Pharmacokinetics and Pharmacodynamics of Intravenous Magnesium Sulfate in Pediatric Acute Asthma Exacerbations.

Abstract

Pediatric asthma exacerbations represent a significant cause of emergency department use and hospitalizations. Despite available treatment options, many children's exacerbations are refractory to standard therapies and require adjunct treatments. The Intravenous Magnesium: Prompt use for Asthma in Children Treated in the Emergency Department study investigated the pharmacology of intravenous magnesium sulfate (IVMg) in treating pediatric asthma exacerbations. Specifically, the objectives of the study included (1) externally validating a previously published population pharmacokinetic model and (2) linking serum magnesium concentrations with outcomes including asthma severity score (efficacy) and hypotension (safety). Data were obtained from 49 children prospectively treated with IVMg (placebo, 50 or 75 mg/kg) after presenting to the pediatric emergency department with an acute asthma exacerbation. Reductions in Pediatric Respiratory Assessment Measure scores were associated with both total and ionized serum magnesium area under the concentration-time curve (AUC_{0-2 h}). Despite frequent study-specific blood pressure monitoring, hypotension was uncommon in IVMg-treated participants (n = 2/31), and no concentration dependence was observed. The findings signal that IVMg may be an efficacious and safe option for treating moderate-severe pediatric acute asthma exacerbations in the ED. Importantly, this study is the first to suggest a serum exposure target (total serum magnesium AUC_{0-2 h} >63.1 mg h/L) reflective of effective IVMg dosing in pediatric acute asthma. While further study in a larger clinical trial is needed to refine and validate this exposure target, these findings support the continued study of IVMg therapy as an adjunct therapeutic option in the setting of pediatric asthma exacerbations.