Ebook Critical care toxicology - Diagnosis and management of the critically poisoned patient (2/E): Part 1

Jeffrey Brent 
Senior Editor
Keith Burkhart · Paul Dargan
Benjamin Hatten · Bruno Megarbane
Robert Palmer · Julian White 
Editors

Critical Care
Toxicology
Diagnosis and Management of the
Critically Poisoned Patient
Second Edition


Critical Care Toxicology


Jeffrey Brent
Senior Editor

Keith Burkhart • Paul Dargan
Benjamin Hatten • Bruno Megarbane
Robert Palmer • Julian White
Editors

Critical Care Toxicology
Diagnosis and Management of
the Critically Poisoned Patient
Second Edition

With 675 Figures and 487 Tables

Senior Editor
Jeffrey Brent
Department of Medicine
Division of Clinical Pharmacology
and Toxicology
University of Colorado
School of Medicine
Aurora, CO, USA
Editors
Keith Burkhart
FDA, Office of New
Drugs/Immediate Office
Center for Drug Evaluation
and Research
Silver Spring, MD, USA

Paul Dargan
Clinical Toxicology
St Thomas’ Hospital
Silver Spring, MD, USA

Benjamin Hatten
Toxicology Associates
University of Colorado
School of Medicine
Denver, CO, USA

Bruno Megarbane

Medical Toxicological Intensive
Care Unit
Lariboisiere Hospital
Paris-Diderot University
Paris, France

Robert Palmer
Toxicology Associates
University of Colorado
School of Medicine
Denver, CO, USA

Julian White
Toxinology Department
Women’s and Children’s Hospital
North Adelaide, SA, Australia

ISBN 978-3-319-17899-8
ISBN 978-3-319-17900-1 (eBook)
ISBN 978-3-319-17901-8 (print and electronic bundle)
DOI 10.1007/978-3-319-17900-1
Library of Congress Control Number: 2017930938
1st edition: # Mosby 2005
# Springer International Publishing AG 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
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The use of general descriptive names, registered names, trademarks, service marks, etc. in this

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The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland


Foreword

Critical Care Toxicology belongs in every critical care unit, emergency department, poison center, library, emergency response center, and on the most easily
reached shelf for anyone interested in or who comes in contact with medical
toxicology. This masterful compilation of information has many attributes,
among which are:
•
•
•
•
•
•
•
•

Evidence based well-referenced information
Editors and authors who are experts in their fields

Concise and clear presentation
Tables that convey critical data
Figures and diagrams that are clinically relevant
Paragraph headers that allow focused access to information
Calculations and formulas that are fully explained
Lists of treatment materials to obtain in advance with contact information of
unusual items
• Therapeutic dosages that are detailed enough to be utilized without additional references
In most cases, diagnostic and therapeutic information can be obtained in a
few minutes given the book’s careful organization. For those patients presenting with complicated or multiple exposures, the structure provides a
straightforward method of rapidly developing and working through a differential diagnosis.
The quality of this book should come as no surprise after looking at the
impressive listing of authors. The editors, each of whom I have known, worked
with, and respected for many years, have selected an international group of
experts whose credibility is unmatched. They represent the best of our profession of medical toxicology and have written a large percentage of the most
important and groundbreaking publications in our field. The editors and
authors are the most sought-after educators in our annual toxicology meetings
around the world and provide clinical expertise as well as leadership and
training for all of us who work in this wide and varied area.
In the preface to the first edition of Critical Care Toxicology, the word
“passion” occurs in the very first sentence. For all of us who have ever written a
scientific monograph, paper, chapter, book, or prepared a teaching session, the
word passion certainly defines a major requirement for preparation of materials
v


vi

that will communicate the knowledge that is intended. It takes time and effort
to write something that will stand the test of time, and when written with

