Best Evidence Topics
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Multiple different bronchodilators unnecessary in acute COPD

Three Part Question

In [patients presenting with an acute exacerbation of COPD] is nebulisation of [a beta 2 agonist alone, ipratropium bromide alone or a combination of the two] more effective at [controlling and improving symptoms]?

Clinical Scenario

A 59 year old man presents with an exacerbation of COPD. You wonder whether it is better to nebulise salbutamol or ipratropium bromide alone, or a combination of the two.

Search Strategy

Medline 1966-11/00 using the OVID interface.
{{[(exp chronic disease OR exp hospitals, chronic disease OR AND (exp lung disease, obstructive OR] OR exp emphysema OR exp pulmonary emphysema OR OR exp bronchitis OR OR exp OR OR airway} AND ( or} AND (exp ipratropium OR ipratropium OR OR OR exp. muscarinic antagonist OR exp brochodilators agents OR OR exp albuterol OR OR beta 2 OR exp terbutaline) AND (exp nebulisers OR OR exp respiratory therapy OR NOT (exp child OR OR exp paediatrics OR LIMIT to human AND english.

Search Outcome

162 papers found of which 157 were irrelevant or of insufficient quality. The remaining 5 papers are shown in the table.

Relevant Paper(s)

Author, date and country Patient group Study type (level of evidence) Outcomes Key results Study Weaknesses
Rebuck AS et al,
51 patients with an acute exacerbation of COPD (148 asthmatics also recruited) Ipratropium vs fenoterol vs both (all nebulised).PRCTFVC, FEV1, MMEFR, PEFR, cardiovascular markers at 45 minNo significant differenceNo sample size calculation. Small groups in each of the treatment arms, thus small differences may go undetected.
FVC, FEV1, MMEFR, PEFR, cardiovascular markers at 90 minNo significant difference
O'Driscoll BR et al,
47 patients with COPD (an asthmatic group also recruited) Salbutamol vs salbutamol plus ipratropium bromidePRCTPEFR on arrival and at one hourNo difference in improvement (P>0.55)No sample size calculation, small groups in each treatment arm, thus important effects can be overlooked. No defined inclusion or exclusion criteria. 20 patients admitted, excluded from study. No actual figures given.
Shrestha M et al,
55 COPD patients with an acute exacerbation (FEV1 <40% of predicted) Isoetharine plus placebo vs isoetharine plus ipratropium bromide (inhaled)PRCTTimes to discharge from ED.Time to discharge 91 minutes less in the salbutamol plus ipratropium group (P<0.05)No sample size calculation. Small numbers. Inhaled therapy
FVC, FEV1No difference
Moayyedi P et al,
62 COPD patients with an acute exacerbation Salbutamol vs salbutamol plus ipratropium bromide (nebulised)PRCTLength of hospital stayNo significant differencePower study retrospectively completed.
Duration of nebuliser therapyNo significant difference
FVC, FEV1No significant difference
Subjective improvement on days 1, 3, 7 and 14.No significant difference
Koutsogiannis Z and Kelly A-M,
?patients presenting to ED with an acute exacerbation of COPD. All patients started with salbutamol and ipratropium nebulisers and then salbutamol vs ipratropium vs salbutamol plus ipratropium.PRCTAbsolute and percentage change in FEV1 at 90 minNo difference between the 2 groups. P=0.36 for absolute change, P=0.56 for % change)No patient numbers given. No sample size calculation. Groups are small thus any differences may be overlooked. All patients had both drugs initially.


There are 5 randomised trials that address the three-part question. All of the studies are of reasonable quality.

Clinical Bottom Line

Initial therapy can be either salbutamol or ipratropium nebulisers alone. There is no evidence to suggest that using both has additional benefit.


  1. Rebuck AS, Chapman KR, Abboud R et al. Nebulized anticholinergic and sympathomimetic treatment of asthma and chronic obstructive airways disease in the emergency room. Am J Med 1987;82:59-64.
  2. O'Driscoll BR, Taylor RJ, Horsley MG et al. Nebulised salbutamol with and without ipratropium bromide in acute airflow obstruction. Lancet 1989;1:1418-20.
  3. Shrestha M, O'Brien T, Haddox R et al Decreased duration of emergency department treatment of chronic obstructive pulmonary disease exacerbations with the addition of ipratropium bromide to beta-agonist therapy. Ann Emerg Med 1991;20:1206-9.
  4. Moayyedi P, Congleton J, Page RL et al. Comparison of nebulised salbutamol and ipratropium bromide with salbutamol alone in the treatment of chronic obstructive pulmonary disease Thorax 1995;50:834-7.
  5. Koutsogiannis Z, Kelly AM. Does high dose ipratropium bromide added to salbutamol improve pulmonary function for patients with chronic obstructive airways disease in the emergency department? Aus New Zealand Med J 2000;30:38-40.