Comparison of the effects of ketamine via nebulization versus different pharmacological approaches in pediatric sedation: a systematic review and meta-analysis of randomized controlled trials.

Background: Nebulized drug delivery is commonly used in pediatric clinical practice. The growing number of literatures have reported the application of nebulized ketamine in pediatric sedation in recent years. This meta-analysis of randomized controlled trials comparing the efficacy and safety of nebulized ketamine versus different pharmacological approaches was conducted to estimate the effects of this technique in pediatric sedation. Methods: We searched PubMed, Embase, and Cochrane Library from inception to Feb 2023. All randomized controlled trials used nebulized ketamine as presurgical and pre-procedural sedatives in children were included. Sedative effects and various adverse events were considered as the outcomes. Results: Ten studies with 727 pediatric patients were enrolled. Compared to nebulized dexmedetomidine, using of ketamine via nebulization showed similar sedation satisfaction (54.79% vs. 60.69%, RR = 0.88, with 95%CI [0.61, 1.27]), success rate of parental separation (57.27% vs. 73.64%, RR = 0.81, with 95%CI [0.61, 1.08]), and mask acceptability (37.27% vs. 52.73%, RR = 0.71, with 95%CI [0.45, 1.10]). However, the using of combination of two medications (nebulized ketamine plus nebulized dexmedetomidine) was associated with better sedative satisfaction (33.82% vs. 68.11%, RR = 0.50, with 95%CI [0.27, 0.92]) and more satisfactory mask acceptance (45.59% vs. 71.01%, RR = 0.69, with 95%CI [0.56, 0.86]). Compared with nebulized ketamine, using of nebulized dexmedetomidine was associated with less incidence of emergence agitation (18.18% vs. 3.33%, RR = 4.98, with 95%CI [1.88, 13.16]). Conclusions: Based on current evidences, compared to nebulized dexmedetomidine, nebulized ketamine provides inconspicuous advantages in pediatric sedation, and it has a relatively high incidence of emergence agitation. Combination of nebulized ketamine and dexmedetomidine might be considered as one preferred option in pediatric sedation as it can provide more satisfactory sedative effects. However, there is insufficient evidence regarding nebulized ketamine versus ketamine administered through other routes and nebulized ketamine versus other sedatives. The overall low or moderate quality of evidence evaluated by the GRADE system also calls for more high-quality studies with larger sample sizes in future. Research registration: The protocol of present study was registered with PROSPERO (CRD42023403226). [ABSTRACT FROM AUTHOR]