肌肉内给予氨甲环酸治疗伴有纤维蛋白溶解亢进的大出血大猪模型。
Intramuscular administration of tranexamic acid in a large swine model of hemorrhage with hyperfibrinolysis.
机构信息
From the Department of Emergency Medicine (C.J.H.), University of Colorado Anschutz Medical Campus; Department of Critical Care (C.J.H.), Children's Hospital Colorado; Department of Emergency Medicine (C.C.S., N.C.W., W.G.W., C.P., V.S.B., T.B.H.-H.), University of Colorado Anschutz Medical Campus, Aurora, Colorado; Department of Emergency Medicine (P.C.N.), Brooke Army Medical Center, Ft Sam Houston, San Antonio, Texas; Department of Biochemistry and Molecular Biology (F.C.), University of Colorado Anschutz Medical Campus, Aurora, Colorado; Department of Emergency Medicine (S.G.S.), Uniformed Services University of the Health Sciences, Bethesda, Maryland; Departments of Anesthesiology (S.G.S.) and Emergency Medicine (S.G.S.), University of Colorado Anschutz Medical Campus, Aurora, Colorado; Uniformed Services University of the Health Sciences (J.K.M.), Bethesda, Maryland; and Brooke Army Medical Center (J.K.M.), JBSA, Fort Sam Houston, Texas.
出版信息
J Trauma Acute Care Surg. 2024 May 1;96(5):735-741. doi: 10.1097/TA.0000000000004207. Epub 2023 Nov 13.
BACKGROUND
Traumatic injury with subsequent hemorrhage is one of the leading causes of mortality among military personnel and civilians alike. Posttraumatic hemorrhage accounts for 40% to 50% of deaths in severe trauma patients occurring secondary to direct vessel injury or the development of trauma-induced coagulopathy (TIC). Hyperfibrinolysis plays a major role in TIC and its presence increases a patient's risk of mortality. Early therapeutic intervention with intravenous (IV) tranexamic acid (TXA) prevents development of hyperfibrinolysis and subsequent TIC leading to decreased mortality. However, obtaining IV access in an austere environment can be challenging. In this study, we evaluated the efficacy of intramuscular (IM) versus IV TXA at preventing hyperfibrinolysis in a hemorrhaged swine.
METHODS
Yorkshire cross swine were randomized on the day of study to receive IM or IV TXA or no treatment. Swine were sedated, intubated, and determined to be hemodynamically stable before experimentation. Controlled hemorrhaged was induced by the removal of 30% total blood volume. After hemorrhage, swine were treated with 1,000 mg of IM or IV TXA. Control animals received no treatment. Thirty minutes post-TXA treatment, fibrinolysis was induced with a 50-mg bolus of tissue plasminogen activator. Blood samples were collected to evaluate blood TXA concentrations, blood gases, blood chemistry, and fibrinolysis.
RESULTS
Blood TXA concentrations were significantly different between administration routes at the early time points but were equivalent by 20 minutes after injection, remaining consistently elevated for up to 3 hours postadministration. Induction of fibrinolysis resulted in 87.18 ± 4.63% lysis in control animals, compared with swine treated with IM TXA, 1.96 ± 2.66% and 1.5 ± 0.42% lysis in the IV TXA group.
CONCLUSION
In the large swine model of hemorrhage with hyperfibrinolysis, IM TXA is bioequivalent and equally efficacious in preventing hyperfibrinolysis as IV TXA administration.
背景
创伤后出血是军人和平民死亡的主要原因之一。创伤后出血占严重创伤患者死亡人数的 40%至 50%，其发生原因是直接血管损伤或创伤诱导的凝血障碍（TIC）的发展。纤溶亢进在 TIC 中起主要作用，其存在增加了患者的死亡风险。早期静脉（IV）给予氨甲环酸（TXA）治疗可预防纤溶亢进和随后的 TIC，从而降低死亡率。然而，在恶劣环境中获得 IV 通路可能具有挑战性。在这项研究中，我们评估了肌肉内（IM）与 IV TXA 预防失血猪纤溶亢进的疗效。
方法
在研究当天，约克夏十字猪被随机分为接受 IM 或 IV TXA 或不治疗。猪在实验前被镇静、插管并确定血流动力学稳定。通过去除 30%的总血容量来诱导控制性出血。出血后，猪接受 1000mg 的 IM 或 IV TXA 治疗。对照动物未接受治疗。在给予 TXA 治疗后 30 分钟，用 50mg 组织型纤溶酶原激活剂诱导纤溶。采集血液样本以评估血液 TXA 浓度、血气、血液化学和纤溶。
结果
在早期时间点，给药途径之间的血液 TXA 浓度有显著差异，但在注射后 20 分钟时等效，在给药后长达 3 小时内持续升高。在对照动物中，纤溶诱导导致 87.18±4.63%的溶解，而 IM TXA 治疗的猪为 1.96±2.66%，IV TXA 组为 1.5±0.42%。
结论
在大出血伴纤溶亢进的大型猪模型中，IM TXA 在预防纤溶亢进方面与 IV TXA 给药等效且同样有效。
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