passion it means that the author has not skipped over anything and left nothing
of importance unaddressed. It requires thorough knowledge of the subject, real
world experience, fully researched literature, and draft after draft until communication is assured. When reading this book, it is apparent that the editors
and authors have achieved their goal.
Before writing this foreword, the editors provided me with some chapters
from the second edition. In reviewing four of them – “Acid-base,” “Hypotension and Shock,” “Seizures,” and “Acute Respiratory Distress Syndrome” – it
was readily apparent that this second edition is an improvement on an already
excellent book. More current materials are included as expected, but using
these chapters as examples the authors have dramatically improved this book.
Acid-base in the critical care setting is a complicated and often difficult issue.
To address that the authors have doubled the length of this chapter and
substantially added information which will be valuable to all who utilize it.
The chapters on hypotension and shock and acute respiratory distress syndrome have been broken out of their previous locations and addressed comprehensively to reflect their importance. The chapter on seizures has also been
doubled in length and contains a considerable amount of new information that
is clearly presented.
The authors have also added speed of access to this book through the use of
a table of contents at the beginning of each chapter. This further enhances the
ability of the reader to get to an answer under emergent circumstances.
The book also has another purpose than just providing critical information
in a clinical setting. It provides a very readable and understandable educational
experience for all those who are studying this area. This must include
addressing controversial areas with which the reader may be familiar and if
not familiar ought to be familiar, and this book engages all of this.
Even those of us who have been in this field for a long time stand to learn
something from this book. The discussion of the strong anion gap in the acidbase chapter coupled with the very practical explanations of the other factors in
this important area is the clearest I have ever read. An area in which I have little
knowledge is malignant hyperthermia, and this chapter provides a clear explanation along with even a phone number and website to get additional updated
information in what is apparently a rapidly evolving issue. The editors clearly
want readers to get the right answers to their questions.
Critical Care Toxicology covers all of the areas in medical toxicology in a

series of well-written chapters following the excellent chapters that provide an
approach to the critically poisoned patient and an understanding of toxic
syndromes. Images of various aspects of toxicological encounters provide
visual reinforcement of the written materials.
The index is very well done and comprehensive. Unlike the 7th edition in
1959 of Nelson’s pediatric text where the editor’s daughter, who hated having
to produce the index, entered under B “Birds, for the” and listed the entire
book, the index of Critical Care Toxicology was obviously prepared by
someone who had a passion for helping readers get to answers.

Foreword


Foreword

vii

Critical Care Toxicology provides a very valuable contribution to all
aspects of medical toxicology from education to, as the title states, critical
care. It should be readily accessible to everyone who may face this issue from
forming a differential diagnosis to rendering care.
Rocky Mountain Poison and Drug Center
Denver, Colorado
USA

Barry H. Rumack
Director Emeritus


Preface to the Second Edition

Those readers who are familiar with the first edition of Critical Care Toxicology (CCT) know that it was about passion – our collective passion for caring
for patients with the group of fascinating physiological derangements caused
by exogenous chemical exposures. While our passion for the field of clinical
toxicology remains unabated, an additional theme that characterizes the second edition of Critical Care Toxicology is scientific evidence.
In the 10 years since the publication of the first edition, a considerable body
of new scientific evidence has emerged, new antidotes have become available,
and systematic reviews and meta-analyses have become more commonplace in
the field of clinical toxicology. Seizing upon the opportunity to provide a
compendium of this accumulated evidence-based knowledge, we have worked
with our chapter authors to assure that they have stayed true to the existing
body of empirical data and, in the many places, where data gaps exist identify
them so that the user of this book will understand the basis for the treatment
recommendations we provide. In order for the user of CCT to quickly discern
the veracity of the evidence supporting the treatment recommendations provided, we have adopted the US Public Health Service’s rating of scientific
evidence. These gradings allow the reader to instantly know the level of
scientific support for various treatment recommendations and thus to be able
to rely most heavily on well-supported therapeutic modalities.
We are highly cognizant of the reality that there are many areas where the
evidence base relating to treatment decisions is insufficient. Nevertheless, the
clinician treating the critically poisoned patient still requires guidance. Given
that so many of our chapter authors represent the world’s authority on their
topic, we have also strongly encouraged them to give their highly informed
opinions on how to proceed in the many areas where there are clear knowledge
gaps. Where they have supplied these opinions they have been identified as
such, and we have worked with them to also explain their thought processes
underlying these opinions.
We are very proud of the group of chapter authors that have been brought
together in CCT. Where possible we have endeavored to recruit a group of
international experts in their respective subject matter who are also experienced clinicians, proficient in the intensive care of patients poisoned by the

toxins and toxicants they have addressed. This quest for such a uniquely
qualified group of chapter authors has required us to seek out scholars from
many areas of the world. Being such highly respected individuals, our chapter
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Preface to the Second Edition

authors are for the most part very busy with their various academic and clinical
pursuits. We are greatly indebted to them for the generous donation of the time
they gave us to not only produce their excellent chapters but also to put up with
our compulsively detailed editing and challenges to them for justification of
the information contained in their chapters. In most instances, they have done
so because they were dedicated to the idea of working with us to achieve the
goals enumerated above.
Critical Care Toxicology is not a static textbook in the traditional sense. The
online version is a living dynamic document that can, and will, be updated as
needed and new chapters will be provided beyond the date of the original
publication of the current edition. In this way, we will feel confident that you,
the reader of CCT, will have the most up-to-date information available to you
in your care of your critically poisoned patients.
Jeffrey Brent
Keith Burkhart
Paul Dargan
Benjamin Hatten
Bruno Megarbane
Robert Palmer
Julian White

