Abstract 376: Comparison of Pre and Post Conditioning With Poloxamer 188 in Rat Model of Severe Hemorrhagic Shock

Abstract

Background: Hemorrhagic shock remains a leading cause of morbidity and mortality after trauma. Poloxamer (P) 188, an FDA-approved copolymer-based cell membrane stabilizer, is a nonionic triblock copolymer believed to prevent cellular injury after ischemia and reperfusion. While post conditioning may be used in a broad range of scenarios, pre-conditioning may add improved efficacy in scenarios where hemorrhage can be expected, the peri-operative period. We have previously demonstrated prolonged survival with P188 post-conditioning however without complete rescue, here we hypothesize pre-conditioning would further improve survival. Methods: 35 male Sprague Dawley rats (564+/-73 g) were anesthetized, ventilated and instrumented. All rats underwent rapid controlled blood loss of 40% estimated blood volume over 30 min, followed by prolonged permissive hypotension for 60 min before re-transfusion of the lost blood to euvolemia and up to 6 hrs of monitoring under general anesthesia. Rats were then randomized to 3 groups: 10 rats received a 0.8 cc iv bolus of 250mg/kg P188 15min before hemorrhage (pre), 12 rats received the same dose of P188 after hemorrhage (post), and 13 control rats only received 0.8 cc vehicle. Primary endpoint was survival time from the start of hemorrhage. Data are median and IQ range; statistics: Kruskal-Wallis and Chi-Square tests, *p<0.05. Results: P188 administration immediately after hemorrhage significantly improved median survival time compared to both the pre and control groups [post *245 (49, 314) min vs. control group; 53 (32-60), vs pre; 59 (24-70) min, p = 0.0174, 0.00045, respectively]. However, there was no significant differences in survival time between pre and control grouyps and there were no differences in survival rate at 6 hours (pre; 0% vs post; 8% vs control; 7%). Conclusion: A bolus of P188 given immediately after a severe hemorrhagic insult prolonged survival time significantly. However, administration of P188 15 min before hemorrhage did not produce a significant prolongation of survival time.P188 is a highly promising compound whose dose, application timing and application duration in severe hemorrhagic shock require more research.