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NEUROLOGIC COMPLICATIONS
OF CRITICAL ILLNESS
SERIES EDITOR
Eva Feldman, MD, PhD, FAAN, FANA
Russell N. DeJong Professor of Neurology
University of Michigan
Contemporary Neurology Series
74 NEUROLOGIC COMPLICATIONS
OF CRITICAL ILLNESS
Third Edition
Eelco F.M. Wijdicks, MD, PhD
75 CLINICAL NEUROPHYSIOLOGY
Third Edition
Jasper R. Daube, MD, and
Devon I. Rubin, MD, Editors
76 PERIPHERAL NEUROPATHIES IN
CLINICAL PRACTICE
Steven Herskovitz, MD, Stephen N. Scelsa,
MD, and Herbert H. Schaumburg, MD
77 CLINICAL NEUROPHYSIOLIOGY OF
THE VESTIBULAR SYSTEM
Fourth Edition
Robert W. Baloh, MD, and
Kevin A. Kerber, MD
78 THE NEURONAL CEROID
LIPOFUSCINOSES (BATTEN DISEASE)
Second Edition
Sara E. Mole, PhD, Ruth D. Williams, MD,
and Hans H. Goebel, MD, Editors
79 PARANEOPLASTIC SYNDROMES
Robert B. Darnell, MD, PhD, and
Jerome B. Posner, MD
80 JASPER’S BASIC MECHANISMS OF
THE EPILEPSIES
Jeffrey L. Noebels, MD, PhD,
Massimo Avoli, MD, PhD,
Michael A. Rogawski, MD, PhD,
Richard W. Olsen, PhD, and
Antonio V. Delgado-Escueta, MD
81 MYASTHENIA GRAVIS AND
MYASTHENIC DISORDERS
Second Edition
Andrew G. Engel, MD
82 MOLECULAR PHYSIOLOGY
AND METABOLISM OF THE
NERVOUS SYSTEM
Gary A. Rosenberg, MD
83 SEIZURES AND EPILEPSY
Second Edition
Jerome Engel, Jr., MD, PhD
84 MULTIPLE SCLEROSIS
Moses Rodriguez, MD, Orhun H. Kantarci, MD,
and Istvan Pirko, MD
85 FRONTOTEMPORAL DEMENTIA
Bruce L. Miller, MD
86 AUTONOMIC NEUROLOGY
Eduardo E. Benarroch, MD
87 EVALUATION AND TREATMENT
OF MYOPATHIES
Second Edition
Emma Ciafaloni, MD, Patrick F. Chinnery,
FRCP, FMedSci, and
Robert C. Griggs, MD, Editors
88 MOTOR NEURON DISEASE IN ADULTS
Mark Bromberg, MD
89 HYPERKINETIC MOVEMENT
DISORDERS
Roger M. Kurlan, MD, Paul E. Green, MD,
and Kevin M. Biglan, MD, MPH
90 THE NEUROLOGY OF EYE MOVEMENTS
Fifth Edition
R. John Leigh, MD, FRCP, and
David S. Zee, MD
91 MIGRAINE
Third Edition
David W. Dodick, MD, and Stephen D.
Silberstein, MD
92 CLINICAL NEUROPHYSIOLOGY
Fourth Edition
Devon Rubin, MD and
Jasper Daube, MD, Editors
93 NEUROIMMUNOLOGY
Bibiana Bielekova, MD, Gary Birnbaum, MD,
and Robert P. Lisak, MD
94 PLUM AND POSNER’S DIAGNOSIS AND
TREATMENT OF STUPOR AND COMA
Fifth Edition
Jerome B. Posner, MD, Clifford B. Saper,
MD, PhD, Nicholas D. Schiff, MD,
and Jan Claassen, MD, PhD
95 CLINICAL NEUROPHYSIOLOGY
Fifth Edition
Devon I. Rubin, MD, Editor
96 PARKINSON DISEASE
Roger L. Albin, MD
97 NEUROLOGIC COMPLICATIONS
OF CRITICAL ILLNESS
Fourth Edition
Eelco F. M. Wijdicks, MD, PhD
NEUROLOGIC COMPLICATIONS
OF CRITICAL ILLNESS
Fourth Edition

Eelco F. M. Wijdicks, MD, PhD, FACP, FNCS

Professor of Neurology
Neurocritical Care Services
Department of Neurology, Mayo Clinic
Rochester, Minnesota
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Library of Congress Cataloging-in-Publication Data

Names: Wijdicks, Eelco F. M., 1954– author. |
Mayo Foundation for Medical Education and Research, sponsoring body.
Title: Neurologic complications of critical illness / Eelco F.M. Wijdicks.
Other titles: Contemporary neurology series.
Description: 4. | New York, NY : Oxford University Press, [2023] |
Series: Contemporary neurology series | Includes bibliographical references and index.
Identifiers: LCCN 2022040676 (print) | LCCN 2022040677 (ebook) |
ISBN 9780197585016 (hardback) | ISBN 9780197585030 (epub) |
ISBN 9780197585047 (online)
Subjects: MESH: Critical Illness | Neurologic Manifestations | Critical Care
Classification: LCC RC350 .N49 (print) | LCC RC350 .N49 (ebook) |
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DOI: 10.1093/med/9780197585016.001.0001

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Contents

Preface xiii

PART I CRITERIA, URGENCY, AND IMPORTANCE

1. INDICATIONS FOR A NEUROLOGIC CONSULT IN

THE INTENSIVE CARE UNIT 3
CATEGORIES OF CONSULTS 4
BENEFITS OF A CONSULTATION 6

2. CONSULTING IN THE INTENSIVE CARE UNIT 9

PREPARATION AND HISTORY-TAKING 9
COMMON REQUESTS FOR CONSULTS IN THE ICU 10

PART II GENERAL CLINICAL NEUROLOGIC PROBLEMS IN

THE INTENSIVE CARE UNIT

3. ACUTE CONFUSIONAL STATE IN THE INTENSIVE CARE UNIT 19

TERMINOLOGY 20
ASSESSMENT OF DELIRIUM 21
NEUROLOGIC EXAMINATION OF THE ACUTELY CONFUSED PATIENT 23
MANAGEMENT OF DELIRIUM 24

4. COMA AND OTHER STATES OF ALTERED AWARENESS IN THE

INTENSIVE CARE UNIT 27
DEFINITIONS OF ALTERED STATES OF CONSCIOUSNESS 27
NEUROLOGIC EXAMINATION OF THE COMATOSE PATIENT 32
CAUSES OF COMA 39
NEUROLOGIC EXAMINATION IN BRAIN DEATH 39

v
vi Contents

5. NEUROLOGIC MANIFESTATIONS OF MUSCLE RELAXANTS AND

DRUGS USED FOR ANALGESIA AND ANESTHESIA IN THE
INTENSIVE CARE UNIT 47
PRINCIPLES OF PHARMACODYNAMICS AND PHARMACOKINETICS IN
CRITICAL ILLNESS 48
EFFECT OF DRUGS ON NEUROMUSCULAR JUNCTION 51
EFFECT OF DRUGS ON LEVEL OF CONSCIOUSNESS 55

6. SEIZURES IN THE INTENSIVE CARE UNIT 63

GENERALIZED TONIC–CLONIC SEIZURES 64
DRUG-INDUCED AND DRUG-WITHDRAWAL SEIZURES 64
SEIZURES AND ACUTE METABOLIC DERANGEMENTS 67
SEIZURES AND STRUCTURAL CENTRAL NERVOUS SYSTEM
ABNORMALITIES 68
CONVULSIVE STATUS EPILEPTICUS 68
NONCONVULSIVE STATUS EPILEPTICUS 72
MANAGEMENT OF SEIZURES AND STATUS EPILEPTICUS 73
OUTCOME 79

7. GENERALIZED WEAKNESS IN THE INTENSIVE CARE UNIT 85

GENERAL CONSIDERATIONS 86
DISORDERS OF THE SPINAL CORD 86
DISORDERS OF PERIPHERAL NERVES 88
DISORDERS OF THE NEUROMUSCULAR JUNCTION 92
DISORDERS OF SKELETAL MUSCLE 93

8. ACUTE FOCAL NEUROLOGIC FINDINGS AND ASYMMETRIES IN

THE INTENSIVE CARE UNIT 103
GENERAL CONSIDERATIONS IN LESION LOCALIZATION 103
BRAIN INJURY PATTERNS 108

9. ACUTE MOVEMENT ABNORMALITIES IN THE INTENSIVE CARE UNIT 111

SEMIOLOGY 112
EMERGENT AND URGENT MOVEMENT ABNORMALITIES 115
 Contents vii

PART III NEUROLOGIC COMPLICATIONS IN MEDICAL AND SURGICAL

INTENSIVE CARE UNITS AND TRANSPLANTATION UNITS

10. NEUROLOGIC COMPLICATIONS OF INVASIVE PROCEDURES IN

THE INTENSIVE CARE UNIT 123
NEUROTOXICITY OF RADIOLOGIC CONTRAST AGENTS 124
CHOLESTEROL EMBOLIZATION 124
AIR EMBOLISM 126
NEUROLOGIC COMPLICATIONS ASSOCIATED WITH SPECIFIC
PROCEDURES 127

11. NEUROLOGIC MANIFESTATIONS OF ACUTE BACTERIAL INFECTIONS

AND SEPSIS 147
BACTERIAL MENINGITIS 147
SPINAL EPIDURAL ABSCESS 151
INFECTIVE ENDOCARDITIS 154
CLOSTRIDIAL SYNDROMES 161
SEPSIS 164

12. NEUROLOGIC MANIFESTATIONS OF VIRAL OUTBREAKS 175

WEST NILE VIRUS NEUROINVASIVE DISEASE 176
TICK- AND MOSQUITO-BORNE ENCEPHALITIS 179
ENDEMIC INFLUENZA 180
SARS-COV-2 (COVID-19) PANDEMIC 183

13. NEUROLOGIC COMPLICATIONS OF CARDIAC ARREST 189

GENERAL CONSIDERATIONS IN RESUSCITATION MEDICINE 190
POSTRESUSCITATION ENCEPHALOPATHY 193
SUPPORTIVE CARE 203
SPECIFIC TREATMENT AND TARGETED TEMPERATURE MANAGEMENT 204

14. NEUROLOGIC MANIFESTATIONS OF ACID–BASE DERANGEMENTS,

ELECTROLYTE DISORDERS, AND ENDOCRINE CRISES 215
ACID–BASE DISORDERS 215
ELECTROLYTE DISORDERS 219
ENDOCRINE EMERGENCIES 232
viii Contents

15. NEUROLOGIC COMPLICATIONS OF ACUTE RENAL DISEASE 249

UREMIC ENCEPHALOPATHY 249
DIALYSIS DYSEQUILIBRIUM SYNDROME 253
POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME 255
NEUROMUSCULAR DISORDERS 260

16. NEUROLOGIC MANIFESTATIONS OF ACUTE HEPATIC FAILURE 269

GENERAL CONSIDERATIONS 270
HEPATIC ENCEPHALOPATHY 270
BRAIN EDEMA IN FULMINANT HEPATIC FAILURE 275

17. NEUROLOGIC COMPLICATIONS ASSOCIATED WITH DISORDERS

OF THROMBOSIS AND HEMOSTASIS 289
GENERAL CONSIDERATIONS 289
DISSEMINATED INTRAVASCULAR COAGULATION 290
THROMBOLYSIS AND ANTICOAGULATION 291
NEOPLASTIC COAGULOPATHIES 295
THROMBOTIC THROMBOCYTOPENIC PURPURA 297

18. NEUROLOGIC COMPLICATIONS OF ACUTE VASCULITIS SYNDROMES 305

GENERAL CONSIDERATIONS 305
LARGE-VESSEL VASCULITIS 307
POLYARTERITIS NODOSA 308
CHURG-STRAUSS SYNDROME 312
GRANULOMATOSIS WITH POLYANGIITIS 313
DRUG-INDUCED VASCULITIS 315

19. NEUROLOGIC COMPLICATIONS IN THE CRITICALLY ILL

PREGNANT PATIENT 321
NEUROLOGY OF PREGNANCY 321
ECLAMPSIA 323
HELLP SYNDROME 326
AMNIOTIC FLUID EMBOLISM 328
NEUROLOGIC COMPLICATIONS OF TOCOLYTIC AGENTS 328
 Contents ix

20. NEUROLOGIC COMPLICATIONS OF CANCER IN THE ICU 333

GOALS OF CARE IN CRITICAL ILLNESS AND ADVANCED CANCER 334
NEURO-ONCOLOGIC EMERGENCIES 334
PARANEOPLASTIC ENCEPHALITIS 336
COMPLICATIONS OF RADIATION AND CHEMOTHERAPY 338
COMPLICATIONS OF CANCER IMMUNOTHERAPY 340

21. NEUROLOGIC COMPLICATIONS OF AORTIC SURGERY 343

SCOPE OF THE PROBLEM 344
VASCULAR ANATOMY OF THE SPINAL CORD 346
NEUROLOGIC FEATURES OF SPINAL CORD INFARCTION 348
DIAGNOSTIC EVALUATION OF SPINAL CORD INFARCTION 350
THERAPEUTIC OPTIONS 353
PLEXOPATHIES 354
AORTIC DISSECTION 354

22. NEUROLOGIC COMPLICATIONS OF CARDIAC SURGERY 361

GENERAL CONSIDERATIONS 362
ISCHEMIC STROKE 366
NEUROPSYCHOLOGIC IMPAIRMENT 373
SEIZURES 374
RETINAL DAMAGE 374
PERIPHERAL NERVE DAMAGE 375

23. NEUROLOGIC COMPLICATIONS OF ACUTE ENVIRONMENTAL

INJURIES 385
THERMAL BURNS 385
SMOKE INHALATION 389
ELECTRICAL BURNS 392
LIGHTNING INJURY 393
ACCIDENTAL HYPOTHERMIA 395
HEAT STROKE 397
NEAR-DROWNING 399
x Contents

24. NEUROLOGIC COMPLICATIONS OF DRUG OVERDOSE, POISONING,

AND TERRORISM 407
THE PRESENTING EMERGENCY AND PRINCIPLES OF TREATMENT 408
SPECIFIC POISONINGS 410
BIOLOGICAL AND CHEMICAL WARFARE 419

25. NEUROLOGIC COMPLICATIONS OF TRAUMATIC BRAIN INJURY 429

CLINICAL SPECTRUM OF HEAD INJURY 430
NEURORADIOLOGIC FINDINGS IN HEAD INJURY 430
GENERAL PRINCIPLES OF MANAGEMENT 440
MANAGEMENT OF INCREASED INTRACRANIAL PRESSURE 442
MANAGEMENT OF TRAUMATIC INTRACRANIAL HEMATOMAS 444
WAR-RELATED BRAIN INJURY 446
MANAGEMENT OF TRAUMATIC CEREBRAL ANEURYSM 446

26. NEUROLOGIC COMPLICATIONS OF TRAUMA TO THE SPINE,

SPINAL CORD, AND NERVES 455
TRAUMA OF SPINE AND SPINAL CORD 455
ACUTE SPINAL CORD INJURY 464
POSTTRAUMATIC NEUROPATHIES ASSOCIATED WITH FRACTURES 467
FAT EMBOLISM SYNDROME 468

27. NEUROLOGIC COMPLICATIONS OF ORGAN TRANSPLANTATION 473

SURGICAL TECHNIQUES OF ORGAN TRANSPLANTATION 474
NEUROLOGIC COMPLICATIONS IN TRANSPLANT RECIPIENTS 479
NEUROLOGIC COMPLICATIONS OF GRAFT-VERSUS-HOST DISEASE 501

PART IV OUTCOME IN CENTRAL NERVOUS SYSTEM CATASTROPHES

28. OUTCOME OF ACUTE INJURY TO THE CENTRAL NERVOUS SYSTEM 513

DESCRIPTION OF OUTCOME CATEGORIES 514
OUTCOME IN ENCEPHALOPATHIES 516
OUTCOME IN STROKE 522
OUTCOME IN HEAD INJURY 524
 Contents xi

OUTCOME IN TRAUMATIC SPINE INJURY 525

OUTCOME IN CENTRAL NERVOUS SYSTEM INFECTIONS 525

PART V CONSULTATIVE NEUROLOGY AND END-OF-LIFE CARE IN

THE INTENSIVE CARE UNIT

29. THE NEUROLOGIST AND END-OF-LIFE CARE IN THE INTENSIVE

CARE UNIT 533
GENERAL CONSIDERATIONS 534
LEGAL ASPECTS OF WITHDRAWAL OF TREATMENT 534
DECISIONS IN WITHDRAWAL OF TREATMENT 535
WITHDRAWAL OF TREATMENT 536
WITHDRAWAL OF TREATMENT IN SPECIAL NEUROLOGIC
CIRCUMSTANCES 537
BRAIN DEATH AND ORGAN DONATION 538
CARDIAC DEATH AND ORGAN DONATION 539

30. THE NEUROLOGIST AND ICU ETHICAL DILEMMAS 545

PRINCIPLES OF COMMUNICATION WITH FAMILIES 546
HOPE 547
FUTILITY 548
GUIDING A FAMILY CONFERENCE 548
THE ETHICS OF COMPASSIONATE SEDATION 550
THE COURTS 550

