Question

• In pediatric patients experiencing asthma exacerbations, does nebulized magnesium with albuterol improve pulmonary function more than nebulized albuterol alone?

Clinical Bottom Lines

1. Nebulized magnesium sulfate along with albuterol improved peak flow at 10 minutes after the treatment was given as compared with albuterol in normal saline and showed a trend toward improvement at 20 minutes.
2. Despite this evident improvement, no conclusions can be made as to whether this improvement will be sustained, whether patients would benefit from more than one treatment, and whether nebulized magnesium treatment will prevent hospital admission and/or intubation or improve overall recovery from an asthma exacerbation.

Summary of Key Evidence

1. 62 patients, aged 5-17 years, experiencing exacerbation of mild to moderate asthma were randomized in a double-blinded fashion to receive a single dose of 2.5 mg of albuterol mixed with 2.5 cc of normal saline or mixed with 2.5 cc of isotonic magnesium sulfate.¹
2. Patients were excluded if they had a temperature >39 degrees C, history of chronic diseases such as BPD or CF, or had received steroids or ipratropium in the past 3 days.
3. The two groups were similar with respect to age, sex, race, height, weight, temperature, presence and duration of DIB and wheezing, HR, RR, pulse ox, and baseline FEV1.
4. Patients in both groups received 2 mg/kg of prednisone after the administration of the study drug and continued to be treated equally with respect to the use of albuterol and other asthma medications.
5. Assuming a mean difference of 15% in FEV1 as significant, the study with the given sample size had a power greater than 80% to yield a statistically significant result.
6. FEV1 was measured initially and then 10 and 20 minutes following the administration of the study drug.
7. At 10 minutes, the mean FEV1 was 1.41 L in the albuterol + magnesium group as compared to 1.13 L in the albuterol + saline group (p=0.03). At 20 minutes, this difference persisted, although was not quite statistically significant (p=0.06).
8. The difference in FEV1 as measured in % predicted, was not significant between the two groups, although at 10 minutes, the albuterol + magnesium group FEV1 was 74.6% as compared to 63.5% in the albuterol + saline group with a p value of 0.07.
9. In comparing FEV1 at 0, 10, and 20 minutes, the differences within each group were significant between 0 and 10 minutes and 0 and 20 minutes but not between 10 and 20 minutes, leading the authors to conclude that the effect of the study drugs occurred primarily in the first 10 minutes.
10. Two of the 31 patients in the magnesium group and 1 of the 31 in the saline group required admission to the hospital. None of the participants showed any side effects from the medications.

Additional Comments

• Despite the significance in difference in FEV1 reported in this study, no attempt at assessing the duration of action or of clinical benefit of nebulized magnesium was made. There was no assessment of whether the earlier improvement in FEV1 seen with magnesium correlated with clinical outcomes or whether more than one treatment with nebulized magnesium would be beneficial. More research is needed.
• The method of action of magnesium is as a calcium antagonist or as a cofactor in enzyme systems involved in the movement of sodium and potassium across membranes, resulting in smooth muscle relaxation and mast cell stabilization.² Inhaled magnesium has an inhibitory effect on methacholine and histamine induced bronchoconstriction.¹
• The use of intravenous magnesium in pediatric patients experiencing moderate to severe asthma exacerbations has been shown to improve pulmonary function and decrease hospital admission rates², although other studies have shown less favorable results³, and overall, evidence is somewhat conflicting, but it seems that IV magnesium sulfate is of more benefit to those with more severe symptoms.⁴
• In a review of studies of both adults and children with asthma exacerbations, the use of nebulized magnesium sulfate in addition to beta-agonists appears to have benefits with respect to improved pulmonary function and there is a trend towards benefit in hospital admission. These benefits are significantly greater in more severe asthma exacerbations.⁵
• Nebulized magnesium did seem to be well tolerated without any adverse effects.^1,5 Studies done to evaluate the efficacy of IV magnesium in asthma have also failed to demonstrate significant adverse effects at the doses used.^2,3,4
  

Citation

1. Mahajan P, et al. Comparison of nebulized magnesium sulfate plus albuterol to nebulized albuterol plus saline in children with acute exacerbations of mild to moderate asthma. J Emerg Med 2004;27:21-5.
2. Ciarallo L, et al. Higher-dose intravenous magnesium therapy for children with moderate to severe acute asthma. Arch Pediatr Adolesc Med 2000;154:979-83.
3. Scarfon R, et al. A randomized trial of magnesium in the emergency department treatment of children with asthma. Annals of Emergency Medicine 2000;36:572-8.
4. Rowe B, et al. Magnesium sulfate for treating exacerbations of acute asthma in the emergency department. The Cochrane Database Syst Rev 2000 Jan 24;(1) CD001490.
5. Blitz M, et al. Inhaled magnesium sulfate in the treatment of acute asthma. Cochrane Database Syst Rev 2005 Jul 20;(3) CD003898.

CAT Author: Amanda Flint, MD

CAT Appraisers: James Gurney, PhD, MD

Date appraised: October 5, 2005