Liberal vs. Restrictive Transfusion Strategies in TBI: A New Perspective!

Traumatic brain injuries (TBI) and subarachnoid hemorrhages (SAH) often impact young, otherwise healthy individuals, leaving them with severe, long-lasting consequences. Mortality is high following these injuries, and survivors frequently face lifelong disabilities. Despite advances in neurocritical care, interventions that improve long-term outcomes remain limited. The brain’s vulnerability to oxygen delivery variations, exacerbated by impaired cerebrovascular autoregulation during acute injuries, heightens concern over anemia's potential impact in neurocritically ill patients.

The TRICC trial [1] (1999) led to widespread adoption of restrictive transfusion strategies in critical care, showing that fewer transfusions were not inferior to more liberal strategies for short-term outcomes. However, this study involved few neurocritically ill patients, leaving questions about optimal transfusion thresholds in this population. In response, the TRAIN trial explored the effects of transfusion strategies on long-term neurological outcomes in patients with TBI, SAH, or intracerebral hemorrhage (ICH).

For patients with traumatic brain injury (TBI), what do you believe is the optimal target hemoglobin (Hg) level?

• 0%>7 g/dL
• 0%>8 g/dL
• 0%>9 g/dL

In the TRAIN trial [2], 850 patients were randomized to either a liberal transfusion strategy (maintaining hemoglobin >9 g/dL) or a restrictive one (>7 g/dL). The primary outcome—neurological function at 6 months—favored the liberal approach, showing fewer unfavorable outcomes (62.6% vs. 72.6%) across all brain injury types. Importantly, no significant differences were observed in mortality, ICU/hospital stay duration, or organ failure rates.

Despite its strengths, TRAIN's heterogeneity in neurocritical injury types has been debated. Traumatic, hemorrhagic, and ischemic injuries differ in pathophysiology, making uniform benefit from a single strategy unlikely. However, subgroup analyses consistently favored the liberal approach across all injury types, supporting its broader applicability.

The findings align with those of the HEMOTION trial [3], which also suggested potential benefits of liberal transfusions for TBI, though statistical significance was not reached. Both trials show liberal strategies improving patient independence and quality of life, underlining the importance of individualized, outcome-focused approaches in neurocritical care.

While concerns about transfusion-related complications remain, TRAIN and HEMOTION showed comparable adverse event rates between strategies. Blood product safety has improved, and the potential benefits of liberal transfusions outweigh the risks in neurocritically ill patients. Furthermore, the widespread implementation of a liberal strategy, even in low-resource settings, is feasible and could significantly improve long-term functional outcomes.

In conclusion, based on the TRAIN and HEMOTION trials, liberal transfusion thresholds should be advocated for neurocritically ill patients with traumatic brain injury aiming for Hg level of >9 g/dL.

References

1. Hébert  PC, Wells  G, Blajchman  MA,  et al; Transfusion Requirements in Critical Care Investigators; Canadian Critical Care Trials Group.  A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. N Engl J Med. 1999;340(6):409-417

2. Taccone  FS, Rynkowski Bittencourt  C, Møller  K,  et al; TRAIN Study Group.  Restrictive vs liberal transfusion strategy in patients with acute brain injury: the TRAIN randomized clinical trial.   JAMA. Published online October 9, 2024. 

3. Turgeon  AF, Fergusson  DA, Clayton  L,  et al; HEMOTION Trial Investigators; Canadian Critical Care Trials Group; Canadian Perioperative Anesthesia Clinical Trials Group; Canadian Traumatic Brain Injury Research Consortium.  Liberal or restrictive transfusion strategy in patients with traumatic brain injury. N Engl J Med. 2024;391(8):722-735.