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Robert C.

Hyzy
Editor

Evidence-Based
Critical Care

A Case Study Approach

123
Evidence-Based Critical Care
Robert C. Hyzy
Editor

Evidence-Based
Critical Care
A Case Study Approach
Editor
Robert C. Hyzy
Division of Pulmonary and Critical Care
University of Michigan
Ann Arbor
MI
USA

ISBN 978-3-319-43339-4ISBN 978-3-319-43341-7(eBook)


DOI 10.1007/978-3-319-43341-7

Library of Congress Control Number: 2017931641

Springer International Publishing Switzerland 2017


This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or
part of the material is concerned, specifically the rights of translation, reprinting, reuse of
illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way,
and transmission or information storage and retrieval, electronic adaptation, computer software,
or by similar or dissimilar methodology now known or hereafter developed.
The use of general descriptive names, registered names, trademarks, service marks, etc. in this
publication does not imply, even in the absence of a specific statement, that such names are
exempt from the relevant protective laws and regulations and therefore free for general use.
The publisher, the authors and the editors are safe to assume that the advice and information in
this book are believed to be true and accurate at the date of publication. Neither the publisher nor
the authors or the editors give a warranty, express or implied, with respect to the material
contained herein or for any errors or omissions that may have been made. The publisher remains
neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Printed on acid-free paper

This Springer imprint is published by Springer Nature


The registered company is Springer International Publishing AG
The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland
This book is dedicated to the memory of Eugene C.Hyzy, MD
Preface

Along with Springer International, I am pleased to offer you our new text-
book entitled Hyzys Evidence-Based Critical Care Medicine: A Case Study
Approach. In medicine, teachable moments usually occur in clinical con-
text, where the engagement in a real case exemplifies principles of diagnosis
or therapy. We have created our new textbook with the teaching moment in
mind: each chapter begins with a real case gleaned from the authors clinical
experience. In order to replicate the teaching dyad, each case poses a question
which offers the reader to process and reflect on the components of the case
before offering and answer.
While medical practice attempts to be evidence-based, common approaches
to diagnosis and management incorporate not only evidence but heuristics
and biases which await either validation or repudiation. Hence, we have
divided the discussion section of each chapter into two segments: the
Principles of Management section and the Evidence Contour section. In
the Principles of Management section, the common approach to the care of
patients having a given condition is presented. Here you will find the nuts and
bolts of what you need to know about the condition and the usual approach to
diagnosis and treatment. Evidence-based approaches are emphasized, where
appropriate. However, medical knowledge is ever evolving. The approach to
many aspects of the diagnosis and treatment of a condition remains the sub-
ject of controversy. In the Evidence Contour section, each author discusses
the aspects of diagnosis and management which are the subject of ongoing
debate in the medical literature. In the way, the reader will appreciate not only
what appears to be known but also what is becoming known about a given
topic.
We believe the approach we have taken with this textbook successfully
bridges the gulf between the traditional encyclopedic sit-on-your-shelf text-
book and the single-hit online reference, each of which lacks the contextual
elements of effective learning. This is a new way to present knowledge in a
medical textbook and should help critical care practitioners, fellows, resi-
dents, allied health professionals, and students expand their critical care
knowledge in an efficient and effective manner. This approach should also
benefit those preparing for board examinations.
I would like to thank the many friends, colleagues, and former fellows
whose labors went to create this book. In particular, I would like to thank my
section editors, Drs. Robert Neumar, David Morrow, Ben Olenchock, Romer
Geocadin, John Kellum, Jonathan Fine, Robyn Scatena, Lena Napolitano,

vii
viii Preface

and Marie Baldisseri. Without their thoughtful and insightful efforts, this
book would not have been possible. I would also like to thank my editors at
Springer, Connie Walsh and Grant Weston for their vision and for seeing this
work through to fruition.

Ann Arbor, MI, USA RobertC.Hyzy, MD


Contents

Part IER- ICU Shock and Resuscitation


Robert W. Neumar

1 Cardiac Arrest Management 3


Ronny M. Otero
2 Post-cardiac Arrest Management  13
Ronny M. Otero and Robert W. Neumar
3 Undifferentiated Shock 25
Sage P. Whitmore
4 Hypovolemic Shock andMassive Transfusion 39
Joshua M. Glazer and Kyle J. Gunnerson
5 Acute Respiratory Failure: NIV Implementation
andIntubation 49
Torben K. Becker and John M. Litell
6 Diagnosis andManagement ofTricyclic
Antidepressant Ingestion 57
Patrick George Minges and Robert W. Shaffer
7 Management ofCalcium Channel Blocker Poisoning 65
David M. Black and Robert W. Shaffer
8 Diagnosis andManagement ofEthylene Glycol Ingestion 73
Christine Martinek Brent and Robert W. Shaffer
9 Accidental Hypothermia  83
Carrie Harvey and Ivan Nathaniel Co

Part II Cardiac Disease


David A. Morrow and Benjamin A. Olenchock

10 Management ofCardiogenic Shock  95


Michael G. Silverman and Benjamin A. Olenchock
11 Management ofAcute Heart Failure 103
Gregory T. Means and Jason N. Katz

ix
x Contents

12 Management ofAcute Coronary Syndrome 111


Arman Qamar and Benjamin M. Scirica
13 Complications ofMyocardial Infarction 121
Brandon M. Jones and Venu Menon
14 Management of Cardiac Tamponade  129
David D. Berg, Gregory W. Barsness,
and Benjamin A. Olenchock
15 Hypertensive Crises  135
Mark Schmidhofer
16 Atrial Fibrillation andOther Supraventricular
Tachycardias 145
Daniel Sedehi
17 Ventricular Arrhythmias  153
Sohaib Tariq and Howard A. Cooper
18 Management of Acute Aortic Syndromes 163
Carol H. Choe and Rohan R. Arya
19 Management of Endocarditis 171
Janek Manoj Senaratne and Sean van Diepen

Part III Respiratory Disease


Robert C. Hyzy

20 Community Acquired Pneumonia 181


Richard G. Wunderink and Mark W. Landmeier
21 Management ofAcute Respiratory Distress Syndrome 189
Robert C. Hyzy
22 Acute Exacerbation ofCOPD: Non-invasive
Positive Pressure Ventilation 199
Kristy A. Bauman
23 Management of Status Asthmaticus  205
Jacob Scott and Ryan Hadley
24 Immunocompromised Pneumonia 215
Robert P. Dickson
25 Venous Thromboembolism intheIntensive Care Unit 221
Scott J. Denstaedt and Thomas H. Sisson
26 Massive Hemoptysis 233
Andrew M. Namen, Norman E. Adair, and David L. Bowton
27 Sedation and Delirium 241
Timothy D. Girard
28 Prolonged Mechanical Ventilation 251
Thomas Bice and Shannon S. Carson
Contents xi

29 Ventilator-Associated Pneumonia andOther


Complications 257
Jennifer P. Stevens and Michael D. Howell
30 Respiratory Failure inaPatient withIdiopathic
Pulmonary Fibrosis 265
Ryan Hadley
31 Weaning from Mechanical Ventilation 273
Ayodeji Adegunsoye and John P. Kress
32 The Post-intensive Care Syndrome 281
Jason H. Maley and Mark E. Mikkelsen
33 Management ofDecompensated Right Ventricular
Failure intheIntensive Care Unit 287
Rana Lee Adawi Awdish and Michael P. Mendez
34 Diffuse Alveolar Hemorrhage  295
Joshua Smith and Mark Daren Williams

Part IV Neurologic Disease


Romergryko G. Geocadin

35 Acute Stroke Emergency Management 303


Pravin George and Lucia Rivera Lara
36 Bacterial Meningitis intheICU 315
Jennifer S. Hughes and Indhu M. Subramanian
37 Management ofIntracerebral Hemorrhage 325
Shamir Haji and Neeraj Naval
38 Status Epilepticus 333
Jharna N. Shah and Christa O'Hana V. San Luis
39 Neuroleptic Malignant Syndrome 343
Kathryn Rosenblatt
40 Traumatic Brain Injury 355
Yogesh Moradiya and Romergryko G. Geocadin
41 Management ofAnoxic Brain Injury  363
Maximilian Mulder and Romergryko G. Geocadin

Part V Renal Disease


John A. Kellum

42 Traditional andNovel Tools forDiagnosis ofAcute


Kidney Injury  375
Fadi A. Tohme and John A. Kellum
43 Management ofAcute Kidney Injury 383
Fadi A. Tohme and John A. Kellum
xii Contents

44 Rhabdomyolysis  393
Saraswathi Gopal, Amir Kazory, and Azra Bihorac
45 Hyponatremia 401
Christian Overgaard-Steensen and Troels Ring

Part VI Endocrine Disease


Jonathan M. Fine and Robyn Scatena

46 Management ofSevere Hyponatremia andSIADH 413


Robyn Scatena
47 Diabetic Ketoacidosis 419
Neal Hakimi and Jonathan M. Fine
48 Thyroid Storm 425
Matthew E. Schmitt and Robyn Scatena
49 Adrenal Insufficiency 433
Amy M. Ahasic and Anuradha Ramaswamy
50 Management ofHyperglycemic Hyperosmolar
Syndrome 441
Elaine C. Fajardo
51 Management ofMyxedema Coma 447
Aydin Uzun Pinar

Part VII Infectious Disease


Robert C. Hyzy

52 Urosepsis  453
Benjamin Keveson and Garth W. Garrison
53 Management ofSepsis andSeptic Shock  457
Rommel Sagana and Robert C. Hyzy
54 Invasive Aspergillus  471
Elaine Klinge Schwartz
55 Management ofStrongyloides Hyperinfection
Syndrome 479
Shijing Jia, Hedwig S. Murphy, and Melissa A. Miller
56 Treatment ofViral Hemorrhagic Fever
inaWell-Resourced Environment 485
Amit Uppal and Laura Evans
57 Management ofSevere Malaria 495
Jorge Hidalgo, Pedro Arriaga,
and Gloria M. Rodriguez-Vega
58 Dengue 509
Pedro Arriaga, Jorge Hidalgo,
and Gloria M. Rodriguez-Vega
Contents xiii

59 Chikungunya 513
Pedro Arriaga and Jorge Hidalgo
60 Leptospirosis 517
Jorge Hidalgo, Gloria M. Rodriguez-Vega, and Pedro Arriaga

Part VIII Gastrointestinal Disease


Robert C. Hyzy

61 Management ofAcute Upper Gastrointestinal


Hemorrhage 527
David Schrift and Carol H. Choe
62 Variceal Hemorrhage 535
Elizabeth A. Belloli and Steven E. Gay
63 Acute Pancreatitis 545
Margaret F. Ragland and Curtis H. Weiss
64 Management ofAcute Liver Failure 551
Jessica L. Mellinger and Robert J. Fontana
65 Acute Lower Gastrointestinal Bleeding  561
Ali Abedi and Anoop M. Nambiar
66 Diagnosis andManagement of Clostridium Difficile
Infection (CDI)  569
Paul C. Johnson, Christopher F. Carpenter,
and Paul D. Bozyk
67 Principles ofNutrition intheCritically Ill Patient  575
Jacqueline L. Gierer, Jill Gualdoni, and Paul D. Bozyk
68 Spontaneous Bacterial Peritonitis 581
Abdul W. Raif Jawid and Indhu M. Subramanian
69 ICU Management ofthePatient withAlcoholic
Liver Disease 589
Jessica L. Mellinger and Robert J. Fontana

Part IX Hematologic Disease


Robert C. Hyzy

70 Diagnosis andManagement ofThrombotic


Thrombocytopenic Purpura 605
Bravein Amalakuhan and Anoop M. Nambiar
71 Acute Leukemia Presentation withDIC 615
Laurie A. Manka and Kenneth Lyn-Kew
72 Disseminated Intravascular Coagulation 619
Mario V. Fusaro and Giora Netzer
73 Hemophagocytic Lymphohistiocytosis  625
Benjamin H. Singer and Hillary A. Loomis-King
xiv Contents

74 ICU Complications ofHematopoietic Stem Cell


Transplantation Including Graft Versus Host Disease  631
Peter C. Stubenrauch, Kenneth Lyn-Kew,
and James Finigan
75 Tumor Lysis Syndrome 641
Himaja Koneru and Paul D. Bozyk
76 Management ofHyperviscosity Syndromes 647
Brian P. O'Connor and Indhu M. Subramanian

Part X Surgical
Lena M. Napolitano

77 Thoracic Trauma 657


Katherine M. Klein and Krishnan Raghavendran
78 Blunt Abdominal Trauma  665
Elizabeth C. Gwinn and Pauline K. Park
79 Abdominal Sepsis andComplicated Intraabdominal
Infections 673
Sara A. Buckman and John E. Mazuski
80 Intestinal Obstruction: Small andLarge Bowel  681
Joseph A. Posluszny Jr. and Fred A. Luchette
81 Management ofAcute Compartment Syndrome 687
Ming-Jim Yang, Frederick A. Moore, and Janeen R. Jordan
82 Extracorporeal Membrane Oxygenation (ECMO)
andExtracorporeal CO2 Removal (ECCO2R) 693
Eric T. Chang and Lena M. Napolitano
83 Management of Acute Thermal Injury 701
Kavitha Ranganathan, Stewart C. Wang and Benjamin Levi
84 Acute Arterial Ischemia 707
Danielle Horne and Jonathan L. Eliason
85 Management ofNecrotizing Soft Tissue Infection 713
Heather Leigh Evans and Eileen M. Bulger
86 Biliary Infections 719
Gregory A. Watson and Andrew B. Peitzman

Part XI Critical Care in Obstetrics


Marie R. Baldisseri

87 Peripartum Cardiomyopathy  729


Hayah Kassis, Maria Patarroyo Aponte,
and Srinivas Murali
88 Management ofAmniotic Fluid Embolism 737
Susan H. Cheng and Marie R. Baldisseri
Contents xv

89 Respiratory Diseases ofPregnancy 743


Nithya Menon and Mary Jane Reed
90 Preeclampsia, Eclampsia andHELLP Syndrome 749
Meike Schuster, Emmie Ruth Strassberg,
and Mary Jane Reed

Part XII Other Conditions


Robert C. Hyzy

91 Management of Severe Skin Eruptions 759


Jad Harb, Andrew Hankinson, and Garth W. Garrison
92 Management of Alcohol Withdrawal Syndromes  765
Lucas A. Mikulic and Garth W. Garrison

Part XIII Medical Ethics


Robert C. Hyzy

93 End ofLife Care intheICU 773


Sameer Shah and Nicholas S. Ward
Index 781
Contributors

AliAbedi, MD, MSc Department of Medicine, Division of Pulmonary


Diseases and Critical Care Medicine, University of Texas Health Science
Center at San Antonio, San Antonio, TX, USA
NormanE.Adair, MD Pulmonary, Allergy and Critical Care Medicine,
Wake Forest University/Wake Forest Baptist Health, Winston-Salem,
NC, USA
AyodejiAdegunsoye, MD Section of Pulmonary & Critical Care,
Department of Medicine, University of Chicago Medicine,
Chicago, IL, USA
AmyM.Ahasic, MD, MPH Department of Internal Medicine,
Section of Pulmonary, Critical Care and Sleep Medicine,
Yale University School of Medicine, New Haven, CT, USA
BraveinAmalakuhan, MD Department of Medicine, Division
of Pulmonary Diseases and Critical Care Medicine, University of Texas
Health Science Center at San Antonio, San Antonio, TX, USA
MariaPatarroyoAponte, MD Cardiovascular Institute,
Allegheny Health Network, Pittsburgh, PA, USA
PedroArriaga, MD Internal Medicine, Karl Heusner Memorial Hospital,
Belize City, Belize
RohanArya, MD Medicine, Division of Pulmonary and Critical Care
Medicine, University of South Carolina School of Medicine,
Columbia, SC, USA
RanaLeeAdawiAwdish, MS, MD Department of Pulmonary
and Critical Care Medicine, Henry Ford Health System, Detroit, MI, USA
MarieR.Baldisseri, MD, MPH, FCCM Critical Care Medicine,
University of Pittsburgh Medical Center, Pittsburgh, PA, USA
GregoryW.Barsness, MD Internal Medicine, Cardiovascular
Diseases and Radiology, Mayo Clinic, Rochester, MN, USA
KristyA.Bauman, MD Pulmonary and Critical Care Medicine,
University of Michigan Health System, Ann Arbor, MI, USA

xvii
xviii Contributors

TorbenKimBecker, MD, PhD Department of Emergency Medicine,


University of Michigan, Ann Arbor, MI, USA
ElizabethA.Belloli, MD Internal Medicine, Division of Pulmonary
& Critical Care Medicine, University of Michigan Health System,
Ann Arbor, MI, USA
DavidD.Berg, MD Department of Medicine, Brigham and Womens
Hospital, Boston, MA, USA
ThomasBice, MD, MSc Pulmonary and Critical Care Medicine,
University of North Carolina Chapel Hill, Chapel Hill, NC, USA
AzraBihorac, MD, MS, FCCM, FASN Department of Anesthesiology/
Division of Critical Care Medicine, University of Florida College of
Medicine, Gainesvile, FL, USA
DavidM.Black, MD Emergency Medicine, University of Michigan
Health System, Ann Arbor, MI, USA
DavidL.Bowton, MD, FCCP, FCCM Department of Anesthesiology,
Section of Critical Care, Wake Forest University/Wake Forest Baptist Health,
Winston-Salem, NC, USA
PaulD.Bozyk, MD Medical Intensive Care Unit, Department of Medicine,
Beaumont Health, Royal Oak, MI, USA
ChristineMartinekBrent, MD Emergency Medicine,
University of Michigan Health System, Ann Arbor, MI, USA
SaraA.Buckman, MD, PharmD Department of Surgery,
Section of Acute and Critical Care Surgery, Washington University,
St. Louis, MO, USA
EileenM.Bulger, MD Surgery, University of Washington,
Seattle, WA, USA
ChristopherF.Carpenter, MD Section of Infectious Diseases
and International Medicine, Department of Medicine, Oakland University,
Beaumont Health, Royal Oak, MI, USA
ShannonS.Carson, MD Pulmonary and Critical Care Medicine,
University of North Carolina Chapel Hill, Chapel Hill, NC, USA
EricT.Chang, MD General Surgery, University of Michigan,
Ann Arbor, MI, USA
SusanH.Cheng, MD, MPH Critical Care Medicine,
University of Pittsburgh Medical Center, Pittsburgh, PA, USA
CarolH.Choe, MD Critical Care Medicine, Lexington Medical Center,
West Columbia, SC, USA
IvanNathanielCo, MD Department of Pulmonary and Critical
Care Medicine, University of Michigan, Ann Arbor, MI, USA
Contributors xix

HowardA.Cooper, MD Inpatient Cardiology, Division of Cardiology,


Westchester Medical Center, Valhalla, NY, USA
ScottJ.Denstaedt, MD Pulmonary and Critical Care Medicine,
University of Michigan Health System, Ann Arbor, MI, USA
RobertP.Dickson, MD Medicine (Pulmonary and Critical Care),
University of Michigan Health System, Ann Arbor, MI, USA
JonathanL.Eliason, MD Section of Vascular Surgery, University
of Michigan, Ann Arbor, MI, USA
HeatherLeighEvans, MD, MS Surgery, University of Washington/
Harborview Medical Center, Seattle, WA, USA
LauraEvans, MD, MSc Division of Pulmonary, Critical Care, and Sleep
Medicine, New York University School of Medicine, New York, NY, USA
ElaineC.Fajardo, MD Internal Medicine Department,
Section of Pulmonary, Critical Care and Sleep Medicine, Yale University
School of Medicine, New Haven, CT, USA
JohnathanM.Fine, MD Internal Medicine, Pulmonary and Critical Section,
Norwalk Hospital, Norwalk, CT, USA
JamesFinigan, MD Department of Medicine, National Jewish Health,
Denver, CO, USA
RobertJ.Fontana, MD Division of Gastroenterology, Department
of Internal Medicine, University of Michigan Medical Center, Ann Arbor,
MI, USA
MarioV.Fusaro, MD Medicine, Division of Pulmonary and Critical Care,
New York Medical College, Westchester Medical Center, Valhalla, NY, USA
GarthW.Garrison, MD Division of Pulmonary and Critical Care Medicine,
University of Vermont Medical Center, Burlington, VT, USA
StevenE.Gay, MD Division of Pulmonary and Critical Care Medicine,
University of Michigan Health System, Ann Arbor, MI, USA
RomergrykoG.Geocadin, MD Neurology, Neurosurgery
and Anesthesiology Critical Care Medicine, Neurosciences Critical
Care Division, Johns Hopkins University School of Medicine,
Baltimore, MD, USA
PravinGeorge, BA, DO Neuroscience Critical Care, Anesthesia Critical
Care Medicine, The Johns Hopkins Hospital, Baltimore, MD, USA
JacquelineL.Gierer, DO Internal Medicine, Beaumont Health,
Royal Oak, MI, USA
TimothyD.Girard, MD, MSCI Division of Allergy, Pulmonary
and Critical Care Medicine and Center for Health Services Research
in the Department of Medicine, Vanderbilt University School of Medicine,
Nashville, TN, USA
xx Contributors

Geriatric Research, Education and Clinical Center (GRECC) Service


and Medical Service, Department of Veterans Affairs Medical Center,
Tennessee Healthcare System, Nashville, TN, USA
JoshuaM.Glazer, MD Emergency Medicine, University of Michigan
Health System, Ann Arbor, MI, USA
SaraswathiGopal, MD Division of Nephrology Hypertension and Renal
Transplantation, Department of Medicine, University of Florida,
Gainesville, FL, USA
JillGualdoni, MD Internal Medicine, Beaumont Health,
Royal Oak, MI, USA
KyleJ.Gunnerson, MD Emergency Medicine, Internal Medicine
and Anesthesiology, Division of Emergency Critical Care,
University of Michigan Health System, Ann Arbor, MI, USA
ElizabethC.Gwinn, MD Acute Care Surgery, University of Michigan,
Ann Arbor, MI, USA
RyanHadley, MD Pulmonary and Critical Care Medicine,
Spectrum Health, Grand Rapids, MI, USA
ShamirHaji, MSc, MD Anesthesia and Critical Care Medicine,
Johns Hopkins Hospital, Baltimore, MD, USA
NealHakimi, MD Medicine, Section of Pulmonary, Critical Care
and Sleep Medicine, Yale University School of Medicine,
New Haven, CT, USA
AndrewHankinson, MD Dermatology, University of Vermont
Medical Center, Burlington, VT, USA
JadHarb, MD Pulmonary and Critical Care Medicine,
University of Vermont Medical Center, Burlington, VT, USA
CarrieE.Harvey, MD Anesthesiology, University of Michigan
Health System, Ann Arbor, MI, USA
JorgeHidalgo, MD, MACP, MCCM, FCCP Adult Intensive Care,
Critical Care Division, Karl Heusner Memorial Hospital,
Belize City, Belize
DanielleHorne, MD, MS Section of Vascular Surgery,
University of Michigan, Ann Arbor, MI, USA
MichaelD.Howell, MD, MPH Center for Healthcare Delivery Science
and Innovation, University of Chicago Medicine, Chicago, IL, USA
JenniferS.Hughes, MD, MS Department of Internal Medicine,
Highland Hospital, Alameda Health System, Oakland, CA, USA
RobertC.Hyzy, MD Critical Care Medicine Unit, Division of Pulmonary
and Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA
Contributors xxi

ShijingJia, MD Internal Medicine, Pulmonary and Critical Care,


University of Michigan, Ann Arbor, MI, USA
PaulC.Johnson, MD Infectious Diseases, Beaumont Health,
Royal Oak, MI, USA
BrandonM.Jones, MD Cardiovascular Medicine and Interventional
Cardiology, Cleveland Clinic Foundation, Cleveland, OH, USA
JaneenR.Jordan, MD, FACS Department of Surgery, University
of Florida, Gainesville, FL, USA
HayahKassis, MD Cardiovascular Institute, Allegheny Health Network,
Pittsburgh, PA, USA
JasonN.Katz, MD, MHS Medicine, Mechanical Heart Program,
Cardiac Intensive Care Unit, Cardiothoracic Intensive Care Unit & Critical
Care Service, Cardiovascular Clinical Trials, University of North Carolina,
Chapel Hill, NC, USA
AmirKazory, MD Medicine/Nephrology, University of Florida,
Gainesville, GA, USA
JohnA.Kellum, MD, MCCM, FACP Critical Care Research,
Center for Critical Care Nephrology, Critical Care Medicine University
of Pittsburgh, Pittsburgh, PA, USA
BenjaminKeveson, MD Division of Pulmonary and Critical Care
Medicine, University of Vermont Medical Center, Burlington, VT, USA
KatherineM.Klein, MD Surgical Critical Care, General Surgery,
Department of Surgery, University of Toledo, Toledo, OH, USA
HimajaKoneru, MD Internal Medicine, Beaumont Health, Royal Oak,
MI, USA
JohnP.Kress, MD Medical Intensive Care Unit, Section of Pulmonary
& Critical Care, Department of Medicine, University of Chicago Medicine,
Chicago, IL, USA
MarkW.Landmeier, MD Department of Pulmonary and Critical Care
Medicine, Northwestern University Feinberg School of Medicine,
Chicago, IL, USA
BenjaminLevi, MD Department of Surgery, University of Michigan
Health Systems, Ann Arbor, MI, USA
JohnM.Litell, DO Department of Emergency Medicine,
Division of Emergency Critical Care, University of Michigan Health
System, Ann Arbor, MI, USA
HillaryA.Loomis-King, MD Internal Medicine, Division of Pulmonary
and Critical Care Medicine, University of Michigan Health System,
Ann Arbor, MI, USA
xxii Contributors

FredA.Luchette, MD, MSc Department of Surgery, Stritch School


of Medicine, Loyola University of Chicago, VA Affairs, Surgical Service
Lines, Edward Hines Jr., Veterans Administration Medical Center,
Maywood, IL, USA
KennethLyn-Kew, MD Medicine, Division of Pulmonary,
Critical Care and Sleep Medicine, National Jewish Health,
Denver, CO, USA
JasonH.Maley, MD Department of Medicine, Hospital of the University
of Pennsylvania, Philadelphia, PA, USA
LaurieA.Manka, MD Department of Medicine, Division of Pulmonary,
Critical Care and Sleep Medicine, Denver, CO, USA
JohnE.Mazuski, MD, PhD Department of Surgery,
Washington University in Saint Louis School of Medicine,
Saint Louis, MO, USA
GregoryT.Means, MD Cardiology, Department of Medicine,
University of North Carolina, Chapel Hill, NC, USA
JessicaL.Mellinger, MD, MSc Division of Gastroenterology,
Department of Internal Medicine, University of Michigan Medical Center,
Ann Arbor, MI, USA
MichaelP.Mendez, MD Department of Pulmonary and Critical Care
Medicine, Henry Ford Health System, Detroit, MI, USA
NithyaMenon, MBBS, MD Pulmonary and Critical Care,
Geisinger Medical Center, Danville, PA, USA
VenuMenon, MD Cardiovascular ICU, Cardiovascular Medicine
and Cardiovascular Imaging, Cleveland Clinic Foundation,
Cleveland, OH, USA
MarkE.Mikkelsen, MD, MSCE Department of Medicine,
Hospital of the University of Pennsylvania, Philadelphia, PA, USA
LucasA.Mikulic, MD Pulmonary and Critical Care Medicine,
University of Vermont Medical Center, Burlington, VT, USA
MelissaA.Miller, MD, MS Internal Medicine, University of Michigan
Medical School, Ann Arbor VA Health System, Ann Arbor, MI, USA
PatrickGeorgeMinges, MD, BS Department of Emergency Medicine,
University of Michigan Hospitals, Ann Arbor, MI, USA
FrederickA.Moore, MD, FACS Department of Surgery,
University of Florida, Gainesville, FL, USA
YogeshMoradiya, MD Neurosurgery, Hofstra Northwell School
of Medicine, Manhasset, NY, USA
Contributors xxiii

DavidA.Morrow, MD, MPH Levine Cardiac Intensive Care Unit,


TIMI Biomarker Program, TIMI Study Group, Department of Medicine,
Cardiovascular Division, Brigham & Womens Hospital, Harvard Medical
School, Boston, MA, USA
MaximilianMulder, MD Neurocritical Care Unit, Department
of Critical Care, Abbott Northwestern Hospital, Minneapolis, MN, USA
SrinivasMurali, MD, FACC Cardiovascular Institute, Allegheny
Health Network Cardiovascular Medicine, Allegheny General Hospital,
Pittsburgh, PA, USA
HedwigS.Murphy, MD, PhD Department of Pathology, University
of Michigan and Veterans Affairs Ann Arbor Health System,
Ann Arbor, MI, USA
AnoopM.Nambiar, MD Department of Medicine, Division of Pulmonary
Diseases and Critical Care Medicine, University of Texas Health Science
Center at San Antonio and the Audie L.Murphy VA Hospital,
South Texas Veterans Health Care System, San Antonio, TX, USA
AndrewM.Namen, MD, FCCP, FAASM Pulmonary, Critical Care,
Allergy & Immunology, Wake Forest University/Wake Forest Baptist Health,
Winston-Salem, NC, USA
LenaM.Napolitano, MD Department of Surgery, Division of Acute
Care Surgery, Trauma and Surgical Critical Care, University of Michigan
Health System, Ann Arbor, MI, USA
NeerajNaval, MD Inpatient Neurosciences & Neurocritical Care,
Lyerly Neurosurgery, Baptist Neurological Institute, Jacksonville, FL, USA
GioraNetzer, MD, MSCE Medicine and Epidemiology,
Division of Pulmonary and Critical Care Medicine, University of Maryland
School of Medicine, Baltimore, MD, USA
RobertW.Neumar, MD, PhD Department of Emergency Medicine,
University of Michigan Medical School, Ann Arbor, MI, USA
BrianP.OConnor, MD, MPH Department of Internal Medicine,
Highland Hospital, Alameda Health System, Oakland, CA, USA
BenjaminA.Olenchock, MD, PhD Department of Medicine,
The Brigham and Womens Hospital and Harvard Medical School,
Boston, MA, USA
RonnyM.Otero, MD Emergency Medicine, University of Michigan
Hospital, Ann Arbor, MI, USA
ChristianOvergaard-Steensen, MD, PhD Department of
Neuroanaesthesiology, Rigshospitalet, Copenhagen, Denmark, USA
PaulineK.Park, MD Acute Care Surgery, University of Michigan,
Ann Arbor, MI, USA
xxiv Contributors

AndrewB.Peitzman, MD Department of Surgery, Trauma and Surgical


Services, University of Pittsburgh School of Medicine, UPMC-Presbyterian,
Pittsburgh, PA, USA
AydinUzunPinar, MD Medical Intensive Care Unit, Department
of Medicine, Section of Pulmonary Critical Care and Sleep Medicine,
Yale School of Medicine, New Haven, CT, USA
JosephA.Posluszny, Jr., MD Surgery, Loyola University Stritch School
of Medicine, Edward Hines Jr. Veterans Administration Medical Center,
Maywood, IL, USA
ArmanQamar, MD Cardiovascular Division, Department of Medicine,
Brigham and Womens Hospital, Harvard Medical School,
Boston, MA, USA
KrishnanRaghavendran, MBBS, MS, FRCS Department of Surgery,
University of Michigan, Ann Arbor, MI, USA
MargaretF.Ragland, MD, MS Department of Medicine,
Northwestern Feinberg School of Medicine, Chicago, IL, USA
AbdulW.RaifJawid, MD Department of Internal Medicine,
Highland Hospital, Alameda Health System, Oakland, CA, USA
AnuradhaRamaswamy, MD, FACP Section of Pulmonary,
Critical Care and Sleep Medicine, Yale University School of Medicine,
New Haven, CT, USA
KavithaRanganathan, MD Department of Surgery, University
of Michigan Health Systems, Ann Arbor, MI, USA
MaryJaneReed, MD, FACS, FCCM, FCCP Critical Care Medicine,
Geisinger Medical Center, Danville, PA, USA
TroelsRing, MD Nephrology, Aalborg University Hospital,
Aalborg, Denmark, USA
LuciaRiveraLara, MD Neurology, Johns Hopkins University,
Baltimore, MD, USA
GloriaM.Rodrquez-Vega, MD, FACP, FCCP, FCCMDepartment
of Critical Care Medicine, Hospital Hima San Pablo Caguas,
Rio Piedras, PR, USA
KathrynRosenblatt, MD Anesthesiology & Critical Care Medicine,
Division of Neuroanesthesia and Neurosciences Critical Care,
Johns Hopkins Hospital, Johns Hopkins University School of Medicine,
Baltimore, MD, USA
RommelSagana, MD Pulmonary & Critical Care, University of Michigan,
Ann Arbor, MI, USA
ChristaOHanaV.SanLuis, MD Neurology, Division of Neurocritical
Care, University of Mississippi Medical Center, Jackson, MS, USA
Contributors xxv

RobynScatena, MD Yale University School of Medicine, Department


of Medicine, Section of Pulmonary, Critical and Sleep, Norwalk Hospital,
Norwalk, CT, USA
MarkSchmidhofer, MS, MD Department of Medicine, University
of Pittsburgh School of Medicine, Heart and Vascular Institute,
UPMC Health System, Pittsburgh, PA, USA
MatthewE.Schmitt, MD Pulmonary, Critical Care and Sleep Medicine,
Norwalk Hospital, Norwalk, CT, USA
DavidSchrift, MD Clinical Internal Medicine, Pulmonary and Critical
Care Medicine, University of South Carolina School of Medicine,
Columbia, SC, USA
MeikeSchuster, DO Maternal Fetal Medicine, Geisinger Medical Center,
Danville, PA, USA
ElaineKlingeSchwartz, MD, FCCP Department of Medicine,
National Jewish Health, Denver, CO, USA
BenjaminM.Scirica, MD, MPH Cardiovascular Division, Department
of Medicine, Brigham and Womens Hospital, Harvard Medical School,
Boston, MA, USA
JacobScott, MD Pulmonary and Critical Care Medicine, Spectrum Health,
Grand Rapids, MI, USA
DanielSedehi, MD Cardiovascular Medicine, Knight Cardiovascular
Institute, Oregon Health and Science University, Portland, OR, USA
JanekManojSenaratne, MD, BMedSci Division of Cardiology,
University of Alberta, Edmonton, AB, Canada
RobertW.Shaffer, MD Department of Emergency Medicine,
University of Michigan Health System, Ann Arbor, MI, USA
SameerShah, MD Pulmonary and Critical Care Medicine, Medicine,
Rhode Island Hospital/Brown University, Providence, RI, USA
JharnaN.Shah, MBBS, MPH Division of Neurosciences Critical Care,
The Johns Hopkins University School of Medicine, Baltimore, MD, USA
MichaelG.Silverman, MD Cardiovascular Division,
Brigham and Womens Hospital, Boston, MA, USA
BenjaminH.Singer, MD, PhD Internal Medicine, Division of Pulmonary
and Critical Care Medicine, University of Michigan Medical School,
Ann Arbor, MI, USA
ThomasH.Sisson, MD Pulmonary and Critical Care Medicine,
University of Michigan Hospital and Health Systems, Ann Arbor, MI, USA
JoshuaSmith, MD Internal Medicine Division of Pulmonary
and Critical Care Medicine, Indiana University School of Medicine,
Indianapolis, IN, USA
xxvi Contributors

JenniferP.Stevens, MD, MS Department of Medicine,


Division of Pulmonary, Critical Care, and Sleep Medicine,
Beth Israel Deaconess Medical Center, Boston, MA, USA
EmmieRuthStrassberg, DO Maternal Fetal Medicine,
Geisinger Health System, Danville, PA, USA
PeterC.Stubenrauch, MD Pulmonary and Critical Care Medicine,
National Jewish Health, Denver, CO, USA
IndhuM.Subramanian, MD Pulmonary and Critical Care Faculty,
Department of Internal Medicine, Highland Hospital,
Alameda Health System, Oakland, CA, USA
SohaibTariq, MD Division of Cardiology, Westchester Medical Center,
Valhalla, NY, USA
FadiA.Tohme, MD Renal & Electrolyte Division,
University of Pittsburgh Medical Center, Pittsburgh, PA, USA
AmitUppal, MD Division of Pulmonary, Critical Care, and Sleep Medicine,
New York University School of Medicine, New York, NY, USA
Seanvan Diepen, MD, MSc Critical Care Medicine, Division of Cardiology,
University of Alberta Hospital, Edmonton, AB, Canada
StewartC.Wang, MD, PhD Burn Surgery, Department of Surgery,
University of Michigan Health Systems, Ann Arbor, MI, USA
NicholasS.Ward, MD Medicine, Division of Pulmonary, Critical Care,
and Sleep Medicine, Alpert/Brown Medical School, Providence, RI, USA
GregoryA.Watson, MD Surgery & Critical Care, University of Pittsburgh
School of Medicine, Pittsburgh, PA, USA
CurtisH.Weiss, MD, MS Pulmonary and Critical Care Medicine,
Northwestern University Feinberg School of Medicine, Chicago, IL, USA
SageP.Whitmore, MD Emergency Medicine, Division of Emergency
Critical Care, University of Michigan Health System, Ann Arbor, MI, USA
MarkDarenWilliams, MD, FCCM, FCCP Pulmonary/Critical Care
Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
RichardG.Wunderink, MD Department of Pulmonary and Critical
Care Medicine, Northwestern University Feinberg School of Medicine,
Chicago, IL, USA
Ming-JimYang, MD, MS Department of Surgery, University of Florida,
Gainesville, FL, USA
Part I
ER- ICU Shock and Resuscitation

RobertW.Neumar
Cardiac Arrest Management
1
RonnyM.Otero

Introduction evolving [8]. Rapid activation of the Chain of


Survival and meticulous attention to early defi-
It is currently estimated that over 300,000 out-of- brillation and chest compressions may lead to
hospital cardiac (OHCA) arrests occur in the greater overall trends in survival.
United States. Over half of OHCA cases are man-
aged by EMS systems [1]. The national average
for survival from an OHCA is approximately Case Presentation
12% however; there is considerable variation by
region and EMS system [2, 3]. Factors associated A 68 year-old male was playing cards at a casino
with an improved survival from OHCA include when suddenly he clutched his chest and became
crew witnessed arrest and bystander CPR [4]. unresponsive. Casino security arrived within less
Survival from witnessed VF arrest decreases by than a minute and applied an automated external
8% for every minute delay in CPR and defibrilla- defibrillator (AED). AED displayed an audio
tion [5]. Overall outcomes correlate with early prompt that no shock was advised. Bystander
implementation of chest compression. There is a cardiopulmonary resuscitation (CPR) was begun
strong suggestion that bystander CPR whether within another 10s. Paramedics arrived and pro-
with chest compression only or standard CPR vided two-rescuer CPR with a compression rate
is associated with better mortality and neurologic of 110 compressions/minute. In the ambulance
outcomes [6, 7]. rescuers used a mechanical compression device
Early effective chest compressions and atten- to administer continuous chest compressions at a
tion to basic life support components are part of rate of 110 and depth of 2.5 inches with manual
high quality CPR.Various organizations have ventilation using a bag mask valve. This support
revisited each of the components of cardiac arrest was continued until their arrival at the hospital in
resuscitation over the last couple of years and approximately 9min. Patient was not intubated
thus the elements of high-quality CPR are ever- in the field. During CPR there was no evidence of
an organized cardiac rhythm. Patient had received
a total of 3 doses of epinephrine totaling 3mg via
Electronic supplementary material The online version
of this chapter (doi:10.1007/978-3-319-43341-7_1) con- humeral intra-osseous line. Upon arrival in the
tains supplementary material, which is available to autho- emergency department endotracheal intubation
rized users. was performed without incident and capnogra-
phy displayed a good waveform with an ETCO2
R.M. Otero
Emergency Medicine, University of Michigan
of 15mm Hg. On arrival emergency physicians
Hospital, Ann Arbor, MI, USA administered another dose of epinephrine while
e-mail: Oteror@umich.edu continuing CPR.At this point the team leader

Springer International Publishing Switzerland 2017 3


R.C. Hyzy (ed.), Evidence-Based Critical Care, DOI10.1007/978-3-319-43341-7_1
4 R.M. Otero

paused and solicited ideas from the team about end-tidal CO2 with chest compression to close to
possible etiologies for persistent pulseless elec- 35mm Hg may signal return of spontaneous cir-
trical activity (PEA). culation (ROSC) [1517].
Achieving a higher blood pressure during
Question What are methods to assess the qual- CPR makes intuitive sense, as thoracic compres-
ity of chest compressions during CPR? sion and thus, cardiac output will be the driving
force behind improving cerebral and systemic
Answer Capnography, arterial blood pressure perfusion. However, the hemodynamics of car-
and coronary perfusion pressure diac arrest is complex and patient-specific factors
may be responsible for the variable responses to
Components of high quality CPR include chest compressions, vasopressors and ventila-
minimizing interruptions of chest compressions tion. One of the main determinants of successful
with a chest compression fraction of >60%, cor- resuscitation is the coronary perfusion pressure
rect chest compression rate and depth. (CPP), which is the difference between the right
Recommended chest compression rates are atrial pressure (or CVP) and aortic pressure dur-
greater than 100 and a depth of 50mm with ing diastole (relaxation phase of chest compres-
allowance for chest recoil between compression sion). In the arrested patient there is a delay until
and minimizing ventilations to no more than there is a complete cessation of flow through the
1012 breaths/minute [912]. The emphasis of cardiac chambers and by 1min there is no flow to
chest compressions over positive pressure venti- the coronary arteries. In a human study a
lation has been supported by studies, which have CPP<15mm Hg was associated with not achiev-
shown a mortality benefit of compression only ing ROSC [18]. In animal studies it has been
CPR in witnessed arrest compared with tradi- shown that higher levels of CPP are required to
tional CPR with compressions and ventilation provide cerebral blood flow when CPR is delayed
[13]. How well chest compressions are meeting [19]. Moreover, in studies where ROSC was
the goal of providing circulatory flow to the brain achieved in humans, it was closely tied to CPP
and vital systems is often difficult to ascertain. and aortic diastolic pressure [20]. CPR guided by
Of the readily available parameters capnogra- blood pressure has also shown improved out-
phy and arterial blood pressure monitoring are comes [21]. In the observational human study
the most easily applied measurements to provide evaluating coronary perfusion pressure as the
feedback of the quality of chest compressions. correlate to ROSC a mean maximal aortic relax-
Close attention to the physiologic response to ation pressure (aka diastole) was 35.211.5, thus
chest compressions is desirable, as studies indi- the diastolic pressure target should be approxi-
cate that even healthcare professionals have poor mately 40mm Hg [18]. In settings where a
recall and variable quality when performing chest patient is instrumented with an arterial and a cen-
compressions [14]. tral venous line, aortic diastolic pressure and
Capnography has long-been seen as a poten- right atrial pressure can be substituted by arterial
tial surrogate for blood flow through heart and diastolic pressure and central venous pressure.
the pulmonary circulation [15]. As the technol- The difference between arterial diastolic pressure
ogy has improved so has the portability. and central venous pressure may provide a rough
Capnography can now be measured by side- estimate of CPP [22]. When the ability to monitor
stream technology in non-intubated patients and CPP is unavailable a strategy to assess the effi-
or mainstream capnography in intubated patients. cacy of chest compressions may depend upon
During cardiopulmonary resuscitation the goal of capnography and diastolic pressure.
high quality chest compressions is to achieve an Lastly, emerging technology, which provides
end-tidal CO2 of 20mm Hg or higher and to instantaneous feedback about the quality of chest
maintain an end-tidal CO2 greater than 10mm compressions is now available. This CPR-sensing
Hg at all times with compressions. A rapid rise in feedback (FB) system often utilizes accelerome-
1 Cardiac Arrest Management 5

ters to detect rate and depth of compressions (79 18) compared to patients with ROSC
while delivering audio cues to the rescuer. (9017) [3].
Currently available CPR-FB systems include the Specific goals of high quality CPR include
Phillips Q-CPR , Zoll Real CPR Help and achieving a compression rate of at least 100120
Physio-Control compression metronome and compression/minute and a compression depth of
Code Stat [23]. It is not known at this time at least 50mm (2 inches) with an upper limit of
whether utilizing these CPR-FB systems 60mm (2.4 inches) [9]. Additionally, high quality
improves outcomes. chest compressions should include a chest com-
pression fraction >60%, meaning when CPR is
performed chest compressions should occupy at
Principles ofManagement least 60% of the resuscitation [9]. Patient position-
ing, vascular or intraosseous access, medication
Standard Approach toResuscitation administration, airway establishment, rhythm
analysis and defibrillation should occupy the
Introduction remaining fraction of time. Maintaining a chest
Achieving optimal outcomes from cardiac arrest compression rate of 100120 compressions/min-
requires collaboration between several disci- ute can lead to rescuer fatigue. Switching com-
plines including pre-hospital providers, emer- pressors every 2min may minimize rescuer fatigue
gency physicians, cardiologists, cardiac but lead to frequent interruptions and may nega-
interventionalist as well as several other medical tively impact chest compression fraction. One sug-
professionals and specialists. All providers in this gestion to decrease this hands-off time is to have
paradigm should understand each others role as rescuers switch from opposite sides of the victim
well as what measures can be expected to be [25]. Between compressions there should be time
offered to a victim of sudden cardiac arrest. allowed for full chest recoil in order for heart to
refill with blood and maximizing CPP.
 ecognition ofSudden Cardiac Arrest
R
The ability of laypersons as well as health profes-  djuncts toCPR: Oxygen
A
sionals to detect a pulse has been reported to be andVentilation
extremely poor [14, 24]. Additionally, agonal During the initial rounds of chest compressions
breaths may be seen for several minutes after car- rescuers should focus on the quality of the com-
diac arrest confounding the confirmation that a pressions and use passive oxygenation with the
patient has arrested. Despite these limitations it is highest concentration of oxygen available at the
best to activate emergency response system as time. The delivery of this oxygen is dependent
soon as a patient is unresponsive with a faint or upon the systemic perfusion that may be estab-
absent pulse. lished by chest compressions.
Attempts to establish a definitive airway
Chest Compressions should be postponed unless there is difficulty
After a pulse check of no more than 10s chest ventilating a patient with a bag valve mask.
compressions should be initiated at once. Health Furthermore, hyperventilation should be avoided
care providers should re-double their efforts to as this has been tied to reducing cardiac output
improve their knowledge and maintain technical [26, 27]. When two providers are resuscitating a
skills relevant to chest compressions. Evidence patient ventilations are delivered in a 30:2
for maintaining these skills may be gleaned from compression-to-ventilation ratio until a definitive
a multi-center study whereby healthcare provid- airway has been established [28]. Using a 1L bag
ers often performed suboptimal chest compres- mask device a second provider should provide
sion rates. Specifically, the mean chest approximately 600cc of tidal volume over 1s.
compression rate was below the recommended This should be performed a total of two times
rate and lowest for patients without ROSC after every 30 compressions. With an advanced
6 R.M. Otero

airway in place rescuers may provide a breath an electrolyte abnormality. If medication toxicity
every 6 s while chest compressions are performed and electrolyte abnormalities are ruled out persis-
continuously. tence of these dysrhythmias should prompt
search for myocardial ischemia.
Defibrillation Different forms of ventricular tachycardia
Defibrillation is indicated for ventricular fibrilla- exist including: monomorphic VT, polymorphic
tion or pulseless ventricular tachycardia. VT, torsade de pointes, right ventricular outflow
Although traditionally monophasic defibrillators tachycardia (idiopathic and arrhythmogenic right
have been used to administer a counter shock, ventricular dysplasia), fascicular tachycardia,
biphasic defibrillators are preferred due to the bidirectional VT and ventricular flutter.
greater first shock success. Newer waveforms Monomorphic VT accounts for the majority of
have been studied which provide patient-specific VT encountered. Most cases of monomorphic
impedance current delivery using biphasic trun- VT are associated with myocardial ischemia.
cated exponential, rectilinear biphasic or pulsed Torsade de pointe is a specific form of polymor-
biphasic wave. At this time there is no specific phic VT where there is progressive widening of
recommendation regarding which waveform is the QT interval. Although most forms of VT are
superior. Current recommendations are to admin- associated with myocardial ischemia there are
ister a single counter shock at an optimal energy forms of idiopathic VT.Of the idiopathic forms
level (between 120 and 360J for biphasic defi- of VT, most cases are due to abnormalities in the
brillators) with minimal interruptions in CPR outflow tract of the right ventricle. A small num-
before and after the shock [28]. In situations ber of these have an anatomically identified focus
requiring repeated defibrillations use manufac- termed arrhythmogenic right ventricular dyspla-
turers guidelines or consider escalating energy. sia. Ventricular flutter is an extreme form of VT
For refractory VF and pulseless VT, administra- that has a sinusoidal appearance and may degrade
tion of epinephrine and an anti-dysrhythmic into ventricular fibrillation. Ventricular flutter
agent should be instituted. usually has a rate >200 beats/min. Thus when
confronted with a patient with refractory ventric-
ular dysrhythmias providers should strongly con-
 earch forPrecipitating Cause
S sider consulting a cardiology specialist to
ofCardiac Arrest evaluate patient for the possibility of a diagnostic
and percutaneous intervention.
Ventricular Dysrhythmias
Survival to discharge for patients with an initial  ulseless Electrical Activity (PEA)
P
rhythm of VT or VF is between 15 and 23% for Patients with PEA have a survival to discharge of
out-of-hospital cardiac arrest and up to 37% for 2.77% for patients with out-of-hospital cardiac
patients with an in-hospital cardiac arrest [29, arrest as compared to patient in an in-hospital car-
30]. Resuscitation team leaders must simultane- diac arrest of only 12% [30, 31]. PEA is defined
ously look for reversible etiologies while admin- as the absence of a pulse when electrical cardiac
istering time-sensitive interventions. Ventricular activity is present. This is further classified as
fibrillation is usually found in patients with true PEA, which is when there is no pulse, the
abnormal myocardial perfusion from a prior presence of an electrical signal but no evidence of
infarct or ongoing ischemia. Similarly ventricular cardiac activity usually detected by echocardiog-
tachycardia usually results from foci below the raphy. Pseudo-PEA is defined as the absence of
AV node which progresses into a wide and regu- a pulse, presence of an electrical signal and car-
lar tachycardia. When confronted with these diac activity observed by echocardiography.
malignant ventricular dysrhythmias diagnostic It is important to make these distinctions, as
considerations include medication toxicity, pre- there is pathophysiologic and prognostic signifi-
existing channelopathy (Brugada syndrome) or cance. True PEA is when electromechanical uncou-
1 Cardiac Arrest Management 7

pling of cardiac cells which propagate an electrical wanes after 6 months thus implementing simu-
signal but the myocytes are unable to coordinate lated resuscitations may be useful in retaining
ventricular contraction. This situation is usually skills [35]. Short debriefing sessions after per-
seen in severe hypoxia, acidosis or necrosis. forming a cardiac resuscitation have been shown
In pseudo-PEA, there is an electrical signal to improve team performance and outcomes [36].
and weak cardiac contractions due to conditions
such as hypovolemia, massive pulmonary embo-
lism or other mechanical impediments to flow. In Evidence Contour
these situations the predominant rhythm is a
tachydysrhythmia.  re Outcomes withMechanical
A
A mnemonic, which has been modified over Compressions Superior toManual
the years to remind providers of the common pre- Compressions DuringActive CPR?
cipitants of PEA, is 4Hs-4Ts. This mnemonic
represents hypoxia, hypovolemia, hypo/hyper- Based upon currently available data mechanical
kalemia and hypothermia as well as thrombosis compressions do not appear to be superior to
(pulmonary emboli), tamponade (cardiac), toxins manual compressions in terms of outcomes.
and tension pneumothorax [32]. Manual compressions are the most readily appli-
Point of care ultrasound whenever possible cable and commonly taught method of providing
should be used to assist clinicians to investigate chest compressions. Despite this many pre-
many of the above-mentioned etiologies. For hospital and hospital systems have chosen to use
instance, a subcostal view on ultrasound may reveal mechanical compression devices to administer
a large pericardial effusion with diastolic collapse chest compression for various logistical reasons.
of right ventricle representing cardiac tamponade Over the last 40 years various technologies
(Video 1.1). A parasternal short axis view may have emerged to provide high quality and con-
demonstrate bowing of the intra-ventricular sep- sistency of chest compressions. These technolo-
tum, the so called D-sign appearance of the left gies are based upon one of two predominant
ventricle being compressed by a volume-over- theories of how chest compressions promote for-
loaded right ventricle contracting against a massive ward flow of blood into the thoracic aorta and
pulmonary embolism (Video 1.2). systemic circulation. The so-called cardiac
Littman etal. proposes a diagnostic guide to pump theory expounds that external chest com-
evaluate causes of PEA which includes evaluat- pressions places pressure simultaneously on the
ing the width of the QRS complexes on EKG as right and left ventricle. During the active com-
well as combining sonographic findings to sug- pression phase a pressure gradient pushes blood
gest whether a mechanical, ischemic or meta- out of ventricles, while closing the atrio-ventric-
bolic cause are to blame [33]. There is no ular valves and then to the pulmonary artery and
randomized study to support ultrasound-guided the aorta. During the decompression phase blood
resuscitations over resuscitations without ultra- re-enters the right and left atrium and feeds coro-
sound but a recent study has suggested a trend nary arteries [37].
that when modifications in traditional approaches The thoracic pump theory relies upon the
employ ultrasound there may be a higher rate of compliance of the whole thorax as the main pres-
ROSC to hospital admission [34]. sure determinant of flow and not on compression
of the heart. During compressions in the tho-
racic pump theory intra-thoracic pressure is
Quality Assurance increased driving blood into the thoracic, extra-
thoracic aorta and other large arteries preferen-
Every cardiac arrest should have some method to tially. This compression however does not seem
monitor the quality of the resuscitation. The abil- to affect the venous system as much due to valves
ity of rescuers to retain critical resuscitation skills and the vast network of venous plexuses. During
8 R.M. Otero

Fig. 1.1Thumper TM piston driven chest compression Fig. 1.2LUCASTM Chest compression device (Used
device (Courtesy of Michigan Instruments, Inc.) with permission of Physio-Control, Inc.)

the decompression phase intra-thoracic pressure


falls below the extra-thoracic pressure and blood
flows to the lungs.
Mechanical compression devices became
available for research and clinical applications
during the 1970s with the Thumper created by
Michigan Instrument which utilized a hydrauli-
cally powered piston to provide chest compres-
sions similar to the cardiac pump theory
(Fig.1.1). Newer devices emerged including the
Lund University Cardiac Arrest System (aka.
LUCAS 1 and 2 ) by Physio Control and the
Auto Pulse by Zoll employ different mecha-
nisms to enhance chest compressions namely
through an active compression and decompres-
sion mode. The LUCAS device is predomi-
nantly a piston-driven device with a suction area
Fig. 1.3 Auto Pulse TM Load distributing chest compres-
which makes contact with the chest (Fig.1.2). sion device (Courtesy of ZOLL Medical Corporation)
The Auto Pulse utilizing a load-distributing
band which wraps around the torso and squeezes
to increase intra-thoracic pressure (Fig.1.3). there are elements of both pump models active
Despite various studies utilizing transthoracic during CPR.
and trans esophageal dopplers to investigate the Advocates of mechanical compressions sup-
hemodynamics during chest compressions there port its consistency of depth and compression
is no consistent data to support either the cardiac rate. Mechanical compressions can maximize
pump or thoracic pump as the main mechanism hands on time compared to manual compres-
of flow during CPR [19, 38]. It is possible that sions due to the fact that there is no need to switch
1 Cardiac Arrest Management 9

rescuers or halt compressions when performing Despite controversy surrounding the use of cen-
defibrillation. Despite these theoretical advan- tral venous oxygen saturation (ScvO2) in the
tages a study completed in 2014 did not show a management of sepsis its application may be
mortality benefit of mechanical CPR over manual used as an estimate of tissue perfusion. ScvO2
compressions [39]. This study, which used the represents the residual oxygen content returning
LUCAS device showed no difference in survival to the right side of the heart after systemic perfu-
or neurologic outcome. The added cost of these sion. Studies have shown that persistently low
devices and their upkeep may prohibit wide- ScvO2 correlates with decrease cardiac output. If
spread use however providers point to the advan- available, chest compressions may be titrated to a
tage of reducing rescuer fatigue and diminishing ScvO2 concentration greater than 30% [45, 46].
risk to rescuers during transport while CPR is in Whether hemodynamic directed resuscitation
progress [40, 41]. leads to better outcomes in humans remains
unknown but if efforts to improve the rate of
bystander CPR and high quality chest compres-
 hat Physiologic Parameters Can
W sions are successful there may be less depen-
Guide theAdministration dence upon the pharmacologic treatment to
ofVasoactive Medications achieve ROSC.
andProvide Feedback
RegardingQuality ofCPR?
References
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H
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Ochoa F, Ramalle-Gomara E, Carpintero J. 2010;3(1):6381.
Competence of health professionals to check carotid 30. Meaney P, Nadkarni V, Kern K.Rhythms and out-
pulse. Resuscitation. 1998;37:1735. comes of adult in-hospital cardiac arrest. Crit Care
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Med. 1985;1985(3):1479. hospital cardiac arrests with initial asystole or pulsel-
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improves chest compression quality during simulated rhythms. Resuscitation. 2013;84(9):12616.
resuscitation. Resuscitation. 2013;84:158590. 32. Kloeck W.A practical approach to the aetiology of
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the accuracy of the diagnosis of cardiac arrest: a sys- tured teaching tool for the evaluation and manage-
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2011;82:14839. 2014;23:16.
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return of spontaneous circulation in human cardiopul- fied treatment in echocardiographically confirmed
monary resuscitation. JAMA. 1990;263:110613. pseudo-pulseless electrical activity in out-of-hospital
19. Andreka P, Frenneaux MP.Haemodynamics of car- cardiac arrest patients with constant end-tidal carbon
diac arrest and resuscitation. Curr Opin Crit Care. dioxide pressure during compression pauses. JInt
2006;12(3):198203. Med Res. 2010;38:145867.
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8713. 36. Edelson D, Litzinger B, Arora V.Improving in-

21. Sutton R, Friess S, Naim M.Patient-centric blood hospital cardiac arrest process and outcomes with
pressure-targeted cardiopulmonary resuscitation performance debriefing. Arch Intern Med. 2008;

improves survival from cardiac arrest. Am JResp Crit 168(10):10639.
Care Med. 2014;190(11):125562. 37. Rudikoff M, Maughan W, Effron M.Mechanisms of
22. Sutton R, Friess S, Maltese M.Hemodynamic-
blood flow during cardiopulmonary resucitation.
directed cardiopulmonary resuscitation during in- Circulation. 1980;61(2):34552.
hospital cardiac arrest. Resuscitation. 2014;85: 38.
Georgiou M, Papathanassoglou E, Xanthos T.
9836. Systematic review of the mechanisms driving effec-
23. Vadeboncoeur T, Bobrow BJ, Cone DC, Chikani V, tive blood flow during adult CPR.Resuscitation.
Abella BS.Instant replay: perform CPR with immedi- 2014;85:158693.
ate feedback. JEMS. 2011;36(3):5063. 39. Rubertsson S, etal. Mechanical chest compressions and
24. Eberle B, Dick W, Schneider T.Checking the carotid simultaneous defibrillation vs conventional cardiopul-
pulse check: diagnostic accuracy of first responders in monary resuscitation in out-of-hospital cardiac arrest:
patients with and without a pulse. Resuscitation. the LINC randomized trial. JAMA. 2014;311(1):5361.
1996;33:10716. 40. Chang WT, Ma MH, Chien KL.Post resuscitation
25. Kim Y, Lee J, Lee D.Differences in hands-off time myocardial dysfunction: correlated factors and prog-
according to the position of a second rescuer when nostic implications following prolonged ventricular
1 Cardiac Arrest Management 11

fibrillation and cardiopulmonary resuscitation. 44. Friess S, Sutton R, French B.Hemodynamic directed
Intensive Care Med. 2007;33:8895. CPR improves cerebral perfusion pressure and brain
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pressions for cardiac arrest. Cochrane Database Syst 1298303.
Rev. 2014;2:146. 45. Rivers E, etal. The clinical implications of continuous
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Post-cardiac Arrest Management
2
RonnyM.Otero andRobertW.Neumar

Introduction Case Presentation

This chapter will review the elements of cardiac A 68-year old male was mowing his lawn, com-
arrest resuscitation that begin after return of plained to his wife that he was having chest pain
spontaneous circulation (ROSC). In-hospital and then collapsed. She called 911 and when
mortality of patients who achieve ROSC long first responder EMTs arrived 5min later, they
enough to be admitted to an ICU averages 60% found him to be unresponsive, not breathing and
with wide inter-institutional variability (40 without a pulse. EMTs initiated cardiopulmonary
80%) [1]. The pathophysiology of post-cardiac resuscitation (CPR) and an automated external
arrest syndrome (PCAS) is composed of four defibrillator (AED) was applied to the patient.
major components: post-cardiac arrest brain The initial rhythm analysis advised a shock,
injury, post-cardiac arrest myocardial dysfunc- and a shock was delivered. After two additional
tion, systemic ischemia/reperfusion response, minutes of CPR the paramedics arrived and
and persistent precipitating pathology [2]. It is found the patient to have a palpable pulse, a sys-
important to recognize that each component is tolic blood pressure of 70mmHg, a narrow com-
potentially reversible and responsive to therapy. plex sinus tachycardia at a rate of 110 on the
A comprehensive multidisciplinary management monitor, and agonal respirations. Prior to trans-
strategy that addresses all components of post- port, a supraglottic airway was placed, bag-valve
cardiac arrest syndrome is needed to optimize ventilation was performed using 100% oxygen,
patient outcomes [3]. In addition, a reliable an intravenous line was placed and 1-L normal
strategy to prognosticate neurologic outcome in saline bolus was initiated. Time from 911 call to
persistently comatose patients is essential to pre- return of spontaneous circulation (ROSC) was
vent premature limitation of care and make pos- 9min.
sible appropriate stewardship of patient care On arrival to the local hospital, the patient
resources [3]. became pulseless again and the monitor revealed
a rhythm of ventricular fibrillation. The patient
was defibrillated with a biphasic defibrillator set
R.M. Otero (*) at 200J.Patient achieved return of spontaneous
Emergency Medicine, University of Michigan
Hospital, Ann Arbor, MI, USA
circulation (ROSC) with narrow complex
e-mail: Oteror@umich.edu tachycardia at a rate of 120 and a blood pressure
R.W. Neumar
of 75/40. The patient was given 500cc IV crystal-
Department of Emergency Medicine, University loid bolus and epinephrine infusion was initiated
of Michigan Medical School, Ann Arbor, MI, USA at titrated to MAP >65mmHg. A femoral arterial

Springer International Publishing Switzerland 2017 13


R.C. Hyzy (ed.), Evidence-Based Critical Care, DOI10.1007/978-3-319-43341-7_2
14 R.M. Otero and R.W. Neumar

line and an internal jugular central venous line An intravascular cooling catheter placed in
were placed. Endotracheal intubation was per- coronary angiography laboratory and target tem-
formed and placement confirmed with waveform perature was set at 33C.Patient was admitted to
capnography and the PetCO2 was 40mmHg. The the cardiac ICU and hypothermic targeted tem-
patient had no eye opening or motor response to perature management was maintained for 24 h
painful stimuli and pupils were fixed and dilated. followed by rewarming to 37C over 16 h
Arterial blood gas demonstrated the following: (0.25C/h). Sedation included propofol and fen-
pH=7.18 PCO2=39 HCO3=16 PaO2=340, tanyl infusion. Continuous EEG revealed a reac-
SpO2=100%, Lactate=4.0. FiO2 was decreased tive baseline with intermittent seizure activity
to achieve SpO2 9496%. A temperature sensing after rewarming that was treated with IV loraze-
bladder catheter was placed and read 36.0C.A pam and valproic acid. Seventy-two hours after
12 lead ECG was immediately obtained (Fig.2.1). rewarming neurologic exam revealed reactive
pupil and positive cornea reflex, with withdrawal
Question What interventions should be per- from painful stimuli. Patient began following
formed next? commands 96 h after rewarming and was extu-
bated on the 6th admission day. He was dis-
Answer Immediate coronary angiography with charged to short-term rehabilitation on the ninth
percutaneous coronary intervention (PCI) and day with neurologic deficits limited to mild short-
hypothermic targeted temperature management. term memory deficit.

