Ebook Surgical decision making beyond the evidence based surgery: Part 1

(BQ) Part 1 book Surgical decision making beyond the evidence based surgery presentation of content: The anatomy of the surgeon’s decision making, the decision making process in sepsis and septic shock, intraoperative endpoints of resuscitation, surgeons and pilots: what do we have in common....

Rifat Latifi Surgical Decision Making Beyond the Evidence Based Surgery 123 Surgical Decision Making Rifat Latifi Surgical Decision Making Beyond the Evidence Based Surgery Rifat Latifi Department of Surgery Westchester Medical Center, New York Medical College Valhalla, NY, USA Department of Surgery University of Arizona Tucson, AZ, USA ISBN 978-3-319-29822-1 ISBN 978-3-319-29824-5 DOI 10.1007/978-3-319-29824-5 (eBook) Library of Congress Control Number: 2016936679 © Springer International Publishing Switzerland 2016 This work is subject to copyright All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed The use of general descriptive names, registered names, trademarks, service marks, etc in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made Printed on acid-free paper This Springer imprint is published by Springer Nature The registered company is Springer International Publishing AG Switzerland To Ronald C Merrell, MD, FACS a mentor, collaborator, and a friend, whose uncompromising vision to make the world better and dedication to care for sick and injured patients have inspired and guided me over the years to make some of the best decisions I have made Rifat Latifi, MD, FACS Foreword For decades, various urban legends have remarked about the ability (or lack of ability) of surgeons to make rapid decisions based on little data, to then reflect upon these decisions, and to learn from their successes and their mistakes Surgical decision-making always starts with the ability to make correct diagnoses regarding a patient’s illness and then to decide if an intervention is indicated either alone or as part of a continuum of care, including medical therapies Medicine is truly a team “sport,” but, fundamentally, each patient deserves to have an individual (captain model): to provide an overall view, to bring together consultants from many fields when necessary, and to present fully the pros and cons of the decided intervention, the risks and potential complications of such intervention, and the consequences of nonintervention to the patient for his/her decision as to what they wish done Underlying this process of surgeon-patient interaction and decision-making is the requirement for up-to-date clinical knowledge regarding best practices, clinical knowledge, and judgment The evolution of surgical clinical knowledge has not always proceeded in a stepwise fashion Historically, surgeons learned from each other by apprenticeship through observing operations and inpatient/outpatient perioperative care More experienced surgeons would travel long distances to learn new techniques that were being introduced by another master surgeon This method evolved into the publication of an individual surgeon’s results in treating a variety of surgical problems in patients, presenting such results in a professional public forum, and defending his/her various surgical approaches Surgical societies and organizations were formed to exchange ideas This was an attempt to improve surgical decision-making from the eighteenth through the twentieth centuries With time, it became apparent that greater knowledge could be obtained by understanding how “an institution” handled certain patients with different diagnoses and how the patients’ outcomes varied based upon their comorbidities and the surgical decisions made before, during, and after operations These retrospective studies taught us “associations” but not causations Later, institutions with large clinical volumes created their own prospective databases from which multiple questions could be answered when the clinical volumes were large enough to provide some statistical validity Interspersed over time have been prospective, randomized, clinical trials in which surgical therapies were instituted based upon randomization of the patients, and certain predetermined outcomes were then measured All of vii viii Foreword these types of studies taken together provide a base of clinical knowledge that assist the decision-making process Yet, each patient is an individual with different genetic and environmental backgrounds, ages, genders, comorbidities, socioeconomic and cultural circumstances, and goals for their lives In addition, the disease processes patients encounter have different durations, severities, prognoses, and potential outcomes Taken together, the complexities of human diseases in patients make physician decision-making difficult despite knowledge of basic sciences and current best practice guidelines This book, written and edited by Dr Latifi and others, provides an important and timely resource for surgical decision-making because it defines and recognizes the many internal and external factors that influence certain surgical decisions for better or worse Several points made in this book deserve emphasis While each operation should have a surgeon’s standard approach, many factors that occur during an operation may alter that approach, requiring surgeon flexibility in techniques used and goals to be obtained Recognizing that each operation is comprised of a team, we agree with Dr Latifi that the surgeon’s leadership ability and his/her ability to communicate effectively the tasks at hand to other members of the team are critical to a successful operation As described by Dr Latifi in Chap 1, managing resources (including time); directing, training, and supporting others; and coping with pressure are some of the critical components of the surgeon’s leadership ability It is that ability that usually determines the patient’s successful outcome This book nicely outlines the generic components of the surgeon’s leadership and decision-making abilities and the factors that influence them It also defines difficult clinical situations—from sepsis and trauma to elective or urgent operations for a variety of pathologic conditions—and provides guidance based on the best current clinical evidence An expert surgical leader combines such guidance with focused training, proper communication for team members, avoidance of intraoperative distractions, and a proper mental state These attributes lead to optimal surgical decision-making, which leads to optimal patient outcomes Maureen D Moore, M.D John M Daly, M.D., F.A.C.S., F.R.C.S.I Prologue Complex surgical procedures carry significant risks and complications Despite the most conscientious preoperative preparations, surprising events may still occur If the operation takes an unplanned turn, the surgeon has to make difficult decisions An absolute must is continuous awareness of the patient’s physiologic status—including fluid status, urine output, use of blood and blood products, bleeding, current medications (such as vasopressors), and biochemical endpoints of resuscitation Even when the operation is going well, the biochemical profile of the patient may not be optimal