Preface to the First Edition

To us, this book is about passion. It is the result of the passion we share for the
clinical challenges we face every day in caring for critically poisoned patients
and in understanding their unique and enchanting pathophysiology and its
therapeutic implications. This is a passion we hope to elicit in all who venture
into the world of clinical toxicology as they read this book. To the medical
toxicologist, the care of the seriously poisoned patients merges the diverse
worlds of critical care, emergency medicine, pharmacology, altered drug
pharmacokinetics (hence the term “toxicokinetics”), diagnostic challenges,
multisystem involvement in often otherwise healthy patients, and the use of
specific and often esoteric treatment strategies and antidotes.
Before embarking on the extraordinarily labor-intensive activity of generating a book of this depth and complexity, we queried the importance of
producing another clinical toxicology textbook. We are aware of several
excellent general clinical toxicology textbooks on the market and appreciate
their attempts to achieve a far greater breadth than the present work. However,
toxicology is such a broad field that general textbooks encompassing all of
clinical toxicology necessarily must limit the extent of their coverage of the
intensive care unit management of major poisonings. Thus, the intensivist, and
critically poisoned patients, deserve a reference that specifically addresses
their needs. This need is made all the more important by the life-threatening
nature of many of these poisonings. Stark evidence of the complexity of just
these issues is that to cover them adequately required 160 chapters and 1633
pages.
Our goal was to have the most knowledgeable and experienced medical
toxicologists author relevant chapters. In order to achieve this goal we drafted
our colleagues with unique experience and expertise worldwide. As witnessed
by our contributor list, all continents, except Antarctica, are represented. We

proudly boast that our collective chapter authors represent a significant proportion of the most experienced critical care toxicologists in the world. Medical toxicologists interested in acute care tend to be domiciled at the bedside, in
poison centers, or both. Because of the highly clinical nature of this book, we
selected authors with a predominantly bedside care orientation.
With the ready access to facts and data via the Internet, the very nature of
hard copy books has changed dramatically. No longer is it necessary for books
to be compendia of facts. However, electronic databases cannot convey the
reasoned clinical approaches and the synthesis of pathophysiology with
xi


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Preface to the First Edition

clinical effects and treatment that characterizes the pages that follow. Certainly,
important physiologic and monitoring parameters as well as drug dosages are
amply provided. The degree to which they are included represents our view of
the best balance between those that are important to know and the desire to
dedicate as much space as necessary to an elucidation of relevant concepts and
a critical discussion of therapeutic controversies. We have embraced rather
than glossed over controversies. The reader will find that this is not simply a
“how to” handbook. Our aim is to provide the practitioner with the data needed
to care for his or her individual patients. As an aid to those who choose to delve
more deeply into the concepts, approaches, and controversies in this book,
chapters are well referenced with primary source citations.
It is our hope and expectation that this book will evoke the same passion in
the reader that the subject does for us.
Jeffrey Brent, M.D., Ph.D.
Kevin L. Wallace, M.D.
Keith K. Burkhart, M.D.

Scott D. Phillips, M.D.
J. Ward Donovan, M.D.
Robert B. Palmer, Ph.D.


Contents

Volume 1
Part I General Management of the Critically Poisoned
Patient . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1

1

The Critically Poisoned Patient . . . . . . . . . . . . . . . . . . . . . . .
J. Ward Donovan, Keith Burkhart, and Jeffrey Brent

3

2

The Diagnostic Process in Medical Toxicology
Anthony F. Pizon, Joseph H. Yanta, and
Greg S. Swartzentruber

...........

29

3

Therapeutic Approach to the Critically Poisoned Patient
Evan S. Schwarz

...

43

4

Extracorporeal Membrane Oxygenation and
Cardiopulmonary Bypass in the Poisoned Patient
William P. Kerns II and Alan C. Heffner

........

