AzTrials
AzTrials

AnesthesiaNCT05525351

The Application and Validation of Triple Drug Response Surface Models on Density Spectral Array in Clinical Anesthesia

An observational study of Anesthesia and Drug Interaction, run by Taipei Veterans General Hospital, Taiwan at 1 site in Taiwan.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial summary

Precision anesthesia is the current trend. The benefits including faster recovery, earlier return to normal activity, increased patient satisfaction and shorter length of stay. In order to avoid unnecessarily deep or too light anesthesia, processed electroencephalogram (EEG) monitors are applied for accurate… Read more about this study

Who is it for?
Ages 25 to 85 years
What is being tested?
Bispectral index (BIS) or Patient State Index (PSI), Propofol and Alfentanil
Type of treatment
Medical device
How many people
60 participants
Where
1 siteTaiwan
Study dates
Oct 2022to Jul 2024
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 25 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study population: NI-VATS (non-intubated Video-Assisted Thoracic Surgery) population: The investigators plan to enroll patients who will receive NI-VATS under general anesthesia. These patients will be screened for eligibility. VATS (Video-Assisted Thoracic Surgery) population: The investigators plan to enroll patients who will receive VATS under general anesthesia. These patients will be screened for eligibility.

Who may be able to join

  • Patients aged between 20 and 85
  • Scheduled for Non-intubated VATS or VATS surgery depending on study arm.
  • American Society of Anesthesiologists (ASA) physical status I to III.

Who cannot join

  • hearing impairment
  • neurologic or behavioral disorders
  • habitual sedative use
  • alcoholism
  • allergy to dexmedetomidine, alfentanil or propofol
  • resting room air SpO2 < 90%.
  • History of upper airway tumors

Trial locations and contacts

1 site in 1 country.

Mei-Yung Tsou, MD. PhD. contact

886-9-38593120

mytsou8095@gmail.com

Taiwan1 site
  • Taipei Veterans General Hospital

    Taipei, 11257

Other trials in Taiwan

About this study

Precision anesthesia is the current trend. The benefits including faster recovery, earlier return to normal activity, increased patient satisfaction and shorter length of stay. In order to avoid unnecessarily deep or too light anesthesia, processed electroencephalogram (EEG) monitors are applied for accurate assessment of the depth of anesthesia (DoA). Bispectral index (BIS) and PSI monitor are among the most widely used. Recently, density spectral array (DSA) has been developed to facilitate the interpretation of EEG signals. Real-time DSA EEG monitoring helps in detecting even subtle changes in the depth of anesthesia and provides more comprehensive information then simple digits.

An emerging field of pharmacodynamics in anesthesia is the response surface models. They describe the interaction of different anesthetics during sedation or anesthesia. Our research team has developed the first comprehensive two-drug response surface models for midazolam and alfentanil during gastrointestinal procedural sedations. However, adequate anesthesia is often achieved with multiple drugs. Two-drug models thus have limited applications. We aim to extend the models into three-drug interactions where it can be used for a broader range of clinical scenarios.

The main goal of the study is to establish and validate the three-drug response surface model by collecting and analyzing EEG parameters (BIS or PSI values, DSA, SEF95 (95% spectral edge frequency) and MF (Median frequency) ) from 60 patients undergoing general anesthesia for thoracic surgeries. We aim to establish the models that help anesthesiologist to achieve rapid emergence, appropriate analgesia, adequate DoA, and patient safety. The secondary aim is to apply this model to provide a guideline for drug dosage adjustment and improve the quality of anesthesia.

Read the detailed description

This is an observational study of the routine clinical practice of anesthesia and surgery with no specific additional interventions required. Types of surgery (non-intubated video-assisted thoracoscopic surgery or video-assisted thoracoscopic surgery) are discussed and decided totally by patients and surgeons.

Data acquisition (Non-intubated video-assisted thoracoscopic surgery, NI-VATS)

  1. After screening for eligible patients, protocol and study details will be thoroughly explained to them.
  2. Each patient received standard anesthetic care of our institute. Strict fasting protocols were followed. A 22 or 20-gauge intravenous catheter was secured for drug administration. Monitors are comprised of ECG (electrocardiography), oxygenation saturation (SpO2) ,NIBP (non-invasive blood pressure)and arterial blood pressure (ABP). ECG, SpO2 and ABP were monitored continuously and NIBP were measured every 60 minutes. Supplemental oxygen was given via high flow nasal cannula, and SpO2 (oxygenation saturation) maintained above 90%. Induction and maintenance of anesthesia is achieved by intravenous propofol, dexmedetomidine and alfentanil. Dosage are according to anesthesiologist's preference. Anesthetic depth was monitored with BIS or PSI monitor.
  3. BIS or PSI monitor is continuously recorded throughout the surgery to collect EEG parameters such as BIS or PSI values, DSA, SEF95 (95% spectral edge frequency) and MF (Median frequency). MOAA/S score would be recorded at induction and emergence phase.
  4. At the end of the procedure, the patient was observed until return of consciousness (MOAA/S > 5). Collected data will be randomly divided into a model training group and a validation group after data acquisition by computer randomization using computer clock as seed.

