A randomized trial of nebulized epinephrine vs albuterol in the emergency department treatment of bronchiolitis

OBJECTIVE: To determine if nebulized epinephrine is more efficacious than nebulized albuterol in the emergency department (ED) treatment of moderately ill infants with bronchiolitis. METHODS: 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. MAIN OUTCOME MEASURES: 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). RESULTS: 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. CONCLUSIONS: 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.     

Randomized,double-blind,placebo-controlled trial of oral albuterol in infants with mild-to-moderate acute viral bronchiolitis

OBJECTIVE: To determine whether oral albuterol is effective in reducing symptomatology of acute viral bronchiolitis in infants with mild-to-moderate illness. STUDY DESIGN: In a randomized, double-blind trial, previously well infants were randomized upon discharge from the emergency department to receive either albuterol (0.1 mg/kg/dose) three times per day or placebo three times per day for 7 days. Daily standardized telephone interviews were conducted for as long as 14 days. The primary outcome was the time to resolution of illness. Secondary outcomes included time to normal feeding, normal sleeping, quiet breathing, resolved cough, and coryza. RESULTS: We studied 129 infants (albuterol, n = 64; placebo, n = 65). Baseline characteristics were similar between groups. The overall mean age was 5.3 months, 60% were male, and 49 of 61 tested infants were positive for respiratory syncytial virus. The median (95% confidence interval) time to resolution of illness (days) was similar: albuterol, 9.0 (8-13); placebo, 8.0 (7-9); P =.3) (log-rank test). There were no significant group differences in any secondary outcome. Health care revisit and admission rates were similar between groups. CONCLUSIONS: No significant group differences in either primary or secondary outcomes in infants treated with oral albuterol versus placebo were found. The widespread use of oral albuterol in this patient group is not recommended.     

Emergency room management of acute bronchiolitis: a randomized trial of nebulized epinephrine

Acute bronchiolitis is a common, potentially life-threatening condition with few therapeutic options. In the present randomized study, we compared the clinical efficacies of nebulized epinephrine and salbutamol in the emergency room management of acute bronchiolitis. Primary outcome measures were improvement in mean respiratory rate, mean oxygen saturation value and severity score. Secondary outcome measures were length of hospital stay, hospitalization and relapse rates. A total of 75 patients were analyzed (36 epinephrine, 39 salbutamol). Both groups experienced a similar pattern of clinical improvement. Hospitalization rates were 8.3% for epinephrine and 5.1% for salbutamol (p > 0.05), whereas relapse rates were 80% for epinephrine and 20% for salbutamol groups (p < 0.001). Respiratory syncytial virus was the most common virus identified (41%). We did not find a difference between salbutamol and epinephrine in terms of clinical improvement, but salbutamol can be a drug of choice due to its lower relapse and hospitalization rates compared to epinephrine.     

Hypertonic (3%) saline Vs 0.9% saline nebulization for acute viral bronchiolitis: A randomized controlled trial

Objective

To compare the length of hospital stay (primary) and improvement in clinical severity scores (secondary) among children with bronchiolitis nebulized with 3 % hypertonic saline or 0.9% saline.

Design

Randomized double blind controlled trial.

Setting

Tertiary care teaching hospital.

Patients

Hospitalized children (1–24 months) with acute bronchiolitis of moderate severity.

Intervention

Nebulization of 4 ml of 3% hypertonic saline or 4 mL of 0.9% saline, along with 2.5 mg salbutamol, at 4-hourly intervals till the patient was ready for discharge.

Results

Baseline characteristics were similar in two groups. Median clinical severity score at admission was 6 (IQR-1) in both the groups. Clinical severity scores monitored afterwards 12-hourly till discharge (132 h) did not show statistically significant differences in 3% and 0.9% saline groups. Mean length of hospital stay (time to reach predefined clinical severity score<3) was 63.93 ± 22.43 h in 3% saline group and 63.51 ± 21.27 h in 0.9% saline group (P=0.878). No adverse events were reported by the parents, caregivers or treating medical attendants in both groups.

Conclusion

Nebulized 3 % saline is not superior to 0.9% saline in infants with clinically diagnosed acute bronchiolitis.     

