近日，比利时布鲁塞尔自由大学Fabio Silvio Taccone团队比较了限制与自由输血对急性脑损伤患者的神经功能预后。该项研究成果发表在2024年10月9日出版的《美国医学会杂志》上。

输血通常用于急性脑损伤患者。在该患者群体中，最佳血红蛋白输注阈值尚不确定。

为了评估两种不同血红蛋白阈值对神经系统预后的影响，以指导急性脑损伤患者的红细胞输注，研究人员在22个国家的72个重症监护室进行了一项多中心、3期临床、平行组、研究者发起、实用、开放标签的随机临床试验。符合条件的患者患有创伤性脑损伤、动脉瘤性蛛网膜下腔出血或脑出血；受伤后前10天内血红蛋白值低于9g/dL；预计在重症监护室住院至少72小时。报名时间为2017年9月1日至2022年12月31日。随访的最后一天是2023年6月30日。

850名患者被随机分配在28天内接受自由（血红蛋白<9 g/dL引发的输血；n=408）或限制性（血红蛋白<7 g/dL触发的输血；n=442）输血策略。主要结局是随机分组后180天出现不良神经预后，定义为格拉斯哥结局量表扩展评分在1到5之间。有14例预先指定的严重不良事件，包括随机化后发生脑缺血。

在完成试验的820名患者中（平均年龄51岁；376名[45.9%]女性），806名患者有主要结局的可用数据，自由策略组393名，限制策略组413名。自由策略组接受的血液中位数为2（IQR，1-3）个单位，限制策略组接受了0（IQR）个单位的血液中位数，绝对平均差为1.0个单位（95%CI，0.87-1.12个单位）。随机分组后180天，自由策略组有246名患者（62.6%）的神经系统预后不良，而限制策略组有300名患者（72.6%）（绝对差异为-10.0%[95%CI，-16.5%至-3.6%]；调整后的相对风险为0.86[95%CI:0.79-0.94]；P=0.002）。输血阈值对180天时神经系统预后的影响在预先指定的亚组中是一致的。自由策略组397名患者中有35名（8.8%）至少发生过一次脑缺血事件，而在限制策略组423名患者中有57名（13.5%）（相对风险，0.65[95%CI，0.44-0.97]）。

研究结果表明，与随机分配到限制性策略的患者相比，随机分配到自由输血策略的急性脑损伤和贫血患者不太可能出现不利的神经结局。

附：英文原文

Title: Restrictive vs Liberal Transfusion Strategy in Patients With Acute Brain Injury: The TRAIN Randomized Clinical Trial

Author: Fabio Silvio Taccone, Carla Rynkowski Bittencourt, Kirsten Mller, Piet Lormans, Manuel Quintana-Díaz, Anselmo Caricato, Marco Antonio Cardoso Ferreira, Rafael Badenes, Pedro Kurtz, Christian Baastrup Sndergaard, Kirsten Colpaert, Leticia Petterson, Herve Quintard, Raphael Cinotti, Elisa Gouvêa Bogossian, Cassia Righy, Serena Silva, Erik Roman-Pognuz, Catherine Vandewaeter, Daniel Lemke, Olivier Huet, Ata Mahmoodpoor, Aaron Blandino Ortiz, Mathieu van der Jagt, Russell Chabanne, Walter Videtta, Pierre Bouzat, Jean-Louis Vincent, TRAIN Study Group, Claudia Díaz, Andrés Saravia, Ahmas Bayrlee, Laura Nedolast, Hussam Elkambergy, Haamid Siddique, Jihad Mallat, Nahla AlJaberi, Samer Shoshan, Ayo Mandi, Bruno De Oliveira, Malligere Prasanna, Rehan Haque, Dnyaneshwar Munde, Sara Chaffee, Fatma Alawadhi, Jamil Dibu, Eija Junttila, Teemu Luoto, Simona teblaj, Jacques Creteur, Dominique Durand, Caroline Abbenhuijs, Nancy Itesa Matumikina, Filippo Annoni, Leda Nobile, Miguel Ulloa Bersatti, Igor Yovenko, Alexander Tsarev, Jasperina Dubois, Evy Voets, Luc Janssen, Luigi Zattera, Leire Pedrosa, Berta Monleon Lopez, Ainhoa Serrano, Nekane Romero-García, Xavier Wittebole, Antonio M DellAnna, Camilla Gelormini, Eleonora Stival, Pilar Marcos Neira, Regina Roig Pineda, Lara Bielsa Berrocal, Maite Misis del Campo

Issue&Volume: 2024-10-09

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, investigator-initiated, 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.

DOI: 10.1001/jama.2024.20424

Source: https://jamanetwork.com/journals/jama/fullarticle/2824930