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MAYO CLINIC CRITICAL
AND NEUROCRITICAL
CARE BOARD REVIEW
EDITED BY

Eelco F. M. Wijdicks, MD, PhD

Chair, Division of Critical Care Neurology
Mayo Clinic, Rochester, Minnesota
Professor of Neurology
Mayo Clinic College of Medicine and Science

James Y. Findlay, MB, ChB

Consultant, Department of Anesthesiology and
Perioperative Medicine
Mayo Clinic, Rochester, Minnesota
Associate Professor of Anesthesiology
Mayo Clinic College of Medicine and Science

William D. Freeman, MD
Consultant, Departments of Critical Care Medicine,
Neurology, and Neurosurgery
Mayo Clinic, Jacksonville, Florida
Professor of Neurology and of Neurosurgery
Mayo Clinic College of Medicine and Science

Ayan Sen, MD
Chair, Department of Critical Care Medicine
Mayo Clinic Hospital, Phoenix, Arizona
Assistant Professor of Emergency Medicine and of Medicine
Mayo Clinic College of Medicine and Science

MAYO CLINIC SCIENTIFIC PRESS OXFORD UNIVERSITY PRESS

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Library of Congress Cataloging-in-Publication Data

Names: Wijdicks, Eelco F. M., 1954– editor. | Findlay, James Y., editor. |
Freeman, William D., editor. | Sen, Ayan.
Title: Mayo Clinic critical and neurocritical care board review / [edited by] Eelco F. M. Wijdicks,
James Y. Findlay, William D. Freeman, Ayan Sen.
Other titles: Critical and neurocritical care board review
Description: New York, NY : Oxford University Press, 2019. |
Includes bibliographical references and index.
Identifiers: LCCN 2019005581| ISBN 9780190862923 (pbk.) | ISBN 9780190862930 (updf) |
ISBN 9780190862947 (epub) | ISBN 9780190862954 (on-line)
Subjects: | MESH: Critical Care | Study Guide
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LC record available at https://lccn.loc.gov/2019005581

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 Preface
Physicians have cared for patients with acute illnesses
throughout history. The terminology related to these
patients has changed. Sick patients became critically
ill patients, and all needed intensive care. After the
devastating poliomyelitis epidemics of the 1950s, a new
specialty of critical care medicine emerged. Initially,
respiratory care units were created for the patients
affected by this severe illness, but soon they were
transformed into intensive care units. Trauma units and
transplant units soon followed. Specialized care for
patients with acute neurologic or neurosurgical disease
was established in parallel with these developments, but
many of the early neuroscience intensive care units were
redesigned wards. Specialized physicians and nursing
staff delivered multidisciplinary care, recognizing that no
one group could function well alone. Inevitably, critical
care for the sickest patients was the only option to give
them a fighting chance to survive.
In the United States, the Society of Critical Care
Medicine brought the specialty clearly into focus in
the early 1970s, and training program guidelines soon
were developed in the United States and abroad. The
Neurocritical Care Society was founded in 2002, and
accreditation was established through the American
Academy of Neurology (United Council of Neurologic
Subspecialties). Most importantly, the American Board
of Medical Specialties has approved creation of a
neurocritical care subspecialty, and Accreditation Council
for Graduate Medical Education–​accredited fellowships
and a new board examination are planned.
Currently, the neurocritical care board examination
combines neurocritical care with general intensive care,
and questions are equally divided between the 2 subjects.
Accordingly, combining both areas of expertise in a single
volume is appropriate.
The chapters in this book correspond with the
key disorders suggested by the United Council of
Neurologic Subspecialties to be studied in preparation
for the examination and to assist with the critical care
board examination. The book is not only detailed in
basic pathophysiologic content but also describes
major disorders and syndromes and their management.
Because of its unprecedented complete coverage of acute
neurologic disorders, it is equally useful as preparation
for the critical care medicine board examination.
The success of board review books hinges on
clarity of the presented information, and we focused
on conciseness and readability. Readers find tables,
explanatory drawings, and bullet points useful, and thus
we included them throughout while keeping the text
specific and informative. We edited the entire text, and
we sought expert advise to fill in our gaps in knowledge
or to verify our additions. All chapters were written and
closely edited by Mayo Clinic faculty. The references are
up-​to-​date and include many guidelines.
Board review books have multiple disclaimers, as
does this one. Use of this book alone will not guarantee
passing the examination(s), and additional texts should
be consulted. The book has more than 500 multiple-​
choice practice questions and answers. References are
included with each answer. The questions are of the type
used on the board examination. Reviewing the questions
may improve one’s ability to take the board examination,
but we all appreciate that (in essence) passing an
examination is directly related to sufficient knowledge
of the topics. We hope you will benefit from studying
this text. It should appeal to any aspiring intensivist in
training. We enjoyed selecting the material for you, and
we definitely learned a few things along the way. We
hope this book will help you pass the examination.
EFM WIJDICKS
JY FINDLAY
WD FREEMAN
A SEN
v
 Table of Contents
Contributors xiii
Section I: Fundamentals of Critical
Care
1 • Respiratory Physiology in Critical Illness 3
Minkyung Kwon, MD and Jose L. Diaz-​Gomez, MD
2 • Mechanical Ventilation: Basic Modes 10
Amelia A. Lowell, RRT, RCP
3 • Mechanical Ventilation: Advanced Modes
Amelia A. Lowell, RRT, RCP
and Bhavesh M. Patel, MD
4 • Cardiovascular System in the Critically Ill Patient 26
Juan G. Ripoll Sanz, MD; Norlalak Jiramethee, MD;
and Jose L. Diaz-​Gomez, MD
5 • Renal Function in Critically Ill Patients
Pramod K. Guru, MBBS, MD
6 • Nutrition in Critical Illness 42
Angela N. Vizzini, RDN, LD/​N
and Mireille H. Hamdan, RDN, LD/​N
Section I: Questions and Answers
Section II: Fundamentals of
Neurocritical Care
7 • Neurologic Examination in Neurocritical Illness 61
Eelco F. M. Wijdicks, MD, PhD
8 • Intracranial Pressure 69
Eelco F. M. Wijdicks, MD, PhD
and William D. Freeman, MD
9 • Cerebrospinal Physiology 74
Joseph Zachariah, MD
10 • Cerebral Circulation and Cerebral Blood Flow 79
Arnoley S. Abcejo, MD and Jeffrey J. Pasternak, MD
11 • Consequences of Anoxia and Ischemia to the
Brain 86
Jennifer E. Fugate, DO
12 • Consequences of Acute Metabolic Changes to the
Brain 92
Sherri A. Braksick, MD and Sara E. Hocker, MD
13 • Consequences of Acute Hypertension to the
Brain 97
17 Katherine M. Oshel, MD and Hani M. Wadei, MD
14 • Coma and Other Altered States
of Consciousness 101
Eelco F. M. Wijdicks, MD, PhD
15 • Neuromuscular Respiratory Failure 109
Maximiliano A. Hawkes, MD
35 and Eelco F. M. Wijdicks, MD, PhD
16 • Neurogenic Breathing Patterns 115
Eelco F. M. Wijdicks, MD, PhD
17 • Neurogenic Cardiac Manifestations 118
Sherri A. Braksick, MD and
50 Eelco F. M. Wijdicks, MD, PhD
18 • Paroxysmal Sympathetic Hyperactivity 122
Kevin T. Gobeske, MD, PhD
Section II: Questions and Answers 125
Section III: Critical Care Disorders
Pulmonary Disorders
19 • Acute Respiratory Distress Syndrome 137
Richard K. Patch III, MD
and James Y. Findlay, MB, ChB
vii
viii Table of Contents

20 • Pulmonary Embolism: An Overview 142 38 • Adrenal Insufficiency in Neurocritically Ill

Brandon T. Nokes, MD and Rodrigo Cartin-​Ceba, MD Patients 246
Carla P. Venegas-​Borsellino, MD
21 • Asthma in the Critically Ill Patient 150 and Santiago Naranjo-​Sierra, MD
Jonathan J. Danaraj, DO and Augustine S. Lee, MD
Gastrointestinal Disorders
22 • Chronic Obstructive Pulmonary Disease
Exacerbation 157 39 • Acute Gastrointestinal Hemorrhage 253
Isabel Mira-​Avendano, MD and Minkyung Kwon, MD Pablo Moreno Franco, MD
and Philip E. Lowman, MD
23 • Pleural Diseases in Critical Care Medicine 161
Karthika R. Linga, MBBS and Neal M. Patel, MD 40 • Paralytic and Obstructive Ileus 259
Juan M. Canabal, MD
24 • Pulmonary Malignancy 166
Ali A. Zaied, MD and Margaret M. Johnson, MD 41 • Acute Liver Failure 264
James Y. Findlay, MB, ChB and
25 • Pulmonary Hypertension and Right-​Sided Heart Eelco F. M. Wijdicks, MD, PhD
Failure in the Critically Ill 171
Charles D. Burger, MD 42 • Acute Perforations of the Gastrointestinal Tract 270
Levan Tsamalaidze, MD and John A. Stauffer, MD
Circulatory and Cardiovascular Disorders
43 • Acute Vascular Disorders of the Intestine 276
26 • Anaphylaxis and Anaphylactic Shock 179 Omar Y. Mousa, MBBS and Surakit Pungpapong, MD
Megan S. Motosue, MD and Gerald W. Volcheck, MD
44 • Abdominal Compartment Syndrome 281
27 • Cardiogenic Shock 183 Daniel J. Johnson, MD
Robert A. Ratzlaff, DO and Jason L. Siegel, MD
Renal Disorders
28 • Acute Coronary Syndrome 190
Siva S. Ketha, MD and Juan Carlos Leoni Moreno, MD 45 • Acute Kidney Injury 287
Ankit Sakhuja, MBBS and Kianoush B. Kashani, MD
29 • Cardiac Rhythm and Conduction Disturbances 197
Yahaira Ortiz Gonzalez, MD and Fred Kusumoto, MD 46 • Acid-​Base Disorders 294
Onur Demirci, MD
30 • Hypertensive Emergencies 207
Denzil R. Hill, MD and James A. Onigkeit, MD 47 • Drug Dosing in Renal Failure 299
Daniel A. Jackson, PharmD, RPh
31 • Cardiopulmonary Resuscitation 211
Richard K. Patch III, MD 48 • Principles of Renal Replacement Therapies 302
Peter M. Fitzpatrick, MD
32 • Vascular Emergencies of the Aorta 216
Tariq Almerey, MD; January F. Moore; 49 • Disorders of Water and Electrolyte Balance 306
and Houssam Farres, MD Yuzana Zaw, MBBS and Mira T. Keddis, MD

Acute Endocrine Disorders Hematologic and Inflammatory Disorders

33 • Pituitary Apoplexy 225 50 • Anemia and Blood Transfusion 319
Sherri A. Braksick, MD Joy D. Hughes, MD; Mariela Rivera, MD;
and Myung S. Park, MD, MS
34 • Diabetes Insipidus 229
Dana Erickson, MD 51 • Hematologic and Oncologic Complications in the
Intensive Care Unit 325
35 • Panhypopituitarism 234 Carl A. Ruthman, MD and Jose C. Yataco, MD
Diane Donegan, MB, BCh and Irina Bancos, MD
52 • Thrombocytopenia and Thrombocytopathy 331
36 • Thyroid Disorders in the Intensive Care Unit 239 Gretchen Johns, MD
John E. Moss, MD
53 • Disseminated Intravascular Coagulation: Clinical
37 • Glycemic Control in Neurocritically Ill Patients 241 Diagnosis and Management 337
Carla P. Venegas-​Borsellino, MD;
Prakash Vishnu, MBBS and Sikander Ailawadhi, MD
Michael A. Pizzi, DO, PhD;
and Santiago Naranjo-​Sierra, MD 54 • Diagnosis and Management of Acquired Bleeding
Disorders 345
Rajiv K. Pruthi, MBBS
 Table of Contents ix

55 • Anticoagulation Monitoring and Reversal 353 71 • Critical Care of Heart-​Lung and Lung Transplant
Theresa N. Kinard, MD Recipients 446
Ramachandra R. Sista, MD
56 • Therapeutic Plasma Exchange for Acute Hematologic
Disorders 359 72 • Clinical Management of Liver Transplant
Jill Adamski, MD, PhD Recipients 453
Bhargavi Gali, MD
57 • Rheumatologic and Autoimmune
Emergencies 363 73 • Clinical Management of Kidney Transplant
Megan L. Krause, MD and Kevin G. Moder, MD Recipients 457
James A. Onigkeit, MD
Sepsis and Other Infectious Diseases
74 • Small Intestinal Transplant 460
58 • Infectious Diseases Complicating Critical Care 369 Ayan Sen, MD
David A. Sotello Aviles, MD
and Walter C. Hellinger, MD Toxicity and Toxins
59 • Antibiotics in the Intensive Care Unit 375 75 • Serotonin Syndrome 467
David A. Sotello Aviles, MD Kevin T. Gobeske, MD, PhD
and Walter C. Hellinger, MD and Eelco F. M. Wijdicks, MD, PhD

60 • Sepsis and Septic Shock 381 76 • Neuroleptic Malignant Syndrome and

Charles R. Sims III, MD and Thomas B. Comfere, MD Hyperthermia 472
J. Ross Renew, MD and Monica Mordecai, MD
Dermatologic Concerns
77 • Clinical Toxicology: Selected Drugs of Abuse and
61 • Dermatologic Emergencies in the Intensive Care Chemical and Biological Warfare Agents 475
Unit 391
Matthew D. Sztajnkrycer, MD, PhD
Matthew R. Hall, MD
Section III: Questions and Answers 483
Trauma and Burns
62 • Initial Approach to the Management of Multisystem
Trauma 397
David S. Morris, MD
Section IV: Neurocritical Illness
63 • Chest and Abdominal Trauma 402 Acute Cerebrovascular Disorders
Joy D. Hughes, MD and David S. Morris, MD
78 • Diagnosis and Management of Hemispheric
64 • Skeletal Trauma 405 Infarction 543
Joshua S. Bingham, MD and Kevin J. Renfree, MD Sanjeet S. Grewal, MD and Benjamin L. Brown, MD

65 • Burns and Electrical Injuries 409 79 • Basilar Artery Occlusion 547

Brandon T. Nokes, MD and Ayan Sen, MD Michael R. Pichler, MD and Jennifer E. Fugate, DO

Cardiothoracic Critical Care 80 • Carotid Artery Disease 555

Nnenna Mbabuike, MD and Rabih G. Tawk, MD
66 • Cardiothoracic Surgery and Postoperative
Intensive Care 417 81 • Adult Primary Central Nervous System
Juan G. Ripoll Sanz, MD and Robert A. Ratzlaff, DO Vasculitis 563
Carlo Salvarani, MD; Robert D. Brown Jr, MD, MPH;
67 • Mechanical Circulatory Assist Devices 424 and Gene G. Hunder, MD
Ayan Sen, MD and Bhavesh M. Patel, MD
82 • Intracerebral and Intraventricular Hemorrhage 570
68 • Extracorporeal Membrane Oxygenation 429 Oana Dumitrascu, MD and Maria I. Aguilar, MD
J. Kyle Bohman, MD and Gregory J. Schears, MD
83 • Aneurysmal Subarachnoid Hemorrhage 577
69 • Cardiac Pacing in the Intensive Care Unit 435 Giuseppe Lanzino, MD and Biagia La Pira, MD
J. William Schleifer, MD; Farouk Mookadam, MB, BCh;
and Harish Ramakrishna, MD 84 • Intracranial Arteriovenous Malformations 585
Kelly D. Flemming, MD and Michael J. Link, MD
Transplant Critical Care
85 • Cerebral Venous and Dural Sinus Thrombosis 594
70 • Clinical Management of Heart Transplant Sara E. Hocker, MD
Recipients 443
Arzoo Sadiqi, BS and Jama Jahanyar, MD, PhD
x Table of Contents

86 • Cervical Arterial Dissection 600 101 • Rapidly Progressive Dementia and Coma 704
Bart M. Demaerschalk, MD Prasuna Kamireddi, MBBS; Jason L. Siegel, MD;
and Dennis W. Dickson, MD
Traumatic Brain and Spine Injury
Neuro-​oncology
87 • Traumatic Brain Injury and Spinal Cord Injury 605
Maya A. Babu, MD 102 • Brain and Spine Tumors 715
Mithun Sattur, MBBS; Matthew E. Welz, MS; and
88 • Traumatic Epidural and Subdural Bernard R. Bendok, MD
Hematomas 614
Patrick R. Maloney, MD and Michelle J. Clarke, MD 103 • Neoplastic Meningitis 722
Alyx B. Porter, MD
89 • Unstable Spinal Fractures 621
William E. Clifton III, MD 104 • Autoimmune Encephalitis 726
and Mark A. Pichelmann, MD Eslam Shosha, MB, BCh and Sean J. Pittock, MD

Acute Central Nervous System Infections 105 • Radiation Therapy 734

Sameer R. Keole, MD
90 • Encephalitis 629
Allen J. Aksamit Jr, MD Postoperative Neurosurgery
91 • Acute Bacterial Meningitis 637 106 • Intensive Care After Spinal Surgery 739
Eelco F. M. Wijdicks, MD, PhD Clarence B. Watridge, MD

92 • Brain Abscess and Spinal Epidural Abscess 642 107 • Intensive Care After Craniotomy 746
Selby G. Chen, MD Kelly Gassie, MD; Belinda G. Bradley, APRN;
Robert E. Wharen Jr, MD;
Acute Neuromuscular Disorders
and Betty Y. S. Kim, MD, PhD
93 • Myasthenia Gravis 651
Maximiliano A. Hawkes, MD
108 • Intensive Care After Neuroendovascular
Procedures 753
and Eelco F. M. Wijdicks, MD, PhD
Mithun Sattur, MBBS; Chandan Krishna, MD;
94 • Guillain-​Barré Syndrome 658 Bernard R. Bendok, MD; and Brian W. Chong, MD
Eelco F. M. Wijdicks, MD, PhD
Section IV: Questions and Answers 759
95 • Amyotrophic Lateral Sclerosis 664
Jennifer M. Martinez-​Thompson, MD
and Nathan P. Staff, MD, PhD Section V: Imaging in Critical Illness
96 • Rhabdomyolysis and Toxic Myopathies 670
Justin C. Kao, MB, ChB and
109 • Radiography and Computed Tomography
of the Chest 785
Margherita Milone, MD, PhD
Barbara L. McComb, MD
97 • Myopathy and Neuropathy Acquired in the Intensive
Care Unit 677 110 • Abdominal Radiography 797
Joseph G. Cernigliaro, MD and David J. DiSantis, MD
Priya S. Dhawan, MD and Jennifer A. Tracy, MD

Miscellaneous Disorders of Acute Brain 111 • Fluoroscopy: Principles and Safety 805
David M. Sella, MD; Glenn M. Sturchio, PhD; and
Injury
Beth A. Schueler, PhD
98 • Status Epilepticus 687
Christopher P. Robinson, DO, MS
112 • Ultrasonography 809
Santiago Naranjo-​Sierra, MD and
and Sara E. Hocker, MD
Lauren K. Ng Tucker, MD
99 • Posterior Reversible Encephalopathy
Syndrome 693 113 • Transesophageal Echocardiography 816
Ryan C. Craner, MD; Farouk Mookadam, MB, BCh;
Sudhir V. Datar, MBBS and Jennifer E. Fugate, DO
and Harish Ramakrishna, MD
100 • Demyelinating Disorders of the Central Nervous Section V: Questions and Answers 827
System 699
Aurelia A. Smith, MD and
Brian G. Weinshenker, MD
 Table of Contents xi

Section VI: Procedures 131 • Essentials of Multimodal Brain Monitoring 925

Jennifer E. Fugate, DO
Airway Procedures and Modes of 132 • Essentials of Cranial Neuroimaging 932
Ventilation E. Paul Lindell, MD
114 • Basics of Airway and Oxygen Delivery Devices 835 Section VI: Questions and Answers 941
Andrew W. Murray, MD

