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 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 analyzed in the groups to which they were randomized. No The study patients were recruited consecutively (i.e. no selection bias). Unsure The patients in both groups were similar with respect to prognostic factors. Yes All participants (patients, clinicians, outcome assessors) were unaware of group allocation. No All groups were treated equally except for the intervention. Unsure Follow-up was complete (i.e. at least 80% for both groups). Yes All patient-important outcomes were considered. Yes The treatment effect was large enough and precise enough to be clinically significant. Yes Financial conflicts of interest. Funded by non-profit sources, and the sponsors had no role in design/analysis/reporting. Minor author disclosures unrelated to the intervention were reported. Results: 820 completed the trial, with 806 having the primary outcome (393 liberal; 413 restrictive). Mean age 51 and 46% women. The type of brain injury was ~59% TBI, 23% SAH, 18% ICH overall. GCS at randomization was 6 [IQR 3–8] and was Hb 85 g/L [IQR ~80 to 88]. A median of two units (IQR 1–3) were transfused in the liberal vs 0 units (IQR 0–1) in restrictive, giving an absolute mean difference 1.0 unit (95% CI 0.87–1.12). Key result: A liberal threshold (Hb <90 g/d) reduced unfavourable neurological outcome at 180 days compared with a restrictive (Hb <70 g/L). Primary Outcome: Unfavourable GOS E 1–5 at 180 days was 63% liberal vs 73% restrictive ARR 10% (95% CI 3.6–16.5) RR 0.86 (95% CI 0.79–0.94), p=0.002. NNT 10 to prevent one additional unfavourable outcome Secondary Outcomes: No statistical difference in 28-day mortality: 21% liberal vs 23% restrictive; RR 0.95 (95% CI 0.74–1.22) No statistical difference in the composite outcome of death/organ failure at day 28, organ failure, or ICU LOS Serious adverse events were similar between groups 1. Performance Bias: Bedside teams knew the assignment (open-label), which can bias outcomes even with masked assessors. The investigators acknowledge awareness of group assignment and incomplete assessment of co-interventions as a limitation. 2. Detection Bias: Cerebral infarction was identified at clinicians’ discretion rather than by systematic imaging, risking underascertainment bias (detection bias). The authors appropriately called the serious adverse event (SAE) data exploratory. 3. Analysis Bias: The primary analysis excluded patients who withdrew consent post‑randomization (modified Intention-to-Treat analysis [mITT]). While common, exclusion after randomization can erode th
