Restrictive vs Liberal Transfusion Strategy in Patients With Acute Brain Injury
Authors: Taccone Fabio Silvio , Rynkowski Carla Bittencourt , Møller Kirsten , Lormans Piet , Quintana-Díaz Manuel , Caricato Anselmo , Cardoso Ferreira Marco Antonio , Badenes Rafael , Kurtz Pedro , Søndergaard Christian Baastrup , Colpaert Kirsten , Petterson Leticia , Quintard Herve , Cinotti Raphael , Gouvêa Bogossian Elisa , Righy Cassia , Silva Serena , Roman-Pognuz Erik , Vandewaeter Catherine , Lemke Daniel , Huet Olivier , Mahmoodpoor Ata , Blandino Ortiz Aaron , van der Jagt Mathieu , Chabanne Russell , Videtta Walter , Bouzat Pierre , Vincent Jean-Louis ,   TRAIN Study Group, Díaz Claudia , Saravia Andrés , Bayrlee Ahmas , Nedolast Laura , Elkambergy Hussam , Siddique Haamid , Mallat Jihad , AlJaberi Nahla , Shoshan Samer , Mandi Ayo , De Oliveira Bruno , Prasanna Malligere , Haque Rehan , Munde Dnyaneshwar , Chaffee Sara , Alawadhi Fatma , Dibu Jamil , Junttila Eija , Luoto Teemu , Šteblaj Simona , Creteur Jacques , Durand Dominique , Abbenhuijs Caroline , Itesa Matumikina Nancy , Annoni Filippo , Nobile Leda , Ulloa Bersatti Miguel , Yovenko Igor , Tsarev Alexander , Dubois Jasperina , Voets Evy , Janssen Luc , Zattera Luigi , Pedrosa Leire , Monleon Lopez Berta , Serrano Ainhoa , Romero-García Nekane , Wittebole Xavier , Dell'Anna Antonio M , Gelormini Camilla , Stival Eleonora , Marcos Neira Pilar , Roig Pineda Regina , Bielsa Berrocal Lara , Misis del Campo Maite , Bendel Stepani , Mejía-Mantilla Jorge H , Marulanda Ángela , Dabrowski Wojciech , Damgaard Nielsen Rune , Harboe Olsen Markus , Ravnholt Jensen Helene , Møller Larsen Ida , Tallarico Roberta , Lucangelo Umberto , Gonzales Perez Maria Isabel , Ichai Carole , Asenhoune Karim , Lakhal Karim , Fernandez-Canal Charlotte , Gay Samuel , Lebouc Marie , Bougon David , Escudier Etienne , Sirodot Michel , Levrat Albrice , Courouau Alix , Duranteau Jacques , Rodrigues Aurore , Makouche Naima , Francony Gilles , Vincent Olivier , Boucheix Perrine , Schilte Clotilde , Adolle Anais , Gargadennec Thomas , Dias Patricia , Desanglois Gwenaelle , Meheut Alexia , Cam Pauline , Meyfroidt Geert , Mebis Liese , Hendrickx Alexandra , Wouters Pieetr , Van Hulle Sylvia , D'Hondt Alain , Beumier Marjorie , Burgeois Marc , Simonet Olivier , Vallot Frederic , Centeno Pablo , Anchorena Matias , Benavente Ximena , D'Onofrio Maximilian , Funes Nydia , Barra de Oca Antonio , Izzo Gabriela , Castelain Charlotte , Soetens Filippo , Arias Mario , Morocho Diego , Jabaja Manuel , Tutillo Diego , Popugaev Stan , Dias Celeste , Perez Solada Elena , Justo Pilar , Lopez Gomez Amparo , Alcantara Sara , Chico Francisco , Garcia Maria Fernanda , Picoita Fabricio , Velasco Eichler Stela , Nonticuri Bianchi Gabriela , Britz João Pedro , Almeida Pimentel Jaqueline , Fernandes Mário Sérgio , Gharsallah Hedi , Hajjej Zied , Samoud Walid , Grebenchikov Oleg , Likhvantsev Valery , Stroiteleva Elena , Markou Nikolaos , Bakali Dimitra , Koutrafouri Dionysia , Subhy Alsheikhly Ahmed , Giacomucci Angelo , Maccherani Sara , Horn Janneke , Elbahnasawy Mohamed , Ahmadi Arezoo , Decaesteker Lien , Decruyenaere Daphne , Demeersseman Ruth , Devriendt Yves , Embo Karen , van Duijn Ditty , Ormskerk Patricia , Glasbergen-van Beijeren Melanie , Njimi Hassane , Cariou Alain , Lelubre Christophe , Ristagno Giuseppe , Stocchetti Nino , Oddo Mauro , De Deyne Cathy , Citerio Giuseppe 
Published: October 2024

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 &amp;lt;9 g/dL; n = 408) or a restrictive (transfusion triggered by hemoglobin &amp;lt;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