Association Between Intravenous Magnesium Therapy in the Emergency Department and Subsequent Hospitalization Among Pediatric Patients With Refractory Acute Asthma: Secondary Analysis of a Randomized Clinical Trial

Abstract

Importance: Despite guidelines recommending administration of intravenous (IV) magnesium sulfate for refractory pediatric asthma, the number of asthma-related hospitalizations has remained stable, and IV magnesium therapy is independently associated with hospitalization.

Objective: To examine the association between IV magnesium therapy administered in the emergency department (ED) and subsequent hospitalization among pediatric patients with refractory acute asthma after adjustment for patient-level variables.

Design, setting, and participants: This post hoc secondary analysis of a double-blind randomized clinical trial of children with acute asthma treated from September 26, 2011, to November 19, 2019, at 7 Canadian tertiary care pediatric EDs was conducted between September and November 2020. In the randomized clinical trial, 816 otherwise healthy children aged 2 to 17 years with Pediatric Respiratory Assessment Measure (PRAM) scores of 5 points or higher after initial therapy with systemic corticosteroids and inhaled albuterol with ipratropium bromide were randomly assigned to 3 nebulized treatments of albuterol plus either magnesium sulfate or 5.5% saline placebo.

Exposures: Intravenous magnesium sulfate therapy (40-75 mg/kg).

Main outcomes and measures: The association between IV magnesium therapy in the ED and subsequent hospitalization for asthma was assessed using multivariable logistic regression analysis. Analyses were adjusted for year epoch at enrollment, receipt of IV magnesium, PRAM score after initial therapy and at ED disposition, age, sex, duration of respiratory distress, previous intensive care unit admission for asthma, hospitalizations for asthma within the past year, atopy, and receipt of oral corticosteroids within 48 hours before arrival in the ED, nebulized magnesium, and additional albuterol after inhaled magnesium or placebo, with site as a random effect.

Results: Among the 816 participants, the median age was 5 years (interquartile range, 3-7 years), 517 (63.4%) were boys, and 364 (44.6%) were hospitalized. A total of 215 children (26.3%) received IV magnesium, and 190 (88.4%) of these children were hospitalized compared with 174 of 601 children (29.0%) who did not receive IV magnesium. Multivariable factors associated with hospitalization were IV magnesium receipt from 2011 to 2016 (odds ratio [OR], 22.67; 95% CI, 6.26-82.06; P < .001) and from 2017 to 2019 (OR, 4.19; 95% CI, 1.99-8.86; P < .001), use of additional albuterol (OR, 5.94; 95% CI, 3.52-10.01; P < .001), and increase in PRAM score at disposition (per 1-U increase: OR, 2.24; 95% CI, 1.89-2.65; P < .001). In children with a disposition PRAM score of 3 or lower, receipt of IV magnesium therapy was associated with hospitalization (OR, 8.52; 95% CI, 2.96-24.41; P < .001).

Conclusions and relevance: After adjustment for patient-level characteristics, receipt of IV magnesium therapy after initial asthma treatment in the ED was associated with subsequent hospitalization. This association also existed among children with mild asthma at ED disposition. Evidence of a benefit of IV magnesium regarding hospitalization may clarify its use in the treatment of refractory pediatric asthma.

Trial registration: ClinicalTrials.gov: NCT01429415.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Zemek reported receiving research grants from the Canadian Institutes of Health Research (CIHR), the Ontario Neurotrauma Foundation, the Physician Services Incorporated Foundation, the CHEO Foundation, the Ontario Brain Institute, the Ontario Strategy for Patient-Supported Research Support Unit, and the National Football League Scientific Advisory Board; serving as clinical research chair in pediatric concussion at the University of Ottawa and on the concussion advisory board for Parachute Canada; and being a minority co-owner and scientific director of 360 Concussion Care. Dr Ducharme reported receiving donations from Jamieson and Trudell Medical; educational funds from Novartis; grants from Covis, GlaxoSmithKlein (GSK), MEDTEQ, and Thorasys; and honoraria from Teva, AstraZeneca, Brunet Pharmacy, Covis, the Federation of Medical Specialists of Quebec, GSK, the Ontario Lung Association, Sanofi, and Thorasys outside the submitted work. Dr Gravel reported receiving grants from the CIHR during the conduct of the study. No other disclosures were reported.