Improving Information Extraction From EEG on Cerebral Anesthetic Drug Effects
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Study Design
Arms and Interventions
| 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.
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University Medical Center Groningen | Groningen | Netherlands | 9713EZ |
Sponsors and Collaborators
- Masimo Corporation
- University Medical Center Groningen
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- STRU0002
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Healthy Volunteers |
|---|---|
| Arm/Group Description | 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). |
| Period Title: Overall Study | |
| STARTED | 46 |
| COMPLETED | 36 |
| NOT COMPLETED | 10 |
Baseline Characteristics
| Arm/Group Title | Healthy Volunteers |
|---|---|
| Arm/Group Description | 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). |
| Overall Participants | 36 |
| Age (years) [Mean (Full Range) ] | |
| Mean (Full Range) [years] |
43.3
|
| Sex: Female, Male (Count of Participants) | |
| Female |
20
55.6%
|
| Male |
16
44.4%
|
| Region of Enrollment (Count of Participants) | |
| Netherlands |
36
100%
|
Outcome Measures
| Title | Patient State Index (PSI) Comparison, Baseline and Emax |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All 36 participants experienced all four interventions: Propofol only (P), Sevoflurane only (S), Propofol with Remifentanil (PR), and Sevoflurane with Remifentanil (SR). |
| Arm/Group Title | Healthy Volunteers |
|---|---|
| Arm/Group Description | 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). |
| Measure Participants | 36 |
| No Drugs, PSI-2 (BL) |
85.1
(0.8)
|
| P, PSI-2 (Emax) |
63.1
(1.9)
|
| PR, PSI-2 (Emax) |
63.1
(1.9)
|
| S, PSI-2 (Emax) |
67.2
(2.3)
|
| SR, PSI-2 (Emax) |
67.2
(2.3)
|
| No Drugs, PSI-1 (BL) |
85.1
(0.8)
|
| P, PSI-1 (Emax) |
63.1
(1.9)
|
| PR, PSI-1 (Emax) |
63.1
(1.9)
|
| S, PSI-1 (Emax) |
0.152
(17.1)
|
| SR, PSI-1 (Emax) |
0.152
(17.1)
|
| Title | Patient State Index (PSI) Comparison, C50 (Sevoflurane, Sevoflurane+Remifentanil) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All 36 participants experienced all four interventions: Propofol only (P), Sevoflurane only (S), Propofol with Remifentanil (PR), and Sevoflurane with Remifentanil (SR). |
| Arm/Group Title | Healthy Volunteers |
|---|---|
| Arm/Group Description | 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). |
| Measure Participants | 36 |
| S, PSI-2 (C50) |
1.22
(3.1)
|
| SR, PSI-2 (C50) |
1.22
(3.1)
|
| S, PSI-1 (C50) |
1.22
(3.1)
|
| SR, PSI-1 (C50) |
1.22
(3.1)
|
| Title | Patient State Index (PSI) Comparison, C50 (Propofol, Propofol+Remifentanil) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All 36 participants experienced all four interventions: Propofol only (P), Sevoflurane only (S), Propofol with Remifentanil (PR), and Sevoflurane with Remifentanil (SR). |
| Arm/Group Title | Healthy Volunteers |
|---|---|
| Arm/Group Description | 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). |
| Measure Participants | 36 |
| P, PSI-2 (C50) |
1.63
(3.7)
|
| PR, PSI-2 (C50) |
1.63
(3.7)
|
| P, PSI-1 (C50) |
1.63
(3.7)
|
| PR, PSI-1 (C50) |
1.63
(3.7)
|
