Sabiston textbook of surgery the biological basis of modern surgical practice, 20 edition 2016 UnitedVRG 1

SABISTON TEXTBOOK of SURGERY BIOLOGICAL BASIS of MODERN SURGICAL PRACTICE The SABISTON TEXTBOOK of SURGERY The BIOLOGICAL BASIS of MODERN SURGICAL PRACTICE 20TH EDITION COURTNEY M TOWNSEND, JR., MD B MARK EVERS, MD Professor Robertson-Poth Distinguished Chair in General Surgery Department of Surgery University of Texas Medical Branch Galveston, Texas Professor and Vice-Chair for Research, Department of Surgery Director, Lucille P Markey Cancer Center Markey Cancer Foundation Endowed Chair Physician-in-Chief, Oncology Service Line UK Healthcare University of Kentucky Lexington, Kentucky R DANIEL BEAUCHAMP, MD J.C Foshee Distinguished Professor and Chairman, Section of Surgical Sciences Professor of Surgery and Cell and Developmental Biology and Cancer Biology Vanderbilt University School of Medicine Surgeon-in-Chief, Vanderbilt University Hospital Nashville, Tennessee KENNETH L MATTOX, MD Professor and Vice Chairman Michael E DeBakey Department of Surgery Baylor College of Medicine Chief of Staff and Chief of Surgery Ben Taub General Hospital Houston, Texas 1600 John F Kennedy Blvd Ste 1800 Philadelphia, PA 19103-2899 ISBN: 978-0-323-29987-9 International Edition ISBN: 978-0-323-40162-3 Copyright © 2017 by Elsevier, Inc All rights reserved Copyright 2012, 2008, 2004, 2001, 1997, 1991, 1986, 1981, 1977, 1972, 1968, 1964, 1960, 1956 by Saunders, an imprint of Elsevier Inc Copyright 1949, 1945, 1942, 1939, 1936 by Elsevier Inc Copyright renewed 1992 by Richard A Davis, Nancy Davis Reagan, Susan Okum, Joanne R Artz, and Mrs Mary E Artz Copyright renewed 1988 by Richard A Davis and Nancy Davis Reagan Copyright renewed 1977 by Mrs Frederick Christopher Copyright renewed 1973, 1970, 1967, 1964 by W.B Saunders Company All rights reserved No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher, except that, until further notice, instructors requiring their students to purchase Sabiston Textbook of Surgery by Courtney M Townsend, Jr., MD, may reproduce the contents or parts thereof for instructional purposes, provided each copy contains a proper copyright notice as follows: Copyright © 2017 by Elsevier Inc This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein) Notices Knowledge and best practice in this field are constantly changing As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility With respect to any drug or pharmaceutical products identified, readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications It is the responsibility of practitioners, relying on their own experience and knowledge of their patients, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein Please change to the following: Library of Congress Cataloging-in-Publication Data Sabiston textbook of surgery : the biological basis of modern surgical practic / [edited by] Courtney M Townsend, Jr, R Daniel Beauchamp, B Mark Evers, Kenneth L Mattox.—20th edition    p ; cm   Textbook of surgery   Preceded by Sabiston textbook of surgery / [edited by] Courtney M Townsend Jr … [et al.] 19th ed 2012   Includes bibliographical references and index   ISBN 978-0-323-29987-9 (hardcover : alk paper)—ISBN 978-0-323-40162-3 (international edition : alk paper)   I.  Townsend, Courtney M., Jr., editor.  II.  Beauchamp, R Daniel, editor.  III.  Evers, B Mark, 1957-, editor.  IV.  Mattox, Kenneth L., 1938-, editor.  V.  Title: Textbook of surgery   [DNLM: Surgical Procedures, Operative General Surgery Perioperative Care WO 500]   RD31   617—dc23    2015035365 Executive Content Strategist: Michael Houston Content Development Specialist: Joanie Milnes Publishing Services Manager: Patricia Tannian Senior Project Manager: Cindy Thoms Book Designer: Renee Duenow Printed in Canada Last digit is the print number:  9  8  7  6  5  4  3  2  To our patients, who grant us the privilege of practicing our craft; to our students, residents, and colleagues, from whom we learn; and to our wives—Mary, Shannon, Karen, and June—without whose support this would not have been possible CONTRIBUTORS Cary B Aarons, MD Assistant Professor of Clinical Surgery University of Pennsylvania Philadelphia, Pennsylvania Andrew B Adams, MD, PhD Assistant Professor Emory Transplant Center Department of Surgery Emory University School of Medicine Atlanta, Georgia Charles A Adams, Jr., MD Chief Division of Trauma and Surgical Critical Care Rhode Island Hospital Associate Professor of Surgery Alpert Medical School of Brown University Providence, Rhode Island Ahmed Al-Mousawi, MD Shriners Hospitals for Children Department of Surgery University of Texas Medical Branch Galveston, Texas Jatin Anand, MD Resident in Cardiothoracic Surgery Division of Cardiovascular and Thoracic Surgery Department of Surgery Duke University Medical Center Durham, North Carolina Nancy Ascher, MD, PhD Professor and Chair Department of Surgery University of California at San Francisco San Francisco, California Stanley W Ashley, MD Chief Medical Officer and Senior Vice President for Medical Affairs Brigham and Women’s Hospital Frank Sawyer Professor of Surgery Harvard Medical School Boston, Massachusetts Paul S Auerbach, MD Professor of Emergency Medicine Redlich Family Professor Stanford University Stanford, California Brian Badgwell, MD Associate Professor of Surgery MD Anderson Cancer Center Houston, Texas Faisal G Bakaeen, MD, FACS Staff Surgeon Department of Thoracic and Cardiovascular Surgery Heart and Vascular Institute Cleveland, Ohio Adjunct Professor The Michael E DeBakey Department of Surgery Baylor College of Medicine Houston, Texas Philip S Barie, MD, MBA, FIDSA, FACS, FCCM Professor of Surgery and Public Health Weill Cornell Medical College New York, New York B Timothy Baxter, MD Vice-Chairman, Department of Surgery Professor, Vascular Surgery Department of Surgery University of Nebraska Medical Center Omaha, Nebraska R Daniel Beauchamp, MD J.C Foshee Distinguished Professor and Chairman Section of Surgical Sciences Professor of Surgery and Cell and Developmental Biology and Cancer Biology Vanderbilt University School of Medicine Surgeon-in-Chief Vanderbilt University Hospital Nashville, Tennessee Yolanda Becker, MD, FACS Professor and Director of Kidney and Pancreas Transplant Division of Transplantation Department of Surgery University of Chicago Pritzker School of Medicine Chicago, Illinois Joshua I.S Bleier, MD Program Director Division of Colon and Rectal Surgery University of Pennsylvania Health System Associate Professor of Clinical Surgery University of Pennsylvania Philadelphia, Pennsylvania Howard Brody, MD, PhD Former Director Institute for the Medical Humanities University of Texas Medical Branch Galveston, Texas vii Contributors Carlos V.R Brown, MD, FACS Associate Professor and Vice Chairman of Surgery University of Texas Southwestern—Austin Trauma Medical Director University Medical Center Brackenridge Austin, Texas Bruce D Browner, MD, MS Gray-Gossling Chair Professor and Chairman Emeritus Department of Orthopaedic Surgery University of Connecticut Farmington, Connecticut Director Department of Orthopaedics Hartford Hospital Hartford, Connecticut Brian B Burkey, MD Vice-Chairman Head and Neck Institute Cleveland Clinic Cleveland, Ohio Joshua Carson, MD Shriners Hospitals for Children Department of Surgery University of Texas Medical Branch Galveston, Texas Steven N Carter, MD Clinical Assistant Professor of Surgery Department of Surgery University of Oklahoma Health Sciences Center Oklahoma City, Oklahoma Howard C Champion, MD Professor of Surgery Uniformed Service University of the Health Sciences Bethesda, Maryland Faisal Cheema, MD, FACS Assistant Professor Division of Vascular Surgery and Endovascular Therapy Department of Surgery University of Texas Medical Branch Galveston, Texas Charlie C Cheng, MD, FACS Assistant Professor Division of Vascular Surgery and Endovascular Therapy Department of Surgery University of Texas Medical Branch Galveston, Texas Kenneth J Cherry, MD Edwin P Lehman Professor of Surgery Division of Vascular and Endovascular Surgery University of Virginia Medical Center Charlottesville, Virginia