or even satisfactory, which may directly affect the outcome In addition, the surgeon must recognize his/her own physiologic status; if tired, for example, cutting corners and making major errors are much more likely In this book, we address these and other elements that are important for the intraoperative decisionmaking process How we as surgeons make intraoperative decisions under what can be inauspicious conditions? That question has not been answered appropriately in the literature When a patient is dying in our hands from bleeding that we cannot control, when irreversible metabolic shock does not respond to anything that we do, when new problems emerge out of the blue, when things go alarmingly wrong: In such dire moments during a carefully planned operation, how we decide what to next and how should we overcome our own fear? Many of us make decisions that later on we cannot explain, that we cannot say why we did things a certain way Usually these are decisions made on the basis of a “gut feeling” or “intuition” or the “gray hair effect,” among other attributes Yet, the anatomy of such decisions is of great importance to all surgeons and to those who work with surgeons In this book, we will review theoretical as well as any objective data that we as surgeons use to make intraoperative decisions The decision we make, often with very limited amount of information, will decide between someone living or dying How we make decisions in split seconds to take someone to the operating room now as opposed to a bit later? How we decide to operate on a dying patient without a CT scan and no laboratory data, just based on the fact that he or she is in shock, just to find liters of blood in the abdomen, a torn vena cava, liver, spleen, or some major blood vessel? When the patient is dying in the operation room, everyone panics, but the surgeon reaches in the open abdomen and compresses the aorta between his/ her fingers, in order to let the team catch up Is there a molecular explanation for this? Non-surgeons have created and put forth many theories and hypotheses in the literature But our collective firsthand experience as surgeons ix x points to a combination of factors contributing to our intraoperative decisionmaking process These factors include education, clinical know-how, mentoring, and the creativity and excellence that come with long practice and with strict discipline The aim of this book is to evaluate the current literature on the subject and to explore what is known and, more importantly, what is not known about this process Frankly, while the surgeon may be considered the “captain of the ship,” there are many aspects of the surgical process that have recently received major public interest, and these aspects are not in the hands of surgeons at all Involvement of these other disciplines—mainly administration, regulations, insurance, and government—has become a priority in many cases Often, we forget that surgery is both a science and an art, and surgeons are the conductors of a symphony that truly needs to run perfectly There are other differences between surgeons and the physicians in many other clinical disciplines While I was a medical student at the University of Prishtina, Kosova, Professor of Surgery Dr Gazmend Shaqiri would tell me and others: “When a patient dies in a medical ward, he or she dies from the disease; however, when the patient dies in surgical ward, the patient dies from the surgery, or more importantly, from the decisions made by the surgeon.” This may be a decision by the surgeon to operate or not to operate While surgical procedures are far more complex than one individual’s decisions during surgery, there are elements to this small surgical microcosm that add additional pressure on the surgeon and how he or she copes with this decision Over the years, I have been reminded often of the consequences of making a decision, both wrong and right When I started this book, I thought it would be a single-author book, somewhat of a real rarity these days However, as the months were passing by and the project was not being completed, I saw the real reason why: I really wanted to have other opinions on the matter I am hoping this book will serve as a good reference or even inspiration for others to explore the subject further I did not and not envision this as a book of algorithms and strict protocols, although in a few chapters such suggestions have been made I wanted myself and the other chapter authors to go a bit “beyond” the surgical decision-making process and inside the surgeon as being I wanted to see if we can explore what makes the surgeon’s brain and heart “buzz” and continue to work nonstop for many hours While at Yale University, before the regulation of working hours for residents, one of my vascular attendings and I operated basically nonstop from Friday morning until Sunday afternoon, with a few “power naps” between cases I thought I was doing “fine” until I went to start my car Now that the adrenaline was gone, I could not even drive myself home I was completely exhausted and could not keep my eyes open I had to call my wife Drita to come pick me up and take me home How was I able to go on for so long while we were operating and yet I could not drive myself the ten miles home? The anatomy and the physiology of the surgeon are addressed in Chapters and We cannot forget that we are not super creatures, despite what everyone may think of us; we are all just human Prologue Prologue xi Have you ever seen a surgeon emotionally “naked,” burnt out, exhausted, disillusioned, and simply tired of everything? Even worse, most of us not talk about the matter until it becomes a real problem Not a pretty picture by any means At this point, you may be thinking of friends and colleagues who committed suicide or were on the brink of doing so Drug and alcohol abuse, difficulties with personal relationships, multiple divorces, or simply becoming obese and not caring for oneself are not uncommon among surgeons We are just human, and yet, like many other professions, we still have to get up and go to work and make some incredible decisions that will affect our patients and their families and, of course, us, and we have to live with those decisions I hope this book will explain some of those decisions and how we make them, but, most importantly, how we live with the decisions we make and how we improve constantly Valhalla, NY, USA Spring 2016 Rifat Latifi, M.D., F.A.C.S The Decision-Making Process in Sepsis and Septic Shock Finally, a meta-analysis including 13 trials with 2525 patients revealed that the mortality benefit of goal-directed therapy was only appreciated when applied early (within h, Relative Risk 0.77; 95 % Confidence Interval, 0.67–0.89; p = 0.0004; I2 = 40 %) and not when the timing was outside of the h or unclear (Relative Risk 0.92; 95 % Confidence Interval, 0.69–1.24; p = 0.59; I2 = 56 %) [89] There have not yet been updates to the Surviving Sepsis Guidelines in light of these new studies What these studies emphasize is that while all components of EDGT may not be necessary, they not definitively display any harm This could be a limitation of only assessing