Date: November 12, 2025 Reference: Taccone et al. Restrictive vs Liberal Transfusion Strategy in Patients With Acute Brain Injury The TRAIN Randomized Clinical Trial. JAMA 2024 Guest Skeptic: Dr. Alex Weiler is an Emergency Department staff physician in the Peterborough Regional Health Centre and is an associate professor with Queen's University Department of Family Medicine. This podcast was recorded live at the Kawartha EM Conference in beautiful Peterborough, Ontario. Case: A 48-year-old woman presents with a sudden, severe headache and brief loss of consciousness. CT/CTA confirms aneurysmal subarachnoid hemorrhage (SAH). She is coiled and admitted to the intensive care unit (ICU) with an external ventricular drain. On ICU day 3, Hb is 8.4 g/dL (or as we say in Canada 84 g/L), she is not actively bleeding, Glasgow Coma Scale (GCS) of 10 with fluctuating attention, and her expected ICU stay is clearly >72 hours. Background: Acute brain injury (ABI) can occur for a variety of reasons, including aneurysmal SAH (like in this case) or trauma. Anemia is common in patients with ABI and can worsen cerebral hypoxia. For decades, ICU transfusion practice drifted toward “restrictive” triggers (Hb <7 g/dL or <70g/L) based on trials in mixed ICU populations. However, brain-injured patients may not behave like the average ICU patient. The brain is uniquely sensitive to oxygen delivery, and secondary ischemia strongly predicts poor neurological outcomes. Small single-center studies and physiologic work suggested higher hemoglobin could improve brain tissue oxygenation; however, prior randomized evidence has been sparse or inconclusive in discrete ABI subgroups (traumatic brain injury [TBI], SAH), leaving real uncertainty about the optimal transfusion threshold for this population. The TRAIN trial was designed to answer a practical question that matters at the bedside: in adults with ABI who are anemic but not exsanguinating, does a liberal transfusion strategy improve downstream neurological outcomes compared with a restrictive strategy? Clinical Question: In adults with acute brain injury (TBI, aneurysmal SAH, or ICH) who are anemic (Hb <90 g/L), does a liberal RBC transfusion threshold (transfuse when Hb <90 g/L) compared with a restrictive threshold (transfuse when Hb <70 g/L) improve 6-month neurological outcomes? Reference: Taccone et al. Restrictive vs Liberal Transfusion Strategy in Patients With Acute Brain Injury The TRAIN Randomized Clinical Trial. JAMA 2024 Population: Adults (18 to 80) in 72 ICUs across 22 countries with TBI, SAH, or ICH. They needed to have an Hb <90 g/L within 10 days of injury and an expected ICU stay of ≥72 hours. Exclusions:Hb >90 g/L, GCS 3 with fixed/dilated pupils, GCS >13 at randomization, active bleeding, expected ICU stay <3 days, prior neurological disease, pregnancy, inability to receive transfusion; others are listed in the flow diagram. Intervention: Liberal strategy (transfuse when Hb <90 g/L for 28 days). Comparison: Restrictive strategy (transfuse when Hb <70 g/L for 28 days). Outcome: Primary Outcome: Unfavourable neurological outcome at 180 days, GOS‑E 1 to 5 (death to severe disability). Secondary Outcomes: 28-day mortality; composite of death or organ failure at day 28; organ failure; ICU/hospital LOS; distribution (“shift”) of GOS‑E; prespecified serious adverse events (cerebral ischemic events, VTE, infections, TRALI, anaphylaxis). Type of Study: A multicenter, pragmatic, parallel group, open-label, RCT Authors’ Conclusions: “Patients with acute brain injury and anemia randomized to a liberal transfusion strategy were less likely to have an unfavorable neurological outcome than those randomized to a restrictive strategy.” Quality Checklist for Randomized Clinical Trials: The study population included or focused on those in the ED. No The patients were adequately randomized. Yes The randomization process was concealed. Yes The patients were
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