Index 553
Preface

Writ large in this book is the premise that the evaluation of a critically ill patient with a neurologic
manifestation or complication is the most demanding neurology consultation. This book, when
first published in 1995, provided a practical guide for every disquieted neurologist who entered
the intensive care unit (ICU). Just about what, as a young neurologist, I would have liked to have
known. Keeping this book up to date requires multiple editions because intensive care is one of
the fastest growing and changing specialties. Now, more than 25 years later, we can look back at
the extraordinary expansion in knowledge of critical illness and better understanding of this field
of neurology. Intensivists understand the issues involved and appreciate that a neurologic com-
plication in any medical or surgically critically ill patient is a major cause of mortality and later
morbidity. If recognized in time, treatment of a neurologic complication may greatly improve the
outcome. But neurocritical care in all its forms is also at times informed uncertainty, and many
clinical observations are not understood.
The framework of consults has also changed. New diseases have appeared, such as neurologic
complications of cancer immunotherapy, and older diseases, such as cyclosporine neurotoxicity
in transplant patients, have become rare occurrences. Neurotoxicities of drugs are better under-
stood (e.g., serotonin syndrome and cefepime neurotoxicity). Recent mosquito- and tick-borne
illness (e.g., Zika virus, Chikungunya, and Eastern equine encephalitis) in the United States has
resulted in intensive care admissions. The world since 2019 has been shaken by the SARS-CoV-2
pandemic with its multiple surges and no ICU spared. The pandemic has been a revelation,
certainly since the end of 2021, when ICUs (and morale) were at a breaking point as a result of
treating an unacceptably large number of unvaccinated patients who became infected with the
delta variant. Neurologic complications of SARS-CoV-2 infection have emerged, and this damaging
respiratory virus became the most common reason to consult neurologists, who, like their colleagues
in other specialties, had the disadvantage of dealing with a new disease. It is a prime example of how
suddenly ICU populations can change and have changed again in 2023.
The new edition has responded to changes in ICU care and changes in the ICU population and
is now thoroughly updated. I have added criteria for consultation and how to co-manage patients.
A consultation is often contingent on the following five perceptions: (1) an evolving situation that
requires neurologic expertise; (2) “something” might not be recognized; (3) an unusual CT scan
that does not appear to explain the condition; (4) movements that could indicate seizures requiring
expert evaluation and electroencephalography (EEG); and (5) the patient’s condition looks grim
but needs corroboration, and the family may request a neurologic opinion. All this is addressed.
Neurologic consultations are often requested when patients remain comatose after CPR, and the
neurologist is asked to have the last word. Failure to awaken after surgery or after extended seda-
tion has been discontinued are other typical examples that trigger a request. We have an obligation
to provide the best evaluation and management when the outcome can go either way. We also
have an obligation to evaluate for futility. Neurologic consultation not only provides diagnostic,
therapeutic, and prognostic advice but may also change the approach to the patient. This is a major
responsibility and not one to be taken lightly.
This edition also has new chapters on the interpretation of focal findings, acute movement
disorders in critical illness, cancer immunotherapy, and ethical dilemmas. A separate section
on interpretation of EEG requests (and how to use it in critically ill patients) is added. Several
new drugs (direct oral anticoagulants [DOACs] and chimeric antigen receptor T-cell therapy
[CAR-T]) have made their way into the ICU and are discussed in detail because their side effects
require specific intervention. There is a wealth of new tables, algorithms, and neuroimaging. I
have added a new section of advice for practical management to each chapter to reconcile theory
and practice.

xiii
xiv Preface

ICUs are challenged with an increasingly growing (and aging) population, and admissions are
increasing. Neurologic complications will increase, too. This clinical text will be helpful to a very
wide audience of healthcare providers and, in particular, for any intensivist and general neurologist
who must manage these patients with extremely complex medical disorders, surgeries, comorbid-
ity, and with different clinical trajectories. The book is also aimed at neurointensivists who consult
in ICUs other than their own. This book reaches beyond neurology and additionally targets emer-
gency physicians, neurosurgeons, transplant and vascular surgeons, internal medicine hospitalists,
pharmacists, allied healthcare providers, and ICU nursing staff.
I appreciate the help of so many. Lea Dacy not only dutifully edited the full manuscript, but
she has always been absolutely necessary to improve the prose. I am grateful for the work by the
illustrators of Mayo Clinic Media Support service and, in particular, David Factor, who predictably
provided beautiful and informative drawings. I appreciate my long-time working relationship with
Oxford University Press, and they are peerless when it comes to academic work.
The interest in the acute neurosciences in practice is the unexpected. I have lived the subject
matter for several decades, and our neurocritical care group sees several hundred patients in ICUs
other than our own Neurosciences ICU each year. I hope the book I set out to write reflects that
experience. The diagnosis and management of neurologic complications in critical illness, in my view,
has always been one of the major pillars of neurocritical care.
March 2023
Eelco Wijdicks
PART I

Criteria, Urgency, and

Importance
Chapter 1
Indications for a Neurologic Consult
in the Intensive Care Unit
CATEGORIES OF CONSULTS
BENEFITS OF A CONSULTATION
Teams working in intensive care units (ICUs) may
bring in a neurologist and for all kinds of reasons.1
When called to action, most neurologists enter-
ing an ICU are immediately confronted with the
complexity of critical illness. The modern ICU is
a unique place, with patients presenting with an
array of different conditions and with consultants
having specific expertise in handling critical ill-
ness. Patients enter the ICU in a life-threatening
state with failing organ systems and become
hypotensive, hypoxemic, hypercapnic, and tachy-
cardic; the initial resuscitation generally does not
concentrate on neurologic manifestations. Most
intensivists briefly check for pupil responses or
major asymmetries, but they accept an altered
level of consciousness as a common consequence
of an evolving critical illness. Some manifesta-
tions may not be considered atypical enough
for an urgent neurologic consult. This logically
implies that neurologists will see a selection of
neurologic manifestations in critical illness.
ICU consultative neurology focuses on those
patients admitted to medical and surgical ICUs
presenting with a de novo neurological prob-
lem related to their illness—questions . . . and
issues concerning the effects of antiseizure and
antiparkinson medication for prior diagnosed
illness are entirely different. These patients
are seen in consultation for diagnosis and
management—often expediently—but remain
under the care of intensivists and surgeons.
The complications observed may be quite spe-
cific (or mundane), but intensivists may intui-
tively feel uncomfortable in overseeing these
new neurologic conditions themselves. They
request not only assistance in identifying the
neurologic disorder but also help in manage-
ment. This is particularly pertinent with recur-
rent seizures or progressive neurologic decline.
Once the patient is seen, continuous attention
is necessary, which may involve prolonged bed-
side care and, later, calls at night from nursing
staff or attending intensivists and, ultimately,
direct management. Interpretation of electro-
encephalograms and neuroimaging is often
repeatedly required.2
3
4 Part I Criteria, Urgency, and Importance
More than in any place in the hospital, ICU
consultations involve questions about de-escalating
care. The attending team and family may consider
withdrawing intensive care or, at least, consider
a do-not-resuscitate status and thus need a neu-
rologist’s input. This involvement partly reflects
the high prevalence of neurologic catastrophes
in patients with a critical illness. Frequently, the
clinical situation is clear, as in persistently coma-
tose survivors after prolonged cardiopulmonary
arrest and in elderly patients with polytrauma
and severe traumatic brain injury; in other situ-
ations, the degree of brain injury may be more
difficult to ascertain. Neurologists are asked
to participate in family conferences, and they
can be helpful in clarifying the bigger picture.
Sometimes, the neurologic complication is a
defining moment, and little more can be done for
the patient. Neurologists can be conclusive and
advise the managing ICU team against treating
a patient in a futile situation. In other situations
the neurologic situation could be misjudged as
irrecoverably poor while there is a possibility for
another more favorable trajectory. This is not an
uncommon scenario, and neurologists can shed
more light on why they think that way. Another
fundamental rule of ICU consultation is to prog-
nosticate decisively when certain but to hold back
when information is incomplete or the clinical
situation is not fully understood.
Critical illness increases the probability of
a neurologic complication, and, according to
current best estimates and excluding perva-
sive delirious states, approximately 10–20% of
patients will develop some sort of neurologic
manifestation. The neurology of critical illness
is an important field that requires more pro-
spective research. The rationale for neurologic
Table 1.1 The field of neurology of
critical illness
Neurologic consultation in the ICU requires a
broad base of medical knowledge
Neurologic consultation provides diagnostic,
therapeutic, and prognostic advice
Neurologic consultation often involves assessment
of abnormalities of responsiveness or seizures
Neurologic consultation may detect an unsuspected
neurologic disorder
Neurologic consultation in the ICU may change
approach to the patient
Neurologic consultation involves end-of-life
decisions for patients
consultation is summarized in Table 1.1 and
shows common clinical neurologic problems
facing the intensive care specialist and consult-
ing neurologist in everyday decisions.
CATEGORIES OF CONSULTS
We must assume that ICU consults are urgent
or emergent. The urgency is often determined
by an inability to understand the full clinical pic-
ture and particularly when the initial presenta-
tion is disturbing. Examples are ICU consults for
acutely impaired consciousness, which require
a quick but comprehensive assessment of the
cause of coma and whether it can be immediately
reversed. Upon receiving a call to consult in the
ICU, we typically expect three clinical scenarios:
acute loss of consciousness, failure of patients
to awaken fully after recuperation from a major
surgical procedure, and occasionally, coma in a
developing but undiagnosed critical illness. We
are often consulted to evaluate and treat delirium,
and we now have a better sense of what this acute
brain dysfunction could entail.3–6
Any consult in a critically ill neurologic
patient must proceed through the steps out-
lined in Table 1.2. Any consult in a critically
ill patient may lead to a diagnosis not initially
considered by the managing team; in our expe-
rience, this occurs rather frequently.7 These
recognized neurologic disorders may all have
major consequences diagnostically, prognosti-
cally, and therapeutically.
Consultations may have a varying degree of
complexity and may involve management of
major acute neurologic injury. Consultation
may evolve from a simple question, to being
physically present, to continuously managing
Table 1.2 Essentials of a neurology
consult in the intensive care unit
Assess details on severity of critical illness
Assess blood pressure and extent of blood pressure
support
Assess drug administration over 5–7 days
Verify onset of symptoms with nursing staff
Assess major confounders
Assess for focal localizing sign
Assess for movements, twitching, new rigidity
Assess for drugs strongly related to movement
disorders

Table 1.3 Reasons for a consult in the
intensive care unit
Acutely comatose
Failure to awaken after resuscitation
Acute focal deficit
Acute agitation
New seizure(s)
Acute repetitive movements
Generalized weakness
Abnormal neuroimaging
Abnormal EEG
an acute injury to the brain or spine and, as
such, may even involve palliation and end-of-
life discussions (Table 1.3).
There is a spectrum of close participation
with the consulting neurologist (Figure 1.1).
In some cases, a consult consists of picking up
the phone and asking an expert, and in many
Figure 1.1. Types of consultations.
1 Indications for a Neurologic Consult 5
intensive care practices, it is often easier to call
a consultant rather than to ask for a formal con-
sult. Both parties often agree that some type of
advice will pragmatically direct testing or treat-
ment. For the intensivist, there may be other
immediately pressing priorities in the complex
care of the patient, and a new neurologic prob-
lem is best solved quickly. Many of the neurology
“curbsides” in the ICU are indeed simple phone
calls to ask a simple question, but some ques-
tions should probably generate a formal consult.
Consultants should generally and deliberately
avoid a practice of mostly taking phone calls for
curbsides, which are a set of quick questions that
pertain to critical illness. These include interpre-
tation of a CT scan of the brain, a question about
electroencephalograph (EEG) interpretation, or
the need for EEG monitoring. Other common
questions are how to manage neurologic medi-
cation such as antiepileptic drugs, assess the risk
of anticoagulation, or interpret specific neuro-
logic manifestations of acute neurologic disease.
It is often better to see the patient briefly and
then determine if a formal consult can be helpful.
The consulting neurologists will also have
to consider the following questions. How can
I best ask pointed questions? Am I able to
provide advice with limited information and
without having the opportunity to examine
the patient in detail? Am I confident enough
to dismiss or diagnose certain CT scan abnor-
malities? Does this clinical problem require a
close follow-up and thus a formal consultation?
Acute (STAT) consults in the ICU are the
most challenging in the hospital because (1)
decisions may have to be made in an evolving
situation; (2) the primary diagnosis may be
unclear and puzzling; (3) neurologic exami-
nation can be compromised when patients
are markedly swollen, jaundiced, immobile,
bruised, or have major operation sites or an
open chest; and (4) none of the neuroimaging
and electrophysiology results may be particu-
larly helpful. Any consulting neurologist will
ask him- or herself the following additional
questions: Are the neurologic findings com-
mensurate with the cause and degree of criti-
cal illness? Are the focal findings significant
or difficult to judge? How is neuroimaging or
electrophysiology best interpreted in the set-
ting of critical illness?2,8–10 Are there urgent
treatment options or treatment adjustments
that have not been considered? Will this neu-
rologic manifestation set the patient back
6 Part I Criteria, Urgency, and Importance
permanently? Can I provide a reliable opin-
ion on the future likelihood of full depen-
dence for the patient, and could this opinion
put an end to the aggressive, constantly esca-
lating care?
BENEFITS OF A CONSULTATION
The need for broad knowledge of critical care
could argue for a separate hospital service
staffed by experienced neurohospitalists or
neurointensivists. It goes to the heart of a long-
standing academic and clinical question (and,
in some centers, a charged debate): Who is
best qualified to see these patients? Many of
us are caught unaware by a variety of presenta-
tions, and as long as experience is gained, it is
better gained by a specialized group. We have
seen several conditions emerge more clearly
as a result of covering all ICU consults with
our neurocritical care services in both Mayo-
affiliated hospitals.
Telemedicine could be ideal for these con-
sults,11–16 but accurate metrics will need to be
developed to show benefit. These could include
(1) seizure control, (2) acute stroke care, (3)
neurosurgical intervention, (4) control of intra-
cranial pressure, and (5) limiting potent seda-
tive drugs and avoiding drug-drug interactions.
Ultimately, a full neurologic examination
leads to new tests (EEG, somatosensory evoked
potential [SSEP], CT scan, MRI, and CSF). All
these tests are highly neurospecific, and recom-
mendations of what to test or add to routine
orders require good communication and, most
importantly, accurate interpretation.
PRACTICAL ADVICE
• A major principle of consultation in the
ICU is to see the patient immediately rather
than paying a belated visit. A serious neuro-
logic illness requiring immediate interven-
tion might go unrecognized. Moreover, the
entire clinical picture may be unclear and
evolving, and neurologic expertise may point
toward the right direction.
• Treatments may be inappropriate, incom-
plete, and incorrect. Errors happen easily
even in the best-equipped, well-staffed ICUs.
• Neurologists should appreciate the pharma-
cology of sedative drugs and use of analgesic
drugs to provide a better assessment.
• Direct communication with the intensivist
might provide a comprehensive clinical course
and timeline of when events occurred.
• Direct communication with the surgeon on
the surgical procedure and possible intra-
operative events can decrease evaluation time
and capture important intraoperative compli-
cations such as hypotension or even CPR.
• The circumstances surrounding critical ill-
ness could make the patient vulnerable to
seizures. However, few patients in the ICU
have seizures; many more undergo EEGs.
Proportionality is necessary.
• A universal question is whether failure to
wean from a ventilator is due to a previously
unappreciated and undiagnosed neurologic
disorder. Early diffuse weakness in ICU may
be undiagnosed amyotrophic lateral sclero-
sis. Late diffuse weakness in ICU is often
sepsis-related or critical illness–associated
polyneuromyopathy.
REFERENCES
1. Wijdicks EFM. Why you may need a neurologist to
see a comatose patient in the ICU. Crit Care. 2016
Jun 20;20(1):193.
2. Rabinstein AA. Continuous electroencephalog-
raphy in the medical ICU. Neurocrit Care. Dec
2009;11(3):445–6. doi:10.1007/s12028-009-9260-6
3. Brown CH. Delirium in the cardiac surgical ICU.
Curr Opin Anaesthesiol. Apr 2014;27(2):117–22.
doi:10.1097/ACO.0000000000000061
4. Ely EW, Shintani A, Truman B, et al. Delirium
as a predictor of mortality in mechanically venti-
lated patients in the intensive care unit. JAMA. Apr
2004;291(14):1753–62. doi:10.1001/jama.291.14.1753
5. Hughes CG, Patel MB, Pandharipande PP.
Pathophysiology of acute brain dysfunction:
What’s the cause of all this confusion? Curr Opin
Crit Care. Oct 2012;18(5):518–26. doi:10.1097/
MCC.0b013e328357effa
6. Pandharipande PP, Girard TD, Jackson JC, et al.
Long-term cognitive impairment after critical ill-
ness. N Engl J Med. Oct 2013;369(14):1306–16.
doi:10.1056/NEJMoa1301372
7. Mittal MK, Kashyap R, Herasevich V, Rabinstein
AA, Wijdicks EF. Do patients in a medical or sur-
gical ICU benefit from a neurologic consultation?
Int J Neurosci. 2015;125(7):512–20. doi:10.3109/
00207454.2014.950374
8. Claassen J, Taccone FS, Horn P, et al. Recommendations
on the use of EEG monitoring in critically ill patients:
Consensus statement from the neurointensive care