115 • Endotracheal Intubation Procedures 840

Matthew J. Ritter, MD
Section VII: Pharmacotherapeutics
116 • Noninvasive Positive Pressure Ventilation 846
Karen W. Hampton, MS, RRT 133 • Anticonvulsant Drugs 955
Anteneh M. Feyissa, MD and Jeffrey W. Britton, MD
117 • Tracheostomy 850
Saba Ghorab, MD and David G. Lott, MD 134 • Effects of Targeted Temperature Management
on Drugs 963
118 • Diagnostic and Interventional Bronchoscopy in the Lauren K. Ng Tucker, MD
Intensive Care Unit 855
Cesar A. Keller, MD 135 • Sedation and Analgesia 967
Juan G. Ripoll Sanz, MD
Cardiovascular and Cardiopulmonary and Jose L. Diaz-​Gomez, MD
Monitoring and Access
136 • Inotropes, Vasopressors, and
119 • Electrocardiographic Monitoring 865 Antihypertensive Agents 972
Pragnesh P. Parikh, MD and
Juan N. Pulido, MD
K. L. Venkatachalam, MD
137 • Antibiotics, Antivirals, and Antifungals 981
120 • Hemodynamic Monitoring 870 David A. Sotello Aviles, MD
Hannelisa E. Callisen, PA-​C;
and Walter C. Hellinger, MD
Stacy L. Libricz, PA-​C, MS; and Ayan Sen, MD
Section VII: Questions and Answers 990
121 • Pulmonary Artery Catheterization 879
Philip E. Lowman, MD

122 • Thoracentesis and Chest Tubes 883 Section VIII: Ethics in the
Staci E. Beamer, MD
Neurointensive Care Unit
123 • Central Line Placement 890
Nicholas D. Will, MD and W. Brian Beam, MD 138 • Palliative and End-​of-​Life Care in the Intensive
Care Unit 997
124 • Interventional Radiology Procedures 892 Maisha T. Robinson, MD
Rahmi Oklu, MD, PhD
139 • Communicating With Families 1001
Neuromonitoring and Procedures Cory Ingram, MD
125 • Intracranial Pressure Monitoring and External 140 • Brain Death 1005
Ventricular Drainage 899 Eelco F. M. Wijdicks, MD, PhD
Maya A. Babu, MD and John L. D. Atkinson, MD
141 • Minimally Conscious State and Persistent Vegetative
126 • Lumbar Puncture 903 State 1008
Christina C. Smith, APRN
David T. Jones, MD
127 • Lumbar Drain 907 142 • Ethical Concerns and Care Before Organ
Jamie J. Van Gompel, MD
Donation 1012
128 • Intraventricular Drug Administration 912 Diane C. McLaughlin, APRN and
William W. Horn Jr, APRN and Lauren K. Ng Tucker, MD
Benjamin L. Brown, MD
Section VIII: Questions and Answers 1015
129 • Transcranial Doppler Ultrasonography 914
Mark N. Rubin, MD
Index 1019
130 • Electroencephalography 918
Amy Z. Crepeau, MD
 Contributors
Arnoley S. Abcejo, MD
Senior Associate Consultant, Department of
Anesthesiology and Perioperative Medicine, Mayo
Clinic, Rochester, Minnesota; Assistant Professor of
Anesthesiology, Mayo Clinic College of Medicine and
Science
Jill Adamski, MD, PhD
Chair, Division of Laboratory Medicine, Mayo Clinic
Hospital, Phoenix, Arizona; Associate Professor of
Laboratory Medicine and Pathology, Mayo Clinic
College of Medicine and Science
Maria I. Aguilar, MD
Consultant, Department of Neurology, Mayo Clinic,
Scottsdale, Arizona; Associate Professor of Neurology,
Mayo Clinic College of Medicine and Science
Sikander Ailawadhi, MD
Consultant, Division of Hematology and Oncology, Mayo
Clinic, Jacksonville, Florida; Associate Professor of
Medicine, Mayo Clinic College of Medicine and Science
Allen J. Aksamit Jr, MD
Consultant, Department of Neurology, Mayo Clinic,
Rochester, Minnesota; Professor of Neurology, Mayo
Clinic College of Medicine and Science
Tariq Almerey, MD
Research Fellow in Surgery, Mayo Clinic School of
Graduate Medical Education, Mayo Clinic College of
Medicine and Science, Jacksonville, Florida
John L. D. Atkinson, MD
Consultant, Department of Neurologic Surgery, Mayo
Clinic, Rochester, Minnesota; Professor of Neurosurgery,
Mayo Clinic College of Medicine and Science
Maya A. Babu, MD
Resident in Neurosurgery, Mayo Clinic School of
Graduate Medical Education, Mayo Clinic College of
Medicine and Science, Rochester, Minnesota
Present address: Harvard Medical School, Boston,
Massachusetts
Irina Bancos, MD
Consultant, Division of Endocrinology, Diabetes,
Metabolism, & Nutrition, Mayo Clinic, Rochester,
Minnesota; Assistant Professor of Medicine, Mayo
Clinic College of Medicine and Science
W. Brian Beam, MD
Consultant, Department of Anesthesiology and
Perioperative Medicine, Mayo Clinic, Rochester,
Minnesota; Assistant Professor of Anesthesiology, Mayo
Clinic College of Medicine and Science
Staci E. Beamer, MD
Senior Associate Consultant, Department of
Cardiovascular and Thoracic Surgery, Mayo Clinic
Hospital, Phoenix, Arizona; Assistant Professor of
Surgery, Mayo Clinic College of Medicine and Science
Bernard R. Bendok, MD
Chair, Department of Neurologic Surgery, Mayo Clinic
Hospital, Phoenix, Arizona; Professor of Neurosurgery,
Mayo Clinic College of Medicine and Science
Joshua S. Bingham, MD
Fellow in Reconstructive Surgery, Mayo Clinic School
of Graduate Medical Education and Instructor in
Orthopedics, Mayo Clinic College of Medicine and
Science, Scottsdale, Arizona
xiii
xiv Contributors
J. Kyle Bohman, MD
Consultant, Department of Anesthesiology and
Perioperative Medicine, Mayo Clinic, Rochester,
Minnesota; Assistant Professor of Anesthesiology, Mayo
Clinic College of Medicine and Science
Belinda G. Bradley, APRN
Lead Nurse Practicioner, Department of Neurologic
Surgery, Mayo Clinic, Jacksonville, Florida
Sherri A. Braksick, MD
Fellow in Critical Care Neurology, Mayo Clinic School
of Graduate Medical Education, Mayo Clinic College of
Medicine and Science, Rochester, Minnesota
Present address: University of Kansas Medical Center,
Kansas City, Kansas
Jeffrey W. Britton, MD
Chair, Division of Epilepsy, Mayo Clinic, Rochester,
Minnesota; Professor of Neurology, Mayo Clinic College
of Medicine and Science
Benjamin L. Brown, MD
Senior Associate Consultant, Department of Neurologic
Surgery, Mayo Clinic, Jacksonville, Florida; Assistant
Professor of Neurosurgery, Mayo Clinic College of
Medicine and Science
Robert D. Brown Jr, MD, MPH
Chair, Division of Stroke and Cerebrovascular Diseases,
Mayo Clinic, Rochester, Minnesota; Professor of
Neurology, Mayo Clinic College of Medicine and
Science
Charles D. Burger, MD
Consultant, Division of Pulmonary, Allergy, and Sleep
Medicine, Mayo Clinic, Jacksonville, Florida; Professor
of Medicine, Mayo Clinic College of Medicine and
Science
Hannelisa E. Callisen, PA-​C
Physician Assistant, Department of Critical Care
Medicine, Mayo Clinic Hospital, Phoenix, Arizona
Juan M. Canabal, MD
Senior Associate Consultant, Department of
Transplantation, Mayo Clinic, Jacksonville, Florida;
Assistant Professor of Medicine, Mayo Clinic College of
Medicine and Science
Rodrigo Cartin-​Ceba, MD
Consultant, Department of Critical Care Medicine, Mayo
Clinic, Scottsdale, Arizona; Associate Professor of
Medicine, Mayo Clinic College of Medicine and Science
Joseph G. Cernigliaro, MD
Chair, Division of Abdominal Imaging, Mayo Clinic,
Jacksonville, Florida; Associate Professor of Radiology,
Mayo Clinic College of Medicine and Science
Selby G. Chen, MD
Senior Associate Consultant, Department of Neurologic
Surgery, Mayo Clinic, Jacksonville, Florida; Assistant
Professor of Neurosurgery, Mayo Clinic College of
Medicine and Science
Brian W. Chong, MD
Consultant, Department of Radiology, Mayo Clinic
Hospital, Phoenix, Arizona; Associate Professor of
Radiology, Mayo Clinic College of Medicine and
Science
Michelle J. Clarke, MD
Consultant, Department of Neurologic Surgery, Mayo
Clinic, Rochester, Minnesota; Professor of Neurosurgery
and of Orthopedics, Mayo Clinic College of Medicine
and Science
William E. Clifton III, MD
Resident in Neurologic Surgery, Mayo Clinic School of
Graduate Medical Education, Mayo Clinic College of
Medicine and Science, Jacksonville, Florida
Thomas B. Comfere, MD
Consultant, Department of Anesthesiology and
Perioperative Medicine, Mayo Clinic, Rochester,
Minnesota; Assistant Professor of Anesthesiology, Mayo
Clinic College of Medicine and Science
Ryan C. Craner, MD
Consultant, Department of Anesthesiology and
Perioperative Medicine, Mayo Clinic Hospital, Phoenix,
Arizona; Assistant Professor of Anesthesiology, Mayo
Clinic College of Medicine and Science
Amy Z. Crepeau, MD
Consultant, Department of Neurology, Mayo Clinic
Hospital, Phoenix, Arizona; Assistant Professor of
Neurology, Mayo Clinic College of Medicine and
Science
Jonathan J. Danaraj, DO
Resident in Pulmonary and Critical Care Medicine, Mayo
Clinic School of Graduate Medical Education, Mayo
Clinic College of Medicine and Science, Jacksonville,
Florida

Sudhir V. Datar, MBBS
Division of Critical Care Neurology, Wake Forest
University Medical Center, Winston-​Salem, North
Carolina; Assistant Professor of Neurology and of
Anesthesiology, Wake Forest School of Medicine
Bart M. Demaerschalk, MD
Consultant, Department of Neurology, Mayo Clinic
Hospital, Phoenix, Arizona; Professor of Neurology,
Mayo Clinic College of Medicine and Science
Onur Demirci, MD
Consultant, Department of Anesthesiology and
Perioperative Medicine, Mayo Clinic, Rochester,
Minnesota; Assistant Professor of Anesthesiology, Mayo
Clinic College of Medicine and Science
Priya S. Dhawan, MD
Resident in Neurology, Mayo Clinic School of Graduate
Medical Education, Mayo Clinic College of Medicine
and Science, Rochester, Minnesota
Present address: University of British Columbia,
Vancouver, British Columbia
Jose L. Diaz-​Gomez, MD
Consultant, Departments of Critical Care Medicine,
Anesthesiology, and Neurosurgery, Mayo Clinic,
Jacksonville, Florida; Associate Professor of
Anesthesiology, Mayo Clinic College of Medicine and
Science
Present address: Private Practice
Dennis W. Dickson, MD
Consultant, Departments of Laboratory Medicine
and Pathology and of Neuroscience, Mayo Clinic,
Jacksonville, Florida; Professor of Laboratory Medicine
and Pathology, Mayo Clinic College of Medicine and
Science
David J. DiSantis, MD
Senior Associate Consultant, Department of Radiology,
Mayo Clinic, Jacksonville, Florida; Professor of
Radiology, Mayo Clinic College of Medicine and
Science
Diane Donegan, MB, BCh
Research Collaborator in Endocrinology, Mayo Clinic
School of Graduate Medical Education, Mayo Clinic
College of Medicine and Science, Rochester, Minnesota
Oana Dumitrascu, MD
Fellow in Vascular Neurology, Mayo Clinic School of
Graduate Medical Education, Mayo Clinic College of
Medicine and Science, Scottsdale, Arizona
Contributors xv
Dana Erickson, MD
Consultant, Division of Endocrinology, Diabetes,
Metabolism, & Nutrition, Mayo Clinic, Rochester,
Minnesota; Associate Professor of Medicine, Mayo
Clinic College of Medicine and Science
Houssam Farres, MD
Consultant, Division of Vascular Surgery, Mayo Clinic,
Jacksonville, Florida; Assistant Professor of Surgery,
Mayo Clinic College of Medicine and Science
Anteneh M. Feyissa, MD
Senior Associate Consultant, Department of Neurology,
Mayo Clinic, Jacksonville, Florida; Assistant Professor
of Neurology, Mayo Clinic College of Medicine and
Science
James Y. Findlay, MB, ChB
Consultant, Department of Anesthesiology and
Perioperative Medicine, Mayo Clinic, Rochester,
Minnesota; Associate Professor of Anesthesiology, Mayo
Clinic College of Medicine and Science
Peter M. Fitzpatrick, MD
Consultant, Division of Nephrology and Hypertension,
Mayo Clinic, Jacksonville, Florida; Assistant Professor
of Medicine, Mayo Clinic College of Medicine and
Science
Kelly D. Flemming, MD
Consultant, Department of Neurology, Mayo Clinic,
Rochester, Minnesota; Associate Professor of Neurology,
Mayo Clinic College of Medicine and Science
William D. Freeman, MD
Consultant, Departments of Critical Care Medicine,
Neurology, and Neurosurgery, Mayo Clinic, Jacksonville,
Florida; Professor of Neurology and of Neurosurgery,
Mayo Clinic College of Medicine and Science
Jennifer E. Fugate, DO
Consultant, Department of Neurology, Mayo Clinic,
Rochester, Minnesota; Assistant Professor of Neurology,
Mayo Clinic College of Medicine and Science
Bhargavi Gali, MD
Consultant, Department of Anesthesiology and
Perioperative Medicine, Mayo Clinic, Rochester,
Minnesota; Assistant Professor of Anesthesiology, Mayo
Clinic College of Medicine and Science
Kelly Gassie, MD
Resident in Neurologic Surgery, Mayo Clinic School of
Graduate Medical Education, Mayo Clinic College of
Medicine and Science, Jacksonville, Florida
xvi Contributors
Saba Ghorab, MD
Resident in Otolaryngology, Mayo Clinic School of
Graduate Medical Education, Mayo Clinic College of
Medicine and Science, Scottsdale, Arizona
Kevin T. Gobeske, MD, PhD
Resident in Critical Care Neurology, Mayo Clinic School
of Graduate Medical Education, Mayo Clinic College of
Medicine and Science, Rochester, Minnesota
Sanjeet S. Grewal, MD
Resident in Neurologic Surgery, Mayo Clinic School of
Graduate Medical Education, Mayo Clinic College of
Medicine and Science, Jacksonville, Florida
Pramod K. Guru, MBBS, MD
Senior Associate Consultant, Department of Critical Care
Medicine, Mayo Clinic, Jacksonville, Florida; Assistant
Professor of Medicine, Mayo Clinic College of Medicine
and Science
Matthew R. Hall, MD
Consultant, Department of Dermatology, Mayo
Clinic, Jacksonville, Florida; Assistant Professor of
Dermatology, Mayo Clinic College of Medicine and
Science
Mireille H. Hamdan, RDN, LD/​N
Dietician, Clinical Nutrition Services, Mayo Clinic,
Jacksonville, Florida; Instructor in Nutrition, Mayo
Clinic College of Medicine and Science
Karen W. Hampton, MS, RRT
Respiratory Therapist, Respiratory Services, Mayo Clinic,
Jacksonville, Florida
Maximiliano A. Hawkes, MD
Fellow in Critical Care Neurology, Mayo Clinic School
of Graduate Medical Education and Assistant Professor
of Neurology, Mayo Clinic College of Medicine and
Science, Rochester, Minnesota
Walter C. Hellinger, MD
Chair, Division of Infectious Diseases, Mayo Clinic,
Jacksonville, Florida; Associate Professor of Medicine,
Mayo Clinic College of Medicine and Science
Denzil R. Hill, MD
Senior Associate Consultant, Department of
Anesthesiology and Perioperative Medicine,
Mayo Clinic, Rochester, Minnesota; Instructor in
Anesthesiology, Mayo Clinic College of Medicine and
Science
Sara E. Hocker, MD
Consultant, Department of Neurology, Mayo Clinic,
Rochester, Minnesota; Associate Professor of Neurology,
Mayo Clinic College of Medicine and Science
William W. Horn Jr, APRN
Nurse Practitioner, Department of Neurologic Surgery,
Mayo Clinic, Jacksonville, Florida
Joy D. Hughes, MD
Research Fellow in General Surgery, Mayo Clinic School
of Graduate Medical Education, Mayo Clinic College of
Medicine and Science, Rochester, Minnesota
Gene G. Hunder, MD
Emeritus Professor of Neurology, Mayo Clinic College of
Medicine and Science, Rochester, Minnesota
Cory Ingram, MD
Senior Associate Consultant, Division of Community
Palliative Medicine, Mayo Clinic, Rochester, Minnesota;
Assistant Professor of Family Medicine and of Palliative
Medicine, Mayo Clinic College of Medicine and Science
Daniel A. Jackson, PharmD, RPh
Pharmacist, Pharmacy Services, Mayo Clinic,
Jacksonville, Florida; Assistant Professor of Pharmacy,
Mayo Clinic College of Medicine and Science
Jama Jahanyar, MD, PhD
Senior Associate Consultant, Department of
Cardiovascular and Thoracic Surgery, Mayo Clinic
Hospital, Phoenix, Arizona; Assistant Professor of
Surgery, Mayo Clinic College of Medicine and Science
Norlalak Jiramethee, MD
Fellow in Critical Care Medicine, Mayo Clinic School of
Graduate Medical Education, Mayo Clinic College of
Medicine and Science, Jacksonville, Florida
Gretchen Johns, MD
Consultant, Department of Laboratory Medicine and
Pathology, Mayo Clinic, Jacksonville, Florida; Assistant
Professor of Laboratory Medicine and Pathology, Mayo
Clinic College of Medicine and Science
Daniel J. Johnson, MD
Chair, Department of Surgery, Mayo Clinic Hospital,
Phoenix, Arizona; Associate Professor of Surgery, Mayo
Clinic College of Medicine and Science
Margaret M. Johnson, MD
Consultant, Division of Pulmonary, Allergy and Sleep
Medicine, Mayo Clinic, Jacksonville, Florida; Associate
Professor of Medicine, Mayo Clinic College of Medicine
and Science

