Intramuscular uptake of tranexamic acid during haemorrhagic shock in a swine model

Intramuscular uptake of tranexamic acid during haemorrhagic shock in a swine model Bakke H.1,2, Fauskevåg O.M. 3, Nielsen E.W. 4,5,6,7, Dietrichs E.S. 8,9 1University Hospital of North Norway, Department of anaesthesia and critical care, Tromsø, Norway 2University Hospital of North Norway, Department of Traumatology, Tromsø, Norway 3University Hospital of North Norway, Division of Diagnostic Services, Tromsø, Norway 4Nordland Hospital, Bodø, Department of Anaesthesia and Critical Care, Bodø, Norway 5Univerity Nord, Bodø, Norway 6University of Oslo , Department of Immunology, Oslo, Norway 7University of Tromsø, Institute of Clinical Medicine, Norway, Norway 8University of Tromsø, Department of Experimental and Clinical Pharmacology, Tromsø, Norway 9University Hospital of North Norway, Department of Clinical Pharmacology, Tromsø, Norway Introduction: Tranexamic acid (TXA) has been shown to reduce mortality in bleeding trauma patients, with greater effect if administered early. Normally administered intravenously, TXA can also be administered intramuscularly, which could be advantageous in low resource and military settings. Intramuscular use has only been tested in healthy patients, and it is likely that shock will reduce intramuscular uptake. Material & Methods: In a prospective experimental study Norwegian landrace pigs (40-50kg)utilised in a surgical course in haemostatic emergency surgery were subjected to various abdominal and thoracic trauma. After 1 hour of surgery the pigs were injected with 15 mg/kg TXA either intravenously or intramuscularly. Blood samples were drawn at 0, 5, 15, 25, 35 ,45, 60 and 80 minutes. The samples were centrifuged and analysed with liquid chromatography-mass spectrometry (LC-MS/MS). Results: Preliminary results from 3 animals in the intramuscular and 2 animals in the intravenous group. Mean plasma concentration with SD of TXA as a function of time is shown in figure 1. Plasma concentration in the intramuscular group was near 10 ug/mL 15 minutes after administration, and rose above 14 ug/mL after 60 minutes. Conclusions: Plasma concentrations reported to inhibit fibrinolysis in vitro is 10 – 17.5 ug/ml (1,2). If this extrapolates to the clinical situation intramuscular administration would yield plasma levels within the lower end of therapeutic range after 15 minutes.In ongoing haemorrhagic shock plasma concentrations of TXA after intramuscular administration were considerably lower than after intravenous administration, but within therapeutic range . References 1. Fietchner et al. Plasma tranexamic acid concentrations during cardiopulmonary bypass. Anesth Analg 2001 May;92(5):1131-6 2. Yee et al. The effective concentration of tranexamic acid for inhibition of fibrinolysis in neonatal plasma in vitro. Anesth Analg. 2001 Oct;117(4):767-72.