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Correspondence |

There Is No Evidence To Support the Use of Aerosolized Magnesium for Acute Asthma FREE TO VIEW

Gustavo J. Rodrigo, MD
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Affiliations: Montevideo, Uruguay,  University of Alberta, Edmonton, Canada

Correspondence to: Gustavo J. Rodrigo, MD, Departamento de Emergencia, Hospital Central de las FF.AA. Av. 8 de Octubre 3020, Montevideo 11600, Uruguay; e-mail: gurodrig@adinet.com.uy



Chest. 2006;130(1):304-306. doi:10.1378/chest.130.1.304-a
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Published online

To the Editor:

I read with interest the systematic review about the use of aerosolized magnesium in acute asthma recently published in CHEST (July 2005) by Blitz et al.1 The authors concluded that nebulized MgSO4, particularly in addition to a β2-agonist, appears to produce benefits with respect to improved pulmonary function and may reduce hospital admissions. However, the data of this review are far from supporting these conclusions. The facts are as follows:

(1) In agreement with the review data, therapy with MgSO4, with or without a β2-agonist, was superior to therapy with β2-agonist alone (standardized mean difference [SMD], 0.30; 95% confidence interval [CI], 0.05 to 0.55; p = 0.02; five studies) with no between-study heterogeneity. However, a careful inspection of the data shows that pulmonary function values of the study of Bessmertny et al2 were entered erroneously: in Table 2 and Figure 2 of their study (at 65 min), the mean values for FEV1 (percentage of predicted) are 68 ± 22.5% for the control group (not for the treatment group as appeared in Fig 1 of the review) and 63 ± 20.6% for the MgSO4 group (not for the control group). This mistake changes the results dramatically (Fig 1 Thus, the effect of aerosolized MgSO4 on posttreatment lung function is not superior to therapy with β2-agonists alone (SMD, 0.16; 95% CI, − 0.08 to 0.41), with low-to-moderate heterogeneity (İ2 = 40.8%). The effect was similar when therapy with β-agonists and MgSO4 was compared with a β-agonist alone (four studies): SMD, 0.21; 95% CI, − 0.05 to 0.48; p = 0.11, with low-to-moderate heterogeneity again (İ2 = 47.6%).

(2) The Cochrane version3of this review showed the same data mistake. In an update of May 22, 2005, and as result of a letter sent by me to the authors, they recognized the mistake and corrected the data. Nevertheless, in an inexplicable form, they modified the standard deviation values of another one of the studies included in the review4 (to almost half of original value).

(3) Recently, we have identified a new randomized in-press study5 on the use of nebulized MgSO4 for acute asthma. When this study is included in the analysis, the results remain without modification. Lung function was similar when MgSO4 and β-agonists were compared with a β-agonist alone (SMD, 0.20; 95% CI, − 0.05 to 0.45; p = 0.12; İ,2 = 31.8%; five studies).

(4) The authors of review1 failed to demonstrate a significant reduction of hospital admissions (with nebulized MgSO4 alone or in combination with β-agonists).

(5) I agree with the authors1 that the addition of anticholinergics to β2-agonist therapy is effective in improving pulmonary function and in reducing the hospital admission rate,,6and that future studies should consider adding nebulized MgSO4 to high doses of inhaled β-agonists plus ipratropium bromide.7

In conclusion, data from the review by Blitz et al1 did not demonstrate any benefit of nebulized MgSO4 alone or in combination with β2-agonists compared with β-agonists alone in terms of pulmonary function or admission rate. So, the use of nebulized MgSO4 should not be considered in the treatment of acute asthma.

The author has no conflict of interest to disclose.

