Therapeutic Mild Hypothermia: Effects on Coagulopathy and Survival in a Rat Hemorrhagic Shock Model

Objective: To determine the effects of therapeutic hypothermia on coagulation parameters during hemorrhagic shock (HS) and fluid resuscitation and on survival, in a rat HS model. Methods: Under light anesthesia and spontaneous breathing, 24 rats underwent HS (phase I) for 90 minutes, during which 2.5 mL/100 g blood was withdrawn over 15 minutes; fluid resuscitation (phase II) for 60 minutes, during which no blood was reinfused but 5.0 mL/100 g lactated Ringer's solution was infused over 30 minutes; and an observation (phase III) without anesthesia until 72 hour. After the volume-controlled hemorrhage, rats were randomized into a hypothermia group (n = 12, 33°C) or a normothermia group (n = 12, 38°C). The rectal temperature in each group was maintained during phases I and II. Whole blood coagulopathy was assessed by Sonoclot analysis (SA) at baseline and the end of phases I and II. Fibrinolysis parameters of thrombin-antithrombin III complex and plasma-α-2-plasmin inhibitor complex were also monitored. Results: At 72 hour, 10 of 12 hypothermia group rats, and 5 of 12 normothermia group rats remained alive (p < 0.05). Fluid resuscitation significantly decreased hematocrit (20% ± 5%) compared with baseline (33% ± 5%; p < 0.05) in all rats. SA showed no significant differences between groups at the end of phase I. However, at the end of phase of II, SA revealed a decreased “clot rate” in hypothermia compared with normothermia (22 clot signal/min ± 11 clot signal/min vs. 34 clot signal/min ± 14 clot signal/min; p < 0.05) and a prolonged “time to peak” in hypothermia (15 minutes ± 5 minutes versus 6 minutes ± 2 minutes; p < 0.05). No differences in thrombin-antithrombin III complex and plasma-α-2-plasmin inhibitor complex values were seen between groups throughout the experiment. Conclusions: Therapeutic mild hypothermia of 33°C did not cause coagulopathy during HS, but did impair SA coagulation parameters during fluid resuscitation, probably because of dilution. Hypothermia also prolonged survival after HS. Impairments to coagulation parameters did not worsen outcomes in the rat HS model.