1439879990

Second Edition

A Guide to Practice

Edited by Gail A. Cresci

Nutrition Support for the Critically Ill Patient

Nutrition Support for the Critically Ill Patient

Cresci

SecondEdition

Completely revised and updated, Nutrition Support for the Critically Ill Patient: A Guide to Practice, Second Edition presents an unbiased, evidence-based examination of critical nutrition across the life cycle. Taking a multidisciplinary approach, each chapter has been carefully designed to provide a comprehensive review of the literature and a detailed exploration of the practical application of this information. With chapters written by experts, you get the most pertinent and current knowledge available, bolstered by tables, figures, and case studies that make the information accessible.

New Coverage in the Second Edition:

Gut microbiota support

Short bowel syndrome

Chronic critically ill phenomenon

Professional nutrition practice guidelines and protocols

Ethical considerations

Quality and performance improvement

Many challenges remain when providing optimal nutrition to all patients under all conditions at all times. Divided into eight sections, the book covers metabolic issues, nutrients for critically ill patients, delivery of nutrition therapy, nutrition therapy throughout the life cycle, special interest groups, specific organ system failure, general systemic failures, and professional issues in the field. It keeps you informed and aware of the continuous accrual of knowledge needed to craft and provide optimal nutrition therapy for the critically ill patient.

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NUTRITION

A Guide to Practice

Nutrition Support for theCritically Ill Patient

Second Edition

Second Edition

A Guide to Practice

Nutrition for theCritically Ill Patient

Boca Raton London New York

CRC Press is an imprint of theTaylor & Francis Group, an informa business

Second Edition

A Guide to Practice

Edited by Gail A. Cresci

Nutrition for theCritically Ill Patient

CRC PressTaylor & Francis Group6000 Broken Sound Parkway NW, Suite 300Boca Raton, FL 33487-2742

2015 by Taylor & Francis Group, LLCCRC Press is an imprint of Taylor & Francis Group, an Informa business

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vContentsForeword ...........................................................................................................................................ixEditor ............................................................................................................................................. xiiiContributors .....................................................................................................................................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 versusNonstressStates....................33

Gail A. Cresci

Chapter 4 Lipid Metabolism: Stress versus Nonstress States ..................................................... 53

Dan L. Waitzberg, Raquel S. Torrinhas, and Letcia 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

vi Contents

Chapter 9 Fluid, Electrolyte, and AcidBase 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 DrugNutrient 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

viiContents

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 forPulmonary Failure ................................................................. 467

Alfredo A. Matos, William Manzanares, and Vctor Snchez 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 andSepsis ................................................................................................................. 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

ix

ForewordDuring 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, health-care 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 special-ized intensive care services in various critical care units by highly talented and motivated com-prehensive 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, espe-cially 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 ill-nesses, 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 malnour-ished 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 50years 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 prac-tice of medicine forever, and will undoubtedly improve the morbidity, mortality, and other out-comes in this vital arena of health-care endeavor as progress continues in the future. During the past 55years 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 peripherally 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 naso-gastric 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 Universityof

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, revo-lutionary, intravenous nutritional substances. Early in my internship year (19611962), 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 gastrointes-tinal 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 1960sbut it was a giant step forward in the right direction. By the time I was the chief resident in surgery in 19661967, the hos-pital 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 moni-toring 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. Itwas 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 devel-oped, 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 Childrens Hospital of Philadelphia, where a severely malnourished infant with multiple congenital anomalies, including

xiForeword

extremely short bowel syndrome (and near death), was nourished entirely by central venous TPN for 45days. 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 malnutri-tionand 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, hyperglyce-mia and insulin use, maintenance of euglycemia, early enteral versus parenteral feeding, overfeed-ing 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 inge-nuity (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, CNSDepartment of Surgery

School of MedicineYale University

New Haven, Connecticut

xiii

EditorGail 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 confer-ence planning committees, serving as chair for the ASPEN planning committee. She is the recipi-ent 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.

xv

Contributors

Mazen AlbeldawiDepartment of Gastroenterology and

HepatologyNCH Healthcare SystemNaples, Florida

Jill BarsaFairview HospitalCleveland Clinic Health SystemCleveland, Ohio

Amy BerryUniversity of Virginia Health SystemCharlottesville, Virginia

Jatinder BhatiaDivision of NeonatologyDepartment of PediatricsGeorgia Regents UniversityAugusta, Georgia

Britta BrownMedical Nutrition TherapyHennepin County Medical CenterMinneapolis, Minnesota

Rex O. BrownDepartment of PharmacyUniversity of Tennessee Health Science CenterandRegional Medical Center at MemphisMemphis, Tennessee

Deborah A. CarpenterAkron Childrens HospitalAkron, Ohio

Ronni ChernoffArkansas Geriatric Education CenterandReynolds Department of GeriatricsUniversity of Arkansas for Medical SciencesLittle Rock, Arkansas

Dian J. ChiangCleveland ClinicCleveland, Ohio

Srinath ChinnakotlaTransplantationBaylor University Medical CenterDallas, Texas

Michael ChristensenUniversity of Tennessee Health Science CenterMemphis, Tennessee

Maria Isabel Toulson Davisson CorreiaMedical SchoolFederal University of Minas GeraisBelo Horizonte, Brazil

Mandy L. CorriganCenter for Human NutritionCleveland ClinicCleveland, Ohio

Gail A. CresciGastroenterology and Center for Human

NutritionCleveland ClinicCleveland, Ohio

Letcia De NardiDepartment of GastroenterologyMedical SchoolUniversity of Sao PauloSao Paulo, Brazil

Roland N. DickersonDepartment of Clinical PharmacyUniversity of Tennessee Health Science CenterandRegional Medical Center at MemphisMemphis, Tennessee

