Abstract

Importance

Blood transfusions are commonly administered to patients with acute brain injury. The optimal hemoglobin transfusion threshold is uncertain in this patient population.

Objective

To assess the impact on neurological outcome of 2 different hemoglobin thresholds to guide red blood cell transfusions in patients with acute brain injury.

Design, Setting, and Participants

Multicenter, phase 3, parallel-group, investigatorinitiated, pragmatic, open-label randomized clinical trial conducted in 72 intensive care units across 22 countries. Eligible patients had traumatic brain injury, aneurysmal subarachnoid hemorrhage, or intracerebral hemorrhage; hemoglobin values below 9 g/dL within the first 10 days after injury; and an expected intensive care unit stay of at least 72 hours. Enrollment occurred between September 1, 2017, and December 31, 2022. The last day of follow-up was June 30, 2023.

Interventions

Eight hundred fifty patients were randomly assigned to undergo a liberal (transfusion triggered by hemoglobin <9 g/dL; n = 408) or a restrictive (transfusion triggered by hemoglobin <7 g/dL; n = 442) transfusion strategy over a 28-day period.

Main Outcomes and Measures

The primary outcome was occurrence of an unfavorable neurological outcome, defined as a Glasgow Outcome Scale Extended score between 1 and 5, at 180 days following randomization. There were 14 prespecified serious adverse events, including occurrence of cerebral ischemia after randomization.

Results

Among 820 patients who completed the trial (mean age, 51 years; 376 [45.9%] women), 806 had available data on the primary outcome, 393 in the liberal strategy group and 413 in the restrictive strategy group. The liberal strategy group received a median of 2 (IQR, 1-3) units of blood, and the restrictive strategy group received a median of 0 (IQR, 0-1) units of blood, with an absolute mean difference of 1.0 unit (95% CI, 0.87-1.12 units). At 180 days after randomization, 246 patients (62.6%) in the liberal strategy group had an unfavorable neurological outcome compared with 300 patients (72.6%) in the restrictive strategy group (absolute difference, −10.0% [95% CI, −16.5% to −3.6%]; adjusted relative risk, 0.86 [95% CI, 0.79-0.94]; P = .002). The effect of the transfusion thresholds on neurological outcome at 180 days was consistent across prespecified subgroups. In the liberal strategy group, 35 (8.8%) of 397 patients had at least 1 cerebral ischemic event compared with 57 (13.5%) of 423 in the restrictive strategy group (relative risk, 0.65 [95% CI, 0.44-0.97]).

Conclusions and Relevance

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.

Trial Registration

ClinicalTrials.gov Identifier: NCT02968654

Key Points

Question How does use of a liberal or restrictive strategy of blood transfusion influence neurological outcome among patients with acute brain injury?

Findings In this randomized clinical trial that included 850 patients with acute brain injury and a hemoglobin level below 9 g/dL, those who were treated with a liberal transfusion strategy triggered by hemoglobin below 9 g/dL had a lower probability of unfavorable neurological outcome at 180 days than those treated with a restrictive strategy triggered by hemoglobin below 7 g/dL (62.6% vs 72.6%, respectively; adjusted relative risk, 0.86).

Meaning A liberal transfusion strategy compared with a restrictive strategy resulted in a lower rate of unfavorable neurological outcome among patients with acute brain injury.

요약

소개 : 대부분의 급성 뇌손상 환자에서 수혈이 시행되지만, 수혈을 위한 최적의 헤모글로빈 수치 적응증은 아직 확립되어 있지 않다. 본 연구는 급성 뇌손상 환자의 치료에서 개방적인 수혈(Liberal transfusion strategy)과 제한적인 수혈(Restrictive transfusion strategy)의 신경학적 결과(neurological outcome)의 차이를 확인하고자 하는 무작위 임상연구이다.

방법 : 급성 뇌손상 이후 10일 이내에 헤모글로빈 수치가 9 g/dL 미만의 빈혈이 발생한 820명의 환자를 대상으로한 다기관 무작위 임상연구이다. 급성 뇌손상에는 외상성 뇌손상, 뇌동맥류 지주막하 출혈, 뇌내출혈을 포함한다. 무작위로 배정된 환자군은 각각 개방적인 수혈(Hb < 9 g/dL일 경우 수혈)과 제한적인 수혈(Hb < 7 g/dL일 경우 수혈)을 받았다. 주요 임상결과(primary outcome)는 좋지 않은 신경학적 결과(unfavorable neurological outcome, 5점 이하의 GOS-E 점수)으로 설정하였다.

결과 : 무작위 배정 및 수혈 180일 후, 개방적인 수혈을 받은 246명의 환자(62.6%)에서 좋지 않은 신경학적 결과를 보였고, 제한적인 수혈을 받은 300명의 환자(72.6%)에서 좋지 않은 신경학적 결과를 보였다.

결론 및 의의 : 급성 뇌손상 환자에서 빈혈이 발생했을 때 개방적인 수혈 전략이 제한적인 수혈 전략에 비해 좋지 않은 신경학적 결과 비율을 낮출 수 있다.