David T. Jones, MD
Consultant, Department of Neurology, Mayo Clinic,
Rochester, Minnesota; Assistant Professor of Neurology,
Mayo Clinic College of Medicine and Science
Prasuna Kamireddi, MBBS
Research Trainee, Department of Neurology, Mayo Clinic,
Jacksonville, Florida
Justin C. Kao, MB, ChB
Fellow in Advanced Clinical Neurology, Mayo Clinic
School of Graduate Medical Education, Mayo Clinic
College of Medicine and Science, Rochester, Minnesota
Kianoush B. Kashani, MD
Consultant, Division of Nephrology and Hypertension,
Mayo Clinic, Rochester, Minnesota; Professor of
Medicine, Mayo Clinic College of Medicine and Science
Mira T. Keddis, MD
Consultant, Division of Nephrology, Mayo Clinic,
Scottsdale, Arizona; Assistant Professor of Medicine,
Mayo Clinic College of Medicine and Science
Cesar A. Keller, MD
Emeritus Professor of Medicine, Mayo Clinic College of
Medicine and Science, Jacksonville, Florida
Sameer R. Keole, MD
Consultant, Department of Radiation Oncology, Mayo
Clinic Hospital, Phoenix, Arizona; Assistant Professor
of Radiation Oncology, Mayo Clinic College of Medicine
and Science
Siva S. Ketha, MD
Research Collaborator, Mayo Clinic, Jacksonville, Florida;
Assistant Professor of Medicine, Mayo Clinic College of
Medicine and Science
Betty Y. S. Kim, MD, PhD
Consultant, Department of Neurologic Surgery, Mayo
Clinic, Jacksonville, Florida; Associate Professor of
Neurosurgery and Assistant Professor of Neuroscience,
Mayo Clinic College of Medicine and Science
Theresa N. Kinard, MD
Consultant, Department of Laboratory Medicine, Mayo
Clinic Hospital, Phoenix, Arizona; Assistant Professor
of Laboratory Medicine and Pathology, Mayo Clinic
College of Medicine and Science
Megan L. Krause, MD
Fellow in Rheumatology, Mayo Clinic School of Graduate
Medical Education, Mayo Clinic College of Medicine
and Science, Rochester, Minnesota
Contributors xvii
Chandan Krishna, MD
Senior Associate Consultant, Department of Neurologic
Surgery, Mayo Clinic Hospital, Phoenix, Arizona;
Assistant Professor of Neurosurgery, Mayo Clinic
College of Medicine and Science
Fred Kusumoto, MD
Consultant, Department of Cardiovascular Diseases, Mayo
Clinic, Jacksonville, Florida; Professor of Medicine,
Mayo Clinic College of Medicine and Science
Minkyung Kwon, MD
Resident in Pulmonary and Critical Care Medicine, Mayo
Clinic School of Graduate Medical Education, Mayo Clinic
College of Medicine and Science, Jacksonville, Florida
Giuseppe Lanzino, MD
Consultant, Departments of Neurologic Surgery and
Radiology, Mayo Clinic, Rochester, Minnesota; Professor
of Neurosurgery, Mayo Clinic College of Medicine and
Science
Biagia La Pira, MD
Research Trainee, Department of Neurologic Surgery,
Mayo Clinic, Rochester, Minnesota
Present address: Private Practice, Rome, Italy
Augustine S. Lee, MD
Chair, Division of Pulmonary, Allergy and Sleep
Medicine, Mayo Clinic, Jacksonville, Florida; Associate
Professor of Medicine, Mayo Clinic College of Medicine
and Science
Juan Carlos Leoni Moreno, MD
Consultant, Department of Transplantation, Mayo Clinic,
Jacksonville, Florida; Instructor in Medicine, Mayo
Clinic College of Medicine and Science
Stacy L. Libricz, PA-​C, MS
Physician Assistant, Department of Critical Care
Medicine, Mayo Clinic Hospital, Phoenix, Arizona;
Instructor in Medicine, Mayo Clinic College of
Medicine and Science
E. Paul Lindell, MD
Consultant, Department of Radiology, Mayo Clinic,
Rochester, Minnesota; Assistant Professor of Radiology,
Mayo Clinic College of Medicine and Science
Karthika R. Linga, MBBS
Fellow in Pulmonary and Critical Care Medicine, Mayo
Clinic School of Graduate Medical Education, Mayo
Clinic College of Medicine and Science, Jacksonville,
Florida
xviii Contributors
Michael J. Link, MD
Consultant, Department of Neurologic Surgery, Mayo
Clinic, Rochester, Minnesota; Professor of Neurosurgery,
Mayo Clinic College of Medicine and Science
David G. Lott, MD
Consultant, Department of Otolaryngology-​Head & Neck
Surgery/​Audiology, Mayo Clinic, Scottsdale, Arizona;
Associate Professor of Otolaryngology, Mayo Clinic
College of Medicine and Science
Amelia A. Lowell, RRT, RCP
Clinical Respiratory Care Specialist, Mayo Clinic
Hospital, Phoenix, Arizona; Assistant Professor of
Anesthesiology, Mayo Clinic College of Medicine and
Science
Philip E. Lowman, MD
Consultant, Department of Critical Care Medicine, Mayo
Clinic, Jacksonville, Florida; Instructor in Medicine,
Mayo Clinic College of Medicine and Science
Patrick R. Maloney, MD
Research Collaborator, Department of Neurologic Surgery,
Mayo Clinic, Rochester, Minnesota
Jennifer M. Martinez-​Thompson, MD
Senior Associate Consultant, Department of Neurology,
Mayo Clinic, Rochester, Minnesota; Assistant Professor
of Neurology, Mayo Clinic College of Medicine and
Science
Nnenna Mbabuike, MD
Fellow in Endovascular Neurosurgery, Mayo Clinic
School of Graduate Medical Education, Mayo Clinic
College of Medicine and Science, Jacksonville, Florida
Present address: University of Pennsylvania Medical
Center, Altoona, Pennsylvania
Barbara L. McComb, MD
Emeritus Associate Professor of Radiology, Mayo Clinic
College of Medicine and Science, Jacksonville, Florida
Diane C. McLaughlin, APRN
Nurse Practitioner, Department of Neurology, Mayo
Clinic, Jacksonville, Florida; Instructor in Neurology,
Mayo Clinic College of Medicine and Science
Margherita Milone, MD, PhD
Consultant, Department of Neurology, Mayo Clinic,
Rochester, Minnesota; Professor of Neurology, Mayo
Clinic College of Medicine and Science
Isabel Mira-​Avendano, MD
Consultant, Division of Pulmonary, Allergy and Sleep
Medicine, Mayo Clinic, Jacksonville, Florida; Assistant
Professor of Medicine, Mayo Clinic College of Medicine
and Science
Kevin G. Moder, MD
Consultant, Division of Rheumatology, Mayo Clinic,
Rochester, Minnesota; Associate Professor of Medicine,
Mayo Clinic College of Medicine and Science
Farouk Mookadam, MB, BCh
Consultant, Department of Cardiovascular Diseases,
Mayo Clinic Hospital, Phoenix, Arizona; Professor of
Medicine, Mayo Clinic College of Medicine and Science
January F. Moore
Special Project Associate, Division of Vascular Surgery,
Mayo Clinic, Jacksonville, Florida
Monica Mordecai, MD
Consultant, Department of Anesthesiology and
Perioperative Medicine, Mayo Clinic, Jacksonville,
Florida; Assistant Professor of Anesthesiology, Mayo
Clinic College of Medicine and Science
Pablo Moreno Franco, MD
Consultant, Department of Transplantation, Mayo Clinic,
Jacksonville, Florida; Assistant Professor of Medicine,
Mayo Clinic College of Medicine and Science
David S. Morris, MD
Consultant, Division of Trauma, Critical Care, & General
Surgery, Mayo Clinic, Rochester, Minnesota
Present address: Intermountain Medical Center,
Murray, Utah
John E. Moss, MD
Consultant, Department of Critical Care Medicine, Mayo
Clinic, Jacksonville, Florida; Assistant Professor of
Medicine, Mayo Clinic College of Medicine and Science
Megan S. Motosue, MD
Resident in Allergy and Immunology, Mayo Clinic School
of Graduate Medical Education, Mayo Clinic College of
Medicine and Science, Rochester, Minnesota
Omar Y. Mousa, MBBS
Fellow in Gastroenterology and Hepatology, Mayo Clinic
School of Graduate Medical Education and Assistant
Professor of Medicine, Mayo Clinic College of Medicine
and Science, Jacksonville, Florida

Andrew W. Murray, MD
Consultant, Department of Anesthesiology and
Perioperative Medicine, Mayo Clinic Hospital, Phoenix,
Arizona; Assistant Professor of Anesthesiology, Mayo
Clinic College of Medicine and Science
Santiago Naranjo-​Sierra, MD
Visiting Research Fellow in Department of Critical Care
Medicine, Mayo Clinic, Jacksonville, Florida
Present address: Hospital Pablo Tobon Uribe, Medellín,
Colombia
Lauren K. Ng Tucker, MD
Consultant, Department of Critical Care Medicine, Mayo
Clinic, Jacksonville, Florida; Assistant Professor of
Medicine, Mayo Clinic College of Medicine and Science
Brandon T. Nokes, MD
Resident in Internal Medicine, Mayo Clinic School of
Graduate Medical Education, Mayo Clinic College of
Medicine and Science, Scottsdale, Arizona
Rahmi Oklu, MD, PhD
Chair, Division of Interventional Radiology, Mayo Clinic
Hospital, Phoenix, Arizona; Professor of Radiology,
Mayo Clinic College of Medicine and Science
James A. Onigkeit, MD
Consultant, Department of Anesthesiology and
Perioperative Medicine, Mayo Clinic, Rochester,
Minnesota; Assistant Professor of Anesthesiology, Mayo
Clinic College of Medicine and Science
Yahaira Ortiz Gonzalez, MD
Resident in Cardiovascular Diseases, Mayo Clinic School
of Graduate Medical Education, Mayo Clinic College of
Medicine and Science, Jacksonville, Florida
Katherine M. Oshel, MD
Consultant, Division of Nephrology and Hypertension,
Mayo Clinic, Jacksonville, Florida; Instructor in
Medicine, Mayo Clinic College of Medicine and Science
Pragnesh P. Parikh, MD
Consultant, Department of Cardiovascular Diseases, Mayo
Clinic, Jacksonville, Florida; Assistant Professor of
Medicine, Mayo Clinic College of Medicine and Science
Myung S. Park, MD, MS
Consultant, Department of Surgery, Mayo Clinic,
Rochester, Minnesota; Associate Professor of Surgery,
Mayo Clinic College of Medicine and Science
Contributors xix
Jeffrey J. Pasternak, MD
Chair, Division of Neuroanesthesia, Mayo Clinic,
Rochester, Minnesota; Associate Professor of
Anesthesiology, Mayo Clinic College of Medicine and
Science
Richard K. Patch III, MD
Consultant, Department of Anesthesiology and
Perioperative Medicine and Division of Critical Care
Medicine, Mayo Clinic, Rochester, Minnesota; Assistant
Professor of Anesthesiology and of Medicine, Mayo
Clinic College of Medicine and Science
Bhavesh M. Patel, MD
Consultant, Department of Critical Care Medicine, Mayo
Clinic Hospital, Phoenix, Arizona; Assistant Professor
of Anesthesiology, of Medicine, and of Neurology, Mayo
Clinic College of Medicine and Science
Neal M. Patel, MD
Consultant, Department of Pulmonary and Critical Care
Medicine, Mayo Clinic, Jacksonville, Florida; Instructor in
Medicine, Mayo Clinic College of Medicine and Science
Mark A. Pichelmann, MD
Consultant, Department of Neurologic Surgery, Mayo
Clinic, Jacksonville, Florida; Assistant Professor of
Neurosurgery, Mayo Clinic College of Medicine and
Science
Michael R. Pichler, MD
Fellow in Cerebrovascular Neurology, Mayo Clinic School
of Graduate Medical Education, Mayo Clinic College of
Medicine and Science, Rochester, Minnesota
Sean J. Pittock, MD
Consultant, Department of Neurology, Mayo Clinic,
Rochester, Minnesota; Professor of Neurology, Mayo
Clinic College of Medicine and Science
Michael A. Pizzi, DO, PhD
Fellow in Critical Care Medicine, Mayo Clinic School of
Graduate Medical Education, Mayo Clinic College of
Medicine and Science, Jacksonville, Florida
Alyx B. Porter, MD
Consultant, Department of Neurology, Mayo Clinic
Hospital, Phoenix, Arizona; Assistant Professor of
Neurology, Mayo Clinic College of Medicine and
Science
xx Contributors
Rajiv K. Pruthi, MBBS
Consultant, Divisions of Hematology, Hematopathology,
and Laboratory Genetics and Genomics, Mayo Clinic,
Rochester, Minnesota; Associate Professor of Medicine,
Mayo Clinic College of Medicine and Science
Juan N. Pulido, MD
Consultant, Department of Anesthesiology, Mayo Clinic,
Rochester, Minnesota
Present address: Private practice, Seattle, Washington
Surakit Pungpapong, MD
Consultant, Department of Gastroenterology and
Hepatology, Mayo Clinic, Jacksonville, Florida;
Associate Professor of Medicine, Mayo Clinic College of
Medicine and Science
Harish Ramakrishna, MD
Consultant, Department of Anesthesiology and
Perioperative Medicine, Mayo Clinic Hospital, Phoenix,
Arizona; Professor of Anesthesiology, Mayo Clinic
College of Medicine and Science
Robert A. Ratzlaff, DO
Consultant, Departments of Critical Care Medicine and
Anesthesiology and Perioperative Medicine, Mayo
Clinic, Jacksonville, Florida; Assistant Professor of
Anesthesiology, Mayo Clinic College of Medicine and
Science
J. Ross Renew, MD
Consultant, Department of Anesthesiology and
Perioperative Medicine, Mayo Clinic, Jacksonville,
Florida; Assistant Professor of Anesthesiology, Mayo
Clinic College of Medicine and Science
Kevin J. Renfree, MD
Consultant, Department of Orthopedic Surgery, Mayo
Clinic Hospital, Phoenix, Arizona; Associate Professor
of Orthopedics, Mayo Clinic College of Medicine and
Science
Juan G. Ripoll Sanz, MD
Resident in Anesthesiology, Mayo Clinic School of
Graduate Medical Education, Mayo Clinic College of
Medicine and Science, Jacksonville, Florida
Matthew J. Ritter, MD
Consultant, Department of Anesthesiology and
Perioperative Medicine, Mayo Clinic, Rochester,
Minnesota; Assistant Professor of Anesthesiology, Mayo
Clinic College of Medicine and Science
Mariela Rivera, MD
Consultant, Department of Surgery, Mayo Clinic,
Rochester, Minnesota; Assistant Professor of Surgery,
Mayo Clinic College of Medicine and Science
Christopher P. Robinson, DO, MS
Fellow in Neurocritical Care, Mayo Clinic School of
Graduate Medical Education, Mayo Clinic College of
Medicine and Science, Rochester, Minnesota
Present address: Department of Neurology and
Neurocritical Care Division, University of Florida,
Gainesville, Florida
Maisha T. Robinson, MD
Consultant, Department of Neurology, Mayo Clinic,
Jacksonville, Florida; Assistant Professor of Neurology,
Mayo Clinic College of Medicine and Science
Mark N. Rubin, MD
Fellow in Vascular Neurology, Mayo Clinic School of
Graduate Medical Education, Mayo Clinic College of
Medicine and Science, Scottsdale, Arizona
Present address: North Shore Neurological Institute,
Glenview, Illinois
Carl A. Ruthman, MD
Resident in Pulmonary and Critical Care Medicine, Mayo
Clinic School of Graduate Medical Education, Mayo Clinic
College of Medicine and Science, Jacksonville, Florida
Arzoo Sadiqi, BS
Research Trainee, Department of Cardiovascular and
Thoracic Surgery, Mayo Clinic Hospital, Phoenix,
Arizona
Ankit Sakhuja, MBBS
Fellow in Critical Care Medicine, Mayo Clinic School of
Graduate Medical Education, and Assistant Professor
of Medicine, Mayo Clinic College of Medicine and
Science, Rochester, Minnesota
Carlo Salvarani, MD
Department of Rheumatology, Azienda Ospedaliera
Arcispedale Sante Maria Nuova, Reggio Emilia, Italy
Mithun Sattur, MBBS
Resident in Neurologic Surgery, Mayo Clinic School of
Graduate Medical Education, Mayo Clinic College of
Medicine and Science, Scottsdale, Arizona
Gregory J. Schears, MD
Consultant, Department of Anesthesiology and
Perioperative Medicine, Mayo Clinic, Rochester,
Minnesota; Professor of Anesthesiology, Mayo Clinic
College of Medicine and Science

J. William Schleifer, MD
Fellow in Cardiovascular Diseases, Mayo Clinic School
of Graduate Medical Education, Mayo Clinic College of
Medicine and Science, Scottsdale, Arizona
Present address: Department of Internal Medicine,
Division of Cardiology, University of Nebraska Medical
Center, Omaha, Nebraska
Beth A. Schueler, PhD
Consultant, Department of Radiology, Mayo Clinic,
Rochester, Minnesota; Associate Professor of Radiology
and Professor of Medical Physics, Mayo Clinic College
of Medicine and Science
David M. Sella, MD
Consultant, Department of Radiology, Mayo Clinic,
Jacksonville, Florida; Assistant Professor of Radiology,
Mayo Clinic College of Medicine and Science
Ayan Sen, MD
Chair, Department of Critical Care Medicine, Mayo
Clinic Hospital, Phoenix, Arizona; Assistant Professor
of Emergency Medicine and of Medicine, Mayo Clinic
College of Medicine and Science
Eslam Shosha, MB, BCh
Research Fellow in Neurology, Mayo Clinic School of
Graduate Medical Education, Mayo Clinic College of
Medicine and Science, Rochester, Minnesota
Jason L. Siegel, MD
Senior Associate Consultant, Department of Neurology,
Mayo Clinic, Jacksonville, Florida; Assistant Professor
of Neurology, Mayo Clinic College of Medicine and
Science
Charles R. Sims III, MD
Senior Associate Consultant, Department of
Anesthesiology and Perioperative Medicine,
Mayo Clinic, Rochester, Minnesota; Instructor in
Anesthesiology, Mayo Clinic College of Medicine and
Science
Ramachandra R. Sista, MD
Senior Associate Consultant, Division of Pulmonary
Medicine, Mayo Clinic, Scottsdale, Arizona
Aurelia A. Smith, MD
Fellow in Multiple Sclerosis and Neuroimmunology,
Mayo Clinic School of Graduate Medical Education,
Mayo Clinic College of Medicine and Science,
Rochester, Minnesota
Contributors xxi
Christina C. Smith, APRN
Nurse Practitioner, Department of Neurologic Surgery,
Mayo Clinic, Jacksonville, Florida; Assistant Professor
of Neurosurgery, Mayo Clinic College of Medicine and
Science
David A. Sotello Aviles, MD
Fellow in Infectious Diseases, Mayo Clinic School of
Graduate Medical Education, Mayo Clinic College of
Medicine and Science, Jacksonville, Florida
Present address: Texas Tech University Health Sciences
Center, Lubbock, Texas
Nathan P. Staff, MD, PhD
Consultant, Department of Neurology, Mayo Clinic,
Rochester, Minnesota; Associate Professor of Neurology,
Mayo Clinic College of Medicine and Science
John A. Stauffer, MD
Consultant, Department of Surgery, Mayo Clinic,
Jacksonville, Florida; Associate Professor of Surgery,
Mayo Clinic College of Medicine and Science
Glenn M. Sturchio, PhD
Consultant, Department of Radiology, Mayo Clinic,
Jacksonville, Florida; Assistant Professor of Physiology,
Mayo Clinic College of Medicine and Science
Matthew D. Sztajnkrycer, MD, PhD
Consultant, Department of Emergency Medicine, Mayo
Clinic, Rochester, Minnesota; Professor of Emergency
Medicine, Mayo Clinic College of Medicine and Science
Rabih G. Tawk, MD
Consultant, Department of Neurologic Surgery, Mayo
Clinic, Jacksonville, Florida; Associate Professor of
Neurosurgery, Mayo Clinic College of Medicine and
Science
Jennifer A. Tracy, MD
Consultant, Department of Neurology, Mayo Clinic,
Rochester, Minnesota; Assistant Professor of Neurology,
Mayo Clinic College of Medicine and Science
Levan Tsamalaidze, MD
Visiting Research Fellow in Surgery, Mayo Clinic School
of Graduate Medical Education, Mayo Clinic College of
Medicine and Science, Jacksonville, Florida
Jamie J. Van Gompel, MD
Consultant, Department of Neurologic Surgery, Mayo
Clinic, Rochester, Minnesota; Associate Professor of
Neurosurgery and Otorhinolaryngology, Mayo Clinic
College of Medicine and Science
xxii Contributors
Carla P. Venegas-​Borsellino, MD
Senior Associate Consultant, Department of Critical Care
Medicine, Mayo Clinic, Jacksonville, Florida
K. L. Venkatachalam, MD
Consultant, Department of Cardiovascular Diseases, Mayo
Clinic, Jacksonville, Florida; Associate Professor of
Medicine, Mayo Clinic College of Medicine and Science
Prakash Vishnu, MBBS
Senior Associate Consultant, Division of Hematology and
Oncology, Mayo Clinic, Jacksonville, Florida; Assistant
Professor of Medicine, Mayo Clinic College of Medicine
and Science
Angela N. Vizzini, RDN, LD/​N
Director, Clinical Nutrition Services, Mayo Clinic,
Jacksonville, Florida; Assistant Professor of Nutrition,
Mayo Clinic College of Medicine and Science
Gerald W. Volcheck, MD
Chair, Division of Allergic Diseases, Mayo Clinic,
Rochester, Minnesota; Associate Professor of Medicine,
Mayo Clinic College of Medicine and Science
Hani M. Wadei, MD
Senior Associate Consultant, Division of Neurology
and Hypertension, Mayo Clinic, Jacksonville, Florida;
Associate Professor of Medicine, Mayo Clinic College of
Medicine and Science
Clarence B. Watridge, MD
Associate Consultant, Department of Neurologic Surgery,
Mayo Clinic, Jacksonville, Florida; Associate Professor
of Neurosurgery, Mayo Clinic College of Medicine and
Science
Present address: Ponte Vedra Beach, Florida
Brian G. Weinshenker, MD
Consultant, Department of Neurology, Mayo Clinic,
Rochester, Minnesota; Professor of Neurology, Mayo
Clinic College of Medicine and Science
Matthew E. Welz, MS
Research Technologist for Neurosurgery, Mayo Clinic
Hospital, Phoenix, Arizona
Robert E. Wharen Jr, MD
Consultant, Department of Neurologic Surgery, Mayo
Clinic, Jacksonville, Florida; Professor of Neurosurgery,
Mayo Clinic College of Medicine and Science
Eelco F. M. Wijdicks, MD, PhD
Chair, Division of Critical Care Neurology, Mayo Clinic,
Rochester, Minnesota; Professor of Neurology, Mayo
Clinic College of Medicine and Science
Nicholas D. Will, MD
Resident in Anesthesiology, Mayo Clinic School of
Graduate Medical Education, Mayo Clinic College of
Medicine and Science, Rochester, Minnesota
Jose C. Yataco, MD
Senior Associate Consultant, Department of Critical Care
Medicine, Mayo Clinic, Jacksonville, Florida
Present address: Memphis, Tennessee
Joseph Zachariah, MD
Fellow in Critical Care Neurology, Mayo Clinic School
of Graduate Medical Education, Mayo Clinic College of
Medicine and Science, Rochester, Minnesota
Present address: Spectrum Hospital, Grand Rapids,
Michigan
Ali A. Zaied, MD
Senior Associate Consultant, Department of Pulmonary,
Critical Care, and Sleep Medicine, Mayo Clinic Health
System—​Northwest Wisconsin, Eau Claire, Wisconsin
Yuzana Zaw, MBBS
Fellow in Nephrology and Hypertension, Mayo Clinic
School of Graduate Education, Mayo Clinic College of
Medicine and Science, Scottsdale, Arizon
 Section

