Association Between Prehospital Tranexamic Acid Administration and Outcomes of Severe Traumatic Brain Injury

Abstract

IMPORTANCEThe development and expansion of intracranial hematoma are associated with adverse outcomes. Use of tranexamic acid might limit intracranial hematoma formation, but its association with outcomes of severe traumatic brain injury (TBI) is unclear.OBJECTIVE To assess whether prehospital administration of tranexamic acid is associated with mortality and functional outcomes in a group of patients with severe TBI. DESIGN, SETTING, AND PARTICIPANTSThis multicenter cohort study is an analysis of prospectively collected observational data from the Brain Injury: Prehospital Registry of Outcome, Treatments and Epidemiology of Cerebral Trauma (BRAIN-PROTECT) study in the Netherlands. Patients treated for suspected severe TBI by the Dutch Helicopter Emergency Medical Services between February 2012 and December 2017 were included. Patients were followed up for 1 year after inclusion. Data were analyzed from January 10, 2020, to September 10, 2020.EXPOSURES Administration of tranexamic acid during prehospital treatment. MAIN OUTCOMES AND MEASURESThe primary outcome was 30-day mortality. Secondary outcomes included mortality at 1 year, functional neurological recovery at discharge (measured by Glasgow Outcome Scale), and length of hospital stay. Data were also collected on demographic factors, preinjury medical condition, injury characteristics, operational characteristics, and prehospital vital parameters.RESULTS A total of 1827 patients were analyzed, of whom 1283 (70%) were male individuals and the median (interquartile range) age was 45 (23-65) years. In the unadjusted analysis, higher 30-day mortality was observed in patients who received prehospital tranexamic acid (odds ratio [OR], 1.34; 95% CI, 1.16-1.55; P < .001), compared with patients who did not receive prehospital tranexamic acid. After adjustment for confounders, no association between prehospital administration of tranexamic acid and mortality was found across the entire cohort of patients. However, a substantial increase in the odds of 30-day mortality persisted in patients with severe isolated TBI who received prehospital tranexamic acid (OR, 4.49; 95% CI, 1.57-12.87; P = .005) and after multiple imputations (OR, 2.05; 95% CI, 1.22-3.45; P = .007).CONCLUSIONS AND RELEVANCE This study found that prehospital tranexamic acid administration was associated with increased mortality in patients with isolated severe TBI, suggesting the judicious use of the drug when no evidence for extracranial hemorrhage is present.

The effect of prehospital tranexamic acid on outcome in polytrauma patients with associated severe brain injury

“…Our data are also in contrast with the results in the study by Bossers et al that showed an increased mortality in isolated severe TBI patients who received prehospital TXA [ 13 ]. The results of this study, however, should be interpreted with caution there were some issues regarding confounding by indication and missing data [ 17 ].…”

“…In contrast, several other studies showed no improvement in survival nor in neurologic outcome in patients with moderate to severe TBI although some studies reported a reduction in progression of intracranial hemorrhage after TXA [ 8 – 12 ]. A recent study showed even an increased mortality in patients with severe isolated TBI if TXA was prehospitally administered [ 13 ].…”

Tranexamic acid in non-traumatic intracranial bleeding: a systematic review and meta-analysis

“…This study concluded that TXA might decrease hematoma expansion on subsequent imaging and not increase the risk of adverse events 38 . However, a further study found that prehospital tranexamic acid administration was associated with increased mortality in patients with isolated severe TBI 39 . The HALT-IT randomized, double-blind, placebo-controlled trial 40 , also published in 2020, did not benefit patients suffering from acute gastrointestinal bleeding on 5 days mortality (RR 0.99, 95CI 0.82 to 1.18).…”

Does Liberal Prehospital and In‐Hospital Tranexamic Acid Influence Outcome in Severely Injured Patients? A Prospective Cohort Study

“…Data even suggest that prehospital TXA was often given in patients with TBI since patients who received prehospital TXA had higher AIShead, were more often prehospitally intubated and had higher PaCO2 with similar pH in ED (suggestive for prehospital hypoventilation) than patients who did not receive prehospital TXA. Several studies have reported various effects of TXA on outcome in TBI from depending on brain injury severity and timing of TXA administration [26] to no difference in outcome after prehospital TXA [27], or even a potential harmful effect of prehospital TXA on mortality in severe TBI patients [28]. The effect of TXA on TBI in this polytrauma population was beyond the scope of this paper.…”