Biochemical and Molecular Mechanisms of Magnesium Sulfate in Pediatric Asthma: A Systematic Review of Therapeutic Efficacy

Abstract

Background: Acute asthma exacerbations are a major cause of pediatric emergency department visits. While intravenous magnesium sulfate (MgSO₄) is recommended for severe, refractory cases, its overall efficacy, optimal dosing, and the role of nebulized administration remain debated. Objective: To systematically review recent evidence on the efficacy and optimal dosing of MgSO₄ for acute asthma exacerbations in children within emergency care settings. Methods: A systematic review was conducted following PRISMA 2020 guidelines. Databases (PubMed, EMBASE, Cochrane, Web of Science) were searched over 5 years for studies involving children (0-18 years) with acute asthma treated with MgSO₄. Nine studies (RCTs, prospective/retrospective cohorts, pharmacokinetic studies) met the inclusion criteria. Data were narratively synthesized by route of administration (IV vs. nebulized). Risk of bias was assessed using Cochrane RoB 2 and ROBINS-I tools. Results: Evidence for efficacy was route-dependent. Intravenous MgSO₄ (typically 40-50 mg/kg) was associated with improved pulmonary function, reduced need for intensive care, and superiority to aminophylline in severe exacerbations. A pharmacokinetic study proposed a serum exposure target (AUC(0-2h) >63.1 mg·h/L). In contrast, evidence for nebulized MgSO₄ was inconsistent, showing either no benefit or non-inferiority to other bronchodilators. Apparent negative associations between IV MgSO₄ use and worse outcomes in retrospective studies were attributed to confounding by indication (i.e., use in sicker patients). The safety profile was favorable. Conclusion: Intravenous MgSO₄ is an effective and safe adjunctive therapy for children with moderate to severe acute asthma exacerbations, supporting current guidelines. Optimal IV dosing centers on a 40-50 mg/kg bolus, with emerging evidence for continuous infusion and pharmacokinetic targets. The role of nebulized MgSO₄ remains uncertain. Future research should focus on dose optimization and high-quality trials for nebulized administration.