mortality as an outcome The work of Rivers and colleagues over a decade ago revolutionized the way that sepsis is considered, leading to increased awareness, earlier identification, and earlier administration of therapies Perhaps the biggest contribution of EDGT is the earlier recognition of sepsis and earlier administration of antimicrobial therapy 10 11 12 Conclusion 13 Sepsis continues to be a frequent cause of mortality in surgical patients Early identification through the use of screening tools designed specifically for surgical patients, early administration of antimicrobials, and source control are all essential for survival from surgical sepsis For patients with severe physiological derangements, planned, staged, and abbreviated procedures may improve patient survival 14 15 16 Acknowledgment There are no identifiable conflicts of interests to report The authors have no financial or proprietary interest in the subject matter or materials discussed in the manuscript 17 References 18 Lagu T, et al Hospitalizations, costs, and outcomes of severe sepsis in the United States 2003 to 2007 Crit Care Med 2012;40:754–61 Hall MJ, Williams SN, DeFrances CJ, Golosinskiy A Inpatient care for septicemia or sepsis: a challenge 19 77 for patients and hospitals NCHS Data Brief 2011;(62):1–8 Moore LJ, et al Sepsis in general surgery: the 2005– 2007 national surgical quality improvement program perspective Arch Surg 2010;145:695–700 Angus DC, et al Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care Crit Care Med 2001;29:1303–10 Moore LJ, Moore FA, Jones SL, Xu J, Bass BL Sepsis in general surgery: a deadly complication Am J Surg 2009;198:868–74 Dombrovskiy VY, Martin AA, Sunderram J, Paz HL Facing the challenge: decreasing case fatality rates in severe sepsis despite increasing hospitalizations Crit Care Med 2005;33:2555–62 Balk RA, Bone RC The septic syndrome Definition and clinical implications Crit Care Clin 1989;5:1–8 American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis Crit Care Med 1992;20:864–874 Levy MM, et al 2001 SCCM/ESICM/ACCP/ATS/ SIS International Sepsis Definitions Conference Crit Care Med 2003;31:1250–6 Rivers E, et al Early goal-directed therapy in the treatment of severe sepsis and septic shock N Engl J Med 2001;345:1368–77 Robson W, Beavis S, Spittle N An audit of ward nurses’ knowledge of sepsis Nurs Crit Care 2007;12:8692 Assunỗóo M, et al Survey on physicians’ knowledge of sepsis: they recognize it promptly? 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Crit Care Clin 2002;18:165–75 Parker MM, et al Profound but reversible myocardial depression in patients with septic shock Ann Intern Med 1984;100:483–90 Jardin F, Brun-Ney D, Auvert B, Beauchet A, Bourdarias JP Sepsis-related cardiogenic shock Crit Care Med 1990;18:1055–60 Turner KL, et al Identification of cardiac dysfunction in sepsis with B-type natriuretic peptide J Am Coll Surg 2011;213:139–46; discussion 146–7 Toma A, Stone A, Green RS, Gray S Steroids for patients in septic shock: the results of the CORTICUS trial CJEM 2011;13:273–6 Groeneveld ABJ, Molenaar N, Beishuizen B Should we abandon corticosteroids during septic shock? No Curr Opin Crit Care 2008;14:384–9 Marik PE, et al Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: consensus statements from an international task force by the American College of Critical Care Medicine Crit Care Med 2008;36:1937–49 Annane D, et al Diagnosis of adrenal insufficiency in severe sepsis and septic shock Am J Respir Crit Care Med 2006;174:1319–26 Sprung CL, et al Hydrocortisone therapy for patients with septic shock N Engl J Med 2008;358:111–24 Vinclair M, et al Duration of adrenal inhibition following a single dose of etomidate in critically ill patients Intensive Care Med 2008;34:714–9 Alday NJ, et al Effects of etomidate on vasopressor use in patients with sepsis or severe sepsis: a propensitymatched analysis J Crit Care 2014;29:517–22 Bruder EA, Ball IM, Ridi S, Pickett W, Hohl C Single induction dose of etomidate versus other induction agents for endotracheal intubation in critically ill patients Cochrane Database Syst Rev 2015;1:CD010225 Chan CM, Mitchell AL, Shorr AF Etomidate is associated with mortality and adrenal insufficiency in sepsis: a meta-analysis* Crit Care Med 2012;40:2945–53 Annane D, et al Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock JAMA 2002;288:862–71 Annane D, Bellissant E, Bollaert P, et al Corticosteroids in the treatment of severe sepsis and septic shock in adults: a systematic review JAMA 2009;301:2362–75 Sligl WI, Milner DA, Sundar S, Mphatswe W, Majumdar SR Safety and efficacy of corticosteroids for the treatment of septic shock: a systematic review and meta-analysis Clin Infect Dis 2009;49:93–101 Blot F, et al Earlier positivity of central-venous- versus peripheral-blood cultures is highly predictive of catheter-related sepsis J Clin Microbiol 1998;36:105–9 The Decision-Making Process in Sepsis and Septic Shock 55 Blot F, et al Diagnosis of catheter-related bacteraemia: a 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intra-abdominal hypertension and abdominal compartment syndrome I definitions Intensive Care Med 2006;32: 1722–32 81 Bernard GR, et al Efficacy and safety of recombinant human activated protein C for severe sepsis N Engl J Med 2001;344:699–709 82 Martí-Carvajal A, Salanti G, Cardona AF Human recombinant activated protein C for severe sepsis Cochrane Database Syst Rev 2008;1, CD004388 doi: 10.1002/14651858.CD004388.pub3 83 Ranieri VM, et al Drotrecogin alfa (activated) in adults with septic shock N Engl J Med 2012;366: 2055–64 84 Kelm DJ, et al Fluid overload in patients with severe sepsis and septic shock treated with early goaldirected therapy is associated with increased acute need for fluid-related medical interventions and hospital death Shock 2015;43:68–73 85 Yealy DM, Kellum JA A randomized trial of protocolbased care for early septic shock N Engl J Med 2014;370:1683–93 86 Cabrera JL, Pinsky MR Management of septic shock: a protocol-less approach Crit Care 2015;19:260 87 ARISE Investigators, et al Goal-directed resuscitation for patients with early septic shock N Engl J Med 2014;371:1496–506 88 Mouncey PR, et al Trial of early, goal-directed resuscitation for septic shock N Engl J Med 2015;372:1301–11 89 Zhang L, Zhu G, Han L, Fu P Early goal-directed therapy in the management of severe sepsis or septic shock in adults: a meta-analysis of randomized controlled trials BMC Med 2015;13:71 Intraoperative Endpoints of Resuscitation Hans Fred García Araque, Patrizio Petrone, Wilson Dario Rodríguez Velandia, and Corrado Paolo Marini Introduction The number of surgical procedures performed in the USA is continuously rising as a result of the increasing life expectancy of the population and of the pathology typically associated with aging As a result, it is more common for the surgeon to be confronted with planning and operating on older patients who have multiple comorbid conditions that increase the risk of complications and the mortality associated with major H.F.G Araque, M.D Hospital Militar Central, Bogotá, Colombia Westchester Medical Center University Hospital, Valhalla, NY, USA Department of Surgery, New