Determining the effective dose of esketamine for mitigating pain during propofol injection by the sequential method

Background: Propofol is an intravenous (IV) anesthetic medication widely used for procedural sedation, operative anesthesia, and in intensive care units (ICUs), but the incidence of pain during IV infusion can reach 28–90%. Ketamine can attenuate pain associated with IV propofol injection through local and central analgesic effects. Ketamine is gradually being transitioned to its S-enantiomer, esketamine, which has a similar mechanism of action. The purpose of our study is to determine the half effective dose (ED 50 ), 95% effective dose (ED 95 ), and 99% effective dose (ED 99 ) of esketamine for attenuating propofol injection pain using the sequential method to provide a reference for optimal dose selection for surgeries and procedures.MethodsWe selected 30 patients, 18–40 years old, who were scheduled to undergo hysteroscopy in the gynecology department of our hospital from June 2021 to June 2022, with a body mass index (BMI) of 18.5–24.9 kg/m 2 ; Mallampati class I or II; and American Society of Anesthesiologists (ASA) Class I or II. Esketamine combined with propofol was used for general anesthesia induction. During induction, the target dose of esketamine was first given via venous access in the left hand of the patient, and 30 s later, a fixed dose of 2 mg/kg (1 ml/s) of propofol was given. Patient perception of pain was scored with the verbal rating scale (VRS) every 5 s after the start of the propofol infusion, and the evaluation was stopped once the patient became unresponsive. The esketamine dose was increased or decreased based on patient’s pain response using the sequential method. The initial dose was 0.2 mg/kg and the subsequent sequential dose was 0.02 mg/kg.ResultsThe ineffective group comprised patients with a positive pain response and the effective group comprised patients with a negative pain response. We found esketamine’s ED 50  = 0.143 mg/kg (0.120, 0.162 mg/kg), ED 95  = 0.176 mg/kg (0.159, 0.320 mg/kg), and ED 99  = 0.189 mg/kg (0.167, 0.394 mg/kg). The esketamine dose and VRS score during propofol injection were significantly different between the two groups (P < 0.05), whereas surgical duration, emergence time, visual analogue scale (VAS) score of postoperative uterine contraction pain, and Riker sedation/anxiety scale (SAS) score were not significantly different. All patients were hemodynamically stable at induction and we observed no obvious adverse reactions.ConclusionSmall doses of esketamine combined with propofol can be safely and effectively used for hysteroscopic surgery. We recommended a dose of 0.2 mg/kg IV esketamine before induction of anesthesia to reduce the pain of propofol injection.Trial registrationChinese Clinical Trial Registry ChiCTR2100048951. Date of registration: July 19, 2021.