Inhaled magnesium sulfate in the treatment of acute asthma

Acute asthma is a common emergency department problem usually treated with systemic corticosteroids, inhaled beta-agonists and a variety of other agents (including inhaled corticosteroids, inhaled anticholinergics, intravenous magnesium sulfate and oxygen). A Cochrane review showed that intravenous treatment with magnesium sulfate was helpful in improving peak expiratory flow measures (patients capacity to breathe more freely) in acute severe exacerbations of asthma. Therefore, we were interested in finding out if inhaled magnesium sulfate is helpful to people suffering an asthma attack and we undertook this review to explore this question.

Inhaled magnesium sulfate is recommended only after someone experiencing an asthma attack has been given bronchodilators, steroids and has failed to respond adequately to them. This review found that using inhaled magnesium sulfate combined with a beta-2-agonist (with or without ipratropium) for an acute asthma attack does not significantly improve pulmonary function (and therefore does not help people to breathe more freely) overall, but there may be improvement in adults with particularly severe asthma attacks, which merits further study The evidence, however, that the addition of nebulised magnesium sulfate is helpful with regard to clinically important outcomes, such as reducing hospital admissions, is not proven by the clinical trials included in this review.

Authors' conclusions: 

There is currently no good evidence that inhaled MgSO4 can be used as a substitute for inhaled β2-agonists. When used in addition to inhaled β2-agonists (with or without inhaled ipratropium), there is currently no overall clear evidence of improved pulmonary function or reduced hospital admissions. However, individual study results from three trials suggest possible improved pulmonary function in those with severe asthma exacerbations (FEV1 less than 50% predicted). Heterogeneity among trials included in this review precludes a more definitive conclusion. Further studies should focus on inhaled MgSO4 in addition to the current guideline treatment for acute asthma (inhaled β2 -agonist and ipratropium bromide). As the evidence suggests that the most effective role of nebulised MgSO4 may be in those with severe acute features and this is where future research should be focused. A set of core outcomes needs to be agreed upon both in adult and paediatric studies to allow improved study comparison in future. 

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Background: 

Asthma exacerbations can be frequent and range in severity from relatively mild to status asthmaticus. The use of magnesium sulfate (MgSO4) is one of numerous treatment options available during acute exacerbations. While the efficacy of intravenous MgSO4 has been demonstrated, little is known of the role of inhaled MgSO4.

Objectives: 

To determine the efficacy of inhaled MgSO4 administered in acute asthma on pulmonary functions and admission rates.

Specific aims: To quantify the effects of inhaled MgSO4 i) in addition to inhaled β2-agonist, ii) in comparison to inhaled β2-agonist alone or iii) in addition to combination treatment with inhaled β2 -agonist and ipratropium bromide.

Search strategy: 

Randomised controlled trials were identified from the Cochrane Airways Group register of trials in September 2012. These trials were supplemented with trials found in the reference list of published studies, studies found using extensive electronic search techniques, as well as a review of the grey literature and conference proceedings.

Selection criteria: 

Randomised (or pseudo-randomised) controlled trials including adults or children with acute asthma were eligible for inclusion in the review. Studies were included if patients were treated with nebulised MgSO4 alone or in combination with β2-agonist and/or ipratropium bromide and were compared with β2-agonist alone or inactive control.

Data collection and analysis: 

Trial selection, data extraction and risk of bias were assessed independently by two review authors. Efforts were made to collect missing data from authors. Results are presented as standardised mean differences (SMD) for pulmonary function and risk ratios (RR) for hospital admission; both are displayed with their 95% confidence intervals (CI).

Main results: 

Sixteen trials (21 references) of unclear and high risk of bias were eligible and included 896 patients who were randomised (838 patients completed). Seven of the 16 included studies involved adults exclusively, three included adults and paediatric patients, four studies enrolled paediatric patients and in the remaining two studies the age of participants was not stated.

The design, definitions, intervention and outcomes were different in all 16 studies; this heterogeneity made direct comparisons difficult (see additional tables 1-3).

The overall risk of bias among the included studies was variable and this is reflected in the 'Summary of findings' table with most outcomes being judged as only moderate or less.

Inhaled magnesium sulfate in addition to inhaled β2-agonist

There was no statistically significant improvement in pulmonary function when inhaled MgSO4 and β2-agonist was compared with β2-agonist alone (SMD 0.23; 95% CI -0.27 to 0.74; three studies, n = 188); however, there was considerable between study heterogeneity. There was no clear advantage in terms of hospital admissions (RR 0.76 95% CI 0.49, 1.16; four studies, n = 249), and there were no serious adverse events reported.

Inhaled magnesium sulfate versus inhaled β2-agonist

The results of pulmonary function in three studies that compared inhaled MgSO4 versus β2-agonist were too heterogeneous to combine; however, two of the studies found poorer lung function on MgSO4. There was no significant difference in terms of hospital admissions in a single small study when MgSO4 was compared to β2-agonist (RR 0.53 95% CI 0.05, 5.31; one study, n = 33), and there were no serious adverse events reported.

Inhaled magnesium sulfate in addition to inhaled β2-agonist and ipratropium

A further comparison has been included in the 2012 update of this review of MgSO4 given in addition to inhaled ipratropium and β2-agonist therapy (as recommended by the GINA guidelines). However, there is not yet enough data for this outcome to come to any definite conclusions, but both small studies in adults with severe asthma exacerbation found improvements in pulmonary function with additional inhaled MgSO4.

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