Twelve-lead ECG reveals an acute anterosep-


tal ST-segment elevation myocardial infarction Principles ofManagement
(STEMI). The patients history of chest pain and
recurrent episodes of VF support acute coronary  verview ofPost-cardiac Arrest
O
syndrome (ACS) as the cause of cardiac arrest. Syndrome
Cardiology was consulted and patient was taken
immediately to the coronary catheterization lab. Post cardiac arrest syndrome is a unique patho-
Coronary angiography revealed left anterior logic state where varying degrees of post-arrest
descending artery occlusion that was success- brain injury, myocardial dysfunction, systemic
fully treated with balloon angioplasty and stent ischemia and reperfusion response, and persis-
placement (Fig.2.2). tent precipitating pathology are observed [2]. The

Fig. 2.1 Twelve lead ECG performed post-ROSC


2 Post-cardiac Arrest Management 15

a b

Fig. 2.2(a) This is an image of a left anterior descending artery prior to angioplasty. (b) Left anterior descending
artery (close up) after successful PCI with angioplasty indicated by increased flow below arrow

severity of these manifestations will vary in each regions of the brain include the hippocampus,
patient. When ROSC is achieved rapidly PCAS cerebellum, caudoputamen, and cortex. The
can be limited or even absent while prolonged mechanisms of brain damage triggered by car-
cardiac arrest can result in PCAS that is refrac- diac arrest and resuscitation are complex, and
tory to all interventions. Between these two many pathways are executed over hours to days
extremes, each component of PCAS when pres- following ROSC.The relatively protracted time
ent is potentially treatable and reversible. Some course of injury cascades and histological
post-cardiac arrest interventions, such as changes suggests a broad therapeutic window for
hypothermic-targeted temperature management, neuroprotective strategies following cardiac
appear to have a favorable impact on multiple arrest. Early clinical manifestations include
components of PCAS while more focused inter- coma, seizures, myoclonus and late manifesta-
ventions such at early PCI specifically address tions ranging from mild short-term memory defi-
the precipitating pathology. A comprehensive cits to persistent vegetative state and brain death.
multidisciplinary approach that addresses all
PCAS components in the appropriate timeframe  ost-cardiac Arrest Myocardial
P
is the best strategy to optimize outcomes. Dysfunction
Post-cardiac arrest myocardial dysfunction is a
 ost Cardiac Arrest Brain Injury
P significant cause of morbidity and mortality after
Post-cardiac arrest brain injury is a common both in- and out-of-hospital cardiac arrest [46].
cause of morbidity and mortality. One study Myocardial dysfunction is manifest by tachycar-
reported that brain damage was the cause of death dia, elevated left ventricular end-diastolic pres-
in 68% of patients that died after ICU admission sure, decreased ejection fraction, reduced cardiac
following out-of hospital cardiac arrest and in output and hypotension. Cardiac output tends to
23% of patient that died after ICU admission fol- improve by 24 h and can return to near normal by
lowing in-hospital cardiac arrest [4]. The unique 72 h in survivors in the absence of other pathol-
vulnerability of the brain is attributed to its lim- ogy [6]. The responsiveness of post-cardiac arrest
ited tolerance of ischemia as well as unique global myocardial dysfunction to inotropic drugs
response to reperfusion. The most vulnerable is well documented in animal studies [7, 8]. If
16 R.M. Otero and R.W. Neumar

acute coronary syndrome or decompensated con- treated. Early hemodynamic optimization is


gestive heart failure were the precipitating pathol- essential to prevent re-arrest, secondary brain
ogy that caused cardiac arrest, the management injury and multi-organ failure. A goal-directed
of post-cardiac arrest myocardial dysfunction approach using physiologic parameters to achieve
becomes more complex. adequate oxygen delivery has been associated
with improved outcomes [19, 20]. This involves
Systemic Ischemia/Reperfusion optimizing preload, arterial oxygen content,
Response afterload, ventricular contractility, and systemic
The whole body ischemia/reperfusion of cardiac oxygen utilization. Appropriate monitoring
arrest with associated oxygen debt causes gener- includes continuous intra-arterial pressure moni-
alized activation of immunological and coagula- toring, arterial and central venous blood gases,
tion pathways increasing the risk of multiple urine output, lactate clearance, and bedside echo-
organ failure and infection [9, 10]. This condition cardiography. When feasible, diagnostic studies
has many features in common with sepsis [11 to rule out treatable persistent precipitating
14]. In addition, activation of blood coagulation pathology should be performed, and treatment
without adequate activation of endogenous fibri- initiated while resuscitation is ongoing.
nolysis may also contribute to microcirculatory The optimal MAP for post-cardiac arrest
reperfusion disorders after cardiac arrest [15, 16]. patients has not been defined by prospective clin-
Finally, the stress of total body ischemia/reperfu- ical trials, and should be individualize for each
sion appears to adversely affect adrenal function patient. Cerebrovascular auto regulation can be
[17, 18]. However, the relationship of adrenal disrupted or right-shifted in post-cardiac arrest
dysfunction to outcome remains controversial. patients suggesting a higher cerebral perfusion
Clinical manifestations of systemic ischemic- pressure is needed to provide adequate brain
reperfusion response include intravascular vol- blood flow [21]. In contrast, ongoing ACS and
ume depletion, impaired vasoregulation, impaired congestive heart failure can be exacerbated by
oxygen delivery and utilization, as well as targeting a MAP higher than what is needed to
increased susceptibility to infection. maintain adequate myocardial perfusion. Higher
systolic and mean arterial pressures during the
Persistent Precipitating Pathology first 24 h after ROSC are associated with better
Post-cardiac arrest syndrome is commonly asso- outcomes in descriptive studies [2224]. In terms
ciated with persisting acute pathology that caused of goal-directed strategies, good outcomes have
or contributed to the cardiac arrest itself. The been achieved in published studies where the
diagnosis and treatment of acute coronary syn- MAP target range was low as 6575mmHg [20]
drome, pulmonary diseases, hemorrhage, sepsis, to as high as 90100mm [25, 26] for patients
and various toxidromes is often complicated in admitted after out-of-hospital cardiac arrest.
the setting of post-cardiac arrest syndrome. For patients with evidence of inadequate oxy-
However, early identification and effective thera- gen delivery or hypotension, preload optimiza-
peutic intervention is essential if optimal out- tion is the first line intervention. Preload
comes are to be achieved. optimization is typically achieved using IV crys-
talloid boluses guided by non-invasive bedside
assessment of volume responsiveness. Patients
Hemodynamic Optimization treated with a goal-directed volume resuscitation
strategy following out-of-hospital cardiac arrest
Post-cardiac arrest patients typically exhibit a typically have positive fluid balance of 23in the
mixed cardiogenic, distributive, and hypovole- first 6 h and 46L positive fluid balance in the
mic state of shock. In addition, persistence of the first 24 h [19, 20].
pathology that caused the cardiac arrest can cause Vasopressor and inotrope infusions should be
a refractory shock state unless definitively initiated early in severe shock states and when
2 Post-cardiac Arrest Management 17

there is an inadequate response to preload opti- diagnosis in an unconscious post-arrest patient


mization. No agent or combination of agents has presents unique challenges. A previous history of
been demonstrated to be superior or improve out- coronary artery disease, significant risk factors,
comes. A reasonable approach is norepinephrine and/or symptoms prior to arrest can contribute to
as the first line vasopressor supplemented by clinical suspicion, but the absence of these does
dobutamine for inotropic support guided by bed- not exclude ACS as the cause. A standard 12-lead
side echocardiography. ECG should be obtained as soon as feasible after
When shock is refractory to preload optimiza- ROSC, with additional right-sided and/or poste-
tion, vasopressors, and inotropes it is critical to rior leads as indicated. Immediate PCI is indi-
identify and treat any persistent acute pathology cated in post-ROSC patients meeting STEMI
that caused the cardiac arrest including acute criteria regardless of neurologic status [3]. In
coronary syndrome (ACS), pulmonary embolism addition, immediate coronary angiography
(PE), or hemorrhage. If no such persistent pathol- should be considered in post-cardiac arrest
ogy exists or the patient is not stable enough to patients that do not meet STEMI criteria but there
undergo definitive intervention, then mechanical is a high clinical suspicion for ACS (see section
circulatory support should be considered (see Evidence Contour). Medical management of
section Evidence Contour). ACS is the same as for non-post-cardiac arrest
patients.

Ventilation andOxygenation
 ypothermic Targeted Temperature
H
The ventilation and oxygenation goals for post- Management
cardiac arrest patients should be normoxia and
normocarbia. Both low (<60mmHg) and high Hypothermic-targeted temperature management
(>300mmHg) arterial PO2 are associated with (HTTM) is recommended for comatose adult
worse outcomes in post-cardiac arrest patients patients who achieve ROSC following cardiac
[27]. Low PaO2 can cause secondary brain arrest independent of presenting cardiac rhythm
hypoxia while high PaO2 can increase oxidative (shockable vs. non-shockable) and location (Out
injury in the brain. The impact of PaCO2 on cere- of Hospital Cardiac Arrest (OHCA) vs.
brovascular blood flow is maintained in post- In-hospital Cardiac Arrest (IHCA)) [3]. Based on
cardiac arrest patients; therefore hypocarbia can current clinical evidence, providers should select
cause secondary brain ischemia and is associated a constant target temperature between 32 and
with worse outcomes [28, 29]. Currently there 36C and maintain that temperature for at least
are no studies to specify which ventilator modes 24 h. Rewarming should be no faster than 0.5C/h
or tidal volumes are optimal in patients resusci- and fever should be prevented for at least 72 h
tated from cardiac arrest but generally an after ROSC.
approach using assist control mode with a tidal Although there are no absolute contraindica-
volume goal in 68cc/kg range is considered tions to HTTM after cardiac arrest, relative con-
standard. Titration of mechanical ventilation traindications may include uncontrolled bleeding
should be aimed at achieving a PaCO2 of or refractory severe shock. Induction of hypo-
45mmHg and a range for PaO2 between 75 and thermia may lead to intense shivering, hypergly-
150mmHg. cemia, diuresis and associated electrolyte
derangements such as hypokalemia and hypo-
phosphatemia [30]. Rewarming may be associ-
Management ofSTEMI andACS ated with mild hyperkalemia and must be
monitored closely.
Acute coronary syndrome is a common cause of When the decision is made to treat the coma-
out-of-hospital cardiac arrest, but making the tose post-cardiac arrest patient with HTTM,
18 R.M. Otero and R.W. Neumar

efforts to achieve and maintain target temperature Seizure Management


should be as soon as feasible. In the ED, practical
methods of rapidly inducing hypothermia include Seizures, nonconvulsive status epilepticus, and
ice packs (applied to the neck, inguinal areas, and other epileptiform activity occurs in 1222% of
axilla), fan cooling of dampened exposed skin, comatose post-cardiac arrest patients, and may
cooling blankets underneath and on top of the contribute to secondary brain injury and prevent
patient, and disabling of ventilator warming cir- awaking from coma [3]. There is no direct evi-
cuits. Rapid intravenous infusion of limited vol- dence that post-cardiac arrest seizure prophylaxis
umes (12L) of 4C saline facilitates induction is effective or improves outcomes. However, pro-
of hypothermia, but additional measures are longed epileptiform discharges are associated
needed to maintain hypothermia. No one cooling with secondary brain injury in other conditions,
strategy or device has been demonstrated to result making detection and treatment of nonconvulsive
in superior clinical outcomes. A number of auto- status epilepticus a priority [33]. Continuous
mated surface cooling devices are now available EEG, initiated as soon as possible following
that use chest and thigh pads and continuous tem- ROSC, should be strongly considered in all
perature feedback from bladder or esophageal comatose survivors of cardiac arrest treated with
temperature probes. Although more invasive, HTTM, to monitor for potentially treatable elec-
automated endovascular cooling systems are also trographic status epilepticus and to assist with
available that require placement of a central neuroprognostication. In the absence of continu-
venous catheter and offer tighter control of tem- ous EEG monitoring, an EEG for the diagnosis of
perature at target. Target core body temperature seizure should be promptly performed and inter-
is best monitored by an indwelling esophageal preted in comatose post-arrest patients. The same
temperature probe, but can be monitored by a anticonvulsant regimens for the treatment of sei-
temperature-sensitive bladder catheter if ade- zures and status epilepticus and myoclonus
quate urine output is present. caused by other etiologies are reasonable to use
Shivering, which inhibits cooling, can be pre- in post-cardiac arrest patients.
vented with sedation and neuromuscular block-
ade. If neuromuscular blockade is continued
during the maintenance phase of therapeutic Neuroprognostication
hypothermia, continuous electroencephalo-
graphic monitoring is strongly encouraged to Accurate neuroprognostication can be extremely
detect seizures, a common occurrence in post- challenging in persistently comatose post-car-
cardiac arrest patients [3]. diac arrest patients, but is essential for appropri-
ate patient care and resource utilization.
Decisions to limit care based on neurologic
Glucose Control prognosis should not be made before 72 h after
ROSC and at least 12 h following rewarming and
Hyperglycemia is common in post-cardiac arrest cessation of all sedative and paralytic medica-
patients, and average levels above 143mg/dL tions [34]. Available neuroprognostication tools
have been strongly associated with poor neuro- include clinical examination, electrophysiologic
logic outcomes [31]. One randomized trial in measurements, imaging studies, and serum bio-
post-cardiac arrest patients compared strict (72 markers. The performance of these tools is
108mg/dL) versus moderate (108144mg/dL) highly dependent on the interval between the
glucose control and found no difference in 30-day achievement of ROSC and the measurement. For
mortality [32]. Based on available evidence, example, bilateral absence of pupillary light
moderate glucose management strategies in place reflex has a false positive rate (FPR) for predict-
for most critically ill patients do not need to be ing poor neurologic outcome of 32% [95% CI
modified for post-cardiac arrest patients. 1948 %] at the time of hospital admission
2 Post-cardiac Arrest Management 19

versus a FPR of 1% [03%] when measured 72 Organ Donation


h after ROSC [35]. In addition to timing, major
confounders such as sedation and neuromuscular Patients that are initially resuscitated from car-
blockade, persistent hypothermia, severe hypo- diac arrest but subsequently die or meet brain
tension, hypoglycemia and other profound meta- death criteria should be evaluated as potential
bolic derangements must be excluded before an organ donors. Multiple studies have found no dif-
assessment for neuroprognostication is per- ference in immediate or long-term function of
formed. Finally, all available clinical data on the transplanted organs from donors who reach brain
reliability of prognostication tools is limited by death after cardiac arrest when compared with
the potential for a self-fulfilling prophecy that donors who reach brain death from other causes
occurs when these tools are used to limit care. [38]. In addition, patients who have withdrawal
Most experts agree that recovery of Glasgow of life support after initial resuscitation from car-
Motor Score (GMS) of flexion or better (i.e. >2) diac arrest based on reliable neuroprognostica-
is a good prognostic sign that precludes the need tion of futility or as part of advanced directives
for further prognostic evaluation. In patients that are candidates for donation after cardiac death
do not recover a GMS >2 by 72 h after ROSC, the (DCD). The list of potential organs successfully
most reliable predictors of poor neurologic out- donated from the patients has expanded from pri-
come (defined by a Cerebral Performance marily kidneys and liver to include heart, lung
Category score of 35) are listed in Table2.1. and intestine. Finally, tissue donation (cornea,
It is recommended that decisions to limit care skin, and bone) is almost always possible if post-
never be based on the results of a single prognos- cardiac arrest patients die.
tication tool [3]. Although a number of published
guidelines from professional societies are avail-
able, the field is rapidly evolving and therefore Evidence Contour
post-arrest neuroprognostication should be
guided by consultation with an experienced neu-  atient Selection forEmergency
P
rocritical care specialist [34, 37]. Establishing a Coronary Angiography
consistent institutional approach based on avail-
able resources and multidisciplinary expertise There are no prospective randomized controlled
will optimize both resource utilization and patient trials demonstrating benefit of immediate coro-
outcomes. nary angiography and PCI in post-cardiac arrest
patients with or without STEMI.However,

Table 2.1 Most reliable predictors of poor neurologic outcome in comatose post-cardiac arrest patients [35]
Sensitivity
Prognostication tool Positive result measurement Timing FPR [95%CI] [95%CI]
Clinical Exam Bilaterally absent pupillary 72h post-ROSC 1% [03%] 19% [1425%]
light reflexes [35]
Status myoclonus [35] During the first 72 h 0% [04%] 16% [1122%]
post-ROSC
Somatosensory evoked Bilaterally absent N20 After rewarming from 1% [03%] 45% [4150%]
potentials (SSEPs) (cortical) SSEP wave [35] HTTM
Electroencephalography Highly malignant pattern After rewarming from 0% [012%] 50% [3961%]
(EEG) [36] HTTM and 4896 h
after ROSC
A.Highly malignant EEG patterns are (1) suppressed background without discharges (amplitude, 10mV, 100% of the
recording), (2) suppressed background with continuous periodic discharges, and (3) surest-suppression background
with or without superimposed discharges (periods of suppression with amplitude <10mV constituting >50% of the
recording)
20 R.M. Otero and R.W. Neumar

multiple observational studies have reported better arrest patients with any presenting rhythm.
survival in both STEMI and NSTEMI post-cardiac Therefore these recommendations represent an
arrest patients that undergo immediate coronary extrapolation of the evidence in patients with wit-
angiography and PCI (when indicated) compared nessed out-of-hospital ventricular fibrillation.
to those that do not undergo immediate coronary This extrapolation is supported by clinical obser-
angiography [3941]. The strength of the recom- vational studies that suggest benefit in these
mendation for post-cardiac arrest patients that patient populations and robust body animal data
meet STEMI criteria is based on extrapolation of demonstrating the neuroprotective effect of
the positive survival benefits for non-cardiac arrest HTTM in cardiac arrest models regardless of
patients. Conversely, the reluctance of interven- arrest rhythm [44, 45]. In addition, HTTM has a
tional cardiologists to perform immediate coro- relatively safe side effect profile limited primar-
nary angiography in NSTEMI patients is similarly ily to shivering and electrolyte shifts. For intu-
based on lack of proven benefit in non-cardiac bated comatose cardiac arrest survivors managed
arrest patients. However, it should be recognized in the ICU setting, the incremental intensity of
that the post-arrest patients are higher risk and do care and cost is modest. One potential concern
not always have ST-elevation with an acutely about treating all comatose post-cardiac arrest
occluded culprit lesion [42]. In a large interna- patients with HTTM is a delay in prognostication
tional post-cardiac arrest registry that included of poor outcome and decision to limit care.
patients undergoing immediate coronary angiog- However, there is international consensus that
raphy with and without STEMI, an occluded cul- neuroprognostication should not be performed
prit vessel was found in 74.3% of patients with before 72 after ROSC.So, awaiting completion
STEMI and 22.9% of patients without STEMI of HTTM therapy does itself delay neuroprog-
[41]. This high incidence of occluded culprit nostication. Moreover, HTTM could delay the
lesions combined with post-cardiac arrest myocar- metabolism of sedative and paralytic agents.
dial dysfunction and the need to maintain adequate Therefore, some experts have recommended
cerebral perfusion pressure to prevent secondary delaying prognostication until 72 h after rewarm-
brain injury argues strongly for immediate coro- ing, which could cause significant delays in neu-
nary angiography in any post-cardiac arrest patient roprognostication. However, the initiation of
when there is a clinical suspicion of ACS, espe- HTTM should not impact decisions to limit care
cially when associated with hemodynamic that are based criteria other than neurologic prog-
instability. nosis, such as terminal illness or previously
unrecognized advanced directives. In such cases
the decision to discontinue HTTM can be consid-
Patient Selection ered in the same way as the decision to discon-
forHypothermicTTM tinue mechanical ventilation or intravenous
pressor therapy.
Although international guidelines consistently
recommend treating all comatose post-cardiac
arrest patients with hypothermic TTM, this prac- Optimizing Hypothermic TTM
tice has not been universally implemented. The
two major clinical trials demonstrating efficacy Most experts agree that the optimal time to initia-
of HTTM limited enrollment to witnessed out-of- tion, target temperature, and duration of HTTM is
hospital cardiac arrest with as shockable (VF/ unknown. Although it theoretically makes sense
VT) presenting rhythm [26, 43]. There have been to achieve target temperature as soon as feasible,
no prospective randomized clinical trials com- there is no clinical data to support this approach.
paring HTTM to normothermia (or no active Even in the two landmark clinical trials, the time
temperature management) in out-of-hospital to target temperature was discordant. In the study
cardiac arrest patients with non-shockable by Bernard the time to target temperature was
presenting rhythms or in in-hospital cardiac reported to be 2 h while in the HACA trial the
2 Post-cardiac Arrest Management 21

median time to target temperature was 8 h (IQR comparisons of HTTM duration in randomized
416 h) [26, 43]. Rapid infusion of cold intrave- clinical trials. No specific cooling technique has
nous saline immediately after ROSC by paramed- been demonstrated to result in superior patient
ics in the field had no impact on outcomes in two outcomes. Therefore the best strategy is the one
randomized clinical trials [46, 47]. Observational that is most feasible to consistently implement at
studies examining time to target temperature are your own institution. Overall, the optimization of
not informative because neurologically devas- HTTM requires additional research, and it is
tated patients are easier to cool due to loss of tem- likely that a personalized approach based on
perature auto regulation. Based on available severity of injury and response to therapy will
evidence achieving target temperature within 4 h emerge as the best strategy.
of ROSC is a reasonable goal.
The target temperature of 3234C in the
original guidelines was based on the target tem-  echanical Support forRefractory
M
perature used in the Bernard and HACA studies Post-cardiac Arrest Cardiogenic
[26, 43]. Subsequent to that, a large multicenter Shock
studied published by Nielsen etal. did not detect
superior outcomes in comatose post-cardiac In post-cardiac arrest patients with refractory
arrest patients who were cooled to 33C com- cardiogenic shock a number of options can be
pared to 36C [48]. It is for this reason that the considered for mechanical circulatory support.
recommended target temperature range was An intra-aortic balloon pump can enhance car-
expanded to 3236C.Although it is theoreti- diac output by approximately 0.5L/min in car-
cally easier to use a higher target temperature, it diogenic shock. Despite early evidence of
does not obviate the need for use of active cool- improved outcomes when IABP was used post-
ing techniques guided by continuous temperature MI, recent studies have not shown a 30-day or 12
monitoring. The recommended duration of ther- month mortality benefit [49, 50]. The newer
apy is again based on the durations used in major peripheral ventricular assist devices Tandem
clinical trials. There have been no prospective HeartTM PVAD (Fig.2.3) and ImpellaTM Recovery

a b

Fig. 2.3(a, b) Thoratec DeviceTM Percutaneous ventric- min depending on size of cannulae (With permission
ular assist device consisting of Tandem Heart pumpTM and Cardiac Assist Inc.)
Tandem Heart cannulaeTM with flow rates from 4 to 5.0L/
22 R.M. Otero and R.W. Neumar

a b

Fig. 2.4(a, b) Impella Device TM Device demonstrating retrograde insertion via aorta into left ventricle proprietary 9Fr
catheter with 2.5L/min flow rate. Inserted under fluoroscopic guidance. (b With permission Abiomed)

(Fig.2.4) are reported to augment cardiac output Council of Southern Africa). Circulation.
by 3.5 and 2.5L/min, respectively. These devices 2008;118(23):245283.
3. Callaway C, Donnino M, Fink E.Post Cardiac Arrest
gain access to the central circulation via large Care: 2015 American Heart Association Guidelines
cannulas, which then use either a centrifugal Update for cardiopulmonary resuscitation and emer-
pump (Tandem HeartTM) or catheter motor with gency cardiovascular care. Circulation. 2015;132
inlet and output (ImpellaTM) via the aorta. In cen- Suppl 1:S46582.
4. Laver S, Farrow C, Turner D.Mode of death after
ters with specialty expertise complete circula- admission to an intensive care unit following cardiac
tory support may be performed using arrest. Intensive Care Med. 2004;30:21268.
veno-arterial extracorporeal membrane oxygen- 5. Herlitz J, Ekstrom B, Wennerblom B.Hospital mor-
ation (VA-ECMO) as a bridge to transplantation tality after out-of-hospital cardiac arrest among
patients found in ventricular fibrillation. Resuscitation.
or bridge to recovery [51]. 1995;29(1):1121.
6. Laurent I, Monchi M, Chiche J.Reversible myocar-
dial dysfunction in survivors of out-of-hospital car-
diac arrest. JAm Coll Cardiol. 2002;40(1):21106.
References 7. Kern KB, Hilwig R, Berg RA.Postresuscitation left
ventricular systolic and diastolic dysfunction: treat-
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2. Neumar R, Nolan JP, Adrie C.Post-Cardiac Arrest dobutamine and levosimendan for management of
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and prognostication. A consensus statement from the Med. 2005;33(3):48791.
International Liaison Committee on Resuscitation 9. Cerchiari E, Safar P, Klein E.Visceral, hematologic and
(American Heart Association, Australian and New bacteriologic changes and neurologic outcome after
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Resuscitation Council of Asia, and the Resuscitation tation. Crit Care Med. 2006;34(12):S45465.
2 Post-cardiac Arrest Management 23

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Opin Crit Care. 2004;10(3):20812. responses to hypercapnia and hypoxia in the recovery
13. Gando S, Nanzaki S, Morimoto Y.Out-of-hospital period following complete and incomplete cerebral
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Buunk G, van der Hoeven JG, Meinders
26(1):3844. AE.Cerebrovascular reactivity in comatose patients
14. Geppert A, Zorn G, Karth G.Soluble selectins and the resuscitated from a cardiac arrest. Stroke. 1997;28:
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cessful cardiopulmonary resuscitation. Crit Care 30. Polderman K.Of ions and temperature: the compli-
Med. 2000;28(7):23605. cated interplay of temperature, fluids, and electrolyte
15. Bottinger B, Motsch J, Bohrer H.Activation of blood on myocardial function. Crit Care. 2013;17(6):1018.
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Circulation. 1995;92(9):25728. within 12h after cardiac arrest might not be neces-
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cardiac arrest: implication of the protein C anticoagu- erate glucose control after resuscitation from ventric-
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17. Hekimian G, Baugnon T, Thuong M.Cortisol levels 2093100.
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resuscitation. Shock. 2004;22(2):1169. troencephelogram monitoring in the intensive care
18. Schultz C, Rivers EP, Feldkamp C.A characterization unit. Anesth Analg. 2009;109(2):50623.
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ing and after human cardiac arrest. Crit Care Med. vors of cardiac arrest: an advisory statement from the
1993;21(9):133947. European Resuscitation Council and the European
19. Gaieski DF, etal. Early goal directed hemodynamic Society of Intensive Care Medicine. Resuscitation.
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20. Sunde K, Pytte M, Jacobsen D.Implementation of a tation and emergency cardiovascular care science with
standardised treatment protocol for post resuscitation treatment recommendations [review]. Circulation.
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2007;73(1):2939. 36. Westhall E, Rossetti A, van Rootselaar A.Standardized
21. Sundgreen C, Larsen F, Herzog T.Autoregulation of EEG interpretation accurately predicts prognosis after
cerebral blood flow in patients resuscitated from car- cardiac arrest. Neurology. 2016;86(16):148290.
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22. Kilgannon JH, etal. Early arterial hypotension is
prognostication after cardiac arrest recommenda-
common in the post-cardiac arrest syndrome and tions from the Swedish resuscitation Council.
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Resuscitation. 2008;79(3):4106. 38. Orioles A, Morrison W, Rossano J.An under-

23. Beylin ME, etal. Higher mean arterial pressure with recognized benefit of cardiopulmonary resuscitation:
or without vasoactive agents is associated with organ transplantation [review]. Crit Care Med.
increased survival and better neurological outcomes 2013;41(12):27949.
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Med. 2013;39(11):19818. induced hypothermia are associated with survival and
24. Kilgannon JH, etal. Arterial blood pressure and neu- functional recovery after out-of-hospital cardiac
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25. Oddo M, etal. From evidence to clinical practice: ated with a clinical benefit in post-cardiac arrest
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Care Med. 2006;34(7):186573. Suppl 1:37.
26. Bernard S, etal. Treatment of comatose survivors of 41. Kern K, Lotun K, Patel N.Outcomes of comatose
out-of-hospital cardiac arrest with induced hypother- cardiac arrest survivors with and without ST-segment
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coronary angiography. JACC Cardiovasc Interv. arrest: a randomized controlled trial. Circulation.
2015;8(8):103140. 2010;122(7):73742.
42. Spaulding CM, etal. Immediate coronary angiogra- 47. Kim F, etal. Effect of prehospital induction of mild
phy in survivors of out-of-hospital cardiac arrest. N hypothermia on survival and neurological status
Engl JMed. 1997;336(23):162933. among adults with cardiac arrest: a randomized clini-
43. Hypothermia after Cardiac Arrest Study Group. Mild cal trial. JAMA. 2014;311(1):4552.
therapeutic hypothermia to improve the neurologic 48. Nielsen N, etal. Targeted temperature management at
outcome after cardiac arrest. N Engl JMed. 33C versus 36C after cardiac arrest. N Engl JMed.
2002;346(8):54956. 2013;369(23):2197206.
44. Testori C, Sterz F, Behringer W.Mild therapeutic 49. Thiele H, etal. Intraaortic balloon support for myo-
hypothermia is associated with favourable outcomes cardial infarction with cardiogenic shock. N Engl
in patients after cardiac arrest with non-shockable JMed. 2012;367:128796.
rhythms. Resuscitation. 2011;82(9):11627. 50. Thiele H, etal. Intra-aortic balloon counterpulsation in
45. Perman S, Grossestreuer A, Wiebe D.The utility of acute myocardial infarction complicated by cardiogenic
therapeutic hypothemia for post-cardiac arrest syn- shock (IABP-SHOCK II): final 12 month results of a
drome patients with an initial nonshockable rhythm. randomised open-label trial. Lancet. 2013;382:163845.
Circulation. 2015;132(22):214651. 51. Stub D, etal. Refractory cardiac arrest treated with
46. Bernard S, Smith K, Cameron P.Induction of thera- mechanical CPR, hypothermia, ECMO and early
peutic hypothermia by paramedics after resuscitation reperfusion (the CHEER trial). Resuscitation. 2015;
from out-of-hospital ventricular fibrillation cardiac 86:8894.
Undifferentiated Shock
3
SageP.Whitmore

Case Presentation total bilirubin 1.8, lipase 120, troponin-I 1.1


(negative <0.10), and INR 1.5. Arterial blood gas
A 39-year-old woman with a history of rheuma- revealed pH7.32, PCO2 28, PO2 64, and lactate
toid arthritis and localized breast cancer status 4.2mmol/L.Pregnancy testing was negative.
post lumpectomy was admitted to the intensive Urinalysis was pending as her urine output was
care unit (ICU) for suspected septic shock from a poor. She was treated empirically with broad-
biliary source. She had presented with right upper spectrum antibiotics and intravenous fluids. After
quadrant abdominal pain worsening over the last 1500mL of saline, the patients heart rate was
3 days. She endorsed lightheadedness, shortness 120, respiratory rate 26, blood pressure 80/54,
of breath, and vomiting, and denied cough or and SpO2 now 90% on 2L nasal cannula. While
fever. On initial examination, her vitals included awaiting diagnostic imaging, a foley catheter,
a heart rate of 110, respiratory rate 22, blood central venous catheter, and arterial line were
pressure 86/58, SpO2 94% on room air, tempera- placed.
ture 37.5C.She was ill appearing, anxious but
alert, visibly dyspneic, with clear heart and lung Question How should the clinician determine
sounds. She had tenderness with voluntary guard- this patients shock type and the appropriate
ing of her right upper quadrant. Her extremities resuscitation strategy?
were cool with delayed capillary refill and 1+
pretibial edema bilaterally. Her electrocardio- Answer Assessment of volume responsiveness
gram showed sinus tachycardia with small T plus bedside echocardiography
wave inversions in the anterior leads and no ST
elevations. Her chest radiograph showed a small This patient presents with clinical features of,
right pleural effusion but was otherwise clear. and risk factors for, multiple shock types with
Pertinent labs included: WBC 13,000, hemoglo- many possible etiologies. The differential diagno-
bin 11.9, platelets 180,000, creatinine 1.9mg/dL, sis includes septic shock due to biliary, gastrointes-
AST 250, ALT 300, alkaline phosphatase 110, tinal, or genitourinary causes, severe pancreatitis,
hemorrhagic shock possibly from a ruptured ovar-
ian or hepatic cyst, adrenal crisis, massive pulmo-
nary embolism, right ventricular failure, cardiac
S.P. Whitmore tamponade, or left ventricular failure. The fact that
Emergency Medicine, Division of Emergency Critical she is more hypotensive after fluids might suggest
Care, University of Michigan Health System,
cardiac failure, or may be due to progression of
Ann Arbor, MI, USA
e-mail: swhitmor@med.umich.edu septic shock. The indications for IV fluid boluses,

Springer International Publishing Switzerland 2017 25


R.C. Hyzy (ed.), Evidence-Based Critical Care, DOI10.1007/978-3-319-43341-7_3
26 S.P. Whitmore

blood products, vasopressors, and inotropes differ cardiogenic, or obstructive [1]. This can be quite
widely among these possibilities, and both under- challenging in patients with multiple comorbidi-
resuscitation and volume overload carry potential ties, difficult body habitus, or atypical physical
harm. exam findings (e.g. cold septic shock or high
After placement of a left subclavian central output cardiac failure).
line and radial arterial line, central venous pres- In the past, static hemodynamic parameters
sure (CVP) averaged 10mmHg, and a pulsus such as central venous pressure (CVP), pulmo-
paradoxus was noted on the arterial pressure nary artery occlusion pressure (PAOP), estimated
waveform. A 90-s bilateral passive leg raise stroke volume (SV), cardiac index (CI), and sys-
resulted in a 12-point drop in systolic blood temic vascular resistance (SVR) obtained inva-
pressure. Based on this, intravenous fluids were sively via central venous and pulmonary artery
discontinued. A bedside echocardiogram dem- catheterization were used to attempt to differenti-
onstrated a dilated inferior vena cava (IVC) with ate cardiac failure, obstruction, hypovolemia, or
no respiratory variation, no pericardial effusion, inappropriate vasodilation. Various combinations
massive dilation of the right ventricle (RV) with of fluids, vasopressors, and inotropes would be
poor RV contractility, marked right-to-left inter- then employed to target certain goals; for exam-
ventricular septal bowing, and a small, hyperdy- ple, CVP of 812mmHg, PAOP of 1215mmHg,
namic left ventricle (LV). A diagnosis of and CI greater than 2.2. CVP-guided fluid man-
cardiogenic shock due to RV failure was made, agement is still emphasized in a number of resus-
and the patient was started on high-flow oxygen citation protocols, including early goal directed
at 15L/min with inhaled nitric oxide blended in therapy of septic shock and the post-cardiac
at 20 parts per million. Norepinephrine and arrest syndrome [2, 3], and utilization of the pul-
dobutamine infusions were initiated. After appli- monary artery catheter (PAC) remains a standard
cation of these therapies, her skin temperature monitoring strategy for patients in cardiogenic
and capillary refill improved, her blood pressure shock or post cardiac surgery. As described in
improved to 110/70, and urine output increased. greater detail below, these parameters are notori-
A formal right upper quadrant ultrasound showed ously unreliable in determining shock type and
no gallstones, gallbladder wall thickening, or predicting response to intravenous fluid.
biliary dilation; her right upper quadrant pain
was attributed to congestive hepatopathy. A CT
of the chest showed no pulmonary embolism. Shock Types
She was scheduled for right heart catheterization
for a suspected index presentation of pulmonary The basic phenotypes of shock are only three:
arterial hypertension. hypovolemic, distributive, and cardiogenic; car-
diogenic shock includes obstructive causes of RV
failure (Fig.3.1). In the modern approach to
Standard Approach undifferentiated shock, it is essential to first rec-
toUndifferentiated Shock ognize that a large proportion of patients in shock
are suffering multiple insults resulting in mixed
Shock is defined as a state of inadequate oxygen shock phenotypes, and therefore a linear approach
delivery to tissues resulting in cellular dysoxia, to diagnosis and management is inappropriate.
which is often accompanied by, but may be com- For example, patients with cardiogenic shock,
pletely independent of, decreased systemic arte- post-cardiac arrest syndrome, or massive hemor-
rial blood pressure [1]. The classic approach to rhage may also suffer distributive shock due to
determining shock type begins with utilizing his- systemic inflammation and vasoplegia [4]; over
tory and cardiopulmonary and skin examinations half of patients with septic shock will develop
to categorize the patients condition into one of cardiac dysfunction during their course [5]; and
four shock types: hypovolemic, distributive, patients with hypotension and severe congestive
3 Undifferentiated Shock 27

Tamponade Myocardial Infarction


Tension PTX Myocarditis
Massive PE Septic Cardiomyopathy
RV Infarction Arrhythmia
Cor Pulmonale Acute Mitral Regurgitation
Pulmonary HTN Critical Aortic Stenosis

RV LV

Cardiogenic

Hypovolemic

Distributive

Hemorrhage Sepsis
GI losses Anaphylaxis
Dehydration SIRS
Capillary leak Massive transfusion
Post-cardiac arrest
Adrenal crisis
Neurogenic

Fig. 3.1 Shock types and examples. RV right ventricle, PTX pneumothorax, PE pulmonary embolism, HTN hyperten-
sion, LV left ventricle, SIRS systemic inflammatory response syndrome, GI gastrointestinal

heart failure may in fact be initially volume intravascular volumethe volume of blood pres-
responsive [6, 7], particularly if they are suffering surized by the elasticity of the distended blood
concomitant gastrointestinal fluid losses, over- vessels in which it is contained. Normally when
diuresis, or occult bleeding. intravascular volume is lost, compensatory veno-
Hypovolemia is categorized as either hemor- constriction maintains an adequate stressed vol-
rhagic or non-hemorrhagic. Mechanistically, ume and thus adequate Pms; however, when a
hypovolemic shock results from inadequate car- patient becomes critically hypovolemic or is sub-
diac output due to diminished stroke volume, ject to inappropriate vasodilation, Pms drops and
which itself is the result of decreased venous venous return to the right atrium falls. The treat-
return. Venous return depends upon maintaining ment is thus replacement of intravascular volume
a gradient of blood flow from large capacitance to restore Pms. In the profoundly vasoplegic
veins in the body towards the right atrium, and patient (e.g. advanced cirrhosis or anaphylaxis),
this gradient depends in part on the difference venous return can be increased by using vasocon-
between mean systemic pressure (Pms) and right strictors such as norepinephrine to increase
atrial pressure (Fig.3.2) [8]. Pms can be thought venous tone and stressed volume [8, 9]; however,
of as the intrinsic blood pressure within the excessive vasoconstriction increases resistance to
venous system and depends on stressed blood flow and may impede venous return.
28 S.P. Whitmore

Fig. 3.2Physiologic Right heart preload (PMS RAP) / R


determinants of right heart
preload. PMS mean systemic
Venules, Veins Vena cava Right atrium
pressure, RAP right atrial
pressure, R resistance, RV
right ventricle Resistance
PMS RAP

Increased by: Increased by: Increased by:

-Stressed volume -Venoconstriction -Intrathoracic pressure


-Vascular tone -Blood viscocity -Pericardial pressure
-RV overload
-Tricuspid regurgitation

Fig. 3.3Physiologic Vasoconstriction Vasodilation


determinants of vascular
tone. Ca++ calcium, NE
norepinephrine, Ag II
angiotensin, AVP arginine
vasopressin, SNS
sympathetic nervous Ca++ AVP 5-HT ANP
system, 5-HT serotonin,
NO nitric oxide, PGE
prostaglandin, ANP atrial NE Ag II NO PGE
natriuretic peptide, ROS
reactive oxygen species
SNS Inflammatory ROS
Thyroxine cytokines
Cortisol

Distributive shock is due to vasoplegia, the cardiopulmonary bypass, post-cardiac arrest syn-
failure to maintain vascular tone, and can occur drome, massive transfusion, adrenal failure, and
via multiple mechanisms. Vascular smooth mus- high cervical spine injury may all result in dis-
cle tone is affected by a balance of several chemi- tributive shock via different mechanisms. The
cal mediators: catecholamines, vasopressin, mainstay of treatment is an adrenergic vasopres-
angiotensin II, and free calcium cause vasocon- sor agent such as norepinephrine or phenyleph-
striction, while prostaglandins, histamine, atrial rine, and other intravenous agents such as
natriuretic peptide, and nitric oxide cause vasodi- ephedrine, vasopressin, angiotensin II, antihista-
lation (Fig.3.3) [4, 10, 11]. Catecholamine mines, corticosteroids, thyroxine, and nitric
induced vasoconstriction is influenced by the oxide scavengers such as methylene blue may be
integrity of the sympathetic nervous system as indicated in certain clinical situations.
well as by adrenal and thyroid function. Nitric Cardiogenic shock is a broad category encom-
oxide induced vasodilation is heightened by his- passing depressed cardiac output related to fail-
tamine, inflammatory cytokines, and possibly ure of either the right ventricle, left ventricle, or
reactive oxygen species during ischemia- both. The causes of obstructive shock such as
reperfusion. The interplay of these factors tension pneumothorax, cardiac tamponade, or
explains why such varied disease processes such massive pulmonary embolism, can be thought of
as septic shock, anaphylactic shock, post- as a subset of cardiogenic shock as they directly
3 Undifferentiated Shock 29

impede the filling and/or output of the right heart.


After a cautious trial of intravenous fluids, the Volume unresponsive
mainstays of treatment are to support hemody-

Stroke volume
namics with a combination of vasopressors and Volume responsive:
inotropes while working to correct any potential 1015 % rise in SV or CO
mechanical lesion (e.g. pericardiocentesis for after 250500 mL fluid
tamponade, tube thoracostomy for tension pneu- challenge
mothorax, thrombolysis for massive pulmonary
embolism, percutaneous coronary intervention Ventricular filling
for ST-elevation myocardial infarction, emergent
valve repair for severe regurgitation, etc.). Fig. 3.4 Starling curve. SV stroke volume, CO cardiac
output
Mechanical ventilation and mechanical circula-
tory devices such as implantable ventricular
assist devices, intraaortic balloon counterpulsa- When caring for patients in shock, the routine
tion, or extracorporeal life support may be needed use of CVP or PAOP to guide fluid management
until resolution or definitive therapy [6]. is not recommended [1]. Despite their wide-
spread use, static measurements such as CVP,
PAOP, or estimated end-diastolic volumes do not
Evidence Contour accurately reflect volume responsiveness or intra-
vascular volume status, even in combination, and
Rarely will one simple shock type exist in isola- even at extreme highs and lows [1214].
tion, and one should approach shock as a poten- Randomized trials and large systematic reviews
tial combination of three simultaneous insults: have not demonstrated that targeting a specific
hypovolemia, vasoplegia, and cardiac dysfunc- CVP or routinely using a PAC are of benefit to
tion. In all-comers with shock, these three param- critically ill patients [1518]. Blindly administer-
eters must be addressed systematically. The two ing intravenous fluids to increase CVP is not rec-
most important maneuvers guiding the resuscita- ommended, as there is a worrisome correlation
tion of undifferentiated shock are (1) assessment between elevated CVP, positive fluid balance
of volume responsiveness and (2) bedside during resuscitation, and mortality, at least in
echocardiography. septic shock [19].
Unlike static filling pressures, dynamic mea-
sures of cardiopulmonary interaction are highly
 ssessment ofVolume
A accurate in determining volume responsiveness
Responsiveness [2025]. In mechanically ventilated patients,
such dynamic measurements include pulse pres-
Accurate assessment of volume responsiveness is sure variation (PPV), stroke volume variation
the most important first step in the resuscitation of (SVV), and plethysmography variation index
a patient in shock, as it directly influences man- (PVI). Variations in pulse pressure (PP), stroke
agement in real time. Volume responsiveness is volume (SV) or plethysmography amplitude
defined as a 1015% increase in stroke volume indicate that cardiac output is linked to changes
(SV) or cardiac output (CO) after the administra- in ventricular filling that occur with swings in
tion of an intravenous fluid challenge, usually intrathoracic pressure, which reflects volume
250500mL of crystalloid, theoretically corre- responsiveness. Respiratory variation of IVC
sponding to the steep portion of the Starling curve diameter (DIVC) using bedside ultrasound may
(Fig.3.4). There are many methods of assessment also be used to predict volume responsiveness,
described, which are divided into static measure- again linking changes in venous return and car-
ments of filling pressure or dynamic measure- diac output with changes in intrathoracic
ments of cardiopulmonary interaction. pressure.
30 S.P. Whitmore

SVV, PPV, and PVI specifically predict left etc.), esophageal Doppler monitoring (EDM)
ventricle (LV) volume responsiveness. During of aortic blood flow (e.g. CardioQ- ODM,
a positive pressure breath, venous return from Deltex Medical, West Sussex, UK), and left
the pulmonary vascular bed to the LV is briefly ventricular outflow tract velocity-time integral
increased; if the LV is volume-responsive, then (LVOT VTi) obtained by transthoracic echo-
PP, SV, and plethysmography amplitude will cardiography (TTE).
transiently increase immediately after each An end-expiratory occlusion (EEO) maneuver
ventilator-delivered breath. However, a posi- can be used to determine volume responsiveness
tive pressure breath at the same time impedes of both the right and left ventricle together. This
the cardiac output of the RVthe source of is essentially an end-expiratory hold for 15 s in a
LV preload. If the LV is volume responsive, passive, mechanically ventilated patient, during
PP and SV will dip after several cardiac cycles which time preload to the right heart and then left
to reflect this decrease in preload to the LV, heart increases. If both the RV and LV are vol-
and then return to baseline during exhalation ume responsive in parallel, then PP, SV, and CI
(Fig. 3.5). There are several minimally inva- will increase during this maneuver. Table3.1
sive methods available to assess SV, including compares these techniques.
pulse contour analysis from arterial pressure There are important limitations to these dynamic
tracings (e.g. FloTrac [Edwards Lifesciences, measurements. Most of these measurements
Irvine, CA], PiCCO [Philips, Netherlands], have only been validated in patients who are in a
LiDCO [LiDCO Group PLC, London, UK], sinus rhythm, completely passive, and receiving

Positive pressure breath, increased intrathoracic pressure


Airway pressure

DECREASE in RV output, distension of IVC


IVC diameter

DIVC

PPV ( SVV)
Arterial pressure

DECREASE in LV stroke volume (after several


cardiac cycles of pulmonary transit time)

Time

Fig. 3.5 Effects of positive pressure ventilation on IVC PPV pulse pressure variation, SVV stroke volume varia-
diameter and stroke volume variation. RV right ventricle, tion, LV left ventricle
IVC inferior vena cava, DIVC change in diameter of IVC,
3 Undifferentiated Shock 31

Table 3.1 Predictors of volume responsiveness during mechanical ventilationa


Threshold for predicting volume
Measurement Technique responsiveness
PPV Arterial waveform tracing >13%
SVV Pulse contour analysis >1013%
Esophageal Doppler monitor
LVOT VTi using TTE
PVI Plethysmography >1015%
DIVC TTE >1218%
PP or CI during EEO Arterial waveform tracing >5% increase
PAC
Pulse contour analysis
Esophageal Doppler monitor
PPV pulse pressure variation, SVV stroke volume variation, LVOT left ventricular outflow tract, VTi velocity-time inte-
gral, TTE transthoracic echocardiography, PVI plethysmography variation index, DIVC change in diameter of inferior
vena cava, PP change in pulse pressure, CI change in cardiac output, EEO end-expiratory occlusion, PAC pulmonary
artery catheter
a
Requirements include: passive patient, tidal volume at least 8mL/kg ideal body weight, sinus rhythm

45o

Starting position Supine with legs elevated Return to baseline position


for 13 min
Check baseline CO Give IV fluid bolus if positive
Recheck CO for positive response
response

Fig. 3.6 Technique for positive passive leg raising. CO cardiac output

volume controlled breaths of at least 8mL/kg tidal the case presentation). Combining SVV or PPV
volumeconditions that apply to very few ICU with an EEO maneuver or bedside echocardiogra-
patients in common practice. Furthermore, using phy will help prevent this misinterpretation. Finally,
indices of LV volume responsiveness in isolation decreased respiratory system compliance (e.g.
may be misleading in patients with RV dysfunction severe ARDS, massive ascites, morbid obesity,
(i.e. massive pulmonary embolism or pulmonary etc.) may decrease the sensitivity of SVV or PPV;
hypertension). These patients will have marked however, the accuracy of EEO appears unaffected
respiratory variation of SV and PP because the LV by changes in compliance or positive end-
is relatively empty and preload dependent; how- expiratory pressure [26, 27].
ever, the RV may be completely volume over- Passive leg raising (PLR) may be the most
loaded. If the RV itself is overloaded, giving accurate and widely applicable assessment of
intravenous fluid will not improve LV output and volume responsiveness (Fig.3.6). For this test, a
may cause hemodynamic deterioration (as seen in patient is laid supine and his/her legs are lifted up
32 S.P. Whitmore

Table 3.2 Thresholds for predicting volume responsive- echocardiography has been demonstrated to assist
ness using passive leg raising (PLR) greatly in the determination of shock etiology in
Threshold for multiple clinical arenas. In the emergency setting,
predicting volume BE (along with multi-organ focused ultrasonogra-
Measurement Technique responsiveness
phy) can accurately differentiate between hypo-
Pulse Arterial waveform Increase
pressure tracing >1215% volemic, cardiogenic, and obstructive causes of
Stroke Pulse contour Increase shock in patients with undifferentiated hypoten-
volume analysis >1215% sion, and allow the examiner to correctly priori-
Esophageal tize the most likely diagnoses in a timely fashion
Doppler with high specificity and accuracy [3134]. A
monitoring
LVOT VTi using simple, standardized approach to bedside ultra-
TTE sound in undifferentiated hypotension has been
PAC shown to reduce diagnostic uncertainty, alter
Cardiac Pulse contour Increase medical management, and influence the diagnos-
output, analysis >1215% tic or therapeutic plan in about one quarter of
Cardiac Esophageal
index Doppler emergency cases [35].
monitoring In the ICU setting, BE within the first 24 h has
LVOT VTi using been shown to significantly alter management in
TTE patients with hypotension, leading to less fluid
PAC
administration and earlier use of inotropic sup-
Quantitative end Increase >5%
tidal CO2 port in many patients, reducing absolute mortal-
LVOT left ventricular outflow tract, VTi velocity-time inte- ity by 10 % in a small series [36]. In the
gral, TTE transthoracic echocardiography, PAC pulmo- perioperative, postoperative, and general ICU
nary artery catheter settings, echocardiography has been shown to
accurately differentiate hypovolemia, volume
to 45 and held up for 13min; if SV, PP, CO or overload, cardiac tamponade, and hemodynami-
CI increase by 1215%, the patient is highly cally significant right or left ventricular dysfunc-
likely to be volume responsive (Table3.2) [26, tion that otherwise may have otherwise gone
28, 29]; continuous cardiac output monitoring is undiagnosed [3740].
preferred for real-time assessments. As a surro- There are several protocols for the use of
gate for increased CO, a 5% or more increase in point-of-care ultrasound in the hypotensive
ECTO2 during PLR is also predictive of volume patient, and the key similarities among them are
responsiveness, although this is not as sensitive the systematic evaluation of cardiac function,
[30]. The PLR retains its accuracy regardless of pericardial effusion, IVC diameter and variabil-
active respiratory efforts, tidal volume, level of ity, pneumothorax, and sources of potential hem-
sedation, or cardiac rhythm. Interpretation may orrhage [41, 42]. When examining a hypotensive
be difficult in cases of massive ascites, abdominal patient with ultrasound, the echocardiographic
compartment syndrome, or high pain response to portion is the most important. The examiner
the maneuver, and it should not be attempted in should start with a subxiphoid view of the heart,
patients with elevated intracranial pressure. determining any obvious decrease in global
contractility as well as the presence of any sig-
nificant pericardial effusion. A large pericardial
Bedside Echocardiography effusion in the presence of hypotension is highly
concerning for tamponade (Fig.3.7). From the
After assessment of volume responsiveness and same location, the IVC should be located and
initiating intravenous fluids as indicated, bedside assessed for respiratory variation, with a varying
echocardiography (BE) is the first test of choice to diameter or collapse suggestive of volume
investigate undifferentiated shock [1]. Bedside responsiveness (Fig.3.8). Parasternal and apical
3 Undifferentiated Shock 33

views should be used to estimate global RV and


LV systolic function (Fig.3.9), RV size com-
pared to LV size, and of utmost importance, the
relationship of the interventricular septum
(Fig.3.10). Dilation of the RV (i.e. RV diameter
approaching or exceeding LV diameter) and bow-
ing of the septum from right to left suggests RV
strain, which should prompt a search for pulmo-
nary embolism or other causes of RV failure, as
well as dissuade the clinician from using large
fluid boluses or positive pressure ventilation if it
can be helped [7]. After the cardiac portion, the
examiner should look for bilateral lung sliding to
rule out pneumothorax, free intraperitoneal fluid
suggestive of hemorrhage, and abdominal aorta
dilation >3cm concerning for aneurysm.
Fig. 3.7 Cardiac tamponade causing right ventricular Echocardiographic patterns of shock type are
collapse (transthoracic echocardiogram, subxiphoid
view). RV right ventricle, LV left ventricle summarized in Table3.3.

a b

c d

Fig. 3.8 IVC variation during respiration (transthoracic virtually no respiratory variation, suggests no response to
echocardiogram, subxiphoid view). a vs. b: roughly 50% fluid bolus. IVC inferior vena cava, RA right atrium, HV
IVC variation, suggests volume responsiveness. c vs. d: hepatic vein
34 S.P. Whitmore

a
A B

C D

Fig. 3.9(a) Global assessment of left ventricular con- ventricular contractility (transthoracic echocardiogram,
tractility (transthoracic echocardiogram, parasternal long parasternal short axis). A vs B: roughly 40% decrease in
axis). A vs. B: roughly 50% decrease in LV cavity, sug- LV cavity, suggests mildly reduced contractility. C vs D:
gests normal contractility. C vs. D: roughly 25% decrease almost no decrease in LV cavity, suggests severely
in LV cavity, suggests moderately depressed contractility. reduced contractility. LV left ventricle, A and C diastole, B
LV left ventricle, MV mitral valve, AV aortic valve, A and and D systole
C diastole, B and D systole. (b) Global assessment of left
3 Undifferentiated Shock 35

b A B

C D

Fig. 3.9(continued)

a b

Fig. 3.10 RV-LV size relationship and position of intra- of the RV with septal flattening (D-sign) and compres-
ventricular septum (transthoracic echocardiogram, para- sion of the LV, indicates RV strain/overload. RV right ven-
sternal short axis). (a) Normal relative RV and LV size, tricle, LV left ventricle, dashed line flattened septum
septum forms a contiguous circle with the LV. (b) Dilation
36 S.P. Whitmore

Table 3.3 Echocardiographic patterns of shock types


Shock type Suggestive echocardiographic findings
Hypovolemia IVC collapsing on active inspiration
Widely variable IVC diameter with respiration
Hyperdynamic RV and LV
Distributive IVC collapsing on active inspiration
Widely variable IVC diameter with respiration
Hyperdynamic RV and LV
Cardiogenic Pneumothoraxabsent lung sliding, identification of lung point
Obstructive Tamponadepericardial effusion+distended, non-varying IVC RV collapse during
diastole
Pulmonary Embolismdistended, non-varying IVC, RV dilation, septal bowing, decreased
RV contractility
CardiogenicRV Distended, non-varying IVC
RV dilation
Septal bowing
Decreased RV contractility
CardiogenicLV Decreased LV contractility
Dilated LV and/or LA distended, non-varying IVC
IVC inferior vena cava, RV right ventricle, LV left ventricle

Summary fluid and aorta caliber, to further differentiate


shock type and guide the use of fluids, pressors,
Medically complex patients in shock should be inotropes, or other specific therapies.
assumed to have multiple shock types occurring
simultaneously, and it may be difficult to dif-
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Hypovolemic Shock andMassive
Transfusion 4
Joshua M.Glazer andKyleJ.Gunnerson

Case Presentation E-FAST views showed no evidence of hemo-


pneumothorax, pericardial fluid, myocardial
A previously healthy 35 year old male presented wall-motion abnormalities, or fluid in the sple-
as a Level I trauma after a motor vehicle acci- norenal or rectovesicular spaces. Trauma-
dent in which he was the restrained driver. There protocol chest and pelvis x-rays were negative.
was extensive intrusion on the front end of the
vehicle requiring extrication of the patient. Question What is the optimal approach to man-
Airbag did not deploy. He was reportedly hypo- agement of this patients presumed traumatic
tensive and confused in the field. An 18 gauge IV hemorrhagic shock; specifically, how should
was placed and a 500mL NS bolus initiated intravascular access, fluid resuscitation, hemody-
prior to arrival. In the Emergency Department, namic end-points, and definitive therapy be
his initial vitals were significant for a heart rate prioritized?
of 140 and blood pressure of 72/48. Primary sur-
vey demonstrated an intact airway, bilateral Answer Hemostatic resuscitation prioritizing
breath sounds, 2+ pulses in all four extremities, damage control surgery & massive transfusion.
and a Glasgow Coma Score (GCS) of 11 with no
obvious focal disability on full exposure. The This patient is exsanguinating, presumably
patient was pale, had a large left-sided frontal secondary to traumatic intraabdominal injury,
scalp contusion, and had obvious bruising of the and demonstrating physiology consistent with
lower chest and right abdomen. A bedside decompensated hemorrhagic shock. Injury mech-
Extended Focused Assessment with Ultrasound anism and physical exam findings are also con-
in Trauma (E-FAST) exam showed free fluid in cerning for concurrent traumatic brain injury. As
Morisons pouch (Fig.4.1). The remaining with all types of shock, prioritization is given to
reversal of the inciting etiology and concurrent
mitigation of tissue hypoperfusion caused by the
J.M. Glazer precipitating shock state.
Emergency Medicine, University of Michigan Health After confirming an intact airway and bilateral
System, Ann Arbor, MI, USA breath sounds, this patients management appro-
K.J. Gunnerson (*) priately focused on cardiovascular optimization
Emergency Medicine, Internal Medicine and and hemodynamic support. Two additional proxi-
Anesthesiology, Division of Emergency Critical Care,
mal 16 gauge peripheral IVs were placed. The
University of Michigan Health System,
Ann Arbor, MI, USA crystalloids which were initiated in the field were
e-mail: kgunners@med.umich.edu discontinued. Non-crossed O+ packed red blood

Springer International Publishing Switzerland 2017 39


R.C. Hyzy (ed.), Evidence-Based Critical Care, DOI10.1007/978-3-319-43341-7_4
40 J.M. Glazer and K.J. Gunnerson

fluids. Markers of tissue perfusion, including


central venous oxygen saturations (ScvO2) and
serial lactate levels, improved and the patient
was taken back to the operating room for
reanastamosis and closure.