viii John D Christein, MD Associate Professor Department of Surgery University of Alabama School of Medicine Birmingham, Alabama Dai H Chung, MD Professor and Chairman Janie Robinson and John Moore Lee Chair Department of Pediatric Surgery Vanderbilt University Medical Center Nashville, Tennessee William G Cioffi, MD Chief Department of Surgery Rhode Island Hospital Professor and Chairman of Surgery Alpert Medical School of Brown University Providence, Rhode Island Michael Coburn, MD Professor and Chairman Scott Department of Urology Baylor College of Medicine Houston, Texas Carlo M Contreras, MD Assistant Professor of Surgery University of Alabama at Birmingham Birmingham, Alabama Lorraine D Cornwell, MD Assistant Professor Cardiothoracic Surgery Baylor College of Medicine Michael E DeBakey VA Medical Center Houston, Texas Marion E Couch, MD, PhD, MBA, FACS Richard T Miyamoto Professor and Chair of Head and Neck Surgery Physician Executive Surgical Services for IU Health Physicians Indiana University School of Medicine Indianapolis, Indiana Merril T Dayton, MD Salt Lake City, Utah Bradley M Dennis, MD Assistant Professor of Surgery Division of Trauma and Surgical Critical Care Department of Surgery Vanderbilt University Medical Center Nashville, Tennessee Contributors Sohum K Desai, MD Resident Division of Neurosurgery Department of Surgery University of Texas Medical Branch Galveston, Texas James S Economou, MD, PhD Beaumont Professor of Surgery Professor of Microbiology, Immunology, and Molecular Genetics Professor of Medical and Molecular Pharmacology University of California—Los Angeles Los Angeles, California Rajeev Dhupar, MD, MBA Assistant Professor Department of Cardiothoracic Surgery Division of Thoracic and Foregut Surgery University of Pittsburgh Medical Center Pittsburgh, Pennsylvania E Christopher Ellison, MD Professor Department of Surgery Ohio State University Columbus, Ohio Jose J Diaz, MD, CNS, FACS, FCCM Professor of Surgery Chief Acute Care Surgery R Adams Cowley Shock Trauma Center University of Maryland Medical Center Baltimore, Maryland Zachary C Dietch, MD Department of Surgery The University of Virginia Health System Charlottesville, Virginia Roger Dmochowski, MD, MMHC, FACS Professor of Urology Director, Pelvic Medicine and Reconstruction Fellowship Department of Urology Professor of Obstetrics and Gynecology Vice Chair, Section of Surgical Sciences Vanderbilt University Medical Center Associate Director of Quality and Safety Executive Director of Risk Prevention Vanderbilt Health System Executive Medical Director for Patient Safety and Quality (Surgery) Associate Chief of Staff Medical Director of Risk Management Vanderbilt University Hospital Nashville, Tennessee Vikas Dudeja, MD Assistant Professor Division of Surgical Oncology Department of Surgery University of Miami Miller School of Medicine Miami, Florida Quan-Yang Duh, MD Professor of Surgery University of California—San Francisco Surgical Service San Francisco VA Medical Center San Francisco, California Timothy J Eberlein, MD Bixby Professor and Chairman Department of Surgery Spencer T and Ann W Olin Distinguished Professor Director, Alvin J Siteman Cancer Center Washington University School of Medicine St Louis, Missouri Stephen R.T Evans, MD Professor of Surgery Georgetown University Medical Center Executive Vice President and Chief Medical Officer MedStar Health Washington, DC B Mark Evers, MD Professor and Vice-Chair for Research Department of Surgery Director Lucille P Markey Cancer Center Markey Cancer Foundation Endowed Chair Physician-in-Chief Oncology Service Line UK Healthcare University of Kentucky Lexington, Kentucky Grant Fankhauser, MD Assistant Professor Division of Vascular Surgery and Endovascular Therapy Department of Surgery University of Texas Medical Branch Galveston, Texas Farhood Farjah, MD, MPH Division of Cardiothoracic Surgery Surgical Outcomes Research Center University of Washington Seattle, Washington Celeste C Finnerty, PhD Shriners Hospitals for Children Department of Surgery Sealy Center for Molecular Medicine Institute for Translational Sciences University of Texas Medical Branch Galveston, Texas Nicholas A Fiore II, MD Private Practice Houston, Texas David R Flum, MD, MPH Professor and Association Chair for Research Surgery Director, Surgical Outcomes Research Center University of Washington Seattle, Washington ix Contributors Yuman Fong, MD Chairman Department of Surgery City of Hope Medical Center Duarte, California Mandy Ford, PhD Associate Professor Emory Transplant Surgery Department of Surgery Emory University School of Medicine Atlanta, Georgia Charles D Fraser, Jr., MD Chief and The Donovan Chair in Congenital Heart Surgery Surgeon-in-Chief, Texas Children’s Hospital Professor of Surgery and Pediatrics Susan V Clayton Chair in Surgery Baylor College of Medicine Houston, Texas Julie A Freischlag, MD Professor of Surgery Vice Chancellor Human Health Services Dean, School of Medicine University of California—Davis Sacramento, California Gerald M Fried, MD, CM, FRCSC, FACS Edward W Archibald Professor and Chairman of Surgery McGill University Montreal, Quebec, Canada Robert D Fry, MD Emilie and Roland DeHellebranth Professor of Surgery Emeritus University of Pennsylvania Philadelphia, Pennsylvania Nasrin Ghalyaie, MD Assistant Professor of Surgery Department of Surgery University of Arizona College of Medicine Tucson, Arizona S Peter Goedegebuure, PhD Research Associate Professor Department of Surgery Washington University School of Medicine St Louis, Missouri Oliver L Gunter, MD, MPH Associate Professor of Surgery Division of Trauma and Surgical Critical Care Vanderbilt University School of Medicine Nashville, Tennessee Jennifer L Halpern, MD Assistant Professor Department of Orthopaedic Surgery Vanderbilt Orthopaedic Institute Nashville, Tennessee x John B Hanks, MD C Bruce Morton Professor and Chief Division of General Surgery Department of Surgery University of Virginia Charlottesville, Virginia Laura R Hanks, MD Resident in Obstetrics and Gynecology Department of Obstetrics and Gynecology University of Rochester School of Medicine and Dentistry Rochester, New York Jennifer W Harris, MD General Surgery Resident Post-Doctoral Research Fellow Markey Cancer Center Lexington, Kentucky Jennifer A Heller, MD Assistant Professor of Surgery Director Johns Hopkins Vein Center Department of Surgery Johns Hopkins Medical Institutions Baltimore, Maryland Jon C Henry, MD Fellow Vascular Surgery University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Antonio Hernandez, MD Associate Professor Department of Anesthesiology Vanderbilt University Medical Center Nashville, Tennessee David N Herndon, MD, FACS Chief of Staff Shriners Hospitals for Children Department of Surgery University of Texas Medical Branch Galveston, Texas Martin J Heslin, MD, MSHA Professor and Director Division of Surgical Oncology Department of Surgery University of Alabama at Birmingham Birmingham, Alabama Asher Hirshberg, MD Director of Emergency Vascular Surgery Kings County Hospital Center Brooklyn, New York Contributors Wayne Hofstetter, MD Professor of Surgery Deputy Chair Department of Thoracic and Cardiovascular Surgery University of Texas MD Anderson Cancer Center Houston, Texas Marc G Jeschke, MD, PhD, FACS, FCCM, FRCS(c) Director, Ross Tilley Burn Centre Department of Surgery Division of Plastic Surgery University of Toronto Sunnybrook Health Sciences Centre Toronto, Ontario, Canada Ginger E Holt, MD Associate Professor Department of Orthopaedic Surgery Vanderbilt Orthopaedic Institute Nashville, Tennessee Howard W Jones III, MD Professor and Chairman Department of Obstetrics and Gynecology Vanderbilt University School of Medicine Nashville, Tennessee Michael D Holzman, MD, MPH Professor of Surgery Department of Surgery Vanderbilt University Medical Center Nashville, Tennessee Bellal Joseph, MD Associate Professor of Surgery University of Arizona Tucson, Arizona Michael S Hu, MD, MPH, MS Post-Doctoral Fellow Division of Plastic and Reconstructive Surgery Department of Surgery Stanford University School of Medicine Stanford, California General