Nebulized albuterol in acute childhood asthma: comparison of two doses

Thirty-three children and adolescents from 5 to 17 years of age with moderate to severe acute asthma were given nebulized albuterol therapy in either a high (0.30 mg/kg body weight) or standard (0.15 mg/kg) dose administered at three hourly intervals in a randomized double-blind study. The high-dose hourly regimen resulted in significantly greater improvement in the forced expiratory volume in 1 second (FEV1). Furthermore, patients receiving the high dose showed a steady improvement in the FEV1 from the start to the end of the study, whereas FEV1 plateaued after the second dose in the standard-dose group. Although a rise in heart rate and a fall in serum potassium level occurred, neither of these changes nor other side effects were different in the two groups. The high-dose therapy resulted in much higher serum albuterol levels than the standard dose. There was no correlation between the drug levels and side effects or initial and subsequent FEV1. It is concluded that occasional hourly high-dose albuterol therapy should be considered for some pediatric patients with acute asthma of moderate severity, especially those who relapse between doses.     

Comparison of albuterol delivered by a metered dose inhaler with spacer versus a nebulizer in children with mild acute asthma.

OBJECTIVE: In children with mild acute asthma, to compare treatment with a single dose of albuterol delivered by a metered dose inhaler (MDI) with a spacer in either a weight-adjusted high dose or a standard low-dose regimen with delivery by a nebulizer. STUDY DESIGN: In this randomized double-blind trial set in an emergency department, 90 children between 5 and 17 years of age with a baseline forced expiratory volume in 1 second (FEV1 ) between 50% and 79% of predicted value were treated with a single dose of albuterol, either 6 to 10 puffs (n = 30) or 2 puffs (n = 30) with an MDI with spacer or 0.15 mg/kg with a nebulizer (n = 30). RESULTS: No significant differences were seen between treatment groups in the degree of improvement in percent predicted FEV1 (P =.12), clinical score, respiratory rate, or O2 saturation. However, the nebulizer group had a significantly greater change in heart rate (P =.0001). Our study had 93% power to detect a mean difference in percent predicted FEV1 of 8 between the treatment groups. CONCLUSION: In children with mild acute asthma, treatment with 2 puffs of albuterol by an MDI with spacer is just as clinically beneficial as treatment with higher doses delivered by an MDI or by a nebulizer.     

Standard dose of inhaled albuterol significantly increases QT dispersion compared to low dose of albuterol plus ipratropium bromide therapy in moderate to severe acute asthma attacks in children

BACKGROUND: Beta-2 agonist therapy has previously shown to increase the QT dispersion (QTd) in asthmatic patients and increased QTd has been well documented in association with cardiac arrhythmias and sudden death. However, the data concerning the effect of low doses of beta-2 agonist therapy in combination with the anticholinergic agents to potentiate bronchodilatation on QTd in asthmatic children are limited. The objectives of this study was to investigate the changes on QTd during both the standard dose of nebulized albuterol therapy and low dose nebulized albuterol plus inhaled ipratropium therapyn to assess the potential arrhythmogenic risk of these two treatment strategies in children with acute asthmatic attacks. METHODS: Forty-three children with the diagnosis of moderate to severe acute asthma were enrolled in the study. Standard dose of nebulized albuterol therapy (0.15 mg/kg) were administered to 20 patients (group 1) and low dose of nebulized albuterol (0.075 mg/kg) plus nebulized ipratropium bromide therapy (250 microg/dose) were given to the remaining 23 patients (group 2). Respiratory distress score, peak expiratory flow rate, arterial blood pressure, O2 saturation, serum potassium and urea nitrogen levels were studied and QT interval parameters were measured from the standard 12-lead electrocardiograms at baseline and after treatment. RESULTS: Significant improvement was achieved in respiratory distress score and peak expiratory flow rate after three dose inhalation. No significant difference was observed between the pre and post-treatment values of serum potassium, blood urea nitrogen, O2 saturation and arterial blood pressure values. The evaluation of the corrected QTd (QTcd) showed that while there was no statistical difference in the pre and post-treatment values in group 2 (30.4+/-3.1 msn vs 32.1+/-3.9 msn), QTcd was found to be significantly increased in group 1 after treatment (29.0+/-3 msn vs 40.6+/-5.1 msn, P<0.0001). CONCLUSION: The data of the present study suggest that the increase of the QTd is more prominent with the use of a standard dose of albuterol compared to low dose albuterol plus ipratropium therapy. Therefore, it may be concluded that a low dose of albuterol plus ipratropium bromide therapy may be preferred to avoid rhythm disturbances in asthmatic children.     

