In infants with bronchiolitis, is epinephrine more effective than placebo in improving clinical outcomes, as measured by clinical score, oxygen saturation and respiratory rate?

Epinephrine is a combined alpha-adrenergic and beta-adrenergic agonist (1). It has been hypothesized that epinephrine would be effective in the treatment of bronchiolitis by causing bronchodilation and by reducing tissue edema via vasoconstriction in the bronchiolar vasculature. The current literature suggests that epinephrine may be effective in the treatment of bronchiolitis for outpatients but not inpatients (grade of recommendation: A, based on a systematic review). Hartling and colleagues (2) completed a systematic review studying the effect of epinephrine on infants with bronchiolitis. The review included only randomized controlled trials, the highest level of evidence for therapy questions (3). Fourteen trials met the inclusion criteria, three of which compared epinephrine with placebo among outpatients. The results indicated that epinephrine was favourable to placebo for short-term benefits among outpatients. In particular, the change in clinical score, determined by measuring various clinical features of bronchiolitis, at 60 min post-treatment (standardized mean difference [SMD] −0.8, 95% CI −1.6 to −0.07), the change in oxygen saturation at 30 min post-treatment (WMD 2.8, 95% CI 1.5 to 4.1), the respiratory rate at 30 min post-treatment (weighted mean difference [WMD] −4.5, 95% CI −8.9 to −0.2) and ‘improvement’ (OR 25.1, 95% CI 5.0 to 127) as defined within the individual studies, all favoured epinephrine. However, there was no significant difference between epinephrine and placebo on admission rates (OR 0.51, 95% CI 0.18 to 1.42), change in clinical score at 30 min post-treatment (SMD −0.55, 95% CI −1.11 to 0.02) or change in oxygen saturation at 60 min post-treatment (WMD 1.20, 95% CI −0.13 to 2.53). Yet, in terms of the overall clinical picture, epinephrine is more effective than placebo in the outpatient population for the treatment of bronchiolitis. For inpatients, there were no group differences in the effectiveness of therapy. Hartling et al (2) included five inpatient randomized controlled studies in their review. They found no significant differences between epinephrine and placebo, except for a change in clinical score at 60 min (SMD −0.5, 95% CI −1.0 to −0.03). One of the randomized controlled studies included in the review deserves particular attention. Wainwright et al (4) conducted a randomized, double-blind, controlled trial comparing nebulized single-isomer epinephrine with placebo in 194 infants. The primary outcomes were length of hospital stay and time until the infant was ready for discharge. The study was of good methodological quality with a Jadad score of four (a score of less than three indicates a poor quality study and a score of five indicates maximum quality) (5). The analysis had a power of 85%, meaning there was an 85% chance of detecting a significant effect, and indicated that treatment with epinephrine had no effect on time in hospital or time until discharge. Also, there were no significant changes in the respiratory rate, blood pressure or respiratory-effort scores after each treatment. It should be noted that infants in the epinephrine group had lower respiratory-effort scores after all treatments, although the difference between the groups was small and clinically trivial. This score was not associated with a shorter hospital stay or a shorter time to discharge. However, heart rate was significantly increased after each treatment with epinephrine, which could theoretically heighten oxygen-utilization costs in vulnerable infants. In fact, among infants who required supplemental oxygen and intravenous fluids, the time until discharge was significantly longer in the epinephrine group than in the placebo group. This suggests that epinephrine is not helpful, and in fact, may be detrimental to inpatient infants. However, this correlation requires further study. The evidence from Wainwright et al's study (4), supports the use of epinephrine in treating outpatients, but not inpatients with bronchiolitis. However, the review had several limitations. For instance, because the trials included in the review had different outcomes, there were few trials within each statistical comparison. Thus, there may not have been enough power to detect a clinically significant effect of epinephrine. The authors note that large, multicentre trials need to be conducted before routine administration among outpatients can be recommended. Second, several different scoring systems were used among the individual studies to determine the clinical score of patients. This prevents adequate comparisons from being made. Therefore, development of a consistent scoring system that measures important clinical changes in patients with bronchiolitis must be developed. Despite these shortcomings, there is substantial evidence to support the use of epinephrine in outpatients for the treatment of bronchiolitis. Terry P Klassen and Kristie Cramer provided overall direction and editorial advice. Lisa Hartling provided editorial advice.

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