1 4 diagnosis, 4 1 5 etiology, 4 1 4 general principles, 4 1 4 laboratory diagnosis, 4 1 5 pathogenesis, 4 1 4-4 1 5 treatment, 4 1 5-4 1 6 Metabolic disorders, 562, 1 076 Metabolic encephalopathy definition, 986 diagnosis, 987-988 due to thiamine deficiency, 989

I

1 1 73

etiology, 986 imaging studies, 989 neurological examination, 987-988 pathogenesis, 987 treatment, 989 Metered-dose inhaler (MDI) , 309, 372 Methadone, 8 8 1 Methemoglobinemia, 5 5 , 3 8 1 Methicillin-resistant Staphylococcus aureus (MRSA) , 409, 45 1 , 457t, 466, 476, 480, 493, 866 Methicillin-susceptible staphylococcal (MSSA) , 466 Methimazole, 603 Methotrexate, 5 5 6 Methylphenidate, 1 1 44 Methylprednisolone, 1 1 28 Methylxanthines, 270, 309, 797t-799t Metoclopramide, 544, l l 44t Metoprolol, 264, 272t Metronidazole, 454t, 545-546, 5 5 1 Micafungin, 455t Micronutrients, 583 Microscopic polyangiitis, 1 1 28 Microsporidium, 492 Midazolam, 1 1 5 , 8 8 1 Middle east respiratory syndrome (MERS) diagnosis, 5 1 2-5 1 3 general principles, 5 1 2-5 1 3 Midodrine, 223 Miller blade, 4, 4f Mineral metabolism disorders calcium disorders, 622-624 general principles, 622 magnesium disorders, 624-625 phosphorus disorders, 625-626 Minnesota balloons, 536 Minnesota cube, 8 1 , 8 l f Minocycline, 93 1 Minute ventilation (VE) , 362 Mirtazapine, 1 1 46 Mitra! regurgitation clinical presentation, 1 83-1 84 etiology and mechanism, 1 83 investigations, 1 84 management, 1 84-1 8 5 pathophysiology, 1 83 Mirra! srenosis (MS), 1 85-1 86 Mnemonic CADRE, 976 Modafinil, 1 1 45 Monnucleoside reverse transcriptase inhibitors (NNRTis), 500 Monoamine oxidase inhibitors (MAOis) , 1 1 46

1 1 74

I n dex

Monophasic waveforms, 34 Monosodium urate (gout), 1 07 Monosodium urate crystals, 1 1 1 Monro-Kellie doctrine, 1 0 3 1 Morphine, l l 5 , 8 8 1 Morphine sulfate, 229 Motility disorders, 5 4 1 Motor innervation, 2 Motor neuron disease, 1 028 Mucin clots, 1 1 0 Mucociliary clearance, 338, 373 Mucocutaneous bleeding, 637 Mucor species, 397, 1 070 Mucosa! biopsies, 5 7 1 Mucosa! ulceration, of the gastroesophageal junction, 85 Mucositis, 475 Multicenter InSync Randomized Clinical Evaluation (MIRACLE) , 290 Multidrug-resistant tuberculosis (MOR-TB), 507 Multifocal atrial tachycardia (MAT), 279, 292 Multilumen catheter, 9 Multiple acid-base disturbances, 4 1 3-4 1 4 Multiple myeloma (MM) , 480 Multiple organ failure (MOF), 907 Multiple-organ dysfunction syndrome (M 0 OS), see also Sepsis background, 965 pathophysiology, 965-966, 967£ 968f risk factors, 96 1 , 962t scoring systems, 965, 966t Muscle biopsy, 1 025, 1 026 Muscular dystrophy, 1 028 Myasthenia gravis (MG), 3 1 9, 974, 1 027 Mycobacteria, 490 Mycobacterium avium complex, 500 Mycobacterium tuberculosis (MTB) , 480, 49 1 , 497, 500, 504-506, 508, 1 070 Mycoplasma pneumoniae, 407, 1 044, 1 049 Myelop roliferative disorders/myelodysplastic syndrome (MPOs)/(MOS, 645 Myeloproliferative neoplasms (MPNs) bleeding, 699 clinical presentation, 699 diagnosis, 699-700, 700t general principles, 698-699 prognosis, 700 surgical procedures, 699 treatment, 700-70 1 Myocardial infarction antithrombotic therapy, 248 arrhythmias complicating, 255, 256t, 257t

background, 246, 247t left ventricular dysfunction (pump failure) , 250-25 1 mechanical complications, 2 5 1 -253, 252f, 253f, 254t pathophysiology, 246, 248f pericarditis, 255 prognosis after, 246 recurrent ischemia/infarction, 246-248, 249f right ventricular infarction, 249-250 thromboembolism, 253, 255 Myocardial infarction (MI), 25, 2 1 2, 2 8 1 -282, 283t Myocarditis, 5 1 0 Myonecrosis, 948, 957 Myopericarditis, 1 90 �-myosin heavy chain, 1 74 Myosin-binding protein, 1 74 Myositis, 5 1 0 Myxedema coma active heating in, 606 clinical features, 605t diagnosis, 605-606 general principles, 604 myocardial band (MB) fraction, 606 parenteral administration of thyroid hormone, 607 pathophysiology, 605 signs, 606 symptoms, 605 treatment, 606-607, 607t N

Na• correction for hyperglycemia, 1 1 49 N-acetylcysteine (NAC), 562 Nachlas tube, 8 1 Naegleria fowleri, 1 044 Naloxone, 879, 982 Narcotics, 54 1 , l l 44t Nasal CPAP, 375 Nasogastric aspiration, 534 Nasogastric tube, 1 036 Nasopharyngeal airway, 2, 3f, 5 Nasopharyngeal bleeding, 8 5 Nasotracheal intubation, 38 1 Native valve endocarditis (NVE), 464 Near-infrared spectroscopy, 1 0 1 Nebulizers, 372 Necrosis, 85 Necrotizing fasciitis, 867-869 Necrotizing muscle infection, 869 Needle cricothyrotomy, 7

