Mild induced hypothermia: Effects on sepsis-related coagulopathy -results from a randomized controlled trial

Abstract

IntroductionCoagulopathy associates with poor outcome in sepsis. Mild induced hypothermia has been proposed as treatment in sepsis but it is not known whether this intervention worsens functional coagulopathy. Materials and methodsInterim analysis data from an ongoing randomized controlled trial; The Cooling And Surviving Septic shock (CASS) study. Patients suffering severe sepsis/septic shock are allocated to either mild induced hypothermia (cooling to 32-34°C for 24hours) or control (uncontrolled temperature). Trial registration: NCT01455116. Thrombelastography (TEG) is performed three times during the first day after study enrollment in all patients. Reaction time (R), maximum amplitude (MA) and patients’ characteristics are here reported. ResultsOne hundred patients (control n=50 and intervention n=50; male n=59; median age 68years) with complete TEG during follow-up were included. At enrollment, 3%, 38%, and 59% had a hypocoagulable, normocoagulable, and hypercoagulable TEG clot strength (MA), respectively.In the hypothermia group, functional coagulopathy improved during the hypothermia phase, measured by R and MA, in patients with hypercoagulation as well as in patients with hypocoagulation (correlation between ΔR and initial R: rho=-0.60, p<0.0001 and correlation between ΔMA and initial MA: rho=-0.50, p=0.0002). Similar results were not observed in the control group neither for R (rho=-0.03, p=0.8247) nor MA (rho=-0.15, p=0.3115). ConclusionMild induced hypothermia did seem to improve functional coagulopathy in septic patients. This improvement of functional coagulopathy parameters during the hypothermia intervention persisted after rewarming. Randomized trials are warranted to determine whether the positive effect on sepsis-related coagulopathy can be transformed to improved survival.