The Skeptics Guide to Emergency Medicine

SGEM#293: CRASH in the US, CRASH in the US, CRASH-2 in the USA


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Date: May 29th, 2020
Reference: Erramouspe et al. Mortality and Complication Rates in Adult Trauma Patients Receiving Tranexamic Acid: A Single-center Experience in the Post–CRASH-2 Era. AEM May 2020
Guest Skeptic: Dr. Corey Heitz is an emergency physician in Roanoke, Virginia. He is also the CME editor for Academic Emergency Medicine.
Case: A 44-year-old male presents to your level 1 trauma center by EMS after a motor vehicle collision. He is hypotensive and tachycardic. You suspect abdomen and pelvic trauma and calculate his injury severity score (ISS) to be 22. Your hospital protocol is to give tranexamic acid (TXA) 1g IV over 10 minutes followed by a 1g infusion over eight hours. You wonder what his over-all chance of dying or developing a thromboembolic event when treated with TXA.
Background: TXA is synthetic derivative of lysine that controls bleeding by inhibiting fibrinolysis and thus stabilizing clots that are formed.  We have covered TXA as a treatment modality a number of times on the SGEM. The evidence for TXA providing a patient-oriented outcome (POO) has been mixed. It seems to work for epistaxis (SGEM#53 and SGEM#210), failed to demonstrate a decrease in all-cause mortality in post-partum hemorrhage (SGEM#214), and did not result in an improved neurologic outcome in hemorrhagic strokes (SGEM#236).
REBEL EM has looked at using TXA for those conditions plus a few others (we will include a table in the show notes). It is unclear if it provides a benefit for gastrointestinal bleeds (GIB). Nebulized TXA shows promise for both post-tonsillectomy bleeding and hemoptysis. However, better studies are needed to confirm these observations.

Dr. Anand Swaminathan and I covered the classic CRASH-2 Trial (SGEM#80). This study published in 2010 showed an absolute mortality reduction of 1.5% in adult trauma patients giving a number needed to treat to prevent one death of 67 (Shakur et al. Lancet 2010)
CRASH-3 was a well-designed, large, multi-centred randomized placebo controlled trial published in October 2019 (The Lancet). It asked if TXA had a mortality benefit in patients with isolated head trauma (SGEM#270)? While there was a suggestion of benefit in a secondary subgroup analysis, the primary outcome demonstrated no statistical difference in head-injury related mortality with TXA compared to placebo (18.5% TXA vs. 19.8% placebo, RR 0.94 [95% CI 0.86 to 1.02]).
One of the limitations to both CRASH-2 and CRASH-3 was the external validity. The majority of sites involved were in middle to low income countries. CRASH-3 had one Canadian site and the USA had no participating centres. Transfusion practices and identification of adverse events may differ in developing countries compared to the USA.

Clinical Question: What is the mortality and thromboembolic events in adult trauma patients receiving TXA an American Level 1 Trauma Center?

Reference: Erramouspe et al. Mortality and Complication Rates in Adult Trauma Patients Receiving Tranexamic Acid: A Single-center Experience in the Post–CRASH-2 Era.
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