I n dex

Neisseria meningitidis, 457t, 459, 46 1 , 480, 487, 702, 938, 1 044 Nesidioblastosis, 635 Neurochemical monitoring, 1 0 1 Neurogenic bladder dysfunction, 1 02 Neuroimaging, 99 Neuroleptic malignant syndrome (NMS) diagnosis, 395 etiology, 394 general principles, 394 pathophysiology, 394-39 5 treatment, 3 9 5 Neurological examination, 98 Neurological monitoring categories, 98 Neurological problems, in ICU altered consciousness, 979-984 brain death, 976 carbon monoxide (CO) poisoning, 1 039-1 040 cerebral fat embolism syndrome, 1 0 4 1 decompression sickness, 1 040- 1 04 1 depressed state o f consciousness, 974 diagnosis, 97 4-977 electrical injuries, 1 039 general principles, 973-974 hiccups, 1 0 4 1 - 1 042 metabolic encephalopathy, 986-989 monitoring ICP and state of consciousness, 97 6 neurological calculations, 1 1 5 0 peripheral nerve disorders, 1 042 prevention of further damage, 977 primary, 974 prognostic and ethical considerations, 977 respiratory support, 976 secondary neurological disease in, 977 secondary severe medical disease in, 977 status epilepticus, 977 suicidal hanging, 1 038 Neuromuscular blocking agents (NMBAs) , 1 1 6-1 17, 1 024, 1 025 Neuro-oncological problems, in ICU hydrocephalus, 1 032- 1 033 increased intracranial pressure (I CP) , 1 0 3 1 - 1 032 postoperative complications, 1 034-1035 seizures, 1 033 spinal tumors, 1 035-1 036 systemic complications secondary to brain tumors, 1 036- 1 037 Neuroprognostication, 1 5 5 Nicardipine, 2 1 2 Nifedipine, l l 44t Nimodipine, 2 1 2

I

1 1 75

Nitrate therapy, 229 Nitrates, 243 Nitric oxide, 374 Nitrogen dioxide (N0 2) , 379 Nitroglycerin, 2 1 2 Nocardia species, 457t, 483, 490, 1 070, 1 093 Nonclostridial myonecrosis, 869 Noncompliant LV, 175 Noncompressing effusions, 1 9 3 Nondepolarizing neuromuscular blocking (NMB) agents, 1 1 7 Non-dihydropyridine calcium channel blockers, 271 Nondihydropyridines, 2 1 2 Nonexertional ("classic") heat stroke, 39 1 Noninflammatory arthritis, 1 07 Noninvasive positive pressure ventilation (NPPV), 363-364 Nonmalignant islet cell adenomatosis, 629 Nonsteroidal anti-inflammatory drug (NSAIDs), 1 93, 522, 799t-80 l t, 877, 885, 886 Norfloxacin, 538 Normothermia, 1 53 Nose, 1 Nosocomial pneumonia, 404, 530 Nosocomial sinusitis, 443 complications, 397 diagnosis, 397 etiology, 397 incidence, 397 sphenoid sinusitis, 398 treatment, 397-398 Nucleoside reverse transcriptase inhibitors (NRTis)-based therapy, 500 Nutritional assimilation, 582 Nutritional calculations, 1 1 52 Nutritional support, in ICU diagnosis, 5 8 1-582 enteral feeding, 5 82-5 83 general principles, 5 8 1 laboratory tests, 5 8 1-582 parenteral feeding, 583 pathogenesis, 5 8 1 subjective global assessment (SGA) , 582 treatment, 5 82-5 83 Nutritional therapy, 408 0

Obesity-hypoventilation syndrome, 320 Obliterative hepatocavopathy, 5 5 5 Obstetric hemorrhage, 887

1 1 76

I n dex

Obstetric patient management, in ICU amniotic fluid embolism, 887 burn injuries, 888 cardiovascular risk, 884 diagnostic radiation exposure, 884-885 gastrointesinal risk, 884 hematologic risk, 884 hemolytic uremic syndrome (HUS)/ thrombotic thrombocytopenic purpura (TTP) , 888 hypertensive disorders of pregnancy (preeclampsia), 886 maternal physiologic adaptation to pregnancy, 884 medications and pregnancy, 885 obstetric hemorrhage, 887 renal risk, 884 respiratory risk, 884 trauma, 888 urinary tract infection (UT!), 884 Obstruction, of airway, 4 Octreotide, 78, 535, 573 Ocular compartment syndrome, 9 5 5 , 957 Odynophagia, 1 92 Oncologic emergencies epidural spinal cord compression (ESCC) , 742-744 hypercalcemia, 744-746, 745t malignant pericardia! effusion, 747 superior vena cava (SVC) syndrome, 738-740, 739t tumor lysis syndrome (TLS), 740-742, 74 l t Open lung biopsy, 408 Open tracheostomy, 65-66 Opioids, 1 1 5- 1 1 6, 802t-803t Opium, 573 OPS!, see Overwhelming postsplenectomy infection (OPS!) Optimal endotracheal tube position, 6 Orbital cellulitis, 397 Organ failure, see Sepsis Orthopnea, 332 Orthosis (bracing) , 1 036 Orthostatic hypotension, 6 1 8 Osmolar gap, 1 1 49 Osmotic demyelination, 421 Osteoarthritis, 1 07 Osteochondroma, 1 07 Osteomyelitis, 397, 444 Osteoradionecrosis, 374 Otogenic infections, 398 Overwhelming postsplenectomy infection (OPS!), 487, 488

Oxacillin, 454t Oxygen therapy, 309-3 1 0, 374 Oxygenation, 1 54 Oxytocin antagonists, 325 p

Pacemaker infection, 292 Pacemaker nomenclature codes, 291 t Pacemaker syndrome, 292 Pacemaker-mediated tachycardia (PMT), 292 Pacing partial arterial carbon dioxide pressure (Paco2), 25, 297 in COPD, 3 1 4 i n pregnant woman, 328r Packed red blood cells (PRBCs), 643 Pain management, of critically ill complications, 882 definition and pathogenesis, 875-876 diagnosis concept of patient-focused sedation and analgesia, 877 delirium, 877 intensity, 876 location, 876 moniroring the degree of sedation, 877 quality of sensation, 876 drugs for, 880-882 general principles, 875 treatment, 877-879 Palmar blushing, 20 Palpitation, 347 Pamidronate (Aredia), 623 Pancreatic duct obstruction, 8 5 1 PAo / Fio 2 ratio, 298 Papilledema, 1 03 1 Paracentesis complications, 76 contraindications, 75 general principles, 74 indications, 74-75, 75r procedure, 76 Parathyroid hormone (PTH), 622 Parenchymal pressure transducer devices, 1 00 Parenteral anticoagulants, 242 Parenteral feeding, 583 Parenteral nutrition, 544, 577 Parenteral therapy, 2 1 1 Parenteral thiamine, 598 Parietal layer, 1 90 Parkinson disease, 5 4 1