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)     

Randomized controlled trial of nebulized adrenaline in acute bronchiolitis

Use of both l -epinephrine and racemic epinephrine (adrenaline) has improved clinical symptoms and composite respiratory scores in acute bronchiolitis. The objective of this randomized double-blind placebo-controlled study was to assess whether there was sufficient improvement in clinical state to reduce hospital admissions. Seventy-five infants aged 1 month to 1 year with a clinical diagnosis of acute bronchiolitis were treated with either 2 ml of 1:1000 nebulized adrenaline or 2 ml of nebulized normal saline administered after baseline assessment and 30 min later. Clinical respiratory parameters were recorded at 15-min intervals for a period of 2 h following the baseline assessment. Admission to hospital was the primary end-point and changes in respiratory parameters were secondary end-points. Fifty percent (19/38) of infants treated with adrenaline were discharged home compared with 38 percent (14/37) of those treated with saline. This 12 percent reduction in rate of admission is not statistically significant (95% CI of difference: −10% to 35%). There was no difference between treated and placebo groups in respiratory rate, oxygen saturation, heart rate or a composite respiratory distress score at 30, 60 or 120 min post-treatment. In this study, nebulized epinephrine did not confer a significant advantage over nebulized saline in the emergency room treatment of acute bronchiolitis.     

Racemic epinephrine compared to salbutamol in hospitalized young children with bronchiolitis; a randomized controlled clinical trial [ISRCTN46561076]

Background  

Bronchiolitis is the most common cause of lower respiratory tract illness in infancy, and hospital admission rates appear to be increasing in Canada and the United States. Inhaled beta agonists offer only modest short-term improvement. Trials of racemic epinephrine have shown conflicting results. We sought to determine if administration of racemic epinephrine during hospital stay for bronchiolitis improved respiratory distress, was safe, and shortened length of stay.     

A meta-analysis of randomized controlled trials evaluating the efficacy of epinephrine for the treatment of acute viral bronchiolitis

BACKGROUND: Controversy exists surrounding the use of bronchodilators for bronchiolitis. Epinephrine hydrochloride is being used with increasing frequency in this group; however, its efficacy has not been systematically reviewed. OBJECTIVE: To systematically review randomized controlled trials comparing inhaled or systemic epinephrine vs placebo or other bronchodilators. DATA SOURCES: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, primary authors, and reference lists. STUDY SELECTION: Studies were included if they (1) were randomized, controlled trials; (2) involved children 2 years or younger with bronchiolitis; and (3) presented quantitative outcomes. DATA EXTRACTION: Two reviewers independently extracted data and assessed study quality. DATA SYNTHESIS: We included 14 studies (7 inpatient, 6 outpatient, and 1 patient status unknown). Thirteen of forty-five comparisons were significant. Among outpatients, results favored epinephrine compared with placebo for clinical score at 60 minutes (standardized mean difference [SMD], -0.81; 95% confidence interval [CI], -1.56 to -0.07), oxygen saturation at 30 minutes (weighted mean difference [WMD], 2.79; 95% CI, 1.50-4.08), respiratory rate at 30 minutes (WMD, -4.54; 95% CI, -8.89 to -0.19), and improvement (odds ratio, 25.06; 95% CI, 4.95-126.91); among inpatients, for clinical score at 60 minutes (SMD, -0.52; 95% CI, -1.00 to -0.03). Among outpatients, results favored epinephrine compared with albuterol sulfate (salbutamol) for oxygen saturation at 60 minutes (WMD, 1.91; 95% CI, 0.38-3.44), heart rate at 90 minutes (WMD, -14.00; 95% CI, -22.95 to -5.05), respiratory rate at 60 minutes (WMD, -7.76; 95% CI, -11.35 to -4.17), and improvement (odds ratio, 4.51; 95% CI, 1.93-10.53); among inpatients, respiratory rate at 30 minutes (WMD, -5.12; 95% CI, -6.83 to -3.41). CONCLUSIONS: Epinephrine may be favorable compared with placebo and albuterol for short-term benefits among outpatients. There is insufficient evidence to support the use of epinephrine among inpatients. Large, multicentered trials are required before routine use among outpatients can be strongly recommended.     

