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

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 PARTICIPANTSA 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 MEASURESThe 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.

Association Between Intravenous Magnesium Therapy in the Emergency Department and Subsequent Hospitalization Among Pediatric Patients With Refractory Acute Asthma

“…A total of 5846 patients were screened for the RCT 17 ; 5028 were excluded or refused participation, 818 were included in the randomization, and 816 constituted the study population for the RCT (409 received inhaled magnesium, and 407 received inhaled placebo) and for this secondary analysis. The median age was 5 years (IQR, 3-7 years), 517 participants (63.4%) were boys, and the median baseline PRAM score was 6 points (IQR, 5-7 points).…”

“…We conducted a post hoc secondary analysis of a multicenter, double-blind, placebo-controlled RCT ( NCT01429415 ) 17 of children aged 2 to 17 years treated at 7 Pediatric Emergency Research Canada EDs for acute asthma from September 26, 2011, to November 19, 2019 (the trial protocol for the RCT is given in Supplement 1 ). This secondary analysis was performed from September to November 2020.…”

“…To provide 80% power at a 2-sided significance level of 5%, using 20 patients with the outcome of interest for each of the 15 a priori–defined variables examined and knowing that 50% of children enrolled in the original study were admitted to the hospital, 17 a sample of at least 300 hospitalized patients was needed for this study. 31 We used proportions and 95% CIs to describe categorical data and means with SDs or medians with interquartile ranges (IQRs) for continuous data.…”

“…To explore the association between asthma severity, IV magnesium therapy, and hospitalization among children with refractory acute asthma, we conducted a secondary analysis of a recent multicenter RCT. 17 The trial found that the administration of nebulized magnesium sulfate with albuterol to children who continued to experience moderate to severe respiratory distress after standardized initial therapy did not convey any benefit compared with placebo with albuterol. 17 Because many children in the trial also received IV magnesium after inhaled magnesium or placebo and asthma severity was measured using the validated Pediatric Respiratory Assessment Measure (PRAM) score, 18 the trial offered a unique opportunity to assess the association between receipt of IV magnesium therapy in the ED and subsequent hospitalization.…”

“… 17 The trial found that the administration of nebulized magnesium sulfate with albuterol to children who continued to experience moderate to severe respiratory distress after standardized initial therapy did not convey any benefit compared with placebo with albuterol. 17 Because many children in the trial also received IV magnesium after inhaled magnesium or placebo and asthma severity was measured using the validated Pediatric Respiratory Assessment Measure (PRAM) score, 18 the trial offered a unique opportunity to assess the association between receipt of IV magnesium therapy in the ED and subsequent hospitalization. We hypothesized that children administered IV magnesium would be more likely to be hospitalized compared with those not given IV magnesium after adjustment for patient-level variables.…”