2015 nutrition support for the critically ill patient a guide to practice second Edition2015UnitedVRG

Second Edition

Nutrition Support for
the Critically Ill Patient
A Guide to Practice

Edited by Gail A. Cresci



Second Edition

Nutrition for the
Critically Ill Patient
A Guide to Practice



Second Edition

Nutrition for the
Critically Ill Patient
A Guide to Practice

Edited by Gail A. Cresci

Boca Raton London New York

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Contents

Foreword............................................................................................................................................ix
Editor.............................................................................................................................................. xiii
Contributors...................................................................................................................................... xv

Section I Metabolic Alterations in the Critically Ill:
Comparison of Nonstressed and Stressed States
Chapter 1 Organic Response to Stress...........................................................................................3
Maria Isabel Toulson Davisson Correia
Chapter 2 Carbohydrate Metabolism: A Comparison of Stress and Nonstress States................ 15
Mary Marian and Susan Roberts
Chapter 3 Protein and Amino Acid Metabolism: Stress versus Nonstress States....................33
Gail A. Cresci
Chapter 4 Lipid Metabolism: Stress versus Nonstress States...................................................... 53
Dan L. Waitzberg, Raquel S. Torrinhas, and Letícia De Nardi

Section II Nutrients for the Critically Ill
Chapter 5 Nutrition Assessment and Monitoring........................................................................ 77
Kavitha Krishnan and Michael D. Taylor
Chapter 6 Energy Expenditure in the Critically Ill Patient.......................................................... 93
David Frankenfield
Chapter 7 Macronutrient Requirements: Carbohydrate, Protein, and Fat................................. 111
Michael D. Taylor, Kavitha Krishnan, Jill Barsa, and Kendra Glassman Perkey
Chapter 8 Micronutrient and Antioxidant Therapy in Adult Critically Ill Patients................... 123
Krishnan Sriram

v


vi

Contents

Chapter 9 Fluid, Electrolyte, and Acid–Base Requirements in the Critically Ill Patient.......... 139
Maria R. Lucarelli, Lindsay Pell Ryder, Mary Beth Shirk, and Jay M. Mirtallo
Chapter 10 Gut Microbiome in the Critically Ill......................................................................... 169
Gail A. Cresci

Section III  Delivery of Nutrition Therapy in the Critically Ill
Chapter 11 Parenteral versus Enteral Nutrition........................................................................... 187
Gail A. Cresci
Chapter 12 Vascular Access in the Critically Ill Patient............................................................. 203
Lindsay M. Dowhan, Jesse Gutnick, and Ezra Steiger
Chapter 13 Enteral Feeding Access in the Critically Ill Patient.................................................. 219
Beth Taylor and John E. Mazuski
Chapter 14 Parenteral Formulations............................................................................................ 237
Michael Christensen
Chapter 15 Enteral Formulations................................................................................................. 259
Ainsley M. Malone
Chapter 16 Complications of Parenteral Nutrition...................................................................... 279
Mandy L. Corrigan
Chapter 17 Enteral Feeding Challenges...................................................................................... 291
Carol Rees Parrish, Joe Krenitsky, and Kendra Glassman Perkey
Chapter 18 Drug–Nutrient Interactions....................................................................................... 313
Rex O. Brown and Roland N. Dickerson

Section IV Nutrition Therapy throughout the Life Cycle
Chapter 19 Nutrition Support during Pregnancy......................................................................... 331
Christina J. Valentine, Joy Lehman, and Carol L. Wagner
Chapter 20 Nutrition Support for the Critically Ill Neonate........................................................ 349
Jatinder Bhatia and Cynthia Mundy

vii

Contents

Chapter 21 Nutrition Support for the Critically Ill Pediatric Patient........................................... 367
Jodi Wolff, Gerri Keller, and Deborah A. Carpenter
Chapter 22 Geriatrics................................................................................................................... 381
Ronni Chernoff

Section V Nutrition Therapy for Special Interests Groups
Chapter 23 Trauma and Acute Care Surgery............................................................................... 397
Michael D. Taylor and Kavitha Krishnan
Chapter 24 Nutrition Support for Burns and Wound Healing.....................................................407
Theresa Mayes and Michele M. Gottschlich
Chapter 25 Solid Organ Transplantation..................................................................................... 433
Jeanette Hasse and Srinath Chinnakotla

