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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Division of Trauma and Surgical Critical Care, University of Southern California, Los Angeles, California 90033-4525, USA. kinaba@surgery.usc.edu
Kenji
K
Inaba
Bernardino C
BC
Branco
Peter
P
Rhee
Bradley
B
Putty
Obi
O
Okoye
Galinos
G
Barmparas
Peep
P
Talving
Demetrios
D
Demetriades
D000818:Animals; D048271:Chitosan / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D006470:Hemorrhage / Q000188:drug therapy; D006490:Hemostatics / Q000008:administration & dosage / Q000627:therapeutic use*; D007421:Intestine, Small / Q000473:pathology; D007616:Kaolin / Q000627:therapeutic use; D007668:Kidney / Q000473:pathology; D008099:Liver / Q000293:injuries* / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D013552:Swine
D006490:Hemostatics; D007616:Kaolin; D048271:Chitosan