Computerized acoustic assessment of treatment efficacy of nebulized epinephrine and albuterol in RSV bronchiolitis

Aim  

We evaluated the use of computerized quantification of wheezing and crackles compared to a clinical score in assessing the effect of inhaled albuterol or inhaled epinephrine in infants with RSV bronchiolitis.     

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.     

雾化吸入高渗盐水治疗婴幼儿毛细支气管炎疗效和安全性的Meta分析

目的评价高渗盐水治疗婴幼儿毛细支气管炎的疗效和安全性,为临床治疗提供依据。方法检索PubMed、EMBASE、Cochrane图书馆、Cochrane临床对照试验库、维普中文科技期刊数据库、中国知网和万方数据库,检索时间均从建库至2011年4月。获得高渗盐水治疗毛细支气管炎的RCT文献。依据随机方法、分配隐藏、盲法、结果数据的完整性、选择性报告研究结果和其他偏倚来源进行文献偏倚评价。应用RevMan 5.1.1软件进行Meta分析,根据异质性结果选择相应的效应模型分析;无法进行Meta分析时采用描述性分析。结果10篇RCT文献进入Meta分析。文献偏倚评价结果显示,8篇文献存在低度偏倚风险,2篇文献存在中度偏倚风险。①高渗盐水组较对照组可显著缩短住院时间（MD=-1.33 d,95%CI:-1.63~-1.03 d, P< 0.000 01）。②高渗盐水组较对照组可显著降低治疗后临床病情严重度评分 (第1天：MD=-0.77,95%CI:-1.30 ~-0.24,P=0.004;第2天：MD=-1.15,95%CI:-1.86~-0.44,P=0.001;第3天:MD=-1.43,95%CI:-1.87 ~-0.99,P<0.000 01)。③高渗盐水组较对照组可显著缩短喘息缓解时间、咳嗽缓解时间和肺部湿啰音消失时间,MD分别为-1.16 d（95%CI:-1.43~-0.89 d,P<0.000 01）、-1.12 d（95%CI:-1.34~-0.89 d,P<0.000 01）和-1.30 d（95%CI:-2.29~-0.32 d,P=0.009）。④高渗盐水组住院率、再住院率、呼吸窘迫评分和治疗后3 d胸部X线片评分与对照组差异均无统计学意义。⑤高渗盐水组未观察到急性支气管痉挛等严重不良反应。结论现有证据显示,高渗盐水治疗毛细支气管炎可显著缩短住院时间,并能降低患儿临床病情严重度评分,可显著缩短喘息缓解时间、咳嗽缓解时间和肺部湿啰音消失时间,未见严重不良反应。     

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??Objective To assess the effects of nebulised hypertonic ??≥ 3%?? saline solution ??NHS?? in infants with acute viral bronchiolitis. Methods The PubMed??EMbase??Cochrane Library ??Issue 5?? 2015???? EMbase?? CBM?? CNKI?? VIP and Wan Fang Data were searched up to January?? 2015 to collect randomized controlled trials ??RCTs?? about the efficacy of NHS in treatment of acute bronchiolitis in infants. Two reviewers independently screened literature according to the inclusion and exclusion criteria?? extracted data?? and assessed methodological quality of included studies. Meta-analysis was then conducted using Metafor software. Results A total of 17 RCTs?? including 14 relatively high qualities RCT?? were finally included. The results of Meta-analysis showed that?? compared with control group?? NHS group had better outcomes in duration ??day?? of hospitalization ??MD??-0.58?? 95%CI??-1.14 to -0.02?? P??0.0428?? and the clinical severity score ??MD in day 1??-0.66?? 95%CI?? -1 to -0.31??P??0.0001???? MD in day 2??-0.8?? 95%CI??-1.18 to -0.41?? P??0.0001?? MD in day 3??-0.93?? 95%CI??-1.54 to -0.32?? P??0.0002???? all with significant differences. In comparison with control group in the department of emergent setting?? NHS group showed the trend of reducing the admission of hospital ??RR??0.75???? but no statistical difference was observed. Conclusion Nebulized HS treatment can significantly shorten the duration of hospitalization and improve the severity score. Due to the efficacy and cost-effectiveness?? HS should be considered for the treatment of acute bronchiolitis in infants during hospitalization.