Neuroprotective Impact of Magnesium Sulfate on Mortality in Sepsis-Associated Encephalopathy: A Propensity-Matched Analysis of Medical Information Mart for Intensive Care IV Database

Introduction: This study aimed to evaluate the association between magnesium sulfate and mortality in patients with Sepsis-Associated Encephalopathy (SAE), given the lack of established therapies and emerging evidence of magnesium's neuroprotective properties. Methods: A retrospective cohort study was conducted using data from SAE patients in the MIMICIV database. Patients were stratified into magnesium sulfate-treated and non-treated groups, with 1:1 Propensity Score Matching (PSM) to adjust for baseline imbalances. Outcomes included 28-day all-cause mortality, in-hospital mortality, and Intensive Care Unit (ICU)/hospital Length of Stay (LOS). Cox regression, Kaplan-Meier analysis, and subgroup assessments were performed. Results: A total of 12,296 patients with SAE who met the inclusion and exclusion criteria participated in this study. Before PSM, magnesium sulfate administration correlated with a 36% reduction in 28-day mortality (17.11% vs. 23.77%; Hazard Ratio HR 0.64, 95% CI 0.58-0.70) and a 43% decrease in in-hospital mortality (14.32% vs. 18.23%; HR 0.57, 95% CI 0.51-0.63) (both p < 0.001). Post-PSM analysis of 7,236 matched patients confirmed consistent benefits (28-day mortality HR 0.66; in-hospital mortality HR 0.62). However, patients treated with magnesium sulfate had longer median ICU LOS (3.87 vs. 2.64 days; p < 0.001) and hospital LOS (10.12 vs. 8.70 days; p < 0.001). Subgroup analyses demonstrated robustness across demographics and comorbidities. Discussion: The significant association between magnesium sulfate and reduced mortality in SAE patients suggests its potential neuroprotective role, possibly mediated through mechanisms such as blood-brain barrier stabilization, anti-inflammatory effects, and N-methyl-D-aspartate (NMDA) receptor antagonism. The observed prolongation of ICU and hospital stay may reflect survivor bias and the necessary time for neurological recovery in these critically ill patients, rather than a direct adverse effect of the therapy. These findings position magnesium sulfate as a promising adjunctive therapy for SAE, warranting a paradigm shift in its consideration for neuroprotection in sepsis. Conclusion: This large-scale retrospective study found that magnesium sulfate administration was associated with reduced 28-day and in-hospital mortality in SAE patients, alongside prolonged length of hospital and ICU stay. These findings highlight magnesium sulfate's potential as an adjunctive SAE therapy, though multicenter randomized trials are warranted to validate this association and optimize dosing protocols.