York Medical College, Valhalla, NY, USA e-mail: hafregar@gmail.com P Petrone, M.D., M.P.H., M.H.A., F.A.C.S C.P Marini, M.D., F.A.C.S (*) Department of Surgery, Westchester Medical Center University Hospital, New York Medical College, Valhalla, NY, USA e-mail: petronep@wcmc.com; patrizio.petrone@gmail.com; marinic@wcmc.com W.D.R Velandia, M.D Department of Surgery, Westchester Medical Center University Hospital, New York Medical College, Valhalla, NY, USA Complejo Hospitalario Universitario de Ferrol, A Coruña, Spain surgical procedures Therefore, the perioperative evaluation and management of the patient has become a major focus of the strategy needed to minimize the risk of complications and to decrease the all-­cause surgical mortality Recently, an acceptably low all-cause mortality ranging between and % has been reported in 230 million patients undergoing surgical procedures as a result of the improvements in monitoring, safety, and the development of surgical checklists [1] However, the increasing number of surgical patients categorized as high-risk with predicted mortality exceeding 10 % demands standardization of the perioperative evaluation and management, as well as the development of specific protocols targeted to preoperative, intraoperative, and postoperative endpoints that can decrease morbidity and mortality in this subset of patients In view of a worldwide yearly number of 25 million surgical procedures in high-risk patients with a potential loss of three million lives each year, it is imperative that the perioperative evaluation and management becomes the major focus of the overall strategy aimed at reducing the risk of complications affecting the functional outcome and death in the high-risk surgical patients Failure to evaluate appropriately high-risk surgical patients and to utilize principles of critical care monitoring preoperatively, intraoperatively, as well as postoperatively has been shown to be associated with increased mortality and morbidity [2] © Springer International Publishing Switzerland 2016 R Latifi, Surgical Decision Making , DOI  10.1007/978-3-319-29824-5_8 81 82 In this chapter, we will focus on specific intraoperative hemodynamic and biochemical endpoints of resuscitation in order to decrease postoperative morbidity and mortality based on the best evidence available  ndpoints of Intraoperative E Resuscitation The endpoints of intraoperative resuscitation depend heavily on the patient’s preoperative condition, including his/her comorbid conditions, the type of surgery being performed and the duration of the surgery itself However, notwithstanding the type of the planned procedure, certain physiological principles apply to all patients undergoing general anesthesia from the standpoint of the relationship between cellular oxygen delivery and consumption during major surgical procedures Furthermore, the endpoints of intraoperative resuscitation depend on the depth and duration of anesthesia, the magnitude of the planned procedure and more importantly, on the risk stratification of the patients with its associated predicted mortality It is well known that during general anesthesia there is an uncoupling between oxygen delivery and oxygen consumption as a result of the anesthetic regimen on the ability of cells to extract oxygen appropriately [3] Despite the decreased metabolic rate that results from a combination of the temperature changes that occur during surgery and the direct effect of anesthesia, most patients incur a significant intraoperative oxygen debt manifested by increased base deficit and lactate levels as a result of a global cellular failure to extract oxygen even in the presence of increased oxygen delivery (DO2) Lugo and associates reported that high-risk surgical patients undergoing general anesthesia have compromised tissue ability to extract oxygen; they showed that oxygen extraction decreased to approximately 14 % from the normal value of 25 % observed preoperatively During anesthesia, venous oxygen saturation (SvO2) increased to 86 % from the preoperative normal value of 75 % [3] Therefore, the intraoperative period for high-risk surgical H.F.G Araque et al patients represents a condition for the development of tissue oxygen debt despite the presence of adequate or even supra-normal DO2 Despite the reduction in metabolic demands from hypothermia and anesthesia, the reduction in oxygen consumption during the intraoperative period of approximately 23 % compared with the preoperative oxygen consumption leads to an increase in base deficit and lactate levels as a result of the incurred oxygen debt Therefore, the intraoperative trend of base deficit and arterial lactate level can be used as markers to identify the development and magnitude of the oxygen debt While Shoemaker and his collaborators have suggested that the intraoperative oxygen debt could be responsible postoperatively for the development of multiple organ dysfunction syndrome (MODS), and ultimately, multiple organ failure (MOF), if not repaid postoperatively within 12–24 h in high-risk surgical patients, other authors not believe that there is a proven correlation between the development of the intraoperative oxygen debt, the time to its repayment, and the subsequent development of MODS [4–6] Therefore, it remains controversial whether the minimization of the intraoperative oxygen debt and its early repayment is a valid endpoint of intraoperative and postoperative resuscitation Clearly, depending on the type and duration of surgery, attention should be directed to the intraoperative variables that may affect the postoperative course of the patient The degree and type of hemodynamic monitoring should be selected based on the preoperative condition of the patient and the type of surgery being performed Simple endpoints that could assure a safe intraoperative and postoperative course in a standard low-risk patient undergoing for example a colon resection such as measurement of heart rate, blood pressure, central venous pressure, and urine output may be inadequate in an operation in a high-risk patient associated with massive fluid shift and blood loss Patients undergoing operations associated with massive fluid shift and blood loss maybe primed to the activation of a more pronounced inflammatory response in the absence of optimization of cellular oxygen delivery and utilization; therefore, these patients may benefit 8  Intraoperative Endpoints of Resuscitation from the measurement of flow-based variables, such as cardiac output and oxygen extraction and utilization, which may be more sensitive indicators of the balance between DO2 and oxygen consumption (VO2) than the traditional measurements of blood pressure and central venous pressure, as well as of urine output It is well known that during surgery there is the development of a functionless third space that causes sequestration of extracellular fluid into a space that does not contribute to the dynamic fluid exchange at the level of the microcirculation The volume of the third space is proportional to the degree of injury and to the type of surgery being performed ranging from mL/kg per hour for relatively minor procedures such