Background Propofol is an intravenous (IV) anesthetic medication widely used for procedural sedation, operative anesthesia, and in intensive care unit (ICU), 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 (ED50), 95% effective dose (ED95), and 99% effective dose (ED99) of esketamine for attenuating propofol injection pain using Dixon’s up-and-down method to provide a reference for optimal dose selection for surgeries and procedures. Methods Thirty gynecological patients undergoing hysteroscopic surgery were enrolled in a sequential method to determine the effective dose of esticketamine for analgesic propofol injection in order of operation. This study was based on the sequential allocation up-and-down rule designed by Dixon, and each patient was induced by esticketamine combined with propofol. 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 dosage of esketamine was increased or decreased up or down according to the patient’s pain response. The initial dose of esketamine was 0.2 mg/kg, and the gradient of adjacent dose was 0.02 mg/kg. If the pain response assessment of the upper patient was positive (+), the dose of esselketamine in the next patient was increased by 0.02 mg/kg; if the pain response assessment of the upper patient was negative (−), the dose of esselketamine in the next patient was decreased by 0.02 mg/kg. The tests were carried out sequentially, with the pain response changing from positive to negative or from negative to positive, and the tests were stopped after at least 6 crossover points, and the effective dose of esticketamine was calculated using probit probability regression analysis. Results The ineffective group comprised patients with a positive pain response and the effective group comprised patients with a negative pain response. The 95% CI was set as the confidence interval of effective dose ED value，and we found esketamine’s ED50 = 0.143 mg/kg (0.120, 0.162 mg/kg), ED95 = 0.176 mg/kg (0.159, 0.320 mg/kg), and ED99 = 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. Bradycardia occurred in only one patient during anesthesia induction, while hemodynamics was stable in the rest of the patients without obvious adverse reactions. Conclusion Small 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 registration Chinese Clinical Trial Registry ChiCTR2100048951. Date of registration: July 19, 2021.

Background In clinical practice, sufentanil has a stronger sedative effect on patients than fentanyl at equivalent doses. This study hypothesized that, at equivalent doses, patients undergoing gynaecologic laparoscopic surgery (GLS) receiving fentanyl would have an earlier emergence from anaesthesia (EA), a shorter time to extubation (TE), and a better degree of wakefulness. Therefore, this study evaluated the effects of equipotent doses of fentanyl and sufentanil on the quality of emergence in patients undergoing GLS. Methods One hundred seven patients scheduled for GLS under general anaesthesia were randomly divided into two groups and were induced with 0.35 µg/kg sufentanil (Group S; n = 55) or 3.5 µg/kg fentanyl (Group F; n = 52). When the GLS was almost over, the patient's abdominal cavity was flushed with warm saline, and 5 µg of sufentanil or 50 µg of fentanyl in a double-blind manner was intravenously injected into the patients. The primary outcomes of the study included EA, TE, the rate of leaving the surgical bed voluntarily and the incidence of endotracheal tube tolerance. The Ramsay Sedation Scale (RSS), and Verbal Rating Scale (VRS) scores at 15 and 30 min in the postanaesthesia care unit (PACU), as well as other adverse events, including nausea and vomiting, itching, delirium, dizziness, chills, and respiratory depression (SpO2 < 95%) in the PACU, were evaluated as secondary outcomes. Results There were no statistically significant dissimilarities between the two groups with respect to baseline characteristics. For recovery, the EA (9.0 ± 4.8 min vs. 8.9 ± 3.0 min; P = 0. 146), TE (9.5 ± 4.7 min vs. 9.0 ± 3.0 min; P = 0.135), rate of leaving the surgical bed voluntarily (31.18% vs. 38.46%; P = 0.976), and incidence of endotracheal tube tolerance (94.55% vs. 96.15%; P = 0.694) were not significantly different between the two groups. In the PACU, the 15-min RSS score (2.07 ± 0.38 vs. 2.15 ± 0.36; P = 0.125), the 30-min RSS score (2.02 ± 0.13 vs. 2.04 ± 0.19; P = 0.207), the 15-min VRS score (0.50 ± 0.57 vs. 0.67 ± 0.55; P = 0.295), and the 30-min VRS score (0.45 ± 0.50 vs. 0.75 ± 0.52; P = 0.102) were not significantly different between Groups S and F. No adverse events, such as nausea, vomiting, pruritus, delirium, and tremors, occurred in either group. The rates of respiratory depression (1.82% vs. 1.92%; P = 0.968) and dizziness (0.00% vs. 4.85%; P = 0.142) were not different between Groups S and F in the PACU. Conclusions The majority of patients scheduled for GLS were able to rapidly and smoothly emerge from anaesthesia. After surgery, similar outcomes, including EA, TE, the incidence of endotracheal tube tolerance, the rate of leaving the surgical bed voluntarily, RSS scores, VRS scores, and adverse events in the PACU, were achieved for the patients between the two anaesthetic protocols.

BackgroundPropofol 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 (ED50), 95% effective dose (ED95), and 99% effective dose (ED99) 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/m2; 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 ED50 = 0.143 mg/kg (0.120, 0.162 mg/kg), ED95 = 0.176 mg/kg (0.159, 0.320 mg/kg), and ED99 = 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.