Figure Jump LinkFigure 1. Pooled SMD (with 95% CI) in pulmonary function (FEV1 and peak expiratory flow) of studies comparing inhaled MgSO4 alone or in combination with β-agonists (treatment) vs β-agonists (control). df = degrees of freedom. Modified from Figure 1 of Blitz et al [1] Besmertny et al [2]. Mean values were correct.).Grahic Jump Location

Drs. Rowe and Blitz and Ms. Blitz have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Blitz, M, Blitz, S, Hughes, R, et al (2005) Aerosolized magnesium sulfate for acute asthma: a systematic review.Chest128,337-344
 
Bessmertny, O, DiGregorio, RV, Cohen, II, et al A randomized clinical trial of nebulized magnesium sulfate in addition to albuterol in the treatment of acute mild-to-moderate asthma exacerbations in adults.Ann Emerg Med2002;39,585-591
 
Blitz M, Blitz S, Beasely R, et al. Inhaled magnesium sulfate in the treatment of acute asthma. Cochrane Database Syst Rev (database online), Issue 3, 2004.
 
Hughes, R, Goldkorn, A, Masoli, M, et al Use of isotonic nebulised magnesium sulphate as an adjuvant to salbutamol in treatment of severe asthma in adults: randomised placebo-controlled trial.2003;361,2114-2117
 
Kokturk, N, Turktas, H, Kara, P, et al A randomized clinical trial of magnesium sulphate as a vehicle for nebulized salbutamol in the treatment of moderate to severe asthma attacks.Pulm Pharmacol Ther2005;18,422-426
 
Rodrigo, GJ, Castro, J Anticholinergics in the treatment of children and adults with acute asthma: a systematic review with meta-analysis.Thorax2005;60,740-746
 
Rodrigo, GJ, Rodrigo, C IV magnesium in the treatment of acute severe asthma [letter]Chest2003;123,1314-1316
 
To the Editor:

We appreciate the opportunity to respond to the issues raised by Dr. Rodrigo and are pleased to see that the review has generated discussion. As was noted in the erratum published by the editors of CHEST in the September 2005 issue, an editorial error was responsible for the publication of an earlier version of the systematic review. While this was an unfortunate consequence of editorial office relocation, the journal immediately recognized the problem and this has been rectified. We refer readers to this detailed explanation of this minor change to the original article.

With respect to the newly identified study Dr. Rodrigo has included in his re-review of the data, we clearly state in the “Materials and Methods” section of our article that the search strategy was current to January 2005. Given the length of the review process, publications identified after this date would be impossible to include in the July 2005 publication. Certainly, the identified article will be considered for inclusion in any future review updates, which will be available from the Cochrane Library. Of concern, this article has been published only as an abstract, and inclusion of abstracts in a review is sometimes problematic. Data changes from abstract to journal publication are common; some reviewers would suggest delaying an update until the full publication of the article or provision of a draft manuscript.14

These two points highlight an important advantage of reviews published in the Cochrane Library compared to traditional article-based reviews. For reviewers such as Dr. Rodrigo who participate in the Cochrane Collaboration, one familiar feature of Cochrane reviews is the update requirement. Article-based reviews are essentially dated by the time they are published. Conversely, Cochrane reviews can be updated when missed publications are included, errors are identified, and/or when new data become available. Since Dr. Rodrigo first notified the Cochrane Collaboration of his concerns, there have been two updates of the review published in the on-line format.5

Overall, the meta-analysis did not show a significant reduction in the hospital admission rate for patients treated with inhaled magnesium sulfate (MgSO4), and that there was not a significant improvement in lung function for all patients. The most impressive benefit of treatment with MgSO4 was observed among patients with severe disease at presentation to the emergency department. Among these patients, the standardized mean difference was 0.57 (95% confidence interval, 0.20 to 0.94; p = 0.003). These trends are similar, albeit less impressive, to those found for treatment with IV MgSO4.6 These results still suggest that a safe, inexpensive, and potentially effective agent such as inhaled MgSO4 should remain a treatment option, especially in patients in whom other evidence-based alternatives have been exhausted. Clearly, additional research will be needed to resolve this important question.

References
Ospina, MB. A critical evaluation of evidence-based emergency medicine. [master’s thesis]. 2004; University of Alberta Medical Sciences, Public Health Sciences, Faculty of Graduate Studies and Research. Edmonton, Alberta:.
 
