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Bronchodilating effects of combined therapy with clinical dosages of ipratropium bromide and salbutamol for stable COPD: comparison with ipratropium bromide alone.

Several studies have suggested that anticholinergics are at least equal to or may be superior to beta agonists in the treatment of stable COPD. However, since most previous studies have been performed to evaluate the bronchodilating effects of these two agents at relatively high doses, the clinical value of combining these two agents still is under debate. The purpose of this study was to determine if combination therapy with ipratropium bromide and salbutamol, in clinically available dosages, is superior in bronchodilation to ipratropium bromide alone. Twenty-six male patients (mean age, 67.5 +/- 5.9 years; FEV1, 0.87 +/- 0.32 L) with stable COPD were studied in randomized, double-blind, placebo-controlled experiments. On five separate days, all the patients received one of the following: (1) 40 micrograms ipratropium bromide, (2) 80 micrograms ipratropium bromide, (3) 40 micrograms ipratropium bromide plus 200 micrograms salbutamol, (4) 80 micrograms ipratropium bromide plus 400 micrograms salbutamol, or (5) placebo, using metered-dose inhalers (MDIs). Spirometry was assessed before and 15, 30, 60, 90, and 120 min after inhalation. Positive FEV1 responses to combined dosages of 80 micrograms ipratropium bromide and 400 micrograms salbutamol were significantly greater than responses to any other treatment regimen. Significantly greater responses also were achieved by combining 200 micrograms salbutamol with 40 micrograms ipratropium bromide compared with 40 micrograms ipratropium bromide alone. Combination therapy with 200 micrograms salbutamol and 40 micrograms ipratropium bromide produced a significantly greater effect on forced vital capacity than therapy with 80 micrograms ipratropium bromide alone. No significant differences were found between the responses induced by therapy with 80 and 40 micrograms ipratropium bromide. No adverse reactions to any regimen were noted throughout the study. In conclusion, combining the standard dosages of ipratropium bromide and salbutamol may provide greater bronchodilation than doubling the standard dosage of ipratropium bromide in patients with COPD.

Aged↗

Pharmacoeconomic evaluation of a combination of ipratropium plus albuterol compared with ipratropium alone and albuterol alone in COPD.

STUDY OBJECTIVE: To conduct a post hoc pharmacoeconomic evaluation of two double-blind, randomized, prospective, parallel group studies comparing the long-term efficacy and safety of ipratropium combined with albuterol in a single inhalational canister against either bronchodilator agent alone in patients with COPD. PATIENTS: One thousand sixty-seven patients with COPD. METHODS: The dose of each bronchodilator was two puffs four times a day (42 microg of ipratropium bromide, 240 microg of albuterol sulfate). Pulmonary function testing was performed on days 1, 29, 57, and 85 of treatment. Outcomes, health-care resource consumption, and costs were compared for the three treatment groups over the 85-day study period. A total of 1,067 patients were randomized in the two studies (albuterol alone, n = 347; ipratropium alone, n = 362; albuterol plus ipratropium, n = 358). RESULTS: Improvement in FEV1 and area under the FEV1 response-time curve from time 0 to 4 h (FEV1AUC0-4) was significantly greater for the combination of albuterol plus ipratropium than either agent alone on all test days. Compared with albuterol, patients receiving ipratropium and ipratropium plus albuterol experienced significantly fewer COPD exacerbations and patient-days of exacerbation. In addition, the increased frequency of exacerbations observed in the albuterol group was associated with a significant increase in the number of patient hospital days and antibiotic and corticosteroid use. As a result, the total cost of treatment over the study period was significantly less for ipratropium ($156 per patient) and ipratropium plus albuterol ($197 per patient) than for albuterol ($269 per patient). Increased cost-effectiveness, defined as total estimated treatment cost per mean change in FEV1AUC0-4, was observed in both treatment arms containing ipratropium. CONCLUSIONS: The inclusion of ipratropium in a pharmacologic treatment regimen is associated with a lower rate of exacerbations in COPD. The result is lower total treatment costs and improved cost-effectiveness.

Adult↗

In patients with COPD, treatment with a combination of formoterol and ipratropium is more effective than a combination of salbutamol and ipratropium : a 3-week, randomized, double-blind, within-patient, multicenter study.

