Nebulized salbutamol with and without ipratropium bromide in the treatment of acute asthma

J Allergy Clin Immunol. 1997 Aug;100(2):165-70. doi: 10.1016/s0091-6749(97)70219-7.


Background: Routine addition of ipratropium bromide to beta-agonist therapy in acute asthma is of uncertain benefit.

Objective: This study was carried out to evaluate: (1) whether nebulized ipratropium (0.5 mg) plus salbutamol (2.5 mg) (Combivent) confers additional bronchodilation over nebulized salbutamol (2.5 mg) alone in patients with acute asthma and (2) whether adjustment for prognostic indicators of outcome influences any benefit seen with ipratropium.

Methods: A double-blind, two-center, randomized, single-dose study was performed in 338 patients with asthma, aged 18 to 55 years, who attended the emergency department for treatment of acute asthma. The primary end point was FEV1 at 90 minutes.

Results: The mean absolute difference in FEV1 at 90 minutes for Combivent compared with salbutamol was 113 ml (SEM +/- 48 ml, p < 0.05). Independent of the study drug received, a poor response to treatment was predicted by frequent use of inhaled beta-agonist before presentation (p < 0.0001), severity of the attack (p < 0.05), and longer duration of attack (p < 0.05). Subjects who had taken more than 10 puffs of inhaled beta-agonist through a metered-dose inhaler or who had serum salbutamol levels of greater than 2 mmol/L on presentation demonstrated no benefit from the addition of ipratropium. Patients with an FEV1 less than 1 L on presentation also responded less well to Combivent, which was explained by the association between severity of attack and greater use of inhaled beta-agonist therapy.

Conclusion: A single dose of nebulized Combivent confers additional bronchodilation over salbutamol alone (p < 0.05) in acute asthma. Patients who exhibited most benefit from the addition of ipratropium were those who had consumed the least inhaled beta-agonist before presentation, not those with the most severe asthma.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Administration, Inhalation
  • Adrenergic beta-Agonists / therapeutic use*
  • Adult
  • Albuterol / therapeutic use*
  • Asthma / drug therapy*
  • Bronchodilator Agents / therapeutic use*
  • Double-Blind Method
  • Drug Combinations
  • Female
  • Humans
  • Ipratropium / therapeutic use*
  • Male
  • Nebulizers and Vaporizers


  • Adrenergic beta-Agonists
  • Bronchodilator Agents
  • Drug Combinations
  • Ipratropium
  • Albuterol