Study on the Effective Dose and Safety of Esketamine in Hysteroscopic Surgery Under Monitored Anesthesia Care

NCT07034963 | Active Not Recruiting Phase 1

• 1 other identifier: XMFHIIT-2025SL092
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 1

Brief Summary

Cervical dilation-induced somatic responses remain a critical challenge in ambulatory hysteroscopic surgery. Esketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, exhibits unique analgesic and sedative properties that may enhance perioperative somatic response inhibition. However, the effective dose of esketamine under dexmedetomidine-remifentanil based monitored anesthesia care (MAC) during ambulatory hysteroscopic surgery remains to be determined. This prospective dose-finding study aimed to establish the median effective dose (ED50) and 95% effective dose (ED95) of esketamine for cervical response suppression. Afterwards, the investigators will conduct an RCT study to evaluate the safety of the dose of esketamine ED95 through the incidence of respiratory depression.

Conditions

Intrauterine Polyp; Intrauterine Synechiae

Keywords

ambulatory hysteroscopic surgery; monitored anesthesia care; esketamine; cervical dilation response; Intrauterine lesion

Outcome Measures

Primary Outcomes (2)

• Cervical dilation-induced somatic responses

  Positive: Body movement or complaint of pain. Negative: No body movement or no reported pain. This scale will be administered during the surgery at the first stage of the research.

  Day 1 (During the surgery at the first stage of the research)

• Incidence of respiratory depression

  The primary outcome is the incidence of respiratory depression, which is defined as SpO2 \<90% or EtCO2 \>55 mmHg. By comparing with the control group, evaluate the safety of ED95 of esketamine by the incidence of respiratory depression at T2-T6 of the second stage of the research. T2: 60 seconds after esketamine injection; T3: During vaginal disinfection; T4: During cervical dilation; T5: During intrauterine operations; T6: In the PACU.

  Day 1 (T2-T6 of the second stage of the research)

Secondary Outcomes (15)

• HR

  Day 1 (T1-T6 of the first and second stages of the research)

• MAP

  Day 1 (T1-T6 of the first and second stages of the research)

• RR

  Day 1 (T1-T6 of the first and second stages of the research)

• SPO2

  Day 1 (T1-T6 of the first and second stages of the research)

• EtCO2

  Day 1 (T2-T6 of the first and second stages of the research)

Study Arms (2)

Determine the ED50 and ED95 of esketamine by Dixon's up-and-down method

EXPERIMENTAL

According to Dixon's up-and-down sequential design, esketamine will be initiated at 0.3 mg∙kg-1 intravenously, followed by dose adjustments (0.02 mg∙kg-1 increments/decrements) based on somatic responses to cervical dilation (positive: any movement; negative: no movement). The tests will continue until six crossover pairs are achieved.

Drug: Determine the ED50 and ED95 of esketamine

Evaluate the safety of the dose of esketamine ED95 by the incidence of respiratory depression

ACTIVE COMPARATOR

The intervention group will be injected with the dose of esketamine ED95; the control group will be injected with remifentanil 1μg∙kg-1. Both groups of patients will receive the same Monitoring Anesthesia Care (MAC) regimen, namely, remifentanil will be continuously pumped at a rate of 5μg∙kg∙h-1 combined with dexmedetomidine (a loading dose of 0.6 μg∙kg-1 for 10 minutes, followed by maintenance dose of 0.4 μg∙kg-1∙h-1). Intravenous injection of 100 mg of flurbiprofen axetil for auxiliary analgesia. Intravenous injection of 4 mg of ondansetron to prevent nausea and vomiting. The study at this stage will evaluate the safety of the dose of esketamine ED95 through the incidence of respiratory depression.

Drug: Intravenous the dose of esketamine ED95; Drug: Intravenous remifentanil 1μg∙kg-1

Interventions

Determine the ED50 and ED95 of esketamine DRUG

According to Dixon's up-and-down sequential design, esketamine will be initiated at 0.3 mg∙kg-1 intravenously, followed by dose adjustments (0.02 mg∙kg-1 increments/decrements) based on somatic responses to cervical dilation (positive: any movement; negative: no movement). The tests will continued until six crossover pairs are achieved.

