Purpose of the Study
Previous studies have demonstrated the benefit of inhaled ipratropium as an adjunct to inhaled β2 bronchodilators in the treatment of acute severe asthma in children. The purpose of this study was to observe children with mild to moderate exacerbations of asthma, comparing the efficacy, safety, and possible synergy of inhaled salbutamol with or without inhaled ipratropium.
Two hundred ninety-eight events in 275 patients were analyzed. The children were 3 to 17 years of age and presented to a single emergency room facility with mild to moderate exacerbations of asthma over a 2½-year period of time. To qualify they also had to be able to reproducibly perform forced oscillometry (a noneffort dependent, quiet breathing/tidal volume measurement of airway resistance) and they required more than one salbutamol treatment.
The study was blinded, randomized, and placebo-controlled for the ipratropium. Patients were excluded if they had a severe asthma exacerbation, or significant comorbidity such as heart disease or cyctic fibrosis. Eligible patients were randomized to one of four treatment groups: high-dose salbutamol (0.15 mg/kg q 60 minutes; maximum dose 5 mg) with or without 250 μg ipratropium; frequent low-dose salbutamol (0.075 mg/kg q 30 minutes) with or without ipratropium. Ipratropium or placebo were given only once 30 minutes after the first salbutamol treatment. The primary endpoint was the change from baseline in respiratory resistance as measured by forced oscillometry. Values were ascertained at the time of the peak effect of both drugs; 30 minutes after salbutamol and 60 minutes after ipratropium. Secondary endpoints were oxygen saturation, the need for oral corticosteroids as a discharge medication, hospital admission, and relapse within 10 days. Prior home treatment and maintenance medications were cofactored into the analysis.
The use of forced oscillometry allowed 69% of the children to participate who would have otherwise been excluded by the inability to reproducibly perform standard spirometry. All treatment groups improved significantly from baseline to 90 minutes (P < .001). There were no differences in the acute management at home nor the physician assessment of severity among the four treatment groups. No group differences were observed in the magnitude of improvement or in the number of patients who required an additional hour of treatment. In a subgroup of children in whom cough and rhonchi were prominent features, the anticholinergic effects of ipratropium did not provide additional benefit beyond salbutamol alone. There were no group differences in the need for corticosteroids, oxygen saturation, hospitalization rates, or relapse rates. The frequent, low-dose regimen of salbutamol was associated with a greater incidence of vomiting than hourly, high-dose salbutamol. There were no group differences in the incidence of other side effects.
In children with a mild to moderate exacerbation of asthma neither frequent low-dose salbutamol nor the addition of inhaled ipratropium provided additional beneficial effect compared with hourly high-dose salbutamol alone.
This is the largest study of its kind and unique in its ability to objectively evaluate changes in lung function in young children who represent a significant population of pediatric asthma patients presenting for acute care for mild to moderate exacerbations. Previous studies have demonstrated the benefit of frequent low-dose albuterol and the synergistic effect of inhaled ipratropium in children with severe exacerbations. This study suggests that these intense strategies may not be necessary for children with mild to moderate exacerbations, economizing on provider time and materials without sacrificing patient outcomes. However, it is possible that higher or more frequent doses of ipratropium may have shown a greater improvement in lung function as suggested in recent studies (Querishi FA, et al. Ann Emerg Med. 1997;29:205–211 and Schuh S, et al. J Pediatr. 1995;126:639–645).