Fundamentals I
of Critical Care
 Respiratory Physiology in Critical Illness
1 MINKYUNG KWON, MD; JOSE L. DIAZ-​G OMEZ, MD
Goals
• Describe the basic lung volumes and capacities and the
fundamentals of breathing mechanics.
• Describe airway resistance, lung compliance, and
thoracic wall compliance as major components of
pulmonary ventilation.
• Distinguish restrictive physiology from obstructive
physiology.
• Describe common patterns of increased work of
breathing and their associated factors.
• Describe the mechanisms of hypoxemia.
Introduction
The fundamental pillars of critical care medicine are the
management of the lungs, heart, and kidneys and the pro-
vision of nutritional support. The practice of critical care
medicine is often defined by abnormal respiratory physiol-
ogy and requires detailed knowledge of lung mechanics,
the mechanism of hypoxia, and the control of breathing.
Therefore, laboratory assessment in pulmonary disorders
is useful (Table 1.1; Box 1.1). Before the lungs can enable
gas exchange, air must move from the upper airway down
a series of branching small airways and reach the alveoli.
In the walls of the alveoli, capillaries form a dense network
and receive blood flowing from the pulmonary artery (from
the right ventricle) before it flows to the pulmonary vein
(and then to the left atrium). Between the capillary net-
work and the alveoli lies a thin blood-​gas barrier through
which oxygen (O2) and carbon dioxide (CO2) move, chiefly
by simple diffusion.
At rest, inspiration and expiration generate tidal volume.
After the tidal volume is exhaled, further forceful expira-
tion generates expiratory reserve volume. The volume of
air remaining in the lung is the residual volume. After rest-
ing inspiration, forceful inspiration to maximal capacity
generates inspiratory reserve volume. Volume that can be
generated by maximal inspiration to maximal expiration is
called vital capacity (Figure 1.1). Normal vital capacity is
around 3 to 5 L, and normal tidal volume is approximately
500 mL. Total minute ventilation is the product of the tidal
volume times the respiratory rate per minute.
Mechanics of Breathing
During rest, inspiration is active and expiration is pas-
sive. The most important muscle of inspiration is the dia-
phragm. When it contracts, the abdominal contents are
forced downward and forward, and the vertical dimension
of the chest cavity is increased. The external thoracic mus-
cles make the rib margins lift and move out, increasing the
transverse diameter of the thorax during forceful inspira-
tion. At functional residual capacity, the rib cage acts as
an outward force that generates negative pleural pressure.
At end-​expiration, the diaphragm prevents the abdominal
organs from encroaching on the thoracic space and influ-
encing the lung in the supine or prone position. During
spontaneous breathing, these muscles expand the lung,
creating even more negative intrapleural pressure and
resulting in inspiration. During mechanical ventilation,
positive pressure from the ventilator expands the chest
wall, but the intrapleural pressure is positive.
Airway Resistance and Lung Compliance
Pulmonary ventilation and the work of breathing depend
on the airway resistance and compliance of the lungs and
the thoracic cage. Airway resistance is the pressure differ-
ence between the alveoli and the mouth divided by the
flow rate. Most airway resistance is produced in medium-​
sized bronchi rather than in small bronchioles. The bron-
chial smooth muscles, located in medium-​sized bronchi,
are innervated by the autonomic nervous system. Stimu­
lation of β-​
adrenergic receptors causes bronchodilation;
3
4 Section I. Fundamentals of Critical Care
Table 1.1 • Useful Laboratory Values in Pulmonary Disorders
Laboratory Value
Arterial blood gas
Hemoglobin, glucose, urea nitrogen,
creatinine, electrolytes, calcium,
phosphorus, thyrotropin
Plasma brain natriuretic peptide
Serum bicarbonate
Alpha1-​antitrypsin
Eosinophils
Procalcitonin
C-​reactive protein
Rheumatologic serology (ANA, RF,
antisynthetase antibodies, CK, aldolase,
SS-​A/​SS-​B, Scl-​70)
Anti-​GBM antibody, ANCA
Polycythemia
Abbreviations: ANA, antinuclear antibody; ANCA, antineutrophil cytoplasmic autoantibody; CK, creatine kinase; COPD,
chronic obstructive pulmonary disease; GBM, glomerular basement membrane; RF, rheumatoid factor.
parasympathetic activity causes bronchoconstriction and
increased airway resistance. Lung volume has an impor-
tant effect on airway resistance: As lung volume decreases,
airway resistance increases. Small airways may even close
completely at low lung volumes.
Lung compliance is defined by the volume change
per unit pressure change. Furthermore, it has 2 compo-
nents: static and dynamic lung compliance.
Static Lung Compliance
Lung tends to collapse at any degree of pulmonary infla-
tion, whereas the chest wall tends to recoil outward. This
natural trend represents compliance of both the lung and
the chest wall in static pressure-​volume curves (Figure 1.2).
Lung compliance changes with various nonparenchymal
conditions. Patients with obesity, ascites, or intra-​abdominal
hypertension have a stiffer chest wall; the lung and total
respiratory system compliance curves shift down and right-
ward. In contrast, massive aspiration, alveolar edema, or
fibrotic lung disease decreases the lung and total respiratory
system compliance. In a patient with acute respiratory dis-
tress syndrome (ARDS), lung volume is further reduced and
compliance is decreased. In addition, the overall volume of
tissue and chest wall may be affected by illness, so that in
ARDS the net effect on pleural pressure is unpredictable.
Static airway pressure of the respiratory system corre-
lates with plateau pressure during mechanical ventilation.
Moreover, the plateau pressure also represents the intra-​
alveolar pressure during use of an end-​ inspiratory hold.
Significance in Pulmonary Disorders
Hypoxia, hypercapnia, acidosis, alkalosis
Nonpulmonary causes of dyspnea
Pulmonary edema due to heart failure
Chronic hypercapnia in COPD or obesity-​hypoventilation
syndrome
Alpha1-​antitrypsin deficiency, obstructive pattern
Allergic asthma, parasitic infection, drug reaction,
syndromes of pulmonary infiltrates with eosinophilia
Bacterial pneumonia
Pneumonia
Interstitial lung disease
Pulmonary hemorrhage
Recurrent hypoventilation or obstructive sleep apnea–​
associated hypoxemia
In passive ventilation, such as when patients are deeply
sedated or paralyzed, the chest wall compliance curve
tracks the pleural pressure. Thus, pressure measured with
an esophageal balloon can be used to approximate these
measures.
Dynamic Lung Compliance
Dynamic pressure-​volume curves during inspiration and
expiration exhibit a different pattern. This phenomenon,
hysteresis, can be explained by surface tension variation
at the alveolar air-​fluid interface during inspiration and
expiration. Pulmonary surfactant, a natural substance
produced by type II epithelial cells in the lung, reduces the
surface tension of the fluid layer lining the alveoli. During
inspiration, alveolar surface tension increases because
pulmonary surfactant spreads over a wider alveolar surface.
The reverse occurs during expiration, when pulmonary
surfactant condenses over a smaller alveolar surface.
Work of Breathing
Work is required to move the lung and the chest wall. The
area under the dynamic pressure-​volume curve of the lungs
is used to estimate the work of breathing (WOB). During
inspiration, the elastic WOB is the work needed to over-
come elastic forces of the chest wall, lung parenchyma,
and alveolar surface tension. In addition, resistive WOB is
needed during inspiration to overcome tissue and airway
resistance. During expiration, only resistive WOB is needed.
Hence, increased WOB occurs with higher breathing rates

Box 1.1 • Interpretation of Blood Gas Data
Step 1. Determine whether the primary condition is
acidemia (pH <7.35) or alkalemia (pH >7.45).
Step 2. Determine whether the disorder is metabolic
(pH and Paco2 changes are in the same direction)
or respiratory (pH and Paco2 changes are in the
opposite direction).
Step 3. Determine whether compensation is adequate.
Metabolic acidosis: Paco2 = (1.5 [HCO3–​]) +
8 (Correction ± 2)
Acute respiratory acidosis: Increase in [HCO3–​] =
∆Paco2/​10 (Correction ± 3)
Chronic respiratory acidosis: Increase in [HCO3–​] =
3.5 (∆Paco2/​10)
Metabolic alkalosis: Increase in Paco2 =
40 + 0.6 (∆HCO3–​)
Acute respiratory alkalosis: Decrease in [HCO3–​] =
2 (∆Paco2/​10)
Chronic respiratory alkalosis: Decrease in [HCO3–​] =
5 (∆Paco2/​10) to 7 (∆Paco2/​10)
Step 4. Calculate the anion gap (AG):
AG = [Na + ] − [Cl − ] + [HCO3− ] − 12 ± 2.
If the AG is elevated (>12), calculate the osmolar
(OSM) gap (normal is <10):
OSM Gap = Measured OSM − (2 [Na + ])
− (Glucose / 18 − SUN / 2.8).
Step 5. If an AG is present, calculate the
delta-​delta ratio:
Delta − Delta Ratio = ∆AG / ∆ [HCO3− ].
If <1, a concurrent non-​AG metabolic acidosis is likely
present. If >2, a concurrent metabolic alkalosis is
likely present.
Abbreviations: Cl–​, chloride; ∆, change in; HCO3–​, bicarbonate;
Na+, sodium; SUN, serum urea nitrogen.
Data from Kaufman DA. Interpretation of arterial blood gases
(ABGs) [Internet]. New York: American Thoracic Society.
c2017 [cited 2017 Sep 5]. Available from: http://​www.thoracic.
org/​professionals/​clinical-​resources/​critical-​care/​clinical-​
education/​abgs.php.
and faster flow rates. With a larger tidal volume, the elastic
WOB is larger. Patients with stiff lungs tend to take small
rapid breaths, and patients with severe airway obstruction
breathe more slowly.
Closing Capacity
Lung cannot be completely empty because of airflow-​
limiting segments in the small airways. Hence, expiration
Chapter 1. Respiratory Physiology in Critical Illness 5
RV RV
FRC Spirogram
ERV
TLC
TV
VC
IC
IRV
Inspiration
Figure 1.1. Standard Lung Volumes and Capacities. After
resting inspiration, forceful inspiration to maximal capacity
generates inspiratory reserve volume. The volume that can
be generated by maximal inspiration to maximal expiration
is the vital capacity (VC). ERV indicates expiratory reserve
volume; FRC, functional residual capacity; IC, inspiratory
capacity; IRV, inspiratory reserve volume; RV, residual vol-
ume; TLC, total lung capacity; TV, tidal volume.
after development of airflow-​ limiting segments is effort
independent. What remains in the lungs when small air-
ways start to close is called the closing capacity. Patients
with airway disease (eg, asthma, chronic obstructive pul-
monary disease [COPD], or cystic fibrosis) are predisposed
to having a higher closing capacity, leaving a large residual
volume. The volume of air expired between closing capac-
ity and residual volume is called the closing volume.
Changes in Lung Mechanics in Acute
Respiratory Failure
In patients who are critically ill with respiratory failure, 2
types of physiologic derangement occur: obstructive and
restrictive.
Obstructive Physiology
In obstructive lung diseases, pulmonary compliance is
normal or increased, but airway resistance is increased,
especially during expiration. As mentioned above, normal
expiration is passive. However, with obstructive physiol-
ogy, such as in patients with asthma or COPD, extra work
is needed for adequate expiration.
Restrictive Physiology
Pneumonia and ARDS are examples of diseases with
restrictive physiology in which compliance of the lung,
or chest wall (or both) is decreased. The static pressure-​
volume curve of the lungs or chest wall (or both) is
shifted rightward. The transpulmonary pressure (alveolar
pressure minus pleural pressure) indicates the pressure
across the alveolus and therefore across the pulmonary
capillary bed. Decreased compliance of the lungs requires
6 Section I. Fundamentals of Critical Care

Total lung
capacity

6
Total lung
Lung Volume, L
compliance

4 Chest
compliance
Functional
residual
capacity
Lung compliance
2 Residual
volume

−20 −15 −10 −5 0 5 10 15 20

Transmural Pressure, cm H2O

Figure 1.2. Compliance Curves. Compliance curves for lung and chest are shown along with total lung compliance. At
small lung volumes, the negative transmural pressure of chest compliance indicates the chest wall’s natural tendency to
spring outward and expand. Lung compliance is high (ie, the slope of the curve is steep) at low lung volumes and decreases
as the lung expands. Functional residual capacity is the summation of transmural pressures generated by the chest wall and
lung when they are equal and opposing.

increased transpulmonary pressure for tidal inspira-
tion. Further, the elastic WOB required for inspiration is
increased and is usually compensated for by rapid shal-
low breathing. The intrinsic causes of restrictive physiol-
ogy are interstitial lung diseases, pneumonia, and ARDS,
and the extrinsic causes include respiratory muscle weak-
ness, chest deformities, cardiomegaly, hemothorax, pneu-
mothorax, empyema, and pleural effusion or thickening.
Respiratory Mechanics Affecting Circulation
Higher transpulmonary pressure leads to greater imped-
ance to right ventricular outflow through the pulmonary
vascular tree. A high right ventricular afterload decreases
right ventricular output. Right ventricular preload depends
on the degree of intrapleural pressure. With mechani-
cal ventilation, intrapleural pressure increases during
inspiration, further decreasing right ventricular preload.
A stiffened chest wall increases intrapleural pressure,
decreasing right ventricular preload further. Use of posi-
tive end-​expiratory pressure and the prone position can
also decrease right ventricular preload by increasing intra-
pleural pressure and stiffening the chest wall, respectively.
Neurogenic Pulmonary Edema
Acute central nervous system events such as acute head
injury, seizure, tumors, and intracranial or subarachnoid
hemorrhages can induce acute pulmonary edema within
minutes or as late as 12 to 24 hours after the event. Besides
having acute shortness of breath from pulmonary edema,
patients may have fever, tachycardia, hypertension, and
leukocytosis from sympathetic surge. The proposed
pathophysiology is that the neuronal damage increases
sympathetic tone with a catecholamine surge, which
subsequently increases systemic vascular resistance and
decreases left ventricular contractility, causing alveo-
lar capillary leakage and eventually leading to a severe
increase in intracranial pressure. Management is primarily
supportive. α-​Blockers can be used, and excessive diuresis
should be avoided. The key is to treat the underlying cen-
tral nervous system insult and the increased intracranial
pressure.
Physiology of Hypoxia
Changes in Diffusing Capacity
in Critical Illness
Gases move across the blood-​gas barrier by diffusion.
The O2 diffusion reserve of the normal lung is enor-
mous. However, in patients with alveolar hypoxia and
thickening of the blood-​gas barrier, O2 diffusion is
challenged.