Principles ofManagement

Hypovolemic Shock

We will first review fundamentals of the manage-


ment of hypovolemic shock regardless of etiol-
ogy, then focus on elements unique to treating
patients with hemorrhagic shock.

 stablish Adequate IV Access


E
Flow rates achieved for potential life-saving fluid
Fig. 4.1 Extended Focused Assessment with Ultrasound
in Trauma (E-FAST) scan showing free fluid surrounding resuscitation depend on the device used. In agree-
the liver border in a polytrauma patient (Reproduced with ment with Poiseuilles law, the ideal cannula
permission of Huang and Fung) should be a short, large-bore (at least 18g), and
placed in a proximal large vein in the upper
cells, along with fresh frozen plasma and pooled extremity. If a central venous catheter (CVC) is
platelets, were rapidly hand-delivered and infused the only available access, the addition of a pres-
in a 1:1:1 ratio per the institutional massive trans- sure bag makes a greater difference on flow rate
fusion protocol. As he is within the 3-h window, than with an equivalent peripheral cannula [1].
tranexamic acid is administered to inhibit fibrino- However, in a resuscitation setting, intraosseous
lysis. Simultaneously, electrolytes were aggres- (IO) access has higher first pass success and
sively repleted and his acidosis corrected. A shorter procedure times, making it preferable to
multidisciplinary Trauma team agreed on a mean CVC insertion if peripheral access cannot be rap-
arterial pressure goal of 75mmHg in an effort to idly obtained [2]. Of the three approved IO sites
maintain cerebral perfusion pressure in the set- (proximal tibia, distal tibia, proximal humerus),
ting of probable traumatic brain injury, remaining the humerus seems to be the superior site in terms
cognizant to avoid overcorrection and resultant of flow rates, drug delivery, and management of
disruption of intrinsic/protective hemostatic infusion pain [3].
mechanisms.
After initial evaluation/stabilization in the  onsider Physiologic Reserve
C
Emergency Department, the patient was trans- Young healthy individuals can maintain end-
ported first for head CT, which did not show organ perfusion and normotension despite sig-
intracranial hemorrhage, then to the operating nificant intravascular loss as a result of their
room for exploratory laparotomy. Damage con- ability to sustain cardiac output through: periph-
trol surgery, including splenectomy and partial eral vasoconstriction, compensatory tachycardia,
small bowel resection without reanastamosis, and catecholamine surge. Thus, substantial
was performed. The patient was then trans- tachycardia and cool extremities should be rec-
ferred to the ICU with an abdominal wound ognized as markers of imminent decompensation
vacuum device in place. Hemodynamic optimi- and cardiovascular collapse in these individuals
zation was continued, utilizing a combination [4]. Conversely, systemic diseases (e.g. chronic
of blood products, pressors, and intravenous kidney disease, hypertension, diabetes, cirrhosis,
4 Hypovolemic Shock andMassive Transfusion 41

chronic heart failure) and/or pharmacotherapies Hemorrhagic Shock


(e.g. alcohol, antihypertensives, anti-arrhythmics,
-blockers, steroids, insulin) can both limit phys- Hemostatic resuscitation refers to the process of
iological reserve and also delay detection of restoring and sustaining normal tissue perfusion
shock when patients do not manifest classic signs to the patient presenting in uncontrolled hemor-
of hypovolemia. rhagic shock, with an emphasis on preservation
of effective clotting.
 onitor Volume Responsiveness
M
Fundamentally, fluid responsiveness means  xpedite Anatomic Control ofBleeding
E
that stroke volume (and thus cardiac output, Immediate control of ongoing hemorrhage is always
given stable heart rate) will improve if fluids are the first priority. This may simply require direct pres-
administered. Administering fluid to a volume sure or other straightforward maneuvers for brisk
unresponsive patient can negatively affect car- external bleeds (e.g. staple closure for scalp wound
diac output directly and has other potential side or nasal pack for epistaxis). Depending on the
effects such as pulmonary edema, abdominal source, however, Gastroenterology, Interventional
compartment syndrome, and cerebral edema. Radiology, or Surgery consultation may be required
Traditionally an increase in stroke volume of for specific hemostatic interventions.
1015% after receiving an adequate bolus (rapid
infusion of at least 250cc) is considered a posi-  tilize Damage Control Surgery
U
tive test of volume responsiveness [5]. Several The initial surgery on a hemodynamically unsta-
techniques and technologies exist to help make ble, actively bleeding patient should be focused
this determination without actually administer- on anatomic control of bleeding, with repair of
ing a volume expander, but each has its own less significant injuries or time-intensive proce-
unique challenges and limitations. Please refer dures deferred. Once hemostasis is achieved, the
to the Undifferentiated Shock chapter for a patient is transferred to the intensive care unit for
more detailed discussion. completion of resuscitation [8]. Subsequent oper-
ative interventions are later performed once the
 dminister theAppropriate Fluid(s)
A patient is hemodynamically stable.
The ideal fluid used to replete intravascular
depletion is very much dependent on the precipi-  llow forPermissive Hypotension
A
tating etiology. With gastrointestinal losses, While the goal of resuscitation in general is to
thoughtful repletion of electrolytes is indicated. restore normal systemic oxygen delivery, during
With acute blood loss, sanguineous resuscitation early resuscitation the advantage of reducing
is clearly preferable. Importantly, tissue perfu- ischemia must be weighed against the iatrogenic
sion and oxygen delivery are the goals, and that prolongation of hemorrhage. Indeed, attempting
optimization of cardiac output and oxygen carry- to achieve normotension during active hemor-
ing capacity are the means. rhage consistently increases mortality [9, 10]. In
penetrating trauma patients, resuscitation to a tar-
 rack Endpoints ofResuscitation
T get minimum MAP of 50mmHg, rather than
Normalization of vital signs alone is insuffi- 65mmHg, significantly decreases postoperative
cient evidence of resolution of shock; indeed, coagulopathy and lowers the risk of early postop-
poor tissue perfusion can often persist and erative death and coagulopathy [11].
lead to ongoing accumulation of oxygen debt
and tissue damage (see Fig.4.2). More appro-  orrect andReverse Augmenting
C
priate markers, which account for perfusion Factors ofCoagulopathy andShock
of the microcirculation, include central In the exsanguinating patient, the so-called lethal
venous oxygen saturation (ScvO2) and lactate triad of coagulopathy, acidosis, and hypothermia
clearance [6, 7]. predict morality and must be corrected (see Fig.4.3).
42 J.M. Glazer and K.J. Gunnerson

Delivery dependent Delivery independent


VO2 VO2

VO2

VO2
SVO2 SVO2
OER
Lactate
OER

Lactate

DO2crit
DO2

Fig. 4.2The relationship between oxygen delivery and where oxygen debt starts to accumulate. DO2=CaO2CO
oxygen consumption in shock. When DO2 decreases to less (normal range: 460650ml/min/m2); VO2=CO (CaO2
than the value for critical delivery (DO2crit), oxygen con- CVO2) (normal range: 96170ml/min/m2); CaO2 (arterial
sumption (VO2) is linearly dependent on the delivery of oxygencontent)=(Hb1.34SaO 2)+(0.003PaO 2);
oxygen to the tissues (DO2). In the delivery-dependent CVO2=(Hb1.34SVO2)+(0.003PVO2). CO cardiac
region, oxygen extraction ratio is maximal and anaerobic output, PaO2 arterial oxygen tension, Hb hemoglobin.
metabolism increases with an associated increase in lactate SVO2 normal range: 70% (5%) [34]
and decrease in SVO2. This region to the left of DO2crit is

 inimize Crystalloid Administration


M
Indiscriminate fluid administration during uncon-
trolled hemorrhage is associated with increased
bleeding. Relative arterial hypertension caused
by augmented cardiac output via the Frank-
Starling relationship, forces more fluid out of the
damaged circulation, and can wash away early
clots. Furthermore, asanguineous crystalloids
dilute the concentration of red cells, clotting fac-
tors, and platelets, impairing both oxygen carry-
ing capacity and the clotting cascade [14].
Fig. 4.3 The so-called lethal triad whereby the combi-
Exogenous fluids are also likely to be cooler than
nation of hypothermia, acidosis, and coagulopathy con- body temperature, contributing to hypothermia.
tribute toward mortality in hemorrhagic shock. Iatrogenic Finally, rapid administration of crystalloids dam-
etiologies for worsening hemorrhage include use of crys- ages the endothelial glycocalyx, leading to
talloids and packed red blood cells (PRBC). Both directly
worsen hypothermia if not warmed and contribute to dilu-
increased extravasation [15].
tional coagulopathy, the latter if platelets and fresh frozen
plasma are not concurrently infused  reserve Formed Clot
P
withAntifibrinolytics
Several studies have demonstrated that patients The CRASH-2 trial randomized 20,000 trauma
with altered coagulation function at the time of hos- patients worldwide to receive either placebo or
pital admission have substantially worse outcomes tranexamic acid, and demonstrated a significant
than similar patients who are not coagulopathic, survival benefit with this therapy when administered
even when controlling for degree of injury within 3h of injury. Interestingly, there was no dif-
[12, 13]. ference in transfusion requirements between the
4 Hypovolemic Shock andMassive Transfusion 43

groups, suggesting that tranexamic acid may have lower in-hospital mortality [18]. Furthermore,
effects in addition to antifibrinolysis. The earlier implementation of a chloride-restrictive resusci-
the drug was administered, the more positive the tation is associated with a significant decrease in
effect [16]. the incidence of acute kidney injury and use of
renal replacement therapy [19]. Commercially
 eplace Losses via Transfusion Therapy
R available chloride-restrictive fluids include the
In the setting of brisk hemorrhage, the ideal fluid crystalloids Lactated Ringers and Plasma-Lyte,
of choice is fresh whole blood (FWB). Blood as well as the colloids albumin and several syn-
provides the intravascular volume expansion thetic gelatin- or hydroxyethyl starch (HES)-
needed to increase cardiac output, the red blood based preparations.
cells necessary for oxygen carrying capacity,
and contains the platelets and clotting factors  ole ofAlbumin
R
which enable hemostasis [17]. Importantly, The Saline versus Albumin Fluid Evaluation
hemoglobin and hematocrit do not change in (SAFE) study showed no significant difference in
acute hemorrhage; indeed, these measurements rate of death or development of organ failure
reflect concentrations of red blood cell content, among ICU patients randomized to normal saline
and will not be affected until compensatory fluid or albumin resuscitation. Subgroup analysis sug-
shifts from the intra- and extra-cellular spaces gests that use of albumin in patients with trau-
dilute the blood. matic brain injury was associated with a
significant increase in rate of death at 2 years
while albumin is associated with a significant
Evidence Contour decrease in the rate of death at 28 days in patients
with severe sepsis [20].
Several aspects regarding the management of
hypovolemic and hemorrhagic shock remain  se andTiming ofPressors
U
without clear consensus. Even in patients with pure hypovolemic shock,
vasopressors can and should be used as a bridge
while volume is infused and then titrated off as
Hypovolemic Shock the volume deficit is overcome [21]. The aim is to
preserve coronary perfusion pressure (CPP) (aor-
The ideal fluid for hypovolemic shock secondary tic diastolic pressure (ADP) pulmonary artery
to asanguineous losses should reliably expand wedge pressure (PAWP)) and thus prevent isch-
intravascular volume; have a sustained effect emic injury and secondary cardiogenic shock.
without accumulation in tissues, and replete Many experts suggest that a target ADP of
whole-body deficits, while minimizing side- 3540mmHg is likely adequate; however, in
effects (electrolyte disturbances, third-spacing, patients with preexisting conditions that increase
acidosis, hemodilution) and cost. Unfortunately, baseline PAWP (e.g. pulmonary hypertension),
no such fluid exists; so much debate exists sur- the ADP goal should be correspondingly
rounding which non-ideal fluid to use. increased [22, 23].

 ormal Saline vs Balanced Solutions


N
Normal saline has traditionally been the most Hemorrhagic Shock
widely-used crystalloid in the United States.
Increasing evidence, however, suggests that exces- Adequately powered clinical trials addressing the
sive chloride loads are associated with negative question of optimal resuscitation of massively
outcomes. Among patients with systemic inflam- bleeding patients are lacking. Instead, a large num-
matory response syndrome (SIRS), chloride- ber of retrospective studies and systematic reviews
restrictive fluid resuscitation is associated with concerning this topic have been published,
44 J.M. Glazer and K.J. Gunnerson

although the interpretation of the currently avail- is 1:1:1 FFP:PLT:RBC.However, close inspection
able data differs substantially. Figure4.4 demon- of many of these studies reveals important limita-
strates a theoretical framework for the treatment of tions in their interpretation, namely a prominent
hemorrhagic shock. Figure4.5 incorporates this effect of survivor bias [24]. While the optimal mas-
information with logistical considerations neces- sive transfusion protocol ratio remains elusive, it
sary for implementing an institutional massive does appear that an early and more balanced
transfusion protocol. approach to transfusion is associated with improved
outcomes [25].
 assive Transfusion Protocol
M
Studies of both military and civilian trauma patients I onized Calcium Repletion
have demonstrated that those receiving high ratios Hypocalcemia can complicate massive transfu-
of both fresh frozen plasma (FFP) and platelets sion as a result of the citrate anticoagulant in
(PLT) to red blood cells (RBC) have the highest blood products (FFP&PLT>PRBC). Formation
survival, suggesting that the ideal transfusion ratio and stabilization of fibrin polymers is dependent

Start of
hemorrhage Hemostasis

Monitoring Correct: Temp, Ca2+, K+, PaO2, PaCO2 Shock Reversal: pH, lactate, ScvO2

Anti-
Tranexamic acid according to CRASH2 and/or VHA
fibrinolytics

VTE prophylaxis

Goal-directed VHA-guided transfusion

Transfusion Ratio
therapy 1: 1: 1
RBC: FFP: PLT
Additional RBC based off Hgb level

Control of hemorrhage
Anatomic
control Uncontrolled hemorrhage

30 min 60 min Time

Fig. 4.4 One reasonable algorithm for treatment of hem- oxygenation/ventilation issues is indicated while tracking
orrhagic shock incorporating principles of hemostatic endpoints of resuscitation including serum pH, lactate,
resuscitation. Of primary importance is anatomic control and ScvO2. RBC red blood cells, FFP fresh frozen plasma,
of bleeding. Concurrently, goal-directed transfusion of PLT platelets, Hgb hemoglobin, VHA viscoelastical
blood products and anti-fibrinolytics are administered to hemostatic assay, VTE venous thromboembolism, Ca2+
preserve cardiac output, oxygen carrying capacity, and the serum calcium, K+ serum potassium, PaO2 partial pressure
ability to form and preserve clots. As with any shock state of oxygen in blood, PaCO2 partial pressure of carbon
correction of electrolyte abnormalities, hypothermia, and dioxide in blood, ScvO2 central venous oxygen saturation
4 Hypovolemic Shock andMassive Transfusion 45

Massive Transfusion Protocol (MTP)


Appropriate Initial Interventions:
Intravenous access 2 large bore IVs and Centrol Venous Cath Identify and Manage Bleeding
Labs: T&S, CBC, Plts, INR, PT, PTT, Fibrinogen, Electrolytes, (Surgery, Angiographic Embolization, Endoscopy)
BUN/Creatinine, ionized calcium
Continual monitoring: VS, U/O, Acid-base status
Aggressive re-warning Adult: 4U RBCs in <4 hours and ongoing bleeding
Prevent / Reverse aicdosis
Correct hypocalcemia: CaGluconate or Cacl
Target goal ionized calcium 1.2 1.3 Clinical Team Activates MTP & Designates Clinical Contact
If use CaCl 1 gm, give slowly IV Clinical Contact phones Blood Bank (BB) at ***- **** and:
Repeat lab testing to evaluate coagulopathy Provides name of clinical contact person to Blood Bank (BB)
Provides MR#, sex, name, location of patient
Stop crystallcid - avoid dilutional coagulopathy
Records name of BB contact, calls if location/contact information changes
Other considerations: Sends person to pick up the cooler
Cell salvage Ensures that MTP protocol elcetronic order is entered
Heparin reversal: Protamine 1mg IV/100 U heparin
Warfarin reversal: Vitamin K 10 mg IV; Consider Prothromin Comp
Chronic Renal Failure + VW Factor; DDAVP 0.3 mg/kg IV x 1 dose
Consider antifibrinoclytics:
BB Prepares MTP Pack; Transfuse as 1:1:1 Ratio
Tranexamic acid 1 gm bolus plus infusion 1 gm over 8 hrs
MTP Pack: 6U RBCs; 4U FFp ; One (1) 5-pack Platelets
Arricar 5 gm IV bolus then 1 gm/hr IV infusion

Additional help Clinical Contact calls BB at


Anesthesia pager ***** Trauma Chief pager ***** Hemostasis & ***** for another MTP pack
resolution of ** MD can adjust pack based on
Rapid Response Team pager *****
coagulopathy? NO labs PRN
General
GeneralGuidelines
Guidelinesfor
forLab-based
Lab-basedBlood
BloodComponent
Component
Replacement
Replacementin
inAdults:
Adults:

Product Threshold Dose YES Repeat Labs


RBCs No threshold MD discretion CBC, Platelets
INR/PT, PTT
FFP INR > 1.5 4 units FFP Fibrinogen Consider rFVIIa
Stop MTP AbG (Ionized
Platelets < 100,000 One 5-pack Plts Calcium, If persistent coagulopathy
Notify BB & return any unused
Potassium, 90 m/kg dose
Cryoprecipitate Fibrinogen < Two 5-packs blood ASAP
Lactate,
100 Cryoprecipitate Resume standard orders Hematocrit)
D/C MTP Electronic order

Fig. 4.5 An institutional Massive Transfusion Protocol component blood products, and triggers for activation and
detailing the initial stabilization steps, necessary contact deactivation
information, relevant electronic medical record orders,

on ionized calcium; additionally, decreased intra- information regarding platelet aggregation, clot
cellular calcium concentration negatively affects strengthening, fibrin cross-linking, and fibrinoly-
all platelet-related activities. Equally importantly, sis, and thus more accurately assess global hemo-
myocardial contractility and systemic vascular static potential. Goal-directed transfusion
resistance are compromised at low ionized cal- utilizing VHAs have been reported to reduce
cium levels. Taking into account beneficial car- bleeding, significantly diminish transfusion
diovascular and coagulation effects, ionized requirements, and improve outcomes in cohort
calcium levels should be maintained above studies [28].
0.9mmol/l [26].
I nvasive Non-surgical Hemorrhage
Point-of-Care Monitoring Control
theHemostatic System In moribund or arresting patients with exsanguinat-
Conventional laboratory tests of coagulation are ing noncompressible hemorrhage in the chest,
insensitive in detection acquired coagulopathy abdomen, or pelvis, resuscitative thoracotomy has
or in guiding procoagulant therapy [27]. traditionally been the intervention of choice in the
Viscoelastical hemostatic assays (VHAs), includ- emergent setting. Unfortunately, after controlling
ing thrombelastography (TEG) and rotational for relatively easily reversible causes of traumatic
thrombelastometry (ROTEM), provide rapid obstructive shock (tension pneumothorax and
46 J.M. Glazer and K.J. Gunnerson

hemopericardium with tamponade), outcomes are monitoring cerebral oxygenation in individual


quite poor and the procedure itself places medical patients can allow liberalization of CPP target and
providers at risk of serious injury [29]. Resuscitative thus facilitate permissive hypotension in the poly-
endovascular balloon occlusion of the aorta trauma patient.
(REBOA) offers a less invasive alternative which
effectively allows intravascular aortic cross-clamp
thereby limiting further hemorrhage and redistrib- References
uting blood supply to the heart and brain while
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 iming andRole ofVasopressors
T 2011;28(3):2012.
2. Leidel BA, Kirchhoff C, Bogner V, Braunstein V,
Studies using animal models of profound hemor- Biberthaler P, Kanz KG.Comparison of intraosseous
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when norepinephrine or vasopressin (AVP) is resuscitation in the emergency department with inacces-
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3. Luck RP, Haines C, Mull CC.Intraosseous access.
phenylephrine have been associated with wors- JEmerg Med. 2010;39(4):46875.
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M.Dynamic arterial elastance to predict arterial pres-
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A, Shapiro NI, etal. Lactate clearance as a predictor
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Surg. 2013;74(4):9991004.
Hemostatic Resuscitation 8. Pohlman TH, Walsh M, Aversa J, Hutchison EM,
withConcurrent Head Injury Olsen KP, Lawrence RR.Damage control resuscita-
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severe head injury (GCS12) compounds the R, Bruttig SP, Capone A, etal. Resuscitation from
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10. Bickell WH, Wall Jr MJ, Pepe PE, Martin RR, Ginger
based therapy and intracranial pressure (ICP) VF, Allen MK, etal. Immediate versus delayed fluid
based therapy [32]. Considering that cerebral isch- resuscitation for hypotensive patients with penetrating
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Welsh FJ, Tsai P, etal. Hypotensive resuscitation
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perfusion pressure (CPP=MAP ICP) is arguably postoperative coagulopathy in trauma patients with
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12. Hess JR, Lindell AL, Stansbury LG, Dutton RP,

be rapidly lowered awaiting decompressive man- Scalea TM.The prevalence of abnormal results of
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13. MacLeod JB, Lynn M, McKenney MG, Cohn SM, 23. Cruickshank JM.The role of coronary perfusion pres-
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67(1):337; discussion 79. mortality in patients with severe trauma: the PROPPR
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Acute Respiratory Failure: NIV
Implementation andIntubation 5
TorbenK.Becker andJohnM.Litell

Case Presentation While non-invasive ventilation has been shown


to be effective and safe in patients with exacerba-
A 65 year-old woman with a history of ischemic tions of COPD and CHF, other conditions are
cardiomyopathy and thromboembolic stroke pre- more controversial. The use of NIV in patients
sented with dyspnea, tachypnea (respiratory rate with pneumonia who progress to acute respiratory
36 breaths/minute), cough, fever, and oxygen failure has been associated with a high failure rate
desaturation to 85% despite non-rebreather mask and rapid deterioration, leading to worse out-
at 10L/min. During her initial resuscitation she comes, including increased mortality. Both NIV
was treated with noninvasive ventilation via (Fig.5.2) and the use of high-flow, heated, humid-
bilevel positive airway pressure (BPAP) ventila- ified oxygen delivered by nasal cannula (Fig.5.3)
tion. Thirty minutes later, the patients oxygen (see section Evidence Contour) may improve
saturation had steadily improved to 94% on FiO2 respiratory and gas exchange parameters, but it is
of 0.7, and her respiratory rate had decreased to challenging to predict which patients will defini-
28, though she remained febrile. Initial diagnos- tively improve with this strategy. Individualized
tics revealed a white blood cell count of 19,500. care and continuous bedside reassessment are
The chest x-ray is shown below in Fig.5.1. essential. In this case, the patient was emergently
intubated and treated with broad-spectrum antibi-
Question What is the next appropriate step in otics prior to ICU admission. After 4 days, she
the management of this patient? was successfully extubated and transferred to the
general medical ward, where she continued to
Answer Depending on her goals of care, this improve prior to discharge on oral antibiotics.
patient should most likely be intubated and
undergo invasive ventilation.
Principles ofManagement

Definition
T.K. Becker (*)
Department of Critical Care Medicine, University Acute respiratory failure manifests as hypox-
of Pittsburgh Medical Center, Pittsburgh, PA, USA emia and/or hypoventilation, which can lead to
e-mail: tbeckermd@gmail.com global ischemia and acid/base disturbances.
J.M. Litell Depending on patient factors and the type of
Department of Emergency Medicine, Division of respiratory failure, patients generally require
Emergency Critical Care, University of Michigan
Health System, Ann Arbor, MI, USA some degree of respiratory support, ranging

Springer International Publishing Switzerland 2017 49


R.C. Hyzy (ed.), Evidence-Based Critical Care, DOI10.1007/978-3-319-43341-7_5
50 T.K. Becker and J.M. Litell

Fig. 5.1 Chest x-ray

from supplemental oxygen via nasal cannula to


high-flow oxygen therapy, non-invasive ventila-
Fig. 5.2 Non-invasive ventilation by full face mask
tion, and invasive ventilation. High-flow oxygen
therapy can be delivered via face mask or high
flow nasal cannula (Fig.5.3). The term non-
invasive ventilation (NIV) encompasses all
forms of mechanically assisted ventilation with-
out an artificial airway in place. NIV refers to
both negative pressure ventilation (no longer
used in clinical practice) and positive pressure
ventilation modes, which include continuous
positive airway pressure (CPAP) and bilevel
positive airway pressure (BPAP) ventilation.
Both are typically delivered via a tightly-fitting
mask, which can be fitted over the nose, nose
and mouth, face, or entire head. CPAP delivers
various air/oxygen ratios at a constant pressure
throughout both inspiration and expiration,
which can improve alveolar recruitment and
capillary oxygen delivery. BPAP provides both
this continuous level of baseline expiratory pos-
itive airway pressure (EPEP) and then a higher
level during inspiration (IPAP). Depending on
the settings, cycling between these two pressure
levels is triggered by the patient and/or a pre-set
rate chosen by the clinician. Fig. 5.3 Hi-flow nasal cannula
5 Acute Respiratory Failure: NIV Implementation andIntubation 51

The theoretical benefit of BPAP over CPAP is combination of patient tolerance and clinical
this additional pressure support during inspiration, effect. If they tolerate the mask, patients often
which can augment the patients tidal volume and describe an initial subjective improvement in
reduce the mechanical work of breathing [1]. their work of breathing. Objective clinical
Because of their impact on intrathoracic pressure, improvement, such as the resolution of pulmo-
both of these modes of NIV can also have hemo- nary rales and jugular venous distension, usu-
dynamic effects, including both preload and after- ally lags somewhat behind.
load reduction. Depending on the patient and BPAP can be a particularly helpful mode in
pathology, these effects can offer additional thera- patients with impaired gas exchange secondary
peutic benefit, but can also exacerbate hemody- to respiratory muscle fatigue, as commonly seen
namic compromise. in patients with acute exacerbations of
COPD.Beyond the alveolar recruitment con-
ferred by the baseline EPAP, the addition of pres-
Indications, Contraindications sure support during inspiration can provide a
andSettings mechanical advantage and thus further decrease
the work of breathing, which otherwise consumes
The most widely accepted indications for the use a tremendous amount of metabolic energy.
of NIV in the acute setting include respiratory Additional IPAP also creates more effective air-
failure due to acute decompensated heart failure way ventilation and CO2 removal. Typical initial
(ADHF) and acute exacerbations of chronic BPAP settings are an EPAP of 5cm H2O and an
obstructive pulmonary disease (COPD). Early IPAP of 10cmH2O.In response to persistent
use of NIV is associated with improved survival respiratory acidosis, IPAP may be increased
in patients with these conditions [2, 3]. Common (usually in increments of 2cm H2O). This
chronic indications include obstructive sleep increases the difference between EPAP and IPAP,
apnea and restrictive diseases of the chest wall, which is the primary contributor to augmented
such as muscular dystrophies and obesity ventilation. In response to persistent hypoxemia,
hypoventilation syndrome. In order for NIV to EPAP may also be increased in increments of
be safe and effective, patients mental status 2cm H2O.This is most likely to augment alveo-
must not be altered to the point where they will lar recruitment and oxygenation. Clinicians
not cooperate with the clinician or tolerate the should be mindful that the pressure required to
face mask, nor should they have impaired inabil- overcome the tone of the lower esophageal
ity to protect their airway from excessive secre- sphincter is approximately 2022cm
tions or emesis. Specifically, this includes all H2O.Keeping the IPAP below this level may
unresponsive and apneic patients, in whom intu- reduce the risk of accidental gastric insufflation,
bation and invasive ventilation is the only rea- vomiting, and possible aspiration.
sonable mode of ventilatory support. Certain
craniofacial abnormalities may also prevent an
effective mask seal.  redictors ofFailure ofNon-invasive
P
Patients with ADHF develop respiratory fail- Ventilation
ure due in part to the presence of pulmonary
edema [1]. CPAP is commonly used in these It is important to recognize when a patient may
patients, as it can provide rapid preload and not improve with NIV.Very limited evidence is
afterload reduction and augment alveolar available to guide decision-making in these
recruitment, improving oxygenation and mini- patients. In a 2003 prospective cohort study of
mizing ongoing coronary ischemia [4]. CPAP is severe dyspnea due to decompensated heart fail-
often initially set at 5cm H2O and titrated to a ure, Giacomini and colleagues derived a crude
52 T.K. Becker and J.M. Litell

protocol that addresses the transition from the include patients with pneumonia and COPD with
emergency department to inpatient care for hypercapnic respiratory failure. This may be due
patients stabilized with NIV.After a 90-min trial to overlap in diagnosis between COPD exacerba-
of NIV, patients who felt subjectively better and tion and true infection [8]. Other possible excep-
tolerated at least a 15-min period of oxygen by tions include neutropenic patients with
reservoir mask were admitted to a general care hematologic malignancy, or recent solid organ
ward. None of these responder patients were transplant recipients with suspected pneumonia,
subsequently intubated or transferred to ICU [5]. possibly because these patients have a higher inci-
Patients who remained tachypneic, acidemic, or dence of viral pneumonia than immunocompetent
hypoxemic after a trial of NIV (6090min), and patients [1114]. Overall, these data are still rela-
those who developed hypotension, were unlike to tively sparse. If NIV is attempted in these patients,
improve. For these non-responder patients, the clinician should provide near-continuous bed-
endotracheal intubation and invasive ventilation side reassessment and not hesitate to intubate if
should be strongly considered, as the role of pro- there is no significant improvement.
longed acute treatment with NIV is still unclear.
Strong evidence outlining safe titration of
NIV in other patient subgroups is lacking. Factors  se inPatients withAsthma
U
to consider include patient comorbidities and Exacerbation
physiologic reserve, as well as the expected time
course of reversibility for the cause of their acute NIV has also been used in patients with acute
respiratory failure. exacerbations of asthma, however there is only
limited evidence to help guide the clinician. The
available studies fail to demonstrate improve-
Evidence Contour ment in mortality or intubation rates, but show an
apparent decrease in hospital admission rates,
Use inPatients withPneumonia hospital length of stay, symptom severity, and
indirect markers of severity, such as pulmonary
The use of NIV in acute respiratory failure has functions tests or arterial blood gases [1518].
been studied for indications other than decompen- However, the are no high-quality studies address-
sated heart failure and COPD [610]. Pneumonia ing the use of NIV in patients with the most
is not considered an appropriate indication for the severe forms of asthma exacerbation, limiting
use of NIV for patients in acute respiratory failure. any conclusion regarding its impact on mortality
Although NIV offers a less invasive intervention and intubation rates in this patient population
for respiratory distress, the NIV failure rate in [19]. For patients with severe asthma exacerba-
patients with pneumonia has been reported as high tions, NIV should be used with caution, in the
as 50% [7]. It is very difficult to predict which context of maximal medical therapy and continu-
patients will improve and which will deteriorate ous bedside reassessment.
[7], and among those who decline there is an
increased incidence of peri-intubation complica-
tions and a significant increase in mortality [9, 10]. Use inPatients withARDS
Several possible explanations for this have been
proposed, such as the increased metabolic Limited evidence suggests that NIV might be
demands in patients with pneumonia, the inability associated with decreased intubation rates in
to adequately clear respiratory secretions, and the select patients with early mild ARDS, however
protracted time course of pneumonia when com- overall mortality rates seem to be unchanged, and
pared to other common indications for very close clinical monitoring is required [20
NIV.Possible exceptions to the poor performance 22]. NIV is not appropriate as a first line approach
of NIV in patients with pulmonary infection for established ARDS, given the importance of
5 Acute Respiratory Failure: NIV Implementation andIntubation 53

careful control of tidal volume and airway pres-  se ofNIV toFacilitate Weaning
U
sure in this syndrome [23]. fromInvasive Ventilation

In addition to its use in patients with acute respi-


 se ofNIV inPatients withAltered
U ratory failure, NIV has also shown some promise
Mental Status for its use in liberating patients from invasive
ventilation. Some evidence supports extubation
As mentioned, one of the most common tradi- to NIV as a safe strategy in certain patients with
tional contraindications for the use of NIV is resolving acute respiratory failure, such as COPD
significantly altered mental status, because of patients with acute on chronic hypercapnia [27].
the concern that these patients have compro- This approach may reduce the incidence of some
mised airway protective reflexes and are not risks associated with prolonged intubation and
able to adequately manage pulmonary or oro- invasive ventilation, such as ventilator-associated
pharyngeal secretions. Vomiting into the posi- pneumonia and tracheostomy rates. NIV use in
tive pressure mask is potentially catastrophic in this context may also reduce the total duration of
these patients. For intoxicated patients with ventilation, as well as ICU and hospital length of
respiratory distress NIV is almost never the saf- stay, without a higher risk of reintubation [1,
est alternative, because of unpredictable toxico- 2729].
kinetics and the risk of vomiting. Though NIV
can be of great utility in patients with acute
exacerbations of COPD, these patients fre- Palliative Care Indications
quently exhibit altered mental status due to
hypercapnia. Low to moderate quality evidence NIV has been used in an attempt to both enhance
suggests that select patients with hypercapnic short term survival and to optimize comfort in
encephalopathy may warrant a trial of NIV if dying patients and those who decline full resusci-
very close monitoring is feasible [24, 25]. Any tative efforts. While mortality among these
such attempt should be aborted if there is no patients remains high, survivors report no
significant improvement in mental status within decrease in their quality of life compared to their
a short period [24]. baseline after the hospitalization, and there are no
apparent negative impacts of NIV on their psy-
chological well-being [30, 31]. The topic remains
 se ofNIV forPreoxygenation Prior
U challenging, in particular because it is difficult to
toIntubation predict in which patients there may be a benefit,
as opposed to merely an extended dying process
In carefully selected patients NIV can be used to with limited ability to communicate, eat, and
maximize preoxygenation prior to intubation drink [32]. Decisions about the use of NIV at the
for acute respiratory failure. By providing high end of life are likely best made on an individual
fractional inspired concentrations of oxygen, patient level, in close collaboration with surro-
eliminating alveolar nitrogen, and recruiting gate decision makers.
atelectatic lung regions, this approach has the
potential to improve oxygenation prior to intu-
bation, and extend the safe apnea time prior to  se ofHigh-Flow Nasal Cannula
U
oxygen desaturation [26]. Patients should gen- asanAlternative toNIV
erally meet the same entry criteria as for the
regular use of NIV, and those who are apneic or The heated high-flow nasal cannula (HFNC) is a
whose airway protective reflexes are in doubt relatively new alternative oxygen delivery device
are likely not appropriate for this relatively that may be of benefit in carefully selected patients
novel use of NIV. with non-hypercapnic acute hypoxic respiratory
54 T.K. Becker and J.M. Litell

failure. In contrast to conventional low-flow nasal mechanical ventilation for patients with exacerba-
tions of COPD.Ann Am Thorac Soc.
cannulae, which provide oxygen flow rates up to
2015;12(3):4029.
approximately 6L/min, HFNC can deliver flow 4. Weitz G, Struck J, Zonak A, Balnus S, Perras B, Dodt
rates in excess of 40L/min. The physical charac- C.Prehospital noninvasive pressure support ventila-
teristics of the device, as well as the addition of a tion for acute cardiogenic pulmonary edema. Eur
JEmerg Med. 2007;14(5):2769. Epub 2007/09/08.
humidifying apparatus and heating circuit, make
5. Giacomini M, Iapichino G, Cigada M, Minuto A,
this a surprisingly comfortable and well-tolerated Facchini R, Noto A, etal. Short-term noninvasive
method of delivering substantial oxygen support pressure support ventilation prevents ICU admittance
[33]. Because it does not involve a tight fitting in patients with acute cardiogenic pulmonary edema.
Chest. 2003;123(6):205761. Epub 2003/06/11.
mask, HFNC is often better tolerated than a con-
6. Carrillo A, Gonzalez-Diaz G, Ferrer M, Martinez-
ventional NIV interface. This technology is rela- Quintana ME, Lopez-Martinez A, Llamas N, etal. Non-
tively new and the evidence supporting its use is invasive ventilation in community-acquired pneumonia
still evolving. Generally speaking, HFNC appears and severe acute respiratory failure. Intensive Care Med.
2012;38(3):45866. Epub 2012/02/10.
to be a safe and effective alternative for alert
7. Carron M, Freo U, Zorzi M, Ori C.Predictors of fail-
patients with certain types of non-hypercapnic ure of noninvasive ventilation in patients with severe
respiratory failure. There is probably insufficient community-acquired pneumonia. JCrit Care.
ventilatory effect to rely on HFNC in patients 2010;25(3):540.e914. Epub 2010/05/04.
8. Confalonieri M, Potena A, Carbone G, Porta RD,
with hypercapnia, and the device offers no airway
Tolley EA, Umberto MG.Acute respiratory failure in
protection. A 2015 multicenter, randomized, open patients with severe community-acquired pneumonia.
label trial compared HFNC, NIV, and standard A prospective randomized evaluation of noninvasive
oxygen therapy in a relatively large cohort of ventilation. Am JRespir Crit Care Med. 1999;160(5
Pt 1):158591. Epub 1999/11/11.
hypoxemic patients [34]. Approximately 6070%
9. Wood KA, Lewis L, Von Harz B, Kollef MH.The use
of these patients had some type of pneumonia. of noninvasive positive pressure ventilation in the
Intubation rates did not differ between the groups, emergency department: results of a randomized clinical
but 90-day mortality was significantly lower in trial. Chest. 1998;113(5):133946. Epub 1998/05/22.
10. Ferrer M, Cosentini R, Nava S.The use of non-

the HFNC group. The reasons for this are unclear.
invasive ventilation during acute respiratory failure
Additionally, NIV confers no mortality or other due to pneumonia. Eur JIntern Med. 2012;23(5):420
benefit over oxygen therapy alone, including 8. Epub 2012/06/26.
HFNC patients, in immunocompromised patients 11. Antonelli M, Conti G, Bufi M, Costa MG, Lappa A,
Rocco M, etal. Noninvasive ventilation for treatment
with hypoxemic respiratory failure [35]. In the
of acute respiratory failure in patients undergoing
absence of additional evidence, the use of HFNC solid organ transplantation: a randomized trial.
is probably best individualized to each patient. JAMA. 2000;283(2):23541. Epub 2000/01/14.
The overall concern about morbidity associated 12. Hilbert G, Gruson D, Vargas F, Valentino R, Gbikpi-
Benissan G, Dupon M, etal. Noninvasive ventilation
with delayed intubation in pneumonia patients
in immunosuppressed patients with pulmonary
supported with NIV probably applies equally to infiltrates, fever, and acute respiratory failure. N Engl
HFNC. JMed. 2001;344(7):4817. Epub 2001/02/15.
13. Hilbert G, Gruson D, Vargas F, Valentino R, Chene G,
Boiron JM, etal. Noninvasive continuous positive air-
way pressure in neutropenic patients with acute respi-
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Diagnosis andManagement
ofTricyclic Antidepressant 6
Ingestion

PatrickGeorgeMinges andRobertW.Shaffer

Introduction altered mental status and seizures. They can cause


profound hypotension through alpha-adrenergic
Tricyclic antidepressant (TCA) overdoses have blockade as well as catecholamine depletion
become less common over the last 20 years as through reuptake inhibition. Finally, they block
their overall use has decreased with the advent of fast sodium channels in the cardiac conduction
safer and more effective antidepressants. Despite system leading to myocardial depression and ven-
their declining popularity in the management of tricular arrhythmias [2].
depression, they continue to be used clinically for Successful treatment of patients poisoned by
conditions including the management of neuro- tricyclic antidepressants hinges on prompt diag-
pathic and chronic pain, cyclic vomiting, noctur- nosis and recognition of the classic EKG findings
nal enuresis, OCD and ADHD.These medications associated with their toxicity. GI decontamina-
continue to be a leading cause of mortality from tion should be considered when patients present
intentional ingestions, and account for nearly half within the first 12 h following an overdose.
of all antidepressant-related deaths [1]. Common Serum alkalinization with sodium bicarbonate is
tricyclic antidepressants in use today include considered the first-line treatment when signs of
amitriptyline, nortriptyline, imipramine, desipra- cardiotoxicity develop. Patients with refractory
mine and doxepin. hypotension may require vasopressor support.
The management of tricyclic antidepressant
poisonings can be quite challenging. Since they
exert their toxicity through several different Case Presentation
mechanisms an understanding of their pharmacol-
ogy is imperative. TCAs all have inherent anti- A 32 year old female with a history notable for
cholinergic effects that may cause tachycardia, depression, migraine headaches, and chronic pel-
vic pain arrived to the emergency department
90min after ingesting approximately sixty 75mg
tablets of amitriptyline. On arrival, she was noted
to be agitated and confused. Her presenting vital
P.G. Minges signs included the following: BP 96/62, P 122,
Department of Emergency Medicine, University
RR18, T37.8, O2 sat (RA) 99%, GCS 13. An
of Michigan Hospitals, Ann Arbor, MI, USA
EKG showed sinus tachycardia with normal
R.W. Shaffer (*)
intervals and normal axis. Blood glucose was
Department of Emergency Medicine, University
of Michigan Health System, Ann Arbor, MI, USA normal, and serum lactate was 3.7. Serum and
e-mail: rshaffer@med.umich.edu urine tox screening was negative. Shortly after

Springer International Publishing Switzerland 2017 57


R.C. Hyzy (ed.), Evidence-Based Critical Care, DOI10.1007/978-3-319-43341-7_6
58 P.G. Minges and R.W. Shaffer

arrival, the patient had a generalized tonic-clonic and sodium bicarbonate were successfully weaned.
seizure that was successfully aborted with 2mg She was successfully extubated and transferred to
IV Ativan. She was subsequently intubated for the inpatient psychiatric service.
airway protection, and 50 g of activated charcoal
was administered through a nasogastric tube.
Upon arrival to the ICU, her blood pressure fell to Principles ofManagement
65/32 and a repeat EKG was obtained (Fig.6.1).
Diagnosis
Question How would you proceed in the man-
agement of this patient? Tricyclic antidepressants have a narrow therapeu-
tic index, and significant CNS and cardiovascular
Answer This patient now exhibits EKG findings toxicity may be seen with ingestions that exceed
that are consistent with fast sodium channel therapeutic doses by as little as three-fold.
blockade due to tricyclic antidepressant toxicity
(Table6.1). Tricyclic Antidepressant Side Effects
Anticholinergic
The patient was immediately given 2meq/kg of Mucosal dryness
IV sodium bicarbonate as a bolus and hydrated Constipation
aggressively with 3 l of normal saline. A sodium Urinary retention
bicarbonate drip was initiated to maintain a goal Confusion
serum pH within the range of 7.457.55. Ventilator Blurred vision
settings were managed accordingly to prevent Aggravation of narrow angle glaucoma
hypercarbia. A repeat EKG was obtained once Anti-alpha-adrenergic
serum alkalinization was achieved and demon- Orthostatic hypotension
strated improvement of the QRS duration to 90ms, Antihistaminic
but the patient remained hypotensive. A norepi- Sedation
nephrine drip was initiated and blood pressure Quinidine-like
improved. Over the ensuing 48 h, norepinephrine Cardiac arrhythmias and block

V1 V4
aVR

aVL V2 V5

aVF V3 V6

Fig. 6.1 12-Lead Electrocardiogram obtained at time of patients presentation


6 Diagnosis andManagement ofTricyclic Antidepressant Ingestion 59

Table 6.1 Clinical features associated with specific toxidromes


HR & BP RR Temp Pupils Bowel sounds Diaphoresis
Anticholinergic
Low potency
antipsychotics
Oxybutinin, Ipratropium
Antihistamines
ACh receptor antagonists
Cholinergic
ACh receptor agonists
AChEls i.e. Donepezil
Opioid
Morphine
Heroin
Hydromorphone
Sympathomimetic
Epinephrine
Cocaine
Amphetamine &
Methylphenidate
Sedative-Hypnotic
Benzos & barbs
Z-drugs (i.e. Zopiclone)

Mental status on presentation has been shown predict risk for seizures, and prolongation
to be predictive of patient outcomes, and most >160ms predicts a risk for ventricular arrhyth-
life-threatening arrhythmias occur within the first mias [4]. Owing to the greater susceptibility of
24 h after ingestion [2]. Owing to rapid GI the right ventricular conduction system to the
absorption, patients may initially appear well and effects of sodium channel blockade, a rightward
then deteriorate rapidly. Serum drug assays that axis shift of the terminal 40ms of the QRS axis
measure specific serum tricyclic antidepressant in the frontal plane will develop; but this finding
levels are not widely available and should not be may be difficult to detect [3]. A more practical
relied on when managing suspected overdose. means for identifying this rightward axis shift is
Because these drugs are highly lipophilic and by noting the presence of a larger than expected
have high volumes of distribution, concentrations R wave amplitude in aVR (Fig.6.2). An ampli-
in brain and myocardium may exceed serum con- tude of the R wave in this lead in excess of 3mm
centrations by as much as 40 to 200-fold, and has been shown to predict risk for seizures and
serum drug levels have not been shown to predict arrhythmias [5].
the clinical course [1, 3].
The single most useful test in identifying tri-
cyclic antidepressant toxicity is the electrocar- Gastrointestinal Decontamination
diogram. The most common early EKG finding
in overdoses is sinus tachycardia, due to anticho- Activated charcoal has been shown to effectively
linergic effects and initial transient catechol- bind tricyclic antidepressants. In a study of
amine excess. As toxicity progresses, tricyclic healthy volunteers activated charcoal given 5min
antidepressants block fast sodium channels in the after oral administration of therapeutic doses of
cardiac conduction system thereby slowing depo- amitriptyline decreased GI absorption by 99%
larization and decreasing contractility. This [6]. Activated charcoal probably has the most
results in a widened QRS complex. Prolongation benefit when administered within 1h of a toxic
of the QRS complex >100ms has been shown to ingestion, but may be considered for up to 2h
60 P.G. Minges and R.W. Shaffer

Fig. 6.2 Prominent termi-


nal R wave (>3mm ampli-
tude) in lead aVR from
electrocardiogram
obtained from a patient
experiencing TCA
overdose

aVR

since the anticholinergic effects of the drug may effect is improved myocardial contractility, nar-
delay gastric emptying [7]. rowing of the QRS complex, and improved elec-
Gastric lavage carries risks such as aspiration, trical stability.
and is not routinely recommended following tri- Dosing and titration guidelines for sodium
cyclic antidepressant ingestion. One randomized bicarbonate have not been well-studied, but most
study demonstrated no significant difference in recommend initiating a bolus of 12meq/kg fol-
patient outcomes when gastric lavage was com- lowed by a continuous infusion to maintain a
bined with the use of activated charcoal [8]. goal serum pH within 7.457.55 and titrating to a
Whole bowel irrigation is typically reserved goal QRS duration of less than 100ms [2, 10].
for overdoses involving sustained-release prepa- The prophylactic use of sodium bicarbonate is
rations or in cases where the drug binds poorly to not supported when EKG abnormalities are
activated charcoal. Therefore, its use is unlikely absent [10]. Serum pH must be monitored closely,
to provide any benefit [7]. and while optimum pH has not been studied, it is
reasonable to not exceed a pH of 7.6. Risks of
marked alkalosis may include impaired tissue
Plasma Alkalinization oxygenation due to shifts in the oxygen dissocia-
tion curve, cerebral vasoconstriction, reduction
Although no randomized-controlled clinical tri- in ionized calcium concentration, intracellular
als exist in support of sodium bicarbonate ther- shift of potassium, and an increased myocardial
apy in the setting of tricyclic antidepressant sensitivity to catecholamines [10].
poisoning, numerous animal studies and human
case reports support its use as a first-line treat-
ment [911]. Sodium bicarbonate has been  anagement ofHypotension
M
shown to both prevent and terminate ventricular andVasopressor Support
dysrhythmias. The benefits of serum alkaliniza-
tion through the use of sodium bicarbonate are Hypotension is a common feature of tricyclic anti-
likely multifactorial. The fraction of drug that is depressant toxicity. These medications decrease
protein-bound increases with alkalinity, and systemic vascular resistance through alpha-adren-
therefore the use of sodium bicarbonate would be ergic blockade. Relative catecholamine depletion
expected to decrease the amount of free drug may occur through their effects on norepinephrine
available for inhibition of sodium channels [2]. reuptake. Additionally, hypotension may occur as
Additionally, increasing serum sodium concen- a direct result of decreased cardiac inotropy [2].
trations may overwhelm the sodium channel Profound hypotension may be refractory to fluid
blockade by increasing the gradient between the resuscitation and alkalinization therapy, and vaso-
intracellular and extracellular space [2]. The net pressors may be indicated. There are very few
6 Diagnosis andManagement ofTricyclic Antidepressant Ingestion 61

studies evaluating the benefit of one such agent benefit of lipid emulsion use in tricyclic antide-
over another [12]. One retrospective case series pressant poisonings have been described. Lipid
suggested norepinephrine may be superior to emulsions may serve as a lipid sink, sequester-
dopamine in these instances [13]. A single case ing intravascular drug from the aqueous phase of
report showed that vasopressin stabilized blood plasma. Secondly, the lipids themselves may
pressure in a patient with hypotension that failed directly provide a supplemental fuel source to the
to respond to high-dose norepinephrine [14]. stressed myocardium. Lastly, a positive inotropic
effect might be seen from increased intracellular
calcium shifts [17, 18]. A few animal studies have
Extracorporeal Elimination been conducted using intravenous lipid emulsions
for the management of tricyclic antidepressant
Because tricyclic antidepressants are lipophilic toxicity, and the reported benefits on hemody-
and highly protein-bound, extracorporeal elimi- namic stability and mortality were mixed [1820].
nation methods such as hemodialysis are ineffec- There are, however, several human case reports of
tive [1]. patients being successfully managed with lipid
emulsions in the setting of refractory hemody-
namic instability when the use of traditional thera-
Seizure Management peutic modalities failed [2124]. Dosing guidelines
for intravenous lipid emulsion therapy for tricyclic
Seizures are common in the setting of significant antidepressant toxicity have not been established.
tricyclic antidepressant overdose and are a predic- Recommended dosing in the setting of systemic
tor of poor outcomes. Seizures may precipitate an toxicity from local anesthetics have been proposed
undesired acidosis that increases TCA toxicity. where a 20% emulsion is administered at a load-
There is little high quality evidence describing ing dose of 1.5ml/kg based on lean body mass
first line anticonvulsant therapy for seizures sec- followed by a continuous infusion of 15ml/kg/h
ondary to TCA overdose. Seizures associated until clinical response is achieved [17, 25]. It is
with TCA overdose are often brief and resolve unclear how to extrapolate dosing of lipid emul-
before abortive medications can be administered. sions for management of tricyclic antidepressant
The use of benzodiazepines has been proposed as overdose given their different pharmacokinetics.
first line therapy. Barbiturates and propofol are The use of lipid emulsion in the management of
second-line agents that have been noted to be overdoses carry theoretical risks including infec-
effective in case reports. These therapies should tion, but serious adverse events have not been
be used in conjunction with the treatment strate- reported [17]. Intravenous lipid therapy may be
gies previously described [15, 16]. considered in cases of refractory cardiovascular
collapse when more traditional treatments fail.

