Improving Information Extraction From EEG on Cerebral Anesthetic Drug Effects

'Study of the Cerebral Effects of Sevoflurane, Propofol and Remifentanil as Measured by the Spontaneous Electro-encephalogram'

This is an interventional, randomized controlled study in health volunteers that involves collecting data on raw EEG waves measuring various combinations of anesthetic drugs during standardized drug titration.

Study Overview

• Status: Completed
• Conditions: Anesthesia
• Intervention / Treatment: Device: SedLine EEG sensor

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9713EZ
    • University Medical Center Groningen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy volunteers aged 18 to 70 years
• Concerning the cognitive function: Volunteers are considered to have sufficient cognitive reserve if they are able to read and comprehend the patient information form, if they can adequately answer the anamnestic questions during the screening process and if they are allowed to provide legitimate written informed consent
• No selection will be made regarding ethnic background.
• For this study no control group has been selected as EEG is compared between episodes rather than between individuals (each volunteer is his/her own control)

Exclusion Criteria:

Volunteer refusal

• Volunteer < 18 years and >70 years
• Pregnancy
• Exclusion criteria are weight less than 70% or more than 130% of ideal body weight
• Neurological disorder (epilepsy, the presence of a brain tumor, a history of brain surgery, hydrocephalic disorders, depression needing treatment with anti-depressive drugs, a history of brain trauma, a subarachnoidal bleeding, TIA or cerebral infarct, psychosis or dementia , schizophrenia, alcohol or drug abuse).
• Diseases involving the cardiovascular system (hypertension, coronary artery disease, prior acute myocardial infarction, any valvular and/or myocardial disease involving decrease in ejection fraction, arrhythmias, which are either symptomatic or require continuous medication/pacemaker/automatic internal cardioverter defibrillator
• Pulmonary Diseases
• Gastric Diseases
• Endocrinologic diseases
• Recent use of psycho-active medication (benzodiazepines, anti-epileptic drugs, parkinson medication, anti-depressant drugs, opioids) or more than 20g of alcohol daily

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Healthy Volunteers; All healthy volunteers will receive four sessions of anesthesia with different common drug combinations while having SedLine EEG sensors placed on their forehead during these sessions to study the effects of these drugs on the brain. The sessions were: propofol (P), sevoflurane (S), propofol with remifentanil (PR), and sevoflurane with remifentanil (SR).	Device: SedLine EEG sensor; Test subjects in each group will receive the same device intervention (SedLine EEG) to monitor their EEG waves.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient State Index (PSI) Comparison, Baseline and Emax	Patient State Index (PSI-1) is a processed EEG parameter that quantifies the level of EEG inhibition. A new algorithm (PSI-2) has been created to improve performance in low power EEG. PSI is unitless. It ranges between 100 and 0 (100 representing 'awake state', 0 denoting 'no detectable electrical brain activity'). PSI-1 and PSI-2 were compared in their correlation with measured propofol and sevoflurane concentrations with or without remifentanil (0, 2 ,or 4 ng/mL) via several estimated PD model parameters. In the data table, BL (Baseline) denotes PSI-2 measurements when no drug is present; Emax denotes PSI in the presence of the maximum drug effect; C50 is the drug concentration which produces 50% of the maximal drug effect (ug/mL for Propofol C50, vol% for Sevoflurane C50).	6 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient State Index (PSI) Comparison, C50 (Sevoflurane, Sevoflurane+Remifentanil)	Patient State Index (PSI-1) is a processed EEG parameter that quantifies the level of EEG inhibition. A new algorithm (PSI-2) has been created to improve performance in low power EEG. PSI is unitless. It ranges between 100 and 0 (100 representing 'awake state', 0 denoting 'no detectable electrical brain activity'). PSI-1 and PSI-2 were compared in their correlation with measured propofol and sevoflurane concentrations with or without remifentanil (0, 2 ,or 4 ng/mL) via several estimated PD model parameters. In the data table, BL (Baseline) denotes PSI-2 measurements when no drug is present; Emax denotes PSI in the presence of the maximum drug effect; C50 is the drug concentration which produces 50% of the maximal drug effect (ug/mL for Propofol C50, vol% for Sevoflurane C50).	6 weeks
Patient State Index (PSI) Comparison, C50 (Propofol, Propofol+Remifentanil)	Patient State Index (PSI-1) is a processed EEG parameter that quantifies the level of EEG inhibition. A new algorithm (PSI-2) has been created to improve performance in low power EEG. PSI is unitless. It ranges between 100 and 0 (100 representing 'awake state', 0 denoting 'no detectable electrical brain activity'). PSI-1 and PSI-2 were compared in their correlation with measured propofol and sevoflurane concentrations with or without remifentanil (0, 2 ,or 4 ng/mL) via several estimated PD model parameters. In the data table, BL (Baseline) denotes PSI-2 measurements when no drug is present; Emax denotes PSI in the presence of the maximum drug effect; C50 is the drug concentration which produces 50% of the maximal drug effect (ug/mL for Propofol C50, vol% for Sevoflurane C50).	6 weeks
Propofol, Sevoflurane, and Remifentanil Interaction.	For all study groups (i.e. P, S, PR, and SR), the estimated PD model parameters that represent remifentanil interactions are Theta1 and Theta2, which are unit-less values. Theta1 and Theta2 are zero for all volunteers not receiving remifentanil. In case an interaction between remifentanil and propofol or sevoflurane exists, the estimate for Theta1 will be significantly different from zero. If the interaction in the 4 ng/mL group exceeds the estimated interaction for the 2 ng/mL group, Theta2 will be significantly higher than zero.	6 weeks