Lindsay M. DowhanCenter for Gut Rehabilitation and TransplantDigestive Disease InstituteCleveland ClinicCleveland, Ohio

xvi Contributors

Stanley J. DudrickDepartment of SurgerySchool of MedicineYale UniversityNew Haven, Connecticut

Arlene EscuroCleveland ClinicCleveland, Ohio

David FrankenfieldMilton S. Hershey Medical CenterHershey, Pennsylvania

Vanessa Fuchs-TarlovskyOncology DepartmentHospital General de MexicoMexico City, Mexico

Kendra Glassman PerkeyRocky Mountain Hospital for Children at PSLDenver, Colorado

Michele M. GottschlichShriners Hospitals for ChildrenCincinnati, Ohio

and

Department of SurgeryCollege of MedicineUniversity of CincinnatiCincinnati, Ohio

Jesse GutnickAdministrative Chief ResidentDepartment of General SurgeryCleveland ClinicCleveland, Ohio

Katherine HallMedical Nutrition TherapyHennepin County Medical CenterMinneapolis, Minnesota

Jeanette HasseTransplantationBaylor University Medical CenterDallas, Texas

Peggy HipskindCenter for Human NutritionCleveland ClinicCleveland, Ohio

A. Christine HummellCleveland ClinicCleveland, Ohio

Elizabeth IsenringFaculty of Health Sciences and MedicineBond UniversityBrisbane, Australia

Gerri KellerAkron Childrens HospitalAkron, Ohio

Joe KrenitskyDigestive Health Center of ExcellenceUniversity of Virginia Health SystemCharlottesville, Virginia

Kavitha KrishnanClinical DietitianFairview HospitalCleveland Clinic Health SystemCleveland, Ohio

Kenneth A. KudskDepartment of SurgeryUniversity of Wisconsin Medical CenterMadison, Wisconsin

Joy LehmanThe Ohio State University Wexner Medical CenterColumbus, Ohio

Mary E. LeichtDepartment of NutritionJohn Peter Smith HospitalFort Worth, Texas

Maria R. LucarelliDivision of Pulmonary, Allergy, Critical Care,

and Sleep MedicineDepartment of Internal MedicineThe Ohio State University Wexner Medical CenterColumbus, Ohio

xviiContributors

Ainsley M. MaloneMount Carmel West HospitalColumbus, Ohio

William ManzanaresFaculty of MedicineDepartment of Critical CareUniversity of the RepublicMontevideo, Uruguay

Mary MarianColleges of Agriculture and Life Sciences/

MedicineThe University of ArizonaTucson, Arizona

Robert MartindaleGeneral Surgery DivisionOregon Health Sciences UniversityPortland, Oregon

Alfredo A. MatosFaculty of MedicineDr. AAM Social Security HospitalUniversity of PanamaPanama City, Panama

Theresa MayesDivision of Nutrition TherapyCincinnati Childrens Hospital Medical CenterCincinnati, Ohio

John E. MazuskiSchool of MedicineBarnes-Jewish HospitalWashington UniversitySt. Louis, Missouri

Mary S. McCarthyCenter for Nursing Science and Clinical

InquiryMadigan Army Medical CenterFort Lewis, Washington

Tom Stone McNeesHolston Valley Medical CenterWellmont Health SystemKingsport, Tennessee

Jeffrey I. MechanickDivision of Endocrinology, Diabetes, and Bone

DiseasesIcahn School of Medicine at Mount SinaiNew York, New York

R.F. MeierDepartment of Gastroenterology, Hepatology

and NutritionKantonsspital BasellandMedical University ClinicLiestal, Switzerland

Jay M. MirtalloCollege of PharmacyThe Ohio State UniversityColumbus, Ohio

Cynthia MundyDivision of NeonatologyDepartment of PediatricsGeorgia Regents UniversityAugusta, Georgia

Vctor Snchez NavaMonterrey Institute of Technology and Higher

EducationMonterrey, Mexico

Mark H. OltermannJohn Peter Smith HospitalFort Worth, Texas

Neha ParekhCenter for Gut Rehabilitation and

TransplantationCleveland ClinicCleveland, Ohio

Carol Rees ParrishDigestive Health Center of ExcellenceUniversity of Virginia Health SystemCharlottesville, Virginia

Lindsay Pell RyderDepartment of PharmacyThe Ohio State University Wexner Medical

CenterColumbus, Ohio

xviii Contributors

Cassandra PogatschnikCenter for Human NutritionandCenter for Gut Rehabilitation and

TransplantationCleveland ClinicCleveland, Ohio

Mary RathCleveland ClinicCleveland, Ohio

Susan RobertsNutrition DepartmentBaylor University Medical CenterDallas, Texas

Mary Krystofiak RussellBaxter Healthcare CorporationDeerfield, Illinois

Rifka C. SchulmanDivision of Endocrinology, Metabolism and

DiabetesLong Island Jewish Medical CenterNew Hyde Park, New York

Denise Baird SchwartzFood and Nutrition ServicesProvidence Saint Joseph Medical CenterBurbank, California

Mary Beth ShirkDepartment of PharmacyThe Ohio State University Wexner

MedicalCenterColumbus, Ohio

Krishnan SriramCook County Health and Hospital SystemsJohn H. Stroger, Jr. HospitalChicago, Illinois

Ezra SteigerDepartment of General SurgeryDigestive Disease InstituteCleveland ClinicCleveland, Ohio

Beth TaylorBarnes-Jewish HospitalSt. Louis, Missouri

and

American College of Critical Care MedicineMt. Prospect, Illinois

Michael D. TaylorDepartment of SurgeryFairview HospitalCleveland Clinic Health SystemCleveland, Ohio

Raquel S. TorrinhasDepartment of GastroenterologyMedical SchoolUniversity of So PauloSo Paulo, Brazil

