The Effects of Midazolam, Dexmedetomidine, and Esketamine on Bispectral Index and Raw Electroencephalogram in Patients Under Propofol-Remifentanil Baseline Anesthesia

NCT07699523 | Not Yet Recruiting DMC

• 1 other identifier: 2026-HX-40
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

This prospective, single-center, randomized interventional study aims to investigate the effects of commonly used adjunct anesthetic drugs on the Bispectral Index (BIS) and electroencephalographic (EEG) activity during total intravenous anesthesia. BIS monitoring is widely used to estimate the depth of anesthesia. However, previous studies suggest that certain anesthetic drugs, particularly dexmedetomidine and esketamine, may alter BIS values independently of the patient's actual level of consciousness. As a result, BIS readings may not always accurately reflect anesthetic depth when multiple drugs are administered together. Adult patients undergoing elective laparoscopic cholecystectomy under standardized propofol-remifentanil anesthesia will be randomly assigned to receive one of the following adjunct drugs: midazolam, dexmedetomidine, esketamine, or no additional study drug (control group). Continuous BIS values and raw EEG signals will be recorded throughout the study period. The primary objective is to compare changes in BIS values among different adjunct anesthetic drugs under otherwise similar anesthetic conditions. The study will also explore corresponding EEG characteristics associated with these changes. The findings are expected to improve understanding of drug-related differences in processed EEG monitoring and provide data for future development of more accurate anesthesia depth assessment methods.

Conditions

Depth of Anesthesia Monitoring; BIS-EEG

Keywords

Bispectral Index; Electroencephalography; Midazolam; Dexmedetomidine; Esketamine; Total Intravenous Anesthesia

Outcome Measures

Primary Outcomes (1)

• Change in Bispectral Index (BIS) value from the pre-intervention baseline

  Change in Bispectral Index value from the stable pre-intervention baseline will be compared among the four study groups after administration of the assigned adjunct anesthetic drug under standardized propofol-remifentanil total intravenous anesthesia. The pre-intervention baseline is defined as the stable BIS value immediately before administration of the assigned adjunct anesthetic drug. The Bispectral Index is a dimensionless electroencephalography-derived index ranging from 0 to 100, with lower values indicating deeper hypnotic states.

  Baseline and 5, 10, 15, 20, 25, 30 minutes after adjunct drug administration

Secondary Outcomes (7)

• Change in mean arterial pressure from pre-intervention baseline

  Baseline and 5, 10, 15, 20, 25, and 30 minutes after adjunct drug administration.

• Change in heart rate from pre-intervention baseline

  Baseline and 5, 10, 15, 20, 25, and 30 minutes after adjunct drug administration.

• Time from discontinuation of anesthetic drugs to airway device removal

  From discontinuation of anesthetic drugs to airway device removal, up to 60 minutes.

• Time to Aldrete score of 10 in the post-anesthesia care unit

  From admission to the post-anesthesia care unit to achievement of an Aldrete score of 10, up to 2 hours.

• Brice questionnaire assessment

  Before discharge from the post-anesthesia care unit, and at 24 and 48 hours after surgery.

Other Outcomes (2)

• Change in pre-specified electroencephalographic spectral features from baseline

  Baseline and 5, 10, 15, 20, 25, and 30 minutes after adjunct drug administration.

• Change in electroencephalographic relative spectral power from baseline

  Baseline and 5, 10, 15, 20, 25, and 30 minutes after adjunct drug administration.

Study Arms (4)

Control Group

ACTIVE COMPARATOR

Participants receive standardized propofol-remifentanil total intravenous anesthesia without administration of the study adjunct anesthetic drug.

Drug: Propofol; Drug: Remifentanil

Midazolam Group

EXPERIMENTAL

Participants receive standardized propofol-remifentanil total intravenous anesthesia plus midazolam according to the study protocol.

Drug: Midazolam; Drug: Propofol; Drug: Remifentanil

Dexmedetomidine Group

EXPERIMENTAL

Participants receive standardized propofol-remifentanil total intravenous anesthesia plus dexmedetomidine according to the study protocol.

Drug: Dexmedetomidine; Drug: Propofol; Drug: Remifentanil

Esketamine Group

EXPERIMENTAL

Participants receive standardized propofol-remifentanil total intravenous anesthesia plus esketamine according to the study protocol.

Drug: Esketamine; Drug: Propofol; Drug: Remifentanil

Interventions

Midazolam DRUG

Midazolam administered as an adjunct to standardized propofol-remifentanil total intravenous anesthesia according to the study protocol.

Midazolam Group

Dexmedetomidine DRUG

Dexmedetomidine administered as an adjunct to standardized propofol-remifentanil total intravenous anesthesia according to the study protocol.

Dexmedetomidine Group

Esketamine DRUG

Esketamine administered as an adjunct to standardized propofol-remifentanil total intravenous anesthesia according to the study protocol.

Esketamine Group

Propofol DRUG

Propofol will be administered as part of standardized total intravenous anesthesia in all study groups.

Control Group; Dexmedetomidine Group; Esketamine Group; Midazolam Group

Remifentanil DRUG

Remifentanil will be administered as part of standardized total intravenous anesthesia in all study groups.

Control Group; Dexmedetomidine Group; Esketamine Group; Midazolam Group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ASA physical status I-II;
• BMI 18-28 kg/m²;
• Scheduled for elective laparoscopic cholecystectomy, with an expected surgical duration from skin incision to completion of wound closure of ≥45 min;
• Planned to receive propofol-remifentanil total intravenous anesthesia, with routine intraoperative BIS monitoring and simultaneous acquisition of raw EEG signals;
• Voluntarily agrees to participate in this study, has signed the informed consent form, and is able to cooperate with the intervention and assessment procedures.

You may not qualify if:

• A confirmed history of psychiatric or neurological disorders, or use of antipsychotics, antidepressants, benzodiazepines, or other sedative-hypnotic drugs within 4 weeks before surgery;
• Cognitive impairment identified by Mini-Cog screening;
• Poorly controlled or untreated hypertension, sinus bradycardia, or severe cardiac conduction block;
• Acute angle-closure glaucoma;
• Known allergy to any required anesthetic drug;
• Difficulty in electrode placement or any condition that may interfere with EEG monitoring.

Sponsors & Collaborators

• China-Japan Friendship Hospital: lead

Study Sites (1)

China-Japan Friendship Hospital

Beijing, Beijing Municipality, 100029, China

Location

MeSH Terms

Interventions

Midazolam; Dexmedetomidine; Esketamine; Propofol; Remifentanil

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Propionates; Acids, Acyclic; Carboxylic Acids; Piperidines

Central Study Contacts

Li

CONTACT

+86-15811578082; lizhao2001@aliyun.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 26, 2026
• First Posted: July 13, 2026
• Study Start: June 30, 2026
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 30, 2027
• Last Updated: July 13, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)