as an open cholecystectomy to greater than 20 mL/ kg per hour for major procedures such as open repair of aortic aneurysm, a pancreaticoduodenectomy, and/or major trauma related procedures Its composition is similar to that of plasma In addition to the development of the third space, large insensitive losses due to evaporation occur in procedures with an open abdomen and/or open chest The evaporative losses increase with increasing duration of surgery and in general are in the order of mL/kg/h 83 will provide an intracytosolic oxygen tension of mmHg, which in turn will result in a mitochondrial oxygen tension of 1.2 mmHg, the value needed for all oxidative processes The maintenance of the intracytosolic oxygen tension is the key regulatory mechanism associated with a downregulated response of the hypoxia inducible factor α and β (HIF-α, HIF-β) In the presence of adequate oxygen tension within the cytosol, the HIF-α will undergo proteasomal degradation after enzymatic hydroxylation by the 4-prolyl-hydroxylases (PHDs); therefore, there will not be an upregulated production of TNF-α and IL-1 via this oxygen sensing pathway Conversely, in the setting of cellular hypoxia, the HIF-α and HIF-β subunits translocate to the nucleus, where they bind as heterodimers to a hypoxia response promoter element (HRE), inducing transcription of numerous genes, including those of nuclear factor κB (NF-­ κB) and toll-like receptors (TLRs) [7] The result is an upregulated inflammatory response It is now well accepted from studies of the hypoxia signaling pathway that hypoxia can induce inflammation in the absence of any other stimulus, including endotoxemia and/or bacteremia We believe that under-resuscitation of patients manifested by increasing base deficit and lactate Oxygen Delivery and Oxygen levels during major surgical procedures associated with massive fluid shift and blood loss Consumption primes the patient to an upregulated inflammaUnder normal physiological conditions, VO2 at tory response, which may in turn be responsible the cellular level is independent of DO2; it is for the development of MODS, via the oxygen maintained constant by a balance between oxy- sensing pathway Therefore, we believe that one gen supply and demand at the organ level through of the more important endpoints of intraoperative complex autoregulatory mechanisms directed at resuscitation is the avoidance of cellular hypoxia matching oxygen supply to the local metabolic by monitoring and attempting to avoid large demands It is noteworthy that autoregulation of increases in the surrogate markers of cellular blood flow (QB) at organ level occurs through hypoperfusion, namely, base deficit and lactate changes in capillary density, namely, the number level While it may not be possible to maintain of open capillary with red cells transit, which both within normal range during major surgical were originally defined in relation to the regula- procedures due to the effects of anesthesia on celtion of QB and not to the regulation of tissue lular oxygen utilization, we suggest that attempts oxygenation should be made to have a downward trend of both Under normal physiological conditions, high-­ base deficit and lactate levels during surgery, demand regions receive increased DO2, whereas avoiding a progression toward values that clearly low-demand regions receive decreased delivery correlate with significant cellular hypoxia from Typically, a DO2 of approximately 1000 mL/m2/min hypoperfusion 84 H.F.G Araque et al The oxygen delivered to an organ is equal to the QB to the organ, indexed to the weight of the organ or body times the arterial oxygen content (CaO2) times a factor of 10 used to transform the units in mL/m2/min where DO2 = QB × CaO2 × 10 (mL / min) (8.1) The arterial oxygen content is depicted by the following equation: CaO2 = (Hg × 1.34 × SaO2 ) + PaO2 × 0.003 (8.2) where Hg is the hemoglobin concentration (g/ dL), 1.34 is the oxygen-binding capacity of Hg, SaO2 is the arterial oxygen saturation (%), and PaO2 is the partial pressure of oxygen (mmHg) in arterial blood Total DO2 indexed to the body weight is the product of cardiac index (CI) times CaO2 times 10: DO2 I = Cl × CaO2 × 10 (mL / m / min) Venous oxygen content is defined by the following equation: CvO2 = (Hg × 1.34 × SvO2 ) + (PvO2 × 0.003) where Hg is the hemoglobin concentration (g/ dL), SvO2 is the venous oxygen saturation (%), and PvO2 is the partial pressure of oxygen (mmHg) in venous blood Oxygen consumption by the Fick principle is the product of QB times the arteriovenous oxygen difference: (VO2 ) = QB × (CaO2 − CvO2 ) In normal conditions, VO2 is 250 mL/min, a small portion of the oxygen delivered to the body The increases in capillary density of perfused capillaries within tissues resulting from the release of intracytosolic adenosine in the setting of decreased redox potential secondary either to hypoxia and/or disoxia is a compensatory response aimed at optimizing the transit time and the diffusion distance, therefore preventing molecular diffusion limitations in the unloading of oxygen The ability to extract oxygen differs significantly among organs in the body, with one organ, the heart, always working at maximum extraction (60 %), therefore, requiring increased flow in the setting of increased demand to maintain oxygen consumption constant (supply dependent) as opposed to the kidney that at baseline extract only % of the oxygen delivered, therefore, can maintain its oxygen consumption constant by increasing extraction in the setting of decreased flow Since CI plays a dominant role in the DO2I equation, the major efforts to maintain or increase tissue perfusion must be directed at optimizing the four variables that affect CO, namely, heart rate, preload, afterload, and contractility taking into consideration the more recent understanding of ventriculoarterial coupling Since the heart rate affects the modulus of chamber stiffness of the left ventricle, it must be optimized (should be kept below 120 bpm) in order to allow the preload recruitment of stroke volume without incurring an increase in pulmonary artery occlusion pressure (left ventricular end-diastolic pressure) with the potential of increased extravascular lung water Preload recruitment with incremental volume loading (250 mL of crystalloids every 10–15 min or more rapidly, if required) of SV is the ideal strategy to increase CO without incurring an increase in myocardial oxygen consumption Of note, since two data points will always yield a straight line, one must acquire at least three data points, while volume loading the ventricle, in order to evaluate the slope of the pressure–volume relationship and in order to make sound clinical decisions regarding the approach to preload, afterload, and cardiac contractility We advise against the use of high-molecular-weight hydroxyethyl starch solutions (>150 kD) as plasma expanders during surgery because of the increased risk of renal dysfunction associated with these solutions, as well as because of their effect on the microcirculation including experimental evidence of upregulation of the pro-inflammatory response and negative effects on the ability of the