Evidence Contour
Hypertonic Saline
Intravenous Lipid Emulsion
One animal study suggested that the use of
The use of intravenous lipid emulsions were first hypertonic saline in the management of tricyclic
reported in the 1990s as an antidote for systemic antidepressant poisonings, when compared to
toxicity from local anesthetic agents. Since that sodium bicarbonate, produced a statistically sig-
time, the use of intravenous lipid emulsion therapy nificant improvement in systolic blood pressure
has been reported in the setting of overdoses of and narrowing of the QRS complex [26]. One
other lipophilic drugs including calcium channel human case report exists for a patient with
blockers, beta blockers, and tricyclic antidepres- refractory ventricular ectopy and widened QRS
sants [17]. Several proposed mechanisms for the complex despite sodium bicarbonate therapy
62 P.G. Minges and R.W. Shaffer

that stabilized upon administration of hypertonic 3. Harrigan RA, Brady RJ.ECG abnormalities in tricy-
clic antidepressant ingestion. Am JEmerg Med.
saline [27]. Clinical studies supporting its use,
1999;17(4):38793.
however, do not exist [2]. 4. Boehnert MT, Lovejoy Jr FH.Value of the QRS dura-
tion versus the serum drug level in predicting sei-
zures and ventricular arrhythmias after an acute
overdose of tricyclic antidepressants. N Engl JMed.
Antiarrhythmic Drugs 1985;313(8):4749.
5. Wolfe TR, Caravati EM, Rollins DE.Terminal 40-ms
Occasionally, ventricular dysrhythmias may not frontal place axis as a marker for tricyclic antidepres-
sant overdose. Ann Emerg Med. 1989;18:34851.
respond to serum alkalinization, and the use of 6. Karkkainen S, Neuvonen PJ.Pharmacokinetics of ami-
antiarrhythmic medications may be necessary. triptyline influenced by oral charcoal and urine pH.Int
Class I antiarrhythmic medications are contrain- JClin Pharmacol Ther Toxicol. 1986;24:32632.
dicated in the setting of tricyclic antidepressant 7. Dargan PI, Colbridge MG, Jones AL.The management
of tricyclic antidepressant poisoning : the role of gut
overdose since they act to inhibit cardiac sodium decontamination, extracorporeal procedures and fab
channels in a similar manner [9]. Other antiar- antibody fragments. Toxicol Rev. 2005;24(3):18794.
rhythmic drugs have negative inotropic effects, 8. Bosse GM, Barefoot JA, Pfeifer MP, Rodgers
which may worsen hypotension in the setting of GC.Comparison of three methods of gut decontami-
nation in tricyclic antidepressant overdose. JEmerg
these overdoses. Lidocaine has traditionally been Med. 1995;13(2):2039.
considered the most reasonable agent in these 9. Sasyniuk BI, Jhamandas V, Valois M.Experimental
instances, but the efficacy is limited to case series amitriptyline intoxication: treatment of cardiac toxicity
[28]. Theoretically, lidocaines rapid binding to with sodium bicarbonate. Ann Emerg Med. 1986;15(9):
10529.
sodium channels may displace the effects of tricy- 10. Blackman K, Brown SF, Wilkes GJ.Plasma alkalini-
clic antidepressants and improve cardiac conduc- zation for tricyclic antidepressant toxicity: a system-
tion. Lidocaine has a stabilizing effect on the atic review. Emerg Med. 2001;13:20410.
myocardium, but unfortunately may slow conduc- 11. Hoffman JR, McElroy CR.Bicarbonate therapy for
dysrhythmia and hypotension in tricyclic antidepres-
tion and depress contractility [29]. Furthermore, sant overdose. Western JMed. 1981;134(1):604.
one must take into consideration the fact that lido- 12. Vernon DD, Banner W, Garrett JS, Dean JM.Efficacy
caine may lower the seizure threshold [30]. of dopamine and norepinephrine for treatment of
Magnesium is an alternative antiarrhythmic hemodynamic compromise in amitriptyline intoxica-
tion. Crit Care Med. 1991;19(4):5449.
that has been investigated with some promise. A 13. Tran TP, Panacek EA, Rhee KJ, Foulke GE.Response
study in rats sought to evaluate magnesium sul- to dopamine vs norepinephrine in tricyclic
fates ability to terminate arrhythmias when com- antidepressant- induced hypotension. Acad Emerg
pared with lidocaine and demonstrated favorable Med. 1997;4(9):8648.
14. Barry JD, Durkovich DW, Williams SR.Vasopressin
results [29]. One small randomized human trial treatment for cyclic antidepressant overdose. JEmerg
suggested that use of magnesium in addition to Med. 2006;31(1):658.
traditional therapeutics decreased ICU length of 15. Ellison DW, Pentel PR.Clinical Features and conse-
stay and mortality, and several case reports quences of seizures due to cyclic antidepressant over-
dose. Am JMed. 1989;7(1):510.
describe the successful use of magnesium to 16. Merigian KS, Browning RG, Leeper KV.Successful
abort ventricular arrhythmias [3133]. treatment of amoxapine-induced refractory status
epilepticus with propofol. Acad Emerg Med.
1995;2(2):12833.
17. Ozcon MS, Weinberg G.Intravenous lipid emulsion
References for the treatment of drug toxicity. JIntensive Care
Med. 2014;29(2):5970.
1. Yates C, Galvao T, Sowinski KM, etal. Extracorporeal 18. Varney SM, Bebarta VS, Vargas TE, Boudreau S,
treatment for tricyclic antidepressant poisoning: rec- Castaneda M.Intravenous lipid emulsion therapy
ommendations from the EXTRIP Workgroup. Semin does not improve hypotension compared to sodium
Dial. 2014;27(4):3819. bicarbonate for tricyclic antidepressant toxicity: a ran-
2. Agrawal P, Nadel ES, Brown DF.Tricyclic antide- domized, controlled pilot study in a swine model.
pressant overdose. JEmerg Med. 2008;34(3):3215. Acad Emerg Med. 2014;21(11):12129.
6 Diagnosis andManagement ofTricyclic Antidepressant Ingestion 63

19. Harvey M, Cave G.Intralipid outperforms sodium saline solution, sodium bicarbonate, and hyperventi-
bicarbonate in a rabbit model of clomipramine toxic- lation. Ann Emerg Med. 1996;32(3):32933.
ity. Ann Emerg Med. 2007;49(2):17885, 185.e14. 27. Mckinney PE, Rasmussen R.Reversal of severe tricyclic
20. Litonius E, Niiya T, Neuvonen PJ, Rosenberg PH.No antidepressant-induced cardiotoxicity with intravenous
antidotal effect of intravenous lipid emulsion in hypertonic saline. Ann Emerg Med. 2003;42(1):204.
experimental amitriptyline intoxication despite sig- 28. Foianini A, Weigand TJ, Benowitz N.What is the role of
nificant entrapment of amitriptyline. Basic Clin lidocaine or phenytoin in tricylic antidepressant-induced
Pharmacol Toxicol. 2012;110(4):37883. cardiotoxicity. Clin Toxicol. 2010;48(4):32530.
21. Blaber MS, Khan JN, Brebner JA, Mccolm R. Lipid 29. Knudsen K, Abrahamsson J.Effects of magnesium
rescue for tricyclic antidepressant cardiotoxicity. sulfate and lidocaine in the treatment of ventricular
JEmerg Med. 2012;43(3):4657. arrhythmias in experimental amitriptyline poisoning
22. Kiberd MB, Minor SF.Lipid therapy for the treatment in the rat. Crit Care Med. 1994;22(3):4948.
of a refractory amitriptyline overdose. CJEM.
30. Pentel PR, Benowitz NL.Tricyclic antidepressant
2012;14(3):1937. poisoningmanagement of arrhythmias. Med Toxicol.
23. Agarwala R, Ahmed SZ, Wiegand TJ.Prolonged use 1986;1:10121.
of intravenous lipid emulsion in a severe tricyclic anti- 31.
Emamhadi M, Mostafazadeh B, Hassanijirdehi
depressant overdose. JMed Toxicol. 2014;10:2104. M.Tricyclic antidepressant poisoning treated by mag-
24. Engels PT, Davidow JS.Intravenous fat emulsion to nesium sulfate: a randomized, clinical trial. Drug
reverse haemodynamic instability from intentional ami- Chem Toxicol. 2012;35(3):3003.
triptyline overdose. Resuscitation. 2010;81(8):10379. 32. Sarisoy O, Babaoglu K, Tukay S, etal. Effect of mag-
25. Weinberg GL.Lipid emulsion infusion: resuscitation nesium sulfate for treatment of ventricular tachycar-
for local anesthetic and other drug overdose. dia in amytriptyline intoxication. Pediatr Emerg Care.
Anesthesiology. 2012;117(1):1807. 2007;23:6468.
26. McCabe JL, Cobaugh DJ, Menegazzi JJ, Fata
33. Knudsen K, Abrahamsson K.Magnesium sulfate in
J.Experimental tricyclic antidepressant toxicity: a the treatment of ventricular fibrillation in amitripty-
randomized, controlled comparison of hypertonic line poisoning. Eur Heart J.1997;18(5):881.
Management ofCalcium Channel
Blocker Poisoning 7
DavidM.Black andRobertW.Shaffer

Introduction Dihydropyridines
Nicardipine
Calcium channel blocker poisonings are the Nifedipine
leading cause of death from cardiovascular Isradipine
medication-related overdoses [1, 2]. Clinical Amlodipine
effects in the poisoned patient may include Felodipine
hypotension, bradycardia, atrioventricular con- Nimodopine
duction disturbances, pulmonary edema, Nisoldipine
stroke, bowel ischemia, altered mental status, Nitrendipine
and cardiac arrest. Many immediate and sus- Non-Dihydropyridines
tained-release preparations exist, hence phar- Verapamil
macokinetics are highly variable. Calcium Diltiazem
channel blockers are generally lipophilic and Bepridil
highly-protein bound, rendering traditional
extracorporeal elimination methods such as
hemodialysis largely ineffective.
Calcium channel blockers act at L-type cal-
cium channels and are generally divided into two
unique pharmacologic classes based on their pre-
ferred sites of action.
Dihydropyridine (i.e. nifedipine, amlodipine)
overdoses primarily cause hypotension with
reflex tachycardia through their peripheral vaso-
dilatory effects on vascular smooth muscle. The
toxicity from non-dihydropyridines (i.e. vera-
pamil, diltiazem), tends to be more severe owing
to their primary effects on the myocardium [3].
D.M. Black This may lead to bradydysrhythmias, depressed
Emergency Medicine, University of Michigan Health
myocardial contractility, and circulatory collapse
System, Ann Arbor, MI, USA
[4]. It should be noted that in severe poisonings
R.W. Shaffer (*)
from either class, this selectivity may be lost [2].
Department of Emergency Medicine, University of
Michigan Health System, Ann Arbor, MI, USA The management of hemodynamically unsta-
e-mail: rshaffer@med.umich.ed ble patients with calcium channel blocker toxicity

Springer International Publishing Switzerland 2017 65


R.C. Hyzy (ed.), Evidence-Based Critical Care, DOI10.1007/978-3-319-43341-7_7
66 D.M. Black and R.W. Shaffer

can be quite challenging, and responses to thera- Answer Impaired insulin secretion due to cal-
peutic interventions can be variable. Traditional cium channel blocker inhibition of pancreatic
therapies include intravenous fluid resuscitation, Beta cells, coupled with increased stress-
and the administration of calcium salts, glucagon, mediated glucose mobilization account for her
and vasopressor agents. Refractory bradycardia hyperglycemia. High-dose insulin euglycemic
and atrioventricular nodal blocks may necessitate therapy should be considered at this point. Her
the use of atropine and temporary pacemakers. metabolic acidosis is secondary to both a lactic
More contemporary treatment strategies includ- acidosis from impaired tissue perfusion, and
ing the use of intravenous lipid emulsions and ketoacidosis similar to that seen with DKA due to
high-dose insulin euglycemic therapy have shown relative hypoinsulinemia.
great promise.
Based on her weight of 50kg, an insulin bolus
of 50 units IV was given followed by an infusion
Case Presentation of 50 units/h. Approximately 45min after initia-
tion of the insulin infusion, her pulse normalized
A 47 year old female with a history of depression to 65 and her blood pressure improved enough to
and chronic migraine headaches was brought to gradually wean the norepinephrine drip. Her glu-
the emergency department by her spouse immedi- cose was monitored every 30min, and ultimately
ately following a witnessed intentional ingestion she did require a continuous dextrose infusion to
of approximately sixty 120mg sustained-release maintain serum glucose concentrations above
verapamil tablets. On arrival, she was alert and 150mg/dL.Her metabolic acidosis improved
oriented. Vital signs were as followed: pulse 62, over the course of several hours, as did her serum
blood pressure 95/62, respiratory rate 16, temper- lactate. Serum electrolytes were monitored
ature 37.2, and pulse oximetry 99% on room air. closely. She developed mild hypokalemia but
Her EKG showed normal sinus rhythm with nor- repletion was not necessary. Approximately 24h
mal intervals. IV access was established and a following admission, the insulin infusion was
liter of normal saline was administered. discontinued and her vitals remained stable. She
Laboratory studies that include routine toxico- was discharged the next morning to an inpatient
logic screening tests were unremarkable. She was psychiatric facility.
treated with 50g of oral activated charcoal and
admitted to the intensive care unit for close moni-
toring. Upon arrival to the ICU, her repeat vital Principles ofManagement
signs revealed a pulse of 42 and blood pressure of
74/42. Her repeat EKG is shown below (Fig.7.1). Gastrointestinal Decontamination
An arterial blood gas was obtained: pH7.12,
pCO2 26, HCO3 12, lactate 7.2 and glucose 350. Activated charcoal effectively binds calcium
An additional 2L of normal saline were rapidly channel blockers and should be administered in
infused. She was treated with 2g of IV calcium patients with stable airways and preserved men-
gluconate, 5mg of IV glucagon followed by a tal status who present within the first 2h follow-
continuous infusion, and a norepinephrine drip ing ingestion. Although clinical evidence
that was titrated for a goal mean arterial pressure supporting the use of multi-dose activated char-
of 65. Despite these measures, she remained coal is lacking, it is reasonable to consider repeat
hypotensive and bradycardic. charcoal dosing when sustained-release prepara-
tions are involved [2, 5]. Gastric lavage is gener-
Question What do you think is causing her ally not recommended since the procedure may
hyperglycemia and what therapeutic increase vagal tone, exacerbate hemodynamic
intervention(s) could be considered at this point instability, and can provoke cardiac arrest [6, 7].
to improve her hemodynamic stability? Whole bowel irrigation may be considered in
7 Management ofCalcium Channel Blocker Poisoning 67

Fig. 7.1 12-lead EKG revealing sinus bradycardia

cases of sustained-release preparations, or when sistent [7, 9]. The response seen with calcium is
decontamination is delayed beyond a time-frame often transient, and repeat dosing may be needed
where activated charcoal would be of benefit [6]. [2]. Despite conflicting evidence regarding ben-
Whole bowel irrigation should be avoided, how- efit, use is generally recommended and adverse
ever, in patients with depressed mental status, effects are rare.
ileus, airway compromise, or hemodynamic
instability [8]. Glucagon
Glucagon increases intracellular cyclic-AMP and
has been shown in animal models to have positive
Hemodynamic Support inotropic and chronotropic effects. Furthermore,
glucagon has been shown, in some cases, to
The initial management of hypotension due to reverse 2nd and 3rd degree heart blocks [10].
calcium channel blocker toxicity should include Evidence for its efficacy in humans is limited to
aggressive intravenous fluid resuscitation. In case reports, and treatment failures have been
more severely poisoned patients, several thera- described [2, 7]. Glucagon dosing is not well-
peutic options may also be considered. established, but an initial dose of 35mg IV fol-
lowed by a continuous infusion has been
Calcium Salts suggested, with an additional dose of 410mg IV
The use of calcium gluconate and calcium chlo- 5min after the initial dose if no response is
ride in the management of calcium channel achieved [6].
blocker toxicity seems intuitive. Increased serum
calcium concentrations would be expected to Atropine
overcome calcium channel blockade via a gradi- Atropine may be considered for symptomatic
ent effect, thereby improving myocardial con- bradycardia, but is often ineffective in the setting
tractility [6]. Animal studies suggest the use of of severe poisonings. Standard advanced cardiac
calcium confers both hemodynamic benefits and life support (ACLS) dosing guidelines should be
improves mortality. Human studies are limited to used. Because of its anticholinergic effects on GI
case series, and the reported benefits are incon- motility, its use may potentiate absorption of
68 D.M. Black and R.W. Shaffer

sustained-release calcium channel blocker for- effects may ameliorate the cardiogenic shock
mulations [6]. seen with calcium channel blocker toxicity.
Animal models suggest the mortality benefit
Vasopressor Support from high-dose insulin therapy is superior to that
When hemodynamic stability cannot be achieved seen with calcium salts, glucagon, and vasopres-
through the use of fluid resuscitation and other sors. One human observational study showed that
initial pharmacologic strategies, vasopressor high-dose insulin therapy resulted in a >10mmHg
support may be necessary. Norepinephrine, sustained increase in systolic blood pressure in
dopamine, epinephrine, isoproterenol, dobuta- all patients receiving high dose insulin boluses
mine, and phenylephrine have all been used to and infusions, and numerous case series and case
achieve improvements in blood pressure, and no reports detail beneficial hemodynamic responses
studies have demonstrated the superiority of one [2, 13, 14].
agent over another [2]. Multiple agents may be Although definitive dosing guidelines have
required simultaneously to achieve hemody- not been established, most recommend an initial
namic stability, and some have reported use of insulin bolus be given at a dose of 1U/kg IV fol-
vasopressor doses far in excess of what would lowed by an infusion 1U/kg/h which may be
typically be considered the referenced maximum titrated upward [6]. Higher bolus doses of 10 U/
[4]. Although improvements in blood pressure kg and infusions up to 22U/kg/h have been
are typically achieved, one must be mindful that reported [3]. The clinical response to high-dose
the increase in systemic vascular resistance will insulin may take 1560min. Many sources
also increase afterload. This may paradoxically advocate initiation of high-dose insulin therapy
lead to an undesirable decrease in cardiac output, very early on in the management of these patients
as well as an increase in the cardiac oxygen (before they become unstable) [6, 14, 15]. Serum
requirement in an already energy-depleted myo- glucose should be monitored every 30min dur-
cardium [3, 6]. ing the initial course of treatment and supple-
mental dextrose should be administered,
High-Dose Insulin Therapy although supplementation may not be necessary
In recent years, high-dose insulin therapy for the if the initial glucose exceeds 300mg/dL [6].
treatment of calcium channel blocker poisonings Mild hypokalemia should be anticipated due to
has gained increasing attention. Calcium channel intracellular shifts and may actually augment
blockers directly inhibit the calcium channel- myocardial cellular function by improving intra-
mediated release of insulin by the pancreas, lead- cellular calcium transport. Potassium repletion
ing to systemic hypoinsulinemia (Fig.7.2). should be considered if serum levels fall below
Because carbohydrates are the preferred meta- 2.83.0mEq/L [12].
bolic substrate of myocardial cells when under
duress, the impairment of intracellular glucose Invasive Circulatory Support
transport secondary to insulin depletion further The use of temporary transcutaneous and trans-
worsens cardiac contractility already impaired by venous pacemakers, and intra-aortic balloon
the calcium channel blockers themselves [11]. pump counter pulsation therapy have been
High-dose insulin restores myocardial glucose described in the setting of severe bradycardia and
utilization and corrects systemic ketoacidosis high-degree atrioventricular blocks in calcium
when present. Insulin has also been shown to channel blocker poisonings when medical man-
have direct positive inotropic effects on myocytes agement fails to adequately reverse cardiogenic
[11]. Furthermore, insulin has been shown to shock [2, 6, 7]. At times, obtaining successful
induce vasodilation which improves microvascu- pacemaker capture may be difficult in these
lar perfusion in tissues including the myocardium patients. Furthermore, improvement in hemody-
[12]. Insulin also promotes increased catechol- namics may be variable owing to the persistent
amine sensitivity [11]. The combination of these impaired cardiac inotropy, and it is unclear based
7 Management ofCalcium Channel Blocker Poisoning 69

Improved hemodynamics

CCB
ingestion
Heart Pancreas
Increased vascular tone Increased inotropy
Blockage
Decreased of L-type
inotropy Ca++
channels

Exogenous
insulin
administration

Increased Decreased
glucose insulin

Normoglycemia

Insulin physiology in CCB overdose

Fig. 7.2 CCB calcium channel blocker. L-type Ca++ channels: voltage-gated calcium channels

on case reports whether pacemakers improve sink, sequestering lipophilic toxins away from
clinical outcomes [7, 16]. There are reports the aqueous plasma phase. In a case report of a
describing the successful use of intra-aortic bal- verapamil overdose, plasma concentrations of this
loon pumps and extracorporeal life support in the drug were nearly undetectable following adminis-
setting of refractory shock due to severe calcium tration of an intravenous lipid emulsion [21]. A
channel blocker poisonings, and these techniques second proposed benefit of intravenous lipid
may be considered on a case by case basis when emulsions is that they directly stimulate insulin
other treatment strategies fail [1719]. secretion [22]. Thirdly, lipids may promote an
increased intracellular calcium concentration in
myocytes counteracting the negative inotropic
Evidence Contour effects seen in these overdoses [23]. Lastly, lipids
may serve as a supplementary fuel source for the
Intravenous Lipid Emulsions myocardium, which prefers to derive energy from
fatty acids under normal conditions [6].
The use of intravenous lipid emulsion therapy in The evidence supporting the use of intrave-
the management of systemic toxicity from local nous lipid emulsions in calcium channel blocker
anesthetics is well-described [6]. More recently, poisonings is limited to animal studies and human
investigators have advocated for the use of intra- case reports. Multiple animal studies d emonstrate
venous lipid emulsions to treat poisonings due to that intravenous lipid emulsions confer a survival
other lipophilic drug classes including tricyclic benefit compared to placebo in verapamil over-
antidepressants, beta blockers, and calcium chan- doses [20]. Multiple human case reports suggest
nel blockers [20]. a temporal hemodynamic response when intrave-
Intravenous lipid emulsion therapy in the con- nous lipid emulsions were used as an adjunct to
text of calcium channel blocker toxicity may be standard treatments [9, 20, 22, 24, 25]. Others
beneficial for several reasons. One proposed report that required vasopressor support greatly
mechanism is that lipid emulsions act as a lipid diminished following initiation of intravenous
70 D.M. Black and R.W. Shaffer

lipid emulsion therapy [23]. Because multiple improvement in hemodynamic stability follow-
confounding therapeutic strategies were used in ing methylene blue administration to a patient
all of these reported cases, the degree in which with an amlodipine overdose that had failed to
intravenous lipid emulsion therapy is beneficial respond to other measures [26]. Another case
remains unclear. report demonstrated a similar effect in a mixed
The optimal dosing for intravenous lipid calcium channel/beta blocker overdose [27].
emulsion has not been established, and recom- While adequate evidence supporting routine use
mendations are extrapolated from guidelines that does not exist, methylene blue might be consid-
exist for the management of local anesthetic tox- ered as a rescue therapy in severe dihydropyri-
icity. Typically, a 20% lipid emulsion solution is dine poisonings that fail to respond to other
administered at a bolus dose of 1.5ml/kg based treatment strategies [28].
on ideal body weight. This is followed by a con-
tinuous infusion of 0.25ml/kg/min until hemo-
dynamic stability persists for at least 10min. Extracorporeal Albumin Dialysis
Some suggest that this bolus may be repeated
twice and the infusion may be doubled when Because calcium channel blockers have high vol-
clinically necessary [6]. The lipemia resulting umes of distribution and are largely protein-
from this treatment may interfere with certain bound, traditional extracorporeal elimination
laboratory assays. strategies including hemodialysis and hemoper-
fusion are generally ineffective. Albumin dialysis
with molecular absorbents recirculating system
Sodium Bicarbonate (MARS) therapy offers the ability to remove
protein-bound toxins that would otherwise not be
Acidosis is a common occurrence in calcium cleared by traditional hemodialysis. This tech-
channel blocker toxicity secondary to diminished nique was successfully in the management of
tissue perfusion and ketoacidosis. Correction of three severely poisoned patients with refractory
the acidosis could theoretically improve hemody- shock due to calcium channel blocker toxicity,
namic stability, but the role of bicarbonate ther- and all three patients survived [29].
apy in these instances is unclear. In severe
overdoses, a widened QRS complex from fast
sodium channel blockade, similar to that seen in References
tricyclic antidepressant toxicity, may occur. The
benefits of sodium bicarbonate in calcium chan- 1. Mowry JB, Spyker DA, Cantilena Jr LR, McMillan N,
Ford M. 2013 Annual Report of the American
nel blocker toxicity is largely anecdotal, but some Association of Poison Control Centers National
advocate for its use when QRS complex prolon- Poison Data System (NPDS): 31st Annual Report.
gation occurs [2]. Clin Toxicol (Phila). 2014;52(10):1032283.
2. Shenoy S, Lankala S, Adigopula S.Management of
calcium channel blocker overdoses. JHosp Med.
2014;9(10):6638.
Methylene Blue 3. Siddiqi TA, Hill J, Huckleberry Y, Parthasarathy
S.Non-cardiogenic pulmonary edema and life-
Methylene blue inhibits guanylate cyclase which threatening shock due to calcium channel blocker
overdose: a case report and clinical review. Respir
subsequently decreases cGMP resulting in inhi- Care. 2014;59(2):e1521.
bition of vascular smooth muscle relaxation. 4. Levine M, Curry SC, Padilla-Jones A, Ruha
Therefore, it might be expected to reverse some AM.Critical care management of verapamil and dil-
of the effects of the dihydropyridine class of cal- tiazem overdose with a focus on vasopressors: a
25-year experience at a single center. Ann Emerg
cium channel blockers. Experience with methy- Med. 2013;62(3):2528.
lene blue in calcium channel blocker toxicity, 5. Thanacoody R, Caravati EM, Troutman B, Hojer J,
however, is limited. One case report described an Benson B, Hoppu K.Position paper update: whole
7 Management ofCalcium Channel Blocker Poisoning 71

bowel irrigation for gastrointestinal decontamination tion during cardiogenic shock after drug intoxication?
of overdose patients. Clin Toxicol. 2015;53(1):512. JEmerg Med. 2010;38(2):1627.
6. Jang DH, Spyres MB, Fox L, Manini AF.Toxin- 18. Masson R, Colas V, Parienti JJ, Lehoux P, Massetti M,
inducedcardiovascular failure. Emerg Med Clin North Charbonneau P, Saulnier F, Daubin C.A comparison
Am. 2014;32(1):79102. of survival with and without extracorporeal life sup-
7. St-Onge M, Dub PA, Gosselin S, Guimont C, port treatment for severe poisoning due to drug intoxi-
Godwin J, Archambault PM, Chauny JM, Frenette cation. Resuscitation. 2012;83(11):14137.
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Juurlink DN, Blais R.Treatment for calcium channel Extracorporeal life support in severe drug intoxica-
blocker poisoning: a systematic review. Clin Toxicol tion: a retrospective cohort study of seventeen cases.
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calcium channel blocker overdose: Primum non acute poisoning: a systematic review of human and
nocere. JEmerg Med. 2010;38(2):1714. animal studies. Clin Toxicol. 2010;48(1):127.
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Clin Toxicol. 2003;41(5):595602. emulsion therapy for intentional sustained-release
11.
Woodward C, Pourmand A, Mazer-Amirshahi verapamil overdose. Resuscitation. 2009;80(5):5913.
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Diagnosis andManagement
ofEthylene Glycol Ingestion 8
ChristineMartinekBrent andRobertW.Shaffer

Case Presentation Over the next 2h, her HR and RR increased


to 125 and 24 respectively. She was placed on
A 46 year old female with a history of depression 4L NC for a room air saturation of 87%. She
arrived at the emergency department by EMS became more confused with a GCS of 10.
with altered mental status. Her husband found Repeat labs were obtained which demonstrated
her in the garage of their home with confusion, a new anion gap of 22 (see below). A repeat
incoherent slurred speech and an unsteady gait. ABG (on 4L O2) showed the following: pH7.22,
By his report, she had seemed well 4h earlier. pO2 58, PCO2 26, HCO3 15, lactate 3.2.
Initial vital signs were as follows: HR 112, BP Measured serum osmoles were obtained and an
145/91, RR 16, O2 99% on RA, and temperature osmolal gap of 40 was calculated. CXR revealed
98.9. Glucose was 127mg/dL.GCS was 14. pulmonary edema without cardiomegaly. Her
There were no signs of trauma, and her physical hypoxia and tachypnea worsened despite
exam, aside from the findings mentioned above, increasing amounts of supplemental oxygen,
was unremarkable. Initial labs including CBC, including 100% NRB.
chemistries and urinalysis were normal. Urine
drug screen was negative. Salicylate, acetamino-
phen, and ethanol were not detected. Calculation and Differential Diagnosis of the
Carboxyhemoglobin level was 1.2%. ABG on Elevated Anion Gap with the Pneumonic
room air revealed: pH7.36, pO2 88, pCO2 35, MUDPILES
HCO3 21, lactate 2.7. Head CT and CXR were
normal. EKG showed sinus tachycardia with nor- Anion Gap = [ Anions ] [ Cations ][ AG ]
mal intervals. IV fluids were initiated. = [ Na + ] ([Cl ] + [HCO3 ])

Methanol

Uremia

C.M. Brent (*) Diabetic Ketoacidosis


Emergency Medicine, University of Michigan Health
System, Ann Arbor, MI, USA
e-mail: martinek@med.umich.edu Propylene Glycol
R.W. Shaffer
Paraldehyde
Department of Emergency Medicine, University of Propofol
Michigan Health System, Ann Arbor, MI, USA

Springer International Publishing Switzerland 2017 73


R.C. Hyzy (ed.), Evidence-Based Critical Care, DOI10.1007/978-3-319-43341-7_8
74 C.M. Brent and R.W. Shaffer

measured ethylene glycol fell below 20mg/dL.Her


Infection renal function remained normal throughout her
Iron clinical course. Her pulmonary edema resolved and
Isoniazid she was extubated on hospital day #2.
Inborn Errors of Metabolism

Lactic Acidosis Principles ofManagement

Ethylene Glycol Diagnosis

Salicylates Ethylene glycol is an organic alcohol with mul-


Starvation ketoacidosis tiple commercial and household purposes, and is
typically the primary compound found in anti-
freeze. It is a colorless liquid, although dyes are
Question How would you proceed in the man- often added by the manufacturer. The taste of
agement of this patient? ethylene glycol is often described as sweet,
and therefore young children frequently fall vic-
Answer The combination of altered mental sta- tim to inadvertent ingestions [1]. Ethylene gly-
tus, progressive development of a high anion gap col is rapidly absorbed by the GI tract and
acidosis and the presence of a marked osmolal clinical intoxication may be apparent within
gap are highly suggestive of toxic alcohol inges- 2030min. Peak serum concentrations can be
tion, either methanol or ethylene glycol. Methanol expected between 1 and 4 h post-ingestion [2].
is a common ingredient in windshield washer Ingestions of as little as 1mL/kg may lead to
fluid and ethylene glycol is commonly found in toxic serum concentrations [3].
antifreeze. Ingestion of isopropyl alcohol, the Diagnosing ethylene glycol poisoning can be
third common toxic alcohol ingestion, elevates quite challenging, as the acute clinical presenta-
the osmolar gap but does not result in an acidosis tion is typically non-specific and may appear
or significant elevation of the anion gap. quite similar to ethanol intoxication. Individuals
with intentional ingestions may not be forthcom-
Given her decline in mental status and pro- ing, or may be too obtunded to provide a history
gressive failure of oxygenation secondary to of ingestion. Prompt initiation of treatment is
development of pulmonary edema, she was intu- imperative, and delays strongly correlate with the
bated and mechanically ventilated. A loading development of acidosis and renal failure once
dose of 15mg/kg intravenous fomepizole treat- toxic metabolites accumulate (Fig.8.2) [4, 5].
ment was immediately initiated to prevent further The gold standard for diagnosis uses gas chroma-
metabolism of the parent alcohol. The cofactors tography to measure serum ethylene glycol lev-
thiamine and pyridoxine were given. Her devel- els, but may take 24 h to perform, and is not
oping acidosis suggested that she had already readily available at most medical facilities [2, 6].
metabolized a substantial portion of the parent Serum measurement of the glycolic acid metabo-
alcohol into its toxic metabolites, and nephrology lite has also been advocated by some, owing to its
was consulted for emergent hemodialysis. Gas stronger correlation with the development of
chromatography for toxic alcohols returned sev- renal complications, but this also requires gas
eral hours later and revealed an ethylene glycol chromatography and therefore carries the same
level of 257mg/dL.Repeat urinalysis demon- limitations [7]. Therefore, the clinician often
strated calcium oxalate crystalluria (Fig.8.1). must utilize surrogate markers when considering
The patient underwent three runs of intermittent a toxic alcohol exposure.
hemodialysis and was continued on IV fomepizole Since ethylene glycol is an osmotically
per protocol. Her gap acidosis normalized and her active substance, the osmolal gap (measured
8 Diagnosis andManagement ofEthylene Glycol Ingestion 75

Fig. 8.1 Calcium oxalate


crystals

osmoles calculated osmoles) will typically several caveats to note when interpreting an
be elevated during the initial phase following osmolal gap, however. Numerous formulas
substantial ingestions. As the parent com- exist for calculating serum osmoles, and there
pound is metabolized, the osmolal gap will is no consensus on which one is superior [2,
gradually decline and a metabolic anion gap 10, 11]. One commonly used formula is as
acidosis will develop (Fig.8.3) [9]. There are follows:

Osmc = 2 Na + 1.15 ( glucose / 18 ) + BUN / 2.8 + EtOH / 4.6

An elevated osmolal gap is non-specific and exceeding 50 was highly suggestive of a toxic
may be seen with various conditions including alcohol ingestion, and that nearly 50% of toxic
ethanol intoxication, alcoholic ketoacidosis, ingestions had osmolal gaps greater than
DKA, renal failure, shock, and after use of 30 [10].
other exogenous osmotically active compounds In the initial phase following ethylene glycol
such as mannitol [10]. Additionally, since the poisoning, the anion gap is typically normal, and
normal reference range for a calculated osmolal then begins to rise approximately 3h post-
gap may be as low as 10mosm, the addition ingestion [2]. When presentation or treatment is
of measured osmoles from a toxic alcohol may delayed, the parent alcohol is metabolized by
not raise this gap beyond the accepted upper alcohol dehydrogenase and aldehyde dehydroge-
limit of +10mosm. This can be understood nase into glycolic acid. Further metabolism of
when considering that an ethylene glycol level glycolic acid is very slow and therefore this com-
of 21mg/dL (the threshold where treatment is pound progressively accumulates resulting in an
recommended) would only be expected to anion gap acidosis. Cardiopulmonary manifesta-
increase serum osmoles by 4mosm [2]. Despite tions are likely both due to the acidemia, as well
these limitations, a large retrospective analysis as the direct toxic effect of glycolic acid. During
suggested that an unexplained osmolal gap this phase, patients may develop tachycardia,
76 C.M. Brent and R.W. Shaffer

Metabolism of ethylene glycol Osmols Acids

Ethylene glycol

Alcohol dehydrogenase (ADH)

Time
Glycoaldehyde A C B

Aldehyde dehydrogenase (ALDH) Fig. 8.3 The mountain: A visual schematic for clarify-
ing the temporal relationship between the anion gap and
osmole gaps in toxic alcohol poisoning. A: Ethylene gly-
col is the predominate form in the serum. Only an osmo-
Glycolic acid lar gap is present. No acidosis or anion gap yet noted. C:
Ethylene glycol is being metabolized. Some glycolic
acid is present. Both an osmolar gap and an anion gap
acidosis are present. B: All the ethylene glycol has been
metabolized to glycolic acid. Osmolar gap no longer
Glyoxylic acid exists. Large anion gap acidosis is present (From Mycyk
and Aks [8]. Reprinted with permission from Elsevier
Limited)

Oxalic acid Furthermore, fluorescence is short-lived during


the first few hours and may be difficult to detect.
Fig. 8.2 Metabolism of ethylene glycol Inter-rater reliability when assessing urinary
fluorescence is poor and fluorescein cannot be
hypotension, myocardial depression and conges- detected when urinary pH falls below 4.5. For
tive heart failure, cerebral edema, and an ARDS- these reasons, this screening test cannot be rec-
type picture [3, 12]. ommended [2, 6, 14].
A small portion of glycolic acid is then fur- As a result of the poor performance of any
ther metabolized into oxalate. Deposition of one marker for the diagnosis of toxic alcohol
calcium oxalate crystals in renal tubules results ingestion, it is recommended by the American
in tubular necrosis and renal failure, and gener- Academy of Clinical Toxicology that the clini-
ally occurs 2472 h post-ingestion. This can cian maintain a high index of suspicion and low
also lead to significant hypocalcemia [2]. threshold for treatment [6]. Diagnostic criteria
Testing for calcium oxalate crystalluria as an and indications for treatment are shown below
adjunct to the diagnosis of ethylene glycol [4, 6, 15].
ingestions has been evaluated. Unfortunately,
crystals are seen in only 3363% of those with
known ingestions, and the baseline prevalence
of crystalluria due to other causes such as Diagnostic Criteria and Indications for
dietary factors make this finding neither sensi- Treatment of Ethylene Glycol Poisoning
tive nor specific [2, 13]. Ethylene glycol level >20mg/dL or
Urine fluorescence is another strategy that Recent history of known ingestion AND
has been evaluated by investigators to aid in osmolal gap >10 or
determination of ethylene glycol ingestions. Strong suspicion of ethylene glycol
Fluorescein is often added to engine coolants by ingestion AND two of the following
manufacturers to facilitate a mechanics ability pH, 7.3
to detect radiator leaks using UV light [2]. In the serum bicarbonate <20
setting of ingestions, fluorescein is excreted osmolal gap >10
unchanged in the urine. However, not all anti- Calcium oxalate crystalluria
freeze preparations contain this compound.
8 Diagnosis andManagement ofEthylene Glycol Ingestion 77

Ventilator andCirculatory Support ethylene glycol concentrations in excess of


20mg/dL [6]. The parent alcohol is then excreted
Ethylene glycol exerts effects on GABA and largely unchanged in the urine. The elimination
Glutamate receptors in a similar manner to etha- half-life of ethylene glycol ranges from 14 to 20
nol. In severe poisonings, respiratory depression h in the setting of ADH inhibition [4, 6, 10]. The
and/or inability to adequately protect ones air- two ADH inhibitors that may be used are ethanol
way may necessitate intubation and mechanical and fomepizole.
ventilation. When an acidosis is present, atten- Prior to the advent of fomepizole, ethanol was
tion to adequate minute ventilation is imperative historically used for ADH blockade. Ethanol is
to allow for adequate respiratory compensation. the natural substrate for ADH, and given its
Hypotension may result from direct vasodila- higher binding affinity over ethylene glycol, it
tation caused by the toxic alcohol, or secondary serves as a competitive inhibitor to toxic alcohol
to myocardial depression due to acidosis. In cases metabolism. The generally accepted regimen for
of congestive heart failure or impending circula- ethanol administration is a loading dose of
tory collapse, vasopressor agents may be needed. 600mg/kg of a 10% solution IV through a cen-
Serial EKGs should be obtained to assess for pro- tral venous catheter, followed by a continuous
longation of the QTc which may be seen when infusion of 110mg/kg/h. The drip is then titrated
hypocalcemia is present. Calcium repletion with a goal serum ethanol concentration between
should be limited to patients who are symptom- 100 and 125mg/dL [6, 17]. This requires close
atic (cardiac arrhythmias, seizures), as this may monitoring, given the unpredictable pharmacoki-
hasten calcium oxalate precipitation in the renal netics of ethanol metabolism. Ethanol adminis-
tubules [16]. The presence of hyperkalemia is tration is not without side effects, and patients
often the result of extracellular shifts due to the must be monitored for deterioration of mental
metabolic acidosis, and treatment should be status, hypoglycemia, hepatitis, and pancreatitis.
reserved for individuals with concerning EKG When no IV ethanol formulation is available, PO
manifestations. An ARDS-like picture may rarely ethanol can be considered using the same serum
develop and should be managed with lung- concentration goal.
protective ventilation. Fomepizole (4-methylpyrazole, Antizole) was
FDA approved in 1997 for use as a competitive
inhibitor of ADH in the setting of toxic alcohol
Gastric Decontamination/Lavage/ ingestions. Its efficacy was supported through a
Charcoal small prospective clinical sub-study of the
Methylpyrazole for Toxic Alcohols (META)
Gastrointestinal decontamination and gastric trial. Patients treated with fomepizole who had
lavage have limited benefit following ethylene normal renal function at the time of treatment ini-
glycol absorption due to its very rapid absorp- tiation had no subsequent kidney injury. It should
tion. Furthermore, toxic alcohols bind poorly to be noted, however, that patients with serum eth-
activated charcoal, and its use is not recom- ylene glycol levels exceeding 50mg/dL also
mended [16]. underwent hemodialysis [13]. Fomepizole, when
compared to ethanol, has the advantage of pre-
dictable pharmacokinetics. Its use is generally
Aldehyde Dehydrogenase (ADH) well-tolerated although patients occasionally
Blockade report side-effects including headaches, nausea,
and dizziness [13, 18]. A loading dose of 15mg/
Inhibition of ADH is the mainstay of treatment kg IV is initiated, followed by 10mg/kg every 12
and prevents metabolism of ethylene glycol into h. Fomepizole may induce its own metabolism
its toxic metabolites, and it is generally accepted via the CYP450 pathway, and dosing should be
that treatment should be initiated for serum increased to 15mg/kg every 12 h for doses
78 C.M. Brent and R.W. Shaffer

beyond 48 h of treatment. In patients undergoing is based on opinion rather than evidence [25].
concurrent dialysis, the dosing frequency should Furthermore, an absolute serum ethylene glycol
be increased to every 4 h, or alternatively a con- concentration does not take into account how
tinuous infusion of 1mg/kg/h can be considered much metabolism has already occurred when
[4, 6, 18, 19]. Because ethanol metabolism is presentations are delayed. Serum glycolate levels
inhibited by fomepizole, ethanol treatment better correlate with the development of acidosis
should not be used concurrently [20]. and renal injury, but again there is no established
threshold for treatment [26].

Hemodialysis
Fomepizole vs Ethanol
ADH blockade disrupts the initial metabolism of
ethylene glycol. The development of an anion Many toxicologists currently advocate fomepi-
gap acidosis, or the presence of renal injury sug- zole as the first-line agent for ADH-blockade [4,
gests significant metabolism of ethylene glycol 19]. This may be, in part, related to less reported
into toxic substrates has already occurred. In adverse events when compared to the use of
these cases, hemodialysis may be required to cor- ethanol [27]. To date, there have been no con-
rect the acidosis and thwart further deterioration trolled clinical trials comparing the efficacy of
of renal function [4, 6, 15, 21]. Although compli- fomepizole to ethanol, and there is a paucity of
cations may occur, hemodialysis may shorten literature on the morbidity and mortality of
hospital length of stays [22]. Indications for patients treated with either intervention [5, 28,
hemodialysis were reported by the American 29]. Recently, Beatty etal. conducted a system-
Academy of Clinical Toxicology in 1999, and atic literature review that included 145 trials
their guidelines have yet to be formally updated (none of which were randomized controlled
[6]. These include: studies) [28]. Two hundred ninety-five patients
with ethylene glycol poisoning were identified
Deteriorating vital signs despite supportive who received either fomepizole, ethanol, or
care. both. A higher mortality was seen in those
Severe metabolic acidosis (<7.257.30) treated with ethanol when compared to fomepi-
Renal failure or severe electrolyte distur- zole (18% vs 4.1%). The author cautioned that
bances not responsive to conventional therapy extrapolated data was often poor or incomplete,
4. Ethylene glycol level >50mg/dL and that literature reporting the use of fomepi-
zole tended to be more current, and that recent
The use of an ethylene glycol concentration advances in medical care may confound these
threshold for hemodialysis has more recently results.
been called into question [4, 23, 24].

ADH Inhibition without Hemodialysis


Evidence Contour
The guidelines published in 1999 by the American
Ethylene Glycol Treatment Threshold Academy of Toxicology advocated initiation of
hemodialysis (HD) when ethylene glycol levels
Historically, a serum ethylene glycol concentra- exceed 50mg/dL [6]. Since that time, there are
tion in excess of 20mg/dL has been considered growing reports of patients with significant ethyl-
to be the potentially toxic level where ADH ene glycol ingestions, some with serum levels
blockade was recommended [6]. This conserva- exceeding 700mg/dL, being treated with fomepi-
tive threshold was likely extrapolated from case zole alone when acidosis and renal impairment
reports involving toxic methanol ingestions, and were absent [15, 24, 30, 31]. Some investigators
8 Diagnosis andManagement ofEthylene Glycol Ingestion 79

have even reported successful management with with doses as low as 0.10.4mL/kg [35, 36].
fomepizole alone when a mild acidosis was pres- Using the same enzymatic pathways as ethylene
ent [3, 32]. This has led some experts to advocate glycol, methanol is metabolized to formaldehyde
for the use of hemodialysis only in cases of sig- then formate. Symptoms of acute ingestion are
nificant acidosis or with signs of renal impair- almost identical to those of ethylene glycol.
ment, irrespective of the initial serum ethylene Metabolic effects are also similar, including
glycol level [4, 15, 19, 23, 32]. However, pro- development of an osmolar gap followed by an
spective studies are necessary to validate these anion gap acidosis. Metabolites of methanol are
recommendations. also profoundly more neurotoxic, and the optic
nerve is particularly vulnerable which can result
in permanent visual impairment [3, 35, 37, 38].
Serum andUrine Alkalization Production of formate is prevented by early use
of fomepizole (preferred) or ethanol, and guide-
In methanol ingestions, there is some limited evi- lines for initiation of these therapies are shown
dence that serum alkalization may promote below [33].
deprotonation of toxic acids into their less toxic
conjugate bases, and might also enhance urinary
excretion [33]. This has not been proven to be of Guidelines for Initiation of Therapies
benefit in the setting of ethylene glycol intoxica- 1. Documented plasma methanol concen-
tions, and alkalization for the sole purpose of tration>20mg/dL (200mg/L)
enhancing elimination is not supported by evi- 2. Documented recent history of ingesting
dence. Sodium bicarbonate therapy may be con- toxic amounts of methanol and osmolal
sidered, however, in instances of refractory gap >10mOsm/kg
acidosis [6]. 3. History or strong clinical suspicion of
methanol poisoning and at least 2 of the
following criteria:
Cofactor Supplementation Arterial pH <7.3
Serum bicarbonate <20 meq/L
Pyridoxine and thiamine are cofactors which (20mmol/L)
facilitate conversion of glycolic acid to non-toxic Osmolal gap <10mOsm/kg H2O
metabolites via alternative metabolic pathways,
potentially diverting metabolism away from the
production of oxalate. While advocated by many,
no clinical trials have substantiated this hypothet-
ical benefit, and supplementation is unlikely to be Diagnostic Criteria and Indications for the
useful in the absence of a pre-existing vitamin Treatment of Methanol Poisoning
deficiency [6, 34]. Documented plasma methanol concen-
tration>20 mg/dL
Documented recent history of ingesting
Other Toxic Alcohols methanol and osmolal gap >10mOsm/kg
History or strong clinical suspicion of
Methanol methanol poisoning and at least two of
the following criteria:
Methanol (aka wood alcohol) was historically Arterial pH <7.3
found in methylate spirits. It is now found in sol- Serum bicarbonate <20meq/L
vents, antifreeze, and certain fuels. The fatal dose (20mmol/L)
is considered to be anywhere between 1 and Osmolal gap <10mOsm/kg H2O
2mL/kg [35], although deaths have been reported
80 C.M. Brent and R.W. Shaffer

Folic acid should be administered in toxic ingestion treated with fomepizole alone a viable
methanol ingestions since it serves as a cofactor therapeutic option. JMed Toxicol. 2010;6(2):1314.
4. Brent J.Fomepizole for ethylene glycol and methanol
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6. Barceloux DG, Krenzelok EP, Olson K, Watson
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Isopropyl alcohol (aka rubbing alcohol) pro- Donovan JW, Wells M, Kulig K, Methylpyrazole for
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Accidental Hypothermia
9
CarrieHarvey andIvanNathanielCo

Abbreviations Case Presentation

C Degrees Celsius A 64 year old male with a history of hypertension


ACLS Advanced Cardiac Life Support and prostate cancer was found unresponsive by
AHA American Heart Association his wife around 0800in their driveway in the mid-
CAVR Continuous arteriovenous dle of February in Toledo, OH.His wife had gone
rewarming to bed before him the night prior and did not real-
CPB Cardiopulmonary bypass ize he was missing until approximately 9h later.
CPR Cardiopulmonary resuscitation He was found on his side in a snow bank near the
CVVHD Continuous venovenous mailbox. Ambient temperature was approxi-
hemodiafiltration mately 2 Fahrenheit. He was unresponsive to
CVVR Continuous venovenous painful stimuli. Emergency Medical Services
rewarming (EMS) was called and the patient was transported
CXR Chest x-ray to the nearest Level I Trauma center with full car-
ECG Electrocardiogram diac surgery capabilities. Transport vital signs
EMS Emergency Medicine Services included undetectable temperature by temporal
IV Intravenous probe, heart rate of 45 beats per minute, blood
PRBC Packed red blood cells pressure of 60/palpation, and agonal respirations.
VA-ECMO Venoarterial extracorporeal En route, he received 2L of warmed crystalloid
membrane oxygenation and was intubated for airway protection. Vital
VF Ventricular fibrillation signs on arrival to the Emergency Department
VT Ventricular tachycardia were remarkable for heart rate of 20 beats per
VV-ECMO Venovenous extracorporeal minute and blood pressure of 50/30. His axillary
membrane oxygenation temperature was unable to be obtained. Foley
catheter was placed and bladder temperature was
24C.Primary survey revealed clear breath
C. Harvey (*) sounds bilaterally, pupils 5mm and fixed bilater-
Department of Anesthesiology, University of ally, and Glascow Coma Scale (GCS) score of 3.
Michigan Health System, Ann Arbor, MI, USA His clothing was removed with no external signs
e-mail: hcarrie@med.umich.edu
of trauma. Cervical spine immobilization was
I.N. Co maintained with a hard cervical collar applied by
Division of Pulmonary and Critical Care Medicine,
University of Michigan, EMS prior to arrival. Electrocardiogram (ECG)
Ann Arbor, MI, USA was obtained with sample rhythm strip shown in

Springer International Publishing Switzerland 2017 83


R.C. Hyzy (ed.), Evidence-Based Critical Care, DOI10.1007/978-3-319-43341-7_9
84 C. Harvey and I.N. Co

Fig. 9.1 Classic electrocardiogram findings in hypothermia. This EKG demonstrates three common findings in hypo-
thermia, including bradycardia, shivering artifact, and J-waves (Image courtesy of lifeinthefastlane.com)

Fig.9.1. Initial arterial blood gas on FiO2 1.0 was surgery available and consultation with the sur-
as follows: pH6.73, paCO2 50mmHg, paO2 geon is necessary to determine which modality is
259mmHg, bicarbonate 4.8mmol/L, base deficit best for the patient. Due to ongoing CPR, the
29.7, SaO2 98%, potassium 5.2mmol/L, and decision was made to initiate VA ECMO with per-
hemoglobin 13.6mmol/L.Toxicology screen was cutaneous venous and arterial cannulation at the
negative. Active rewarming with warm humidi- bedside. The heater on the ECMO circuit was set
fied air, warm intravenous fluids, and warm fluid to 37C and rewarming was started as soon as
lavage of the stomach and bladder was initiated. cannulation was complete. CPR continued until
After 30min, pulse was unobtainable with ven- the patient was rewarmed to 30C, at which point
tricular fibrillation noted on telemetry. defibrillation was again attempted with successful
Cardiopulmonary resuscitation (CPR) was initi- conversion to normal sinus rhythm. After 4h of
ated and he was defibrillated once at ECMO, his temperature and blood pressure had
200J.Ventricular fibrillation persisted and repeat normalized. Repeat arterial blood gas on FiO2 0.5
core temperature was 25C. was: pH7.38, paCO2 39mmHg, paO2 92mmHg,
bicarbonate 22.6mmol/L, base deficit 2.2, SaO2
Question What is the next best step in rewarm- 99%, potassium 3.7mmol/L, and hemoglobin
ing this patient? 10.5mmol/L.He received broad-spectrum antibi-
Answer Initiate rewarming via extracorporeal otics for high likelihood of aspiration and contin-
cardiopulmonary resuscitation (ECPR) ued warm IV fluids due to presumed cold diuresis.
After 24h, the patient was awake and following
When pulse and signs of life are absent in commands with no evidence of acute respiratory
hypothermia, treatment with extracorporeal distress syndrome. ECMO support was stopped
rewarming with extracorporeal membrane oxy- and the patient was extubated the following day
genation (ECMO) or cardiopulmonary bypass without incident. Neurologic exam was normal.
(CPB) is recommended. ECMO can be initiated He developed AKI requiring 3 days of dialysis,
in two modes: veno-venous (VV) or veno-arterial but had complete renal recovery. He was dis-
(VA) depending on the presence of innate and pre- charged home after 1 week with no functional or
served cardiac function. This hospital has cardiac neurologic impairment.
9 Accidental Hypothermia 85

Principles ofManagement hypothermia should be obtained by a focused his-


tory and physical exam. These include trauma,
Diagnosis infection, toxic ingestion, endocrinopathy (e.g.
myxedema coma), metabolic derangements, and
Hypothermia is defined as a core body tempera- stroke [1].
ture of less than 35C (95F) and is classified by
severity; mild, moderate, or severe (Table9.1)
[1]. Standard thermometers do not read below Patient Monitoring
34C, therefore, accurate measurement of core
temperature should be obtained by esophageal, Due to the dramatic hemodynamic changes that
bladder, or rectal probes [2]. If core temperature can occur with hypothermia and rewarming, all
cannot be readily measured, the Swiss staging patients should be closely monitored with
system (Table9.2) can be used to guide manage- telemetry, continuous pulse oximetry, frequent
ment based on clinical symptoms [3]. Additional blood pressure checks, and core temperature
risk factors for development of accidental hypo- probe [3]. Pulse oximetry is often difficult to
thermia include extremes of age, ethanol abuse, measure due to peripheral vasoconstriction and
and malnutrition [2]. arterial blood gas may be the only way to assess
With cold exposure, the body attempts to oxygen content. There is also limited data to
increase heat production by increasing circulat- suggest that forehead pulse oximetry may be
ing epinephrine, which leads to tachycardia, more accurate than fingertip devices in hypo-
increased minute ventilation, peripheral vasocon- thermia [5]. The authors recommend pre-emp-
striction, and shivering [4]. If exposure persists, tive placement of defibrillator pads if there is
these compensatory mechanisms are over- any concern for development of ventricular
whelmed, resulting in decreased metabolic dysrhythmias. The prognostic value of end-
demand, cessation of shivering, and ultimately tidal carbon dioxide monitoring in cardiac
death [3]. The effects of hypothermia by organ arrest secondary to accidental hypothermia has
system are summarized in Table9.3 and repre- not been studied.
sent typical clinical findings.
Finally, any underlying medical conditions
that may have contributed to development of Adjunctive Testing

Table 9.1 Classification of hypothermia Once the diagnosis of hypothermia is confirmed


by core temperature measurement, additional
Mild 3532C
testing should include basic laboratory studies,
Moderate <32 to 28C
toxicology screen, ECG, and chest radiograph
Severe <28 to 24C
(CXR). Typical laboratory findings are listed in
Table9.4. Slowed cardiac conduction manifests
Table 9.2 Swiss staging system of hypothermia as a variety of ECG changes, the most common
Stage Clinical symptoms of which is the Osborne wave (Fig.9.2), seen in
I Conscious, shivering approximately 80% of hypothermic patients [7].
II Altered mental status, no shivering Baseline CXR is recommended due to the inher-
III Unconscious, no shivering ent risk of aspiration pneumonia in this patient
IV No vital signsa population. CT head imaging in all hypothermic
Data from Brown etal. [3] patients is not clearly indicated but should be
The estimated core temperature in stage I, II, and III cor- considered if altered mental status is present
respond to mild, moderate, and severe hypothermia,
respectively despite temperature >32C or signs of head
a
Loss of vital signs general occurs when the core tempera- trauma are present [1]. Further workup should be
ture is below 24C pursued on an individual basis if associated
86 C. Harvey and I.N. Co

Table 9.3 Clinical findings in hypothermia


Organ system Mild Moderate Severe
Neurologic Apathy Dilated pupils Areflexia
Confusion Paradoxical undressing Coma
Ataxia Stupor
Cardiovascular Tachycardia Bradycardia Ventricular dysrhythmias
Atrial fibrillation Asystole
Hypotension
Pulmonary Tachypnea Bradypnea Pulmonary edema
Renal High urine output High urine output Oliguria
Metabolic Hyperglycemia Variable blood glucose Hypoglycemia
No shivering Shivering No shivering
Respiratory alkalosis Mixed metabolic and Mixed metabolic and
respiratory acidosis respiratory acidosis
Data from Mulcahy and Watts [1]

trauma, infection, or other medical condition is Table 9.4Common laboratory derangements in


suspected. hypothermia
Typical
Test result Comments
Rewarming Hematocrit High Due to
hemoconcentration from
cold dieresis
There are four general approaches to rewarming: Potassium High Potassium>12 mmol/L
passive, active external, active internal, and extra- considered universally
corporeal [8]. The best method depends on the fatal [3, 6]
severity of hypothermia and resources available Creatinine High
to the provider, although there are no random- Creatine High Should be checked
ized, controlled trials regarding treatment kinase routinely as time down
often unknown
approach. The average rates of rewarming for
PT/PTT High Due to coagulation
each method are listed in Table9.5. cascade enzyme
Passive rewarming is applicable to all hypo- denaturation at colder
thermic patients and should begin in the pre- temperature; reported
hospital setting, with removal of wet clothing, values may be normal as
blood heated prior to
application of blankets or foil insulator, and pro- testing
tection from the environment [9]. This method Arterial blood Variable Recommend using
alone is only effective if shivering is present, oth- gas uncorrected values [1]
erwise, active rewarming is necessary. Lactate High
Active external rewarming assumes circula-
tion is intact and can return warmed blood to the microwave and then shaken to ensure uniform
core. Examples include warm blankets, radiant heating prior to infusion [12].
heat lamps, forced air device (e.g. Bair HuggerTM), Extracorporeal rewarming is the most effec-
and warm water immersion [10]. tive method, with up to 6C/h rate of rewarming,
Active internal rewarming includes warm but also the most invasive and resource intensive
humidified air (42C), warm intravenous (IV) [13, 14]. Hemodialysis is generally the most
fluids (42C), body cavity lavage (gastric, tho- readily available, but requires an adequate blood
racic, peritoneal, bladder), intravascular devices, pressure to tolerate the procedure. Continuous
and peritoneal dialysis [1, 11]. If a commercial arteriovenous rewarming (CAVR) or continuous
fluid warmer is not available, non-dextrose con- venovenous rewarming (CVVR) can be achieved
taining fluids can be warmed in a conventional via percutaneous access and a countercurrent
9 Accidental Hypothermia 87

Fig. 9.2 Osborne wave.


Osborne wave, or J wave, is
frequently seen in
hypothermia, although it is
not pathognomonic for the
condition. It is character-
ized by a positive deflection
at the J point (negative in
aVR and V1) and is usually
seen best in the precordial
leads. The height of the J
wave generally corresponds
to the degree of hypother-
mia [7] (Image courtesy of
lifeinthefastlane.com)

Table 9.5 Rewarming techniques Hypothermia Without aPulse


Technique Rate (C/h)
Removal of wet clothing, insulation 0.5 The 2010 American Heart Association (AHA)
Warm environment, warm oral fluids, 2 guidelines provide recommendations on
active movement advanced cardiac life support (ACLS) modifica-
Forced-air heating device, warm IV fluids 0.13.4 tions in hypothermia, although these are based on
Peritoneal dialysis 13 expert opinion and case reports only (level of evi-
Hemodialysis 24 dence C):
Thoracic lavage 3
Venovenous ECMO 4 (a) If a patient does not have a pulse, ACLS should
Venoarterial ECMO 6 be immediately initiated, unless one of the fol-
Cardiopulmonary bypass 9 lowing is present: valid Do Not Resuscitate
Data from Brown etal. [3] order, patient is frozen solid, there is ice in the
airway, core temperature is <10C, the patient
heat exchanger (e.g. Belmont Rapid Infuser) was submerged for more than 1h, or there is
[15, 16]. Both methods utilize the patients blood obvious lethal injury [1, 3, 19].
pressure to drive the blood through the device. (b) If ventricular fibrillation (VF) or ventricu-
CVVR by continuous venovenous hemodiafiltra- lar tachycardia (VT) is present, defibrilla-
tion (CVVHD) has also been shown to be effec- tion should be attempted [20]. The number
tive in a case report [17]. Veno-arterial ECMO of attempts that should be made if VF or
and CPB require the most resources and exper- VT persists has not been established. The
tise, but bypasses the native circulation and can AHA guidelines state that it may be reason-
therefore be used in patients in cardiac arrest. able to perform further defibrillation (Class
For patients with stable hemodynamic IIb recommendation), while most treatment
parameters, active rewarming with a forced air algorithms recommend only one shock
device, warm humidified air, and warm IV fluids until the patient is rewarmed to 30C [1, 3].
is generally sufficient to achieve normothermia (c) There is a theoretical concern for toxic accumu-
[18]. If these initial measures are not sufficient, lation of ACLS drugs due to reduction in drug
a patient can undergo more invasive rewarming. metabolism in severe hypothermia. The AHA
Thoracic lavage and ECMO carry considerable guidelines state that the safety of administration
risk and should be reserved for those patients or withholding of medication is unclear, but that
with cardiac instability [11]. Expert opinion rec- it is reasonable to consider administration of a
ommends ECMO if required resources are vasopressor according to standard ACLS guide-
available [3, 11]. lines (Class IIb recommendation). Similarly,
88 C. Harvey and I.N. Co

expert opinion recommends up to three doses of ventions whenever possible. There are no guide-
epinephrine, with re-evaluation once the patient lines regarding inter-hospital transfer and this
is rewarmed to 30C [3, 18]. decision should be made on a case-by-case basis
In patients with return of spontaneous circula- with the consulting cardiac surgeon.
tion after cardiac arrest, multi-organ failure As mentioned above, there are certain circum-
should be anticipated and treated similar to any stances in which CPR should not be initiated.
other critically ill patient. Some experts also provide recommendations on
when to stop an ongoing resuscitation. All experts
agree that a patient should receive aggressive
Other Supportive Care resuscitation including CPR until core tempera-
ture is at least 30C.A recent review article sug-
The majority of patients will present with hypovo- gests that if asystole secondary to hypothermia
lemia secondary to cold diuresis and will conse- persists despite rewarming to 32C, termination
quently require aggressive fluid resuscitation. In of CPR should be considered as the cardiac arrest
one study of 38 severely hypothermic patients is likely irreversible [3]. Similarly, markedly ele-
who received warmed IV fluids, the average vol- vated potassium is considered a marker of hypoxia
ume load was 4.8L [20]. Hyperglycemia (mild before hypothermia and therefore negatively
hypothermia) and hypoglycemia (severe hypo- associated with outcome. Most experts agree that
thermia) are also common, thus, serum glucose resuscitation is futile if the potassium level is
level should be obtained and treated accordingly. >12mmol/L [3, 6]. The highest potassium level in
Alcohol intoxication should prompt consideration patients that survived was 7.9mmol/L in an adult
of thiamine and alert the provider to the potential [23] and 11.8mmol/L in a child [24].
for alcohol withdrawal. It is recommended that
broad-spectrum antibiotics be given to those
patients at risk for associated infection, such as Pediatric Patients
neonates, the elderly, and the homeless, as those
with infection often respond poorly to rewarming In general, the management of pediatric acciden-
[21]. There is no evidence for empiric steroids, tal hypothermia is the same as adults. Pediatric
unless there is high clinical suspicion for adrenal Advanced Life Support (PALS) should be used in
insufficiency as the cause of hypothermia [1]. place of the ACLS algorithm. Pathophysiology
and principles of rewarming are similar, with suc-
cessful resuscitation via ECMO and CPB reported
Disposition in the pediatric population. Hypothermia second-
ary to submersion is more common in pediatric
Those patients who presented with mild hypo- patients and carries a worse prognosis due to asso-
thermia that responded to rewarming methods, ciated asphyxia. The longest duration of submer-
have a clear history of cold exposure, and have no sion with full neurologic recovery was 66min and
evidence of an underlying disease or injury can used ECMO for rewarming [25]. Guidelines for
be safely discharged home. All other patients cessation of resuscitation are similar to adults.
require hospital admission, usually to the inten-
sive care unit (ICU), for continued monitoring
and supportive care. Evidence Contour
In patients with cardiac arrest, the survival rate
without neurologic impairment is higher in patients Withholding CPR
treated with ECMO (4763%) as compared to
those without (<37 %) [3, 22, 23]. Therefore, As stated above, the 2010 AHA guidelines rec-
patients with cardiac instability or arrest should be ommend ACLS if a pulse cannot be palpated.
taken to the nearest facility capable of these inter- However, it can be difficult to palpate a pulse in a
9 Accidental Hypothermia 89

cold, stiff patient and many experts now advocate Selection ofExtracorporeal Support
that CPR should be held if other signs of life are
present, which include spontaneous respirations, There are no randomized controlled trials com-
spontaneous movement, or adequate cardiac paring the various rewarming modalities.
activity is visualized on bedside echocardiogra- Expert opinion recommends that a hypother-
phy [1, 3]. Given the profound decrease in meta- mic patient who has hemodynamic instability
bolic demand, it is hypothesized that any following accidental hypothermia should
organized rhythm (i.e. bradycardia or adequate undergo extracorporeal support. VA ECMO is
echocardiographic evidence of cardiac activity) the mode of ECMO preferred as it provides
provides enough perfusion to the body in hypo- cardiac support in addition to rewarming [27].
thermia. Additionally, there is a long-standing Selection of modality for rewarming will
belief that sudden movement of a hypothermic depend on resources available at the physi-
patient may irritate the myocardium and induce a cians institution.
dysrhythmia, such as in CPR [26]. This hypoth-
esis has never been directly studied in humans.
Thus, in a hypothermic patient with a pulse, Transcutaneous Pacing
spontaneous movement and/or respiration, or
with bedside echo evidence of adequate cardiac Classic teaching in hypothermia has been to avoid
activity, ACLS should be held. Otherwise, con- any manipulation of the heart rate due to concern
tinuation of ACLS should be initiated per the of inducing a ventricular dysrhythmia. However, a
AHA guidelines. case report of two patients reported successful
rewarming using CAVR with c oncomitant trans-
cutaneous pacing [28]. In both cases, pacing was
 egree ofRewarming inCardiac
D required to maintain blood pressure so that CAVR
Arrest could be used. There were no reported dysrhyth-
mias and both patients had normal neurologic out-
Given the neuroprotective effect of induced comes. Still, it is hypothesized that bradycardia
hypothermia following cardiac arrest, it is recom- and hypotension in hypothermia may not be
mended that a patient with accidental hypother- harmful due to the reduced metabolic require-
mia and cardiac arrest undergo therapeutic ments. A trial of transcutaneous pacing is reason-
hypothermia for 24 h. able but should not delay the initiation of
rewarming.

