The University of Chicago Pritzker School of Medicine, Chicago, Illinois.
Missouri State University, Springfield, Missouri.
J Surg Res. 2024 Oct;302:798-804. doi: 10.1016/j.jss.2024.08.003. Epub 2024 Sep 2.
Tranexamic acid (TXA) is an antifibrinolytic drug that has been demonstrated to reduce head injury-related mortality when given within 2 h of injury in patients with traumatic brain injury and intracranial hemorrhage. It is usually administered via intravenous (IV) access, which can be difficult to obtain in prehospital and austere settings. Intraosseous (IO) access is fast and offers an alternative when IV access proves challenging; however, TXA administration via IO access has never been studied in humans. We sought to determine if the total drug exposure of TXA given in the prehospital setting in patients with moderate or severe brain injury differs based on route of administration.
We performed a retrospective analysis of prospectively collected data from the prehospital TXA for traumatic brain injury trial (NCT01990768). Participants who received TXA via IO administration were compared to those who received TXA via IV administration and stratified by renal function category based on the Kidney Disease Improving Global Outcomes criteria. The area under the plasma drug concentration-time curve (AUC) was calculated using the trapezoidal rule (Phoenix WinNonlin 8.3, Certara, Princeton NJ) to obtain total drug exposure. The inverse variance method was used to combine observations within strata and calculate mean differences.
Of the 966 participants enrolled in the trial, 345 participants received a 2-g TXA prehospital bolus (11 IO, 334 IV); 312 participants received a 1-g TXA prehospital bolus followed by a 1-g TXA infusion in-hospital over 8 h (13 IO, 299 IV). After exclusion because of missing data and extreme estimated AUC, 233 IV and eight IO participants in the 2-g bolus arm and 152 IV and eight IO participants in the 1-g bolus 1-g infusion arm remained. Participants did not differ by age, sex, race, ethnicity, body mass index, serum creatinine, estimated glomerular filtration rate, or clot lysis at 30 min on thromboelastography. No difference in the mean AUCs were observed between IV and IO for either the 2-g bolus group (-2.6 μ g/mL/h [IO] compared to IV, 95% confidence interval: -28.4 to 23.3 μ g/mL/h) or the 1-g bolus/1-g infusion group (-13.0 μ g/mL/h [IO] compared to IV, 95% confidence interval: -236.2 to 210.3 μ g/mL/h).
These preliminary data suggest that the administration of TXA via IO and IV routes may result in similar total drug exposure. Further studies incorporating larger numbers with clinical outcomes are needed to confirm this finding.
氨甲环酸(TXA)是一种抗纤维蛋白溶解药物,已证明在创伤性脑损伤和颅内出血患者受伤后 2 小时内使用可降低与头部损伤相关的死亡率。它通常通过静脉内(IV)途径给药,在院前和恶劣环境中,这可能很难获得。骨内(IO)通路快速,并且在 IV 通路有困难时提供了替代方法;但是,尚未在人体中研究过通过 IO 通路给予 TXA。我们试图确定在中度或重度脑损伤患者中,在院前环境中给予 TXA 的总药物暴露是否因给药途径而异。
我们对创伤性脑损伤 TXA 院前治疗试验(NCT01990768)前瞻性收集的数据进行了回顾性分析。比较了通过 IO 给药组和通过 IV 给药组的 TXA 接受者,并根据肾脏疾病改善全球结果(KDIGO)标准按肾功能类别进行分层。使用梯形规则(Phoenix WinNonlin 8.3,Certara,新泽西州普林斯顿)计算血浆药物浓度-时间曲线下面积(AUC),以获得总药物暴露量。采用方差倒数法对各层内的观察值进行组合,并计算均值差。
在该试验中纳入的 966 名参与者中,有 345 名参与者接受了院前 2g TXA 推注(11 例 IO,334 例 IV);312 名参与者接受了院前 1g TXA 推注,随后在院内 8 小时内输注 1g TXA(13 例 IO,299 例 IV)。由于数据缺失和估计 AUC 极端,排除了 2g 推注臂的 233 例 IV 和 8 例 IO 参与者和 1g 推注 1g 输注臂的 152 例 IV 和 8 例 IO 参与者。参与者在年龄,性别,种族,民族,体重指数,血清肌酐,估算肾小球滤过率或血栓弹力图 30 分钟时的凝块溶解方面无差异。在 2g 推注组中,IV 和 IO 之间的 AUC 均值无差异(-2.6μg/mL/h [IO] 与 IV 相比,95%置信区间:-28.4 至 23.3μg/mL/h),在 1g 推注/1g 输注组中也无差异(-13.0μg/mL/h [IO] 与 IV 相比,95%置信区间:-236.2 至 210.3μg/mL/h)。
这些初步数据表明,通过 IO 和 IV 途径给予 TXA 可能会导致相似的总药物暴露。需要进一步研究,纳入更多具有临床结局的患者以确认这一发现。