Restrictive vs Liberal Transfusion Strategy in Traumatic Brain Injury A Secondary Analysis of the TRAIN Trial
et al
2026년09월08일
JAMA Neurol. Published online: September 8, 2026.
DOI:10.1001/jamanetwokropen.2026.32555
Abstract
Importance Anemia is a prevalent condition among patients with traumatic brain injury (TBI); however, the optimal hemoglobin (Hb) threshold to initiate red blood cell transfusion (RBCT) is not well defined.
Objective To assess which of 2 different Hb thresholds for guiding RBCT in patients with anemia and TBI is associated with a more favorable neurological outcome.
Design, Setting, and Participants This was a preplanned secondary analysis of the Transfusion Strategies in Acute Brain Injured Patients multicentric randomized clinical trial, conducted in 72 intensive care units across 22 countries between September 1, 2017, and December 31, 2022. Follow-up was completed June 30, 2023. Only patients with TBI were included in the present analysis, conducted from February to May 2025.
Intervention Liberal (transfusion at Hb <9 g/dL [to convert to g/L, multiply by 10.0]) vs restrictive (transfusion at Hb <7 g/dL) RBCT strategy over a maximum of 28 days.
Main Outcomes and Measures The primary outcome was the occurrence of unfavorable neurological outcome, defined as a Glasgow Outcome Scale Extended score of 1 to 5 (overall range, 1-8, with higher scores indicating more favorable outcome) at 180 days. In addition, 14 prespecified serious adverse events, including infection and cerebral ischemia, were assessed. Data were analyzed using both the intention-to-treat and per-protocol principles.
Results Of 486 patients who presented with TBI (mean [SD] age, 46.8 [17.6] years; 347 [71.4%] male), 475 were included in the primary outcome analysis: 236 were randomized to the liberal transfusion strategy group and 239 to the restrictive transfusion strategy group. Both groups had similar baseline characteristics. In total, 534 RBCTs were administered in the liberal transfusion strategy group, compared with 246 RBCTs in the restrictive group. At 180 days after randomization, 138 patients (58.5%) in the liberal group had unfavorable neurological outcome compared with 161 patients (67.4%) in the restrictive group (relative risk [RR], 0.86 [95% CI, 0.75-1.00]; P = .047; fragility index = 1). There were no significant differences in the occurrence of secondary outcomes (eg, 28-day mortality: 42 of 240 [17.5%] vs 51 of 244 [20.9%]; RR, 0.84 [95% CI, 0.58-1.21]; P = .34) or serious adverse events (eg, RR, 1.13 [95% CI, 0.88-1.43]; P = .34 for infection and RR, 0.87 [95% CI, 0.40-1.90]; P = .72 for cerebral ischemia). After adjustment for several confounders, being randomized to the liberal group was associated with a lower observed probability of unfavorable neurological outcome (odds ratio, 0.60 [95% CI, 0.38-0.94]; P = .03).
Conclusions and Relevance In this secondary analysis of a multicenter randomized clinical trial, a liberal RBCT strategy was associated with a lower risk than a restrictive RBCT strategy of unfavorable neurological outcome at 180 days among patients with TBI. These findings should be interpreted with caution in light of the inherent uncertainty of the estimate.
Trial Registration ClinicalTrials.gov Identifier: NCT02968654
Key Points
Question Is the use of a liberal vs a restrictive red blood cell transfusion strategy associated with more favorable neurological outcome among patients with traumatic brain injury (TBI)?
Findings In this prespecified secondary analysis of a randomized clinical trial including 475 patients with TBI and hemoglobin levels below 9 g/dL, patients treated with a liberal transfusion strategy vs a restrictive strategy had a lower probability (58.5% vs 67.4%) of unfavorable neurological outcome at 180 days.
Meaning These findings suggest that a liberal transfusion strategy is associated with a lower rate of unfavorable neurological outcome compared with a restrictive strategy among patients with TBI.
요약
· 중요성 : 빈혈은 외상성 뇌손상(TBI) 환자에서 흔하게 나타나는 상태이지만, 적혈구 수혈(RBCT)을 시작하기 위한 최적의 헤모글로빈(Hb) 기준치는 명확하게 확립되어 있지 않다.
· 목적: 빈혈을 동반한 TBI 환자에서 적혈구 수혈을 결정하기 위한 두 가지 서로 다른 Hb 기준치 중 어느 전략이 더 양호한 신경학적 예후와 관련되는지를 평가하고자 하였다
· 설계, 환경 및 참가자 : Transfusion Strategies in Acute Brain Injured Patients(TRAIN) 다기관 무작위 임상시험의 사전 계획된 이차 분석이다. 원 연구는 2017년 9월 1일부터 2022년 12월 31일까지 22개국 72개 중환자실에서 수행되었으며, 추적관찰은 2023년 6월 30일에 완료되었다. 이번 분석에는 TBI 환자만 포함하였으며, 분석은 2025년 2월부터 5월까지 수행되었다.
· 중재 : 최대 28일 동안 자유로운(liberal) 적혈구 수혈 전략(Hb <9 g/dL에서 수혈)과 제한적(restrictive) 수혈 전략(Hb <7 g/dL에서 수혈)을 비교하였다. [Hb를 g/L로 환산하려면 10.0을 곱한다.]
· 주요 평가 변수 및 측정: 무작위 배정 후 180일째 불량한 신경학적 예후의 발생으로 정의하였다. 불량한 신경학적 예후는 Glasgow Outcome Scale Extended(GOSE) 점수 1~5점으로 정의하였다. GOSE의 전체 범위는 1~8점이며, 점수가 높을수록 더 양호한 예후를 의미한다. 또한 감염과 뇌허혈을 포함한 사전에 정의된 14개의 중대한 이상반응을 평가하였다. 자료는 intention-to-treat(ITT) 원칙과 per-protocol(PP) 원칙을 모두 적용하여 분석하였다.
· 결과 :
전체 TBI 환자: 486명
일차 결과 분석: 475명
- Liberal: 236명
- Restrictive: 239명
평균 연령: 46.8세
남성: 71.4%
적혈구 수혈 횟수
- Liberal: 534회
- Restrictive: 246회
180일 불량한 신경학적 예후 (GOSE 1–5)
- Liberal: 58.5% (138명)
- Restrictive: 67.4% (161명)
- RR 0.86 (95% CI 0.75–1.00), P=.047
- Fragility index = 1
28일 사망률
- Liberal: 17.5%
- Restrictive: 20.9%
- RR 0.84, P=.34 → 유의한 차이 없음
감염: RR 1.13, P=.34 → 차이 없음
뇌허혈: RR 0.87, P=.72 → 차이 없음
보정 분석: OR 0.60 (95% CI 0.38–0.94), P=.03
핵심 수치: 180일 불량 예후 58.5% vs 67.4%, RR 0.86, P=.047 → Liberal 수혈군에서 불량한 신경학적 예후가 더 적었습니다.
· 결론 및 의의 : 이 다기관 무작위 임상시험의 이차 분석에서 TBI 환자에게 자유로운 적혈구 수혈 전략을 적용한 경우 제한적 수혈 전략에 비해 180일째 불량한 신경학적 예후의 위험이 더 낮은 것과 관련되어 있었다. 그러나 효과 추정치에 내재된 불확실성을 고려하여 이러한 결과는 신중하게 해석해야 한다.
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