• HarmonMatthew B AMBALaboratory of Experimental Intensive Care and Anaesthesiology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands; Department of Intensive Care Medicine, Amsterdam University Medical Centers, Univ, Nanon F L Heijnen, Sanne de Bruin, Niek H Sperna Weiland, MeijersJoost C MJCMDepartment of Experimental Vascular Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands; Department of Molecular and Cellular Haemostasis, Sanquin, Amsterdam, the Netherlands., Anita M de Boer, Marcus J Schultz, Janneke Horn, and Nicole P Juffermans.
• Laboratory of Experimental Intensive Care and Anaesthesiology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands; Department of Intensive Care Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands. Electronic address: m.b.a.harmon@lumc.nl.
• Br J Anaesth. 2021 Jun 1; 126 (6): 1111-1118.

BackgroundDysregulation of coagulation occurs commonly in sepsis, ranging from mild coagulopathy with decreased platelets to disseminated intravascular coagulation (DIC). We investigated the effect of induced normothermia on coagulation during lipopolysaccharide (LPS)-induced endotoxaemia in healthy volunteers.MethodsTwelve volunteers received an infusion of bacterial lipopolysaccharide (Escherichia coli; 2 ng kg-1) and were assigned to either induced normothermia or control. Induced normothermia to maintain core temperature at 37°C consisted of external surface cooling, cold i.v. fluids, and medication to reduce shivering (buspirone, clonidine, and magnesium sulphate). The primary outcome was the DIC score (International Society on Thrombosis and Haemostasis guideline). Prothrombin time (PT), activated partial thromboplastin time (aPTT), D-dimer, plasma von Willebrand factor (vWf), and rotational thromboelastometry (ROTEM) were measured before and 1, 3, 6, and 8 h after LPS infusion. Differences between groups were tested with a mixed effects model.ResultsIn control subjects, lipopolysaccharide caused a fever, transiently decreased platelet levels and lowered activated partial thromboplastin time, while prolonging prothrombin time and increasing D-Dimer and vWf levels. Normothermia prevented the DIC-score exceeding 4, which occurred in 50% of control subjects. Normothermia also reduced the fall in platelet count by 67x109 L-1([95%CI:27-107]; p=0.002), aPTT (mean difference:3s [95%CI:1-5]; p=0.005) and lowered vWf levels by 89% ([95%CI:6-172]; p=0.03), compared to the fever group. ROTEM measurements were unaffected by lipopolysaccharide.ConclusionIn human endotoxaemia, induced normothermia decreases markers of endothelial activation and DIC. Maintaining normothermia may reduce coagulopathy in hyperinflammatory states.Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.

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