Section VI  Specific Organ System Failure
Chapter 26 Nutrition in the Critically Ill Patient with Intestinal Failure..................................... 457
Cassandra Pogatschnik, Neha Parekh, and Ezra Steiger
Chapter 27 Nutrition Support for Pulmonary Failure.................................................................. 467
Alfredo A. Matos, William Manzanares, and Víctor Sánchez Nava
Chapter 28 Renal Failure............................................................................................................. 483
Tom Stone McNees
Chapter 29 Nutrition for the Critically Ill Patient with Hepatic Failure...................................... 497
Mazen Albeldawi, Peggy Hipskind, and Dian J. Chiang
Chapter 30 Nutrition for the Critically Ill Cardiac Patient.......................................................... 511
A. Christine Hummell

Chapter 31 Nutrition Support in Neurocritical Care................................................................... 519
Arlene Escuro and Mary Rath
Chapter 32 Nutritional Support in Acute Pancreatitis................................................................. 535
R.F. Meier


viii

Contents

Section VII  General Systemic Failures
Chapter 33 Nutrition Support in the General Surgery ICU Patient............................................. 551
Amy Berry and Kenneth A. Kudsk
Chapter 34 Nutritional Support during Systemic Inflammatory Response Syndrome
and Sepsis.................................................................................................................. 567
Mark H. Oltermann and Mary E. Leicht
Chapter 35 Nutrition Therapy in Patients with Cancer and Immunodeficiency.......................... 589
Vanessa Fuchs-Tarlovsky and Elizabeth Isenring
Chapter 36 Nutrition Support in the Chronically Critically Ill Patient.......................................605
Rifka C. Schulman and Jeffrey I. Mechanick
Chapter 37 Nutrition Therapy for the Obese Critically Ill Patient.............................................. 619
Britta Brown and Katherine Hall

Section VIII  Professional Issues
Chapter 38 Ethical Considerations in the Critically Ill Patient................................................... 635
Denise Baird Schwartz
Chapter 39 Instituting Professional Nutrition Practice Guidelines
and Protocols: In the Intensive Care Unit................................................................. 653
Malissa Warren, Robert Martindale, and Mary S. McCarthy
Chapter 40 Quality and Performance Improvement in the Intensive Care Unit......................... 667

Mary Krystofiak Russell


Foreword
During the latter half of the twentieth century and to the present day, critical care of seriously ill
or injured patients has evolved to become the highest priority for most, especially skilled, healthcare teams in most hospitals in the United States and throughout the world. Indeed, we are rapidly
approaching the point at which hospitalized patients will consist of those requiring highly specialized intensive care services in various critical care units by highly talented and motivated comprehensive teams of health-care professionals, using state-of-the-art knowledge and technology,
and those with complex acute or chronic disorders or conditions that cannot be treated adequately
or practically on an ambulatory basis, or in an alternate health maintenance and care facility, or at
home. The vast majority of patients requiring medical and/or surgical services will be treated in
same-day or short-stay facilities and discharged promptly to their homes or to appropriate assisted
living facilities for recovery, convalescence, and rehabilitation. Many of the hospitalized patients
will belong to opposite ends of the life cycle, that is, the pediatric and geriatric age groups, especially the latter group, which is the most rapidly increasing segment of the population in this ­country.
Not only do these cadres of hospitalized patients experience the highest incidences of critical illnesses, complications, and collateral conditions, but a majority of them will also exhibit some form
of undernutrition or malnutrition prior to, or at, admission or will develop nutritional deficiencies
or aberrations during the course of their diagnostic and therapeutic interventions throughout their
hospitalization. The adage that “No disease process, injury, or major disorder can be expected to
respond as favorably to therapeutic medical and/or surgical treatments when the patient is malnourished or undernourished as when the patient is optimally nourished” remains as true today as when
it was first uttered, perhaps by Hippocrates, centuries ago. This fact alone justifies the production of
this second edition of Nutrition Therapy for the Critically Ill Patient: A Guide to Practice by Gail
A. Cresci, PhD, RD, and the distinguished cast of colleagues and authors that she has assembled
to share their vast expertise, in depth and in a broad field of nutrition-related topics. Moreover, in
more than three dozen chapters, the editor and her contributors have conscientiously and effectively
addressed and dealt with the most important of the myriad complex aspects of nutrition therapy in
critically ill patients, which is highly essential to their survival and subsequently to the quality of
their lives.
The advancements in the field of both critical care and nutrition therapy during the past 50 years
have been truly phenomenal, have occurred in symbiosis with each other, have revolutionized the
care and management of critically ill patients, have saved countless lives, have changed the practice of medicine forever, and will undoubtedly improve the morbidity, mortality, and other outcomes in this vital arena of health-care endeavor as progress continues in the future. During the
past 55 years of my education, training, and practice of medicine, surgery, and nutrition support,