Controlled trial of nebulized albuterol in children younger than 2 years of age with acute asthma.

To determine the response to nebulized beta 2 agonist, 28 children younger than 2 years of age who visited the emergency department during an episode of acute asthma were studied. Each subject had a previous history of recurrent wheezing episodes. They were randomly assigned to receive two administrations of either nebulized albuterol (0.15 mg/kg per dose) or placebo (normal saline) with oxygen, 1 hour apart. After two nebulizations, the albuterol-treated patients had a greater improvement in clinical status (respiratory rate, degree of wheezing and accessory muscle use, total clinical score, and arterial oxygen saturation) than the placebo group. None of the patients in the albuterol group experienced a decrease of arterial oxygen saturation of greater than or equal to 2%. It is concluded that a trial of nebulized beta 2 agonists is warranted in the treatment of acute asthma in infants and young children.     

Efficacy of nebulized budesonide compared to oral prednisolone in acute bronchial asthma

To evaluate the efficacy of nebulized budesonide compared to oral prednisolone early in the emergency room management of acute asthma, we conducted a double-blind, placebo-controlled trial. Eighty children, 2 years to 12 years of age, with acute moderate attacks of asthma, were randomized into two groups. One group received nebulized salbutamol (0.15 mg/kg) and placebo at half-hourly intervals for three doses, and a single dose of oral prednisolone (2 mg/kg) (prednisolone group) and other group received three doses of nebulized salbutamol and budesonide (800 microg) at half-hourly intervals and a single dose of placebo tablets (budesonide group). The baseline characteristics of the two groups were similar, but after three doses of nebulization oxygen saturation, respiratory rate, pulmonary index and respiratory distress score were significantly improved in the budesonide group compared to prednisolone group (p < 0.01). The proportion of patients who were fit for discharge at the end of 2 h after the third dose of nebulization was significantly higher in the budesonide group than in the prednisolone group (22/ 41, 54% vs 7/39, 18%, p < 0.001). The data suggest that a combination of nebulized salbutamol and budesonide should be preferred in the emergency room management of children with acute moderate to severe exacerbation of asthma and who are not on prior oral or inhaled steroid therapy.     

Efficacy of adding nebulized ipratropium bromide to nebulized albuterol therapy in acute bronchiolitis.

Nebulized ipratropium bromide is though to be synergistic with albuterol in therapy for acute childhood asthma. Because the efficacy of ipratropium in bronchiolitis is uncertain and some infants with bronchiolitis do not respond to nebulized albuterol alone, the following study was undertaken. In this double-blind, placebo-controlled trial, 69 infants between 6 weeks and 24 months of age who exhibited the first episode of acute bronchiolitis were randomly assigned to receive either nebulized albuterol (0.15 mg/kg per dose) and ipratropium bromide (250 micrograms per dose) (group A, n = 36) or nebulized albuterol and normal saline (placebo) (group B, n = 33) for two doses, 1 hour apart. The two groups were comparable at baseline. Both therapies resulted in clinically significant improvement. However, the addition of ipratropium resulted in no additional benefit with respect to decrease in the respiratory rate (mean decreases 10.6/min vs decreases 8.6/min, P = .86), accessory muscle score (range 0 through 3) (decreases 0.92 vs decreases 0.82, z = -0.44), wheeze score (range 0 through 3) (decreases 0.94 vs 0.85, z = -0.20), oxygen saturation (increases 0.25% vs increases -0.33%, P = .86), or hospitalization rate (17 vs 10). The number of "nonresponders" and "clear responders" was also very similar in both groups. No toxicity was noted. The increase in heart rate was mild and similar in both groups (increases 6.7 vs increases 11.1). The power of the study to detect a difference between the two treatment groups in the respiratory rate change > or = 8/min is greater than 90%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Treatment of asthma crises in children with nebulized salbutamol