STUDY OBJECTIVES: To compare the efficacy of adding formoterol or salbutamol to regular ipratropium bromide treatment in COPD patients whose conditions were suboptimally controlled with ipratropium bromide alone. DESIGN: A randomized, double-blind, double-dummy, two-period, crossover clinical trial. SETTING: Twenty-four clinics and university medical centers in nine countries. PATIENTS: One hundred seventy-two patients with baseline FEV(1) < or = 65% predicted, with FEV(1) reversibility to salbutamol not exceeding the normal variability of the measurement, and symptomatic despite regular treatment with ipratropium bromide. INTERVENTIONS: Each patient received two treatments in random order: either inhaled formoterol dry powder, 12 microg bid, in addition to ipratropium bromide, 40 microg qid for 3 weeks, followed by salbutamol, 200 microg qid, in addition to ipratropium, 40 microg qid for 3 weeks, or vice versa. MEASUREMENTS AND RESULTS: Efficacy end points included morning premedication peak expiratory flow (PEF) during the last week of treatment (primary end point), the area under the curve (AUC) for FEV(1) measured for 6 h after morning dose on the last day of treatment, and symptom scores (from daily diary recordings). Morning PEF and the AUC for FEV(1) were significantly better for formoterol/ipratropium than for salbutamol/ipratropium (p = 0.0003 and p < 0.0001, respectively). The formoterol/ipratropium combination also induced a greater improvement in mean total symptom scores (p = 0.0042). The safety profile of the two treatments was comparable. CONCLUSIONS: In COPD patients requiring combination bronchodilator treatment, the addition of formoterol to regular ipratropium treatment is more effective than the addition of salbutamol.

Adult↗

Ipratropium bromide (Atrovent) as inhalation powder. A double-blind study of comparison with ipratropium as a pressure aerosol in patients with reversible airways obstruction.

The bronchospasmolytic effects of 40 micrograms ipratropium bromide (Atrovent) given either as an aerosol (2 puffs of 20 micrograms) or as a powder inhalation were compared in a double-blind cross-over study. Following a randomisation list the drug was given on 2 successive days to 20 patients with stable bronchospasm in whom it had previously been shown that the bronchial obstruction was reversible after administration of 40 micrograms ipratropium bromide as an aerosol (with an increase over the baseline value of the FEV1 of at least 15% 1 h after drug administration). The effects of the two presentations of ipratropium bromide were followed by respiratory function tests from 15 min to 6 h after administration of the drug. With both formulations excellent bronchospasmolytic effects were noted in each of the parameters measured. The peak of the effects was noted approximately 1 h after the inhalations. Six hours later there was still a significant improvement in comparison with the baseline values. There was no significant difference between the results with the two different formulations. Inhalation powder of ipratropium bromide was well tolerated and there were no complaints of irritation or coughing. It would appear, therefore, to be a valuable alternative to the pressure aerosol.

Administration, Intranasal↗

Standard and double dose ipratropium bromide and combined ipratropium bromide and inhaled metaproterenol in COPD.

Inhaled ipratropium bromide (IPR) is effective in the management of COPD. The purpose of this study was to determine if doubling the standard dose of IPR resulted in greater bronchodilation and if the addition of an inhaled beta-agonist was superior to standard dose IPR alone. Twelve male patients with stable COPD completed a double blind, randomized trial. On each of three consecutive days, following baseline spirometry, all patients inhaled two puffs of IPR. This was followed by either two additional puffs of IPR, two puffs of metaproterenol (META), or two puffs of placebo. All inhalants were delivered by an InspirEase spacer. Spirometry was repeated at 30, 60, 120, and 180 minutes. The group mean percentage increases in the FEV1 and FVC from baseline were similar at all times tested for the three protocols. In conclusion, for the group, there was no objective benefit to doubling the standard dose of IPR or combining IPR with META. Two of 12 patients benefited from combining the two bronchodilators. A potential sequence for bronchodilator testing is suggested.

Administration, Inhalation↗

[Ipratropium Bromide, an Anticholinergic Bronchodilator/Behavior of airways resistance in patients with reversible respiratory obstruction following inhalation of various doses of ipratropium bromide].