I n dex

Paroxysmal nocturnal hemoglobinuria (PNH) clinical presentation, 702 diagnosis, 702 general principles, 70 1-702 prognosis, 703 treatment, 702-703 Partial arterial of carbon dioxide pressure (Paco 2) , 1 32 Partial arterial of oxygen pressure (Pao, ) , 1 32, 297 Partial cuff deflation techniques, 376 Pasteurella multocida, 865 Patellar tap, 1 06 Patient-controlled analgesia (PCA), 880 Patient-controlled epidural analgesia (PCEA), 880 Pedal edema, 1 9 5 Penetrating atherosclerotic ulcer (PAU), 204-205 Penetrating trauma, during pregnancy, 888 Penicillin G procaine, l l 44t Penicillins, 327, 885 Peptic ulcer disease, 52 1 , 522 Peptostreptococcus, 40 1 Percent oxyhemoglobin saturation (Sao2), 1 32 Percutaneous bedside tracheosromy, 54 Percutaneous coronary intervention (PCI), 237 Percutaneous dilarational rracheostomy, 7 Percutaneous endoscopic jejunostomy (PEJ), 91 Percutaneous suprapubic cystostomy complications, 1 04 contraindications, 1 03 indications, 1 02 postprocedure considerations, 1 04 procedure, 1 03-1 04 Percutaneous tracheostomy, 66-67 Percutaneous rransheparic embolization, 78 Percutaneous ventricular assist device, 1 65- 1 66 Pericardia! disease, critical care constrictive pericardiris, 1 95-197 general principles, 1 90- 1 9 1 pericardia! effusion and cardiac ramponade, 1 93-1 9 5 pericardiris, 1 9 1 - 1 93 Pericardia! effusion, 40 Pericardia! space, 19 0 Pericardia! tamponade, 1 94, 2 0 5 Pericardiocentesis, 19 5 complications, 4 3 definition, 39 diagnostic studies, 43

1 1 77

diagnostic vs. therapeutic, 39 diseases affecting pericardium, 39 pericardia! anatomy, 39 postprocedure considerations chest radiograph, 43 monitoring, 42 transthoracic echocardiogram, 43 procedure considerations, 40 fluid evacuation, 42 material preparation, 40 needle advancement, 42 needle entry site selection, 4 1 needle insertion, 4 1 -42 patient preparation, 40 sire preparation, 4 1 tamponade, 42 Pericardiris, 255 diagnosis, 1 9 1-1 93, 1 92f treatment, 1 93 Pericardium, 1 90 Perioperative hypertension, 2 1 1 Peripheral edema, 1 69 Peripheral nerve disorders, 1 042 Peritoneal access, 439 Peritoneal defense mechanisms, 844 Peritoneal dialysate, 439 Peritoneal dialysis (PD), 436, 439 Peritoneal signs, 549 Peritonitis, 439 Permanent pacemakers (PPMs) complications, 292 general principles, 290, 29 1 t indications, 290, 29 l t monitoring, 293 procedure, 292 Pesticides, 804r-8 l 4r Pharmacologic calculations, 1 1 50, 1 1 52 Pharyngeal abscess, 64 Phenobarbital, 394, 1 033 Phenothiazines, 54 1 , 879 Phenylephrine, 6, l l 44r Phenylpropanolamine, l l 44r Phenytoin, 556, 596, 1 033 Phlebitis, 265 Phosphate binders, 626 Phosphodiesterase inhibitors, 670t, 671 Phosphorus disorders, 625-626 Phytonadione, 688 Pigmented villonodular synovitis, 1 07 Piperacillin/razobactam, 452r, 484, 493 Plague (Yersinia pestis}, 383 Plasma glucose concentration and hyperglycemia, 5 87

1 1 78

I n dex

Plasma osmolality (Posm), 4 1 9, 421 Plasma potassium disorders general principles, 424 hyperkalemia, 426 hypokalemia, 424-425 Plasma sodium (PNa) disorders as a determinant of plasma osmolaliry, 4 1 9 general principles, 4 1 9 Plasmapheresis, 706 Plasmodium falciparum, 5 1 5 Plastic syringes, 1 33 Platelet disorders, 637 Platelets, 724-726, 725t Pleural disease complications, 3 5 5 diagnosis, 3 5 4 etiology, 3 5 3 general principles, 353 pathophysiology, 353-354 treatment, 354-3 5 5 Pleural effusion, 45 Pleural fibrosis, 320 Pleural symphysis, 48 Pneumocystis jirovecii, 405, 480, 483, 490, 492, 493, 1 070, 1 079, 1 093 Pneumocystis pneumonia (PCP) , 735, 1 1 28 diagnosis, 496 etiology, 495 pathogenesis, 495 treatment, 496t, 497 Pneumomediastinum, 328 Pneumonia, 63, 949 clinical presentation, 406 community-acquired (CAP), 404 diagnosis, 407-408 diagnostic testing, 407-408 etiology, 405-406 history, 407 in ICU patients, 404 laboratory tests, 407 nosocomial, 404, 530 pathogenesis:, 405 physical examination, 407 serology, 407 sputum examination, 407 rreatment, 408-409 ventilator-associated (YAP) , 404 Pneumothorax, 45, 50, 5 1 , 328, 328t diagnosis, 356 etiology, 3 5 5 general principles, 3 5 5 pathophysiology, 35 5-356 thoracic trauma, 9 5 1 , 953 rreatment, 356-357

Polyarteritis nodosa (PAN), 1 1 29 Polycythemia vera (PV) bleeding, 699 clinical presentation, 699 diagnosis, 699-700, 700t incidence of, 699 treatment, 70 1 Polydipsia, 1 034 Polymerase chain reaction tests, 94 Polymorphonuclear (PMN) cell count, 1 1 0 Polymyositis, 1 07, 1 1 1 5-1 1 1 6 Polyuria, 1 034 Portal gastropathy, 522 Portal hypertension, 533, 564 Portopulmonary hypertension, 566 Positive end-expiratory pressure (PEEP) , 56, 64, 363, 9 1 6 Post-cardiac arrest diagnosis, 1 5 1 general principles, 1 50 neuroprognostication, 1 5 5 persistent precipitating pathology, 1 5 1 post-cardiac arrest brain injury, 1 5 1 post-cardiac arrest myocardial dysfunction, 1 5 1 systemic inflammatory response syndrome (SIRS) , 1 5 1 treatment coronary revascularizarion, 1 53-1 54 glucose control, 1 54 hemodynamics, 1 54 induced hypothermia, 1 52- 1 5 3 oxygenation, 1 54 persistent precipitating pathology, 1 54 seizures, 1 54 ventilation, 1 5 1 , l 52t Post-cardiac arrest syndrome (PCAS), 1 50 Postdural puncture headache (PPH), 96-97 Postextubation, 7 Postmyocardial infarction pericarditis, 1 9 3 Postobstructive diuresis, 1 04 Postresuscitation syndrome, 388 Posttransplant lymphoproliferative disease (PTLD), 1 068, 1 07 1 Potassium phosphate, 593 Pralidoxime, 383 Prasugrel (Effient) , 666t Prazosin, l l 44t Predisposition, infection, response and organ dysfuncrion (PIRO), 964-965 Prednisone, 644 Preemptive analgesia, 878 Pregnancy, 75

