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11 evidence based practice of critical care, 2e, 2016


EVIDENCE-BASED PRACTICE
of

CRITICAL CARE
second edition

Clifford S. Deutschman, MS, MD, FCCM
Vice Chair, Research, Department of Pediatrics
Professor of Pediatrics and Molecular Medicine
Hofstra North Shore-LIJ School of Medicine
New Hyde Park, New York
Investigator, Feinstein Institute for Medical Research
Manhasset, New York

Patrick J. Neligan, MA, MB, FRCAFRCSI
Department of Anaesthesia and Intensive Care
University College Galway
Galway, Ireland

iii



1600 John F. Kennedy Blvd.
Ste 1800
Philadelphia, PA 19103-2899
EVIDENCE-BASED PRACTICE OF CRITICAL CARE,
SECOND EDITION

ISBN: 978-0-323-29995-4

Copyright © 2016 by Elsevier, Inc. All rights reserved.
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Notices
Knowledge and best practice in this field are constantly changing. As new research and experience
broaden our understanding, changes in research methods, professional practices, or medical
treatment may become necessary.
Practitioners and researchers must always rely on their own experience and knowledge in
evaluating and using any information, methods, compounds, or experiments described herein. In
using such information or methods they should be mindful of their own safety and the safety of
others, including parties for whom they have a professional responsibility.
With respect to any drug or pharmaceutical products identified, readers are advised to check the
most current information provided (i) on procedures featured or (ii) by the manufacturer of each
product to be administered, to verify the recommended dose or formula, the method and duration
of administration, and contraindications. It is the responsibility of practitioners, relying on their
own experience and knowledge of their patients, to make diagnoses, to determine dosages and the
best treatment for each individual patient, and to take all appropriate safety precautions.
To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors,
assume any liability for any injury and/or damage to persons or property as a matter of products
liability, negligence or otherwise, or from any use or operation of any methods, products,
instructions, or ideas contained in the material herein.
Previous edition copyrighted 2010.
Library of Congress Cataloging-in-Publication Data
Deutschman, Clifford S., editor. | Neligan, Patrick J., editor.
Evidence-based practice of critical care / [edited by] Clifford S. Deutschman, Patrick J. Neligan.
Second edition. | Philadelphia, PA : Elsevier, [2016] |
Includes bibliographical references and index.
LCCN 2015041109 | ISBN 9780323299954 (pbk. : alk. paper)
| MESH: Critical Care. | Evidence-Based Medicine. | Intensive Care Units.
LCC RC86.7 | NLM WX 218 | DDC 616.02/8—dc23 LC record
  available at http://lccn.loc.gov/2015041109

Senior Content Strategist: Suzanne Toppy
Senior Content Development Specialist: Jennifer Ehlers
Publishing Services Manager: Patricia Tannian
Senior Project Manager: Claire Kramer
Design Direction: Julia Dummitt

Printed in the United States of America
Last digit is the print number: 9 8 7 6 5 4 3 2 1


To my family:
Chris, who makes everything possible—and worthwhile
Cate, Nicki, and Beth, who are now adults, and still make us proud every day,
and Linus, who makes it entertaining.
To my former colleagues in the
Surgical Intensive Care Unit at the Hospital of the University of Pennsylvania
(including my coauthor):
For tolerating 20 years of “Teaching by Confrontation” without ever taking it personally.
To my new colleagues at
the Cohen Children’s Medical Center and
the Feinstein Institute for Medical Research:
We will figure it out.
Clifford S. Deutschman, MS, MD
New York

To Diane, David, Conor, and Kate and to my parents Maurice and Dympna Neligan
for their continued support and wisdom.
Patrick J. Neligan, MA, MB, FRCAFRCSI


Contributors
Gareth L. Ackland, PhD, FRCA, FFICM

William Harvey Research Institute
Queen Mary University of London
London, United Kingdom
Chapter 48 What Is the Role of Autonomic ­Dysfunction
in Critical Illness?

Dijillali Annane, MD

General Intensive Care Unit
Raymond Poincaré Hospital (AP-HP)
University of Versailles SQY
Laboratory of Inflammation and Infection U1173 INSERM
Garches, France
Chapter 71 Is There a Place for Anabolic ­Hormones in
Critical Care?

Pierre Asfar, MD, PhD

Département de Réanimation Médicale et de Médecine
Hyperbare
Centre Hospitalier Universitaire Angers
Angers, France
Chapter 40 What MAP Objectives Should Be Targeted in
Septic Shock?

John G. Augoustides, MD, FASE, FAHA

Professor
Anesthesiology and Critical Care
Perelman School of Medicine
University of Pennsylvania
Philadelphia, Pennsylvania
Chapter 52 When Is Hypertension a True Crisis, and How
Should It Be Managed in the Intensive Care Unit?
Chapter 82 Which Anticoagulants Should Be Used in the
Critically Ill Patient? How Do I Choose?

Hollman D. Aya, MD

Clinical and Research Fellow
Intensive Care Department
St. George’s University Hospitals NHS Foundation Trust
London, United Kingdom
Chapter 84 Does ICU Admission Improve Outcome?

Lorenzo Ball, MD

IRCCS AOU San Martino-IST
Department of Surgical Sciences and Integrated
Diagnostics
University of Genoa
Genoa, Italy
Chapter 8 How Does One Evaluate and Monitor
Respiratory Function in the Intensive Care Unit?

Arna Banerjee, MD

Associate Professor of Anesthesiology, Surgery, and
Medical Education
Department of Anesthesiology and Critical Care
Vanderbilt University Medical Center
Nashville, Tennessee
Chapter 73 How Does One Diagnose, Treat, and Reduce
Delirium in the Intensive Care Unit?

John Bates, MD

Anaesthesia and Intensive Care Medicine
University Hospital Galway
Galway, Ireland
Chapter 24 How Do I Transport the Critically Ill Patient?

S. V. Baudouin, MD, FRCP, FICM

Department of Anaesthesia
Royal Victoria Infirmary
Newcastle upon Tyne, United Kingdom
Chapter 36 Are Anti-inflammatory Therapies in ARDS
Effective?

Michael Bauer, MD

Center for Sepsis Control and Care
Department of Anesthesiology and Critical Care Medicine
Jena University Hospital
Jena, Germany
Chapter 68 How Does Critical Illness Alter the Liver?

Jeremy R. Beitler, MD, MPH

Division of Pulmonary and Critical Care Medicine
University of California, San Diego
San Diego, California
Chapter 28 What Is the Clinical Definition of ARDS?

Rinaldo Bellomo, MD, FCICM

Australia and New Zealand Intensive Care Research Centre
Department of Epidemiology and Preventive Medicine
Monash University
Melbourne, Australia
Chapter 5 Do Early Warning Scores and Rapid Response
Teams Improve Outcomes?

François Beloncle, MD

Département de Réanimation Médicale et de Médecine
Hyperbare
Centre Hospitalier Universitaire Angers
Angers, France
Chapter 40 What MAP Objectives Should Be Targeted in
Septic Shock?

vii


viii    Contributors

Kimberly S. Bennett, MD, MPH

Associate Professor
Pediatric Critical Care
University of Colorado School of Medicine
Denver, Colorado
Chapter 11 Is Extracorporeal Life Support an EvidenceBased Intervention for Critically Ill Adults with ARDS?

Paulomi K. Bhalla, MD

Fellow, Division of Neurocritical Care
Neurology
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania
Chapter 63 How Should Aneurysmal Subarachnoid
Hemorrhage Be Managed?

Maneesh Bhargava, MD

Assistant Professor of Pulmonary, Allergy, Critical Care,
and Sleep Medicine
University of Minnesota Medical School
Minneapolis, Minnesota
Chapter 32 Do Patient Positioning in General and Prone
Positioning in Particular Make a Difference in ARDS?

Alain F. Broccard, MD

St Vincent Seton Specialty Hospital
Indianapolis, Indiana
Chapter 32 Do Patient Positioning in General and Prone
Positioning in Particular Make a Difference in ARDS?

Josée Bouchard, MD

Division of Nephrology
Department of Medicine
University of Montreal
Montreal, Canada
Chapter 56 How Does One Optimize Care in Patients at
Risk for or Presenting with Acute Kidney Injury?

Naomi E. Cahill, RD, PhD

Department of Public Health Sciences
Queen’s University
Kingston, Ontario, Canada
Chapter 67 Is It Appropriate to “Underfeed” the Critically
Ill Patient?

Andrea Carsetti, MD

Anaesthesia and Intensive Care Unit
Department of Biomedical Sciences and Public Health
Università Politecnica delle Marche
Ancona, Italy
Department of Intensive Care Medicine
St George’s University Hospitals NHS Foundation Trust
London, United Kingdom
Chapter 84 Does ICU Admission Improve Outcome?

Maurizio Cecconi, MD

Department of Intensive Care
St. George’s Hospital
London, United Kingdom
Chapter 84 Does ICU Admission Improve Outcome?

Celina D. Cepeda, MD

Division of Pediatric Nephrology
Pediatric Department
Rady Children’s Hospital
Division of Nephrology and Hypertension
Department of Medicine
University of California, San Diego
San Diego, California
Chapter 56 How Does One Optimize Care in Patients at
Risk for or Presenting with Acute Kidney Injury?

Maurizio Cereda, MD

Assistant Professor of Anesthesia and Critical Care
Department of Anesthesia and Critical Care
Perelman School of Medicine at the University of
Pennsylvania
Philadelphia, Pennsylvania
Chapter 10 How Does Mechanical Ventilation Damage
Lungs? What Can Be Done to Prevent It?

John Chandler, MD, BDS, FDSRCS,
FCARCSI

Consultant in Anaesthesia and Intensive Care
Cork University Hospital
Cork, Ireland
Chapter 24 How Do I Transport the Critically Ill Patient?

Randall M. Chesnut, MD, FCCM, FACS

Integra Endowed Professor of Neurotrauma
Department of Neurological Surgery
Department of Orthopaedic Surgery
Adjunct Professor
School of Global Health
Harborview Medical Center
University of Washington
Seattle, Washington
Chapter 61 Is It Really Necessary to Measure Intracranial
Pressure in Brain-Injured Patients?

