Matt Harmon

118 Chapter six Abstract Background Dysregulation of coagulation is an important characteristic of sepsis, ranging from mild consumption coagulopathy to disseminated intravascular coagulation (DIC). In this study, we aimed to investigate the effect of induced normothermia on coagulation during lipopolysaccharide (LPS)-induced endotoxemia in healthy volunteers. Methods A total of 12 volunteers received an LPS-infusion of 2ng/kg and were assigned to either the fever group or the induced normothermia group. Induced normothermia (37°C) consisted of external surface cooling using the Arctic Sun© device, cooled intravenous fluids (4°C) and medication to reduce shivering (buspirone, clonidine and magnesium sulphate). Conventional coagulation tests, plasma levels of von Willebrand factor (vWf) and rotational thromboelastometry (ROTEM) were measured prior to- and at 1, 3, 6, and 8 hours after LPS-infusion. Differences between groups were tested with a mixed effects model. Results LPS caused a transient decrease in platelet levels and in activated partial thromboplastin time (aPTT), while prolonging prothrombin time (PT). LPS also increased D-Dimer and vWf levels compared to baseline. Induced normothermia inhibited the decrease in platelet levels (p= 0.002), aPTT (p=0.005) and vWf levels (p=0.03) compared to the fever group. Induced normothermia also improved calculated DIC scores compared to volunteers with fever (p=0.04). ROTEM measurements were largely unaffected by LPS. Conclusion In human endotoxemia, induced normothermia decreases makers of endothelial activation and DIC and should be further studied as a potential treatment in hyperinflammatory states with consumption coagulopathy, such as sepsis.