I n dex

Premature ventricular contractions (PVCs), 264 Prerenal azotemia, 427 Pressors, 885 Pressure control (PC) , 359-360 Pressure support (PS) , 359 Pressure ulcers epidemiology, 872 pathophysiology, 872 prevention, 872-873 wound classification, 873 wound management, 873-874 Procainamide, 265, 272t, 1 1 44t Prognathic ability, 2 Prognostication, 1 43-1 44 Propafenone, 266, 272t Propofol, 1 1 3, 8 8 1 Propranolol, 272t, 596 Propylthiouracil (PTU) , 603 Prostacyclin, 438, 706 Prosthetic valve endocarditis (PYE) , 1 86-1 87, 464 Prosthetic valve thrombosis, 1 86 Protamine, 682 Protected specimen brush (PSB) cultures, 407 Proteus mirabilis, 490 Proteus species, 471 Prothrombin time (PT) , 638-640, 639t Proron pump inhibitors (PP!s) , 529, 544 Providencia species, 471 Pseudocysts, 578 Pseudogout, 1 1 1 2 Pseudohemoptysis, 330 Pseudomembranous croup, 400 Pseudomonas aeruginosa, 37 1 , 398, 452t--454t, 457t, 480, 482--484, 486, 492 Pseudomonas species, 468, 47 1 , 943 Psoriatic arthritis, 1 07 Psychiatric issues, in ICU suicide, 1 1 37- 1 1 39, l 1 38t treatment of agitation and delirium, 1 1 32-1 1 36 Pulmonary arterial circuit, 332 Pulmonary artery catheter (PAC), standard, 25 clinical uses, 30 insertion procedure, 26-28 Pulmonary artery catheterization cardiac output measurement, 28-29 complications, 29 indications, 25-26 objectives, 25

I

1 1 79

PA perforation, 29 postprocedure considerations, 28-30 pressure and waveform interpretation, 28 procedure, 26-28 types of catheters, 25 Pulmonary artery occlusion pressure (PAOP), 28 Pulmonary calculations, 1 1 48 Pulmonary capillaritis, 1 1 30 Pulmonary compromise, 542 Pulmonary disease, 566 Pulmonary edema, 325 Pulmonary embolus, 1 036 Pulmonary histoplasmosis, 5 0 1 Pulmonary hypertension classification, 345, 346t computerized tomography, 349 definitions, 345 diagnosis, 347-3 50 etiology, 34 5 , 34 7 t laboratory evaluation, 348 normal pulmonary circulation, 345-346 radiographic findings, 348 right heart catheterization, 349 RV pressure overload, 346-347 transthoracic Doppler echocardiography (DE), 348-349 treatment, 350-3 5 1 ventilation-perfusion lung scan (V/Q scan), 349 Pulmonary parenchymal disease, 320 Pulmonary toxicity, 736 Pulmonary vascular resistance, 1 1 48 Pulmonary vasodilator therapy, 350 Pulsation, 1 37 Pulse contour analysis, 1 22 Pulse Index Continuous Cardiac Output (PiCCO) , 894 Pulse oximetry, 1 20, 893 Pulseless ventricular tachycardia (VT) , 33 Pulsus paradoxus, 1 94 Pump failure, from inspiratory respiratory muscle fatigue, 365 P2Y12 inhibitors, 664, 666t Pyelonephritis, 1 04 Pyrazinamide, 506, 507 Pyrimethamine, 499 Q

Quadriplegia, 64 Quadruple-lumen catheter, 26 Quetiapine, 1 1 3 5

1 1 80

I n dex

Quinidine gluconate, 5 1 5 Quinine, 5 1 8 R

Radial artery cannulation, 17, 20-2 1 Radiation therapy, I 036 Radiographic contrast media anaphylaxis, 1 1 23-1 1 24 Raloxifene, 707 Receptive aphasia, 983 Recombinant tissue plasminogen activator (r-TPA), 1 86 Rectal biopsy, 1 77 Rectal ulcers, 522 Red blood cells (RBCs) , 724, 725t Reflex tachycardia, 2 1 2 Refractory bleeding, 643 Remifentanil, 1 1 6 Renal failure, 1 1 5 in ALF, 5 6 1 from myoglobinemia, 9 5 7 Renal replacement therapy (RRT), 437 Reperfusion syndrome, 957 Reperfusion therapy, 240-242, 240f, 24 1 t Respiratory acid-base disorders, 299-300 Respiratory acidosis, 299, 300t, 1 1 50 Respiratory alkalosis, 299, 1 1 5 0 Respiratory compensation, 4 1 3 Respiratory failure extrapulmonary causes diagnosis, 320-32 1 differential diagnosis, 320 etiology and pathophysiology, 3 1 9-320 general principles, 3 1 9 hypercapnic respiratory failure, 320 laboratory testing, 3 2 1 and lateral curvature o f the spine (scoliosis) , 320 measurements of MIP and MEP, 320 medical history analysis, 320 peripheral nervous system dysfunction, 319 supplemental oxygen for, 32 1 systemic myopathies, 320 techniques of airway hygiene, 321 treatment, 321 upper airway obstruction, 320-32 1 use of mechanical ventilatory assistance, 321 viral capacity measurements, 320 management of diagnosis, 30 I and efficiency of gas exchange, 297

general principles, 297-298 pathophysiology, 298-300, 300t treatment, 3 0 1 -302 in pregnancy diagnosis, 325 etiology, 322-325, 324t general principles, 322, 323t heparin therapy, 327 hypotension, 326 intubation of the pregnant patient, 326 and maternal malnutrition, 326 mechanical ventilation (MV) , 326 nutrition, 326 radiology, 325 reversal of hypotension, 326 treatment, 326-328, 326t, 328t Respiratory infections, 325 Respiratory monitoring, 1 20, 376-377 Restrictive cardiomyopathies (RCMs) background, 1 76-1 77 diagnosis, 1 77- 178, I 77f pathophysiology, 1 77 prognosis, 1 78 treatment, 178 Resuscitation of burns, 945 gastroesophageal balloon tamponade, 80 for hemorrhagic shock (HS) end points, 905 fluid, 904 pitfalls, 905-906 response to, 904-905 Reteplase (Retavase) , 684t Reticular activating system (RAS) , 979 Return of spontaneous circulation (ROSC), 1 50 Rhabdomyolysis, 957 Rheumatoid arthritis (RA), 1 07, 1 1 07-1 1 08, 1 1 09t- l l l l t, 1 1 1 2 general principles, 1 1 07 neurological problems, 1 1 08 pulmonary, 1 1 08 treatment, 1 1 08, 1 1 09t- l I l l t Rheumatologic disorders, in ICU antiphospholipid antibody syndrome, 1 1 1 5 crystal arthropathy, 1 1 1 2-1 1 1 3, I 1 1 3t idiopathic inflammatory myositis, 1 1 1 5- 1 1 1 6 rheumatoid arthritis, 1 1 07-1 1 08, 1 1 09t- l l I l t, 1 1 1 2 scleroderma, 1 1 1 6- 1 1 1 7 septic arthritis, 1 1 1 3-1 1 1 5, I I 14t systemic lupus erythematosus, 1 1 1 6 Rhinoscleroma, 400