Meredith Collard, MD

Department of Anesthesiology and Critical Care
Perelman School of Medicine
University of Pennsylvania
Philadelphia, Pennsylvania
Chapter 6 What Are the Indications for Intubation in the
Critically Ill Patient?

Maya Contreras, MD, PhD, FCARCSI

Department of Anesthesia
St. Michael’s Hospital
Toronto, Ontario, Canada
Chapter 31 Is Permissive Hypercapnia Useful in ARDS?

David J. Cooper, MD, BM, BS

Australian and New Zealand Intensive Care–Research
Centre
School of Public Health and Preventive Medicine
Monash University
Alfred Hospital Campus
The Alfred Hospital
Melbourne, Australia
Chapter 9 What Is the Optimal Approach to Weaning and
Liberation from Mechanical Ventilation?


Contributors    ix

Craig M. Coopersmith, MD

Professor of Surgery
Department of Surgery
Associate Director
Emory Critical Care Center
Vice Chair of Research
Department of Surgery
Director
Surgical/Transplant Intensive Care Unit
Emory University Hospital
Atlanta, Georgia
Chapter 46 Is Selective Decontamination of the Digestive
Tract Useful?

David Cosgrave, MB, BCh, BAO

Anaesthesia SPR
University Hospital Galway
Galway, Ireland
Chapter 24 How Do I Transport the Critically Ill Patient?

Cheston B. Cunha, MD

Assistant Professor of Medicine
Division of Infectious Disease
Medical Director, Antimicrobial Stewardship Program
Rhode Island Hospital and the Miriam Hospital
Brown University Alpert School of Medicine
Providence, Rhode Island
Chapter 17 What Strategies Can Be Used to Optimize
Antibiotic Use in the Critically Ill?

Gerard F. Curley, PhD, MB, MSc, FCAI,
FJFICM

Departments of Anesthesia and Critical Care
Keenan Research Centre for Biomedical Science of St
Michael’s Hospital
St. Michael’s Hospital
Department of Anesthesia and Interdepartmental Division
of Critical Care
University of Toronto
Toronto, Ontario, Canada
Chapter 39 What Is the Role of Empirical Antibiotic
Therapy in Sepsis?

Randall J. Curtis, MD

Professor
Division of Pulmonary and Critical Care Medicine
A. Bruce Montgomery–American Lung Association Endowed
Chair in Pulmonary and Critical Care Medicine
Section Head
Harborview Medical Center
Director
Cambia Palliative Care Center of Excellence
Harborview Medical Center
Seattle, Washington
Chapter 87 What Factors Influence a Family to Support a
Decision Withdrawing Life Support?

Allison Dalton, MD

Assistant Professor of Anesthesia and Critical Care
Department of Anesthesia and Critical Care
University of Chicago
Chicago, Illinois
Chapter 15 How Do I Manage Hemodynamic
Decompensation in a Critically Ill Patient?

Kathryn A. Davis, MD, MTR

Medical Director
Epilepsy Monitoring Unit
Assistant Professor of Neurology
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania
Chapter 65 How Should Status Epilepticus Be Managed?

Daniel De Backer, MD, PhD

Department of Intensive Care
Erasme University Hospital
Brussels, Belgium
Chapter 13 What Is the Role of Invasive Hemodynamic
Monitoring in Critical Care?

Clifford S. Deutschman, MS, MD, FCCM

Vice Chair, Research, Department of Pediatrics
Professor of Pediatrics and Molecular Medicine
Hofstra North Shore–LIJ School of Medicine
New Hyde Park, New York
Investigator, Feinstein Institute for Medical Research
Manhasset, New York
Chapter 1 Critical Care Versus Critical Illness
Chapter 37 What Is Sepsis? What Is Septic Shock? What
Are MODS and Persistent Critical Illness?
Chapter 49 Is Sepsis-Induced Organ Dysfunction an
Adaptive Response?
Chapter 52 When Is Hypertension a True Crisis, and How
Should It Be Managed in the Intensive Care Unit?

Margaret Doherty, BMedSci, MB BCh BAO,
FFARCSI, EDIC
Interdepartmental Division of Critical Care Medicine
University Health Network
University of Toronto
Toronto, Ontario, Canada
Chapter 30 What Is the Best Mechanical Ventilation
Strategy in ARDS?

Tom Doris, MD FRCA

Department of Anaesthesia
Royal Victoria Infirmary
Newcastle upon Tyne, United Kingdom
Chapter 36 Are Anti-inflammatory Therapies in ARDS
Effective?


x    Contributors

Todd Dorman, MD, FCCM

Senior Associate Dean for Education Coordination
Associate Dean Continuing Medical Education
Professor and Vice Chair for Critical Care
Department of Anesthesiology and Critical Care Medicine
Joint Appointments in Medicine, Surgery, and the School
of Nursing
Johns Hopkins University School of Medicine
Baltimore, Maryland
Chapter 85 How Should Care Within an Intensive Care
Unit or an Institution Be Organized?

Tomas Drabek, MD, PhD

Associate Professor of Anesthesiology
Scientist
Safar Center for Resuscitation Research
University of Pittsburgh School of Medicine
Pittsburgh, Pennsylvania
Chapter 22 Is Hypothermia Useful in Managing Critically
Ill Patients? Which Ones? Under What Conditions?

Stephen Duff, MB BCh

St. Vincent’s University Hospital
Dublin, Ireland
Chapter 9 What Is the Optimal Approach to Weaning and
Liberation from Mechanical Ventilation?

Eimhin Dunne, MRCS, PG Dip (Clin pharm)
Critical Care Clinical Fellow
King’s College Hospital
London, United Kingdom
Chapter 18 Is Prophylaxis for Stress Ulceration Useful?

Ali A. El Solh, MD, MPH

Division of Pulmonary, Critical Care, and Sleep Medicine
Department of Medicine and Department of Social and
Preventive Medicine
State University of New York at Buffalo School of
Medicine and Biomedical Sciences and School of Public
Health and Health Professions
VA Western New York Healthcare System
Buffalo, New York
Chapter 23 What Are the Special Considerations in the
Management of Morbidly Obese Patients in the Intensive
Care Unit?

E. Wesley Ely, MD, MPH

Professor of Medicine
Associate Director of Research GRECC
Center for Health Services Research
Department of Allergy, Pulmonary, and Critical Care
Medicine
Vanderbilt University Medical Center
Nashville, Tennessee
Chapter 73 How Does One Diagnose, Treat, and Reduce
Delirium in the Intensive Care Unit?

Andrés Esteban, MD, PhD

Departamento de Cuidados Intensivos
CIBER de Enfermedades Respiratorias
Hospital Universitario de Getafe
Madrid, Spain
Chapter 28 What Is the Clinical Definition of ARDS?

Laura Evans, MD

Associate Professor
Department of Medicine
New York University School of Medicine
New York, New York
Chapter 43 Do the Surviving Sepsis Campaign
Guidelines Work?

Niall D. Ferguson, MD, FRCPC, MSc

Interdepartmental Division of Critical Care Medicine
University Health Network
University of Toronto
Toronto, Ontario, Canada
Chapter 30 What Is the Best Mechanical Ventilation
Strategy in ARDS?

Jonathan Frogel, MD

Assistant Professor
Anesthesiology and Critical Care
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania
Chapter 53 How Does One Prevent or Treat Atrial
Fibrillation in Postoperative Critically Ill Patients?

Jakub Furmaga, MD

Assistant Professor of Emergency Medicine
Faculty in Medical Toxicology
University of Texas Southwestern Medical Center
Dallas, Texas
Chapter 79 How Do I Diagnose and Manage Patients
Admitted to the ICU After Common Poisonings?

Ognjen Gajic, MD

Professor of Medicine
Pulmonary and Critical Care Medicine
Mayo Clinic
Rochester, Minnesota
Chapter 12 What Factors Predispose Patients to Acute
Respiratory Distress Syndrome?

Alice Gallo De Moraes, MD

Department of Medicine–Division of Pulmonary and
Critical Care
Mayo Clinic
Rochester, Minnesota
Chapter 12 What Factors Predispose Patients to Acute
Respiratory Distress Syndrome?

Erik Garpestad, MD

Associate Chief, Pulmonary, Critical Care, and Sleep Division
Director, Medical ICU
Associate Professor
Tufts University School of Medicine
Boston, Massachusetts
Chapter 7 What Is the Role of Noninvasive Ventilation in
the Intensive Care Unit?

Hayley B. Gershengorn, MD

Departments of Medicine and Neurology
Albert Einstein College of Medicine
Montefiore Medical Center
Bronx, New York
Chapter 3 Have Critical Care Outcomes Improved?


Contributors    xi

Emily K. Gordon, MD

Assistant Professor
Anesthesiology and Critical Care
Perelman School of Medicine
University of Pennsylvania
Philadelphia, Pennsylvania
Chapter 52 When Is Hypertension a True Crisis, and How
Should It Be Managed in the Intensive Care Unit?
Chapter 82 Which Anticoagulants Should Be Used in the
Critically Ill Patient? How Do I Choose?

W. Robert Grabenkort, PA MMSc, FCCM

Director
Nurse Practitioner/Physician Assistant Residency
Program
Emory Critical Care Center
Emory Healthcare
Atlanta, Georgia
Chapter 86 What Is the Role of Advanced Practice Nurses
and Physician Assistants in the ICU?

Guillem Gruartmoner, MD

Department of Critical Care
Corporació Sanitària Universitària Parc Taulí
Hospital de Sabadell
Universitat Autònoma de Barcelona
Barcelona, Spain
Department of Intensive Care
Erasmus Medical Center
Rotterdam, The Netherlands
Chapter 42 How Can We Monitor the Microcirculation in
Sepsis? Does It Improve Outcome?

