Effect of racemic epinephrine and salbutamol on clinical score and pulmonary mechanics in infants with bronchiolitis. A randomized, controlled trial of the effectiveness of nebulized therapy with epinephrine compared with albuterol and saline in infants hospitalized for acute viral bronchiolitis. Additive effects of dexamethasone in nebulized salbutamol or L-epinephrine treated infants with acute bronchiolitis. Epinephrine and dexamethasone in children with bronchiolitis. A randomized trial of nebulized epinephrine vs albuterol in the emergency department treatment of bronchiolitis. Randomized, placebo-controlled trial of albuterol and epinephrine at equipotent beta-2 agonist doses in acute bronchiolitis. High volume normal saline alone is as effective as nebulized salbutamol-normal saline, epinephrine-normal saline, and 3% saline in mild bronchiolitis. A randomized trial comparing the efficacy of epinephrine with salbutamol in the treatment of acute bronchiolitis. Comparative efficacy of combined nebulized salbutamol with ipratropium bromide and nebulized adrenaline to treat children with acute bronchiolitis. Short term effects of adrenaline in bronchiolitis: a randomised controlled trial. A multicenter, randomized, double-blind, controlled trial of nebulized epinephrine in infants with acute bronchiolitis.
To test the efficacy of a combined alpha- and beta-receptor agonist in acute bronchiolitis, we compared inhaled racemic epinephrine with salbutamol in a double-blind, crossover, randomized protocol. Twenty-four infants, 4.6 +/- 0.5 (mean +/- SEM) months of age, with their first episode of bronchiolitis were tested. After sedation with chloral hydrate, a clinical score and pulmonary mechanics measurements using simultaneous signals of airflow volume and transpulmonary pressure were recorded. After baseline measurements, infants received either nebulized salbutamol, 0.03 ml/kg, or racemic epinephrine, 0.1 ml/kg. Thirty minutes later, there was a significant decrease in clinical score after treatment with racemic epinephrine compared with the baseline score (p < 0.001); this difference was not present after salbutamol inhalation (p = 0.42). Only 13 patients had a decrease in clinical score after salbutamol therapy, in comparison with 20 infants treated with racemic epinephrine (p < 0.01). Both drug decreased respiratory rate, but the decrease was greater after the use of racemic epinephrine (p < 0.001). There was a significant decrease in inspiratory, expiratory, and total pulmonary resistance after treatment with racemic epinephrine compared with baseline values (p < 0.01) but no significant change after salbutamol inhalation. There was no significant correlation between the clinical score and pulmonary mechanics either at baseline or after drug treatment. We conclude that racemic epinephrine is superior to salbutamol in the treatment of infants with their first episode of acute bronchiolitis. In previously well infants hospitalized with acute viral bronchiolitis, the effectiveness of repeated nebulized therapy with epinephrine (EPI) was compared with treatment with albuterol (ALB) or saline placebo (PLAC).
                In this randomized, double-blind, parallel-group, controlled trial, infants received study nebulizations every 1 to 6 hours and were assessed twice daily by the research team. The primary outcome was length of hospital stay (LOS). Secondary outcomes included the time from admission until the infant had normal hydration, oxygenation, and minimal respiratory distress.
                A total of 149 infants were randomized; 50 were allocated to receive racemic EPI, 51 were given ALB, and 48 received PLAC. Baseline characteristics and pre-enrollment symptoms, signs, and therapy were similar between groups. There were no group differences in the primary outcome measure, mean LOS (hours)(+/- SD): EPI = 59.8 (62), ALB = 61.4 (54), and PLAC = 63.3 (47); P =.95 by intent-to-treat analysis. Group differences were not statistically significant in any of the secondary outcomes.
                There were no group differences in the effectiveness of therapy for infants hospitalized with bronchiolitis. Based on these results, we do not recommend routine use of either nebulized EPI or ALB in this patient group. Although it is the most common lower respiratory infection of infancy, the optimal treatment for acute bronchiolitis is still controversial. The aim of this study was to compare the early and late effects of nebulized L-epinephrine (EPI) and intramuscular dexamethasone (DEX) combination therapy with nebulized salbutamol (SAL) and dexamethasone combination and bronchodilators alone in outpatients with acute bronchiolitis.
