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

July 8, 2026 updated by: Li Zhao, China-Japan Friendship Hospital

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
120

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • China
    • Beijing Municipality
      • Beijing, Beijing Municipality, China, 100029

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

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

Exclusion Criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Control Group
Participants receive standardized propofol-remifentanil total intravenous anesthesia without administration of the study adjunct anesthetic drug.
Drug: Propofol
Propofol will be administered as part of standardized total intravenous anesthesia in all study groups.
Drug: Remifentanil
Remifentanil will be administered as part of standardized total intravenous anesthesia in all study groups.
Experimental: Midazolam Group
Participants receive standardized propofol-remifentanil total intravenous anesthesia plus midazolam according to the study protocol.
Drug: Propofol
Propofol will be administered as part of standardized total intravenous anesthesia in all study groups.
Drug: Remifentanil
Remifentanil will be administered as part of standardized total intravenous anesthesia in all study groups.
Drug: Midazolam
Midazolam administered as an adjunct to standardized propofol-remifentanil total intravenous anesthesia according to the study protocol.
Experimental: Dexmedetomidine Group
Participants receive standardized propofol-remifentanil total intravenous anesthesia plus dexmedetomidine according to the study protocol.
Drug: Propofol
Propofol will be administered as part of standardized total intravenous anesthesia in all study groups.
Drug: Remifentanil
Remifentanil will be administered as part of standardized total intravenous anesthesia in all study groups.
Drug: Dexmedetomidine
Dexmedetomidine administered as an adjunct to standardized propofol-remifentanil total intravenous anesthesia according to the study protocol.
Experimental: Esketamine Group
Participants receive standardized propofol-remifentanil total intravenous anesthesia plus esketamine according to the study protocol.
Drug: Propofol
Propofol will be administered as part of standardized total intravenous anesthesia in all study groups.
Drug: Remifentanil
Remifentanil will be administered as part of standardized total intravenous anesthesia in all study groups.
Drug: Esketamine
Esketamine administered as an adjunct to standardized propofol-remifentanil total intravenous anesthesia according to the study protocol.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in Bispectral Index (BIS) value from the pre-intervention baseline
Time Frame: Baseline and 5, 10, 15, 20, 25, 30 minutes after adjunct drug administration
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in mean arterial pressure from pre-intervention baseline
Time Frame: Baseline and 5, 10, 15, 20, 25, and 30 minutes after adjunct drug administration.
Change in mean arterial pressure (MAP) 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.
Baseline and 5, 10, 15, 20, 25, and 30 minutes after adjunct drug administration.
Change in heart rate from pre-intervention baseline
Time Frame: Baseline and 5, 10, 15, 20, 25, and 30 minutes after adjunct drug administration.
Change in heart rate (HR) from the stable pre-intervention baseline will be compared among the four study groups after administration of the assigned adjunct anesthetic drug.
Baseline and 5, 10, 15, 20, 25, and 30 minutes after adjunct drug administration.
Time from discontinuation of anesthetic drugs to airway device removal
Time Frame: From discontinuation of anesthetic drugs to airway device removal, up to 60 minutes.
The time interval from discontinuation of anesthetic drugs to removal of the airway device will be recorded.
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
Time Frame: From admission to the post-anesthesia care unit to achievement of an Aldrete score of 10, up to 2 hours.
The time from admission to the post-anesthesia care unit to achievement of an Aldrete score of 10 will be recorded. The Aldrete score ranges from 0 to 10, with higher scores indicating better post-anesthesia recovery.
From admission to the post-anesthesia care unit to achievement of an Aldrete score of 10, up to 2 hours.
Brice questionnaire assessment
Time Frame: Before discharge from the post-anesthesia care unit, and at 24 and 48 hours after surgery.
The Brice questionnaire will be used to assess postoperative recall and awareness-related events.
Before discharge from the post-anesthesia care unit, and at 24 and 48 hours after surgery.
Postoperative pain score
Time Frame: At admission to the post-anesthesia care unit, before discharge from the post-anesthesia care unit, and at 24 and 48 hours after surgery.
Postoperative pain intensity will be assessed using the numeric rating scale (NRS).
At admission to the post-anesthesia care unit, before discharge from the post-anesthesia care unit, and at 24 and 48 hours after surgery.
Postoperative analgesic medication use
Time Frame: From admission to the post-anesthesia care unit to 48 hours after surgery.
Use of postoperative analgesic medications, including opioid and non-opioid analgesics (e.g., NSAIDs), in the post-anesthesia care unit and hospital ward will be recorded and compared among study groups.
From admission to the post-anesthesia care unit to 48 hours after surgery.

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in pre-specified electroencephalographic spectral features from baseline
Time Frame: Baseline and 5, 10, 15, 20, 25, and 30 minutes after adjunct drug administration.
Pre-specified electroencephalographic spectral features, including alpha-to-delta power ratio, frontal alpha power, alpha peak frequency, and burst suppression ratio, will be evaluated and compared among study groups at baseline and after administration of the assigned adjunct anesthetic drug.
Baseline and 5, 10, 15, 20, 25, and 30 minutes after adjunct drug administration.
Change in electroencephalographic relative spectral power from baseline
Time Frame: Baseline and 5, 10, 15, 20, 25, and 30 minutes after adjunct drug administration.
Relative power spectral density of delta, theta, alpha, beta, and gamma frequency bands will be compared among study groups at baseline and after administration of the assigned adjunct anesthetic drug.
Baseline and 5, 10, 15, 20, 25, and 30 minutes after adjunct drug administration.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
China-Japan Friendship Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 30, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 30, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 30, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 26, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 8, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 13, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 13, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 8, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2026-HX-40

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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