Pharmacokinetics of tranexamic acid (TXA) delivered by expeditious routes in a swine model of polytrauma and hemorrhagic shock

ABSTRACT

Objective

Hemorrhage is the leading cause of preventable death in civilian trauma centers and on the battlefield. One of the emerging treatment options for hemorrhage in austere environments is tranexamic acid (TXA). However, the landscape is not amenable to the current delivery standard. This study compared the pharmacokinetics of TXA via a standard 10-minute intravenous infusion (IV infusion), intravenous rapid push over 10 s (IV push), and intramuscular injection (IM) in a swine polytrauma and hemorrhagic shock model (trauma group) compared to uninjured controls (control group).

Methods

Thirty swine were randomized to the trauma or control group. Following anesthesia, the trauma group experienced a simulated blast injury and 40% controlled hemorrhage. Subjects in both groups were then randomized to receive 1 g/10 mL TXA via IV infusion, IV push, or IM. Animals were monitored for four hours with serial blood sampling. Serum TXA concentrations were measured by liquid chromatography with tandem mass spectrometry (LC-MS/MS) and analyzed.

Results

The time to maximum TXA concentration (T_max) was not affected by trauma in IV infusion or IV push, but was affected in the IM administration with T_max significantly slower than the control group (p = 0.016). The minimum effective serum concentration of TXA (C_eff, 10 µg/mL) was reached in less than one minute with IV infusion and instantaneously with IV push. Despite lower bioavailability, the time to reach C_eff (T_eff) was achieved via IM administration in less than 10 minutes for both groups (6.4 minutes trauma vs. 2.1 minutes control).

Conclusions

In austere prehospital environments, an alternative to intravenous infusion of a life-saving medication is desired. Administration of TXA via all three methods reached the level needed to cause substantial inhibition of fibrinolysis within 10 minutes. The IV push method showed similar pharmacokinetics to IV infusion of TXA but can be delivered quickly without sacrificing an access site for 10 minutes.

Key words:

• tranexamic acid
• pharmacokinetics
• polytrauma
• hemorrhage
• swine

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Acknowledgements

The authors would like to thank and acknowledge LCDR Jared Verga and the Naval Medical Center Portsmouth animal facility staff for their efforts on this study.

Additional information

Funding

This work was supported by funding from RDT&E 6.6 funding in support of Clinical Infrastructure, Naval Medical Center Portsmouth and by the CIP1 Funds from the Navy Surgeon General Grant.