Thirty-two children were treated with nebulized salbutamol for acute asthma. Seventy-five per cent of the treatments were efficient, either after a first nebulization at 0.15 mg/kg (47% = group I), or after a second nebulization 45 min later, at 0.05 mg/kg (27% = group II). Twenty-five per cent of the treatments (group III) were inefficient or only partly efficient. The clinical tolerance was good except in two children. Group I and II presented differences only for the auscultation score. Children from group I and II were older and had less severe asthma than those from group III. On the basis of this study, nebulized salbutamol appears to be an affective and safe treatment for acute asthma. The repeated administration of low doses, shortly after the first nebulization increases the quality of the response.     

Ipratropium bromide plus nebulized albuterol for the treatment of hospitalized children with acute asthma

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 microg 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 beta-2 agonists confers no significant enhancement of clinical outcome for the treatment of hospitalized children with status asthmaticus.     

Randomized trial of the addition of ipratropium bromide to albuterol and corticosteroid therapy in children hospitalized because of an acute asthma exacerbation.

OBJECTIVE: To determine whether the addition of inhaled ipratropium bromide to inhaled albuterol and systemic corticosteroid therapy was more efficacious than inhaled albuterol and systemic corticosteroids alone in the inpatient treatment of acute asthma exacerbations in children. DESIGN: Double-blind, randomized, placebo-controlled trial. SETTING: Pediatric inpatient unit of a tertiary urban hospital. PARTICIPANTS: Eighty children (aged 1-18 years) hospitalized because of an acute asthma exacerbation. INTERVENTION: Children were randomized to receive either nebulized ipratropium bromide, 250 microg, or nebulized isotonic sodium chloride solution, 1 mL. All children received albuterol and systemic corticosteroids. MAIN OUTCOME MEASURES: The primary outcome variable was a validated clinical asthma score, measured at baseline and every 6 hours for 36 hours. Secondary outcome measures included the forced expiratory volume in 1 second, the oxygen saturation, the number of doses of inhaled study drug, the time to an inhaled drug-dosing interval of 4 hours, and the length of the hospital stay. RESULTS: There were no differences between groups on baseline characteristics. The intention-to-treat analysis, using repeated-measures analysis of variance, showed no significant (P =.07) difference between the groups in the clinical asthma score over time. There were also no significant differences between groups on secondary outcomes. CONCLUSION: The addition of nebulized ipratropium bromide to nebulized beta(2)-agonist and corticosteroid therapy in the treatment of children hospitalized because of asthma (following intensive emergency department treatment) confers no extra benefit.     

Nebulized albuterol in acute bronchiolitis

In a double-blind, placebo-controlled trial, 40 infants between 6 weeks and 24 months of age who had a first episode of wheezing and other signs and symptoms of bronchiolitis were randomly assigned to receive either nebulized albuterol (0.15 mg/kg/dose) or placebo (saline solution) for two administrations 1 hour apart. The albuterol therapy resulted in a significantly greater improvement in the accessory muscle score (decreases 0.70 vs decreases 0.30; p = 0.03), oxygen saturation (increases 0.71% vs decreases 0.47%; p = 0.01) after one dose, and in the accessory muscle score (decreases 0.86 vs decreases 0.37; p = 0.02), respiratory rate (decreases 19.6% vs decreases 8.0%; p = 0.016), and oxygen saturation (increases 0.76% vs decreases 0.79%; p = 0.015) after two doses of the drug. The response to therapy was similar in infants younger and those older than 6 months of age. The heart rate rose slightly more in the albuterol group (increases 7.76 from baseline) versus the placebo group (decreases 6.79). There were no other side effects of the treatment. Of the 34 children from whom nasal specimens were obtained by swab for viral identification, 24 had positive test results (21 for respiratory syncytial virus, 1 for parainfluenza, 1 for paramyxovirus, and 1 for influenza A). We conclude that nebulized albuterol constitutes a safe and effective treatment of infants with bronchiolitis.     

