Severe controlled hemorrhage resuscitation with small volume poloxamer 188 in sedated miniature swine.

BACKGROUND The surfactant poloxamer 188 (P188) has been shown to improve survival following hemorrhage. This study used P188 as a small volume resuscitation product in a sedated, sexually mature, male miniature swine severe hemorrhage model for potential improvement in rate and time of survival. METHODS Fourteen swine were anesthetized, catheterized for hemorrhage and resuscitation and allowed to recover from anesthesia. The animals were sedated and hemorrhaged 60% of estimated blood volume (∼39 mlkg(-1)) exponentially over 1h. Following hemorrhage the animals were treated with either 1.33 mlkg(-1) of P188 (150 mgml(-1); 7 swine) or the P188 citrate vehicle (7 swine) given as an i.v. infusion over 2 min without additional resuscitation fluids. The data were compared with control data from sedated swine similarly hemorrhaged, but with no resuscitation (untreated; n=16). RESULTS Median (95% CI) survival time for the untreated control swine was 55.8 (36.5-86) min with a 6% survival at 180 min. Median survival time of 161 (80-180) min for the P188 swine was significantly greater than control (p=0.0186), whereas the citrate vehicle median survival time of 91 (32-180) min was not significantly different from control or P188. At the survival target time of 180 min, survival rates were not significantly different among the three groups. TEG data from swine demonstrated anti-coagulant properties of P188. This was confirmed with human blood ex vivo. CONCLUSION In the presence of severe controlled hemorrhage, P188 improved median survival time. However, retardation of blood clotting raises concerns as to its use in the presence of uncontrolled hemorrhage.