cells to extract oxygen [8, 9] With respect to the use of blood transfusion to increase DO2 and VO2 at the cellular level, one must be familiar with the effects of storage and the age of the transfused red blood cells on their ability to unload oxygen and to negotiate the 8  Intraoperative Endpoints of Resuscitation microcirculation following the storage related changes that occur and due to the documented increase in nosocomial infections and adult respiratory distress syndrome associated with the transfusion of non-leukodepleted stored red blood cells While the transfusion of stored blood will increase DO2 by increasing the hemoglobin level, it may not yield a corresponding increase in oxygen utilization due to the depletion of 2,3 diphosphoglycerate (2,3-DPG) and the morphologic changes in the red cells associated with storage, which increase the hemoglobin oxygen affinity and compromise the unloading of oxygen at cellular level The normal P50 of 27 mmHg of non-stored red blood cells decreases to a P50 of mmHg after prolonged storage (>14 days) decreasing the unloading of oxygen to approximately % The administration of old blood, defined as blood older than 14 days, has been shown to compromise oxygen availability and utilization in the splanchnic circulation as measured by monitoring of the intragastric mucosal pH, as well as an increased morbidity and mortality in patients undergoing cardiac surgery [10, 11] The detrimental effect of the transfusion of old stored blood is more evident in the low shear rate districts of the body where the effect of the depletion of 2,3-DPG leads to a more compromised unloading of oxygen It takes between 16 and 24 h to have the complete restoration of the 2,3-DPG and the normalization of the oxygen hemoglobin dissociation curve Therefore, to increase oxygen utilization at cellular level during surgery one must consider using fresh or ultra-fresh blood, namely, blood stored for days or less The use of pure alpha agonist agents such as phenylephrine or strong alpha agonists with minimal beta agonist activity such as norepinephrine should be avoided because it increases systolic blood pressure by increasing the afterload at the expense of SV. An increase in afterload will increase the end-systolic pressure point without a corresponding increase in SV; therefore, it will increase thermodynamic waste (increased pressure in mmHg for displacement of mL SV) (Fig 8.1) We advise against the use of vasopressin to maintain or raise mean blood pressure 85 during surgical procedures on the gastrointestinal tract involving the performance of gastrointestinal anastomoses because of its negative effect on splanchnic blood flow and mucosal oxygen tension [12] An individualized goal-directed therapy aimed at optimizing the balance of DO2 and VO2 with a restrictive fluid therapy using flow-­ based hemodynamic parameters should be used in high-risk surgical patients The ideal monitoring methodologies include arterial waveform analysis with either stroke volume or pulse pressure variations and the intraoperative use of esophageal Doppler monitoring with disposable probes in order to assess the functional status of the left ventricle and to optimize ventriculo-­ arterial coupling The preemptive use of hemodynamically guided perioperative therapy has been shown to decrease morbidity and mortality in high-risk surgical patients [13] Arterial Base Deficit The measurement of arterial blood gases is a daily practice in many operating rooms The arterial base deficit obtained from the gas analysis of the arterial blood is a very useful tool widely used to help monitoring surgical patients in order to determine the global balance between DO2 and VO2 It is a superior marker of adequacy of tissue perfusion because it alerts the physician to the presence of occult hypoperfusion because it increases even when arterial blood pressure is normal Its use to predict the need for blood transfusion in trauma patients, to consider implementing damage control surgery, as well as its prognostic value in trauma patients is supported by level I and II evidence [14–16] Base deficit is defined as the amount of base required to raise the serum pH of 1 L of whole blood to 7.40 at a temperature of 37 °C and a PCO2 of 40 mmHg Zakrison et al have shown that there is not a significant, clinically important difference between arterial and venous base deficit, even in the presence of shock and in the ­elderly [17] Venous sampling for measurement of base deficit is easier to in the perioperative setting, in the emergency department, and in the 86 H.F.G Araque et al ESP1 Left ventricular pressure (mmHg) 150 C1 B1 ESP 100 C B D Vo 50 A D1 75 150 Left ventricular volume (ml) Fig 8.1  Effect of increasing afterload with vasopressors on the P–V loop Illustrated is the pressure–volume relation for the left ventricle over an entire cardiac cycle The area ABCD represents the energy added to the aortic root by the ventricular contraction The heat dissipated in the ventricular wall during isovolumic relaxation is represented by the area contained within the triangle C, V0, D The end-systolic volume is 50 mL at the end-systolic pressure of 100 mmHg Of note, no work is done on the aortic root during isovolumic contraction from point A to B because the volume of the ventricle is unchanged Work, however, is done on the aortic root from the opening of the aortic valve to end-systole, from point B to C. The stroke volume of 100 mL, the difference between the end-­ diastolic volume of 150 mL minus the end-systolic vol- ume of 50 mL, is generating an aortic root end-systolic pressure of 100 mmHg Therefore, the effective elastance of the aortic root, namely, the end-systolic pressure divided by the stroke volume, is 1.0 mmHg/mL, an optimal ventricular-arterial coupling with optimal efficiency Following the administration of a vasopressor, such as norepinephrine and/or phenylephrine, there is an increase in the afterload (impedance) facing the left ventricle The pressure has increased from the ESP to ESP1; however, the result is more energy wasted as heat dissipation during isovolumic relaxation as depicted by the C1, V0, D1 triangle and decreased efficiency of ventricular-arterial coupling as shown by an end-systolic pressure 150 mmHg divided by a stroke volume of 75 mL, yielding a mmHg/1 mL ratio intensive care unit It is also associated with less pain as compared to arterial sampling As it has been mentioned before, inadequate tissue DO2 causes anaerobic metabolism, which is proportional to the depth, duration, and complexity of the procedure being performed, which typically is reflected in the base deficit and lactate level Due to the impaired oxygen utilization by patients undergoing general anesthesia, it is unlikely that normalization of the base deficit may occur at the end of the surgical procedure We suggest that changes in base deficit over time, which are more predictive than absolute values from the standpoint of outcome, should be monitored and minimization of an increase in base deficit should be one of the endpoints of intraoperative resuscitation An attempt should be made to improve the base deficit throughout the operative