Anesthesia
Conditions
Keywords
Electroencephalography, pharmacological
Brief summary
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.
Interventions
DEVICESedLine EEG sensor
Test subjects in each group will receive the same device intervention (SedLine EEG) to monitor their EEG waves.
Sponsors
University Medical Center Groningen
Masimo Corporation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
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 *
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Patient State Index (PSI) Comparison, Baseline and Emax | 6 weeks | 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). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Patient State Index (PSI) Comparison, C50 (Sevoflurane, Sevoflurane+Remifentanil) | 6 weeks | 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). |
| Patient State Index (PSI) Comparison, C50 (Propofol, Propofol+Remifentanil) | 6 weeks | 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). |
| Propofol, Sevoflurane, and Remifentanil Interaction. | 6 weeks | 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. |
Countries
Netherlands
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Healthy Volunteers Thirty-six healthy volunteers received 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). | 36 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Investigator decision | 1 |
| Overall Study | No show by subject | 1 |
| Overall Study | Unable to place EEG sensors on patient | 1 |
| Overall Study | Withdrawal by Subject | 7 |
Baseline characteristics
| Characteristic | Healthy Volunteers |
|---|---|
| Age, Continuous | 43.3 years |
| Region of Enrollment Netherlands | 36 Participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 36 | 0 / 36 | 0 / 36 | 0 / 36 |
| other Total, other adverse events | 1 / 36 | 2 / 36 | 1 / 36 | 7 / 36 |
| serious Total, serious adverse events | 0 / 36 | 0 / 36 | 0 / 36 | 0 / 36 |
Outcome results
Primary
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).
Time frame: 6 weeks
Population: All 36 participants experienced all four interventions: Propofol only (P), Sevoflurane only (S), Propofol with Remifentanil (PR), and Sevoflurane with Remifentanil (SR).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Volunteers | Patient State Index (PSI) Comparison, Baseline and Emax | No Drugs, PSI-2 (BL) | 85.1 index | Standard Error 0.8 |
| Healthy Volunteers | Patient State Index (PSI) Comparison, Baseline and Emax | P, PSI-2 (Emax) | 63.1 index | Standard Error 1.9 |
| Healthy Volunteers | Patient State Index (PSI) Comparison, Baseline and Emax | PR, PSI-2 (Emax) | 63.1 index | Standard Error 1.9 |
| Healthy Volunteers | Patient State Index (PSI) Comparison, Baseline and Emax | P, PSI-1 (Emax) | 63.1 index | Standard Error 1.9 |
| Healthy Volunteers | Patient State Index (PSI) Comparison, Baseline and Emax | PR, PSI-1 (Emax) | 63.1 index | Standard Error 1.9 |
| Healthy Volunteers | Patient State Index (PSI) Comparison, Baseline and Emax | SR, PSI-1 (Emax) | 0.152 index | Standard Error 17.1 |
| Healthy Volunteers | Patient State Index (PSI) Comparison, Baseline and Emax | S, PSI-2 (Emax) | 67.2 index | Standard Error 2.3 |
| Healthy Volunteers | Patient State Index (PSI) Comparison, Baseline and Emax | SR, PSI-2 (Emax) | 67.2 index | Standard Error 2.3 |
| Healthy Volunteers | Patient State Index (PSI) Comparison, Baseline and Emax | No Drugs, PSI-1 (BL) | 85.1 index | Standard Error 0.8 |
| Healthy Volunteers | Patient State Index (PSI) Comparison, Baseline and Emax | S, PSI-1 (Emax) | 0.152 index | Standard Error 17.1 |
Other Pre-specified
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).
Time frame: 6 weeks
Population: All 36 participants experienced all four interventions: Propofol only (P), Sevoflurane only (S), Propofol with Remifentanil (PR), and Sevoflurane with Remifentanil (SR).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Volunteers | Patient State Index (PSI) Comparison, C50 (Propofol, Propofol+Remifentanil) | P, PSI-2 (C50) | 1.63 ug/mL | Standard Error 3.7 |
| Healthy Volunteers | Patient State Index (PSI) Comparison, C50 (Propofol, Propofol+Remifentanil) | PR, PSI-2 (C50) | 1.63 ug/mL | Standard Error 3.7 |
| Healthy Volunteers | Patient State Index (PSI) Comparison, C50 (Propofol, Propofol+Remifentanil) | P, PSI-1 (C50) | 1.63 ug/mL | Standard Error 3.7 |
| Healthy Volunteers | Patient State Index (PSI) Comparison, C50 (Propofol, Propofol+Remifentanil) | PR, PSI-1 (C50) | 1.63 ug/mL | Standard Error 3.7 |
Other Pre-specified
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).
