Anticholinergic Treatment in Asthma
ABSTRACT & COMMENTARY
Synopsis: Among children with severe exacerbations of asthma, the addition of an anticholinergic, atropine-like agent (nebulized ipatropium) to standard albuterol and corticosteroid therapy significantly decreased the hospitalization rate.
Source: Qureshi F, et al. Effect of nebulized ipatropium on the hospitalization rate of children with asthma. N Engl J Med 1998;339:1030-1035.
Qureshi and associates from the emergency Department (ED) at the Children’s Hospital of the King’s Daughters in Norfolk, Va., had previously demonstrated that the addition of ipatropium, an anticholinergic drug, to standard albuterol therapy significantly improved the pulmonary function of children experiencing an acute asthmatic attack. Because other small studies did not show a beneficial effect, Qureshi et al designed a large, double-blind, prospective study to determine whether the addition of anticholinergic therapy with nebulized ipatropium to their standard ED therapy with albuterol and corticosteroids would reduce hospitalization rates of children with an acute exacerbation of asthma.
Nearly 500 children, 2-8 years old who presented at the ED with an acute exacerbation of asthma, were enrolled in the study. All children were treated with 2.5-5.0 mg of nebulized albuterol delivered by a face mask every 20 minutes for three treatments. They were given oral prednisone, 2 mg/kg, with the second albuterol treatment. At the time of the second nebulization treatment, the children were randomized to have either 500 mcg of ipatropium or a placebo added to their second and third albuterol nebulization solutions.
The initial severity of each child’s episode was rated either by the percentage of the predicted peak expiratory flow rate or an asthma scoring system based on signs and symptoms. Only children with moderate or severe exacerbations of asthma were enrolled in the study.
A total of 434 children—215 in the treatment group and 219 in the control group—completed the study. Except for a slight predominance of girls in the treatment group, there was no significant difference between the groups as a whole or between groups stratified according to the severity of the asthmatic exacerbation. The decision of whether to admit a child to the hospital was made by the attending physician based on objective changes in the measurements of clinical and pulmonary function and according to oxygen saturation (< 94% or > 94% in room air).
Overall, the rate of hospitalization was lower in the ipatropium group (59 of 215 children, 27.4%) than in the placebo group (80 of 219, 36.5%), P = 0.05. For patients classified as severe, the addition of ipatropium significantly reduced the need for hospitalization (51 of 136 treatment children, 37.5% compared to 71 of 135 control children, 52.6%; P = 0.02).
Comment by Thomas Dolan, MD, FAAP
This is an excellently controlled study consisting of a control group of 219 patients and an "ipatropium" group of 215 patients. In addition to using peak flow rates that are usually not obtainable before age 5, all patients were assessed using an asthma score consisting of five variables: signs and symptoms, respiratory rate, O2 saturation, auscultation retractions, and dyspnea.
Both groups of children were treated with nebulized albuterol every 20 minutes for three doses. Two mgm of prednisone or prednisolone, to a maximum dose of 60 mgm, was given orally with the second albuterol treatment. Patients who responded to the first or second dose of albuterol were eliminated from the study, as they were unlikely candidates for hospitalization. Children in the treatment group received 500 mcg of ipatropium with the second and third doses of albuterol. Children in the control group received normal saline with the albuterol. There was an overall 10% reduction in admissions for patients receiving ipatropium, mainly in severe patients (16% reduction).
It makes good sense to consider adding ipatropium to an emergency room protocol for treatment of acute asthmatic attacks. Ipatropium is an anticholinergic, parasympathetic agent that acts primarily on the choline receptors in larger airways. Albuterol is a sympathomimetic agent acting primarily on beta-agonist receptors that are chiefly found in the small airways. In a similar study, Schuh showed that combined albuterol ipatropium therapy greatly reduced hospital admission rates, particularly in more severe patients.1 Other studies in the literature show that ipatropium is an excellent second-line drug in the treatment of asthma. I would favor earlier use of ipatropium because the longer an attack of asthma lasts, the more difficult it is to stop.
I would suggest that ipatropium inhalation be included in the first nebulization treatment (along with albuterol) in patients who are referred to the ED because they have not responded to 2-3 nebulized treatments at home, as well as to patients in the ED who have shown little or no response after two treatments of albuterol. Ipatropium is well tolerated with few systemic atropine side effects. One manufacturer is already providing a premixed mixture of albuterol and ipatropium for metered dose inhalers. (Dr. Dolan is Professor of Pediatric Pulmonology at the Yale University School of Medicine.)
References
1. Schuh S, et al. Efficacy of frequent nebulized ipatropium bromide added to frequent high-dose albuterol in severe childhood asthma. J Pediatr 1995;126:639-645.
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