Also known as: Remifentanil will be continuously pumped at a rate of 5μg∙kg∙h-1 combined with dexmedetomidine (a loading dose of 0.6 μg∙kg-1 for 10 minutes, followed by maintenance dose of 0.4 μg∙kg-1∙h-1).

Determine the ED50 and ED95 of esketamine by Dixon's up-and-down method

Intravenous the dose of esketamine ED95 DRUG

The intervention group will be injected with the dose of esketamine ED95.

Also known as: Remifentanil will be continuously pumped at a rate of 5μg∙kg∙h-1 combined with dexmedetomidine (a loading dose of 0.6 μg∙kg-1 for 10 minutes, followed by maintenance dose of 0.4 μg∙kg-1∙h-1).

Evaluate the safety of the dose of esketamine ED95 by the incidence of respiratory depression

Intravenous remifentanil 1μg∙kg-1 DRUG

The control group will be injected with remifentanil 1μg∙kg-1.

Also known as: Remifentanil will be continuously pumped at a rate of 5μg∙kg∙h-1 combined with dexmedetomidine (a loading dose of 0.6 μg∙kg-1 for 10 minutes, followed by maintenance dose of 0.4 μg∙kg-1∙h-1).

Evaluate the safety of the dose of esketamine ED95 by the incidence of respiratory depression

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Aged 18 - 55 years;
• ASA physical status Ⅰ or Ⅱ;
• Body mass index (BMI) 18 - 28 kg∙m-2;
• Scheduled for elective diagnostic/therapeutic hysteroscopy.

You may not qualify if:

• (i) Pharmacological contraindications:
• Known hypersensitivity to study medications (esketamine, remifentanil, dexmedetomidine);
• Opioid or benzodiazepine medications dependence;
• Analgesic/psychotropic medication use within 48 hours preoperatively;
• Participation in any other drug clinical trial within the preceding three months.
• (ii) Comorbidities:
• Significant cardiopulmonary dysfunction (NYHA III-IV, FEV₁/FVC \<70%);
• Hepatic impairment (Child-Pugh B/C);
• Uncontrolled hypertension, intracranial hypertension, intraocular hypertension or hyperthyroidism;
• Neurological/psychiatric conditions (epilepsy, schizophrenia, depression);
• Active gastroesophageal reflux disease (GERD-Q score ≥8). (iii) Airway/Perioperative Risks:
• Anticipated difficult airway (Mallampati III-IV, thyromental distance \<6 cm) or airway stenosis;
• Non-fasted status (solids \<8h, clear fluids \<2h preoperatively).

Sponsors & Collaborators

• The First Affiliated Hospital of Xiamen University: lead

Study Sites (1)

Department of Anesthesiology, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Road, Xiamen, China

Xiamen, Fujian, 361000, China

Location

Related Publications (1)

• Yan L, Wang X, Wei J, Zhang M, Yang B. Prospective Dose-Finding of Esketamine for Suppressing Cervical Dilation Response in Ambulatory Hysteroscopy Under Monitored Anesthesia Care. Drug Des Devel Ther. 2025 Dec 7;19:10835-10845. doi: 10.2147/DDDT.S557340. eCollection 2025.

  PMID: 41393327 DERIVED

MeSH Terms

Conditions

Gynatresia

Interventions

Dexmedetomidine

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Lijuan Yan

  Department of Anesthesiology, The First Affiliated Hospital of Xiamen University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Scientific Research Secretary of the Anesthesiology Department

Model Details: This research will be divided into two stages. (i) In Phase one, a prospective dose discovery study using the Dixon sequential method will be conducted, aiming to determine the median effective dose (ED50) and 95% effective dose (ED95) of esketamine in inhibiting cervical response. The test will continue until six cross-pairings are obtained. The sample size is approximately 33. (ii) The investigators will conduct a single-center, randomized, double-blind controlled trial in Phase Two to evaluate the safety of the esketamine ED95 dose under the monitoring anesthesia care program based on the incidence of respiratory depression. The intervention group will be injected with the dose of esketamine ED95; the control group will be injected with remifentanil 1μg∙kg-1. Both groups of patients will receive the same sedation regimen. The sample size is approximately 62.

Study Record Dates

• First Submitted: May 29, 2025
• First Posted: June 24, 2025
• Study Start: June 26, 2025
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2028
• Last Updated: July 24, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)