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Original Investigation
November 24, 2020

Effect of Nebulized Magnesium vs Placebo Added to Albuterol on Hospitalization Among Children With Refractory Acute Asthma Treated in the Emergency Department: A Randomized Clinical Trial

Author Affiliations
  • 1Division of Pediatric Emergency Medicine, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
  • 2Research Institute, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
  • 3Division of Respiratory Medicine, Research Institute, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
  • 4Ontario Child Health Support Unit, SickKids Research Institute, Toronto, Ontario, Canada
  • 5Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
  • 6Research Institute, Clinical Research Services, The Hospital for Sick Children, Toronto, Ontario, Canada
  • 7Department of Biostatistics, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
  • 8Divisions of Pediatric Emergency Medicine and Clinical Pharmacology and Toxicology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
  • 9Departments of Pediatrics and Emergency Medicine, Alberta Children’s Hospital, University of Calgary, Calgary, Alberta, Canada
  • 10Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada
  • 11Department of Pediatrics and Emergency Medicine, Children’s Hospital of Eastern Ontario, University of Ottawa, Ottawa, Ontario, Canada
  • 12CHEO Research Institute, Ottawa, Ontario, Canada
  • 13Department of Pediatric Emergency Medicine, CHU Sainte-Justine, Montréal, Quebec, Canada
  • 14Department of Pediatrics and of Social and Preventive Medicine, Université de Montréal, Montréal, Quebec, Canada
  • 15Departments of Pediatrics, Emergency Medicine, and Physiology & Pharmacology, Alberta Children’s Hospital, Calgary, Alberta, Canada
  • 16Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
  • 17Division of Pediatric Emergency Medicine, British Columbia Children’s Hospital, University of British Columbia, Vancouver, British Columbia, Canada
  • 18Departments of Pediatrics and Emergency Medicine, Stollery Children’s Hospital, University of Alberta, Edmonton, Alberta, Canada
  • 19Pediatrics/Pediatric Emergency Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
  • 20Children’s Hospital Research Institute of Manitoba, Winnipeg, Manitoba, Canada
  • 21Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada
  • 22Children’s Hospital Research Institute of Manitoba, Winnipeg, Manitoba, Canada
  • 23Pharmacy Department, The Hospital for Sick Children, Toronto, Ontario, Canada
  • 24Sections of Pediatric Emergency Medicine and Gastroenterology, Departments of Pediatrics and Emergency Medicine, Alberta Children’s Hospital, Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
JAMA. 2020;324(20):2038-2047. doi:10.1001/jama.2020.19839
Visual Abstract. Effect of Nebulized Magnesium vs Placebo Added to Albuterol Among Children With Refractory Acute Asthma
Effect of Nebulized Magnesium vs Placebo Added to Albuterol Among Children With Refractory Acute Asthma
Key Points

Question  What is the effectiveness of nebulized magnesium in children and adolescents with acute asthma in the emergency department who remain in moderate or severe respiratory distress after evidence-based standardized initial therapy?

Findings  In this randomized clinical trial that included 816 patients, nebulized magnesium with albuterol, compared with placebo with albuterol, did not significantly decrease the rate of hospitalization for asthma within 24 hours (43.5% vs 47.7%, respectively).

Meaning  The findings do not support use of nebulized magnesium with albuterol among children with refractory acute asthma.

Abstract

Importance  While intravenous magnesium decreases hospitalizations in refractory pediatric acute asthma, it is variably used because of invasiveness and safety concerns. The benefit of nebulized magnesium to prevent hospitalization is unknown.

Objective  To evaluate the effectiveness of nebulized magnesium in children with acute asthma remaining in moderate or severe respiratory distress after initial therapy.

Design, Setting, and Participants  A randomized double-blind parallel-group clinical trial from September 26, 2011, to November 19, 2019, in 7 tertiary-care pediatric emergency departments in Canada. The participants were otherwise healthy children aged 2 to 17 years with moderate to severe asthma defined by a Pediatric Respiratory Assessment Measure (PRAM) score of 5 or greater (on a 12-point scale) after a 1-hour treatment with an oral corticosteroid and 3 inhaled albuterol and ipratropium treatments. Of 5846 screened patients, 4332 were excluded for criteria, 273 declined participation, 423 otherwise excluded, 818 randomized, and 816 analyzed.

Interventions  Participants were randomized to 3 nebulized albuterol treatments with either magnesium sulfate (n = 410) or 5.5% saline placebo (n = 408).

Main Outcomes and Measures  The primary outcome was hospitalization for asthma within 24 hours. Secondary outcomes included PRAM score; respiratory rate; oxygen saturation at 60, 120, 180, and 240 minutes; blood pressure at 20, 40, 60, 120, 180, and 240 minutes; and albuterol treatments within 240 minutes.

Results  Among 818 randomized patients (median age, 5 years; 63% males), 816 completed the trial (409 received magnesium; 407, placebo). A total of 178 of the 409 children who received magnesium (43.5%) were hospitalized vs 194 of the 407 who received placebo (47.7%) (difference, −4.2%; absolute risk difference 95% [exact] CI, −11% to 2.8%]; P = .26). There were no significant between-group differences in changes from baseline to 240 minutes in PRAM score (difference of changes, 0.14 points [95% CI, −0.23 to 0.50]; P = .46); respiratory rate (0.17 breaths/min [95% CI, −1.32 to 1.67]; P = .82); oxygen saturation (−0.04% [95% CI, −0.53% to 0.46%]; P = .88); systolic blood pressure (0.78 mm Hg [95% CI, −1.48 to 3.03]; P = .50); or mean number of additional albuterol treatments (magnesium: 1.49, placebo: 1.59; risk ratio, 0.94 [95% CI, 0.79 to 1.11]; P = .47). Nausea/vomiting or sore throat/nose occurred in 17 of the 409 children who received magnesium (4%) and 5 of the 407 who received placebo (1%).

Conclusions and Relevance  Among children with refractory acute asthma in the emergency department, nebulized magnesium with albuterol, compared with placebo with albuterol, did not significantly decrease the hospitalization rate for asthma within 24 hours. The findings do not support use of nebulized magnesium with albuterol among children with refractory acute asthma.

Trial Registration  ClinicalTrials.gov Identifier: NCT01429415

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