Intramuscular administration of tranexamic acid in a large swine model of hemorrhage with hyperfibrinolysis

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.