Howard Jeffrey T, Stockinger Zsolt T, Cap Andrew P, Bailey Jeffrey A, Gross Kirby R
United States Army Institute of Surgical Research (J.T.H., A.P.C., K.R.G.), Battlefield Health and Trauma Center for Human Integrative Physiology (J.T.H.), Department of Defense Joint Trauma System (Z.T.S.), Joint Base San Antonio-Fort Sam Houston, Texas; Bureau of Medicine and Surgery (Z.T.S.), US Navy, Falls Church, Virginia; Department of Surgery (J.A.B.), Uniformed Services University of the Health Sciences (J.A.B.); and Walter Reed National Military Medical Center (J.A.B.), Bethesda, Maryland.
J Trauma Acute Care Surg. 2017 Oct;83(4):579-588. doi: 10.1097/TA.0000000000001613.
Tranexamic acid (TXA) has been previously reported to have a mortality benefit in civilian and combat-related trauma, and was thus added to the Joint Theater Trauma System Damage Control Resuscitation Clinical Practice Guideline. As part of ongoing system-wide performance improvement, the use of TXA has been closely monitored. The goal was to evaluate the efficacy and safety of TXA use in military casualties and provide additional guidance for continued use.
A total of 3,773 casualties were included in this retrospective, observational study of data gathered from a trauma registry. The total sample, along with three subsamples for massive transfusion patients (n = 784), propensity-matched sample (n = 1,030), and US/North Atlantic Treaty Organization (NATO) military (n = 1,262), was assessed for administration of TXA and time from injury to administration of TXA. Outcomes included mortality and occurrence of pulmonary embolism and deep vein thrombosis. Multivariable proportional hazards regression models with robust standard error estimates were used to estimate hazard ratios (HR) for assessment of outcomes while controlling for covariates.
Results of univariate and multivariate analyses of the total sample (HR, 0.97; 95% confidence interval [CI], 0.62-1.53; p = 0.86), massive transfusion sample (HR, 0.84; 95% CI, 0.46-1.56; p = 0.51), propensity-matched sample (HR, 0.68; 95% CI, 0.27-1.73; p = 0.34), and US/NATO military sample (HR, 0.76; 95% CI, 0.30-1.92; p = 0.48) indicate no statistically significant association between TXA use and mortality. Use of TXA was associated with increased risk of pulmonary embolism in the total sample (HR, 2.82; 95% CI, 2.08-3.81; p < 0.001), massive transfusion sample (HR, 3.64; 95% CI, 1.96-6.78; p = 0.003), US/NATO military sample (HR, 2.55; 95% CI, 1.73-3.69; p = 0.002), but not the propensity-matched sample (HR, 3.36; 95% CI, 0.80-14.10; p = 0.10). TXA was also associated with increased risk of deep vein thrombosis in the total sample (HR, 2.00; 95% CI, 1.21-3.30; p = 0.02) and US/NATO military sample (HR, 2.18; 95% CI, 1.20-3.96; p = 0.02).
In the largest study on TXA use in a combat trauma population, TXA was not significantly associated with mortality, due to lack of statistical power. However, our HR estimates for mortality among patients who received TXA are consistent with previous findings from the CRASH-2 trial. At the same time, continued scrutiny and surveillance of TXA use in military trauma, specifically for prevention of thromboembolic events, is warranted.
Therapeutic, level IV.
此前有报道称氨甲环酸(TXA)对 civilian 和与战斗相关的创伤有降低死亡率的益处,因此被纳入联合战区创伤系统损伤控制复苏临床实践指南。作为全系统持续绩效改进的一部分,TXA 的使用受到密切监测。目标是评估 TXA 在军事伤亡中的疗效和安全性,并为继续使用提供更多指导。
本回顾性观察研究纳入了从创伤登记处收集的 3773 例伤亡数据。对总样本以及大量输血患者的三个子样本(n = 784)、倾向匹配样本(n = 1030)和美国/北大西洋公约组织(NATO)军队样本(n = 1262)进行评估,以确定 TXA 的使用情况以及从受伤到使用 TXA 的时间。结局包括死亡率、肺栓塞和深静脉血栓形成的发生率。使用具有稳健标准误差估计的多变量比例风险回归模型来估计风险比(HR),以在控制协变量的同时评估结局。
总样本(HR,0.97;95%置信区间[CI],0.62 - 1.53;p = 0.86)、大量输血样本(HR,0.84;95%CI,0.46 - 1.56;p = 0.51)、倾向匹配样本(HR,0.68;95%CI,0.27 - 1.73;p = 0.34)和美国/北约军队样本(HR,0.76;95%CI,0.30 - 1.92;p = 0.48)的单变量和多变量分析结果表明,使用 TXA 与死亡率之间无统计学显著关联。在总样本(HR,2.82;95%CI,2.08 - 3.81;p < 0.001)、大量输血样本(HR,3.64;95%CI,1.96 - 6.78;p = 0.003)、美国/北约军队样本(HR,2.55;95%CI,1.73 - 3.69;p = 0.002)中,使用 TXA 与肺栓塞风险增加相关,但倾向匹配样本中未发现此关联(HR,3.36;95%CI,0.80 - 14.10;p = 0.10)。TXA 在总样本(HR,2.00;95%CI,1.21 - 3.30;p = 0.02)和美国/北约军队样本(HR,2.18;95%CI,1.20 - 3.96;p = 0.02)中也与深静脉血栓形成风险增加相关。
在关于战斗创伤人群使用 TXA 的最大规模研究中,由于缺乏统计学效力,TXA 与死亡率无显著关联。然而,我们对接受 TXA 治疗患者死亡率的 HR 估计与 CRASH - 2 试验先前的结果一致。同时,有必要对军事创伤中 TXA 的使用进行持续审查和监测,特别是预防血栓栓塞事件。
治疗性,IV 级。