                A total of 69 infants aged 2-21 months who were admitted to the Pediatrics Department of the Faculty of Medicine, Mersin University, with acute bronchiolitis were included in a randomized, placebo-controlled, prospective trial study. Patients were assigned to receive either nebulized L-epinephrine (3 mg) or salbutamol (0.15 mg/kg) and 15 min later, either dexamethasone 0.6 mg/kg or placebo (PLA), intramuscularly, in a double-blind randomized fashion. The study groups were: epinephrine + dexamethasone group (group 1, n=23), salbutamol + dexamethasone group (group 2, n=23), epinephrine + placebo group (group 3, n=11), and salbutamol + placebo group (group 4, n=12). The outcome measures were heart rate, respiratory rate and Respiratory Distress Assessment Instrument (RDAI) score determined at 30, 60, 90 and 120 min, 24 h, and 5 days after the first therapy. Patients were then followed-up during the subsequent 2 months for the prevalance of respiratory complaints regarding bronchial hyperreactivity.
                There were no significant differences between the outcome variables of the four groups within the first 120 min and at 24 hours, or between the rates of requirement of a second dose of the same bronchodilator. However, fifth day RDAI score values of both DEX groups were significantly lower than that of SAL + PLA group (P=0.000 and P=0.01, respectively). The fifth day score value of group 1 was also significantly better than that value of EPI + PLA group but not different from group 2.
                A single dose of intramuscular dexamethasone added to nebulized L-epinephrine, or salbutamol therapies resulted in better outcome measures than bronchodilators alone in the late phase (fifth day) of mild to moderate degree bronchiolitis attack. However, effects of EPI + DEX combination was not different from SAL + DEX combination. Although numerous studies have explored the benefit of using nebulized epinephrine or corticosteroids alone to treat infants with bronchiolitis, the effectiveness of combining these medications is not well established.
                We conducted a multicenter, double-blind, placebo-controlled trial in which 800 infants (6 weeks to 12 months of age) with bronchiolitis who were seen in the pediatric emergency department were randomly assigned to one of four study groups. One group received two treatments of nebulized epinephrine (3 ml of epinephrine in a 1:1000 solution per treatment) and a total of six oral doses of dexamethasone (1.0 mg per kilogram of body weight in the emergency department and 0.6 mg per kilogram for an additional 5 days) (the epinephrine-dexamethasone group), the second group received nebulized epinephrine and oral placebo (the epinephrine group), the third received nebulized placebo and oral dexamethasone (the dexamethasone group), and the fourth received nebulized placebo and oral placebo (the placebo group). The primary outcome was hospital admission within 7 days after the day of enrollment (the initial visit to the emergency department).
                Baseline clinical characteristics were similar among the four groups. By the seventh day, 34 infants (17.1%) in the epinephrine-dexamethasone group, 47 (23.7%) in the epinephrine group, 51 (25.6%) in the dexamethasone group, and 53 (26.4%) in the placebo group had been admitted to the hospital. In the unadjusted analysis, only the infants in the epinephrine-dexamethasone group were significantly less likely than those in the placebo group to be admitted by day 7 (relative risk, 0.65; 95% confidence interval, 0.45 to 0.95, P=0.02). However, with adjustment for multiple comparisons, this result was rendered insignificant (P=0.07). There were no serious adverse events.
                Among infants with bronchiolitis treated in the emergency department, combined therapy with dexamethasone and epinephrine may significantly reduce hospital admissions. (Current Controlled Trials number, ISRCTN56745572.)
                2009 Massachusetts Medical Society To determine if nebulized epinephrine is more efficacious than nebulized albuterol in the emergency department (ED) treatment of moderately ill infants with bronchiolitis.
                Sixty-six patients between 0 and 12 months of age with new-onset wheezing, an antecedent upper respiratory tract infection, and a clinical score (Respiratory Distress Assessment Instrument) of 8 to 15 were randomized in a double-blind fashion to receive either 0.9 mg/kg of nebulized 2.25% racemic epinephrine (n = 34) or 0.15 mg/kg of nebulized 0.5% albuterol sulfate (n = 32) at 0, 30, and 60 minutes.
                Primary outcome measures were clinical score and respiratory rate. Secondary outcome measures were room air oxygen saturation, elapsed time to meeting clinical criteria for ED discharge, hospitalization rate, and proportion of patients relapsed within 72 hours of ED discharge (relapse rate).
