Prolonged targeted temperature management compromises thrombin generation: A randomised clinical trial.

Abstract

To investigate whether prolonged compared with standard duration of targeted temperature management (TTM) compromises coagulation. Comatose survivors after out-of-hospital cardiac arrest (n=82) were randomised to standard (24h) or prolonged (48h) duration of TTM at 33±1°C. Blood samples were drawn 22, 46 and 70h after attaining the target temperature. Samples were analysed for rotational thromboelastometry (ROTEM^® (EXTEM^®, INTEM^®, FIBTEM^® and HEPTEM^®)) and thrombin generation using the Calibrated Automated Thrombogram^® assay. With the 22-h sample, we revealed no difference between groups in the ROTEM^® and thrombin generation results beside a slightly higher EXTEM^® and INTEM^® maximum velocity in the prolonged group (p-values≤0.04). With the 46-h sample, ROTEM^® showed no differences when using EXTEM^®; however, 11% (p<0.01) longer clotting time and 12% (p<0.01) longer time to maximum velocity were evident in the prolonged group than in the standard group when using INTEM^®. The prolonged group had reduced thrombin generation compared with the standard group as indicated by 30% longer lag time (p=0.04), 106nM decreased peak concentration (p<0.001), 36% longer time to peak (p=0.01) and 411 nM*minute decreased endogenous thrombin potential (p<0.001). With the 70-h sample, no differences in ROTEM^® results were found between groups. However, the prolonged group had reduced thrombin generation indicated by longer lag time, decreased peak concentration and longer time to peak (all p-values≤0.02) compared with the standard group. Prolonged TTM in post-cardiac arrest patients impairs thrombin generation. ClinicalTrials.gov identifier: NCT02258360.