I n dex

Rhonchi, 304 Rib fractures, 952 Ricin, 383 Rickettsia rickettsii, 5 1 7 Rifampin, 506, 507 Rifaximin, 566 Right ventricle ejection fraction (RVEF), 26 Right ventricular infarction, 249-250 Riluzone, 93 1 Ritodrine, 325 Rituximab, 706, 1 1 28 Rocky Mountain spotted fever (RMSF) diagnosis, 5 1 7 general principles, 5 1 7 pathogenesis, 5 1 7 treatment, 5 1 7 Rocuronium, 1 1 7 Romiplostim, 709 Ruxolotinib, 70 1 RV ejection fraction PAC, 25 s

Salicylate, 632 Salmonella species, 480, 487, 490, 492, 493 Salmonella typhi, 1 044 Schistosomiasis, 1 044 Schizophrenia, 1 1 34 Scleroderma, I 07, 1 1 1 6- 1 1 1 7 Scleroderma renal crisis, 1 1 1 7 Sclerotherapy, 78, 535-536 Secondary extremity compartment syndrome, 955, 957 Secondary prophylaxis, 502 Sedative hypnotic, 8 l 4t-820t Seizures, 1 033 Seldinger technique, 1 04 Selective serotonin reuptake inhibitors (SSRis) , 1 1 45, l 145t Self-adhesive pads, 35 Semiopen tracheostomy, 67 Sengstaken-Blakemore balloons/tube, 8 1 , 82f, 536 Sepsis, 641 cholestasis of, 5 5 7 diagnosis clinical presentation, 963 inflammatory source identification, 963-965 , 964t predisposition, infection, response and organ dysfunction (PIRO), 964-965 general principles definitions, 959, 960-96 l t, 961 epidemiology, 9 6 1

I

1 1 81

multiple-organ dysfunction syndrome background, 965 pathophysiology, 965-966, 967f, 968f scoring systems, 965, 966t pathophisiology end-organ consequences, 963 infection, 961 mediators, 963 pathogen induction, 961-962 toll-like receptors, 962-963 treatment antibiotics and source control, 970 early goal-directed therapy, 968-970 sepsis care adjuncts, 970-971 time-dependent disease, 966, 968, 969t Septic arthritis, 1 06, 444, 1 1 1 3-1 1 1 5, l 1 14t Septic shock, 959 Seronegative spondyloarthropathy, 1 07 Serotonin reuptake inhibitors, 395 Serotonin-norepinephrine reuptake inhibitors (SNRis) , 1 1 45-1 146, 1 1 45t Serratia species, 471 Serum creatine kinase (CK) , 1 025 Serum osmolality, 1 1 49 Serum procalcitonin, 447---4 4 8 Serum sickness, 1 07 Serum T3 concentrations, 6 1 0 Serum T4 concentrations, 6 1 2 Sevelamer, 626 Severe acute respiratory syndrome (SARS), 325 diagnosis, 5 1 2 general principles, 5 1 2 pathogenesis, 5 1 2 treatment, 5 1 2 Severe neutropenia, 4 79 Shock cardiogenic, 892, 896-897 classification, 890-892 definition, 890 description, 890 diagnosis, 893 distributive, 892, 897 endocrine, 892 etiology, 890-892 hemodynamic monitoring, 894-895 hypovolemic, 890-89 1 , 8 9 l t, 8 96 obstructive, 8 9 1 -892, 8 96 pathophysiology, 892-893 resuscitation end points, 895 treatment, 895-896

1 1 82

I n dex

Sick euthyroid syndrome, in ICU alterations in serum-binding proteins, 609-6 1 0 alterations i n the pituitary-thyroid axis, 609 diagnosis, 6 1 2-6 1 4 etiology, 608 general principles, 608 L-T3 treatment, 6 1 4 pathophysiology, 608-6 1 2 stages, 6 1 0-6 1 2 thyroid function tests, 6 1 2-6 1 4, 6 1 3t treatment, 6 1 4-6 1 5 Sinopulmonary infections, 443 Sinus tachycardia, 34 Sinusoidal obstruction syndrome, 5 5 5 Skin and soft tissue infections, 443-444 Skin puncture, 1 3, 1 4 Slow continuous ultrafiltration (SCUF), 437 Slow low efficiency dialysis (SLED), 437 Smallpox (Vario/a major}, 382 Smoke inhalation, 380-38 1 Snake bite, 642 Sniffing position, 6 Sodium nitroprusside, 2 1 2, 885 Sodium phosphate, 626 Sodium thiosulfate, 383 Sonography, 557 Sorbitol-containing medication suspensions, 542 Sotalol, 272 t Sphenoid sinusitis, 398 Spinal cord trauma airway management, 928 American Spinal Injury Association (ASIA) grading scale, 924, 925t assessment of spinal column stability, 927, 927f, 928f decompressive surgery, 929 epidemiology and clinical significance, 924 hospital management, 928-929 initial assessment and stabilization, 926 neurological decompression, 929 neurological injury, 924-925, 925t neuroprotective agents, 93 1 pathophysiology, 926 restorative/regenerative strategies, 93 1 sequelae and complications, 929-93 1 steroid dosage, 929 treatment, 928-929 Spine injuries, 65 Splanchnic vasoconstriction, 528 Spondyloarthropathies, 1 07

Spontaneous bacterial peritonitis (SBP), 565-566 Spontaneous perforation, 840 Staphylococcal enterotoxin B, 382 Staphylococcus aureus, 50, 340, 405, 439, 444, 4 5 1 , 457t, 464, 465, 468, 469, 47 1 , 475, 480, 483, 485, 490, 5 1 0, 865, 943 Staphylococcus epidermidis, 439 Staphylococcus species, 566 Statins, 243 Status epilepticus, nonconvulsive, 973, 977, 983 Steatohepatitis, 5 5 5 Stem cell transplant (SCT), 479, 485 Stenotrophomonas maltophilia, 458t Sternal fracture, 953 Sternocleidomastoid muscle (SCM) , 12 Stinging insect venom anaphylaxis, 1 1 23 Storage pool disorders, 650 Streptococcus, 1 044, 1 049 Streptococcus bovis, 464 Streptococcus mitis, 464 Streptococcus mutans, 464 Streptococcus pneumoniae, 340, 45 8t, 459, 46 1 , 480, 487, 490, 492, 5 1 0, 938, 1 044 Streptococcus pyogenes, 475 Streptococcus sanguis, 464 Streptococcus species, 566 Streptomycin, 506, 507, 5 1 7, 885 Stress ulcer syndrome (SUS) complications, 530 definition, 527 description, 527 diagnosis, 528 etiology, 527 mortality rates, 527 mucosa! damage, 528 pathogenesis, 528 prognosis, 527 treatment, 528-530 Stroke, 974 Stroke volume, calculation of, 122 Strongyloides stercoralis, 1 070 ST-segment elevation myocardial infarction acute kidney injury, 244 adjunctive antithrombotic therapy, 242-243 antiischemic therapy, 243 cardiac biomarkers, 238 complications, 244 diagnosis, 237-238, 238t, 239t differential diagnosis, 237