Pulmonary Vascular Resistance
Pulmonary vascular resistance is usually small and can fur-
ther decrease by recruitment and distention of capillaries.
Pulmonary vascular resistance increases at high and low
lung volumes. Hypoxia, serotonin, histamine, thrombox-
ane A2, and endothelin constrict pulmonary vasculature.
Hypoxia constricts small pulmonary arteries probably by
the direct effect of the low Po2 on vascular smooth muscle.
This mechanism, called hypoxic pulmonary vasoconstric-
tion, directs blood flow away from poorly ventilated areas
of the diseased lung in the adult.
Nitric oxide, phophodiesterase inhibitors, calcium chan-
nel blockers, and prostacyclin dilate pulmonary vascula-
ture. Inhaled pulmonary vasodilators such as nitric oxide
or inhaled phophodiesterase inhibitors reduce vascular
tone locally in the well-​ventilated regions, causing a shift in
blood flow away from unventilated regions toward better-​
ventilated regions. Inhaled nitric oxide has been shown
to reduce shunting and improve arterial oxygenation in
patients with ARDS. Use of intravenous pulmonary vaso-
dilators, such as prostacyclin, does not change Pao2 much
in patients with ARDS and pulmonary hypertension, prob-
ably because of the mixed effects of reduced pulmonary
arterial pressure, increased cardiac output, and worsened
intrapulmonary shunt.
In contrast, systemic vasodilators can produce hypox-
emia. Systemic vasodilators increase cardiac output, impair
hypoxic vasoconstriction in both well-​ventilated and poorly
ventilated pulmonary vasculature, and change intracardiac
pressure or pulmonary arterial pressure, thereby altering
the distribution of pulmonary blood flow. Nitroprusside,
hydralazine, nitroglycerine, nifedipine, dopamine, and
dobutamine can produce this effect.
Physiology of Hypoxemia
The 5 mechanisms of hypoxemia are hypoventilation,
perfusion (V̇ /​Q̇ )
diffusion limitation, shunt, ventilation-​
mismatch, and low inspiratory O2 pressure.
Hypoventilation
Hypoventilation always increases the alveolar Pco2,
which leads to lower alveolar Pao2 unless additional O2 is
inspired. The treatment is to provide additional O2.
Diffusion Limitation
Diffusion of gases is limited when the blood-​gas barrier is
thickened.
Shunt
This refers to blood that enters the arterial system with-
out going through ventilated areas of the lung. Hypoxemia
resulting from a shunt does not improve after adding O2.
If the shunt is caused by mixed venous blood, its size
can be calculated from the shunt equation. Shunt is an
Chapter 1. Respiratory Physiology in Critical Illness 7
important cause of hypoxemia in patients with ARDS and
pneumonia.
V̇/​Q̇ Mismatch
̇ ̇ mismatch is the most common cause of hypoxemia,
V/Q
especially in the perioperative period after general
anesthesia. A patient with V/Q ̇ ̇ mismatch has a problem
with either ventilation (air going in and out of the lungs)
or perfusion (O2 and CO2 diffusion at the alveoli and the
pulmonary arteries). V/Q ̇ ̇ ratios compare the amount of air
reaching the alveoli to the amount of blood reaching the
alveoli. The V/Q ̇ ̇ ratio describes the gas exchange in any
single lung unit. Regional differences in the V/Q ̇ ̇ ratio in
the upright lung cause regional changes in gas exchange.
The normal V/Q ̇ ̇ ratio is about 1, and decreases or increases
in the ratio indicate changes in the alveolar gas and end-​
capillary blood composition. V/Q ̇ ̇ mismatch impairs the
uptake or elimination of all gases by the lung. Although
CO2 elimination is impaired by V/Q ̇ ̇ mismatch, it can be
corrected by increasing the ventilation to the alveoli. In
contrast, hypoxemia resulting from V/Q ̇ ̇ mismatch cannot
be resolved by increased ventilation. The difference in the
CO2 and O2 responses results from their own dissociation
curve characteristics. Clinically, regions with low or high
̇ ̇ ratios cause hypoxemia, impaired CO elimination,
V/Q
2
and increased WOB in COPD patients.
Low Inspiratory O2 Pressure
Low inspiratory O2 pressure causes hypoxemia even
with a normal alveolar-​ arterial difference in the partial
pressure of O2.
Changes in Dead Space in Critical Illness
Dead space is the volume (not a space) that is ventilated
but does not participate in perfusion. There are 2 types
of dead space: anatomical dead space and physiologic
dead space. Anatomical dead space, normally about 150
mL, is the volume of the conducting airways. Physiologic
dead space is the volume of gas that does not eliminate
CO2. Because physiologic dead space includes airway and
alveolar dead space, it is increased in many lung diseases.
Furthermore, increased V/Q ̇ ̇ mismatch and shunt are the
most likely contributors to increased dead space in ARDS.
Supplemental O2 and CO2 Retention
in COPD Patients
High fractional supplemental O2 may cause CO2 retention
in COPD patients because supplemental O2 may increase
the partial pressure of O2 in the alveoli (Pao2) in lung
units with a low V/Q ̇ ̇ ratio, inhibiting regional hypoxic
pulmonary vasoconstriction and increasing blood flow to
these units. Consequently, blood is diverted away from
better-​
ventilated regions, converting them to lung units
with high V/Q̇ ̇ ratios, which increases wasted ventilation.
8 Section I. Fundamentals of Critical Care
Supplemental O2 may cause CO2 retention in COPD
patients through a second mechanism, the Haldane effect.
In this phenomenon, increased Pao2 decreases the bind-
ing of both hydrogen ions and CO2 to hemoglobin, thereby
increasing the amount of physically dissolved CO2 and
Pco2. The decreased respiratory drive from low Paco2 is a
less likely cause.
In clinical practice, COPD patients who receive supple-
mental O2 to maintain normal Pao2 do not retain clinically
significant levels of CO2. The use of noninvasive mechani-
cal ventilation can alleviate Co2 retention while providing
enough O2 in COPD patients.
Indexes of Oxygenation
Of the several indexes of oxygenation that are used, 2
are discussed here: the alveoli-​arterial (A-​a) gradient and
the ratio of Pao2 to the fraction of inspired O2 (Fio2). Both
are O2 tension–​ based indexes (calculated from Po2) as
opposed to a concentration-​based index, such as the shunt
index (calculated from the arterial O2 content). The A-​a
gradient and the Pao2/​Fio2 ratio can be affected by the fol-
lowing factors: a shunt, V̇/Q̇ mismatch, congenital heart
disease, cardiac output, Fio2, temperature, low Pco2, and
O2 extraction.
A-​a Gradient
The A-​a gradient is the gradient between an alveolus and
the arterial blood, expressed in millimeters of mercury.
Pao2 is calculated with the following simplified formula
(using the sea level barometric pressure of 760 mm Hg,
water vapor pressure at 37°C of 47 mm Hg, and a respira-
tory quotient of 0.8-​0.9):
PAO2 = (FIO2 × 713) – (PaCO2 × 1.25).
Subsequently, the A-​a gradient is calculated as follows:
A-a Gradient = PAO2 – PaO2 .
The normal value of the A-​a gradient is 7 mm Hg in young
patients and 14 mm Hg in elderly patients at 21% Fio2.
The A-​a gradient is increased with a higher Fio2, V̇/Q̇ ̇ mis-
match, a diffusion defect, an intracardiac shunt, or an
increased O2 extraction ratio. A high Paco2 due to alveolar
hypoventilation results in a normal A-​a gradient, and this
is the most useful situation for using the A-​a gradient.
Pao2/​Fio2 Ratio
At sea level, the Pao2/​Fio2 ratio is normally more than
500 mm Hg; that is, Pao2 should exceed Fio2 by 500 times in
normal lung. The Pao2/​Fio2 ratio is used for risk stratification,
such as in the Berlin definition of ARDS (eg, <100 indicates
severe ARDS). The Pao2/​Fio2 ratio, in contrast to the A-​a gra-
dient, cannot be used to distinguish hypoxemia due to alve-
olar hypoventilation from hypoxemia due to other causes.
Like the A-​a gradient, the Pao2/​Fio2 ratio is dependent on
Fio2 and is highly dependent on the O2 extraction ratio.
Summary
• Pulmonary ventilation depends on airway resistance
and the compliance of the lungs and the thoracic cage.
• Lung compliance is defined by the volume change
per unit pressure change. Massive aspiration, alveolar
edema, ARDS, or fibrotic lung disease decreases lung
compliance.
• A higher breathing rate is accompanied by faster flow
rates and larger viscous WOB. With a larger tidal
volume, the elastic work is larger.
• Restrictive physiology can occur in patients with
pneumonia or ARDS. In these conditions, the
compliance of the lung or chest wall (or both) is
decreased.
• With obstructive physiology, airway resistance is
increased, especially during expiration.
• If transmural pressure for the lungs is zero, the
system is neither inflating nor deflating. For a given
ventilator volume, the lateral distance between plateau
pressure and the chest wall compliance curve is the
transpulmonary pressure.
• The 5 mechanisms of hypoxemia are hypoventilation,
̇ ̇ mismatch, and low
diffusion limitation, shunt, V/Q
inspiratory O2 pressure.
• Dead space is the volume that is ventilated but does
not participate in perfusion.
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 2 Mechanical Ventilation: Basic Modes
AMELIA A. LOWELL, RRT, RCP
Goals
• Understand the basic physiology of mechanical
ventilation.
• Discuss the basic modes of mechanical ventilation.
• Discuss safety and comfort measures with mechanical
ventilation settings.
Introduction
The main goal of mechanical ventilation is to unload the
respiratory muscles to facilitate oxygenation and ventila-
tion. This is accomplished by providing a minute venti-
lation (V̇ e) (respiratory rate × tidal volume [Vt]) that will
result in adequate alveolar ventilation coupled with sup-
plemental oxygen and a mean airway pressure that will
result in adequate arterial oxygenation.
Physiology of Mechanical
Breathing Assistance
The respiratory equation of motion demonstrates that the
work or negative pressure that the respiratory apparatus
must generate to displace volume from the atmosphere
into the lungs (Pmusc) is determined by the resistance to
gas flow and the compliance of the lungs.
Volume
Pmusc = + (Resistance × Flow)
Compliance
Negative Pressure Ventilation (Normal
Breathing)
When circulating hydrogen ion levels (whose major deter-
minant is carbon dioxide) are elevated in the brain stem
(medulla oblongata central chemoreceptor trigger zone),
they trigger respiratory drive by means of the phrenic and
10
intercostal nerves, resulting in contraction of the diaphragm
and intercostal muscles. The diaphragm contracts down-
ward into the abdominal cavity and, together with the acti-
vated intercostal muscles, pulls the chest wall, pleural cavity,
and alveoli open. When the lungs recoil, alveolar pressure
increases (compared to the pressure at the mouth), the pres-
sure gradient is reversed, and gas flows out of the lungs.
Positive Pressure Ventilation
Positive pressure ventilation (PPV) provides ventila-
tor support to a patient by creating a pressure gradient
between the ventilator circuit and the patient’s lungs. The
respiratory equation of motion can be modified to include
the work done by the ventilator (Pvent):
Volume
Pmusc + Pvent = + (Resistance × Flow)
Compliance
Mechanical Ventilator Systems
The typical critical care ventilator is electrically powered
and pneumatically or turbine driven. The graphical user
interface allows the user to select settings and review
alphanumeric and waveform data. The gas enters the
machine through two 55-​psig high-​pressure hoses: 1 sup-
plies oxygen and 1 supplies air. The amount of oxygen in
the gas mixture is determined by the user-​selected fraction
of inspired oxygen (Fio2). The gas flow passes through the
output control valve to the inspiratory limb and through
the endotracheal tube to the patient’s lungs. When the
inspiratory phase is complete, the gas travels through the
expiratory limb back to the ventilator.
Since the upper airway is bypassed after endotracheal
intubation, the inspiratory gas must be heated and humidi-
fied before entering the lungs. Warming and humidifying

are accomplished with either a heated reservoir humidifier
chamber or a heat-​moisture exchanger.
Operation of a
Mechanical Ventilator
Five basic principles must be understood before operating
a mechanical ventilator.
Flow
The output gas flow is determined by the desired volume
to be delivered over the inspiratory phase.
Volume
Flow =
Time
Volume
The volume of gas delivered is determined by the set flow
rate and the inspiratory time.
Volume = Flow × Time
Pressure
Pressure is determined by the amount of resistance the gas
flow encounters as it makes its way through the ventilator
circuit and airways.
Pressure = Flow × Resistance
The 2 important pressures monitored during mechanical
ventilation are the peak inspiratory pressure (PIP) and the
plateau pressure (Pplat) (Figure 2.1). The PIP is measured
at the end of the inspiratory phase of each breath under
dynamic flow conditions and generally reflects the amount
of resistance the gas encounters as it moves through the ven-
tilator and respiratory system. The Pplat is measured during
a breath hold at the end of inspiration and generally reflects
the compliance of the respiratory system. It is sometimes
referred to as alveolar distending pressure.
Resistance
Resistance is created as the gas flows through the ventilator
circuit and airways. Increased airway resistance is caused
by any obstruction to gas flow, which may be intraluminal
(secretions and bronchoconstriction) or extraluminal (the
weight of the chest wall and abdomen).
∆ Pressure
Resistance =
Flow
Compliance
Compliance is a measure of change in volume for given
pressure. The amount of gas delivered is proportional to
Chapter 2. Mechanical Ventilation: Basic Modes 11
PIP
Pressure
PEEP
Pplat
Inspiratory hold
Time
Figure 2.1. Pressures Monitored During Mechanical
Ventilation. Peak inspiratory pressure (PIP) is measured at
the end of the inspiratory phase. Plateau pressure (Pplat)
is measured at the end of inspiration during a breath hold.
Airway resistance (Raw) is the difference between PIP and
Pplat. PEEP indicates positive end-​expiratory pressure.
the amount of pressure it takes to move the gas through
the system.
∆Volume
Compliance =
∆Pressure
For every 1 cm H2O of pressure applied to the system,
normal lungs should receive 60 to 100 mL of gas. Lung
compliance is measured in 2 ways. Static compliance is
calculated with the Pplat (the amount of pressure in the
lungs during an inspiratory hold). Dynamic compliance is
calculated with the PIP and is not as useful clinically as the
static measurement.
VT Delivered (in mL)
Static Compliance =
Pplat − PEEP
For example, if a patient has an exhaled Vt of 500 mL, a
Pplat of 25 cm H2O, and a positive end-​expiratory pres-
sure (PEEP) of 5 cm H2O, the static compliance is 500 mL/​
(25 cm H2O -​5 cm H2O) = 25 mL/​cm H2O. Clinically this
would represent poor lung compliance.
Phases of a Mechanical Breath
Initiation and Triggering
A mechanical breath is initiated by 2 methods: mechanical
(timed) or patient triggered (Figure 2.2).
A mechanical (timed) breath is delivered at a set time
interval. For example, if the clinician sets a respiratory rate
of 10 breaths/​min, a breath will be delivered by the machine
every 6 seconds.
12 Section I. Fundamentals of Critical Care
20
Pressure or flow
delivery variable
Pressure, cm H2O
10
Inhalation
0
0 1
Trigger variable
Figure 2.2. Phases of a Mechanical Breath. Pressure-​time curve shows when different variables affect the inspiratory phase.
Trigger sensitivity determines the ventilator’s response
to a patient’s inspiratory effort. When the diaphragm con-
tracts, the ventilator measures either the decrease in pres-
sure (pressure trigger) or the volume displacement (flow
trigger) in the circuit. A patient can generally trigger a breath
more easily when a flow trigger is selected.
Inspiratory Phase
When the breath is triggered, gas is released into the ven-
tilator circuit. During this time, the circuit achieves maxi-
mum pressure and the Vt is delivered to the lungs.
Expiratory Phase
Cycling is the change from the inspiratory phase to the
expiratory phase. The expiratory phase is initiated by 2
methods: One is by timing. The respiratory rate and the
inspiratory time are set, and the expiratory time is a func-
tion of both. For example, if the respiratory rate is 10
breaths/​min and the inspiratory time is 1 second, the expi-
ratory phase is 5 seconds. With the second method, the
inspiratory phase is stopped when the flow has decelerated
to a certain percentage of peak flow. This method is used
for spontaneous breaths when the inspiratory time and
respiratory rate are variable instead of being set.
Ventilator Modes
Ventilator mode describes the level of support that the ven-
tilator provides the patient (Table 2.1). It does not describe
the method of breath delivery (volume controlled [VC] or
pressure controlled [PC]). Although only 3 basic modes are
Cycling variable
Exh
ala
tion
2 3 4 5
Time, s
described here, all modes of mechanical ventilation with
modern ventilators allow the patient to trigger or initi-
ate a breath. The modes vary in how the patient-​triggered
breaths are delivered.
Continuous Mandatory Ventilation
The commonly used term for continuous mandatory ven-
tilation (CMV) mode is assist control (AC). The clinician
selects a minimum respiratory rate, Vt, and flow rate or
inspiratory pressure and inspiratory time, and the venti-
lator delivers a breath at that interval. An assisted breath
occurs when the patient triggers the ventilator. In response
to the patient’s effort the machine delivers a breath with
the same settings as the mechanically timed breath. In
summary, the machine delivers a minimum Vė , and if the
patient triggers breaths above the set rate, those breaths
will be assisted.
Intermittent Mandatory Ventilation
With intermittent mandatory ventilation (IMV), like AC
mode, the ventilator delivers a minimum Vė determined by
the settings (rate and volume or pressure). The critical dif-
ference between AC and IMV is how the patient-​triggered
breath is delivered. With AC, those breaths are mandatory
by definition; with IMV, they can be both spontaneous and
mandatory. With IMV, total Vė consists of a combination of
controlled and spontaneous breaths.
Continuous Spontaneous Ventilation
In continuous spontaneous ventilation (CSV), all breaths
are spontaneous. They are all patient triggered and cycled.
 Chapter 2. Mechanical Ventilation: Basic Modes 13

Table 2.1 • Ventilator Modes and Settings

Mode and Settinga RRb Vt Flow, L/​min Insp Time, s PS

AC-​VC 14-​20 6-​8 mL/​kg IBW ≥60 Not set Not set
AC-​PC 14-​20 Inspiratory pressure to Not set 0.6-​1.0 Not set
achieve 6-​8 mL/​kg IBW
SIMV-​VC 14-​20 6-​8 mL/​kg IBW ≥60 Not set Inspiratory pressure to achieve
Vt of 6-​8 mL/​kg IBW
SIMV-​PC 14-​20 Inspiratory pressure to Not set 0.6-​1.0 Inspiratory pressure to achieve
achieve 6-​8 mL/​kg IBW Vt of 6-​8 mL/​kg IBW
CSV Not set Not set Not set Not set Inspiratory pressure to achieve
Vt of 6-​8 mL/​kg IBW

Abbreviations: AC, assist control; CSV, continuous spontaneous ventilation; IBW, ideal body weight; Insp, inspiratory; PC, pressure controlled; PS,
pressure support; RR, respiratory rate; SIMV, synchronized intermittent mandatory ventilation; VC, volume controlled; Vt, tidal volume.
a
For each of these modes and settings, the fraction of inspired oxygen is 0.21 to 1.0, and the positive end-​expiratory pressure is at least 5 cm H2O.
b
RR in breaths per minute.

The only variable that is set is the pressure support (inspi-
ratory pressure). This mode is commonly referred to as
pressure support ventilation (PSV).
Breath Types
Mandatory
A breath is considered mandatory when it is delivered at a
timed interval. There are 2 types of mandatory breaths: 1)
With VC breaths, the user selects a Vt and flow rate to
deliver the volume to the lungs. Volume is guaranteed
and airway pressure varies depending on changes in the
patient’s lung mechanics (compliance and resistance).
2) With PC breaths, the user selects a driving pressure,
and the Vt delivered to the patient is based on the lung
compliance.
Spontaneous
A spontaneous breath is both triggered and cycled by the
patient. This means that the timing of breaths and the
inspiration to expiration (I:E) ratio vary according to the
patient’s breathing pattern. Called a pressure-​ supported
breath, the inspiratory pressure is set and the Vt delivered
to the patient is based on lung compliance. The breath
delivery is the same as for a PC breath, but the terminology
is different because it refers to a patient-​triggered breath.
Summary of Mode and Breath Type
The combination of mode and breath type determines the
overall ventilation strategy. If AC mode is chosen, the man-
datory and patient-​triggered breaths can be either VC or
PC. If synchronized IMV (SIMV) is chosen, the mandatory
breath can be VC or PC and the patient-​triggered breath
is spontaneous (pressure supported). In CSV mode, all
breaths are spontaneous.
Determining Ventilator Settings
When choosing ventilator settings, the first step is to deter-
mine the treatment goals in terms of gas exchange, safety,
and comfort for the patient (Box 2.1).
Gas Exchange
Oxygenation
Oxygen delivery and adequate tissue oxygenation are given
priority in the treatment of the critically ill. However, both
hypoxia and hyperoxia are related to adverse outcomes.
A U-​shaped relationship exists between Pao2 and hospi-
tal mortality among all intensive care unit patients receiv-
ing mechanical ventilation. The lowest mortality rates
have been observed among patients with a Pao2 of 110 to
150 mm Hg; mortality increases if Pao2 is less than 67 mm
Hg or greater than 225 mm Hg. Specifically, hyperoxemia
increases mortality among patients who have had cardiac
arrest or traumatic brain injury. An oxygenation strategy
should aim to reverse arterial hypoxemia while avoiding
hyperoxemia.
Ventilation
Mechanical ventilation can facilitate improvement of alve-
olar ventilation and gas exchange. The goal Paco2 should
normalize pH. As evidence has emerged on the detrimental
effects of high ventilator pressures and large tidal volumes,
a strategy called permissive hypercapnia has become an
acceptable practice for treating patients with acute respi-
ratory distress syndrome (ARDS). The strategy requires
caution if a patient has a neurologic condition because
elevated Paco2 levels can increase intracranial pressures,
cause agitation or depressed consciousness, and decrease
the seizure threshold.
For patients with intracranial hypertension, therapeu-
tic hyperventilation to lower the Paco2 to 26 to 30 mm Hg
14 Section I. Fundamentals of Critical Care
Box 2.1 • Targets for Ventilator Settings
Safety
Blood pressure
Systolic blood pressure >90 mm Hg
Mean arterial pressure >65 mm Hg
Peak inspiratory pressure <35 cm H2O
Plateau pressure <30 cm H2O
Auto-​PEEP—​none
Tidal volume, 6-​8 mL/​kg IBW
Gas exchange
Spo2 >88%
Arterial blood gas analysis
pH 7.40
Paco2, 35-​45 mm Hg
Pao2 >60 mm Hg
Comfort
Synchrony—​patient is comfortable
Abbreviations: IBW, ideal body weight; PEEP, positive
end-​expiratory pressure; Spo2, oxygen saturation by pulse
oximetry.
can be used as a temporizing measure when clinical her-
niation complicates intracranial hypertension from cerebral
edema, intracranial hemorrhage, or tumor. In contrast, after
traumatic brain injury, prolonged, prophylactic, induced
hyperventilation with Paco2 of 25 mm Hg or less is not rec-
ommended and should be avoided during the first 24 hours
after injury.
Safety
Barotrauma and Volutrauma Prevention
Pulmonary barotrauma from mechanical ventilation
refers to alveolar rupture due to elevated transalveolar
pressure. Air leaks into extra-​ alveolar tissue result in
various conditions, including pneumothorax, pneumo-
mediastinum, pneumoperitoneum, and subcutaneous
emphysema. The incidence of injury can be up to 50%
but has been drastically reduced with the evolution
of low Vt (lung-​ protective) ventilation. Additionally,
mechanical ventilation can cause trauma to the lung as
in ventilator-​induced lung injury or ventilator-​associated
lung injury. Repeated overdistention of the alveoli and
cyclic atelectasis are the principal causes of alveolar
injury during PPV. In the landmark Acute Respiratory
Distress Syndrome Network (ARDSnet) trial, mortality
decreased by 22% with use of a low Vt (lung-​protective)
strategy. Therefore, the most effective strategies to mini-
mize injury are to maintain a low Pplat (<30 cm H2O) and
a Vt of 6 to 8 mL/​kg ideal body weight (IBW) and to avoid
dynamic hyperinflation.
Hemodynamic Stability
Mechanical ventilation and PPV can also have a consid-
erable effect on hemodynamics. As positive pressure is
applied to the thoracic cavity, the intrathoracic veins are
compressed and the central venous and right atrial pres-
sures are elevated. The result is a decrease in venous return
to the right side of the heart and a resultant decrease in
right ventricular stroke volume, preload, and pulmonary
blood flow. Additionally, high impedance encountered by
blood returning to the right side of the heart causes blood to
pool in the abdominal visceral vasculature and the brain.
The pooling of blood in the abdomen can remove blood
from the general circulation and contribute to decreased
left ventricular stroke volume. The resistance to cerebral
drainage may also increase intracranial pressure.
In patients with decreased lung compliance (eg, ARDS),
a high-​PEEP open lung strategy is often used. The pressure
remaining in the alveoli at the end of inspiration can com-
press the adjacent pulmonary vasculature and impede pul-
monary blood flow. The increased intrapleural pressure can
impede venous return and further reduce cardiac output.
In patients with normal cardiopulmonary systems,
this effect is usually minimal and compensated for by an
increased heart rate, systemic and peripheral vascular resis-
tance, and peripheral shunting of blood. Conditions that
may prevent a patient from compensating include sympa-
thetic blockade, spinal anesthesia, spinal cord transection,
and polyneuritis.
Auto-​PEEP
Alveolar pressure at the end of passive expiration may
exceed the set PEEP when the expiratory phase cannot be
completed to the fully relaxed position of the respiratory
system before the next inspiration begins. This results in
unintended pressure in the lungs at the end of exhala-
tion, which can negatively affect hemodynamics, induce
pulmonary barotrauma, increase the work of breathing,
cause dyspnea, cause patient-​ ventilator synchrony, and
interfere with the effectiveness of pressure-​regulated ven-
tilation. Identifying the cause is important for determining
treatment. The cause may be inappropriate timing settings
(expiratory time too short) or patient physiology (obstruc-
tive disease).
Comfort
Supporting the patient’s physiologic needs is not the
only concern during mechanical ventilation. Ensuring
patient-​ventilator synchrony (PVS) should be a prior-
ity for all clinicians. Asynchrony is a cause of ineffective
ventilation, impaired gas exchange, lung overdistention,
increased work of breathing, and patient discomfort. The
4 categories of asynchrony are flow, trigger, cycling, and
mode. All result from inappropriate matching of the ven-
tilator settings and the patient’s ventilatory demand or the

