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Original Investigation
December 7, 2020

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

Author Affiliations
  • 1Department of Anesthesiology, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
  • 2Department of Surgery, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
  • 3Trauma Research Unit Department of Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
  • 4Department of Anesthesiology, Radboud University Medical Center, Nijmegen, the Netherlands
  • 5Helicopter Emergency Medical Service Lifeliner 3, Nijmegen, the Netherlands
  • 6Department of Neurology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
  • 7Department of Anesthesiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
  • 8Department of Neurosurgery, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
  • 9Helicopter Emergency Medical Service Lifeliner 1, Amsterdam, the Netherlands
JAMA Neurol. 2021;78(3):338-345. doi:10.1001/jamaneurol.2020.4596
Key Points

Question  Is there an association between prehospital tranexamic acid administration and outcomes after severe traumatic brain injury (TBI)?

Findings  In this multicenter cohort study of 1827 patients, prehospital administration of tranexamic acid was associated with a statistically significant increase in the odds of mortality in patients with isolated severe TBI. No evidence of an association was observed in the overall cohort, including in patients with combined intracranial and extracranial injuries.

Meaning  Results of this study suggest that prehospital administration of tranexamic acid could lead to increased mortality in patients with isolated severe TBI.


Importance  The 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 Participants  This 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 Measures  The 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.

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