Timing ofExtracorporeal Support


Endovascular Rewarming
It remains unclear if aggressive extracorporeal
rewarming with VA or VV ECMO should be ini- Successful rewarming of a patient using an endo-
tiated in patients without associated cardiac vascular device has been reported [29, 30]. This
arrest. Some authors do recommend ECMO in device is the same as those used for therapeutic
patients with hemodynamic instability who do hypothermia following cardiac arrest, which
not respond to initial medical management [3]. requires only percutaneous central venous access.
Conversely, one prospective study of 38 patients This method had a rewarming rate of 3C/h,
with severe hypothermia without cardiac arrest which is similar to thoracic lavage and may there-
found that 92% of the patients could be success- fore be an efficient, less invasive alternative in
fully rewarmed to normothermia via forced air facilities in which extracorporeal rewarming is
device, warmed inhaled oxygen, and warmed IV not available. Similar to other active internal
fluids within 10h, including 14 of 17 patients methods, the endovascular approach requires that
with unstable hemodynamic parameters [20]. the patient have a pulse.
90 C. Harvey and I.N. Co

Core Afterdrop 11. Plaisier BR.Thoracic lavage in accidental hypother-


mia with cardiac arrest report of a case and review
of the literature. Resuscitation. 2005;66(1):99104.
A commonly taught phenomenon of active exter- 12. Lindhoff GA, MacG Palmer JH.An assessment of the
nal rewarming is core afterdrop, which is defined thermal safety of microwave warming of crystalloid
as continued core cooling despite rewarming. fluids. Anaesthesia. 2000;55(3):2514.
13. Husby P, Andersen KS, Owen-Falkenberg A, Steien
The prevailing theory was that peripheral vasodi-
E, Solheim J.Accidental hypothermia with cardiac
lation from external rewarming could lead to arrest: complete recovery after prolonged resuscita-
both distributive shock and return of peripheral tion and rewarming by extracorporeal circulation.
acidemic blood to the core. This has largely been Intensive Care Med. 1990;16(1):6972.
14. Tiruvoipati R, Balasubramanian SK, Khoshbin E,

refuted by subsequent studies that argue that
Hadjinikolaou L, Sosnowski AW, Firmin RK.
shock occurs secondary to inadequate fluid resus- Successful use of venovenous extracorporeal mem-
citation in the context of cold diuresis. Studies in brane oxygenation in accidental hypothermic cardiac
which active external rewarming is paired with arrest. ASAIO. 2005;51(4):4746.
15. Bruer A, Wrigge H, Kersten J, Rathgeber J, Weyland
accurate core temperature measurement with an
W, Burchardi H.Severe accidental hypothermia:
esophageal probe and concurrent warm IV fluid rewarming strategy using a veno-venous bypass
administration do not report afterdrop [10, 20]. system and a convective air warmer. Intensive Care
Med. 1999;25(5):5203.
16. Gentilello LM, Cobean RA, Offner PJ, Soderberg RW,
Jurkovich GJ.Continuous arteriovenous rewarming:
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1. Mulcahy A, Watts M.Accidental hypothermia: an 17. Komatsu S, Shimomatsuya T, Kobuchi T, Nakajima
evidence-based approach. Emergency Medicine M, Amaya H, Konishi S, etal. Severe accidental
Practice, EBMedicine.net. 2009;11(1). hypothermia successfully treated by rewarming strat-
2. Auerbach PS.Wilderness medicine. 6th ed. Philadelphia: egy using continuous venovenous hemodiafiltration
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3. Brown DJA, Brugger H, Boyd J, Paal P.Accidental 18. Soar J, Perkins GD, Abbas G, Alfonzo A, Barelli A,
hypothermia. N Engl JMed. 2012;367(20):19308. Bierens JJLM, etal. European Resuscitation Council
4. Sessler DI.Thermoregulatory defense mechanisms. Guidelines for Resuscitation 2010 Section 8. Cardiac
Crit Care Med. 2009;37(7 Suppl):S20310. arrest in special circumstances: Electrolyte abnormal-
5. MacLeod DB, Cortinez LI, Keifer JC, Cameron D, ities, poisoning, drowning, accidental hypothermia,
Wright DR, White WD, etal. The desaturation hyperthermia, asthma, anaphylaxis, cardiac surgery,
response time of finger pulse oximeters during mild trauma, pregnancy, electrocution. Resuscitation.
hypothermia. Anaesthesia. 2005;60(1):6571. 2010;81(10):140033.
6. Monika BM, Martin D, Balthasar E, Stefan L, Roland 19. Vanden Hoek TL, Morrison LJ, Shuster M, Donnino
D, Lars E, etal. The Bernese Hypothermia Algorithm: M, Sinz E, Lavonas EJ, etal. Part 12: cardiac arrest in
a consensus paper on in-hospital decision-making and special situations: 2010 American Heart Association
treatment of patients in hypothermic cardiac arrest at Guidelines for Cardiopulmonary Resuscitation and
an alpine level 1 trauma centre. Injury. 2011;42(5): Emergency Cardiovascular Care. Circulation.
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7. Mustafa S, Shaikh N, Gowda RM, Khan IA. 20. Rggla M, Frossard M, Wagner A, Holzer M, Bur A,
Electrocardiographic features of hypothermia. Rggla G.Severe accidental hypothermia with or
Cardiology. 2005;103(3):1189. without hemodynamic instability: rewarming without
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JJLM.Accidental hypothermia: rewarming treatments, Wochenschr. 2002;114(89):31520.
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cal centre. Resuscitation. 2010;81(11):15505. LR.Rewarming rates in urban patients with hypother-
9. Lundgren P, Henriksson O, Naredi P, Bjrnstig U.The mia: prediction of underlying infection. Acad Emerg
effect of active warming in prehospital trauma care Med. 2006;13(9):91321.
during road and air ambulance transportation a clini- 22. Farstad M, Andersen KS, Koller ME, Grong K, Segadal
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Part II
Cardiac Disease

DavidA.Morrow and BenjaminA.Olenchock


Management ofCardiogenic
Shock 10
MichaelG.Silverman andBenjaminA.Olenchock

Case Presentation normal flow. The patient remained hypotensive,


requiring vasopressor support with norepineph-
A 60 year-old man with known coronary artery rine to maintain a blood pressure of 80/60mmHg.
disease complained to coworkers of intermittent
chest pain for several days prior to admission. On Question What is the next step in management
the morning of admission, he developed crushing to optimize this patients hemodynamics and
chest pain at work and then lost consciousness. treat his shock?
Coworkers phoned 911 and performed
CPR.Emergency Medical Technicians arrived Answer Initiation of mechanical circulatory
15min later, and reported an initial cardiac rhythm support.
of ventricular fibrillation. He was successfully
resuscitated, and a post arrest ECG was then per- For patients in cardiogenic shock (CS) from an
formed (Fig.10.1). The hospitals ST-elevation acute myocardial infarction (MI) who continue to
myocardial infarction (STEMI) team was acti- have hypotension and inadequate cardiac output
vated from the field, and the patient was trans- despite revascularization and pharmacotherapy, it
ported to the Emergency Department. Upon is reasonable to consider the use of mechanical
arrival he was hypoxemic and hypotensive. He circulatory support. This patient underwent place-
was intubated prior to emergent coronary angiog- ment of an intra-aortic balloon pump (IABP) and
raphy. Coronary angiogram revealed a complete placement of a flow-directed pulmonary artery
occlusion at the site of a prior proximal left ante- catheter for invasive hemodynamic monitoring.
rior descending (LAD) coronary artery stent His initial hemodynamics were notable for an
(Fig.10.2) as well as a 70% stenosis of the mid elevated pulmonary capillary wedge pressure
right coronary artery. After much difficulty, a wire (PCWP) of 29mmHg and a low cardiac index of
was passed through the proximal LAD blockage 1.5L/min, confirming the diagnosis of CS.With
and the artery was re-stented with restoration of placement of the IABP there was mild improve-
ment in his hemodynamics, and he was admitted
to the Cardiac Intensive Care Unit (CICU) for
ongoing management. A transthoracic echocar-
diogram was obtained, which demonstrated a
M.G. Silverman B.A. Olenchock (*) severely reduced ejection fraction of 15% with
Division of Cardiovascular Medicine, Department
anterior and anteroseptal wall akinesis and global
of Medicine, The Brigham and Womens Hospital
and Harvard Medical School, Boston, MA, USA hypokinesis of the remaining wall segments. Over
e-mail: bolenchock@partners.org the next 1218 h, despite the IABP and increasing

Springer International Publishing Switzerland 2017 95


R.C. Hyzy (ed.), Evidence-Based Critical Care, DOI10.1007/978-3-319-43341-7_10
96 M.G. Silverman and B.A. Olenchock

Fig. 10.1 Admission ECG

doses of pharmacologic support with vasopres-


sors/inotropes, his hemodynamics remained mar-
ginal with worsening renal failure. In the setting
of progressive shock, the patient was brought
back to the catheterization lab to upgrade his
mechanical circulatory support to a TandemHeart
percutaneous left ventricular assist device
(LVAD). Although his filling pressures and car-
diac output improved with the increased mechani-
cal circulatory support, his overall clinical picture
continued to deteriorate, and his family ultimately
decided to transition his goals of care to comfort
measures only. His mechanical and pharmaco-
logic supports were withdrawn and he expired.

Principles ofManagement

Diagnosis Fig. 10.2 Coronary angiogram, LAO Caudal view, dem-


onstrating stent thrombosis of LAD (arrow)
Cardiogenic shock (CS) occurs in roughly 8% of
individuals who present with STEMI, while 80% of
CS cases are due to an acute MI [1, 2]. The diagno- 18mmHg [3]. Invasive hemodynamics with a pul-
sis of CS can be made based on the following estab- monary arterial catheter have been recommended
lished clinical criteria: (1) Hypotension systolic and are often used to help confirm the diagnosis of
blood pressure<90mmHg for more than 30min or CS and help guide management [3, 5, 6].
the need for vasopressor/mechanical support to
achieve this blood pressure; (2) pulmonary edema
or evidence of elevated left ventricular filling pres- Early Revascularization
sures; (3) evidence of end-organ hypoperfusion
with at least one of the following: altered mental The most significant advance in treatment of CS
status, cold clammy skin or extremities, urine out- has been the implementation of early revascular-
put less than 30ml/h, or elevated serum lactate ization of the infarct-related artery, which has led
greater than 2mmol/L [24]. The hemodynamic to a significant decrease in mortality [4]. The
criteria for CS include a cardiac index (CI) of less Should We Emergently Revascularize Occluded
than 2.2L/min/m2 as well as a PCWP greater than Coronaries for Cardiogenic Shock (SHOCK)
10 Management ofCardiogenic Shock 97

trial randomized 302 patients with CS from an sures and systemic vascular resistance [11].
acute MI to undergo either emergency revascu- Since dobutamine can decrease blood pressure,
larization (152 patients) or initial medical stabili- it is often used in conjunction with vasopressors
zation (150 patients) [7]. Patients underwent to improve cardiac output in the setting of CS
revascularization with either percutaneous coro- from acute MI [2, 4]. Milrinone also increases
nary intervention (PCI) or coronary artery bypass heart rate, stroke volume, and cardiac output
grafting (CABG). Although the primary endpoint while decreasing left ventricular filling pres-
of 30 day all-cause mortality was not signifi- sures and systemic vascular resistance. However,
cantly different between the revascularization because milrinone can cause more significant
and the medical-therapy groups (46.7 % and vasodilation and hypotension, it is not a pre-
56.0% respectively, p=0.11), there was a signifi- ferred inotropic agent in CS from acute MI [4].
cant difference between the respective groups at Although inotropes and vasopressors can
6 months favoring the revascularization group improve cardiac output and blood pressure, they
(50.3% versus 63.1%, p=0.027). The 13% abso- also increase myocardial oxygen demand,
lute risk reduction persisted at longer term follow increase risk for arrhythmias, and can impair
up of 1 and 6 years [7, 8]. As a result of this trial, microcirculation; therefore their use should be
current guidelines give early revascularization limited to the lowest dose for the shortest dura-
with either PCI or CABG a class Ib recommenda- tion possible [2, 4, 11].
tion [3, 5, 9]. The goal of inotropic/vasopressor support is to
maintain end-organ perfusion. In general, a target
of a mean arterial pressure>=65mmHg is rea-
Vasopressors/Inotropes sonable. However, evidence of organ function
(mental status, renal function, absence of bio-
Vasopressors and inotropes are often required to chemical evidence of organ ischemia) is more
treat patients with CS [2]. Dopamine and important.
Norepinephrine are commonly used vasopressors
that were compared in a randomized control trial
including 1,679 patients with shock, of whom  ercutaneous Mechanical Circulatory
P
280 were classified as having CS.The overall Support
trial demonstrated an increased burden of arrhyth-
mic events in the dopamine treated group com- Given the limitations of pharmacologic support
pared with the norepinephrine treated group, with vasopressors and inotropes to maintain ade-
although there was no difference in the primary quate blood pressure and tissue perfusion, there
endpoint of all-cause mortality. However, in the has been much interest in the use of percutaneous
predefined subgroup of 280 patients with CS, mechanical circulatory support (MCS). There are
norepinephrine was associated with a signifi- now multiple device options, and over the past
cantly lower death rate compared to dopamine several years there has been a significant increase
[10]. As a result, the European Society of in the use of percutaneous MCS [12]. Currently
Cardiology (ESC) guidelines recommend norepi- available devices include the intra-aortic balloon
nephrine over dopamine for medical manage- pump (IABP), the Impella micro-axial rotary
ment of hypotension from CS, and the American pumps (2.5, CP, and 5.0), the TandemHeart
College of Cardiology (ACC)/American Heart continuous flow centrifugal pump, and percuta-
Association (AHA) guidelines caution that there neous venoarterial extracorporeal membrane
may be, excess hazard associated with the use oxygenation (v-a ECMO). These devices all
of dopamine in CS [3, 5]. require anticoagulation and have been associated
Inotropic support with dobutamine increases with adverse events including limb ischemia,
heart rate, stroke volume, and cardiac output, stroke, infection, and hemolysis. The ACC/AHA
while decreasing left ventricular filling pres- guidelines give a class IIa recommendation for
98 M.G. Silverman and B.A. Olenchock

Table 10.1 Comparison of device characteristics and hemodynamics


Impella Impella Impella
IABP 2.5 CP 5.0 TandemHeart ECMO
Hemodynamic 0.51.0 2.5 3.74.0 5.0 4.0 4.07.0
support (L/min)
Pump mechanism Pneumatic Axial flow Axial flow Axial flow Centrifugal Centrifugal
Effect on LV Reduced Reduced Reduced Reduced Reduced Reduced
pre-load
Effect on LV Reduced Neutral Neutral Neutral Increased Increased
afterload
IABP intra-aortic balloon pump, ECMO extracorporeal membrane oxygenation, LV left ventricle

the use of IABP in patients with CS after STEMI, in the left atrium via femoral venous access and
whereas the ACC/AHA and the ESC give a IIb transseptal puncture (Fig.10.4). The outflow can-
recommendation for the use of alternative percu- nula is placed in the lower abdominal aorta or the
taneous left ventricular assist devices (LVADs) in iliac artery via femoral arterial access.
patients with CS [3, 5, 9]. The different devices Oxygenated blood is aspirated from the left
are discussed here and in Table10.1. atrium into the inflow cannula, and is then
pumped into the lower abdominal aorta or the
I ntra-Aortic Balloon Pump iliac artery via the outflow cannula. The
The IABP is placed in the descending thoracic TandemHeart increases afterload because
aorta via femoral arterial access. The pneumatic blood is pumped retrograde towards the left ven-
device inflates during diastole, raising diastolic tricle [2, 4].
blood pressure, and deflates during systole, low-
ering left ventricular afterload. Figure10.3 dem-  enoarterial Extracorporeal Membrane
V
onstrates the typical IABP waveforms. The IABP Oxygenation (v-a ECMO)
can increase stroke volume and cardiac output up The percutaneous v-a ECMO system includes a
to 0.51.0L/min [4]. The IABP is widely avail- centrifugal pump, heat exchanger, and oxygen-
able and is the most commonly used mechanical ator. The inflow cannula is placed in the right
support device, although it provides limited atrium via femoral venous access, and the out-
hemodynamic support [2]. flow cannula is placed in the descending thoracic
aorta via femoral arterial access. V-a ECMO can
I mpella 2.5, CP, and5.0 provide up to 4.07.0L/min of biventricular cir-
The axial flow device is typically placed via fem- culatory support (bypasses both the right and left
oral arterial access retrograde across the aortic ventricle) as well as respiratory support.
valve and provides support by aspirating blood Limitations are that it does not directly unload
from the left ventricle and pumping it into the the left ventricle, it increases afterload, and
ascending aorta (Fig.10.4). The 2.5 and CP can requires additional staffing [2, 4].
provide up to 2.5L/min and 3.74.0L/min of
support, respectively, and both can be placed per-
cutaneously. The 5.0 can provide up to 5.0L/min  emporary Surgical Mechanical
T
of support, but requires a surgical cut down of Circulatory Support
either the femoral or axillary artery [2, 4].
When percutaneous MCS is inadequate, tempo-
TandemHeart rary surgical MCS with a surgically placed VAD
This continuous flow centrifugal device is placed can provide support for both the right and left
percutaneously and can deliver up to 4.0L/min of ventricle with increased flow (up to 10L/min)
circulatory support. The inflow cannula is placed [13]. These surgically placed VADs can also be
10 Management ofCardiogenic Shock 99

Intra-aortic Balloon Pump (IABP) Evidence Contour

There are several aspects in the management of


patients with CS from an acute MI for which
clinical equipoise still exists.

augmentation
systolic

diastolic
unloading

Multivessel Revascularization

Although the SHOCK trial demonstrated the ben-


efit of early culprit vessel revascularization in CS
from STEMI, the optimal revascularization strat-
Ao egy among individuals with multivessel disease
remains unclear. A critical eye toward these data
afterload will note that the primary endpoint was not met
reduction and thus all additional analyses in the SHOCK
trial were inherently exploratory. Nonetheless,
since no other strategies have proven effective in
IABP
CS, early revascularization remains the paradigm.
Nearly of individuals who present with CS
ECG
from acute MI have multivessel coronary disease
[14]. Current ESC guidelines recommend multi-
Fig. 10.3 Intra-aortic balloon pump (IABP) pressure vessel PCI (class IIa) for individuals with CS who
waveforms, with IABP inflation set to 2:1. The IABP is have multivessel coronary artery disease [9]. The
inflated in early diastole at the timing of the dichrotic
notch, augmenting blood pressure during diastole, thus
ACC/AHA guidelines do not give an overt recom-
augmenting coronary perfusion pressure. The balloon mendation, but do recognize shock or severe heart
deflates in late diastole, lowering aortic end diastolic pres- failure as a clinical scenario in which acute revas-
sure, decreasing afterload on the left ventricle, and cularization of significant stenosis in noninfarct
unloading the left ventricle during systole
arteries can be justified [5]. The current evidence
as it relates to patients with CS comes from non-
left in place for weeks to months if necessary, randomized studies looking at outcomes associ-
providing a longer term temporary solution while ated with multivessel PCI in CS from acute
waiting for recovery or as a bridge to transplant. MI.Two of these trials demonstrated significant
The CentriMag VAD (magnetically levitated harm associated with multivessel PCI, one trial
rotor) and the Abiomed AB5000TM (pneumati- demonstrated significant benefit, and one demon-
cally driven external ventricle) are two examples strated no change in mortality [1417]. There is
of temporary surgical MCS. an ongoing prospective randomized control trial
There are three outcomes of Mechanical in Europe, the CULPRIT-SHOCK trial
Circulatory Support: (1) Recovery, i.e. improve- (Clinicaltrials.gov: NCT01927549), which seeks
ment in hemodynamics such that MCS can be to answer this question.
removed. (2) Implantation of a durable LVAD, or
in rare circumstances, heart transplantation. (3)
Progressive multisystem organ dysfunction and Mechanical Circulatory Support
death. There are little data regarding the optimal
patient selection and timing of percutaneous Although the use of percutaneous mechanical circu-
MCS, and we recommend that each patient be latory support is increasing, there are limited data
evaluated on an individualized basis with input supporting this practice. The Intra-aortic Balloon
from a multidimensional team. Pump in Cardiogenic Shock II (IABP-SHOCK II)
100 M.G. Silverman and B.A. Olenchock

Tandem Heart Impella

Fig. 10.4 Images of percutaneous LVADs: Tandem Heart and Impella

Trial randomized 600 patients with CS from acute bleeding in patients with percutaneous LVADs
MI to IABP versus no IABP.All participants were versus IABP.Importantly, the Impella device
supposed to undergo early revascularization and used in the randomized control trial was the
receive guideline driven medical therapy. At 30 2.5. It remains unclear if the higher flow
days there was no difference in the primary end- Impella devices (CP and 5.0) would be asso-
point of all-cause mortality, and these results per- ciated with lower mortality when compared to
sisted at 12 month follow up [18, 19]. As a result, IABP.There are no randomized control trials
the ESC has recently changed their recommenda- that have evaluated the use of v-a ECMO in CS
tion for IABP in CS from acute MI to a class III despite its widespread use for this indication.
indication [9]. Despite the lack of evidence, both the ACC/
A meta-analysis was published in 2009 com- AHA and the ESC recommend consideration
paring the effect of percutaneous left ventricu- of mechanical circulatory support for patients
lar assist devices (LVADs) versus IABP on with CS from acute MI [3, 5]. Given the high
hemodynamics and 30-day mortality [20]. The mortality rate associated with CS in acute MI,
meta- analysis included two trials comparing it is likely that the use of percutaneous mechan-
the TandemHeart to IABP and one comparing ical c irculatory support will continue notwith-
the Impella to IABP.There was a significant standing the lack of hard outcome data.
improvement in hemodynamics (higher cardiac Additionally, these devices improve hemody-
index, higher MAP, and lower PCWP) with per- namic parameters and provide a critical bridge
cutaneous LVADs compared to IABP.However, to further clinical decision making, including
there was no difference in 30 day mortality, and considerations of durable VADs, cardiac trans-
there was a significantly increased risk of plant evaluations, and goals of care discussions
10 Management ofCardiogenic Shock 101

with the patients family and proxies. Future complicating acute myocardial infarction. JAMA.
2006;295:25115.
clinical trials are needed to better define patient
9. Windecker S, Kolh P, Alfonso F, Collet JP, Cremer J,
selection, choice of mechanical support, and Falk V, Filippatos G, Hamm C, Head SJ, Juni P,
optimal timing for device placement. Kappetein AP, Kastrati A, Knuuti J, Landmesser U,
Laufer G, Neumann FJ, Richter DJ, Schauerte P,
Sousa Uva M, Stefanini GG, Taggart DP, Torracca L,
Valgimigli M, Wijns W, Witkowski A, Authors/Task
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C, Sule S, Jain D, Gotsis W, Ahmed A, Frishman WH, Cardiology (ESC) and the European Association for
Fonarow GC.Trends in incidence, management, and Cardio-Thoracic Surgery (EACTS) Developed with
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G, Fernandez-Aviles F, Gershlick AH, Giannuzzi P, J.Pharmacologic therapies for acute cardiogenic
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A, Widimsky P, Zahger D.ESC guidelines for the trends in the utilization of short term mechanical cir-
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Westaby S, Anastasiadis K, Wieselthaler
4. Werdan K, Gielen S, Ebelt H, Hochman GM.Cardiogenic shock in ACS.Part 2: role of
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HM, Linderbaum JA, Morrow DA, Newby LK, JS.Percutaneous coronary intervention for cardio-
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White HD, Talley JD, Buller CE, Jacobs AK, Slater Louvard Y, Lefevre T, Garot P.Primary percutaneous
JN, Col J, McKinlay SM, LeJemtel TH.Early revas- coronary intervention in patients with acute myocar-
cularization in acute myocardial infarction compli- dial infarction, resuscitated cardiac arrest, and cardio-
cated by cardiogenic shock. SHOCK Investigators. genic shock. The role of primary multivessel
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8. Hochman JS, Sleeper LA, Webb JG, Dzavik V, Buller JH, Lee SH, Jeong MH, Choi DJ, Kim YJ, Gwon
CE, Aylward PE, Col J, White HD.Early revascular- HC.Percutaneous coronary intervention for noncul-
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Crit Care Med. 2014;47:1725. K, Schuler G.Intraaortic balloon counterpulsation in
18. Thiele H, Zeymer U, Neumann F-J, Ferenc M, Olbrich acute myocardial infarction complicated by cardio-
H-G, Hausleiter J, Richardt G, Hennersdorf M, genic shock. Final 12-month results of the randomised
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Management ofAcute Heart
Failure 11
GregoryT.Means andJasonN.Katz

Case Presentation atinine of 1.6mg/dL, and NT-pro-B-type natri-


uretic peptide level of 4800ng/mL.An
A 55 year old male with history of coronary electrocardiogram showed sinus tachycardia with
artery disease (CAD), chronic systolic heart fail- a chronic left bundle branch block. Initial cardiac
ure, and chronic obstructive pulmonary disease enzymes were negative. He was short of breath
(COPD) presented to the hospital with 5 days of and mildly hypoxic, with a room air oxygen satu-
cough, exertional dyspnea, and fatigue. The ration of 90%. A chest x-ray showed a right-
patients past medical history was notable for a sided pleural effusion and some subtle interstitial
remote history of emergent percutaneous coro- infiltrates bilaterally. The patient was admitted to
nary intervention for an acute anterior myocar- the inpatient hospitalist service, where he was
dial infarction complicated by systolic heart treated with intravenous (IV) ceftriaxone for
failure. His left ventricular ejection fraction community- acquired pneumonia, bronchodila-
(LVEF) was most recently noted to be 25%. He tors and oral prednisone for a COPD flare, and
had an implantable cardioverter-defibrillator given some IV fluids to treat acute renal failure
(ICD) for primary prevention. He had not been presumed to have been pre-renal in etiology.
seen by his cardiologist in several years. Over the course of several days, the patient
Upon arrival to the emergency department, the became increasingly more short of breath. He
patient was found to have a white blood cell was also noted to be more lethargic and less
count of 15K, serum sodium of 123mEq/L, cre- responsive. Laboratory analysis revealed an
increasing serum creatinine and persistent hypo-
Electronic supplementary material The online version natremia. Serial electrocardiograms (ECGs)
of this chapter (doi:10.1007/978-3-319-43341-7_11) con- revealed no dynamic changes suggestive of isch-
tains supplementary material, which is available to autho- emia, and cardiac biomarkers demonstrated a
rized users.
low-level elevation in cardiac-specific troponin.
He was transferred to the intensive care unit
G.T. Means (*)
Cardiology, Department of Medicine, University of (ICU) for management of hypotension and respi-
North Carolina, Chapel Hill, NC, USA ratory distress. There he was tachypneic and a
e-mail: gmeans@unch.unc.edu blood gas analysis revealed new metabolic acido-
J.N. Katz sis with associated respiratory compensation. His
Medicine, Mechanical Heart Program, Cardiac extremities were cool. A Foley catheter was
Intensive Care Unit, Cardiothoracic Intensive Care
placed with no return of urine.
Unit & Critical Care Service, Cardiovascular Clinical
Trials, University of North Carolina, The patient was placed on supplemental oxy-
Chapel Hill, NC, USA gen, given intermittent IV furosemide, and started

Springer International Publishing Switzerland 2017 103


R.C. Hyzy (ed.), Evidence-Based Critical Care, DOI10.1007/978-3-319-43341-7_11
104 G.T. Means and J.N. Katz

on a dopamine infusion for hypotension. Despite hours, supported by high-dose parenteral diuretic
increasing dosages of dopamine and furosemide, therapy.
the patient remained hypotensive and anuric. A swan-ganz catheter was placed in order to
Given an increasing work of breathing, he was assess the patients invasive hemodynamics, on
intubated and mechanically ventilated. his present level of circulatory support, and
revealed a pulmonary artery (PA) pressure of
Question What complications should be con- 50/30, mean PA pressure of 37mmHg, central
sidered when instituting invasive mechanical venous pressure of 13mmHg, Fick cardiac out-
ventilation for this patient? put of 6.2L/min, Fick cardiac index of 2.8L/min/
m2, and a mixed venous oxygen saturation of
Answer Worsening acidosis and progressive 68%. Over the next 3 days, IABP support was
cardiovascular collapse. gradually weaned from a 1:1 to 1:3 assist ratio to
ensure the patient would maintain stable hemo-
The decision to pursue intubation and mechan- dynamics off mechanical support. Subsequently,
ical ventilation for a patient with cardiogenic the device was removed while systemic antico-
shock should not be taken lightly. While hemo- agulation was held. On the fifth ICU day, the
dynamic instability and refractory respiratory patient was successfully liberated from mechani-
failure may make invasive ventilation unavoid- cal ventilation and transitioned to a nasal can-
able, complications should be anticipated. The nula. Unfortunately, multiple attempts to wean
patient was given benzodiazepines and neuro- his dobutamine infusion resulted in hemody-
muscular blockade to facilitate intubation. namic perturbation and worsening renal dysfunc-
Shortly after this, he became considerably more tion. He was ultimately transferred out of the ICU
hypotensive. He was placed on the ventilator for ongoing care, with plans to consider more
with an assist-control mode and 100% FIO2. His durable advanced heart failure therapies includ-
dopamine dosing was rapidly escalated and he ing home inotropic support, implantable left ven-
was given an ampule of sodium bicarbonate. His tricular assist device, or heart transplantation.
respiratory rate was initially set at 15 breaths per
minute, but when an ABG showed a pH of 7.2
and worsening metabolic acidosis, his ventilator Principles ofManagement
rate was quickly increased to provide more
appropriate respiratory compensation. Diagnosis
Given his unrelenting cardiogenic shock, an
intra-aortic balloon pump (IABP) was placed Acute Heart Failure (AHF) is a complex clinical
emergently at the bedside. This resulted in an syndrome which results from any structural or
immediate improvement in the patients mean functional impairment of ventricular filling or
arterial blood pressure. A dobutamine infusion ejection of blood. AHF may occur either due to
was then added to his pharmacologic regimen heart failure with reduced ejection fraction
for simultaneous afterload reduction and inotro- (HFrEF) or heart failure with preserved ejection
pic support. An hour after balloon counterpulsa- fraction (HFpEF). While HFrEF is simply char-
tion and inotropic therapy, the patients metabolic acterized by decreased cardiac contractility,
acidosis had completely resolved. A serum lac- HFpEF is commonly a result of diastolic dys-
tate which was initially markedly elevated function represented by impaired left ventricu-
had returned to the normal range. Serial ABGs lar relaxation and/or increased left ventricular
demonstrated resolution of his systemic acidosis filling pressures. HFpEF is often seen in asso-
and improvement in his hypoxemia, thus allow- ciation with comorbidities such as chronic
ing his ventilator to be weaned. Additionally, the hypertension and diabetes, and its prevalence
patients urine output improved over several increases with age. Diagnosis of HFpEF is aided
11 Management ofAcute Heart Failure 105

by echocardiography which can show abnormal doses of loop diuretics, a second diuretic agent
trans-mitral valve and/or pulmonary vein flow (e.g. metolazone, chlorothiazide) may be added
hemodynamics or impaired mitral annular (ACC/AHA Class IIA, LOE B). Use of a continu-
relaxation. ous diuretic infusion has not been shown to be
Dietary indiscretions, medication non-more effective than bolus therapy but may be con-
compliance, uncontrolled hypertension, arrhyth- sidered for ease of dosing. Potential diuretic-
mias, infections, catecholamine surge, valvular related side effects that can negatively impact
dysfunction, and ischemia are just a few of the patient outcomes include electrolyte disturbances
known triggers of acute decompensation. Elevated (hyponatremia, hypokalemia, and hypomagnese-
cardiac filling pressures classically produce symp- mia), metabolic alkalosis, ototoxicity, hyperurice-
toms of dyspnea, orthopnea, and paroxysmal noc- mia, and hypotension. It is important to serially
turnal dyspnea. Patients may also have evidence of monitor clinical signs, daily weights, urine output,
peripheral or pulmonary edema. Potential etiologies and electrolytes during treatment to determine the
for AHF include, but are not limited to, myocardial adequacy of decongestion and to avoid the untow-
ischemia/infarction, acute on chronic HFpEF or ard consequences of volume contraction (ACC/
HFrEF, acute or fulminant myocarditis, myocardial AHA Class I, LOE C). Under-treatment is com-
contusion, septic shock with myocardial depres- mon among hospitalized patients as seen in the
sion, acute valvular heart disease, cardiac arrhyth- Acute Decompensated Heart Failure National
mias, drug-related cardiotoxicity, profound Registry (ADHERE), and failure to achieve ade-
metabolic derangements, peripartum cardiomyopa- quate volume removal can be considered an
thy, or stress-induced cardiomyopathy [1, 2]. important risk factor for hospital readmission [3].
A thorough history and physical examination
are necessary to determine a cause of acute heart
failure in order to develop a comprehensive diag- Intravenous Vasodilators
nostic and management plan for each affected
patient. Complementary studies include labora- Nitrates, such as nitroglycerin (10350 mcg/
tory evaluation to risk-stratify the individual with minute) and sodium nitroprusside (5300 mcg/
AHF (Fig.11.1), ECG, and imaging modalities minute) promote smooth muscle relaxation,
(including echocardiography [Video 11.1] and resulting in decongestion and reduced cardiac
chest radiography). An ischemic evaluation with filling pressures. Unpredictable patient
myocardial perfusion imaging or cardiac cathe- responses to therapy and the risk for associated
terization can often be helpful in determining hypotension, however, mandate careful hemo-
whether ischemia is contributing to cardiac dynamic monitoring during treatment and the
decompensation. Interrogating a patients ICD, if consideration of ICU admission for all individu-
present, can also help to elucidate if arrhythmias als receiving parenteral nitrates. Nitroprusside
may be precipitating or preceding heart failure. has been shown to improve cardiac output,
maintain adequate mean arterial pressures, and
improve clinical outcomes in patients with
Diuretic Therapy acutely decompensated heart failure [4].
Nitroglycerin has a relatively short half-life and
Fluid removal through intravenous diuresis is an rapid onset of action. In AHF with significant
essential management strategy for AHF patients pulmonary congestion, nitroglycerin can
that present with congestion (2013 American improve arterial oxygenation and hemodynam-
College of Cardiology (ACC)/American Heart ics through venous vasodilation. Duration of
Association (AHA) Heart Failure Management vasodilator therapy may be limited by hypoten-
Guidelines Class I, Level of Evidence (LOE) B). If sion, drug tachyphylaxis (nitroglycerin), and
unable to achieve effective diuresis with escalating thiocyanate toxicity (nitroprusside).
106 G.T. Means and J.N. Katz

Fig. 11.1 Acute decom-


pensated heart failure
patient classification
(Adapted from Nohria and
Lewis [20], with
permission)

 mergent Mechanical Circulatory


E gestion that PA catheters improved mortality; it
Support did, however, result in increased adverse events
such as infection, pulmonary infarction, and
In situations of hemodynamic instability and bleeding [6]. It has widely been assumed that the
reduced cardiac output that is refractory to phar- morbidity of PA catheterization is primarily
macologic intervention, mechanical circulatory related to operator experience [7]. Despite their
support may be needed to reduce afterload and unproven mortality benefit, PA catheters remain
augment diastolic perfusion pressure (see Chap. a viable diagnostic tool particularly in challeng-
10, Management of Cardiogenic Shock). ing cases of AHF.The 2013 ACC/AHA guide-
lines for heart failure management recommend
PA catheter use in cases of refractory hypoten-
Evidence Contour sion, difficult volume status determination, renal
function deterioration despite therapy, and to
Pulmonary Artery (PA) Catheters guide inotrope therapy titration (Class IIA (LOE
C)) [2].
PA catheterization allows direct measurement of
cardiac filling pressures, pulmonary arterial
pressures, cardiac output, and calculation of both Inotropic Agents
systemic and pulmonary vascular resistance.
Widespread adoption of this technology in all Management of AHF is often limited by low
critically ill patients was tempered by findings blood pressure and systemic hypoperfusion.
which suggested an increased cost, mortality, Inotropic agents (e.g. dopamine, dobutamine,
and length of stay [5]. Specific to the heart fail- and milrinone) can augment contractility and
ure population, the Evaluation Study of chronotropy, resulting in increased stroke volume
Congestive Heart Failure and Pulmonary Artery and cardiac output (Table11.1). These goals are
Catheterization Effectiveness (ESCAPE) trial often accomplished with a tradeoff of increasing
was conducted to assess the role of PA catheter- myocardial oxygen demand, increased heart rate,
guided therapy in hospitalized individuals with and increased risk for tachyarrhythmias.
AHF.Similar to other studies, there was no sug- Improved hemodynamic response, however, has
11 Management ofAcute Heart Failure 107

Table 11.1 Intravenous inotropic agents used in management of HF


Typical infusion dose
Adrenergic agonists (mcg/kg/min) CO HR SVR PVR Possible adverse effects
Dopamine 510 Headache, nausea,
1015 arrhythmia
Dobutamine 2.55 Hyper- or hypotension,
520 headache, arrhythmia,
hypersensitivity
PDE inhibitor
Milrinone 0.1250.75 Hypotension, arrhythmia
Adapted from Yancy etal. [21]. With permission from Wolters Kluwer Health, Inc.
Abbreviations: CO cardiac output, HR heart rate, PDE phosphodiesterase, PVR pulmonary vascular resistance, SVR
systemic vascular resistance

not always translated into improved patient sur- Ultrafiltration


vival. The Outcomes of a Prospective Trial of
Intravenous Milrinone for Exacerbations of The use of ultrafiltration (UF) to enhance cardiac
Chronic Heart Failure (OPTIME-CHF) investi- decongestion has been examined extensively as
gators and data from the ADHERE registry an adjunct to diuresis. UF can remove excess
showed that these agents may actually increase fluid and small solutes via a dialysis circuit.
mortality when compared to standard diuretic or Initial small randomized controlled trials have
vasodilator therapies in AHF patients [810]. supported the utility and safety of UF when com-
Therefore, inotropes are best used for short peri- pared to traditional loop diuretics [13]. A follow-
ods in the ICU in situations suggestive of emerg- up trial, the Ultrafiltration Versus Intravenous

ing cardiogenic shock and end-organ failure. Diuretics for Patients Hospitalized for Acute
Inotropes can also be employed as a bridge to Decompensated Heart Failure (UNLOAD) study,
other definitive management strategies or used found that UF achieved greater net weight loss
for palliative care purposes. and reduced re-hospitalization rates at 90 days
[14]. However, subsequent studies have not con-
sistently corroborated these findings [15], and
 iuretic Dosing Intermittent
D have suggested a potentially greater adverse-
VersusContinuous event rate and cost-of-care among UF-treated
individuals. The financial implications and
Patients presenting with AHF and congestion potential morbidity of UF must therefore be
should receive intravenous loop diuretics as pro- weighed carefully in any decision to initiate ther-
gressive bowel wall edema may limit oral diuretic apy. The most recent AHA/ACC guidelines
absorption and efficacy. Less well understood is maintain a Class IIA (LOE B) recommendation
the differences between adopting a continuous for UF in patients refractory to standard diuresis.
infusion or interval dosing diuretic strategy. The
Diuretic Optimization Strategies Evaluation
(DOSE) trial compared intermittent IV diuresis Nesiritide
to a continuous infusion strategy, and found them
to have a similar effect on subjective symptoms Nesiritide, a form of synthetic B-type natriuretic
and renal function [11]. A more recent meta- peptide (BNP), is a potent vasodilating agent that
analysis evaluating ten randomized control trials may reduce cardiac filling pressures and improve
similarly found no difference in resulting renal ventricular unloading. Reported side-effects of this
function, electrolyte disturbances, length of hos- drug have included hypotension and acute renal
pitalization, or cardiac or all-cause mortality failure. In a large, multicenter, randomized trial, the
between these two approaches [12]. Acute Study of the Clinical Effectiveness of
108 G.T. Means and J.N. Katz

Nesiritide in Decompensated Heart Failure Masoudi FA, McBride PE, McMurray JJ, Mitchell JE,
(ASCEND-HF) study found that use of this drug Peterson PN, Riegel B, Sam F, Stevenson LW, Tang
WH, Tsai EJ, Wilkoff BL, American College of
did not improve patient survival, reduce readmis- Cardiology Foundation/American Heart Association
sion rates, or augment end-organ function when Task Force on Practice Guidelines. 2013 ACC/AHA
compared to placebo [16]. Therefore, while still Guideline for the Management of Heart Failure.
available, its routine use has been discouraged, and Circulation. 2013;128:e240327.
3. Fonarow GC, ADHERE Scientific Advisory
it is often only considered for patients with substan- Committee. The Acute Decompensated Heart Failure
tially elevated systemic vascular resistance in whom National Registry (ADHERE): opportunities to
intensive vasodilation may be advantageous. improve care of patients hospitalized with acute
decompensated heart failure. Rev Cardiovasc Med.
2003;4 Suppl 7:S2130.
4. Mullens W, Abrahams Z, Francis GS, Skouri HN,
Renal-Dose Dopamine Starling RC, Young JB, Taylor DO, Tang WH.Sodium
nitroprusside for advanced low-output heart failure.
At lower doses (12.5mg/kg/min), dopamine pre- JAm Coll Cardiol. 2008;52(3):2007.
5. Connors Jr AF, Speroff T, Dawson NV, Thomas C,
dominantly activates renal dopamine receptors, Harrell Jr FE, Wagner D, Desbiens N, Goldman L, Wu
with little systemic adrenergic stimulation. Diuresis AW, Califf RM, Fulkerson Jr WJ, Vidaillet H, Broste
in AHF is often limited by deteriorating renal func- S, Bellamy P, Lynn J, Knaus WA.The effectiveness of
tion, hypokalemia, and hyponatremia. Therefore, a right heart catheterization in the initial care of criti-
cally ill patients SUPPORT Investigators. JAMA.
low-dose dopamine strategy has been considered a 1996;276(11):88997.
possible treatment for diuretic-refractory patients. 6. Binanay C, Califf RM, Hasselblad V, OConnor CM,
In 2010, results of the Dopamine in Acute Shah MR, Sopko G, Stevenson LW, Francis GS, Leier
Decompensated Heart Failure (DAD-HF) trial CV, Miller LW, ESCAPE Investigators and ESCAPE
Study Coordinators. Evaluation study of congestive
showed that low-dose furosemide plus low-dose heart failure and pulmonary artery catheterization
dopamine resulted in less hypokalemia and less effectiveness: the ESCAPE trial. JAMA. 2005;293:
renal insufficiency, but with similar 60-day mortal- 57280.
ity, rates of readmission, and hospital lengths-of- 7. Iberti TJ, Fischer EP, Leibowitz AB, Panacek EA,
Silverstein JH, Albertson TE.A multicenter study of
stay [17]. A follow-up investigation the Dopamine physicians knowledge of the pulmonary artery
in Acute Decompensated Heart Failure II (DAD-HF catheter. Pulmonary Artery Catheter Study Group.

II) trial was stopped prematurely after finding JAMA. 1990;264:292832.
that the dopamine arm had a greater incidence of 8. Cuffe MS, Califf RM, Adams Jr KF, Benza R, Bourge R,
Colucci WS, Massie BM, OConnor CM, Pina I, Quigg
tachycardia with no demonstrable effect on the pri- R, Silver MA, Gheorghiade M, Outcomes of a
mary endpoint of all-cause mortality or re- Prospective Trial of Intravenous Milrinone for
hospitalization [18]. More recently, the Renal Exacerbations of Chronic Heart Failure (OPTIME-
Optimization Strategies Evaluation (ROSE-AHF) CHF) Investigators. Short-term intravenous milrinone
for acute exacerbation of chronic heart failure: a random-
trial similarly evaluated the use of low-dose dopa- ized controlled trial. JAMA. 2002;287(12):15417.
mine (2 mcg/kg/min) in patients hospitalized with 9. Abraham WT, Adams KF, Fonarow GC, Costanzo
AHF [19]. In this case, low-dose dopamine failed MR, Berkowitz RL, LeJemtel TH, Cheng ML, Wynne
to improve urine output or renal function. Despite J, ADHERE Scientific Advisory Committee and
Investigators, ADHERE Study Group. In-hospital
limited supporting evidence in AHF, however, low- mortality in patients with acute decompensated heart
dose dopamine continues to be used clinically and failure requiring intravenous vasoactive medications:
carries a Class IIB (LOE B) designation. an analysis from the Acute Decompensated Heart
Failure National Registry (ADHERE). JAm Coll
Cardiol. 2005;46(1):5764.
10. Stevenson LW.Clinical use of inotropic therapy for
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1. Hollenberg SM, Kavinsky CJ, Parrillo JE.Cardiogenic 4927.
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2. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey Jr Stevenson LW, Goldsmith SR, LeWinter MM, Deswal
DE, Drazner MH, Fonarow GC, Geraci SA, Horwich A, Rouleau JL, Ofili EO, Anstrom KJ, Hernandez AF,
T, Januzzi JL, Johnson MR, Kasper EK, Levy WC, McNulty SE, Velazquez EJ, Kfoury AG, Chen HH,
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Givertz MM, Semigran MJ, Bart BA, Mascette AM, sated heart failure. N Engl JMed. 2011;365(1):
Braunwald E, OConnor CM, NHLBI Heart Failure 3243.
Clinical Research Network. Diuretic strategies in 17. Giamouzis G, Butler J, Starling RC, Karayannis G,
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Engl JMed. 2011;364(9):797805. K, Kirlidis T, Tsaknakis T, Skoularigis J, Westermann
12. Wu M, Chang NC, Su CL, Hsu YH, Chen TW, Lin D, Tschpe C, Triposkiadis F.Impact of dopamine
YF, Wu CH, Tam KW.Loop diuretic strategies in infusion on renal function in hospitalized heart failure
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Kraemer M, Mackedanz S, Sobotka PA, Schollmeyer M, pensated heart failure II trial. Late Breaking Trials 2,
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Bart BA, Teerlink JR, Jaski BE, Fang JC, Feller ED, Butler J, Deswal A, Felker GM, OConnor CM,
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Semigran MJ, Felker GM, Chen HH, Hernandez AF, 20. Nohria A, Lewis E, Stevenson LW.Medical manage-
Anstrom KJ, McNulty SE, Velazquez EJ, Ibarra JC, ment of advanced heart failure. JAMA. 2002;287(5):
Mascette AM, Braunwald E, Heart Failure Clinical 62840.
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Effect of nesiritide in patients with acute decompen- Guidelines. Circulation. 2013;128:e240327.
Management ofAcute Coronary
Syndrome 12
ArmanQamar andBenjaminM.Scirica

Case Presentation He was treated by primary PCI with drug-eluting


stent placement. The patient had an uneventful
A 65 year-old man with history of hypertension, hospital course and was discharged on aspirin,
hypercholesterolemia and diabetes mellitus pre- ticagrelor, metoprolol, atorvastatin and lisinopril.
sented with two hours of severe substernal chest
pain radiating to left arm in addition to diapho-
resis and nausea. At the time of presentation to Principles ofManagement
the emergency department, his electrocardio-
gram showed inferior and posterior ST-segment Diagnosis
elevations (Fig.12.1) and serum troponin T was
0.30ng/mL (reference range <0.01ng/mL). He Acute coronary syndrome (ACS) refers to spec-
was treated with aspirin, intravenous nitroglyc- trum of conditions associated with acute myocar-
erin, ticareglor, metoprolol, atorvastatin, and dial ischemia and/or infarction that are most
heparin. frequently due to sudden decrease in coronary
blood flow from an atherothrombotic obstruction.
Question What approach should guide this The first step in the management of patients with
patients further management? ACS is prompt recognition, as beneficial effects
of therapy are greater when started soon after pre-
Answer All patients with acute coronary syn- sentation, and steadily decline in the hours that
drome with ST-segment elevation myocardial follow the first signs of myocardial injury. The
infarction (STEMI) should undergo emergent most common symptom that prompts the diag-
reperfusion therapy with primary percutaneous nostic evaluation of ACS is chest discomfort.
coronary intervention (PCI) or fibrinolysis. Classification of patients presenting with ACS is
based on electrocardiogram. Patients with persis-
This patient underwent emergent invasive cor- tent ST-segment elevation are deemed as having
onary angiography, which revealed a discrete ST-segment elevation ACS (STE-ACS) due to the
90% lesion in the proximal right coronary artery. presumed acute complete coronary occlusion and
are candidates for immediate reperfusion therapy
with either primary angioplasty or fi brinolysis.
A. Qamar B.M. Scirica (*) Absence of ST-segment elevation in a patient with
Cardiovascular Division, Department of Medicine,
ACS suggests non-ST segment elevation ACS
Brigham and Womens Hospital, Harvard Medical
School, Boston, MA, USA (NSTE-ACS) (Fig.12.2), which is further classi-
e-mail: bscirica@partners.org fied on the basis of biomarkers of myocardial

Springer International Publishing Switzerland 2017 111


R.C. Hyzy (ed.), Evidence-Based Critical Care, DOI10.1007/978-3-319-43341-7_12
112 A. Qamar and B.M. Scirica

Fig. 12.1 EKG demonstrating inferior and posterior ST-segment elevations in a patient with STEMI

necrosis. In an appropriate clinical setting, if the CAD contributes to an imbalance between oxy-
biomarkers are elevated the patient is classified as gen demand and supply, e.g., coronary endothe-
having a non-ST segment elevation MI (NSTEMI), lial dysfunction, coronary artery spasm, coronary
otherwise, without elevated biomarkers; the embolism, tachy-/bradyarrhythmias, anemia,
patient should be diagnosed with unstable angina respiratory failure, hypotension, and hyperten-
(UA) (Fig.12.3). The primary diagnostic bio- sion with or without left ventricular hypertrophy
markers of ACS are Troponin T and Troponin I. (Type 2 MI). We typically reserve the term acute
With contemporary troponin assays, CK-MB and coronary syndrome for patients with acute ath-
myoglobin are less useful for diagnosis of erothrombosis (Type 1 MI).
ACS.However, patients with end-stage-renal dis- Once the diagnosis of STEMI, NSTEMI or
ease and no clinical evidence of ACS could have unstable angina is made, the acute management
chronically elevated troponins. With conventional of the patient involves achievement of several
assays, this is more common with cardiac tropo- goals followed by initiation of therapy that may
nin T than cardiac troponin I.In the diagnosis of improve the long-term prognosis.
ACS, cardiac troponin values must manifest an
acute pattern consistent with the ischemic symp-
toms and electrocardiographic changes. I nitial Assessment andEarly Risk
ECG abnormalities and elevated biomarkers Stratification
in isolation are insufficient to make the diagnosis
of ACS, and must be interpreted in an appropriate Clinical assessment of a patient with ACS should
clinical context. MI must be discriminated from begin as soon as the patient arrives in the emer-
other acute and chronic causes of myocardial gency department and continues in hospital
injury, such as pulmonary embolism, severe sep- wards or the intensive care units. Initial assess-
sis, and end-stage renal disease, which occur ment includes evaluation for hemodynamic sta-
commonly in the intensive care setting. Moreover, bility and early risk stratification. A 12-lead ECG
MI may be further classified into those caused by should be obtained in all patients with suspected
acute atherothrombotic coronary events (Type 1 ACS within 10min after first medical contact and
MI) and those caused by supplydemand mis- immediately read by an experienced physician.
match, as is seen in instances of myocardial Early risk stratification in patients with ACS is
injury with necrosis where a condition other than critical to identify those at higher risk of adverse
12 Management ofAcute Coronary Syndrome 113

Fig. 12.2 EKG demonstrating diffuse T wave inversion (a) and ST depression in patients with NSTE-ACS (b)

Fig. 12.3Acute coronary


syndromes
114 A. Qamar and B.M. Scirica

cardiac events and may benefit from a more oxygen in normoxic patients with ACS may
aggressive therapeutic approach [14]. Analyses increase myocardial injury and mortality [8, 9].
from several large clinical trials have established
a number of predictors of adverse outcomes Nitrates Patients with continuing chest pain
among patients with STEMI, NSTEMI and should be initially treated with sublingual nitro-
unstable angina. However, with need for emer- glycerin (0.30.4mg) every 5min for up to three
gent reperfusion therapy through primary angio- doses. If ischemic pain persists, intravenous
plasty or fibrinolysis in patients with STEMI, nitroglycerin should be considered if not contra-
their clinical utility in early therapeutic decision- indicated. Nitrates should not be administered to
making is less relevant to STEMI patients. Some patients with severe aortic stenosis, or patients
of the early predictors of poor outcome from who received a phosphodiesterase-5 inhibitor,
STEMI include age, tachycardia, low blood pres- and should be cautiously used in patients with
sure, Killip class (Table12.1), time to reperfu- suspected right ventricular infarction due to their
sion, diabetes mellitus, anterior infarct location, dependence on pre-load [10].
smoking status, renal function and elevated bio-
marker. Examples of validated risk score include Morphine In patients with ACS, it is reasonable
the TIMI risk score for STEMI [5] and NSTEMI/ to administer intravenous morphine for analgesia
UA [6] and the GRACE Risk Score [7]. if the patient has continued chest pain despite
maximally tolerated anti-ischemic medications.
NSAIDS (except aspirin) in patients with ACS
Initial Medical Therapy are associated with increased risk of major
adverse cardiac events; therefore, its use in ACS
Patients with STEMI, NSTEMI and unstable patients is not recommended [11].
angina are treated with similar medical regimens,
with the exception of fibrinolysis, which should Beta-Adrenergic Blockers In patients with
be limited to STEMI patients. The timing of ini- ACS beta-blockers decrease myocardial isch-
tiation of medication may vary between STEMI emia and frequency of ventricular arrhythmias
and NSTEMI/UA. and increase long term survival [12]. Oral beta-
blocker therapy should be initiated within the
Anti-ischemic Therapy first 24 h in patients who do not have signs of HF,
Oxygen Supplemental oxygen should be admin- evidence of low-output state, increased risk for
istered to patients with ACS with arterial oxygen cardiogenic shock (>70years of age, systolic
saturation less than 90%, respiratory distress, blood pressure <120mmHg, heart rate >110bpm
cyanosis or other higher risk features of hypox- or heart rate <60bpm) or other contraindications
emia. The value of supplemental oxygen therapy to beta-blockade (e.g., PR interval >0.24s, sec-
in ACS patients without hypoxia is unclear, as ond- or third-degree heart block without a cardiac
several studies have suggested that supplemental pacemaker, active asthma, or documented reac-
tive airway disease). Beta-blockers should be
titrated to decrease the heart rate to less than 70/
min while maintaining a systolic blood pressure
Table 12.1Killip classification of acute myocardial
infarction above 120mmHg. A non-dihydropyridine cal-
cium channel blocker (CCB) (e.g., verapamil or
Class I No evidence of heart failure
diltiazem) should be considered in patients in
Class II Findings consistent with mild to moderate
heart failure (S3 gallop, lung rales less whom beta-blockers are contraindicated.
than one-half way up the posterior lung
fields or jugular venous distension) Statin therapy High-intensity statin (atorvas-
Class III Overt pulmonary edema tatin 80mg or rosuvastatin 40mg) should be
Class IV Cardiogenic shock started or continued in all patients with ACS
12 Management ofAcute Coronary Syndrome 115

