Nebulized epinephrine for croup in children: an updated systematic review

To review and update the clinical evidence on the use of nebulized epinephrine for croup in children.

The protocol was registered with PROSPERO (CRD420251160013). Our search encompassed PubMed (MEDLINE), Embase, Web of Science, Scopus, the Cochrane Library databases for randomized controlled trials (RCTs) investigating epinephrine for the treatment of croup. The search covered the period from database inception to July 3, 2026. We also searched two clinical trials registries: the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and clinicaltrials.gov (searched 03 July 2026). We included studies that reported epinephrine in the treatment of croup in children. This systematic review was reported in accordance with the PRISMA 2020 guidelines.

A total of 12 studies were included in the analysis, with 325 patients in the treatment group and 347 in the control group. The meta-analysis revealed that nebulised epinephrine significantly improved croup severity score at 30 min post-administration (SMD = -1.48, 95% CI [-2.83, -0.13]). However, this effect was not sustained. At 2 h, the between group difference was no longer statistically significant (SMD = -0.51, 95% CI [-1.11, 0.09]). Regarding hospital stay, although the point estimate suggested a clinically meaningful reduction (MD = -25.1 h, 95% CI [-52.34, 2.15]), the wide confidence interval crossed zero and the difference did not reach statistical significance (P = 0.07).

Nebulized epinephrine significantly improved croup score at 30 min, but its sustained effect at 2 h remains inconclusive due to unstable sensitivity analysis. No significant reduction in hospital stay was observed (P = 0.07). Routine use for shortening hospital stay is not supported by current evidence, although it remains a valuable early intervention in moderate-to-severe acute settings.

https://www.crd.york.ac.uk/PROSPERO/recorddashboard, PROSPERO CRD420251160013.