Pediatrics
A randomized trial of magnesium in the emergency department treatment of children with asthma*

Presented at the American Academy of Pediatrics annual meeting, San Francisco, October 1998.
https://doi.org/10.1067/mem.2000.111060Get rights and content

Abstract

Study Objective: Magnesium sulfate has been shown to benefit asthmatic children and adults with poor responses to initial β2-agonist therapy in the emergency department. We sought to determine whether the routine early administration of high-dose magnesium would benefit moderate to severely ill children with acute asthma. Methods: This was a randomized, double-blind, placebo-controlled trial of 54 children 1 to 18 years of age who presented to the ED of a tertiary care children’s hospital with a moderate to severe asthma exacerbation. After receiving a nebulized albuterol treatment (0.15 mg/kg) and methylprednisolone (1 mg/kg), patients were randomly assigned to receive either 75 mg/kg of magnesium sulfate (maximum 2.5 g) or placebo. Thereafter, all patients were treated with frequent nebulized albuterol following a structured protocol. The main outcome was degree of improvement as assessed by Pulmonary Index scores over 120 minutes. Secondary outcomes included hospitalization rates and time required to meet discharge criteria. Results: The mean change in Pulmonary Index score from baseline to 120 minutes was 2.83 for the magnesium group compared with 2.66 for the placebo group (95% confidence interval –1.24 to 1.60). Eleven (46%) of 24 magnesium-treated patients were hospitalized compared with 16 (53%) of 30 in the placebo group (95% confidence interval –19% to 34%). There were no statistically significant differences between the groups with respect to time required to meet discharge criteria. Conclusion: The routine administration of high-dose magnesium to moderate to severely ill children with asthma, as an adjunct to initial treatment with albuterol and corticosteroids, was not efficacious. [Scarfone RJ, Loiselle JM, Joffe MD, Mull CC, Stiller S, Thompson K, Gracely EJ. A randomized trial of magnesium in the emergency department treatment of children with asthma. Ann Emerg Med. December 2000;36:572-578.]

Introduction

In the United States, 4.8 million children have asthma, the most prevalent chronic disease of childhood.1 The self-reported prevalence rate for asthma increased 75% from 1980 to 1994, with an increase of 160% among children from birth to 4 years.2 This increased prevalence has been accompanied by increasing morbidity and mortality. From 1980 to 1994, the national hospitalization rate for asthmatic children from birth to 4 years increased 47%, while the national death rate for asthma among children and adults has more than doubled from 1975 to 1995.2

For patients in the emergency department with a moderate to severe asthma exacerbation, the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health recommends aggressive use of β2-agonists and systemic corticosteroids.3 However, several clinical trials have shown that patients with this degree of illness treated with β2-agonists and corticosteroids alone typically have an incomplete response and frequently (19% to 50%) require hospitalization.4, 5, 6, 7, 8 In each of 2 separate trials, 31% of children in the ED with moderate to severe exacerbations treated with prednisone and frequent, intermittently nebulized albuterol for 4 hours required hospitalization.4, 5 Therefore, it would seem that many patients with a moderate to severe exacerbation might benefit from therapy with additional medications.

Reports of the use of magnesium sulfate to treat acute asthma first appeared in the literature more than 60 years ago.9, 10 However, there are no specific recommendations provided by the NHLBI guidelines for the use of magnesium to treat status asthmaticus, and although it has been shown to be effective for asthmatic patients with the most severe disease, it has not been well studied among those with more moderate illness. The early literature reports on magnesium therapy consisted mostly of small case series.11, 12, 13, 14, 15, 16, 17, 18, 19 To date, there have been few prospective, randomized studies assessing the efficacy of magnesium for acutely ill asthmatic patients in the ED.20, 21, 22, 23, 24 Ciarallo et al20 found that the administration of 25 mg/kg of magnesium to asthmatic children with poor response to initial β2-agonist therapy resulted in significant improvements.20 Skobeloff et al21 found similar effects among very ill, β2-agonist–unresponsive adults, and Bloch et al22 demonstrated a magnesium benefit among a small subset of severely ill adults. However, Green and Rothrock23 found that the routine early administration of magnesium to a more mildly ill population of adults with acute asthma did not alter outcome.

We hypothesized that the routine early administration of high-dose magnesium would benefit moderate to severely ill children with asthma, irrespective of the response to initial β2-agonist therapy. The primary study outcome in this randomized, double-blind, placebo-controlled clinical trial was the change in a clinical asthma score over time. Secondary outcome measures included hospitalization rates and time required to meet discharge criteria.

Section snippets

Materials and methods

Candidates eligible for the study were patients between 1 and 18 years with a past history of at least 1 episode of wheezing who presented to the ED with a moderate to severe asthma exacerbation (defined as a Pulmonary Index [PI] score of 8 to 13, Table 1).

. Pulmonary index.

ScoreRespiratory Rate (breaths/min)*WheezingInspiratory/Expiratory RatioAccessory Muscle UseOxygen Saturation (%)
0≤30None2:1None99–100
131–45End expiration1:1+96–98
246–60Entire expiration1:2++93–95
3>60Inspiration and

Results

Sixty-two children were examined by investigators and met eligibility criteria. Of these, 8 refused to participate, leaving 54 study subjects. Twenty-four children were treated with magnesium and 30 with placebo. At entry, there were no significant differences between the 2 treatment groups with respect to sex or race, although subjects treated with magnesium were older (P =.04, Table 2).

. Comparison of patients at study entry.

VariableGroup
MagnesiumPlacebo
No. of patients2430
Mean age, mo (±SD)81

Discussion

This study found that the routine administration of high-dose magnesium to moderate to severely ill asthmatic children, early in the course of their ED care and irrespective of their response to albuterol, did not result in additional clinical improvement. There were no significant differences found between the magnesium and control groups with respect to change in PI score from baseline, and the study had adequate power to minimize the risk of a type II error. Similarly, there were no

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    *

    Address for reprints: Richard J. Scarfone, MD, Division of Emergency Medicine, The Children’s Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104; 215-590-1944, fax,215-590-4454; E-mail [email protected].

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