Exploration of Appropriate BIS Range and Propofol Effect-site Concentration During Total Intravenous Anesthesia With Concomitant Adjuvants.

NCT07736352 | Not Yet Recruiting

• 1 other identifier: 2026-HX-39
• Study Type: interventional
• Target: 100
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical trial is to determine the appropriate Bispectral Index (BIS) range and propofol effect-site concentration required to maintain adequate anesthesia depth during total intravenous anesthesia (TIVA) combined with midazolam, dexmedetomidine, or esketamine in patients undergoing unilateral knee replacement surgery. The main questions it aims to answer are:

1. 1.What are the appropriate BIS range and propofol effect-site concentration for maintaining adequate anesthesia depth when combined with each of the three medications (midazolam, dexmedetomidine, or esketamine) during TIVA?
2. 2.How these combination regimens affect the quality of recovery and postoperative pain in patients？
3. 3.Receive one of four anesthesia regimens during surgery: propofol alone, propofol combined with midazolam, dexmedetomidine, or esketamine.
4. 4.Undergo a stepwise reduction of propofol effect-site concentration towards the end of surgery.
5. 5.Have their consciousness assessed using the isolated forearm technique, while BIS, EEG signals, and vital signs are continuously monitored throughout the procedure.
6. 6.Have their recovery quality and postoperative pain assessed after surgery.

Conditions

Knee Osteoarthritis; Replacement, Knee; Elective Surgical Patients; ASA Class I/II Patients

Outcome Measures

Primary Outcomes (2)

• BIS value

  BIS value recorded at the first occurrence of IFT positivity or any predefined clinical sign of inadequate anesthesia.

  From the start of the intra-operative stepwise reduction phase until the first occurrence of IFT positivity or any predefined clinical sign of inadequate anesthesia, assessed up to 30 minutes.

• Propofol Effect-Site Concentration

  Propofol effect-site concentration recorded at the first occurrence of IFT positivity or any predefined clinical sign of inadequate anesthesia.

  From the start of the intra-operative stepwise reduction phase until the first occurrence of IFT positivity or any predefined clinical sign of inadequate anesthesia, assessed up to 30 minutes.

Secondary Outcomes (6)

• Modified Brice Questionnaire

  From PACU admission to 48 hours postoperatively. Assessed before PACU discharge, 24 hours and 48 hours postoperatively.

• Time from Discontinuation of Anesthetics to Laryngeal Mask Airway Removal

  From discontinuation of anesthetics to LMA removal, assessed up to 60 minutes.

• Time to Modified Aldrete Score of 10 in the Post Anesthesia Care Unit

  From PACU admission to Modified Aldrete Score of 10, assessed up to 60 minutes.

• Adverse Events During Emergence from Anesthesia

  From discontinuation of anesthetics to PACU discharge, assessed up to 2 hours.

• Postoperative Pain Intensity Measured by Numeric Rating Scale

  From PACU admission to 48 hours postoperatively. Assessed at PACU admission, PACU discharge, 24 hours and 48 hours postoperatively.

Study Arms (4)

Propofol + Remifentanil

SHAM COMPARATOR

Drug: Propofol + Remifentanil

Propofol + Remifentanil + Midazolam

EXPERIMENTAL

Drug: Propofol + Remifentanil +Midazolam

Propofol + Remifentanil + Dexmedetomidine

EXPERIMENTAL

Drug: Propofol + Remifentanil + Dexmedetomidine

Propofol + Remifentanil + Esketamine

EXPERIMENTAL

Drug: Propofol + Remifentanil + Esketamine

Interventions

Propofol + Remifentanil +Midazolam DRUG

Participants in this arm will receive total intravenous anesthesia (TIVA) with propofol and remifentanil during the maintenance period. After placement of the knee prosthesis, the isolated forearm technique (IFT) will be initiated. Participants will wear headphones playing recorded standardized instructions. Rocuronium (0.3 mg/kg) will be administered via the non-dominant arm. Midazolam (2 mg) will be administered intravenously.The propofol plasma-site concentration will be set to 1.8 μg/mL, then reduced in stepwise decrements of 0.3 μg/mL, with each concentration maintained for 5 minutes, until any of the following endpoints is reached: (1) positive IFT response , (2) BIS \> 60 sustained for 1 minute, (3) electroencephalogram signs of arousal, or (4) clinical judgment by the anesthesiologist that anesthesia depth is inadequate.

