title: Magnesium sulphate in acute severe asthma in children (MAGNETIC): a randomised, placebo-controlled trial.
abstract: 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  National Institute for Health Research Health Technology Assessment Programme.
authors.affiliation: School of Medicine, Cardiff University, Cardiff, UK. Electronic address: powellc7@cardiff.ac.uk.
authors.forename: Colin
authors.initials: C
authors.lastname: Powell
authors.affiliation: Department of Biostatistics, University of Liverpool, Liverpool, UK.
authors.forename: Ruwanthi
authors.initials: R
authors.lastname: Kolamunnage-Dona
authors.affiliation: School of Medicine, Cardiff University, Cardiff, UK; Department of Biostatistics, University of Liverpool, Liverpool, UK.
authors.forename: John
authors.initials: J
authors.lastname: Lowe
authors.affiliation: Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK.
authors.forename: Angela
authors.initials: A
authors.lastname: Boland
authors.affiliation: Department of Public Health, University of Warwick, Coventry, UK.
authors.forename: Stavros
authors.initials: S
authors.lastname: Petrou
authors.affiliation: Department of Respiratory Paediatrics, Children's Hospital for Wales, Cardiff, UK.
authors.forename: Iolo
authors.initials: I
authors.lastname: Doull
authors.affiliation: School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Kerenza
authors.initials: K
authors.lastname: Hood
authors.affiliation: Department of Biostatistics, University of Liverpool, Liverpool, UK.
authors.forename: Paula
authors.initials: P
authors.lastname: Williamson
mesh_terms: D000208:Acute Disease; D000280:Administration, Inhalation; D000293:Adolescent; D000420:Albuterol / Q000008:administration & dosage; D000927:Anticonvulsants / Q000008:administration & dosage; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007275:Injections, Intravenous; D009241:Ipratropium / Q000008:administration & dosage; D008278:Magnesium Sulfate / Q000008:administration & dosage*; D008297:Male; D012132:Respiratory Muscles / Q000187:drug effects / Q000503:physiopathology*; D012189:Retrospective Studies; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants; D001993:Bronchodilator Agents; D008278:Magnesium Sulfate; D009241:Ipratropium; D000420:Albuterol