Fig. 12.4 AHA/ACC recommendations for initial anti-thrombotic therapy in NSTE-ACS (From Amsterdam etal. [2].
Reprinted with permission from Elsevier Limited)

without contraindication. Statins in ACS reduces Antiplatelet Therapy


cardiac deaths, recurrent MI, need for repeat In the absence of an absolute contraindication,
revascularization, and stroke [13]. antiplatelet therapy with aspirin and a P2Y12
inhibitor is indicated in all patients with ACS.
Anti-thrombotic Therapy
All patients with ACS, in the absence of contra- Aspirin Uncoated aspirin (325mg) should be
indications, should receive aspirin, a second administered to all patients with ACS without
antiplatelet agent, and an anticoagulant. The contraindications as early as possible on pre-
AHA/ACC guidelines for anti-thrombotic med- sentation, and a maintenance dose of aspirin
ical management of NSTE-ACS is provided in (81162mg daily) should be continued
Fig.12.4. indefinitely.
116 A. Qamar and B.M. Scirica

P2Y12 receptor inhibitors P2Y12 receptor


inhibitors are administered to patients with ACS by 10mg/day). Ticagrelor as com-
according to the type of presentation and how pared with clopidogrel significantly
they are treated: reduces rate of death from vascular
causes, MI, or stroke [14].
In addition to aspirin, a P2Y12 inhibitor
STEMI patients should be administered for at least 12
Primary PCI- In patients with months to all patients with ACS [16].
STEMI treated with primary PCI, a
loading dose of a P2Y12 receptor
inhibitor should be given as early as Glycoprotein IIb/IIIa Inhibitors In patients
possible (clopidogrel [600mg fol- with very high risk features including, mark-
lowed by 75mg/day], ticagrelor edly elevated troponin, recurrent ischemic dis-
[180mg followed by 90mg BID], or comfort, dynamic ECG changes, or
prasugrel [60mg followed by 10mg/ hemodynamic instability not treated with a
day]). Ticagrelor as compared with P2Y12 inhibitor, a IIb/IIIa inhibitor (abcix-
clopidogrel significantly reduces rate imab, eptifibatide or tirofiban) may be consid-
of death from vascular causes, MI, or ered at the time of PCI.
stroke [14].
Fibrinolysis- In patients with STEMI Anticoagulation In patients with ACS, antico-
treated with fibrinolysis, clopidogrel agulation is recommended for all patients, in addi-
[300mg loading dose for tion to antiplatelet therapy irrespective of initial
age<=75year old or 75mg for treatment strategy. Anticoagulation is continued
>75year old, followed by 75mg/ for 48 h or until PCI is performed. Anticoagulation
day] should be administered at the options include:
time of presentation.
NSTEMI/UA patients
PCI- In patients with NSTEMI/UA
undergoing PCI with stenting should Unfractionated heparin (UFH) (initial
receive a loading dose of a P2Y12 loading dose of 60IU/kg (maximum
inhibitor at the time of the procedure 4,000IU) with initial infusion of 12IU/kg
(clopidogrel [600mg followed by per hour (maximum 1,000IU/h) adjusted
75mg/day], ticagrelor [180mg fol- per activated partial thromboplastin time),
lowed by 90mg BID], or prasugrel Low-molecular weight heparin (LMWH)
[60mg followed by 10mg/day]). (1mg/kg subcutaneous (SC) every 12 h
Ticagrelor and Prasugrel, as com- (reduce dose to 1mg/kg SC once daily in
pared with clopidogrel, significantly patients with creatinine clearance [CrCl]
reduce rate of death from vascular <30mL/min)). LMWH has been shown
causes, MI, or stroke [14, 15]. to be superior to UFH in STEMI patients
Other NSTEMI/UA patients- In treated with fibrinolysis.
patients with NSTEMI/UA treated Bivalirudin (0.10mg/kg loading dose
with either an early invasive approach followed by 0.25mg/kg per hour [only
or an ischemia driven approach in patients managed with an early inva-
should receive either clopidogrel sive strategy]), or
(600mg followed by 75mg/day) or Fondaparinux (2.5mg SC daily [only in
ticagrelor (180mg followed by 90mg NSTEMI/UA; additional heparin needed
BID), or prasugrel (60mg followed if patients received PCI]).
12 Management ofAcute Coronary Syndrome 117

Early Reperfusion STEMI; (2) the risks associated with fibrinolytic;


andRevascularization (3) the timing of presentation relative to symp-
tom onset; and (4) the anticipated transfer time
STEMI for primary PCI.In general, fibrinolysis may be
In patients with STEMI, rapid restoration of preferred in early presenting patients, particu-
myocardial blood flow reduces mortality [17]. larly when accompanied by a large myocardial
Current guidelines recommend primary PCI territory at risk, and the time to PCI is anticipated
within 90min or less for STEMI patients with to be longer than 90120min. Primary PCI
symptom onset within 12 h, who arrive at PCI- should be favored in late presenters, those with
capable hospital or 120min or less for those who shock, and when the diagnosis of STEMI is in
initially present to a non-PCI capable hospital doubt, or contraindications to fibrinolysis exist.
and are then transferred to a PCI-capable hospital
[1, 4]. Figure12.5 provides a flow diagram for NSTE-ACS
revascularization decisions in STEMI patient. In patients with NSTE-ACS who have refractory
Fibrinolytic therapy, unless contraindicated angina, hemodynamic or electrical instability an
should be initiated in patients with STEMI who immediate invasive coronary angiography should
cannot receive primary PCI within 120min of be performed with intent to perform revasculariza-
first medical contact (Table12.2). Decisions tion if appropriate based on coronary anatomy.
whether to transfer a patient for PCI vs. immedi- Furthermore, NSTE- ACS patients who have an
ate administration of a fibrinolytic should take elevated risk of adverse cardiac events should be
into account (1) the risk of complications of the treated with an early invasive strategy (coronary

STEMI patient who is a


candidate for reperfusion

Initially seen at a
nonPCI-capable
hospital+
Initially seen at a
PCI-capable
hospital DIDO time 30 min

Send to cath lab


for primary PCI
Transfer for Administer fibrinolytic
FMC-device time primary PCI agent within 30 min of
90 min arrival when
FMC-device anticipated FMC-
(Class I, LOE: A) time as soon as device >120 min
possible and
120 min (Class l, LOE: B)

(Class l, LOE: B)
Diagnostic angiogram
Urgent transfer for Transfer for
PCI for patients angiography and
with evidence of revascularization
failed reperfusion within 324 h for
or reocclusion other patients as
part of an
invasive strategy+
Medical PCI CABG (Class lla, LOE: B)
therapy only
(Class lla, LOE: B)

Fig. 12.5 AHA/ACC recommendations for reperfusion therapy choice in STEMI (From OGara etal. [1]. Reprinted
with permission from Elsevier Limited)
118 A. Qamar and B.M. Scirica

Table 12.2 Fibrinolytic regimens for STEMI


Patency rate
(90-min TIMI 2 or
Fibrinolytic agent Dose Fibrin specificitya Antigenic 3 flow)
Fibrin-specific
Tenecteplase (TNK-tPA) Single IV weight- ++++ No 85%
based bolusb
Reteplase (rPA) 10 U+10-U IV ++ No 84%
boluses given 30min
apart
Alteplase (tPA) 90-min weight-based ++ No 7384%
infusionc
Non-fibrin-specific
Streptokinased 1.5 million units IV No Yese 6068%
given over 3060min
From OGara etal. [1]. Reprinted with permission from Elsevier Limited
IV indicates intravenous, rPA reteplase plasminogen activator, TIMI thrombolysis in myocardial infarction, TNK-tPA
tenecteplase tissue-type plasminogen activator, tPA tissue-type plasminogen activator
a
Strength of fibrin specificity; ++++ is more strong, ++ is less strong
b
30mg for weight <60kg; 35mg for 6069kg; 40mg for 7079kg; 45mg for 8089kg; and 50mg for 90kg
c
Bolus 15mg, infusion 0.75mg/kg for 30min (maximum 50mg), then 0.5mg/kg (maximum 35mg) over the next
60min; total dose not to exceed 100mg
d
Streptokinase is no longer marketed in the United States but is available in other countries
e
Streptokinase is highly antigenic and absolutely contraindicated within 6 months of previous exposure because of the
potential for serious allergic reaction

angiography with intent to perform revasculariza- instead, they are treated with fibrinloysis as the ini-
tion within 24 h of admission) [18]. However, a tial reperfusion therapy. Initial studies showed no
delayed invasive strategy (coronary angiography clinical benefit with routine early PCI after success-
with intent to perform revascularization within ful fibrinolysis [20]. However, one study showed a
2572 h of admission) is reasonable for NSTE-ACS strategy of immediate transfer to a PCI-capable hos-
patients at low risk of adverse clinical events. pital within 6 h after successful fibrinolysis for PCI
Fibrinolytic therapy should not be used for reperfu- to be associated with lower incidence of primary
sion in patients with NSTE-ACS [19]. composite endpoint of death, recurrent MI, heart
failure or cardiogenic shock compared to standard
therapy alone with delayed coronary angiography
Evidence Contour or rescue PCI when indicated [21]. A strategy of
routine transfer and angiography at 324h is rea-
Several aspects of management in a patient sonable in patients who have undergone initial
with ACS remain without consensus. Recent reperfusion therapy with a fibrinolytic.
trials have attempted to settle uncertainty
behind many approaches involved in the care of
patients with ACS.  ulprit Only vs Complete
C
Revascularization inSTEMI

 outine Early PCI AfterSuccessful


R STEMI patients with obstructive non-culprit
Thrombolysis inSTEMI lesions are at increased risk of major adverse car-
diac events. However, past guidelines recommend
Many patients with STEMI present to hospitals that revascularization of culprit lesions only unless
are not PCI-capable and cannot undergo PCI within complicated by cardiogenic shock. Results from
the timelines suggested in current guidelines, observational and small randomized controlled
12 Management ofAcute Coronary Syndrome 119

trials (RCTs), though suggest potential benefit P2Y12 inhibitor for 12 months in patients treated
with complete revascularization in STEMI with a DES.Two recent randomized trials have
patients with obstructive non-culprit lesions. Such demonstrated that dual antiplatelet therapy
a strategy may be reasonable in selected patients beyond 12 months, compared with aspirin alone,
who have residual critical disease after primary reduced risk of stent thrombosis and major car-
PCI.Data from ongoing large RCTs will help to diac events, in particular in those patients with
define any role and timing of routine PCI of non- prior ACS [25, 26].
culprit stenoses in patients with STEMI [22].

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Complications ofMyocardial
Infarction 13
BrandonM.Jones andVenuMenon

Case Presentation hemoglobin 15.5mg/dL, serum creatinine


1.2mg/dl, and cardiac troponin I 6.06 ug/L.She
A 61 year old woman with a history of hyperten- was brought emergently to the cardiac catheter-
sion, tobacco abuse, and Wolf-Parkinson-White ization laboratory where she was found to have
syndrome with prior ablation 15 years ago, pre- 100% occlusion of a dominant, mid-left circum-
sented to the emergency department via ambu- flex artery. She underwent successful PCI with
lance with 4 days of indigestion and generalized placement of two overlapping drug-eluting stents,
chest discomfort, with more severe pain lasting and restoration of TIMI 3 flow to the infarct
several hours. EMS noted her to be tachycardic related artery (Table13.1). At the conclusion of
with HR 102bpm, and hypotensive with BP the case, the patient became agitated and pulse
83/61mmHg. The following 12-lead ECG was oximetry showed 88% saturation despite admin-
obtained (Fig.13.1). istering 100% oxygen by non-rebreather face-
The initial physical exam was notable for an mask. Blood-pressure was 78/58mmHg at this
anxious and diaphoretic patient with elevated time, and the patient required endotracheal intu-
jugular venous pressure, crackles at the lung bation and the initiation of vasopressor medica-
bases, and a left ventricular S3 with a soft sys- tions to stabilize her blood pressure.
tolic murmur adjacent to the lower left sternal
boarder. Initial blood tests showed WBC 12.5, Question What is the differential diagnosis for
the patients hemodynamic and respiratory
decompensation, and what should be done next
to confirm the diagnosis?
Electronic supplementary material The online version of
this chapter (doi:10.1007/978-3-319-43341-7_13) contains Answer The differential diagnosis must include
supplementary material, which is available to authorized mechanical complications of AMI including ven-
users. tricular septal rupture (VSR) (Video 13.1), papil-
B.M. Jones lary muscle rupture leading to acute mitral
Cardiovascular Medicine and Interventional regurgitation (MR) (Video 13.2), or free-wall
Cardiology, Cleveland Clinic Foundation, rupture leading to pseudoaneurysm or cardiac
Cleveland, OH, USA
tamponade (Video 13.3). Other etiologies to be
V. Menon (*) considered include RV infarction, acute blood
Pulmonary and Critical Care,
loss, iatrogenic hypotension secondary to medi-
Geisinger Medical Center,
Danville, PA, USA cation, and cath lab complications such as aortic
e-mail: menonv@ccf.org dissection or coronary perforation. The most

Springer International Publishing Switzerland 2017 121


R.C. Hyzy (ed.), Evidence-Based Critical Care, DOI10.1007/978-3-319-43341-7_13
122 B.M. Jones and V. Menon

Fig. 13.1 12-lead ECG

Table 13.1 TIMI flow definitions rapid way to confirm the diagnosis is with
TIMI Grade 0 There is no antegrade flow beyond immediate, trans-thoracic echocardiography.
(no perfusion) the point of occlusion
TIMI Grade 1 The contrast material passes The patient has demonstrated hemodynamic
(penetration beyond the area of obstruction but instability despite patency of the infarct related
without hangs up and fails to opacify the
perfusion) entire coronary bed distal to the
artery in the setting of a delayed presentation of
obstruction for the duration of the acute myocardial infarction (AMI). Based on her
cineangiographic filming sequence clinical and hemodynamic findings she is now
TIMI Grade 2 The contrast material passes across Killip Class IV (Table13.2). Understanding the
(partial the obstruction and opacifies the etiology of her hemodynamic instability is now
perfusion) coronary bed distal to the
obstruction. However, the rate of
crucial to guide further management. While this
entry of contrast material into the may represent LV failure in the setting of a large
vessel distal to the obstruction or MI, it is unusual that an isolated infarction in the
its rate of clearance from the distal distribution described will account for these find-
bed (or both) are perceptibly
slower than its entry into or
ings. Mechanical complications of MI, as listed
clearance from comparable areas above, must be considered and rapidly identified
not perfused by the previously or excluded. In this specific case, the bedside echo
occluded vessel e.g., the opposite demonstrated a severe, eccentric jet of mitral
coronary artery or the coronary
bed proximal to the obstruction
regurgitation. On a subsequent trans-esophageal
TIMI Grade 3 Antegrade flow into the bed distal echocardiogram (TEE), the diagnosis was con-
(complete to the obstruction occurs as firmed to be due to rupture and flail of the papil-
perfusion) promptly as antegrade flow into the lary muscle with prolapse into the left atrium
bed proximal to the obstruction, during systole. An image from the trans-
and clearance of contrast material
from the involved bed as rapid as esophageal echocardiogram obtained in the stan-
clearance from an uninvolved bed dard 4-chamber view is provided in Fig.13.2. The
in the same vessel or the opposite patient was taken emergently to the operating
artery room where a bioprosthetic mitral valve replace-
Data from Chesebro etal. [16] ment was performed. The patient was successfully
13 Complications ofMyocardial Infarction 123

discharged to a sub-acute nursing facility on hos- s ustained hypotension despite adequate intravas-
pital day 15, and made a full recovery. cular volume. Cardiogenic shock complicates
between 5 and 8% of cases of AMI in contempo-
rary databases and trials. Mortality for AMI in
Standard Approach toManagement general is <5% in contemporary series, but can
exceed 50% in patients with shock [1]. The most
Epidemiology common cause of shock after AMI is left ven-
tricular (LV) failure which represents 80% of
Cardiogenic shock in the peri-infarct setting is cases, but mechanical complications of AMI
defined as inadequate tissue perfusion and must be considered including isolated right ven-
tricular (RV) infarct, ventricular septal rupture
(VSR), free-wall rupture with ensuing cardiac
Table 13.2 Killip Class definitions
tamponade, and papillary muscle rupture leading
30-day to acute mitral regurgitation (MR). Data from the
mortality (in
Definition 1967) (%) SHOCK trial and the subsequent SHOCK regis-
Killip No clinical signs of heart <6 try documented the most common etiologies of
Class I failure cardiogenic shock among 1,422 patients after
Killip Signs of heart failure including <17 AMI (Fig.13.3) [2].
Class rhales or crackles in the lower
II lung fields, an S3, or elevated
jugular venous pressure
Diagnosis
Killip Frank, acute pulmonary 38
Class edema.
III The first step in managing patients with cardio-
Killip Cardiogenic shock or 81 genic shock after AMI is to identify the cause.
Class hypotension (measured as Specifically, one must attempt to differentiate
IV systolic blood
between mechanical complications that require
pressure<90 mmHg) and
evidence of peripheral immediate operative treatment as compared to LV
vasoconstriction (oliguria, failure alone. A rapid but thorough physical exami-
cyanosis, or sweating) nation is important in any patient with AMI and
Data from Killip and Kimball [17] shock. Cardiac auscultation may reveal the

Fig. 13.2Trans-
esophageal
echocardiogram
124 B.M. Jones and V. Menon

characteristic, harsh, holosystolic murmur of a d isplay a pulsus paradoxus along with the Kussmaul
VSR or a softer, apical murmur consistent with sign (increase in JVD with inspiration) which is
acute mitral regurgitation. Cardiac tamponade may usually absent in patients with cardiac tamponade.
be suspected based on jugular venous distention Physical exam may be challenging due to the
(JVD) and a pulsus paradoxus, or Becks triad of degree of hypotension, the need for mechanical
hypotension, distended neck veins, and muffled ventilation, and the physical environment. The
heart sounds. Patients with RV infarction may murmur of acute MR may be soft and difficult to
appreciate due to rapid elevation in left atrial pres-
sures. Similarly a large VSR in the setting of hypo-
tension may also be under appreciated.
Practically speaking, most mechanical compli-
cations of AMI can be definitively diagnosed by
prompt, bedside, trans-thoracic echocardiography
(TTE). In patients who are brought immediately to
the cardiac catheterization lab and/or in whom
echocardiography is not immediately available or
is inconclusive, the diagnosis can be made by LV
angiography and/or right heart catheterization.
Using a balloon-tipped catheter, VSR can usually
be confirmed by demonstrating a step-up in the
oxygen saturation of blood sampled from the right
ventricle or pulmonary artery as compared to the
right atrium, reflecting shunting of oxygenated
Fig. 13.3 Etiology of suspected cardiogenic shock in the blood from the LV to the RV through the ruptured
combined SHOCK trial registry and trial (total n=1422, septum, and subsequent mixing with relatively
only first 232 trial patients are included). Other includes deoxygenated blood returning to the right side of
shock caused by prior severe valvular disease, dilated car-
diomyopathy, excess beta-blockade/calcium channel the heart (Fig.13.4). Comparatively, patients with
blockade, hemorrhage, and procedural complications. severe mitral regurgitation will likely have tall
Aortic dissection, pulmonary embolism, and dynamic v-waves in the pulmonary capillary wedge tracing
subaortic outflow obstruction should also be considered. without a s ignificant step-up in oxygen saturations.
LVF left ventricular failure, MR mitral regurgitation, RVF
right ventricular failure, VSR ventricular septal rupture Importantly, not all mitral regurgitation in the
(Reproduced with permission from Menon, Heart, 2002 setting of AMI is due to papillary muscle rupture,
[2] with permission from BMJ Publishing Group Ltd) and it is important to distinguish MR due to LV

Fig. 13.4 Oximetry run


and shunt fraction SVC 67% 89%
calculation in a patient PA % Sat Artery % Sat RA
Qp/Qs =
with an apical VSR % Sat Artery % Sat PA
showing a step up in the
RV where there is mixing LA 99% 69%
Qp/Qs =
of venous blood with RA 99% 89%
99%
oxygenated blood from the
left ventricle that is 69%
30%
crossing the apical septal Qp/Qs =
10%
defect. Note: RA sat can be LV
estimated by (3 89% 99% Qp/Qs = 3
SVC+IVC)/4. Note: A RV
peripheral arterial sat is 75%
IVC
usually used as a surrogate VSR
for LV saturation
13 Complications ofMyocardial Infarction 125

dilation or posterior mitral leaflet restriction in the survival. Other mechanical support devices that
setting of an akinetic inferior wall (Video 13.4), have been used include the TandemHeart,
neither of which would typically be m anaged with Impella, and veno-arterial extra-corporeal mem-
emergent surgery. Thus, there should be a low brane oxygenation (ECMO). In this emergent
threshold to proceed to trans-esophageal echocar- setting, mechanical support is usually utilized as
diography (TEE) when the mechanism for the MR a bridge to decision. In those who stabilize and
is ambiguous on surface echocardiogram. recover, support is subsequently withdrawn. In
others who continue to be unstable, destination
support with an LVAD or consideration of the
Management ofLV Failure LVAD as a bridge to transplantation may be con-
sidered. Finally in the group of patients where
When LV failure is felt to be responsible for car- care may be deemed futile, support is not per-
diogenic shock, the next step in management is to formed or may be subsequently withdrawn.
ensure complete revascularization, as was clearly
demonstrated in the SHOCK trial [1]. Patients
with ongoing hemodynamic embarrassment  anagement ofMechanical
M
despite revascularization may require urgent Complications
mechanical support, most commonly in the form
of an intra-aortic balloon pump (IABP). Inotropic Mechanical complications of AMI have become
and vasopressor agents are sometimes used in less common in the era of early reperfusion, but
emergent situations to stabilize hemodynamics, mortality for these patients remains high
but have not been shown to improve hospital (Fig.13.5) [3]. Medical management of papillary

Fig. 13.5 Survival among 5,745 patients undergoing pri- complication of which 15 were papillary muscle rupture,
mary percutaneous coronary intervention (PCI) after 30 were free wall rupture with tamponade, and 10 were
ST-elevation myocardial infarction in the APEX-AMI ventricular septal rupture (Adapted from French [3] with
trial. A total of 52 patients (0.91%) had a mechanical permission from Elsevier Limited)
126 B.M. Jones and V. Menon

muscle rupture and VSR is limited, but involves are very unlikely to survive long enough for
afterload reduction with intravenous sodium surgery to be done electively, so this data is
nitroprusside. IABP placement is considered rou- mostly reflective of survival bias. Many have
tine care in hemodynamically unstable patients. hypothesized however that the particularly poor
The only definitive management strategy is surgi- outcomes with immediate surgery may be in part
cal repair, although a variety of mechanical sup- due to the weak, friable tissue of an acute infarct
port devices have been used to temporarily which holds sutures poorly. Thus, some experi-
stabilize hemodynamically unstable patients who enced centers have attempted a strategy of full
were not initially felt to be candidates for surgery. mechanical support with a planned, delayed sur-
When the diagnosis of a mechanical complica- gery in select patients, although the success of
tion can be made prior to primary percutaneous this strategy is currently limited to case reports
coronary intervention (PCI), immediate collabo- [6, 7]. In general, patients who are considered
ration between the interventional cardiologist acceptable candidates for immediate repair based
and cardiac surgeon is needed to determine the on factors including comorbidities, willingness
optimal approach for prompt restoration of coro- of the patient to pursue an aggressive strategy,
nary flow, while also considering the competing and comfort of the surgeon/medical center in
need to limit the administration of dual- managing the patient, should undergo surgical
antiplatelet therapy in patients undergoing emer- repair without delay.
gent surgery. In some cases, balloon angioplasty
without stent placement, followed by combined
coronary artery bypass graft placement with Percutaneous Closure ofVSR
immediate mechanical repair, may be the pre-
ferred option. Given the exciting evolution of structural cardiac
interventions over the past decade, many have
considered options for percutaneous closure of
Evidence Contour acute VSR, either as a definitive strategy, or as a
bridge to surgery after initial stabilization. This
Timing ofSurgery inVentricular strategy has been attempted for both primary
Septal Rupture closure and in the treatment of residual shunts
after surgical repair. Unfortunately, when
The optimal timing for surgery in unstable attempted in the immediate, post-infarct period,
patients with ventricular septal rupture is contro- or in patients with cardiogenic shock, mortality
versial given the exceedingly high mortality of remains high, similar to surgical series [8]. The
patients who are operated on in the immediate, procedure can be done safely however, and with
post-infarct period [4]. Complexity of the opera- technical success in the overwhelming majority
tion, relative surgical inexperience, acute right of cases. Thus, procedures done in the acute set-
ventricular dysfunction from infarction, ischemia ting should likely be limited to patients who are
or volume overload, patient comorbidities, or not initially surgical candidates, and undertaken
exposure to potent antiplatelet treatment prior to with the goal of reducing shunt fraction and
surgery may all contribute towards this finding. improving hemodynamic stability as a bridge to
The overall mortality of patients in the Society of a more definitive surgical repair. For patients in
Thoracic Surgeons National Database for patients the sub-acute to chronic period whose comor-
with VSR was 42.9%, but was significantly bidities continue to prevent definitive repair, per-
higher (>60%) in patients who underwent sur- cutaneous closure is an especially attractive
gery in the first 24 h, as compared to 18.4% in option, and initial clinical series have shown
patients in whom the repair was delayed until excellent success and low 30-day mortality in
after 7 days [5]. Unfortunately, unstable patients these populations [913].
13 Complications ofMyocardial Infarction 127

Intra-aortic Balloon Pump Database. Ann Thorac Surg. 2012;94(2):43643; dis-


cussion 434.
6. Tsai MT, Wu HY, Chan SH, Luo CY.Extracorporeal
IABP use in patients with cardiogenic shock after membrane oxygenation as a bridge to definite surgery
AMI has come under scrutiny given the results of in recurrent postinfarction ventricular septal defect.
the IABP-SHOCK II trial which failed to show a ASAIO J.2012;58(1):889.
7. Neragi-Miandoab S, Michler RE, Goldstein D,
difference in 30-day mortality among patients
DAlessandro D.Extracorporeal membrane oxygen-
that were randomized to IABP placement vs. ation as a temporizing approach in a patient with
open label controls [14]. Although well per- shock, myocardial infarct, and a large ventricle septal
formed, IABP placement in this study was per- defect; successful repair after six days. JCard Surg.
2013;28(2):1935.
formed only after revascularization and it
8. Thiele H, Kaulfersch C, Daehnert I, Schoenauer M,
included large subsets of patients with NSTEMI Eitel I, Borger M, etal. Immediate primary transcath-
ACS and post cardiac arrest. Criticisms of this eter closure of postinfarction ventricular septal
study have also included a high cross-over rate defects. Eur Heart J.2009;30(1):818.
9. Assenza GE, McElhinney DB, Valente AM, Pearson
with 10% of patients undergoing IABP place-
DD, Volpe M, Martucci G, etal. Transcatheter closure
ment despite randomization to the control group, of post-myocardial infarction ventricular septal rup-
and a trend toward higher utilization of LV assist ture. Circ Cardiovasc Interv. 2013;6(1):5967.
devices in the control group. Most clinicians feel 10. Holzer R, Balzer D, Amin Z, Ruiz CE, Feinstein J,
Bass J, etal. Transcatheter closure of postinfarction
that IAPB utilization continues to be a useful
ventricular septal defects using the new Amplatzer
adjunct in the hemodynamically unstable patient muscular VSD occluder: Results of a U.S.Registry.
with AMI.Based on the IABP SHOCK II trial Catheter Cardiovasc Interv. 2004;61(2):196201.
however, its utilization has been downgraded to a 11. Maltais S, Ibrahim R, Basmadjian AJ, Carrier M,
Bouchard D, Cartier R, etal. Postinfarction ventricu-
Class IIa LOE B recommendation from the 2013
lar septal defects: towards a new treatment algorithm?
ACCF/AHA guidelines on management of Ann Thorac Surg. 2009;87(3):68792.
ST-elevation MI [15]. Importantly, the IABP- 12. Bialkowski J, Szkutnik M, Zembala M.Ventricular
Shock II trial was not powered to look at the util- septal defect closure importance of cardiac surgery
and transcatheter intervention. Kardiol Pol. 2007;
ity of IABP placement in the setting of VSR,
65(8):10224.
where it is considered routine care. 13. Demkow M, Ruzyllo W, Kepka C, Chmielak Z,

Konka M, Dzielinska Z, etal. Primary transcatheter
closure of postinfarction ventricular septal defects
with the Amplatzer septal occluder- immediate results
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1. Hochman JS, Sleeper LA, White HD, Dzavik V, Wong 14. Thiele H, Zeymer U, Neumann FJ, Ferenc M, Olbrich
SC, Menon V, etal. One-year survival following early HG, Hausleiter J, etal. Intraaortic balloon support for
revascularization for cardiogenic shock. JAMA. 2001; myocardial infarction with cardiogenic shock. N Engl
285(2):1902. JMed. 2012;367(14):128796.
2. Menon V, Hochman JS.Management of cardiogenic 15. OGara PT, Kushner FG, Ascheim DD, Casey Jr DE,
shock complicating acute myocardial infarction. Chung MK, de Lemos JA, etal. 2013 ACCF/AHA
Heart. 2002;88(5):5317. guideline for the management of ST-elevation myo-
3. French JK, Hellkamp AS, Armstrong PW, Cohen E, cardial infarction: a report of the American College of
Kleiman NS, OConnor CM, etal. Mechanical com- Cardiology Foundation/American Heart Association
plications after percutaneous coronary intervention in Task Force on Practice Guidelines. JAm Coll Cardiol.
ST-elevation myocardial infarction (from APEX- 2013;61(4):e78140.
AMI). Am JCardiol. 2010;105(1):5963. 16. Chesebro JH, etal. Thrombolysis in Myocardial

4. Jones BM, Kapadia SR, Smedira NG, Robich M, Infarction (TIMI) Trial, Phase I: a comparison
Tuzcu EM, Menon V, etal. Ventricular septal rupture between intravenous tissue plasminogen activator and
complicating acute myocardial infarction: a contem- intravenous streptokinase. Clinical findings through
porary review. Eur Heart J.2014;35(31):20608. hospital discharge. Circulation. 1987;76(1):14254.
5. Arnaoutakis GJ, Zhao Y, George TJ, Sciortino CM, 17. Killip T, Kimball JT.Treatment of myocardial infarc-
McCarthy PM, Conte JV.Surgical repair of ventricu- tion in a coronary care unit. A two year experience
lar septal defect after myocardial infarction: outcomes with 250 patients. Am JCardiol. 1967;20(4):
from the Society of Thoracic Surgeons National 45764.
Management ofCardiac
Tamponade 14
DavidD.Berg, GregoryW.Barsness,
andBenjaminA.Olenchock

Case Presentation low-normal QRS voltages (Fig.14.1). A chest


x-ray showed stable reticular opacities in the
A 64-year-old man with a remote history of stage right middle and lower lobes at the sites of prior
IIIa adenocarcinoma of the lung treated with che- radiation treatment, as well as a prominent car-
motherapy and radiation presented to the emer- diomediastinal silhouette. A bedside echocardio-
gency department complaining of left-sided chest gram was performed which showed a large
pain and dyspnea. He had been diagnosed with a circumferential pericardial effusion with early
pulmonary embolism 2 weeks prior and was right ventricular (RV) diastolic collapse and
started on warfarin at that time. He felt well until exaggerated reciprocal respiratory variation in
the night before his current presentation when he mitral and tricuspid early-diastolic inflow veloci-
became acutely dyspneic while lying in bed. His ties (Fig.14.2 and Video 14.1).
triage vital signs were notable for a heart rate of
106 beats per minute (bpm), blood pressure of Question What is the appropriate next step in
92/70 mmHg, and respiratory rate of 28 breaths the management of the patients pericardial
per minute. A pulsus paradoxus of 18 mmHg was effusion?
measured by manual sphygmomanometer. A
12-lead ECG showed sinus tachycardia with Answer With few exceptions, patients with clin-
ical and supportive echocardiographic evidence
of cardiac tamponade should undergo emergent
drainage of the pericardial effusion by percutane-
Electronic supplementary material The online version of
ous needle pericardiocentesis. Isotonic fluids can
this chapter (doi:10.1007/978-3-319-43341-7_14) contains
supplementary material, which is available to authorized modestly increase cardiac output and mean arte-
users. rial pressure in about half of patients with tam-
D.D. Berg B.A. Olenchock (*)
ponade [1], but the results are generally transient,
Department of Medicine, Division of Cardiovascular and this intervention should not substitute for or
Medicine, Brigham and Womens Hospital and delay pericardiocentesis.
Harvard Medical School,
Boston, MA, USA
e-mail: bolenchock@partners.org
In this case, the patient was given a 500mL
bolus of normal saline over 10min with transient
G.W. Barsness
Department of Cardiovascular Diseases, Division of
improvement in his systolic blood pressure. The
Ischemic Heart Disease and Critical Care Cardiology, cardiac catheterization laboratory was activated
Mayo Clinic, Rochester, MN, USA and the patient was given two units of fresh

Springer International Publishing Switzerland 2017 129


R.C. Hyzy (ed.), Evidence-Based Critical Care, DOI10.1007/978-3-319-43341-7_14
130 D.D. Berg et al.

Fig. 14.1 Admission ECG

Fig. 14.2Pulse-wave
Doppler of mitral inflow
in the apical four chamber
view, showing >25%
respirophasic variation in
diastolic inflow velocities

f rozen plasma to reverse a supratherapeutic INR intensive care unit for ongoing monitoring, and
of 4.2. The pericardial space was accessed over the ensuing 48 hours, the output from his
through a subxiphoid approach using echocardio- pericardial drain tapered off to zero. A repeat
graphic and fluoroscopic guidance. The pericar- transthoracic echocardiogram showed a small
dial pressure was measured at 24 mmHg. A residual pericardial effusion without evidence of
pericardial drain was placed, 850mL of bloody tamponade, and the drain was removed.

fluid was removed, and the pericardial pressure Pericardial fluid analysis revealed a markedly
was reduced to 0 mmHg. His symptoms dramati- elevated red blood cell count (2 million/l) with
cally improved and his blood pressure increased negative culture and cytology. The clinical pic-
to 132/78 mmHg. He was admitted to the cardiac ture was felt to be consistent with a hemorrhagic
14 Management ofCardiac Tamponade 131

pericardial effusion due to excessive anticoagula- s imultaneously within the same patient. A variant
tion in the setting of subclinical radiation-induced form of cardiac tamponade associated with sys-
pericardial disease. temic hypertension has also been described [7],
and pericardial friction rubs can sometimes be
heard in lieu of muffled heart sounds in patients
Principles ofManagement with concomitant pericarditis [8].
The hallmark of cardiac tamponade is a para-
Hemodynamic Derangements doxical pulse (i.e., pulsus paradoxus), which is
defined by a drop in systolic arterial pressure of
Cardiac tamponade occurs when fluid accumu- greater than 10 mmHg during inspiration [2].
lates in the intrapericardial space, increasing intra- This occurs because the total intracardiac volume
pericardial pressure and impairing cardiac filling is relatively fixed due to the elevated intrapericar-
[2]. Tamponade is a continuum from mild impair- dial pressure. As venous return to the right side of
ment in cardiac filling to complete circulatory col- the heart increases with inspiration, the interven-
lapse [3]. The primary determinant of the tricular septum shifts to the left in an exaggerated
hemodynamic significance of a pericardial effu- fashion that further reduces left ventricular (LV)
sion is the intrapericardial pressure, which is stroke volume. The pulsus paradoxus can be
related to the volume of the effusion and the peri- measured in the intensive care unit by cuff sphyg-
cardial pressure-volume relationship. The latter is momanometry, pulse oximetry waveform analy-
heavily influenced by the chronicity of the effu- sis, or arterial waveform analysis when an arterial
sion, and hence slowly accumulating pericardial line is present [9]. The patient should not be
fluid can lead to a large effusion without the devel- asked to breathe deeply during blood pressure
opment of tamponade [4]. As intrapericardial pres- measurement since this can falsely exaggerate
sure increases, right and left-sided atrial and blood pressure variation over the respiratory
ventricular pressures also increase to maintain cycle. It is important to remember that several
end-diastolic volume. At some point, generally in other conditions can produce a pulsus paradoxus,
the range of 1520 mmHg, the intrapericardial including constrictive pericarditis, pulmonary
pressure approaches intracavitary pressures with embolism, hypovolemic shock, and severe
consequent reduction in ventricular transmural obstructive lung disease.
pressure and end-diastolic volume [5]. The heart
attempts to maintain cardiac output by increasing
contractility and heart rate, but these compensa- Non-invasive Diagnostic Testing
tory mechanisms are quickly exhausted and pro-
gressive circulatory collapse ensues. A 12-lead electrocardiogram (ECG) should be
obtained in all patients with suspected cardiac
tamponade. The characteristic abnormalities seen
Clinical Findings on ECG are decreased QRS voltage and electrical
alternans. Low QRS voltage is a non-specific
The classical findings of cardiac tamponade were finding that is also seen in infiltrative myocardial
reported in 1935 by a thoracic surgeon named disease, pulmonary disease, and obesity.
Claude Beck, who described the triad of hypoten- Electrical alternans, defined as beat-to-beat varia-
sion, elevated jugular venous pressure, and muf- tion in QRS amplitude related to anterior-
fled heart sounds in a series of surgical patients posterior swinging of the heart, is not sensitive
with cardiac tamponade due to intrapericardial but is relatively specific for cardiac tamponade
hemorrhage [6]. Although this constellation of [10]. The combination of P wave and QRS alter-
symptoms has remained the core clinical triad of nans further increases specificity [10].
tamponade, individual components may not be Transthoracic echocardiography is the imag-
seen in all patients and often do not occur ing modality of choice for evaluating the size,
132 D.D. Berg et al.

location, and degree of hemodynamic impair- 7. Severe dilation of the inferior vena cava (IVC)
ment caused by a pericardial effusion [11, 12]. (i.e., IVC plethora)
Several echocardiographic findings support the
diagnosis of tamponade [12, 13]: It is important to remember that cardiac tam-
ponade is a clinical and hemodynamic diagnosis.
1. Right atrial inversion for greater than one- If the clinical picture is consistent with cardiac
third of systole tamponade, the most important echocardio-
2. Right ventricular diastolic collapse (best graphic finding is the presence of a pericardial

appreciated in the parasternal long-axis and effusion. In this case, Doppler evaluation should
subcostal views) not delay expeditious treatment.
3. Reciprocal respiratory variation in RV and LV
volumes and consequent septal shifting (best
appreciated in the apical four-chamber view) Invasive Diagnostic Testing
4. Exaggerated reciprocal respiratory variation
(>25%) in mitral and tricuspid early-diastolic Invasive hemodynamic monitoring with a pulmo-
inflow velocities (i.e., E velocities) nary arterial catheter can provide additional evi-
5. Increase in the flow velocity integral in the dence for the diagnosis of cardiac tamponade.
pulmonary artery and decrease in the flow Supportive findings include equalization of dia-
velocity integral in the aorta during inspira- stolic pressures between cardiac chambers, which
tion (i.e., echocardiographic pulsus produces a characteristic blunted y-descent in
paradoxus) the right atrial tracing (Fig.14.3), and reciprocal
6. Reduced early-diastolic mitral annular tissue respirophasic variation in right and left-sided
Doppler velocity (i.e., E velocity) filling pressures [10]. Invasive monitoring is

Fig. 14.3 Right atrial


tracing demonstrating
blunted y-descent in a
patient with cardiac
tamponade
14 Management ofCardiac Tamponade 133

g enerally not necessary for diagnosing tampon- to fluid removal, and the pericardial fluid analysis
ade, and should be reserved for circumstances in should include specific gravity, cell count and dif-
which there is diagnostic uncertainty (e.g., hyper- ferential, total protein content, gram stain and cul-
tensive cardiac tamponade). It is also necessary ture for detection of bacteria (including
for the diagnosis of effusive-constrictive pericar- tuberculosis) and fungi, and cytology. When the
ditis (see section Evidence Contour) [14]. amount of pericardial fluid drained decreases to
less than 50mL per day, the catheter can generally
be removed [10]. In rare cases, paradoxical hemo-
Closed Pericardiocentesis dynamic deterioration and pulmonary edema asso-
ciated with ventricular dysfunction have been
In most cases, the treatment of cardiac tamponade reported after pericardial drainage. Known as peri-
should be oriented toward emergent drainage of cardial decompression syndrome (PDS), this com-
the pericardial effusion by percutaneous needle plication remains poorly understood [19].
pericardiocentesis. Intravascular volume expan-
sion with isotonic fluid resuscitation can lead to
modest and transient increases in cardiac output Surgical Drainage
and systolic blood pressure in about half of
patients. Since volume expansion also acutely Open pericardiocentesis is the preferred approach
increases left ventricular diastolic pressures, it is for treating tamponade that results from intra-
generally recommended that no more than 500mL pericardial bleeding due to myocardial rupture or
be administered [1, 15]. Positive inotropes are of aortic dissection. Loculated effusions and effu-
limited efficacy because endogenous adrenergic sions with excessive fibrinous material (e.g., clot-
activation is generally near maximal [2]. Intubation ted hemopericardium) may also require a surgical
should be avoided because positive- pressure approach. In these cases, surgery is generally per-
mechanical ventilation will further reduce ventric- formed through a limited subxiphoid incision.
ular transmural pressure and diastolic filling [10]. Most malignant pericardial effusions can be
Before proceeding with closed pericardiocente- treated with closed pericardiocentesis with a low
sis, it should be confirmed that there is clear clini- recurrence rate [20]. When hemodynamically
cal evidence of tamponade (including a pulsus significant malignant effusions do recur, they
paradoxus >10mmHg), and that the effusion is should generally be treated with open pericardio-
large enough anteriorly to safely access the fluid centesis and creation of a pericardial window
via a percutaneous approach. Whenever possible, [18]. Multiple pericardial biopsies, with or with-
the procedure should be performed by an experi- out pericardioscopic guidance, should be
enced provider in the cardiac catheterization labo- obtained at the time of surgery [21].
ratory. In the setting of circulatory collapse, a
bedside pericardiocentesis may be performed
emergently. Real-time transthoracic echocardio- Evidence Contour
graphic guidance is often used to identify the opti-
mal percutaneous approach (generally subxiphoid), Effusive-Constrictive Pericarditis
and has been shown to reduce procedural compli-
cations including myocardial puncture [16, 17]. Effusive-constrictive pericarditis (ECP) is a clini-
When the procedure is done in the cardiac cathe- cal syndrome in which constriction of the vis-
terization laboratory, fluoroscopic guidance and ceral pericardium occurs in the presence of a
invasive hemodynamic monitoring can also be tense pericardial effusion. It has been best char-
useful. Once the pericardial space has been acterized in patients presenting with cardiac tam-
accessed, a guidewire is passed through the sheath ponade who have persistently elevated right atrial
to facilitate introduction of a pigtail catheter [18]. pressure (i.e., failure to fall by 50% or to a new
Intrapericardial pressure should be measured prior level below 10 mmHg) after removal of the
134 D.D. Berg et al.

p ericardial fluid [22]. It is estimated that ECP 11. Cheitlin MD, Armstrong WF, Aurigemma GP, etal.
ACC/AHA/ASE 2003 guideline update for the c linical
complicates 510% of cases of clinical tampon-
application of echocardiography: summary article: a
ade, though there is significant geographic varia- report of the American College of Cardiology/American
tion in the prevalence [22]. In most cases, the Heart Association Task Force on Practice Guidelines
definitive treatment of ECP is pericardiectomy. (ACC/AHA/ASE Committee to Update the 1997
Guidelines for the Clinical Application of
Since invasive hemodynamic monitoring is
Echocardiography). Circulation. 2003;108(9):114662.
not routinely needed to diagnose cardiac tam- 12. Authors/Task Force M, Adler Y, Charron P, etal. 2015
ponade, there is interest in developing non-inva- ESC Guidelines for the diagnosis and management of
sive criteria to identify patients at higher risk of pericardial diseases: The Task Force for the Diagnosis
and Management of Pericardial Diseases of the
ECP who should undergo cardiac catheteriza-
European Society of Cardiology (ESC) Endorsed by:
tion at the time of pericardiocentesis [14]. The European Association for Cardio-Thoracic Surgery
Echocardiography and cardiac magnetic reso- (EACTS). Eur Heart J.2015;36(42):292164.
nance imaging have been explored but not yet 13. Wann S, Passen E.Echocardiography in pericardial
disease. JAm Soc Echocardiogr. 2008;21(1):713.
systematically correlated with invasive parame-
14. Syed FF, Ntsekhe M, Mayosi BM, Oh JK.Effusive-
ters [14]. In addition, it has been suggested that constrictive pericarditis. Heart Fail Rev. 2013;18(3):
patients with ECP have a distinct pattern of 27787.
immune activation when compared with patients 15. Sagrista-Sauleda J, Angel J, Sambola A, Alguersuari
J, Permanyer-Miralda G, Soler-Soler J.Low-pressure
who have effusive but non-constrictive pericar-
cardiac tamponade: clinical and hemodynamic pro-
dial disease [23]. Further investigation into file. Circulation. 2006;114(9):94552.
these differences may ultimately lead to the 16. Silvestry FE, Kerber RE, Brook MM, etal.

identification of novel serum or pericardial bio- Echocardiography-guided interventions. JAm Soc
Echocardiogr. 2009;22(3):21331; quiz 3167.
markers for the diagnosis of ECP.
17. Vayre F, Lardoux H, Pezzano M, Bourdarias JP,

Dubourg O.Subxiphoid pericardiocentesis guided by
contrast two-dimensional echocardiography in car-
diac tamponade: experience of 110 consecutive
References patients. Eur JEchocardiogr. 2000;1(1):6671.
18. Tsang TS, Enriquez-Sarano M, Freeman WK, etal.
1. Sagrista-Sauleda J, Angel J, Sambola A, Permanyer- Consecutive 1127 therapeutic echocardiographically
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Circulation. 2006;113(12):162232. DeCaro MV, Marhefka GD.Patient characteristics
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5. Shabetai R.Pericardial and cardiac pressure. cancer patients undergoing percutaneous pericardio-
Circulation. 1988;77(1):15. centesis for pericardial effusion. JAm Coll Cardiol.
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E.Elevated arterial blood pressure in cardiac tampon- biopsy: improvement with extensive sampling
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Hypertensive Crises
15
MarkSchmidhofer

Case Presentation Bedside ultrasound showed his optic nerve


sheath to be 5.3mm in diameter, B lines in both
A 67-year-old man was driven to the emergency lung fields, and hyperdynamic left ventricular
room by his wife when he began acting strangely function without regional wall motion abnormal-
and massaging his sternum. He previously had ities or valvular dysfunction. His electrocardio-
been reasonably healthy, with past medical his- gram (ECG) is shown in Fig.15.1.
tory significant for hypertension and hyperlipid- Basic metabolic profile demonstrated a plasma
emia. His prescribed medications included glucose of 139, creatinine of 1.4mg/dL and a
hydrochlorothiazide 12.5mg daily, enalapril BUN of 30mg/dL.His CBC was within normal
5mg twice daily, amlodipine 10mg daily, cloni- limits. Urinalysis showed trace proteinuria, mod-
dine 0.3mg twice daily, combination simvastatin est red blood cells, and no casts. His cardiac tro-
and ezetimibe, 81mg of aspirin, and prn ibupro- ponin was normal.
fen. His wife reported that his prescriptions all
ran out 2 days prior to admission. Question What is the diagnosis?
Physical examination revealed an overweight,
restless man who was oriented to name and loca- Answer Hypertensive crisis.
tion but not the date. When asked if he was having
chest discomfort, he looked up quizzically and The patient presented with significant hyperten-
rubbed his forehead. He was afebrile, respiratory sion and end-organ dysfunction including hyper-
rate was 28 breaths per minute, heart rate was 115 tensive encephalopathy, acute kidney injury, and
beats per minute, and blood pressure was 235/130. myocardial ischemia by ECG.He was treated with
His lungs were clear to auscultation. Cardiac IV labetalol and intravenous nitroglycerin. Within
exam revealed a regular S1 and S2, an S3 and the first hour, his blood pressure was reduced to
prominent S4, but no murmurs. His abdomen was 210/115. Labetalol and nitroglycerin were both up-
soft and non-tender. He had no edema. Neurologic titrated and furosemide was administered. Head
exam revealed no focal deficits. CT showed no acute abnormalities. Upon obtain-
ing further history, his wife mentioned that he was
a recreational drug user, and the previous day had
used cocaine. Urine drug screen was positive.
Benzodiazepines were started. An arterial line was
M. Schmidhofer placed for invasive blood pressure monitoring. A
Department of Medicine, University of Pittsburgh repeat cardiac troponin was elevated at 4.3.
School of Medicine, Heart and Vascular Institute, Over the course of the next 24 h, his blood
UPMC Health System, Pittsburgh, PA, USA
e-mail: schmidhoferm@upmc.edu pressure came down to 175/100 and heart rate

Springer International Publishing Switzerland 2017 135


R.C. Hyzy (ed.), Evidence-Based Critical Care, DOI10.1007/978-3-319-43341-7_15
136 M. Schmidhofer

Fig. 15.1 Admission EKG

to 90. His mentation improved, he said he was 180mmHg) accompanied by evidence of acute
having no chest discomfort, his lungs were end organ involvement, most commonly mani-
clear to auscultation, and the S3 was no longer fested by mental status changes, stroke, aortic
audible. The following day his previous oral dissection, or renal dysfunction. The initial dif-
anti-hypertensive regimen was reinstituted. 2 ferential diagnosis should include acute myocar-
days later, he had an exercise stress SPECT dial infarction, aortic dissection, stroke (ischemic
myocardial perfusion study, which demon- or hemorrhagic), subarachnoid hemorrhage,
strated no evidence of ischemia, and an ejection renal disease, drugs (such as amphetamines,
fraction of 60%. He was discharged home the cocaine, or dietary indiscretion with MAO inhibi-
following day. tors), head trauma, and other causes of autonomic
overactivity such as pheochromocytoma, auto-
nomic dysfunction, or antihypertensive drug
Principles ofManagement withdrawal [1].
Traditionally, fundoscopic examination is used
Diagnosis to identify papilledema and other hallmarks of
hypertension. However, few non-ophthalmologists
Hypertensive crisis is defined as uncontrolled are skilled at fundoscopic examination, and
hypertension (diastolic blood pressure neuro-ophthalmologists only agree on the Frisen
120mmHg and/or systolic blood pressure grading of 36% of the time [2].
15 Hypertensive Crises 137

previously been up regulated due to beta-


Modified Frisen Scale blockade. Thus, withdrawal is more commonly
Papilledema Grade, major findings seen with cessation of short acting as opposed to
long acting agents [6].
0 (Normal) The diagnosis of hypertensive encephalopathy
1 (Minimal degree of edema) C shaped is one of exclusion. Posterior reversible encepha-
halo that is subtle and grayish, with a lopathy syndrome (PRES) presents with head-
temporal gap; obscures underlying reti- ache, vomiting, altered mental status and seizures,
nal details with loss of gray-white differentiation and cere-
2 (Low degree of edema) Circumferential bral edema, largely in the posterior portions of
halo the brain (Fig.15.3) [7]. While it usually resolves
3 (Moderate degree of edema) Obscuration with treatment, there can be permanent deficits if
of 1 segment of major blood vessels not treated promptly.
leaving disc
4 (Marked degree of edema) Total obscura-
tion on the disc of a segment of a major Treatment ofHypertensive Crises
blood vessel on the disc
5 (Severe degree of edema) Obscuration of Patients with hypertensive crisis require intensive
all vessels on the disc and leaving the disc care unit admission and careful monitoring; given
the usual need for parenteral treatment, an arterial
Modified from Scott CJ Arch Ophthalmol line for continuous monitoring of the response to
2010;128(6):705 therapy should be placed in most cases. Selection
of a specific agent(s) is tailored to the clinical sce-
nario. Treatment goal is a reduction of systolic
Optic disk diameter greater than 5mm by ocu- blood pressure by 10% during the first hour, and
lar ultrasound (Fig.15.2) has been shown to 25% during the first 24h. In most instances the
detect intracranial pressure greater than 20 with goal is not to quickly normalize the blood pres-
an AUC of 0.93 [3]. sure, but to lower it in order to abort the crisis.
The patient in this case had evidence of pul- Many patients have had long-standing hyperten-
monary edema and thus received diuretics; how- sion and have auto-regulated their vasculature, and
ever, many patients with hypertensive crises are therefore a higher than normal blood pressure may
volume depleted, and in the absence of obvious be needed for adequate organ perfusion. After
volume overload, diuretics should generally be about 24 h of adequate control, patients are
avoided [5]. Renal injury from hypertensive cri- switched to an oral regimen. Management of acute
sis is manifest clinically by hematuria and creati- aortic dissection and ischemic stroke are excep-
nine elevation. Pathologically, renal injury is tions to these goals (see Chapters 11 and 12).
described as hypertensive nephrosclerosis, with
necrosis of renal capillaries and onion skinning
of small renal arterioles. Pharmacotherapy (Table15.1)
Withdrawal syndromes from cessation of anti-
hypertensive therapy are common. Mechanisms (a) Esmolol as an ultra-short acting beta blocker
are different depending on the discontinued med- with an almost immediate onset, and the
ication. Clonidine withdrawal is seen commonly, half-life is only 9min.
and attributed to a rapid return of catecholamine (b) Labetalol is a combined alpha- and beta-

secretion that has been suppressed during treat- adrenergic receptor blocker with a rapid
ment. Symptoms from beta blocker withdrawal onset. It is considered safe in patients with
are related to drug half-life versus the speed of active coronary disease because its beta-
down regulation of adrenergic receptors that had blockade does not cause reflex tachycardia.
138 M. Schmidhofer

Fig. 15.2Ocular ultra-


sound with optic nerve
measurement 3mm poste-
rior to retina arrows indi-
cate edges of the optic
nerve (Image courtesy of
Phil Lamberty, MD)

toxicity especially (but not only) when used at


high doses, for periods longer than 2448 h, or
in renal insufficiency.
(d) Nitroglycerin is predominantly a venodila-
tor, though intravenously at higher doses it
also has arteriolar dilating effects. Its anti-
hypertensive effects are less potent than
nitroprusside. Prolonged use can cause
methemoglobinemia.
(e) Nicardipine is a calcium channel antagonist,
and is an effective drug, but it has a longer
onset of action and half-life. It is used in sub-
arachnoid and intracranial hemorrhage
because it may reduce cerebral vasospasm,
and does not increase intracranial pressure as
may occur with nitroprusside.
(f) Hydralazine as a direct arteriolar dilator. It
can cause reflex tachycardia. Its use is
generally limited to pregnant women who
cannot use other agents.
Fig. 15.3 Axial flair image of MRI of patient with PRES, (g) Less commonly used agents:
demonstrating high signal activity (arrow) confined to the Clevidipine is a short acting dihydropyri-
white matter in a posterior distribution (Image courtesy of
Barton F Branstetter IV, MD) dine calcium channel blocker, with an
elimination time of between 5 and 15min.
(c) Sodium nitroprusside is a potent arteriolar It is an arteriolar dilator, and it is adminis-
vasodilator that has onset within a minute, and tered in a lipid emulsion, and is contrain-
lasts for about 10min. It is metabolized to dicated in patients with allergies to eggs
cyanide and can lead to cyanide or thiocyanate or soy products [9].
Table 15.1 Drugs used for the treatment of hypertensive crises
Contraindications and
Drug Dose Onset Duration Role Caveats Adverse effects Cost/Day
Sodium nitroprusside 0.25g/kg/min to Seconds 12min after Aortic dissection (in Avoid with CVA, ICH, Nausea, cyanate & $12$252
max of 8g/kg/min stopping conjunction with SAH.Caution in renal thiocyanate toxicity,
beta-blocker), insufficiency rates increased intracranial
hyperadrenergic >4g/kg/min can pressure, decreased
conditions, cause toxic levels in cerebral blood flow,
15 Hypertensive Crises

encephalopathy 3h (15) coronary steal


Nitroglycerine 5g/min titrate by 25min 510min Cardiac ischemia, CHF, Concurrent use PDE-5 Decreased CO $4$12
5g/min every hyperadrenergic states, inhibitors. NTG is headache, dizziness
15min to max of encephalopathy, renal mostly a venodilator
100g/min failure until high doses, care
in patients who are
volume depleted,
tachyphylaxis
common
Nicardipine 5mg/h increase by 510min 24h Aortic dissection in Tachyphylaxis, avoid Headache, flushing, $87$262
2.5mg increments q conjunction with beta calcium channel nausea, reflex
20min to max of blocker, cardiac blockers in CHF tachycardia, edema
15mg/h ischemia, stroke, CNS
bleed, hyperadrenergic
conditions,
encephalopathy, renal
failure
Clevidipine 12mg/h double 24min 520min Conjunction with beta Egg or soy allergy Headache, flushing, $260$1300
every 90 s to max of blocker, CHF, cardiac nausea, reflex
16mg/h ischemia, stroke, CNS tachycardia
bleed, hyperadrenergic
conditions,
encephalopathy, renal
failure
Fenoldopam 0.10.6g/kg/min 510min 1015min Renal failure aortic Glaucoma Hypotension, $163$985
titrate q15min dissection in headache,
conjunction with beta tachycardia, nausea,
blocker flushing
(continued)
139
Table 15.1(continued)
140

Contraindications and
Drug Dose Onset Duration Role Caveats Adverse effects Cost/Day
Labetolol 20mg bolus; repeat 510min 36h Myocardial ischemia; Bradycardia, heart $276
boluses of 2080mg hyperadrenergic states, block, bronchospasm
q10min or 2mg/min aortic dissection,
drip to total of encephalopathy
300mg/day
Esmolol 50g/kg load over 15min 1530min Myocardia ischemia, Bradycardia, heart $1270
1min; infusion at hyperadrenergic states, block, bronchospasm $19,501
2050g/kg/min aortic dissection,
titrate by 25g/kg/ encephalopathy
min q 10min to max
of 300g/kg/min
Enalaprilat 1.25mg over 5min 15min 46h Caution with renal Renal insufficiency, $5$20
titrate by 1.25mg insufficiency hyperkalemia.
increments q12 h to Unpredictable results
max of 5mg q6 h depending on plasma
renin levels
Phentolamine 510mg repeat 12min 510min Adrenergic crisis Reflex tachycardia, $6902
q515min or drip at headache, nausea $172,000
0.25mg/min
Hydralazine 1020mg bolus 10min 26h Pregnancy Reflex tachycardia $25
q30min until target results inconsistent
BP reached prolonged effect
Costs are as of 2015in a single teaching hospital
M. Schmidhofer
15 Hypertensive Crises 141

Fenoldopam as a dopamine agonist, and is  valuation forSecondary Causes


E
the only intravenous agent that increases ofHypertension
renal blood flow. It can increase intraocu-
lar pressure so should not be used in The prevalence of secondary hypertension is
patients with glaucoma [10]. higher in patients who have presented with a
Phentolamine is a nonselective alpha- hypertensive crisis compared with those who
adrenergic receptor blocker, and its use have not. Evaluation should be considered as
is largely in patients with pheochromo- guided by clinical presentation. Ten to forty-five
cytoma or tyramine ingestion in patients percent of patients with hypertensive crises have
who are on monoamine oxidase inhibi- renal artery stenosis [11]. Common secondary
tors. In these latter instances, one causes and suggested diagnostic strategies are
should not use beta-blockers until suf- outlined in Table15.3.
ficient alpha blockade has been Treatment of cocaine-induced hypertension
achieved; doing so could remove the includes benzodiazepines to reduce the central
vasodilatation of beta-1 stimulation, stimulatory effects of the cocaine, calcium
making the alpha mediated constriction antagonists, alpha blockers, and either nitroglyc-
worse. erin, nitroprusside, or clevidipine. Beta blockers
Enalaprilit is an intravenous form of enal- are generally avoided because of the risk of
april. The blood pressure response to this removing beta-1 mediated vasodilation [12].
agent can be variable because its action is
dependent on plasma volume and renin
activity. If the patient is hypovolemic with Evidence Contour
high plasma renin, excessive hypotension
has been reported. There are few high quality studies comparing
(h) Suggested drugs for specific clinical scenar- various treatment modalities and outcomes for
ios are shown in Table15.2. hypertensive crises. Those studies that are avail-

