Neonatal Extubation Failure Prevention Trial Using Nebulised Epinephrine (NEPTUNE): A Randomized Controlled Trial

To evaluate whether epinephrine nebulization, when used in addition to standard care, reduces extubation failure (EF) in term and preterm neonates.

A parallel, randomized controlled superiority trial was conducted in a tertiary-care neonatal intensive care unit (NICU) between May 2023 and July 2024. Due to the nature of the intervention, blinding was not feasible. A total of 158 ventilated neonates (ventilation duration: 48 h to 2 weeks) were enrolled at the point of planned extubation and randomized to either the standard care group (SG) or the epinephrine nebulization group (EG). The primary outcome was extubation failure, defined as the need for reintubation within 48 h. Secondary outcomes included reintubation beyond 48 h, time to reintubation, serial Silverman-Anderson scores post-extubation, incidence of laryngeal edema, duration of non-invasive respiratory support, post-extubation and total hospital stay, mortality, and adverse effects.

The incidence of EF within 48 h was not significantly different in the EG and SG groups (14.8% vs 24.7%; P = 0.119) by intention-to-treat analysis. Per-protocol analysis showed EF of 9.2% in EG vs 24.7% in SG (P = 0.020). The post-extubation Silverman-Anderson scores showed no significant differences at immediate, 4, 8, or 12-h assessments; however, at 24 h, the EG demonstrated significantly lower scores suggestive of lesser respiratory distress compared with the SG [2.13 (1.06) vs 2.62 (1.40); P = 0.030]. Rates of laryngeal edema, adverse events including tachycardia, hypertension, peripheral vasoconstriction, ventilator-associated pneumonia, and antibiotic requirement did not differ significantly between groups.

Epinephrine nebulization administered after extubation did not reduce the incidence of extubation failure in ventilated neonates.