I have been privileged to witness and/or participate in a virtual revolution in the care of critically
ill patients, which, in retrospect, borders on the unbelievable. When I was a medical student from
1957 to 1961 at the University of Pennsylvania School of Medicine, the only formal nutrition taught
in the curriculum was a one-hour lecture on vitamin deficiencies; clinical intravenous therapy
consisted of p­ eripherally administered 5% dextrose in water, saline, or lactated Ringers solution
with added vitamin C and the B complex vitamins, and some potassium; tube feedings were used
rarely and usually consisted of blenderized house diets infused into the stomach by a large nasogastric tube or occasionally through a large gastrostomy tube; jejunostomy tube feedings, usually
consisting of blenderized foods, were highly problematic, and no special partially digested food
substrates acceptable for infusion into the duodenum or jejunum had yet been developed; and no
intensive care, critical care, or special care units were available in the Hospital of the University of

ix


x

Foreword

Pennsylvania, which comprised largely multiple 40-bed Florence Nightingale Wards, and some
semiprivate two-bed rooms and private single-bed rooms. Caring for critically ill patients at that
time was difficult and frustrating, without adequate designated special space, special skilled nurses,
special dieticians/nutritionists, and special equipment, supplies, resources, and access. Moreover, it
was well known among the medical students and house officers that a critically ill patient was more
likely to receive more, better, and more effective care in an open ward than in a relatively isolated
and confined private or semiprivate room.
Several events during my senior year in medical school and my internship transformed both me
and the hospital as health-care providers. The Department of Surgery acquired limited amounts of
experimental intravenous protein hydrolysate solutions and intravenous cottonseed oil emulsion for
limited patient use, and I was privileged to participate in some clinical trials of these new, revolutionary, intravenous nutritional substances. Early in my internship year (1961–1962), I became
acutely aware of, and deeply disturbed by, the lethal effect of severe malnutrition and undernutrition

upon the outcomes of major surgical patients, especially those with complex problems requiring
multiple operative procedures. Even more disconcerting to me was our inability to provide adequate
nutrition to patients with major disabilities of, or other impediments to, the use of the gastrointestinal tract. This stimulated me to undertake basic and clinical investigations, which eventually led
to the development of the first successful technique of long-term total parenteral nutrition (TPN).
During the same time period, the hospital remodeled a small area to create its first four-bed
surgical intensive care unit (SICU) and another similar area to create an acute coronary care unit
(CCU). I was actually the first house officer assigned to the rudimentary SICU that had four beds,
each having access to an oxygen supply for delivery by mask or nasal cannula, suction apparatus, a
4 in. diameter continuous EKG monitor, and a skilled nurse (the most important feature). I was the
indwelling house officer, and I had a reclining chair in which I could rest or even nap occasionally
during the month of my rotation while attending to the continual needs of the most critically ill
surgical patients in the hospital. Such was critical care in the early 1960s—but it was a giant step
forward in the right direction. By the time I was the chief resident in surgery in 1966–1967, the hospital had added three 12-bed special care units, each individually designed and equipped to provide
critical care specifically for patients with surgical, cardiac, or pulmonary problems. Modern monitoring equipment, ventilators, respirators, defibrillators, external cardiac pacing units, supplies and
equipment for emergency tracheostomy, venous cutdowns, arterial lines, insertion of chest tubes,
ostomy care, and portable fluoroscopic and x-ray equipment were added to the armamentarium of
the critical care team.
Although these units were the premier care stations for critically ill patients, they also served as
a source of invaluable new information and knowledge as we studied the effects of our efforts upon
the patients’ clinical courses and outcomes. However, perhaps the most profound advance in this
critical area was the acquisition of the first extramural NIH Clinical Research Center in the United
States by the Department of Medicine faculty of the Hospital of the University of Pennsylvania.
It was there that I was able to carry out the most finite and elegant nutritional and metabolic studies
in critically ill patients, with the help and support of an elite, skilled, motivated, conscientious staff
of nurses, dietitians, technicians, and physicians who were dedicated to practicing their professions
with utmost precision and proficiency in a most collegial and collaborative manner. Intravenous
infusion pumps, central venous catheters and infusion lines, laminar airflow areas, and regimens
for long-term continuous central venous infusion of TPN were introduced and perfected there to the
point that our results could be evaluated, validated, and shared with the critical care community,
not only of the United States but also of the world. Principles, practices, and procedures were developed, tested, and standardized as much as possible to ensure their optimal safety and effectiveness