Christina J. ValentineCincinnati Childrens HospitalCincinnati, Ohio

Carol L. WagnerThe Medical College of South CarolinaCharleston, South Carolina

Dan L. WaitzbergDepartment of GastroenterologyUniversity of So PauloSo Paulo, Brazil

Malissa WarrenPortland VA Medical CenterPortland, Oregon

Jodi WolffRainbow Babies and Childrens HospitalCleveland, Ohio

Section I

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

31 Organic Response to StressMaria Isabel Toulson Davisson Correia

INTRODUCTION

The organic response to stressfirst described as the metabolic response to trauma, in 1942, by Sir David Cuthbertsonis 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 depend-ing 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

CONTENTS

Introduction ........................................................................................................................................3Stress ..................................................................................................................................................4Historical Perspective ........................................................................................................................5Organic Response to Stress ................................................................................................................6

Ebb and Flow Phases.....................................................................................................................6Glucose and Protein Metabolism ..................................................................................................7Fluid and Electrolyte Response .....................................................................................................8Endocrine Response ......................................................................................................................8

HypothalamicPituitaryAdrenal Axis ....................................................................................8Thyrotropic Axis.......................................................................................................................9Somatotropic Axis .................................................................................................................. 10Lactotropic Axis ..................................................................................................................... 10Luteinizing HormoneTestosterone Axis ............................................................................... 10

Inflammatory Response ............................................................................................................... 10Immunologic Response ............................................................................................................... 12

Conclusions ...................................................................................................................................... 12References ........................................................................................................................................12

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

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 mortal-ity related to it. In surgical stress, especially under major elective conditions, its 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 electro-lyte balance, among others, are of paramount importance and should be dealt in a multimodal approach to decrease the organic response to trauma [26]. 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 patients outcome [2,5,79]. The severity of the hypermetabolic phenomena thereafter might lead to the systemic inflammatory response syndrome (SIRS), the amplified gener-alized 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

Trauma Macrophages IL-1 Incr. temp

Sympatheticnervous system

Incr. WBCIncr. IgG

Catecholamines

1. Tachycardia

ADH

Prolactin

Cortisol andaldosterone

GHACTHAngiotensin 2

Renin

Limbic system

2. Tachypnoea3. Vasoconstriction

Ascendingreticular formation

Ant. pituitary Post. pituitary

Hypovolemicshock Hypothalamus

FIGURE 1.1 Organic response to stress.

TABLE 1.1Organic 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

5Organic Response to Stress

changes, or emotional factors. The bodys response to these factors will depend on their magni-tude, 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 elab-orate corticotropin- releasing hormone (CRH) and activate the hypothalamicpituitary 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, respira-tion, 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 Cuthbertsons 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 increas-ing 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 overexag-gerated, life could be jeopardized.

The concept that illness was associated with an increased excretion of nitrogen leading to nega-tive 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 1C in temperature was associated with a 13% increase in the metabolic rate.

Cuthbertsons 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 mea-sured 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 fol-lowing 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 suppres-sion 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


with neuroendocrine alterations but it is also accompanied by inflammatory responses and mediators as well as immunologic dysfunctions.

ORGANIC RESPONSE TO STRESS (TABLE 1.2)

Ebb and Flow PhasEs

Cuthbertson [1] originally divided the organic response into an ebb and a flow phase. The ebb phase begins immediately after injury and typically lasts 1224h, if the initial injury is under control. However, this phase may last longer depending on the severity of trauma and the adequacy of resus-citation. The ebb phase may equate with prolonged and untreated shock, a circumstance that is more often seen in experimental animals than in clinical practice. It is characterized by tissue hypoperfu-sion and a decrease in overall metabolic activity. In order to compensate this, catecholamines are discharged with norepinephrine being the primary mediator of the ebb phase. Norepinephrine is released from peripheral nerves and binds to beta1 receptors in the heart and alpha and beta2 recep-tors in peripheral and, to a lesser degree, splanchnic vascular beds. The most important effects are the cardiovascular, because norepinephrine is a potent cardiac stimulant, causing increased contrac-tility and heart rate and vasoconstriction. These phenomena are attempts to restore blood pressure and increase cardiac performance and maximal venous return.

Hyperglycemia may be seen during the ebb phase. The degree of hyperglycemia parallels the severity of injury. Hyperglycemia is promoted by hepatic glycogenolysis secondary to catechol-amine release and by direct sympathetic stimulation of glycogen breakdown.

Some authors have investigated the ebb phase in experimental animals and human beings [18] and have noticed important aspects, such as that after sustained long fractures, with concomitant great loss of blood, there is an impairment of vasoconstriction, which is not seen in bleeding events alone, such as that seen in duodenal ulcer bleeding. In another study, Childs et al. [19] showed an effect of injury on impairing thermoregulation in injured subjects who presented with reduced vaso-constriction in response to cold stimulus.

The onset of the flow phase that encompasses the catabolic and anabolic phases is signaled by high cardiac output with the restoration of oxygen delivery and metabolic substrate. The duration of this phase depends on the severity of injury or the presence of infection and development of com-plications (Table 1.3). It typically peaks around the third to the fifth day, subsides by 710days, and merges into an anabolic phase over the next few weeks. During this hypermetabolic phase, insulin release is high but elevated levels of catecholamines, glucagon, and cortisol counteract most of its metabolic effects.

TABLE 1.2Organic Response to Stress

The organic response is related to

Magnitude (severity)

Duration (the longer the more severe)

Nutritional status of the patient (malnourished patients do worse)

Associated diseases (increase morbidity and mortality)

Diabetes

Heart disease

Pulmonary

Immunologic

Others


Increased mobilization of amino acids and free fatty acids from peripheral muscles and adipose tissue stores result from this hormonal imbalance. Some of these released substrates are used for energy productioneither directly as glucose or through the liver as triglyceride. Other substrates contribute to the synthesis of proteins in the liver, where humoral mediators increase production of acute phase reactants. Similar protein synthesis occurs in the immune system for the healing of damaged tissues. While this hypermetabolic phase involves both catabolic and anabolic processes, the net result is a significant loss of protein, characterized by negative nitrogen balance and also decreased fat stores. This leads to an overall modification of body composition, characterized by losses of protein, carbohydrate, and fat stores, accompanied by enlarged extracellular (and, to a lesser extent, intracellular) water compartments.

