E EDITORIAL

We Cant Go Home Again: Advances in the Resuscitation of Patients with Polytrauma

Michael J. Murray, MD, PhD

ecommendations for the resuscitation of patients who have sustained blunt or penetrating trauma continue to evolve, especially for those patients who present with, or who develop, coagulopathy (defined as requiring more than 10 U of packed red blood cells [pRBCs] over 24 hours). During the Vietnam War, Miller et al.1 noted that those patients who present with hemorrhagic shock are at high risk for developing coagulopathy, partly because of the resuscitation-related dilution of coagulation factors, including dilutional thrombocytopenia. Two decades later, Bickell et al.2 subsequently conducted a somewhat controversial prospective study demonstrating that the resuscitation of trauma victims with crystalloid fluids before hospital arrival was associated with increased morbidity and mortality. The study was controversial because it was one of the early studies of prehospital patients who were randomly assigned to the experimental group or the conventional treatment group without their consent but with IRB approval of the study.3 Without societal willingness to approve such studies, the care of patients in extremis who are unable to consent (as most of us understand consent) to enrollment in a prospective randomized study would have been significantly delayed. As it was, and as it is with most such results, the time (the hysteresis) before the results of the study were incorporated into clinical practice was more than 10 years. During the early days of Operation Enduring Freedom and Operation Iraqi Freedom, forward surgical teams and personnel at combat support hospitals cared for a number of soldiers who developed abdominal compartment syndrome, which arises secondary to a number of factors, one of which is the amount of crystalloid administered. On the basis of such observations and studies such as Bickell et al.,2 the current recommendations of the U.S. Militarys Joint Theater Trauma System advise clinicians to limit the amount of crystalloid used to resuscitate wounded soldiers.4 Other studies conducted during the past decade, including TRICC,5 SAFE,6 and FOCUS,7 have affected practice perhaps more quickly, having done so because they supported a gestalt

From the Trauma and Critical Care Medicine, Landstuhl Regional Medical Center, Landstuhl Germany. Accepted for publication August 28, 2012. The author declares no conflicts of interest. The opinions or assertions contained herein are the private views of the author and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense. Reprints will not be available from the author. Address correspondence to Michael J. Murray, MD, PhD, Landstuhl Regional Medical Center, CMR 402 Box 2564, APO AE 09180. Address e-mail to michael.murray@amedd.army.mil Copyright 2012 International Anesthesia Research Society
DOI: 10.1213/ANE.0b013e3182730d04