Data acquisition (Video-assisted thoracoscopic surgery, VATS)

  1. After screening for eligible patients, protocol and study details will be thoroughly explained to them.
  2. Each patient received standard anesthetic care of our institute. Strict fasting protocols were followed. A 22 or 20-gauge intravenous catheter was secured for drug administration. Monitors are comprised of ECG (electrocardiography), oxygenation saturation (SpO2) ,NIBP (non-invasive blood pressure)and arterial blood pressure (ABP). ECG, SpO2 and ABP were monitored continuously and NIBP were measured every 60 minutes. Induction and maintenance of anesthesia is achieved by intravenous propofol, dexmedetomidine, alfentanil and neuromuscular blocking agents. Dosage are according to anesthesiologist's preference. Anesthetic depth was monitored with BIS or PSI.
  3. After double lumen endotracheal tube placement, FiO2: 100 % and fresh gas flow at 1~6 L/m was set. BIS or PSI monitor is continuously recorded throughout the surgery to collect EEG parameters such as BIS or PSI values, DSA, SEF95 (95% spectral edge frequency) and MF (Median frequency). MOAA/S score would be recorded at induction and emergence phase
  4. At the end of the procedure, endotracheal tube was removed if the patient was breathing smoothly. The patient was observed until return of consciousness (MOAA/S > 5). Collected data will be randomly divided into a model training group and a validation group after data acquisition by computer randomization using computer clock as seed.

Model building, assessment and validation (both groups)

  1. Collected data were fed to a pharmacokinetic simulation software (TIVA trainer Version 9.1) to calculate second-by-second plasma and effect-site drug concentration changes for all three drugs. The training patient group is used for model training. The bootstrap technique is used with 2000 iterations. Model fit was optimized using -2 Log likelihood (-2LL).
  2. MOAA/S, BIS or PSI models would be constructed.
  3. The results are validated with the validation patient data to confirm its clinical utility.

Receiver operating characteristics (ROC) curve analysis is used to assess the quality of model prediction. ROC and area under the curve (AUC) will be compared between the training and validation group.

Being tested
Bispectral index (BIS) or Patient State Index (PSI), Propofol, Alfentanil, Dexmedetomidine
Keywords
Three-drug response surface model, Thoracic surgery, Bispectral index, Patient state index, propofol, dexmedetomidine, opioid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Bispectral index (BIS) or Patient State Index (PSI)Device

    After giving routine anesthetic medications, the investigators assess the depth of anesthesia based on bispectral index (BIS) or Patient State Index (PSI). BIS is maintained between 40 - 60 and PSI between 25 - 50. The vital signs, BIS or PSI are recorded automatically and continuously through computerized software. Upon conclusion of the surgery or examination, the patient is observed until return of consciousness (MOAA/S = 5) before sending them to the recovery unit.

  • PropofolDrug

    The investigators assess the depth of anesthesia based on bispectral index (BIS) or Patient State Index (PSI) after routine drug regimen is given. BIS is maintained between 40 and 60 and or PSI between 25 and 50. The drug doses are given as a part of routine anesthesia practice and is identical regardless of study participation. Propofol is given via target control pump with typical target effect-site propofol concentration 1-5 ug/mL according to patient condition, BIS or PSI value and DSA. The timing and doses are recorded for backend analysis. At the conclusion of the surgery or examination, the patient is observed in the surgery or examination room until return of consciousness before sending them to the recovery unit.

  • AlfentanilDrug

    The investigators assess the depth of anesthesia based on bispectral index (BIS) or Patient State Index (PSI) after routine drug regimen is given. BIS is maintained between 40 and 60 and or PSI between 25 and 50. The drug doses are given as a part of routine anesthesia practice and is identical regardless of study participation. Typical alfentanil ranged from 0~1000mcg according to patient condition, BIS or PSI value and DSA. The timing and doses are recorded for backend analysis. At the conclusion of the surgery or examination, the patient is observed in the surgery or examination room until return of consciousness before sending them to the recovery unit.