GlucosE and ProtEin MEtabolisM

Glucose is always fundamental independently of which organic response phase the patient is in. Dr. Jonathan Rhoads pointed out that providing 100 g of glucose guarantees energy to cells that solely rely on this substrate such as neurons and red cells and allows the body to use fat stores and some muscle protein for the remaining energy needs [20]. During simple starvation without any stress condition, glucose infusion inhibits hepatic gluconeogenesis, but after injury, despite the high con-centration of circulating glucose, gluconeogenesis prevails.

The amino acids released from protein catabolism in muscle are largely taken up by the liver for new glucose production, rather than being used as fuel to meet energy demands. The latter are provided by the fat reserve (about 80%90%) [21]. The reason why injured patients need such a high rate of endogenous glucose production may be explained by the high demand of injured tissues for glucose. Wilmore et al. showed that patients with severe burns in one leg and with minor injury to the other had a fourfold increase of glucose uptake by the burnt limb [22]. At the same time, the burnt leg produced higher amounts of lactate, suggesting anaerobic respiration. The lactate is then returned to the liver for gluconeogenesis, in the so-called Cori cycle, which is metabolically expensive. One mole of glucose yields two ATP through glycolysis, but via glu-coneogenesis costs three ATP. This may contribute to the underlying increase in the metabolic rate (Figure 1.2).

Insulin has an anabolic or storage effect by synthesizing large molecules from small molecules and inhibiting catabolism. It also promotes glucose oxidation and glycogen synthesis, whereas it inhibits glycogenolysis and gluconeogenesis. On the other hand, the catabolic hormones, such as catecholamines, cortisol, and glucagons, enhance glycogenolysis and gluconeogenesis.

TABLE 1.3Metabolic Response to Stress

The ebb and flow phases

Glucose and protein metabolism

Fluid and electrolyte response

Endocrine response

HPA

Thyrotropic axis

Somatotropic axis

Lactotropic axis

Luteininizing hormone-testosterone axis

Inflammatory response

Immunologic response


Fluid and ElEctrolytE rEsPonsE

Hypovolemia prevails in the ebb phase and is entirely reversible with appropriate fluid administra-tion. However, in the absence of volume resuscitation, within 24h, mortality is nearly uniform [23]. The patients initial response to hypovolemia is targeted to keep adequate perfusion to the brain and the heart in detriment of the skin, fat tissue, muscles, and intra-abdominal structures. The oliguria, which follows injury, is a consequence of the release of antidiuretic hormone (ADH) and aldosterone. Secretion of ADH from the supraoptic nuclei in the anterior hypothalamus is stimulated by volume reduction and increased osmolality. The latter is mainly due to increased sodium content of the extra-cellular fluid. Francis Moore coined the terms the sodium retention phase and sodium diuresis phase of injury to describe the antidiuresis of both salt and water in the flow phase [24]. Volume receptors are located in the atria and pulmonary arteries, and osmoreceptors are located near ADH neurons in the hypothalamus. ADH acts mainly on the connecting tubules of the kidney but also on the dis-tal tubules to promote reabsorption of water. Aldosterone acts mainly on the distal renal tubules to promote reabsorption of sodium and bicarbonate and increase excretion of potassium and hydrogen ions. Aldosterone also modifies the effects of catecholamines on cells, thus affecting the exchange of sodium and potassium across all cell membranes. The release of large quantities of intracellu-lar potassium into the extracellular fluid is a consequence of protein catabolism and may cause a rise in serum potassium, especially if renal function is impaired. Retention of sodium and bicarbon-ate may produce metabolic alkalosis with impairment of the delivery of oxygen to the tissues. After injury, urinary sodium excretion may fall to 1025 mmol/24h and potassium excretion may rise to 100200mmol/24h. Intracellular fluid and exogenously administered fluid accumulate preferentially in the extracellular third space because of increased vascular permeability and relative increase in interstitial oncotic pressure. This is the reason most patients become so edematous after the first days following injury and resuscitation.

EndocrinE rEsPonsE

HypothalamicPituitaryAdrenal AxisThe hypothalamus secretes CRH in response to the stress stimuli. CHR stimulates the pro-duction, by the pituitary, of adrenocorticotropic hormone (ACTH), also known as corticotro-pin, which as its name implies, stimulates the adrenal cortex. More specifically, it triggers

GlucoseLiver Peripheral tissue

Glucose

Pyruvate

Acetyl-CoA

Citrate

Fumarate

Oxaloacetate

Lactate

Alanina

FatsAminoacids

Aminoacids

Aminogroup

Glutamine

KidneyGut

Liver

Alphaamino

FIGURE 1.2 Aerobic glycolysis and Cori cycles.


the secretion of glucocorticoids, such as cortisol, and has little control over the secretion of aldosterone, the other major steroid hormone from the adrenal cortex. CRH itself is inhibited by glucocorticoids, making it part of a classical negative feedback loop (Figures 1.1 and 1.3). It seems that the secretion of aldosterone is most likely under the control of an activated reninangiotensin system.

Hypercortisolism acutely shifts carbohydrate, fat, and protein metabolism, so that energy is instantly and selectively available to vital organs such as the brain, and anabolism is thus delayed. Intravascular fluid retention and the enhanced inotropic and vasopressor response to catecholamines and angiotensin II offer hemodynamic advantages in the fight and flight response. This hypercorti-solism can be interpreted as an attempt of the organism to mute its own inflammatory cascade, thus protecting itself against over-responses [25].