Jacob T. Gutsche, MD

Assistant Professor
Cardiothoracic and Vascular Section
Anesthesiology and Critical Care
Perelman School of Medicine
University of Pennsylvania
Philadelphia, Pennsylvania
Chapter 26 How Do I Diagnose and Treat Pulmonary
Embolism?
Chapter 52 When Is Hypertension a True Crisis, and How
Should It Be Managed in the Intensive Care Unit?

Scott Halpern, MD, PhD

Associate Professor of Medicine, Epidemiology, and
Medical Ethics and Health Policy
Director
Fostering Improvement in End-of-Life Decision Science
Program
Deputy Director
Center for Health Incentives & Behavioral Economics
Department of Medical Ethics and Health Policy
Perelman School of Medicine
University of Pennsylvania
Philadelphia, Pennsylvania
Chapter 83 How Can Critical Care Resource Utilization in
the United States Be Optimized?

Ivan Hayes, MD

Consultant Intensivist
Cork University Hospital
Cork, Ireland
Chapter 18 Is Prophylaxis for Stress Ulceration Useful?

Nicholas Heming, MD

General Intensive Care Unit
Raymond Poincaré Hospital (AP-HP)
University of Versailles SQY
Garches, France
Chapter 71 Is There a Place for Anabolic Hormones in
Critical Care?

Daren K. Heyland, MD

Department of Critical Care Medicine
Queen’s University
Clinical Evaluation Research Unit
Kingston General Hospital
Kingston, Ontario, Canada
Chapter 67 Is It Appropriate to “Underfeed” the Critically
Ill Patient?

Nicholas S. Hill, MD

Investigator
Pulmonary Hypertension Clinic at Rhode Island Hospital
Providence, Rhode Island
Chief of the Pulmonary, Critical Care, and Sleep Division
at Tufts-New England Medical Center
Professor of Medicine
Tufts University School of Medicine
Boston, Massachusetts
Chapter 7 What Is the Role of Noninvasive Ventilation in
the Intensive Care Unit?

Eliotte Hirshberg, MD, MS

Critical Care Attending Physician
Intermountain Medical Center
Associate Professor
Internal Medicine
Division of Pulmonary and Critical Care Medicine
Assistant Professor (Adjunct) Pediatrics
Division of Critical Care
University of Utah
Salt Lake City, Utah
Chapter 11 Is Extracorporeal Life Support an EvidenceBased Intervention for Critically Ill Adults with ARDS?

R. Duncan Hite, MD

Professor and Chairman
Department of Critical Care Medicine
Respiratory Institute
Cleveland Clinic
Cleveland, Ohio
Chapter 11 Is Extracorporeal Life Support an EvidenceBased Intervention for Critically Ill Adults with ARDS?


xii    Contributors

Steven M. Hollenberg, MD

Gabriella Jäderling, MD, PhD

Richard S. Hotchkiss, MD

Marc G. Jeschke, MD, PhD, FACS, FCCM,
FRCS(C)

Professor of Medicine
Cooper Medical School of Rowan University
Director, Coronary Care Unit
Cooper University Hospital
Camden, New Jersey
Chapter 54 Is Right Ventricular Failure Common in the
Intensive Care Unit? How Should It Be Managed?
Professor of Anesthesiology, Medicine, Surgery, Molecular
Biology and Pharmacology
Washington University School of Medicine
St. Louis, Missouri
Chapter 38 Is There Immune Suppression in the Critically
Ill Patient?

Can Ince, PhD

Department of Intensive Care
Erasmus Medical Center
Rotterdam, The Netherlands
Chapter 42 How Can We Monitor the Microcirculation in
Sepsis? Does It Improve Outcome?

Margaret Isaac, MD

Assistant Professor of Medicine
Attending Physician
General Internal Medicine and Palliative Care
University of Washington/Harborview Medical Center
Seattle, Washington
Chapter 87 What Factors Influence a Family to Support a
Decision Withdrawing Life Support?

Shiro Ishihara, MD

Biomarkers and Heart Diseases
UMR-942
Institut National de la Santé et de la Recherche Médicale
(INSERM)
Paris, France
Nippon Medical School Musashi-Kosugi Hospitals
Kanagawa, Japan
Chapter 50 How Do I Manage Acute Heart Failure?

Theodore J. Iwashyna, MD, PhD

Associate Professor, Department of Internal Medicine
Faculty Associate, Survey Research Center, Institute for
Social Research
Research Scientist, Center for Clinical Management
Research
Ann Arbor VA Health Services Research and Development
Co-Director, Robert Wood Johnson Foundation Clinical
Scholars Program
Ann Arbor, Michigan
Chapter 4 What Problems Are Prevalent Among Survivors
of Critical Illness and Which of Those Are Consequences of
Critical Illness?

Department of Anesthesiology
Surgical Services and Intensive Care
Karolinska University Hospital
Stockholm, Sweden
Chapter 5 Do Early Warning Scores and Rapid Response
Teams Improve Outcomes?

Professor at the University of Toronto
Department of Surgery
Division of Plastic Surgery
Department of Immunology
Director, Ross Tilley Burn Centre
Sunnybrook Health Sciences Centre
Chair in Burn Research
Senior Scientist
Sunnybrook Research Institute
Toronto, Ontario, Canada
Chapter 76 How Should Patients with Burns Be Managed
in the Intensive Care Unit?

Lewis J. Kaplan, MD

Section Chief
Surgical Critical Care
Philadelphia VA Medical Center
Associate Professor of Surgery
Division of Trauma, Surgical Critical Care, and Emergency
Surgery
Perelman School of Medicine
University of Pennsylvania
Philadelphia, Pennsylvania
Chapter 75 What Is Abdominal Compartment Syndrome
and How Should It Be Managed?

Scott E. Kasner, MD

Professor of Neurology University of Pennsylvania
Director
Comprehensive Stroke Center
University of Pennsylvania Health System
Philadelphia, Pennsylvania
Chapter 64 How Should Acute Ischemic Stroke Be
Managed in the Intensive Care Unit?

Colm Keane, MD

Department of Anaesthesia and Intensive Care
National University of Ireland
Galway, Ireland
Chapter 41 What Vasopressor Agent Should Be Used in the
Septic Patient?

Mark T. Keegan, MB, MRCPI, MSc

Professor
Division of Critical Care
Department of Anesthesiology
Mayo Clinic and Mayo Clinic College of Medicine
Rochester, Minnesota
Chapter 69 How Is Acute Liver Failure Managed?


Contributors    xiii

Leo G. Kevin, MD, FCARCSI

Benjamin A. Kohl, MD

Fiona Kiernan, MB BCh BAO, B Med Sc,
FCAI, MSc

Andreas Kortgen, MD

Department of Anaesthesia
University College Hospitals
Galway, Ireland
Chapter 33 Is Pulmonary Hypertension Important in
ARDS? Should We Treat It?

Professor of Anesthesiology
Sidney Kimmel Medical College of the Thomas Jefferson
University
Philadelphia, Pennsylvania
Chapter 51 How Is Cardiogenic Shock Diagnosed and Managed
in the Intensive Care Unit?

Department of Anesthesia and Intensive Care
RCSI Smurfit
Beaumont Hospital
Dublin, Ireland,
Chapter 39 What Is the Role of Empirical Antibiotic
Therapy in Sepsis?

Center for Sepsis Control and Care
Department of Anesthesiology and Critical Care Medicine
Jena University Hospital
Jena, Germany
Chapter 68 How Does Critical Illness Alter the Liver?

Ruth Kleinpell, PhD, RN, FAAN, FCCM

Department of Anesthesia
Critical Illness and Injury Research Centre
Keenan Research Centre for Biomedical Science
St. Michael’s Hospital
Departments of Anesthesia, Physiology, and Interdepartmental Division of Critical Care Medicine
University of Toronto
Toronto, Ontario, Canada
Chapter 31 Is Permissive Hypercapnia Useful in ARDS?

Director, Center for Clinical Research and Scholarship
Rush University Medical Center
Professor, Rush University College of Nursing
Chicago, Illinois
Chapter 86 What Is the Role of Advanced Practice Nurses
and Physician Assistants in the ICU?

Kurt Kleinschmidt, MD

Professor of Emergency Medicine
Division Chief and Program Director, Medical Toxicology
University of Texas Southwestern Medical School
Dallas, Texas
Chapter 79 How Do I Diagnose and Manage Patients
Admitted to the ICU After Common Poisonings?

Patrick M. Kochanek, MD, FCCM

Professor and Vice Chairman
Department of Critical Care Medicine
Professor of Anesthesiology, Pediatrics and Clinical and
Translational Science
Director, Safar Center for Resuscitation Research
University of Pittsburgh School of Medicine
Pittsburgh, Pennsylvania
Chapter 22 Is Hypothermia Useful in Managing Critically
Ill Patients? Which Ones? Under What Conditions?

W. Andrew Kofke, MD

Professor
Director of Neuroscience in Anesthesiology and Critical
Care Program
Co-Director Neurocritical Care
Co-Director Perioperative Medicine and Pain Clinical
Research Unit
Department of Anesthesiology and Critical Care
Department of Neurosurgery
University of Pennsylvania
Philadelphia, Pennsylvania
Chapter 62 How Should Traumatic Brain Injury Be
Managed?

John G. Laffey, MD, MA, FCAI

Francois Lamontagne, MD

Assistant Professor
Department of Medicine
Division of Internal Medicine
Faculty of Medicine and Health Sciences
Université de Sherbrooke
Sherbrooke, Québec, Canada
Chapter 34 Inhaled Vasodilators in ARDS: Do They Make
a Difference?

Meghan Lane-Fall, MD

Assistant Professor of Anesthesiology and Critical Care at
the Hospital of the University of Pennsylvania
Core Faculty
Center for Healthcare Improvement and Patient Safety
Department of Medicine
Senior Fellow
Leonard Davis Institute of Health Economics
Philadelphia, Pennsylvania
Chapter 6 What Are the Indications for Intubation in the
Critically Ill Patient?

Michael Lanspa, MD, MS

Adjunct Assistant Professor
Department of Pulmonary and Critical Care Medicine
Intermountain Medical Center and University of Utah
Salt Lake City, Utah
Chapter 11 Is Extracorporeal Life Support an EvidenceBased Intervention for Critically Ill Adults with ARDS?

