How should tranexamic acid be administered in haemorrhagic shock? - continuous serum concentration measurements in a swine model

Abstract Background: Tranexamic acid (TXA) reduces mortality in trauma patients. Intramuscular (i.m.) administration could be advantageous in low-resource and military settings. Achieving the same serum concentration as i.v. administration is important to achieve equal mortality reduction. Therefore, we aimed to investigate whether dividing an i.m. dose of TXA between two injection sites, and whether an increase in dose, would lead to serum concentrations comparable to those achieved by i.v. administration. Methods: Norwegian landrace pigs (n = 29) from a course in haemostatic emergency surgery were given tranexamic acid 1h after start of surgery. Blood samples were drawn at 0, 5,10, 15, 20, 25, 35, 45, 60 and 85 min. The samples were centrifuged and serum TXA concentrations quantified with liquid chromatography–tandem mass spectrometry (LC–MS/MS). The use of two injection sites was compared to distributing the dose on one injection site, and a dose of 15 mg/kg was compared to a dose of 30 mg/kg. All i.m. groups were compared to i.v. administration. Results: The groups were in a similar degree of shock. Increasing the i.m. dose from the standard of 15 mg/kg to 30 mg/kg resulted in significantly higher serum concentrations of TXA, comparable to those achieved by i.v. administration. Distributing the i.m. dose on two injection sites did not affect drug-uptake, as shown by equal serum concentrations. Conclusions: For i.m. administration of TXA, 30 mg/kg should be the standard dose. With a short delay, i.m. administration will provide equal serum concentrations as i.v. administration, above what is considered necessary to inhibit fibrinolysis.