Serum ACTH was found to be low in chronic critical illness, while cortisol concentrations remained elevated, suggesting that cortisol release may be driven through alternative pathways, possibly involving endothelin [26].

Thyrotropic AxisSerum levels of T3 decrease, within 2h after surgery or trauma, whereas T4 and Thyroid stimulat-ing hormone (TSH) briefly increase. Apparently, low levels of T3 are due to a decreased peripheral conversion of T4. Subsequently, circulating levels of TSH and T4 often return to normal levels, whereas T3 levels remain low. It is important to mention that the magnitude of T3 decrease has been found to reflect the severity of illness. Several cytokine mediators, mainly tumor necrosis factor (TNF), interleukin-1 (IL-1), and interleukin-6 (IL-6), have been investigated as putative mediators of the acute low T3 levels [27]. Teleologically, the acute changes in the thyroid axis may reflect an attempt to reduce energy expenditure, as in starvation.

A somewhat different behavior is seen in patients remaining in intensive care units for longer periods. It has been seen that there is a low-normal TSH values and low T4 and T3 serum concentra-tions. This seems to be reduced due to reduced hypothalamic stimulation of the thyrotropes, in turn leading to reduced stimulation of the thyroid gland. Endogenous dopamine and prolonged hyper-cortisolism may play a role in this phenomenon. When exogenous dopamine and glucocorticoids are given, hypothyroidism is provoked or aggravated, in critical illness [28].

HypothalamusCRHs

PituitaryACTH

+

+

Adrenal

Cortisol

Inhibits CRH

Stressors

FIGURE 1.3 The hypothalamicpituitaryadrenal axis.


Somatotropic AxisCirculating levels of GH become elevated, and the normal GH profile, consisting of peaks alternating with virtually undetectable troughs, is altered with peak GH and interpulse concentrations being high and the GH pulse frequency being elevated. This happens throughout the first hours or days of an insult, be it surgery, trauma, or infection. In physiological situations, GH is released from the pituitary somato-tropes in a pulsatile fashion, under the interactive control of the hypothalamic GH-releasing hormone (GHRH), which is stimulatory, and somatostatin, which exerts an inhibitory effect. Apparently, after stress, it seems that withdrawal of the inhibitory effect of somatostatin and the increased availability of stimulatory GH-releasing factors (hypothalamic or peripheral) could hypothetically be involved. Ithas also been suggested that there seems to be acquired peripheral resistance to GH, and these changes are brought about by the effects of cytokines, such as TNF alpha, IL-1, and IL-6 [29]. GH exerts direct lipolytic, insulin-antagonizing, and immune- stimulating actions. Such changes prioritize essential sub-strates such as glucose, free fatty acids, and amino acids toward survival rather than anabolism.

In chronic illness, the changes in the somatotropic axis are different. GH secretion is chaotic and reduced compared with the acute phase. Although the nonpulsatile fraction is still elevated and the number of pulses is high, mean nocturnal GH serum concentrations are scarcely elevated and sub-stantially lower than in the acute phase of stress. One of the possibilities that explain this situation is that the pituitary is taking part in the multiple organ failure syndrome becoming unable to synthesize and secrete GH [29]. Another explanation could be that the lack of pulsatile GH secretion is due to increased somatostatin tone or to reduced stimulation by endogenous releasing factors, such as GHRH.

Lactotropic AxisProlactin was among the first hormones known to have increased serum concentrations after acute physical or psychological stress [29]. This increase might be mediated by oxytocin, dopaminergic pathways, or vasoactive intestinal peptide (VIP). Inflammatory cytokines may be the triggering factor. Changes in prolactin secretion in response to stress might contribute to altered immune func-tion during the course of critical illness. In mice, inhibition of prolactin release results in impaired lymphocyte function, depressed lymphokine-dependent macrophage activation, and death from normally nonlethal exposure to bacteria [30]. It remains unclear if hyperprolactinemia contributes to the vital activation of the immune cascade, after the onset of critical illness. In the chronic setting of critical illness, serum prolactin levels are no longer as high as in the acute phase.

Luteinizing HormoneTestosterone AxisTestosterone is the most important endogenous anabolic steroid hormone. Therefore, changes within the luteinizing hormonetestosterone axis in the male may be relevant for the catabolic state in criti-cal illness, in which there are low testosterone levels. The exact cause is unclear, but cytokines may once again be enrolled in this phenomenon [31]. Hypothesizing over the low testosterone levels, it may be important to switch off anabolic androgen secretion, in acute stress, in order to conserve energy and metabolic substrates for vital functions [32].

In chronic states, circulating testosterone levels become extremely low, in fact almost undetect-able. Endogenous dopamine, estrogens, and opiates might be the cause for the low levels.

inFlaMMatory rEsPonsE

The local inflammatory response is part of the bodys attempt to restore homeostasis, particularly healing, which in most situations after injury is successful (Figure 1.4). However, at times, this is not the case and deviations occur, leading to a perpetuated response that may jeopardize survival such as in the SIRS. In the latter, inflammation is triggered at sites remote from the site of initial injury. In some cases, SIRS progresses to multiple organ dysfunction syndrome (MODS), which is associated with high mortality rates.


The physiologic inflammatory response to trauma is a complex cellular and molecular event, in which inflammatory cells such as polymorphonuclear cells (PMNs), macrophages, and lymphocytes are recruited to the site of injury and secrete inflammatory mediators. The endothelium at the site of injury also participates. PMNs are the first cells arriving at the site of injury and release potent oxi-dizing molecules, including hydrogen peroxide, hypochlorous acid, oxygen-free radicals, proteolytic enzymes, and vasoactive substances, such as leukotrienes, eicosanoids, and platelet-activating factor (PAF). There is evidence that PAF is partially responsible for the increased permeability in sepsis and shock [33]. Oxygen-free radicals are proinflammatory molecules causing lipid peroxidation, inactiva-tion of enzymes, and consumption of antioxidants. PMNs release proteolytic enzymes, which activate the kinin/kallikrein system. In turn, this system stimulates the release of angiotensin II, bradykinin, and activated plasminogen. Bradykinin causes vasodilatation and mediates increased vascular permeability.

