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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Control Group | Active Comparator | Participants receive standardized propofol-remifentanil total intravenous anesthesia without administration of the study adjunct anesthetic drug. |
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| Midazolam Group | Experimental | Participants receive standardized propofol-remifentanil total intravenous anesthesia plus midazolam according to the study protocol. |
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| Dexmedetomidine Group | Experimental | Participants receive standardized propofol-remifentanil total intravenous anesthesia plus dexmedetomidine according to the study protocol. |
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| Esketamine Group | Experimental | Participants receive standardized propofol-remifentanil total intravenous anesthesia plus esketamine according to the study protocol. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Midazolam | Drug | Midazolam administered as an adjunct to standardized propofol-remifentanil total intravenous anesthesia according to the study protocol. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline and 5, 10, 15, 20, 25, and 30 minutes after adjunct drug administration. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in pre-specified electroencephalographic spectral features from baseline | 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. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Li | Contact | +86-15811578082 | lizhao2001@aliyun.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| China-Japan Friendship Hospital | Beijing | Beijing Municipality | 100029 | China |
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| Dexmedetomidine | Drug | Dexmedetomidine administered as an adjunct to standardized propofol-remifentanil total intravenous anesthesia according to the study protocol. |
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| Esketamine | Drug | Esketamine administered as an adjunct to standardized propofol-remifentanil total intravenous anesthesia according to the study protocol. |
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| Propofol | Drug | Propofol will be administered as part of standardized total intravenous anesthesia in all study groups. |
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| Remifentanil | Drug | Remifentanil will be administered as part of standardized total intravenous anesthesia in all study groups. |
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| 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. | 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. | 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. | 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. | 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). | 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. | From admission to the post-anesthesia care unit to 48 hours after surgery. |
| Change in electroencephalographic relative spectral power from baseline | 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. |
| ID | Term |
|---|---|
| D008874 | Midazolam |
| D020927 | Dexmedetomidine |
| C000629870 | Esketamine |
| D015742 | Propofol |
| D000077208 | Remifentanil |
| ID | Term |
|---|---|
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011422 | Propionates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D010880 | Piperidines |
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