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

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. 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. How these combination regimens affect the quality of recovery and postoperative pain in patients？

Participants will:

1. Receive one of four anesthesia regimens during surgery: propofol alone, propofol combined with midazolam, dexmedetomidine, or esketamine.
2. Undergo a stepwise reduction of propofol effect-site concentration towards the end of surgery.
3. Have their consciousness assessed using the isolated forearm technique, while BIS, EEG signals, and vital signs are continuously monitored throughout the procedure.
4. Have their recovery quality and postoperative pain assessed after surgery.

Conditions

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

Interventions

DRUG

Propofol + Remifentanil +Midazolam

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.

DRUG

Propofol + Remifentanil + Dexmedetomidine

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.

DRUG

Propofol + Remifentanil + Esketamine

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.

DRUG

Propofol + Remifentanil

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.

Sponsors & Collaborators

• China-Japan Friendship Hospital

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-08-01

Primary Completion

2027-01-31

Completion

2027-07-31