Hetastarch during initial resuscitation from trauma.

At the end of the 20th century, the Institute of Medicine reviewed the state of the art for combat casualty and civilian trauma care. Intravenous saline (or crystalloid) solutions were typically the first-line therapy for hypovolemic shock patients to compensate for acute blood loss before transfusions could be safely administered.1 In the first decade of the 21st century, little has changed; isotonic crystalloids remain the standard of care. There are promising data on the salutary actions of several different colloid or hypertonic solutions relative to isotonic crystalloids2–6; but to date, virtually no randomized controlled trial has reported a significant survival benefit of these novel solutions. As of 2006, there were at least 32 randomized controlled trials comparing albumin to crystalloid solutions in 8,452 critically ill patients with hypovolemia or burns, and there was no evidence that albumin reduced mortality when compared with cheaper alternatives.7 As of 2007, there were at least 55 randomized controlled trials of colloids compared with crystalloids, and there was no evidence that colloids reduced the risk of death compared with crystalloids in 7,754 patients with trauma or burns or after surgery.8 As of 2008, a review of 70 trials in 4,375 patients found no evidence that any one colloid solution is safer or more effective than any other.9 Because colloids are not associated with an improvement in survival and because they are more expensive than crystalloids, some thought that leaders, especially in the civilian sector, are convinced that continued use of colloids in trauma patients cannot be justified outside the context of randomized controlled trials.8 For the military, on the other hand, colloids and other low-volume resuscitation solutions are attractive alternatives, because they have unique advantages in austere environments where supplies are limited and evacuation times can be delayed. For these logistic reasons because of its reduced weight and size relative to saline solutions, Hextend (HEX, 6% hetastarch in lactated electrolyte buffer; www.hospira.com) was recommended for fluid resuscitation of combat casualties.10,11 HEX is a colloid approved by the US Food and Drug Administration that is indicated for use in hypovolemia during elective surgery.12 Despite these recommendations, saline solutions are still commonly used on the battlefield. Furthermore, many civilian or military clinicians avoid any artificial colloid solutions after trauma because of generalized concerns about anaphylaxis,1 coagulopathy,13 and/or catastrophic bleeding.14 In fact, the few studies that have addressed the coagulation profile of HEX have been inconclusive15–18; and there are no data on the safety and efficacy of HEX at the doses typically used for initial trauma resuscitation, except for several previous studies in various animal models.19–23 Ogilvie et al.24 attempted to fill this gap by examining the safety and efficacy of HEX at a Level I trauma center, with particular focus on the risk of coagulopathy. From June to December 2008, HEX was available as a therapeutic option for all nonburn patients. At the discretion of the admitting surgeon, 500 mL to 1,000 mL of HEX was administered during initial fluid resuscitation. Apart from this initial bolus of HEX, care was otherwise identical in all patients and in exact accordance with advanced trauma life support guidelines. Fluids, blood products, vasopressors, and/or any other drugs were administered as needed. Review of pharmacy records and nursing notes was approved by the Institutional Review Board of the University of Miami and by the Clinical Trials Office of Jackson Memorial Hospital with waiver of informed consent. This study was registered as NCT00527098 on www.clinicaltrials.gov. There were 1,714 admissions; 805 received HEX and 909 did not. The characteristics and demographics were identical between the two groups in terms of age, gender, hemodynamics, laboratory values, Glasgow coma scale score, and Injury Severity Score at the scene and on admission to the trauma resuscitation unit. With standard of care, the population was primarily male (78.9%) with blunt injury (72.8%); with standard of care HEX, the distribution was similar for gender (80.9%) and type of trauma (74.7%). These values are typical for any large, mostly urban, trauma population.24 With HEX versus standard of care, there were reduced early deaths (p 0.0001) and overall mortality (5.2% vs. 8.9%; p 0.0035) by univariate analysis. Results were similar after penetrating injury only (p 0.0016) and in those with severe injury, defined by the Glasgow coma scale score 9 (p 0.0013) or Injury Severity Score 26 (p 0.0142). Consistent with early salvage of otherwise lethal injury, after HEX, more required admission to the intensive care unit (40.9% vs. 34.5%; p 0.0334) and transfusions of blood (34.4% vs. 20.2%; p 0.0014) or plasma (20.7% vs. 12.2%; p 0.0251). Consistent with safety, in the intensive care unit Submitted for publication February 11, 2011. Accepted for publication March 14, 2011. Copyright © 2011 by Lippincott Williams & Wilkins From the Divisions of Trauma and Surgical Critical Care, Dewitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida. Supported, in part, by grant N140610670 from the Office of Naval Research. Address for reprints: Kenneth G. Proctor, PhD, Dewitt Daughtry Family Department of Surgery, Divisions of Trauma and Surgical Critical Care, University of Miami Miller School of Medicine, Miami, FL 33136; email: kproctor@miami.edu.