Long-term preclinical evaluation of the intracorporeal use of advanced local hemostatics in a damage-control swine model of grade IV liver injury.

The purpose of this study was to evaluate the long-term efficacy and safety of kaolin- and chitosan-based hemostatic agents for hemorrhage control in a 14-day survival, damage-control swine model of Grade IV liver injury. A total of 48 anesthetized pigs (40 kg) underwent a 35% total blood volume bleed, cooling to 34°C and a standardized liver injury. The animals were randomized to standard gauze control (SG, n = 12), QuikClot Combat Gauze (QCCG, n = 12), Celox (CX, n = 12), or Celox Gauze (CXG, n = 12) packing. At 15 minutes, shed blood was calculated, followed by damage-control closure. At 48 hours, pack removal and definitive closure was performed. At 14-day sacrifice, the liver, kidney, heart, lung, and small bowel standard intra-abdominal organs were sampled for histopathological examination. Uncontrolled blood loss at 2 minutes demonstrated internal consistency of the injury. Blood loss at 15 minutes was significantly lower in the CX and QCCG arms (SG, 11.1 ± 1.1 mL/kg; QCCG, 5.3 ± 1.2 mL/kg; CX, 5.7 ± 1.2 mL/kg; and CXG, 10.1 ± 1.3 mL/kg; p = 0.002). Forty-eight-hour survival was 50.0% for SG, 58.3% for QCCG, 83.3% for CX, and 41.7% for CXG (p = 0.161). Fourteen-day survival was 41.7% (5) for SG, 50.0% (6) for QCCG, 58.3% (7) for CX, and 41.7% (5) for CXG (p = 0.821). Four CX and two QCCG deaths were caused by bowel obstruction; one SG death was caused by sepsis; the remainder was caused by blood loss.Histopathology in one CX animal demonstrated eosinophilic material within a coronary vessel consistent with granule embolization. Celox and QuikClot Combat Gauze were effective hemostatic adjuncts to standard intracavitary damage-control packing. The hemostasis was durable, facilitating pack removal, and definitive closure at reoperation. There was however an increase in the development of intra-abdominal adhesions resulting in small bowel obstruction. The potential for distant embolization of granular agents warrants further investigation.