Costs and effectiveness of spacer versus nebulizer in young children with moderate and severe acute asthma

OBJECTIVE: To compare the costs and effectiveness of albuterol by metered dose inhaler (MDI) and spacer versus nebulizer in young children with moderate and severe acute asthma. DESIGN: Randomized, double-blind, placebo-controlled trial in an emergency department at a children's hospital. The participants were children 1 to 4 years of age with moderate to severe acute asthma. Patients assigned to the spacer group received albuterol (600 microg) by MDI by spacer (AeroChamber) followed by placebo by nebulizer (n = 30). The nebulizer group received placebo MDI by spacer followed by 2.5 mg albuterol by nebulizer (n = 30). Treatments were repeated at 20-minute intervals until the patient was judged to need no further doses of bronchodilator, or a total of 6 treatments. RESULTS: Clinical score, heart rate, respiratory rate, auscultatory findings, and oxygen saturation were recorded at baseline, after each treatment, and 60 minutes after the last treatment. Baseline characteristics and asthma severity were similar for the treatment groups. The spacer was as effective as the nebulizer for clinical score, respiratory rate, and oxygen saturation but produced a greater reduction in wheezing (P =.03). Heart rate increased to a greater degree in the nebulizer group (11.0/min vs 0.17/min for spacer, P <.01). Fewer children in the spacer group required admission (33% vs 60% in the nebulizer group, P =.04, adjusted for sex). No differences were seen in rates of tremor or hyperactivity. The mean cost of each emergency department presentation was NZ$825 for the spacer group and NZ$1282 for the nebulizer group (P =.03); 86% of children and 85% of parents preferred the spacer. CONCLUSION: The MDI and spacer combination was a cost-effective alternative to a nebulizer in the delivery of albuterol to young children with moderate and severe acute asthma.     

Comparison of racemic albuterol and levalbuterol for treatment of acute asthma

OBJECTIVE: To determine whether levalbuterol resulted in fewer hospital admissions than racemic albuterol when used for treatment of acute asthma.Study design A randomized, double-blind, controlled trial was conducted in the emergency department (ED) and inpatient asthma care unit of an urban tertiary children's hospital. Children age 1 to 18 years (n=482) provided a total of 547 enrollments. Patients received a nebulized solution of either 2.5 mg racemic albuterol or 1.25 mg levalbuterol every 20 minutes (maximum six doses). Patients admitted to the asthma care unit were treated in a standardized fashion by using the same blinded drug assigned in the ED. Hospitalization rate was the primary outcome. RESULTS: Hospitalization rate was significantly lower in the levalbuterol group (36%) than in the racemic albuterol group (45 %, P=.02). The adjusted relative risk of admission in the racemic group compared with the levalbuterol group was 1.25 (95% confidence interval, 1.01-1.57). Hospital length of stay was not significantly shorter in the levalbuterol group (levalbuterol, 44.9 hours; racemic albuterol, 50.3 hours; P=.63). No significant adverse events occurred in either group. CONCLUSIONS: Substituting levalbuterol for racemic albuterol in the ED management of acute asthma significantly reduced the number of hospitalizations.     