Macrophages are activated by cytokines and engulf invading organisms. They also debride necrotic host tissue and elaborate additional cytokines. TNF alpha (synthesized by macrophages) and IL-1 beta (synthesized by macrophages and endothelial cells) are the proximal proinflammatory mediators. These cytokines initiate the elaboration and release of other cytokines, such as IL-6. Monocytes, macrophages, neutrophils, T and B cells, endothelial cells, smooth muscle cells, fibroblasts, and mast cells secrete this cytokine. It is probably the most potent inductor of acute phase response, although its exact role in the inflammatory response remains unclear. On the other hand, it is considered to be the most reliable prog-nostic indication of outcome, particularly in sepsis because it reflects the severity of injury [34].

Il-8 belongs to a group of mediators known as chemokines because of their ability to recruit inflammatory cells to the sites of injury. It is synthesized by monocytes, macrophages, neutrophils, and endothelial cells. It is also used as an index of magnitude of systemic inflammation and it seems to be able to identify those patients who will develop MODS [35]. High levels of IL-6 and IL-8 in alveolar washouts, 2h after injury, have been reported, suggesting that the alveoli might be the first structures suffering with the metabolic response to stress [36]. These high levels might be used, in the future, as prognostic factors to the development of multiorgan dysfunction syndrome.

IL-4 and IL-10 are anti-inflammatory cytokines, synthesized by lymphocytes and monocytes and exert similar effects. They inhibit the synthesis of TNF alpha, IL-1, IL-6, and IL-8.

Nitric oxide (NO) is elaborated by various cell types, including endothelial cells, neurons, mac-rophages, smooth muscle cells, and fibroblasts. NO mediates vasodilatation and regulates vascular tone. NO is probably a key mediator in the pathophysiology of stress and shock.

Acute-phase reactants are produced in the liver in response to injury in order to maintain homeo-stasis. Its production is induced by cytokines. These proteins function as opsonins (C-reactive protein),

IL-1 TNF IL-6

+

SIRS

IL-4 IL-10 IL-13 IL-1 RA sIL-6R sTNFR

Proinflammatory

IL-8

Anti-inflammatory

FIGURE 1.4 Most common cytokes produced in SIRS.


protease inhibitors (alpha1-proteinase), hemostatic agents (fibrinogen), and transporters (transferring). Albumin is a negative acute phase protein and its synthesis is curtailed by inflammation.

iMMunoloGic rEsPonsE

The inflammatory mediators (TNF-, IL-1, and IL-6) release substrates, from host tissues, to sup-port T and B lymphocyte activity and, therefore, create a hostile environment for invading patho-gens. This is an integral part of the bodys response to infection and injury. Such inflammatory mediators raise body temperature and produce oxidant substrates that initiate downregulation of the process once invasion has been defeated. Nonetheless, this mechanism poses considerable cost to the host and according to its magnitude and duration might lead to the SIRS. The latter might cause the MODS, in some patients. The majority of patients survive SIRS without developing early MODS and, after a period of relative clinical stability, manifest a compensatory anti-inflammatory response syndrome (CARS) with suppressed immunity and diminished resistance to infection.

The interaction between the innate and adaptive immune systems seems to be important inductor of both SIRS and CARS. T cells from the adaptive immune system play a role in the early SIRS response to injury and in CARS. Other possible mediators of CARS include prostaglandins of the E series. Also, products of complement activation seem to induct TNF alpha production. In summary, the SIRS, which regularly occurs after serious injury and in some cases proves fatal to the individual, has been partially characterized by both clinical and animal researches. However, the triggering mechanisms and signal-ing systems involved in inducing and maintaining it are incompletely understood and defined.

CONCLUSIONS

The organic response consists of the complex hydroelectrolytic, hematological, hormonal, metabolic, inflammatory, and immunologic changes that follow injury or trauma. It is the bodys life- saving process that will definitely impact on patients outcomes according to the way it is approached. Therefore, it is currently accepted that the best way to face such situation is by providing a series of multimodal attitudes, which encompass good nutrition status, short preoperative fasting time, intraoperative body temperature control, adequate fluid administration, pain control and early oral or enteral nutrition, as well as early mobilization among others. Most of these recommendations are easily accomplished at very low cost.

In summary, the organic response is a physiological phenomenon that tries to protect the body against any aggression. However, when it is too intense and lasts for longer periods, it is associated with higher morbidity and mortality. In order to avoid such situation, it is of utmost importance to be aware of the different facets and comply with the several attitudes that might be able to decrease the magnitude of the response. Nonetheless, these interventions, especially those that have tried to abrogate it, should be seen with caution and under protocol control because attenuating or abolish-ing the organic response may not be without risk, with the latter placing responsibility on the care provider to be fully aware of the possible side effects. Future research, especially in the area of genetics and molecular biology, will no doubt help understand several aspects not currently known.

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12. DuBois EF. Basal Metabolism in Health and Disease. Philadelphia, PA: Lea & Febiger, 1924. 13. Cannon WB. The Wisdom of the Body, 2nd edn. New York: Norton Co., 1932. 14. Selye HT. The general adaptation syndrome and the diseases of adaptation. Journal of Clinical

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15

2 Carbohydrate MetabolismA Comparison of Stress and Nonstress States

Mary Marian and Susan Roberts

INTRODUCTION

Carbohydrates (CHOs) are the primary source of energy for human cells and usually comprise 45%65% of energy consumed yielding 4 kcal/g substrate. Glucose is an essential fuel for the brain and central nervous tissue. Additionally, CHOs are vital to the composition of RNA and DNA, coenzymes, glycoproteins, and glycolipids. There are several forms of CHO including monosaccha-rides, disaccharides and oligosaccharides, and polysaccharides such as starch and fibers.1,2

CHOs are defined chemically as an aldehyde or ketone derivative of polyhydric alcohol or compounds that yield such molecules on hydrolysis.

