The ED50 and ED95 of esketamine for preventing early postoperative pain in patients undergoing laparoscopic cholecystectomy: a prospective, double-blinded trial

Abstract

Background: This study aims to estimate the safety, efficacy, and median effective dose (ED50) of esketamine for preventing early postoperative pain in patients undergoing laparoscopic cholecystectomy.

Methods: 54 patients undergoing laparoscopic cholecystectomy were prospectively randomized into two groups (group C and group E). Different doses of esketamine were intravenously administered before the skin incision in Group E. The patients in group C received the same dose of saline at the same time. General population characteristics were recorded. The median effective dose (ED50) and 95% effective dose (ED95) were calculated using Dixon's up-and-down method. Hemodynamic parameters were monitored, and pain intensity was assessed using a visual analog scale. We also recorded the condition of anesthesia recovery period and postoperative adverse reactions.

Results: The ED50 of esketamine for preventing early postoperative pain was 0.301 mg/kg (95%CI: 0.265-0.342 mg/kg), and the ED95 was 0.379 mg/kg (95%CI: 0.340-0.618 mg/kg), calculated by probability unit regression. Heart rate (HR) was significantly lower in the esketamine group compared to the control at the skin incision (p < 0.05). The total VAS score at resting was significantly lower in the esketamine group compared to the control group during the awakening period (p < 0.05). There was no significant difference between the two groups regarding the incidence of adverse reactions (p > 0.05).

Conclusions: In this study, esketamine can prevent early postoperative pain effectively. The ED50 and ED95 of esketamine for controlling early postoperative pain were 0.301 mg/kg and 0.379 mg/kg, respectively.

Trial registration: ChiCTR2200066663, 13/12/2022.

Keywords: ED50; ED95; Esketamine; Laparoscopic cholecystectomy; Postoperative pain.

Fig. 1

Dixon and Massey up-and-down plot line chart. The sequence of patients receiving esketamine in Group E. The quality of analgesia was measured using VAS (from 0 to 10) and was defined as ineffective (VAS score ≥ 3) or effective (VAS score<3)

Fig. 2

Flow diagram

Fig. 3

Dose-response curve of esketamine for preventing early postoperative pain in patients undergoing laparoscopic cholecystectomy

Fig. 4

Heart rate (HR) and mean arterial pressure (MAP) at different time points during surgery. Data are expressed as mean (standard deviation) or median (interquartile range). T₀: BL, baseline; pre-operation. T₁: at the time of skin incision. T₂: the gallbladder dissection off the liver bed by the electric knife. * p < 0.05 vs. control group