section of the ESICM. Intensive Care Med. Aug
2013;39(8):1337–51. doi:10.1007/s00134-013-2938-4
9. Oddo M, Carrera E, Claassen J, Mayer SA, Hirsch LJ.
Continuous electroencephalography in the medical
intensive care unit. Crit Care Med. Jun 2009;37(6):2051–
6. doi:10.1097/CCM.0b013e3181a00604
10. Young GB. Continuous EEG monitoring in the ICU:
Challenges and opportunities. Can J Neurol Sci. Aug
2009;36 Suppl 2:S89–91.
11. Guinemer C, Boeker M, Furstenau D, et al. Telemedicine
in intensive care units: Scoping review. J Med Internet
Res. Nov 2021;23(11):e32264. doi:10.2196/32264
12. Lilly CM, McLaughlin JM, Zhao H, et al. A multi-
center study of ICU telemedicine reengineering of
adult critical care. Chest. Mar 2014;145(3):500–507.
doi:10.1378/chest.13-1973
1 Indications for a Neurologic Consult 7
13. Lilly CM, Zubrow MT, Kempner KM, et al. Critical
care telemedicine: Evolution and state of the art. Crit
Care Med. Nov 2014;42(11):2429–36. doi:10.1097/
CCM.0000000000000539
14. Weiss B, Paul N, Balzer F, Noritomi DT, Spies
CD. Telemedicine in the intensive care unit: A
vehicle to improve quality of care? J Crit Care. Feb
2021;61:241–6. doi:10.1016/j.jcrc.2020.09.036
15. Welsh C, Rincon T, Berman I, et al. TeleICU inter-
disciplinary teams. Crit Care Nurs Clin N Am.
2021;33:459–70.
16. O’Shea AM, Reisinger HS, Panos R, et al.
Association of interactions between Tele-critical
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10.1177/1357633X221107993
Chapter 2
Consulting in the Intensive Care Unit
PREPARATION AND HISTORY-TAKING
As implied earlier, consults in the intensive
care unit (ICU) to evaluate and manage an
acute neurologic clinical problem are in stark
contrast to other requested hospital con-
sults. As this book demonstrates, neurologic
complications of critical illness are usually
of considerable complexity.1–11 Even enter-
ing the ICU can make one feel unsettled,
especially when patients have major trauma,
open chest or abdominal wounds, multiple
ongoing medical complications, and certainly
when patients are connected to an extra-
corporeal membrane oxygenation machine.
Some comatose patients are markedly swol-
len, jaundiced, and immobile. And then there
is polypharmacy with many potent sedatives.
In these situations, an adequate neurologic
assessment may seem a worthless undertak-
ing (Figure 2.1).
The clinical interpretation of a vexing neu-
rologic problem in the ICU requires skill and
full understanding of its immediacy. Before
we dive into the nitty-gritty of neurological
consultation in the medical and surgical ICU,
this chapter paints the larger picture of what
a neurologic consult in the ICU could entail.
COMMON REQUESTS FOR CONSULTS
IN THE ICU
PREPARATION AND
HISTORY-TAKING
First and foremost, gathering essential infor-
mation may be difficult, with some of this
information hidden in not easily accessible
drop-down menus on the patient’s monitor.
In other cases, particularly in recently trans-
ferred patients with long ICU stays, informa-
tion must be abstracted from an excessive
number of notes of variable granularity.
The second step is to gain an understanding
of the severity of the patient’s critical illness.
Two main factors must be taken into consider-
ation: history and recent clinical course. In the
ICU, the history is often reconstructed from
fragments of observations by the patient’s fam-
ily, nursing observations, attending consultant
notes, and, less often, from communication
with the patient. Therefore, the patient’s his-
tory could be potentially inaccurate, seriously
limiting a full assessment of neurologic com-
plications. A simple matter-of-fact question
such as “When were these signs first noted?”
may be difficult to answer reliably. In such
complex cases, direct communication with the
9
10 Part I Criteria, Urgency, and Importance
Figure 2.1. Critically ill 77-year-old man in a cardiovascular intensive care unit. The complexity of care (mechanical ventila-
tion, dialysis, and multipharmacy) can seriously hinder the neurologic examination for consulting physicians.
attending intensivist or surgeon is required and
could decrease evaluation time substantially.
As a rule, consultants evaluating patients
with a postoperative complication also need
to have a good understanding of the opera-
tive technique and surgical decisions (e.g.,
avoidance measures, anesthetic interventions).
Consultants evaluating patients with neuro-
logic manifestations of the CNS in the setting
of a major medical illness must be aware of the
patient’s prior hemodynamic instability, degree
of organ dysfunction, coagulation status, and
pharmacy regimen. For patients with general-
ized weakness, consultants must determine the
patient’s prior use of neuromuscular blockers
and intravenous corticosteroids and should be
able to correctly interpret electrodiagnostic
studies.
COMMON REQUESTS FOR
CONSULTS IN THE ICU
Most consults are prompted by very specific
neurologic signs that have been detected by
the nursing staff or attending physician during
rounds. Obviously, the threshold for consulting
a neurologist is variable and depends on the
recognition of neurologic signs and the comfort
level of some intensivists—less familiar with
disorders of the nervous system—in handling
these complications. In other circumstances,
the patient’s failure to improve medically (e.g.,
inability to be liberated from the ventilator),
acute coma, or failure to become fully coher-
ent and alert over a matter of days after surgery
may trigger a consultation.1,3,7 There may also
be a convincing need to transfer the patient to
a more specialized neurosciences ICU.
These situations are challenging for both
the neurologist approaching the bedside and
the intensivist trying to grasp the full clinical
picture. The quality and amount of informa-
tion available to the consulting neurologist can
be disconcerting. The consult request may be
summarized in only a few words (“new neu-
rologic event,” “periodic twitching,” or “unre-
sponsive”). Several consults are about pupil
asymmetries (because the eyes are exam-
ined frequently), and most are not concern-
ing. Another common but potentially urgent
category is the patient with “altered mental
status.” The term “altered mental status” has
achieved classic standing, although not for
its accuracy because it may mean anything.
This category of neurologic deficits—patients
who are agitated and less responsive—may

appear less worrisome. Patients are confused
and may not respond quickly, rarely fixate on
objects, and cannot follow simple commands.
Some can speak; others are unable to respond.
We assume that, in most situations, these
patients have an acute brain dysfunction from
sepsis-associated encephalopathy, new-onset
acute renal or liver failure, or a combination.
Posterior reversible encephalopathy syndrome
(PRES) is so prevalent that it is often listed at
the top of the differential diagnosis and, if the
circumstances are right, should be investigated
with MRI. Unfortunately, for many years, neu-
rologists had a tendency to describe any patient
with an encephalopathy as having “multifacto-
rial metabolic encephalopathy” and would list
the abnormalities that make up the patient’s
critical illness. None of this advanced an
understanding of these complicated patients.
More experience in examining and following
these patients has resulted in better efforts
to understand the true nature of acute brain
dysfunction. One principle is to set apart the
major driver of neurologic manifestations, but
it is equally accepted now to consider other
possible explanations such as structural injury.
Acute confusional state or delirium may trig-
ger a consult, but many intensivists recognize
this entity and treat it appropriately.3–6 Without
a doubt, the most difficult situation is to assess
a patient with decreased or increased arousal,
abnormal perception, abnormal attention, and
incoherent language. Within this category of
patients are those with apraxia and aphasia
(Chapter 3). Many ICU patients have agitated
delirium or “sundowning” due to preexisting
dementia or alcohol withdrawal. An unex-
plained observation is that delirium correlates
with prolonged ICU stay (and increased mor-
tality), but none of the clinical trials that have
aggressively treated patients in delirium have
shown an improved mortality rate.
There are some other urgent consults.
Consults for new-onset seizures or new move-
ment abnormalities are comparatively fre-
quent. A new focal finding (e.g., hemiparesis or
marked asymmetry) is less common. Consults
are often for newly perceived asymmetries. It is
a major challenge to recognize an acute stroke
during a critical illness or after a major vascular
procedure. Patients may have a delayed pre-
sentation or delayed recognition, particularly
when anesthetic drugs have been used and
are still washing out in the postoperative phase
2 Consulting in the ICU 11
of surgery. The challenge here is early recog-
nition to allow an endovascular intervention
because IV thrombolysis is contraindicated.
Acute ischemic stroke may warrant endovascu-
lar treatment if the situation allows. (CT scan
may already show a matured infarct.) Consults
in surgical and trauma ICUs are often related
to diagnostic evaluation of new spinal cord
injury and traumatic brain injury, but in most
instances, other specialties are involved (i.e.,
neurosurgery).
A special category is consultation for a trans-
plant recipient. This may have already started
before transplantation (e.g., fulminant hepatic
failure) because the attending intensivist or
surgeon values the presence of a neurologist.
Another special category is the patient admit-
ted with a left ventricular assist device (LVAD)
and new neurologic symptoms. Discussions
on discontinuing or improving anticoagulation
often involve a neurologist.
In the surgical ICU, consults may involve
the sudden appearance of paraplegia after
awakening from anesthesia. Acute spinal cord
infarction might indicate immediate placement
of a lumbar drain to reduce CSF spinal pres-
sure and improve residual spinal blood flow. In
each of these scenarios, prompt decisions are
warranted and can improve outcome if proper
measures are taken. Urgent consultation for a
possible complication of carotid artery surgery
involves assessment for possible ischemic stroke
or management of blood pressure and heart
rate instability. (The latter is mostly managed
by a neurointensivist, but a general neurolo-
gist should be aware of this major complication
involving damage to the baroreceptors.)
Generalized weakness in the ICU is very
common and nearly always prompts a neuro-
logic consult. Most neurologists expect (and
diagnose) critical illness polyneuropathy, criti-
cal illness myopathy, or both. One could argue
that, in fact, this myopathy is the most com-
mon cause of weakness in the ICU. The preva-
lence of ICU-acquired weakness is high in
survivors of critical illness and will increase as
more patients survive multiorgan failure, sep-
sis, and other fulminant infections. Failure to
wean off the ventilator (or unexplained reintu-
bations) is another trigger for a comprehensive
neurologic assessment, and a neurologic disor-
der other than critical illness polyneuropathy
may be found. Finally, consults may involve
an explanation of neuroimaging findings or the
12 Part I Criteria, Urgency, and Importance
interpretation of an ordered electroencepha-
lograph (EEG) in a patient with an undefined
repetitive movement).
Failure to awaken or prolonged unconscious-
ness is a very common consult, and requests
may be vague and not immediately alarming
(“altered mental status”). Such a consult needs
an immediate response; the neurologist must
see and examine the patient.
Several issues are pertinent. (More details
on examination and classification are found in
Chapter 4.)
First, a patient’s failure to awaken after
urgent cardiovascular repair is an ominous
sign. A devastating ischemic stroke involving
multiple arterial territories is a frequent cause
of failure to awaken.7 Its mechanism may be
hypotension or multiple emboli. Hypotension
can be implicated only if it persists for a con-
siderable period. In addition to perioperative
hypotension and cardiac resuscitation during
surgery, multiple embolic events are possible
reasons for multiple cerebral infarctions. In
some patients, the surgical approach and anes-
thetic support were without obvious distress to
the patient, and the cause for multiple cerebral
infarctions may remain unresolved. However,
the risk of embolization is significant for
patients with severe atherosclerotic disease of
the ascending aorta, and embolization almost
certainly occurs at the time of clamping.
Second, evaluation of impaired consciousness
in patients requiring intensive care for acute
medical illness starts with a series of important
questions (Table 2.1). The answers could narrow
down the list of causes of impaired conscious-
ness by a simple process of elimination.
Because triggers such as hypotension and
coagulopathies are common, neurologists
should focus on finding structural causes even if a
Table 2.1 Questions to family members and nursing staff concerning patients in
the intensive care unit with impaired consciousness
Family
• Illicit drug use?
• Alcohol abuse?
• Circumstance in which patient was found
(apneic, cyanotic, seizing)?
• Prior illness or constitutional symptoms?
• Recent medication adjustments or newly
started drugs?
• Prior, comorbid conditions?
pharmacologic cause of coma is likely. Therefore,
after location is determined, neuroimaging fol-
lows, and the combination of clinical and neuro-
imaging results can lead to specific actions. CT
of the brain (or CT angiogram in cases suggest-
ing an embolus to a major cerebral artery) is a
mandatory diagnostic test and currently has an
acquisition time of less than 10 min. A CT can
document generalized cerebral edema, cerebral
hemorrhage, and ischemic stroke with swelling,
but its diagnostic yield is low for anoxic–ischemic
brain injury and in the period early after trau-
matic head injury. If structural damage is pres-
ent, it should be correlated to the depth of coma.
A significant shift of the midline structures (sep-
tum pellucidum, calcified pineal gland) due to
a new mass, hydrocephalus, or intraventricular
hemorrhage must be recognized in patients with
rapidly deepening coma.
A normal CT scan in a patient with a meta-
bolic derangement or organ dysfunction does
not exclude a structural cause and, if feasible,
should be followed by MRI. Causes of coma
in patients with initially normal CT results are
presented in Table 2.2 for easy reference.
MRI has come to the fore as a diagnostic tool
in ICUs, and if anesthesia support is available,
it may be used to identify or exclude struc-
tural damage for comatose patients. However,
transport to the MRI suite takes the critically
ill patient out of the critical care environment,
and, once there, necessary support (vasopres-
sors, mechanical ventilator) is inadequate and,
in some instances, can jeopardize the patient’s
safety. In our experience, fewer than half of
comatose patients can be transported to the
MRI suite without difficulties. Therefore, the
yield of abnormalities and consequences for
management should be high before ordering
an MRI.
Nursing staff or attending consultant
• Intraoperative cardiopulmonary resuscitation?
• Intraoperative hypotension?
• Presence of asymptomatic interval after surgery?
• Hypotension requiring vasopressors?
• Hypoxemia requiring high level of positive
end-expiratory pressure?
• Myoclonus, eye deviation, eyelid blinking?