with minimal complications, morbidity, and mortality. Special nutrient solutions were developed for
patients with renal, liver, and pulmonary failures and metabolic lipodystrophies. Our most notable
achievement, however, occurred in the neonatology intensive care unit of our Children’s Hospital of
Philadelphia, where a severely malnourished infant with multiple congenital anomalies, including


Foreword

xi

extremely short bowel syndrome (and near death), was nourished entirely by central venous TPN for
45 days. She was the first infant to exhibit normal growth and development long term while being
fed exclusively intravenously. This demonstration revolutionized the care of premature infants and
all critically ill infants with severely compromised gastrointestinal tracts and secondary malnutrition—and changed the practice of neonatology forever.
The relevance of nutrition therapy for the critically ill patient was obvious, largely as a result
of these basic studies, and has spawned myriad investigations in virtually all aspects of nutritional
and metabolic support, orally, enterally, parenterally, and in various combinations. Nonetheless,
many questions remain to be answered and many problems beg resolution in this vital area of
health care as we strive to achieve perfection in nutrition and metabolic support. This textbook, by
virtue of the many important areas addressed by the many expert clinician-scientists, will serve
to provide the most up-to-date, state-of-the-art data, information, experience, technology, and
techniques to help keep both novices and experts informed and aware of the continuous accrual
of knowledge applicable to the optimal care of the critically ill patient. However, the reader will
also be aware that controversies still exist regarding nutrition therapy, especially in critically ill
patients. Among them are optimal dietary composition, early feeding to target goals, hyperglycemia and insulin use, maintenance of euglycemia, early enteral versus parenteral feeding, overfeeding and refeeding syndrome, and the composition and prudent use of lipid emulsions. Additionally,
the compositions of amino acid, vitamin, trace element, and immune-enhancing formulations, and
their appropriate use, are still controversial. Problems persist relevant to obesity prevention, arrest,
and reversal, on one hand, and to the management of various cachexia problems on the other.
Persistent areas of special feeding problems include cancer patients, geriatric patients, premature
neonates and surgical infants, and patients with severe short bowel syndrome, especially those

with associated liver failure. Obviously, much remains to challenge our interests, talents, and ingenuity (and especially, our motivation, persistence, and resilience) as we strive to provide optimal
nutrition to all patients under all conditions at all times. As we do so, we will find this guide to
practice to be an invaluable asset in our quest to craft and provide optimal nutrition therapy for the
critically ill patient. For that, we are deeply indebted to nutritionist and editor Gail A. Cresci and
her collaborating authors for so generously sharing with us their expertise, experience, knowledge,
counsel, skills, and wisdom.
Stanley J. Dudrick, MD, FACS, FACN, CNS
Department of Surgery
School of Medicine
Yale University
New Haven, Connecticut



Editor
Gail A. Cresci, PhD, RD, LD, is an associate staff in the Department of Gastroenterology,
Hepatology and Pathobiology at the Cleveland Clinic and assistant professor of medicine at the
Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio. She has more than 25  years of
clinical experience practicing in critical care with a focus on surgery and gastrointestinal disorders.
Dr. Cresci is the author of numerous peer-reviewed journal articles, book chapters, abstracts, and
videos and currently serves on the editorial boards of several journals. She lectures extensively, both
nationally and internationally and has held numerous positions within the American Society for
Parenteral and Enteral Nutrition (ASPEN), the Academy of Nutrition and Dietetics, and the Society
of Critical Care Medicine.
Dr. Cresci is the past chair of Dietitians in Nutrition Support, a practice group within the
Academy of Nutrition and Dietetics. She has served on multiple national and state society conference planning committees, serving as chair for the ASPEN planning committee. She is the recipient of numerous honors and awards, including the American Dietetic Association Excellence in
Practice of Clinical Nutrition, the ASPEN Distinguished Nutrition Support Dietitian Advanced
Clinical Practice Award, the ASPEN Promising New Investigator Award, and the Academy of
Nutrition and Dietetics Excellence in Practice Dietetics Research Award.

