TY - JOUR
T1 - Induced normothermia ameliorates the procoagulant host response in human endotoxaemia
AU - Harmon, Matthew B. A.
AU - Heijnen, Nanon F. L.
AU - de Bruin, Sanne
AU - Sperna Weiland, Niek H.
AU - Meijers, Joost C. M.
AU - de Boer, Anita M.
AU - Schultz, Marcus J.
AU - Horn, Janneke
AU - Juffermans, Nicole P.
N1 - Publisher Copyright: © 2021 The Authors
PY - 2021/6/1
Y1 - 2021/6/1
N2 - Background: Dysregulation 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. Methods: Twelve 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. Results: In 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. Conclusion: In human endotoxaemia, induced normothermia decreases markers of endothelial activation and DIC. Maintaining normothermia may reduce coagulopathy in hyperinflammatory states.
AB - Background: Dysregulation 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. Methods: Twelve 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. Results: In 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. Conclusion: In human endotoxaemia, induced normothermia decreases markers of endothelial activation and DIC. Maintaining normothermia may reduce coagulopathy in hyperinflammatory states.
KW - coagulation
KW - cooling
KW - endotoxaemia
KW - fever
KW - induced normothermia
KW - inflammation
KW - sepsis
UR - http://www.scopus.com/inward/record.url?scp=85105628450&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.bja.2021.02.033
DO - https://doi.org/10.1016/j.bja.2021.02.033
M3 - Article
C2 - 33896590
SN - 0007-0912
VL - 126
SP - 1111
EP - 1118
JO - British Journal of Anaesthesia
JF - British Journal of Anaesthesia
IS - 6
ER -