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

NCT05525351 | Unknown DMC FDA Drug FDA Device

• 1 other identifier: 2021-02-019B
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Anesthesia; Drug Interaction; Anesthesia; Functional

Keywords

Three-drug response surface model; Thoracic surgery; Bispectral index; Patient state index; propofol; dexmedetomidine; opioid

Outcome Measures

Primary Outcomes (5)

• 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.

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

• 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.

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

• 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.

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

• 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.

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

• 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.

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

Secondary Outcomes (1)

• Modified Observer's Assessment Alertness Scale(MOAA/S) score

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

Study Arms (2)

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.

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.

Device: Bispectral index (BIS) or Patient State Index (PSI); Drug: Propofol; Drug: Alfentanil; Drug: Dexmedetomidine

Interventions

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.

NI-VATS (Non-intubated video-assisted thoracoscopic surgery); VATS (video-assisted thoracoscopic surgery)

Propofol DRUG

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.

NI-VATS (Non-intubated video-assisted thoracoscopic surgery); VATS (video-assisted thoracoscopic surgery)

Alfentanil DRUG

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.

NI-VATS (Non-intubated video-assisted thoracoscopic surgery); VATS (video-assisted thoracoscopic surgery)

Dexmedetomidine DRUG

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.

NI-VATS (Non-intubated video-assisted thoracoscopic surgery); VATS (video-assisted thoracoscopic surgery)

Eligibility Criteria

• Age: 25 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Taipei Veterans General Hospital, Taiwan: lead

Study Sites (1)

Taipei Veterans General Hospital

Taipei, 11257, Taiwan

Location

Related Publications (8)

• 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.

  PMID: 29793588 BACKGROUND

• 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.

  PMID: 27192475 BACKGROUND

• 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.

  PMID: 22728781 BACKGROUND

• 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.

  PMID: 24557102 BACKGROUND

• 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.

  PMID: 26831450 BACKGROUND

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

  PMID: 4907643 BACKGROUND

• 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.

  PMID: 2286697 BACKGROUND

• 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.

  PMID: 30367683 BACKGROUND

MeSH Terms

Interventions

Propofol; Alfentanil; Dexmedetomidine

Intervention Hierarchy (Ancestors)

Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Fentanyl; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Imidazoles; Azoles

Study Officials

• Mei-Yung Tsou, MD. PhD.

  Taipei Veterans General Hospital; National Yang-Ming University

  STUDY DIRECTOR

Central Study Contacts

Mei-Yung Tsou, MD. PhD.

CONTACT

886-9-38593120; mytsou8095@gmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2022
• First Posted: September 1, 2022
• Study Start: October 1, 2022
• Primary Completion: July 1, 2023
• Study Completion: July 1, 2024
• Last Updated: September 7, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)