79

5

Post-Resuscitation Management of the Poisoned Patient . . . 101
Michael Lynch and Jon C. Rittenberger

6

Psychiatric Issues in the Critically Poisoned Patient . . . . . . . 117
J. J. Rasimas and Gregory L. Carter

7

Poisoning in Pregnancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159
Kevin F. Maskell Jr., Kirk L. Cumpston,
Timothy B. Erickson, and Jerrold B. Leikin

8

Geriatric Poisoning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193
Janetta L. Iwanicki

9

Intensive Care of Pediatric Poisoning Cases . . . . . . . . . . . . . 205
Prashant Joshi and Mitchell P. Ross

10

The Critically Poisoned Worker . . . . . . . . . . . . . . . . . . . . . . . 223
Michael G. Holland

11

Complications of Chronic Alcoholism That Affect
Critical Illness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 249
Alison L. Jones
xiii


xiv

Contents

12

Extracorporeal Substance Removal . . . . . . . . . . . . . . . . . . . . 267
Monique J. Cormier and Marc Ghannoum

13

Poisoning Fatalities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 279
Philippe E. Hantson

Part II

Toxic Syndromes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

293

14

The Assessment and Management of Hypotension
and Shock in the Poisoned Patient . . . . . . . . . . . . . . . . . . . . . 295
Florian Eyer

15

Acid–Base Balance in the Poisoned Patient . . . . . . . . . . . . . . 325
Stephen W. Borron

16

Treatment of Acute Respiratory Distress Syndrome
in the Poisoned Patient . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 359
Dylan W. de Lange

17

Toxicant-Induced Hepatic Injury . . . . . . . . . . . . . . . . . . . . . . 385
Kim Dalhoff

18

Toxicant-Induced Renal Injury
Joshua D. King

19

Toxicant-Induced Alterations in Consciousness
Jerrold B. Leikin and Andrea Carlson

20

Toxicant-Induced Seizures
Philippe E. Hantson

21

Cardiac Conduction and Rate Disturbances . . . . . . . . . . . . . 475
Hallam Gugelmann and Neal Benowitz

22

Toxicant-Induced Torsade de Pointes . . . . . . . . . . . . . . . . . . . 509
Jonas Höjer and Donna Seger

23

Anticholinergic Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . 519
William J. Boroughf

24

Serotonin Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 539
Peter R. Chai and Edward W. Boyer

25

Sympathomimetic Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . 549
Andrew M. King, Eric R. Malone, and Cynthia K. Aaron

26

Toxicant-Induced Immunological Reactions . . . . . . . . . . . . . 569
Jenny M. Stitt and Stephen C. Dreskin

27

Withdrawal Syndromes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 591
Adhi N. Sharma and Robert J. Hoffman

28

Acute Radiation Injuries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 605
Ziad N. Kazzi

. . . . . . . . . . . . . . . . . . . . . . . 409
. . . . . . . . . . 425

. . . . . . . . . . . . . . . . . . . . . . . . . . . 447


Contents

xv

29

Malignant Hyperthermia . . . . . . . . . . . . . . . . . . . . . . . . . . . . 619
Henry Rosenberg, Dorothea Hall, and Harvey Rosenbaum

30

Toxicant-Induced Hematologic Syndromes . . . . . . . . . . . . . . 643
Steven C. Curry and A. Min Kang

31

Neuroleptic Malignant Syndrome . . . . . . . . . . . . . . . . . . . . . . 661
Rebecca E. Bruccoleri and Michael J. Burns

32

Toxicant-Induced Rhabdomyolysis . . . . . . . . . . . . . . . . . . . . . 679
G. Patrick Daubert

Part III Medication Safety in the Intensive Care Unit . . . . . . . . .

691

33

Adverse Drug Reactions in the Intensive Care Unit . . . . . . . 693
Philip Moore and Keith Burkhart

34

Medication Errors and Drug–Drug Interactions in the
Intensive Care Unit . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 741
Brenna Farmer and Luke Yip

Part IV

Medications: Cardiovascular . . . . . . . . . . . . . . . . . . . . . . . .

749

35

Alpha-2 Adrenergic and Imidazoline Receptor
Agonists: Clonidine, Dexmedetomidine, and Related

Antihypertensives, Decongestants, and Sedatives . . . . . . . . . 751
Anthony J. Tomassoni

36

Beta-Receptor Antagonists . . . . . . . . . . . . . . . . . . . . . . . . . . . 771
Michael Levine and Jeffrey Brent

37

Calcium Channel-Blocking Agents . . . . . . . . . . . . . . . . . . . . . 787
Maude St-Onge and Jeffrey Brent

38

Digitalis Glycosides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 807
Bruno Mégarbane

39

Sodium Channel-Blocking Antidysrhythmics . . . . . . . . . . . . 821
Silas W. Smith

40

Sodium Nitroprusside . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 843
Steven C. Curry and Meghan B. Spyres

41

Sympathomimetic Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . 851
Robert J. Hoffman and Lewis S. Nelson

Part V Medications: Decongestant/Antihistaminergic/
Bronchodilatory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
42

867

Antihistamines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 869
Jerry W. Snow and R. Brent Furbee


xvi

43

Contents

Theophylline and Other Methylxanthines . . . . . . . . . . . . . . . 883
Ann-Jeannette Geib

Part VI

Medications: Psychotropic . . . . . . . . . . . . . . . . . . . . . . . . . .