I n dex

ECG, 237-238 general principles, 237 glycemic control, 244 history, 23 7 pathophysiology, 237 physical examination, 237 reperfusion therapy, 240-242, 240f, 24 l t Subarachnoid fluid-coupled devices, 1 00 Subarachnoid tumor, 1 032 Subclavian vein (SCV) , 9 Subdural devices, 1 00 Subdural empyema, 397 Submandibular space infection, 4 0 1 Succinylcholine, 1 1 6, 1 1 7 Sucralfate, 529 Sugiura procedure, 537 Suicidal hanging, 1 038 Suicide description, 1 1 37 general principles, 1 1 37 risk factors, 1 1 37, 1 1 38t treatment, 1 1 37-1 1 39, 1 1 38t Sulfonamides, 885 Sulfonylurea overdose, 629 Sulfonylureas, 629 Sulfur dioxide (S0 2) , 379 Superior mesenteric artery (SMA) embolism, 859 thrombosis, 85 9-860 Superior vena cava (SVC) syndrome diagnosis, 738-739, 739t etiology, 738 glucocorticoids, 740 supportive care, 740 treatment, 739-740 Suppurative jugular venous thrombosis, 4 0 1 Supraglottitis airway management, 400 antibiotics, 400 characteristic presentation, 399 clinical evaluation, 399 clinical presentation, 398 corticosteroids, 400 diagnostic tests, 399 differential diagnosis, 400 etiology, 399 helium-oxygen mixture, 400 pathogenesis, 399 Supraventricular tachycardias (SVTs) atrial fibrillation, 27 1 , 273-276, 274f, 275f atrial fibrillation post-cardiac surgery, 276 atrial flutter, 276 atrioventricular nodal reentrant tachycardia (AVNRT), 276-277

I

1 1 83

atrioventricular reentrant tachycardia (AVRT) , 277 definition, 268 diagnosis, 268-270, 269f ectopic atrial tachycardia, 278 management of, 270, 27 l f, 272t-273t MAT, 279 mechanisms underlying, 268 specific arrhythmias and therapies, 271-279 Wolff-Parkinson-White syndrome (WPW), 277-278 Surgery acute mediastinitis, 84 1-842 acute pancreatitis, 8 50-85 5 compartment syndrome o f abdominal cavity, 8 6 1 -864 epistaxis, 837-839 esophageal perforation, 840-841 intra-abdominal infections, 844-849 mesenteric ischemia, 857-860 necrotizing fasciitis and other soft tissue infections, 865-871 pain management, 875-882 pressure ulcers, 872-874 wound infections, 447 Surgical debridement after fluid resuscitation, 868 Sympathomimetics/pressor agents, 541 Synchronized intermittent mechanical ventilation (SIMV) , 367 Syncope, 1 7 4 autonomic control/reflex-mediated, 221 of cardiac etiology, 2 1 6 cardiac evaluation, 2 1 9-22 1 , 220t causes, 2 1 6, 2 1 7t-2 1 8t diagnosis, 2 1 7-22 1 differential diagnosis, 2 1 6 etiology, 2 1 6, 2 1 7t-2 1 8t general principles, 2 1 6 history, 2 1 8 indication fo r implantation of ICD in patients with, 222t indications for cardiac tests in patients with, 220t initial diagnostic evaluation, 2 1 7, 2 1 8 laboratory tests, 2 1 9 1 2-lead electrocardiogram, 2 1 9 neurological evaluation, 22 1 pathophysiology, 2 1 6 physical examination, 2 1 8-2 1 9 psychiatric evaluation, 2 l 8t treatment, 22 1-223

1 1 84

I n dex

Syndrome of inappropriate antidiuretic hormone secretion (SIADH), 4 1 9 Synovial fluid analysis, 1 0 9 Systemic asphyxiant, 823t-827t Systemic inflammatory response syndrome (SIRS), 1 5 1 , 955, see also Sepsis Systemic lupus erythematosus (SLE), 1 07, 1 1 16 Systemic opioid analgesia, 879 Systemic vascular resistance, 1 1 48 T

Tachyarrhythmias, 282, 284, 284t, 6 0 1 Tachycardia, 89 1 , 8 9 3 Tamoxifen, 707 Tamponade, 1 94-1 9 6 Target organ damage (TOD), 208 Tazobactam, 484, 493 T-cell immunosuppression diagnosis, 492-493 etiology, 492 general principles, 4 9 1 -492 pathophysiology, 492 treatment, 493-494 Telangiectasia, 522 Temperature monitoring, in ICU, 1 1 8 Tenecteplase (TNKase), 684t Terbucaline, 325 Tetanus diagnosis, 477 general principles, 477 pathogenesis, 477 treatment, 477-478 Tetracycline, 885 Thalidomide, 707-708 Therapeutic hypothermia (TH) clinical application of, 388 general principles, 387 induction phase, 388 maintenance phase, 388 pathophysiology, 388 rewarming phase, 388 Thermal diffusion, 99 Thermistor, 26 Thermodilution, 1 2 1 Thiazide diuretics, 596 Thiazides, l 1 44r Thiazolidinediones, 629 Thoracentesis general principles, 5 8 indications and contraindications, 5 8 interpretation o f pleural fluid analysis, 61

posrprocedure considerations, 60 procedure, 5 8-60 Thoracic aortic aneurysm (TAA) , 205 Thoracic trauma diagnosis, 9 5 1-952 etiology, 9 5 1 general principles, 9 5 1 immediate lifesaving interventions, 952 treatment, 952-953 Thoracic vertebrae, 2 Thoracotomy, 952 Thrombocytopenia, 642, 734 Thromboembolic disease, 322-323 Thromboembolic-deterrent (T.E.D.) hose, 1 037 Thromboembolism, 34, 253, 255, 276, 327 Thrombohemorrhagic events, in myeloproliferarive neoplasms bleeding, 699 clinical presentation, 699 diagnosis, 699-700, 700r general principles, 698-699 prognosis, 70 1 surgical procedures, 699 treatment, 700-70 1 Thrombolysis, 1 86 Thrombolyric therapy, 695 Thrombosis, 22-23 Thrombotic thrombocytopenic purpura (TTP) , 888 Thyroid autoantibodies, 614 Thyroid cartilage, 64 Thyroid emergencies myxedema coma, 604-607 thyroid storm, 600-604 Thyroid stimulating hormone (TSH), 609 Thyroid storm clinical features, 601 r diagnosis, 600-603, 602r general principles, 600 pathophysiology, 600 treatment, 603, 604r Thyroid tumors, 64 Thyromental distance, 2 Thyrotoxicosis, 623 Thyroxine (T4), 608 Ticlopidine (Ticlid), 666t Tidal volume (Vt) , 3 6 1 Tigecycline, 453t Tilt table rest, 220r, 22 1 Tinzaparin (Innohep), 675r Tirofiban, 230, 669t Tissue Doppler imaging, 1 2 5 Tissue ischemia, 956