David Lappin, MD

Galway University Hospitals
Galway, Ireland
Chapter 57 What Is the Role of Renal Replacement Therapy
in the Intensive Care Unit?


xiv    Contributors

Michael Lava, MD

John Lyons, MD

Joshua M. Levine, MD

Larami MacKenzie, MD

Fellow in Pulmonary and Critical Care
Emory University School of Medicine
Atlanta, Georgia
Chapter 29 What Are the Pathologic and Pathophysiologic
Changes That Accompany Acute Lung Injury and ARDS?
Chief
Division of Neurocritical Care
Department of Neurology
Co-Director
Neurocritical Care Program
Associate Professor
Departments of Neurology, Neurosurgery, and
Anesthesiology and Critical Care
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania
Chapter 63 How Should Aneurysmal Subarachnoid
Hemorrhage Be Managed?
Chapter 64 How Should Acute Ischemic Stroke Be
Managed in the Intensive Care Unit?
Chapter 65 How Should Status Epilepticus Be Managed?

Andrew T. Levinson, MD, MPH

Assistant Professor of Medicine
Warren Alpert School of Medicine at Brown University
Providence, Rhode Island
Chapter 2 What Lessons Have Intensivists Learned During
the Evidence-Based Medicine Era?

Mitchell M. Levy, MD

Professor of Medicine
Chief, Division of Pulmonary, Critical Care, and Sleep
Medicine
Warren Alpert Medical School at Brown University
Director of the Medical Intensive Care Unit
Rhode Island Hospital
Providence, Rhode Island
Chapter 2 What Lessons Have Intensivists Learned During
the Evidence-Based Medicine Era?

Department of Surgery
Emory University
Atlanta, Georgia
Chapter 46 Is Selective Decontamination of the Digestive
Tract Useful?
Associate Director
Neurocritical Care
Abington Jefferson Health
Abington, Pennsylvania
Chapter 62 How Should Traumatic Brain Injury Be
Managed?

Anita K. Malhotra, MD

Assistant Professor of Anesthesiology
Director, Critical Care Anesthesia Fellowship
Penn State Hershey Medical Center
Hershey, Pennsylvania
Chapter 26 How Do I Diagnose and Treat Pulmonary
Embolism?

Joshua A. Marks, MD

Fellow
Division of Traumatology, Surgical Critical Care, and
Emergency Surgery
Department of Surgery
Perelman School of Medicine at the University of
Pennsylvania
Philadelphia, Pennsylvania
Chapter 10 How Does Mechanical Ventilation Damage
Lungs? What Can Be Done to Prevent It?

Brian Marsh, MD

Anaesthesia and Intensive Care Medicine
Mater Misericordiae University Hospital
Dublin, Ireland
Chapter 18 Is Prophylaxis for Stress Ulceration Useful?

John C. Marshall, MD, FRCSC

Vice Chair for Pediatric Laboratory Research
Department of Anesthesiology
Division of Pediatric Anesthesia
Columbia University College of Physicians and Surgeons
Columbia University Medical Center
New York, New York
Chapter 49 Is Sepsis-Induced Organ Dysfunction an
Adaptive Response?

Scientist
Keenan Research Center for Biomedical Science of the Li
Ka Shing Knowledge Institute
St. Michael’s Hospital
Professor
Surgery/General Surgery
University of Toronto
Toronto, Ontario, Canada
Chapter 47 Is Persistent Critical Illness an Iatrogenic
Disorder?

José Angel Lorente, MD

Greg S. Martin, MD, MSc

Richard J. Levy, MD

Departamento de Cuidados Intensivos
CIBER de Enfermedades Respiratorias
Hospital Universitario de Getafe
Universidad Europea de Madrid
Madrid, Spain
Chapter 28 What Is the Clinical Definition of ARDS?

Professor and Associate Division Director for Critical Care
Division of Pulmonary, Allergy, and Critical Care
Emory University School of Medicine
Director of Research, Emory Center for Critical Care
Section Chief for Pulmonary, Allergy, and Critical Care
Grady Memorial Hospital
Atlanta, Georgia
Chapter 29 What Are the Pathologic and Pathophysiologic
Changes That Accompany Acute Lung Injury and ARDS?


Contributors    xv

Allie M. Massaro, MD

Resident
Department of Neurology
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania
Chapter 64 How Should Acute Ischemic Stroke Be
Managed in the Intensive Care Unit?

Claire Masterson, MSc, PhD

Department of Anesthesia
Keenan Research Centre in the Li Ka Shing Knowledge
Institute
Critical Illness and Injury Research Centre
Keenan Research Centre for Biomedical Science
St. Michael’s Hospital
Departments of Anesthesia and Physiology
University of Toronto
Toronto, Ontario, Canada
Chapter 31 Is Permissive Hypercapnia Useful in ARDS?

Virginie Maxime, MD

General Intensive Care Unit
Raymond Poincaré Hospital (AP-HP)
University of Versailles SQY
Laboratory of Cell Death Inflammation and Infection
Garches, France
Chapter 71 Is There a Place for Anabolic Hormones in
Critical Care?

Danny McAuley, MD, MRCP, DICM

Professor and Consultant in Intensive Care Medicine
Regional Intensive Care Unit
Royal Victoria Hospital
The Wellcome Wolfson Institute for Experimental
Medicine
Queen’s University Belfast
Belfast, Northern Ireland
Chapter 35 Do Nonventilatory Strategies for Acute
Respiratory Distress Syndrome Work?

Kevin W. McConnell, MD

Department of Surgery and Emory Center for Critical
Care
Atlanta, Georgia
Chapter 70 How Does Critical Illness Alter the Gut? How
Does One Manage These Alterations?

Gráinne McDermott, MB BCh, FCARCSI,
FJFICM

Consultant in Cardiothoracic Anaesthesia
Harefield Hospital
Middlesex, United Kingdom
Chapter 41 What Vasopressor Agent Should Be Used in the
Septic Patient?

Bruce A. McKinley, PhD

Professor of Surgery
Department of Surgery
University of Florida College of Medicine
Gainesville, Florida
Chapter 25 Are Computerized Algorithms Useful in
Managing the Critically Ill Patient?

Maureen O. Meade, MD

Critical Care Consultant
Hamilton Health Sciences
Professor
Department of Medicine
McMaster University
Hamilton, Ontario, Canada
Chapter 34 Inhaled Vasodilators in ARDS: Do They Make
a Difference?

Alexandre Mebazaa, MD, PhD

Biomarkers and Heart Diseases
UMR-942
Institut National de la Santé et de la Recherche Médicale
(INSERM)
Department of Anesthesiology and Intensive Care
Lariboisière-Saint-Louis University Hospital
Assistance Publique–Hôpitaux de Paris
Université Paris Diderot
Paris, France
Chapter 50 How Do I Manage Acute Heart Failure?

Ravindra L. Mehta, MD

Professor of Clinical Medicine
Associate Chair for Clinical Research
Department of Medicine
Director, UC San Diego CREST and Masters of Advanced
Studies in Clinical Research Program
University of California San Diego Health System
San Diego, California
Chapter 56 How Does One Optimize Care in Patients at
Risk for or Presenting with Acute Kidney Injury?

Jaume Mesquida, MD

Department of Critical Care
Corporació Sanitària Universitària Parc Taulí
Hospital de Sabadell
Universitat Autònoma de Barcelona
Barcelona, Spain
Chapter 42 How Can We Monitor the Microcirculation in
Sepsis? Does It Improve Outcome?

B. Messer, FRCA, MRCP, DICM

Department of Anaesthesia
Royal Victoria Infirmary
Newcastle upon Tyne, United Kingdom
Chapter 36 Are Anti-inflammatory Therapies in ARDS
Effective?

Imran J. Meurling, MB BCh BAO, MRCPUK

Specialist Registrar in Respiratory Medicine
Galway University Hospital
National University of Ireland
Galway, Ireland
Chapter 27 Should Exacerbations of COPD Be Managed in
the Intensive Care Unit?

Rohit Mittal, MD

Department of Surgery and Emory Center for Critical Care
Atlanta, Georgia
Chapter 70 How Does Critical Illness Alter the Gut? How
Does One Manage These Alterations?


xvi    Contributors

Xavier Monnet, MD, PhD

Service de reanimation
Paris-Sud University Hospitals
Paris-Sud University
Orsay, France
Chapter 16 What Are the Best Tools to Optimize the
Circulation?

Alan H. Morris, MD

Professor of Internal Medicine
Adjunct Professor of Biomedical Informatics
University of Utah School of Medicine
Director, Urban Central Region Pulmonary Laboratories
Intermountain Healthcare
Salt Lake City, Utah
Chapter 11 Is Extracorporeal Life Support an EvidenceBased Intervention for Critically Ill Adults with ARDS?

Vikramjit Mukherjee, MD

Instructor of Medicine
Assistant Director of Critical Care
NYU Langone Hospital for Joint Diseases
New York, New York
Chapter 43 Do the Surviving Sepsis Campaign Guidelines
Work?

Taka-Aki Nakada, MD, PhD

Chiba University Graduate School of Medicine
Department of Emergency and Critical Care Medicine
Chiba, Japan
Chapter 19 Should Fever Be Treated?

Patrick J. Neligan, MA, MB, FRCAFRCSI

Department of Anaesthesia and Intensive Care
University College Galway
Galway, Ireland
Chapter 1 Critical Care Versus Critical Illness
Chapter 41 What Vasopressor Agent Should Be Used in the
Septic Patient?
Chapter 58 How Should Acid-Base Disorders Be Diagnosed
and Managed?

Alistair Nichol, PhD, MB

Australian and New Zealand Intensive Care–Research
Centre
School of Public Health and Preventive Medicine
Monash University
Alfred Hospital Campus
Melbourne, Australia
Chapter 9 What Is the Optimal Approach to Weaning and
Liberation from Mechanical Ventilation?

