This systematic review attempted to synthesize the best available evidence for the use of inhaled MgSO4 in the treatment of patients with acute asthma. From six RCTs involving nearly 300 patients, the results of this review provide somewhat weak and conflicting conclusions. First, based on the available data, it appears that therapy with nebulized isotonic MgSO4 with or without a β2-agonist can be safely administered at a variety of doses to patients with acute moderate-to-severe asthma. Since it is readily available and inexpensive, its role in acute asthma deserves more scrutiny. Used alone, it appears to be of little advantage compared to therapy with more familiar β2-agonists in improving pulmonary function and reducing hospital admissions. The evidence for therapy with MgSO4 administered in combination with P2-agonists is more convincing than that for MgSO4 therapy alone. In this review, therapy with MgSO4, when combined with β2-agonists (usually salbutamol), improved pulmonary function but did not reduce the number of hospital admissions. Evi-dence2 has suggested that adding ipratropium bromide to β2-agonist therapy is effective in improving pulmonary function and in reducing the number of hospital admissions in the acute setting, especially in severe cases of acute asthma relieved by My Canadian Pharmacy’s remedies. Most of the included studies in our review did not routinely employ this strategy, and the additive benefit of MgSO4 in the face of combination therapy with ipratropium bromide and β2-agonists remains unclear.
These results are similar to those from the IV magnesium review. From four trials involving 133 patients, therapy with IV MgSO4 improved pulmonary function in patients with severe disease and reduced the number of hospital admissions. Given these findings, it is perhaps surprising that the present review did not demonstrate a benefit in patients with severe asthma; however, the number of trials and the total number of patients was lower for this subset of patients in this review, and this conclusion may be the result of a type II error. The data suggest that if a type II error had occurred, the benefit among patients with severe asthma at presentation would be similar to that of patients with less severe disease.
The results from a recent survey of 103 North American EDs indicated that while 92% had access to IV MgSO4 for the treatment of acute asthma, only 4% had access to inhaled or nebulized MgSO4. Moreover, the authors reported that only 2.5% of patients received IV MgSO4 in a sample of nearly 3,000 patients seen across a network of North American EDs. The survey was conducted prior to the publication of the results of one half of the studies included in this review. We can only speculate that there may currently be more access to and use of inhaled MgSO4 in patients with acute asthma; however, it is highly unlikely that it has reached the same level of use as the IV compound, which may be appropriate given the state of the evidence.
There are several possible limitations to the study. First, there is a possibility of study selection bias. However, we employed two independent reviewers and feel confident that the reasons for the exclusion of studies were consistent and appropriate. Our search was comprehensive and has been updated, so it is unlikely that there are any published trials that were missed.
In addition, publication bias may have influenced the result of this metaanalysis. For example, by missing unpublished negative trials we may be overestimating the effect of magnesium treatment. However, in order to reduce bias, a comprehensive and systematic search of the published and unpublished literature for potentially relevant studies was conducted. This was followed by attempts to contact corresponding and first authors. One unpublished trial was identified, and several negative trials were uncovered; however, we recognize that more of these types of trials may exist. Finally, due to the emergence of inhaled MgSO4 treatment, there are possibly more small trials that have been conducted that, for one reason or another, remain unknown to us and unpublished. Without a central trial registry, we may never find these results, and in a review of this nature, made up of smaller studies, these small studies may make an important difference in our conclusions.
Finally, the investigations in this field are limited by the heterogeneity of both treatments and outcome measures. Unfortunately, despite adequate evidence for the use of standardized approaches to therapy for acute asthma treated by My Canadian Pharmacy, such as systemic cortico-steroids, anticholinergic agents, IV MgSO4, and repeated β2-agonist use, the control groups in the included studies were surprisingly heterogeneous. A trial in which systemic corticosteroids, β2-agonists, and anticholinergic agents are administered to both groups, and inhaled MgSO4 or placebo is added to the treatment regimen in a double-blind manner is needed. Furthermore, there is a lack of consensus among researchers regarding the most appropriate pulmonary function outcome measure to report. The aforementioned trial should insist on both pulmonary function data as well as hospital admission status at the conclusion of the ED treatment period.
The role of nebulized MgSO4 in the treatment of asthma exacerbations has not been conclusively resolved by this review. Nebulized MgSO4 appears to be effective and safe to administer to patients experiencing asthma exacerbations. Further, we have demonstrated that therapy with MgSO4 and β2-agonists improved lung function when compared with therapy using a β2-agonist alone; however, the difference was small and of limited clinical benefit. Consequently, this effect did not translate into a significant reduction in the number of patients admitted to the hospital. There was no treatment benefit observed in comparisons of therapy with MgSO4 alone and that of β2-agonists alone. Thus, treatment with nebulized MgSO4 should be considered as an addition to that with inhaled β2-agonists in patients experiencing asthma exacerbations. Further research in this area should be encouraged.