I n dex

Tocolytic-induced pulmonary edema, 325, 328t Tocolytics, 886 Toll-like receptors (TLRs), 962-963 Torsades de pointes (TDP), 1 1 36 Total parenteral nutrition (TPN)-related liver injury, 5 5 5 Toxic megacolon definition, 548 endoscopy, 5 5 0 history, 548-549 laboratory studies, 549-5 5 0 physical examination, 549 radiologic studies, 5 5 0 surgery, 5 5 1-552 treatment, 5 50-5 52 Toxic procoagulant molecules, 642 Toxic shock syndrome (TSS), 870-871 diagnosis, 475 general principles, 475 pathogenesis, 475 treatment, 475-476 Toxoplasma cruzi, 1 070 Toxoplasma gondii, 490, 492, 1 044, 1 070, 1 093 Toxoplasma species, 94 Toxoplasmic encephalitis (TE) diagnosis, 499 etiology/pathogenesis, 499 general principles, 498-499 treatment, 499 TPN steatosis, 5 5 7 Trachea, 2 Tracheal stenosis, 67 Tracheobronchial aspiration, 542 Tracheobronchitis, 340 Tracheoinnominate artery fistula, 67-68 Tracheostomy, 338 1 anatomy of trachea, 63-64 general principles, 63 indications, 64 for obese people, 64 open technique, 65-66 percutaneous technique, 66-67 percutaneous vs. open tracheostomy, 68 postprocedure considerations, 67-68 semiopen, 67 Transcranial Doppler flow velociry, 99 Transcutaneous electrical nerve stimulation (TENS), 878 Transesophageal echocardiography (TEE), 36, 125, 1 7 5 , 1 82, 1 84, 1 86, 200, 466 indications, l 30t

I

1 1 85

limitations, 129 postprocedure considerations, 1 3 0 special preparations for, 1 29t standard examination, 1 26, 1 29-1 3 0 Transfusion therapy acute hemolytic transfusion reaction (AHTR), 727 allergic transfusion reaction, 729 citrate toxiciry, 729 cryoprecipitate, 726-727 delayed hemolytic transfusion reaction, 727 febrile nonhemolyric transfusion reaction, 729 fresh frozen plasma (FFP/FP24) , 726 infectious risks, 727, 728t platelets, 724-726, 725t red blood cells, 724, 725t transfusion risks, 727-729, 728t Transfusion-associated circulatory overload (TACO), 728-729 Transfusion-related acute lung injury (TRALI) , 304, 727-728 Transjugular intrahepatic portosystemic shunt (TIPS), 78, 525, 536-537, 655 Translaryngeal intubation, 3 3 8 Transplantation challenges, 1 0 5 5 considerations heart, 1 0 5 5 hematopoietic cell, 1 0 5 5 kidney, 1 054 liver, 1 054 lung, 1 0 5 5 pancreas and islet, 1 054 small bowel, 1 054 general principles, 1 052- 1 0 5 3 heart transplant recipients early allograft failure, 1 095 general principles, 1 092 heart-lung recipients, 1 096-1 097 immunosuppression, 1 094- 1 095 postoperative considerations, 1 093- 1 094 infection diagnosis, 1 070- 1 0 7 1 general principles, 1 069-1 070 pathogenesis, 1 070 therapy, 1 07 1 kidney transplant recipients general principles, 1 073 intraoperative care, 1 074 perioperative care, 1 074

1 1 86

I n dex

Transplantation (Continued) postoperative considerations, 1 074- 1 076 pretransplant evaluation, 1 073-1 074 malignancy diagnosis, 1 0 7 1 general principles, 1 07 1 pathogenesis, 1 07 1 therapy, 1 072 organ shortage and solutions, 1 053- 1 054 pancreas transplant recipients general principles, 1 077 intraoperative considerations, 1 078-1 079 postoperative care and considerations, 1 079- 1 084 pretransplant evaluation, 1 077-1 078 rejection complications, 1 069 diagnosis, 1 067-1 068 general principles, I 067 pathogenesis, I 067 therapy, 1 068- 1 069 Transport of critically ill patients care provided, 9 1 5 caution, 9 1 5 equipment considerations, 9 1 7 essentials, 9 1 5 indications, 9 1 6 monitoring, 9 1 5 patient evaluation, 9 1 6-9 1 7 postprocedure considerations, 9 1 8 procedure, 9 1 6-9 1 8 team composition, 9 1 8 transport physiology, 9 1 8 Transthoracic Doppler echocardiography (DE) , 348-349 Transthoracic echocardiography (TTE) , 466 Transverse myelitis (TM) , 1 044, 1 046 Trauma, 64 abdominal, 933-940 advanced trauma life support (ATLS), 9 1 1 AMPLE, 9 1 1 causes of, 9 1 0 centers and trauma systems, 9 1 3 complications, 888 general principles, 888 initial trauma care, 9 1 1 measuring injury severity/performance improvement/trauma registries, 9 1 2-9 1 3 military experience, 9 1 0 spinal cord, 924-93 1 treatment, 888 Trauma-induced coagulopathy, 643

Trauma/internal derangement, 1 07 Traumatic asphyxia, 953 Traumatic brain injury (TB!) cardiopulmonary complications, 922 cerebral salt wasting, 922 coagulopathy, 922 deep venous thrombosis and pulmonary embolus, 922 diabetes insipidus, 922 diagnosis, 920-92 1 , 920t etiology, 9 1 9 ICP monitoring, 92 1 , 922 nutrition, 922 pathophysiology, 9 1 9-920 principles, 9 1 9 seizures, 922 syndrome of inappropriate antidiuretic hormone (SIADH), 922 treatment, 921-922 Traumatic compartment syndromes complications, 957 diagnosis, 956-957 etiology, 955 general principles, 9 5 5 pathophysiology, 9 5 6 treatment, 9 5 7 Trendelenburg position, 1 3 , 326 Treponema pallidum, 1 044 Trichosporon species, 483 Tricyclic antidepressants (TCAs) , 1 1 46 Triiodothyronine (T3), 608 Trimethoprim-sulfamethoxazole (TMPSMX), 455t, 476, 497, 1 1 44t Triple airway maneuver, 5 Tropomyosin, 1 74 Troponin T, 1 74 Trousseau sign, 623 Trousseau's syndrome, 64 1 Tube migration, 8 5 Tube thoracostomy, 952 Tuberculin skin test (TST) , 504, 505 Tuberculosis (TB), 325 complications, 508 diagnosis, 497, 505-506 etiology, 497, 504 general principles, 497, 504 pathogenesis, 497 pathophysiology, 504-505 treatment, 497, 506-508 Tularemia diagnosis, 5 1 6-5 1 7 general principles, 5 1 6 pathogenesis, 5 1 6 treatment, 5 1 7