Sara Nikravan, MD

Clinical Assistant Professor
Director of Critical Care Ultrasound and Focused Bedside
Echocardiography
Stanford University Department of Anesthesiology,
Perioperative, and Pain Medicine
Division of Critical Care Medicine
Stanford, California
Chapter 14 Does the Use of Echocardiography Aid in the
Management of the Critically Ill?

Mark E. Nunnally, MD, FCCM

Professor
Department of Anesthesia and Critical Care
The University of Chicago
Chicago, Illinois
Chapter 60 How Does Critical Illness Alter Metabolism?

Michael O’Connor, MD FCCM

Professor
Section Head of Critical Care Medicine
Department of Anesthesia and Critical Care
The University of Chicago
Chicago, Illinois
Chapter 15 How Do I Manage Hemodynamic
Decompensation in a Critically Ill Patient?

Stephen R. Odom, MD

Assistant Professor of Surgery
Beth Israel Deaconess Medical Center
Boston, Massachusetts
Chapter 59 What Is the Meaning of a High Lactate? What
Are the Implications of Lactic Acidosis?

Steven M. Opal, MD

Professor of Medicine, Infectious Disease Division
The Alpert Medical School of Brown University
Providence, Rhode Island
Chief, Infectious Disease Division
Memorial Hospital of Rhode Island
Pawtucket, Rhode Island
Chapter 17 What Strategies Can Be Used to Optimize
Antibiotic Use in the Critically Ill?

Anthony O’Regan, MD

Consultant Respiratory Physician
Galway University Hospital
Galway, Ireland
Chapter 27 Should Exacerbations of COPD Be Managed in
the Intensive Care Unit?

John O’Regan, MD

Nephrology Division
University Hospital Galway
Galway, Ireland
Chapter 57 What Is the Role of Renal Replacement Therapy
in the Intensive Care Unit?

Michelle O’Shaughnessy, MD

Division of Nephrology
Stanford University School of Medicine
Palo Alto, California
Chapter 57 What Is the Role of Renal Replacement Therapy
in the Intensive Care Unit?

Pratik P. Pandharipande, MD, MSCI

Professor of Anesthesiology and Surgery
Division of Anesthesiology Critical Care Medicine
Vanderbilt University Medical Center
Nashville, Tennessee
Chapter 73 How Does One Diagnose, Treat, and Reduce
Delirium in the Intensive Care Unit?


Contributors    xvii

Prakash A. Patel, MD

Assistant Professor
Anesthesiology and Critical Care
Perelman School of Medicine
University of Pennsylvania
Philadelphia, Pennsylvania
Chapter 82 Which Anticoagulants Should Be Used in the
Critically Ill Patient? How Do I Choose?

Andrew J. Patterson, MD, PhD

Executive Vice Chair
Larson Professor of Anesthesiology
University of Nebraska Medical Center
Omaha, Nebraska
Chapter 14 Does the Use of Echocardiography Aid in the
Management of the Critically Ill?

Paolo Pelosi, MD

IRCCS AOU San Martino-IST
Department of Surgical Sciences and Integrated
Diagnostics
University of Genoa
Genoa, Italy
Chapter 8 How Does One Evaluate and Monitor
Respiratory Function in the Intensive Care Unit?

Anders Perner, MD, PhD

Department of Intensive Care
Copenhagen University Hospital–Rigshospitalet
Copenhagen, Denmark
Chapter 20 What Fluids Should I Give to the Critically Ill
Patient? What Fluids Should I Avoid?

Ville Pettila, MD, PhD

Department of Intensive Care Medicine
Bern University Hospital (Inselspital)
University of Bern
Bern, Switzerland
Division of Intensive Care Medicine
Department of Perioperative, Intensive Care, and Pain
Medicine
University of Helsinki and Helsinki University Hospital
Helsinki, Finland
Chapter 9 What Is the Optimal Approach to Weaning and
Liberation from Mechanical Ventilation?

Matthew Piazza, MD

Resident
Department of Neurosurgery
University of Pennsylvania
Philadelphia, Pennsylvania
Chapter 80 How Should Acute Spinal Cord Injury Be
Managed in the ICU?

Michael R. Pinsky, MD, Dr hc

Department of Critical Care Medicine
University of Pittsburgh
Pittsburgh, Pennsylvania
Chapter 16 What Are the Best Tools to Optimize the
Circulation?

Lauren A. Plante, MD, MPH

Director
Maternal-Fetal Medicine
Professor
Departments of Obstetrics and Gynecology and
Anesthesiology
Drexel University College of Medicine
Philadelphia, Pennsylvania
Chapter 78 How Should the Critically Ill Pregnant Patient
Be Managed?

Jean-Charles Preiser, MD, PhD

Professor
Department of Intensive Care
Erasme University Hospital
Universite Libre de Bruxelles
Brussels, Belgium
Chapter 21 Should Blood Glucose Be Tightly Controlled in
the Intensive Care Unit?

Peter Radermacher, MD

Institut für Anästhesiologische Pathophysiologie und
Verfahrensentwicklung
Universitätsklinikum Ulm
Ulm, Germany
Chapter 40 What MAP Objectives Should Be Targeted in
Septic Shock?

Patrick M. Reilly, MD, FACS

Professor of Surgery
Chief
Division of Trauma, Surgical Critical Care, and Emergency
Surgery
Department of Surgery
Perelman School of Medicine at the University of
Pennsylvania
Philadelphia, Pennsylvania
Chapter 74 How Should Trauma Patients Be Managed in
the Intensive Care Unit?

Andrew Rhodes, MD

Professor of Intensive Care Medicine
Divisional Chair
Children’s, Women’s, Diagnostics, Therapies and Critical
Care
St. George’s University Hospitals NHS Foundation Trust
London, United Kingdom
Chapter 84 Does ICU Admission Improve Outcome?

Zaccaria Ricci, MD

Pediatric Cardiac Intensive Care Unit
Department of Pediatric Cardiac Surgery
Bambino Gesù Children’s Hospital, IRCCS
Rome, Italy
Chapter 55 How Does One Rapidly and Correctly Identify
Acute Kidney Injury?

Claudio Ronco, MD

Division of Nephrology and Hypertension
Department of Medicine
University of California, San Diego
San Diego, California
Chapter 55 How Does One Rapidly and Correctly Identify
Acute Kidney Injury?


xviii    Contributors

James A. Russell, MD, FRCP(C)
Professor of Medicine
Principal Investigator
Centre for Heart Lung Innovation
University of British Columbia
St. Paul’s Hospital
Vancouver, British Columbia, Canada
Chapter 19 Should Fever Be Treated?

Ho Geol Ryu, MD

Assistant Professor
Department of Anesthesiology and Pain Medicine
Seoul National University
Seoul, South Korea
Master of Public Health
Johns Hopkins Bloomberg School of Public Health
Baltimore, Maryland
Chapter 85 How Should Care Within an Intensive Care
Unit or an Institution Be Organized?

Noelle N. Saillant, MD

Fellow
Division of Traumatology, Surgical Critical Care, and
Emergency Surgery
University of Pennsylvania School of Medicine
Philadelphia, Pennsylvania
Chapter 72 How Do I Diagnose and Manage Acute
Endocrine Emergencies in the ICU?
Chapter 75 What Is Abdominal Compartment Syndrome
and How Should It Be Managed?

R. Matthew Sailors, BE

James Schuster, MD

Associate Professor
Chief of Neurosurgery, Penn Presbyterian Medical Center
Director of Neuro-Trauma
Department of Neurosurgery
University of Pennsylvania
Perelman School of Medicine
Philadelphia, Pennsylvania
Chapter 80 How Should Acute Spinal Cord Injury Be
Managed in the ICU?

Mike Scully, MD

Consultant Anaesthetist/Senior Lecturer
Anaesthesia and Critical Care
National University of Ireland
Galway, Ireland
Chapter 45 How Do I Diagnose and Manage CatheterRelated Bloodstream Infections?

Mara Serbanescu, MD

Emory University School of Medicine
Atlanta, Georgia
Chapter 70 How Does Critical Illness Alter the Gut? How
Does One Manage These Alterations?

Ronaldo Sevilla Berrios, MD

Department of Critical Care and Hospitalist Medicine
UPMC Hamot
Erie, Pennsylvania
Chapter 12 What Factors Predispose Patients to Acute
Respiratory Distress Syndrome?

Assistant Program Director
Department of Surgery
University of Florida College of Medicine
Gainesville, Florida
Chapter 25 Are Computerized Algorithms Useful in
Managing the Critically Ill Patient?

Carrie A. Sims, MD, MS, FACS

Danielle K. Sandsmark, MD, PhD

Brian P. Smith, MD

Babak Sarani, MD, FACS, FCCM

Andrew C. Steel, BSc, MBBS, MRCP,
FRCA, FFICM, FRCPC, EDIC

Assistant Professor of Neurology, Neurosurgery, and
Anesthesiology/Critical Care
Division of Neurocritical Care
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania
Chapter 62 How Should Traumatic Brain Injury Be
Managed?
Associate Professor of Surgery
George Washington University
Washington, District of Columbia
Chapter 81 When Is Transfusion Therapy Indicated in
Critical Illness and When Is It Not?

Naoki Sato, MD, PhD

Cardiology and Intensive Care Medicine
Nippon Medical School Musashi-Kosugi Hospital
Kawasaki, Japan
Chapter 50 How Do I Manage Acute Heart Failure?

Associate Professor of Surgery
University of Pennsylvania School of Medicine
Philadelphia, Pennsylvania
Chapter 72 How Do I Diagnose and Manage Acute
Endocrine Emergencies in the ICU?
Assistant Professor of Surgery
The Hospital of the University of Pennsylvania
Assistant Professor of Surgery
VA Medical Center of Philadelphia
Philadelphia, Pennsylvania
Chapter 74 How Should Trauma Patients Be Managed in
the Intensive Care Unit?

Interdepartmental Division of Critical Care Medicine
Toronto General Hospital
University of Toronto
Toronto, Ontario, Canada
Chapter 30 What Is the Best Mechanical Ventilation
Strategy in ARDS?


