Hemostatic and pharmacologic resuscitation: Results of a long-term survival study in a swine polytrauma model

Hasan B. Alam, Kristopher B. Hamwi, Michael Duggan, Karim Fikry, Jennifer Lu, Eugene Y. Fukudome, Wei Chong, Athanasios Bramos, Kyuseok Kim, George Velmahos

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


Background: We have previously demonstrated that valproic acid (VPA), a histone deacetylase inhibitor, and spray-dried plasma (SDP) improve early survival after lethal hemorrhage and polytrauma, but their effect on long-term survival and organ function remains untested. Methods: Yorkshire swine (n = 27; 6-8/group) underwent a protocol simulating different phases of trauma care: (1) prehospital-rib fracture, soft-tissue injury, hemorrhage (50% blood volume), 30 minutes of shock, and infusion of 0.9% saline (3× shed blood); (2) early hospital/treatment-grade IV liver (partial amputation of the median lobe) and grade V splenic (transection of spleen into three pieces) injuries to simulate rupture of contained hematomas, followed by 30 minutes of uncontrolled hemorrhage. Animals were treated with (a) Hextend (6% hetastarch), (b) fresh whole blood (FWB), (c) SDP, and (d) VPA (300 mg/kg) plus Hextend. VPA was given during the prehospital phase, and the volumes of Hextend, FWB and SDP (reconstituted in water) matched shed blood; (3) repair/resuscitation-liver injury was controlled by suture control of the transected edge, and splenic injury was treated by partial splenectomy; 1 hour after repair of injuries, surviving animals were fully resuscitated with packed red blood cells; and (4) monitoring-survival was monitored for 7 days (primary endpoint), and blood samples were drawn serially to measure organ function. Results: Only 25% of the Hextend-treated animals survived. Addition of VPA improved survival to only 50% (p = 0.28), whereas treatment with SDP and FWB increased survival significantly to 83% and 100%, respectively (p < 0.05). Surviving animals showed no long-term organ dysfunction, postoperative hemorrhage, and delayed complications. Conclusions: In a clinically relevant lethal polytrauma model, administration of SDP significantly improves survival without any long-term organ dysfunction or complications.

Original languageEnglish (US)
Pages (from-to)636-645
Number of pages10
JournalJournal of Trauma - Injury, Infection and Critical Care
Issue number3
StatePublished - Mar 2011
Externally publishedYes


  • Acidosis
  • Blood
  • Coagulopathy
  • Hemodilution
  • Histones
  • Hypothermia
  • Injury
  • Liver
  • Plasma
  • Polytrauma
  • Resuscitation
  • Spleen
  • Spray dried
  • Valproic acid

ASJC Scopus subject areas

  • Surgery
  • Critical Care and Intensive Care Medicine


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