Surgery Resident Department of Surgery John A Burns School of Medicine University of Hawaii Honolulu, Hawaii Eric S Hungness, MD, FACS Associate Professor of Surgery and Medical Education S David Stulberg Research Professor Northwestern University Feinberg School of Medicine Chicago, Illinois Kelly K Hunt, MD Professor Department of Breast Surgical Oncology University of Texas MD Anderson Cancer Center Houston, Texas Jeffrey Indes, MD, FACS Assistant Professor of Surgery and Radiology Associate Program Director, Vascular Surgery Yale University School of Medicine New Haven, Connecticut Patrick G Jackson, MD, FACS Assistant Professor of Surgery Chief, Division of General Surgery MedStar Georgetown University Hospital Washington, DC Eric H Jensen, MD Assistant Professor of Surgery University of Minnesota Minneapolis, Minnesota Lauren C Kane, MD Associate Surgeon Texas Children’s Hospital Assistant Professor of Surgery and Pediatrics Baylor College of Medicine Houston, Texas Jae Y Kim, MD Assistant Professor Division of Thoracic Surgery City of Hope Cancer Center Duarte, California Charles W Kimbrough, MD The Hiram C Polk, Jr., MD Department of Surgery University of Louisville School of Medicine Louisville, Kentucky Mahmoud N Kulaylat, MD Associate Professor Department of Surgery Jacobs School of Medicine and Biomedical Sciences University of New York—Buffalo Buffalo, New York Terry C Lairmore, MD Professor of Surgery Director, Division of Surgical Oncology Baylor Scott and White Healthcare Texas A&M University System Health Science Center College of Medicine Temple, Texas Christian P Larsen, MD, DPhil Dean and Vice President for Health Affairs Mason Professor of Transplantation Surgery Emory Transplant Center Department of Surgery Emory University School of Medicine Atlanta, Georgia xi CHAPTER 4  Shock, Electrolytes, and Fluid 47 SYMPTOM COMPLEX OF SHOCK General appearance and reactions Mental state Apathy Delayed responses Depressed cerebration Weak voice Listless or restlessness Countenance Drawn–anxious Lusterless eyes Sunken eyeballs Ptosis of upper lids (slight) Upward rotation of eyeballs (slight) Neuromuscular state Hypotonia Muscular weakness Tremors and twitchings Involuntary muscular movements Difficulty in swallowing Neuromuscular tests Depressed tendon reflexes Depressed sensibilities Depressed visual and auditory reflexes General but variable symptoms Thirst Vomiting Diarrhea Oliguria Visible or occult blood in vomitus, and stools Skin and mucous membranes Circulation and blood Skin Pale, livid, ashen gray Slightly cyanotic Moist, clammy Mottling of dependent parts Loose, dry, inelastic, cold Superficial veins Collapsed and invisible Failure to fill on compression or massage Inconspicuous jugular pulsations Mucous membranes Pale, livid, slightly cyanotic Heart Apex sounds feeble Rate, usually rapid Conjunctiva Glazed, lusterless Radial pulse Usually rapid Small volume “feeble,” “thready” Tongue Dry, pale, parched, shriveled Respiration and metabolism Respiration Variable but not dyspneic Usually increased rate Variable depth Occasional deep sighs Sometimes irregular or phasic Temperature Subnormal, normal, supernormal Basal metabolic rate reduced (?) Brachial blood pressures Lowered Pulse pressure small Retinal vessels Narrowed Blood volume Reduced Blood chemistry Hemoconcentration or hemodilution Venous O2 decreased A-V O2 difference increased Arterial CO2 reduced Alkali reserve reduced FIGURE 4-2  Wiggers’ description of symptom complex of shock (From Wiggers CJ: Present status of shock problem Physiol Rev 22:74, 1942.) To keep the dogs’ BP at 40 mm Hg, Wiggers had to continually withdraw additional blood during this “compensated” stage of shock During compensated shock, the dogs could use their reserves to survive Water was recruited from the intracellular compartment as well as from the extracellular space The body tried to maintain the vascular flow necessary to survive However, after a certain period, he found that to keep the dogs’ BP at the arbitrary set point of 40 mm Hg, he had to reinfuse shed blood; he termed this phase uncompensated or irreversible shock Eventually, after a period of irreversible shock, the dogs died If the dogs had not yet gone into the uncompensated phase, any type of fluid used for resuscitation would have made survival likely In fact, most dogs at that stage, even without resuscitation, would self-resuscitate by going to a water source Once they entered the uncompensated phase of shock, however, their reserves were exhausted; even if blood was given back, the survival rates were better if additional fluid of some sort was administered Uncompensated shock is surely what Gross meant by “unhinging of the machinery of life.” Currently, hemorrhagic shock models are classified as involving either controlled or uncontrolled hemorrhage The Wiggers prep is controlled hemorrhage and is referred to as pressure-controlled hemorrhage Another animal model that uses controlled hemorrhage is the volume-controlled model Arguments against this model include the inconsistency of the blood volume from one animal to another and the variability in response Calculation of blood volume is usually based on a percentage of body weight (typically, 7% of body weight), but such percentages are not exact and result in variability from one animal to another However, proponents of the volume model and critics of the pressure model argue that a certain pressure during hypotension elicits a different response from one animal to another Even in the pressure-controlled 48 SECTION I  Surgical Basic Principles hemorrhage model, animals vary highly in regard to when they go from compensated shock to uncompensated shock The pressure typically used in the pressure-controlled model is 40 mm Hg; the volume used in the volume-controlled model is 40% The variance in the volume-controlled model can be minimized by specifying a narrow weight range for the animals (e.g., rats within 10 g, large animals within pounds) It is also important to have the same experimenters doing the exact same procedure at the same time of the day in animals that were prepared and hydrated the exact same way The ideal model is uncontrolled hemorrhage, but its main problem is that the volume of hemorrhage is uncontrolled by the nature of the experiment Variability is the highest in this model even though it is the most realistic Computer-assisted pressure models can be used that mimic the pressures during uncontrolled shock to reduce the artificiality of the pressure-controlled model Fluids How did the commonly used IV fluids, such as normal saline, enter medical practice? It is often taken for granted, given the vast body of knowledge in medicine, that they were adopted through a rigorous scientific process, but that was not necessarily the case Normal saline has a long track record and is extremely useful, but we now know that it also can be harmful Hartog Jakob Hamburger, in his in vitro studies of red cell lysis in 1882, incorrectly suggested that 0.9% saline was the concentration of salt in human blood This fluid is often referred to as physiologic or normal saline, but it is neither physiologic nor normal Supposedly, 0.9% normal saline originated during the cholera pandemic that afflicted Europe in 1831, but an examination of the composition of the fluids used by physicians of that era found no resemblance to normal saline The origin of the concept of normal saline remains unclear.7 In 1831, O’Shaughnessy described his experience in the treatment of cholera: Universal stagnation of the venous system, and rapid cessation of the arterialization of the blood, are the earliest, as well as the most characteristic effects Hence the skin becomes blue—hence animal heat is no longer generated— hence the secretions are suspended; the arteries contain black blood, no carbonic acid is evolved from the lungs, and the returned air of expiration is cold as when it enters these organs.8 O’Shaughnessy wrote those words at the age of 22, having just graduated from Edinburgh Medical School He tested his new method of infusing IV fluids on a dog and observed no ill effects Eventually, he