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

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.