Efficacy of frequent nebulized ipratropium bromide added to frequent high-dose albuterol therapy in severe childhood asthma,☆☆,,★★

Presented in part at the Society for Pediatric Research meeting in Seattle, Wash., May 2, 1994.
https://doi.org/10.1016/S0022-3476(95)70368-3Get rights and content

Abstract

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 1 second [FEV1], <50% of the predicted value) were enrolled into a randomized double-blind three-arm placebo-controlled trial comparing three groups: group 1, three doses of nebulized ipratropium bromide within 60 minutes (250 μg/dose); group 2, one dose of ipratropium; group 3, no ipratropium. All patients were also treated with three doses of nebulized 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 comparable at baseline. At 120 minutes, the mean percentage of predicted FEV1 improved from 33.4% to 56.7% in group 1, from 34.2% to 52.3% in group 2, and from 35.4% to 48.4% in group 3 (p = 0.0001). The differences between groups were larger in those children with a baseline FEV1 ≤30% of the predicted value: FEV1 increased 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 1, 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 FEV1 ≤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)

Section snippets

METHODS

The study design was a double-blind, randomized, placebo-controlled trial with three study groups: all patients received three nebulizations of albuterol in combination with either no ipratropium, one dose of ipratropium, or three doses of ipratropium. The study took place in the emergency department of the Hospital for Sick Children, Toronto, between October 1991 and December 1993. Included in the study were children with an acute asthma attack who were 5 through 17 years of age and were able

RESULTS

During the study period (Oct. 15, 1991, to Dec. 12, 1993) 1586 children more than 5 years of age with asthma were seen in our ED; 435 of these arrived while the nurse was on duty (usually between 2 and 10 PM). The exclusions comprised 204 patients with baseline FEV1 50% of the predicted value or greater, 33 patients previously enrolled in this study, 21 with coexistent medical problems, 32 children who did not perform the pulmonary function test satisfactorily, 15 whose condition was unstable

DISCUSSION

Our study shows a significant benefit of the addition of repeated doses of nebulized ipratropium to frequent high-dose albuterol therapy in children with severe acute asthma. This benefit seems especially marked in children with very severe baseline status, in whom this regimen also resulted in lower hospitalization rates.

Ipratropium is an acetylcholine antagonist. Although parasympathetic fibers occur primarily in the larger airways,17 ipratropium may have a generalized action throughout the

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  • Cited by (0)

    From the Divisions of Emergency, Clinical Pharmacology, and Chest, the Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada

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    Supported by the Ontario Ministry of Health (Emergency Medical Services) and Boehringer Ingelheim.

    Reprint requests: Suzanne Schuh, MD, Emergency Department, Hospital for Sick Children, 555 University Ave., Toronto, Ontario M5G 1X8, Canada.

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    0022-3476/95/$3.00 + 0 9/25/62808

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