xiii



Contributors
Mazen Albeldawi
Department of Gastroenterology and
Hepatology
NCH Healthcare System
Naples, Florida
Jill Barsa
Fairview Hospital
Cleveland Clinic Health System
Cleveland, Ohio
Amy Berry
University of Virginia Health System
Charlottesville, Virginia
Jatinder Bhatia
Division of Neonatology
Department of Pediatrics
Georgia Regents University
Augusta, Georgia

Dian J. Chiang
Cleveland Clinic
Cleveland, Ohio
Srinath Chinnakotla
Transplantation
Baylor University Medical Center
Dallas, Texas

Michael Christensen
University of Tennessee Health Science Center
Memphis, Tennessee
Maria Isabel Toulson Davisson Correia
Medical School
Federal University of Minas Gerais
Belo Horizonte, Brazil
Mandy L. Corrigan
Center for Human Nutrition
Cleveland Clinic
Cleveland, Ohio

Britta Brown
Medical Nutrition Therapy
Hennepin County Medical Center
Minneapolis, Minnesota

Gail A. Cresci
Gastroenterology and Center for Human
Nutrition
Cleveland Clinic
Cleveland, Ohio

Rex O. Brown
Department of Pharmacy
University of Tennessee Health Science Center
and
Regional Medical Center at Memphis
Memphis, Tennessee

Letícia De Nardi
Department of Gastroenterology
Medical School
University of Sao Paulo
Sao Paulo, Brazil

Deborah A. Carpenter
Akron Children’s Hospital
Akron, Ohio
Ronni Chernoff
Arkansas Geriatric Education Center
and
Reynolds Department of Geriatrics
University of Arkansas for Medical Sciences
Little Rock, Arkansas

Roland N. Dickerson
Department of Clinical Pharmacy
University of Tennessee Health Science Center
and
Regional Medical Center at Memphis
Memphis, Tennessee
Lindsay M. Dowhan
Center for Gut Rehabilitation and Transplant
Digestive Disease Institute
Cleveland Clinic
Cleveland, Ohio
xv

xvi

Stanley J. Dudrick
Department of Surgery
School of Medicine
Yale University
New Haven, Connecticut
Arlene Escuro
Cleveland Clinic
Cleveland, Ohio

Contributors

Peggy Hipskind
Center for Human Nutrition
Cleveland Clinic
Cleveland, Ohio
A. Christine Hummell
Cleveland Clinic
Cleveland, Ohio

David Frankenfield
Milton S. Hershey Medical Center
Hershey, Pennsylvania

Elizabeth Isenring
Faculty of Health Sciences and Medicine
Bond University
Brisbane, Australia

Vanessa Fuchs-Tarlovsky
Oncology Department
Hospital General de Mexico
Mexico City, Mexico

Gerri Keller
Akron Children’s Hospital
Akron, Ohio

Kendra Glassman Perkey
Rocky Mountain Hospital for Children at PSL
Denver, Colorado
Michele M. Gottschlich
Shriners Hospitals for Children
Cincinnati, Ohio
and
Department of Surgery
College of Medicine
University of Cincinnati
Cincinnati, Ohio
Jesse Gutnick
Administrative Chief Resident
Department of General Surgery
Cleveland Clinic
Cleveland, Ohio
Katherine Hall
Medical Nutrition Therapy
Hennepin County Medical Center
Minneapolis, Minnesota
Jeanette Hasse