A dose- and time-response study using different doses of an inhaled derivative of atropine, (8r)-3alpha-hydroxy-8-isopropyl-1 aH, 5aH-tropaniumbromide-(+/-)-tropate (Sch 1000, ipratropium bromide, Atrovent) was performed in 12 patients with reversible chronic obstructuve airways disease. The drug was shown to be an effective bronchodilator with the typical action of reducing airways resistance with 2 puffs (0.02 mg per puff). Increasing the dose to 4 and 8 puffs did not produce any relevant difference in time response. The onset of action was rapid and reached a maximum between 30 and 60 min after inhalation. The duration of bronchodilation was maintained during the observation period of 3 h. 30 min after inhalation the results corresponded to those following the inhalation of 2 puffs of orciprenaline (0.75 mg per puff). Isolated side-effects were independent of the dosage.

Adult↗

[Ipratropium bromide in controlled clinical trials. Short communication (II): Time-response measurements of pulmonary function after ipratropium bromide and isoprenaline].

(8R)-3alpha-Hydroxy-8-isopropyl-1alphaH, 5alphaH, 5alphaH-tropaniumbromide (+/-)-tropate (ipratropiumbromide, Sch 1000, Atrovent) was compared with isoprenaline in a cross-over study with randomized selection in 12 stable asthmatics, using total airways resistance (Rt) measured by whole-body plethysmography, peak expiratory flow (PEF) and pulse rate as parameters. 2 puffs ipratropiumbromide (0.02 mg per puff) or isoprenaline (0.1 mg per puff) were administered by metered dose inhaler and measurements taken at 5, 20, 35, 50, 90 min, 2, 3, 4, and 6 h later. Drugs were given on alternate days. Rt decreased significantly (p less than 0.001) for 4 h to 53% of the initial value after ipratropiumbromide and to 70% of the initial value after isoprenaline, but only for about 2 h after the latter. The maximum 20-min effect on Rt was almost the same for both drugs. The difference in the time course of the bronchodilation was also significant. The rise in PEF after 4 h following ipratropiumbromide was similarly highly significant (p less than 0.001); as for Rt the time course for both drugs ran nearly parallel. Neither substance caused a significant rise in pulse rate at the dosages used.

Airway Resistance↗

The role of ipratropium bromide in the emergency management of acute asthma exacerbation: a metaanalysis of randomized clinical trials.

STUDY OBJECTIVE: This study was conducted to determine whether the addition of inhaled ipratropium to inhaled beta-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 beta-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 beta-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 (FEV1), 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 FEV1 (95% confidence interval [CI] 3.8% to 10.9%), corresponding to an absolute improvement in FEV1 in the ipratropium/ beta-agonist group, which was 100 mL (95% CI 50 to 149 mL) above that seen for the group that received beta-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/ beta-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 beta2 -agonists. CONCLUSION: There is a modest statistical improvement in airflow obstruction when ipratropium is used as an adjunctive treatment to beta2 -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/ beta-agonist therapy in acute adult asthmatic exacerbations, since the addition of ipratropium seemed to provide physiologic evidence of benefit without risk of adverse effects.

Acute Disease↗

Ipratropium bromide nasal spray 0.03% and beclomethasone nasal spray alone and in combination for the treatment of rhinorrhea in perennial rhinitis.