Increasing Metered Dose Inhaler Use for Acute Asthma Exacerbations in the Pediatric Emergency Department: A Quality Improvement Challenge

Pediatric asthma is the most common chronic condition in children and results in significant disease burden and healthcare costs. The mainstay of asthma treatment is inhaled albuterol, and different modalities of albuterol delivery have been shown to affect healthcare quality measures. Albuterol delivered via metered-dose inhaler with a valved holding chamber (MDI/VHC) has been shown to be at least as effective as nebulized albuterol while also reducing medication side effects, admission rates, length of stay in the emergency department (ED) and overall costs. However, a culture of nebulized albuterol still predominates in the ED. Quality Improvement methodology is well suited to address this healthcare quality problem. The goal of this article is to utilize The Model for Improvement framework to provide a review and a critique of the literature regarding the transition to MDI/VHCs from nebulizers in the acute care of children with asthma exacerbations.     

Acute asthma, salbutamol and hyperglycaemia

The effects of frequent high-dose nebulized salbutamol on plasma glucose concentrations were studied in 12 children (mean age 60 months) with acute severe asthma. There was a significant difference between mean initial glucose levels and peak levels. We conclude that hyperglycaemia can be produced in children as a result of nebulized salbutamol.     

Co-administration of salbutamol and fluticasone for emergency treatment of children with moderate acute asthma.

This study aimed to compare the efficacy of nebulized therapy with salbutamol alone or in combination with fluticasone. In a randomized, double-blind clinical trial, 150 children with moderate acute asthma were randomly assigned to receive by nebulizations either (i) three doses of salbutamol 30 microl/kg per dose, each dose administered every 15 min, (ii) three doses of salbutamol plus two doses of fluticasone 500 microg/dose at 15 and 30 min after first dose of salbutamol, or (iii) three doses of salbutamol/fluticasone 500 microg/dose, each combined dose administered every 15 min. Pulse oxymetry (SaO2), peak expiratory flow (PEF) and Wood et al. (Am J Dis Child, 123, 1972, 123) clinical scale were evaluated at baseline, 15, 30, 45, 60, 90 and 120 min after the first nebulization. Patients in the three groups significantly improved since 15 min after the first nebulization. We did not observe differences in the recovery of SaO2 and PEF among the three groups of treatment (p > 0.10). In group 3, children showed better clinical response at 120 min than the other two groups (p < 0.05). No significant adverse effects were observed with any treatment. To summarize, in children with acute moderate asthma, nebulized salbutamol at an accumulated dose of 90 mul/kg plus fluticasone at an accumulated dose of 1500 microg produced better clinical relief after 2 h. However, similar PEF and SaO2 responses were observed with salbutamol alone or in combination with different doses of fluticasone.     

Addition of ipratropium to nebulized albuterol in children with acute asthma presenting to a pediatric office

A prospective, randomized, double-blind study was conducted to determine whether there was any benefit to the addition of ipratropium to a single nebulized albuterol treatment in infants and children with mild to moderate acute asthma presenting to a pediatric office. There were no significant differences between the albuterol group and the combined albuterol-ipratropium group in the relief of the respiratory distress, disposition of the patients from the office, or in the incidence of relapse. The addition of ipratropium to nebulized albuterol is of no added benefit in the treatment of infants and children with mild-to-moderate acute asthma presenting to a pediatric office.     

Benefits of ipratropium bromide in the management of asthmatic crises in the emergency department]

BACKGROUND: To determine if the addition of ipratropium bromide in the emergency department (ED) for the treatment of childhood asthma reduces rates of hospitalization and relapses for moderate and severe exacerbations. METHODS: Patients were given an oral corticosteroid treatment (2 mg/kg) and received every 20 minutes either three nebulizations with albuterol (0.15 mg/kg) and ipratropium bromide (250 micrograms) or six nebulizations with albuterol alone (control group). The primary end point was the need for hospitalization, additional nebulizations or a relapse during the following week. Secondary end point included the effect of age. RESULTS: One hundred and forty three children, two to 15 years old, were randomized to ipratropium or control groups and 121 were evaluated on day seven. As a whole, the control group was less often hospitalized or in relapse than those treated with three nebulizations of albuterol and ipratropium (17.5% vs 37.9%, p < 0.02). The ipratropium group reached the same result after three additional albuterol nebulizations. The benefit of anticholinergic therapy was observed for children less than six years of age who had a similar rate of success (73.5 vs 75.7%). CONCLUSION: The association of ipratropium bromide to the first three doses of the albuterol protocol for acute asthma did not act as well as six nebulizations of albuterol alone. The effect was age dependent and two to six years old children needed more attention. Nevertheless the hospitalization rate did not support the use of ipratropium compared with repeated albuterol nebulizations.     