Contributors    xix

Yuda Sutherasan, MD

IRCCS AOU San Martino–IST
Department of Surgical Sciences and Integrated
Diagnostics
University of Genoa
Genoa, Italy
Division of Pulmonary and Critical Care Unit
Department of Medicine
Ramathibodi Hospital
Mahidol University
Bangkok, Thailand
Chapter 8 How Does One Evaluate and Monitor
Respiratory Function in the Intensive Care Unit?

Rob Mac Sweeney, PhD

Isaiah R. Turnbull, MD, PhD

Assistant Professor of Surgery
Washington University School of Medicine
St. Louis, Missouri
Chapter 38 Is There Immune Suppression in the Critically
Ill Patient?

Amit Uppal, MD

Assistant Professor
Division of Pulmonary, Critical Care, and Sleep Medicine
New York University School of Medicine
New York, New York
Chapter 43 Do the Surviving Sepsis Campaign Guidelines
Work?

Regional Intensive Care Unit
Royal Victoria Hospital
Belfast, Northern Ireland
Chapter 35 Do Nonventilatory Strategies for Acute
Respiratory Distress Syndrome Work?

Emily Vail, MD

Waka Takahashi, MD, PhD

Carrie Valdez, MD

Chiba University Graduate School of Medicine
Department of Emergency and Critical Care Medicine
Chiba, Japan
Chapter 19 Should Fever Be Treated?

Daniel Talmor, MD

Department of Anesthesia, Critical Care, and Pain
Medicine
Beth Israel Deaconess Medical Center
Harvard Medical School
Boston, Massachusetts
Chapter 59 What Is the Meaning of a High Lactate? What
Are the Implications of Lactic Acidosis?

B. Taylor Thompson, MD

Division of Pulmonary and Critical Care Unit
Department of Medicine
Massachusetts General Hospital
Harvard Medical School
Boston, Massachusetts
Chapter 28 What Is the Clinical Definition of ARDS?

Aurelie Thooft, MD

Intensive Care Unit
Erasme Hospital
Brussels, Belgium
Chapter 21 Should Blood Glucose Be Tightly Controlled in
the Intensive Care Unit?

Samuel A. Tisherman, MD, FACS, FCCM,
FCCP

Professor of Surgery
RA Cowley Shock Trauma Center
University of Maryland
Baltimore, Maryland
Chapter 77 What Is the Best Approach to Fluid
Management, Transfusion Therapy, and the Endpoints of
Resuscitation in Trauma?

Department of Anesthesiology
Columbia University
New York, New York
Chapter 3 Have Critical Care Outcomes Improved?
Chief Resident, General Surgery
Department of Surgery
The George Washington University Hospital
Washington, District of Columbia
Chapter 81 When Is Transfusion Therapy Indicated in Critical
Illness and When Is It Not?

Joy Vijayan, MD

Division of Neurology
National University Hospital
Singapore
Chapter 66 How Should Guillain-Barré Syndrome Be
Managed in the ICU?

Gianluca Villa, MD

International Renal Research Institute
San Bortolo Hospital
Vicenza, Italy
Department of Health Science
Section of Anaesthesiology and Intensive Care
University of Florence
Department of Anaesthesia and Intensive Care
Azienda Ospedaliero-Universitaria Careggi
Florence, Italy
Chapter 55 How Does One Rapidly and Correctly Identify
Acute Kidney Injury?

Jean-Louis Vincent, MD, PhD

Department of Intensive Care
Erasme University Hospital
Université libre de Bruxelles
Brussels, Belgium
Chapter 44 Has Outcome in Sepsis Improved? What Has
Worked? What Has Not Worked?


xx    Contributors

Jason Wagner, MD, MSHP

Division of Pulmonary, Allergy, and Critical Care
Medicine
Perelman School of Medicine
University of Pennsylvania
Philadelphia, Pennsylvania
Chapter 83 How Can Critical Care Resource Utilization in
the United States Be Optimized?

Criona M. Walshe, MD, FCARCSI

Department of Anaesthesia
Beaumont Hospital
Dublin, Ireland
Chapter 33 Is Pulmonary Hypertension Important in
ARDS? Should We Treat It?

Scott L. Weiss, MD

Assistant Professor of Critical Care and Pediatrics
Department of Anesthesia and Critical Care
The Children’s Hospital of Philadelphia
University of Pennsylvania Perelman School of Medicine
Philadelphia, Pennsylvania
Chapter 49 Is Sepsis-Induced Organ Dysfunction an
Adaptive Response?

Stuart J. Weiss, MD, PhD

Section Chief
Cardiovascular Anesthesia
Department of Anesthesiology and Critical Care
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania
Chapter 53 How Does One Prevent or Treat Atrial
Fibrillation in Postoperative Critically Ill Patients?

Hannah Wunsch, MD, MSc

Department of Critical Care Medicine
Sunnybrook Health Sciences Center
Department of Anesthesiology
University of Toronto
Toronto, Ontario, Canada
Chapter 3 Have Critical Care Outcomes Improved?

Debbie H. Yi, MD

Instructor of Emergency Medicine
Fellow in Neurology
University of Pennsylvania
Philadelphia, Pennsylvania
Chapter 65 How Should Status Epilepticus Be Managed?

Felix Yu, MD

Division of Pulmonary, Critical Care and Sleep Medicine
Tufts Medical Center
Boston, Massachusetts
Chapter 7 What Is the Role of Noninvasive Ventilation in
the Intensive Care Unit?

Evin Yucel, MD

Cooper Medical School of Rowan University
Camden, New Jersey
Chapter 54 Is Right Ventricular Failure Common in the
Intensive Care Unit? How Should It Be Managed?

Nobuhiro Yuki, MD, PhD

Departments of Medicine and Physiology
Yong Loo Lin School of Medicine
National University of Singapore
Singapore
Chapter 66 How Should Guillain-Barré Syndrome Be
Managed in the ICU?

Fernando Zampieri, MD

Intensive Care Unit
Emergency Medicine Discipline
Hospital das Clínicas
University of São Paulo
São Paulo, Brazil
Chapter 11 Is Extracorporeal Life Support an EvidenceBased Intervention for Critically Ill Adults with ARDS?

Ting Zhou, MD

Department of Neurology
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania
Chapter 63 How Should Aneurysmal Subarachnoid
Hemorrhage Be Managed?


Preface
We are delighted to present the second edition of our
textbook Evidence-Based Practice of Critical Care. It is a bit
surprising to realize that it has been 5 years since the first
edition was released. It seems as if we finished our editing
only a few months ago, and we were grateful to be done.
The reception has also been surprising, and again, we are
grateful to the many critical care practitioners who have
purchased the book and complimented us on its value.
What is most surprising of all is the degree to which a new
edition is justified. The practice of critical care medicine
has changed immeasurably in the past 5 years, and the evidence base that supports care delivery has grown with it.
These changes (Chapter 2) make it imperative that the contents of this book also change.
Several basic principles that had only begun to emerge
5 years ago now appear to be more firmly established.
Many generate a sense of hope and a belief that care is
improving and will continue to do so.
•We may be doing better—but maybe not. ­Determining
if outcomes from critical illness have improved is problematic (Chapter 3), and determining just what has
worked and what has not (Chapter 44) may be even
more difficult.
•The consistent application of proven interventions is
beneficial (Chapter 43), but just what interventions
should be applied (and when they should be applied)
may be more difficult to determine (Chapters 10, 11,
18–22, 31, 32, 34, 36, 39, 46, 57, 61, 67, 71, 81, and 82).
•

Patients survive critical illness but often at a cost
(Chapter 3). Survivors may be plagued by debilitating
dysfunction in their musculoskeletal and peripheral
­
nervous systems, irreversible respiratory defects, cognitive deficits that hamper performance of the activities
of daily living, and psychological abnormalities such
as posttraumatic stress disorder and even delirium. Attention has now turned to understanding the problems
facing survivors and to generating patient networks to
support them.
•Critical illness most often develops outside of the intensive care unit (ICU), and that is where treatment needs
to begin. However, success depends on identifying and
intervening as early as possible, and not all attempts
to make this happen have been successful (Chapter 5).
For it to be successful, intervention for vascular disorders such as stroke, myocardial infarction, and cardiac arrest requires early identification of patients, and
these patients should be rapidly transported to centers
where the appropriate care can be provided by expert
­practitioners who have access to the most advanced
technology (Chapters 22 and 64). New approaches to the
definitions of sepsis and acute respiratory distress syndrome (ARDS) have been accompanied by i­dentification
of simple clinical criteria that improve our ability to recognize at-risk patients in the hope that we can initiate

management at an earlier point in the natural history
of these disorders (Chapters 28 and 37). With earlier
initiation of fluids and antibiotic therapy, some at-risk
­patients may never require care in an ICU.
•Some of the criteria that served as key identifiers of
critically ill patients are no longer germane. For example, it is now recognized that the identification of
patients who have sepsis with inflammatory markers (e.g., temperature, heart rate, respiratory rate, and
white blood cell count, the SIRS [systemic inflammatory response syndrome] criteria) is too nonspecific and
identifies a ­multitude of individuals with infection or
other inflammatory disorders who do not have sepsis
and whose risk of having sepsis is low. One result is
the derivation of new definitions for sepsis and sepsis-related diagnoses and the associated validation of
better clinical criteria to better identify patients with
infection who are at high risk for mortality and morbidity (Chapter 37).
•Our understanding of the pathophysiology of several
key disorders, notably sepsis and ARDS, has improved.
Sepsis is no longer viewed in terms of excessive inflammation; it is now recognized that there are aspects of the
syndrome that reflect profound immunosuppression
(Chapter 38) and others that do not involve immunology at all. Indeed, sepsis may reflect an adaptive response
to a profound metabolic defect that cannot, as yet, be
identified (Chapter 49). Likewise, our understanding
of the effects of critical illness on specific organ systems
(Chapters 10, 13, 29, 54, 55, 61, 68, 70, 72, and 81) and
the way in which specific organ systems determine the
development and course of critical illness (Chapters 15,
27, 50, 51, and 68) has been profoundly altered. Finally,
what is “normal” in the absence of critical illness may
not be “normal” when critical illness is present and vice
versa (Chapters 8, 19, 21, 31, 40, 41, and 52).
•We have come to recognize that host and nonhost factors beyond the acute illness itself determine whether a
patient becomes critically ill (Chapters 12, 23, and 78).
•More is not necessarily better, and in some aspects of
treatment “more” may be detrimental. Although administration of fluids has been a mainstay of critical care
practice since its inception, we now recognize that there
are limits that, if exceeded, may make matters worse
(Chapters 20, 75, 77, and 81). Overuse of mechanical ventilation is clearly detrimental (Chapters 9 and 10), and it
may be best to avoid intubation altogether (­Chapter 7).
Intervention to maintain blood pressure or other hemodynamic measures is not always indicated (Chapter 41),
and, even when appropriate, it is not at all clear when
intervention needs to be instituted (Chapter 40).
•Not all of the things we monitor need to be monitored,
but we also misuse monitoring tools (Chapters 8, 13, 14,
16, 58, 59, and 61).
xxi