Propofol + Remifentanil + Midazolam

Propofol + Remifentanil + Dexmedetomidine DRUG

Participants in this arm will receive total intravenous anesthesia (TIVA) with propofol and remifentanil during the maintenance period. After placement of the knee prosthesis, the isolated forearm technique (IFT) will be initiated. Participants will wear headphones playing recorded standardized instructions. Rocuronium (0.3 mg/kg) will be administered via the non-dominant arm. Dexmedetomidine 1 μg/kg infused over 10 minutes.The propofol plasma-site concentration will be set to 1.8 μg/mL, then reduced in stepwise decrements of 0.3 μg/mL, with each concentration maintained for 5 minutes, until any of the following endpoints is reached: (1) positive IFT response , (2) BIS \> 60 sustained for 1 minute, (3) electroencephalogram signs of arousal, or (4) clinical judgment by the anesthesiologist that anesthesia depth is inadequate.

Propofol + Remifentanil + Dexmedetomidine

Propofol + Remifentanil + Esketamine DRUG

Participants in this arm will receive total intravenous anesthesia (TIVA) with propofol and remifentanil during the maintenance period. After placement of the knee prosthesis, the isolated forearm technique (IFT) will be initiated. Participants will wear headphones playing recorded standardized instructions. Rocuronium (0.3 mg/kg) will be administered via the non-dominant arm. Esketamine (0.3 mg/kg) will be administered intravenously.The propofol plasma-site concentration will be set to 1.8 μg/mL, then reduced in stepwise decrements of 0.3 μg/mL, with each concentration maintained for 5 minutes, until any of the following endpoints is reached: (1) positive IFT response , (2) BIS \> 75 sustained for 1 minute, (3) electroencephalogram signs of arousal, or (4) clinical judgment by the anesthesiologist that anesthesia depth is inadequate.

Propofol + Remifentanil + Esketamine

Propofol + Remifentanil DRUG

Participants in this arm will receive total intravenous anesthesia (TIVA) with propofol and remifentanil during the maintenance period. After placement of the knee prosthesis, the isolated forearm technique (IFT) will be initiated. Participants will wear headphones playing recorded standardized instructions. Rocuronium (0.3 mg/kg) will be administered via the non-dominant arm. The propofol plasma-site concentration will be reduced in stepwise decrements of 0.3 μg/mL, with each concentration maintained for 5 minutes, until any of the following endpoints is reached: (1) positive IFT response , (2) BIS \> 60 sustained for 1 minute, (3) electroencephalogram signs of arousal, or (4) clinical judgment by the anesthesiologist that anesthesia depth is inadequate.

Propofol + Remifentanil

Eligibility Criteria

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

You may qualify if:

• Age 18 to 65 years
• American Society of Anesthesiologists (ASA) physical status I or II
• Body Mass Index (BMI) 18 to 30 kg/m²
• Scheduled for elective unilateral total knee replacement surgery
• Willing to participate in the study and signed informed consent form, and able to comply with the intervention and assessment procedures

You may not qualify if:

• History of neurological disorders
• Cognitive dysfunction assessed by the Mini-Cog scale
• History of antipsychotic or sedative medication use in the past 4 weeks
• Poorly controlled or untreated hypertension
• Sinus bradycardia, cardiac conduction block, or severe heart failure
• Acute angle-closure glaucoma
• Allergic to intravenous anesthetics
• Hearing impairment, could not cooperate in intervention and evaluation
• Contraindications to tourniquet use on the upper arm

Sponsors & Collaborators

• China-Japan Friendship Hospital: lead

MeSH Terms

Conditions

Osteoarthritis, Knee

Interventions

Propofol; Remifentanil; Dexmedetomidine; Esketamine

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

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

Central Study Contacts

MA

CONTACT

+86-10-84205882; maye_1316@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Doctor

Study Record Dates

• First Submitted: July 16, 2026
• First Posted: July 30, 2026
• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): July 31, 2027
• Last Updated: July 30, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share