Obstetric Anaesthesia and Intensive Care Unit, Jeanne de Flandre Women's Hospital, Lille University Medical Centre, Lille, France; Groupe de Recherche sur les formes Injectables et les Technologies Associées, ULR 7365, Université de Lille, Lille, France.
Groupe de Recherche sur les formes Injectables et les Technologies Associées, ULR 7365, Université de Lille, Lille, France.
Br J Anaesth. 2022 Dec;129(6):937-945. doi: 10.1016/j.bja.2022.08.033. Epub 2022 Oct 13.
The optimal dose of tranexamic acid to inhibit hyperfibrinolysis in postpartum haemorrhage is unclear. Tranexamic Acid to Reduce Blood Loss in Hemorrhagic Cesarean Delivery (TRACES) was a double-blind, placebo-controlled, randomised, multicentre dose-ranging study to determine the dose-effect relationship for two regimens of intravenous tranexamic acid vs placebo.
Women experiencing postpartum haemorrhage during Caesarean delivery were randomised to receive placebo (n=60), tranexamic acid 0.5 g (n=57), or tranexamic acid 1 g i.v. (n=58). Biomarkers of fibrinolytic activation were assayed at five time points, with inhibition of hyperfibrinolysis defined as reductions in the increase over baseline in D-dimer and plasmin-antiplasmin levels and in the plasmin peak time.
In the placebo group, hyperfibrinolysis was evidenced by a mean increase over baseline [95% confidence interval] of 93% [68-118] for D-dimer level at 120 min and 56% [25-87] for the plasmin-antiplasmin level at 30 min. A dose of tranexamic acid 1 g was associated with smaller increases over baseline (D-dimers: 38% [13-63] [P=0.003 vs placebo]; plasmin-antiplasmin: -2% [-32 to 28] [P=0.009 vs placebo]). A dose of tranexamic acid 0.5 g was less potent, with non-significant reductions (D-dimers: 58% [32-84] [P=0.06 vs placebo]; plasmin-antiplasmin: 13% [18-43] [P=0.051]). Although both tranexamic acid doses reduced the plasmin peak, reduction in plasmin peak time was significant only for the 1 g dose of tranexamic acid.
Fibrinolytic activation was significantly inhibited by a dose of intravenous tranexamic acid 1 g but not 0.5 g. Pharmacokinetic-pharmacodynamic modelling of these data might identify the best pharmacodynamic monitoring criteria and the optimal tranexamic acid dosing regimen for treatment of postpartum haemorrhage.
NCT02797119.
目前，尚不清楚抑制产后大出血中纤维蛋白溶解亢进所需氨甲环酸的最佳剂量。氨甲环酸减少剖宫产出血（TRACES）是一项双盲、安慰剂对照、随机、多中心剂量范围研究，旨在确定两种静脉内氨甲环酸方案与安慰剂相比的剂量效应关系。
在剖宫产术中发生产后出血的妇女被随机分为安慰剂组（n=60）、氨甲环酸 0.5 g 组（n=57）或氨甲环酸 1 g 组（n=58）。在五个时间点检测纤维蛋白溶解激活的生物标志物，抑制纤维蛋白溶解亢进的定义为 D-二聚体和纤溶酶-抗纤溶酶水平与纤溶酶峰值的增加与基线相比的降低。
在安慰剂组中，在 120 分钟时 D-二聚体水平的平均增加（95%置信区间）为基线的 93%[68-118]，在 30 分钟时纤溶酶-抗纤溶酶水平的平均增加为基线的 56%[25-87]，表明纤维蛋白溶解亢进。氨甲环酸 1 g 的剂量与基线的增加较小（D-二聚体：38%[13-63]，P=0.003 与安慰剂相比；纤溶酶-抗纤溶酶：-2%[-32 至 28]，P=0.009 与安慰剂相比）。氨甲环酸 0.5 g 的剂量效果较弱，差异无统计学意义（D-二聚体：58%[32-84]，P=0.06 与安慰剂相比；纤溶酶-抗纤溶酶：13%[18-43]，P=0.051）。虽然两种氨甲环酸剂量均降低了纤溶酶峰值，但仅 1 g 剂量的氨甲环酸降低了纤溶酶峰值时间。
静脉内氨甲环酸 1 g 的剂量可显著抑制纤维蛋白溶解亢进，但 0.5 g 剂量则无此作用。对这些数据进行药代动力学-药效学模型分析可能会确定最佳药效学监测标准和治疗产后出血的最佳氨甲环酸给药方案。
NCT02797119。