xxii    Preface
•In aggregate, the results of many studies are equivocal, especially when the study results are negative.
Examples of trials in which intervention did not significantly alter outcome but where opposite results in
different subpopulations negate each other abound.
For example, the results of the ALVEOLI/EXPRESS
and LOVs trials indicate that use of high positive endexpiratory pressure (PEEP) did not provide a statistically significant benefit over low PEEP in the management
of ARDS (Chapter 30). However, in a population of
morbidly obese patients, high PEEP is likely ­essential
(Chapter 23). Likewise, the FACTT trial suggested that
liberal fluid management offered no measurable benefit over conservative fluid management, a finding that
is likely correct, unless the patient has ongoing fluid
losses (e.g., bleeding, ascites) that would not be
adequately replaced with a conservative approach.

Thus, targeting more specific populations for intervention may be necessary.
•Making the patient an active participant in, rather than a
passive recipient of, care in critical illness may be advantageous.
Finally, we would like to thank all of the authors of the
chapters in this book. Reading and editing the chapters has
been hugely enjoyable and thought provoking, and we finish with the realization that we are only at the beginning of
our understanding of critical illness and in the development
of critical care. More than anything else, that is what lies
behind the excitement we feel as we present this new edition.
Clifford S. Deutschman
Patrick J. Neligan
May 2015


1

Critical Care Versus Critical
Illness
Patrick J. Neligan, Clifford S. Deutschman

Intensive care units (ICUs) were developed in the 1950s
to treat patients with two distinct problems. In some
cases, ICU care was required to provide an intervention
to support organ dysfunction—mechanic ventilation for
acute respiratory failure.1,2 Conversely, ICUs also permitted intensive monitoring of a patient whose physiologic
condition might change abruptly, that is, observation of
patients undergoing a “stress response” following surgery or trauma or patients with cardiac or neurologic
conditions that might suddenly change.3,4 Over time,
technologic evolution has enhanced our ability to care
for both types of patients. In addition to ventilators, it is
now possible to support patients with life-threatening,
acute organ dysfunction with renal replacement therapy, vasoactive drugs or even ventricular assist devices,
exogenous metabolic support, and more. At the same
time, we can directly monitor the function of areas such
as the heart, the lungs, the brain, the gastrointestinal
(GI) tract, and the kidneys. Over the years, the distinction between the two forms of technology has blurred:
we monitor patients who require life-sustaining therapy,
and we support organs in patients who are at high risk
to prevent deterioration. The difference between the two
types of patients remains. There are patients who will
most often have a predictable response to a major perturbation of homeostasis following high-risk (e.g., cardiac,
neurologic, vascular, transplant, and upper GI) surgery,
trauma, a myocardial infarction (MI) or arrhythmia,
stroke, or subarachnoid hemorrhage. These patients may
require intervention to allow the damage to heal, but, by
and large, they require careful monitoring and observation as they traverse a course whose length, magnitude,
and complications are predictable.5,6 Conversely, patients
who have sustained shock, sepsis, or direct/progressive
damage to an organ system require support, and monitoring is used to determine if that support is working. In
short, there are ICU patients who are at risk of becoming critically ill, and there are patients who are critically
ill (Fig. 1-1). In this introductory chapter, we explore the
differences and emphasize that the most important tasks
facing modern medicine are to determine where the transition occurs and to prevent those at risk for critical illness from becoming critically ill.

THE PERIOPERATIVE/POSTINJURY
STRESS RESPONSE
In contrast to critical illness, the biology underlying the
stress response to surgery or trauma is well-characterized,
predictable, and, absent comorbidities that may be effected,
adaptive.5,6 Cuthbertson first described the stress response
over 80 years ago.5 Since then, a number of brilliant investigators and clinicians have added to our understanding
of its biology.7-9 We now recognize that “stress” provokes
inflammation and that the purpose of inflammation is
restoration of a biologic “steady state,” where cellular, tissue, organ system, and, ultimately, organism-wide activity
fluctuates around some mean level of behavior and maintenance of interaction and cooperation on these same levels.6 In most cases, the overwhelming imperative driving
inflammation is a need to repair, replace, or compensate for
damage to cells and tissues.6 This damage may result from
physical injury (trauma), from interruption of blood supply (e.g., stroke, MI), or from invasion of microorganisms
that “hijack” normal cellular metabolism.

CRITICAL ILLNESS
Critical illness is characterized by acute, potentially lifethreatening organ dysfunction that requires therapy. It is
often precipitated by the same disturbances that provoke
inflammation. The initiator may be “shock,” whose origin
can often, but not universally, be traced to circulatory failure or to infection that overwhelms endogenous responses.
The common denominator is a profound insult to homeostasis on the cellular level that exceeds endogenous corrective responses. However, the manner in which these states
result in abnormal organ function is unknown.
Critically ill patients may present to primary care, to
the emergency department (ED), or on the hospital wards.
They represent a small subset of patients; the vast majority of individuals with deviations from “health,” for
example, those with inflammation or even shock, respond
to initial therapy. A few, however, become acutely critically ill. Acute critical illness is often unanticipated and
may not follow a predictable stress response trajectory.
3


4    Section I CRITICAL CARE AND CRITICAL ILLNESS
ED, trauma bay,
ward, OR

“Damage”

Inflammation

Organ
dysfunction

Unstable

“Big” surgery,
poly-trauma,
comorbidities

Critical
illness

ICU

Normal
recovery

Death

Recovery

Figure 1-1  The critical care–critical illness paradigm. ED, emergency
department; ICU, intensive care unit; OR, operating room.

With early recognition and appropriate therapy, many
critically ill patients will recover. Once again, however,
a subset will deteriorate further, to a state of persistent
critical illness with multiorgan dysfunction (see Chapter
37). This state may persist for weeks and thus can appear
stable, but it is also highly abnormal, with defects in
most organ systems.10,11 Once again, many patients will
recover. However, it is increasingly clear that this recovery is incomplete. Many patients who have undergone a
prolonged ICU course are left with persistent respiratory,
cardiac, neuromuscular, and cognitive dysfunction.12-15
Some may remain ventilator dependent; others will have
a variant of posttraumatic stress disorder.13 Recent studies
suggest that, in the United States, there may be upward of
700,000 ICU survivors each year, many of whom require
ongoing support, but many others whose ongoing problems escape detection.16

INFLAMMATION VERSUS CRITICAL
ILLNESS: BIOLOGIC PERSPECTIVES
Both inflammation and critical illness are, at the core,
responses to significant, and often extreme, perturbation of
homeostasis, the biologic steady state. As a result, there is
a tendency to assume that therapy appropriate for one will
also be effective for the other. There is, indeed, some truth to
this assumption. As an example, in both inflammation and
critical illness, an initial imperative is the restoration of substrate delivery to and waste removal from cells. However,
the profound change that differentiates inflammation from
critical illness has been characterized by some as a loss of a
cell’s ability to use substrate, or the creation of a by-product
that cannot be removed by ordinary means. Consider the
cellular need for oxygen. Inadequate delivery may reflect
abnormalities in the lungs, with impaired gas exchange,
or in the circulation, where the cardiovascular system is

unable to transfer oxygen itself, or oxygen-­
containing
molecules or cells, to tissues for use. Cells can often meet
energy demands by means of glycolysis alone, bypassing the electron transport chain, and generating lactate and hydrogen ions. Recycling of lactate requires an
intact circulation for delivery to the liver. Acidosis is corrected by buffering with the production of carbon dioxide
(CO2), which must be excreted by ventilation. Thus, a clinician’s initial response would be to enhance oxygen uptake
by increasing the inspired concentration, restoring the circulation with fluid, and, perhaps, increasing the oxygencarrying capacity with red blood cells. This same fluid
will restore hepatic flow and allow for the conversion of
lactate to pyruvate. Improving gas removal with mechanical ventilation will facilitate CO2 removal. This approach
may be effective when directed toward inflammation secondary to tissue damage, where oxygen use is diverted to
support white blood cells, the primary effectors of tissue
repair, and where delivery is inadequate because damaged
tissue is essentially avascular. This response is self-­limiting
because capillary angiogenesis takes about 4 days,17 after
which exogenous support can be weaned. However, a
more profound insult, or one that is not addressed in a
timely manner, may do more than limit oxygen availability or divert its use. Damage to mitochondria, which is a
hallmark of sepsis, will impair the ability of a cell to use
oxygen irrespective of availability.18,19 Thus, restoration of
gas exchange or cardiovascular function will not, in and
of itself, be sufficient to restore homeostasis. As a result,
organ dysfunction may not improve or resolve with these
standard measures—a hallmark of critical illness that is
often unrecognized or unappreciated. Unfortunately, the
distinction between stress and critical illness is not always
clinically self-evident, and this lack of distinction leads to
diagnostic and therapeutic dilemmas whose resolution, for
the moment, is intensely problematic.

