Inhaled anticholinergics and short-acting beta(2)-agonists versus short-acting beta2-agonists alone for children with acute asthma in hospital

Cochrane Database Syst Rev. 2014 Jul 31;2014(7):CD010283. doi: 10.1002/14651858.CD010283.pub2.


Background: Inhaled anticholinergics given in addition to β2-agonists are effective in reducing hospital admissions in children presenting to the emergency department with a moderate to severe asthma exacerbation. It seems logical to assume a similar beneficial effect in children hospitalised for an acute asthma exacerbation.

Objectives: To assess the efficacy and safety of anticholinergics added to β2-agonists as inhaled or nebulised therapy in children hospitalised for an acute asthma exacerbation. To investigate the characteristics of patients or therapy, if any, that would influence the magnitude of response attributable to the addition of anticholinergics.

Search methods: We identified trials from the Cochrane Airways Group Specialised Register of trials (CAGR), which is derived through systematic searches of bibliographic databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, AMED and PsycINFO and through handsearching of respiratory journals and meeting abstracts. The search is current to November 2013.

Selection criteria: Randomised trials comparing the combination of inhaled or nebulised anticholinergics and short-acting β2-agonists versus short-acting β2-agonists alone in children one to 18 years of age hospitalised for an acute asthma exacerbation were eligible.

Data collection and analysis: Two review authors independently assessed the methodological quality of trials and extracted data; disagreement was resolved by consensus or with the input of a third review author, when needed. Primary outcomes were duration of hospital stay and serious adverse events. Secondary outcomes included admission and duration of stay in the intensive care unit (ICU), ventilation assistance, time to short-acting β2-agonists spaced at four hours or longer, supplemental asthma therapy, duration of supplemental oxygen, change from baseline in asthma severity, relapse after discharge, adverse health effects and withdrawals.

Main results: 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.

Authors' conclusions: 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.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Acute Disease
  • Administration, Inhalation
  • Adolescent
  • Adrenergic beta-2 Receptor Agonists / administration & dosage*
  • Anti-Asthmatic Agents / administration & dosage*
  • Asthma / drug therapy*
  • Child
  • Child, Preschool
  • Cholinergic Antagonists / administration & dosage*
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Hospitalization
  • Humans
  • Infant
  • Ipratropium / administration & dosage
  • Nebulizers and Vaporizers
  • Randomized Controlled Trials as Topic


  • Adrenergic beta-2 Receptor Agonists
  • Anti-Asthmatic Agents
  • Cholinergic Antagonists
  • Ipratropium