Marx, WF, Cloft, HJ, Do, HM, et al The fate of neuroradiologic abstracts presented at national meetings in 1993: rate of subsequent publication in peer reviewed, indexed journals.Am J Neuroradiol1999;20,1173-1177
 
Rubin, HR, Redelmeier, DA, Wu, AW, et al How reliable is peer review of scientific abstracts? Looking back at the 1991 Annual Meeting of the Society of General Internal Medicine.J Gen Intern Med1993;8,255-258
 
Tramer, M, Reynolds, DJM, Moore, RA, et al Impact of covert duplicate publication on meta-analysis: a case study.BMJ1997;315,635-640
 
Blitz M, Blitz S, Beasely R, et al. Inhaled magnesium sulfate in the treatment of acute asthma. Cochrane Database System Reviews 2005, Issue 3.
 
Rowe BH, Bretzlaff JA, Bourdon C, et al. Magnesium sulfate for treating exacerbations of acute asthma in the emergency department. Cochrane Database System Rev 2000, Issue 1.
 

Figures

Figure Jump LinkFigure 1. Pooled SMD (with 95% CI) in pulmonary function (FEV1 and peak expiratory flow) of studies comparing inhaled MgSO4 alone or in combination with β-agonists (treatment) vs β-agonists (control). df = degrees of freedom. Modified from Figure 1 of Blitz et al [1] Besmertny et al [2]. Mean values were correct.).Grahic Jump Location

Tables

References

Blitz, M, Blitz, S, Hughes, R, et al (2005) Aerosolized magnesium sulfate for acute asthma: a systematic review.Chest128,337-344
 
Bessmertny, O, DiGregorio, RV, Cohen, II, et al A randomized clinical trial of nebulized magnesium sulfate in addition to albuterol in the treatment of acute mild-to-moderate asthma exacerbations in adults.Ann Emerg Med2002;39,585-591
 
Blitz M, Blitz S, Beasely R, et al. Inhaled magnesium sulfate in the treatment of acute asthma. Cochrane Database Syst Rev (database online), Issue 3, 2004.
 
Hughes, R, Goldkorn, A, Masoli, M, et al Use of isotonic nebulised magnesium sulphate as an adjuvant to salbutamol in treatment of severe asthma in adults: randomised placebo-controlled trial.2003;361,2114-2117
 
Kokturk, N, Turktas, H, Kara, P, et al A randomized clinical trial of magnesium sulphate as a vehicle for nebulized salbutamol in the treatment of moderate to severe asthma attacks.Pulm Pharmacol Ther2005;18,422-426
 
Rodrigo, GJ, Castro, J Anticholinergics in the treatment of children and adults with acute asthma: a systematic review with meta-analysis.Thorax2005;60,740-746
 
Rodrigo, GJ, Rodrigo, C IV magnesium in the treatment of acute severe asthma [letter]Chest2003;123,1314-1316
 
Ospina, MB. A critical evaluation of evidence-based emergency medicine. [master’s thesis]. 2004; University of Alberta Medical Sciences, Public Health Sciences, Faculty of Graduate Studies and Research. Edmonton, Alberta:.
 
Marx, WF, Cloft, HJ, Do, HM, et al The fate of neuroradiologic abstracts presented at national meetings in 1993: rate of subsequent publication in peer reviewed, indexed journals.Am J Neuroradiol1999;20,1173-1177
 
Rubin, HR, Redelmeier, DA, Wu, AW, et al How reliable is peer review of scientific abstracts? Looking back at the 1991 Annual Meeting of the Society of General Internal Medicine.J Gen Intern Med1993;8,255-258
 
Tramer, M, Reynolds, DJM, Moore, RA, et al Impact of covert duplicate publication on meta-analysis: a case study.BMJ1997;315,635-640
 
Blitz M, Blitz S, Beasely R, et al. Inhaled magnesium sulfate in the treatment of acute asthma. Cochrane Database System Reviews 2005, Issue 3.
 
Rowe BH, Bretzlaff JA, Bourdon C, et al. Magnesium sulfate for treating exacerbations of acute asthma in the emergency department. Cochrane Database System Rev 2000, Issue 1.
 
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