Randomized controlled trial of ipratropium bromide and frequent low doses of salbutamol in the management of mild and moderate acute pediatric asthma. Ipratropium bromide added to asthma treatment in the pediatric emergency department. Frequent administration by inhalation of salbutamol and ipratropium bromide in the initial management of severe acute asthma in children. Ipratropium and fenoterol in the treatment of acute asthma. Efficacy of nebulized ipratropium in severely asthmatic children. Comparison of inhaled metaproterenol, inhaled atropine sulfate, and their combination in treatment of children with acute asthma. Effect of nebulized ipratropium on the hospitalization rates of children with asthma. Is it useful to add an anticholinergic treatment to beta 2-adrenergic medication in acute asthma attack? Comparison of inhaled terbutaline and inhaled terbutaline plus ipratropium bromide in acute asthmatic children. Combined salbutamol and ipratropium bromide by inhalation in the treatment of severe acute asthma. Efficacy of frequent nebulized ipratropium bromide added to frequent high-dose albuterol therapy in severe childhood asthma.
To compare the effectiveness and safety of alternative nebulized drug protocols in children with mild or moderate asthma exacerbations.
                We conducted a blinded, randomized, controlled trial with a 2 x 2 factorial design. Two interventions, nebulized salbutamol in frequent low doses (0.075 mg/kg every 30 minutes) and the addition of ipratropium bromide (250 micrograms), were compared with salbutamol in hourly high doses (0.15 mg/kg every 60 minutes) in children with mild or moderate acute asthma. The primary end point was the improvement in respiratory resistance. Secondary end points included oxygen saturation, corticosteroid use, patient disposition, and relapse status.
                A total of 298 participants aged 3 to 17 years were studied, and 15% were admitted to the hospital; 14% of the children had relapses. No increased bronchodilation was associated with frequent low doses versus hourly high doses of salbutamol (RR = 0.9 [95% confidence interval 0.7, 1.3]) or the addition of ipratropium bromide versus placebo (RR = 1.0 [0.8, 1.3]). No group differences were observed in secondary end points. Salbutamol in frequent low doses was associated with increased vomiting (RR = 2.5 [1.1, 6.0]).
                Our results do not support the use of frequent low doses of nebulized salbutamol or the addition of ipratropium bromide compared with hourly high doses of salbutamol in children with mild or moderate asthma. To determine if the addition of ipratropium bromide to the emergency department (ED) treatment of childhood asthma reduces time to discharge, number of nebulizer treatments before discharge, and the rate of hospitalization.
                Patients >12 months of age were eligible if they were to be treated according to a standardized ED protocol for acute asthma with nebulized albuterol (2.5 mg/dose if weight <30 kg, otherwise 5 mg/dose) and oral prednisone or prednisolone (2 mg/kg up to 80 mg). Subjects were randomized to receive either ipratropium (250 microg/dose) or normal saline (1 mL/dose) with each of the first three nebulized albuterol doses. Further treatment after the first hour was determined by physicians blinded to subject group assignment. Records were reviewed to determine the length of time to discharge home from the ED, number of doses of albuterol given before discharge, and the number of patients admitted to the hospital.
                Four hundred twenty-seven patients were randomized to ipratropium or control groups; these groups were similar in all baseline measures. Among patients discharged from the ED, ipratropium group subjects had 13% shorter treatment time (mean, 185 minutes, vs control, 213 minutes) and fewer total albuterol doses (median, three, vs control, four). Admission rates did not differ significantly (18%, vs control, 22%).
                The addition of three doses of ipratropium to an ED treatment protocol for acute asthma was associated with reductions in duration and amount of treatment before discharge. 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 less than or equal to 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 micrograms/kg (0.03 cc/kg), followed by six consecutive doses of 50 micrograms/kg (0.01 cc/kg) at 20-minute intervals. In one group of subjects, 250 micrograms (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. A double-blind, randomized trial was carried out in 48 children to assess the effects of inhaled ipratropium bromide, fenoterol or a combination of both drugs in treating their moderately severe acute asthma. Doses were adjusted according to the age of the patients and administered by nebulizer. Measurements of pulse rate and respiratory rate and assessment of the severity of symptoms were made at fixed intervals during the first 2 hours on treatment. Repeat nebulizations were given, if necessary, at 2-hourly intervals. The results suggested that fenoterol provided the most adequate treatment and there was no evidence to indicate that the addition of ipratropium produced any improved benefit. 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.