Table 2.2 Probable causes of coma in
critically ill patients with normal initial
CT findings
Anoxic–ischemic encephalopathy
Drug overdose
Neurotoxicity from chemotherapeutic agents or
immunosuppressive agents
Diffuse axonal brain injury
Acute central nervous system infection
Fat embolization
Acute basilar artery occlusion
Cholesterol embolization
Central pontine myelinolysis
Diffuse intravascular coagulation
Thrombotic thrombocytopenic purpura
Central nervous system vasculitis
Prolonged hypoglycemia
Acute severe hyponatremia
Acute severe hypercalcemia
Acute nonketotic hyperglycemia
Metabolic acidosis
Acute hypercapnia with hypoxemia
Adrenal crisis
Acute hypothyroidism
Acute hyperthyroidism
Acute uremia
Acute hyperammonemia
Recent laboratory values should be obtained,
and the medical records should be scrutinized
for trends. CSF examination is needed when
meningitis is suspected and should be consid-
ered in critically ill patients with spinal anes-
thesia, traumatic brain injury, trauma, and
evidence of paranasal sinusitis.
The role of EEG, including its place in the
detection of nonconvulsive status epilepticus, is
discussed in other chapters, but all too often,
only dysrhythmic slowing and triphasic waves
are seen.7 Except for documentation of subtle
seizures, EEG has generally lost its practical
value in these situations, relinquishing useful-
ness to neuroimaging, particularly diffusion-
weighted MRI. Whether nonconvulsive status
epilepticus is underdiagnosed in critically ill
patients remains debatable, and we have docu-
mented only a few verifiable instances of non-
convulsive status epilepticus in the medical or
surgical ICU over the past decades.
Third, another reason for consultation is a
request to explain failure of patients to awaken
after discontinuation of sedation, and this may,
despite everything, be a common cause of
impaired consciousness. A prolonged, lingering
2 Consulting in the ICU 13
Table 2.3 Information gathering for
a critically ill patient with impaired
consciousness and prior use of
sedation
• Chart drugs, doses, and serum levels (if available)
• Review drug toxicology screen, serum-urine (if
available)
• Assess factors that delay washout of drugs (e.g.,
liver or kidney function)
• Assess and reconstruct any plausible
pharmacodynamic and pharmacokinetic effects;
calculate 5 × half-life period
• Review possible neurotoxic drugs
• Consider antagonists (e.g., flumazenil, naloxone)
sedative effect is an obvious consideration but
could be difficult to quantify, let alone prove
(Table 2.3). Reconstruction of the pharmaco-
dynamics and pharmacokinetics is useful.
Often alkalosis, drug interactions, and large
doses of sedative drugs change elimination to
zero-order kinetics, which directly contributes
to prolonged sedation (Chapter 2). Drug levels
should be measured if possible. For any drug,
the consultant should obtain the metabolic
half-life and calculate the time remaining to
clearance, assuming full elimination. Patients
who do not fully awaken after withdrawal of
sedatives, narcotic agents, or combinations
of these agents are frequently jaundiced and
often have recently been given a benzodiaze-
pine (midazolam) or a narcotic drug (fentanyl).
Both drugs are designed to clear through the
liver and therefore may accumulate. Prolonged
sedation occurs after many days of accumulated
metabolites, and further observation over time
may be required.
Fourth, consults are requested for patients
who become acutely comatose while they are
critically ill, and these patients commonly have
a catastrophic neurologic illness. A large propor-
tion of patients in our experience have a devas-
tating intracerebral hematoma or subarachnoid
hemorrhage. These disorders, which may be
the inaugural presentation, typically occur in
patients with systemic fungemia, coagulopathies,
or a ruptured mycotic aneurysm from endocar-
ditis. Acute basilar artery occlusion due to an
embolus can complicate dissection of the thoracic
aorta, valve repair, and cardiac transplantation.
Rapidly deepening loss of consciousness in
patients with multiple traumatic injuries should
point to fat embolization, evolving epidural or
14 Part I Criteria, Urgency, and Importance
subdural hematoma, or enlarging hemorrhagic
contusions with mass effect and edema. Acute
coma can occur after correction of hyponatre-
mia, cardiac resuscitation, and carbon monox-
ide poisoning, all of which are manifestations of
extensive demyelination of both hemispheres.
Typically, patients who seem to be doing very
well suddenly and unexpectedly lapse into a
deep coma and succumb.
If failure to awaken occurs after traumatic
brain injury and the patient has been admit-
ted directly to the operating room from the
emergency department, intracranial contusion
or extraparenchymal hematoma should be con-
sidered. Patients taken directly to the operating
room with life-threatening, blunt abdominal
trauma may have additional head injury, sub-
dural hematoma, or epidural hematoma that
was not apparent on initial examination. A uni-
lateral, fixed pupil may suddenly occur during
surgical repair of a vascular injury or abdomi-
nal exploration for trauma. (Pupillary light
reflexes are the only brainstem reflexes that
can be monitored during general anesthesia.)
Extraparenchymal hematomas may become
evident on CT after 24 hr.
Acute electrolyte imbalance is a relatively
frequent cause of postoperative confusion,
progressive drowsiness, or coma. Increased
levels of antidiuretic hormone associated
with decreased serum osmolality and hyper-
osmolar urine are typical during the first few
postoperative days. When hypotonic fluids are
used, renal handling of free water is impaired
because renal function decreases after the use
of inhalational anesthetics, barbiturates, and
opioids. Hyponatremia can occur rapidly and
typically results in seizures, apnea, and cardiac
arrhythmias, often at sodium levels below 110
mEq/L. Other common causes of acute post-
operative hyponatremia are administration
of large doses of hypotonic fluids to patients
with impaired ability to excrete water after
transurethral prostatectomy and administra-
tion of oxytocin to patients during obstetric
procedures.
Fifth, failure to awaken after transplanta-
tion requires a separate discussion. Neurologic
complications in the early postoperative phase
of cardiac transplantation have decreased in
recent years. Much of the decrease is due to
meticulous attention to removing all residual
atrial tissues or thrombi. Also, the use of a
more precise everting anastomosis may have
decreased intracardiac thrombus formation on
the suture interface and thereby the resultant
massive embolic showers and cerebral infarc-
tions. Therefore, impaired consciousness after
heart transplantation is infrequently due to a
structural lesion in the CNS. Without local-
izing neurologic findings, the most common
cause of unresponsiveness is drug-induced
coma. Narcotic agents are often used liber-
ally in cardiac transplant recipients to decrease
pain and overcome postoperative hypertension.
These agents (usually morphine and fentanyl)
may cause significant postoperative sedation.
Typically, high doses of narcotic agents are
given intraoperatively such as fentanyl (with
diazepam) or sufentanil (with lorazepam).
Naloxone (0.04–0.08 mg) reverses the effects
of narcotic agents. However, failure to awaken
may originate with the marked hypotension
that occurs intraoperatively, with episodes
of significant hypoxemia, or more often, with
cardiac resuscitation for asystole or ventricu-
lar fibrillation. Cardiac arrest can occur in the
immediate postoperative phase and can be
devastating. In these patients, the most common
clinical problems associated with perioperative
cardiac arrest are hypovolemia, tamponade,
and overdose of potent vasodilators.
Neurologic evaluation in the first several days
after a lung transplant is difficult because most
patients are sedated, paralyzed, and mechani-
cally ventilated. Some programs dictate con-
tinuing mechanical ventilation to decrease
stress on the critical tracheal anastomosis,
but most patients are rapidly weaned within
36 hr. Pulmonary hemorrhage and infection
may dominate the early postoperative course.
Impaired consciousness, therefore, may reflect
the hypoxemia associated with pulmonary
edema from reperfusion injury to the graft.
Impaired consciousness and acute con-
fusional state occur in a large proportion of
patients with liver transplantation. Many
metabolic abnormalities are present, but none
significantly contributes to the diminished
alertness of the patients. With a new function-
ing liver, the level of alertness should improve
rapidly.
Patients with fulminant hepatic failure
are prone to increased intracranial pressure
because of brain edema, and liver transplanta-
tion is their only hope for survival. Return of
consciousness to baseline level takes days, and
these patients typically have more prolonged
 2 Consulting in the ICU 15

awakening in the postoperative phase. In addi-
tion, the use of barbiturates perioperatively
to control increased intracranial pressure
may contribute substantially to postoperative
altered consciousness.
Treatment of comatose patients involves
management of increased intracranial pres-
sure, neurosurgical evacuation of a new mass,
treatment of seizures, and correction of labora-
tory abnormalities. Patients who remain coma-
tose need careful examination to determine
the chances of awakening and to prognosticate
later disability if they improve. Supportive care
can be provided if prognosis is uncertain and
should include placement of a tracheostomy
and percutaneous gastrostomy, meticulous skin
and eye care, and physiotherapy measures to
prevent contractions. A comprehensive discus-
sion on care can be found in another text.5
Finally, another common issue is whether the
patient has an undiagnosed neurologic disease
of the peripheral nervous system. Acute exac-
erbation of chronic obstructive pulmonary dis-
ease often leads to mechanical ventilation and,
frequently, a tracheostomy, and these patients,
if not already in a poor nutritional state before
admission, will have an emaciated appear-
ance. It is therefore not unthinkable that the
combination of CO2 retention before endo-
tracheal intubation, difficulty with liberating
from the ventilator, and abnormal pulmonary
function tests (inspiratory and expiratory pres-
sures) points toward a neuromuscular disorder.
Clinical distinction between a myopathy, a poly-
neuropathy, or a neuromuscular disorder is dif-
ficult if all four limbs are flaccid and other signs
are lacking.
Electrodiagnostic testing is often a part of the
evaluation, but interpretation requires exper-
tise, and muscle or nerve biopsy may bring a
more definitive classification. Quantitative anal-
ysis of motor unit potentials, which requires
cooperation by the patient, may be difficult in
very weak, confused, and agitated patients. At
least three motor nerves (distal latency, ampli-
tude, and conduction velocity) and three sen-
sory nerves (amplitude and conduction velocity)
should be studied and followed by needle inser-
tion in multiple muscles. The most common
electrophysiologic abnormalities are listed in
Table 2.4, and more details on the differential
diagnosis can be found in Chapter 7.
Phrenic nerve stimulation in a patient with
diffuse muscle weakness strongly points to a
critical illness polyneuropathy if both sides are
abnormal.6 Abnormal blink reflexes are found

Table 2.4 Electrophysiological features of major neuromuscular disorders

associated with critical illness
Disorder NCV and EMG findings Special considerations
Critical illness Reduced CMAP amplitude, short Lack of direct stimulation of muscle
myopathy duration, early recruitment may be diagnostic
Critical illness Reduced CMAP and SNAP Reduced sensory potentials may be
polyneuropathy amplitudes, decreased recruitment, due to ankle edema or underlying
fibrillation potentials, positive systemic illness, such as diabetes
sharp waves mellitus; phrenic nerve stimulation
abnormalities are diagnostic
Myasthenia gravis or Reduced CMAP amplitude, Higher diagnostic yield with proximal
prolonged NMBA decremental response with muscles than with distal muscles,
effect 3-Hz repetitive stimulation higher yield with facial stimulator
Acute polyradiculopathy Prolonged distal latency, reduced Absence of blink responses and
(GBS or CIDP) motor velocities, conduction block prolonged F-wave latency may be
diagnostic
Motor neuron disease Polyphasic waveforms with late Typical asymmetrical distributions,
components, poor recruitment, early abnormal phrenic nerve CMAP
widespread fibrillation and diaphragm denervation
potentials, normal SNAP
CIDP, chronic inflammatory demyelinating polyneuropathy; CMAP, compound muscle action potential; EMG, electromyography; GBS,
Guillain-Barré syndrome; MG, myasthenia gravis; NCV, nerve conduction velocity; NMBA, neuromuscular blocking agent; SNAP, sensory
nerve action potential.
16 Part I Criteria, Urgency, and Importance
only in inflammatory polyneuropathies and thus
may be helpful in ambiguous cases. F-wave
responses may also be useful if they document
delayed responses disproportionate to abnor-
malities in nerve conduction, suggesting abnor-
mal conduction in the proximal segments of
peripheral motor nerves.
PRACTICAL ADVICE
We can conclude that “participatory” and
“well-informed” are two adjectives that ideally
sum up the neurologist’s demeanor in the ICU
while pondering over the presenting problem.
• Consultations in the medical and surgical
ICUs can be divided into separate catego-
ries, each with different complexity. Failure
to awaken, acute agitation, new focal find-
ings, a movement disorder, seizure, and
severe muscle weakness are reasons to con-
sult a neurologist. These consults—by their
nature—require immediate attention and
prompt evaluation.
• Treatment could decrease morbidity
(e.g., drainage of an epidural abscess in
a febrile patient, early treatment of sei-
zures in immunosuppression-associated
neurotoxicity).
• The impact of these consults on outcome in
the current ICU environment remains to be
studied prospectively.
REFERENCES
1. Bleck TP. Neurological disorders in the intensive care
unit. Semin Respir Crit Care Med. Jun 2006;27(3):201–
9. doi:10.1055/s-2006-945531
2. Gustafson OD, Williams MA, McKechnie S, Dawes
H, Rowland MJ. Musculoskeletal complications fol-
lowing critical illness: A scoping review. J Crit Care.
Dec 2021;66:60–66. doi:10.1016/j.jcrc.2021.08.002
3. Howard RS. Neurological problems on the ICU. Clin
Med (Lond). Apr 2007;7(2):148–53. doi:10.7861/
clinmedicine.7-2.148
4. Mittal MK, Kashyap R, Herasevich V, Rabinstein
AA, Wijdicks EF. Do patients in a medical or surgi-
cal ICU benefit from a neurologic consultation?
Int J Neurosci. 2015;125(7):512–20. doi:10.3109/
00207454.2014.950374
5. Pizzi M, Ng L. Neurologic complications of solid organ
transplantation. Neurol Clin. Nov 2017;35(4):809–23.
doi:10.1016/j.ncl.2017.06.013
6. Sanap MN, Worthley LI. Neurologic complications of
critical illness. Part II: Polyneuropathies and myopa-
thies. Crit Care Resusc. Jun 2002;4(2):133–40.
7. Sanap MN, Worthley LI. Neurologic complications of
critical illness. Part I: Altered states of consciousness
and metabolic encephalopathies. Crit Care Resusc.
Jun 2002;4(2):119–32.
8. Wijdicks EF. Why you may need a neurologist to
see a comatose patient in the ICU. Crit Care. Jun
2016;20(1):193. doi:10.1186/s13054-016-1372.8
9. Wijdicks EF. The scope of neurology of critical illness.
Handb Clin Neurol. 2017;141:443–7. doi:10.1016/
B978-0-444-63599-0.00024-7
10. Wijdicks EF. The neurologic consultation:
Pointers and takeaways for intensivists. Intensive
Care Med. Jun 2020;46(6):1267–70. doi:10.1007/
s00134-020-06055-w
11. Wijdicks EF. Identifying encephalopathies from
acute metabolic derangements. J Intern Med. 2022
Dec;292(6):846-857.
PART II

General Clinical Neurologic

Problems in the Intensive
Care Unit
Chapter 3
Acute Confusional State in the
Intensive Care Unit
TERMINOLOGY
INITIAL ASSESSMENT OF DELIRIUM
Patients who are confused and less responsive
may, in comparison to the unconscious patient,
appear less concerning. Patients in a confusional
state may not respond quickly, rarely fixate on
objects, and cannot understand simple tasks
or nursing requests. Some can speak; others
are unable to voice anything intelligible. Some
exhibit extremely wild behaviors; others are
more subdued when hallucinating. Delirium
has several similarly disturbed components
(arousal, language, perception, orientation,
mood, sleep), which make clinical classification
difficult. Restlessness can be associated with
pallor, sweating, tachycardia, and wide pupils.
Most patients are hyper-aroused, with incoher-
ent, rambling speech, and little comprehensible
verbal output. Orientation to time is impaired
first, followed by place.
Management of delirium may increase length
of stay, often due to related complications (e.g.,
aspiration), and these could be iatrogenic (over-
sedation).2–5 Agitated or delirious patients are
NEUROLOGIC EXAMINATION OF THE
ACUTELY CONFUSED PATIENT
MANAGEMENT
frequently seen after a major surgical procedure,
and cardiac surgery with long extracorporeal cir-
culation times is a notorious cause.6–8 Delirium
often occurs in patients with Parkinson’s disease
undergoing surgery.9 Recently, unusually high
dose requirements for sedation, analgesics, and
neuromuscular blockade have been reported in
patients with SARS-CoV-2 (COVID-19; see
Chapter 12), and the treatment of resulting
delirium contributed to prolonged mechanical
ventilation and delayed awakening.
Consults are triggered when agitation
becomes uncontrollable. The liaison psychiatrist
is asked to assist with adjustments to treatment
and to consider long-term care, the neurologist
is asked to exclude serious structural neurologic
disease, and both are asked to suggest medica-
tion. Consulting neurologists may continue to
assist in management.
Delirium can accompany acute neurologic
disease: for example, a lesion in the limbic
cortex or frontal regions or in the caudate
19
20 Part II General Clinical Neurologic Problems
nucleus may cause severe agitation (but also
periods of extreme quietness) because of
interruption of connecting fibers to the frontal
lobes. But although DSM-5 criteria for delir-
ium include numerous other acute neurologic
conditions, most cases of delirium in medical
or surgical ICUs are not a result of a new struc-
tural injury.
Acute confusional state and delirium
commonly affect elderly patients, who may
be notably susceptible because of an underly-
ing (and not previously recognized) dementia.
In these instances, family members confirm a
gradual decline in performance and produc-
tivity before being admitted for other reasons.
Taking the time to explore the patient’s prior
functioning with family often reveals earlier
episodes of disconcerting behavior in demand-
ing circumstances. Delirium of the elderly in
intensive care settings might be more common
than appreciated, and recent studies have found
that it may occur in up to 50% of ICU patients;
this figure increases to 80% when patients are
on a mechanical ventilator. ICU delirium sub-
stantially impacts costs and is directly related to
protracted ICU stay for management.
We must distinguish delirium from acute ill-
ness or withdrawal from prior used alcohol or
illicit drugs, although our clinical ability to dis-
cern differences remains provisional. This chap-
ter summarizes the evolving terminology and
management of delirium in the ICU.
TERMINOLOGY
For centuries, delirium was a settled diagnosis,
but there was an interest in renaming the disor-
der. “Clouding of consciousness” was used in the
DSM–III. “Delirium” returned later. In DSM-5,
delirium is defined as “disturbance of conscious-
ness with reduced ability to focus, sustain, or shift
attention. Dementia must be excluded as a reason
to explain change in cognition or perceptual dis-
turbance. The disorder develops over time, and
there must be evidence that delirium is caused
by medical disorder.” For most neurologists,
“delirium” was seen as a hyper-alert state with
hyperactive autonomic nervous system and total
disorientation. A hypo-alert state would be clas-
sified as “encephalopathy.” Later, this workable
terminology was followed by many synonyms
and then a more recent serious attempt to
reduce the number of designations of types of
delirium to simply hyperactive, hypoactive,
and mixed. Others have added subsyndromal
delirium, a state between no delirium and
clinical delirium.10,11 The proposed definition of
hypoactive delirium describes a patient charac-
terized by reduced attention and a paucity of
movement, as opposed to hyperactive delirium,
which is characterized by increased attention and
agility and an exaggerated response to a simple
stimulus. Some have inaccurately suggested this
state be called catatonic retardation.12 Mixed
forms are a combination of hypoactive and hyper-
active delirium. Studies have found hyperactive
delirium to be far less common than hypoactive
delirium or a mixed form. Others have suggested
the term “delirium disorder,” but this new term
does not further clarify the disorder.13
In the ICU, hypoactive delirium is the most
difficult to detect, and unless a validated screen-
ing tool is developed and tested, it will remain
one of the most problematic designations for
any neurologist. It is difficult to determine
how much obtundation or how little respon-
siveness qualifies as hypoactive delirium. Any
drowsy patient lacks concentration and atten-
tion and is unable to think clearly. The term
“encephalopathy” may not be ideal but is much
better understood than “hypoactive delirium.”
Moreover, and more importantly, introducing
the word “delirium” may dramatically increase
the prevalence and perhaps lead to unneces-
sary treatment.
Phenotypes, subphenotypes, and even endo-
types are being introduced.11 Recently, clini-
cal phenotypes of delirium were defined as
hypoxic, septic, sedative-associated, or meta-
bolic (renal or liver dysfunction) delirium, add-
ing further to the melee of terminology.10,11
Generally, terminology evolves with further
understanding of the disorder at hand; the over-
whelming concern here is that with attempts at
new terminology and poorly defined boundar-
ies, this is not the case. This new terminology
has received little approbation from neurolo-
gists. Throughout history, delirium was linked
with agitation. In fact, the word “delirium”
derives from the Latin delirio- or delirare,
which means to deviate from a straight line, to
be crazy, deranged, out of one’s wits, to dote, to
rave. There is nothing silent about it.
Thus, we can only conclude that the current
terminology of delirium is equivocal. Once we
change the terminology and accept “quiet delir-
ium” (or its halfway station term “subsyndromic
delirium”), we struggle to distinguish it from
 3 Acute Confusional State 21

acute encephalopathy, and neurologists may ASSESSMENT OF DELIRIUM

feel forced to integrate it into yet another term
such as “delirium disorder.” As with any poorly
understood disorder and unclassifiable patho-
physiology, there is a range of opinions. But to
simplify matters and to develop a practical plan
of action, here we call it “delirium” if there is
agitation or another manifestation of bewilder-
ment, and we call it “acute encephalopathy” in
other cases. We must, however, acknowledge
that we have little understanding of the patho-
physiologic mechanisms of the acute confu-
sional state and delirium (Box 3.1).
Consults are rarely introduced as delirium.
The more typical phrase is “altered mental sta-
tus,” and it quickly becomes clear that there
is ongoing delirium. If we take acute agitation
as a starting point, we can look at a number of
diagnostic possibilities and initial approaches
for management (Figure 3.1).
In the overwhelming proportion of cases,
either critical illness or ICU pharmacology is a
major factor.19 Commonly used drugs that can
cause or worsen delirium are benzodiazepines,

