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

Lijuan Yan,1,* Xiao Wang,2,* Jianfei Wei,3 Meiqin Zhang,4,5 Bin Yang1 1Department of Anesthesiology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, People’s Republic of China; 2Department of Ultrasound, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, People’s Republic of China; 3Department of Anesthesiology, The First Hospital of Zhangzhou China Merchants Economic and Technological Development Zone, Zhangzhou, People’s Republic of China; 4Department of Medical Affairs, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China; 5Xiamen Daytime Medical Management Quality Control Center, Xiamen, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bin Yang, Email [email protected] Meiqin Zhang, Email [email protected]: 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.Methods: 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.Results: 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).Conclusion: 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.Clinical Trial Registration: ClinicalTrials.gov (identifier: NCT07034963). Principal Investigator: Lijuan Yan.Plain Language Summary: This study determined the optimal dose of esketamine by testing different doses in thirty patients, finding that 0.39 mg∙kg− 1 effectively prevented patient movement and discomfort during cervical dilation in ambulatory hysteroscopy. Patients showed minimal movement during cervical dilation, while blood pressure and heart rate remained stable. Notably, no episodes of respiratory depression occurred. The most common side effect was temporary, mild dizziness, which resolved quickly without treatment. Importantly, patients recovered within about 20 minutes. This allowed for same-day discharge and was associated with high satisfaction with their care. This study provides anesthesiologists with robust, evidence-based guidance for using esketamine to enhance patient comfort and streamline recovery in ambulatory settings. Keywords: cervical dilation response, effective dose, esketamine, hysteroscopy, monitored anesthesia care