Efficacy of Nebulized Ipratropium in Severely Asthmatic Children

doi:10.1016/S0196-0644(97)70269-5

Annals of Emergency Medicine

Volume 29, Issue 2, February 1997, Pages 205-211

Presented at the Pediatric Academic Societies annual meeting, Washington DC, May 1996.

https://doi.org/10.1016/S0196-0644(97)70269-5 Get rights and content

Abstract

Study objective: To determine the effect of adding the nebulized anticholinergic drug ipratropium bromide to standard therapy compared with standard therapy alone for acute severe asthma (peak expiratory flow rate [PEFR] <50% of predicted) in children presenting to the emergency department. Methods: Ninety children aged 6 to 18 years were randomly assigned to two groups in a prospective, double-blind, placebo-controlled study performed in the ED of an urban children's hospital. All children received nebulized albuterol solution (.15 mg/kg) every 30 minutes, and all received oral steroids with the second dose of albuterol. Children in group 1 received ipratropium bromide (500 μg/dose) with the first and third dose of albuterol; those in group 2 received saline placebo instead of ipratropium. Pulmonary functions (PEFR and 1-second forced expiratory volume [FEV₁]) and physiologic measurements were assessed every 30 minutes up to 120 minutes. By chance, the baseline values for percent of predicted PEFR and FEV₁ differed between the two groups. Therefore a multivariate model accounting for both time and baseline effects was used to compare the response between groups. Results: On average, and adjusting for baseline measures, children in the ipratropium group had a significantly greater improvement in percent of predicted PEFR than did children in the placebo group at 60 minutes (P=.02), 90 minutes (P=.002), and 120 minutes (P<.0001). The improvement in percent predicted FEV₁ was significantly greater for children in the ipratropium group only at 120 minutes (P=.013). Nine children (20%) from the ipratropium group and 14 (31.1%) from the control group were admitted (P=.33, χ²). There were no significant adverse effects attributable to the ipratropium, and there was no relation between ipratropium use and changes in pulse, respiratory rate, blood pressure, or oxygen saturation. Conclusion: We detected significant improvement in pulmonary function studies over 120 minutes in children with severe asthma who were given nebulized ipratropium combined with albuterol and oral steroids, compared with children who received the standard therapy. Further study is needed to determine whether early use of ipratropium decreases the need for hospitalization. [Qureshi F, Zaritsky A, Lakkis H: Efficacy of nebulized ipratropium in severely asthmatic children. Ann Emerg Med February 1997; 29:205-211.]

Section snippets

INTRODUCTION

Asthma is a disease process characterized by reversible airway obstruction that is caused by a combination of mucosal inflammation and edema, smooth muscle contraction, and increased secretions.¹ Bronchodilators and antiinflammatory agents both play a major role in the treatment of acute exacerbations of asthma.

Anticholinergic agents were the first effective bronchodilators to be used in the treatment of asthma², but they were supplanted by the adrenergic agonists in the early 1900s. Despite

MATERIALS AND METHODS

Children between the ages of 6 and 18 years with a known history of asthma who presented to the ED of the Children's Hospital of the King's Daughters with an acute asthma exacerbation were considered for enrollment in the study. An asthma exacerbation was defined as increased difficulty breathing, wheezing and worsening of the child's usual symptoms, or deterioration of pulmonary functions. Patients had to demonstrate the ability to perform reliable pulmonary function testing.

Children whose

RESULTS

The demographic and baseline physiologic measurements in each group are summarized in Table l.

. Baseline parameters (mean ± SD).

Parameters	Ipratropium (n=45)	Saline Control (n=45)
Age(years)	12.4±3.3	11.6±2.5
M/F	26/19	29/16
White/black/other	6/36/3	4/41/0
Pulse	114.8±18.9	115.0±18.4
Systolic blood pressure (mm Hg)	122±11	119±12
Diastolic blood pressure (mm Hg)	70±10	68±10
Respirations	33.2±8.9	32.3±5.8
Oxygen saturation (%)	94.4±2.2	93.9±2.2
FEV₁ (% predicted)	37.5±13.8*	31.1±12.4
PEFR (% predicted)	34.2±9.8*	29.5±19.2

DISCUSSION

Our study revealed a significant improvement in pulmonary function when ipratropium bromide was added to a regimen of inhaled albuterol and oral steroids in children with severe exacerbations of asthma. This improvement in bronchodilation was not accompanied by any adverse effects. We postulated that children with significant airway obstruction would have reduced pulmonary drug delivery initially. This reasoning previously led to the recommendation to use higher doses (.15 mg/kg) of inhaled

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^☆: From the Pediatric Emergency Medicine Section*, the Department of Pediatrics‡, and the Center for Pediatric Research§, Children's Hospital of The King's Daughters, Eastern Virginia Medical School, Norfolk, Virginia.

^☆☆: Reprint no.47/1/79100

^★: Address for reprints: Faiqa Qureshi, MD, Pediatric Emergency Medicine, Children's Hospital of the King's Daughters, 601 Children's Lane, Norfolk, Virginia 23507, 757-668-9225, Fax 757-668-7568

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Efficacy of Nebulized Ipratropium in Severely Asthmatic Children☆,☆☆,★

Abstract

Section snippets

INTRODUCTION

MATERIALS AND METHODS

RESULTS

DISCUSSION

J Allergy Clin Immunol

J Pediatr

Respir Med

Ann Emerg Med

Chest

Br J Dis Chest

Am J Med

Lancet

Chest

J Allergy Clin Immunol

J Pediatr

J Allergy Clin Immunol

J Pediatr

Historical review of the use of parasympatholytic agents in the treatment of respiratory disorders

Postgrad Med J

Parametric models for covariance structure

Analysis of repeated measures data

Guidelines for the Diagnosis and Management of Asthma. Report 91-3042

Autonomic control of airway smooth muscle and airway secretions

Am Rev Respir Dis

Anticholinergic, antimuscarinic bronchodilators

Am Rev Respir Dis

Role of anticholinergics in asthma

Ann Allergy