905

44

Antipsychotics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 907
Bradley L. Demeter and Michael J. Burns

45

Anxiolytics, Sedatives, and Hypnotics
C. William Heise and Daniel E. Brooks

46

Barbiturates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 955
Steven J. Walsh and Kenneth D. Katz

47

Bupropion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 965
Peter Wu and David Juurlink

48

Cyclic Antidepressants
Mark K. Su

49

Lithium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 991
Eric J. Lavonas and Jeffrey Brent

50

Monoamine Oxidase Inhibitors . . . . . . . . . . . . . . . . . . . . . . . 1009
Ayrn D. O’Connor and Kirk C. Mills

51

Serotonergic Antidepressants . . . . . . . . . . . . . . . . . . . . . . . . . 1027
Andrew H. Dawson

. . . . . . . . . . . . . . . . . . 935

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 975

Volume 2
Part VII

Medications: Anticonvulsant . . . . . . . . . . . . . . . . . . . . . . . 1041

52

Hydantoin Anticonvulsants: Phenytoin and
Fosphenytoin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1043
Frank LoVecchio

53

Iminostilbene Anticonvulsants: Carbamazepine and
Oxcarbazine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1053
Hwee Min Lee and Andis Graudins

54

Second Generation Anticonvulsants: Gabapentin,
Lamotrigine, Levetiracetam, and Topiramate . . . . . . . . . . . . 1065
M. P. Emswiler and Kirk L. Cumpston

55

Valproic Acid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1083
Wayne R. Snodgrass and Chia Wei Hsu


Contents

xvii

Part VIII

Medications: Neuromuscular

. . . . . . . . . . . . . . . . . . . . . . 1095

56

Antiparkinsonian Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1097
Steven J. Walsh and Kenneth D. Katz

57

Baclofen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1119
Erin Stewart and Laura M. Tormoehlen

58

Centrally Acting Muscle Relaxants . . . . . . . . . . . . . . . . . . . . 1133
Madeline L. McCarthy and Carl R. Baum

Part IX

Medications: Analgesic/Anti-Inflammatory

. . . . . . . . . . 1143

. . . . . . . . . . . . . . . . . . . . . . . . . 1145

59

Acetaminophen/Paracetamol
D. Nicholas Bateman

60

Methotrexate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1171
Yedidia Bentur and Yael Lurie

61

Nonsteroidal Anti-Inflammatory Drugs . . . . . . . . . . . . . . . . . 1219
Kimberlie A. Graeme

62

Opioids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1237
Scott Lucyk and Lewis S. Nelson

63

Salicylates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1251
Steven C. Curry and Meghan B. Spyres

Part X

Medications: Antimicrobial . . . . . . . . . . . . . . . . . . . . . . . . . . 1269

64

Chloroquine and Quinine . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1271
Alison L. Jones

65

Isoniazid and Related Hydrazines . . . . . . . . . . . . . . . . . . . . . 1287
Cynthia Koh, Alicia B. Minns, and Richard F. Clark

66

Rifampin, Dapsone, and Vancomycin . . . . . . . . . . . . . . . . . . . 1299
Cyrus Rangan and Richard F. Clark

Part XI

Medications: Hematologic . . . . . . . . . . . . . . . . . . . . . . . . . . 1311

67

Iron . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1313
Sean M. Bryant and Jerrold B. Leikin

68

Oral Anticoagulants
George Sam Wang

69

Thrombolytics, Heparin and Derivatives,
and Antiplatelet Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1341
Robert A. Raschke and Steven C. Curry

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1325


xviii

Contents

Part XII

Medications: Miscellaneous . . . . . . . . . . . . . . . . . . . . . . . . 1361

70

Antidiabetic Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1363
Jenna M. LeRoy and Samuel J. Stellpflug

71

Antitubulin Agents: Colchicine, Vinca Alkaloids, and
Podophyllin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1387
Jerry W. Snow, Louise W. Kao, and R. Brent Furbee

Part XIII

Drugs of Abuse . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1411

72

Amphetamines and Their Derivatives . . . . . . . . . . . . . . . . . . 1413
Nicholas J. Connors and Robert S. Hoffman

73

Arylcyclohexamines: Ketamine, Phencyclidine, and
Analogues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1439
James H. Ho and Paul I. Dargan

