Effect of early intravenous magnesium sulfate on clinical outcomes in patients with moderate to severe traumatic brain injury: a study protocol for a randomized controlled trial.

Background: Traumatic brain injury (TBI) is associated with substantial mortality and long-term disability worldwide. Acute respiratory distress syndrome (ARDS), as a common complication in moderate-to-severe TBI, further aggravates clinical outcomes and resource utilization. However, effective interventions to prevent TBI-associated ARDS remain limited. This trial aims to evaluate whether early intravenous magnesium sulfate reduces the risk of ARDS and improves clinical outcomes in patients with moderate-to-severe TBI. Methods: This protocol outlines a randomized, controlled, double-blind clinical trial involving 164 adults (18-75 years) with moderate-to-severe TBI (Glasgow Coma Scale [GCS] 3-12) within 8 h of injury. Participants will be stratified by baseline GCS (3-8 vs. 9-12) and randomized 1:1 to the intravenous magnesium sulfate group (initial 2 g over 30 min within 8 h, then 2 g daily for 5 days; total 12 g) or an identical placebo group. Both groups will receive guideline-directed standard TBI care. The primary endpoint is a 28-day hierarchical composite (all-cause mortality, then new-onset ARDS within days 1-7, then ≤ 20% increase in PaO₂/FiO₂ AUC from baseline over days 0-5). The hierarchical composite primary endpoint will be analyzed using the win-ratio method. Secondary outcomes include ICU and hospital length of stay, complications, and serial biomarker changes. Follow-up assessments will be conducted on day 28 and at 6 months post-treatment. Discussion: If effective, this low-cost intervention could be readily incorporated into standard TBI care and help prevent TBI-associated ARDS. Clinical Trial Registration: Chinese Clinical Trial Registry, identifier ChiCTR2600120684.