{
  "abstract": "Objective To evaluate the effectiveness of early administration of excitatory amino acid (EAA) inhibitors on long-term neurological outcomes in adults with acute moderate to severe traumatic brain injury (TBI).Design Systematic review and meta-analysis of randomised controlled trials (RCTs).Data sources MEDLINE, EMBASE, Cochrane CENTRAL, Web of Science, WHO International Clinical Trials Registry Platform and ClinicalTrials.gov from inception to January 2026.Study selection RCTs comparing EAA inhibitors with placebo, standard care or any other interventions were included. Trials enrolled adult patients (≥18 years) with moderate to severe TBI (Glasgow Coma Scale score ≤12) receiving the intervention within the acute phase of care (first week).Data extraction and synthesis Pairs of reviewers independently screened trials, extracted data, assessed the risk of bias (RoB) with the Cochrane RoB tool 2 and graded the certainty of evidence using the Grades of Recommendation, Assessment, Development and Evaluation approach. Random effects models were used for all effect measures and trial sequential analyses (TSA) were performed for each outcome.Main outcome measures The primary outcome was long-term neurological function at 6 months (or the nearest earlier time point), assessed with the Glasgow Outcome Scale (GOS) or extended version (GOS-E), using the classical definitions of an unfavourable outcome (GOS 1–3 or GOS-E 1–4).Results 28 trials enrolling 4238 patients were included. Early administration of EAA inhibitors was not associated with reduced unfavourable neurological outcomes (relative risk 0.93 (95% CI (0.84 to 1.03); I²=40%; 15 trials, n=3613, moderate certainty). No statistically significant difference was observed based on EAA inhibitor type, timing or duration of administration, RoB or TBI severity. Mortality, intensive care unit lengths of stay and mean intracranial pressure were not statistically different between groups, but hospital length of stay was reduced in the EAA inhibitors group. The early use of EAA inhibitors was not associated with adverse events (low certainty). TSA showed insufficient power for the primary outcome.Conclusions In adults with moderate to severe TBI, the early administration of EAA inhibitors was not associated with a reduction of unfavourable neurological outcomes. Further high-quality and adequately powered RCTs are required to clarify their role in TBI management.PROSPERO registration number CRD42025635527.",
  "authors": [
    {
      "affiliations": [
        "CHU de Québec-Université Laval Research Center, Population Health and Optimal Health Practice Research Unit (Trauma-Emergency-Critical Care Medicine), CHU de Québec-Université Laval, Québec City, Québec, Canada",
        "Department of Anesthesiology and Critical Care Medicine, Brest University Hospital Centre, Brest, France"
      ],
      "name": "Marwan Bouras"
    },
    {
      "affiliations": [
        "CHU de Québec-Université Laval Research Center, Population Health and Optimal Health Practice Research Unit (Trauma-Emergency-Critical Care Medicine), CHU de Québec-Université Laval, Québec City, Québec, Canada"
      ],
      "name": "Olivier Costerousse"
    },
    {
      "affiliations": [
        "CHU de Québec-Université Laval Research Center, Population Health and Optimal Health Practice Research Unit (Trauma-Emergency-Critical Care Medicine), CHU de Québec-Université Laval, Québec City, Québec, Canada",
        "Department of Anesthesiology and Critical Care Medicine, Université Laval, Faculté de Médecine, Québec City, Québec, Canada"
      ],
      "name": "Michael Verret"
    },
    {
      "affiliations": [
        "CHU de Québec-Université Laval Research Center, Population Health and Optimal Health Practice Research Unit (Trauma-Emergency-Critical Care Medicine), CHU de Québec-Université Laval, Québec City, Québec, Canada"
      ],
      "name": "Sarah O’connor"
    },
    {
      "affiliations": [
        "Department of Internal Medicine, Sections of Critical Care Medicine, of Hematology and of Medical Oncology, University of Manitoba, Winnipeg, Manitoba, Canada",
        "Research Institute of Oncology and Hematology, CancerCare Manitoba, Winnipeg, Manitoba, Canada"
      ],
      "name": "Ryan Zarychanski"
    },
    {
      "affiliations": [
        "CHU de Québec-Université Laval Research Center, Population Health and Optimal Health Practice Research Unit (Trauma-Emergency-Critical Care Medicine), CHU de Québec-Université Laval, Québec City, Québec, Canada"
      ],
      "name": "Marc-Aurèle Gagnon"
    },
    {
      "affiliations": [
        "CHU de Québec-Université Laval Research Center, Population Health and Optimal Health Practice Research Unit (Trauma-Emergency-Critical Care Medicine), CHU de Québec-Université Laval, Québec City, Québec, Canada"
      ],
      "name": "Tomas H Torkomyan"
    },
    {
      "affiliations": [
        "CHU de Québec-Université Laval Research Center, Population Health and Optimal Health Practice Research Unit (Trauma-Emergency-Critical Care Medicine), CHU de Québec-Université Laval, Québec City, Québec, Canada"
      ],
      "name": "Antoine Ouellet"
    },
    {
      "affiliations": [
        "CHU de Québec-Université Laval Research Center, Population Health and Optimal Health Practice Research Unit (Trauma-Emergency-Critical Care Medicine), CHU de Québec-Université Laval, Québec City, Québec, Canada",
        "Department of Anesthesiology and Critical Care Medicine, Division of Critical Care Medicine, Université Laval, Faculté de Médecine, Québec City, Québec, Canada"
      ],
      "name": "Francois Lauzier"
    },
    {
      "affiliations": [
        "Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada",
        "Division of Critical Care, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada"
      ],
      "name": "Shane English"
    },
    {
      "affiliations": [
        "CHU de Québec-Université Laval Research Center, Population Health and Optimal Health Practice Research Unit (Trauma-Emergency-Critical Care Medicine), CHU de Québec-Université Laval, Québec City, Québec, Canada",
        "Department of Preventive and Social Medicine, Universite Laval, Faculte de Médecine, Québec City, Québec, Canada"
      ],
      "name": "Lynne Moore"
    },
    {
      "affiliations": [
        "CHU de Québec-Université Laval Research Center, Population Health and Optimal Health Practice Research Unit (Trauma-Emergency-Critical Care Medicine), CHU de Québec-Université Laval, Québec City, Québec, Canada",
        "Department of Anesthesiology and Critical Care Medicine, Division of Critical Care Medicine, Université Laval, Faculté de Médecine, Québec City, Québec, Canada"
      ],
      "name": "Alexis F Turgeon"
    }
  ],
  "title": "Excitatory amino acid inhibitors in adults with acute moderate to severe traumatic brain injury: a systematic review and meta-analysis",
  "uid": "1027dc8c-a454-56a6-9491-30f749e9c835"
}