                Both treatment groups experienced a similar pattern of change in mean clinical score, respiratory rate, and room air saturation over time. There were no significant differences between the groups by these same measures at any time. The median time at which infants were well enough for ED discharge was 90 minutes in the epinephrine-treated group vs 120 minutes in the albuterol-treated group (P =.01). Sixteen infants (47.1%) in the epinephrine-treated group were hospitalized compared with 12 infants (37.5%) in the albuterol-treated group (relative risk, 1.25; 95% confidence interval, 0.71-2.22). Relapse rate was 18.8% (3/16) in the epinephrine-treated group and 42.1% (8/19) in the albuterol-treated group (relative risk, 0.45; 95% confidence interval, 0.14-1.41). Adverse effects occurred infrequently.
                Although the patients treated with epinephrine were judged well enough for ED discharge significantly earlier than the patients treated with albuterol, epinephrine was not found to be more efficacious than albuterol in treating moderately ill infants with bronchiolitis. Our objective was to determine if nebulized racemic epinephrine is more efficacious than nebulized albuterol or saline placebo in the treatment of bronchiolitis in the outpatient setting when dosing is equivalent in terms of beta-2 agonist potency. Sixty-five patients between ages 6 weeks and 24 months with a diagnosis of bronchiolitis, defined as first-time wheezing, upper respiratory symptoms and/or fever, and a Respiratory Distress Assessment Instrument score of at least 4, were randomized to receive 5 mg nebulized albuterol, 5 mg nebulized racemic epinephrine, or an equivalent volume of placebo at 0, 30, and 60 min. The primary outcome measure was need for hospital admission or home oxygen. Secondary outcome measures were changes in clinical scores and oxygen saturations. There were no significant statistical differences between groups in terms of need for hospital admission or outpatient management with home oxygen therapy. There were no differences between groups in terms of changes in clinical scores or oxygen saturations. Racemic epinephrine and albuterol at equivalent doses had no effect on the need for hospitalization or supplemental oxygen in bronchiolitis in the outpatient setting compared to nebulized saline placebo, though this study may have missed less dramatic clinical effects due to small sample size.
                2005 Wiley-Liss, Inc. The objective of this study was to investigate the effectivenesses of nebulized salbutamol, epinephrin, 3% saline, and normal saline (0.9% NaCl) in the treatment of mildly affected infants with acute bronchiolitis. We enrolled 186 children (mean age 9.5 +/- 5.3 months, range 1.5-24 months, 65.1% male) with a first episode of wheezing diagnosed as mild bronchiolitis in emergency department. Patients were randomized in a double-blind fashion to receive 4 ml dose either of 1.5 mg epinephrine plus normal saline (group 1; n = 38) or 1.5 mg epinephrine plus 3% saline (group 2; n = 39) or 2.5 mg salbutamol plus normal saline (group 3; n = 36) or 2.5 mg salbutamol plus 3% saline (group 4; n = 36) or normal saline alone (group 5; n = 37) at 0 and 30 min. Thus, all treatment modalities included high amount of NaCl (72-240 mg). Clinical score, oxygen saturation and heart rate were assessed at 0, 30, 60, and 120 min. After discharge, patients were reassessed by telephone contact at 48 hr and 6 months. The baseline characteristics were similar in all groups (P > 0.05). The outcome of patients at 120 min was found significantly better than the baseline values (P < 0.05). There were no significant differences between the outcome variables of the groups (P > 0.05). No adverse effects attributable to nebulized therapy were seen. In conclusion, all treatment modalities used in this study, including a total of 8 ml normal saline inhalation at 30-min interval showed clinically significant and swift improvement in mildly affected ambulatory infants with acute bronchiolitis.
