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.
Department of Intensive Care Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands.
Br J Anaesth. 2021 Jun;126(6):1111-1118. doi: 10.1016/j.bja.2021.02.033. Epub 2021 Apr 23.
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.
Twelve volunteers received an infusion of bacterial lipopolysaccharide (Escherichia coli; 2 ng kg) 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.
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 67x10 L([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.
In human endotoxaemia, induced normothermia decreases markers of endothelial activation and DIC. Maintaining normothermia may reduce coagulopathy in hyperinflammatory states.
脓毒症常伴有凝血功能紊乱，从血小板减少的轻度凝血病到弥漫性血管内凝血（DIC）不等。我们研究了在健康志愿者中，诱导正常体温对脂多糖（LPS）诱导的内毒素血症期间凝血的影响。
12 名志愿者接受细菌脂多糖（大肠杆菌；2ng/kg）输注，并分为诱导正常体温组或对照组。诱导正常体温以维持核心体温在 37°C 包括外部表面冷却、冷静脉输液和减少寒战的药物（丁螺环酮、可乐定和硫酸镁）。主要结局是 DIC 评分（国际血栓和止血学会指南）。在 LPS 输注前和输注后 1、3、6 和 8 小时测量凝血酶原时间（PT）、活化部分凝血活酶时间（aPTT）、D-二聚体、血浆血管性血友病因子（vWf）和旋转血栓弹性测定法（ROTEM）。采用混合效应模型检验组间差异。
在对照组中，脂多糖引起发热，短暂性血小板计数降低，活化部分凝血活酶时间延长，同时延长凝血酶原时间，增加 D-二聚体和 vWf 水平。正常体温可防止 50%的对照组 DIC 评分超过 4。正常体温还可使血小板计数下降减少 67x10 L（[95%CI：27-107]；p=0.002），aPTT（平均差值：3s [95%CI：1-5]；p=0.005）和 vWf 水平降低 89%（[95%CI：6-172]；p=0.03），与发热组相比。脂多糖对 ROTEM 测量无影响。
在内毒素血症中，诱导正常体温可降低内皮激活和 DIC 的标志物。维持正常体温可能会减少在过度炎症状态下的凝血功能障碍。