                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.
                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.
                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. The separate and combined effects of inhaled metaproterenol and atropine sulfate were evaluated in the treatment of 44 episodes of acute asthma occurring in 35 children ranging in age from 13 months to 13 years. Peak expiratory flow rate and pulmonary index were measured before and after each of up to three inhalation treatments. Significant improvement in peak flow rate (P less than .04) was noted after the second inhalation of metaproterenol both with and without the combination of atropine sulfate compared with the effects of atropine alone. Patients treated with metaproterenol and metaproterenol combined with atropine also experienced fewer therapeutic failures (2/15 and 2/16, respectively) compared with those treated with atropine (6/13, P less than .02). Pulmonary index scores did not differ among the treatment groups. Inhaled metaproterenol appears to be more effective than inhaled atropine sulfate in the treatment of children with acute asthma. The addition of inhaled atropine sulfate appears to offer no advantage over treatment with inhaled metaproterenol alone. Anticholinergic medications such as ipratropium improve the pulmonary function of patients with acute exacerbations of asthma, but their effect on hospitalization rates is uncertain.
                We conducted a randomized, double-blind, placebo-controlled study of 434 children (2 to 18 years old) who had acute exacerbations of moderate or severe asthma treated in the emergency department. All the children received a nebulized solution of albuterol (2.5 or 5 mg per dose, depending on body weight) every 20 minutes for three doses and then as needed. A corticosteroid (2 mg of prednisone or prednisolone per kilogram of body weight) was given orally with the second dose of albuterol. Children in the treatment group received 500 microg (2.5 ml) of ipratropium bromide with the second and third doses of albuterol; children in the control group received 2.5 ml of normal saline at these times.
                Overall, the rate of hospitalization was lower in the ipratropium group (59 of 215 children [27.4 percent]) than in the control group (80 of 219 [36.5 percent], P=0.05). For patients with moderate asthma (indicated by a peak expiratory flow rate of 50 to 70 percent of the predicted value or an asthma score of 8 to 11 on a 15-point scale), hospitalization rates were similar in the two groups (ipratropium: 8 of 79 children [10.1 percent]; control: 9 of 84 [10.7 percent]). For patients with severe asthma (defined as a peak expiratory flow rate of <50 percent of the predicted value or an asthma score of 12 to 15), the addition of ipratropium significantly reduced the need for hospitalization (51 of 136 children [37.5 percent], as compared with 71 of 135 [52.6 percent] in the control group; P=0.02).