Transplantation
Baylor University Medical Center
Dallas, Texas

Joe Krenitsky
Digestive Health Center of Excellence
University of Virginia Health System
Charlottesville, Virginia
Kavitha Krishnan
Clinical Dietitian
Fairview Hospital
Cleveland Clinic Health System
Cleveland, Ohio
Kenneth A. Kudsk
Department of Surgery
University of Wisconsin Medical Center
Madison, Wisconsin
Joy Lehman
The Ohio State University Wexner Medical Center
Columbus, Ohio
Mary E. Leicht
Department of Nutrition
John Peter Smith Hospital
Fort Worth, Texas
Maria R. Lucarelli
Division of Pulmonary, Allergy, Critical Care,
and Sleep Medicine
Department of Internal Medicine
The Ohio State University Wexner Medical Center
Columbus, Ohio

xvii

Contributors

Ainsley M. Malone
Mount Carmel West Hospital
Columbus, Ohio
William Manzanares
Faculty of Medicine
Department of Critical Care
University of the Republic
Montevideo, Uruguay
Mary Marian
Colleges of Agriculture and Life Sciences/
Medicine
The University of Arizona
Tucson, Arizona
Robert Martindale
General Surgery Division
Oregon Health Sciences University
Portland, Oregon
Alfredo A. Matos
Faculty of Medicine
Dr. AAM Social Security Hospital
University of Panama
Panama City, Panama
Theresa Mayes
Division of Nutrition Therapy

Cincinnati Children’s Hospital Medical Center
Cincinnati, Ohio

Jeffrey I. Mechanick
Division of Endocrinology, Diabetes, and Bone
Diseases
Icahn School of Medicine at Mount Sinai
New York, New York
R.F. Meier
Department of Gastroenterology, Hepatology
and Nutrition
Kantonsspital Baselland
Medical University Clinic
Liestal, Switzerland
Jay M. Mirtallo
College of Pharmacy
The Ohio State University
Columbus, Ohio
Cynthia Mundy
Division of Neonatology
Department of Pediatrics
Georgia Regents University
Augusta, Georgia
Víctor Sánchez Nava
Monterrey Institute of Technology and Higher
Education
Monterrey, Mexico
Mark H. Oltermann
John Peter Smith Hospital
Fort Worth, Texas

John E. Mazuski
School of Medicine
Barnes-Jewish Hospital
Washington University
St. Louis, Missouri

Neha Parekh
Center for Gut Rehabilitation and
Transplantation
Cleveland Clinic
Cleveland, Ohio

Mary S. McCarthy
Center for Nursing Science and Clinical
Inquiry
Madigan Army Medical Center
Fort Lewis, Washington

Carol Rees Parrish
Digestive Health Center of Excellence
University of Virginia Health System
Charlottesville, Virginia

Tom Stone McNees
Holston Valley Medical Center
Wellmont Health System
Kingsport, Tennessee

Lindsay Pell Ryder

Department of Pharmacy
The Ohio State University Wexner Medical
Center
Columbus, Ohio


xviii

Cassandra Pogatschnik
Center for Human Nutrition
and
Center for Gut Rehabilitation and
Transplantation
Cleveland Clinic
Cleveland, Ohio
Mary Rath
Cleveland Clinic
Cleveland, Ohio
Susan Roberts
Nutrition Department
Baylor University Medical Center
Dallas, Texas
Mary Krystofiak Russell
Baxter Healthcare Corporation
Deerfield, Illinois
Rifka C. Schulman
Division of Endocrinology, Metabolism and
Diabetes
Long Island Jewish Medical Center
New Hyde Park, New York

Denise Baird Schwartz
Food and Nutrition Services
Providence Saint Joseph Medical Center
Burbank, California
Mary Beth Shirk
Department of Pharmacy
The Ohio State University Wexner
Medical Center
Columbus, Ohio
Krishnan Sriram
Cook County Health and Hospital Systems
John H. Stroger, Jr. Hospital
Chicago, Illinois
Ezra Steiger
Department of General Surgery
Digestive Disease Institute
Cleveland Clinic
Cleveland, Ohio

Contributors

Beth Taylor
Barnes-Jewish Hospital
St. Louis, Missouri
and
American College of Critical Care Medicine
Mt. Prospect, Illinois
Michael D. Taylor
Department of Surgery
Fairview Hospital