74

Cathinones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1485
Rachelle Abouchedid and David M. Wood

75

Cocaine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1525
Ruben Olmedo, Christopher Yates, and Robert S. Hoffman

76

Gamma-Hydroxybutyrate and Its Related Analogues
Gamma-Butyrolactone and 1,4-Butanediol . . . . . . . . . . . . . . 1555
David M. Wood

77

Hallucinogens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1587
Curtis P. Snook

78

Synthetic Cannabinoid Receptor Agonists . . . . . . . . . . . . . . . 1609
Andrew A. Monte

Part XIV

Chemical Agents: Metals and Related Substances . . . 1617

79

Antimony and Nickel . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1619
Matthew D. Sztajnkrycer

80

Arsenic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1639
Michael J. Kosnett

81

Cadmium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1669
Jan Meulenbelt

82

Lead . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1675
Michael J. Kosnett

83

Mercury . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1705
Irma de Vries


Contents

xix

84

Phosphorous . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1719
Emily B. Austin and Marco L. A. Sivilotti

85

Thallium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1733
Sean H. Rhyee

Part XV

Chemical Agents: Solvents, Glycols, and Alcohols . . . 1741

86

Ethylene Glycol and Other Glycols . . . . . . . . . . . . . . . . . . . . 1743
Knut Erik Hovda, Kenneth McMartin, and Dag Jacobsen

87

Isopropyl Alcohol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1761
Heath A. Jolliff

88

Methanol and Formaldehyde . . . . . . . . . . . . . . . . . . . . . . . . . 1769
Knut Erik Hovda, Kenneth McMartin, and Dag Jacobsen

Part XVI Chemical Agents: Pesticides . . . . . . . . . . . . . . . . . . . . . . . 1787
89

Chlorophenoxy Herbicides . . . . . . . . . . . . . . . . . . . . . . . . . . . 1789
Sally M. Bradberry and J. Allister Vale

90

Fumigants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1797
Matthew Zuckerman

91

Fungicides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1811
Annette M. Lopez and Daniel Sudakin

92

Organophosphate and Carbamate Insecticide . . . . . . . . . . . . 1829
J. Allister Vale and Sally M. Bradberry

93

Paraquat and Diquat . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1855
Michael Eddleston

94

Phosphate and Phosphine . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1875
Ashish Bhalla

95

Rodenticides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1887
Ryan Chuang and Jennie A. Buchanan

Part XVII

Chemical Agents: Gases and Vapors . . . . . . . . . . . . . . . 1909

96

Carbon Monoxide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1911
Christopher Hoyte

97

Cyanide: Hydrogen Cyanide, Inorganic Cyanide Salts, and
Nitriles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1929
Steven C. Curry and Meghan B. Spyres

98

Hydrocarbons and Halogenated Hydrocarbons . . . . . . . . . . 1951
Jakub Furmaga, Kurt Kleinschmidt, and Kapil Sharma


xx

Contents

99

Hydrogen Sulfide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1963
Aaron Skolnik and C. William Heise

100

Irritant and Toxic Pulmonary Injuries . . . . . . . . . . . . . . . . . . 1973
Joseph K. Maddry

Part XVIII

Chemical Agents: Caustics and Corrosives . . . . . . . . . 2003

101

Caustics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2005
Diane P. Calello

102

Hydrofluoric Acid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2021
Kennon Heard

Volume 3
Part XIX

Natural Toxins: Marine . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2031

103

Ciguatera . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2033
Shaun Greene

104

Marine Vertebrates, Cnidarians, and Mollusks . . . . . . . . . . . 2045
L. Keith French and B. Zane Horowitz

105

Scombroid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2075
Mark A. Suguitan and Rama B. Rao

106

Tetrodotoxin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2085
Chen-Chang Yang

Part XX

Natural Toxins: Mushrooms . . . . . . . . . . . . . . . . . . . . . . . . 2101

107

Overview of Mushroom Poisoning . . . . . . . . . . . . . . . . . . . . . 2103
Michael C. Beuhler

108

Cyclopeptide-Containing Mushrooms: The Deadly
Amanitas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2129
Thomas Zilker and Heinz Faulstich

109

Gyromitra Mushrooms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2149
Daniel E. Brooks and Kimberlie A. Graeme

Part XXI

Natural Toxins: Plants and Herbals . . . . . . . . . . . . . . . . . 2161
. . . . . . . . . . . . . . . . . 2163

110

Overview of Plant and Herbal Toxicity
Philip Aplin

111

Anticholinergic Plants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2175
Robert N. E. French and Frank G. Walter