BACKGROUND: Perennial rhinitis is a common condition that affects up to 10% to 20% of the population. Multiple agents are frequently administered since no single agent provides complete relief. Studies assessing the benefit/risk of combined therapy are important especially for newly approved agents such as ipratropium bromide nasal spray 0.03%, a topical anticholinergic agent, approved specifically for the treatment of rhinorrhea in allergic and non-allergic perennial rhinitis. OBJECTIVE: To compare the efficacy and safety of the combined use of ipratropium bromide nasal spray 0.03% (42 microg per nostril tid) and beclomethasone dipropionate nasal spray (84 microg per nostril bid) against that of either active agent alone for the treatment of rhinorrhea. DESIGN: Multicenter, 6-week, double-blind, randomized active- and placebo-controlled, parallel trial. SETTING: Allergist and general practitioner clinical practices. PATIENTS: Five hundred thirty-three patients with perennial rhinitis (279 allergic and 274 non-allergic), 8 to 75 years of age, who had at least a mild degree of severity of rhinorrhea for a minimum of 2 hours per day during the 1 week screening period as well as congestion or sneezing also of at least mild severity. INTERVENTION: Either (1) ipratropium bromide nasal spray 0.03% (42 microg per nostril tid) plus beclomethasone dipropionate nasal spray (84 microg per nostril bid), (2) ipratropium bromide nasal spray 0.03% (42 microg per nostril tid) alone, (3) beclomethasone dipropionate nasal spray (84 microg per nostril bid) alone, or (4) vehicle [matching placebo nasal spray for the ipratropium bromide (2 sprays per nostril tid)] or beclomethasone dipropionate (2 sprays per nostril bid). MAIN OUTCOME MEASURE: Severity and duration of rhinorrhea, and patient and physician global assessment of control of rhinorrhea. RESULTS: Ipratropium bromide nasal spray plus beclomethasone nasal spray was more effective than either active agent alone or vehicle in reducing the average severity and duration of rhinorrhea during 4 weeks of treatment. The advantage of ipratropium bromide plus beclomethasone nasal spray was evident by the first day of combined treatment and continued throughout the 2-week treatment period. Ipratropium bromide nasal spray had a faster onset of action during the first week of treatment and reduced the duration of rhinorrhea more than beclomethasone. Beclomethasone nasal spray was more effective in reducing the severity of congestion and sneezing than ipratropium. In patients who had not responded well to a nasal steroid prior to participation in the study based on a questionnaire administered at screening, ipratropium bromide was as effective in the steroid non-responders as steroid responders, whereas beclomethasone was more effective in steroid responders. Combined active therapy was well tolerated with no increase in adverse events over that seen previously with ipratropium bromide or beclomethasone nasal spray alone. CONCLUSIONS: The combined use of ipratropium bromide nasal spray with beclomethasone dipropionate nasal spray is more effective than either active agent for the treatment of rhinorrhea, and does not result in a potentiation of adverse drug reactions. Ipratropium bromide nasal spray 0.03% alone should be considered in patients for whom rhinorrhea is the primary symptom, and its use in combination with a nasal steroid should be considered in patients where rhinorrhea is one of the predominant symptoms, or in patients with rhinorrhea not fully responsive to other therapy.

Administration, Inhalation↗

The use of ipratropium bromide for the management of acute asthma exacerbation in adults and children: a systematic review.

Ipratropium bromide is a quaternary anticholinergic bronchodilator that is commonly used to treat obstructive lung disease. Although ipratropium is not usually employed as a first-line bronchodilator to treat chronic asthma, it has been used extensively in hospital emergency departments as adjunctive therapy for the emergency treatment of acute asthma exacerbation. This review will summarize the physiological actions of ipratropium and the rationale for its use as an anticholinergic bronchodilator. Evidence available from randomized trials and from two meta-analyses is summarized to determine whether the addition of inhaled ipratropium to inhaled beta2-agonist therapy is effective in the treatment of acute asthma exacerbation in children and adults. Published reports of randomized, controlled trials assessing the use of ipratropium and concurrent beta2-agonists in adult acute asthma exacerbation were identified by a search of electronic databases, as well as by hand searching. Data from 10 studies of adult asthmatics, reporting on a total of 1377 patients, were pooled in a meta-analysis using a weighted-average method. Use of nebulized ipratropium/beta2-agonist combination therapy was associated with a pooled 7.3% improvement in forced expiratory volume in 1 sec [95% confidence interval (CI), 3.8-10.9%] and a 22.1% improvement in peak expiratory flow (95% CI, 11.0-33.2%) compared with patients who received beta2-agonist without ipratropium. For the three trials in adults reporting hospital admission data (n = 1064), adult patients receiving ipratropium had a relative risk of hospitalization of 0.80 (95% CI, 0.61-1.06). Similarly, randomized controlled studies of pediatric asthma exacerbation and a meta-analysis of pediatric asthma patients suggest that ipratropium added to beta2-agonists improves lung function and also decreases hospitalization rates, especially among children with severe exacerbations of asthma. The adult and pediatric studies did not report any severe adverse effects attributable to ipratropium when it was used in conjunction with beta2-agonists. In conclusion, there is a modest statistical improvement in airflow obstruction when ipratropium is used as an adjunctive to beta2-agonists for the treatment of acute asthma exacerbation. In pediatric asthma exacerbation, use of ipratropium also appears to improve clinical outcomes; however, this has not been definitively established in adults. It would seem reasonable to recommend the use of combination ipratropium/beta2-agonist therapy in acute asthmatic exacerbation, since the addition of ipratropium seems to provide physiological evidence of benefit without risk of adverse effects.

Acute Disease↗

Ipratropium bromide HFA.

