The role of ipratropium bromide in the emergency management of acute asthma exacerbation: A metaanalysis of randomized clinical trials

Study 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 u se of ipratropium and beta-agonists in asthma were identified by a search o f the MEDLINE, EMBASE, CINAHL, Biological Abstracts on CD, the Cochrane Lib rary, and Current Contents databases. Bibliographies from identified studie s and from review articles were manually searched. Published and unpublishe d 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 t o beta-agonists in adult patients with acute asthma exacerbation presenting to a hospital emergency department or similar acute care setting. Data wer e extracted independently by 2 reviewers. For eligible trials, the mean per cent change in peak expiratory flow rate (PEFR), or forced expiratory volum e in one second (FEV1), and their SDs were assessed in the ipratropium-trea ted 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 FE V1 (95% confidence interval [CI] 3.8% to 10.9%), corresponding to an absolu te improvement in FEV1 in the ipratropium/beta-agonist group, which was 100 mL(95% CI 50 to 149 mt) above that seen for the group that received beta-a gonist without ipratropium. Similarly, the pooled estimate of treatment eff ect 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 combinatio n group. When these data were combined using effect size as a common measur e, 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 hospita lization of .73 (95% CI .53 to .99). The use of ipratropium was not associa ted with any severe adverse effects when used in conjunction with beta(2)-a gonists. Conclusion: There is a modest statistical improvement in airflow obstructio n when ipratropium is used as an adjunctive treatment to beta(2)-agonists f or the treatment of acute asthma exacerbation. Although the clinical signif icance of this improvement in airflow obstruction remains unclear, it would seem reasonable to recommend the use of combination ipratropium/beta-agoni st therapy in acute adult asthmatic exacerbations, since the addition of ip ratropium seemed to provide physiologic evidence of benefit without risk of adverse effects.