| Title | Propofol, Sevoflurane, and Remifentanil Interaction. |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 18 participants experienced the remifentanil 2 ng/mL intervention, and 18 participants experienced the remifentanil 4 ng/mL intervention. |
| Arm/Group Title | Healthy Volunteers |
|---|---|
| Arm/Group Description | 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). |
| Measure Participants | 36 |
| Theta1, PSI-2 (P) |
0
(0)
|
| Theta1, PSI-2 (S) |
0
(0)
|
| Theta1, PSI-2 (PR 2ng/mL) |
-0.135
(20.8)
|
| Theta1, PSI-2 (SR 2ng/mL) |
-0.135
(20.8)
|
| Theta1, PSI-1 (P) |
0
(0)
|
| Theta1, PSI-1 (S) |
0
(0)
|
| Theta1, PSI-1 (PR 2ng/mL) |
-0.135
(20.8)
|
| Theta1, PSI-1 (SR 2ng/mL) |
-0.135
(20.8)
|
| Theta2, PSI-2 (P) |
0
(0)
|
| Theta2, PSI-2 (S) |
0
(0)
|
| Theta2, PSI-2 (PR 4ng/mL) |
0.816
(62.3)
|
| Theta2, PSI-2 (SR 4ng/mL) |
0.816
(62.3)
|
| Theta2, PSI-1 (P) |
0
(0)
|
| Theta2, PSI-1 (S) |
0
(0)
|
| Theta2, PSI-1 (PR 4ng/mL) |
0.816
(62.3)
|
| Theta2, PSI-1 (SR 4ng/mL) |
0.816
(62.3)
|
Adverse Events
| Time Frame | ||||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | Healthy Volunteers, Propofol (P) | Healthy Volunteers, Sevoflurane (S) | Healthy Volunteers, Propofol With Remifentanil (PR) | Healthy Volunteers, Sevoflurane With Remifentanil (SR) | ||||
| Arm/Group Description | 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). | 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). | 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). | 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). | ||||
All Cause Mortality |
||||||||
| Healthy Volunteers, Propofol (P) | Healthy Volunteers, Sevoflurane (S) | Healthy Volunteers, Propofol With Remifentanil (PR) | Healthy Volunteers, Sevoflurane With Remifentanil (SR) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/36 (0%) | 0/36 (0%) | 0/36 (0%) | 0/36 (0%) | ||||
Serious Adverse Events |
||||||||
| Healthy Volunteers, Propofol (P) | Healthy Volunteers, Sevoflurane (S) | Healthy Volunteers, Propofol With Remifentanil (PR) | Healthy Volunteers, Sevoflurane With Remifentanil (SR) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/36 (0%) | 0/36 (0%) | 0/36 (0%) | 0/36 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Healthy Volunteers, Propofol (P) | Healthy Volunteers, Sevoflurane (S) | Healthy Volunteers, Propofol With Remifentanil (PR) | Healthy Volunteers, Sevoflurane With Remifentanil (SR) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/36 (2.8%) | 2/36 (5.6%) | 1/36 (2.8%) | 7/36 (19.4%) | ||||
| Cardiac disorders | ||||||||
| Short phase of nodale ECG rhythm | 0/36 (0%) | 0 | 0/36 (0%) | 0 | 0/36 (0%) | 0 | 1/36 (2.8%) | 1 |
| General disorders | ||||||||
| Vomiting | 0/36 (0%) | 0 | 2/36 (5.6%) | 2 | 0/36 (0%) | 0 | 2/36 (5.6%) | 2 |
| Temporary numb sensation in hand | 1/36 (2.8%) | 1 | 0/36 (0%) | 0 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||
| Pain at arterial line site | 0/36 (0%) | 0 | 0/36 (0%) | 0 | 0/36 (0%) | 0 | 1/36 (2.8%) | 1 |
| Renal and urinary disorders | ||||||||
| Urine tract infection | 0/36 (0%) | 0 | 0/36 (0%) | 0 | 1/36 (2.8%) | 1 | 2/36 (5.6%) | 2 |
| Vascular disorders | ||||||||
| Hypotension | 0/36 (0%) | 0 | 0/36 (0%) | 0 | 0/36 (0%) | 0 | 1/36 (2.8%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Vikram Ramakanth |
|---|---|
| Organization | Masimo |
| Phone | |
| clinicalresearchdept@masimo.com |
- STRU0002