  • DexmedetomidineDrug

    The investigators assess the depth of anesthesia based on bispectral index (BIS) or Patient State Index (PSI) after routine drug regimen is given. BIS is maintained between 40 and 60 and or PSI between 25 and 50. The drug doses are given as a part of routine anesthesia practice and is identical regardless of study participation. Typical Dexmedetomidine ranged from 0.5-1 ug/kg/hr according to patient condition, BIS or PSI value and DSA. The timing and doses are recorded for backend analysis. At the conclusion of the surgery or examination, the patient is observed in the surgery or examination room until return of consciousness before sending them to the recovery unit.

Study groups in NCT05525351
Study groupRoleWhat they receive
NI-VATS (Non-intubated video-assisted thoracoscopic surgery)This is a purely observational study of the routine anesthetic practice involving the simultaneous use of three drugs. Types of surgery (non-intubated video-assisted thoracoscopic surgery or video-assisted thoracoscopic surgery) are discussed and decided totally by patients and surgeons independently. NI-VATS: induction and maintenance are achieved by propofol, alfentanil and dexmedetomidine. Patients are monitored with standard monitors (electrocardiography, Non-invasive blood pressure, and pulse oximetry), arterial blood pressure (ABP) and bispectral index (BIS) or Patient State Index (PSI) monitor. Patients are observed in the recovery unit with designate nursing staff until full conscious recovery before discharge.
Receives: Device: Bispectral index (BIS) or Patient State Index (PSI); Drug: Propofol; Drug: Alfentanil; Drug: Dexmedetomidine
VATS (video-assisted thoracoscopic surgery)This is a purely observational study of the routine anesthetic practice involving the simultaneous use of three drugs. Types of surgery (non-intubated video-assisted thoracoscopic surgery or video-assisted thoracoscopic surgery) are discussed and decided totally by patients and surgeons independently. NI-VATS: induction and maintenance are achieved by propofol, alfentanil and dexmedetomidine. Patients are monitored with standard monitors (electrocardiography, Non-invasive blood pressure, and pulse oximetry), arterial blood pressure (ABP) and bispectral index (BIS) or Patient State Index (PSI) monitor. Patients are observed in the recovery unit with designate nursing staff until full conscious recovery before discharge.
Receives: Device: Bispectral index (BIS) or Patient State Index (PSI); Drug: Propofol; Drug: Alfentanil; Drug: Dexmedetomidine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Bispectral index (BIS) value or Patient state index (PSI) value

    Our study records these parameters on an observational basis. Anesthetic management remains identical regardless of patient participation or not. The recorded BIS or PSI value reading is uniform and contains only a unitless number ranging from 0 to 100. Different procedures do not give different units. These values are part of anesthetic depth evaluation and the recordings are aggregated to perform fit in a mathematic model.

    Measured: EEG are recorded starting from anesthesia induction, and stopped after emergence when surgery ends as a part of routine anesthesia.

  2. EEG frequency

    Our study records these parameters on an observational basis. Anesthetic management remains identical regardless of patient participation or not. Raw EEG data are recorded and analyzed afterwards. Spectral analysis of the alpha, beta, gamma, theta and delta features will be performed. Individual band powers are summed separately. EEG frequency will be recorded continuously during the total anesthesia time to perform fit in a mathematic model.

    Measured: EEG are recorded starting from anesthesia induction, and stopped after emergence when surgery ends as a part of routine anesthesia.

  3. Power of the EEG signal

    Our study records these parameters on an observational basis. Anesthetic management remains identical regardless of patient participation or not. Raw EEG data are recorded and analyzed afterwards. Spectral analysis of the alpha, beta, gamma, theta and delta features will be performed. Individual band powers are summed separately. Power of the EEG signal represents amount of activity in certain frequency bands. Power of the EEG signal will be recorded continuously during the total anesthesia time to perform fit in a mathematic model.

    Measured: EEG are recorded starting from anesthesia induction, and stopped after emergence when surgery ends as a part of routine anesthesia.

  4. Spectral edge frequency 90 (SEF 90)

    Our study records these parameters on an observational basis. Anesthetic management remains identical regardless of patient participation or not. Raw EEG data are recorded and analyzed afterwards. Spectral analysis of the alpha, beta, gamma, theta and delta features will be performed. Individual band powers are summed separately. Spectral edge frequency 90 (SEF 90) represents the frequency below which 90 % of the EEG power is located. SEF 90 will be recorded continuously during the total anesthesia time to perform fit in a mathematic model.

    Measured: EEG are recorded starting from anesthesia induction, and stopped after emergence when surgery ends as a part of routine anesthesia.

