Nebulized Epinephrine Versus Placebo in Infants with Moderate-to-Severe Bronchiolitis: A Randomized Controlled Trial

Background: International guidelines do not support the routine use of nebulized epinephrine for acute viral bronchiolitis. Despite its vasoconstrictive and bronchodilator properties, evidence remains inconclusive. Objectives: Day-6 fraction of inspired oxygen (FiO₂) adjusted for baseline FiO₂ was designated as the principal outcome; however, this outcome hierarchy was not prospectively prespecified. The analysis compared day-6 FiO₂, adjusted for baseline FiO₂, between nebulized racemic epinephrine and placebo; peripheral capillary oxygen saturation (SpO₂), respiratory rate (RR), and heart rate (HR) were secondary outcomes. Methods: This randomized, single-blind, placebo-controlled trial included 26 infants aged 0-12 months with moderate-to-severe bronchiolitis requiring respiratory support. Participants were allocated 1:1 to nebulized racemic epinephrine (group A, n = 13) or isotonic saline placebo (group B, n = 13). Outcomes were measured at baseline (T0), day 3 (T1), and day 6 (T2). The primary analysis used ANCOVA to compare T2 FiO₂ while adjusting for T0 FiO₂; mixed repeated-measures ANOVA assessed longitudinal trajectories. Results: The adjusted T2 FiO₂ difference between groups was -0.43 percentage points (95% CI -3.43 to 2.57; p = 0.772). Adjusted T2 differences were also non-significant for SpO₂ (p = 0.058), RR (p = 0.093), and HR (p = 0.487). FiO₂ decreased over time (p = 1.99 × 10^-4), but the group-by-time interaction was not significant (p = 0.108); no interaction was observed for SpO₂, RR, or HR (p = 0.296, p = 0.187, and p = 0.352, respectively). Conclusions: Nebulized racemic epinephrine did not improve the trajectories of oxygen requirement, SpO₂, RR, or HR compared with placebo; improvements over time were observed in both groups.