Box 3.1 Pathophysiologic Mechanisms of Delirium

The pathogenesis of the acute confused state that we call “delirium” is unknown.
We have identified risk factors, which could provide a window into neuronal dys-
function and functional disconnection, but we cannot escape the conclusion that
there is little understanding, striking differences of interpretation, and excessive
speculation. The bottom line is that a solid framework does not exist. For years,
there was a search for structural changes in delirium tremens—the archetype of
delirium—and nothing was found. Some studies have shown that ethanol selec-
tively inhibits N-methyl-D-aspartate (NMDA) receptors that transmit the excit-
atory effects of the neurotransmitter glutamate. The depressive effect of alcohol on
NMDA receptors (NMDARs) results in compensatory up-regulation of these recep-
tors and consequent brain hyperexcitability that emerges upon the withdrawal of
alcohol.14–16
The known association between cognitive disorders and delirium has created
interest in pathways of cholinergic deficiency that have been associated with
several types of dementias. When examined as potential pathogenesis of delirium,
again nothing definitive is found. Virtually all neurotransmitters (and combina-
tions) have been implicated, and this has led to the modern idea of pharmacologic
manipulation (e.g., dopamine antagonists, acetylcholinerase inhibitors, and mela-
tonin substitution). Cholinergic deficiency is one emerging pathway to treatment
when delirium is associated with sepsis syndrome.17 There are other associations
between peripheral levels of insulin-like growth factor-1 (IGF-1), C-reactive pro-
tein (C-RP), interleukin-6 (IL-6), and postoperative delirium.18 Their significance is
unknown.
There is a clear understanding that these patients have a major global brain dys-
function, but many decades of research have not improved our understanding of
the pathophysiologic processes or the transient effect of a major illness on neuronal
circuitry. Truthfully, there is only indirect evidence implicating neurotransmitters,
based on the fact that certain drugs improve agitation either through stimulation or
toning down of these neurotransmitters. Examples are (1) quetiapine or olanzapine
and serotonin; (2) dexmedetomidine and noradrenaline; (3) propofol, ketamine,
and NMDA; and (4) haloperidol and dopamine. Also, because critical illness in
trauma or sepsis is associated with inflammation, cytokine signal substances like
IL-1 or IL-6 and tumor necrosis factor could potentially cross the blood–brain bar-
rier or enter elsewhere to cause microglial dysfunction.
22 Part II General Clinical Neurologic Problems

Figure 3.1. Algorithm for evaluation and management of agitation in the intensive care unit.
D/C, discontinue.

opioids, corticosteroids, aluminum-containing how to ameliorate the manifestation of delir-

antacids, beta-adrenergic blockers, tacrolimus, ium by removing these triggers.
cyclosporin, and histamine-receptor antagonists Postoperative delirium may occur in 25–50%
with high doses administered (Table 3.1). of elderly patients, frequently in orthopedic sur-
Prediction of delirium, contrary to what gery patients or with use of anticholinergics and
might be claimed, is not robust, and most barbiturates as anesthetic drugs.20 Postoperative
physicians can only categorize patients as pain may be a factor causing delirium, and pain
being in high- or low-vulnerability categories may increase the risk of delirium by early dis-
(Figure 3.2). There may be so many different turbance of the sleep–wake cycle. There is no
risk factors in the ICU that it becomes irrel- conclusive evidence for a significant association
evant to sort out which one predominates and of hypoxemia or hypocapnia with delirium.
Delirium after organ transplantation is most
related to cyclosporine or tacrolimus neuro-
toxicity and occurs in 20–30% of transplant
Table 3.1 Categories of drugs
associated with delirium
Adrenocorticosteroids Opioid agonistsa
α-Adrenergic agonists Penicillins
α-Adrenergic blockers Phenothiazines
Aluminum-containing Quinolone
antacidsa antibiotics
Aminoglycoside antibiotics Sulfonamides
β-Adrenergic blockersa Tacrolimusa
Benzodiazepinesa Tetracyclines
Butyrophenones Thiazide diuretics
Calcium-channel blockers Tricyclic and
Cephalosporins tetracyclic
Cyclosporinea antidepressants
Digoxine
Histamine receptor
antagonistsa
a
If delirium is present, administration of these drugs
should be discontinued first. Figure 3.2. Predisposing factors in delirium.

recipients. Delirium is more common in patients
who undergo a liver transplant for alcoholic dis-
ease. Alcohol withdrawal does not offer a good
explanation for this because serum alcohol lev-
els measured before transplant are normal in
these patients if they have been in a rehabilita-
tion program, and transplant surgeons require
sobriety. The pathogenesis of delirium requires
further study because agitation may jeopardize
safety through dislodgment of lines.
Delirium is more commonly associated with
cardiac surgery and intra-aortic balloon-pump
procedures and may occur in one-third of
these patients. However, incidence studies of
delirium after cardiac surgery are complicated,
and results are probably not reliable because of
small sample size, changing classification over
time, and heterogeneous patient diagnosis.
NEUROLOGIC EXAMINATION OF
THE ACUTELY CONFUSED PATIENT
Acute confusional state and delirium are
conceptually related but differ in severity.
Neurologic examination of cognition in ICU
patients is frustrating and often fragmentary.
Only patients with mild manifestations can give
reliable responses to the test questions. Acute
confusional states, however, can be graded by
testing recall (e.g., naming three unrelated
objects: “apple” “Mr. Johnson,” “tunnel”), atten-
tion (repeating a series of digits, telephone num-
ber), or calculation (counting down from 100 by
subtracting 7). Writing and reading a complete
sentence, copying a cube, and following complex
commands (e.g., take this paper, fold it in half,
and put it to the left of your body) test agraphia,
apraxia, and alexia as more specific neurobehav-
ioral disorders.
In any newly confused or delirious patient,
clues may suggest a structural lesion rather
than more common physiologic brain dysfunc-
tion. These may include neglect of the left side,
hemiparesis, and denial of blindness.
These confusional states are more typically
characterized by impairment of all mental
faculties and a condition of “being out of
touch” with surroundings. Thus, attention
and memory, logical thinking, orientation, and
mathematical skills are abnormal, with a cha-
otic perception of surroundings. The capacity
to recall parts of the day, procedures, discus-
sions with physicians, and visits by family is
3 Acute Confusional State 23
lost, and patients often look bewildered at their
restraints. Patients may yell and swear and are
generally noisy; they will try to get out of bed or
move into a diagonal position in bed dangling
their legs over the edge. Coherent conversation
is not possible, and directions are not followed.
Although sleep hygiene in ICUs is typically
fragmented, sleep-and-wake patterns for these
patients are disturbed and random. Snoring
during the day becomes excessive from seda-
tive drugs administered the night before for
nocturnal agitation.
As alluded to earlier, patients with a critical ill-
ness are at high risk for delirium, and triggers or
predisposing factors are consistent throughout
studies. These include advanced age, dementia,
Parkinson’s disease, surgery, fever, infections
(particularly in the urinary tract), visual impair-
ment, polypharmacy, and use of psychoactive
drugs. There are also risk factors induced by
critical illness. These include hypoxemia, acute
electrolyte imbalances, congestive heart failure,
sepsis, any acute infection, hyperthermia, and
the development of a new neurologic illness
such as an ischemic stroke or infection.
It is important to distinguish between
alcohol-related delirium and other causes, not
only because the manifestations might be dif-
ferent but also because there might be differ-
ent therapeutic approaches. Alcohol-related
delirium is characterized by profound percep-
tual disturbances, hallucinations. and tremor
(tremens). The level of awareness fluctuates, and
systemic manifestations emerge. Hallucinations
can be vivid and frightening.
Warning signs of delirium tremens have been
identified (Table 3.2). Delirium tremens poses
complex management issues and typically
begins on the third or fourth day after a patient
stops drinking alcohol. Delirium tremens is
characterized by involuntary tugging at sheets,
picking at imaginary objects, intensified tremor,
and severe confusion, often accompanied by
Table 3.2 Warning signs with delirium
tremens
Pulse ≥120/min
Systolic blood pressure >180 mm Hg
Respirations >30/min or <10/min
Temperature >38.5°C
Seizures
Difficult to arouse
Increasing use of benzodiazepines
24 Part II General Clinical Neurologic Problems

agitation and (typically visual) hallucinations MANAGEMENT OF DELIRIUM

or tactile tachycardia, sweating, and hyperten-
sive episodes. Extremely severe manifestations
are surprisingly uncommon (with estimates of
5% of patients withdrawing from alcohol), but
they are potentially life-threatening, especially
in critically ill patients. The syndrome typically
lasts for 5 days once it has begun, and duration
is probably not affected by treatment.
Identification of delirium has been stan-
dardized by the CAM–ICU score (Table 3.3)
used by nursing staff to alert physicians and
administer medication when certain thresh-
olds are reached. Concerns about its reliability
remains including how sedative infusions affect
nurses’ ability to evaluate delirium.3
Looking at the predictive factors of acute agita-
tion and delirium (Figure 3.2), one could argue
in favor of correcting these triggers. Although
delirium may be prevented by simple mea-
sures in already low-risk patients (Table 3.4),
it is unclear if the same measures will temper
delirium in critically ill patients. Most patients
will need multi-pharmacotherapy.
Management of patients with acute confusion
and delirium requires knowledge of the effects
of certain sedative drugs. It is common practice
to withdraw anticholinergic drugs such as meto-
clopramide, H2 blockers, promethazine, and
diphenhydramine.

Table 3.3 Confusion Assessment Method for the Intensive Care Unit
(CAM-ICU)
Feature 1: Acute Onset or Fluctuating Course: Positive if you answer “yes” to either 1A or 1B.
1A: Is the patient different from his/her baseline mental status?
1B: Has the patient had any fluctuation in mental status in the past 24 hr as evidenced by fluctuation on
a sedation scale (e.g., RASS), GCS, or previous delirium assessment?
Feature 2: Inattention: Positive if either score for 2A or 2B is <8. Attempt the ASE letters first. If
patient can perform this test and the score is clear, record this score and move to Feature 3. If patient is
unable to perform this test or the score is unclear, then perform the ASE Pictures. If you perform both
tests, use the ASE Pictures’ results to score the Feature.
2A: ASE Letters: Record score (enter NT for not tested). Directions: Say to the patient, “I am going
to read you a series of 10 letters. Whenever you hear the letter ‘A’, indicate by squeezing my hand.”
Read letters from the following letter list in a normal tone. S A V E A H A A R T Scoring: Errors are
counted when patient fails to squeeze on the letter “A” and when the patient squeezes on any letter
other than “A.”
Score 2A (score out of 10)
2B: ASE Pictures: Record score (enter NT for not tested). Directions are included on the picture
packets.
Score 2 B (score out of 10)
Feature 3: Disorganized Thinking. Positive if the combined score is <4.
3A: Yes/No Questions (Use either Set A or Set B, alternate on consecutive days if necessary):
Set A Set B
1. Will a stone float on water? 1. Will a leaf float on water?
2. Are there fish in the sea? 2. Are there elephants in the sea?
3. Does one pound weigh more than 3. Do two pounds weigh more than
two pounds? one pound?
4. Can you use a hammer to pound a nail? 4. Can you use a hammer to cut wood?
Score____ (Patient earns 1 point for each correct answer out of 4)
3B: Command: Say to patient: Hold up this many fingers.” (Examiner holds two fingers in front of
patient.)
“Now do the same thing with the other hand.” (Not repeating the number of fingers.) *If patient
is unable to move both arms, for the second part of the command, ask patient, “Add one more
finger.”
Score____ (Patient earns 1 point if able to successfully complete the entire command)
Combined Score (3A + 3B):______ (out of 5)
Feature 4: Altered Level of Consciousness: Positive if the Actual RASS score is anything other than
“0” (zero)
Overall CAM-ICU: (Features 1 and 2 and either Feature 3 or 4 = CAM-ICU positive)

