In this episode, I’ll discuss tranexamic acid’s effects on mortality for trauma patients based on time given post-injury.
Trauma guidelines have incorporated giving tranexamic acid within 3 hours of injury, citing the CRASH-2 study as rationale for this recommendation. But the idea that time from injury to treatment matters for tranexamic acid was not pulled from the main results of the CRASH-2 study, rather it was from an exploratory analysis.
A group of authors recently discussed in Annals of Emergency Medicine that this exploratory analysis has not been reproduced in other studies. They also highlight the possibility of imprecise timing data given that CRASH-2 was conducted in low and middle income countries and the person performing data entry for the study was simply prompted to record the “estimated number of hours since injury”.
Therefore these authors sought to perform their own exploratory analysis based on the Prehospital Tranexamic Acid for Severe Trauma (PATCH-Trauma) trial, which enrolled adults with major trauma and suspected trauma-induced coagulopathy. Patients in this study were given tranexamic acid in the pre-hospital setting as a bolus dose of 1 g IV before hospital admission, followed by a 1-g infusion over 8 hours after arrival at the hospital or matched placebo.
In this cohort of over 1000 patients, the median time from injury to 1st dose of tranexamic acid was 79 minutes. The authors found that the risk of 28-day mortality increased as time to treatment increased, with benefit most pronounced up to 90 minutes. Beyond 90 minutes, the possibility of no benefit from tranexamic acid could not be excluded. The mortality rate for the tranexamic acid group who recieved it within 90 minutes of time from injury was 17%, vs 25% for placebo.
The authors conlcuded:
The optimal therapeutic window for TXA after trauma may be within 90 minutes.
Curiously, the journal’s editors added this analysis to a capsule summary of the article:
The optimal time to TXA treatment may be a window within 90 minutes after injury. Guidelines should not change until confirmation data exist.
While it is normally the case that prospective data should be used to inform major practice changes, should this be the case when the competing data sets are both exploratory analyses? Why should the older one be given precedent without consideration to things like the precision of the data collection in each study? Especially because another study of tranexamic acid in the prehospital setting also found in a post hoc analysis that the mortality benefit seemed confined to the group of patients that got tranexamic acid within 1 hour of injury.
This seems like a hasty claim by the journal editors and I would not be surprised if clinicians and eventually guidelines decide that a shorter window from time of injury to treatment is preferred for tranexamic acid use in patients with trauma.
The topic in this episode is inspired by an in-depth training available to members of my Hospital Pharmacy Academy. The Hospital Pharmacy Academy is my online membership site that will teach you practical critical care and hospital pharmacy skills you can apply at the bedside so that you can become confident in your ability to save lives and improve patient outcomes. To get immediate access to this and many other resources to help in your practice, go to pharmacyjoe.com/academy.
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