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2013 ; 17
(45
): v-vi, 1-216
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MAGNEsium Trial In Children (MAGNETIC): a randomised, placebo-controlled trial
and economic evaluation of nebulised magnesium sulphate in acute severe asthma in
children
#MMPMID24144222
Powell CV
; Kolamunnage-Dona R
; Lowe J
; Boland A
; Petrou S
; Doull I
; Hood K
; Williamson PR
Health Technol Assess
2013[Oct]; 17
(45
): v-vi, 1-216
PMID24144222
show ga
BACKGROUND: There are few data on the role of nebulised magnesium sulphate
(MgSO4) in the management of acute asthma in children. Those studies that have
been published are underpowered, and use different methods, interventions and
comparisons. Thus, no firm conclusions can be drawn. OBJECTIVES: Does the use of
nebulised MgSO4, when given as an adjunct to standard therapy in acute severe
asthma in children, result in a clinical improvement when compared with standard
treatment alone? DESIGN: Patients were randomised to receive three doses of MgSO4
or placebo, each combined with salbutamol and ipratropium bromide, for 1 hour.
The Yung Asthma Severity Score (ASS) was measured at baseline, randomisation, and
at 20, 40, 60 (T60), 120, 180 and 240 minutes after randomisation. SETTING:
Emergency departments and children's assessment units at 30 hospitals in the UK.
PARTICIPANTS: Children aged 2-15 years with acute severe asthma. INTERVENTIONS:
Patients were randomised to receive nebulised salbutamol 2.5 mg (ages 2-5 years)
or 5 mg (ages ? 6 years) and ipratropium bromide 0.25 mg mixed with either 2.5 ml
of isotonic MgSO4 (250 mmol/l, tonicity 289 mOsm; 151 mg per dose) or 2.5 ml of
isotonic saline on three occasions at approximately 20-minute intervals. MAIN
OUTCOME MEASURES: The primary outcome measure was the ASS after 1 hour of
treatment. Secondary measures included 'stepping down' of treatment at 1 hour,
number and frequency of additional salbutamol administrations, length of stay in
hospital, requirement for intravenous bronchodilator treatment, and intubation
and/or admission to a paediatric intensive care unit. Data on paediatric quality
of life, time off school/nursery, health-care resource usage and time off work
were collected 1 month after randomisation. RESULTS: A total of 508 children were
recruited into the study; 252 received MgSO4 and 256 received placebo along with
the standard treatment. There were no differences in baseline characteristics.
There was a small, but statistically significant difference in ASS at T60 in
those children who received nebulised MgSO4 {0.25 [95% confidence interval (CI)
0.02 to 0.48]; p = 0.034} and this difference was sustained for up to 240 minutes
[0.20 (95% CI 0.01 to 0.40), p = 0.042]. The clinical significance of this gain
is uncertain. Assessing treatment-covariate interactions, there is evidence of a
larger effect in those children with more severe asthma exacerbations ( p =
0.034) and those with a shorter duration of symptoms ( p = 0.049). There were no
significant differences in the secondary outcomes measured. Adverse events (AEs)
were reported in 19% of children in the magnesium group and 20% in the placebo
group. There were no clinically significant serious AEs in either group. The
results of the base-case economic analyses are accompanied by considerable
uncertainty, but suggest that, from an NHS and Personal Social Services
perspective, the addition of magnesium to standard treatment may be
cost-effective compared with standard treatment only. The results of economic
evaluation show that the probability of magnesium being cost-effective is over
60% at cost-effectiveness thresholds of £1000 per unit decrement in ASS and
£20,000 per quality-adjusted life-year (QALY) gained, respectively; it is noted
that for some parameter variations this probability is much lower, reflecting the
labile nature of the cost-effectiveness ratio in light of the small differences
in benefits and costs shown in the trial and the relation between the main
outcome measure (ASS) and preference based measures of quality of life used in
cost-utility analysis (European Quality of Life-5 Dimensions; EQ-5D).
CONCLUSIONS: This study supports the use of nebulised isotonic MgSO4 at the dose
of 151 mg given three times in the first hour of treatment as an adjuvant to
standard treatment when a child presents with an acute episode of severe asthma.
No harm is done by adding magnesium to salbutamol and ipratropium bromide, and in
some individuals it may be clinically helpful. The response is likely to be more
marked in those children with more severe attacks and with a shorter duration of
exacerbation. Although the study was not powered to demonstrate this fully, the
data certainly support the hypotheses that nebulised magnesium has a greater
clinical effect in children who have more severe exacerbation with shorter
duration of symptoms. TRIAL REGISTRATION: Current Controlled Trials
ISRCTN81456894. FUNDING: The National Institute for Health Research Health
Technology Assessment programme.
|Acute Disease
[MESH]
|Asthma/*drug therapy
[MESH]
|Bronchodilator Agents/administration & dosage/adverse effects/*therapeutic use
[MESH]
|Child
[MESH]
|Child, Preschool
[MESH]
|Cost-Benefit Analysis
[MESH]
|Double-Blind Method
[MESH]
|Drug Therapy, Combination
[MESH]
|Emergency Service, Hospital
[MESH]
|Female
[MESH]
|Humans
[MESH]
|Magnesium Sulfate/administration & dosage/adverse effects/*therapeutic use
[MESH]