procedure with an attempt at normalization, which would indicate that the patient does not have ongoing cellular hypoperfusion potentially priming the patient to the development of MODS. Initial base deficit levels and time to its normalization have been shown to correlate with the need for transfusion and the risk of MODS and death in trauma patients [18] However, there are no data on the impact of monitoring intraoperative base deficit on survival While there is a physiological basis to so, there is no evidence supporting its utility from the standpoint of postoperative morbidity and mortality 8  Intraoperative Endpoints of Resuscitation With respect to the use of the intraoperative base deficit as a surrogate marker for serum lactate, we must point out that the base deficit can mislead the surgeon as to the actual measurement of serum lactate The reported ROC area under the curve for base deficit to predict increased lactate level is 0.58, just above the guessing value of 0.50 [19] Therefore, the intraoperative resuscitation should not be guided by base deficit with or without anion gap as the sole criterion, but it should be guided by a combination of both in conjunction with the measurement of serum lactate concentration Of note, elevation of base deficit without a corresponding increase in serum lactate level can be observed in patients with hyperchloremia from successful resuscitation with normal saline Lactate During the past years, there has been an increasing acceptance to use lactate as a marker to guide the perioperative resuscitation of trauma, sepsis, and cardiac surgery patients, as well as to use lactate levels to identify unexpected major bleeding and to identify patients with severe sepsis Lactate-based goal-directed therapy has been shown to minimize the incidence of ongoing occult hypoperfusion and to improve outcomes in surgical and trauma patients by decreasing the development of the intraoperative oxygen debt [20] However, lactate clearance, namely, the rate of decline in lactate concentration, as a target of goal-directed therapy in septic patients who not have an oxygen debt may be actually associated with worse outcome [21] Lactate Metabolism Lactate produced by glycolysis from the skin (25 %), muscles (25 %), red cells (20 %), brain (20 %), and intestine (10 %) is metabolized by the liver (60 %) and to a much lesser degree by the cortex of the kidney (30 %) In normal physiologic normoxic conditions and in the absence of cytosolic pH mediated, sepsis and/or gene inhibi- 87 tion of the phosphofructokinase enzyme, the pacemaker of the anaerobic glycolysis, the anaerobic glycolysis favors the formation of lactate from the pyruvate acting as the proton acceptor from NADH2 In this setting, the lactate pyruvate ratio is 10:1, typically associated with a normal NADH/NAD ratio, which in turn is associated with a normal cytosolic ATP/ADP ratio and no net increase in cytosolic H+ concentration (no acidosis) Conversely, in the setting of cellular hypoxia, mitochondrial oxidative phosphorylation is blocked with a consequent inhibition of synthesis of ATP and the reoxidation of NADH This causes an increase in the NADH/NAD ratio and a decrease in the cytosolic ATP/ADP ratio and the degradation of ATP to adenosine, inorganic phosphate and an increased concentration of H+ (acidosis) The decreased redox potential prevents the utilization of the pyruvate via its conversion into oxaloacetate by the pyruvate carboxylase Therefore, the increase in lactate production from cellular hypoxia is the result of the increase in pyruvate and its conversion to lactate stemming from the decreased redox potential; this is responsible for the increased lactate/pyruvate ratio and the increased concentration of cytosolic H+ (acidosis) The hypoxic release of adenosine is aimed at decreasing the tone of the precapillary sphincters which regulate the number of open capillaries with red cells transit (capillary density) improving the conditions for gas diffusion and ultimately, restoration of the redox potential (Fig 8.2) Of note, accelerated glycolysis from a major stress response and/or the release of endogenous catecholamines or the administration of exogenous catecholamines exceeding the capability of the pyruvate dehydrogenase complex to metabolize the pyruvate to acetyl-CoA in order to allow it to enter the Krebs Cycle will cause an increase in lactate proportional to the pyruvate due to the conversion of pyruvate to lactate Prolongation of lactate clearance in critically ill surgical patients has been shown to correlate with outcome In a study by McNelis and associates, mortality increased from 3.9 % in surgical patients who were able to normalize their lactate levels within 24 h to 13.3 % in those who had 88 H.F.G Araque et al Vasodilatation Adenosine L/P > 20 ATP AMP pH pH No ∆ ADP + Pi + H+ L/P < 20 + ADP + Pi + H = ATP Lactate/Pyruvate NADH/NAD+ L/P =K x [NADH/NAD] x H+ Fig 8.2  Lactate excess with and without acidosis The lactate/pyruvate ratio is the mirror image of the NADH/ NAD ratio In normal conditions when the energy state of the cell is within normal range, the NADH/NAD ratio is normal, and the L/P ratio is less than 20 In the setting of an increase in lactate proportional to pyruvate with a ratio less than 20, there is adequate energy to provide synthesis of ATP from ADP and Pi and hydrogen ions, therefore there is no net increase in cytosolic hydrogen ions and no change in pH. In contrast, when the L/P ratio is greater than 20, the energy state of the cell is compromised, therefore, there is hydrolysis of ATP in ADP, Pi, with an increase in the hydrogen ions concentration, hence, cellular acidosis The subsequent hydrolysis of ADP to AMP and then adenosine is aimed at inducing a relaxation of the precapillary sphincters in order to increase local blood flow and hence oxygen availability at cellular level to restore the redox potential and cellular pH normal levels of lactate within 48 h to 100 % in patients who were unable to reach normal lactate levels within 72 h of the septic insult [22] Further evidence supporting the utility of lactate clearance as a prognostic tool in trauma patients has been provided by Regnier et al [23] We suggest the serial measurement of intraoperative lactate levels every h in high- and very high-risk surgical patients (10–19 % and >20 % predicted mortality) in order to guide fluid and inotropic therapy using flow-based monitoring tools followed by postoperative measurement every h until normalization of two values The addition of continuous or intermittent mixed SvO2 measurements to the serial monitoring of lactate levels can provide additional information regarding whether an abnormally elevated lactate level reflects an imbalance between oxygen transport and oxygen demand One of the intraoperative endpoints of goal-directed resuscitation includes minimizing the increase in serum lactate level that may be associated with a degree of oxygen debt, which may in turn prime the patient to the development of MODS via upregulated oxygen sensing pathways At this time, there is supporting evidence for the utility of normalization of the lactate level as one of the