Cleveland Clinic Health System
Cleveland, Ohio
Raquel S. Torrinhas
Department of Gastroenterology
Medical School
University of São Paulo
São Paulo, Brazil
Christina J. Valentine
Cincinnati Children’s Hospital
Cincinnati, Ohio
Carol L. Wagner
The Medical College of South Carolina
Charleston, South Carolina
Dan L. Waitzberg
Department of Gastroenterology
University of São Paulo
São Paulo, Brazil
Malissa Warren
Portland VA Medical Center
Portland, Oregon
Jodi Wolff
Rainbow Babies and Children’s Hospital
Cleveland, Ohio


Section I
Metabolic Alterations in the
Critically Ill: Comparison of
Nonstressed and Stressed States

1

Organic Response to Stress
Maria Isabel Toulson Davisson Correia

CONTENTS
Introduction......................................................................................................................................... 3
Stress................................................................................................................................................... 4
Historical Perspective......................................................................................................................... 5
Organic Response to Stress.................................................................................................................6
Ebb and Flow Phases..................................................................................................................... 6
Glucose and Protein Metabolism...................................................................................................7
Fluid and Electrolyte Response......................................................................................................8
Endocrine Response....................................................................................................................... 8
Hypothalamic–Pituitary–Adrenal Axis.....................................................................................8
Thyrotropic Axis....................................................................................................................... 9
Somatotropic Axis................................................................................................................... 10
Lactotropic Axis...................................................................................................................... 10
Luteinizing Hormone–Testosterone Axis................................................................................ 10
Inflammatory Response................................................................................................................ 10
Immunologic Response................................................................................................................ 12
Conclusions....................................................................................................................................... 12
References.........................................................................................................................................12

INTRODUCTION
The organic response to stress—first described as the metabolic response to trauma, in 1942, by Sir
David Cuthbertson—is a physiologic phenomenon secondary to any insult to the body. Cuthbertson
[1] introduced the terms ebb and flow to describe the phases of hypo- and hypermetabolism that

follow traumatic injury. Such phenomenon is triggered by multiple stimuli, including arterial and
venous pressure derangements, changes in volume, osmolality, pH, and arterial oxygen content.
Also, pain, anxiety, and toxic mediators from tissue injury and infection trigger the organic response
(Table 1.1). These stimuli reach the hypothalamus stimulating the sympathetic nervous system and
the adrenal medulla. This physiological response to an insult might become pathological depending on the intensity and duration of injury. The organic response can be seen as the fight or flight
response to adverse phenomena that can become highly associated with increased morbidity and
mortality if perpetuated for long periods. The ultimate goal of the organic response is to restore
homeostasis. Intermediate goals are to limit further blood loss; to increase blood flow, allowing
greater delivery of nutrients and elimination of waste products; and to debride necrotic tissue and
to initiate wound healing.
Currently, with the development of medical sciences, the once simple metabolic response to
stress (represented by the ebb and flow phases) has evolved into a complicated and intricate web of
responses. Therefore, a better appropriate denomination such as the organic response to stress that
encompasses several body compartments should be used. Although, one cannot fully go against

3


4

Nutrition Support for the Critically Ill Patient: A Guide to Practice

TABLE 1.1
Organic Response to Stress: Triggering Factors
•
•
•
•
•
•

•
•
•

Body temperature (hypo- and hyperthermia)
Excessive bleeding (shock)
Fluid and electrolyte derangements
Infection
Inflammation
Pain
Poor nutritional status
Prolonged fasting
Psychological problems

Trauma

Ascending
reticular formation
Hypovolemic
shock

Macrophages

Limbic system

Hypothalamus
Ant. pituitary

Renin
Angiotensin 2

ACTH

GH

Incr. temp
Incr. WBC
Incr. IgG

Sympathetic
nervous system

Catecholamines

Post. pituitary

Prolactin

Cortisol and
aldosterone

IL-1

ADH

1. Tachycardia
2. Tachypnoea
3. Vasoconstriction

FIGURE 1.1  Organic response to stress.

its development, recognizing its magnitude and knowing its different particularities might help
minimize the risks of perpetuating its duration, leading to the reduction of morbidity and mortality related to it. In surgical stress, especially under major elective conditions, it’s important for
surgeons to be aware that a perfect anatomic operation maybe followed by a disastrous outcome
if patients are not metabolically conditioned. Undernutrition, pain control, and fluid and electrolyte balance, among others, are of paramount importance and should be dealt in a multimodal
approach to decrease the organic response to trauma [2–6]. Therefore, it is extremely important
to be acquainted with the complex mechanisms of the organic response (Figure 1.1) in order to act
early and, maybe, prevent some of its deleterious effects.
The magnitude of the response and the adequate initial approach are determinant factors that
might influence the patient’s outcome [2,5,7–9]. The severity of the hypermetabolic phenomena
thereafter might lead to the systemic inflammatory response syndrome (SIRS), the amplified generalized body response, which may culminate with multiorgan dysfunction and death.