Ipratropium bromide is a nonselective antagonist of the muscarinic receptors located on airway smooth muscle, and is delivered via a metered-dose inhaler (MDI). Because of the requirement to phase out chlorofluorocarbon (CFC)-propelled MDIs, the ipratropium bromide inhalation aerosol MDI has been redesigned with a hydrofluoroalkane as the propellant (ipratropium bromide HFA). Ipratropium bromide HFA has recently been approved in the US for the maintenance treatment of bronchospasm associated with COPD. Ipratropium bromide HFA 42 microg four times daily (one dose [42 microg] is delivered via two puffs of the inhaler) demonstrated comparable efficacy to that of ipratropium bromide CFC 42 microg four times daily, as measured by spirometric testing, in a large, randomized, double-blind, placebo-controlled, 12-week trial in patients with stable COPD. Similarly, four-times-daily ipratropium bromide HFA 42 microg and ipratropium bromide CFC 42 microg provided a comparable degree of bronchodilation in patients with stable COPD during a 1-year, open-label study primarily designed to assess safety. In both studies, the tolerability profiles of ipratropium bromide HFA and ipratropium bromide CFC were comparable. The most common adverse events were related to respiratory system disorders. During the 1-year study, dry mouth was reported by 1.3% and 0.7% of patients in the ipratropium bromide HFA or ipratropium bromide CFC groups.

Administration, Inhalation↗

A comparison of the bronchodilating effects of salmeterol, salbutamol and ipratropium bromide in patients with chronic obstructive pulmonary disease.

Bronchodilator efficacy of salbutamol (200 micrograms), salmeterol (50 micrograms) and ipratropium bromide (40 micrograms) aerosols has been compared in 16 patients with stable chronic obstructive pulmonary disease (COPD) using a double-blind placebo controlled cross-over design. When absolute changes in FEV1 were used as the response criterion, efficacy of the three drugs was significantly better than placebo (P < 0.05). The onset of bronchodilatation after ipratropium bromide was slower than after salbutamol, but ipratropium induced more and longer-lasting bronchodilatation than the adrenergic drug. Salmeterol was slower but its duration was longer than salbutamol. The onset of the effect of salmeterol was slower than ipratropium bromide, but salmeterol showed, on average, superior bronchodilator efficacy compared with the anticholinergic agent, sustaining bronchodilation longer than ipratropium bromide (responses to salmeterol were significantly (P < 0.05) greater than those to ipratropium bromide from 4-12 h time period, but from 15 min to 1 h time periods response to ipratropium bromide exceeded salmeterol). The mean FEV1 area under the curve was significantly (P < 0.05) larger after salmeterol when compared to ipratropium bromide and salbutamol. Moreover, the mean FEV1 area under the curve after ipratropium bromide was significantly (P < 0.05) higher than that after salbutamol. In any case, our data showed individual differences in patient response. We conclude that salmeterol compares favourably with ipratropium bromide in terms of effects on lung function at clinically recommended doses because it has a longer duration of action than ipratropium bromide. The longer dosing intervals, which may enhance compliance, encourage its administration in patients with COPD.

Administration, Inhalation↗

Randomized, double-blind, placebo-controlled trial of intravenous salbutamol and nebulized ipratropium bromide in early management of severe acute asthma in children presenting to an emergency department.

