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NCT Number: NCT07736352

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

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.

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Key information

Conditions

Knee Osteoarthritis ASA Class I/II Patients Arthritis Elective Surgical Patients Joint Diseases Musculoskeletal Diseases Osteoarthritis Osteoarthritis, Knee Replacement, Knee Rheumatic Diseases

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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

Treatment and study plan

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 + 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 + 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

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.

Primary outcomes

  1. BIS value

    Time frame: 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.

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

  2. Propofol Effect-Site Concentration

    Time frame: 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 recorded at the first occurrence of IFT positivity or any predefined clinical sign of inadequate anesthesia.

Secondary outcomes

  1. Modified Brice Questionnaire

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

    The presence of intra-operative awareness with recall is assessed using the Modified Brice Questionnaire. The questionnaire explores the patient's memory of the peri-operative period through structured questions.

  2. Time from Discontinuation of Anesthetics to Laryngeal Mask Airway Removal

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

    From discontinuation of anesthetics to LMA removal. Successful removal is defined as the patient being awake, able to open mouth on command, and having return of protective reflexes, without signs of respiratory distress.

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

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

    Time from post anesthesia care unit (PACU) admission until the first attainment of a Modified Aldrete Score of 10. The Modified Aldrete Score assesses five domains: consciousness, activity, respiration, blood pressure, and oxygen saturation, each scored from 0 to 2, with a maximum total score of 10. A score of 10 indicates the patient has achieved optimal recovery in all five domains.

  4. Adverse Events During Emergence from Anesthesia

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

    Adverse events during the period from anesthetic discontinuation to PACU discharge are recorded.

  5. Postoperative Pain Intensity Measured by Numeric Rating Scale

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

    Pain intensity is assessed using the Numeric Rating Scale, an 11-point scale from 0 to 10, where 0 represents "no pain" and 10 represents "the worst imaginable pain". Patients are asked to rate their current pain intensity at each assessment time point. The Numeric Rating Scale is a widely used and validated measure for postoperative pain assessment.

  6. Analgesic Consumption

    Time frame: From PACU admission to 48 hours postoperatively. Recorded during PACU stay, 24 hours and 48 hours postoperatively.

    Total amount of rescue analgesic medication administered to the patient from PACU admission to 48 hours postoperatively.

Study contacts

Contact information is provided by the study sponsor or research team.

MA

CONTACT

[email protected]

+86-10-84205882

Sponsors and collaborators

Lead sponsor

China-Japan Friendship Hospital

Other

Registry information

Official study title

A Prospective, Randomized Study to Determine the Appropriate Bispectral Index Range and Propofol Effect-Site Concentration During Total Intravenous Anesthesia Combined With Midazolam, Dexmedetomidine or Esketamine.

Important dates

Study start
2026
Primary completion
2027
Study completion
2027
First posted
Jul 30, 2026
Registry last updated
Jul 30, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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