Table 3.4 Non-pharmacologic
measures to reduce delirium
prevalence
Early physical and occupational therapy
Sleep enhancement (reduction of light and noise)
Music therapy
Improved daylight exposure
Single-room ICU
Minimize disruptions to sleep
Hearing and vision aids for those with impairments
Pain control
Avoid physical restraints when able
Reorientation to environment
None of these intuitive measures are proven efficacious.
If a rapid effect is desired, IV lorazepam
is infused at 0.01–0.1 mg/kg/h intravenously.
Midazolam may be used at 0.02 mg/kg/h to ini-
tiate therapy.21 There is a consensus to avoid
benzodiazepines unless there is an alcohol-
withdrawal delirium or withdrawal from benzo-
diazepines. The evidence that benzodiazepines
are a risk factor for delirium is strong.
Haloperidol has been traditionally used.
Haloperidol is administered intravenously at
an initial dose of 0.5–1.0 mg for mildly agi-
tated patients and 5–10 mg for those who are
severely agitated. Onset of action is 30 min via
IV. If the patient’s condition remains unstable,
the initial dose is doubled every 30 min until
control is established. Once control of agita-
tion is achieved with the loading dose, 50% of
the total loading dose is given as a maintenance
dose divided into 6- to 8-hr intervals. Titration
is to the lowest dose that controls symptoms. IV
administration and higher doses carry a greater
risk of QTc prolongation and torsades de pointe.
Dosages need to be significantly decreased in
the elderly and in those with hepatic failure. A
recent prospective clinical trial found no better
outcome in treated patients and questionable
effectiveness. (Nearly all patients needed rescue
treatment.)22
Atypical antipsychotic drugs such as risperi-
done, olanzapine, or quetiapine, which show
anecdotal evidence of a good effect, can be
used but may take 2 hr for effect. We have far
more often used 5-10 mg IV olanzapine (up to
30 mg daily), which has a rapid effect and low
rates (<3%) of respiratory depression. There
is a lower risk of QTc prolongation compared
with haloperidol. A consensus found 100 mg of
quetiapine in divided doses up to 200 mg orally
every 12 hr for a maximum 10 days to be very
3 Acute Confusional State 25
helpful in patients with underlying dementia
and postoperative agitation. At a low dose of 1.7
mg/d, on average, risperidone is effective in the
majority of patients.
Dexmedetomidine has also emerged as a very
effective drug23 when loaded with 1 μg/kg IV
followed by continuous infusion starting at
0.2–0. 7 μg/kg. Unfortunately, hypotension and
bradycardia are common. Another effective agent
for the treatment of alcohol withdrawal syn-
drome is phenobarbital24 at 130 mg IV every
15 min until the patient’s symptoms are con-
trolled, not exceeding 15 mg/kg in the first day.
PRACTICAL ADVICE
What is it like to be delirious? We do not know
because patients do not know, and they can-
not recall much in detail.1 All they know is
what they have been told they did. They do not
remember a delirious state because they do not
register (awareness) and do not store memo-
ries, pointing to a major brain dysfunction most
certainly provoked by the amnestic properties
of anesthetic drugs. We do not understand
what underlies this global brain dysfunction.
Clinicians have expressed concern regarding a
possible association of delirium with long-term
cognitive impairment and dementia. This asso-
ciation may not be causal, and it is not known
if more aggressive treatment will reduce the
risk of later cognitive impairment. Recent stud-
ies found that acceleration of cognitive decline
is seen with any hospitalization in predisposed
patients.25–27 The decline is more pronounced
after nonelective compared to elective hospi-
talizations and after hospitalizations for medical
compared to surgical indications. Therefore, we
cannot exclude the possibility that patients who
experience delirium already had undiagnosed
cognitive impairment made worse following
treatment in the ICU. The main takeaways for
the clinician are:
• Drowsiness is not hypoactive delirium.
• Delirium has become a blanket term for what
most neurologists consider encephalopathy.
• Agitated delirium requires multiple treatment
approaches.
• ICU tools to recognize delirium for nursing
staff are available and questionably helpful.
• IV medication first; other measures (restraints,
reduced noise and visits) later.
26 Part II General Clinical Neurologic Problems
• IV dexmedetomidine is quickly becoming a
standard treatment.
• Olanzapine, risperidone, quetiapine, haloper-
idol, phenobarbital, and valproate acid28–30 are
good options.
This approach in assessment and management is
currently the most reasonable advice. It remains
to be seen if the pathogenesis of delirium can be
better understood.
REFERENCES
1. Wijdicks EFM, Rabinstein AA. What is it like to be
delirious? Neurocrit Care. 2022 Aug;37(1):1–5.
2. Ely EW, Gautam S, Margolin R, et al. The impact of
delirium in the intensive care unit on hospital length of
stay. Intensive Care Med. Dec 2001;27(12):1892–900.
doi:10.1007/s00134-001-1132-2
3. Ely EW, Margolin R, Francis J, et al. Evaluation of
delirium in critically ill patients: Validation of the
Confusion Assessment Method for the Intensive Care
Unit (CAM-ICU). Crit Care Med. Jul 2001;29(7):1370–
9. doi:10.1097/00003246-200107000-00012
4. Pandharipande P, Cotton BA, Shintani A, et al. Prevalence
and risk factors for development of delirium in surgical
and trauma intensive care unit patients. J Trauma. Jul
2008;65(1):34–41. doi:10.1097/TA.0b013e31814b2c4d
5. Pun BT, Ely EW. The importance of diagnosing and
managing ICU delirium. Chest. Aug 2007;132(2):624–
36. doi:10.1378/chest.06-1795
6. Dyer CB, Ashton CM, Teasdale TA. Postoperative
delirium: A review of 80 primary data-collection
studies. Arch Intern Med. Mar 1995;155(5):461–5.
doi:10.1001/archinte.155.5.461
7. Parikh SS, Chung F. Postoperative delirium in the
elderly. Anesth Analg. Jun 1995;80(6):1223–32.
doi:10.1097/00000539-199506000-00027
8. Robinson TN, Eiseman B. Postoperative delirium in
the elderly: Diagnosis and management. Clin Interv
Aging. 2008;3(2):351–5. doi:10.2147/cia.s2759
9. Golden WE, Lavender RC, Metzer WS. Acute post-
operative confusion and hallucinations in Parkinson
disease. Ann Intern Med. Aug 1989;111(3):218–22.
doi:10.7326/0003-4819-111-3-218
10. Stollings JL, Kotfis K, Chanques G, Pun BT,
Pandharipande PP, Ely EW. Delirium in critical ill-
ness: Clinical manifestations, outcomes, and manage-
ment. Intensive Care Med. Oct 2021;47(10):1089–103.
doi:10.1007/s00134-021-06503-1
11. Bowman EML, Cunningham EL, Page VJ, McAuley
DF. Phenotypes and subphenotypes of delirium: A
review of current categorisations and suggestions for
progression. Crit Care. Sep 2021;25(1):334. doi:10.1186/
s13054-021-03752-w
12. Maldonado JR. Acute brain failure: Pathophysiology,
diagnosis, management, and sequelae of delirium.
Crit Care Clin. Jul 2017;33(3):461–519. doi:10.1016/
j.ccc.2017.03.013
13. Oldham MA, Holloway RG. Delirium disorder:
Integrating delirium and acute encephalopathy.
Neurology. Jul 2020;95(4):173–8. doi:10.1212/
WNL.0000000000009949
14. Wijdicks EFM. The discovery of acute alcohol with-
drawal as a cause of delirium. Neurocrit Care. Mar
2021:1–4.doi:10.1007/s12028-021-01196-2
15. Nagy J. Alcohol related changes in regulation of NMDA
receptor functions. Curr Neuropharmacol. Mar
2008;6(1):39–54. doi:10.2174/157015908783769662
16. Lovinger DM, White G, Weight FF. Ethanol inhibits
NMDA-activated ion current in hippocampal neurons.
Science. Mar 1989;243(4899):1721–4. doi:10.1126/
science.2467382
17. Adamis D, van Gool WA, Eikelenboom P. Consistent
patterns in the inconsistent associations of Insulin-like
growth factor 1 (IGF-1), C-reactive protein (C-RP)
and interleukin 6 (IL-6) levels with delirium in surgi-
cal populations: A systematic review and meta-analysis.
Arch Gerontol Geriatr. 2021;97:104518. doi:10.1016/
j.archger.2021.104518
18. Noah AM, Almghairbi D, Evley R, Moppett IK. Pre-
operative inflammatory mediators and postoperative delir-
ium: Systematic review and meta-analysis. Br J Anaesth.
Sep 2021;127(3):424–34. doi:10.1016/j.bja.2021.04.033
19. Brown TM. Drug-induced delirium. Semin Clin
Neuropsychiatry. Apr 2000;5(2):113–24. doi:10.153/
SCNP00500113
20. Hughes CG, Boncyk CS, Culley DJ, et al. American
Society for Enhanced Recovery and Perioperative Quality
Initiative Joint Consensus Statement on postoperative
delirium prevention. Anesth Analg. Jun 2020;130(6):
1572–90. doi:10.1213/ANE.0000000000004641
21. Wijdicks EFM, Clark SL. Neurocritical Care
Pharmacotherapy: A Clinician’s Manual. 1st ed.
Oxford University Press; 2018.
22. Andersen-Ranberg NC, Poulsen LM, Perner A, et al.
Haloperidol for the treatment of delirium in ICU
patients. N Engl J Med. Dec 2022;387(26):2425–35.
doi:10.1056/NEJMoa2211868
23. Pandharipande PP, Sanders RD, Girard TD, et al.
Effect of dexmedetomidine versus lorazepam on out-
come in patients with sepsis: An a priori-designed anal-
ysis of the MENDS randomized controlled trial. Crit
Care. 2010;14(2):R38. doi:10.1186/cc8916
24. Oks M, Cleven KL, Healy L, et al. The safety and utility
of phenobarbital use for the treatment of severe alco-
hol withdrawal syndrome in the medical intensive care
unit. J Intensive Care Med. Sep 2020;35(9):844–50.
doi:10.1177/0885066618783947
25. James BD, Wilson RS, Capuano AW, et al. Cognitive
decline after elective and nonelective hospitalizations
in older adults. Neurology. Feb 2019;92(7):e690–9.
doi:10.1212/WNL.0000000000006918
26. Schulte PJ, Warner DO, Martin DP, et al. Association
between critical care admissions and cognitive trajectories
in older adults. Crit Care Med. Aug 2019;47(8):1116–24.
doi:10.1097/CCM.0000000000003829
27. Sprung J, Knopman DS, Petersen RC, et al.
Association of hospitalization with long-term cogni-
tive trajectories in older adults. J Am Geriatr Soc.
Mar 2021;69(3):660–8. doi:10.1111/jgs.16909
28. Quinn NJ, Hohlfelder B, Wanek MR, et al. Prescribing
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ium in the Intensive Care Unit. Ann Pharmacother.
2021;55(3):311–17.
29. Herman JA, Urman RD, Urits I, Kaye AD, Viswanath
O. The effect of a dexmedetomidine infusion on delir-
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30. Tiberio PJ, Prendergast NT, Girard TD. Pharmacologic
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Clin Chest Med. 2022 Sep;43(3):411–24.
Chapter 4
Coma and Other States of Altered
Awareness in the Intensive Care Unit
DEFINITIONS OF ALTERED STATES OF
CONSCIOUSNESS
NEUROLOGIC EXAMINATION OF THE
COMATOSE PATIENT
Critically ill patients are hardly ever sharp;
their attention tends to fade away, and they
may fall wearily asleep. The ability to stay
awake diminishes with a downward spiral in
organ function, and this precarious wake-
fulness may become even more affected by
sedative drugs. Impaired consciousness, not
to mention acute confusion and delirium,
emerges when the CNS becomes part of a
critical illness. The brain of a patient could
become permanently injured after enduring an
overwhelming systemic infection complicated
by marginal oxygenation and blood pressures
trending downward. The CNS can also sustain
damage from trauma, environmental injury, or
an intricate surgical procedure.
In this chapter, I discuss the clinical diagno-
sis of altered states of consciousness in critical
illness, but I also juxtapose coma with other
types of acute disturbances of consciousness
(excluding delirium, which was discussed in
CAUSES OF COMA
NEUROLOGIC EXAMINATION IN
BRAIN DEATH
the previous chapter). This chapter mainly
focuses on classification and recognition. The
first course of action is to determine whether
the patient is comatose from a lesion causing
mass effect in one hemisphere, in both hemi-
spheres, or in the posterior fossa. Next is to
determine whether structural brain injury, sei-
zures, a toxin, or acute metabolic or endocrine
derangement are responsible for persistent loss
of consciousness.
DEFINITIONS OF ALTERED STATES
OF CONSCIOUSNESS
Normal consciousness implies being awake and
aware of self and environment. It requires an
arousal stimulus (ascending reticular forma-
tion in the upper brainstem) and intact con-
tent, coherence of thought, and mental activity
27
28 Part II General Clinical Neurologic Problems
(cerebral hemispheres).1,2 Arousal disturbances
lead to diminished alertness. Content distur-
bances lead to diminished awareness and
inattention, disorientation, and lack of integra-
tion of perception and processing memory. In a
sense, altered arousal involves an altered state of
awareness, and these two components are inter-
related but sometimes dissociated. One can be
awake and aware, awake but not aware, or not
awake and not aware.
Consciousness is traditionally dichotomized
into two components in a conceptually useful
approach. The content of consciousness includes
all cognitive functions, emotions, and intuitions
of the brain. The level of consciousness refers
to global alertness and behavioral responsivity.
Several key anatomical structures control the
conscious state: the ascending reticular activat-
ing system (ARAS) in the midbrain and upper
pons, the diencephalon (thalamus and hypo-
thalamus), anterior cingulate cortex, associa-
tion cortices (precuneus and cuneus), and the
cortex proper (Figure 4.1). The neurochemistry
driving this complex system consists of several
important neurotransmitters: norepinephrine
(originating from the locus ceruleus and pontine
Figure 4.1. Brain regions critically involved in generating
and maintaining cortical activation and the waking state.
These areas, maximally active during waking, include the
ascending reticular activating system (ARAS) of the dorsal
brainstem, the midline-medial and intralaminar thalamo-
cortical projection system, and the basal forebrain.
lateral tegmentum), dopamine (ventral tegmen-
tum), serotonin (raphe nuclei), acetylcholine
(basal forebrain), histamine (posterior hypo-
thalamus), and orexin-hypocretin (lateral hypo-
thalamus). As the target of all incoming signals,
the thalamus is central in governing conscious-
ness and relays and gates information diffusely
to brain networks.
Major mechanisms of coma involve destruc-
tive lesions of the thalamus or diffuse connec-
tions to the cortex or ARAS. These structures
can be directly damaged or injured by com-
pression or shifts, and the changes often alter
consciousness permanently. More selective
lesions involving a unilateral hemisphere or
thalamus will not substantially impair long-term
consciousness.
It is often difficult to determine the state of
awareness in critically ill patients. They may
look about, seem distracted and detached, fidget
constantly, and fail to focus on anything until
they catch sight of the doctor or nurse entering
the room.
The impact of sedation on the state of
awareness of the critically ill patient varies
substantially. In some patients, a dreamlike
state exists, with temporary awakening occur-
ring during pain-causing procedures. Many
pharmacologic sedating agents produce a
calming effect, but some patients may feel
“closed in” when blanketed with sedative
agents, or they may lack any urge to signal
discomfort or fear. Some patients may experi-
ence invasive procedures as painless manip-
ulations, prodding, or sticking, which may
explain the patient’s easy compliance with the
attending staff; in other patients, because of
the perception of impending pain, any close
contact causes agitation.
It is practically useful to subject these patients
to neurologic scrutiny and to distinguish differ-
ent categories of unconsciousness and mimick-
ers. The disorders of consciousness are listed
here to facilitate conversations between neu-
rologists and intensivists in day-to-day practice.
Locked-in syndrome is a rare condition,
and patients have a normal awareness but
complete body paralysis except for voluntary
vertical eye movements. Structural lesions in
the base of the pons spare the pathways to
the oculomotor nuclei in the mesencepha-
lon, so that patients continue to communicate
through vertical eye movements and blinking.
They cannot move their limbs, grimace, or
 4 Coma and Other States of Altered Awareness
swallow. Hearing is intact, but later vocalizing
is not possible through a capped tracheostomy
cannula. The medulla oblongata is spared.
Central chemoreceptors in the ventral surface
of the medulla are intact, and thus there is nor-
mal respiratory drive. Consciousness may still
be reduced when the tegmentum or thalamus
(e.g., with a top of the basilar artery occlusion)
is involved. Variants of this classic syndrome
are common, with patients retaining some
motor movements and later regaining ability
to speak. Locked-in syndrome should be dif-
ferentiated from paralysis of all muscle (and
eye) movement by paralytic agents.
Hypersomnia is an increase in sleeping time
with normal sleep patterns, a situation often
caused by sleep deprivation, metabolites of
sedative drugs, or acute hepatic or renal failure.
Acute brainstem lesions involving the tegmen-
tum or bilateral lesions of the paramedian dorsal
thalamus may also dampen arousal.
Coma is a state of unresponsiveness in which
the patient lies with eyes closed and cannot be
aroused to stimuli. Self-awareness is absent. At
best, there is only eye opening to pain, or eyes
are open with no tracking or fixation. Brainstem
reflexes can be intact or variably absent.
Movements are pathologic motor responses
(decorticate or decerebrate) or no response at
all. In most patients, it is a transient state, recov-
ering into a minimally conscious state and better.
However, a devastating injury (often anoxic-
ischemic insult) causes persistent coma.3–6
Minimally conscious state (MCS) has been
identified as a separate category and is best
placed between severe disability and persistent
vegetative state (PVS). The boundaries of this
condition remain difficult to define, but currently
it is understood as patients who open eyes after
prodding, track a finger, or reach for an object
but with no higher level of communication,
intellectual thinking, or recall of prior events,
even simple ones.7 Verbalization of syllables
or brief sentences may occur. Responses are
very slow, inconsistent, and often unreliable.8
The long-term outcome of patients in a MCS—
often a result of major brain injury—is not
exactly known. Some rehabilitation physicians
have subclassified MCS into MCS with lan-
guage (MCS+) or without language (MCS−).
Additionally, functional MRI-based categoriza-
tion has revealed a patient subset fulfilling all
PVS criteria but showing command-following
response on functional MRI (cognitive motor
29
dissociation or CMD). Another patient sub-
set, higher-order cortex-motor dissociation
(HMD), exhibits cortical response to auditory
stimuli, again without evident awareness. (The
clinical relevance of these fMRI subsets are yet
unknown.)
Persistent vegetative state. The appearance
of intensive care units (ICUs) and mechanical
ventilation has allowed patients with devastating
brain injuries to survive. While deeply coma-
tose during the acute phase, some patients
transition to a different clinical state in which
they regain awake-and-sleep cycles but remain
unaware of their surroundings. This clini-
cal syndrome—named “persistent vegetative
state” in the early 1970s—describes patients
with no evidence of a functioning mind. This
state has also been referred to as “unrespon-
siveness wakefulness syndrome” because of
the alleged negative connotation of the word
“vegetative,” but this term is no improvement
and more confusing to family members.9 After
prolonged coma, patients begin to have periods
of spontaneous eye-opening but do not visually
fixate or track objects with their eyes and may
gradually emerge from coma due to exten-
sive injury to the brain. This complete lack
of awareness becomes associated with sleep–
wake cycles and opening of the eyes but with-
out any expression or recognition of external
stimuli. There are often roving eye movements
with nystagmoid jerks. Visual tracking to shown
objects is absent. Brainstem function, including
respiratory drive, is largely preserved, and the
damage is in multiple cortical areas. Injury may
be predominantly in both thalami, interrupting
the thalamocortical circuits. The diagnosis of
PVS is rarely made with certainty in the ICU,
and several weeks of close observation on the
ward are needed before even considering the
diagnosis. The condition is considered irrevers-
ible after a year in such a state, and recovery to
awareness is exceptional.
Brain death is a term used for irreversible loss
of all clinical brainstem function. The diagnosis is
based on a set of strict clinical criteria and signifies
the patient has died. After excluding confound-
ers, this implies documentation of permanently
lost consciousness, no motor response to pain
stimuli, absent brainstem reflexes, and absent
respiratory drive after the respiratory centers are
maximally stimulated with a CO2 challenge.10
The pathophysiologic mechanisms of altered
consciousness are discussed in Box 4.1.
30 Part II General Clinical Neurologic Problems

