Frequent administration by inhalation of salbutamol and ipratropium bromide in the initial management of severe acute asthma in children

doi:10.1016/0091-6749(88)90214-X

Journal of Allergy and Clinical Immunology

Volume 81, Issue 1, January 1988, Pages 16-20

https://doi.org/10.1016/0091-6749(88)90214-X Get rights and content

Abstract

A study was performed to compare the efficacy and safety of two therapeutic regimens for the treatment of children presenting to the emergency department with acute asthma. A regimen of inhaled salbutamol alone was compared to inhaled salbutamol combined with ipratropium bromide. Twenty-five children ranging in age from 5 to 15 years were enrolled in the study. Children with FEV₁ ⩽55% predicted were eligible to participate in the study. Subjects were randomized in a double-blind fashion into one of two treatment groups. Both groups received an initial dose of salbutamol by nebulizer of 150 μg/kg (0.03 cc/kg), followed by six consecutive doses of 50 μg/kg (0.01 cc/kg) at 20-minute intervals. In one group of subjects, 250 μg (1.0 ml) of ipratropium bromide respirator solution was added to the salbutamol administered at the time of the initial inhalation, and at 40 and 80 minutes, whereas the remaining subjects received a placebo with salbutamol at those times. Formal one-way statistical ANOVA with change in percent predicted FEV₁ as a response variable confirmed there was a statistically significant difference at all time points caused by drug regimen during the 150-minute observation period. There was no significant difference in side effects reported in the two groups. Significant additional bronchodilation achieved with salbutamol and ipratropium bromide together indicates that there is likely a substantial cholinergic element to the bronchospasm observed in acute exacerbations of asthma in the pediatric age group.

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Cited by (76)