reported that the aim of his method was to restore blood to its natural specific gravity and to restore its deficient saline matters His experience with human cholera patients taught him that the practice of bloodletting, then highly common, was good for “diminishing the venous congestion” and that nitrous oxide (laughing gas) was not useful for oxygenation In 1832, Robert Lewins reported that he witnessed Thomas Latta injecting extraordinary quantities of saline into veins, with the immediate effects of “restoring the natural current in the veins and arteries, of improving the color of the blood, and [of ] recovering the functions of the lungs.” Lewins described Latta’s saline solution as consisting of “two drachms of muriate, and two scruples of carbonate, of soda, to sixty ounces of water.” Later, however, Latta’s solution was found to equate to having 134 mmol/liter of Na+, 118 mmol/liter of Cl−, and 16 mmol/liter of HCO3− FIGURE 4-3  Sydney Ringer, credited for the development of lactated Ringer’s solution (From Baskett TF: Sydney Ringer and lactated Ringer’s solution Resuscitation 58:5–7, 2003.) During the next 50 years, many reports cited various recipes used to treat cholera, but none resembled 0.9% saline In 1883, Sydney Ringer reported on the influence exerted by the constituents of the blood on the contractions of the ventricle (Fig 4-3) Studying hearts cut out of frogs, he used 0.75% saline and a blood mixture made from dried bullocks’ blood.9 In his attempts to identify which aspect of blood caused better results, he found that a “small quantity of white of egg completely obviates the changes occurring with saline solution.” He concluded that the benefit of “white of egg” was because of the albumin or the potassium chloride To show what worked and what did not, he described endless experiments with alterations of multiple variables However, Ringer later published another article stating that his previously reported findings could not be repeated; through careful study, he realized that the water used in his first article was actually not distilled water, as reported, but rather tap water from the New River Water Company It turned out that his laboratory technician, who was paid to distill the water, took shortcuts and used tap water instead Ringer analyzed the water and found that it contained many trace minerals (Fig 4-4) Through careful and diligent experimentation, he found that calcium bicarbonate or calcium chloride—in doses even smaller than in blood—restored good contractions of the frog ventricles The third component that he found essential to good contractions was sodium bicarbonate He knew the importance of the trace elements He also stated that fish could live for weeks unfed in tap water but would die in distilled water in a few hours, minnows, for instance, died in an average of 4.5 hours Thus, the three ingredients that he found essential were potassium, calcium, and bicarbonate Ringer’s solution soon became ubiquitous in physiologic laboratory experiments In the early 20th century, fluid therapy by injection under the skin (hypodermoclysis) and infusion into the rectum CHAPTER 4  Shock, Electrolytes, and Fluid They consist of: Calcium 38.3 per million 4.5 ” 23.3 ” 7.1 ” Combined carbonic acid 78.2 ” Sulfuric acid 55.8 ” Chlorine 15 ” Silicates 7.1 ” 54.2 ” Magnesium Sodium Potassium Free carbonic acid FIGURE 4-4  Sidney Ringer’s report of contents in water from the New River Water Company (From Baskett TF: Sydney Ringer and lactated Ringer’s solution Resuscitation 58:5–7, 2003.) (proctoclysis) became routine Hartwell and Hoguet reported its use in intestinal obstruction in dogs, laying the foundation for saline therapy in human patients with intestinal obstruction As IV crystalloid solutions were developed, Ringer’s solution was modified, most notably by pediatrician Alexis Hartmann In 1932, wanting to develop an alkalinizing solution to administer to his acidotic patients, Hartmann modified Ringer’s solution by adding sodium lactate The result was lactated Ringer’s (LR) or Hartmann’s solution He used sodium lactate (instead of sodium bicarbonate); the conversion of lactate into sodium bicarbonate was sufficiently slow to lessen the danger posed by sodium bicarbonate, which could rapidly shift patients from compensated acidosis to uncompensated alkalosis In 1924, Rudolph Matas, regarded as the originator of modern fluid treatment, introduced the concept of the continued IV drip but also warned of potential dangers of saline infusions He stated, “Normal saline has continued to gain popularity but the problems with metabolic derangements have been repeatedly shown but seem to have fallen on deaf ears.” In healthy volunteers, modernday experiments have shown that normal saline can cause abdominal discomfort and pain, nausea, drowsiness, and decreased mental capacity to perform complex tasks The point is that normal saline and LR solutions have been formulated for conditions other than the replacement of blood, and the reasons for the formulation are archaic Such solutions have been useful for dehydration; when they are used in relatively small volumes (1 to liters per day), they are well tolerated and relatively harmless; they provide water, and the human body can tolerate the amounts of electrolytes they contain Over the years, LR has attained widespread use for treatment of hemorrhagic shock However, normal saline and LR are mostly permeable through the vascular membrane, but they are poorly retained in the vascular space After a few hours, only about 175 to 200 mL of a 1-liter infusion remains in the intravascular space In countries other than the United States, LR is often referred to as Hartmann’s solution, and normal saline is referred to as physiologic (sometimes even spelled fisiologic) solution With the advances in science in the last 50 years, it is difficult to understand why advances in resuscitation fluids have not been made Blood Transfusions Concerned about the blood that injured patients lost, Crile began to experiment with blood transfusions As he stated, “After many accidents, profuse hemorrhage often led to shock before the patient reached the hospital Saline solutions, adrenalin, and precise surgical technique could substitute only up to a point for 49 the lost blood.” At the turn of the 19th century, transfusions were seldom used Their use waxed and waned in popularity because of transfusion reactions and difficulties in preventing clotting in donated blood Through his experiments in dogs, Crile showed that blood was interchangeable: he transfused blood without blood group matching Alexis Carrel was able to sew blood vessels together with his triangulation technique, using it to connect blood vessels from one person to another for the purpose of transfusions However, Crile found Carrel’s technique too slow and cumbersome in humans, so he developed a short cannula to facilitate transfusions By the time World War II occurred, shock was recognized as the single most common cause of treatable morbidity and mortality At the time of the Japanese attack on Pearl Harbor on December 7, 1941, no blood banks or effectual blood transfusion facilities were available Most military locations had no stocks of dried pooled plasma Although the wounded of that era were evacuated quickly to a hospital, the mortality rate was still high IV fluids of any kind were essentially unavailable, except for a few liters of saline manufactured by means of a still in the operating room IV fluid was usually administered by an old Salvesen flask and reused rubber tube Often, a severe febrile reaction resulted from the use of that tubing The first written documentation of resuscitation in World War II patients was year after Pearl Harbor, in December 1942, in notes from the 77th Evacuation Hospital in North Africa E D Churchill stated, “The wounded in action had for the most part either succumbed or recovered from any existing shock before we saw them However, later cases came to us in shock, and some of the early cases were found to be in need of whole blood transfusion There was plenty of reconstituted blood plasma available However, some