Abstract

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. 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. 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. Intravenous magnesium sulfate therapy (40-75 mg/kg). 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. 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). 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. ClinicalTrials.gov: NCT01429415.

Highlights

  • Acute asthma exacerbations are a leading cause of pediatric emergency department (ED) visits and related hospitalizations, with associated costs of approximately $4 billion annually in the US.[1]

  • Multivariable factors associated with hospitalization were IV magnesium receipt from 2011 to 2016 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 Pediatric Respiratory Assessment Measure (PRAM) score at disposition

  • After adjustment for patient-level characteristics, receipt of IV magnesium therapy after initial asthma treatment in the ED was associated with subsequent hospitalization

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Summary

Introduction

Acute asthma exacerbations are a leading cause of pediatric emergency department (ED) visits and related hospitalizations, with associated costs of approximately $4 billion annually in the US.[1] systemic corticosteroids, inhaled β2 agonists, and anticholinergics are recommended for the management of severe exacerbations, some children are resistant to this therapy, in part owing to genetic polymorphisms.[2,3,4] For children experiencing ongoing respiratory distress after initial management, intravenous (IV) magnesium therapy represents a potential second-line treatment option. A 2017 report from the Pediatric Health Information System Data Collaborative[16] found that the use of IV magnesium was increasing, 36% of children hospitalized for asthma received IV magnesium. Neither study found an association between IV magnesium and lower hospitalization rates or lower likelihood of being treated in the intensive care unit.[15,16]

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