Effect of an esketamine-based opioid-sparing perioperative regimen on early postoperative anxiety in women undergoing total laparoscopic hysterectomy: a randomized participant- and outcome-assessor-blinded controlled trial

Background Postoperative anxiety is common after hysterectomy and may impair recovery. We evaluated whether an esketamine-based opioid-sparing perioperative regimen could reduce early postoperative anxiety in women undergoing total laparoscopic hysterectomy. Methods In this single-center, randomized, participant- and outcome-assessor-blinded controlled trial, women aged 45–60 years were assigned 1:1 to Group K or Group C. Group K received an esketamine-based opioid-sparing perioperative regimen comprising esketamine during anesthesia induction and maintenance and esketamine-containing patient-controlled intravenous analgesia, together with lower protocol-specified sufentanil and remifentanil dosing. Group C received a conventional opioid-based perioperative regimen, with normal saline used as the study-drug control. The primary outcome was the Self-Rating Anxiety Scale (SAS) score on postoperative day 1 (POD 1). Secondary outcomes included POD three anxiety, quality of recovery, pain, sleep, postoperative nausea and vomiting, and neuropsychiatric adverse events. Results Of 170 randomized patients, 167 were included in the modified intention-to-treat analysis (83 in Group C and 84 in Group K). POD 1 SAS scores assessed 24 h after surgery were lower in Group K than in Group C, whereas no significant between-group difference was observed at 72 h after surgery (POD 3), after completion of PCIA. Group K also had higher QoR-15 scores, lower POD 1 pain and insomnia scores, and longer device-estimated total and deep sleep duration. No statistically significant between-group differences were observed in the incidences of the recorded common adverse events. Conclusion An esketamine-based opioid-sparing perioperative regimen was associated with lower SAS scores at 24 h after surgery during the early postoperative treatment period; however, this between-group difference was not maintained at 72 h after completion of PCIA. Clinical Trial Registration [ https://www.chictr.org.cn/historyversionpub.html?regno=ChiCTR2300074484 ]: identifier [ChiCTR2300074484].