cases were in dire need of whole blood We had no transfusion sets, although such are available in the United States: no sodium citrate; no sterile distilled water; and no blood donors.” The initial decision to rely on plasma rather than on blood appears to have been based in part on the view held in the Office of the Surgeon General of the Army and in part on the opinion of the civilian investigators of the National Research Council Those civilian investigators thought that in shock, the blood was thick and the hematocrit level high On April 8, 1943, the Surgeon General stated that no blood would be sent to the combat zone Seven months later, he again refused to send blood overseas because of the following: (1) his observation of overseas theaters had convinced him that plasma was adequate for resuscitation of wounded men; (2) from a logistics standpoint, it was impractical to make locally collected blood available farther forward than general hospitals in the combat zone; and (3) shipping space was too sparse Vasoconstricting drugs such as epinephrine were condemned because they were thought to decrease blood flow and tissue perfusion as they dammed the blood in the arterial portion of the circulatory system During World War II, out of necessity, efforts to make blood transfusions available heightened and led to the institution of blood banking for transfusions Better understanding of hypovolemia and inadequate circulation led to the use of plasma as a favored resuscitative solution, in addition to whole blood replacement Thus, the treatment of traumatic shock greatly improved The administration of whole blood was thought to be extremely effective, so it was widely used Mixed with sodium citrate in a 6 : 1 ratio to bind the calcium in the blood, which prevented clotting, worked well 50 SECTION I  Surgical Basic Principles However, no matter what solution was used—blood, colloids, or crystalloids—the blood volume seemed to increase by only a fraction of what was lost In the Korean War era, it was recognized that more blood had to be infused for the blood volume lost to be adequately regained The reason for the need for more blood was unclear, but it was thought to be due to hemolysis, pooling of blood in certain capillary beds, and loss of fluid into tissues Considerable attention was given to elevating the feet of patients in shock PHYSIOLOGY OF SHOCK Bleeding Research and experience have both taught us much about the physiologic responses to bleeding The Advanced Trauma Life Support (ATLS) course defines four classes of shock (Table 4-1) In general, that categorization has helped point out the physiologic responses to hemorrhagic shock, emphasizing the identification of blood loss and guiding treatment Shock can be thought of anatomically at three levels (Fig 4-5) It can be cardiogenic with extrinsic abnormalities (such as tension pneumothorax, hemothorax, or tamponade) or intrinsic abnormalities (such as pump failure due to infarct, cardiac failure, contusion, cardiac laceration) Injury to large vessels can cause shock if they are bleeding At the level of the small vessels, shock is due to neurogenic dysfunction or sepsis The four classes of shock as taught in the ATLS course are problematic as they were not rigorously tested and proven Those who generated the ATLS table admit that the classes were fairly arbitrary and were not necessarily based on rigorous scientific TABLE 4-1  ATLS Classes of Hemorrhagic Shock Blood loss (%) Central nervous system Pulse (beats/min) Blood pressure Pulse pressure Respiratory rate Urine (mL/hr) Fluid CLASS I CLASS II CLASS III CLASS IV 0-15 Slightly anxious 30 Crystalloid 15-30 Mildly anxious >100 Normal Decreased 20-30/min 20-30 Crystalloid 30-40 Anxious or confused >120 Decreased Decreased 30-40/min 5-15 Crystalloid + blood >40 Confused or lethargic >140 Decreased Decreased >35/min Negligible Crystalloid + blood Cardiogenic shock Extrinsic (tamponade) Intrinsic (failure, ischemia) Hemorrhagic Distributive Sepsis Neuro FIGURE 4-5  Types of shock CHAPTER 4  Shock, Electrolytes, and Fluid data Patients in shock not always have the physiologic changes as taught in the ATLS course, and a high degree of variance exists among patients, particularly in children and older patients Children, in general, seem to be able to compensate, even after large volumes of blood loss, because of the higher water composition of their bodies However, when they decompensate, it can be rapid Progression into hemorrhagic shock can be a large step off the cliff rather than a gradual decent Older patients not compensate well; when they start to collapse physiologically, the process can be devastating because their ability to recruit fluid is not as good and their cardiac reserves are less The problem with the signs and symptoms classically shown in the ATLS classes is that in reality, the manifestations of shock can be confusing and difficult to assess For example, is an individual patient’s change in mental status caused by blood loss, traumatic brain injury (TBI), pain, or illicit drugs? The same dilemma applies for respiratory rate and skin changes Are alterations in a patient’s respiratory rate or skin caused by pneumothorax, rib fractures, or inhalation injury? To date, despite the many potential methods of monitoring shock, none has been found as clinically useful as BP As clinicians, we all know that there is a wide range of normal BPs The question often is this: What is the baseline BP of the patient being treated? When a seemingly normal BP is found, is that hypotension or hypertension compared with the patient’s normal BP? How we know how much blood has been lost? Even if blood volume is measured directly (relatively faster bedside methods are now available using tagged red cells), what was the patient’s baseline blood volume? To what blood volume should the patient be resuscitated? The end point of resuscitation has been elusive The variance in all of the variables makes assessment and treatment a challenge One important factor to recognize is that clinical symptoms are relatively few in patients who are in class I shock The only change in class I shock is anxiety according to the ATLS course Is the anxiety after injury from blood loss, pain, trauma, or drugs? A heart rate higher than 100 beats/min has been used as a physical sign of bleeding, but evidence of its significance is minimal Brasel and collegues10 have shown that heart rate was neither sensitive nor specific in determining the need for emergent intervention, the need for packed red blood cell (PRBC) transfusions in the first hours after an injury, or the severity of the injury Heart rate was not altered by the presence of hypotension (systolic BP < 90 mm Hg) In patients who are in class II shock, we are taught that their heart rate is increased, but again, this is a highly unreliable marker; pain and mere nervousness can also increase heart rate The change in pulse pressure—the difference between systolic and diastolic pressure—is also difficult to identify because the baseline BP of patients is not always known The change in pulse pressure is thought to be caused by an epinephrine response constricting vessels, resulting in higher diastolic pressures It is important to recognize that the body compensates well Not until patients are in class III shock does BP supposedly decrease At this stage, patients have lost 30% to 40% of their blood volume; for an average man weighing 75 kg (168 pounds), this equates to liters of blood loss (Fig 4-6) It is helpful to remember that a can of soda or beer is 355 mL; a six-pack is 2130 mL Theoretically, if a patient is hypotensive from blood loss, we are looking for a six-pack of blood Small amounts of blood loss should not result in hypotension Whereas intracranial bleeding can cause hypotension in the last stages of herniation, it is almost impossible that it is the result of a large volume of blood 51 FIGURE 4-6  Liters of blood lost for class III shock, or 40% of liters, according to the ATLS loss intracranially as there is not enough space there It is critical to recognize uncontrolled bleeding and even more critical to