Subcutaneous Tranexamic Acid Achieves Comparable Serum Concentrations to Intramuscular Administration During Haemorrhagic Shock in a Swine Model

BACKGROUND: Tranexamic acid is an antifibrinolytic agent reducing mortality when administered to trauma patients with haemorrhagic shock. This mortality reduction is time sensitive. Increased intramuscular dose administration has proven an effective alternative to intravenous administration in several studies and is used by some emergency medical services. However, subcutaneous administration has not been studied. Previous research indicates that subcutaneous tissue blood flow is more compromised during shock than muscle perfusion. Determining subcutaneous absorption is crucial to evaluate its potential as an alternative route and to assess the effect of accidental subcutaneous injection during intended intramuscular administration. METHODS: In this experimental study using historical intramuscular and intravenous control groups, a total of six Norwegian Landrace pigs (40-50 kg) used in a trauma surgery course were subjected to various abdominal and thoracic traumas. After 1 h of surgery, the animals received tranexamic acid 30 mg/kg subcutaneously. Serum was sampled at 0, 5, 15, 25, 35, 45, 60, and 85 min after administration. Tranexamic acid serum concentration was measured using liquid chromatography-tandem mass spectrometry and compared to intramuscular and intravenous groups from previous studies, in which animals had received tranexamic acid 30 mg/kg intramuscular (n = 7) or 15 mg/kg intravenous (n = 8). RESULTS: There was no statistical difference in serum concentrations between subcutaneous and intramuscular administration. Mean (±standard deviation) concentration after administration at 10, 45, and 85 min were 41.4 μg/mL (±19.0), 39.1 μg/mL (±8.9), and 33.4 μg/mL (±5.8), and for IM concentrations were 41.8 μg/mL (±18.9), 39.9 μg/mL (±7.8), and 44.2 μg/mL (±21.8). At 5 min, the concentration of both SC and IM administration was approximately half those observed after IV administration, but all concentrations were well above the 10-17 μg/mL concentration needed to inhibit fibrinolysis. CONCLUSIONS: Although subcutaneous blood flow is sensitive to shock, serum tranexamic acid concentrations after subcutaneous administration in shocked pigs were comparable to those achieved after intramuscular administration. Intramuscular administration should remain the preferred secondary route after the standard intravenous route, but inadvertent subcutaneous injection is likely to achieve therapeutic serum concentrations. EDITORIAL COMMENT: This observational study in pigs undergoing hemorrhagic shock compared subcutaneous tranexamic acid administration to historical intravenous and intramuscular controls and found that plasma concentrations were comparable between routes. This suggests that inadvertent subcutaneous dosing during intramuscular injection likely achieves therapeutic levels. While promising, these results rely on historical controls and warrant further confirmatory studies. Intramuscular administration remains the preferred alternative to intravenous dosing for now.