Department of Anesthesiology & Critical Care, University of California, San Diego, La Jolla, California.
Department of Bioengineering, University of California, San Diego, La Jolla, California.
J Surg Res. 2022 Nov;279:89-96. doi: 10.1016/j.jss.2022.05.028. Epub 2022 Jun 22.
Whole blood (WB) or blood products are not always immediately available for repletion of lost intravascular volume in trauma/hemorrhagic shock (T/HS), and thus, resuscitation with crystalloid solutions is often necessary. Recently, we have shown enteral tranexamic acid (TXA) to be effective as a mild protease inhibitor in blood-resuscitated T/HS by counteracting proteolytic activity in and leaking from the gut with resultant preservation of systemic vascular integrity. We hypothesized that enteral TXA would improve hemodynamic stability after T/HS in the absence of blood reperfusion.
We directly compared resuscitation with enteral TXA versus intravenous (IV) TXA in conjunction with lactated Ringer's solution (LR) or WB reperfusion in an experimental T/HS model. Rats were subjected to laparotomy and exsanguinated to a mean arterial blood pressure of 35-40 mm Hg for 90 min, followed by LR or WB reperfusion and monitored for 120 min. TXA was administered via IV (10 mg/kg) or enteral infusion (150 mM) 20 min after establishment of hemorrhage for 150 min.
Animals resuscitated with LR were unable to restore or maintain a survivable mean arterial blood pressure (>65 mm Hg), regardless of TXA treatment route. In contrast, rats reperfused with WB and given TXA either enterally or IV displayed hemodynamic improvements superior to WB controls.
Results suggest that the beneficial hemodynamic responses to enteral or IV TXA after experimental T/HS depend upon reperfusion of WB or components present in WB as TXA, regardless of delivery mode, does not have appreciable hemodynamic effects when paired with LR reperfusion.
在创伤/失血性休克（T/HS）中，并非总能立即获得全血（WB）或血液制品来补充丢失的血容量，因此通常需要使用晶体溶液进行复苏。最近，我们发现肠内给予氨甲环酸（TXA）通过与肠道内和漏出的蛋白酶活性相互作用，作为一种轻度蛋白酶抑制剂，在血液复苏的 T/HS 中是有效的，从而维持全身血管完整性。我们假设，在没有血液再灌注的情况下，肠内给予 TXA 会改善 T/HS 后的血流动力学稳定性。
我们在实验性 T/HS 模型中直接比较了肠内 TXA 与静脉（IV）TXA 联合乳酸林格氏液（LR）或 WB 再灌注的复苏效果。大鼠接受剖腹手术并放血至平均动脉血压 35-40mmHg 持续 90 分钟，然后进行 LR 或 WB 再灌注，并监测 120 分钟。在出血后 20 分钟给予 TXA 静脉（10mg/kg）或肠内输注（150mM），持续 150 分钟。
用 LR 复苏的动物无法恢复或维持可存活的平均动脉血压（>65mmHg），无论 TXA 治疗途径如何。相比之下，用 WB 再灌注并给予肠内或 IV TXA 的大鼠表现出优于 WB 对照的血流动力学改善。
结果表明，实验性 T/HS 后肠内或 IV TXA 的有益血流动力学反应取决于 WB 或 WB 中存在的成分的再灌注，无论给予模式如何，与 LR 再灌注联合使用时，TXA 都没有明显的血流动力学作用。
