Salbutamol treatment of acute severe asthma in the ED: MDI versus hand-held nebulizer

Abstract

The objectives of this study were to compare the efficacy of salbutamol delivered by either metered-dose inhaler plus spacer (MDI-spacer) or by wet nebulization (NEB), and to determine the relationships between physiologic responses and plasma salbutamol concentrations. Asthmatic patients presenting to the emergency department (ED) with acute severe asthma (forced expiratory volume in the first second [FEV 1] less than 50% of predicted) were enrolled in a randomized, double-blind, parallel-group study. The MDI-spacer group received salbutamol, delivered via MDI into a spacer device, in four puffs actuated in rapid succession at 10-minute intervals (2.4 mg/h). The NEB group was treated with nebulized salbutamol, 1.5 mg, via nebulizer at 15-minute intervals (6 mg/h). Doses were calculated on the basis of the percentage of total dose that reaches the lower airway with both methods. The protocol involved 3 hours of this treatment. Mean peak expiratory flow rate (PEFR) and FEV 1 improved significantly over baseline values for both groups ( P = .01). However, there were no significant differences between both groups for PEFR and FEV 1 at any point studied. The examination of the relationships between cumulative dose of salbutamol and change in FEV 1 showed a significant linear relationship ( P = .01) for both methods (MDI r = .97; NEB r = .97). The regression equations showed that for every 1 mg of salbutamol by MDI-spacer, 2.5 mg are needed from nebulization to have equal therapeutic response. At the end of treatment, the salbutamol plasma levels were 10.1 ± 1.6 ng/ml for the MDI-spacer group and 14.4 ± 2.3 ng/ml for the NEB group ( P = .0003). Both groups showed a nonsignificant heart rate decrease. A significant group-by-time interaction means that differences between groups increased with time ( P = .04). Additionally, the NEB group presented a higher incidence of tremor ( P = .03) and anxiety ( P = .04), reflecting larger systemic absorption of salbutamol. These data indicate that when doses used are calculated on the basis of the percentage of total drug that reaches the lower airway, there was equivalent bronchodilatation after salbutamol administered by either MDI-spacer or nebulization in patients with acute severe asthma. However, nebulizer therapy produced greater side effects related to the increase in salbutamol absorption and higher plasma level.