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

N/ANot Yet RecruitingNCT07699523

China-Japan Friendship Hospital120 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

DIAGNOSTIC

Masking

SINGLE

Enrollment

120

Conditions

Depth of Anesthesia Monitoring

Interventions

MidazolamDRUG

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

DexmedetomidineDRUG

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

EsketamineDRUG

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

PropofolDRUG

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

RemifentanilDRUG

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

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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.

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

Secondary Outcomes

Change in mean arterial pressure from pre-intervention baseline

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.

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

Change in heart rate from pre-intervention baseline

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.

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

Time from discontinuation of anesthetic drugs to airway device removal

The time interval from discontinuation of anesthetic drugs to removal of the airway device will be recorded.

Time frame: 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

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.

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

Brice questionnaire assessment

The Brice questionnaire will be used to assess postoperative recall and awareness-related events.

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

Postoperative pain score

Postoperative pain intensity will be assessed using the numeric rating scale (NRS).

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 analgesic medication use

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.

Time frame: From admission to the post-anesthesia care unit to 48 hours after surgery.