Two cumulative doses of salbutamol delivered by metered dose inhaler (MDI) with a pear-shaped spacer were compared (400 micrograms vs 600 micrograms at 10-minute intervals). Twenty-two patients (mean age 35.1 +/- 11.1 years) with acute exacerbation of asthma were randomly selected, in a double-blind fashion, to receive salbutamol delivered with MDI into a spacer device in 4 puffs at 10- minute intervals (100 micrograms or 150 micrograms per actuation) during 3 hours (1200 micrograms or 1800 micrograms each 30 minutes). Mean peak expiratory flow rate (PEFR) and forced expiratory volume in the first second (FEV1) improved significantly over baseline values for both groups (P < .001). Nevertheless, there were no significant differences between both groups for PEFR and FEV1 at any time point studied. A significant net reduction of heart rate was observed in the 400 microgram group (P < .01). On the other hand, a significant increase in heart rate was observed in the 600 microgram group (P < .001). The QTc interval did not show a significant prolongation, and the two groups presented moderate decreases of serum potassium levels. There was a significant dose-related increase (P = .027) in Sao2. Additionally, the 600 microgram group generated a serum glucose level increase from 0.85 +/- 0.12 mg/100 mL to 1.04 +/- 0.25 mg/100 mL (P = .02), with a higher incidence in 4 symptoms (tremor, headache, palpitations, and anxiety). These data support the notion that the treatment of acute asthma patients in the emergency department setting with salbutamol, 2.4 mg/h, delivered by MDI and spacer (4 puffs at 10-minute intervals) produces satisfactory bronchodilation, low serum concentration, and minimal extrapulmonary effects. However, an increase of 50% of the dose (600 micrograms at 10-minute intervals) produced a nonsignificant, slightly better therapeutic response but with greater side effects, probably related to higher salbutamol levels.