stop bleeding before patients go into class III shock It is more important to recognize blood loss than it is to replace blood loss A common mistake is to think that trauma patients are often hypotensive; the reality is that hypotension is rare in trauma patients (occurring less than 6% of the time) In addition, the ATLS course, which is designed for physicians who are not surgeons, does not recognize many subtle but important aspects of bleeding The concepts of the course are relatively basic However, surgeons know that there are some nuances of the varied responses to injuries in both animals and humans In the case of arterial hemorrhage, for example, we know that animals not necessarily manifest tachycardia as their first response when bleeding but actually become bradycardic It is speculated that this is a teleologically developed mechanism because bradycardic response reduces cardiac output and minimizes free uncontrolled exsanguination A bradycardic response to bleeding is not consistently shown in all animals, including humans Some evidence shows that this response, termed relative bradycardia, does often occur in humans Relative bradycardia is defined as a heart rate below 100 beats/min when the systolic BP is below 90 mm Hg When bleeding patients have relative bradycardia, their mortality rate is lower Up to 44% of hypotensive patients who are not bleeding have relative bradycardia However, patients with a heart rate below 60 beats/min are usually moribund Bleeding patients with a heart rate of 60 to 90 beats/min have the highest survival rate compared with patients who are tachycardic (a heart rate of more than 90 beats/min).11 The physiologic response to bleeding also subtly differs according to whether the source of bleeding is arterial or venous Arterial bleeding is obviously a problem, but it often stops temporarily on its own; the human body has evolved to trap the blood loss in adventitial tissues, and the transected artery will spasm and thrombose A lacerated artery can actually bleed more than a transected artery as the spasm of the lacerated artery can enlarge the hole in the vessel Thrombosis of the artery sometimes does not occur in transected or lacerated vessels Arterial bleeding, when constantly monitored, can result in rapid hypotension as there is a leak in the arterial system Because the arterial system does not have valves, the recorded BP can drop early even before large-volume loss has occurred In these patients with arterial bleeding, hypotension may occur soon, but because ischemia has 52 SECTION I  Surgical Basic Principles not yet had a chance to occur, measurements of lactate or base deficit often yield normal results Venous bleeding, however, is typically slower, and the human body can compensate It provides the time for recruitment of water from the intracellular and interstitial spaces Large volumes of blood can be lost before hypotension ensues Because venous or capillary bed bleeding is slower and the body has a chance to compensate, there is more time for ischemia, and thus there is time for lactate and base deficit results to be abnormal Venous blood loss can be massive before hypotension occurs It is generally taught that the hematocrit or hemoglobin level is not reliable in predicting blood loss That is true for patients with a high hematocrit or hemoglobin level, but in patients resuscitated with fluids, a rapid drop in the hematocrit and hemoglobin levels can occur immediately Bruns and associates12 have shown that the hemoglobin level can be low within the first 30 minutes after patients arrive at trauma centers Therefore, although patients with a high or normal hemoglobin level may have significant bleeding, a low hemoglobin level, because it occurs rapidly, can reflect the true extent of blood loss Infusion of acellular fluids often will dilute the blood and decrease the hemoglobin levels even further The lack of good indicators to distinguish which patients are bleeding has led many investigators to examine heart rate variability or complexity as a potential new vital sign Many clinical studies have shown that heart rate variability or complexity is associated with poor outcome, but this has yet to catch on, perhaps because of the difficulty of calculating it Heart rate variability or complexity would have to be calculated using software, with a resulting index on which clinicians would have to rely This information would not be available by merely examining patients Another issue with heart rate variability or complexity is that the exact physiologic mechanism for its association with poor outcome has yet to be elucidated.13 This new vital sign may be programmable into currently used monitors, but its usefulness has yet to be confirmed Hypotension has been traditionally set, arbitrarily, at 90 mm Hg and below Eastridge and coworkers14 have suggested that hypotension be redefined as below 110 mm Hg In 2008, Bruns and colleagues15 confirmed the concept, showing that a prehospital BP below 110 mm Hg was associated with a sharp increase in mortality and that 15% of patients with BP below 110 mm Hg would eventually die in the hospital As a result, they recommended redefining prehospital triage criteria In older patients, normal vital signs may miss occult hypoperfusion as these patients often have increased lactate and base deficit levels Shock Index Because heart rate and systolic BP independently are not accurate at identifying hemorrhagic shock and because the increase in heart rate does not always accompany a decrease in systolic BP, the shock index (SI), which uses these two variables together, has been studied to determine if it would be of use SI is defined as heart rate divided by systolic BP It has been shown to be a better marker for assessing severity of shock than heart rate and BP alone It has utility not only in trauma patients but also in sepsis, obstetrics, myocardial infarction, stroke, and other acute critical illnesses In the trauma population, it has been shown to be more useful than heart rate and BP alone, and it has also been shown to be of benefit specifically in the pediatric and geriatric populations It has been correlated with need for interventions such as blood transfusion and invasive procedures including operations SI is known as a hemodynamic stability indicator However, SI does not take into account the diastolic BP, and thus a modified SI (MSI) was created MSI is defined as heart rate divided by mean arterial pressure High MSI indicates a value of stroke volume and low systemic vascular resistance, a sign of hypodynamic circulation In contrast, low MSI indicates a hyperdynamic state MSI has been considered a better marker than SI for mortality rate prediction Although SI or MSI is better than heart rate and systolic BP alone, the combination of these variables will undoubtedly be more useful There are additional studies showing that more complex calculations with more variables are more useful than simpler ones For example, taking into account the age, mechanism of injury, Glasgow Coma Scale (GCS) score, lactate levels, hemoglobin levels, and other physiologic parameters will result in statistically better prediction than with one individual vital sign It is intuitive that the addition of variables would be more predictive of outcome That is why the presence of an experienced surgeon is critical; in a few seconds, the astute clinician will quickly take into account multiple variables, including gender, age, GCS score, mechanism of injury, and other parameters Whereas SI and MSI are statistically more accurate than one individual parameter, there is no substitute for the experienced clinician at the bedside This may be the reason that these parameters, such as SI and MSI, have not been widely adopted Lactate and Base Deficit Lactate has been an associated marker of injury, and possibly ischemia, and has stood the test of time.16 However, new data question the cause and role of lactate The emerging information is confusing; it suggests that we may not understand lactate for what it truly implies Lactate has long been thought to be a byproduct of anaerobic metabolism and