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Mild induced hypothermia and coagulation and platelet function in patients with septic shock: Secondary outcome of a randomized trial

April 12, 2023

Abstract
Coagulation abnormalities and microthrombi contribute to septic shock, but the impact of body temperature regulation on coagulation in patients with sepsis is unknown. We tested the hypothesis that mild induced hypothermia reduces coagula- tion and platelet aggregation in patients with septic shock. Secondary analysis of ran- domized controlled trial. Adult patients with septic shock who required mechanical ventilation from eight intensive care units in Denmark were randomly assigned to mild induced hypothermia for 24 h or routine thermal management. Viscoelastogra- phy and platelet aggregation were assessed at trial inclusion, after 12 h of thermal management, and 24 h after inclusion. A total of 326 patients were randomized to mild induced hypothermia (n = 163) or routine thermal management (n = 163). Mild induced hypothermia slightly prolonged activated partial thromboplastin time and thrombus initiation time (R time 8.0 min [interquartile range, IQR 6.6–11.1] vs. 7.2 min [IQR 5.8–9.2]; p = .004) and marginally inhibited thrombus propagation (angle 68 [IQR 59–73] vs. 71 [IQR 63–75]; p = .014). The effect was also present after 24 h. Clot strength remained unaffected (MA 71 mm [IQR 66–76] with mild induced hypothermia vs. 72 mm (65–77) with routine thermal management, p = .9). The proportion of patients with hyperfibrinolysis was not affected (0.7% vs. 3.3%; p = .19), but the proportion of patients with no fibrinolysis was high in the mild hypothermia group (8.8% vs. 40.4%; p < .001). The mild induced hypothermia group had lower platelet aggregation: ASPI 85U (IQR 50–113) versus 109U (IQR 74–148, p < .001), ADP 61U (IQR 40–83) versus 79 U (IQR 54–101, p < .001), TRAP 108 (IQR 83–154) versus 119 (IQR 94–146, p = .042) and COL 50U (IQR 34–66) versus 67U (IQR 46–92, p < .001). In patients with septic shock, mild induced hypothermia slightly impaired clot initiation, but did not change clot strength. Platelet aggregation was slightly impaired. The effect of mild induced hypothermia on viscoelastography and platelet aggregation was however not in a range that would have clinical implica- tions. We did observe a substantial reduction in fibrinolysis. KEYWORDS
coagulopathy, sepsis, septic shock, therapeutic hypothermia.
Editorial Comment
Sepsis affects coagulation and in this study, the additional effect of mild hypothermia on sepsis- induced coagulopathy was assessed. While clinically significant effects of hypothermia on coag- ulation were not found, fibrinolysis was inhibited. Mild hypothermia is not a common treatment for sepsis, but the findings may be transferable to other clinical situations where mild hypother- mia is used and coagulation abnormalities are common.