V. O. Ogbeifun1, W. I. McKinley2, A. J. Benjamin2, Z. C. Newman7, M. Y. Munar4, C. E. Barbosa9, P. E. Pramuka9, K. D. McGovern3, R. K. Nordgren10, M. A. Schreiber5, S. E. Rowell2 1Missouri State University, Springfield, MO, USA 2University Of Chicago, Department Of Surgery, Chicago, IL, USA 3University of Illinois Urbana – Champaign, Champaign, IL, USA 4Oregon State University, College Of Pharmacy, Portland, OR, USA 5Oregon Health And Science University, Portland, OR, USA 7University Of Chicago, School Of Medicine, Chicago, IL, USA 9University Of Chicago, Chicago, IL, USA 10University Of Chicago, Department Of Public Health Sciences, Chicago, IL, USA
Introduction: Tranexamic acid (TXA) is an antifibrinolytic drug that has been demonstrated to reduce mortality when given within 3 hours of injury in two randomized trials in patients with traumatic brain injury (TBI). It is usually administered via intravenous (IV) access, which can be difficult to obtain in a pre-hospital setting. Intraosseous (IO) access is fast and offers an alternative when IV access proves challenging, however, TXA administration via IO access has never been studied in humans. We sought to determine if the total drug exposure of TXA given in the prehospital setting in patients with moderate or severe brain injuries differs based on the route of administration.
Methods: We performed a retrospective analysis of prospectively collected data from the Prehospital TXA for the TBI trial. Patients who received TXA via IO administration were compared to those who received TXA via IV administration and stratified by renal function category based on the Kidney Disease Improving Global Outcomes (KDIGO) criteria. The area under the plasma drug concentration-time curve (AUC) was calculated using the trapezoidal rule (Phoenix WinNonlin 8.3, Certara, Princeton NJ) to obtain total drug exposure. The inverse variance method was used to combine observations within strata and calculate mean differences, displayed in Forest plots (Figure 1).
Results: Of 966 patients enrolled in the trial, 345 patients received a 2g TXA pre-hospital bolus (11 IO, 334 IV); 312 patients received a 1g TXA pre-hospital bolus followed by a 1g TXA infusion in-hospital over 8 hours (13 IO, 299 IV). In the IO group, 8 patients were excluded (6 AUCs not calculated; 2 extreme outliers) leaving 16 patients (8 in the 2g arm, 8 in the 1g + 1g arm). In the IV group, 5% with extreme values were excluded leaving 385 patients (233 in the 2g arm and 152 in the 1g + 1g arm). Patients did not differ by age, BMI, and eGFR. No difference in the mean AUCs was observed between IV and IO for either the 1g + 1g group (-2.6 ug/mL/h, 95% CI -28.4 ug/mL/h to 23.3 ug/mL/h) or the 2g bolus group (-13.0 ug/mL/h, 95% CI -236.2 to 210.3).
Conclusion: These preliminary data suggest that the administration of TXA via IO and IV routes may result in similar total drug exposure. Further studies incorporating larger numbers with clinical outcomes are needed to confirm this finding.
