Randomized, double-blind, placebo-controlled trial of intravenous salbutamol and nebulized ipratropium bromide in early management of severe acute asthma in children presenting to an emergency department

BACKGROUND In acute severe asthma, treatment must be initiated early to reverse the pathophysiology that may render airways less responsive to bronchodilation. The addition of nebulized ipratropium bromide to initial emergency department therapy improves pulmonary function, but it is unclear whether this approach results in earlier hospital discharge. The early use of bolus intravenous salbutamol has also been shown to improve outcome, including earlier discharge. We therefore assessed the relative benefits of intravenous salbutamol and nebulized ipratropium bromide in the early management of acute severe asthma in children by a double-blind, randomized, controlled trial. METHODS This study was undertaken at a tertiary children’s hospital, The Children’s Hospital at Westmead, The Royal Alexandra Hospital for Children, Westmead, Sydney, Australia. Only children with severe acute asthma as determined by the National Asthma Campaign guidelines criteria and pulmonary index were included. All children received initial nebulized salbutamol therapy (2.5–5 mg salbutamol in 4 mL of normal saline depending on age) at initial emergency department presentation. If asthma remained severe 20 mins later, an intravenous cannula was inserted and intravenous methylprednisolone (1 mg/kg) was administered to all children receiving nebulized salbutamol every 20 mins. Children were then randomized to one of three groupsintravenous salbutamol (15 μg/kg as a single bolus over 10 mins), ipratropium bromide (250 μg), or intravenous salbutamol plus ipratropium bromide. All observers were blinded to treatment groups. Children were randomly assigned to receive a single-dose intravenous bolus of either saline or salbutamol and either nebulized saline or ipratropium bromide determined by a number generated randomly in the hospital pharmacy. The primary outcomes were recovery time and discharge time of each group. Respiratory and hemodynamic monitoring were continuous during the first 2 hrs of the study and then children were monitored clinically for 24 hrs. RESULTS A total of 55 children with acute severe asthma were entered into the study over an 18-month period. The three groups were similar demographically, with a mean age of 5.9 yrs, and mean duration of attack of 19.6 hrs. No side effects or treatment intolerance were reported. Children in the groups that received intravenous salbutamol had a significant reduction in recovery time to achieving second hourly inhaled salbutamol (p =