EBM Review Series: Restrictive vs Liberal Transfusion Strategy in Patients With Acute Brain Injury
VACEP Evidence-Based Medicine for General Emergency Physicians Series
Authors: Bianca Mayfield, DO PGY-3 & Donald Engle, MD | Naval Medical Center Portsmouth
Reviewer: Ryan Danko, MD PGY-3 & Jordan Tozer, MD | VCU Health
The VACEP Evidence-Based Medicine Review Series allows Virginia emergency medicine residents and attendings to share and analyze a recent peer-reviewed clinical study. You can also read the full article, “Restrictive vs Liberal Transfusion Strategy in Patients With Acute Brain Injury” from the Journal of the American Medical Association, Volume 332 Number 19.
THE CASE
A 51-year-old man with a history of hypertension presents to the emergency department with sudden-onset altered mental status. EMS reports the symptoms began abruptly while he was at home. On arrival, the patient is intubated for a Glasgow Coma Scale (GCS) of 7. CT imaging reveals a subarachnoid hemorrhage, and his hemoglobin level is 8 g/dL. While awaiting ICU bed placement, you consider:
Should your ED management include transfusion of packed red blood cells?
BACKGROUND
Traumatic brain injury (TBI) is a common presentation in emergency medicine, accounting for roughly 2 million ED visits annually in the U.S., with over 250,000 hospitalizations and 50,000 deaths. Many of these patients receive red blood cell transfusions, but the ideal hemoglobin threshold has remained unclear.
The 1999 TRICC trial showed that in critically ill patients, maintaining a hemoglobin between 7 and 9 g/dL was safe. As a result, restrictive transfusion strategies became the norm. The 2024 HEMOTION trial suggested that more liberal thresholds (≥10 g/dL) might improve neurologic outcomes in TBI patients, but the results were not statistically significant. Given the lack of a clear answer, the TRAIN trial was conducted to help define best practices for transfusion in acute brain injury.
STUDY SUMMARY
The TRAIN (Transfusion Strategies in Acute Brain Injured Patients) trial was a multicenter, open-label, randomized controlled trial that enrolled 850 adults (ages 18–80) with traumatic brain injury, aneurysmal subarachnoid hemorrhage, or intracerebral hemorrhage, each with hemoglobin <9 g/dL, GCS ≤13, and an expected ICU stay of ≥72 hours.
Patients were randomized to:
Liberal strategy: transfuse if hemoglobin <9 g/dL
Restrictive strategy: transfuse if hemoglobin <7 g/dL
Primary Outcome:
Unfavorable neurologic outcome at 180 days, defined as a Glasgow Outcome Scale Extended (GOS-E) score of 1 through 5 out of 8:
Death
Vegetative state
Lower severe disability (dependent for care, limited function at home)
Upper severe disability (independent at home but unable to resume normal activities)
Low moderate disability (independent at home but dependent outside)
Upper moderate disability (able to return to work even with special arrangement)
Low good recovery (return to normal life with minor neurological or psychological deficits
Upper good recovery (resumption of normal life without disabling deficits)
Baseline GOS-E was not documented; scores were assessed at 6 months.
Key Results:
Liberal group: 62.6% had an unfavorable outcome
Restrictive group: 72.6% had an unfavorable outcome
Absolute risk reduction: 10%
Adjusted relative risk: 0.86 (95% CI, 0.76 to 0.97; P = .002)
Number Needed to Treat (NNT): 10 — for every 10 patients treated with a liberal transfusion strategy, 1 additional patient had a better neurologic outcome
The liberal group also had fewer new cerebral ischemic events, indicating a lower rate of secondary brain injury from reduced perfusion after the initial insult.
There was no difference in secondary outcomes between groups including 28-day mortality (20.7% vs 22.5), organ failure (78.6% vs 77.5%) and ICU length of stay (21.4 days vs 22.5 days)
About the EBM Review Series
This is a literature review series started by the University of Virginia’s Josh Easter, MD, MSc, a VACEP board member working to connect the academic community in Virginia. We invite each residency in Virginia (and D.C.) to create a faculty/resident team to submit and review articles. Sign up to submit one.
Goals
Provide a brief monthly synopsis of a high yield article germane to the practice of emergency medicine for distribution to all VACEP members
Provide an opportunity for a peer reviewed publication and invited presentation for faculty and trainees
Foster an academic community focused on evidenced based medicine for emergency medicine residency programs in the region
STRENGTHS and LIMITATIONS:
Strengths:
This was a large, randomized, international study, which enhances generalizability to a wide variety of clinical settings. The study groups were well-matched at baseline, including similar GCS scores, hemoglobin levels, and injury mechanisms. Importantly, the outcome measure—functional status at six months—was both patient-centered and clinically meaningful, making the results directly applicable to real-world decision-making.
Limitations:
Enrollment was slower than anticipated, requiring two sample size adjustments. The trial was unblinded, and ICU clinicians were aware of group assignments, potentially introducing bias. Neuroprognostication was not standardized, meaning decisions about withdrawing life- sustaining therapy were left to individual teams, which may have influenced long-term outcomes. Additionally, some patients received transfusions before randomization, narrowing the difference in transfusion exposure between groups.
CASE CONCLUSION
Given your patient’s subarachnoid hemorrhage and hemoglobin of 8 g/dL, you decide to transfuse to a goal hemoglobin of ≥9 g/dL. This is supported by the TRAIN trial, which showed a modest but meaningful improvement in long-term neurologic outcome with a liberal transfusion strategy.
DISCUSSION
The TRAIN trial provides strong evidence that liberal transfusion thresholds (Hb ≥9 g/dL) may improve outcomes in patients with moderate to severe brain injury. While restrictive transfusion strategies are well supported in general critical care, the brain appears to be more sensitive to anemia. Transfusing earlier may reduce secondary ischemic injury and improve recovery. For emergency physicians, this trial offers practical guidance. In patients with traumatic or hemorrhagic brain injury and hemoglobin <9 g/dL, early transfusion is now a reasonable and evidence-based approach.
REFERENCES
Taccone FS, Rynkowski CB, Møller K, et al. Restrictive vs Liberal Transfusion Strategy in Patients With Acute Brain Injury: The TRAIN Randomized Clinical Trial. JAMA. 2024;332(19):1623–1633. doi:10.1001/jama.2024.20424
Hébert PC, Wells G, Blajchman MA, et al. A Multicenter, Randomized, Controlled Clinical Trial of Transfusion Requirements in Critical Care. N Engl J Med. 1999;340(6):409–417.
Burns KEA, Meade MO, Lessard MR, et al. Liberal vs Restrictive Red Blood Cell Transfusion Strategy in Traumatic Brain Injury: The HEMOTION Randomized Clinical Trial. JAMA. 2024;331(12):1095–1105.
DISCLAIMER
The views expressed in this review are those of the author(s) and do not reflect the official policy or position of the Department of the Navy, Department of Defense, or the United States Government. This work was prepared by military service members as part of their official duties. Title 17 U.S.C. §105 provides that copyright protection is not available for any work of the United States Government.