STRESS
Stress is a term applied to the fields of physiology and neuroendocrinology and refers to those
forces or factors that cause disequilibrium to an organism and therefore threaten homeostasis
[10]. The stressors might be a consequence of physical injury, mechanical disruptions, chemical


Organic Response to Stress

5

changes, or emotional factors. The body’s response to these factors will depend on their magnitude, duration, as well as the nutritional status of the patient. Complex sensory systems trigger
reflex nervous system responses to the stressors that alert the central nervous system (CNS) of
the disturbance. In the CNS, neurons of the paraventricular nucleolus of the hypothalamus elaborate corticotropin-­releasing h­ ormone (CRH) and activate the hypothalamic–pituitary–­adrenal
axis (HPA). In addition, other areas of the brain also signal the peripheral autonomic nervous
system. These two latter systems elicit an integrated-response, referred to collectively as the stress
response, which primarily controls bodily functions such as arousal, cardiovascular tone, respiration, and intermediate metabolism [1]. Other functions such as feeding and sexual behavior are
suppressed, while cognition and emotion are activated. In addition, gastrointestinal activity and
immune/inflammatory responses are altered.

HISTORICAL PERSPECTIVE
Sir David Cuthbertson, a chemical pathologist in Glasgow, was the first physician studying the
metabolic response to injury in the early part of the twentieth century, by following patients
with long bone fractures [1]. However, long before Cuthbertson’s studies, John Hunter, in his
Treatise on the Blood, Inflammation and Gunshot Wounds [11], was the first to question the
paradox of the response to injury by saying, “Impressions are capable of producing or increasing natural actions and are then called stimuli, but they are likewise capable of producing too
much action, as well as depraved, unnatural, or what we commonly call diseased action.” He
must have intuitively perceived that nature might have created these responses in order to have
some advantages in terms of recovery, but he also noticed that if the responses were overexaggerated, life could be jeopardized.
The concept that illness was associated with an increased excretion of nitrogen leading to negative nitrogen balance was defined in the late nineteenth century. During the First World War, studies
carried out by DuBois [12] showed that an increase in 1°C in temperature was associated with a 13%
increase in the metabolic rate.
Cuthbertson’s findings were derived from questions aroused by orthopedic surgeons who were
eager to find out why patients with fractures of the distal third of the tibia were slow to heal. His
studies were negative in the sense that he could not offer the exact explanation to the question, but
at the same time, he came up with something much more interesting and fundamental. He measured the excretion of calcium, phosphorus, sulfate, and nitrogen in the urine and found that the
amount of excreted phosphorous and sulfate in relation to calcium was higher than expected if all
these elements had come from the bone. He went on to show that this was a catabolic phenomenon
related to breakdown of protein, reflecting an increase in metabolic rate. The association between
the systemic metabolic response and hormonal elaboration was soon sought, but this approach
was initially hampered by methodological problems. The investigations carried out by Cannon
[13] on the autonomic nervous system suggested the increased catecholamine response to illness
as one of the explanations of the physiologic responses seen by Cuthbertson. Later, Selye proposed
corticosteroids as the main mediators of the protein catabolic response [14]. However, the following question still remained unanswered: what was the signal that initiated and propagated the
immediate elaboration of the adrenal cortical hormones? Hume [15] and Egdahl [16] showed that
in injured dogs (operative injury or superficial burn to the limbs) with intact sciatic nerves or spinal
cords, there was an increase of adrenal hormones, contrary to what happened in those animals
with transected nerves or spinal cords, in whom the response was abated. From the investigated
setting, it was possible to identify afferent nervous signals as essential components to trigger the

HPA stress response.
Allison et al. [17] showed that such organic response was also associated with suppression of insulin release, followed by a period of insulin resistance and with high glucagon and
growth hormone (GH) levels. Recently, the organic response has been associated not only