Effect of Subanesthetic Doses of Esketamine on Early Postoperative Pain Sensitivity in Patients Undergoing Salpingectomy: A Randomized Clinical Trial.

PURPOSE: Postoperative pain sensitivity is a key target for perioperative analgesic care, linked to acute severe pain and chronic pain risk. This study aimed to investigate whether perioperative subanesthetic esketamine attenuates early postoperative pain sensitivity in patients undergoing emergency laparoscopic salpingectomy for ectopic pregnancy.

METHODS

This randomized controlled trial enrolled patients with ectopic pregnancy undergoing laparoscopic salpingectomy, randomly assigned 1:1 to esketamine or control. Patients in the esketamine group received an intravenous bolus of esketamine 0.25 mg/kg during surgery, followed by a patient-controlled intravenous analgesia (PCIA) solution containing esketamine (1 mg/kg) and sufentanil (1 μg/kg). The control group received a PCIA solution containing a higher dose of sufentanil (2 μg/kg) with equivalent volumes of normal saline instead of esketamine. The primary outcome was postoperative pain sensitivity, assessed by the Pain Sensitivity Questionnaire (PSQ) at postoperative day 1, 2, and 7. Secondary outcomes included the Numeric Rating Scale (NRS) pain scores, the 17-item Hamilton Depression Rating Scale (HAMD-17) scores, serum prostaglandin E2 (PGE2), brain-derived neurotrophic factor (BDNF) levels, and adverse events.

RESULTS

A total of 84 patients were enrolled and randomized (42 per group), with 80 completing the trial (42 in the esketamine group, 38 in the control group). For the primary outcome, repeated-measures ANOVA revealed a significant main effect of group on PSQ-total scores (F(1,78) = 9.881, P = 0.002). These beneficial effects were consistently observed across both PSQ subscales (PSQ-minor: P = 0.002; PSQ-moderate: P = 0.002). Dynamic NRS pain scores were significantly lower at 30 minutes post-surgery (median [IQR]: 3.0 [2.0-4.0] vs. 4.0 [2.0-5.0]; 95% CI for difference: 0.57-2.42; P<0.001). HAMD-17 scores showed a downward trend without significant difference (P=0.125). Serum BDNF levels were significantly higher in the esketamine group compared with controls (P <0.05), whereas PGE2 levels showed no significant between-group difference (P >0.05).

CONCLUSION

Perioperative subanesthetic esketamine may provide modest improvement in early postoperative pain sensitivity, and may serve as a useful adjunct in multimodal postoperative analgesia for emergency laparoscopic salpingectomy.