Time frame: 6 weeks
Population: All 36 participants experienced all four interventions: Propofol only (P), Sevoflurane only (S), Propofol with Remifentanil (PR), and Sevoflurane with Remifentanil (SR).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Volunteers | Patient State Index (PSI) Comparison, C50 (Sevoflurane, Sevoflurane+Remifentanil) | S, PSI-2 (C50) | 1.22 %vol | Standard Error 3.1 |
| Healthy Volunteers | Patient State Index (PSI) Comparison, C50 (Sevoflurane, Sevoflurane+Remifentanil) | SR, PSI-2 (C50) | 1.22 %vol | Standard Error 3.1 |
| Healthy Volunteers | Patient State Index (PSI) Comparison, C50 (Sevoflurane, Sevoflurane+Remifentanil) | S, PSI-1 (C50) | 1.22 %vol | Standard Error 3.1 |
| Healthy Volunteers | Patient State Index (PSI) Comparison, C50 (Sevoflurane, Sevoflurane+Remifentanil) | SR, PSI-1 (C50) | 1.22 %vol | Standard Error 3.1 |
Other Pre-specified
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.
Time frame: 6 weeks
Population: 18 participants experienced the remifentanil 2 ng/mL intervention, and 18 participants experienced the remifentanil 4 ng/mL intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Volunteers | Propofol, Sevoflurane, and Remifentanil Interaction. | Theta2, PSI-2 (PR 4ng/mL) | 0.816 Index | Standard Error 62.3 |
| Healthy Volunteers | Propofol, Sevoflurane, and Remifentanil Interaction. | Theta2, PSI-1 (P) | 0 Index | Standard Error 0 |
| Healthy Volunteers | Propofol, Sevoflurane, and Remifentanil Interaction. | Theta2, PSI-1 (S) | 0 Index | Standard Error 0 |
| Healthy Volunteers | Propofol, Sevoflurane, and Remifentanil Interaction. | Theta2, PSI-1 (PR 4ng/mL) | 0.816 Index | Standard Error 62.3 |
| Healthy Volunteers | Propofol, Sevoflurane, and Remifentanil Interaction. | Theta1, PSI-2 (P) | 0 Index | Standard Error 0 |
| Healthy Volunteers | Propofol, Sevoflurane, and Remifentanil Interaction. | Theta1, PSI-2 (S) | 0 Index | Standard Error 0 |
| Healthy Volunteers | Propofol, Sevoflurane, and Remifentanil Interaction. | Theta1, PSI-2 (PR 2ng/mL) | -0.135 Index | Standard Error 20.8 |
| Healthy Volunteers | Propofol, Sevoflurane, and Remifentanil Interaction. | Theta1, PSI-2 (SR 2ng/mL) | -0.135 Index | Standard Error 20.8 |
| Healthy Volunteers | Propofol, Sevoflurane, and Remifentanil Interaction. | Theta1, PSI-1 (P) | 0 Index | Standard Error 0 |
| Healthy Volunteers | Propofol, Sevoflurane, and Remifentanil Interaction. | Theta1, PSI-1 (S) | 0 Index | Standard Error 0 |
| Healthy Volunteers | Propofol, Sevoflurane, and Remifentanil Interaction. | Theta1, PSI-1 (PR 2ng/mL) | -0.135 Index | Standard Error 20.8 |
| Healthy Volunteers | Propofol, Sevoflurane, and Remifentanil Interaction. | Theta1, PSI-1 (SR 2ng/mL) | -0.135 Index | Standard Error 20.8 |
| Healthy Volunteers | Propofol, Sevoflurane, and Remifentanil Interaction. | Theta2, PSI-2 (P) | 0 Index | Standard Error 0 |
| Healthy Volunteers | Propofol, Sevoflurane, and Remifentanil Interaction. | Theta2, PSI-2 (S) | 0 Index | Standard Error 0 |
| Healthy Volunteers | Propofol, Sevoflurane, and Remifentanil Interaction. | Theta2, PSI-2 (SR 4ng/mL) | 0.816 Index | Standard Error 62.3 |
| Healthy Volunteers | Propofol, Sevoflurane, and Remifentanil Interaction. | Theta2, PSI-1 (SR 4ng/mL) | 0.816 Index | Standard Error 62.3 |