Tightly regulated, glucose concentration in the blood is maintained within a narrow range (70105 g/dL) that ensures a steady source of glucose to the brain.1 Blood glucose levels are regulated by both metabolic and hormonal mechanisms. The major hormones controlling blood glucose levels are insulin, glucagon, and epinephrine, but glucocorticoids, thyroid hormone, and growth hormone can also play a role.1

FED STATE

CHO metabolism during the fed state is characterized by an increase in blood glucose levels, fats, amino acids, and their metabolites. Following ingestion, CHO is digested by a variety of enzymes including salivary and pancreatic amylase, maltase, sucrose, and lactase. The latter three enzymes break down disaccharides and oligosaccharides further into monosaccharides (glucose, galactose, and fructose), which are then absorbed in the proximal intestine. The absorption of glucose occurs

CONTENTS

Introduction ...................................................................................................................................... 15Fed State ........................................................................................................................................... 15Starvation .........................................................................................................................................20Stress Response ................................................................................................................................20

Alterations in Glucose Metabolism ............................................................................................. 21Implications for Nutrition Support ...................................................................................................23

Insulin Resistance and Glycemic Control ................................................................................... 23Recommendations for Glucose Provision ...................................................................................25Preoperative Carbohydrate Loading ............................................................................................26

Refeeding Syndrome ........................................................................................................................27Conclusion .......................................................................................................................................29References ........................................................................................................................................29


through sodium-dependent glucose transporters.3 Glucose uptake into tissues requires a number of facilitated glucose transporter molecules and/or insulin, and glucose transporters are expressed on glucose-requiring tissues (e.g., the liver, brain, skeletal muscle, kidneys, adipocytes, skin, and blood cells). Glucose is then phosphorylated and either oxidized by the tissues for energy or stored as glycogen or triacylglycerols, depending on the metabolic state of the host. Both storage forms of glucose can both serve as an available energy source for use when needed.4

Glucose not needed for immediate energy is stored in the liver and muscle as glycogen, through a process called glycogenesis.2 Glycogen plays a principle role in metabolism serving as a ready source of glucose to maintain blood glucose levels. A larger amount (approximately three to four times) of glycogen is stored in the muscle compared to that stored in the liver. Muscle glycogen is used only by the myocytes for energy, whereas hepatic glycogen can be released into the systemic circulation for glucose homeostasis and use by other body tissues.2

Glucose is metabolized in the cells through glycolysis, an anaerobic process that occurs in the cell cytoplasm.2 During glycolysis, glucose is converted to pyruvate resulting in the production of adenosine triphosphate (ATP) (see Figure 2.1).5 Pyruvate can be metabolized under anaerobic condi-tions to form lactate. During anaerobic metabolism, six molecules of ATP are formed. Additionally, pyruvate can be transaminated to the amino acid alanine, carboxylated to oxaloacetate, or decar-boxylated to acetyl CoA (see Figure 2.2).6 The Krebs cycle, as illustrated in Figure 2.3, serves as the final common pathway for the oxidation of many fuel molecules. CHOs, amino acids, and lipids can enter the Krebs cycle after being converted to acetyl CoA.6

Following an increase in the blood glucose level as well as certain amino acids and fatty acids, the -cells in the islets of Langerhans in the pancreas secrete the anabolic hormone insulin, which promotes the storage of nutrients. Incretins (gastrointestinal hormones), glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide-1 (GLP-1) also play a role in glucose homeostasis. Like insulin, they are released in response to a meal and act on the pancreatic -cells, thereby stimulating insulin secretion.1 Insulin secretion results in the

-glucose

Glucose 6-phosphate (G6P)

Dihydroxyacetonephosphate (DHAP)

-glyceraldehyde3-phosphate

Fructose 6-phosphate (F6P)

1,3-diphosphoglycerate (1,3-DPG)

3-phosphoglycerate

2-phosphoglycerate

Phosphoenolpyruvate (PEP)

Pyruvate

Fructose 1,6-diphosphate (FDP)

ATP

NADH+H

ATP

ATP

ATP

FIGURE 2.1 Two stages of glycogen. (Reprinted with permission from Welborn, M.B. and Moldawer, L.L., Glucose metabolism, in: Rombeau, J.L. and Rolandelli, R.H. (eds.), Clinical Nutrition Enteral and Tube Feeding, 3rd edn., WB Saunders Co., Philadelphia, PA, 1997, pp. 6180.)

17Carbohydrate Metabolism

disposal of glucose within the tissues as glycogen in the liver and muscle, triglyceride synthesis, and amino acid transport and synthesis into proteins in the insulin-sensitive peripheral tissues, primarily the skeletal muscle. Following cellular uptake, the majority of glucose is metabolized to pyruvate via glycolysis to provide energy for cellular processes, while some is stored as gly-cogen (see Figure 2.1).2,5

A decrease in the blood glucose level, or hypoglycemia, is the main stimulus for the secretion of glucagon from the -cells of the islets of Langerhans in the pancreas. Glucagon, the major counter-regulatory hormone of insulin, is primarily responsible for signaling the production of glucose from endogenous sources through the activation of hepatic glycogenolysis (the breakdown of glycogen stores) and gluconeogenesis and mobilization of fatty acids from the adipose tissue.1 The gluco-corticoids such as cortisol, secreted by the adrenal cortex, also stimulate the secretion of glucagon as well as secretion of gluconeogenic precursors from the peripheral tissues. Glucocorticoids also inhibit glucose utilization by extrahepatic tissues.1