BACKGROUND: In acute severe asthma, treatment must be initiated early to reverse the pathophysiology that may render airways less responsive to bronchodilation. The addition of nebulized ipratropium bromide to initial emergency department therapy improves pulmonary function, but it is unclear whether this approach results in earlier hospital discharge. The early use of bolus intravenous salbutamol has also been shown to improve outcome, including earlier discharge. We therefore assessed the relative benefits of intravenous salbutamol and nebulized ipratropium bromide in the early management of acute severe asthma in children by a double-blind, randomized, controlled trial. METHODS: This study was undertaken at a tertiary children's hospital, The Children's Hospital at Westmead, The Royal Alexandra Hospital for Children, Westmead, Sydney, Australia. Only children with severe acute asthma as determined by the National Asthma Campaign guidelines criteria and pulmonary index were included. All children received initial nebulized salbutamol therapy (2.5-5 mg salbutamol in 4 mL of normal saline depending on age) at initial emergency department presentation. If asthma remained severe 20 mins later, an intravenous cannula was inserted and intravenous methylprednisolone (1 mg/kg) was administered to all children receiving nebulized salbutamol every 20 mins. Children were then randomized to one of three groups: intravenous salbutamol (15 microg/kg as a single bolus over 10 mins), ipratropium bromide (250 microg), or intravenous salbutamol plus ipratropium bromide. All observers were blinded to treatment groups. Children were randomly assigned to receive a single-dose intravenous bolus of either saline or salbutamol and either nebulized saline or ipratropium bromide determined by a number generated randomly in the hospital pharmacy. The primary outcomes were recovery time and discharge time of each group. Respiratory and hemodynamic monitoring were continuous during the first 2 hrs of the study and then children were monitored clinically for 24 hrs. RESULTS: A total of 55 children with acute severe asthma were entered into the study over an 18-month period. The three groups were similar demographically, with a mean age of 5.9 yrs, and mean duration of attack of 19.6 hrs. No side effects or treatment intolerance were reported. Children in the groups that received intravenous salbutamol had a significant reduction in recovery time to achieving second hourly inhaled salbutamol (p =.008) compared with those administered inhaled bronchodilator alone. The addition of ipratropium bromide to intravenous salbutamol provided no significant further benefit in terms of nebulizer therapy (intravenous salbutamol compared with intravenous salbutamol plus ipratropium bromide). Children administered intravenous salbutamol ceased supplemental oxygen therapy earlier than those administered ipratropium alone at 12 hrs post-randomization (p =.0003). Children administered intravenous salbutamol could be discharged from the hospital 28 hrs earlier than those administered ipratropium bromide (p =.013). CONCLUSION: Children administered intravenous salbutamol for severe acute asthma showed a more rapid recovery time, which resulted in earlier discharge from the hospital than those administered inhaled ipratropium bromide. There was no additional benefit obtained by combining ipratropium bromide and intravenous salbutamol administration.

Adolescent↗

Efficacy of nebulized ipratropium in severely asthmatic children.

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 micrograms/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, chi 2). 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.

Adolescent↗

Bronchodilator responses to salbutamol followed by ipratropium bromide in partially reversible airflow obstruction.

We have performed a retrospective survey on 296 patients, who attended the Respiratory Function Unit at Guy's Hospital to have their bronchodilator responses (BR) tested. The aim of the study was to see the effect of ipratropium bromide (IB) in a group of patients with incomplete reversibility after salbutamol (S). Patients were routinely given salbutamol and ipratropium bromide sequentially by inhalation, and spirometric changes were recorded after each drug. We identified two groups: Group A, 95 patients with FEV1 response greater than or equal to 0.2 l after either drug and FEV1 less than 80% predicted after salbutamol; and, Group B, 49 with change in FEV1 less than 0.02 l, FVC less than 80% predicted after salbutamol and an improvement in FVC greater than or equal to 0.33 l. Seventy-nine of the 95 patients in Group A also had an FVC response. In Group A, age was negatively correlated with response to salbutamol (r = -0.41, P less than 0.0001), and within Group B baseline FVC was negatively correlated with response to ipratropium bromide (r = -0.30, P = 0.03). There were no differences in age, sex, or doses given to each group (median dose: salbutamol, 800 micrograms, ipratropium bromide 120 micrograms). Baseline FEV1 and FVC (% predicted) were significantly higher in FEV1 responders. Mean (SD) FEV1 were 43% (14) in Group A vs. 29% (14) in Group B, while FVC were 62% (16) vs. 47% (13), P less than 0.001. Responses to ipratropium bromide were more frequent in Group B; in Group A 87% improved after salbutamol and 26% after ipratropium bromide, while in Group B 68% responded to salbutamol and 47% to ipratropium bromide (P = 0.03). Most patients responded to salbutamol, but in 33% ipratropium bromide had an additional effect. The FEV1 response to salbutamol declined with age. Isolated volume responders had more severe airflow obstruction, had less responses to salbutamol and were more likely to show a response to ipratropium bromide. These results support a trial of ipratropium bromide in patients with inadequate beta responsiveness, especially in those with severe airflow obstruction.

Administration, Inhalation↗

Airway response of horses with COPD to dry powder inhalation of ipratropium bromide.