INFLAMMATION VERSUS CRITICAL
ILLNESS: THERAPEUTIC PERSPECTIVES
An unfortunate extension of our difficulties in distinguishing a stress response from critical illness is a persistent tendency to assume that what works for one group will also
work for the other. Examples abound. The following is a
summary of several of the most important examples, both
historically and therapeutically:
• Fluid resuscitation in sepsis: In a landmark 2001 study by
Rivers and colleagues,20 researchers studied patients
with suspected infection who were thought to have
sepsis and compared fluid resuscitation using standard
endpoints such as blood pressure (BP) to alternatives
that focused on tissue oxygen delivery, for example, venous oxygen saturation (SvO2) or central venous pressure (CVP). This single center study demonstrated a
remarkable improvement in outcome using the latter
approach. However, three recent multicenter studies applying essentially the same paradigm failed to duplicate
the original findings.21-23 A number of possible explanations have been advanced, but it is essential to note
that in “inflammation,” adequate resuscitation may be


Chapter 1  Critical Care Versus Critical Illness    5
reflected in measures such as CVP and SvO2. However,
sepsis involves a pathologic defect in either the microcirculation or the mitochondria so that oxygen delivery
or extraction cannot be corrected with fluid alone.18,24
Unfortunately, the entry criteria in both the initial Rivers
trial and the subsequent multicenter trials cannot truly
distinguish inflammation and hypovolemia secondary
to suspected infection for sepsis, a state of critical illness
that reflects early organ dysfunction that is difficult to
detect. Fluid resuscitation that is appropriate for one
may be ineffective, and even excessive, for the other.
Ventilator management in acute lung injury/acute respira•
tory distress syndrome (ARDS): A series of studies by a
network of United States–based investigators and others have examined therapeutic approaches to lung injury. The most important of these “ARDSnet” studies
is the initial “ARMA” trial, demonstrating that limiting
tidal volumes to 6 cc/kg body weight is associated with
better outcomes than use of larger (10 to 12 cc/kg) volumes.25 The diagnosis of ARDS was based on the standard criteria: hypoxemia, reflected in a decreased ratio
of arterial oxygen tension (Pao2) to fraction of oxygen in
the inspired gas (Fio2), the presence of bilateral “patchy”
infiltrates on chest radiographs, and no evidence that the
abnormalities were of cardiogenic origin. Conversely, for
decades, anesthesiologists have administered tidal volumes in the 10 to 12 cc/kg range in the operating room.
Many, if not most, postoperative patients have abnormal
Pao2/Fio2 ratios and abnormal chest radiographs. This
is especially true for patients undergoing cardiac surgery. Postoperatively, though, the great majority of these
patients do not require more than supplemental oxygen.
Even in those who are maintained with mechanic ventilation into the postoperative period, exogenous support
is rarely needed for more than a short period. All surgical patients have capillary leak as part of the inflammation induced by tissue injury. This “stress response”
results in mild hypoxemia and “wet” lungs. In contrast,
patients with ARDS have lung dysfunction. Postoperative patients have inflammation; patients with ARDS
have critical illness.
• Determination of outcome: The management of patients
with sepsis has been an important focus of critical care
practice for more than a decade.26-28 Attempts to consolidate limited positive multicenter clinical trials in
critical care have resulted in international and national
clinical practice management guidelines. Perhaps the
most widely disseminated involve the Surviving Sepsis
Campaign (SSC) guidelines for the management of sepsis. The SSC (www.survivingsepsis.org) has been effective in increasing awareness of early sepsis and perhaps
in advancing the implementation of therapy that may
improve outcome.29 Importantly, recent studies from
the United States and Australasia have demonstrated
that mortality from sepsis has decreased to surprisingly
low levels—under 10% in one multi-­institutional U.S.
health system30 and under 20% when more broadly
applied over a 12-year period in Australia and New
Zealand.31 However, personal communications from
intensivists in the three industrialized European countries suggest that, despite use of some or all elements
of the SSC guidelines, mortality may be as high as 50%

(personal communications, Mervyn Singer, M.D.). The
expressed opinion of those practicing in the United
Kingdom, Germany, and Italy is that many patients
diagnosed with sepsis and admitted to ICUs in the
United States and Australasia would be managed in
the EDs of other countries. If these patients responded
to ED management, they would not be admitted to the
ICU and would not be identified as “septic.” To further
complicate matters, Gaieski et al.32 applied four different methods of defining “sepsis” to a single U.S. patient
dataset and found a 3.5-fold variation in the incidence
and a 2-fold variation in mortality. Clearly, some of the
patients diagnosed with sepsis in the United States and
Australasian databases were undergoing inflammation
in response to infection. Again, differentiating inflammation from critical illness is profoundly important.
Intensive insulin therapy: In 2001, Van den Berghe and

­colleagues33 published a much sited clinical trial that
randomized patients to intensive insulin therapy (ITT)
(glucose levels maintained between 80 and 110 mg/dL),
as opposed to “normal care” (glucose levels treated when
above 180 mg/dL). The study was based on the knowledge that hyperglycemia is associated with a number of
untoward outcomes in critically ill patients and demonstrated a statistically significant 3.4% absolute reduction in the risk of death at 28 days in the surgical ICU
of a major hospital in Leuven, Belgium. The paucity of
interventions that improve outcomes in critical care and
the fact that insulin is inexpensive and easy to administer led to wide adoption of ITT. Although Van den
Berghe et al.33 clearly documented the need for careful
monitoring of blood glucose levels and the risk of hypoglycemia, these potential complications were largely ignored. “Tight glycemic control” was even considered a
key performance indicator in many ICUs34 and became
a component of the first SSC guidelines.26 However,
some elements of the study methodology suggested
that the near-universal adoption of IIT might be problematic. Specifically germane to this discussion is the
fact that more than 60% of the patients who entered into
the study had recently undergone cardiac surgery, and
virtually all were seen either postoperatively or posttraumatically. A follow-up study by the Van den Berghe group35 applied the same protocol to patients in the
medical ICU of the same institution and failed to demonstrate outcome benefits. In addition, somewhat problematic trials were stopped early because of concerns
that high levels of hypoglycemia might cause harm.36,37
Finally, the 2008 NICE SUGAR (Normoglycaemia in
Intensive Care Evaluation Survival Using Glucose Algorithm Regulation) trial applied the Leuven protocol
to more than 6000 patients and demonstrated that, if
anything, tight glycemic control may worsen outcomes
in critical care,38 likely as a result of hypoglycemia.39
Although the IIT episode contains many lessons, it
remains a textbook demonstration of the difference between inflammation (e.g., the response to surgery, especially when cardiopulmonary bypass is involved) and
critical illness, which was more likely to be represented
in the population from the Leuven Medical ICU and the
multicenter trials. Importantly, the mortality of untreated patients in the Leuven Surgical ICU was about 8%,34


6    Section I CRITICAL CARE AND CRITICAL ILLNESS
whereas that of the same group in the Leuven Medical
ICU was 40%,35 which clearly demonstrated that they
were different.
Monitoring the heart: The widely held belief that there is

a need to monitor substrate delivery to tissues has led
to the development of a wide variety of hemodynamic
monitoring devices. Conventional monitoring of the circulation involves using heart rate (HR), mean arterial
pressure (MAP), urinary output, and CVP. The optimal
MAP is unknown.40,41 CVP does not measure volume
responsiveness,42 and high CVPs have been associated
with adverse outcomes.43 More important, the meaning
of a change in CVP is entirely dependent on the model
of cardiovascular function used. A rise in CVP in the
Frank-Starling formulation of cardiac function (which
focuses on the determinants of ventricular output),
where it serves as a surrogate for preload, should result
in an increased stroke volume (SV).44 However, in the
Guyton model, where the focus in on ventricular filling,
a similar increase in CVP will reduce the gradient for
flow into the ventricle and thus will decrease SV.45 The
“normal” urinary output of more than 0.5 mL/kg/hr is
actually a “minimum” hourly output and is based on
theoretic calculations involving the maximal capacity
to concentrate the urine and the “average” daily nitrogen load to be eliminated. There are many reasons why
these numbers may not be germane either in individual
patients or in the setting of either stress or critical illness. Importantly, there are no studies demonstrating
that achieving this target affects the development of renal injuries.
One way in which to more accurately monitor cardiac
function is to directly measure the effects of a change in
volume on cardiac output (or to eliminate the effects of
HR on SV).46 For two decades, pulmonary artery catheters
(PACs) were extensively used to monitor both perioperative and critically ill patients. Use has declined because
a large randomized trial of PACs in ICUs failed to demonstrate a mortality benefit.47 However, this study was
performed on approximately 2000 patients undergoing
high-risk surgery; the overall mortality was under 8%,
likely too low to be an appropriate endpoint. Given the
nature of the patient population and the low mortality, it is
likely that many of the patients entered into this trial were
not critically ill.
Parenthetically, the incidence of renal insufficiency in
the PAC group was 7.4%, whereas it was 9.8% in the standard care group, generating a P value of .07, just above the
threshold for significance. Indeed, if one more patient in
the standard care group had developed renal insufficiency,
or one less patient in the PAC group had not, the use of
PACs might have increased.
In summary, it is imperative that critical care practitioners do not confuse inflammation and critical illness.
Examples of the dangers inherent in failure to account
for these differences, beyond those detailed here, abound.
Both may require enhanced surveillance and intensive
monitoring, but the need for intervention and, if necessary,
the time course during which intervention is required are
likely to be different. Inappropriately applied therapy is
both expensive and potentially dangerous.

AUTHORS’ RECOMMENDATIONS
• Not all patients in ICUs are critically ill; patients admitted after
surgery or for monitoring may need to be managed differently
than critically ill patients.
• Research data derived from the perioperative (including surgical ICUs) literature may not be applicable in critical illness.
• The perioperative realm provides a useful laboratory for
new therapies or monitors; however, it is characterized by a
controlled and curtailed stress response, recovery from which is
predictable.
• Acute critical illness is characterized by organ dysfunction.
• Persistent critical illness likely reflects an underlying disease
process that is different from either stress or acute critical illness, and interventions designed for one may be ineffective or
even harmful in the other.

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