Population Health Research Institute, Hamilton, ON, Canada (A.L., E.P.B-C., R.P.W., I.C., J.V., R.K., K.B., S.I.B., M.H.M., J.S., S.Y., P.J.D.).
Surgery (A.L., R.P.W.), McMaster University, Hamilton, ON, Canada.
Circulation. 2024 Oct 22;150(17):1315-1323. doi: 10.1161/CIRCULATIONAHA.124.069606. Epub 2024 Apr 8.
Although intravenous tranexamic acid is used in cardiac surgery to reduce bleeding and transfusion, topical tranexamic acid results in lower plasma concentrations compared with intravenous tranexamic acid, which may lower the risk of seizures. We aimed to determine whether topical tranexamic acid reduces the risk of in-hospital seizure without increasing the risk of transfusion among cardiac surgery patients.
We conducted a multicenter, double dummy, blinded, randomized controlled trial of patients recruited by convenience sampling in academic hospitals undergoing cardiac surgery with cardiopulmonary bypass. Between September 17, 2019, and November 28, 2023, a total of 3242 patients from 16 hospitals in 6 countries were randomly assigned (1:1 ratio) to receive either intravenous tranexamic acid (control) through surgery or topical tranexamic acid (treatment) at the end of surgery. The primary outcome was seizure, and the secondary outcome was red blood cell transfusion. After the last planned interim analysis, when 75% of anticipated participants had completed follow up, the data and safety monitoring board recommended to terminate the trial, and upon unblinding, the operations committee stopped the trial for safety.
Among 3242 randomized patients (mean age, 66.0 years; 77.7% male), in-hospital seizure occurred in 4 of 1624 patients (0.2%) in the topical group, and 11 of 1628 patients (0.7%) in the intravenous group (absolute risk difference, -0.5% [95% CI, -0.9 to 0.03]; =0.07). Red blood cell transfusion occurred in 570 patients (35.1%) in the topical group and in 433 (26.8%) in the intravenous group (absolute risk difference, 8.3% [95% CI, 5.2-11.5]; =0.007). The absolute risk difference in transfusion of ≥4 units of red blood cells in the topical group compared with the intravenous group was 8.2% (95% CI, 3.4-12.9).
Among patients undergoing cardiac surgery, topical administration of tranexamic acid resulted in an 8.3% absolute increase in transfusion without reducing the incidence of seizure, compared with intravenous tranexamic acid.
URL: https://www.clinicaltrials.gov; Unique identifier: NCT03954314.
尽管心脏手术中使用静脉注射氨甲环酸可减少出血和输血，但与静脉注射氨甲环酸相比，局部应用氨甲环酸会导致较低的血浆浓度，这可能降低癫痫发作的风险。我们旨在确定局部应用氨甲环酸是否可以降低心脏手术患者住院期间癫痫发作的风险，而不增加输血的风险。
我们在学术医院进行了一项多中心、双盲、随机对照试验，采用便利抽样法招募接受体外循环心脏手术的患者。2019 年 9 月 17 日至 2023 年 11 月 28 日，来自 6 个国家 16 家医院的 3242 名患者被随机分为两组（1:1 比例），分别在手术中接受静脉注射氨甲环酸（对照组）或手术结束时接受局部氨甲环酸（治疗组）。主要结局是癫痫发作，次要结局是红细胞输血。在最后一次计划的中期分析时，当预计参与者的 75%完成随访后，数据和安全监测委员会建议终止试验，在揭盲后，操作委员会出于安全考虑停止了试验。
在 3242 名随机患者中（平均年龄 66.0 岁；77.7%为男性），局部组 1624 名患者中有 4 名（0.2%）发生院内癫痫发作，静脉组 1628 名患者中有 11 名（0.7%）（绝对风险差异，-0.5%[95%CI，-0.9 至 0.03]；=0.07）。局部组有 570 名（35.1%）患者和静脉组有 433 名（26.8%）患者输血（绝对风险差异，8.3%[95%CI，5.2-11.5]；=0.007）。局部组与静脉组相比，输注≥4 单位红细胞的绝对风险差异为 8.2%（95%CI，3.4-12.9）。
与静脉注射氨甲环酸相比，心脏手术患者局部应用氨甲环酸可导致输血增加 8.3%，但不降低癫痫发作的发生率。
