Treatment of acute asthma. Lack of therapeutic benefit and increase of the toxicity from aminophylline given in addition to high doses of salbutamol delivered by metered-dose inhaler with a spacer

Chest. 1994 Oct;106(4):1071-6. doi: 10.1378/chest.106.4.1071.


We conducted a randomized, double-blind, placebo-controlled study to determine if intravenous aminophylline adds any benefit to high doses of inhaled salbutamol in patients who presented for treatment of acute asthma. We studied 94 patients (mean age, 35.6 +/- 11.2 years) with moderate to severe acute asthma. All patients received therapy with salbutamol delivered with metered-dose inhaler (MDI) into a spacer device (Volumatic) in four puffs (400 micrograms) at 10-min interval, and intravenous hydrocortisone (500 mg). Patients were randomly assigned to receive either a loading dose of intravenous aminophylline followed by a routine infusion (n = 45) or an equal volume of placebo as a loading dose and infusion (n = 49). The two groups showed no differences in measurements of peak expiratory flow, FEV1, and FVC at baseline and at the end of treatment. However, the patients treated with aminophylline had significantly more adverse effects (p < 0.05). There were no differences in the final mean dose of salbutamol (6.3 +/- 44.5 mg for the placebo group and 5.8 +/- 4.2 mg for the aminophylline group), hospital admission rate (10.2 percent for the placebo group and 9.0 percent for the aminophylline group), and mean duration of Emergency Department treatment (2.5 +/- 1.83 h for the placebo group and 2.37 +/- 1.75 h for the aminophylline group). The results were similar when the patients were divided in accord with the degree of respiratory obstruction (baseline FEV1 < 30 percent of predicted) and theophylline level at 30 min of treatment (placebo group patients with theophylline level < 10 mg/L vs aminophylline group patients with theophylline level > or = 10 mg/L). We conclude that intravenous aminophylline adds to the toxicity but not the efficacy of inhaled salbutamol in the treatment of acute exacerbations of asthma.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Acute Disease
  • Administration, Inhalation
  • Adult
  • Albuterol / administration & dosage*
  • Albuterol / therapeutic use
  • Aminophylline / administration & dosage*
  • Aminophylline / adverse effects*
  • Aminophylline / therapeutic use
  • Asthma / drug therapy*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Emergencies
  • Female
  • Humans
  • Hydrocortisone / administration & dosage
  • Hydrocortisone / therapeutic use
  • Infusions, Intravenous
  • Injections, Intravenous
  • Male
  • Nebulizers and Vaporizers


  • Aminophylline
  • Albuterol
  • Hydrocortisone