ABSTRACT Background Emergence delirium (ED) is a common complication in pediatric anesthesia. Although intranasal dexmedetomidine (DEX) is widely used, its application is constrained by a slow onset, residual risk of ED in some patients, and risks such as bradycardia and hypotension. Esketamine (ESK), an NMDA receptor antagonist, may provide a faster onset and reduce these side effects. Objective This study compared the efficacy and safety of intranasal DEX‐ESK combination versus DEX alone as premedication for anesthesia induction in pediatric patients undergoing surgery. Methods Electronic databases (PubMed, Web of Science, Scopus, CINAHL, and Embase) were systematically searched for randomized controlled trials (RCTs). The primary outcomes included the ED incidence and the onset of sedation. Secondary outcomes included mask acceptance score, FLACC pain score, post‐anesthesia care unit (PACU) length of stay, and adverse events. A random‐effects model generated pooled effect estimates—risk ratios (RRs) with 95% confidence intervals (CIs) for dichotomous outcomes and mean differences (MDs) with 95% CIs for continuous outcomes. Prediction intervals were also reported to reflect the expected range of effects in future similar studies. Trial Sequential Analysis was performed. The certainty of evidence for each outcome was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Results Five RCTs encompassing 466 pediatric patients were included in the quantitative synthesis. The DEX‐ESK combination was associated with a reduction in ED incidence (RR = 0.58; 95% CI: 0.35–0.97; p = 0.04) and a shorter time to sedation onset (MD = −3.95 min; 95% CI: −4.77 to −3.14; p < 0.01). Secondary analyses demonstrated improved mask acceptance (MD = −0.77; 95% CI: −1.27 to −0.27; p < 0.01), reduced FLACC pain scores (MD = −0.36; 95% CI: −0.70 to −0.02; p = 0.04), and shorter PACU length of stay (MD = −1.83 min; 95% CI: −2.75 to −0.91; p < 0.01). Adverse event incidence did not differ significantly between groups. Conclusion The intranasal DEX‐ESK combination was associated with improved outcomes compared with DEX monotherapy for pediatric premedication including reductions in ED incidence, a modest acceleration in sedation onset, improved mask acceptance, and slightly shorter PACU length of stay, without an increased risk of adverse events. This combination may represent a feasible and safe premedication option for pediatric patients. Trial Registration PROSPERO: CRD420251236740
Lateiresh et al. (Tue,) studied this question.