Magnesium sulphate in acute severe asthma in children (MAGNETIC): a randomised, placebo-controlled trial
Colin Powell1, Ruwanthi Kolamunnage-Dona2, John Lowe3
1School of Medicine, Cardiff University, Cardiff, UK.
Background:
Little evidence is available for the effect of nebulised magnesium sulphate (MgSO(4)) in acute asthma in children. We assessed the effect of MgSO(4) treatment in children with severe acute asthma.
Methods:
In this randomised placebo-controlled, multi-centre, parallel trial, we enrolled children (aged 2-16 years) with severe acute asthma who did not respond to standard inhaled treatment from 30 hospitals in the UK. Children were randomly allocated (1:1) to receive nebulised salbutamol and ipratropium bromide with either 2·5 mL of isotonic MgSO(4) (250 mmol/L; 151 mg per dose; MgSO(4) group) or 2·5 mL of isotonic saline (placebo group) on three occasions at 20-min intervals. Randomisation was done with a computer-generated randomisation sequence, with random block sizes of two to four. Both patients and researchers were masked to treatment allocation. The primary outcome measure was the Yung Asthma Severity Score (ASS) at 60 min post-randomisation. We used a statistical significance level of p<0·05 for a between-group difference, but regarded a between-group difference in ASS of 0·5 as the minimal clinically significant treatment effect. Analysis was done by intention to treat. This trial is registered with controlled-trials.com, number ISRCTN81456894.
Findings:
Between Jan 3, 2009, and March 20, 2011, we recruited and randomly assigned 508 children to treatment: 252 to MgSO(4) and 256 to placebo. Mean ASS at 60 min was lower in the MgSO(4) group (4·72 [SD 1·37]) than it was in the placebo group (4·95 [SD 1·40]; adjusted difference -0·25, 95% CI -0·48 to -0·02; p=0·03). This difference, however, was not clinically significant. The clinical effect was larger in children with more severe asthma exacerbation (p=0·03) and those with symptoms present for less than 6 h (p=0·049). We detected no difference in the occurrence of adverse events between groups.
Interpretation:
Overall, nebulised isotonic MgSO(4), given as an adjuvant to standard treatment, did not show a clinically significant improvement in mean ASS in children with acute severe asthma. However, the greatest clinical response was seen in children with more severe attacks (SaO(2)<92%) at presentation and those with preceding symptoms lasting less than 6 h.
Funding:
National Institute for Health Research Health Technology Assessment Programme.
Insights
Nebulised magnesium sulphate (MgSO(4)) did not significantly improve acute severe asthma in children. However, it showed greater benefit in severe attacks and symptoms under 6 hours.
Area of Science:
- Pediatric Emergency Medicine
- Respiratory Medicine
- Clinical Pharmacology
Background:
- Limited evidence exists on nebulised magnesium sulphate (MgSO(4)) for acute pediatric asthma.
- Severe acute asthma in children requires effective treatment options.
Purpose of the Study:
- To assess the efficacy of nebulised magnesium sulphate (MgSO(4)) as an adjunct treatment for severe acute asthma in children.
- To evaluate the impact of MgSO(4) on asthma severity scores and clinical outcomes.
Main Methods:
- A multi-centre, randomised, placebo-controlled, parallel trial involving 508 children (aged 2-16 years) with severe acute asthma.
- Participants received either nebulised MgSO(4) or saline (placebo) alongside standard inhaled treatment over three 20-minute intervals.
- The primary outcome was the Yung Asthma Severity Score (ASS) at 60 minutes post-randomisation.
Main Results:
- The mean ASS at 60 minutes was slightly lower in the MgSO(4) group (4.72) compared to the placebo group (4.95), with a statistically significant but not clinically significant difference (p=0.03).
- A greater clinical effect was observed in children with more severe asthma exacerbations (p=0.03) and those with symptom duration less than 6 hours (p=0.049).
- No significant difference in adverse events was noted between the MgSO(4) and placebo groups.
Conclusions:
- Nebulised isotonic MgSO(4) as an adjunct to standard treatment did not provide a clinically significant improvement in mean ASS for children with acute severe asthma.
- The greatest clinical response to MgSO(4) was observed in children presenting with more severe attacks (SaO(2)<92%) and shorter symptom duration (<6 hours).
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