Combination of epinephrine and dexamethasone may reduce hospitalization in children with bronchiolitis

Article Outline

• Question
• Design
• Setting
• Participants
• Intervention
• Outcomes
• Main Results
• Conclusions
• Commentary
• References
• Copyright

Plint A, Johnson D, Patel H, Wiebe N, Correll R, Brant R, et al. Epinephrine and dexamethasone in children with bronchiolitis. N Engl J Med 2009;360:2079-89.

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Question 

Among infants with bronchiolitis, how effective is a combination of nebulized epinephrine and oral corticosteroids at preventing hospitalization?

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Design 

Randomized controlled trial.

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Setting 

Eight Canadian pediatric emergency departments.

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Participants 

800 infants (6 weeks to 12 months of age) with bronchiolitis.

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Intervention 

One group received 2 treatments of nebulized epinephrine (epinephrine 3 mL in a 1:1000 solution per treatment) and a total of 6 oral doses of dexamethasone (1.0 mg/kg of body weight in the emergency department and 0.6 mg/kg 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).

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Outcomes 

Hospital admission within 7 days after the initial visit to the emergency department.

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Main Results 

Baseline clinical characteristics were similar among the 4 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 = .02, number needed to treat = 11). However, with adjustment for multiple comparisons, this result was rendered insignificant (P = .07). There were no serious adverse events.

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Conclusions 

Among infants with bronchiolitis treated in the emergency department, combined therapy with dexamethasone and epinephrine may significantly reduce hospital admissions.

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Commentary 

Identifying effective treatments for children with bronchiolitis has proven elusive. In part, this is due to the heterogenous cause of wheezing, which can range from episodic wheezing (often caused by viral infections) to multifactorial wheezing that can be triggered by a variety of factors and often resulting in asthma.¹ A meta-analysis showed limited short-term benefit from epinephrine,² and it is well known that children with asthma respond to corticosteroids. Plint et al were surprised to find a synergistic effect between epinephrine and dexamethasone, which reduced the frequency of hospitalization for children in this study. In addition, there are likely many factors that influence the decision to hospitalize a child, such as the distance to the hospital, the ability of the parents to care for their ill child, and the availability of health care resources. While a number needed to treat of 11 to prevent 1 hospitalization might be appealing, there are several caveats to these results. First, the dose of corticosteroids used in this study is quite high, and there is still limited knowledge of potential risks associated with this treatment. Second, when the authors adjusted their results for the multiple comparisons that were made, the difference in hospitalization was no longer statistically significant. One area of future research would be to look at the subgroups of infants who respond better to corticosteroids and look for possible biomarkers that may even include virus identification techniques. Although we await follow-up studies to provide stronger evidence, it is prudent to provide supportive care and close monitoring for children with an initial episode of wheezing. Monitoring these infants in the general pediatrician's office does not require high-tech medicine—just some relatively straightforward clinical algorithims.¹

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References 

1. Frey U, vonMutius E. The challenge of managing wheezing in infants. N Engl J Med. 2009;360:2130–2133
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2. Hartling L, Wiebe N, Russell K, Patel H, Klassen TP. Epinephrine for bronchiolitis. Cochrane Database Syst Rev. 2004;1:CD003123-CD003123
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