Efficacy and Safety of Intranasal Dexmedetomidine Combined with Esketamine for Premedication in Children Undergoing Laser Treatment for Burn Scars: A Randomised Self-Controlled Crossover Trial

Abstract Background Children undergoing repeated laser treatment for burn scars require effective premedication to support sedation and cooperation. We compared intranasal dexmedetomidine plus esketamine with esketamine alone. Methods In this single-centre, randomised, two-period crossover trial, 24 children aged 2–6 years received both regimens, with 12 per sequence and 63–76 days between sessions. The combination comprised intranasal dexmedetomidine (25 µg at 10.7–19.3 kg or 50 µg at 19.4–28.0 kg) plus intranasal esketamine 0.5 mg/kg; the comparator was esketamine 0.5 mg/kg alone. Both preceded general anaesthesia. Primary outcomes were Ramsay Sedation Scale (RSS) scores, time to RSS ≥ 3, separation-anxiety, mask-acceptance and Pediatric Anesthesia Emergence Delirium (PAED) scores. Physiological variables and total propofol were secondary outcomes. Mixed-effects models accounted for treatment period, sequence and within-child correlation; Holm adjustment covered nine primary-outcome comparisons. Results All children completed both periods. RSS scores were higher with the combination, with the most consistent differences at 30 min and before induction (both Holm-adjusted P < 0.001). Two children had RSS 6 at both assessments. Separation-anxiety and mask-acceptance scores were lower (Holm-adjusted P = 0.004 and P < 0.001). PAED scores were lower by 1.33 points (95% confidence interval [CI] 0.47–2.19; Holm-adjusted P = 0.016); no score was ≥ 10. Time to RSS ≥ 3 was shorter by 3.83 min (95% CI 1.85–5.81; Holm-adjusted P = 0.003). Secondary analyses estimated 6.15 mg lower weight-adjusted propofol use (95% CI 2.40–9.91) and lower mean arterial pressure, heart rate and respiratory rate. Scheduled oxygen saturation was 95%–99%; no child required assisted ventilation or treatment for hypotension or bradycardia. Conclusions Adding intranasal dexmedetomidine to esketamine improved pre-induction sedation and perioperative behavioural scores. Secondary findings suggest lower propofol requirements. The combination warrants further evaluation as needle-free premedication for burn-scar laser treatment, with appropriate monitoring. Trial registration: Chinese Clinical Trial Registry, ChiCTR2500106780. Registered on 30 July 2025.