SGEM#492: Give Blood – To Anemic Patients with Acute Brain Injuries

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 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 the protection of randomization. A pure ITT analysis better preserves unbiased comparisons. Attrition and missing data can bias estimates (the authors did perform sensitivity analyses, which were consistent). 4. Heterogeneous Acute Brain Injury Etiologies: Pooling TBI, SAH, and ICH increases generalizability but risks effect modification across pathologies. Subgroup analyses largely aligned, but power for interaction is limited. We need to be skeptical of subgroup findings because of multiplicity and low power.  5. Non‑Standardized Neuroprognostication: Prognostication practices were not standardized across centers, which can influence functional outcomes and mortality decisions. The authors correctly note this as a limitation. While mortality was similar between groups, this can mitigate but not eliminate this potential bias. Comment on the Authors’ Conclusion Compared to the SGEM Conclusion: We generally agree with the authors’ conclusions. SGEM Bottom Line: An anemic brain is not a happy brain. In adults with acute brain injury and Hb ≤90 g/L, targeting a 90 g/L transfusion threshold modestly improved 6-month functional outcomes vs a 70 g/L trigger, without a mortality signal and with fewer cerebral ischemic events. Case Resolution: This patient’s Hb was 84 g/L. Therefore, we suggest giving her a transfusion of one unit of packed red blood cells to keep her Hb ≥ 90 g/L. Dr. Alex Weiler Clinical Application We need to remember that this applies to: Adults (18–80) with ABI (TBI, aneurysmal SAH, ICH) in the first 10 days, not actively bleeding, expected to require ICU care ≥72 h, and with Hb between 70 to 90 g/L. Outside of this group (massive hemorrhage, exsanguination, pregnancy, severe comorbidity extremes), extrapolate cautiously. When Hb drops below 90 g/L in eligible ABI patients, it’s reasonable to transfuse RBCs to target at least this threshold, aiming to reduce unfavourable neurological outcomes by ~10%. Use shared decision-making with neurocritical care about triggers, especially if there is clinical concern for cerebral ischemia. Don’t expect a 28-day mortality benefit or shorter ICU stays. The signal here is better functional recovery, not survival. And don’t forget to maintain standard ABI bundles (BP, oxygenation/ventilation, fever control, DVT prophylaxis). What Do I Tell the Patient/Family?  After a brain injury, the brain needs plenty of oxygen to heal. The oxygen is carried in the blood by hemoglobin. When hemoglobin levels are too low, the brain may not get enough oxygen, which can make recovery harder. Your hemoglobin is too low. We recommend a blood transfusion now to bring the hemoglobin up to a safer range. This is part of our effort to give the brain the best chance to heal. Keener Kontest: Last week’s winner was Steven Stelts from NZ. He knew the pending legislation to address HCW violence is the Save Healthcare Workers Act (H.R. 3178 / S. 1600), which would establish federal criminal penalties for assaulting healthcare workers.  Listen to the SGEM podcast for this week’s question. If you know, then send an email to thesgem@gmail.com with “keener” in the subject line. The first correct answer will receive a shoutout on the next episode. Remember to be skeptical of anything you learn,