presence of auto-​PEEP. Classic neural injury patterns of
breathing include Biot respiration, apneustic breathing,
and central neurogenic hyperventilation or hypoventila-
tion breathing, which are frequently associated with asyn-
chrony. Generally, PC or pressure-​supported breaths are
more comfortable than VC, and spontaneous modes are
more comfortable than AC or SIMV. Although sedation is
sometimes necessary to facilitate PVS, all attempts must
be made to match the ventilator output and settings to the
patient’s demand. Modern mechanical ventilators have
been designed to address these issues by creating modes
that more closely match normal physiologic breathing pat-
terns and breath dynamics.
Ventilator Settings
Respiratory Rate
The respiratory rate is determined by the goal for Vė . The
clinician first calculates the Vt and then uses a rate that
guarantees a minimum Vė , which is 5 L/​min for an adult.
For example, if the Vt is 500 mL, a rate of 10 breaths/​min
is needed to achieve 5 L/​min. The rate is then titrated to
meet the goals of ventilation. The most effective way to
improve ventilation (ie, decrease Paco2) is to increase the
respiratory rate. The limitation of this strategy is the reduc-
tion in total cycle time (TCT). For example, a rate of 20
breaths/​min results in a TCT of 3 seconds. If the inspira-
tory time is fixed at 1 second and the rate is increased to
30 breaths/​min, the resultant TCT is 2 seconds and the I:E
ratio is 1:1, with a 1-​second exhalation. That rate would
impair ventilation and potentially induce air trapping and
reduce venous return and cardiac output.
Flow
With VC breaths, the flow is set. With PC breaths, the
flow is a product of the inspiratory time setting. When
determining the optimum flow rate, 2 factors must be
considered: the desired inspiratory time and the patient
inspiratory flow demand. A flow rate that is too low or too
high will cause patient-​ventilator dysynchrony. A flow set-
ting of at least 60 L/​min will generally satisfy both.
Inspiratory Time and the I:E Ratio
An inspiratory time of 0.6 to 1.0 seconds generally satis-
fies innate neural timing with an I:E ratio of at least 1:2.
With VC breaths, the inspiratory time is a product of the set
volume and set flow rate (volume = flow × time). With PC
breaths, the time is set by the clinician.
Tidal Volume
The currently accepted Vt is 4 to 8 mL/​kg IBW. An initial
Vt of 6 or 8 mL/​kg IBW should be titrated down to keep
Chapter 2. Mechanical Ventilation: Basic Modes 15
Pplat less than 28 cm H2O and driving pressure less than
15 cm H2O.
Inspiratory Pressure
In a PC or pressure-​supported breath, the delivered Vt is a
result of the inspiratory driving pressure (Pi), the inspira-
tory time, and lung mechanics. The Pi is set to achieve the
desired Vt while maintaining safe lung pressures. A rea-
sonable strategy to determine the Pi is to start with 10 cm
H2O, observe the resultant Vt, and then titrate to achieve
the desired Vt.
Oxygenation
To prevent alveolar cycling and derecruitment in acute
lung injury, high levels of PEEP are necessary to counter-
balance the increased lung mass resulting from edema,
inflammation, and infiltrations and to maintain normal
functional residual capacity. It is generally accepted that
application of physiologic PEEP of 5 cm H2O is necessary
in all patients with an artificial airway because the epiglot-
tis cannot close. When the PEEP is titrated up in response
to hypoxia or atelectasis, the hemodynamics and cardio-
pulmonary interaction must be monitored.
The Fio2 present in the gas mixture should be the lowest
Fio2 needed to achieve the goal oxygen saturation by pulse
oximetry (Spo2).
Summary
• Setting of the mechanical ventilator requires
knowledge of flow, pressure, and volume relationships.
• Ventilator mode selection is based on the level of
support required to assist Vė ; breath type selection is
largely based on lung mechanics and patient comfort.
• Clinicians must consider the patient’s physiologic
needs for assistance with oxygenation and ventilation
and the safety concerns of administering PPV while
attempting to facilitate PVS.
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 Mechanical Ventilation: Advanced Modes
3 AMELIA A. LOWELL, RRT, RCP; BHAVESH M. PATEL, MD
Goals
• Describe indications for advanced mechanical
ventilator modes, and describe their limitations.
• Describe advanced ventilator modes and engineering
principles.
• Describe adjunctive monitoring and therapies for
patients with acute respiratory disease who are
undergoing mechanical ventilation.
Introduction
Chapter 2 (“Mechanical Ventilation: Basic Modes”) dis-
cusses the 3 basic ventilator modes (assist control, intermit-
tent mandatory ventilation, and continuous spontaneous
ventilation), the 2 breath types (mandatory and sponta-
neous), and the 2 methods of breath delivery (volume
controlled and pressure controlled). The present chapter
focuses on advanced modes and modalities of therapy
for patients receiving mechanical ventilation. The term
advanced must be interpreted with caution because many
of the newer modes of ventilation do not have substantial
evidence of superiority to the basic modes of ventilation
for patient outcomes. Rather, advanced refers to the engi-
neering controls.
Dual-​Control Ventilation
The advantage of volume-​ controlled breath delivery is
that the operator can control the tidal volume and minute
ventilation. The advantage of pressure-​controlled breath
delivery is that the operator can control the total airway
pressure and inspiratory time, and the patient benefits
from a variable flow pattern, which can be more comfort-
able. Dual-​control ventilation combines the benefits of
controlling airway pressure, delivering a target tidal vol-
ume, and using a variable flow rate.
Adaptive Pressure Control
Ventilator manufacturers use various names for breath-​to-​
breath dual-​control modes, such as the following: pressure-​
regulated volume control (SERVO-​i ventilator; MAQUET
Cardiovascular, LLC); VC+ (Puritan Bennett 840 ventilator;
Medtronic); adaptive pressure ventilation (Hamilton-​ G5
ventilator; Hamilton Medical); and auto-​flow (Dräger venti-
lators; Draeger, Inc). Regardless of the terminology, though,
the clinician selects a target tidal volume, and the ventila-
tor adjusts the driving pressure (within the range set by the
clinician) to deliver that volume. The ventilator provides
the lowest pressure needed to deliver the target tidal vol-
ume and adjusts the pressure according to measurements
of lung mechanics, including dynamic compliance. If the
applied pressure delivers a tidal volume that is lower than
the target, the ventilator increases the pressure; if the tidal
volume is higher than the target, the ventilator decreases
the pressure. The main difference between ventilator
designs is the algorithm by which the pressure is changed.
For example, the VC+ increases or decreases the pressure
by 3 cm H2O breath to breath.
The benefit of breath-​ to-​
breath dual control is that
the ventilator makes changes according to the patient’s
dynamic work of breathing and lung compliance. The
disadvantage is that if the patient’s work of breathing
increases and the muscular inspiratory effort increases, the
tidal volume tends to increase. In response to the increased
tidal volume, which is not due to improved lung compli-
ance, the ventilator decreases the driving pressure, which
increases the work of breathing, and the cycle continues.
Therefore, the clinician must closely monitor the driving
pressure to determine whether the ventilator response is
appropriate.
17
18 Section I. Fundamentals of Critical Care
These modes have several advantages: They provide
more stable gas exchange than pressure control ventilation,
they provide better patient-​ventilator synchrony than con-
ventional volume control ventilation, and they probably
require less human time at the bedside to ensure that the
patient’s ventilatory demands are met. However, there is no
clear evidence that these modes improve patient outcomes.
Advanced Closed-​Loop Ventilation
Achieving patient-​ventilator synchrony is a constant strug-
gle and is rarely completely achieved. Integrating the ven-
tilator with sophisticated software to monitor and adjust
to dynamic changes in the patient’s lung compliance,
elastance, and effort has the potential to vastly improve
ventilation so that it not only facilitates gas exchange but
also avoids lung injury and improves synchrony. However,
there is little evidence to support the use of advanced
closed-​loop modes, and superiority has not been demon-
strated for any mode.
Neurally Adjusted Ventilatory Assist
Neurally Adjusted Ventilatory Assist (NAVA) is a propri-
etary mode of ventilation on the SERVO-​i ventilator that
uses a nasogastric catheter to detect the electrical activity
of the diaphragm and assist the patient’s breathing. It can
be applied to noninvasive and invasive mechanical venti-
lation. The proposed advantage of NAVA is that the ventila-
tor coordinates the initiation of the breath with the patient’s
neuromuscular effort and thereby improves patient-​
ventilator synchrony. Another advantage is that breath
triggering is not affected by air leaks or auto–​positive end-​
expiratory pressure (PEEP). Two electromyographic elec-
trodes are placed on either side of the patient’s diaphragm.
The signal can be used to initiate the breath or monitor the
discrepancy between neuromuscular effort and ventilator
output. A potential issue with using the electrical activ-
ity of the diaphragm as the main triggering mechanism is
faulty nasogastric catheter placement or faulty electrode
placement. The first large randomized controlled trial of
NAVA in acute respiratory distress syndrome (ARDS), the
NAVA in Acute Respiratory Failure (NAVIATOR) trial, is
underway and will help determine the role of NAVA in
ventilator management. The existing evidence suggests
that NAVA can help improve patient-​ventilator synchrony,
decrease sedation, and improve sleep quality and patient
comfort scores.
Proportional Assist Ventilation
Proportional assist ventilation software on the Puritan
Bennett 840 ventilator is based on the concept of patient-​
driven ventilation that was first described in the early
1990s. The software couples neuroventilatory demand
with ventilator output by using the respiratory equation
of motion, which accounts for the compliance and elas-
tance of the lung and the patient’s effort and generates a
proportional driving pressure. The operator does not pre-
set the pressure, flow, or volume. Instead, the clinician
sets the target level of assistance (percentage of support)
according to the workload that a patient must overcome to
breathe. For example, at 75% support, the ventilator per-
forms 75% of the work to deliver a breath and the patient
performs 25%. Work of breathing is measured in Joules
per liter and reflects the change in pressure for a given
volume per breath. The clinician can monitor the patient’s
work of breathing and adjust ventilator support accord-
ing to the goals of care. It is indicated only for patients
who are breathing spontaneously and have an ideal body
weight greater than 25 kg. It is contraindicated if a patient
has respiratory depression from either sedation or other
causes and if a patient has a bronchocutaneous fistula or
pleural leak.
Adaptive Support Ventilation
Adaptive Support Ventilation is a proprietary mode of
ventilation (Hamilton Medical). It is a closed-​loop venti-
lation that uses positive or negative feedback from mea-
surements of respiratory mechanics to adjust the level of
support that the patient receives. The clinician sets the
percentage of minute volume (25%-​350%) that the ven-
tilator will target according to patient height and disease
type, the upper pressure limit to deliver a breath, PEEP,
and fraction of inspired oxygen. The ventilator adjusts
the level of support depending on the patient’s physio-
logic conditions and uses existing modes to support the
patient. For example, if the patient’s respiratory rate is
higher than the calculated target (based on the percent-
age of minute volume target), the ventilator uses pressure
support ventilation; if the patient is apneic, the ventila-
tor switches to pressure control ventilation and uses
synchronized intermittent mandatory ventilation when
the patient’s respiratory rate is lower than the target. The
ventilator changes are based on the Otis equation, which
states that for a given level of alveolar ventilation, there is
an optimal respiratory rate for reduced work of breathing.
Additionally, the percentage of minute volume, ideal body
weight, and disease phenotype determine the target tidal
volume to which the ventilator adjusts the driving pres-
sure for achieving the target.
Acute Respiratory Distress Syndrome
Various new strategies to improve gas exchange and pro-
tect the lungs have emerged for managing the ventilator in
patients with ARDS.

Pressure, cm H2O Thigh
Tlow
Time, s
Figure 3.1. Pressure-​Time Curve for Airway Pressure Release Ventilation. During the long inspiratory time (Thigh), the driv-
ing pressure is high (Phigh); during the short expiratory release time (Tlow), the pressure applied is low (Plow).
(From Daoud EG. Airway pressure release ventilation. Ann Thorac Med. 2007 Oct;2[4]‌:176-​9; used with permission.)
Airway Pressure Release Ventilation
Airway pressure release ventilation (APRV) is an evolu-
tion of inverse-​ratio ventilation that uses a long inspira-
tory time (Thigh) and a short expiratory release time (Tlow).
The driving pressure during Thigh is called Phigh, and the
pressure applied during Tlow is called Plow (Figure 3.1).
This is similar to setting the ventilator in pressure control
mode with an applied driving pressure (pressure control
setting) and an applied PEEP. The main difference is that
during Thigh, Plow plateaus and the patient triggers spon-
taneous breaths during Thigh. Functionally, the ventilator
allows the patient to breathe at a high continuous posi-
tive airway pressure for the set time and then decreases
the pressure during Tlow. The Tlow facilitates ventilation
(carbon dioxide removal) while limiting full exhalation
and thus creating auto-​ PEEP and improving alveolar
recruitment.
Clinicians and ventilator manufacturers use various set-
tings, which are collectively called APRV. Two categories
of strategies have been defined: fixed APRV and personal-
ized APRV. Fixed APRV uses a Thigh (<90% total cycle time)
and a fixed Tlow. In personalized APRV, the Tlow is adjusted
by analyzing the slope of the expiratory flow curve and the
Plow is set at 0 cm H2O (Figure 3.2). In a review of 30 years of
data from using various methods of applying APRV, there
was no statistically significant worse outcome when APRV
was used instead of other conventional modes of mechani-
cal ventilation. Personalized APRV has been shown to
stabilize alveoli and decrease the incidence of ARDS in
clinically relevant animal models and in trauma patients.
The hemodynamic effects of high ventilation pressures and
hypercapnia must be monitored for successful application
of this mode.
Chapter 3. Mechanical Ventilation: Advanced Modes 19
Spontaneous breath
Phigh
Plow
Recruitment Maneuvers
A recruitment maneuver is the application of airway pres-
sure for increasing transpulmonary pressure transiently
to facilitate the opening of collapsed alveoli and improve
gas exchange. Various techniques are used, but a definitive
conclusion on the best method has not been reached. All
maneuvers involve increasing the PEEP; some accomplish
this by incrementally increasing PEEP, and others increase
it quickly to reach a high PEEP (≥30 cm H2O) and hold it
for a short period. In the Alveolar Recruitment for Acute
Respiratory Distress Syndrome Trial (ART), investigators
found an increase in 28-​day mortality when recruitment
maneuvers were used instead of standard ARDS Network
protocols. This finding confirmed that lung-​ protective
ventilation is the standard of care for ARDS patients, and
recruitment maneuvers should not be performed routinely.
Prone Position
In supine hospitalized patients, the dorsal pleural pressure is
increased because of the weight of the heart, abdominal vis-
cera, and ventral lungs (which is even greater with ARDS).
While the dorsal alveoli are collapsed, the gravitational vas-
cular pressure gradient improves perfusion to this region
and produces a low-​ ventilation–​high-​
perfusion mismatch
and shunt manifesting as hypoxemia. Historically, prone
positioning was reserved as a final effort to improve oxygen-
ation but was not associated with improved mortality. In the
landmark Prone Positioning in Severe ARDS (PROSEVA)
trial, mortality decreased when patients were placed in a
prone position soon after they were assigned to the prone
group and for at least 16 consecutive hours. Current guide-
lines support prone positioning for more than 12 hours a day
for patients with severe ARDS (Figure 3.3).
20 Section I. Fundamentals of Critical Care

A B
Normal ARDS
Pressure, cm H2O

60 60
Thigh Tlow
30 30

Flow, L/min
0 0
Plow Phigh

e
lop
pe

°s
lo
°s

30
Flow, L/min

-30 -30

45
-45/-60=0.75 -45/-60=0.75
-60 -60

0.5 0.45
0 3 6 9 0 3 0 3

Time, s Time, s

Figure 3.2. Strategies for Setting Expiratory Duration (Tlow). A, Airway pressure release ventilation pressure-​time and flow-​
time curves show short release phase (Tlow), time at high pressure (Thigh), pressure at inspiration (Phigh), and pressure at expira-
tion (Plow). With a short Tlow, Plow never reaches 0 cm H2O (measured as tracheal pressure and indicated by the green line). B,
In acute respiratory distress syndrome (ARDS), the rate of lung collapse is more rapid than in normal lungs, as indicated by
the steeper slope.
(From Jain SV, Kollisch-​Singule M, Sadowitz B, Dombert L, Satalin J, Andrews P, et al. The 30-​year evolution of airway pressure release ven-
tilation [APRV]. Intensive Care Med Exp. 2016 Dec;4[1]‌:11. Epub 2016 May 20; used under Creative Common Attribution License [http://​
creativecommons.org/​licenses/​by/​2.0/​].)

