SGEM#270: CRASH-3 TXA for Traumatic Head Bleeds?

Date: October 14th, 2019 Reference: CRASH-3 Trial Collaborators. 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. The Lancet October 2019 Guest Skeptic: Dr. Salim Rezaie currently works as a community emergency physician at Greater San Antonio Emergency Physicians (GSEP), where he is the director of clinical education. He is also the creator and founder of REBEL EM and REBEL Cast, a free, critical appraisal blog and podcast that tries to cut down knowledge translation gaps of research to bedside clinical practice. Case: A 42-year-old man falls off a backyard deck. He arrives at the emergency department via EMS with a Glasgow Coma Scale (GCS) score of 10 and both pupils reactive. He is hemodynamically stable and sent for a STAT head CT. It demonstrates a traumatic intracranial hemorrhage. You wonder if you should give tranexamic acid (TXA) while you wait for neurosurgery to call you back. Background: TXA is a synthetic derivative of lysine that inhibits fibrinolysis and thus stabilizing clots that are formed. We have covered TXA as a treatment for bleeding 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, fails to cause a decrease in all-cause mortality in post-partum hemorrhage, does not demonstrate an improved neurologic outcome in hemorrhagic strokes but does have 1.5% absolute mortality reduction in adult trauma patients. Epistaxis – SGEM#53 and SGEM#210 Post-Partum Hemorrhage – SGEM#214 Stroke due to Intracranial Hemorrhage – SGEM#236 CRASH-2 Trial – SGEM#80 REBEL EM has also looked at TXA for those conditions plus a few others. 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. Zehtabchi et al published a SRMA of TXA for traumatic brain injuries (TBI). They found only two high-quality randomized control trials with 510 patients having TBI that met inclusion criteria. The results were no statistical difference in in-hospital mortality or unfavorable neurologic functional status. However, there was a statistical reduction in intracranial hematoma expansion size with TXA compared to placebo. Clinical Question: Does TXA have mortality benefit in patients with isolated head trauma? Reference: CRASH-3 Trial Collaborators. 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. The Lancet October 2019 Population: Adult patients 16 years and older with traumatic brain injuries with GCS score of 12 or lower or any intracranial bleed on CT scan and no extracranial bleeding treated within 3 hours of injury Excluded: Age less than 16 years of age, extracranial bleeding, or greater than 8 hours since injury (limited to greater than 3 hours from September, 2016) Intervention: TXA 1g infused over 10 minutes followed by an infusion of another 1g over 8 hours Comparison: Saline placebo Outcome: Primary Outcome: Head injury-related deaths within 28 days Secondary Outcomes: Early head injury deaths (<24hrs), all-cause and cause specific mortality, disability, vascular occlusive events (myocardial infarctions, stroke, venous thromboembolism), seizures, complications, neurosurgery, days in the intensive care unit (ICU), adverse events within 28 days and subgroup analyses. Authors’ Conclusions: “Our results show that tranexamic acid is safe in patients with TBI and that treatment within 3 h of injury reduces head injury-related death. Patients should be treated as soon as possible after injury.”