To determine the effects of the dry powder inhalation (DPI) of ipratropium bromide (ipratropium) on the airways of health horses and the dose-response curve in horses suffering from chronic obstructive pulmonary disease (COPD) by means of pulmonary function tests, five healthy horses were first studied. Ipratropium (2400 micrograms ipratropium horse-1) was contained in gelatine capsules and administered using a dry powder device connected to an adapted face mask. Pulmonary function tests were recorded before inhalation and 15 and 60 min after inhalation. No modification of pulmonary function was observed. The airway response to ipratropium DPI was then determined in six horses suffering from COPD. To induce airway obstruction, the horses were bedded on straw and fed hay. When the maximal change in pleural pressure during tidal breathing exceeded 1.96 kPa, pulmonary function tests were recorded before DPI, and 15 and 60 min post-inhalation. Placebo (six capsules horse-1) or ipratropium (600, 1200 and 2400 micrograms horse-1) was administered in a randomized order to each horse using the dry powder device and the adapted face mask. Neither ipratropium nor placebo DPI affected respiratory frequency (f) or tidal volume (VT). Inhalation of 600 micrograms ipratropium horse-1 resulted in a delayed decrease of total pulmonary resistance (RL) whereas dynamic compliance (Cdyn) was improved (although not significantly) at both times of measurement when compared with values following placebo inhalation. Simultaneous decreased RL and increased Cdyn, was observed within 15 min after DPI of 1200 micrograms ipratropium horse-1 and persisted for the 1 h duration of the experiment. Doubling the dose also improved pulmonary function but not significantly more than following inhalation of 1200 micrograms ipratropium. No systemic side effects were observed in either group of horses.

Administration, Inhalation↗

A randomised controlled comparison of tiotropium nd ipratropium in the treatment of chronic obstructive pulmonary disease. The Dutch Tiotropium Study Group.

BACKGROUND: A study was undertaken to evaluate and compare the efficacy and safety of tiotropium and ipratropium during long term treatment in patients with stable chronic obstructive pulmonary disease (COPD). METHODS: 288 patients of mean (SD) age 65 (8) years and forced expiratory volume in one second (FEV(1)) 41 (12)% predicted participated in a 14 centre, double blind, double dummy, parallel group study and were randomised after a run in period of two weeks to receive either tiotropium 18 microg once daily from a dry powder inhaler (HandiHaler; two thirds of patients) or ipratropium 40 microg four times daily from a metered dose inhaler (one third of patients) for a period of 13 weeks. Outcome measures were lung function, daily records of peak expiratory flow (PEF), and the use of concomitant salbutamol. FEV(1) and forced vital capacity (FVC) were measured one hour before and immediately before inhalation (mean value of the two measurements on test day 1 was the baseline value while on all other test days it was known as the trough FEV(1) and FVC), and 0.5, 1, 2, 3, 4, 5, and 6 hours after inhalation of the study drug on days 1, 8, 50, and 92. RESULTS: During treatment tiotropium achieved a significantly greater improvement than ipratropium (p<0.05) in trough, average, and peak FEV(1) levels and in trough and average FVC levels. The trough FEV(1) response on days 8, 50, and 92 ranged between 0.15 l (95% CI 0.11 to 0.19) and 0.16 l (95% CI 0.12 to 0.20) for tiotropium and between 0.01 l (95% CI -0.03 to 0.05) and 0.03 l (95% CI 0.01 to 0. 07) for ipratropium. The trough FVC response on days 8, 50, and 92 ranged between 0.34 l (95% CI 0.28 to 0.40) and 0.39 l (95% CI 0.31 to 0.47) for tiotropium and between 0.08 l (95% CI 0.00 to 0.16) and 0.18 l (95% CI 0.08 to 0.28) for ipratropium. On all test days tiotropium produced a greater improvement in FEV(1) than ipratropium starting three hours after inhalation (p<0.05). During treatment weekly mean morning and evening peak expiratory flow (PEF) was consistently better in the tiotropium group than in the ipratropium group, the difference in morning PEF being significant up through week 10 and in evening PEF up through week 7 of treatment (p<0.05). The use of concomitant salbutamol was also lower in the tiotropium group (p<0.05). The only drug related adverse event was dry mouth (tiotropium 14.7%, ipratropium 10.3% of patients). CONCLUSIONS: Tiotropium in a dose of 18 microg inhaled once daily using the HandiHaler was significantly more effective than 40 microg ipratropium four times daily in improving trough, average, and peak lung function over the 13 week period. The safety profile of tiotropium was similar to ipratropium. These data support the use of tiotropium as first line treatment for the long term maintenance treatment of patients with airflow obstruction due to COPD.

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