Clinicians have been deterred from timely use of the
prone position by logistic challenges, including physically
turning or placing the patient on a rotating bed while main-
taining the airway and vascular access devices. Patients
usually have an increased amount of oral secretions and a
higher risk of endotracheal tube obstruction and pressure
ulcers, all of which can be managed with careful monitor-
ing. Patients who should be excluded are those with ocular,
facial, or neck trauma; spinal instability; recent sternotomy
or large ventral surface burn; increased intracranial pressure
(ICP); massive hemoptysis; or high risk of requiring cardio-
pulmonary resuscitation or defibrillation. Hemodynamic
monitoring and the phlebostatic axis should be adjusted for
the ventral position of the right atrium.
Extracorporeal Life Support
When conventional mechanical ventilation does not ade-
quately facilitate gas exchange without inducing further
organ injury, or if total heart failure is recognized, extracor-
poreal life support may be used. Extracorporeal life sup-
port facilitates gas exchange outside the body by passing
blood through a membrane that can oxygenate the blood or
remove carbon dioxide from the blood by using the native
circulation or pump-​driven blood flow. Mechanical ven-
tilation may continue to be required to meet oxygenation
and ventilation requirements. The general strategy for
selecting ventilator settings during extracorporeal mem-
brane oxygenation is to maintain global oxygen delivery
while using lung-​protective and right ventricular protec-
tive strategies: maintaining ultra-​low tidal volumes (4 mL/​
kg ideal body weight), low respiratory rates (10 breaths
per minute), moderate PEEP (10 cm H2O), and relatively
low plateau pressure (<25 cm H2O). In general, challenges
include selecting and locating the cannula, providing
anticoagulation, being aware of drug circuit interactions,
and maintaining blood protective flows while optimizing
regional delivery of oxygen to organs.
Esophageal Pressure Monitoring
The best estimate of alveolar distending pressure is the pla-
teau pressure obtained during an end-​inspiratory pause.
The plateau pressure provides information on static lung
compliance, guides ventilator management to decrease
driving pressures, and is the hallmark of risk reduction
in ARDS (by maintaining plateau pressure <30 cm H2O).
However, the value of this measurement is limited because
it estimates the pressure in the alveoli but does not directly
measure it. A more accurate measurement of the amount
of pressure required to open the lung is transpulmo-
nary pressure, which can be measured indirectly with an
 Chapter 3. Mechanical Ventilation: Advanced Modes 21

Supine position Prone position

Minutes
Ventral Dorsal

– Blood flow +
Isolated lung Shape matching Shape matching
No gravity Gravity Gravity

A B C D E F

Figure 3.3. Effects of Prone Positioning on Diseased Lungs in a Patient With Acute Respiratory Distress Syndrome. A, Original
shape (dorsal side is larger). B, Alveolar units are larger ventrally. C, Gravity affects ventilation and perfusion. D, Immediately
after patient is placed in prone position, pulmonary blood flow in dorsal regions is unchanged. E, Dorsal regions of lungs
are recruited (more than ventral derecruitment), and ventral regions are compressed (but compressive effects are dampened
by shape matching). F, Oxygenation improves as transpulmonary pressure and regional inflation distribution become more
homogeneous.
(From Koulouras V, Papathanakos G, Papathanasiou A, Nakos G. Efficacy of prone position in acute respiratory distress syndrome patients: a
pathophysiology-​based review. World J Crit Care Med. 2016 May 4;5[2]‌:121-​36.)

esophageal catheter. Transpulmonary pressure is the dif-
ference between alveolar pressure and pleural pressure.
Esophageal pressure is the surrogate for pleural pressure
and can be measured continuously or during an end-​
inspiratory or end-​expiratory hold. The esophageal pres-
sure is the amount of pressure applied outside the lung and
accounts for extrathoracic causes of increased airway pres-
sure such as abdominal distention, obesity, and pregnancy.
Transpulmonary Pressure = Palv − Pes
Monitoring of Pes allows more accurate titration of PEEP,
measurement of tidal volumes and inspiratory pressures,
assessment of lung recruitment ability, and management
of patient-​ventilator synchrony (autotriggering, ineffective
triggers, and trigger delays). Evidence supports the use
of Pes in patients with ARDS to guide PEEP titration and
improve oxygenation.
High-​Frequency Oscillatory Ventilation
High-​frequency oscillatory ventilation differs from conven-
tional mechanical ventilation in that it uses an oscillatory
pump to deliver a fast respiratory rate measured in hertz
(up to 900 breaths per minute) in an intubated patient. The
purpose is to recruit alveoli and hold them open at a con-
stant mean airway pressure with a low tidal volume (also
called amplitude). The respiratory rate (in hertz) is set
directly while the mean airway pressure is set by adjust-
ing the flow rate and expiratory back-​pressure valve. The
amplitude is determined by the hertz setting and the size
of the endotracheal tube. After being evaluated in adults in
6 randomized controlled trials, high-​frequency oscillatory
ventilation is not recommended for use in patients who
have moderate or severe ARDS because the trials showed
either no benefit or serious patient harm.
Nitric Oxide
Inhaled nitric oxide has been used for decades to treat per-
sistent pulmonary hypertension in neonates, which is the
only indication for its use approved by the US Food and
Drug Administration. When inhaled directly, nitric oxide,
a selective pulmonary vasodilator, dilates the pulmonary
vasculature that it contacts by increasing the concentration
of cyclic guanosine monophosphate through the action of
22 Section I. Fundamentals of Critical Care

Injury from lung to brain

Hypoxemia
Common injurious
Injury from brain to lung predisposing factors Hypercapnia or hypocapnia
Increase in intracranial Fever Impaired respiratory system
pressure mechanics
Sepsis
Catecholamine release Release of mediators
Trauma
Neuroinflammation (humoral, Neurotoxic factors
neural, cellular) Hemodynamic impairment
Activation of epithelium and
Failure of cholinergic Excessive fluids and endothelium
anti-inflammatory pathway vasopressors
Recruitment of macrophages
Hyperdopaminergic states Drug exposure
Dyspnea or air hunger
Hyperosmolar therapy Metabolic disturbances
Asynchronies
Liver and renal failure
Ventilator-induced lung and
muscle injury

Figure 3.4. Interactions Between the Brain and Lungs in Critically Ill Patients Receiving Mechanical Ventilation.
(From Blanch L, Quintel M. Lung-​brain cross talk in the critically ill. Intensive Care Med. 2017 Apr;43[4]‌:557-​9. Epub 2016 Oct 6; used
with permission.)

guanylate cyclase. It is rapidly scavenged by hemoglobin,
thereby decreasing its systemic vasodilatory effect. It is
delivered through a proprietary system, the INOmax DSIR
(Mallinckrodt Pharmaceutical), which monitors oxygen,
nitric oxide, and nitrogen dioxide levels and can be used
through a mechanical ventilation circuit, high-​flow nasal
cannula or oxygen mask, or low-​flow nasal cannula. It is
used in patients who have ARDS with hypoxemic respira-
tory failure, in patients with right-​sided heart failure (as an
afterload reduction agent), in conjunction with ventricular
assist device placement, and with heart or lung (or heart
and lung) transplant despite lack of supporting evidence.
The only well-​established use in adults is for vasodilator
challenges. In patients with ARDS, inhaled nitric oxide
improves oxygenation and ventilation-​ perfusion match-
ing, but it has not been shown to improve survival at any
time point in any patient population.
Special Considerations for Patients With
Neurologic Disease
Respiratory failure is the most common complication
in traumatic brain injury, occurring in 20% to 25% of
patients, and acute lung injury is increasingly described
as a systemic complication of severe head injury that
negatively affects outcomes. Massively increased sympa-
thetic activity and the flood of inflammatory molecules
have been proposed as mechanistic causes of lung injury
and may render the lung more susceptible to the negative
effects of mechanical ventilation (also called the double hit
model). When patients with brain injury require mechani-
cal ventilation, the clinician must balance what is good for
the lungs with what is good for the brain (Figure 3.4).
Intrathoracic Pressure
The intrathoracic pressure (ITP) during positive pressure
ventilation is the pressure required to deliver a tidal vol-
ume (either directly controlled as pressure control ventila-
tion or indirectly applied as volume control ventilation)
and the amount of PEEP applied to the end of exhalation.
Maintenance of peak pressures less than 35 cm H2O and
plateau pressures less than 30 cm H2O helps protect the
lungs from barotrauma and volutrauma (pneumothorax,
acute lung injury, and ARDS). Additionally, excess driv-
ing pressure has been linked to increased mortality among
patients with ARDS. The patient with brain injury is more
susceptible to lung damage because of the double hit
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degrees F.—and are immediately succeeded by marked increase in
the severity of the symptoms, both mental and physical, especially if
the attacks follow each other in rapid succession or last for a number
of days. They may be due to hemorrhage, embolism, or effusion,
and be marked by any or all of the usual symptoms and sequences
of those conditions, permanent or transient. General and aural
vertigo are not uncommon.

The muscular tremor before the last stages varies in different

muscles—excessive perhaps in the tongue, moderate in the fingers,
and so on. It may also seem slight as compared with the other
symptoms, or, on the other hand, be enormously exaggerated in
certain groups of muscles out of all proportion to all other indications.
At the end extreme and constant tremulousness accompanies every
voluntary movement.

Spastic paralysis, muscular tension, contractures, rigidity of the most

persistent character seem at times to be under the influence of the
will, although of cortical origin and in a certain sense automatic, like
convulsions.

The knee-jerk is changed in somewhat more than half the cases, a

little oftener exaggerated than abolished; but sometimes the reflexes
are enormously increased all over the body, so that a strong puff of
air in the face even will set the arms and legs going like a jumping-
jack. I have twice seen the patellar reflex abolished in one leg, and
so marked in the other as to seem to me exaggerated.24 I have also
known it to disappear absolutely in both legs two weeks after it had
been found to be excessively exaggerated. It also varies under
conditions of rest, fatigue, excitement, etc. Intense pain in the joints
occurs, and I have found it where the knee-jerk was exaggerated, in
one case giving rise in a physician to the delusion that his arms and
elbows had been resected. This may disappear in time. Charcot's
joint disease has been observed.
24 There was no evidence, and there had been no history, of a hemiplegic attack in
either case.
In the final stages the bones are fragile and easily break;
hemorrhages under the periosteum or perichondrium arise from
trifling force or injury, giving rise to hæmatomata, the most common
of which are on parts exposed to pressure, etc., as the ear. The
patient is confined to his bed, fed like a small child, demented, hardly
able to articulate the extravagant delusions which form such a
grotesque contrast to his actual state, until the mind is as incapable
of forming or receiving ideas as of expressing thoughts; and the
body is simply a filthy, helpless mass of humanity, dying of
exhaustion or decay, unless lung gangrene, bed-sores superficial
and deep, necrobiosis, exhausting diarrhœa, pneumonia, pulmonary
consumption, perhaps asphyxia from an epileptic fit or choking, have
followed incontinence of urine and feces to the fatal end, or heart
failure or apoplexy have closed the scene.

PATHOLOGY AND MORBID ANATOMY.25—General paralysis of the insane

is, according to Mendel, following Rokitansky's idea, a connective-
tissue disease, affecting the nerve-cells and tissues secondarily,
while Tuczek and Wernicke think that the primary disease is of the
nerve-elements (primäre Atrophie der Nervenelemente)—a diffuse
interstitial cortical encephalitis on the one hand, or a diffuse
parenchymatous cortical encephalitis on the other. There is also, in
well-marked cases, atrophy of the white substance, due, according
to general opinion of pathologists, to primary interstitial encephalitis
ending in sclerosis.
25 For a detailed statement of the post-mortem appearances in general paralysis
compare Spitzka's Insanity, pp. 218-243; Beiträge zur pathologischen Anatomie und
zur Pathologie der Dementia Paralytica, von Dr. Franz Tuczek; Die Progressive
Paralyse der Irren, von Dr. E. Mendel; Lehrbuch der Gehirnkrankheiten, von Dr. C.
Wernicke, iii. pp. 536-541. Westphal's classical work is not referred to, as his latest
views and others of interest are given in a report of a discussion by the German
Association of Alienists in the Allgemeine Zeitschrift für Psychiatrie, iv. 1883, pp. 634-
638 and 648-654. In the third number of the Neurol. Centralblatt, Mendel reports an
autopsy of a patient diagnosticated to have melancholia, who died a violent death,
where he thought that he found evidence of the early stage of general paralysis in
moderate opacity of the pia mater, with nodules as large as a pin's head in both
 parietal regions, and in slight indications of diffuse interstitial inflammation of the
cortex, the blood-vessels in the frontal convolutions being extensively filled with white
blood-corpuscles.

In the majority of cases there is pachymeningitis, often extensive and

excessive, with hemorrhages, but which may be no more than is
quite commonly found in persons dying of phthisis or chronic
nephritis. There is also, usually, leptomeningitis, with adhesions to
the cortex, especially of the anterior and antero-lateral portions, so
firm that the arachnoid cannot be removed without tearing off
portions of the brain; but it is sometimes scarcely observed, and may
be no more than is found in persons dying simply of old age. The pia
may be in places thickened, opaque, and without adhesions.
Ependymitis is usual.

In the terminal stage of general paralysis there is well-marked

atrophy (with compensatory serous effusion), which is, as a rule,
most marked in the cortex of the brain, but which is of varying
degrees in its different portions. Rarely there is scarcely any atrophy
of the cortex. The central portion of the brain may be of leathery
consistence, but usually shows marked sclerosis, which also may
affect its different portions and the different ganglia very differently.
The changes resulting from inflammatory, degenerative, and atrophic
processes are general and profound.

An opinion is beginning to obtain that general paralysis is primarily a

disease of the small cerebral blood-vessels, functional or vaso-
motor; and Meynert holds that the transition line between that stage,
which he considers curable, and organic disease may be recognized
clinically.

In general paralysis, as in other mental diseases, the nervous

discharge is accompanied by a greater disturbance in the structure
of the gray substance of the brain, a more extensive decompounding
of it, and consequently by a more complete exhaustion of nervous
force than in healthy mental processes. Longer periods of rest and
improved nutrition are therefore necessary to restore healthy
function. In general paralysis, as in all other mental diseases
dependent upon destructive disease of the brain, there is not only
decompounding, but decomposing and disintegrating, of the
structure of the brain.

Posterior spinal sclerosis is frequently found. If alone or

predominating over sclerosis of the lateral columns of the cord, the
knee-jerk is abolished if the morbid process has gone far enough. If
descending degeneration of the lateral columns is chiefly found, and
is sufficiently advanced, the knee-jerk is increased. At least one of
these forms of sclerosis exists in the vast majority of cases.

There is also a distinctly syphilitic disease of the smaller cerebral

arteries, together with a diffuse parenchymatous and interstitial
encephalitis of syphilitic origin. At present we have no means of
differentiating it at the autopsy from general paralysis following a
subacute or chronic course, except inferentially from the presence of
other evidences of syphilis. It is not always possible, therefore, to
distinguish between syphilis and a syphilitic diathesis as the chief
factor in diffuse encephalitis.

DIAGNOSIS.—Although a well-marked case of general paralysis is

unmistakable, the diagnosis in the early stages or in obscure cases
may be extremely difficult. The varying degrees in which the various
portions of the cortex, medullary portion, and different ganglia of the
brain may be involved in the morbid process naturally give rise to a
great variety in the symptoms, mental and physical, sensory and
motor, emotional and intellectual, and in the relative preponderance
of one or another in individual cases. The usual symptoms of any
form of mental disease may for a time obscure the dementia which
sooner or later must appear in general paralysis, and which, as has
already been said, is the only mental symptom universally present in
all cases. This mental impairment must also be associated with
progressive muscular loss of power, although the relation of the two
symptoms to each other, the degree to which a given amount of the
one leads to a fair inference of a certain amount of the other, is liable
to the greatest variation, the range of which can only be learned by
observation and experience. There is a certain quality to the
dementia, as already described, which is often sufficient of itself to
establish the diagnosis with a practised physician.

The early mental symptoms may simulate those of cerebral

neurasthenia, in which the patient thinks that there is decided mental
impairment, although there is no progressive dementia. The tremor
in neurasthenia is greater and more universal than in the stage of
general paralysis with which it might be confounded, and the
subjective symptoms are much more prominent.

Muscular malaise and pains throughout the body give rise to the
diagnosis of malaria or rheumatism, in which there may be loss of
power, but no ataxia or dementia.

The sclerosis may be predominating or pronounced in the basal

ganglia and bulbar nuclei, giving occasion for a hasty diagnosis of
labio-glosso-pharyngeal paralysis, until it is found that the clinical
history of that disease is not followed. In the same way, any motor or
sensory ganglia or nerve-roots may be so early implicated in the
degenerative process as to mislead the physician into giving
attention to only the local symptoms.

Once I have known the early convulsions of general paralysis in a

very self-conscious woman mistaken for hysteria, the mental
impairment and physical weakness having been overlooked on
account of the prominence of the convulsive attacks and the
hysterical symptoms, which may be a complication of any form of
insanity in young and middle-aged people, particularly women.

It is not uncommon for the attacks to so thoroughly resemble

epilepsy as to be mistaken for it, the dementia not being observed or
being supposed to be the ordinary mental deterioration generally
following epilepsy. In such cases the progressive dementia, ataxia,
and muscular weakness may advance so slowly as to entirely
escape observation for a long time, and give rise to the confident
diagnosis of epilepsy for five or six years. Epilepsy, however, arising
in a vigorous, middle-aged person without evident cause, should
always suggest the suspicion of syphilis, cerebral tumor, or general
paralysis, when careful scrutiny of all the symptoms will show where
it belongs.

Embolisms, hemorrhages, cerebral effusions, more or less diffuse

encephalitis from an injury to the head, sometimes give rise to the
suspicion of general paralysis, until it is found that its characteristic
progressive symptoms do not appear, but chiefly when the history of
the case has not been definitely ascertained, or when the usual
symptoms of those conditions are not well marked.

Chronic endarteritis, arterio-sclerosis, atheroma of the cerebral

arteries may be so diffused as to simulate general paralysis,
especially in drunkards and syphilitics, but the symptoms do not
advance in the manner characteristic of that disease.

Multiple cerebro-spinal sclerosis of the descending form may be

confounded with general paralysis while the symptoms are obscure
and consist in change of character, when, indeed, organic disease
can only be suspected to be present.

Lead has been known to attack the central nervous system in such a
way as to produce an intellectual apathy and muscular weakness
somewhat resembling the early stage of the demented form of
general paralysis, but without its ataxic symptoms and its regular
progress. The presence of lead in the urine, and the marked
improvement from the use of iodide of potassium, tonics, and
electricity, are sufficient to establish the diagnosis.

Chronic and persistent alcoholism is always attended with some

mental impairment, which may so resemble the dementia of general
paralysis, with marked moral perversion, mental exaltation, grand
delusions, muscular tremor, ataxic symptoms, and impaired
muscular power, as to make the diagnosis doubtful for several
months, until removal of the cause (alcohol) in the course of time
causes the symptoms to so abate as to make the real character of
the disease evident.
I have once seen chronic interstitial nephritis without its usual
prominent symptoms and with mild uræmic convulsions mistaken for
general paralysis.

A tumor of the brain, if not attended with the common symptom of

vomiting, may be the cause of convulsions and headache
resembling those often seen in general paralysis. Optic neuritis or
atrophy is usual in cerebral tumor, but rare in a stage of general
paralysis so early that the diagnosis might be doubtful.

Hemorrhagic pachymeningitis also now and then simulates an

obscure case of general paralysis in the early stage, but a few weeks
at most settle any doubts in the matter.

Although diffuse cerebral syphilis is more apt to be associated with

distinctly localized symptoms than the demented form of general
paralysis, and although it is characterized by a mental apathy and
physical torpor which follow a more regular course with more definite
symptoms, resulting in a slow decay, yet there may be doubtful
cases in which the differential diagnosis is impossible, and in which
antisyphilitic treatment does not throw any light on the subject.
Syphilitic new growths, endarteritis, and meningitis may so far
improve from the use of mercury or the iodide of potassium as to end
in an apparent cure, but in those cases the symptoms are not so
marked as to make an exact diagnosis always possible. A distinct
syphilitic cachexia is presumptive evidence of syphilitic encephalitis
when there is doubt whether the syphilis is the cause or the
diathesis.

