Comparison of nebulized salbutamol with nebulized ipratropium bromide in acute asthma
Abstract
Twelve patients admitted to hospital with an acute attack of bronchial asthma were studied. Six were treated initially with nebulized salbutamol solution by inhalation and 1 hour later by ipratropium bromide given in the same way; the other six were treated first with ipratropium bromide and 1 hour later by salbutamol. Ipratropium bromide was shown to be as effective as salbutamol when used as the initial bronchodilator but salbutamol produced significant further improvement when given 1 hour after ipratropium.
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Cited by (46)
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.
A meta-analysis of the effects of ipratropium bromide in adults with acute asthma
1999, American Journal of MedicinePurpose: To review the literature to determine whether inhaled ipratropium bromide provides additive benefits to adults with acute asthma who are being treated with beta-agonists in an emergency department.
SUBJECTS AND METHODS: English-language studies, both published (1978 to 1999) and unpublished, were retrieved using Medline, Science Citation Index, Current Contents, bibliographic reviews of primary research, review articles, consultation with experts, and the register of Medical Editors’ Trial Amnesty. Only randomized, double-blind, controlled trials that enrolled patients having an exacerbation of asthma were included. The main outcome measure was pulmonary function; hospital admission rate was also evaluated.
RESULTS: Ten studies including 1,483 adults with acute asthma were selected (mean age 32 ± 13 years, 36% men). The overall effect size in SD units of pulmonary function showed a significant benefit from ipratropium (effect size 0.14, 95% confidence interval [CI]: 0.04 to 0.24, P = 0.008). Study-specific effect sizes ranged from 0.03 to 0.63. This pooled effect size was equivalent to a 10% (95% CI: 2% to 18%) increase in forced expiratory volume in 1 second (FEV1) or peak expiratory flow in the ipratropium group compared with the control group. Analysis of the four studies that included patients with extreme obstruction (FEV1 or peak flow <35% of predicted at presentation) showed substantial improvement with ipratropium therapy (effect size 0.38, 95% CI: 0.09 to 0.67). In the five trials (1,186 patients) that studied the effect of ipratropium administration on hospital admissions, pooled results revealed that ipratropium reduced admission rates significantly (odds ratio 0.62, 95% CI: 0.44 to 0.88, P = 0.007).
CONCLUSIONS: The addition of ipratropium to beta-agonist therapy offers a statistically significant, albeit modest, improvement in pulmonary function, as well as a reduction in the rate of hospital admissions.
The role of ipratropium bromide in the emergency management of acute asthma exacerbation: A metaanalysis of randomized clinical trials
1999, Annals of Emergency MedicineStudy objective: This study was conducted to determine whether the addition of inhaled ipratropium to inhaled β-agonist therapy is effective in the treatment of adults with acute asthma exacerbation. Methods: Published reports of randomized, controlled trials assessing the use of ipratropium and β-agonists in asthma were identified by a search of the MEDLINE, EMBASE, CINAHL, Biological Abstracts on CD, the Cochrane Library, and Current Contents databases. Bibliographies from identified studies and from review articles were manually searched. Published and unpublished reports in English, French, and Italian were identified and assessed for inclusion in the metaanalysis. Randomized, double-blind, placebo-controlled trials were selected in which ipratropium was used as adjunctive therapy to β-agonists in adult patients with acute asthma exacerbation presenting to a hospital emergency department or similar acute care setting. Data were extracted independently by 2 reviewers. For eligible trials, the mean percent change in peak expiratory flow rate (PEFR), or forced expiratory volume in one second (FEV 1 ), and their SDs were assessed in the ipratropium-treated and control groups. The effect of ipratropium on hospitalization rates and adverse effects were also analyzed. Results: Data from 10 studies, reporting on a total of 1,377 patients with asthma, were pooled using a weighted average method. Compared with placebo, the use of ipratropium was associated with a pooled 7.3% improvement in FEV 1 (95% confidence interval [CI] 3.8% to 10.9%), corresponding to an absolute improvement in FEV 1 in the ipratropium/ β-agonist group, which was 100 mL (95% CI 50 to 149 mL) above that seen for the group that received β-agonist without ipratropium. Similarly, the pooled estimate of treatment effect in trials that reported data as PEFR was 22.1% (95% CI 11.0% to 33.2%), corresponding to an absolute peak expiratory flow improvement of 32 L/min (95% CI 16 to 47 L/min) in favor of the ipratropium/ β-agonist combination group. When these data were combined using effect size as a common measure, the use of ipratropium was associated with a summary effect size of .38 (95% CI .27 to .48). Effect sizes were negatively correlated with baseline mean expiratory flows, suggesting that studies enrolling patients with more severe airflow obstruction showed greater absolute benefits of combination bronchodilator therapy. For the 3 trials reporting hospital admission data (n=1,031), patients receiving ipratropium had a relative risk of hospitalization of .73 (95% CI .53 to .99). The use of ipratropium was not associated with any severe adverse effects when used in conjunction with β 2 -agonists. Conclusion: There is a modest statistical improvement in airflow obstruction when ipratropium is used as an adjunctive treatment to β 2 -agonists for the treatment of acute asthma exacerbation. Although the clinical significance of this improvement in airflow obstruction remains unclear, it would seem reasonable to recommend the use of combination ipratropium/ β-agonist therapy in acute adult asthmatic exacerbations, since the addition of ipratropium seemed to provide physiologic evidence of benefit without risk of adverse effects.[Stoodley RG, Aaron SD, Dales RE: The role of ipratropium bromide in the emergency management of acute asthma exacerbation: A metaanalysis of randomized clinical trials. Ann Emerg Med July 1999;34:8-18.]