Table 15.2 Suggested drugs in particular clinical scenarios


Clinical scenario Suggested drugs
Cardiac ischemia Nitroglycerin, nitroprusside, or nicardipine plus a beta blocker
such as esmolol, labetalol, or metoprolol
Pulmonary edema/congestive heart failure Nitroglycerin, nitroprusside, or clevidipine; add beta blocker
if tachycardic
Aortic dissection Nitroprusside, clevidipine, or fenoldopam plus beta blocker
such as labetalol or esmolol
Renal dysfunction (hematuria or worsening Fenolodopam [16]
creatinine)
Catecholamine excess (pheochromocytoma, drug Nicardipine, clevidipine, nitroprusside; benzodiazepines for
withdrawal, cocaine, amphetamines) cocaine
Hypertensive encephalopathy Nicardipine, clevidipine, fenoldopam
Ischemic stroke (if BP >220/120 if not receiving Nicardipine, clevidipine, fenoldopam
thrombolytics, or >185/110 if receiving
thrombolytics)
Intracerebral hemorrhage (if BP >200 or mean Nimodopine, nicardipine, clevidipine, fenoldopam
>150)
Subarachnoid hemorrhage (if BP >160) Labetalol, nicardipine, clevidipine plus PO nimodopine for
spasm reduction
Pregnancy (>150/100) Labetalol, hydralazine, nitroglycerine if associated pulmonary
edema
142 M. Schmidhofer

Table 15.3 More common causes of secondary hypertension and suggested testing strategies
Cause Screening test Definitive test
Chronic renal disease UA/creatinine/renal ultrasound
Renovascular disease Duplex Doppler MRI, CT angiography
Coarctation of aorta BP arms and legs Echo, MRI, CT angiography
Primary aldosteronism Plasma and urinaryK Urinary aldosterone after salt
Plasma aldosterone/renin ratio load; adrenal CT; adrenal
vein sampling
Cushings disease Dexamethasone suppression
Pheochromocytoma Plasma free metanephrines
Urine metanephrines, catecholamines
(falsely elevated during stress)

able generally are observational, demonstrating general, however, most physicians avoid
the ability of an agent to achieve target blood beta blockers.
pressures in what timeframe, or comparing a
newer drug with an established agent, (e.g., clevi-
dipine versus nitroprusside, or nicardipine with
labetalol); in general, they demonstrate that all References
agents described in this chapter have utility in
appropriate circumstances, without clear superi- 1. Elliott WJ.Clinical features in the management of
selected hypertensive emergencies. Prog CV Dis.
ority of one versus another. 2006;48(5):31625.
2. Sinclair AJ, Burdon MA, Matthews TD, Jacks A,
Lawdwn M, Sivaguru A, Ball AK.Rating papilloe-
Specific Subsets ofPatients dema: an evaluation of the Frisen classification in
withHypertensive Crisis May Warrant idiopathic intracranial hypertension. JNeurol.
Specific Treatment Approaches 2012;259(7):140612.
3. Kimberly HH, Shah S, etal. Correlation of optic nerve
sheath diameter with direct measurement of intracra-
(a) Blood pressure control for acute neurologic nial pressure. Acad Emerg Med. 2008;15:2014.
syndromes. As discussed above, recom- 4. Marik PR, Varon J.Hypertensive crises. Chest.
mended target blood pressures vary in differ- 2007;131:194962.
5. Hart GR.Withdrawl syndromes and the cessation of
ent neurologic syndromes, and clear guidance anti-hypertensive therapy. Arch Int Med. 1981;141:
is not available for any of them (see Chapter 11257.
34) [8, 13]. 6. Servillo G, Bifulco F, DeRobertis E, Piazza O, Striano
(b) The use of beta blockers in cocaine intoxica- P, Tortora F, Striajno S, Tufano R.Posterior reversible
encephalopathy syndrome in intensive care medicine.
tion is unclear. The concern is that beta- Intensive Care Med. 2007;33:2306.
blockade removes the beta mediated 7. Jauch EC, Saver JL, Adams HP, Bruno A, Connors JJ,
vasodilatation and thus can make the hyper- Demaerschalk BM, Khatri P, McMullan PW, Qureshi
tension worse, and can make vasospasm AI, Rosenfield K, Scott PA, Summers DR, Wang DZ,
Wintermark M, Yonas H.Guidelines for the early
worse. Given the significant recidivism rate, management of patients with acute stroke: a guideline
having patients on chronic beta-blockade for healthcare professionals from the American Heart
may be unwise. However, in the presence of Association/American Stroke Association. Stroke.
LV dysfunction or significant arrhythmias, 2013;44:870947.
8. Varon J.Treatment of acute severe hypertension.
the benefits may outweigh the risk, and at Drugs. 2008;68(3):28397.
least one study raises the possibility that 9. Elliot WJ, Weber RR, Roy F, Nelson KS, Oliner CM,
beta-blockers are not detrimental [14]. In Fumo MT, Gretler D, Mccray G, Murphy MB.Renal
15 Hypertensive Crises 143

and hemodynamic effects of fenoldopam versus nitro- 13. Dattilo PB, Hailpern SP, Fearon K, Sohal D, Nordin
prusside in severe hypertension. Circulation. 1990;81: C.Beta blockers are associated with reduced risk of MI
9707. after cocaine use. Ann Emerg Med. 2008;51:11725.
10. Kitiyakara C, Guzman NJ.JASN. 1998;9(1):13342. 14. Shusterman NH, Elliott WJ, White WB.Fenoldopam
11. Maraj S, Figueredo V, Morris L.Cocaine and the but not nitroprusside improves renal function in
heart. Clin Cardiol. 2010;33(5):2649. severely hypertensive patients with normal or
12. Rothwell PM.Blood pressure in acute stroke; what impaired baseline creatinine. Am JMed. 1993;95:
questions remain? Lancet. 2015;385:5825. 1618.
Atrial Fibrillation andOther
Supraventricular Tachycardias 16
DanielSedehi

Case Presentation central pulses. He had 2+ pitting edema to his


knees. He had no focal neurological deficits and
A 49 year old male with a history of non-ischemic his abdominal exam was unremarkable. His labs
cardiomyopathy presented with worsening dys- demonstrated a creatinine at 1.8mg/dL, a sodium
pnea on exertion, nausea, and three days of of 130mmol/L, a potassium of 4.3mmol/L, and
altered sensorium. A recent echocardiogram a magnesium of 2.3mg/dL.His lactate was 2.5.
demonstrated severely reduced left ventricular ECG is shown in Fig.16.1.
ejection fraction (LVEF) of 1520%, moderate-
to-severe functional mitral regurgitation, a dilated Question What is this rhythm?
left ventricle, and a severely enlarged left atrium.
At his prior office visits, electrocardiograms Answer Atrial fibrillation
demonstrated sinus rhythm. He had been on a
stable medical regimen of carvedilol 12.5mg This ECG demonstrates an irregularly irregu-
twice daily, lisinopril 40mg daily, spironolactone lar rhythm without discernable p-waves, consis-
25mg daily, furosemide 40mg twice daily and tent with atrial fibrillation (AF). The patient
he has not missed any of his medications. He presented in cardiogenic shock. It was uncertain
denied dietary indiscretion or symptoms of infec- whether the AF was simply one manifestation of
tion. His heart rate was 106 beats per minute, his decompensated heart failure or whether the
blood pressure 88/60mmHg, respiratory rate 26, onset of AF with a rapid ventricular rate was the
temperature 98.8F, and oxygen saturation 90% primary reason for his decompensation, due to the
on room air. On examination, he had cool extrem- rapid rate and loss of atrial contribution to ven-
ities, elevated jugular venous pressure to the tricular filling. The duration of the arrhythmia was
mandible while seated at 90, bilateral rales half unknown, so the patient could not safely undergo
way up his lung fields, a prominent S3 gallop, a elective cardioversion without anticoagulation
3/6 holosysolic murmur best at the apex radiating and transesophageal echocardiography (TEE) to
to the axilla, and irregularly irregular, thready verify the absence of atrial thrombus. Because he
was not hypotensive, immediate direct current
cardioversion (DCCV) was not performed.
Options for control of the ventricular rate were
D. Sedehi limited by his cardiogenic shock. He was admit-
Cardiovascular Medicine, Knight Cardiovascular
ted to the ICU where a heparin drip was initiated,
Institute, Oregon Health and Science University,
Portland, OR, USA and he was treated with intravenous furosemide.
e-mail: sedehi@ohsu.edu With diuresis alone, his shock state resolved, his

Springer International Publishing Switzerland 2017 145


R.C. Hyzy (ed.), Evidence-Based Critical Care, DOI10.1007/978-3-319-43341-7_16
146 D. Sedehi

Fig. 16.1 12 Lead ECG with atrial fibrillation

creatinine, sodium, and lactate normalized, but longer than 7 days), or permanent [1]. Physical
his symptoms of dyspnea persisted. He underwent exam demonstrates an irregularly irregular
a TEE guided cardioversion, restoring sinus heart rate on auscultation of the heart and pal-
rhythm. He ultimately was discharged home with pation of the pulse. ECG findings include a
follow up with electrophysiology. variable R-R interval, with no discernable
P-wave preceding each QRS complex. R-R
variability may be less apparent at elevated
Principles ofManagement heart rates (Fig.16.2).
Echocardiograms demonstrate absence of A
Diagnosis waves on pulse- and continuous-wave Doppler of
the mitral valve in the apical views, along with a
Conditions which increase the risk for new single E wave on M-Mode of the mitral valve in
onset AF: the parasternal long axis view (Fig.16.3).
AF may be asymptomatic or associated with a
spectrum of symptoms ranging from palpitations
Triggers for Atrial Fibrillation to those of heart failure or cardiogenic shock,
Acute/chronic pulmonary: pneumonia, severe dyspnea, and lack of energy.
pulmonary embolism, COPD exacerba-
tion, sleep apnea
Heart failure, myocardial infarction, mitral
Physiologic Effects
valve disease
Cardiac or thoracic surgery
The deleterious effects of AF come in two pri-
Acute or chronic hyperthyroidism, alcohol
mary categories: hemodynamic embarrassment
use
and cardioembolism. Hemodynamically, AF
results in the lack of mechanical contraction of
the left atrium, resulting in depressed preload of
The incidence of AF increases steadily with the left ventricle. In the setting of heart failure
advancing age. AF is commonly classified into with reduced ejection fraction (HFrEF) or severe
three categories: paroxysmal, persistent (sustained aortic stenosis, this acute loss of atrial kick can
16 Atrial Fibrillation andOther Supraventricular Tachycardias 147

Fig. 16.2 R-R variability with very high ventricular rates

Fig. 16.3Mitral inflow


pattern in atrial fibrilla-
tion, with no atrial con-
traction, just passive filling
(E wave only, no A wave)

result in a meaningful decline in cardiac stroke This model has been validated and helps clinicians
volume and cardiac output [2]. Patients with and patients understand the long term risk for
heart failure with preserved ejection fraction embolic events [6].
(HFpEF) are exquisitely sensitive to preload so Another model, the HAS-BLED score, uses
acutely lowering their preload conditions can similar inputs, but can help calculate the possibil-
have rapid deleterious effects on their cardiac ity of a severe bleeding event during anticoagula-
function. The same principle applies to patients tion (e.g. http://www.mdcalc.com/has-bled-score-
with hypertrophic obstructive cardiomyopathy for-major-bleeding-risk/) (Table16.2) [7]. These
(HOCM) and pulmonary hypertension [3]. In models help predict risk of ischemic events over
structurally normal hearts, some patients may be the course of years, so apply less to the acute
quite symptomatic from the loss of the atrial inpatient management of patients with AF.
kick, and others may be asymptomatic. In
many asymptomatic patients, their first sign of
the arrhythmia is an embolic event such as a Treatment Strategies
stroke [4].
A patients risk of embolic events such as Aligned with physiologic effects, treatment of
cerebrovascular accidents (CVAs) or ischemic AF has two main goals: hemodynamic and
bowel can be calculated using a prognostic model embolic risk mitigation. There are two potential
such as the CHADS2-Vasc score that is available strategies to mitigate the hemodynamic impact
through a variety of online risk calculators (e.g. of AF rate control and rhythm control. Long-
http://www.mdcalc.com/cha2ds2-vasc-score-for- term outpatient management of AF was assessed
atrial-fibrillation-stroke-risk/) (Table16.1) [5]. in the AFFIRM trial and despite long-standing
148 D. Sedehi

Table 16.1 CHADS2-Vasc score [5] Table 16.2 HAS-BLED score [7]
Risk factor Score Points
Congestive heart failure/LV dysfunction 1 Letter Clinical characteristic awarded
Hypertension 1 H Hypertension 1
Age75 y 2 A Abnormal renal and liver 1 or 2
function (1 point each)
Diabetes mellitus 1
S Stroke 1
Stroke/TIA/TE 2
B Bleeding 1
Vascular disease (prior myocardial infarction, 1
peripheral artery disease, or aortic plaque) L Labile INRs 1
Age 6574 y 1 E Elderly 1
Sex category (i.e. female gender) 1 D Drugs or alcohol (1 point each) 1 or 2

debate as to the applicability of the outcome, no whom AF worsens their symptoms from heart
significant mortality benefit to rhythm control failure. The options for rhythm control include
was identified [8]. Inpatient management of AF antiarrhythmic medications, direct current car-
is more guided by symptoms and clinical dioversion (DCCV), and/or catheter ablation.
presentation. DCCV should be considered in patients who are
displaying evidence of cardiogenic shock, not
Rate Control solely defined as low blood pressures, but with
Patients with AF frequently present with rapid evidence of end organ hypoperfusion possibly
ventricular rates which drive their symptoms. contributed to by loss of atrial contraction. This
Heart rate control is achieved by two main can be particularly important in preload depen-
classes of medications: beta-blockers and cal- dant states such as severe aortic stenosis and
cium channel blockers. Both classes of medica- hypertrophic obstructive cardiomyopathy.
tions slow AV nodal conduction and exert Antiarrhythmic medications are used in accor-
negative inotropic effects. Care must be exer- dance with ACC/AHA guidelines and emphasize
cised with the use of these agents, particularly the importance of structural heart disease and
in patients with HFrEF, because of their nega- coronary artery disease in the selection of the saf-
tive inotropic effects. Diltiazem carries a greater est and most effective medication (Fig.16.4; see
risk of inducing cardiogenic shock and even ACCF/AHA guidelines http://content.onlinejacc.
death in patients with HFrEF, especially if they org/article.aspx?articleid=1854230) [1].
are in a decompensated state, versus metoprolol.
Esmolol may be a reasonable option with very Stroke Prevention
rapid offset that can be trialed in patients who Anticoagulation is critical in patients with
may not tolerate rate controlling agents with AF.Commonly used medications include intra-
negative inotropic effects. Digoxin has modest venous unfractionated heparin or subcutaneous
efficacy but is sometimes the best alternative low-molecular weight heparin. Prior to undergo-
when beta-blockers and calcium channel block- ing DCCV or chemical cardioversion, patients
ers are not tolerated. Extrapolation of data from need to be therapeutic on anticoagulation and
the RACE 2 trial suggests that targeting a heart most should undergo a TEE, assessing for the
rate of less than 110bpm is a safe management presence of left atrial appendage thrombus, if a
strategy, assuming hemodynamic stability prolonged period of anticoagulation (4weeks)
(Table16.3) [9]. is not possible prior to elective cardioversion
[10]. If an atrial thrombus is present, it is
Rhythm Control recommended to maintain therapeutic anticoagu-
This method is preferred for patients with acute lation for at least 1 month, after which a repeat
hemodynamic collapse, acute severe symptom- TEE should be performed to assess for resolution
atic AF with controlled rates, and patients in of the thrombus [11]. With no thrombus present
16 Atrial Fibrillation andOther Supraventricular Tachycardias 149

Table 16.3 Common dosage of intravenous medications for rate control of AF


Intravenous administration Usual oral maintenance dose
Beta blockers
Metoprolol tartrate 2.55.0mg IV bolus over 2min; up to 3 doses 25100mg BID
Esmolol 500 mcg/kg IV bolus over 1min, then 50300 N/A
mcg/kg/min IV
Nondihydropyridine calcium
channel antagonists
Verapamil 0.0750.15mg/kg IV bolus over 2min; may 180480mg QD (ER)
give an additional 10.0mg after 30min if no
response, then 0.005mg/kg/min infusion
Diltiazem 0.25mg/kg IV bolus over 2min, then 120360mg QD (ER)
515mg/h
Others
Digoxin 0.25mg IV with repeat dosing to a maximum 0.1250.25mg QD
of 1.5mg over 24h
Amiodaronea 300mg IV over 1h, then 1050mg/h over 24h 100200mg QD
a
Amiodarone should not be used when cardioversion is contraindicated such as in patients not previously
anticoagulated

Fig. 16.4 ACCF/AHA guidelines for selection of antiarrhythmic drug therapy for AF

in the left atrial appendage, DCCV can be per- period. For patients who acutely develop AF
formed safely while on anticoagulation. The within the hospital or the exact time of onset is
highest risk of embolic phenomena is present known via symptomatology, risk benefit ratio lies
within the first month after DCCV, so diligence in favor of DCCV without TEE guidance if done
must be applied to anticoagulation during this within the first 48 hours [1].
150 D. Sedehi

 ther Supraventricular Tachycardias


O Table 16.4 Differential of short- and long-RP tachycardias
(SVT) Short RP tachycardias Long RP tachycardias
Typical AV nodal reentrant Atrial tachycardia
Aside from AF, other non-sinus supraventricular tachycardia
tachycardias are common in critically ill patients. AV reentrant tachycardia using Sinus tachycardia
Like AF, these are narrow complex tachycardias accessory pathway
Atrial tachycardia with first Atrial flutter
unless there is aberrant conduction. These are typi-
degree AV block
cally divided according to the relationship between
Junctional tachycardia AV reentrant
the R-wave and the P-wave, so called short- or long- tachycardia
RP tachycardia. See Table16.4 and Fig.16.5 for the
differential of short- and long-RP tachycardia.
Hemodynamically, these SVTs can have simi- of stay and morbidity [14]. Strategies here often
lar features to AF.In the setting of hemodynamic focus on rhythm control, most often achieved
instability and hypotension, DCCV is an appro- with the antiarrhythmic amiodarone [15].
priate first response. Diagnosis and acute man- Anticoagulation with heparin products may pose
agement often fall under the same action, as a prohibitive risk for bleeding, so discussion with
many SVTs rely on the AV node for completing the surgical team is recommended prior to initia-
their circuit. Breaking that circuit, either with a tion of anticoagulation in these patients.
vagal maneuver or administration of intravenous
adenosine, can both reveal and abolish the re-
entrant rhythm (Fig.16.6). Concurrent Inotropic Support
To identify the rhythm, it is recommended to
have a 12 lead rhythm strip recording while The onset of AF can complicate management of
administering adenosine, so as to capture the ter- patients with cardiogenic shock on intravenous
mination of the rhythm and possibly to reveal inotropic support. In these patients, rhythm con-
underlying re-entrant rhythm by unveiling flutter trol is not always possible as the adrenergic stim-
waves (Table16.5). ulus from the inotropic infusions is significantly
Certain rhythms, such as atrial flutter, can benefit arrhythmogenic. Rapid ventricular rates are
from a standard catheter ablation, otherwise, treat- frequently encountered, and rate control is both a
ment with beta-blockers is recommended for short challenge and there are no clinical studies to
and long term management. If these do not maintain serve as a guide to therapy. Amiodarone and
sinus rhythm, catheter ablation may be attempted. digoxin can be used in these cases, mainly for
their rate control effects. Care must be exercised
with digoxin in elderly patients, along with those
Evidence Contour impaired kidney function. Amiodarone should be
used with caution in patients with underlying
Despite the prevalence of AF (>9% of Medicare lung, liver, or thyroid disease.
patients in 2010) management still is quite chal-
lenging [12]. Certain populations of patients
present challenges in dealing with this disease. Rhythm Control inHFrEF

In a subset of the AFFIRM trial, rhythm control


 igh Bleeding Risk inPost-operative
H was preferred in patients with HFrEF [16]. In
Cardiac Surgery Patients patients with HFrEF and cardiac resynchroniza-
tion therapy devices, rhythm control has a lower
Some studies have demonstrated a near 25% risk mortality [17]. For these reasons, it is recom-
for the development of post-operative AF in mended to try a rhythm control strategy for
patients undergoing cardiothoracic surgery [13]. patients with HFrEF who are still symptomatic
The development of AF increases hospital length with rate controlled AF [1].
16 Atrial Fibrillation andOther Supraventricular Tachycardias 151

Fig. 16.5(a) Short RP a Short RP b Long RP


tachycardia, (b) Long RP
tachycardia (Courtesy: RP
Icyberrounds.com)
PR RP PR

Fig. 16.6 Termination of SVT with adenosine (Courtesy: emedu.org)

Table 16.5 Effect of adenosine on short RP and long RP tachycardias


Short RP tachycardias Effect of adenosine Long RP tachycardias Effect of adenosine
Typical AV nodal reentrant Terminates Atrial tachycardia Creates AV-block revealing
tachycardia underlying atrial tachycardia and
slowing the ventricular rate
AV reentrant tachycardia Terminates Sinus tachycardia Creates AV-block revealing
using accessory pathway underlying atrial rhythm and
slowing the ventricular rate
Atrial tachycardia with Creates AV-block Atrial flutter Creates AV-block revealing
first degree AV block revealing underlying underlying atrial flutter and slowing
atrial tachycardia and the ventricular rate
slowing the
ventricular rate
Junctional tachycardia Terminates AV reentrant Terminates
tachycardia

Cardiology Committee for Practice Guidelines and


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lism in atrial fibrillation using a novel risk factor- Gandino A, Cemin R, etal. Colchicine Reduces
based approach: the euro heart survey on atrial Postoperative Atrial Fibrillation. Circulation.
fibrillation. Chest. 2010;137(2):26372. 2011;124(21):22905.
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Vemmou A, Koroboki E, etal. CHADS2, CHA2DS2- Mangano DT, etal. Atrial fibrillation following coronary
VASc, and long-term stroke outcome in patients without artery bypass graft surgery: predictors, outcomes, and
atrial fibrillation. Neurology. 2013;80(11):100917. resource utilization. MultiCenter Study of Perioperative
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HJGM, Lip GYH.A novel user-friendly score (HAS- 15. Mitchell LB, Exner DV, Wyse DG, Connolly CJ,
BLED) to assess 1-year risk of major bleeding in Prystai GD, Bayes AJ, etal. Prophylactic oral ami-
patients with atrial fibrillation: the Euro Heart Survey. odarone for the prevention of arrhythmias that
Chest. 2010;138(5):1093100. American College of begin early after revascularization, valve replace-
Chest Physicians. ment, or repair: PAPABEAR: a randomized con-
8. Wyse DG, Waldo AL, DiMarco JP, Domanski MJ, trolled trial. JAMA American Medical Association.
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atrial fibrillation. N Engl JMed. 2002;347(23): ated with fewer heart failure symptoms: insights from
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YS, Tijssen JGP, Alings AM, etal. Lenient versus Auricchio A, Santini M, etal. Cardiac resynchroniza-
strict rate control in patients with atrial fibrillation. N tion therapy in patients with atrial fibrillation: the
Engl JMed. 2010;362(15):136373. CERTIFY study (Cardiac Resynchronization Therapy
10. Klein AL.Cardioversion guided by transesophageal in Atrial Fibrillation Patients Multinational Registry).
echocardiography: the ACUTE Pilot Study: a ran- JACC Heart Fail. 2013;1(6):5007.
Ventricular Arrhythmias
17
SohaibTariq andHowardA.Cooper

Case Presentation Question What approach should be taken in


management of multiple recurrences of ventricu-
A 71 year old male with a history of hyperten- lar arrhythmias over a short period of time, i.e.
sion, hyperlipidemia, and coronary artery dis- VT storm?
ease, with coronary artery bypass grafting 15
years earlier, presented with repeated episodes of Answer Antiarrhythmic medications and cor-
lightheadedness over the course of several hours. rection of the arrhythmia trigger(s).
In the emergency department he was found to be
in monomorphic VT at a rate of 206 beats per The patient was initially treated with intra-
minute (Fig.17.1). He was urgently cardioverted venous amiodarone and external defibrillation
to normal sinus rhythm and administered a for episodes of VT.A temporary transvenous
150mg bolus of intravenous amiodarone fol- pacemaker was inserted to prevent bradycardia
lowed by a continuous infusion. A 12-lead elec- in the setting of intermittent complete atrioven-
trocardiogram revealed non-specific T-wave tricular block. Electrolytes were repleted.
abnormalities. Subsequently, he had intermittent Intravenous lidocaine was added for break-
episodes of third degree atrioventricular block through episodes of VT.Benzodiazepines
with a ventricular escape rhythm at 50 beats per were administered to ameliorate anxiety.
minute. Initial laboratory investigation was sig- Echocardiography showed left ventricular sys-
nificant for potassium of 3.9mEq/L, magnesium tolic dysfunction, with an estimated ejection
of 1.8mg/dL, white blood cell count of 22.6K, fraction of 30%. Right heart catheterization
and cardiac troponin I of 0.13ng/mL.He was revealed elevated intracardiac filling pressures
transferred to the cardiac intensive care unit and a cardiac index of 1.9L/min/m2. An endo-
where he continued to have frequent episodes of myocardial biopsy was negative for signs of
monomorphic VT. inflammation or myocarditis. Left heart cathe-
terization demonstrated severe native three ves-
sel disease with an atretic left internal mammary
artery (LIMA) graft to the left anterior descend-
ing (LAD) coronary artery, and patent vein
S. Tariq grafts to obtuse marginal (OM2), diagonal
Division of Cardiology, Westchester Medical Center,
Valhalla, NY, USA
branch (D1), and right coronary artery (RCA).
A drug eluting stent was placed in mid
H.A. Cooper (*)
Inpatient Cardiology, Division of Cardiology,
LAD.There was no significant elevation in
Westchester Medical Center, Valhalla, NY, USA serum troponin levels. No further episodes of
e-mail: howard.cooper@wmchealth.org VT were observed, even after discontinuation

Springer International Publishing Switzerland 2017 153


R.C. Hyzy (ed.), Evidence-Based Critical Care, DOI10.1007/978-3-319-43341-7_17
154 S. Tariq and H.A. Cooper

Fig. 17.1 Monomorphic ventricular tachycardia

of lidocaine. The patient received an implant-  lassification ofVT


C
able cardioverter defibrillator (ICD) and was Ventricular arrhythmias are subdivided into
discharged home on a long-acting beta blocker. non-sustained (premature ventricular contrac-
Three weeks later the patient presented with tions and non-sustained VT) and sustained
pre-syncope and palpitations. ICD interrogation (defined as VT lasting for more than 30 s or
revealed multiple episodes of VT resulting in VF). VT may be monomorphic or polymorphic,
defibrillator shocks. Intravenous amiodarone with torsades de pointes representing a specific
was initiated, but VT continued to recur. An form of polymorphic VT occurring in the set-
intra-aortic balloon pump was placed with sub- ting of a prolonged QT interval. Electrical
sequent resolution of the VT.He then underwent storm is defined as 3 or more episodes of sus-
electro-anatomic mapping followed by radiofre- tained VT, VF, or appropriate ICD therapies
quency catheter ablation, after which he had no during a 24-h period. This condition has vari-
further VT. ably been referred to as VT storm or VT
cluster. An important subgroup of electrical
storm is incessant VT, which refers to repeated
Principles ofManagement recurrence within 5min of a technically suc-
cessful therapy. Management of sustained ven-
Diagnosis tricular arrhythmias is essential aspect of
critical care medicine.
Ventricular arrhythmias include a broad spec-
trum of rhythm disorders, which may have no  onitoring andTesting
M
clinical consequence or may result in sudden Patients presenting with a suspicion of ventricular
cardiac death. Patients at high risk for ventricu- arrhythmias should undergo continuous electrocar-
lar arrhythmias are those with ischemic heart diographic monitoring in a setting in which appro-
disease, myocarditis, underlying structural priate care can be rapidly deployed. A 12-lead
heart disease, inherited or acquired channelopa- ECG should be obtained at baseline and assessed
thies, drug intoxication, electrolyte derange- for evidence of ischemia, underlying structural
ment, and hyperthyroidism (Table17.1). heart disease, and the various channelopathies,
However, ventricular arrhythmias may occur in such as long QT syndrome or Brugada syndrome
the absence of any of these predisposing fac- (Fig.17.2). Every attempt should be made to obtain
tors. The diagnosis of ventricular arrhythmias a 12-lead ECG during the occurrence of a ventricu-
may be suggested by the clinical presentation, lar arrhythmia. Confirmation of the presence of a
but confirmation requires electrocardiographic ventricular arrhythmia may require prolonged
recording. electrocardiographic monitoring (inpatient or
17 Ventricular Arrhythmias 155

Table 17.1 Approach to common etiologies of ventricular arrhythmias


Etiology History Evaluation Treatment
Myocardial ischemia Chest pain, dyspnea ECG, echocardiography, Coronary revascularization,
stress testing, coronary beta blockers, intra-aortic
angiography balloon pump, ablation
Channelopathies Syncope, family ECG, exercise testing, Removal of QT-prolonging
history of sudden provocative pharmacological drugs, intravenous
death testing magnesium, potassium
replacement, temporary
pacing, sympathectomy, ICD
Myocarditis Flu-like symptoms, ECG, echocardiography, Amiodarone, beta blockers,
chest pain cardiac MRI, ICD, steroids in selected
endomyocardial biopsy cases where indicated for
subtypes of myocarditis
Electrolyte imbalance Renal failure, Serum electrolytes, ECG Correction of electrolytes
dehydration
Cardiomyopathy Symptoms of heart Echocardiography, coronary Amiodarone, beta blockers,
failure angiography, cardiac MRI ICD
Sarcoidosis Lung involvement Cardiac MRI, biopsy Steroid therapy,
immunomodulating agents,
ICD
Arrhythmogenic right Palpitations, ECG, cardiac MRI, genetic Beta blockers, ICD,
ventricular syncope, dyspnea, testing amiodarone
cardiomyopathy family history
Drug intoxication Drug abuse, use of ECG, serum drug levels Stop offending agent
QT prolonging
medications or
digoxin
Hyperthyroidism Anxiety, Thyroid hormone studies Beta blockers,
palpitations, heat glucocorticoids, anti-thyroid
intolerance medications

a b

Fig. 17.2 Electrocardiographic tracings in Brugada syndrome. (a) Type 1; coved type ST-T segment configuration.
(b) Type 2; saddle back pattern
156 S. Tariq and H.A. Cooper

a c

Fig. 17.3(a) Monomorphic ventricular tachycardia. ture beat. (c) Supraventricular tachycardia with aberrancy.
Atrioventricular dissociation can be seen. (b) Ventricular Atrioventricular dissociation and fusion beats are absent.
tachycardia with fusion beat (hybrid complex of supra- RS complexes in precordial leads are evident
ventricular and ventricular activation) followed by a cap-

outpatient) (Fig.17.3), or invasive electrophys- General Measures


iologic testing. Once the diagnosis of a ven-
tricular arrhythmia has been confirmed, further Non-sustained VT (Fig.17.4) is encountered
studies should be obtained as clinically indi- very commonly in the intensive care unit among
cated in order to elucidate the underlying patients with structural heart disease. In general,
cause. These may include: serum electrolyte no specific therapy is required for asymptomatic
testing, thyroid studies, screening for drugs of patients other than electrolyte repletion and
abuse, echocardiography, cardiac magnetic treatment of the underlying condition. For fre-
resonance imaging, coronary angiography, quent or symptomatic non-sustained VT, how-
endomyocardial biopsy, exercise electrocardi- ever, treatment with beta blockers should be
ography, and provocative pharmacological considered. Patients who are not otherwise can-
testing. A family medical history should be didates for an ICD for primary prevention of
assessed for sudden death or known cardiomy- sudden death, for example, those with non-sus-
opathies. Myocardial ischemia should be con- tained VT, a history of MI, and moderate left
sidered in all cases of polymorphic VT and ventricular systolic dysfunction (EF >35 to
ventricular fibrillation with coronary angiogra- 40%), may be considered for electrophysiology
phy being appropriate early in the evaluation in study (EPS) when stable in order to determine if
most cases. an ICD is indicated.
17 Ventricular Arrhythmias 157

Fig. 17.4 Non-sustained ventricular tachycardia

In patients with sustained ventricular Beta Blockers


arrhythmias, it is essential that diagnostics and
treatments be implemented simultaneously Beta blockers should be used in the initial phase
(Fig.17.5). For patients with cardiac arrest of treatment for most patients with ventricular
from pulseless VT or VF, guideline-directed arrhythmias [2]. These drugs play an important
ACLS including rapid defibrillation should role in reducing ischemia, decreasing sympa-
be implemented immediately. When an ICD is thetic tone, and increasing the fibrillation thresh-
present, device interrogation and, if necessary, old. Nonrandomized data suggests that
reprogramming should be performed by a qual- intravenous propranolol may be the beta blocker
ified practitioner to ensure the delivery of of choice in this setting. However, short-acting
appropriate therapy and to avoid shocks for metoprolol is a reasonable alternative that is used
non-life-threatening arrhythmias [1]. Triggers commonly in clinical practice. In patients with
of ventricular arrhythmias such as ischemia, relative hypotension, esmolol is preferred due to
electrolyte imbalances, decompensated heart its very short half-life [3]. The beta blocker dose
failure, bradycardia, drug intoxication, and should be titrated to maintain a heart rate of
hyperthyroidism, should be identified and 4560 beats per minute. Insufficient advance-
treated. Heart failure is an under-recognized ment of beta blocking agents is a common error
trigger for new or a significant change in pat- in the management of patients with symptomatic
tern of ventricular arrhythmias in patients with VT.Nevertheless, beta blocker therapy may be
structural heart disease. In patients with VT limited by bradycardia, hypotension, heart block,
storm requiring multiple shocks, pain control and bronchospasm.
and sedation with narcotics and/or benzodiaze-
pines should be provided to aid in reducing
sympathetic tone. In patients with VT that is Amiodarone
refractory to these measures, it is often benefi-
cial to intubate and deeply sedate such patients Intravenous amiodarone blocks fast sodium
to further suppress sympathetic activation from channels and L-type calcium channels, and inhib-
pain and anxiety. its norepinephrine release. Amiodarone is highly
A multi-disciplinary approach is appropriate effective, and has been proven to be superior to
for most patients with sustained ventricular other antiarrhythmic agents in suppressing ven-
arrhythmias requiring intensive care. The critical tricular arrhythmias [46]. Amiodarone is given
care specialist should work closely with the elec- as 150mg bolus over 10min (300mg IV push for
trophysiology team, and also consider consulta- cardiac arrest) followed by a continuous infusion,
tion with interventional cardiologists and/or with supplemental boluses given as needed for
specialists in advanced heart failure as dictated arrhythmia recurrence. Because of its potential to
by the specific needs of the patient. cause severe phlebitis, intravenous amiodarone
158 S. Tariq and H.A. Cooper

Fig. 17.5 Algorithm for assessment and Sustained Ventricular Arrhythmia (VT, VF, ICD shocks)
management of sustained ventricular
arrhythmias. VT ventricular tachycardia, VF
ventricular fibrillation, ACLS advanced ACLS if pulseless
CICU admission
cardiac life support, CICU cardiac intensive
care unit, EP electrophysiology, ICD EP consult
implantable cardioverter defibrillator, IABP
Sedatives, analgesics
intra-aortic balloon pump, ECMO
Consider intubation
extracorporeal membrane oxygenation
ICD present?

Yes No

Interrogate device Assess for triggers (Refer to Table 1)


Confirm shocks appropriate Beta blockers
Reprogram as indicated Amiodarone

Ischemia present?

Yes No

Lidocaine
IABP
Revascularization

Incessant Treatment Successful Recurrent despite drugs

ECMO Consider ICD VT ablation


Sympathetic denervation
Ethanol ablation

should be administered via central venous access administration of lidocaine was associated with
whenever possible. During short-term use, amio- reduced survival compared to amiodarone [8]. In
darone has few side effects but can occasionally the absence of acute ischemia, lidocaine use
cause hypotension. Although amiodarone can should be considered if sustained ventricular
increase the QTc interval, precipitation of tors- arrhythmias are refractory to beta blockers and
ades de pointes occurs rarely (<1.0%) [7]. amiodarone. Lidocaine is administered as a bolus
dose of 0.50.75mg/kg every 510min (maxi-
mum 300mg total) until the arrhythmia is sup-
Lidocaine pressed, followed by an infusion at 14mg/min.
A second bolus of lidocaine 0.5mg/kg after
Lidocaine blocks fast sodium channels in a use- 2040min should be considered because of sig-
dependent fashion and does not prolong the QT inter- nificant redistribution of the drug. Notable side
val. It is effective in suppressing ventricular effects include bradycardia and central nervous
arrhythmias occurring in the setting of acute ischemia, system toxicity. Lidocaine is metabolized in the
but otherwise lidocaine has weak antiarrhythmic liver and excreted in the urine. Lidocaine should
properties [5]. In patients resuscitated from VF, be administered with caution and the mainte-
17 Ventricular Arrhythmias 159

nance dose adjusted downward in patients with play an essential role in suppressing sympathetic
liver disease or decompensated heart failure. activity and should be used in addition to amiod-
Daily serum lidocaine levels should be monitored arone to maintain rhythm stability. Other than in
(therapeutic range: 1.55 mcg/mL) and the dose the setting of acute ischemia, intravenous lido-
adjusted accordingly. caine is only modestly effective in terminating
ventricular arrhythmias but may be a useful
adjunct when amiodarone and beta blockade
Digoxin Immune Fab have been unsuccessful.

In patients with sustained ventricular arrhythmias


due to digoxin toxicity, anti-arrhythmic drugs are Mechanical Circulatory
not effective. Digoxin specific Fab antibody Support IABP
should be administered, and temporary pacing
should be instituted in the presence of advanced Placement of an IABP may be useful in the
AV block. Common arrhythmias due to digoxin short-term management of patients with refrac-
toxicity are: tory ventricular arrhythmias, particularly in the
setting of acute ischemia and/or decompensated
heart failure, when initial pharmacotherapy and
Atrioventricular block reversal of identified triggers have been unsuc-
Ectopic atrial tachycardia cessful. The IABP is placed percutaneously, and
Junctional rhythm may be implanted at the bedside in unstable
Ventricular premature beats patients. IABPs increase coronary perfusion,
Ventricular tachycardia relieve ischemia, and unload the left ventricle,
Ventricular fibrillation potentially serving as a bridge until a more
Sinus bradycardia definitive treatment may be implemented. The
Sinoatrial block effectiveness of the IABP in refractory ventricu-
lar arrhythmias has been demonstrated in sev-
eral case series [9]. Adverse effects are
uncommon, but include bleeding, infection, and
Evidence Contour limb ischemia.

There are very few randomized trials addressing


the acute management of ventricular arrhyth-  dvanced Mechanical Circulatory
A
mias. Therefore, much of the treatment is based Support ECMO
on expert opinion and experience. In particular,
the treatment of ventricular arrhythmias which In rare cases, when VT is incessant and hemody-
are refractory to the standard treatments outlined namically significant, complete mechanical circu-
above remains an area of great uncertainty. latory support may become necessary.
Veno-arterial extracorporeal membrane oxygen-
ation (V-A ECMO) involves using a centrifugal
Anti-arrhythmic Drug Therapy pump to remove blood from the venous system,
circulate it through an oxygenator, and return
There are limited randomized data to guide anti- oxygenated blood to the arterial circulation.
arrhythmic drug therapy of VT.Intravenous ami- ECMO can be instituted either percutaneously or
odarone is widely used as the initial surgically. In case series, ECMO has shown to
anti-arrhythmic agent due to its high efficacy and facilitate termination of ventricular arrhythmias
excellent short-term safety profile. Beta blockers when other treatments had been exhausted [10].
160 S. Tariq and H.A. Cooper

In addition, ECMO supports the coronary circula- had previously failed anti-arrhythmic drug ther-
tion, relieves hypoxia, preserves vital organ perfu- apy and VT ablation, bilateral surgical cardiac
sion, and allows time to proceed to other definitive sympathetic denervation resulted in a clinically
treatments. Complications are fairly common, significant reduction in the number of ICD shocks
particularly bleeding and limb ischemia. in 90% of patients and a shock-free survival rate
of 50% at 1 year [15].

Radiofrequency Catheter Ablation


References
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and may be useful in critically ill patients with 1. Moss AJ, Schuger C, Beck CA, Brown MW, Cannom
ventricular arrhythmias in whom other modali- DS, Daubert JP, etal. Reduction in inappropriate ther-
apy and mortality through icd programming. N Engl
ties have been unsuccessful. This technique,
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can be technically challenging, particularly in the Kosar EM.Treating electrical storm: sympathetic
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3. Brodine WN, Tung RT, Lee JK, Hockstad ES, Moss
support is often useful to allow for proper map- AJ, Zareba W, etal. Effects of beta-blockers on
ping when the VT is poorly tolerated. Catheter implantable cardioverter defibrillator therapy and sur-
ablation has been demonstrated to be efficacious vival in the patients with ischemic cardiomyopathy
(from the multicenter automatic defibrillator implan-
in treating refractory electrical storm, with a reduc-
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tion in recurrent VT and cardiac death [11, 12]. 4. Connolly SJ, Dorian P, Roberts RS, Gent M, Bailin S,
Vascular injury, thromboembolism, and cardiac Fain ES, etal. Comparison of beta-blockers, amioda-
tamponade are potential complications. rone plus beta-blockers, or sotalol for prevention of
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In patients with recurrent VT despite drug ther-
Emerg Med J.2013;68:3927.
apy and catheter ablation, transcoronary ethanol 6. Levine JH, Massumi A, Scheinman MM, Winkle RA,
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recurrence of VT in a small group of highly
8. Dorian P, Cass D, Schwartz B, Cooper R, Gelaznikas
selected patients after failed radiofrequency abla- R, Barr A.Amiodarone as compared with lidocaine
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9. Fotopoulos GD, Mason MJ, Walker S, Jepson NS,
Patel DJ, Mitchell AG, etal. Stabilisation of medi-
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Chu JJ, etal. Extracorporeal life support to terminate
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Management ofAcute Aortic
Syndromes 18
CarolH.Choe andRohanR.Arya

Case Presentation Question What is the initial approach to the


management of a patient with acute aortic
A 42-year-old man with a history of hypertension dissection?
presented to the Emergency Department (ED)
with complaints of severe chest and back pain. Answer Blood pressure control, evaluation for
He reported the pain started shortly after lifting involvement of the aortic root, or end-organ
his wife in a bear hug while celebrating malperfusion.
Valentines Day. He had no relief of his symp-
toms with acetaminophen or ibuprofen, so his Acute aortic dissection, regardless of the loca-
wife called emergency medical services. On tion, requires strict blood pressure control and
arrival to the ED, he was noted to be hypertensive admission to an intensive care unit (ICU).
(172/101mmHg), diaphoretic, and complaining Ascending aortic dissections are a surgical
of severe, sharp chest pain radiating to his back. emergency and need immediate evaluation by

He had nausea and progressively worsening
shortness of breath. His blood work was unre-
markable, including cardiac troponin. ECG
showed mild non-specific ST segment abnormal-
ities. Initial chest roentogram (CXR) was signifi-
cant for pulmonary edema and a widened
mediastinum (Fig.18.1). CTA of the chest was
done and shown in Fig.18.2.

Electronic supplementary material The online version of


this chapter (doi:10.1007/978-3-319-43341-7_18) contains
supplementary material, which is available to authorized
users.
C.H. Choe (*)
Critical Care Medicine, Lexington Medical Center,
West Columbia, SC, USA
e-mail: chchoe@lexhealth.org
R.R. Arya
Medicine, Division of Pulmonary and Critical
Care Medicine, University of South Carolina School Fig. 18.1 Initial chest x-ray with evidence of pulmonary
of Medicine, Columbia, SC, USA edema and widened mediastinum

Springer International Publishing Switzerland 2017 163


R.C. Hyzy (ed.), Evidence-Based Critical Care, DOI10.1007/978-3-319-43341-7_18
164 C.H. Choe and R.R. Arya

Concurrent to the patients blood pressure


control, a STAT CTA chest was obtained upon
the patients arrival, and was read as a dissection
of the aortic arch starting at the innominate artery
(brachiocephalic trunk) and extending to the
descending aorta. Cardiothoracic Surgery and
Vascular Surgery evaluated the patient and opted
to medically manage him as the ascending aorta
was not involved. Twelve hours later, a transtho-
racic echocardiogram (TTE) was performed and
was concerning for aortic valve involvement. A
transesophageal echocardiogram (TEE) was
immediately performed which confirmed ascend-
Fig. 18.2 CTA chest showing the dissection flap (black ing aortic dissection with aortic insufficiency
arrow) at the level of the descending aorta without pericardial tamponade (Figs.18.3, 18.4,
and 18.5, Video 18.1 and 18.2).

cardiothoracic surgeons with emergent repair. All


other dissections are usually managed with strict Principles ofManagement
blood pressure control and urgent Cardiothoracic
and Vascular Surgery consultations, unless there Definition
is evidence of end-organ hypoperfusion [13].
As pain can contribute to elevated blood pres- Acute aortic syndromes comprise a spectrum of
sures, the patient was given 4mg Morphine IV disease involving the aorta, including penetrating
with a modest improvement in his pain. However, aortic ulcers (PAU), intramural hematomas
he continued to have significant anxiety, shortness (IMH), and aortic dissection [2, 4]. Intramural
of breath and diaphoresis. After a discussion with hematomas develop as a result of a micro-tear
the patient and his family, he was orotracheally within the vasa vasorum resulting in an intrame-
intubated. An arterial line was placed into his dial hematoma that is characterized by the absence
right radial artery and his pressures were noted to of an aortic entry or exit tear. The prevalence of
be 170/100smmHg. Bilateral upper extremity IMH in patients found to have aortic dissections
cuff pressures correlated with pressures obtained ranges from 4 to 22%. The IMH may evolve to
from his arterial line. He was started on an esmolol overt dissection or even rupture, with progression
drip at 10 mcg/kg/minute. This agent was quickly that may occur suddenly or be heralded by ongo-
titrated up to 150 mcg/kg/minute (maximum infu- ing acute aortic syndrome. Fifty to 80% may
sion rate of 300 mcg/kg/minute) in order to obtain resolve completely but patients may also progress
a goal heart rate <60 beats per minute (bpm) and to dissection or develop an aneurysm later in their
a systolic blood pressure <120mmHg. Despite disease course. Resolution occurs more often in
high doses of esmolol with a heart rate <60bpm, younger patients, and those with aortic diame-
the patients blood pressure remained uncon- ter<44.5cm, hematoma thickness <1cm, and
trolled so a nitroprusside infusion was started at therapy with beta-blockers [1, 2, 5, 6].
0.25 mcg/kg/minute and increased up to 0.35 Penetrating aortic ulcers represent atheroscle-
mcg/kg/minute (maximum dose 2mcg/kg/min- rotic plaques that have ulcerated into the medial
ute). Blood pressures remained poorly controlled layer of the aortic wall. The high pressure pulsa-
with the two agents and so a third agent, labetalol tile flow of blood through the aorta can cause fur-
was added at 1mg/minute and increased up to ther erosion of this ulcerated plaque which, in
6mg/minute. The initiation of labetalol improved turn, can result in instability of the aortic wall and
his BP and the esmolol drip was weaned off. can lead to IMH, dissection, and even aortic
18 Management ofAcute Aortic Syndromes 165

Fig. 18.3 Apical 5 cham-


ber view demonstrating
marked dilatation of the
proximal ascending aorta
and dissection flap
(arrow). AoV aortic valve,
LV left ventricle, LA left
atrium (Image courtesy of
Priscilla Peters, BA,
RDCS, FASE)

Fig. 18.4 Apical 5 cham-


ber view revealing aortic
regurgitation. White arrow
points to the dissection
flap. Red asterisk (*) at
area of aortic regurgitation
(Image courtesy of
Priscilla Peters, BA,
RDCS, FASE)

rupture. These lesions are uncommon in the descending aorta is distal to the left subclavian
ascending aorta because high flow is protective artery. The DeBakey and the Stanford classifica-
against atherosclerosis. However, if present, they tions are the two most frequently utilized classifi-
usually rupture and are commonly fatal. Lesions cation systems. The DeBakey classification
in the ascending aorta can initially be treated system divides the dissection into 3 types. Type I
medically with close observation. PAUs more involves both the ascending and descending aorta;
commonly arise in the descending thoracic aorta Type II affects the ascending aorta only; and Type
[2, 46]. III is a dissection distal to the left subclavian
Anatomically, the ascending aorta is the sec- artery. The Stanford classification simplifies this
tion proximal to the brachiocephalic trunk and the further. The dissection either affects the ascending
166 C.H. Choe and R.R. Arya

Fig. 18.5Off-axis
transesophageal
echocardiogram revealing
an ascending aortic
dissection with a dissection
flap (arrow)

aorta (Type A) or it remains distal to the left due to lesser availability and longer duration of
subclavian (Type B) [7]. Isolated aortic arch dis- image acquisition. TTE and TEE are other
sections do not fit neatly into any of these classifi- modalities that may be used to evaluate the aorta,
cation types, and there is debate as to whether particularly in a hemodynamically unstable
they should be grouped with Type A or Type B patient for whom transport out of the department
dissections. Some have argued that the natural would be unsafe [2, 10, 11]. Although the quality
history approximates more closely that of Type B of echocardiograms is operator dependent, TTE
dissections and as such, isolated arch dissections generally has a sensitivity of 5983% and a spec-
do not require emergent surgical intervention. ificity of 6393% for diagnosing an ascending
Other experts disagree [7, 8] (Fig.18.6). aortic dissection [5]. TEE has a sensitivity of
Risk factors for acute aortic dissection are var- close to 100% with a specificity of 89% for iden-
ied. Hypertension is a predominant risk factor [9] tifying an ascending aortic dissection, although it
but other factors include bicuspid aortic valve, can be as low as 3155% for descending aortic
cocaine use, Marfan syndrome (and other con- aneurysms [6].
nective tissue disorders), blunt trauma, preg-
nancy, weight lifting (Valsalva maneuvers),
previous aortic surgery, and large-vessel vasculi- Medical Management
tis, among others [1].
All Type B dissections, and rarely Type A dissec-
tions, are initially medically-managed with strict
Diagnosis blood pressure control. Although no randomized
trials have been conducted, beta-blockers have
Chest pain is a ubiquitous presenting complaint. been the mainstay of treatment. An esmolol,
In a patient with hypertension and chest pain labetalol, or propranolol continuous infusion is
radiating to the back, acute aortic syndrome must initiated in order to reduce shear force (dP/dt)
be considered and ruled out. While angiography exerted on the aortic wall. Unless hypotension is
had previously been the gold standard, CTA of present, the goal systolic blood pressure is
the chest is now the standard of care to diagnose 100120mmHg and the target heart rate is 5060
aortic dissection given its widespread availability beats per minute [1, 3]. Esmolol is often favored
and ease of use. MRI may also be used to aug- as the initial agent as it is short-acting and can be
ment findings although it is not the diagnostic rapidly weaned off if the patient experiences
study of choice for emergently imaging the aorta severe hypotension or bronchospasm (patients
18 Management ofAcute Aortic Syndromes 167

a b c

Fig. 18.6 Different types of aortic dissection. DeBakey Stanford Type A. (c) Stanford type B (Image courtesy of
classification: (a) DeBakey Type 1. (b) DeBakey Type 2. J.Heuser/Creative Commons)
(c) DeBakey Type 3. Stanford classification: (a, b)

with severe COPD or asthma). If blood pressure aortic dissection. Surgery may be necessary if
is still poorly controlled with intravenous beta- there is refractory chest pain or extension. Both
antagonist agents, nitroprusside may be added. conditions should be recognized as part of the
Nitroprusside should never be started as the ini- spectrum of acute aortic diseases that require
tial agent as it may promote reflex tachycardia close monitoring and treatment. They require
and increase dP/dt, thus propagating the dissec- lifelong anti-hypertensive therapy and repeat aor-
tion flap. If blood pressures are still poorly con- tic imaging at 3, 6, 9 and 12 months based on the
trolled or if beta-blocker use is contraindicated, size of the aorta [2, 5].
an infusion of a non-dihydropyridine calcium- Upon discharge, beta-blocking agents,
channel blocker may be used [1]. calcium- channel blockers, or angiotensin-
Patients with PAU and IMH are treated with converting enzyme inhibitors should be pre-
blood pressure control similar to that used in scribed to maintain blood pressure control. The
168 C.H. Choe and R.R. Arya

International Registry of Acute Aortic Dissection shear stress and decrease heart rate. Other aspects
(IRAD) researchers found that, in general, beta- of diagnosing and treating dissections, however,
blockers were associated with mortality benefit are still under significant debate.
in Type A dissections and in patients that were
treated surgically, while patients with medically-
managed Type B dissections had improved sur- Diagnosis ofAortic Dissection
vival if discharged home with calcium channel
blockers [3]. Various biomarkers have been evaluated to deter-
mine their usefulness in ruling out aortic dissec-
tion. Of the possible biomarkers, D-dimer seems
Surgical Intervention to have the most clinical utility. D-dimer assays
may be significantly elevated (greater than
Dissections involving the ascending aorta confer 1600ng/mL) in the first 6h [3, 4] and may be
a high early mortality risk [12]. Previous studies used to assist in the assessment of patients with
reported a 1% per hour mortality risk in patients suspected dissection. A low D-dimer level
with an untreated acute Type A aortic dissection (<500ng/mL) may offer a sufficiently high nega-
[13]. Mortality is reduced from 90% without sur- tive predictive value to rule out aortic dissection
gical intervention to less than 20% with surgery [17]. However, professional guidelines do not
[13, 14]. Type B dissections are initially managed endorse routine use of d-dimer for this purpose.
conservatively with strict blood pressure control Other novel biomarkers are currently under
unless there is evidence of malperfusion, persis- investigation.
tent pain, or refractory hypertension; in such
cases, emergent vascular surgery consultation
and intervention is warranted. Delayed surgical  edical Management ofType
M
intervention via endovascular repair is preferred ADissection
to the open approach [9, 15, 16].
While surgical intervention has been established
as the standard of care for an ascending aortic
Complications dissection, some proponents recommend that in
patients with advanced age, coma, acute renal
Aortic rupture and complications such as hypo- failure, shock, or need for re-do operation, medi-
tension, neurologic deficits, shock, cardiac tam- cal management alone may be warranted as the
ponade, pulse deficits, and kidney failure confer risk of surgery is prohibitive [18, 19]. Other con-
an even higher mortality rate [12]. Also, visceral siderations for medical management are given to
malperfusion and extremity ischemia may occur. patients with completed stroke, co-morbid condi-
tions that preclude a good quality of life, prior
aortic valve replacement, and presentation to the
Evidence Contour hospital more than 4872h after onset of aortic
dissection [19].
A guideline-based approach to the management
of patients with aortic dissection is provided in
Fig. 18.7. However, the optimal approaches to  urgical Intervention forAortic Arch
S
diagnose and manage aortic dissection are still Dissections
under investigation. Although no randomized
control trials have been conducted to evaluate the Treatment of aortic arch dissections is a matter of
best anti-hypertensive medication(s) to treat some controversy. In the DeBakey classification
acute aortic syndromes, the mainstay of treat- system, the aortic arch is a separate entity that is
ment is to start with an agent that will reduce not clearly accounted for. As such, several studies
18 Management ofAcute Aortic Syndromes 169

Acute aortic
dissection

1. Initiate immediate medical management.


2. In house management or transfer to another facility

Check BP in both arms and treat highest reading

Hypotension or shock
Yes No

Anatomy based Pain control BP Control (lV)


management -IV Opiates - Beta blocker
- Diltiazem
- Verapamil

Type B Type A
- Fluid boluses to obtain - Emergent surgical consult
- MAP >70 mmHg - Fluid boluses to obtain MAP >70 mmHg
- Review imaging for cause - If still hypotensive use vasopressors Goal SBP < 120 mmHg?
- Consider TEE
- Surgical consultation
Yes No

Etiology of hypotension Ascending aorta Add IV vasodilator


amenable to surgery Yes Yes involvement? to titrate
to < 120 mmHg
Surgical or interventional
No management
No

Ongoing medical management


-Close hemodynamic monitoring
-Keep SBP < 120 mmHg

Yes

Complications requiring surgical or


interventional management
- Malperfusion syndrome Transition to outpatient
- Extension of dissection No - Transition to oral medications
- Aneurysm expansion - Surveillance imaging
- Uncontrolled hypertension

Fig. 18.7 Management of patients with aortic dissection


170 C.H. Choe and R.R. Arya

have evaluated whether aortic arch dissections 6. Meredith EL, Masani ND.Echocardiography in the
emergency assessment of acute aortic syndromes. Eur
require surgical intervention or if medical man-
JEchocardiogr. 2009;10(1):i319.
agement alone is sufficient in uncomplicated 7. Lempel JK, Frazier AA, Jeudy J, etal. Aortic arch
cases. The initial IRAD studies showed that there dissection: a controversy of classification. Radiology.
was no difference in in-hospital mortality when 2014;271(3):84855.
8. Tsai TT, Isselbacher EM, Trimarchi S, etal. Acute
comparing Type B dissections with or without
type B aortic dissection: does aortic arch involvement
aortic arch involvement. Additionally, it was affect management and outcomes? Insights from the
found that aortic arch involvement was not an International Registry of Acute Aortic Dissection
independent risk factor for mortality [8]. (IRAD). Circulation. 2007;116(11 Suppl):I1506.
9. Nienaber CA, Clough RE.Management of acute aor-
Recently, the German Registry for Acute Aortic
tic dissection. Lancet. 2015;385:80011.
Dissection Type A (GERAADA) study evaluated 10. Evangelista A, Carro A, Moral S, etal. Imaging

early mortality and new neurologic and malper- modalities for the early diagnosis of acute aortic syn-
fusion deficits among different surgical drome. Nat Rev Cardiol. 2013;10(8):47786.
11. Nienaber CA.The role of imaging in acute aortic syn-
approaches for aortic arch replacement. They
dromes. Eur Heart JCardiovasc Imaging. 2013;14(1):
found that while there were more complications 1523.
in the immediate post-operative period for the 12. Hagan PG, Nienaber CA, Isselbacher EM, etal. The
population treated with total arch replacement, International Registry of Acute Aortic Dissection
(IRAD): new insights into an old disease. JAMA.
there was no significant difference in 30-day
2000;283(7):897903.
mortality between the hemiarch and total arch 13. Bonser RS, Ranasinghe AM, Loubani M, etal.

groups [20]. They did not, however, compare Evidence, lack of evidence, controversy, and debate in
arch replacement to medical management strate- the provision and performance of the surgery of acute
type A aortic dissection. JAm Coll Cardiol. 2011;
gies. Nevertheless, other natural history studies
58(24):245574.
suggest the risk of progression of isolated arch 14. Skripochnik E, Friedman P, Michler RE, Neragi-

dissection is high and some experts argue for rou- Miandoab S.The outcome of surgical management of
tine surgical management. Because of this uncer- type A aortic dissection. Asian Cardiovasc Thorac
Ann. 2013;22(6):68793.
tainty, we favor a team-based approach to
15. Kuratani T.Best surgical option for arch extension of
evaluation and individualized decision-making. type B dissection: the endovascular approach. Ann
Cardiothorac Surg. 2014;3(3):2929.
16. ODonnell S, Geotchues A, Beavers F, etal.

