CRASH 3 – TXA for TBI

October 25, 2019

Written by Clay Smith

Spoon Feed
TXA appears to have a slight 28-day mortality benefit in traumatic brain injury (TBI) patients with a GCS ≥9, especially when given early.

Why does this matter?
CRASH 2 found that TXA decreased mortality from bleeding in trauma patients. But it didn’t reduce transfusion requirement.

CRASH 3 – Heads Up!
This was a double blinded RCT with 9,127 included patients with TBI (GCS ≤12 or injury on CT) who received TXA or placebo within 3 hours. Included patients also could not have obvious extracranial bleeding. Patients were given TXA 1g over 10 minutes plus 1g over the next 8 hours. There were initially >12,000 patients, but only those who received it in <3 hours were included. Groups were well matched. In all patients given drug in under 3 hours, mortality at 28 days due to head injury was 18·5% TXA vs 19·8% placebo (risk ratio, RR 0·94, 95%CI 0·86–1·02). In the sensitivity analysis in which patients with GCS 3 or non-reactive pupils were excluded, 28-day mortality due to head injury was 12·5% TXA vs. 14·0% placebo (RR 0·89, 95%CI 0·80–1·00). In the subgroup with CGS 9-15, “mild to moderate head injury,” mortality was 166/2846 (5·8%) vs. 207/2769 (7·5%); RR 0·78, 95%CI 0·64–0·95. There was no mortality difference in the subgroup with more severe head injury, GCS 3-8. For less severe head injury cases, the earlier it was given, the greater the improvement in mortality. TXA was again safe to use, with no increase in clotting-related vascular events or other adverse outcomes. Among survivors, there was no improvement in TXA vs placebo in patient-centered disability, such as percentage confined to bed or who were unable to wash or dress themselves – each had about 12-13% with those bad outcomes. My take is that TXA appears to have a slight benefit in patients with a GCS ≥9, especially when given early. I think I would want it and would want my family to receive it. It is cheap, safe, and may help.

Another Spoonful

• See this comprehensive review on REBEL EM. It is excellent.

• EM Nerd feels dissatisfied. Hard to disagree.

• The Skeptics Guide to EM did a podcast the day this paper came out! That’s impressive!

• EM Lit of Note laments that all-cause mortality is unchanged, and I love this quote regarding no improvement in disability, “The ultimate flavor of their observations are somewhat embittered by these loamy morsels.” Read more about the loamy morsels here.

Source
Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomised, placebo-controlled trial. Lancet. October 14 2019.

Reviewed by Thomas Davis