Prospective Dose-Finding of Esketamine for Suppressing Cervical Dilation Response in Ambulatory Hysteroscopy Under Monitored Anesthesia Care.

Abstract

<h4>Background</h4>Cervical dilation during ambulatory hysteroscopy often triggers somatic responses that challenge patient comfort and procedure smoothness. While esketamine's unique analgesic profile could address this, its effective dose within a dexmedetomidine-remifentanil monitored anesthesia care (MAC) protocol is undefined.<h4>Methods</h4>In this prospective, double-blind, dose-finding study, 30 women received a standardized MAC protocol (dexmedetomidine 0.6 μg∙kg^-1 loading dose followed by 0.4 μg∙kg^-1∙h^-1, with remifentanil 5 μg∙kg^-1∙h^-1). Esketamine was administered via Dixon's up-and-down sequential design (initial dose 0.3 mg∙kg^-1; increments/decrements 0.02 mg∙kg^-1) before cervical dilation. Positive response is defined as the absence of purposeful movement. The median effective dose (ED50) and 95% effective dose (ED95) were calculated using probit regression.<h4>Results</h4>30 patients completed the study. The ED50 of esketamine was 0.36 mg∙kg^-1 (95% CI 0.35-0.37) and the ED95 was 0.39 mg∙kg^-1 (95% CI 0.37-0.42). Hemodynamic stability was maintained (mean arterial pressure change ≤15% from baseline) with no respiratory depression. Adverse events were self-limiting dizziness (66.7%) and nausea (6.7%). Recovery was swift, with a time to meet post-anesthesia care unit (PACU) discharge criteria of 17.93±3.30 min, and patient satisfaction was high (median score 9/10, IQR 8-10).<h4>Conclusion</h4>Under dexmedetomidine-remifentanil MAC, esketamine 0.39 mg∙kg^-1 (ED95) effectively suppresses the cervical dilation response, promotes hemodynamic and respiratory stability, and facilitates a rapid, enhanced recovery after surgery (ERAS)-compliant recovery. This dose-finding study provides a practical and effective anesthetic combination for clinical implementation in ambulatory hysteroscopy.<h4>Clinical trial registration</h4>ClinicalTrials.gov (identifier: NCT07034963). Principal Investigator: Lijuan Yan.

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