Liberal Blood Transfusion After Traumatic Brain Injury May Hold Benefit

A liberal blood transfusion strategy didn’t reduce the risk
of an unfavorable neurologic outcome at 6 months in critically ill
patients with traumatic brain injury (TBI) but showed other possible
benefits, the HEMOTION trial found.

An unfavorable outcome occurred in 68.4% of the liberal-strategy
group and 73.5% of the restrictive-strategy group (adjusted difference
5.4 percentage points, 95% CI -2.9 to 13.7), according to Alexis
Turgeon, MD, of CHU de Québec-Université Laval in Canada, and
co-authors.

However,
the liberal strategy was tied to higher scores in some, but not all,
measures of functional independence and quality of life, the researchers
reported in the New England Journal of Medicine. The findings were presented simultaneously at the Critical Care Reviewsmeeting in Belfast, Ireland.

Outcomes significantly favored the liberal group for the following
secondary endpoints, with differences compared with restrictive
transfusion of:

• 4.34 points in overall Functional Independence Measure scores
• 5.19 points in EuroQol visual analogue scale scores
• 0.06 points in the EuroQol five-dimension, five-level utility index scores

Between
group differences were not significant for Quality of Life after Brain
Injury scores or Patient Health Questionnaire-9 scores for depression.
Minimally important differences for TBI have not been established for
these measures and no adjustment was made for multiple comparisons, the
researchers noted.

“The combined incidence of death and major disability was not
statistically different between the two groups, but seemed [to be]
favoring the liberal strategy in all analyses,” Turgeon said in a
statement.

“In
light of the overall results of our study and considering the safety of
current blood transfusions, the liberal strategy is probably the option
that should be preferred in the acute phase of care to improve
long-term prognosis following TBI,” he suggested. “By improving oxygen
transport to the brain during the acute phase of care, it may be
possible to save more nerve cells in the days following a TBI, thereby
preventing additional brain damage.”

Anemia develops in most critically ill patients with TBI and may
reduce oxygen to the brain and contribute to poor outcomes. Trials of
transfusion strategies in critically ill adults and children showed no mortality benefit in maintaining high hemoglobin levels.

“However, these trials included very few patients with neurologic
injuries and focused on mortality; they thus provide insufficient
guidance for the care of patients with traumatic brain injury, for whom
long-term neurologic function is the most important outcome,” Turgeon
and co-authors wrote.

“Clinical
guidelines and reviews comparing the effects of liberal transfusion
strategies with those of restrictive transfusion strategies emphasize
that current data are not sufficient to guide transfusion practices in
patients with traumatic brain injury,” they added.

From September 2017 to April 2023, HEMOTION
randomized 742 adults with moderate or severe TBI and anemia to receive
transfusion of red cells according to a liberal strategy (transfusions
triggered by a hemoglobin level ≤10 g/dL) or a restrictive strategy
(transfusions started at a hemoglobin ≤7 g/dL). The study was conducted
in 34 hospitals in Canada, the United Kingdom, France, and Brazil.

Trial inclusion criteria specified a Glasgow Coma Scale score of 3 to
12 (scores range from 3 to 15, and lower scores indicate lower levels
of consciousness). Most participants were men (72.7%), the mean age was
about 48, and 73.2% had severe traumatic brain injury. More than
two-thirds had extracranial injuries.

The primary endpoint was an unfavorable outcome at 6 months on the Glasgow Outcome Scale-Extended
(GOS-E). Scores on this scale range from 1 (death) to 8 (a full return
to normal life). HEMOTION researchers defined an unfavorable outcome
using a sliding dichotomy of GOS-E scores, according to the prognosis of
each patient at baseline. Secondary outcomes included mortality,
functional independence, quality of life, and depression at 6 months.

The
relative risk of an unfavorable GOS-E outcome in the liberal group
versus the restrictive group was 0.93 (95% CI 0.83-1.04). Findings were
consistent across patients with the worst, intermediate, and best
predicted prognoses and in sensitivity analyses.

Mortality was 26.8% in the liberal group and 26.3% in the restrictive
group at 6 months. Venous thromboembolic events occurred in 8.4% of
each group. Acute respiratory distress syndrome emerged in 3.3% of the
liberal-approach group and 0.8% of the restrictive group.

The trial recruited only patients with anemia, which is a population
that tends to have more severe TBI at baseline, Turgeon and co-authors
noted. “Detection of small treatment effects becomes more challenging as
the baseline risk increases,” they observed. In addition, the liberal
and restrictive groups had some imbalances at baseline.