  5. Median frequency (MF)

    Our study records these parameters on an observational basis. Anesthetic management remains identical regardless of patient participation or not. Raw EEG data are recorded and analyzed afterwards. Spectral analysis of the alpha, beta, gamma, theta and delta features will be performed. Individual band powers are summed separately. The median frequency represents the frequency below and above which lies 50% of the total power in the EEG. MF will be recorded continuously during the total anesthesia time to perform fit in a mathematic model.

    Measured: EEG are recorded starting from anesthesia induction, and stopped after emergence when surgery ends as a part of routine anesthesia

Secondary outcomes (1)
  1. Modified Observer's Assessment Alertness Scale(MOAA/S) score

    Our study records these parameters on an observational basis. Anesthetic management remains identical regardless of patient participation or not. MOAA/S is a unitless score between 0 and 5 and is applicable in different anesthesia settings. Different procedures do not give different MOAA/S units. Return of consciousness is defined by a score of MOAA/S greater than 4. The score is a part of anesthetic depth evaluation and the recordings are aggregated to perform fit in a mathematic model.

    Measured: MOAA/S score will be recorded specifically at induction and emergence phase

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Sep 2022
  2. Study startOct 2022 (estimated)
  3. Primary completionJul 2023 (estimated)
  4. Study completionJul 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05525351
Sponsor's protocol ID
2021-02-019B
Status last verified
Sep 2022
First submitted
11 Aug 2022
Last updated
7 Sep 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
Yes
Individual data sharing
No

Publications

  • Liou JY, Ting CK, Teng WN, Mandell MS, Tsou MY. Adaptation of non-linear mixed amount with zero amount response surface model for analysis of concentration-dependent synergism and safety with midazolam, alfentanil, and propofol sedation. Br J Anaesth. 2018 Jun;120(6):1209-1218. doi: 10.1016/j.bja.2018.01.041. Epub 2018 Apr 17.

    PubMed 29793588
  • Liou JY, Ting CK, Mandell MS, Chang KY, Teng WN, Huang YY, Tsou MY. Predicting the Best Fit: A Comparison of Response Surface Models for Midazolam and Alfentanil Sedation in Procedures With Varying Stimulation. Anesth Analg. 2016 Aug;123(2):299-308. doi: 10.1213/ANE.0000000000001299.

    PubMed 27192475
  • LaPierre CD, Johnson KB, Randall BR, Egan TD. A simulation study of common propofol and propofol-opioid dosing regimens for upper endoscopy: implications on the time course of recovery. Anesthesiology. 2012 Aug;117(2):252-62. doi: 10.1097/ALN.0b013e31825fb1b2.

    PubMed 22728781
  • Ting CK, Johnson KB, Teng WN, Synoid ND, Lapierre C, Yu L, Westenskow DR. Response surface model predictions of wake-up time during scoliosis surgery. Anesth Analg. 2014 Mar;118(3):546-53. doi: 10.1213/ANE.0000000000000094.

    PubMed 24557102
  • Liou JY, Ting CK, Huang YY, Tsou MY. Previously published midazolam-alfentanil response surface model cannot predict patient response well in gastrointestinal endoscopy sedation. J Chin Med Assoc. 2016 Mar;79(3):146-51. doi: 10.1016/j.jcma.2015.11.002. Epub 2016 Jan 28.

    PubMed 26831450
  • [40 years of scientific-research work in medicine]. Patol Fiziol Eksp Ter. 1969 May-Jun;13(3):91-4. No abstract available. Russian.

    PubMed 4907643
  • Chernik DA, Gillings D, Laine H, Hendler J, Silver JM, Davidson AB, Schwam EM, Siegel JL. Validity and reliability of the Observer's Assessment of Alertness/Sedation Scale: study with intravenous midazolam. J Clin Psychopharmacol. 1990 Aug;10(4):244-51.

    PubMed 2286697
  • de Heer IJ, Bouman SJM, Weber F. Electroencephalographic (EEG) density spectral array monitoring in children during sevoflurane anaesthesia: a prospective observational study. Anaesthesia. 2019 Jan;74(1):45-50. doi: 10.1111/anae.14458. Epub 2018 Oct 27.

    PubMed 30367683

Questions about this trial

What is this clinical trial studying?

An observational study of Anesthesia and Drug Interaction, run by Taipei Veterans General Hospital, Taiwan at 1 site in Taiwan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 7 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Mei-Yung Tsou, MD. PhD. (886-9-38593120, mytsou8095@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Bispectral index (BIS) value or Patient state index (PSI) value (time frame: EEG are recorded starting from anesthesia induction, and stopped after emergence when surgery ends as a part of routine anesthesia.). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05525351, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Sep 2022.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in