Testing of blood products in a polytrauma model: Results of a multi-institutional randomized preclinical trial

Hasan B. Alam, Leticia M. Bice, Muhammad U. Butt, S. David Cho, Michael A. Dubick, Michael Duggan, Michael S. Englehart, John B. Holcomb, Melanie S. Morris, M. Dale Prince, Martin A. Schreiber, Christian Shults, Jill L. Sondeen, Malek Tabbara, Brandon H. Tieu, Samantha A. Underwood

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

Introduction: Trauma-induced coagulopathy, acidosis, and hypothermia form a "lethal triad" that is difficult to treat and is associated with extremely high mortality. This study was performed at three academic centers to evaluate whether resuscitation with blood components could reverse the coagulopathy in a complex polytrauma model. Methods: Yorkshire swine (40 ± 5 kg) were subjected to a three-phase protocol: (a) "Prehospital" phase ≤ femur fracture, hemorrhage (60% blood volume), and 30 minutes shock + infusion of saline (3 × shed blood) + induction of hypothermia (33°C); (b) "Early hospital" phase ≤ grade V liver injury; and (c) "Operative" phase≤ liver packing. After liver packing, the animals (n ≤ 60) were randomized to the following groups: (1) Sham-instrumentation and anesthesia without hemorrhage/injuries, (2) fresh whole blood (FWB), (3) 6% hetastarch (Hextend), (4) fresh frozen plasma/packed RBCs in 1:1 ratio (1:1 FFP/PRBC), and (5) FFP alone. Treatment volumes were equal to the volume of shed blood. Hemodynamic and physiologic parameters and coagulation profile (thrombelastography, prothrombin time, activated partial thromboplastin time, international normalized ratio, and platelets) were monitored during the experiment and for 4 hours posttreatment. Results: At the end of prehospital phase, animals had developed significant acidosis (lactate >5 mmol/L and base deficit >9 mmol/L) and coagulopathy. Posttreatment mortality rates were 85% and 0% for the Hextend and blood component treated groups, respectively (p < 0.05). Hemodynamic parameters and survival rates were similar in groups that were treated with blood products (FWB, FFP, and FFP:PRBC). Animals treated with FFP and Hextend had significant anemia compared with the groups that received red blood cells (FWB and FFP:PRBC). Treatment with FFP and FFP:PRBC corrected the coagulopathy as effectively as FWB, whereas Hextend treatment worsened coagulopathy. Conclusions: In this reproducible model, we have shown that trauma-associated coagulopathy is made worse by hetastarch, but it can be rapidly reversed with the administration of blood components. Impressively, infusion of FFP, even without any red blood cells, can correct the coagulopathy and result in excellent early survival.

Original languageEnglish (US)
Pages (from-to)856-864
Number of pages9
JournalJournal of Trauma - Injury, Infection and Critical Care
Volume67
Issue number4
DOIs
StatePublished - Oct 1 2009

Keywords

  • Acidosis
  • Coagulopathy
  • Hemorrhage
  • Hypothermia
  • Liver injury
  • Plasma
  • Polytrauma
  • Shock

ASJC Scopus subject areas

  • Surgery
  • Critical Care and Intensive Care Medicine

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