Gluconeogenesis, which entails the use of non-CHO substrates (amino acids and fat) for conver-sion to glucose, serves as a mechanism to ensure a steady source of glucose is always available. The liver is the major site of gluconeogenesis, but the kidney is also able to produce glucose and release it into the circulation via gluconeogenesis.7 Gluconeogenesis occurs during stress when inadequate glucose substrate is available. The hormones, glucagon, cortisol, and epinephrine stimulate the pro-cess, while insulin suppresses it. Gluconeogenesis can also be inhibited by hyperglycemia indepen-dent of hormonal levels. During times of stress, enhanced gluconeogenesis persists despite elevated serum glucose and insulin levels.2

During the postabsorptive state, the body relies on endogenous fuel production to meet meta-bolic requirements. This state is characterized by the release, interorgan transfer, and oxidation of endogenous fatty acids and the continued release of glucose from liver glycogen stores and skeletal release of amino acids. Glycogen stores within the muscle serve as a ready source of glucose within the muscle, and circulating insulin levels remain low.1,2

Healthy adults require approximately 200 g of CHO per day to meet metabolic demands and provide the brain with adequate glucose (the adult brain requires approximately 140 g/day).1,2 When blood glucose levels fall below a critical level, headache, slurred speech, confusion, seizures, uncon-sciousness, coma, and death can result if energy substrate for brain activity is reduced.7 To avoid

Glucose

Glycolysis

PyruvateTransamination

Oxaloacetate Acetyl CoA

Reduction

LactateAlanine

Oxidativedecarboxylation

Carboxylation

FIGURE 2.2 Possible fates of pyruvate. (Reprinted with permission from DeLegge, M.H. and Ridley, C., Nutrient digestion, absorption, and excreation, in: Gottschlich, M.M., Fuhrman, M.P., Hammond, K.A., Holcombe, B.J., and Seidner, D.L. (eds.), The Science and Practice of Nutrition Support: A Case-Based Core Curriculum, Kendall/Hunt Publishing Co., Dubuque, IA, 2001, pp. 116.)


these circumstances, glucose levels are generally tightly controlled by a variety of physiological controls, including glycogenolysis and gluconeogenesis, with each providing approximately 50% of endogenously produced glucose in the postabsorptive state.2

Blood glucose and insulin levels start declining with blood glucagon levels increasing approxi-mately an hour after meal consumption. During the fasted state, both blood glucose and serum insulin levels continually decline. Glucose transport into the muscle and fat stores also decrease as a result. Due to changes in the plasma glucose-to-glucagon ratio, glycogenolysis ensues resulting in inhibition of hepatic glycogen synthesis. Figure 2.4 summarizes the substrate fluxes associated with both the fasted and fed states.8

CoASHCOO

CH2

CH2

HO C COO

Citrate

Aconitase

H2O

H2O

COO

COO

CH2

Isocitratedehydrogenase

Isocitratedehydrogenase

-Ketoglutarate

-Ketoglutaratedehydrogenase

Oxalosuccinate

HO H

H

C

C COO

COO

COO

CH2COO

CH2

CH2CO2

H

C O

C COO

COO

COO

Oxaloacetate

Tricarboxylicacidcycle

COOCitrate

synthase

Acetyl CoA

CH3

MalatedehydrogenaseCH2

CH2HO HC

C

C S CoA

O

O

COO

COOCCoASH

CoASH

GTP

GDP

Pi

O

COO

CH2

CH2

COO

FAD

FADH2

Fumarate

Fumarase

L-Malate

COO

COO

H2O

H2O

HC

CH

COO

CH2CH2

C

S CoA

O

COO CO2

Isocitrate

NAD+

NAD + H+

NAD H+ H

NAD+

NAD H+ H+

NAD+

Succinyl CoA

Succinyl CoAsynthetaseSuccinate

Succinatedehydrogenase

COO

CH2

CH

C COO

COO

cis-Aconitate

Aconitase

FIGURE 2.3 Krebs cycle. (Reprinted with permission from DeLegge, M.H. and Ridley, C., Nutrient diges-tion, absorption, and excreation, in: Gottschlich, M.M., Fuhrman, M.P., Hammond, K.A., Holcombe, B.J., and Seidner, D.L. (eds.), The Science and Practice of Nutrition Support: A Case-Based Core Curriculum, Kendall/Hunt Publishing Co., Dubuque, IA, 2001, pp. 116.)

19Carbohydrate Metabolism

FA

TG

Glycerol-3-P

Adipose

Adipose

FA

TG

Muscle

Glycogen

Pyruvate Lactate

Lactate

CO2

CO2

G-6-P

Glycogen

Glycogen

Chylomicrons

Glucose

Gut

Glycogen

G-6-P

TG

TG

VLDL-TG

Glucose

(a)

(b)

Liver

Liver

Muscle

FA

Pyruvate

Pyruvate

Lactate

Lactate

CO2

CO2

G-6-P

G-6-P

TG

FA

FA

Glycerol-3-P

TG

VLDL-TG

FA

FIGURE 2.4 Substrate fluxes in fasted (a) and fed (b) critically ill patients. (Reprinted with permission from Wolfe, R.R. and Martini, W.Z., World J. Surg., 24, 639, 2000.)


In summary, glucose homeostasis is regulated by a number of mechanisms, designed to maintain an optimal serum glucose concentration. Following ingestion, digestion, and absorption of CHOs, hormonal substances are released, which result in CHO metabolism and storage. In the postab-sorptive state, other hormonal changes occur to provide tissues, especially the brain, with a steady supply of glucose until dietary CHO is consumed again.

STARVATION

To meet the bodys energy needs during s

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