Comparison of esketamine combined with dexmedetomidine versus propofol combined with midazolam on drug-induced sleep endoscopy: a randomized controlled trial

Drug-induced sleep endoscopy (DISE) is widely used to evaluate upper airway obstruction in patients with obstructive sleep apnea syndrome (OSAS). We aimed to compare the sedative efficacy and safety of esketamine combined with dexmedetomidine versus propofol combined with midazolam for sedation in patients undergoing DISE. This prospective, single-center, assessor-blinded, randomized controlled trial was conducted among patients scheduled for DISE between July 2025 and December 2025. Participants were enrolled and randomized into two groups: the experimental group (esketamine-dexmedetomidine) and the control group (propofol-midazolam). Polysomnography (PSG) was used to determine sleep stages, and the bispectral index (BIS) was used to assess sedation depth. Endoscopy was initiated after patients reached non-rapid eye movement sleep stage 2 (N2). The primary outcome was the time required to reach N2 sleep confirmed by PSG. Secondary outcomes included the first-pass success rate, BIS values, oxygen saturation (SpO₂), and the incidence of adverse events (body movement, hypoxemia, tachycardia, bradycardia, and other procedure-related events) during the procedure. A total of 50 patients were enrolled and randomly assigned to the experimental group ( n = 25) or the control group ( n = 25). All patients successfully completed the DISE procedure and achieved N2 sleep confirmed by PSG. The time required to reach N2 sleep was slightly shorter in the experimental group than in the control group, with median (interquartile range [IQR]) values of 188.0 (170.0-229.0) seconds and 214.0 (189.0-253.5) seconds, respectively; however, this difference did not reach statistical significance ( p = 0.067). Meanwhile, preliminary exploratory analyses showed a higher first-pass success rate (96% vs. 36%; unadjusted p < 0.001) and a lower incidence of hypoxemia (20% vs. 48%; unadjusted p < 0.05) in the experimental group during the procedure. Esketamine-dexmedetomidine and propofol-midazolam effectively induced N2 sleep and allowed completion of DISE. Exploratory analyses suggest that the esketamine-dexmedetomidine regimen may potentially improve procedural conditions and respiratory safety, though these findings are hypothesis-generating and require confirmation in larger, adequately powered studies. Chinese Clinical Trial Registry (ChiCTR2500102931), first registered on 05/21/2025.