Endovascular management of acute aortic dissections.
References JVasc Surg. 2011;54(5):12839.
17. Suzuki T, Distante A, Zizza A, etal. Diagnosis of
1. De Len Ayala IA, Chen Y-F.Acute aortic dissection: acute aortic dissection by D-dimer: the International
an update. Kaohsiung JMed Sci. 2012;28(6): Registry of Acute Aortic Dissection Substudy on
299305. Biomarkers (IRAD-Bio) experience. Circulation.
2. Sheikh AS, Ali K, Mazhar S.Acute aortic syndrome. 2009;119(20):27027.
Circulation. 2013;128(10):11227. 18. Centofanti P, Flocco R, Ceresa F, etal. Is surgery
3. Suzuki T, Isselbacher EM, Nienaber CA, etal. Type- always mandatory for type A aortic dissection? Ann
selective benefits of medications in treatment of acute Thorac Surg. 2006;82(5):165863; discussion 1664.
aortic dissection (from the International Registry of 19. Feldman M, Shah M, Elefteriades JA.Medical man-
Acute Aortic Dissection [IRAD]). Am JCardiol. agement of acute type A aortic dissection. Ann Thorac
2012;109(1):1227. Cardiovasc Surg. 2009;15(5):28693.
4. Bossone E, Suzuki T, Eagle KA, Weinsaft JW. 20. Easo J, Weigang E, Hlzl PPF, etal. Influence of oper-
Diagnosis of acute aortic syndromes: imaging and ative strategy for the aortic arch in DeBakey type I
beyond. Herz. 2013;38(3):26976. aortic dissection: analysis of the German Registry for
5. Baliga RR, Nienaber CA, Bossone E, etal. The role of Acute Aortic Dissection Type A.J Thorac Cardiovasc
imaging in aortic dissection and related syndromes. Surg. 2012;144(3):61723.
JACC Cardiovasc Imaging. 2014;7(4):40624.
Management ofEndocarditis
19
JanekManojSenaratne andSeanvan Diepen

Case Presentation c eftriaxone. A transthoracic echocardiogram


reported a mildly dilated left ventricle with normal
A 56 year old male with a history of hypertension systolic function, a trileaflet aortic valve with
presented with a 2 month history of fevers, chills, severe aortic insufficiency, and a large 15mm aor-
anorexia, and weight loss with a 2 week history of tic valve vegetation (Fig.19.1, Videos 19.1 and
worsening dyspnea and pedal edema. At the time 19.2). A computed tomography (CT) scan of his
of presentation, he had a blood pressure of head reported a left frontal subacute infarction
90/27mmHg, with a heart rate of 80 beats per min, with associated petechial hemorrhage.
temperature of 38.0C, and required 8 L/min of
oxygen to maintain saturations of 94%. On exam, Question How should this patients native valve
his jugular venous pressure was 7cm above the infective endocarditis (IE) be managed?
sternal angle. He had bilateral lung crackles, a
grade III/VI decrescendo diastolic murmur along Answer Antimicrobial therapy and aortic valve
the left lower sternal border, and bilateral pitting replacement.
edema. His white blood cell count was 14,000
cells/L.Two sets of blood cultures were drawn All patients with IE should be initiated on
and empiric vancomycin, gentamicin, and cipro- early empiric guideline-recommended antibiotic
floxacin were initiated. At 9h, blood cultures were therapy, and antimicrobials should be further
positive for pansensitive Streptococcus oralis and guided by culture and sensitivities. Patients with
his antimicrobial t herapy was changed to severe mitral or aortic insufficiency causing con-
gestive heart failure should be referred for early
cardiac surgery to repair or replace the incompe-
Electronic supplementary material The online version of tent valve. Prior to surgery, this patient under-
this chapter (doi:10.1007/978-3-319-43341-7_19) contains went a coronary CT scan, which reported a
supplementary material, which is available to authorized
users.
calcium score of 0. This test was done instead of
a coronary angiogram to reduce the risk of dis-
J.M. Senaratne lodging the vegetation. A dental consultation
Department of Critical Care Medicine, University of excluded an oral abscess source. On post-
Alberta, Edmonton, AB, Canada admission day 2, he developed shock (blood
S. van Diepen (*) pressure 70/20mmHg) and flash pulmonary
Department of Critical Care Medicine, Division of edema (Fig.19.2). The patient was stabilized
Cardiology, University of Alberta,
Edmonton, AB, Canada with non-invasive mechanical ventilation and
e-mail: sv9@ualberta.ca vasopressors. Dopamine was selected to increase

Springer International Publishing Switzerland 2017 171


R.C. Hyzy (ed.), Evidence-Based Critical Care, DOI10.1007/978-3-319-43341-7_19
172 J.M. Senaratne and S. van Diepen

Fig. 19.1Transthoracic echocardiogram documenting view. Continuous wave Doppler signal of the aortic valve
an aortic valve vegetation and severe aortic insufficiency with a very short pressure half time suggestive of severe
in the parasternal long axis view and the 5-chamber apical aortic insufficiency

with a bioprosthetic valve. He was extubated and


transferred to the surgical ward on post-operative
day 2, and discharged home on post-operative
day 6. An echocardiogram prior to discharge
showed a normally functioning aortic bioprosthe-
sis with no signs of infective endocarditis.
Ceftriaxone was continued for a total of 6 weeks.

Principles ofManagement

Epidemiology

The incidence of infective endocarditis is between


3 and 10 episodes per 100,000 person-years with a
peak incidence during the ages of 7080 of 14.5
Fig. 19.2 Chest x-ray on post-admission day 2 showing
episodes per 100,000 person-years [25]. Risk
severe pulmonary edema
factors for IE include advanced age, poor denti-
tion, injection drug use, structural heart disease
his blood pressure and his heart rate, with the (specifically valvular and congenital heart d isease),
intent of shortening diastolic filling time [1]. He the presence of prosthetic heart valves, and the
underwent an emergent aortic valve replacement presence of an intravascular catheter [610]. The
19 Management ofEndocarditis 173

most common micro-organisms responsible for Table 19.2(continued)


native valve IE in order of likelihood are listed in 2. Evidence of endocardial involvement
Table19.1 [11]. a. Echocardiography positive for IE
 Vegetation
 Abscess
Diagnosis  New partial dehiscence of prosthetic valve
b. N ew valvular regurgitation
Modified Duke criteria incorporate patient risk Minor criteria
factors, physical exam findings, laboratory stud- 1. Predisposition
ies, and echocardiographic imaging to diagnose  Predisposing heart condition
IE (Table19.2) [12]. Importantly, three sets of Injection drug use
2. Fever temperature>38 Celsius
3. Vascular phenomena
Table 19.1 Common causative microorganisms in infec-
tive endocarditis [11] Major arterial emboli
Septic pulmonary infarcts
Microorganism Frequency (%)
Mycotic aneurysm
Staphylococcus aureus 31
Intracranial haemorrhages
Coagulase-negative staphylococcus 11
Conjunctival haemorrhages
Viridans group streptococci 17
 Janeway lesions
Streptococcus bovis 6
4. Immunologic phenomena
Other streptococci 6
Glomerulonephritis
Enterococcus species 10
Oslers nodes
HACEK organisms 2
Roths spots
Fungi/yeast 2
Rheumatoid factor
Polymicrobial 1
5. Microbiological evidence
Negative cultures 10
Positive blood culture but does not meet a major
Other 4 criterion
Abbreviation: HACEK organisms include Haemophilus Serological evidence of active infection with
species, Aggregatibacter/Actinobacillus actinomycetem- microorganism consistent with IE
comitans, Cardiobacterium hominis, Eikenella corrodens,
Diagnosis
and Kingella species
Data from Murdoch etal. [11] Definite IE Possible IE
2 major criteria 1 major and 1 minor
Table 19.2Modified Duke criteria for infective criteria
endocarditis 1 major and 3 minor 3 minor criteria
criteria
Major criteria
5 minor criteria
1. Blood cultures positive for IE
Data from Li etal. [12]
a. Typical IE microorganism from two separate blood
cultures
 Viridans streptococci peripheral venous blood cultures (aerobic and
 Streptococcus bovis anaerobic) should be obtained from two sites
 HACEK group
(spatial separation) at 30min intervals (temporal
 Community-acquired enterococci
separation) prior to initiating antimicrobial ther-
b. M icroorganism consistent with IE from
apy [1, 2]. Cultures should be investigated for
persistently positive blood cultures
 Two blood cultures drawn>12 h apart
typical and fastidious (e.g. HACEK organisms)
 All of three or a majority of4 separate blood
pathogens. A transthoracic echocardiogram
cultures (with first and last sample drawn at least (TTE) is the first recommended imaging test in
1 h apart) IE [1, 2]. Recognizing the TTE sensitivity of
c. Single positive blood culture for Coxiella burnetii 4063% and specificity of 98% [13, 14], a fol-
or phase 1 IgG antibody titer>1:800 low-up transesophageal echocardiogram (TEE)
174 J.M. Senaratne and S. van Diepen

is recommended when: the TTE is non-diagnostic, persistent vegetations; (6) vegetation>15mm;


the TTE is negative with a high index of suspi- (7) prosthetic valves with relapsing infections.
cion of IE, structural cardiac complications are
suspected, the patient has a prosthetic heart valve
or an intra-cardiac device, or there is Follow-Up Evaluation
Staphylococcus aureus bacteremia [1, 2]. The
reported sensitivity of TEE is 90100% [14, 15]. Daily blood cultures should be drawn until the
The reported negative predictive value of the resolution of bacteremia. New infectious signs
original Duke Criteria is 92% [16]. (e.g. fever) or clinical evidence of structural com-
plications (e.g. heart failure or valvular regurgita-
tion) merits re-initiating blood culture
Antimicrobial Therapy surveillance as described in the diagnosis section.
Electrocardiographic surveillance is particularly
For acutely ill patients, an empiric antibiotic regi- important in patients at risk for new atrioventric-
men of intravenous vancomycin, gentamicin, and ular block including those with aortic valve endo-
ciprofloxacin or amoxicillin-clavulanate and gen- carditis, microorganisms prone to peri-valvular
tamicin has been recommended [2]. However, ini- abscess formation (e.g. Staphylococcus aureus),
tial empiric therapy should take into account local and patients with new atrioventricular block. We
patterns of antibiotic resistance. In patients with recommend routine electrocardiographic surveil-
prosthetic valves within 1 year of surgery, empiric lance until blood cultures are negative and inter-
therapy with vancomycin, gentamicin, and mittently throughout the course of antimicrobial
rifampin is recommended; rifampin should be ini- therapy particularly in patients at high risk of
tiated once cultures have cleared so as to reduce new atrioventricular block including those with
development of resistance [2]. Antimicrobial ther- aortic valve endocarditis and microorganisms
apy and duration should be tailored to the specific prone to peri-valvular abscess. Serial echocardio-
organism and sensitivity according to published graphic imaging has been recommended for both
guidelines. The duration of therapy consists of a diagnosis and follow-up. A study in 2004 reported
minimum of 46 weeks of intravenous antibiot- that in patients with a clinical suspicion of IE and
ics; the duration should be guided by guideline a negative first TTE or TEE echocardiogram, a
organism-specific recommendations [2]. second or third TTE diagnosed an additional
26.7% of patients with IE, while a second or
third TEE diagnosed an additional 19.7% [18].
Indications forSurgery Repeat imaging is also recommended when a
new complication of IE is suspected (e.g. recur-
Cardiac surgery is recommended in the treat- rent fever, new murmur, new embolus). At the
ment of IE in the following situations [1, 17]: completion of therapy, current guidelines, based
(1) aortic or mitral valve obstruction or regurgi- largely on expert opinion, recommend follow-up
tation with heart failure, shock, severe regurgi- echocardiography to detect any new silent com-
tation, or echocardiographic evidence of plication or any residual vegetation [1, 2].
hemodynamic deterioration (early mitral valve
closure or pulmonary hypertension); (2) locally
uncontrolled infection or extension (abscess, Evidence Contour
fistula, aneurysm, heart block, or enlarging veg-
etation); (3) fungal, multidrug resistant, or Although antimicrobial therapy and cardiac sur-
highly resistant organisms; (4) Persistent bacte- gery are well established in the management of
remia>510 days despite appropriate antimi- IE, there are several aspects of IE management
crobial therapy; (5) recurrent embolization with that remain controversial or less well defined.
19 Management ofEndocarditis 175

 iming ofNon-emergent
T findings upgraded the diagnosis of IE from
Surgery inIE possible to definite in 34% of patients [24].

Pending further outcome based studies, we do
In patients without an emergent or urgent indica- not recommend routine neuroimaging in neuro-
tion for cardiac surgery, there is little evidence to logically asymptomatic patients.
guide the timing of non-urgent surgery for
IE.Early surgery may reduce the risk of systemic
embolization of vegetations, whereas later sur-  iming ofSurgery inIE withSeptic
T
gery may facilitate the resolution of bacteremia Cerebral Embolic Strokes
and reduce the risk of infecting new bioprosthetic
material. A recent small randomized study of Embolic events from IE are associated with an
patients with left sided valvular IE with severe increase in-hospital mortality [25]. Patients who
mitral or aortic valve disease, and a vegetation require cardiac surgery after an embolic stroke
>10mm but no other indications for surgery were have a potential risk of hemorrhagic transforma-
randomized to early-surgery within 48 h versus tion with coronary artery bypass pump anti-
conventional care. Early surgery significantly coagulation. Given this additional risk, the
reduced the composite end point of death and optimal timing for surgery in patients with
embolic events (3% versus 23%, p =0.03) and no embolic complications remains unclear. An
differences in prosthetic valve IE recurrence was observational study compared early surgery (17
observed suggesting a possible benefit with early days after ischemic stroke) to late surgery
cardiac surgery [19]. (>7days after ischemic stroke) and found no dif-
ference in in-hospital or 1 year mortality [26].
Other studies, however, have reported higher in-
Neuroimaging inIE hospital mortality and cerebral exacerbation rates
associated with early surgery [27]. Until ade-
A reported 2250% of IE cases are complicated quately powered randomized trials are per-
by a systemic embolization, with 65% of these formed, the appropriate timing of surgery will
events involving the central nervous system [20, remain uncertain and treatment timing decisions
21]. Cerebral emboli can cause strokes, mycotic should be individualized.
aneurysms, and lead to hemorrhagic transforma-
tion. There are no guidelines for neuroimaging
test selection; however we recommend the fol-  alve Repair VersusValve
V
lowing approach: (1) All patients with new neu- Replacement
rologic signs or symptoms should initially be
evaluated with a non-contrast CT scan of the There is very little high quality evidence to guide
head. (2) Magnetic resonance imaging can be the choice of valve repair versus valve replace-
considered in symptomatic patients with a nor- ment in the setting of IE.Valve repair is theoreti-
mal CT scan or to better define CT findings. (3) cally more appealing given that the lack of
CT or magnetic resonance angiography can be prosthetic material reduces the risk of recurrence
used to evaluate mycotic aneurysms. Their role, of IE [2830]. A systematic review and meta-
however, in patients with early stroke symptoms analysis of 24 observational studies compared a
to guide endovascular therapy is unclear in this total of 470 patients who underwent mitral valve
population and should be made in conjunction repair while 724 patients underwent valve replace-
with a neurologist [22, 23]. In neurologically ment. Patients who underwent mitral valve repair
asymptomatic IE patients, a small case series has had lower in-hospital (2.3% versus 14.4%) and
reported that 79% of patients had cerebral mag- long-term (7.8% versus 40.5%) mortality [31].
netic resonance imaging abnormalities and these However, this evidence is limited by the potential
176 J.M. Senaratne and S. van Diepen

for residual confounding in observational studies infective endocarditis in the Delaware Valley, 1988
1990. Am JCardiol. 1995;76:9336.
and the lack of randomized studies.
5. van der Meer J, Thompson J, Valkenburg H, Michel M.
Epidemiology of bacterial endocarditis in the
Netherlands. 1. Patient characteristics. Arch Intern
Cardiac Device Related IE Med. 1992;152:18638.
6. Griffin MR, Wilson WR, Edwards WD, OFallon WM,
Kurland LT.Infective endocarditis. Olmsted County,
The risk of IE in patients with pacemakers or Minnesota, 1950 through 1981. JAMA. 1985;254:
implantable cardioverter defibrillators ranges from 1199202.
1.82 to 1.90 per 1000-device years [32, 33]. The 7. McKinsey DS, Ratts TE, Bisno AL.Underlying car-
diac lesions in adults with infective endocarditis. The
diagnosis of IE is more difficult in this population
changing spectrum. Am JMed. 1987;82:6818.
because blood cultures are negative in 23%, the sen- 8. Grover FL, Cohen DJ, Oprian C, Henderson WG,
sitivity of the Duke criteria is lower, and TEEs have Sethi G, Hammermeister KE.Determinants of the
a higher false negative rate [33]. Medical therapy occurrence of and survival from prosthetic valve
endocarditis. Experience of the Veterans Affairs
alone has been associated with increased morbidity
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Part III
Respiratory Disease

RobertC.Hyzy
Community Acquired Pneumonia
20
RichardG.Wunderink andMarkW.Landmeier

Case Presentation Because of additional concern for meliodosis,


the patient was started on ceftazidime, azithromy-
A 31 year old male with a history of diabetes cin, and vancomycin. He developed progressive
mellitus type 1 and recent skin infection of the hypoxemia and agitation, at which time he was
neck (for which he underwent incision and drain- intubated and started on mechanical ventilation.
age and levofloxacin treatment) presented to the Bronchoscopic bronchoalveolar lavage (BAL) of
emergency department with a three day history of the right lower lobe revealed 240 WBCs with 81%
fever, cough productive of bloody sputum, and neutrophils. Sampling of a rapidly progressing
shortness of breath. He had recently returned pleural effusion showed a pleural fluid pH6.95,
from a trip to Asia. He was tachycardic but nor- glucose 44mg/dL and LDH 1842IU/L.Gram
motensive and had an oxygen saturation of 93% stain of both fluids revealed clusters of gram posi-
on 3L nasal cannula. WBC count was 21.8K/UL tive cocci. Chest tube drainage of the right pleural
with 90% neutrophils, BUN and creatinine were space was performed. Urinary antigen testing for
8mg/dL and 1.0mg/dL, respectively, and glu- Streptocococcus pneumoniae and fungal serolo-
cose >350mg/dL.Suspicion of cavitary pneumo- gies were negative. He was empirically switched
nia on chest radiograph was confirmed by from vancomycin to linezolid. BAL and pleural
computed tomography (Fig.20.1). fluid cultures grew methicillin-resistant
Staphylococcus aureus (MRSA). Serum immuno-
Question What would be the best empirical globulins (IGs) were subsequently found to be
therapy for this patient? very low and he was given IVIG.After a prolonged
ICU course, he was ultimately discharged to an
Answer Ceftriaxone, azithromycin, and acute rehabilitation facility and subsequently
linezolid. returned to full functional status. He continues to
receive intermittent outpatient IVIG.

Principles ofManagement

Site-of-Care Decisions
R.G. Wunderink (*) M.W. Landmeier
Department of Pulmonary and Critical Care Patients admitted to the ICU with severe
Medicine, Northwestern University Feinberg School community-acquired pneumonia (CAP) g enerally
of Medicine, Chicago, IL, USA
e-mail: r-wunderink@northwestern.edu fall into one of two categories: (1) those whose

Springer International Publishing Switzerland 2017 181


R.C. Hyzy (ed.), Evidence-Based Critical Care, DOI10.1007/978-3-319-43341-7_20
182 R.G. Wunderink and M.W. Landmeier

Fig. 20.1 Representative image of the CT chest upon admission

symptom severity or co-morbid conditions require aggressive approach will lead to improved out-
ICU admission at presentation and (2) those who comes. Using the presence of 3 IDSA/ATS
transfer to the ICU later because of progressive minor criteria (Table20.1) [2] in the ED, a before/
decline despite receiving inpatient therapy. after quality improvement project demonstrated
Patients in need of mechanical ventilation or decreased mortality (adjusted odds ratio [OR]
vasopressor support because of septic shock auto- 0.24, 95% confidence interval [CI] 0.090.670,
matically require intensive care. However, the p=0.006), fewer delayed ICU transfers (14.8%
decision to admit to the ICU is more difficult when vs. 32%, p<0.001), and minimal increase in
such obvious needs are not present. Early identifi- direct admissions to the ICU when an aggressive
cation of patients likely to deteriorate is important pre-ICU assessment and resuscitation protocol
as increased mortality is associated with ICU was utilized [3].
transfer for delayed respiratory failure or onset of The Pneumonia Severity Index (PSI) and
septic shock. Pooled analysis of four prospective CURB-65 Score, while useful in predicting
CAP studies, of which 138 had delayed-transfer 30-day mortality and need for hospital admis-
compared to 315 direct Emergency Department sion, have limited ability to predict the need for
(ED) to ICU admissions, demonstrated that the intensive respiratory monitoring or vasopressor
delayed-transfer group had higher 28-day mortal- support initially. In addition to the IDSA/ATS
ity (23.4% vs. 11.7%, p<0.02) and hospital length minor criteria, several other scores such as
of stay (13days vs. 7 days, p<0.001) in propen- SMART-COP [4] generally have very good
sity-matched analysis [1]. sensitivity if the threshold is set optimally.
While some delayed transfers to the ICU rep- However, such scoring tools will lead to a sig-
resent progressive pneumonia despite appropri- nificant increase in ICU admissions if followed
ate treatment, many patients have subtle clinical rigorously, and they require prospective
findings upon presentation that predict a more validation.
20 Community Acquired Pneumonia 183

Table 20.1 IDSA/ATS minora criteria for severe com- patient. Growth inhibition by antibiotics
munity acquired pneumonia
decreases the diagnostic yield of both tests but
Respiratory rateb30 breaths/min less so when S. aureus or gram-negative bacilli
PaO2/FiO2 ratiob250 are the predominant pathogen [2]. Pleural fluid
Multilobar infiltrates sampling is necessary in a CAP patient with a
Confusion/disorientation large pleural effusion (either upon admission or
Uremia (BUN level, 20mg/dL) one which develops after empirical treatment for
Leukopeniac (WBC count, <4000 cells/mm3) CAP), as a complicated pleural space requires
Thrombocytopenia (platelet count, <100,000 cells/ adequate drainage.
mm3)
Urinary antigen testing has reasonable sensitiv-
Hypothermia (core temperature, <36C)
ity and excellent specificity for detecting
Hypotension requiring aggressive fluid resuscitation
Streptococcus pneumoniae and Legionella pneu-
Modified and reproduced with permission from Oxford
University Press on behalf of the Infectious Disease mophila serogroup 1. The test can stay positive for
Society of America. Mandell etal. [2] over 3 days in patients with S. pneumoniae and for
a
Other considerations include hypoglycemia (in a non- weeks with L. pneumophila [2]. Although antibi-
diabetic patient), acute alcoholism/withdrawal, hypona- otic sensitivity data cannot be obtained, the test is
tremia, unexplained metabolic acidosis, elevated lactate
level, cirrhosis and asplenia qualitatively important to verify that an antibiotic
b
Need for noninvasive ventilation can substitute for a regimen adequately covers such pathogens.
respiratory rate >30 breaths/min or PaO2/FiO2<250 Viral testing is important, especially in the
c
As a result of infection alone appropriate season. A positive influenza test in a
critically-ill patient should be an impetus for anti-
Diagnostic Testing viral therapy, which can hasten disease resolution
and decrease spread.
Aggressive diagnostic testing is most useful in
those with severe CAP requiring ICU admission
and in those with risk factors for Microbial Culprits
healthcare-
associated pneumonia (HCAP). In
such patients, the probability of finding a patho- Microorganisms responsible for CAP in the ICU
gen resistant to usual CAP empirical therapy (e.g. mirror those of the outpatient setting, with the
Staphylococcus aureus or Pseudomonas aerugi- addition of gram-negative pathogens and
nosa) is increased, and identification of a specific MRSA.A review of 9 studies of patients with
pathogen can lead to tailored antimicrobials, thus CAP admitted to the ICU showed that the most
decreasing cost and exposure to unnecessary common typical bacterial pathogens were S.
medications [5]. pneumoniae, L. pneumophila, Haemophilus influ-
In a patient invasively ventilated, direct access enzae, aerobic gram-negative bacilli, and S.
to the lower respiratory tract provides the oppor- aureus [7]. The relative frequency of atypical
tunity to perform an endotracheal aspirate or pathogens in the ICU setting is unclear because of
bronchoalveolar lavage (BAL). Moreover, bron- heterogeneity in diagnostic technique but is
choscopic BAL can be useful in those where spu- approximately 20 % [2]. Respiratory viruses,
tum or blood cultures do not yield a pathogen. In either as a pure or co-infection, can be detected in
a prospective study of 262 patients admitted with up to 49% of severe pneumonias. Common cul-
CAP, fiberoptic bronchoscopic BAL provided prits include parainfluenza virus, human meta-
additional diagnostic value in 49% of patients pneumovirus, influenza A and B, respiratory
who could not expectorate sputum and 52% who syncytial virus, and adenovirus [8, 9]. Much less
had treatment failure 72 h after admission [6]. common viral pathogens include coronaviruses,
Blood and sputum cultures generally have low such as the SARS virus and Middle East respira-
sensitivity but should still be performed upon tory syndrome coronavirus (MERS-CoV),
transfer to the ICU, even in the non-intubated parechoviruses, and enteroviruses.
184 R.G. Wunderink and M.W. Landmeier

Epidemiologic risk factors are helpful to sug- Empirical Versus Pathogen-Directed


gest less common etiologies (Table20.2). Therapy
Structural lung disease (e.g. COPD with repeated
exacerbations or bronchiectasis), prior hospital- With severe CAP, timely diagnosis and adequate
ization and healthcare exposure pose an increased empirical antimicrobial therapy are paramount.
risk of Pseudomonas, chronic alcoholism is a Retrospective analysis of 2731 adult patients
risk for other gram-negative pathogens with septic shock, the majority of whom had a
(Klebsiella pneumoniae or Acinetobacter spe- pulmonary primary site of infection, demon-
cies), and end-stage renal disease, injection drug strated that each hour delay in initiation of appro-
use, prior influenza infection, and prior treatment priate antibiotic therapy after the onset of
with fluoroquinolones pose an increased risk of hypotension was associated with a mean decrease
S. aureus [2]. in survival of 7.6% [10]. Consideration of the

Table 20.2 Epidemiologic conditions and/or risk factors related to specific pathogens in community-acquired
pneumonia
Condition Commonly encountered pathogen(s)
Alcoholism Streptococcus pneumoniae, oral anaerobes, Klebsiella pneumoniae,
Acinetobacter species, Mycobacterium tuberculosis
COPD and/or smoking Haemophilus influenzae, Pseudomonas aeruginosa, Legionella species,
S. pneumoniae, Moraxella catarrhalis, Chlamydophila pneumoniae
Aspiration Gram-negative enteric pathogens, oral anaerobes
Lung abscess CA-MRSA, oral anaerobes, endemic fungal pneumonia, M. tuberculosis,
atypical mycobacteria
Exposure to bat or bird droppings Histoplasma capsulatum
Exposure to birds Chlamydophila psittaci (if poultry: avian influenza)
Exposure to rabbits Francisella tularensis
Exposure to farm animals or Coxiella burnetti (Q fever)
parturient cats
HIV infection (CD4>200) S. pneumoniae, H. influenzae, M. tuberculosis
HIV infection (CD4<200) The pathogens listed for early infection plus Pneumocystis jirovecii,
Cryptococcus, Histoplasma, Aspergillus, atypical mycobacteria (especially
Mycobacterium kansasii), P. aeruginosa, H. influenzae
Hotel or cruise ship stay in previous Legionella species
2 weeks
Travel to/residence in southwestern Coccidioides species, Hantavirus
United States
Travel to/residence in Southeast and Burkholderia pseudomallei, avian influenza, SARS
East Asia
Influenza active in community Influenza, S. pneumoniae, Staphylococcus aureus, H. influenzae
Cough >2weeks with whoop or Bordetella pertussis
post tussive vomiting
Structural lung disease (e.g., Pseudomonas aeruginosa, Burkholderia cepacia, S. aureus
bronchiectasis)
Injection drug use S. aureus, anaerobes, M. tuberculosis, S. pneumoniae
Endobronchial obstruction Anaerobes, S. pneumoniae, H. influenzae, S. aureus
Modified and reproduced with permission from Oxford University Press on behalf of the Infectious Disease Society of
America. Mandell etal. [2]
CA-MRSA community-acquired methicillin-resistant Staphylococcus aureus, COPD chronic obstructive pulmonary
disease, SARS severe acute respiratory syndrome
20 Community Acquired Pneumonia 185

need to alter an empirical regimen to cover spe- parapneumonic effusion (CPPE) or empyema [12].
cific (and perhaps drug-resistant) organisms is a Frank pus or a positive pleural fluid gram stain or
major consideration when a patient is transferred culture indicate an infected pleural space and need
to the ICU while already on standard empirical for immediate drainage. However, pleural fluid
antimicrobial coverage for CAP. gram stain and culture can be negative in CPPE or
In the absence of risk factors for HCAP or drug- empyema. In such situations, pleural fluid chemistry
resistant pathogens, adequate coverage of S. pneu- is the most efficient way to assess the effusion [12].
moniae and L. pneumophila is crucial. Combination A meta-analysis showed pleural fluid pH to have the
antibiotics with a beta-lactam (cefotaxime, ceftri- highest diagnostic accuracy in detecting a compli-
axone, or ampicillin-sulbactam) and either a mac- cated effusion, followed by glucose and lactate
rolide or fluoroquinolone is recommended. A dehydrogenase (LDH) [13]. While optimal thresh-
recent prospective randomized trial demonstrated olds are still a matter of debate, a pH <7.28, glucose
improved clinical outcomes for combination ther- <40mg/dL and/or LDH level >1000IU/L suggests
apy compared to beta-lactam monotherapy, con- CPPE or empyema and the necessity for pleural
firming multiple observational studies showing drainage to achieve a good outcome [12, 14].
better clinical outcomes and decreased mortality If the pleural space is not evacuated in CPPE,
with combination therapy, especially for bactere- fibrinous adhesions develop, and neutrophils and
mic pneumococcal pneumonia [2]. bacteria accumulate leading to empyema.
For suspected Pseudomonas CAP, dual ther- Optimal therapy for CPPE and empyema hinges
apy is required and can take the form of one of on adequate antibiotic coverage and pleural
three initial combinations: drainage [15]. If pleural loculations develop,
multiple thoracostomy tubes may be needed
1. anti-pneumococcal anti-pseudomonas beta-

along with intrapleural instillation of fibrinolytic
lactam (piperacillin-tazobactam, cefepime,
agents [12]. A randomized controlled trial of
imipenem, or meropenem) plus fluoroquino-
intrapleural DNase with concomitant tissue plas-
lone (ciprofloxacin or levofloxacin), or
minogen activator (TPA) in patients with empy-
2. beta-lactam plus an aminoglycoside and azithro-
ema showed a lower rate of surgical referral and
mycin, or
hospital length of stay compared with placebo
3. beta-lactam plus an aminoglycoside and an
and individual agents alone [16]. Lysis of adhe-
anti-pneumococcal fluoroquinolone
sions or decortication via video-assisted thoraco-
For MRSA pneumonia linezolid is superior to scopic surgery (VATS) or thoracotomy may be
vancomycin, particularly if a toxin-secreting necessary if less invasive measures fail. The tim-
community-acquired strain is the culprit [2]. A ing of surgical referral and type of surgical
randomized double-blind trial comparing line- maneuver, though, largely depend on the patient
zolid to dose-adjusted vancomycin for treatment and severity of illness.
of MRSA-proven HAP or HCAP demonstrated In contrast, uncomplicated parapneumonic
eradication of MRSA and clinical cure were sta- effusions are usually exudates with pleural fluid
tistically better with linezolid, and linezolid had pH >7.28 and normal glucose. As these effusions
less incidence of nephrotoxicity [11]. In the set- are reactive, they should resolve with continued
ting of methicillin-susceptible S. aureus, beta- antibiotic therapy.
lactam therapy is still the treatment of choice.

Evidence Contour
Parapneumonic Effusions
Several aspects of severe CAP management
In the presence of a CAP-related pleural effusion, remain without consensus, including the assess-
thoracentesis can distinguish between uncompli- ment of risk for multidrug resistant (MDR) patho-
cated parapneumonic effusion (UPPE), complicated gens, adjuvant assessment tools, and treatments.
186 R.G. Wunderink and M.W. Landmeier

 isk ofMultidrug Resistant (MDR)


R hemolysin, may result in the characteristic severe
Pathogens pulmonary hemorrhage of both the MRSA and
MSSA infections [18]. Antibiotic therapy that
Empirical antibiotic therapy for severe CAP hinges also suppresses toxin production provides better
on the risk for drug resistant organisms. Over the outcomes and improved survival, as illustrated in
last decade HCAP has been used to describe the a retrospective study of PVL-positive CAP [19].
entity wherein patients develop pneumonia out- Clindamycin and linezolid have been shown to
side the hospital yet have pathogens usually asso- suppress in-vitro formation of PVL, alpha-
ciated with HAP or VAP, such as MDR hemolysin, and toxic shock syndrome toxin 1,
gram-negative bacilli and MRSA.Criteria for whereas vancomycin and beta-lactams have no
HCAP and the resultant number of patients who effect [18]. The benefit of clindamycin combined
should get broad- spectrum empirical therapy with a beta-lactam for MSSA CAP is unclear,
remain subject to debate. Using any risk factor for with a recent prospective analysis demonstrating
drug-resistant pathogens (DRP) leads to antibiotic that nearly 18% of CA-MRSA isolates were
overtreatment, while ignoring risk factors is asso- clindamycin resistant; whether antibiotic growth
ciated with undertreatment and adverse outcomes inhibition detected by MIC-susceptibility tests
[5]. In a prospective observational study, Shindo correlates with toxin-suppression activity, though,
etal. found six independent risk factors for patho- is unclear [20, 21]. While the preferred treatment
gens resistant to the usual CAP antibiotics: (1) for PVL-positive MSSA CAP is still unclear, line-
hospitalization2days during the previous 90 zolid appears the most reasonable choice for
days, (2) antibiotic use during the previous 90 CA-MRSA CAP in light of its potential to sup-
days, (3) non-ambulatory status, (4) tube feedings, press exotoxin and offer faster eradication of
(5) immunocompromised status, and (6) use of other MRSA clones. The rapid bactericidal activ-
gastric acid suppression medications [17]. ity of ceftaroline, a cephalosporin with MRSA
Presence of three or more risk factors should activity, may obviate the need to suppress exo-
prompt a physician to consider broad-spectrum toxin production, but data are still very limited.
antibiotic therapy, as the frequency of drug resis-
tant pathogens may be as high as 43%. These cri-
teria work equally well as the previous definition Procalcitonin
of HCAP, and a strategy for initial antibiotic selec-
tion based on these risk factors may result in far Procalcitonin (PCT), a peptide released in response
less empirical broad-spectrum therapy while still to bacterial infection but suppressed by interferons
identifying the majority who need it. induced by viral infections, has the potential to dis-
tinguish between bacterial and viral causes of pneu-
monia and potentially guide antibiotic decisions. In
Drugs toSuppress Toxin withMRSA a prospective study of CAP, clinicians were encour-
aged (PCT level >0.25mcg/L) or discouraged (PCT
A community-acquired MRSA (CA-MRSA) level <0.1mcg/L) from using antibiotics based on
clone, distinct from that usually causing HCAP, procalcitonin cutoffs. PCT guidance reduced total
HAP or VAP, has emerged as a cause of pneumo- antibiotic exposure, antibiotic prescriptions on
nia with striking necrotizing features. Methicillin admission, and antibiotic treatment duration without
resistance results from a different staphylococcal adversely affecting clinical outcomes [22]. Further
cassette chromosome type (SCCmec type IV), analysis has shown that persistently elevated PCT
which also includes a gene encoding Panton- levels are associated with adverse outcomes such as
Valentine leukocidin (PVL) and other exotoxins. the development of pneumonia complications and
Presence of PVL may explain the associated neu- death [23]. A similar benefit on shortening antibiotic
tropenia while other exotoxins, such as alpha- duration with a PCT-driven protocol has been found
20 Community Acquired Pneumonia 187

in several studies of severe sepsis. Despite these gation in low- and high-risk patients with community-
studies, PCT has not been FDA approved for this acquired pneumonia. Eur JMicrobiol Infect Dis.
2005;24:2419.
indication in the US. 7. File TM.Community-acquired pneumonia. Lancet.
2003;362:19912001.
8. Karhu J, Ala-Kokko TI, Vuorinen T, etal. Lower
Corticosteroids respiratory tract virus findings in mechanically venti-
lated patients with severe community-acquired pneu-
Death in CAP may result from either failure to monia. Clin Inf Dis. 2014;59(1):6270.
9. Choi SH, Hong SB, Ko GB, etal. Viral infection in
eradicate the microorganism or from inappropri-
patients with severe pneumonia requiring intensive
ate (and perhaps exaggerated) host response to care unit admission. Am JRespir Crit Care Med.
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tension before initiation of effective antimicrobial
severe CAP with corticosteroids.
therapy is the critical determinant of survival in human
While a small prospective study [24] and sev- septic shock. Crit Care Med. 2006;34(6):158996.
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roid administration in severe CAP, a larger Linezolid in methicillin-resistant Staphylococcus
aureus nosocomial pneumonia: a randomized, con-
randomized double-blinded trial evaluating the
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chemical analysis in parapneumonic effusions. Am
Conversely, in a highly selected group of patients
JRespir Crit Care Med. 1995;151:17008.
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with less treatment failure [27]. sions. Eur Respir J.2009;34:13839.
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16. Rahman NM, Maskell NA, West A, etal. Intrapleural
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9. Sicot N, Khanafer N, Meyssonnier V, etal. Methicillin
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minor criteria aid pre-intensive care unit resuscitation Prevalence of methicillin-resistant Staphylococcus
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J.2014;43:85262. monia. Clin Inf Dis. 2012;54(8):112633.
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Hydrocortisone infusion for severe community- steroids on treatment failure among hospitalized
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Management ofAcute Respiratory
Distress Syndrome 21
RobertC.Hyzy

Case Presentation ventilation in order to avoid ventilator associated


lung injury (VALI). This patient was started on
A 53 year old woman with a history of alcohol assist control mechanical ventilation with a tidal
abuse, pancreatitis, hypertension and COPD pre- volume of 350ml and 100% FiO2. Neuromuscular
sented with 3 days epigastric pain, nausea, vomit- blockade with cisatracurium was initiated. The
ing and decreased oral intake in addition to depth of paralysis was monitored with train of
respiratory symptoms which included a week of four nerve stimulation and the depth of sedation
cough with white sputum. At the time of presen- with midazolam and fentanyl was assessed via bi-
tation to the hospital her alcohol level was 207, spectral analysis. Over the next 12h her PEEP
lipase was 838, white blood cell count was was increased to 16cm H2O and her FiO2 was
12.8K.She was started on IV hydration and decreased to 40%. During this time the patients
received benzodiazepines for incipient alcohol plateau airway pressure ranged between 26 and
withdrawal when her mental status became delir- 28cm H2O.She was treated with broad spectrum
ious. Over the course of the next 12 h her oxygen- antibiotics, vancomycin, pip-tazo and azithromy-
ation progressively deteriorated and she was cin. Results of a culture obtained from a mini-
intubated. Post intubation chest x-ray and a rep- BAL specimen failed to grow any pathogenic
resentative image from the CT scan performed organisms. Cisatracurium was discontinued after
are below (Figs.21.1 and 21.2). 48h. At that time, solu-medrol was begun at a
dose of 1mg/kg body weight. The patient had had
Question What approach should guide this already been on an insulin drip but the glucose
patients ventilator management? target range was changed to less than 110mg/dL
from the usual less than 150mg/dL at that time.
Answer Lung Protective Ventilation Daily sedation holidays were instituted to assess
mental functioning and a physical therapy consult
All patients with the acute respiratory distress was initiated to promote mobility. The patient
syndrome should be treated with lung protective remained hemodynamically stable with good
renal function and diuresis with furosemide was
initiated, resulting in a negative fluid balance of
2400ml on the third ICU day and about 12 L/day
subsequently. Gas exchange remained satisfac-
R.C. Hyzy tory such that on the fourth ICU day PEEP was
Division of Pulmonary and Critical Care Medicine,
University of Michigan, Ann Arbor, MI, USA decreased to 5cm H2O.By that time the patient
e-mail: rhyzy@umich.edu was able to march in place at the bedside and take

Springer International Publishing Switzerland 2017 189


R.C. Hyzy (ed.), Evidence-Based Critical Care, DOI10.1007/978-3-319-43341-7_21
190 R.C. Hyzy

Fig. 21.2Representative section of chest CT from


patient in case study demonstrating bilateral alveolar infil-
trates with mild compressive atelectasis in the dependent
lung zones

Fig. 21.1 Chest x-ray of patient with ARDS from case


study showing bilateral alveolar infiltrates
nostic criteria for acute lung injury and
ARDS.Although easily calculated the P/F ratio
a brief walk into the hall outside of her room. did not account for the effect of mean airway
Later that day the patient was weaned and extu- pressure on oxygenation. The Berlin criteria for
bated. She was transferred out of the ICU to the ARDS, published in 2012 [2], did away with the
general medical ward the following day. concept of acute lung injury (ALI) in favor of
classifying ARDS as mild, moderate or severe.
ARDS severity is based on oxygenation criteria
Principles ofManagement which also accounts to some extent, for the appli-
cation of positive airway pressure. The diagnosis
Risk Factors forARDS andDiagnosis of ARDS is based on clinical presentation and
physiology. Diffuse alveolar damage is usually
Several risk factors for the development of ARDS seen histopathologically, but may be absent even
have been identified. The lung injury prediction in cases of severe ARDS [3].
score (LIPS) is a model which incorporates know
risk factors and predicts the likelihood of devel-  erlin Definition ofARDS
B
oping ARDS accordingly [1] (Table21.1). Many Timing
patients with multiple risk factors do not develop Within 1 week of a known clinical insult or
ARDS as even patients with a LIPS score of more new or worsening respiratory symptoms
than 7 only develop ARDS less than half of the Chest Imaging
time. In the case presentation above the patients Bilateral opacities not fully explained by
history of chronic alcohol ingestion was a predis- effusions, lobar/lung collapse, or nodules
posing risk factor for the development of ARDS Origin of Edema
in what was likely to have been an aspiration Respiratory failure not fully explained by
pneumonia, which itself in another risk factor. cardiac failure or fluid overload
The PaO2 to FiO2 (P/F) ratio, a measure of Need objective assessment (e.g. echocar-
oxygenation impairment was part of the old diography) to exclude hydrostatic edema if
American European Consensus Conference diag- no risk factor present
21 Management ofAcute Respiratory Distress Syndrome 191

Table 21.1 Lung injury prediction score (LIPS)


LIPS points Examples
Predisposing conditions (1) Patient with history of alcohol abuse with septic shock
from pneumonia requiring FiO2>0.35in the emergency room:
Sepsis+shock+pneumonia+alcohol abuse+FiO2>0.35
1+2+1.5+1+2=7.5
Shock 2
Aspiration 2
Sepsis 1
Pneumonia 1.5
High-risk surgerya
Orthopedic spine 1
Acute abdomen 2
Cardiac 2.5
Aortic vascular 3.5
High-risk trauma (2) Motor vehicle accident with traumatic brain injury, lung
contusion, and shock requiring FiO2>0.35 Traumatic brain
injury+lung contusion+shock+FiO2>0.35 2+1.5+2+2=7.5
 Traumatic brain injury 2
Smoke inhalation 2
Near drowning 2
Lung contusion 1.5
Multiple fractures 1.5
Risk modifiers
Alcohol abuse 1
Obesity (BMI>30) 1 (3) Patient with history of diabetes mellitus and urosepsis
with shock Sepsis+shock+diabetes 1+21=2
Hypoalbuminemia 1
Chemotherapy 1
FiO2>0.35 (>4 L/min) 2
Tachypnea (RR>30) 1.5
SpO2<95% 1
Acidosis (pH<7.35) 1.5
Diabetes mellitusb 1
Reprinted with permission of the American Thoracic Society. Copyright 2016 American Thoracic Society
From Gajic etal. [1]
The American Journal of Respiratory and Critical Care Medicine is an official journal of the American Thoracic
Society
Definition of abbreviations: BMI body mass index, RR respiratory rate, SpO2 oxygen saturation by pulse oximetry
a
Add 1.5 points if emergency surgery
b
Only if sepsis

Oxygenation Severe ARDS The PaO2/FiO2 is


Mild ARDS The PaO2/FiO2 is 100mmHg on ventilators setting that
>200mmHg, but 300mmHg, on venti- include PEEP 5cm H2O
lator settings that include positive end-
expiratory pressure (PEEP) or continuous
positive airway pressure (CPAP) 5cm Lung Protective Ventilation
H2O.
Moderate ARDS The PaO2/FiO2 is Avoiding over distension of the lung during
>100mmHg, but 200mmHg, on ventila- mechanical ventilation of ARDS patients is called
tor settings that include PEEP 5cm H2O. lung protective ventilation (LPV). LPV reduces
192 R.C. Hyzy

hospital and 28 day mortality [4], presumably by dependent lung zones. Dependent lung zones are
decreasing lung inflammation and avoiding the not ventilated due to the weight of the lung, i.e.
fibrinoproliferative phase of this condition. The compressive atelectasis. In between the two
largest trial to date demonstrating this was done zones is an area of lung which distends and col-
by the NIH sponsored ARDS Network, whose lapses with each delivered ventilator breath, a
results were published in 2000 [5]. The approach phenomenon termed cyclic atelectasis. In animal
undertaken in this trial, the utilization of a tidal models cyclic atelectasis produces lung injury.
volume of less than 6.5cc/kg of ideal body weight Optimizing the recruitment of additional areas of
(IBW) (but at least 4cc/kg) and maintaining a pla- collapsed lung with PEEP in order to mitigate the
teau pressure of less than 30cm of H2O has effect of cyclic atelectasis is the rationale behind
become the standard treatment to provide open lung ventilation. Meta-analysis of several
mechanical ventilation to patients with large clinical trials demonstrated a mortality ben-
ARDS.The calculation of ideal body weight is efit to open lung ventilation [8]. However, each of
based on height: the three large trials used for this analysis indi-
vidually failed to demonstrate a mortality benefit.
Male IBW ( kg ) = 50 + 0.91( cm height 152.4 ) To the extent that the large clinical trials did not
Female IBW ( kg ) = 45.5 + 0.91( cm height 152.4 ) demonstrate harm with higher levels of PEEP,
such as an increased rate of pneumothorax, clini-
Plateau airway pressure is not a threshold vari- cians may choose to use the open lung approach
able [6] and it should be maintained as low as in their patients. Several approaches to performing
realistically possible, even though in the open lung ventilation are available. A study eval-
ARDSNet trial tidal volume was allowed to uating the effect of PEEP on lung recruitment, as
increase up to 8cc/kg as long as plateau pressure evaluated by CT scan, suggested the best tradeoff
remained under 30cm H2O.The ARDS Network between lung recruitment while simultaneously
approach is the standard approach to lung protec- avoiding lung overdistension was obtained via a
tive ventilation. However, multiple other high PEEP strategy similar to that utilized in the
approaches have been championed, each ostensi- Lung Open Ventilation Study (LOVS) [9]
bly offering a refinement of the basic lung protec- (Table21.2).
tive ventilation approach of the ARDSNet. In a
retrospective analysis of several of the large trials,
a low driving pressure (P) was found to be better Prone Ventilation
correlated with ARDS mortality than tidal volume
or plateau pressure [7]. Driving pressure is the A large randomized, multi-center trial, PROSEVA,
pressure being applied by the ventilator to distrib-demonstrated an impressive mortality benefit to
ute gas to the recruited portion of the lungs which patients who underwent prone ventilation 18 h
are not collapsed from compressive atelectasis per day [10]. Prone ventilation can be considered
caused by the weight of the lung in the dependent to be a form of open lung ventilation. This trial
lung zones. In a patient not making spontaneous addressed criticisms of earlier, negative trials of
respiratory efforts P can be estimated as plateau prone ventilation in that the study subjects with
pressure minus PEEP in cm H2O. ARDS had a severe oxygenation defect, were
proned for long periods of time daily and a proto-
colized lung protective approach was used in the
Open Lung Ventilation control group, the original ARDS network
approach [11]. Using the low PEEP ARDS
Avoiding alveolar overdistension with a low tidal Network approach in the control group, while
volume is the established mechanism of avoiding appropriate, leaves open the question as to
ventilator-associated lung injury. In the supine whether proning adds incremental benefit to
ARDS patient delivered gas is distributed to non- patients who are already receiving higher levels
21 Management ofAcute Respiratory Distress Syndrome 193

Table 21.2 Example of open-lung high positive end- extensions of basic lung protective ventilation
expiratory pressure (PEEP) strategy
and essentially are attempts to find the optimal
FIO2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 approach.
PEEP 510 1018 1820 20 20 2022 22 2224

Additional Risk Factors


of PEEP (see open lung ventilation, below). In
addition, patients underwent neuromuscular Vitamin D supplementation in critically ill
blockade, which itself may have a beneficial patients who are severely deficient has been
effect on outcome. Despite these concerns, prone shown to decrease hospital mortality [14]. Low
ventilation has assumed an important place as a prehospital levels of vitamin D are associated
rescue modality in the treatment of severe ARDS with an increased risk of respiratory failure [15],
patients who have not responded to a conven- and may be common in patients at risk for or hav-
tional lung protective strategy. ing ARDS [16]. The NIH PETAL Network in
conducting a randomized trial of high dose vita-
min D in deficient patients at risk for ARDS.
Fluid Management Cytomegalovirus reactivation (CMV) is com-
mon in critically ill immunocompetent patients
Volume removal via diuretic administration can and portends a worse outcome in patients com-
shorten the duration of mechanical ventilation in pared to CMV negative patients [17]. In one
patients who are recovering from ARDS.The series, immunocompetent patients with ARDS
Fluid and Catheter Therapy Trial of the ARDS were found to have a histologic evidence of
Network demonstrated an average of 2.5day CMV pneumonia on open lung biopsy in 18 of
increase in ventilator free days with a fluid con- 37 cases of ARDS [18]. A NIH sponsored trial is
servative approach [12]. In addition, in patients examining whether the administration of ganci-
in whom the total protein is less than 6.0 g/dL, clovir improves outcomes in CMV antibody pos-
the addition of albumin for 72 h helped promote itive patients with acute respiratory failure and
fluid loss in ARDS patients and improved oxy- ARDS [19].
genation [13].

Subgroups andSubphenotypes
Supportive Care
Because ARDS is a clinical syndrome, with an
Other important aspects of care pertain more array of risk factors, and not a disease per se,
generally to the care of all patients receiving attempts have been made to evaluate ARDS sub-
invasive mechanical ventilation. These include groups from several standpoints. Sepsis induced
the early and successful use of enteral alimen- ARDS has a worse outcome than that due to other
tation, a daily sedation awakening trial, delir- causes [20]. As is evident from lung biopsy and
ium screening and management, early mobility, autopsy series clinical classification as either
and treating the underlying illness such as pneumonia or ARDS is frequently at odds with
pneumonia. tissue findings [3, 21]. In addition the histopa-
thology likely evolves over time, with pneumonia
and/or diffuse alveolar damage yielding to
Evidence Contour fibrotic changes. Rather than determining which
subcategory of ARDS a patient manifests on the
Several aspects of management in the patient basis of causal risk, more relevant to treatment
with ARDS remain without consensus in the face and outcome may be subclassification based on
of available clinical trials. Several of these are clinical manifestations. ARDS patients demon-
194 R.C. Hyzy

strate different amounts of recruitable lung with Pplat. An accompanying editorial suggested, in
administered PEEP [22]. Patients showing reality, this approach was a means to justify the
improvements in oxygenation due to lung recruit- use of higher PEEP levels than customarily
ment with PEEP may have a lower mortality than employed (i.e. > 22cm H2O). Also, the validity
those who do not [23]. Additionally, ARDS of using esophageal pressure as an estimate of
patients with a hyperinflammatory subphenotype pleural pressure has been questioned [26]. A
have a higher mortality regardless of the ascribed larger, multi-center trial is being conducted to
cause for ARDS [24]. It remains to be determined confirm these results [27]. This approach can be
identification of subgroups based on recruitabil- considered in patients in whom the chest wall is
ity or hyperinflammatory subphenotypes repre- likely contributing to alveolar pressure, such as
sent different histopathologies (pneumonia patients who are post-operative from abdominal
versus diffuse alveolar damage versus fibrosis) or surgery, are morbidly obese, have ascites or have
will lead to improved outcomes by varying the a chest wall deformity such as scoliosis, provided
approach to therapy on that basis. the necessary equipment and expertise are
available.

Helmet Ventilation
 ressure Limited Mechanical
P
Noninvasive ventilation with a helmet interface, Ventilation
rather than the more conventional face mask, was
shown in a pilot randomized trial of ARDS patients Pressure-limited modes of mechanical ventila-
to decrease the rate of intubation. This observation tion, including airway pressure release ventila-
awaits confirmation in a larger trial [24a]. tion (APRV), bi-level, and pressure-controlled
inverse ratio ventilation are all ways of providing
lung protective ventilation. Ostensibly, pressure
Transpulmonary Pressure limited modes offer an advantage of less varia-
tion in transpulmonary pressure and a lower tidal
Plateau airway pressure, measured after a deliv- volume to functional residual capacity alveolar
ered tidal volume, reflects lung and chest wall strain ratio, which would be offer a salutary effect
compliance. The contribution of the chest wall, on VALI [28]. Additionally, APRV and bi-level
which includes the abdominal compartment, can ventilation offer the additional putative benefit of
confound the utilization of plateau pressure as a allowing spontaneous breathing, which might
guide to lung protective ventilation by suggesting help prevent ventilator-induced respiratory mus-
the lung is being overdistended when in fact this cle weakness [29] and more completely ventilate
is not the case. By subtracting an estimation of lung zones near the diaphragm. Despite adher-
pleural pressure made by readings taken by an ents, to date, the superiority of this approach to
esophageal balloon (Pes) from the measured pla- volume cycled ventilation has not been demon-
teau pressure (Pplat) an estimate of transpulmo- strated [30].
nary pressure (PL) may be determined and used to
guide lung protective ventilation.
Neuromuscular Blockade
PL = Pplat - Pes

A mortality benefit was observed in a single A large, multicenter randomized trial demon-
center randomized trial which used this approach strated a mortality benefit in patients who
[25]. The results may have been influenced by the received 48h of neuromuscular blockade fol-
enrollment of more than 60% post abdominal lowing the onset of ARDS [31]. Less baro-
surgery patients, a population in whom the trauma was observed in the paralysis group,
abdominal compartment is likely to make a sig- whereas a greater incidence of neuromuscular
nificant contribution to the chest wall and thereby weakness was not. Because the Kaplan-Meier
21 Management ofAcute Respiratory Distress Syndrome 195

survival curves did not separate until 14 days, randomized to ECMO who did not receive
the mechanistic benefit of this approach has ECMO, concerns regarding whether the benefit
been challenged. In addition this study has been seen in this study represents the modality itself
criticized for lacking a more rigorous approach or the benefit of regionalization of care to a spe-
to the assessment of neuromuscular weakness. cialty hospital is a concern. Use of ECMO has
Some support is given to this study by a data- been prevalent during recent H1N1 outbreaks,
base analysis study which demonstrated a mor- when young patients with few if any co-
tality benefit in patients with a pulmonary morbidities developed ARDS refractory to more
source of sepsis and respiratory failure who commonplace ventilator approaches to oxygen-
underwent neuromuscular blockade within the ation [37]. Another randomized trial of ECMO
first 48 h for reasons other than intubation [32]. in ARDS patients is currently underway in
Additionally, in an animal model spontaneous Europe [38].
breathing caused regional alveolar overdisten-
sion near the diaphragm due to Pendelluft venti-
lation which did not occur in paralyzed animals Corticosteroids
[33]. Hence the notion that spontaneous breath-
ing provides better ventilation to lung zones Most meta-analyses have not suggested con-
near the diaphragm may not be valid. The NIH firmed a mortality benefit to the use of cortico-
sponsored PETAL (Prevention and early treat- steroids in patients with ARDS.The LaSRS
ment of acute lung injury) Network is conduct- study performed by the ARDS Network is the
ing a clinical trial to re-evaluate whether largest trial to date examining whether cortico-
neuromuscular blockade benefits patients with steroids benefit ARDS patients [39]. No mortal-
severe ARDS. ity benefit was ultimately observed although a
significantly greater of patient days alive and
off assisted breathing (ventilator-free days).
 igh Frequency Oscillatory
H An initial mortality benefit in favor of the ste-
Ventilation (HFOV) roids may have been lost among the 20 patients
who returned to assisted breathing, as opposed
Two large, randomized multi-center trials to 6in the control group. Whether this was due
published in 2012, OSCILLATE and OSCAR, to tapering steroids after weaning or the devel-
failed to show benefit to this clearly open-lung opment of neuromuscular weakness is unclear.
approach [34, 35]. Critics suggested that con- Although an increased morality was seen in
cerns regarding volume status and effects on LaSRS among patients who were started on cor-
the right ventricle may have contributed ticosteroids beyond 14 days of mechanical ven-
adversely to the findings. To the extent that the tilation for ARDS the confidence intervals were
OSCILLATE trial showed an increased mor- large. This has resulted in some authors warn-
tality in the HFOV group this approach cannot ing against starting corticosteroids beyond 14
be recommended at present for adults with days. If given, corticosteroids should be admin-
ARDS. istered at a dose of 1mg per kg body weight
twice per day with a taper over 28 days. Tight
glycemic control may play a role in minimizing
 xtra Corporeal Membrane
E the risk of neuromuscular weakness [40].
Oxygenation (ECMO) Corticosteroid administration may result in pro-
longed viral replication in patients with ARDS
A mortality benefit was observed in the British due to H1N1 influenza. A higher mortality has
CESAR trial among patients randomized to be been reported in observational series in these
transported to the specialty center to receive patients and corticosteroid administration is
ECMO on an intent-to-treat basis [36]. As the best avoided early on in the care of influenza
mortality benefit was accounted for by patients patients with ARDS [41].
196 R.C. Hyzy

Inhaled Vasodilators and acute respiratory distress syndrome: systematic


review and meta-analysis. JAMA. 2010;303:865.
9. Chiumello D, Cressoni M, Carlesso E, etal. Bedside
Trials of inhaled nitric oxide have failed to yield selection of positive end-expiratory pressure in mild,
positive results. Meta-analyses have suggested moderate and severe acute respiratory distress syn-
that while oxygenation improves not mortality drome. Crit Care Med. 2014;42:252.
10. Gurin C, Reignier J, Richard JC, Beuret P, Gacouin
benefit accrues from the use of this agent [42].
A, Boulain T, Mercier E, Badet M, Mercat A, Baudin
Iloprost (synthetic PGI2) also increases pO2. O, Clavel M, Chatellier D, Jaber S, Rosselli S,
However, no large clinical trials have been per- Man