Restrictive vs Liberal Transfusion Strategy in Patients With Acute Brain Injury
Fabio Silvio Taccone, Carla Bittencourt Rynkowski, Kirsten Møller, Piet Lormans, Manuel Quintana‐Díaz, Anselmo Caricato, Marco Antonio Cardoso Ferreira, Rafael Badenes, Pedro Kurtz, Christian Baastrup Søndergaard, Kirsten Colpaert, Letícia Petterson, Hervé Quintard, Raphaël Cinotti, Elisa Gouvêa Bogossian, Cássia Righy, Serena Silva, Erik Roman‐Pognuz, Catherine Vandewaeter, Daniel Lemke, Olivier Huet, Ata Mahmoodpoor, Aaron Blandino Ortíz, 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 M. Luoto, Simona Šteblaj, Jacques Créteur, D. 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 López, Ainhoa Serrano, Nekane Romero-García, Xavier Wittebole, Antonio Maria Dell’Anna, Camilla Gelormini, Eleonora Stival, Pilar Marcos-Neira, Regina Roig Pineda, Lara Bielsa Berrocal, Maite Misis del Campo, Stepani Bendel, Jorge Mejía-Mantilla, Ángela Marulanda, Wojciech Dąbrowski, Rune Damgaard Nielsen, Markus Harboe Olsen, Helene Ravnholt Jensen, Ida Møller Larsen, Roberta T. Tallarico, Umberto Lucangelo, Maria Isabel Gonzales Perez, Carole Ichai, Karim Asenhoune, Karim Lakhal, Charlotte Fernandez-Canal, Samuel Gay, Marie Lebouc, David Bougon, Étienne Escudier, Michel Sirodot, Albrice Levrat, Alix Courouau, Jacques Duranteau, Aurore Rodrigues, Naima Makouche, Gilles Francony
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. Trial Registration: ClinicalTrials.gov Identifier: NCT02968654.