Autoinjector-based delivery of tranexamic acid provides pharmacokinetic efficacy in a porcine model of uncontrolled hemorrhage.

Abstract

Hemorrhage remains the principal cause of death on the battlefield. It is suggested that Tranexamic acid (TXA) can improve survival of severely-bleeding casualties. The intravenous approach is not always available in the pre-hospital setting. It was shown that for every 15 min delay, the efficiency of TXA decreases by 10 %. This study was designed to assess the pharmacokinetic, pharmacodynamic, and pre-clinical efficacy of a TXA autoinjector in uncontrolled hemorrhage in swine. Non-compressible hemorrhage was induced by laparoscopic partial liver resection. TXA was administered intramuscularly by autoinjector (n = 25) or intravenously (control, n = 5). Blood levels of TXA and dynamics of clot formation were determined. Euthanasia was performed ninety minutes after injury followed by a laparotomy for the measurement of free blood and clots in the abdomen. The TXA levels in the autoinjector group exceeded the effective therapeutic threshold within <5 min and remained above the 10 mg/L threshold throughout the experiment. Intra-abdominal blood volumes, hemodynamic parameters, and indices of clot formation were similar between autoinjector-delivered and intravenouslyadministered groups. Autoinjector-based TXA provides sustained, anti-fibrinolytic levels within 2-5 min of administration in a swine model of uncontrolled hemorrhage emphasizing its important.