                (c) 2009 Wiley-Liss, Inc. This randomized, double-blind trial compared the efficacy of nebulized epinephrine with salbutamol in the treatment of infants with acute bronchiolitis. The mean percent oxygen saturation at 60 minutes was significantly higher in the epinephrine group. Thirty-three percent of the patients in epinephrine group were admitted to the hospital compared with 81% of the salbutamol group (p = 0.003). We conclude that nebulized epinephrine is more efficacious than salbutamol for infants with acute bronchiolitis seen in an emergency department. As the efficacy of combined nebulized salbutamol & ipratropium bromide as well as L-adrenaline to treat acute bronchiolitis is not well studied among the Bangladeshi infants, this study was carried out to see their efficacy in acute bronchiolitis and to compare their effectiveness. This randomized clinical trial was done among 60 children aged less than 02 years, admitted in the department of Pediatrics, Dhaka Medical College Hospital, during January through December 2005 with acute bronchiolitis. After a quick initial assessment, nebulization were done twice at 6 hours interval with the mentioned drugs, group wise (one group with salbutamol plus ipratropium bromide and other group with L-adrenaline alone) and the outcomes were assessed after 30 minutes of each nebulization in respect to oxygen saturation and clinical modified respiratory distress assessment instrument (MRDAI) scores. The results were analyzed by using SPSS version 10.0 and at a p value of </=0.05, the test was considered significant. The clinical characteristics were similar in both the groups. After 02 doses of nebulizations by the studied drugs, a significant improvement in respect to oxygen saturation and MRDAI score were noted among the children in both the groups, compared to their baseline status (p=0.000). However, L-adrenaline showed more efficacy (MRDAI, p=0.021; SaO2, p=0.034) than combined Salbutamol & Ipratropium bromide. Both L-adrenaline and combined salbutamol & ipratropium bromide were found effective in acute bronchiolitis but L-adrenaline was found more effective. A large multi-centre clinical trial is recommended. Airway narrowing in acute bronchiolitis does not respond to inhaled bronchodilators but does to adrenaline when compared to bronchodilators. Influences of supportive care were not considered in previous treatment studies.
                Short term effects of nebulised adrenaline and saline placebo were compared in infants with moderately severe acute bronchiolitis. Thirty eight infants were recruited, 19 in each treatment group. After stabilisation, infants received a single 3 ml dose of either levo-adrenaline (3 mg) or 0.9% saline placebo via Pari-BABY nebuliser driven with 6 l/min oxygen for three minutes. Changes in respiratory rate (RR), heart rate (HR), oxygen saturation (SpO(2)), Respiratory Distress Assessment Instrument (RDAI), and activity levels were assessed at 20 minutes intervals at times -20, 0, 20, 40, and 60 minutes around treatment. Respiratory virology and chest x ray were performed.
                Supportive therapy prior to study treatment resulted in significant reductions in RR (by 4.3 breaths/min) and HR (by 4.6 beats/min); there were no changes in SpO(2) or RDAI. There were no further changes in any parameter in either treatment group at any assessment time after treatment.
                No improvement was shown with inhaled adrenaline in acute bronchiolitis, when compared with supportive care or placebo. Improvements noted pretreatment question whether prior noted improvements were through supportive care or pharmacological interventions. The treatment of infants with bronchiolitis is largely supportive. The role of bronchodilators is controversial. Most studies of the use of bronchodilators have enrolled small numbers of subjects and have examined only short-term outcomes, such as clinical scores.
                We conducted a randomized, double-blind, controlled trial comparing nebulized single-isomer epinephrine with placebo in 194 infants admitted to four hospitals in Queens-land, Australia, with a clinical diagnosis of bronchiolitis. Three 4-ml doses of 1 percent nebulized epinephrine or three 4-ml doses of normal saline were administered at four-hour intervals after hospital admission. Observations were made at admission and just before, 30 minutes after, and 60 minutes after each dose. The primary outcome measures were the length of the hospital stay and the time until the infant was ready for discharge. The secondary outcome measures were the degree of change in the respiratory rate, the heart rate, and the respiratory-effort score and the time that supplemental oxygen was required.
                There were no significant overall differences between the groups in the length of the hospital stay (P=0.16) or the time until the infant was ready for discharge (P=0.86). Among infants who required supplemental oxygen and intravenous fluids, the time until the infant was ready for discharge was significantly longer in the epinephrine group than in the placebo group (P=0.02). The need for supplemental oxygen at admission had the greatest influence on the score for severity of illness and strongly predicted the length of the hospital stay and the time until the infant was ready for discharge (P<0.001). There were no significant changes in the respiratory rate, blood pressure, or respiratory-effort scores from before each treatment to after each treatment. The heart rate was significantly increased after each treatment with epinephrine (P=0.02 to P<0.001).
                The use of nebulized epinephrine did not significantly reduce the length of the hospital stay or the time until the infant was ready for discharge among infants admitted to the hospital with bronchiolitis.
                Copyright 2003 Massachusetts Medical Society