Profound melancholia is not so often as varying gloom or moderate

despondency a symptom of general paralysis. When it is such, there
are developed in time the other marks of that disease, and it will only
be necessary to hold the diagnosis in reserve for their appearance.
The melancholia masks the dementia unless it is very carefully
sought for, and the tremor may be as marked in melancholia as in
the early stage of general paralysis, but more universal.
Acute mania is not uncommonly mistaken for general paralysis,
when, as often happens, the delusions are as expansive and the
tremor as great in the mania as in general paralysis; and it may be
several months before the differential diagnosis can be made with
certainty. In the presence of a high degree of maniacal excitement,
with great emotional agitation and muscular tremor, it is difficult to
establish the fact of the existence or not of dementia in doubtful
cases until it is well developed. Acute mania has been known to
constitute the prodromal period of general paralysis for a number of
years.

Primary mental deterioration cannot be always differentiated from

general paralysis of the demented type in its early stage. After the
age of sixty the probabilities are in favor of primary mental
deterioration in doubtful cases, but general paralysis occurs—
seldom, to be sure—up to the age of sixty-five.

Early senile dementia may simulate general paralysis of the

subacute form, but has not its clinical history. General paralysis of
the quiet, insidious type and primary mental deterioration have been
called premature senility. The three diseased conditions have certain
points of similarity, and the pathological processes involved in them
do not differ sufficiently to authorize the assumption that they are not
closely related, if not simply variations, due to age and other causes,
in one morbid process.

Finally, the mental impairment caused by the prolonged use of

bromide of potassium and hydrate of chloral has been mistaken for
general paralysis, until a critical examination unmistakably showed
the presence of the well-known symptoms of those drugs.

In examining the patient it is especially important to avoid leading

questions, as in general paralysis and in those conditions which
simulate its early stage the mind is in a condition to readily fall into
the train of thought suggested to it. The fact should be kept in mind,
too, that the symptoms in early general paralysis are so variable as
to be sometimes quite evident, and at other times not to be got at
with certainty at all or only after long and patient examination; that
they sometimes quite disappear under the influence of complete
mental and bodily rest; and that in all stages, until near the end, such
complete remissions may occur as to make the diagnosis,
independent of the history of the case, difficult if not impossible.

A gentleman once committed an offence characteristic of general

paralysis in marrying a pretty servant-girl while temporarily away
from his home. His wife, daughters, and friends saw that the act was
so contrary to his natural character that he was placed in an insane
asylum and kept there several weeks under observation for an
opinion as to his responsibility. He appeared so well in the absolute
quiet and rest that he was declared sane, tried, and sentenced to the
State prison, where he showed his marked mental impairment as
soon as he was set to work. He could not concentrate his mind
sufficiently for the simplest labor, and a couple of years later he was
sent to the insane asylum to die, a complete mental and physical
wreck, in the late stage of general paralysis.

PROGNOSIS.—The very few reported cures in so common a disease

as general paralysis, and the circumstances under which they have
been reported, lead to the suspicion that there was an error in
diagnosis or that the mistake was made of supposing a remission to
be a cure, as has often happened. The course of the disease is more
rapid in men than women, and in young persons than in the older.
From the galloping cases of a couple of months to those slowly
advancing, with long remissions, over twenty years, the average,
including the prodromal period, is probably not far from five (perhaps
six) years. Collected from asylum statistics, it is given as from two to
three years. When I am sure of the diagnosis, I generally say that the
patient may die within twenty-four hours (of paralysis of the heart,
from suffocation by an accident in an epileptic attack, from choking,
from cerebral hemorrhage or effusion, or suddenly with cerebral
symptoms of which the autopsy gives no satisfactory explanation),
within a short time of intercurrent disease, especially diarrhœa or
pneumonia, or that he may live several years, as he probably will,
and possibly have a remission, during which he may lead for a while
somewhat the same kind of life as other people.
Persons presenting symptoms which can in no way be positively
distinguished from those at the beginning of the prodromal period of
general paralysis recover, but not many come under the physician's
care so early. We are not yet in a position to say whether they were
suffering from a mild, transient illness or from what would otherwise
have become serious organic disease.

TREATMENT.—Life may be prolonged in general paralysis, and usually

is prolonged, by the use of such measures as contribute to the
patient's comfort, and which in a general way have already been
considered under the head of treatment of mental disease on a
previous page.

In my experience, stimulating tonics, wine, and even coffee, increase

the morbid cerebral energy of the early stage of the disease, but are
sometimes of use later. Cod-liver oil and the hypophosphites do
better, and many of the disagreeable symptoms of the period of loss
of control over the involuntary muscles are relieved by strychnia.
Ergot and the judicious use of the bromides abate the cerebral
congestion. Gastro-intestinal disorders, when not controlled by
attention to diet, require the usual treatment.

Iodide of potassium in the large or small dose, and mercury, I have

never found to benefit those cases of general paralysis with a
previous history of syphilis. On the contrary, they have proved
debilitating and harmful.

When furious excitement is not relieved by prolonged warm baths,

with cool applications to the head if possible, and quiet, chloral is of
use, and sometimes opium and its preparations.

Frequently-repeated violent convulsions, the epileptic state, are

usually at once mitigated by chloral given by the rectum; the
inhalation of nitrite of amyl is reported also to have been of use.

There are few cases in which I find that morphine does not quiet
restlessness, calm delusions, abate distressing hallucinations, and
make the patient generally more comfortable; and I give it freely,
seldom more than twice a day, often almost daily, for two or three
years. In this way it can be used in quite moderate doses. Coca also
relieves symptoms.

Rest and quiet are most important in all stages of the disease. This
can be best accomplished in a quiet private house in the country,
which can be made a virtual hospital, and next in a private asylum.
But such care is beyond the reach of the vast majority of the insane,
to whom the public asylum becomes a necessity. Wherever they are,
an orderly life is best for them, with as little irritating interference with
their ways or control of them as is possible.

If the results of treatment are in the highest degree unsatisfactory,

and consist chiefly in meeting symptoms as they come up, without
hope of permanent recovery, it is not impossible that when we can
put the patient under treatment at the very beginning of his disease,
as we can now do in pulmonary consumption, the prognosis in the
former disease may change as much for the better as it has changed
in the latter.

A general paralytic is at any time liable to congestive or maniacal

attacks of short duration, and so is always, potentially, a dangerous
person. In the prodromal period the risk is small; in all stages there
will, in the majority of cases, be some warning; but in the developed
disease the only safe way is to have some responsible person near
at hand, both to prevent the patient from doing harm to others and to
save him from injuring himself, whether by intent or through not
knowing better than to wander off or fall into all sorts of accidents. In
many conditions several should be readily available, or else the
security of an asylum must be sought.

In the treatment of general paralysis by society the same rule should

obtain as in all forms of insanity—that distinct mental disease is
presumptive proof of irresponsibility, or at least of limited
responsibility; that a diseased mind means lessened intellectual
power throughout and diminished ability to choose the right and
avoid the wrong; that there are changes in circulation or nutrition, or
some unknown condition in the brain, especially in general paralysis,
by virtue of which the mental state and power of self-control vary
from time to time, and as a result of which a person seeming
responsible one day may have been quite irresponsible some
previous day.

INSANITY FROM GROSS LESIONS OF THE BRAIN (tumors, new growths of

all kinds, exostoses, spicules or portions of depressed bone,
embolisms, hemorrhages, wounds, injuries, cysticerci, etc.) is
attended with the usual indications of those conditions which may
determine diffuse disorders of the brain, giving rise to any of the
symptoms of the various psycho-neuroses and cerebro-psychoses.
The lowered mental and moral tone after cerebral hemorrhages is a
matter of common observation, and after one an individual is rarely
observed to be fully himself again.

The PROGNOSIS is very unfavorable. Although there are rare cases of

improvement, the tendency is toward profound dementia.

CEREBRAL SYPHILITIC INSANITY comes either under the head of the

insanity last described or belongs to the slowly-advancing dementia
with final paralysis already referred to under the head of Diagnosis in
General Paralysis, and called by some authorities on mental disease
pseudo-paralytic dementia from syphilis.

Antisyphilitic treatment is of value in the first class of cases, and

although most of the recoveries end in relapses and incurability, the
prolonged use of iodide of potassium seems sometimes to effect a
permanent cure. It is claimed that similar treatment is followed by the
same result in the cases of dementia with paresis, but the weight of
authority, and certainly my own experience, are against that
statement.

CHRONIC ALCOHOLIC INSANITY depends upon the vascular and other

changes due to abuse of alcohol so long continued that the
pathological condition has become organic and incurable. It is
commonly associated with delusions of suspicion or persecution. It
may be a purely moral insanity, with gross beliefs rather than
distinctly insane delusions, and it rarely fails to be at least that when
the persistent excessive drinking is kept up until the age of beginning
dissolution of the brain. It then gives rise to all sorts of embarrassing
complications in regard to property, family relations, and wills.
Chronic alcoholic insanity may take the form of mild dementia, by
virtue of which the patient cannot control himself, but can be easily
kept within bounds of reasonable conduct by various degrees of
restraint, from the constant presence of a responsible person to the
seclusion of an asylum. In well-marked cases this dementia is
associated with muscular weakness, tremor, and exhilaration to such
an extent as to simulate general paralysis. It is then called by some
—especially French—writers pseudo-paralytic dementia from
alcohol.

The condition is susceptible of improvement by removal of the

cause, alcohol, and by a carefully-regulated life, hydropathic
treatment, etc., but complete recoveries cannot be expected.

SECONDARY DELUSIONAL INSANITY is slowly developed from various

mental diseases, incurable or uncured, where the progress to
marked dementia is slow, by the persistence of delusions in those
forms of insanity characterized by delusions. It is chronic and
incurable. In melancholia and mania the mental depression and the
exaltation and motor excitement disappear to a great extent, and
there are left a slowly-advancing dementia, confusion, and
expanding delusions, with apathy or with agitation, for which the
asylum is the only safe place unless physical weakness makes the
patient harmless. It is either a terminal state in which many forms of
insanity end, or a stage through which they pass to terminal
dementia. It depends upon incurable, and therefore organic,
changes in the brain, like all incurable insanity, although those
changes are not yet determined exactly. It might be a question
whether chronic delusional insanity properly belongs under the head
of Organic Mental Diseases, and a similar criticism may be made
regarding terminal dementia. But in this paper no definite
classification of insanity is attempted, because our knowledge of the
subject is still so indefinite, although the several mental diseases are
grouped in a certain order for convenience to the reader and the
writer; and this order of course approximately follows natural lines.

TERMINAL DEMENTIA is the end to which most of the insanity not

resulting in recovery finally comes. The features marking the disease
in its early stages for the most part disappear, leaving all the
functions of the mind impaired in all degrees up to total extinction—
the whole character on a lower plane. It is the disease which to so
great an extent crowds the wards of insane asylums and
almshouses with the (1) agitated or (2) apathetic chronic insane, the
worst of whom are mental and physical wrecks, squatting on floors,
uttering an unintelligible jargon, noisy, filthy, without intelligence for
the simplest natural wants. Their chief function, under the prevalent
methods of construction and management of lunatic hospitals in
most places, is to blight with a certain feeling of hopelessness many
of the curable insane who are obliged to go for rest and quiet to
institutions where the overwhelming majority of the inmates are
manifestly and painfully incurable.

French writers include a great part of chronic delusional insanity

(secondary confusional insanity, Wahnsinn, secundäre Verrücktheit)
and terminal dementia (Blödsinn) under one head, démence; and
with much reason, as it is not always possible to differentiate
between the two.

The proper TREATMENT of the incurable, demented insane should

provide not only that they be not at large, where they annoy the
strong and the well, but also that they shall not disturb the insane
who are acutely ill and in need of treatment suited to sick people,
and whose chances of recovery at best are none too favorable.
Experiments, now quite numerous, have shown that the lives and
occupations of many of them may be made not entirely unlike those
to which they were reared, and that nearly all may be suitably
provided for without the expensive hospitals and appliances
necessary for the proper treatment of acute mental disease.

A comparison of countries in which there is and is not a

comprehensive system of State supervision of the insane by a
competent board seems to me to reveal so unquestionably the fact
that such a system alone provides the proper protection for the
insane, and the needed variety and uniformly high standard of
excellence in the provisions for their treatment, that I hope to see the
medical profession using its vast influence upon public opinion to
secure it.

If we meet in the wards of our insane asylums hopeless mental and

physical wrecks, if we find there the extremity of human
wretchedness, the supreme control of all that is evil or vile in our
nature, the worst antitypes of all the virtues, so, on the other hand,
nowhere else do we see such struggles for the mastery of the better
impulses, such efforts against such odds to hold back the mind in an
unequal fight. Nowhere else, too, are developed finer sympathy,
more beautiful unselfishness, more generous charity, or more heroic
resignation where no hope in life remains but for death.

The State has taken charge of these most unfortunate people,

shutting up behind the same locked doors and barred windows
people of all social grades, often mingling together in one presence
the so-called criminal insane, insane criminals, idiots, imbeciles,
epileptics, paralytics, the chronic insane, and the demented, with
patients suffering from acute mental disease. Some of them are
unconscious of their condition, many are better off than ever before,
but others are painfully alive to their situation and surroundings, fully
aware of the gravity of their illness, keenly sensitive to the
distressing sights and associations, disturbed by the noises, and
discouraged by the many chances of becoming like the worst
incurables around them. The State cannot evade the responsibility of
seeing that their confinement is made the least rigorous, wretched,
and injurious possible.
HYSTERIA.
 BY CHARLES K. MILLS, M.D.

DEFINITION.—Hysteria is a functional disease of the cerebro-spinal

axis, characterized either by special mental symptoms or by motor,
sensory, vaso-motor, or visceral disorders related in varying degree
to abnormal psychical conditions.

This, like all other definitions of hysteria, is imperfect. No absolutely

satisfactory definition can well be given. It is not abnormal ideation,
although this is so often prominent; it is not emotional exaltation,
although this may be a striking element; it is not perversion of
reflexes and of sensation, although these may be present. Some
would make it a disease of the womb, others an affection of the
ovaries; some regard it as of spinal, others as of cerebral origin;
some hold it to be a disease of the nerves, others claim that it is a
true psychosis; but none of these views can be sustained.

Sir James Paget1 says of hysterical patients that they are as those
who are color-blind. They say, “I cannot;” it looks like “I will not,” but it
is “I cannot will.” Although, however, much of the nature of hysteria is
made clear in this explanation, hysteria is not simply paralysis of the
will. A true aboulomania or paralysis of the will occurs in non-
hysterical patients, male and female, and of late years has been
studied by alienists.
1 “Clinical Lecture on the Nervous Mimicry of Organic Diseases,” Lancet for October,
November, and December, 1873.

In many definitions the presence of a spasmodic seizure or

paroxysm is made the central and essential feature; but, although
convulsions so frequently occur, typical hysterical cases pass
through the whole course of the disorder without suffering from
spasm of any kind.
In a general neurosis a definition, well considered, should serve the
purpose of controlling and guiding, to a large extent at least, the
discussion of the subject.

The definition given asserts that hysteria is a functional disease. In

the present state of knowledge this is the only ground that can be
taken. It is claimed that in a strict sense no disease can be regarded
as functional; but it is practically necessary to use such terms as
functional in reference to affections in which disordered action
without recognizable permanent alteration of structure is present.
Temporary anatomical changes must sometimes be present in
hysteria; organic disease may be a complication in special cases;
post-mortem appearances may occasionally be found as accidents
or coincidences; it is possible that structural alterations may result
from hysteria; but no pathologist has as yet shown the existence of a
special morbid anatomy underlying as a permanent basis the
hysterical condition.

The mental, motor, sensory, and other phenomena of hysteria

cannot be explained except by regarding the cerebro-spinal nervous
system as the starting-point or active agency in their production.

The term vaso-motor is used in a broad sense to include not only

peripheral vascular disturbances, but also cardiac, respiratory,
secretory, and excretory affections of varying type. Some of these
disorders are also visceral, but under visceral affections are also
included such hysterical phenomena as abdominal phantom tumors,
hysterical tympanites, and the like.

That all hysterical phenomena are related in varying degree to

abnormal psychical conditions may perhaps, at first sight, be
regarded as open to dispute and grave doubt. It is questionable
whether in every case of hysteria the relation of the symptoms to
psychical states could be easily demonstrated. I certainly do not look
upon every hysterical patient as a case of insanity in the technical
sense, but hold that a psychical element is or has been present,
even when the manifestations of the disorder are pre-eminently
physical. James Hendrie Lloyd,2 in a valuable paper, has ably
sustained this position, one which has been held by others, although
seldom, if ever, so clearly defined as by this writer.
2 “Hysteria: A Study in Psychology,” Journal of Nervous and Mental Disease, vol. x.,
No. 4, October, 1883.

The alleged uterine origin of hysteria has been entirely disregarded

in the definition. This has been done intentionally. It is high time for
the medical profession to throw off the thraldom of this ancient view.
The truth is, as asserted by Chambers,3 that hysteria “has no more
to do with the organs of reproduction than with any other of the
female body; and it is no truer to say that women are hysterical
because they have wombs, than that men are gouty because they
have beards.”
3 Brit. Med. Journ., December 21, 1861, 651.

SYNONYMS.—Hysterics, Vapors. Many Latin and other synonyms

have been used for hysteria: most of these have reference to the
supposed uterine origin of the disease, as, for instance, Uteri
adscensus, Asthma uteri, Vapores uterini, Passio hysterica,
Strangulatio uterina seu Vulvæ. Some French synonyms are Maladie
imaginaire, Entranglement, and Maux ou attaques de nerfs. Other
French synonyms besides these have been used; most of them are
translations from the Latin, having reference also to the uterine
hypothesis. In our language it is rare to have any other single word
used as a synonym for hysteria. Sir James Paget4 introduced the
term neuromimesis, or nervous mimicry, and suggested that it be
substituted for hysteria, and neuromimetic for hysterical.
Neuromimesis is, however, not a true synonym. Many cases of
hysteria are cases of neuromimesis, but they are not all of this
character. Among the desperate attempts which have been made to
originate a new name for hysteria one perhaps worthy of passing
notice is that of Metcalfe Johnson,5 who proposes to substitute the
term ganglionism, as giving a clue to the pathology of hysteria. His
main idea is that hysteria exhibits a train of symptoms which are
almost always referable to the sympathetic or ganglionic nervous
system. This is another of those half truths which have misled so
many. The term hysteria, from the Greek ὑστερα, the uterus,
although attacked and belabored, has come to stay; it is folly to
attempt to banish it.
4 Op. cit.

5 Med. Times and Gaz., 1872, ii. 612.

METHOD OF DISCUSSING THE SUBJECT.—It is hard to decide upon the

best method of discussing the subject of hysteria. One difficulty is
that connected with the question whether certain affections should
be considered as independent disorders or under some subdivisions
of the general topic of hysteria. Certain great phases of hysteria are
represented by hystero-epilepsy, catalepsy, ecstasy, etc.; but it will
best serve practical ends to treat of these in separate articles. They
have distinctive clinical features, and are capable of special definition
and discussion.

HISTORY AND LITERATURE.—To give a complete history of hysteria it

would be necessary to traverse the story of medicine from the time
of Hippocrates to the present. A complete bibliography would require
an immense volume. Volume vi. of the Index Catalogue of the
Library of the Surgeon-General's Office, United States Army, which
has appeared during the present year (1885), contains a
bibliography of nearly seventeen double-column pages, most of it in
the finest type. The references are to 318 books and 914 journals.
The number of books and articles cited as having appeared in
different languages is as follows: Latin, 99; Greek, 2; German, 180;
British, 177; American, 159; French, 449; Italian, 75; Spanish, 45;
Swedish, 12; miscellaneous, 34. Even this wonderful list probably
only represents a tithe of the works written on this subject. Those
desirous of studying it from a bibliographical point of view can do so
by consulting this great work.

Many as are the names and voluminous as is the literature, certain

names and certain works are pre-eminent—Sydenham, Laycock,
and Skey in England; Tissot, Briquet, Charcot, and Landouzy in
France; Stahl, Frank, Eulenburg, and Jolly in Germany; and in