is routinely perceived to be an end waste product that is completely unfavorable Physiologists are now questioning this paradigm and have found that lactate behaves more advantageously than not An analogy would be that firefighters are associated with fires, but that does not mean that firefighters are bad, nor does it mean that they caused the fires Research has shown that lactate increases in muscle and blood during exercise It is at its highest level at or just after exhaustion Accordingly, it was assumed that lactate was a waste product We also know that lactic acid appears in response to muscle contraction and continues in the absence of oxygen In addition, accumulated lactate disappears when an adequate supply of oxygen is present in tissues Recent evidence indicates that lactate is an active metabolite, capable of moving between cells, tissues, and organs, where it may be oxidized as fuel or reconverted to form pyruvate or glucose It now appears that increased lactate production and concentration, as a result of anoxia or dysoxia, are often the exception rather than the rule Lactate seems to be a shuttle for energy; the lactate shuttle is now the subject of much debate The end product of glycolysis is pyruvic acid Lack of oxygen is thought to convert pyruvate into lactate However, lactate formation may allow carbohydrate metabolism to continue through glycolysis It is postulated that lactate is transferred from its site of production in the cytosol to neighboring cells and to a variety of organs (e.g., heart, liver, and kidney), where its oxidation and continued metabolism can occur Lactate is also being studied as a pseudohormone as it seems to regulate the cellular redox state, through exchange and conversion into pyruvate and through its effects on the ratio CHAPTER 4  Shock, Electrolytes, and Fluid of nicotinamide adenine dinucleotide to nicotinamide adenine dinucleotide (reduced)—the NAD+/NADH ratio It is released into the systemic circulation and taken up by distal tissues and organs, where it also affects the redox state in those cells Further evidence has shown that it affects wound regeneration, with promotion of increased collagen deposition and neovascularization Lactate may also induce vasodilation and catecholamine release and stimulate fat and carbohydrate oxidation Lactate levels in blood are highly dependent on the equilibrium between production and elimination from the bloodstream The liver is predominantly responsible for clearing lactate, and acute or chronic liver disease affects lactate levels Lactate was always thought to be produced from anaerobic tissues, but it now seems that a variety of tissue beds that are not undergoing anaerobic metabolism produce lactate when they are signaled of distress In canine muscle, lactate is produced by moderate-intensity exercise when the oxygen supply is ample A high adrenergic stimulus also causes a rise in lactate as the body prepares for or responds to stress A study of climbers of Mount Everest showed that the resting PO2 on the summit was about 28 mm Hg and decreased even more during exercise The blood lactate level in those climbers was essentially the same as at sea level even though they were in a state of hypoxia.17 Such facts have allowed us to question lactate and its true role In humans, lactate may be the preferred fuel in the brain and heart; in these tissues, infused lactate is used before glucose at rest and during exercise Because it is glucose sparing, lactate allows glucose and glycogen levels to be maintained In addition to lactate’s being preferred in the brain, evidence seems to indicate that lactate also has a role as being protective to brain tissues in TBI.18 Lactate fuels the human brain during exercise The level of lactate, whether it is a waste product or a source of energy, seems to signify tissue distress from anaerobic conditions or other factors.19 During times of stress, there is a release of epinephrine and other catecholamines, which also causes a release of lactate Base deficit, a measure of the number of millimoles of base required to correct the pH of a liter of whole blood to 7.4, seems to correlate well with lactate level, at least in the first 24 hours after an injury Rutherford, in 1992, showed that a base deficit of was associated with a 25% mortality rate in patients older than 55 years without a head injury or in patients younger than 55 years with a head injury When base deficit remains elevated, most clinicians believe that it is an indication of ongoing shock One of the problems with base deficit is that it is commonly influenced by the chloride from various resuscitation fluids, resulting in a hyperchloremic nongap acidosis In patients with renal failure, base deficit can also be a poor predictor of outcome; in the acute stage of renal failure, a base deficit of less than 6 mmol/ liter is associated with poor outcome.20 With the use of hypertonic saline (HTS), which has three to eight times the sodium chloride concentration as normal saline, depending on the concentration used, in trauma patients, the hyperchloremic acidosis has been shown to be relatively harmless However, when HTS is used, base deficit should be interpreted with caution Compensatory Mechanisms When needed, blood flow to less critical tissues is diverted to more critical tissues The earliest compensatory mechanism in response to a decrease in intravascular volume is an increase in sympathetic activity Such an increase is mediated by pressure receptors or baroreceptors in the aortic arch, atria, and carotid bodies A decrease in pressure inhibits parasympathetic discharge while 53 norepinephrine and epinephrine are liberated and causes adrenergic receptors in the myocardium and vascular smooth muscle to be activated Heart rate and contractility are increased; peripheral vascular resistance is also increased, resulting in increased BP However, the various tissue beds are not affected equally; blood is shunted from less critical organs (e.g., skin, skeletal muscle, and splanchnic circulation) to more critical organs (e.g., brain, liver, and kidneys) Then, the juxtaglomerular apparatus in the kidney—in response to the vasoconstriction and decrease in blood flow— produces the enzyme renin, which generates angiotensin I The angiotensin-converting enzyme located on the endothelial cells of the pulmonary arteries converts angiotensin I to angiotensin II In turn, angiotensin II stimulates an increased sympathetic drive, at the level of the nerve terminal, by releasing hormones from the adrenal medulla In response, the adrenal medulla affects intravascular volume during shock by secreting catechol hormones— epinephrine, norepinephrine, and dopamine—which are all produced from phenylalanine and tyrosine They are called catecholamines because they contain a catechol group derived from the amino acid tyrosine The release of catecholamines is thought to be responsible for the elevated glucose level in hemorrhagic shock Although the role of glucose elevation in hemorrhagic shock is not fully understood, it does not seem to affect outcome.21 Cortisol, also released from the adrenal cortex, plays a major role in that it controls fluid equilibrium In the adrenal cortex, the zona glomerulosa produces aldosterone in response to stimulation by angiotensin II Aldosterone is a mineralocorticoid that modulates renal function by increasing recovery of sodium and excretion of potassium Angiotensin II also has a direct action on the renal tubules: reabsorbing sodium The control of sodium is a primary way that the human body controls water absorption or secretion in the kidneys One of the problems in shock is that the release of hormones is not infinite; the supply can be exhausted This regulation of intravascular fluid status is further affected by the carotid baroreceptors and the atrial natriuretic peptides Signals are sent to the supraoptic and paraventricular nuclei in the brain Antidiuretic hormone (ADH) is released from the pituitary, causing retention of free water at the level of the kidney Simultaneously, volume is recruited from the extravascular and cellular spaces A shift of water