A Pilot Placebo-Controlled Randomized Trial of Repeated High-Dose Intravenous Magnesium Sulphate and High-Dose Nebulized Budesonide for Severe Asthma in the Paediatric Emergency Department

Abstract

Objective

Determine if high-dose intravenous magnesium with/without nebulized budesonide for children with acute severe asthma is safe and reduces time to medical readiness for discharge compared to standard intravenous magnesium.

Methods

Either 2 doses of intravenous magnesium or 1 dose and placebo, each with/without high-dose nebulized budesonide, were given in a double-blind randomized trial to study patients in addition to standard-of-care asthma treatment. Time to medical readiness for discharge was the primary outcome. The proportion of patients discharged at 12, 18, and 24 h, asthma severity scores at 4, 8, 12, and 24 h, and safety of high-dose magnesium were secondary outcomes. Follow-up was 1 week.

Results

Covid-19 intervened to stop recuitment at 70% of the estimated 218 children planned. Primary and secondary results were similar for the 4 groups. High-dose magnesium was safe on clinical and laboratory assessment. Exploratory analysis combining IV high-dose magnesium groups compared to standard magnesium showed improvement of discharge ratio at 12 h for the former. 40/78 patients (51.2%) in high-dose magnesium versus 26/75 patients (34.6%) in the standard magnesium arms ready for discharge, p = 0.038, absolute risk reduction 16.6%,95% CI, 0.93% to 31.1%. There was a trend toward improvement of PRAM score at 4 and 8 h in the nebulized budesonide groups compared to placebo and no significant difference in seeking post-discharge outpatient or need for inpatient care.

Conclusions

High-dose magnesium appeared safe with only a modest possible benefit of medical readiness for discharge at 12 h. There was a reduction in asthma severity score at 4 and 8 h from nebulized budesonide.

Trial Registration: clinicaltrials.gov, ID #NCT 02455687