Anticholinergic bronchodilators versus beta2-sympathomimetic agents for acute exacerbations of chronic obstructive pulmonary disease

Shortness of breath is the main complaint of persons with chronic obstructive pulmonary disease (COPD). This symptom worsens during an exacerbation or 'flare' of COPD. Trials comparing ipratropium bromide versus beta-agonists showed no significant difference in short-term or long-term effects (24 hours) on ease of breathing. Side effects of these drugs were reported by only a minority of patients and include dry mouth and tremor, and a 'strange feeling' after drug administration.

Authors' conclusions: 

There was no evidence that the degree of bronchodilation achieved with ipratropium bromide was greater than that using a short-acting beta2-agonist. The combination of a beta2-agonist and ipratropium did not appear to increase the effect on FEV1 more than either used alone.

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Background: 

Inhaled bronchodilators form the mainstay of treatment for acute exacerbations of COPD. Two types of agent are used routinely, either singly or in combination: anticholinergic agents and beta2-sympathomimetic agonists.

Objectives: 

To assess the effect of anti-cholinergic agents on lung function and dyspnea in patients with acute exacerbations of COPD, compared with placebo or short-acting beta-2 agonists.

Search strategy: 

We searched the Cochrane Airways Group Specialised Register using pre-specified terms. We also searched references listed in each included trial for additional trial reports. Searches were current as of October 2005 and will be updated annually.

Selection criteria: 

We included studies if the participants were adult patients with a known diagnosis of COPD and had symptoms consistent with criteria for acute exacerbation of COPD. All randomized controlled trials that compared inhaled ipratropium bromide or oxitropium bromide to appropriate controls were considered. Appropriate control treatments included placebo, other bronchodilating agents, or combination therapies. Studies of acute asthma or ventilated patients were excluded.

Data collection and analysis: 

Two reviewers assessed all trials that appeared to be relevant who independently selected trials for inclusion. Differences were resolved by consensus.

Main results: 

Four trials compared the short-term effects of ipratropium bromide versus a beta2-agonist. Short-term changes in FEV1 (up to 90 minutes) showed no significant difference between beta2-agonist and ipratropium bromide treated patients. The differences were similar among the studies and when combined: Weighted Mean Difference (WMD) 0.0 liters (95% Confidence Interval (95% CI) -0.19 to 0.19). There was no significant additional increase in change in FEV1 on adding ipratropium to beta2-agonist: WMD 0.02 liter (95% CI -0.08 to 0.12). Long-term effects (24 hours) of the ipratropium bromide and beta2-agonist treatment combination were similar: WMD 0.05 liters (95% CI -0.14 to 0.05).

Neither of two studies found significant changes in PaO2, either short- or long-term, with ipratropium versus beta-agonist, although one showed an increase in PaO2 in subjects receiving ipratropium bromide at 60 minutes. Adverse drug reactions included dry mouth and tremor.

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