                Among children with a severe exacerbation of asthma, the addition of ipratropium bromide to albuterol and corticosteroid therapy significantly decreases the hospitalization rate. The aim of our study was to determine whether the combination of an anticholinergic treatment with a beta 2-adrenergic medication is a more effective treatment for acute asthma attack than the two treatments individually. The association of salbutamol-ipratropium was compared to treatment with salbutamol and ipratropium alone. It was a prospective double-blind study in children with acute asthma attack, participating as outpatients. Their clinical history and characteristics of bronchial obstruction were recorded on a standard form. Afterwards, they were included in one of the three following study groups: group one, 100 micrograms/inh salbutamol; group two, 20 micrograms/inh ipratropium; group three, 100 micrograms/inh of salbutamol plus 20 micrograms/inh ipratropium. There were 40 patients in each group, with Tal score +/- 5 and PEF < 80% of the predicted value. They were evaluated at the beginning (0 min), and at 15, 30, 45, 60, 80, 100 and 120 min. Each patient was treated with two inhalations of the study medication and was then evaluated for variations in Tal score. The mean age was 7.3 years; Tal score was 5.6, 5.6 and 6.0 at 0 min (p > 0.05). Decrease in Tal score after 15 min meant p < 0.01 for salbutamol-ipratropium and salbutamol vs. ipratropium. At 30 min p < 0.05 for salbutamol-ipratropium vs. salbutamol, and at 45 min p < 0.01 for salbutamol-ipratropium vs. salbutamol. PEF at 0 min was 70.9%, 71.3% and 68.6% (p > 0.05) increasing after 15 min. At 30 min p < 0.05 for salbutamol-ipratropium vs. salbutamol, and p < 0.01 vs. ipratropium. At 45 min p < 0.01 for salbutamol-ipratropium vs. salbutamol and ipratropium. A total 4.7 doses of salbutamol were needed to improve the asthma attack, 5.3 of ipratropium and 3.7 of salbutamol-ipratropium, with p < 0.01 for salbutamol-ipratropium vs. salbutamol and ipratropium. We conclude that the combination of salbutamol and ipratropium is more effective than each medication alone in treating acute asthma attacks in pediatric patients. Twenty asthmatic children, aged 4 to 15 years, consisting of 14 boys and 6 girls, were studied during acute episodes of asthmatic attacks. A group of 10 children each received either inhaled terbutaline 0.5 mg or inhaled terbutaline 0.5 mg followed by ipratropium bromide 0.04 mg 15 minutes later through a 750-ml volumetric spacer. Significant increases in FEV1 over the baseline were observed from 2 minutes to 2 hours and from 2 minutes to 6 hours following the first and second regimen respectively. A slightly greater increase and longer duration in FEV1 were observed in the combined drug treatment and very slight decreases in systolic and diastolic blood pressure below the base-line were observed. Neither regimen showed any serious adverse effect on the heart rate and respiratory rate. nan The objective of this trial was to determine the efficacy of frequent nebulized ipratropium added to high-dose albuterol therapy in children with severe asthma.
                One hundred twenty children (5 to 17 years) of age) with severe acute asthma (forced expiratory volume in 1 second (FEV1), < 50% of the predicted value) were enrolled into a randomized double-blind three-arm placebo-controlled trial comparing three groups: group 1, three doses of nebulized ipratropium bromide within 60 minutes (250 micrograms/dose); group 2, one dose of ipratropium; group 3, no ipratropium. All patients were also treated with three doses of nebulized albuterol within 60 minutes (0.15 mg/kg per dose). Pulmonary function and clinical measures were assessed every 20 minutes for up to 120 minutes.
                The groups were comparable at baseline. At 120 minutes, the mean percentage of predicted FEV1 improved from 33.4% to 56.7% in group 1, from 34.2% to 52.3% in group 2, and from 35.4% to 48.4% in group 3 (p = 0.0001). The differences between groups were larger in those children with a baseline FEV1 < or = 30% of the predicted value: FEV1 increased from 24.5% to 50.9% in group 1, from 25.0% to 39.8% in group 2, and from 25.9% to 36.5% in group 3 (p = 0.0001). In group 1, 38% of the patients were hospitalized after the study, 44% in group 2, and 46% in group 3 (p value not significant). However, in patients with FEV1 < or = 30%, the hospitalization rates were 27% in group 1, 56% in group 2, and 83% in group 3 (p = 0.027). There were no toxic effects attributable to ipratropium.
                The addition of repeated doses of nebulized ipratropium to frequent high-dose albuterol therapy in patients with acute severe asthma is both safe and more effective than albuterol alone; its use in patients with very severe asthma may reduce hospitalizations.
A single dose of an anticholinergic agent is not effective for the treatment of mild and moderate exacerbations and is insufficient for the treatment of severe exacerbations. Adding multiple doses of anticholinergics to beta2 agonists appears safe, improves lung function and would avoid hospital admission in 1 of 12 such treated patients. Although multiple doses should be preferred to single doses of anticholinergics, the available evidence only supports their use in school-aged children with severe asthma exacerbation. There is no conclusive evidence for using multiple doses of anticholinergics in children with mild or moderate exacerbations.