Comprehensive Summary
The study by Johnson et al. evaluated the feasibility and safety of administering intravenous magnesium (IVMg) according to protocol in children presenting with severe acute asthma in the emergency department. This multicenter, randomized, double-blind, placebo-controlled pilot trial was conducted across three tertiary pediatric emergency departments between September 2022 and May 2023. A total of 52 children (49 treated: mean age 6.3 years; 35 male) were selected to receive standardized care alongside one of three randomized treatments: placebo (saline 1 mL/kg, max. 40 mL), IVMg 50 mg/kg (max. 2 g), or IVMg 75 mg/kg (max. 3 g). Feasibility outcomes included the administration of the study drug within the first 90 minutes of albuterol dose, adherence to protocolized blood pressure (BP) monitoring, and serial blood draws in order to standardize a pharmacokinetic/pharmacodynamic (PK/PD) model. Within the 52 patients in trial, 34 (65.4%) were able to receive their randomly assigned drug within the 90 minutes of their albuterol dosage, highlighting the difficulty with consistently meeting a 90-minute goal. From the 542 planned BP measurements, 486 (89.7%) were completed on time. From the emergency department, 38 out of the 52 children (73.1%) were admitted and hospitalized for their severe asthma. Within two hours of treatment, 2 of the 18 patients administered the placebo experienced hypotension. From the IVMg (at both the 50 mg/Kg and 75 mg/Kg dosage), only 2 of the 31 patients (6.5%) experienced hypotension within 2 hours treatment. However, with the small sample sizes, there can be no statistical conclusions made on the treatment method and the probability of a child experiencing hypotension. No new safety signals were identified. In busy pediatric EDs, early IVMg, based on preliminary data, appears feasible and safe. Still, despite sample sizes not providing statistical power and significance, there appears to be an indication that administration of treatment with 90 minutes of admittance can be difficult. In the scope of pediatric emergency care, the data collected supports a larger trial to test the clinical benefit of standard protocols and using combined PK/PD models to refine dosage.
Outcomes and Implications
Since only 49 of the 90 eligible patients were administered care under the scope of the trial, the statistical power of the trial is insufficient to determine the difference in hospitalization rates between experimental groups. The authors note that hospitalizations are multifactorial, shaped by nonclinical considerations as well as illness severity. Early IVMg administration is clinically important given it may provide an adjunct therapy for children with severe acute asthma who do not respond to initial bronchodilators and steroids. Demonstrating feasibility and safety in busy pediatric EDs is a necessary precursor to border adoption. A larger adequately powered trial is needed to confirm clinical benefit, refine dosing via PK/PD modeling, and guide practical integration of IVMg into pediatric asthma management.