Management of acute asthma in Canada: An assessment of emergency physician behaviour
1997, Journal of Emergency MedicineThe study objective was to asssess Canadian emergency physicians for their management preferences and their compliance with recently developed guidelines for treatment of acute asthma in adults. The design was a cross-sectional survey sent to members of the Canadian Association of Emergency Physicians (CAEP) and to the emergency department (ED) directors of all Canadian hospitals with more than 25 beds in November 1992. ED directors who had not responded were sent a second survey in January 1993. The response rates for the survey were 60.1% () for ED directors and 53.4% () for CAEP members. Respondents were more likely to be from larger hospitals and to have completed some training beyond general practice level (CCFP, CCFP-EM, ABEM, FRCPC). There were wide variations among respondents in the use of objective measurements of asthma severity (forced expiratory volume in 1 s [FEV1] and peak expiratory flow rates [PEFR]), dosing of bronchodilators, and utilization of systemic corticosteroids. Forty-six percent of respondents used the FEV1 “occasionally” (22.3%) or “never” (23.8%), and 26.7% used PEFR “occasionally” (15.8%) or “never” (10.9%) in asthma management Ninety-seven percent used nebulized beta agonist “always” (71.3%) or “often” (25.6%), but only 48.5% used the metered dose inhaler (MDI) “always” (11%) or “often” (37.5%). More than a quarter of respondents (27.2%) used doses of beta agonists that were less than those recommended (>every 30–60 min). Oral corticosteroids were prescribed at discharge only “occasionally” (51.1%), “seldom” (18.9%), or “never” (6.5%) in 76.6% of physicians. Physicians with more training were more likely to assess and treat patients according to current asthma treatment guidelines. The survey shows that many Canadian emergency physicians did not follow published recommendations for the care of patients with acute asthma. This finding was especially so with regard to objective evaluation of airflow, aggressive use of beta-agonists, the use of corticosteroids, and in making appropriate arrangements for patient discharge and follow-up.
The influence of parasympatholytics on the resolution of acute attacks of asthma
1997, American Journal of MedicinePURPOSE: To evaluate the role of parasympatholytics in the resolution of acute attacks of asthma.
METHODS: This study employed a prospective sequential design in which the influence of 0.5 and 1.0 mg of ipratropium bromide on peak expiratory flow rates (PEFR), hospital admissions, and length of stay (LOS) in the emergency department (ED) was evaluated. The parasympatholytic was added to a well-investigated standard therapeutic regimen that was anchored by the use of repetitive doses of albuterol, and employed pretested decision algorithms.
RESULTS: One hundred and thirty-one patients received ipratropium (I) and 123 who did not (NI) served as controls. There were no significant pretreatment between group differences in gender, racial composition, clinical signs and symptoms, or PEFR. The presence of ipratropium in the regimen did not influence discharge/admission patterns, LOS, the rate of improvement of the patients, or the level of PEFR achieved.
CONCLUSION: Anticholinergic agents such as ipratropium are not first-line treatments for acute asthma. They do not add any therapeutic benefit to the effects of albuterol given in divided doses over 1 hour, nor do they facilitate recovery in patients whose immediate response to sympathomimetics is impaired.
Efficacy of nebulized ipratropium in severely asthmatic children
1997, Annals of Emergency MedicineStudy 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.]