Dose-response relationships of intravenously administered terbutaline in children with asthma

The bronchodilator effect of three successive stable plasma terbutaline levels was studied in 10 children with asthma. Each terbutaline plateau was achieved by giving a rapid intravenous infusion of terbutaline, 0.9 microgram/kg, followed by a continuous infusion for 2 hours. Mean plasma terbutaline concentrations (18, 36, and 53 nmol/L at the three plateaus) were found to correlate linearly with the maintenance dose of terbutaline (2.4, 4.5, and 6.3 micrograms/kg/hr, respectively). Mean forced expiratory volume in 1 second increased from 65% to 96%, and mean forced mid-expiratory flow from 32% to 71% of the predicted normal value during the study (p less than 0.01); maximum bronchodilation was obtained at mean terbutaline levels of about 30 nmol/L (range 20 to 60). Effective plasma terbutaline levels were associated with side effects such as headache and tremor in all patients. In addition, heart rate increased from 84 to 116 beats/min, systolic blood pressure rose from 115 to 129 mm Hg, and diastolic blood pressure dropped from 72 to 61 mm Hg during the study. We conclude that a loading dose of 2 micrograms terbutaline per kilogram of body weight over 5 minutes, followed by a continuous infusion of 4.5 micrograms terbutaline per kilogram per hour, is suitable for treatment of severe bronchoconstriction in children. Because of interindividual variations in drug metabolism and clinical effect, dose adjustment should be evaluated at regular intervals.     

Randomized trial of salbutamol in acute bronchiolitis

To test whether nebulized salbutamol (albuterol) is safe and efficacious for the treatment of young children with acute bronchiolitis, we enrolled 83 children (median age 6 months, range 1 to 21 months) in a randomized, double-blind clinical trial. Participants received two treatments at 30-minute intervals of either nebulized salbutamol (0.10 mg/kg in 2 ml 0.9% saline solution) or a similar volume of 0.9% saline solution placebo. Outcome measures were the respiratory rate, pulse oximetry, and a clinical score based on the degree of wheezing and retractions. Patients in the salbutamol arm had significantly greater improvement in clinical scores after the initial treatment (p = 0.04). There was no difference between the groups in oxygen saturation (p = 0.74); patients treated with salbutamol had a small increase in heart rate after two treatments (159 +/- 16 vs 151 +/- 16; p = 0.03). We conclude that salbutamol is safe and effective for the initial treatment of young children with acute bronchiolitis.     

Dose-response relationship of inhaled metaproterenol sulfate in preschool children with mild asthma

The dose-response relationship of single doses of nebulized metaproterenol sulfate 5% inhalant solution was evaluated by placebo-controlled, parallel-group study of 30 children, aged 3 to 6 years old, with stable asthma. Total respiratory resistance, the primary variable used to assess response, was measured by the forced oscillation method for a period of 6 hours from the start of inhalation. When comparisons were made between metaproterenol sulfate and saline, only 0.01 and 0.02 mL/kg showed significant bronchodilation (P less than .05) in percent change from baseline and area under the curve. However, no significant differences were seen between these doses. Moreover, the effect was sustained for 3 hours with both higher doses. Minimal side effects were observed. Metaproterenol sulfate 5% inhalant solution at a dose of 0.01 mL/kg seems to be optimal to elicit significant and sustained bronchodilatory response in preschool children with mild asthma.