Box 4.1 Pathophysiologic Mechanisms of Coma

The different clinical states of unconsciousness relate to different defects in neuro-
nal networks underlying consciousness, and some specific patterns are emerging.
Connections between thalamus, frontal cortex (particularly cingulate cortex), parietal
cortex (cuneus and precuneus cortex), and, ultimately, the brainstem play an important
role and, when damaged, result in abnormal awareness and wakefulness (Figure 4.1).2
The processes that govern normal consciousness are only partly understood.
More recent insight has emerged because of functional MRI and positron emission
tomography (PET) studies.2 One of the critical anatomical parts has been defined
under the term “ascending reticular activating system.” This system, located in the
rostral brainstem, targets the thalamus, which, in turn, disperses connections to
the cortex and vice versa, creating the thalamic–cortical circuitry.11 One column
of the system projects to the medial thalamic nuclei, interlaminar nuclei, and
ventromedial nuclei; another column remains ventral and courses through the
lateral hypothalamus to reach the basal forebrain neurons, which in turn modulate
cortical activity as well.11
The function discharged by the ascending reticular activating system is
arousal. Another major system, the limbic system, contributes not to arousal
but to mood, affect, motivation, and memory. Amnestic syndromes are mostly
a consequence of involvement of the hippocampus, an important component
that projects to the mamillary body and anterior thalamic nucleus.
Arousal is determined not only by intact connections but also by neuro-
transmitters (Figure 4.2). Excitatory glutaminergic neurons of the reticular formation
project to the nonspecific thalamocortical systems. The reticular retinal nucleus of
the thalamus may be a key component in gating interchange and in regulating
sleep–wake cycles and depth of sleep.12 The reticular retinal nucleus also contains
a large amount of inhibitory γ-aminobutyric acid (GABA) that can be recruited
to further modulate neuronal traffic and control excitability. Noradrenergic neu-
rons also modulate arousal. These cells are in the locus ceruleus, a small group
of pigmented cells localized in the lateral part of the upper pons. The role of this
structure is currently thought to be enhancement of vigilance, particularly with
unexpected stimuli. If damaged, it prevents the development of rapid eye move-
ment (REM) sleep and reduces total sleep time. Other monoamines, such as sero-
tonin and histamine, originating from raphe nuclei in the median brainstem and
from the hypothalamus, enhance wakefulness through ascending projections to
the thalamus, basal forebrain, and cortex.
The cholinergic system projects from the dorsal pontomesencephalic tegmentum
to subcortical relays and from the basal forebrain to the cerebral cortex. Its func-
tion is not only to enhance attention but also to retain recent memories and create
REM sleep.
This model, albeit oversimplified, can explain disorders of consciousness dis-
cussed in other chapters of this book. For example, benzodiazepines, barbitu-
rates, and propofol specifically enhance GABA activity and lower excitation,
inducing drowsiness, sleep, and coma. Benzodiazepines act on endogenous
receptors in the cortex and midbrain and on opioid target receptors throughout
the brain. In hepatic encephalopathy, GABA-mediated inhibition has been sug-
gested as a mechanism, as well as down-regulation of glutamate N-methyl-D-
aspartate receptors, both of which disrupt a sensible balance of excitation and
inhibition.
(continued)
Another random document with
no related content on Scribd:
end, last of all, came that intolerable old tun of sack and godless
ruffler, Sir John Oldcastle (now risen from the dead for the third
time), fat-faced, purple with the spirit of bygone and lamented drink,
smiling his hospitable, wide smile upon all the world, leering at the
women, wallowing about in his saddle, proclaiming his valorous
deeds as fast as he could lie, taking the whole glory of Agincourt to
his single self, measuring off the miles of his slain and then
multiplying them by 5, 7, 10, 15, as inspiration after inspiration came
to his help--the most inhuman spectacle in England, a living,
breathing outrage, a slander upon the human race; and after him
came, mumming and blethering, his infamous lieutenants; and after
them his “paladins,” as he calls them, the mangiest lot of starvelings
and cowards that was ever littered, the disgrace of the noblest
pageant that England has ever seen. God rest their souls in the
place appointed for all such!
There was a moment of prayer at the Temple, the procession
moved down the country road, its way walled on both sides by
welcoming multitudes, and so, by Charing Cross, and at last to the
Abbey for the great ceremonies. It was a grand day, and will remain
in men’s memories.

That was as much of it as the spirit correspondent could let me

have; he was obliged to stop there because he had an engagement
to sing in the choir, and was already late.
The contrast between that old England and the present England is
one of the things which will make the pageant of the present day
impressive and thought-breeding. The contrast between the England
of the Queen’s reign and the England of any previous British reign is
also an impressive thing. British history is two thousand years old,
and yet in a good many ways the world has moved further ahead
since the Queen was born than it moved in all the rest of the two
thousand put together. A large part of this progress has been moral,
but naturally the material part of it is the most striking and the easiest
to measure. Since the Queen first saw the light she has seen
invented and brought into use (with the exception of the cotton gin,
the spinning frames, and the steamboat) every one of the myriad of
strictly modern inventions which, by their united powers, have
created the bulk of the modern civilization and made life under it
easy and difficult, convenient and awkward, happy and horrible,
soothing and irritating, grand and trivial, an indispensable blessing
and an unimaginable curse--she has seen all these miracles, these
wonders, these marvels piled up in her time, and yet she is but
seventy-eight years old. That is to say, she has seen more things
invented than any other monarch that ever lived; and more than the
oldest old-time English commoner that ever lived, including Old Parr;
and more than Methuselah himself--five times over.
Some of the details of the moral advancement which she has seen
are also very striking and easily graspable.
She has seen the English criminal laws prodigiously modified, and
200 capital crimes swept from the statute book.
She has seen English liberty greatly broadened--the governing
and lawmaking powers, formerly the possession of the few, extended
to the body of the people, and purchase in the army abolished.
She has seen the public educator--the newspaper--created, and
its teachings placed within the reach of the leanest purse. There was
nothing properly describable as a newspaper until long after she was
born.
She has seen the world’s literature set free, through the institution
of international copyright.
She has seen America invent arbitration, the eventual substitute
for that enslaver of nations, the standing army; and she has seen
England pay the first bill under it, and America shirk the second--but
only temporarily; of this we may be sure.
She has seen a Hartford American (Doctor Wells) apply
anæsthetics in surgery for the first time in history, and for all time
banish the terrors of the surgeon’s knife; and she has seen the rest
of the world ignore the discoverer and a Boston doctor steal the
credit of his work.
She has seen medical science and scientific sanitation cut down
the death rate of civilized cities by more than half, and she has seen
these agencies set bounds to the European march of the cholera
and imprison the Black Death in its own home.
 She has seen woman freed from the oppression of many
burdensome and unjust laws; colleges established for her; privileged
to earn degrees in men’s colleges--but not get them; in some regions
rights accorded to her which lifted her near to political equality with
man, and a hundred bread-winning occupations found for her where
hardly one existed before--among them medicine, the law, and
professional nursing. The Queen has herself recognized merit in her
sex; of the 501 lordships which she has conferred in sixty years, one
was upon a woman.
The Queen has seen the right to organize trade unions extended
to the workman, after that right had been the monopoly of guilds of
masters for six hundred years.
She has seen the workman rise into political notice, then into
political force, then (in some parts of the world) into the chief and
commanding political force; she has seen the day’s labor of twelve,
fourteen, and eighteen hours reduced to eight, a reform which has
made labor a means of extending life instead of a means of
committing salaried suicide.
But it is useless to continue the list--it has no end.
There will be complexions in the procession to-day which will
suggest the vast distances to which the British dominion has
extended itself around the fat rotundity of the globe since Britain was
a remote unknown back settlement of savages with tin for sale, two
or three thousand years ago; and also how great a part of this
extension is comparatively recent; also, how surprisingly speakers of
the English tongue have increased within the Queen’s time.
When the Queen was born there were not more than 25,000,000
English-speaking people in the world; there are about 120,000,000
now. The other long-reign queen, Elizabeth, ruled over a short
100,000 square miles of territory and perhaps 5,000,000 subjects;
Victoria reigns over more territory than any other sovereign in the
world’s history ever reigned over; her estate covers a fourth part of
the habitable area of the globe, and her subjects number about
400,000,000.
It is indeed a mighty estate, and I perceive now that the English
are mentioned in the Bible:
“Blessed are the meek, for they shall inherit the earth.”
 The Long-Reign Pageant will be a memorable thing to see, for it
stands for the grandeur of England, and is full of suggestion as to
how it had its beginning and what have been the forces that have
built it up.
I got to my seat in the Strand just in time--five minutes past ten--for
a glance around before the show began. The houses opposite, as far
as the eye could reach in both directions, suggested boxes in a
theater snugly packed. The gentleman next to me likened the groups
to beds of flowers, and said he had never seen such a massed and
multitudinous array of bright colors and fine clothes.
These displays rose up and up, story by story, all balconies and
windows being packed, and also the battlements stretching along the
roofs. The sidewalks were filled with standing people, but were not
uncomfortably crowded. They were fenced from the roadway by red-
coated soldiers, a double stripe of vivid color which extended
throughout the six miles which the procession would traverse.
Five minutes later the head of the column came into view and was
presently filing by, led by Captain Ames, the tallest man in the British
army. And then the cheering began. It took me but a little while to
determine that this procession could not be described. There was
going to be too much of it, and too much variety in it, so I gave up
the idea. It was to be a spectacle for the kodak, not the pen.
Presently the procession was without visible beginning or end, but
stretched to the limit of sight in both directions--bodies of soldiery in
blue, followed by a block of soldiers in buff, then a block of red, a
block of buff, a block of yellow, and so on, an interminable drift of
swaying and swinging splotches of strong color sparkling and
flashing with shifty light reflected from bayonets, lance heads, brazen
helmets, and burnished breastplates. For varied and beautiful
uniforms and unceasing surprises in the way of new and unexpected
splendors, it much surpassed any pageant that I have ever seen.
I was not dreaming of so stunning a show. All the nations seemed
to be filing by. They all seemed to be represented. It was a sort of
allegorical suggestion of the Last Day, and some who live to see that
day will probably recall this one if they are not too much disturbed in
mind at the time.
 There were five bodies of Oriental soldiers of five different
nationalities, with complexions differentiated by five distinct shades
of yellow. There were about a dozen bodies of black soldiers from
various parts of Africa, whose complexions covered as many shades
of black, and some of these were the very blackest people I have
ever seen yet.
Then there was an exhaustive exhibition of the hundred separate
brown races of India, the most beautiful and satisfying of all the
complexions that have been vouchsafed to man, and the one which
best sets off colored clothes and best harmonizes with all tints.
The Chinese, the Japanese, the Koreans, the Africans, the
Indians, the Pacific Islanders--they were all there, and with them
samples of all the whites that inhabit the wide reach of the Queen’s
dominions.
The procession was the human race on exhibition, a spectacle
curious and interesting and worth traveling far to see. The most
splendid of the costumes were those worn by the Indian princes, and
they were also the most beautiful and richest. They were men of
stately build and princely carriage, and wherever they passed the
applause burst forth.
Soldiers, soldiers, soldiers, and still more and more soldiers and
cannon and muskets and lances--there seemed to be no end to this
feature. There are 50,000 soldiers in London, and they all seemed to
be on hand. I have not seen so many except in the theater, when
thirty-five privates and a general march across the stage and behind
the scenes and across the front again and keep it up till they have
represented 300,000.
In the early part of the procession the colonial premiers drove by,
and by and by after a long time there was a grand output of foreign
princes, thirty-one in the invoice.
The feature of high romance was not wanting, for among them
rode Prince Rupert of Bavaria, who would be Prince of Wales now
and future king of England and emperor of India if his Stuart
ancestors had conducted their royal affairs more wisely than they
did. He came as a peaceful guest to represent his mother, Princess
Ludwig, heiress of the house of Stuart, to whom English Jacobites
still pay unavailing homage as the rightful queen of England.
 The house of Stuart was formally and officially shelved nearly two
centuries ago, but the microbe of Jacobite loyalty is a thing which is
not exterminable by time, force, or argument.
At last, when the procession had been on view an hour and a half,
carriages began to appear. In the first came a detachment of two-
horse ones containing ambassadors extraordinary, in one of them
Whitelaw Reid, representing the United States; then six containing
minor foreign and domestic princes and princesses; then five four-
horse carriages freighted with offshoots of the family.
The excitement was growing now; interest was rising toward the
boiling point. Finally a landau driven by eight cream-colored horses,
most lavishly upholstered in gold stuffs, with postilions and no
drivers, and preceded by Lord Wolseley, came bowling along,
followed by the Prince of Wales, and all the world rose to its feet and
uncovered.
The Queen Empress was come. She was received with great
enthusiasm. It was realizable that she was the procession herself;
that all the rest of it was mere embroidery; that in her the public saw
the British Empire itself. She was a symbol, an allegory of England’s
grandeur and the might of the British name.
It is over now; the British Empire has marched past under review
and inspection. The procession stood for sixty years of progress and
accumulation, moral, material, and political. It was made up rather of
the beneficiaries of these prosperities than of the creators of them.
As far as mere glory goes, the foreign trade of Great Britain has
grown in a wonderful way since the Queen ascended the throne.
Last year it reached the enormous figure of £620,000,000, but the
capitalist, the manufacturer, the merchant, and the workingmen were
not officially in the procession to get their large share of the resulting
glory.
Great Britain has added to her real estate an average of 165 miles
of territory per day for the past sixty years, which is to say she has
added more than the bulk of an England proper per year, or an
aggregate of seventy Englands in the sixty years.
But Cecil Rhodes was not in the procession; the Chartered
Company was absent from it. Nobody was there to collect his share
of the glory due for his formidable contributions to the imperial
estate. Even Doctor Jameson was out, and yet he had tried so hard
to accumulate territory.
Eleven colonial premiers were in the procession, but the dean of
the order, the imperial Premier, was not, nor the Lord Chief Justice of
England, nor the Speaker of the House. The bulk of the religious
strength of England dissent was not officially represented in the
religious ceremonials. At the Cathedral that immense new industry,
speculative expansion, was not represented unless the pathetic
shade of Barnato rode invisible in the pageant.
It was a memorable display and must live in history. It suggested
the material glories of the reign finely and adequately. The absence
of the chief creators of them was perhaps not a serious
disadvantage. One could supply the vacancies by imagination, and
thus fill out the procession very effectively. One can enjoy a rainbow
without necessarily forgetting the forces that made it.
LETTERS TO SATAN
(1897)
 SWISS GLIMPSES
I
If Your Grace would prepay your postage it would be a pleasant
change. I am not meaning to speak harshly, but only sorrowfully. My
remark applies to all my outland correspondents, and to everybody’s.
None of them puts on the full postage, and that is just the same as
putting on none at all: the foreign governments ignore the half
postage, and we who are abroad have to pay full postage on those
half-paid letters. And as for writing on thin paper, none of my friends
ever think of it; they all use pasteboard, or sole leather, or things like
that. But enough of that subject; it is painful.
I believe you have set me a hard task; for if it is true that you have
not been in the world for three hundred years, and have not received
into your establishment an educated person in all that time, I shall be
obliged to talk to you as if you had just been born and knew nothing
at all about the things I speak of. However, I will do the best I can,
and will faithfully try to put in all the particulars, trivial ones as well as
the other sorts. If my report shall induce Your Grace to come out of
your age-long seclusion and make a pleasure tour through the world
in person, instead of doing it by proxy through me, I shall feel that I
have labored to good purpose. You have many friends in the world;
more than you think. You would have a vast welcome in Paris,
London, New York, Chicago, Washington, and the other capitals of
the world; if you would go on the lecture platform you could charge
what you pleased. You would be the most formidable attraction on
the planet. The curiosity to see you would be so great that no place
of amusement would contain the multitude that would come. In
London many devoted people who have seen the Prince of Wales
only fifteen hundred or two thousand times would be willing to miss
one chance of seeing him again for the sake of seeing you. In Paris,
even with the Tsar on view, you could do a fairly good business; and
in Chicago--Oh, but you ought to go to Chicago, you know. But
further of this anon. I will to my report, now, and tell you about
Lucerne, and how I journeyed hither; for doubtless you will travel by
the same route when you come.
I kept house a few months in London, with my family, while I
arranged the matters which you were good enough to intrust me
with. There were no adventures, except that we saw the Jubilee.
Afterward I was invited to one of the Queen’s functions, which was a
royal garden party. A garden is a green and bloomy countrified
stretch of land which--But you remember the Garden of Eden; well, it
is like that. The invitation prescribed the costume that must be worn:
“Morning dress with trousers.” I was intending to wear mine, for I
always wear something at garden parties where ladies are to be
present; but I was hurt by this arbitrary note of compulsion, and did
not go. All the European courts are particular about dress, and you
are not allowed to choose for yourself in any case; you are always
told exactly what you must wear; and whether it is going to become
you or not, you are not allowed to make any changes. Yet the court
taste is often bad, and sometimes even indelicate. I was once invited
to dine with an emperor when I was living awhile in Germany, and
the invitation card named the dress I must wear: “Frock coat and
black cravat.” To put it in English, that meant swallow-tail and black
cravat. It was cold weather, too, the middle of winter; and not only
that, but ladies were to be present. That was five years ago. By this
time the coat has gone out, I suppose, and you would feel at home
there if you still remember the old Eden styles.
As soon as the Jubilee was fairly over we broke up housekeeping
and went for a few days to what is called in England “an hotel.” If we
could have afforded an horse and an hackney cab we could have
had an heavenly good time flitting around on our preparation
errands, and could have finished them up briskly; but the buses are
slow and they wasted many precious hours for us. A bus is a sort of
great cage on four wheels, and is six times as strong and eleven
times as heavy as the service required of it demands--but that is the
English of it. The bus aptly symbolizes the national character. The
Englishman requires that everything about him shall be stable,
strong, and permanent, except the house which he builds to rent. His
own private house is as strong as a fort. The rod which holds up the
lace curtains could hold up an hippopotamus. The three-foot flagstaff
on his bus, which supports a Union Jack the size of a handkerchief,
would still support it if it were one of the gates of Gaza. Everything
he constructs is a deal heavier and stronger than it needs to be. He
built ten miles of terraced benches to view the Jubilee procession
from, and put timber enough in them to make them a permanent
contribution to the solidities of the world--yet they were intended for
only two days’ service.
When they were being removed an American said, “Don’t do it--
save them for the Resurrection.” If anything gets in the way of the
Englishman’s bus it must get out of it or be bowled down--and that is
English. It is the serene self-sufficient spirit which has carried his flag
so far. He ought to put his aggressive bus in his coat of arms, and
take the gentle unicorn out.
We made our preparations for Switzerland as fast as we could;
then bought the tickets. Bought them of Thomas Cook & Sons, of
course--nowadays shortened to “Cook’s,” to save time and words.
Things have changed in thirty years. I can remember when to be a
“Cook’s tourist” was a thing to be ashamed of, and when everybody
felt privileged to make fun of Cook’s “personally conducted” gangs of
economical provincials. But that has all gone by, now. All sorts and
conditions of men fly to Cook in our days. In the bygone times travel
in Europe was made hateful and humiliating by the wanton
difficulties, hindrances, annoyances, and vexations put upon it by
ignorant, stupid, and disobliging transportation officials, and one had
to travel with a courier or risk going mad. You could not buy a railway
ticket on one day which you purposed to use next day--it was not
permitted. You could not buy a ticket for any train until fifteen minutes
before that train was due to leave. Though you had twenty trunks,
you must manage somehow to get them weighed and the extra
weight paid for within that fifteen minutes; if the time was not
sufficient you would have to leave behind such trunks as failed to
pass the scales. If you missed your train, your ticket was no longer
good. As a rule, you could make neither head nor tail of the railway
guide, and if your intended journey was a long one you would find
that the officials could tell you little about which way to go;
consequently you often bought the wrong ticket and got yourself lost.
But Cook has remedied all these things and made travel simple,
easy, and a pleasure. He will sell you a ticket to any place on the
globe, or all the places, and give you all the time you need, and as
much more besides; and it is good for all trains of its class, and its
baggage is weighable at all hours. It provides hotels for you
everywhere, if you so desire; and you cannot be overcharged, for the
coupons show just how much you must pay. Cook’s servants at the
great stations will attend to your baggage, get you a cab, tell you
how much to pay cabmen and porters, procure guides for you, or
horses, donkeys, camels, bicycles, or anything else you want, and
make life a comfort and a satisfaction to you. And if you get tired of
traveling and want to stop, Cook will take back the remains of your
ticket, with 10 per cent off. Cook is your banker everywhere, and his
establishment your shelter when you get caught out in the rain. His
clerks will answer all the questions you ask, and do it courteously. I
recommend Your Grace to travel on Cook’s tickets when you come;
and I do this without embarrassment, for I get no commission. I do
not know Cook. (But if you would rather travel with a courier, let me
recommend Joseph Very. I employed him twenty years ago, and
spoke of him very highly in a book, for he was an excellent courier--
then. I employed him again, six or seven years ago--for a while. Try
him. And when you go home, take him with you.)
That London hotel was a disappointment. It was up a back alley,
and we supposed it would be cheap. But, no, it was built for the
moneyed races. It was all costliness and show. It had a brass band
for dinner--and little else--and it even had a telephone and a lift. A
telephone is a wire stretched on poles or underground, and has a
thing at each end of it. These things are to speak into and to listen
at. The wire carries the words; it can carry them several hundred
miles. It is a time-saving, profanity-breeding, useful invention, and in
America is to be found in all houses except parsonages. It is dear in
America, but cheap in England; yet in England telephones are as
rare as are icebergs in your place. I know of no way to account for
this; I only know that it is extraordinary. The English take kindly to the
other modern conveniences, but for some puzzling reason or other
they will not use the telephone. There are 44,000,000 people there
who have never even seen one.
 The lift is an elevator. Like the telephone, it also is an American
invention. Its office is to hoist people to the upper stories and save
them the fatigue and delay of climbing. That London hotel could
accommodate several hundred people, and it had just one lift--a lift
which would hold four persons. In America such an hotel would have
from two to six lifts. When I was last in Paris, three years ago, they
were using there what they thought was a lift. It held two persons,
and traveled at such a slow gait that a spectator could not tell which
way it was going. If the passengers were going to the sixth floor, they
took along something to eat; and at night, bedding. Old people did
not use it; except such as were on their way to the good place,
anyhow. Often people that had been lost for days were found in
those lifts, jogging along, jogging along, frequently still alive. The
French took great pride in their ostensible lift, and called it by a
grand name--ascenseur. An hotel that had a lift did not keep it
secret, but advertised it in immense letters, “Il y a une ascenseur,”
with three exclamation points after it.
In that London hotel--But never mind that hotel; it was a cruelly
expensive and tawdry and ill-conditioned place, and I wish I could do
it a damage. I will think up a way some time. We went to Queenboro
by the railroad. A railroad is a--well, a railroad is a railroad. I will
describe it more explicitly another time.
Then we went by steamer to Flushing--eight hours. If you sit at
home you can make the trip in less time, because then you can
travel by the steamer company’s advertisement, and that will take
you across the Channel five hours quicker than their boats can do it.
Almost everywhere in Europe the advertisements can give the facts
several hours’ odd in the twenty-four and get in first.
II
We tarried overnight at a summer hotel on the seashore near
Flushing--the Grand Hôtel des Bains. The word Grand means
nothing in this connection; it has no descriptive value. On the
Continent, all hotels, inns, taverns, hash houses and slop troughs
employ it. It is tiresome. This one was a good-enough hotel, and
comfortable, but there was nothing grand about it but the bill, and
even that was not extravagant enough to make the title entirely
justifiable. Except in the case of one item--Scotch whisky. I ordered a
sup of that, for I always take it at night as a preventive of toothache. I
have never had the toothache; and what is more, I never intend to
have it. They charged me a dollar and a half for it. A dollar and a half
for half a pint; a dollar and a half for that wee little mite--really hardly
enough to break a pledge with. It will be a kindness to me if Your
Grace will show the landlord some special attentions when he
arrives. Not merely on account of that piece of extortion, but because
he got us back to town and the station next day, more than an hour
before train time.
There were no books or newspapers for sale there, and nothing to
look at but a map. Fortunately it was an interesting one. It was a
railway map of the Low Countries, and was of a new sort to me, for it
was made of tiles--the ground white, the lines black. It could be
washed if it got soiled, and if no accident happens to it it will last ten
thousand years and still be as bright and fine and new and beautiful
then as it is to-day. It occupied a great area of the wall, and one
could study it in comfort halfway across the house. It would be a
valuable thing if our own railway companies would adorn their
waiting rooms with maps like that.
We left at five in the afternoon. The Dutch road was admirably
rough; we went bumping and bouncing and swaying and sprawling
along in a most vindictive and disorderly way; then passed the
frontier into Germany, and straightway quieted down and went
gliding as smoothly through the landscape as if we had been on
runners. We reached Cologne after midnight.
But this letter is already too long. I will close it by saying that I was
charmed with England and sorry to leave it. It is easy to do business
there. I carried out all of Your Grace’s instructions, and did it without
difficulty. I doubted if it was needful to grease Mr. Cecil Rhodes’s
palm any further, for I think he would serve you just for the love of it;
still, I obeyed your orders in the matter. I made him Permanent
General Agent for South Africa, got him and his South Africa
Company whitewashed by the Committee of Inquiry, and promised
him a dukedom. I also continued the European Concert in office,
without making any change in its material. In my opinion this is the
best material for the purpose that exists outside of Your Grace’s own
personal Cabinet. It coddles the Sultan, it has defiled and degraded
Greece, it has massacred a hundred thousand Christians in Armenia
and a splendid multitude of them in Turkey, and has covered
civilization and the Christian name with imperishable shame. If Your
Grace would instruct me to add the Concert to the list of your publicly
acknowledged servants, I think it would have a good effect. The
Foreign Offices of the whole European world are now under your
sovereignty, and little attentions like this would keep them so.
 A WORD OF ENCOURAGEMENT FOR OUR