Contents

xxi

112

Cardiotoxic Plants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2187
Barbarajean Magnani and Alan D. Woolf

113

Poison Hemlock . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2205
Frederick W. Fiesseler and Richard D. Shih

114

Toxalbumins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2213
Jennifer A. Oakes and Richard Y. Wang

115

Water Hemlock . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2225
Edward W. Cetaruk

Part XXII Natural Toxins: Scorpions . . . . . . . . . . . . . . . . . . . . . . . . . 2237
. . . . . . . . . . . . . . . . . . . . 2239

116

Overview of Scorpion Envenoming
Julian White

117

Middle East and North African Scorpions . . . . . . . . . . . . . . . 2255
Yona Amitai

118

North American Scorpions . . . . . . . . . . . . . . . . . . . . . . . . . . . 2269

Michael Levine and Anne-Michelle Ruha

Part XXIII

Natural Toxins: Snakes . . . . . . . . . . . . . . . . . . . . . . . . . . . 2277

119

Overview of Snake Envenoming . . . . . . . . . . . . . . . . . . . . . . . 2279
Julian White

120

African Snakes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2319
Jean-Philippe Chippaux, Julian White, and
Abdulrazaq G. Habib

121

Asian Snakes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2343
Aniruddha Ghose and Julian White

122

Australian and Pacific Snakes . . . . . . . . . . . . . . . . . . . . . . . . . 2405
Julian White

123

European Snakes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2441

Luc de Haro and David Boels

124

Non-Front-Fanged Colubroid Snakes
Scott A. Weinstein

125

North American Coral Snakes and Related Elapids . . . . . . . 2493
Jeffrey N. Bernstein

126

Rattlesnakes and Other North American Crotalids
Anne-Michelle Ruha

127

South and Central American Snakes . . . . . . . . . . . . . . . . . . . 2527
Ceila Maria Sant’Ana Malaque and José María Gutiérrez

. . . . . . . . . . . . . . . . . . 2453

. . . . . . . 2503


xxii

Contents

Part XXIV

Natural Toxins: Spiders . . . . . . . . . . . . . . . . . . . . . . . . . . 2549
. . . . . . . . . . . . . . . . . . . . . . 2551

128

Overview of Spider Envenoming
Julian White

129

Australian Funnel Web Spiders . . . . . . . . . . . . . . . . . . . . . . . 2565
Julian White

130

Loxosceles Spiders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2577
Ceila Maria Sant’Ana Malaque, Richard S. Vetter, and
Marlene Entres

131

Widow and Related Lactrodectus Spiders
Jeena Jacob and Julian White

Part XXV

Natural Toxins: Miscellaneous

. . . . . . . . . . . . . . . 2595

. . . . . . . . . . . . . . . . . . . . 2607

132

Botulism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2609
B. Zane Horowitz

133

Massive Bee Envenomation . . . . . . . . . . . . . . . . . . . . . . . . . . . 2627
Hui Wen Fan and Jorge Kalil

Part XXVI

Threat Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2637

134

Chemical Terrorism Incidents and Intensive Care . . . . . . . . 2639
R. Steven Tharratt and Timothy E. Albertson

135

Nerve Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2655
Mahdi Balali-Mood, Beeta Balali-Mood, and
Kia Balali-Mood

136

Sulfur Mustard . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2683
Dirk Steinritz and Horst Thiermann

Part XXVII Antidotes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2713
137

Antidigitalis Fab Fragments . . . . . . . . . . . . . . . . . . . . . . . . . . 2715
Bruno Mégarbane

138

Atropine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2725
Robert N. E. French and Frank G. Walter

139

Calcium Edetate (Calcium Disodium EDTA)
Michael J. Kosnett

140

Cyanide-Binding Antidotes: Dicobalt Edetate and
Hydroxocobalamin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2737
Vikhyat S. Bebarta

141

Cyproheptadine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2747

Karen E. Simone

. . . . . . . . . . . . 2733


Contents

xxiii

142

Dantrolene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2757
Blaine E. Benson

143

Deferoxamine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2771
F. Lee Cantrell

144

4-Dimethylamino Phenol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2779
Thomas Zilker and Peter Eyer

145

Dimercaprol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2791
Michael J. Kosnett

146

Ethanol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2795
Tammi H. Schaeffer

147

Euglycemic Insulin Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . 2801
Kristin Engebretsen

148

Flumazenil . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2811
Allyson Kreshak and Stephen Munday

149

Folic and Folinic Acids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2819
Michelle A. Hieger and S. Rutherfoord Rose

