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Introduction Tranexamic acid (TXA) improves survival in traumatic hemorrhage, but difficulty obtaining intravenous (IV) access may limit its use in austere environments, given its incompatibility with blood products. The bioavailability of intramuscular (IM) TXA in a shock state is unknown. We hypothesized that IM and IV administration have similar pharmacokinetics and ability to reverse in vitro hyperfibrinolysis in a swine-controlled hemorrhage model. Methods Twelve Yorkshire cross swine were anesthetized, instrumented, and subjected to a 35% controlled hemorrhage, followed by resuscitation. During hemorrhage, they were randomized to receive a 1 g IV TXA infusion over 10 min, 1 g IM TXA in two 5 mL injections, or 10 mL normal saline IM injection as a placebo group to assess model adequacy. Serum TXA concentrations were determined using liquid chromatography-mass spectrometry, and plasma samples supplemented with tissue plasminogen activator (tPA) were analyzed by rotational thromboelastometry. Results All animals achieved class III shock. There was no difference in the concentration-time areas under the curve between TXA given by either route. The absolute bioavailability of IM TXA was 97%. IV TXA resulted in a higher peak serum concentration during the infusion, with no subsequent differences. Both IV and IM TXA administration caused complete reversal of in vitro tPA-induced hyperfibrinolysis. Conclusion The pharmacokinetics of IM TXA were similar to IV TXA during hemorrhagic shock in our swine model. IV administration resulted in a higher serum concentration only during the infusion, but all levels were able to successfully correct in vitro hyperfibrinolysis. There was no difference in total body exposure to equal doses of TXA between the two routes of administration. IM TXA may prove beneficial in scenarios where difficulty establishing dedicated IV access could otherwise limit or delay its use.

BACKGROUND The resuscitation of patients in shock is materially intensive and many patients are refractory to maximal therapy. We hypothesized that partial inflation of an intra-aortic balloon, termed Endovascular Perfusion Augmentation for Critical Care (EPACC), would minimize material requirements while improving physiologic metrics. METHODS Swine underwent a 25% controlled bleed and 45 min of complete aortic occlusion to create a severe ischemia-reperfusion shock state. Animals received either standardized critical care (SCC) composed of IV fluids and norepinephrine delivered through an algorithmically controlled platform or EPACC in addition to SCC. Physiologic parameters were collected, and blood was sampled for analysis. Primary outcomes were total IV fluids and average MAP during the critical care phase. Differences (P