Comparison of the anaesthetic efficacy and safety of different doses of esketamine combined with propofol in hysteroscopic surgery: a randomised, double-blind controlled trial

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• Picked for Anesthesiology and Pain Medicine (paper of the day, 3 November 2026): Randomized trial compares esketamine doses for opioid-sparing procedural anesthesia

Abstract

BACKGROUND: Hysteroscopy is increasingly performed under day-surgery total intravenous anaesthesia, but propofol alone provides insufficient analgesia and the routine adjunct of opioids is associated with respiratory depression and emetic complications. Esketamine, the S-enantiomer of ketamine, offers analgesia together with sympathomimetic support and represents a promising opioid-sparing alternative; however, its optimal dose for combination with propofol in this setting has not been firmly established. METHODS: In this prospective, randomised, double-blind, controlled trial, 160 women aged 18-60 years (ASA I-II) scheduled for elective hysteroscopy were assigned to four groups using computer-generated random numbers: K1 (esketamine 0.15 mg/kg), K2 (esketamine 0.3 mg/kg), K3 (esketamine 0.5 mg/kg) or S (sufentanil 0.1 µg/kg). All patients received an induction dose of propofol 1.5 mg/kg followed by maintenance infusion of 4-6 mg·kg⁻¹·h⁻¹. The primary outcomes were postoperative pain (Numeric Rating Scale, NRS) and total intra-operative propofol consumption; secondary outcomes were perioperative haemodynamics, recovery time and adverse events. After exclusion of three patients with major protocol deviation, 157 patients were analysed (K1 = 40, K2 = 38, K3 = 40, S = 39). RESULTS: Demographics, surgical and anaesthesia times were comparable between groups. NRS scores at 10 and 30 min post-recovery were significantly lower in groups K2, K3 and S than in group K1 (p < 0.001). Mean arterial pressure at the start of surgery (T2, immediately after the start of surgery) and at the end of surgery (T3) was significantly higher in K1 than in the other three groups (p < 0.001). Total propofol consumption did not differ between groups (p = 0.95). The incidence of intra-operative hypertension was significantly greater in K1 (22.5%) than in K2 (0%), K3 (5.0%) and S (5.1%) (p = 0.002), and the incidence of SpO₂ < 90% was significantly greater in S (20.5%) than in K1 (0%), K2 (5.3%) and K3 (5.0%) (p = 0.004). The incidence of emergence agitation differed among groups, with the highest incidence observed in K3 (10.0%) (p = 0.034). CONCLUSIONS: Among the regimens tested, esketamine 0.3 mg/kg combined with propofol 1.5 mg/kg was associated with a favourable balance of analgesia, haemodynamic stability and safety. The 0.15 mg/kg dose was associated with higher postoperative pain scores and a higher incidence of intra-operative hypertension, while 0.5 mg/kg was associated with a higher incidence of agitation and a longer recovery time without additional analgesic benefit at 30 min. All three esketamine doses were associated with a lower incidence of hypoxaemia than the sufentanil regimen. CLINICAL REGISTER NUMBER: The trial was registered in the Chinese Clinical Trial Registry (ChiCTR2400092022) with the retrospective registration date 2024/11/07.

Abstract as published, via PubMed.