title: The role of ipratropium bromide in the emergency management of acute asthma exacerbation: a metaanalysis of randomized clinical trials.
abstract: OBJECTIVE
  This study was conducted to determine whether the addition of inhaled ipratropium to inhaled beta-agonist therapy is effective in the treatment of adults with acute asthma exacerbation.
  
  
  METHODS
  Published reports of randomized, controlled trials assessing the use of ipratropium and beta-agonists in asthma were identified by a search of the MEDLINE, EMBASE, CINAHL, Biological Abstracts on CD, the Cochrane Library, and Current Contents databases. Bibliographies from identified studies and from review articles were manually searched. Published and unpublished reports in English, French, and Italian were identified and assessed for inclusion in the metaanalysis. Randomized, double-blind, placebo-controlled trials were selected in which ipratropium was used as adjunctive therapy to beta-agonists in adult patients with acute asthma exacerbation presenting to a hospital emergency department or similar acute care setting. Data were extracted independently by 2 reviewers. For eligible trials, the mean percent change in peak expiratory flow rate (PEFR), or forced expiratory volume in one second (FEV1), and their SDs were assessed in the ipratropium-treated and control groups. The effect of ipratropium on hospitalization rates and adverse effects were also analyzed.
  
  
  RESULTS
  Data from 10 studies, reporting on a total of 1,377 patients with asthma, were pooled using a weighted average method. Compared with placebo, the use of ipratropium was associated with a pooled 7.3% improvement in FEV1 (95% confidence interval [CI] 3.8% to 10.9%), corresponding to an absolute improvement in FEV1 in the ipratropium/ beta-agonist group, which was 100 mL (95% CI 50 to 149 mL) above that seen for the group that received beta-agonist without ipratropium. Similarly, the pooled estimate of treatment effect in trials that reported data as PEFR was 22.1% (95% CI 11.0% to 33.2%), corresponding to an absolute peak expiratory flow improvement of 32 L/min (95% CI 16 to 47 L/min) in favor of the ipratropium/ beta-agonist combination group. When these data were combined using effect size as a common measure, the use of ipratropium was associated with a summary effect size of.38 (95% CI.27 to.48). Effect sizes were negatively correlated with baseline mean expiratory flows, suggesting that studies enrolling patients with more severe airflow obstruction showed greater absolute benefits of combination bronchodilator therapy. For the 3 trials reporting hospital admission data (n=1,031), patients receiving ipratropium had a relative risk of hospitalization of .73 (95% CI.53 to .99). The use of ipratropium was not associated with any severe adverse effects when used in conjunction with beta2 -agonists.
  
  
  CONCLUSIONS
  There is a modest statistical improvement in airflow obstruction when ipratropium is used as an adjunctive treatment to beta2 -agonists for the treatment of acute asthma exacerbation. Although the clinical significance of this improvement in airflow obstruction remains unclear, it would seem reasonable to recommend the use of combination ipratropium/ beta-agonist therapy in acute adult asthmatic exacerbations, since the addition of ipratropium seemed to provide physiologic evidence of benefit without risk of adverse effects.
authors.affiliation: Department of Pharmacy, University of Ottawa Heart Institute, and the Department of Medicine, Ottawa General Hospital, University of Ottawa, Ottawa, Ontario, Canada. saaron@ogh.on.ca
authors.forename: R G
authors.initials: RG
authors.lastname: Stoodley
authors.forename: S D
authors.initials: SD
authors.lastname: Aaron
authors.forename: R E
authors.initials: RE
authors.lastname: Dales
mesh_terms: D000208:Acute Disease; D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000627:therapeutic use; D000328:Adult; D001249:Asthma / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D015987:Effect Modifier, Epidemiologic; D004638:Emergency Treatment / Q000379:methods*; D005541:Forced Expiratory Volume / Q000187:drug effects; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D009241:Ipratropium / Q000494:pharmacology / Q000627:therapeutic use*; D010366:Peak Expiratory Flow Rate / Q000187:drug effects; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D016896:Treatment Outcome
chemical_list: D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D009241:Ipratropium