I n dex

Tumor compression, of the spinal cord, 1 035 Tumor lysis syndrome (TLS), 736 Cairo-Bishop definition, 74 l t diagnosis, 74 1 etiology, 74 1 pathophysiology, 740 prevention and treatment, 74 1 -742 Tumor necrosis factor (TNF)-a, 608 Type 1 deiodinase (D I ) , 608 Type 2 deiodinase (D2), 608 u

Ulcerative colitis, 548 Ulcerative colitis/regional enteritis, 1 07 Ultrasonographic-guided cannulation, 22 Ultrasound, see Intensive care unit Umbilicus, 73, 76 Unfractionated heparin (UFH) , 23 1 , 327, 67 1 , 672t, 690, 694, 695t, 704-705, 710 Unintentional hypothermia diagnosis, 386 etiology, 385 general principles, 385 pathogenesis, 38 5-386 treatment, 386-387 Unstable angina (UA)/non-ST-segment elevation myocardial infarction (NSTEMI) anticoagulant therapy, 231-232 antiplatelet therapy, 230-23 1 coronary revascularization, 232, 233f definition, 224 diagnosis, 224-225 dual-antiplatelet therapy, 233 ECG changes in, 225 GP IIb/IIIa inhibitors, 227 initial evaluation and risk stratification, 225-227, 226t, 227t invasive vs. conservative strategy, 230 long-term secondary prevention., 232-233, 234f management, 227-234 pathophysiology, 224 physical examination, 225 sequence of events in, 224 scents, 232 thrombolysis in myocardial infarction (TIMI) risk score for, 226-227, 227t thrombolytic therapy, 232 treatment strategy, 227, 228f

I

1 1 87

Upper airway infections deep space neck infections, 401-403 nosocomial sinusitis, 397-398 otogenic infections, 398 supraglottitis, 398-400 Uremia, 1 078 Urethral catheterization, 1 02, 1 04 Urinary bladder, 1 02 Urinary Legionella antigen, 407 Urinary tract infections (UTis) , 443 catheter-associated, 472 complications, 47 1 , 474 diagnosis, 4 72 etiology, 471 Gram-negative bacteria, 471 Gram-positive bacteria, 47 1 noncatheter-associated, 471 nosocomial, 471 pathophysiology, 471-472 requiring ICU, 471 treatment, 472-473 urinalysis, 4 72 Urine chloride concentration, 4 1 5 Urologic complications, posttransplantation, 1 075 Ursodeoxycholic acid, 557 v

Vagus innervation, 2 Valsalva maneuver, 270 Valve replacement, 1 8 1 , 1 82 Valvular heart disease, 1 80-1 87 Vancomycin, 408, 439, 454t, 476, 484, 546, 5 5 1 , 572-573, 885 Vancomycin-resistant enterococci (VRE) , 47 1 , 473 Variceal bleeding clinical presentation, 534 diagnosis, 534 endoscopy, 534 mortality rate, 533 pathophysiology, 533-534 portal hypertension, 533 resuscitation, 534 treatment, 534-538 Varicella, 325 Varicella zoster virus (VZV) , 94, 484, 1 044 Varicella-zoster infection, 325 Varices, 522 Vascular abnormalities, 642 Vascular disease, 430 Vascular ectasias, 522 Vasculitis, 1 07, 522

1 1 88

I n dex

Vasculitis, in ICU central nervous system, 1 1 30- 1 1 3 1 Churg-Strauss syndrome (CSS), 1 1 28- 1 1 29 cryoglobulinemic, 1 1 29-1 1 30 granulomatosis with polyangiitis (GPA) , 1 1 27-1 1 28 microscopic polyangiitis, 1 1 28 polyarteritis nodosa (PAN), 1 1 29 pulmonary capillaritis, 1 1 30 Vasoactive pharmacologic therapy and balloon tamponade, combined technique, 78 Vasopressors for hemorrhagic shock, 906 mean arterial pressure and cardiac dysfunction, 969-970 spinal tumors, I 036 Vecuronium, 1 1 7 Venipuncture, 1 1 , 1 2 Venlafaxine, 1 1 45-1 1 46 Venous air embolism, 324, 324t, 328t Venous blood gas (VBG), 1 32 Venous cannulation, 1 37 Venous drainage flows, I 02 Venous thromboembolism (VTE) clinical presentation, 6 9 1 -693 diagnosis, 693, 693t, 694t general principles, 690 prevention, 690-69 1 , 69 ! t, 692t treatment, 693t-698t, 694-698 Ventilation, 1 5 1 , 15 2 t Ventilator-associated pneumonia (VAP) , 53, 397, 404 Ventilator-dependent, with tracheostomy, 376 Ventricular fibrillation, 394 Ventricular hypertrophy, 40 Ventricular myocardium, 1 77 Ventricular tachycardia (VT), 33 definitions, 258 diagnosis, 25 9-260, 260f, 26 1 f, 262f ECG criteria, 259-260, 260f, 26 1 f, 262f monomorphic, 258, 259f nonsustained, 258 pharmacologic therapies, 264-266 polymorphic, 258, 259f sinusoidal, 258, 259f treatment, 260-264

Ventriculoperitoneal (VP) shunt, 94 Verapamil, 175, 272t Vidarabine, I 048 Videolaryngoscopes, 7 Viral cultures, 94 Viral infections, 735 Virchow triad, 709 Visceral layer, 1 9 0 Viscosity, of synovial fluid, 1 1 0 Visual evoked potentials (VEPs), I O I Vitamin K antagonists (VKAs) , 673, 680t-68 1 t Von Willebrand disease (VWD), 646t, 649-50, 838 Voriconazole, 455t, 485 V/Q mismatch, 299, 301 w

Warfarin, 243, 273t, 686t, 688, 860, I 037 Water deficit in hypernatremia, 1 1 49 Weaning noninvasive positive-pressure ventilation (NPPV) , 367 SB trial, 367 Wernicke encephalopathy, 598 West Nile Virus (WNV), 94 diagnosis, 5 1 6 general principles, 5 1 6 pathogenesis, 5 1 6 treatment, 5 1 6 Whipple triad, 628 Whole bowel irrigation, 832b Withdrawal syndrome, 827t-83 I t Wolff-Parkinson-White syndrome (WPW), 277-278 Wound exploration, 73 Wounds botulism, 476 classification, 873 infection, I 075 management, 873-874 WWHHHHIMPS mnemonic, 1 1 33, 1 1 33t z

Zero drift, 20 Zero referencing, 20 Zoledronate (Zometa), 623