BLUSHING EXILES | (1898)

... Well, what do you think of our country now? And what do you
think of the figure she is cutting before the eyes of the world? For
one, I am ashamed--(Extract from a long and heated letter from a
Voluntary Exile, Member of the American Colony, Paris.)

And so you are ashamed. I am trying to think out what it can have
been that has produced this large attitude of mind and this fine flow
of sarcasm. Apparently you are ashamed to look Europe in the face;
ashamed of the American name; temporarily ashamed of your
nationality. By the light of remarks made to me by an American here
in Vienna, I judge that you are ashamed because:
1. We are meddling where we have no business and no right;
meddling with the private family matters of a sister nation; intruding
upon her sacred right to do as she pleases with her own,
unquestioned by anybody.
2. We are doing this under a sham humanitarian pretext.
3. Doing it in order to filch Cuba, the formal and distinct disclaimer
in the ultimatum being very, very thin humbug, and easily detectable
as such by you and virtuous Europe.
4. And finally you are ashamed of all this because it is new, and
base, and brutal, and dishonest; and because Europe, having had
no previous experience of such things, is horrified by it and can
never respect us nor associate with us any more.
Brutal, base, dishonest? We? Land thieves? Shedders of innocent
blood? We? Traitors to our official word? We? Are we going to lose
Europe’s respect because of this new and dreadful conduct?
Russia’s, for instance? Is she lying stretched out on her back in
Manchuria, with her head among her Siberian prisons and her feet in
Port Arthur, trying to read over the fairy tales she told Lord Salisbury,
and not able to do it for crying because we are maneuvering to
treacherously smouch Cuba from feeble Spain, and because we are
ungently shedding innocent Spanish blood?
Is it France’s respect that we are going to lose? Is our unchivalric
conduct troubling a nation which exists to-day because a brave
young girl saved it when its poltroons had lost it--a nation which
deserted her as one man when her day of peril came? Is our
treacherous assault upon a weak people distressing a nation which
contributed Bartholomew’s Day to human history? Is our ruthless
spirit offending the sensibilities of the nation which gave us the Reign
of Terror to read about? Is our unmanly intrusion into the private
affairs of a sister nation shocking the feelings of the people who sent
Maximilian to Mexico? Are our shabby and pusillanimous ways
outraging the fastidious people who have sent an innocent man
(Dreyfus) to a living hell, taken to their embraces the slimy guilty one,
and submitted to a thousand indignities Emile Zola--the manliest
man in France?
Is it Spain’s respect that we are going to lose? Is she sitting sadly
conning her great history and contrasting it with our meddling, cruel,
perfidious one--our shameful history of foreign robberies,
humanitarian shams, and annihilations of weak and unoffending
nations? Is she remembering with pride how she sent Columbus
home in chains; how she sent half of the harmless West Indians into
slavery and the rest to the grave, leaving not one alive; how she
robbed and slaughtered the Inca’s gentle race, then beguiled the
Inca into her power with fair promises and burned him at the stake;
how she drenched the New World in blood, and earned and got the
name of The Nation with the Bloody Footprint; how she drove all the
Jews out of Spain in a day, allowing them to sell their property, but
forbidding them to carry any money out of the country; how she
roasted heretics by the thousands and thousands in her public
squares, generation after generation, her kings and her priests
looking on as at a holiday show; how her Holy Inquisition imported
hell into the earth; how she was the first to institute it and the last to
give it up--and then only under compulsion; how, with a spirit
unmodified by time, she still tortures her prisoners to-day; how, with
her ancient passion for pain and blood unchanged, she still crowds
the arena with ladies and gentlemen and priests to see with delight a
bull harried and persecuted and a gored horse dragging his entrails
on the ground; and how, with this incredible character surviving all
attempts to civilize it, her Duke of Alva rises again in the person of
General Weyler--to-day the most idolized personage in Spain--and
we see a hundred thousand women and children shut up in pens
and pitilessly starved to death?
Are we indeed going to lose Spain’s respect? Is there no way to
avoid this calamity--or this compliment? Are we going to lose her
respect because we have made a promise in our ultimatum which
she thinks we shall break? And meantime is she trying to recall
some promise of her own which she has kept?
Is the Professional Official Fibber of Europe really troubled with
our morals? Dear Parisian friend, are you taking seriously the daily
remark of the newspaper and the orator about “this noble nation with
an illustrious history”? That is mere kindness, mere charity for a
people in temporary hard luck. The newspaper and the orator do not
mean it. They wink when they say it.
And so you are ashamed. Do not be ashamed; there is no
occasion for it.
 DUELING
(Vienna, Austria, 1898)

T his pastime is as common in Austria to-day as it is in France. But

with this difference--that here in the Austrian states the duel is
dangerous, while in France it is not. Here it is tragedy, in France it is
comedy; here it is a solemnity, there it is monkeyshines; here the
duelist risks his life, there he does not even risk his shirt. Here he
fights with pistol or saber, in France with a hairpin--a blunt one. Here
the desperately wounded man tries to walk to the hospital; there they
paint the scratch so that they can find it again, lay the sufferer on a
stretcher, and conduct him off the field with a band of music.
At the end of a French duel the pair hug and kiss and cry, and
praise each other’s valor; then the surgeons make an examination
and pick out the scratched one, and the other one helps him on to
the litter and pays his fare; and in return the scratched one treats to
champagne and oysters in the evening, and then “the incident is
closed,” as the French say. It is all polite, and gracious, and pretty,
and impressive. At the end of an Austrian duel the antagonist that is
alive gravely offers his hand to the other man, utters some phrases
of courteous regret, then bids him good-by and goes his way, and
that incident also is closed. The French duelist is painstakingly
protected from danger, by the rules of the game. His antagonist’s
weapon cannot reach so far as his body; if he gets a scratch it will
not be above his elbow. But in Austria the rules of the game do not
provide against danger, they carefully provide for it, usually.
Commonly the combat must be kept up until one of the men is
disabled; a nondisabling slash or stab does not retire him.
For a matter of three months I watched the Viennese journals, and
whenever a duel was reported in their telegraphic columns I scrap-
booked it. By this record I find that dueling in Austria is not confined
to journalists and old maids, as in France, but is indulged in by
military men, journalists, students, physicians, lawyers, members of
the legislature, and even the Cabinet, the bench, and the police.
Dueling is forbidden by law; and so it seems odd to see the makers
and administrators of the laws dancing on their work in this way.
Some months ago Count Badeni, at that time chief of the
government, fought a pistol duel here in the capital city of the Empire
with Representative Wolf, and both of those distinguished Christians
came near getting turned out of the Church--for the Church as well
as the state forbids dueling.
In one case, lately, in Hungary, the police interfered and stopped a
duel after the first innings. This was a saber duel between the chief
of police and the city attorney. Unkind things were said about it by
the newspapers. They said the police remembered their duty
uncommonly well when their own officials were the parties
concerned in duels. But I think the underlings showed bread-and-
butter judgment. If their superiors had carved each other well, the
public would have asked, “Where were the police?” and their place
would have been endangered; but custom does not require them to
be around where mere unofficial citizens are explaining a thing with
sabers.
There was another duel--a double duel--going on in the immediate
neighborhood at the time, and in this case the police obeyed custom
and did not disturb it. Their bread and butter was not at stake there.
In this duel a physician fought a couple of surgeons, and wounded
both--one of them lightly, the other seriously. An undertaker wanted
to keep people from interfering, but that was quite natural again.
Selecting at random from my record, I next find a duel at Tranopol
between military men. An officer of the Tenth Dragoons charged an
officer of the Ninth Dragoons with an offense against the laws of the
card table. There was a defect or a doubt somewhere in the matter,
and this had to be examined and passed upon by a court of honor.
So the case was sent up to Lemberg for this purpose. One would like
to know what the defect was, but the newspaper does not say. A
man here who has fought many duels and has a graveyard says that
probably the matter in question was as to whether the accusation