that less may be more when managing critically ill patients. During this time period, the transfusion threshold, the hemoglobin level at which patients are administered RBCs, has gone from 10 g/dL to 8 g/dL and is now hovering closer to 7 g/dL, even for patients who are at higher risk of having coronary artery disease.7 The SAFE study demonstrated that resuscitation with a colloid (albumin) of patients once they were admitted to the intensive care unit (ICU) did not affect outcome.6 The 6S study (Scandinavian Starch for Severe Sepsis/Septic Shock Trial)8 demonstrated that patients with severe sepsis resuscitated with hydroxyethyl starch (130/0.42) had an increased risk of death at day 90 and were more likely to have required renal replacement therapy, as compared with those receiving Ringers acetate solution. The results of CHEST (Crystalloid versus Hydroxyethyl Starch Trial),9 which randomized several thousand patients who were in ICUs to receive either crystalloid or hydroxyethyl starch, were released in October of this year, and though the investigators did not find an increased incidence of death at 90 days, they did confirm the results of the 6S study in that more patients who received hydroxyethyl starch required renal replacement therapy. However, if these studies show that albumin is no better than crystalloid and that hydroxyethyl starch may be worse than crystalloid, albeit when infused in a slightly different population, that is, patients in ICUs and not patients requiring resuscitation in a field environment, emergency department, or operating room, perhaps crystalloid is not the culprit some thought it to be; instead, perhaps it is the volume of fluid administered to bleeding patients that results in coagulopathy. I hasten to point out that the previously cited studies were conducted in the prehospital environment or in the ICU or during the perioperative period not specifically limited to the operating room in actively bleeding patients. In the latter setting, a slightly different resuscitation strategy is the norm.10 However, when the results of all of these studies are taken together, many contend that the net results support the concept of damage-control surgery or resuscitation.11 The most important goal of resuscitation is to stop the bleeding from whatever source to avoid the need to administer large volumes of any fluid. When fluid must be administered, one should replace what was lost (i.e., ideally, with whole blood if many trauma surgeons had their preference)12 or as a ratio of pRBCs to fresh frozen plasma of 1:113 or of pRBCs to fresh frozen plasma to platelets of 1:1:1.4 The latter observations have been called into question because of the survival basis inherent in some of the observational studies that support a fixed ratio of blood products when resuscitating coagulopathic patients. The reality, though, is that, even if the bleeding is stopped immediately and providers use whichever RBC product in
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E EDITORIAL
which they fervently believe, with a hemoglobin target of only 7 g/dL to 9 g/dL, most anesthesiologists will administer IV fluid. The goal is to maintain preload and left ventricular output; with a lower hemoglobin concentration and lower oxygen content, oxygen delivery is very dependent on cardiac output. A recent multicenter survey demonstrated that physicians in the ICU continue to administer large volumes of fluid, the choice of which varies by country,14 and I suspect that the same is true in most operating rooms. But are these physiologic goals, once the foundation of resuscitation in shock, still valid? In this issue of Anesthesia & Analgesia, Tobin and Varon15 review the basis for damage-control resuscitation and for the use of blood products in managing the coagulopathy associated with trauma. They provide an excellent review of the survival bias inherent in several of these observational studies, as mentioned earlier. Of more scientific validity, as they describe, is that, at least in 1 study, the use of tranexamic acid has been associated with an improvement in outcome. The use of recombinant Factor VIIa is more controversial; many proponents interpret the results of disparate studies to their advantage. The overview provided by Tobin and Varon15 is more compelling in putting this debate in perspective. Of more importance, perhaps, they review the most recent development in resuscitation, the concept of hypotensive resuscitation with a goal of a systolic blood pressure of 90 mm Hg in patients with polytrauma, or 100 mm Hg in patients with head injury, until the bleeding can be controlled. Vasopressin is reviewed as a vasoconstrictor used to maintain systemic blood pressure at a goal considerably less than was once acceptable. Maintenance of systemic blood pressure by increasing systemic vascular resistance in contradistinction to the maintenance of pressure by increasing cardiac output (and parenthetically oxygen delivery) seems counterintuitive to what we were once taught and understand about cardiovascular and cellular