endpoints of intraoperative resuscitation Of note, while there is good evidence that shows that intraoperative goal-directed therapy reduces morbidity and mortality in very high-risk surgical patients, it has not been shown to have the same efficacy in intermediate- and low-risk surgical patients Venous Oxygen Saturation (SvO2) The global oxygen extraction can be estimated from the measure of SvO2 Pulmonary artery and/or superior vena cava ScvO2 is considered a surrogate marker of the balance between oxygen demand and supply in tissues In normal conditions, SvO2 is 75 % consistent with an oxygen extraction ratio of 25 %, typically associated with a normal base deficit and lactate level In the setting of decreasing oxygen delivery as a 8  Intraoperative Endpoints of Resuscitation 89 Oxygen consumption 60% 45% 35% 25% 8.2 Oxygen delivery in ml/kg/min Fig 8.3  Relationship between DO2, VO2, O2Ex, and anaerobic threshold In normal conditions, VO2 remains supply independent as DO2 decreases due to increased extraction However, when the extraction ratio approaches 60 %, the anaerobic threshold, DO2, and VO2 become lin- early dependent, therefore the patient is now in a state of supply dependent VO2 Any further increase or decrease in DO2 will be accompanied by a corresponding increase or decrease in VO2 The level of critical DO2 documented by Shibutani et al is 8.2 mL kg/min [24] result of either decreased flow or oxygen carrying capacity, oxygen extraction increases in order to maintain tissue oxygen consumption constant (Fig 8.3) The increased extraction is represented by a decreasing SvO2 with a supply independent lactate production until the point of critical oxygen delivery, associated with an extraction ratio of 60 % (SvO2 40 %) at which point oxygen consumption and lactate production are both supply dependent As shown by Shibutani et al., the critical level of oxygen delivery in patients undergoing general anesthesia is 8.2 mL/kg/min; at this level of oxygen delivery, lactate production becomes supply dependent implying that a further decrease in oxygen delivery will cause a decreased oxygen consumption and a consequent increase in lactate level [24] A decreasing SvO2 in the absence of acutely decreasing hemoglobin indicates decreasing flow as a result of decreasing CO One of the issues regarding the use of a specific value or range of values of either SvO2 or ScvO2 as one of the endpoints of intraoperative resuscitation involves the effect of anesthesia on mixed SvO2 and with respect to ScvO2 the location of the tip of the central venous catheter, whether it is in the superior vena cava as opposed to the right atrium While there is evidence that targeting intraoperative resuscitation to mixed SvO2 in high-risk surgical patients is beneficial because it identifies at an earlier stage occult hypoperfusion compared with increases in lactate levels, its value is limited by the fact that while decreasing SvO2 reflects an unbalance between oxygen delivery and consumption, a higher SvO2 does not assure the absence of an ongoing oxygen debt As previously mentioned, during general anesthesia it is not uncommon to observe SvO2 values higher than 80 % in patients with preserved myocardial function, normal Hg concentration, and SaO2 > 98 % [3] Therefore, mixed SvO2 cannot be used in isolation as an endpoint of resuscitation Its trend must be correlated with other biomarkers such as base deficit and lactate levels in order to guide intraoperative therapy and minimize the risk of under-resuscitation during complex procedures in high-risk patients While Rivers et al have reported improved outcome in septic patients treated with an early goal-directed therapy targeted to a ScvO2 ≥ 70 %, two recent multicenter randomized control trials (ProCESS and ARISE) have failed to reproduce similar results [25–27] However, it is important to underline two crucial differences between the more recent trials and the trial by Rivers: the first involves a ScvO2 of 48 % in Rivers’ experimental group in contrast to significantly higher values in the two recent trials (71 % for the ProCESS and 73 % for the ARISE); the second involves the evolution of treatment of septic patients over the 90 past 14 years with respect to the early implementation of antibiotic administration, fluid resuscitation, and source control which has now become the standard of care We continue to believe that current recommendations should include targeting hemodynamic resuscitation to an ScvO2 of 70 % or to an SvO2 of 65 % The last consensus on circulatory shock and hemodynamic monitoring suggest that a low ScvO2 indicates inadequate oxygen transport, especially in the context of hyperlactatemia; therefore, in patients with a central venous catheter, measurements of ScvO2 may help assess flow related abnormalities requiring further hemodynamic monitoring and targeted therapy [28] Based on recently published data demonstrating that low ScvO2 is associated with an increased risk of postoperative complications in patients undergoing major abdominal surgery, we suggest that one of the intraoperative endpoints of resuscitation should be the achievement of ScvO2 > 70 % [29] However, it is important to underline that a high ScvO2 in isolation does not necessarily preclude the development of postoperative complications Venous-to-Arterial CO2 Difference Tissue CO2 represents the balance between its production from the local metabolic processes and its removal from the perfused capillaries A rising value is caused by decreased local blood flow and not by increased production The venous arterial carbon dioxide difference (PCO2 gap) is the difference in the partial pressure of carbon dioxide (PCO2) between central venous blood and arterial blood The PCO2 gap is inversely proportional to the number of perfused capillaries A difference of ≥6 mmHg may be used to identify tissue hypoperfusion, even when the ScvO2 is ≥70 % It may be a particularly useful added marker to identify underresuscitated patients during complex surgical procedures, particularly in high-risk patients It reflects regional microcirculatory perfusion; therefore, it may be a useful adjunctive endpoint H.F.G Araque et al of intraoperative resuscitation in order to avoid an upregulated inflammatory response at cellular level from the activation of the oxygen sensing pathways [30, 31] Habicher et al in a retrospective study described the PCO2 gap as a marker to detect global and microcirculatory hypoperfusion in postoperative cardiac surgical patients They observed increased lactate levels, increased duration of mechanical ventilation, and longer intensive care unit stay in patients with an ScvO2 > 70 % but with a PCO2 gap >8 mmHg [32] Further evidence supporting the utility of the central venous-to-arterial carbon dioxide pressure difference [P(cv−a)CO2] in the perioperative settings during high-risk surgery has been provided by Futier et al [31] In his study involving 70 patients undergoing high-risk surgery, the 24 patients suffering complications had a significantly lower mean and minimum ScvO2 compared to patients without complications, 78 ± 4 versus 81 ± 4 % and 67 ± 6 versus 72 ± 6 %, respectively, p