Bouthors Anne-Sophie, Gilliot Sixtine, Sentilhes Loïc, Hennart Benjamin, Jeanpierre Emmanuelle, Deneux-Tharaux Catherine, Lebuffe Gilles, Odou Pascal
Anaesthesia Intensive Care Unit, Jeanne de Flandre Women's Hospital, Lille University Medical Centre, F-59037, Lille, France; Univ. Lille, ULR 7365 - GRITA - Groupe de Recherche sur les formes Injectables et les Technologies Associées, F-59000, Lille, France.
Univ. Lille, ULR 7365 - GRITA - Groupe de Recherche sur les formes Injectables et les Technologies Associées, F-59000, Lille, France; Central Pharmacy, Lille University Medical Centre, F-59037, Lille, France.
Best Pract Res Clin Anaesthesiol. 2022 Dec;36(3-4):411-426. doi: 10.1016/j.bpa.2022.08.004. Epub 2022 Aug 31.
In the last decades, tranexamic acid (TXA) has emerged as an essential tool in blood loss management in obstetrics. TXA prophylaxis for postpartum haemorrhage (PPH) has been studied in double-blind, placebo-controlled, randomized clinical trials (RCTs). Given the small observed preventive effect, the systematic use of TXA for vaginal and/or caesarean deliveries remains controversial. The result of a pharmacokinetic modelling suggests that relative to intravenous administration, intramuscular administration may be an equally effective alternative route for preventing PPH and may enable access to this drug in low-resource countries. Prophylaxis is currently studied in high-risk populations, such as women with prepartum anaemia or placenta previa. TXA effectively reduces blood loss and PPH-related morbidity and mortality during active PPH, as demonstrated by high-grade evidence from large RCTs. The drug has a good safety profile: in most cases, only mild gastrointestinal or visual adverse events may be observed. TXA use does not increase the risk of serious adverse events, such as venous or arterial thromboembolism, seizures, or acute kidney injury. The TRACES in vivo analysis of biomarkers of TXA's antifibrinolytic effect have suggested that a dose of at least 1 g is required for the treatment of PPH. The TRACES pharmacokinetic model suggests that because TXA can be lost in the haemorrhaged blood, a second dose should be administered if the PPH continues or if severe coagulopathy occurs. Future pharmacodynamic analyses will focus on the appropriateness of TXA dosing regimens with regard to the intensity of fibrinolysis in catastrophic obstetric events.
在过去几十年中,氨甲环酸(TXA)已成为产科失血管理的重要工具。氨甲环酸预防产后出血(PPH)已在双盲、安慰剂对照的随机临床试验(RCT)中进行了研究。鉴于观察到的预防效果较小,系统性地将氨甲环酸用于阴道分娩和/或剖宫产仍存在争议。药代动力学建模结果表明,相对于静脉给药,肌肉注射可能是预防产后出血的同样有效的替代途径,并且可能使资源匮乏国家的人们能够获得这种药物。目前正在高危人群中研究预防措施,例如产前贫血或前置胎盘的妇女。大型随机对照试验的高级别证据表明,在活动性产后出血期间,氨甲环酸可有效减少失血量以及与产后出血相关的发病率和死亡率。该药物具有良好的安全性:在大多数情况下,仅可能观察到轻度胃肠道或视觉不良事件。使用氨甲环酸不会增加严重不良事件的风险,如静脉或动脉血栓栓塞、癫痫发作或急性肾损伤。氨甲环酸抗纤溶作用生物标志物的体内TRACES分析表明,治疗产后出血至少需要1克剂量。TRACES药代动力学模型表明,由于氨甲环酸可能会在出血血液中流失,如果产后出血持续或发生严重凝血病,应给予第二剂。未来的药效学分析将侧重于氨甲环酸给药方案在灾难性产科事件中纤维蛋白溶解强度方面的适宜性。