Collaborators and Investigators

• Sponsor: Masimo Corporation
• Collaborators: University Medical Center Groningen

Publications and helpful links

General Publications

• Su H, Eleveld DJ, Struys MMRF, Colin PJ. Mechanism-based pharmacodynamic model for propofol haemodynamic effects in healthy volunteers☆. Br J Anaesth. 2022 May;128(5):806-816. doi: 10.1016/j.bja.2022.01.022. Epub 2022 Mar 3.
• Ramaswamy SM, Kuizenga MH, Weerink MAS, Vereecke HEM, Struys MMRF, Belur Nagaraj S. Frontal electroencephalogram based drug, sex, and age independent sedation level prediction using non-linear machine learning algorithms. J Clin Monit Comput. 2022 Feb;36(1):121-130. doi: 10.1007/s10877-020-00627-3. Epub 2020 Dec 14.
• Ramaswamy SM, Kuizenga MH, Weerink MAS, Vereecke HEM, Struys MMRF, Nagaraj SB. Novel drug-independent sedation level estimation based on machine learning of quantitative frontal electroencephalogram features in healthy volunteers. Br J Anaesth. 2019 Oct;123(4):479-487. doi: 10.1016/j.bja.2019.06.004. Epub 2019 Jul 18.
• Kuizenga MH, Colin PJ, Reyntjens KMEM, Touw DJ, Nalbat H, Knotnerus FH, Vereecke HEM, Struys MMRF. Test of neural inertia in humans during general anaesthesia. Br J Anaesth. 2018 Mar;120(3):525-536. doi: 10.1016/j.bja.2017.11.072. Epub 2017 Dec 1.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 16, 2013
• Primary Completion (ACTUAL): June 4, 2015
• Study Completion (ACTUAL): June 4, 2015

Study Registration Dates

• First Submitted: January 9, 2014
• First Submitted That Met QC Criteria: January 21, 2014
• First Posted (ESTIMATE): January 23, 2014

Study Record Updates

• Last Update Posted (ACTUAL): May 2, 2018
• Last Update Submitted That Met QC Criteria: March 30, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Electroencephalography; pharmacological
• Other Study ID Numbers: STRU0002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes