PEDIATRIC PHARMACOLOGY AND THERAPEUTICS Efficacy of frequent ipratropium bromide added high-dose albuterol therapy childhood asthma nebulized to frequent in severe Suzanne Schuh, MD, David W, Johnson, MD, Sheilagh Callahan, RN, Gerald Canny, MD, and Henry Levison, MD From the Divisions of Emergency, Clinical Pharmacology, and Chest, the Department of Pedi- atrics, Hospital for Sick Children, Toronto, Ontario, Canada Objective: The objective of this trial was to determine the efficacy of frequent nebulized ipratropium added to high-dose albuterol therapy in children with severe asthma. Methods: One hundred twenty children (5 to 17 years) of age) with severe acute asthma (forced expiratory volume in I second [FEV1], <50% of the predicted value) were enrolled into a randomized double-blind three-arm placebo-con- trolled trial comparing three groups: group I, three doses of nebulized ipratro- pium bromide within 60 minutes (250/~g/dose); group 2, one dose of ipratropium; group 3, no ipratropium. All patients were also treated with three doses of neb- ulized albuterol within 60 minutes (0.15 mg/kg per dose). Pulmonary function and clinical measures were assessed every 20 minutes for up to 120 minutes. Results: The groups were corn parable at baseline. At 120 minutes, the mean per- centage of predicted FEV1 improved from 33.4% to 56.7% in group I, from 34.2% to 52.3% in group 2, and from 35.4% to 48.4% in group 3 (p = 0.0001). The differ- ences between groups were larger in those children with a baseline FEV4 __<30% of the predicted value: FEV1increased from 24.5% to 50.9% in group 1, from 25.0% to 39.8% in group 2, and from 25.9% to 36.5% in group 3 (p =0.0001). In group I, 38% of the patients were hospitalized after the study, 44% in group 2, and 46% in group 3 (p value not significant). However, in patients with FEV~ ~30%, the hospitalization rates were 27% in group 1, 56% in group 2, and 83% in group 3 (p = 0.027). There were no toxic effects attributable to ipratropium. Conclusion: The addition of repeated doses of nebulized ipratropium to frequent high-dose albuterol therapy in patients with acute severe asthma is both safe and more effective than albuterol alone; its use in patients with very severe asthma may reduce hospitalizations. (J PEDIATR 1995;126:639"45) Supported by the Ontario Ministry of Health (Emergency Medi- cal Services) and Boehringer Ingelheim. Presented in part at the Society for Pediatric Research meeting in Seattle, Wash., May 2, 1994. Submitted for publication Sept. 28, 1994; accepted Dec. 15, 1994. Reprint requests: Suzanne Schuh, MD, Emergency Department, Hospital for Sick Children, 555 University Ave., Toronto, Ontario M5G 1XS, Canada. Copyright © 1995 by Mosby-Year Book, Inc. 0022-3476/95/$3.00 + 0 9/25/62808 Frequent administration of nebulized ¢/; agonists and of corticosteroids at the time of onset has been shown to be more effective than less aggressive therapy for acute exac- erbations of asthma. 1-5 However, many children do not re- spond adequately to this regimen and require prolonged treatment and hospitalization. Nebulized ipratropium bro- mide, an acetylcholine antagonist, has been used as an ad- junct to therapy for asthma in Europe and in Canada for almost a decade. Well-executed studies have demonstrated, 639