Poloxamer 188 Improves Autoresuscitation in Pigs with Severe Traumatic Hemorrhage

Abstract

IntroductionPoloxamer 188 (P188) is a copolymer surfactant. Its protective effects against ischemic injury, cardiomyopathy, and intracerebral hemorrhage have been shown in studies from rats and mice. The underlying protective mechanisms are unclear. This study investigated its effects on blood volume in pigs after severe traumatic hemorrhage and hypotensive resuscitation.MethodsTwenty anesthetized and instrumented pigs were randomized into saline (n=10) and P188 (n=10) groups. Femur fracture was performed in each pig's left leg, followed by hemorrhage of 55% of estimated blood volume and 15 min shock period. Afterwards, pigs were resuscitated with small volume of saline (4ml/kg) or P188 (1.33 ml/kg of P188 200mg/ml, plus 2.67 ml/kg saline). Indocyanine green dye (5ml of 1mg/ml) was injected before femur and hemorrhage and 15 min after P188 administration with blood samples taken accordingly to determine changes of blood volume and Hct. Pigs were monitored for 6h or until death.ResultsAll baseline measurements are similar between the two groups. Femur and hemorrhage reduced mean arterial pressure to 54±6% of baseline values and reduced blood volume from 104±4 ml/kg to 67±4 ml/kg (both p<0.05) and reduced Hct from 31±1% to28±1% in the saline resuscitated group. Less reduction was observed with P188 resuscitation in blood volume (from 98±3 ml/kg to 74±3 ml/kg, p<0.05 compared to baseline and to saline values), with a consistent larger drop in Hct (31±1% to 24±1%, p<0.05 compared to baseline and to saline values). Survival time was similar between the saline (225±45 min) and P188 (235±78 min) groups.ConclusionsFollowing severe traumatic hemorrhage and small volume resuscitation in pigs, P188 improved autoresuscitation, but did not affect short term survival.Support or Funding InformationUS Army Medical Research and Materiel Command