physiology, but Tobin and Varon cite interesting animal data and case reports and observational studies of patients. Time will tell whether they are clairvoyant, but there can be no doubt that the resuscitation of patients who have sustained polytrauma has changed dramatically from what it once was, a wide-open IV line delivering liter on liter of crystalloid and nonheme-containing colloid. We cant go home again, nor would most of us desire to do so. Some readers will be early adapters, or at least try these new approaches cautiously; some will be resistant, and a few will never change. Irrespective of what we as individuals do, on the basis of experience gained by military physicians in recent conflicts and by physicians in civilian trauma centers, our resuscitation of patients who have sustained major trauma will continue to evolve and improve through research, observation, and experience. As perioperative physicians, it behooves us to be cognizant of these developments. E
DISCLOSURES: REFERENCES 1. Miller RD, Robbins TO, Tong MJ, Barton SL. Coagulation defects associated with massive blood transfusions. Ann Surg 1971;174:794801 2. Bickell WH, Wall MJ Jr, Pepe PE, Martin RR, Ginger VF, Allen MK, Mattox KL. Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injuries. N Engl J Med 1994;331:11059 3. Biros MH, Lewis RJ, Olson CM, Runge JW, Cummins RO, Fost N. Informed consent in emergency research. Consensus statement from the Coalition Conference of Acute Resuscitation and Critical Care Researchers. JAMA 1995;273:12837 4. US Army. Joint Theater Trauma System Clinical Practice Guideline: Compartment Syndrome (CS) and the Role of Fasciotomy in Extremity War Wounds. Washington, DC: Department of Defense, 2012 5. Hbert PC, Wells G, Blajchman MA, Marshall J, Martin C, Pagliarello G, Tweeddale M, Schweitzer I, Yetisir E. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med 1999;340:40917 6. Finfer S, Norton R, Bellomo R, Boyce N, French J, Myburgh J. The SAFE study: saline vs. albumin for fluid resuscitation in the critically ill. Vox Sang 2004;87 Suppl 2:12331 7. Carson JL, Terrin ML, Noveck H, Sanders DW, Chaitman BR, Rhoads GG, Nemo G, Dragert K, Beaupre L, Hildebrand K, Macaulay W, Lewis C, Cook DR, Dobbin G, Zakriya KJ, Apple FS, Horney RA, Magaziner J; FOCUS Investigators. Liberal or restrictive transfusion in high-risk patients after hip surgery. N Engl J Med 2011;365:245362 8. Perner A, Haase N, Guttormsen AB, Tenhunen J, Klemenzson G, neman A, Madsen KR, Mller MH, Elkjr JM, Poulsen LM, Bendtsen A, Winding R, Steensen M, Berezowicz P, Se-Jensen P, Bestle M, Strand K, Wiis J, White JO, Thornberg KJ, Quist L, Nielsen J, Andersen LH, Holst LB, Thormar K, Kjldgaard AL, Fabritius ML, Mondrup F, Pott FC, Mller TP, Winkel P, Wetterslev J; 6S Trial Group; Scandinavian Critical Care Trials Group. Hydroxyethyl starch 130/0.42 versus Ringers acetate in severe sepsis. N Engl J Med 2012;367:12434 9. Myburgh JA, Finfer S, Bellomo R, Billot L, Cass A, Gattas D, Glass P, Lipman J, Liu B, McArthur C, McGuinness S, Rajbhandari D, Taylor CB, Webb SA; the CHEST Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Hydroxyethyl starch or saline for fluid resuscitation in intensive care. N Engl J Med 2012 Oct 17 [Epub ahead of print] 10. American Society of Anesthesiologists Task Force on Perioperative Blood Transfusion and Adjuvant Therapies. Practice guidelines for perioperative blood transfusion and adjuvant therapies: an updated report by the american society of anesthesiologists task force on perioperative blood transfusion and adjuvant therapies. Anesthesiology 2006;105:198208 11. Holcomb JB, Jenkins D, Rhee P, Johannigman J, Mahoney P, Mehta S, Cox ED, Gehrke MJ, Beilman GJ, Schreiber M, Flaherty SF, Grathwohl KW, Spinella PC, Perkins JG, Beekley AC, McMullin NR, Park MS, Gonzalez EA, Wade CE, Dubick MA, Schwab CW, Moore FA, Champion HR, Hoyt DB, Hess JR. Damage control resuscitation: directly addressing the early coagulopathy of trauma. J Trauma 2007;62:30710 12. Spinella PC. Warm fresh whole blood transfusion for severe hemorrhage: U.S. military and potential civilian applications. Crit Care Med 2008;36:S3405 13. Borgman MA, Spinella PC, Perkins JG, Grathwohl KW, Repine T, Beekley AC, Sebesta J, Jenkins D, Wade CE, Holcomb JB. The ratio of blood products transfused affects mortality in patients receiving massive transfusions at a combat support hospital. J Trauma 2007;63:80513 14. Finfer S, Liu B, Taylor C, Bellomo R, Billot L, Cook D, Du B, McArthur C, Myburgh J; SAFE TRIPS Investigators. Resuscitation fluid use in critically ill adults: an international cross-sectional study in 391 intensive care units. Crit Care 2010;14:R185 15. Tobin JM, Varon AJ. Update in trauma anesthesiology: perioperative resuscitation management. Anesth Analg 2012;115:132633

Name: Michael J. Murray, MD, PhD. Contribution: This author wrote the manuscript. Attestation: Michael J. Murray attests that the work is original and all his own writing. This manuscript was handled by: Jerrold H. Levy, MD, FAHA.

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