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Abstract & Commentary
Source: Wainwright C, et al. A multicenter, randomized, double-blind, controlled trial of nebulized epinephrine in infants with acute bronchiolitis. N Engl J Med 2003;349:27.
Acute viral bronchiolitis is the most common lower respiratory tract infection in infants and results in hospitalization of approximately 1% of this age group annually. Treatment is largely supportive, including supplemental oxygen, ventilatory support, and intravenous fluid hydration as needed. The disease is characterized by bronchiolar narrowing and obstruction from airway edema, mucus, inflammatory cellular infiltration, and sloughed epithelial debris. Accordingly, many have proposed that a combination of beta-adrenergic therapy (to improve airway constriction) and alpha-adrenergic stimulation (to reduce airway edema and obstruction) may have utility in acute bronchiolitis.
In this multi-center Australian study, infants diagnosed and hospitalized with acute bronchiolitis were randomized to receive three nebulized doses (each 4 mL) of either 1% epinephrine solution (99 infants) or placebo normal saline solution (95 infants) at four-hour intervals. Patients received other standard therapies as indicated in this double-blind study. Infants with a history of significant cardiac disease or respiratory disease (such as cystic fibrosis or neonatal lung disease) were excluded, as were any patients who had received either steroids or bronchodilators just preceding presentation.
The investigators found no significant difference in either length of hospital stay (58.8 vs 69.5 hrs for the epinephrine and placebo groups, respectively, p = 0.16) or time to discharge readiness (as determined by need for supplemental oxygen and intravenous hydration) (46.5 vs 47.7 hours, respectively, p = 0.86). In addition, there was no difference in duration of need for supplemental oxygen (54.0 vs 58.8 hours, respectively, p = 0.64). Furthermore, no differences occurred in either group before or after each treatment dose in terms of respiratory rate, blood pressure, or respiratory-effort score (a score based on physical examination findings of nasal flaring, neck findings, and chest retractions). Heart rate, however, did significantly increase after each epinephrine dose.
Based on their findings, the authors conclude that the use of an inhaled bronchodilator with both alpha-adrenergic and beta-adrenergic effects does not produce clinically relevant improvement or reduce the length of stay for infants with acute bronchiolitis.
Commentary by Theodore C. Chan, MD, FACEP
Rates of hospitalization for infants with acute bronchiolitis have markedly increased in the past two decades.1 Despite this increase, treatment remains largely supportive—primarily supplemental oxygen and intravenous hydration. Inhaled bronchodilators have been touted as a potential treatment, with a few small studies demonstrating short-term improvement in clinical scores, but no significant impact on oxygenation and hospitalization.2
This well-designed, large study failed to find any significant benefit for nebulized epinephrine compared to placebo for infants hospitalized with acute bronchiolitis. Defining the diagnostic criteria for the disease can be problematic in studies on acute bronchiolitis. In this study, the authors set clinical criteria which included infants presenting with a history of upper respiratory tract infection and clinical findings of respiratory distress, wheezing or crackles. These criteria could include infants with a presentation of reactive airway disease or asthma who very well may have responded to bronchodilators. Interestingly, the authors found no difference in epinephrine responsiveness in patients with a history of a first-degree relative with asthma, eczema, or hay fever.
Dr. Chan, Associate Clinical Professor of Medicine, Emergency Medicine, University of California, San Diego, is on the editorial board of Emergency Medicine Alert.
1. Shay DK, et al. Bronchiolitis-associated hospitalizations among U.S. children 1980-1996. JAMA 1999;282:1440.
2. Kellner J, et al. Bronchodilators for bronchiolitis. Cochrane Database Syst Rev 2000;2:CD001266.