Combined inhaled anticholinergics and beta2-agonists for initial treatment of acute asthma in children.
BACKGROUND
Several randomized controlled trials have examined, with conflicting results, the efficacy of the addition of anticholinergics to beta2 agonists in acute pediatric asthma. The pooling for a larger number of randomized controlled trials may provide not only greater power for detecting group differences and also provide better insight into the influence of patients' characteristics and treatment modalities on efficacy.


OBJECTIVE
The aims of this study were to estimate the therapeutic and adverse effects attributable to the addition of inhaled anticholinergics to beta2 agonists in acute pediatric asthma.


METHODS
We searched Medline (1966 to April 2000), Embase (1980 to April 2000), Cinahl (1982 to April 2000) and reference lists of studies. We also contacted drug manufacturers and trialists.


METHODS
Randomised trials comparing the combination of inhaled anticholinergics and beta2 agonists with beta2 agonists alone in children aged 18 months to 17 years with acute asthma.


METHODS
Assessments of trial quality and data extraction were done by two reviewers independently.


RESULTS
Of the 40 identified trials, 13 were relevant and eight of these were of high quality. The addition of a single dose of anticholinergic to beta2 agonists did not reduce hospital admission [RR=0.93 (95% CI: 0.65, 1.32)]. However, significant group differences in lung function supporting the combination of anticholinergics and beta2-agonists were observed 60 minutes [SMD=0.57 (95% CI:0.21, 0.93)] and 120 minutes [SMD=0.53 (95% CI: 0.17, 0.90)] after the dose of anticholinergic. In contrast, the addition of multiple doses of anticholinergics to beta2 agonists reduced the risk of hospital admission by 25% [RR=0.75 (95% CI: 0.62,0.89)] in children with predominantly moderate and severe exacerbations. Twelve (95% CI: 8, 32) children would need to be treated to avoid one admission. When restricting this strategy to children with severe exacerbations, seven (95% CI: 5, 20) children need to be treated to avoid an admission. At 60 minutes after the last anticholinergic inhalation, a weighted mean group difference of 9.68 in change in % predicted FEV1 [95% CI:5.70, 13.68] favored anticholinergic use. In the two studies where anticholinergics were systematically added to every beta2 agonist inhalation, irrespective of asthma severity, no group differences were observed for the few available outcomes. There was no increase in the amount of nausea, vomiting or tremor in patients treated with anticholinergics.


CONCLUSIONS
A single dose of an anticholinergic agent is not effective for the treatment of mild and moderate exacerbations and is insufficient for the treatment of severe exacerbations. Adding multiple doses of anticholinergics to beta2 agonists appears safe, improves lung function and would avoid hospital admission in 1 of 12 such treated patients. Although multiple doses should be preferred to single doses of anticholinergics, the available evidence only supports their use in school-aged children with severe asthma exacerbation. There is no conclusive evidence for using multiple doses of anticholinergics in children with mild or moderate exacerbations.
Plotnick
L H
LH
The Montreal Childrens' Hospital, Room C538E, 2300 Tupper Street, Montreal, Quebec, CANADA, H3H 1P3. drlaurie@total.net
Ducharme
F M
FM
D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D002648:Child; D018680:Cholinergic Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006801:Humans; D016032:Randomized Controlled Trials as Topic
D000318:Adrenergic beta-Agonists; D018680:Cholinergic Antagonists