Abstract: Seven randomised trials were included, four of which reported usable data on 472 children with asthma one to 18 years of age who were admitted to paediatric wards. No trials included patients admitted to the ICU. The anticholinergic used, ipratropium bromide 250 μg, was given every one to eight hours over a period from four hours to the entire length of the hospital stay. Two of four trials (50%) contributing data were deemed of high methodological quality. The addition of anticholinergics to β2-agonists showed no evidence of effect on the duration of hospital admission (mean difference (MD) -0.28 hours, 95% confidence interval (CI) -5.07 to 4.52, 3 studies, 327 participants, moderate quality evidence) and no serious or non-serious adverse events were reported in any included trials. As a result of the similarity of trials, we could not explore the influence of age, admission site, intensity of anticholinergic treatment and co-interventions on primary outcomes. No statistically significant group difference was noted in other secondary outcomes, including the need for supplemental asthma therapy, time to short-acting β2-agonists spaced at four hours or longer, asthma clinical scores, lung function and overall withdrawals for any reason. In children hospitalised for an acute asthma exacerbation, no evidence of benefit for length of hospital stay and other markers of response to therapy was noted when nebulised anticholinergics were added to short-acting β2-agonists. No adverse health effects were reported, yet the small number of trials combined with inadequate reporting prevent firm reassurance regarding the safety of anticholinergics. In the absence of trials conducted in ICUs, no conclusion can be drawn regarding children with impending respiratory failure. These findings support current national and international recommendations indicating that healthcare practitioners should refrain from using anticholinergics in children hospitalised for acute asthma.

Plain-language summary: In reviewing evidence available until November 2013, we found seven eligible studies of children hospitalised with acute asthma; four of these studies (472 children one to 18 years of age) contributed data to the review. Four studies compared the combination of anticholinergics (ipratropium bromide) and beta2-agonists versus the same dose of beta2-agonists alone. Included studies enrolled both girls and boys, with a gender ratio ranging from 59% to 73% males. No additional benefit was noted by adding anticholinergics to β2-agonists in terms of duration of hospital stay in patients compared to those who received beta2-agonists alone. Two of four trials (50%) contributing data were deemed of high methodological quality. No trial reported information on serious adverse events. No statistically significant group difference was noted in other markers of response to therapy, that is, the need for supplemental asthma therapy, time to short-acting beta2-agonists spaced at four hours or longer, asthma clinical scores, lung function and overall withdrawals for any reason. No apparent benefit is derived from adding anticholinergics to beta2-agonists in children hospitalised for an acute asthma exacerbation, that is, beyond initial treatment in the emergency department. No adverse health effects were reported, yet the small number of trials combined with inadequate reporting prevents firm reassurance regarding the safety of anticholinergics. In the absence of trials conducted in the intensive care unit (ICU), no conclusion can be drawn regarding children with very severe exacerbations who are admitted to the ICU. Our findings support the ongoing recommendations provided by national and international guidelines. This review is based on a small number of identified trials conducted in children with acute asthma. All trials contributing to the primary outcome are of high methodological quality, but they are few. As the addition of new trials may change the conclusion, the quality of evidence was downgraded from high to moderate. Additional and larger trials are needed.