occurs as hydrostatic pressures fall in the intravascular compartment At the capillary level, hydrostatic pressures are also reduced because the precapillary sphincters are vasoconstricted more than the postcapillary sphincters Lethal Triad The triad of acidosis, hypothermia, and coagulopathy is common in resuscitated patients who are bleeding or in shock from various factors Our basic understanding is that inadequate tissue perfusion results in acidosis caused by lactate production In the shock state, the delivery of nutrients to the cells is thought to be inadequate, so adenosine triphosphate (ATP) production decreases The human body relies on ATP production to maintain homeostatic temperatures ATP is the source of heat in all homeothermic (warm-blooded) animals Thus, if ATP production is inadequate to maintain body temperature, the body will trend toward the ambient temperature For most human patients, this is 22° C (72° F), the temperature inside typical hospitals The resulting hypothermia then affects the efficiency of enzymes, which work best at 37° C For surgeons, the critical problem with hypothermia is that the coagulation cascade depends on enzymes that are affected by hypothermia If enzymes are not functioning 54 SECTION I  Surgical Basic Principles optimally because of hypothermia, coagulopathy worsens, which, in surgical patients, can contribute to uncontrolled bleeding from injuries or the surgery itself Further bleeding continues to fuel the triad The optimal method to break the “vicious circle of death” is to stop the bleeding and the causes of hypothermia In most typical scenarios, hypothermia is not spontaneous from ischemia but is induced because of use of room temperature fluid or cold blood products Acidosis Bleeding causes a host of responses During the resuscitative phase, the lethal triad (acidosis, hypothermia, and coagulopathy) is frequent in severely bleeding patients, most likely because of two major factors First is the decreased perfusion causing lactic acidosis, and consumptive coagulopathy The second is the resuscitation injury from the amount and type of fluid infused contributing to hypothermia if the fluid is not warmed and dilutional coagulopathy Some believe that the acidotic state is not necessarily undesirable because the body tolerates acidosis better than alkalosis Oxygen is more easily offloaded from the hemoglobin molecules in the acidotic environment Basic scientists who try to preserve tissue ex vivo find that cells live longer in an acidotic environment Correcting acidosis with sodium bicarbonate has classically been avoided as it is treating a number or symptom when the cause needs to be addressed Treating the pH alone has shown no benefit, but it can lead to complacency The patients may appear to be better resuscitated, but the underlying cause of the acidosis has not been adequately addressed It is also argued that rapidly injecting sodium bicarbonate can worsen intracellular acidosis because of the diffusion of the converted CO2 into the cells The best fundamental approach to metabolic acidosis from shock is to treat the underlying cause of shock In the surgeon’s case, it is blood loss or ischemic tissue However, some clinicians believe that treating the pH has advantages because the enzymes necessary for the coagulation cascade work better at an optimal temperature and optimal pH Coagulopathy can contribute to uncontrolled bleeding, so some have recommended treating acidosis with bicarbonate infusion for patients in dire scenarios Treating acidosis with sodium bicarbonate may have a benefit in an unintended and unrecognized way Rapid infusion of bicarbonate is usually accompanied by a rise in BP in hypotensive patients This rise is usually attributed to correcting the pH; however, sodium bicarbonate in most urgent scenarios is given in ampules The 50-mL ampule of sodium bicarbonate has 1 mEq/ mL—in essence, similar to giving a hypertonic concentration of sodium, which quickly draws fluid into the vascular space Given its high sodium concentration, a 50-mL bolus of sodium bicarbonate has physiologic results similar to 325 mL of normal saline or 385 mL of LR Essentially, it is like giving small doses of HTS Sodium bicarbonate quickly increases CO2 levels by its conversion in the liver, so if the minute ventilation is not increased, respiratory acidosis can result THAM (tromethamine; tris[hydroxymethyl] aminomethane) is a biologically inert amino alcohol of low toxicity that buffers CO2 and acids It is sodium free and limits the generation of CO2 in the process of buffering At 37° C, the pKa of THAM is 7.8, making it a more effective buffer than sodium bicarbonate in the physiologic range of blood pH In vivo, THAM supplements the buffering capacity of the blood bicarbonate system by generating sodium bicarbonate and decreasing the partial pressure of CO2 It rapidly distributes to the extracellular space and slowly penetrates the intracellular space, except in the case of erythrocytes and hepatocytes, and it is excreted by the kidney Unlike sodium bicarbonate, which requires an open system to eliminate CO2 to exert its buffering effect, THAM is effective in a closed or semiclosed system, and it maintains its buffering ability during hypothermia THAM acetate (0.3 M, pH 8.6) is well tolerated, does not cause tissue or venous irritation, and is the only formulation available in the United States THAM may induce respiratory depression and hypoglycemia, which may require ventilatory assistance and the administration of glucose The initial loading dose of THAM acetate (0.3 M) for the treatment of acidemia may be estimated as follows: THAM (in mL of 0.3 M solution) = lean body weight (in kilograms) × the base deficit (in mmol/liter ) The maximal daily dose is 15 mmol per kilogram per day for an adult (3.5 liters of a 0.3 M solution in a patient weighing 70 kg) It is indicated in the treatment of respiratory failure (acute respiratory distress syndrome [ARDS] and infant respiratory distress syndrome) and has been associated with the use of hypothermia and permissive hypercapnia (controlled hypoventilation) Other indications are diabetic and renal acidosis, salicylate and barbiturate intoxication, and increased intracranial pressure (ICP) associated with brain trauma It is used in cardioplegic solutions and during liver transplantation Despite these attributes, THAM has not been documented clinically to be more efficacious than sodium bicarbonate Hypothermia Hypothermia can be both beneficial and detrimental A fundamental knowledge of hypothermia is of vital importance in the care of surgical patients The beneficial aspects of hypothermia are mainly a result of decreased metabolism Injury sites are often iced, creating vasoconstriction and decreasing inflammation through decreased metabolism This concept of cooling to slow metabolism is also the rationale behind using hypothermia to decrease ischemia during cardiac, transplant, pediatric, and neurologic surgery Also, amputated extremities are iced before reimplantation Cold water near-drowning victims have higher survival rates, thanks to preservation of the brain and other vital organs The Advanced Life Support Task Force of the International Liaison Committee of Resuscitation now recommends cooling (to 32° C to 34° C for 12 to 24 hours) of unconscious adults who have spontaneous circulation after out-of-hospital cardiac arrest caused by ventricular fibrillation Induced hypothermia is vastly different from spontaneous hypothermia, which is typically from shock, inadequate tissue perfusion, or cold fluid infusion Medical or accidental hypothermia is vastly different from trauma-associated hypothermia (Table 4-2) The survival rates after accidental hypothermia range from about 12% to 39% The average temperature drop is to about 30° C (range, 13.7° C to 35.0° C) That lowest recorded temperature in a survivor of accidental hypothermia (13.7° C, or 56.7° F) was in an extreme skier in Norway; she was trapped under the ice and eventually fully recovered neurologically TABLE 4-2  Classification of Hypothermia Mild Moderate Severe TRAUMA ACCIDENTAL 36°-34° C 34°-32° C