Efficacy and safety of three esketamine-based sedation regimens for adults undergoing flexible fibreoptic bronchoscopy: a randomized clinical trial

Abstract Esketamine exerts favorable sedative and analgesic effects and represents a promising alternative to opioids. However, the comparative efficacy of esketamine combined with various sedatives remains unclear. This study aimed to evaluate the efficacy and safety of propofol, remimazolam or dexmedetomidine respectively combined with esketamine for flexible fibreoptic bronchoscopy (FFB) in adult patients. A total of 130 patients scheduled for flexible fibreoptic bronchoscopy were randomly allocated into three groups: propofol-esketamine group (PE group), remimazolam-esketamine group (RE group), and dexmedetomidine-esketamine group (DE group). All patients received standardized nasopharyngeal airway placement. Manual ventilation was provided when necessary during flexible fibreoptic bronchoscopy. The primary outcome was the incidence of hypoxaemia (defined as SpO₂ < 90% for a duration of > 10 s). Secondary outcomes included hemodynamic changes, cough scores, recovery time, rescue propofol bolus dose and frequency, rescue propofol administration, incidence of intraoperative and postoperative adverse events, satisfaction scores of bronchoscopists and patients, and patients’ willingness to undergo repeat bronchoscopy. Overall, 128 patients were included in the final analysis, 43, 42 and 43 in the PE, RE and DE groups, respectively. The incidences of hypoxaemia in the PE, RE, and DE groups were 34.88%, 26.19%, and 6.98%, respectively ( P = 0.007), with the DE group being significantly lower than the PE group ( P < 0.05). Binary logistic regression confirmed DE as an independent protective factor for hypoxaemia after adjusting for rescue propofol use (adjusted OR = 0.082, 95%CI: 0.018–0.365, P = 0.001). The DE group showed smaller heart rate fluctuations than the PE group at T2 and T3, and than the RE group at T3 ( P < 0.05). The SpO₂ in the DE group was higher than in the PE group at T4 ( P < 0.05). The recovery time in the PE group was shorter than in the RE group ( P < 0.05). For adverse events, the incidence of tachycardia in the PE group was higher than in the DE group (60.47% vs. 32.56%, P < 0.05), and the incidence of injection pain in the PE group was higher than in the RE and DE groups (32.56% vs. 4.76% vs. 0%, P < 0.05). This trial compared three opioid-free intravenous sedation regimens for short-duration flexible fibreoptic bronchoscopy. Dexmedetomidine combined with esketamine reduced the incidence of hypoxaemia and exhibited smaller heart rate fluctuations during the procedure compared with the propofol–esketamine regimen. The incidence of hypoxaemia and other adverse events associated with remimazolam combined with esketamine was between the other two regimens, but the recovery time was relatively prolonged. Trial registration ChiCTR2500102944. This study was registered before enrollment (May 22, 2025). Available at: https://www.chictr.org.cn/showprojEN.html?proj=255510 .