150

Fomepizole . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2829
Kenneth McMartin, Knut Erik Hovda, and Dag Jacobsen

151

Immunotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2843
Steven A. Seifert and Brandon J. Warrick

152

Lipid Resuscitation Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . 2859
Jeffrey Brent and Michael Levine

153

Methylene Blue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2867
Jack Clifton II and Jerrold B. Leikin

154

N-Acetylcysteine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2879
Eric Villeneuve and Sophie Gosselin

155

Nitrites . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2889
Bruce D. Anderson

156

Octreotide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2897
Bryan D. Hayes

157

Opioid Receptor Antagonists . . . . . . . . . . . . . . . . . . . . . . . . . 2907
Scott Lucyk and Lewis S. Nelson

158

Oximes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2913
J. Allister Vale

159

D-Penicillamine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2929
Cristy Eidelman and Jennifer A. Lowry

160

Pentetic Acid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2937
Shikha Kapil and Ziad N. Kazzi


xxiv

Contents

161

Physostigmine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2943
William J. Boroughf

162

Prussian Blue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2957
Pierre-André Dubé and Sophie Gosselin

163

Pyridoxine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2963
Ashleigh Kennedy and Tammi H. Schaeffer

164

Sodium Bicarbonate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2967
Sara K. Lookabill, Anna Rouse Dulaney,
Greene Shepherd, and William P. Kerns II

165

Succimer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2987
Michael J. Kosnett

166

Thiamine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2993
Alfred Aleguas Jr.

167

Thiosulfate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3001
F. Lee Cantrell

168

Unithiol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3005
Michael J. Kosnett

Appendix: Sympathomimetic Pressors
Jeffrey Brent

. . . . . . . . . . . . . . . . . . . . . . 3009

Grading System for Levels of Evidence Supporting
Recommendations in Critical Care Toxicology, 2nd Edition . . . . . . 3017
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3019


About the Editors

Jeffrey Brent holds the rank of Distinguished Clinical Professor of Medicine,
in the Division of Clinical Pharmacology and Toxicology, at the University of
Colorado, School of Medicine. He holds secondary appointments in the
Departments of Emergency Medicine and Pediatrics and in the Colorado
School of Public Health.
Dr. Brent has received numerous awards and honors during his professional
career. Among these are multiple career achievement awards, including the
Louis Roche Award by the European Association of Poisons Centres and
Clinical Toxicologists, the Career Achievement Award by the American
Academy of Clinical Toxicology, the Ellenhorn Award by the American
College of Medical Toxicology, and the Clinical Translational Toxicology
Career Achievement Award by the Society of Toxicology.
A former President of the American Academy of Clinical Toxicology,
Dr. Brent has also served on the board of directors of the American College
of Medical Toxicology.
Dr. Brent has served as a consultant to the World Health Organization and
to several US government agencies, including the Department of Health and
Human Services, and the National Vaccine Program. Currently, he is an active

consultant with the US Food and Drug Administration.
Dr. Brent is Director of a large National Institutes of Health and Food and
Drug Administration supported multicenter research group in clinical toxicology known as the Toxicology Investigators Consortium.

xxv


xxvi

Keith K. Burkhart Dr. Burkhart is the Senior Advisor for Medical Toxicology and Lead Medical Officer for the Biomedical Informatics Team in the
Division of Applied Regulatory Science in the Office of Clinical Pharmacology within the Office of Translational Science in the Center for Drug Evaluation and Research at the FDA. He is board certified in Emergency Medicine
and Medical Toxicology. He is a Clinical Professor of Emergency Medicine at
the Penn State University. He practices critical care toxicology at the
PinnacleHealth Hospital System. He is the former Medical Director of the
Penn State Poison Center. Dr. Burkhart received his medical toxicology
training at the Rocky Mountain Poison Center in Denver. He received his
emergency medicine training at the University of Cincinnati. He is a graduate
of the former Medical College of Pennsylvania, now Drexel University. He is a
past President of the American College of Medical Toxicology. His FDA work
focuses upon using bioinformatics and cheminformatics tools to data mine the
FDA Adverse Event Reporting System to learn mechanistic insights into drug
safety issues.

Paul Dargan Professor Paul I Dargan is a Consultant Physician and Clinical
Toxicologist and Clinical Director at Guy’s and St Thomas’ NHS Foundation
Trust, London, UK. He is also a Professor of Clinical Toxicology at King’s
College London. He has an active research program with a focus on recreational drug toxicity, new psychoactive substances, prescription medicine misuse, self-poisoning (in particular, paracetamol/acetaminophen), and heavy

About the Editors