Treatment
2008, Pediatric Respiratory Medicine
Comparison of nebulized ipratropium bromide with salbutamol vs salbutamol alone in acute asthma exacerbation in children
2006, Annals of Allergy, Asthma and Immunology
Despite multiple doses of β₂-agonists in the treatment of acute asthma exacerbation, significant residual airways obstruction often remains.
To determine whether the addition of inhaled ipratropium bromide to salbutamol provides improvement in lung function and clinical asthma symptoms in young children with acute asthma exacerbation.
This study was a prospective, double-blind randomized control trial of children aged 3 to 15 years who presented with an acute asthma exacerbation at the emergency department or outpatient clinic of Thammasat University Hospital, Pathumthani, Thailand, between September 2001 and February 2003. Subjects were randomized to receive 3 doses of nebulized salbutamol mixed with isotonic sodium chloride solution (control) or ipratropium bromide (treatment) every 20 minutes. Additional doses of salbutamol were given every 30 minutes as needed. Asthma outcome measures were evaluated 40, 70, 100, and 120 minutes after baseline. Primary outcomes were the differences in percent change in asthma clinical score and percent change in peak expiratory flow rate (PEFR) from baseline. Secondary outcomes included change in percent predicted PEFR.
Of 74 children randomized and enrolled in the trial, 71 had complete data for analysis. Thirty-three children were in the control group and 38 were in the treatment group. Both the percent change in PEFR and the change in percent predicted PEFR at any time were higher in the treatment group, but these findings were not statistically significantly different. The number of subjects with at least a 100% percent predicted PEFR at any time point was greater in the treatment group.
Although this study did not demonstrate a significant advantage in clinical score and PEFR, the trend toward additional effect of ipratropium bromide was consistent with previous studies.
The role of anticholinergics in acute asthma treatment: An evidence-based evaluation
2002, Chest
The role for anticholinergic medications in acute asthma is not well-defined. Thus, the use of therapy with anticholinergics and β₂-agonists, either simultaneously or in sequence, has produced positive as well as negative results in trials. Therefore, the current recommendations for the use of these drugs in the emergency department (ED) and hospital management of asthma exacerbations are not precise. This review answers the following question: what level of evidence is available in the literature to support the use of anticholinergic medications in combination with β₂-agonists in acute asthma patients? We limited the search on our therapy question to systematic reviews of randomized trials and/or randomized controlled trials not included in the reviews. After an extensive review of the most relevant evidence, the following conclusions may be emphasized. (1) The use of multiple doses of ipratropium bromide are indicated in the ED treatment of children and adults with severe acute asthma. The studies reported a substantial reduction in hospital admissions (30 to 60%; number needed to treat, 5 to 11) and significant differences in lung function favoring the combined treatment. No apparent increase in the occurrence of side effects was observed. (2) The use of single-dose protocols of ipratropium bromide with β₂-agonist treatment produced, particularly in children with more severe acute asthma, a modest improvement in pulmonary function without reduction in hospital admissions; in adults, the data showed a similar increase in pulmonary function with an approximately 35% reduction in the hospital admission rate. In patients with mild-to-moderate acute asthma, there is no apparent benefit from adding a single dose of an anticholinergic medication.
Ipratropium bromide plus nebulized albuterol for the treatment of hospitalized children with acute asthma
2001, Journal of Pediatrics
Citation Excerpt :
Separate pooled analyses5,13 of 1064 adults from 3 trials found a reduction in hospitalization rate from combination therapy, but the reported magnitude of this reduction was different for each analysis and was statistically significant in only one. For children treated in the ED setting, most of the trials demonstrate small but significant additional enhancement of lung function,14-17 clinical outcome,7,18 or both6 in at least a subset of subjects randomized to combination therapy. Reliance on peak expiratory flow measurements, small sample size, or exclusion of children with more severe acute obstruction may explain why some trials19-21 failed to detect enhanced bronchodilation from the addition of anticholinergic agents.
Objective: To determine whether the addition of repeated doses of nebulized ipratropium bromide (IB) to a standardized inpatient asthma care algorithm (ACA) for children with status asthmaticus improves clinical outcome. Study design: Children with acute asthma (N = 210) age 1 to 18 years admitted to the ACA were assigned to the intervention or placebo group in randomized double-blind fashion. Both groups received nebulized albuterol, systemic corticosteroids, and oxygen according to the ACA. The intervention group received 250 μg IB combined with 2.5 mg albuterol by jet nebulization in a dosing schedule determined by the ACA phase. The placebo group received isotonic saline solution substituted for IB. Progression through each ACA phase occurred based on assessments of oxygenation, air exchange, wheezing, accessory muscle use, and respiratory rate performed at prescribed intervals. Results: No significant differences were observed between treatment groups in hospital length of stay (P =.46), asthma carepath progression (P =.37), requirement for additional therapy, or adverse effects. Children >6 years (N = 70) treated with IB had shorter mean hospital length of stay (P =.03) and more rapid mean asthma carepath progression (P =.02) than children in the placebo group. However, after adjustment was done for baseline group differences, the observed benefit of IB therapy in older children no longer reached statistical significance. Conclusion: The routine addition of repeated doses of nebulized IB to a standardized regimen of systemic corticosteroids and frequently administered β-2 agonists confers no significant enhancement of clinical outcome for the treatment of hospitalized children with status asthmaticus. (J Pediatr 2001;138:51-8)
Effect of continuously nebulized ipratropium bromide plus albuterol on emergency department length of stay and hospital admission rates in patients with acute bronchospasm: A randomized, controlled trial
1999, Chest
To compare the outcome of patients with acute bronchospasm treated with continuously nebulized albuterol plus ipratropium bromide vs albuterol alone.
The Emergency Department (ED) at the University of California San Francisco Medical Center.
Patients ≥ 18 years old presenting to the ED with acute bronchospasm and a peak expiratory flow rate (PEFR) of < 70% predicted.
This was a prospective, randomized, double-blind, placebo-controlled trial. Subjects were treated with either a combination of albuterol (10 mg/h) plus ipratropium bromide (1.0 mg/h) or albuterol alone via continuous nebulization for a maximum of 3 h. Vital signs, Borg dyspnea score, and PEFR were recorded hourly. Primary outcome measures were improvement in PEFR, hospital admission rates, and length of stay in the ED.
Data was analyzed for 67 subjects. The mean age (± SD) was 47.5 ± 18.8, and mean initial PEFR was 44.8 ± 12.5% of predicted. The median length of stay for all subjects was 225 min, and 31% of all subjects were admitted. Patients given combination therapy averaged 6.3% greater improvement in PEFR compared with control subjects (95% confidence interval [CI], −15% to 27%. The odds ratio for admission with combination therapy was 0.88 (95% CI, 0.28 to 2.8). The median length of stay in the ED was 35 min shorter for those receiving combination treatment (210 vs 245 min; p = 0.03). However, when adjusted for initial PEFR, there was no statistically significant difference (p = 0.26).
Although the direction of all three outcome measures favored combination therapy, there was no statistically significant difference between ED patients with acute bronchospasm receiving continuous albuterol plus ipratropium bromide and those receiving albuterol alone.
Combination of ipratropium bromide and salbutamol in children and adolescents with asthma: A meta-analysis
2021, PLoS ONE

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Original articleFrequent administration by inhalation of salbutamol and ipratropium bromide in the initial management of severe acute asthma in children

Abstract

J Pediatr

J Pediatr

J Pediatr

Am J Med

J Pediatr

An evaluation of initial management of acute asthma in children

Pediatrics

Original article
Frequent administration by inhalation of salbutamol and ipratropium bromide in the initial management of severe acute asthma in children