Trial Outcomes & Findings for Improving Information Extraction From EEG on Cerebral Anesthetic Drug Effects (NCT NCT02043938)

NCT ID: NCT02043938

Last Updated: 2018-05-02

Results Overview

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).

Recruitment status

COMPLETED

Study phase

Target enrollment

46 participants

Primary outcome timeframe

6 weeks

Results posted on

2018-05-02

Participant Flow

Participant milestones

Participant milestones
Measure	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).
Overall Study STARTED	46
Overall Study COMPLETED	36
Overall Study NOT COMPLETED	10

Reasons for withdrawal

Reasons for withdrawal
Measure	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).
Overall Study Withdrawal by Subject	7
Overall Study Unable to place EEG sensors on patient	1
Overall Study No show by subject	1
Overall Study Investigator decision	1

Baseline Characteristics

Improving Information Extraction From EEG on Cerebral Anesthetic Drug Effects

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Healthy Volunteers n=36 Participants 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).
Age, Continuous	43.3 years n=5 Participants
Sex: Female, Male Female	20 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants
Region of Enrollment Netherlands	36 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Healthy Volunteers n=36 Participants 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).
Patient State Index (PSI) Comparison, Baseline and Emax No Drugs, PSI-2 (BL)	85.1 index Standard Error 0.8
Patient State Index (PSI) Comparison, Baseline and Emax P, PSI-2 (Emax)	63.1 index Standard Error 1.9
Patient State Index (PSI) Comparison, Baseline and Emax PR, PSI-2 (Emax)	63.1 index Standard Error 1.9
Patient State Index (PSI) Comparison, Baseline and Emax S, PSI-2 (Emax)	67.2 index Standard Error 2.3
Patient State Index (PSI) Comparison, Baseline and Emax SR, PSI-2 (Emax)	67.2 index Standard Error 2.3
Patient State Index (PSI) Comparison, Baseline and Emax No Drugs, PSI-1 (BL)	85.1 index Standard Error 0.8
Patient State Index (PSI) Comparison, Baseline and Emax P, PSI-1 (Emax)	63.1 index Standard Error 1.9
Patient State Index (PSI) Comparison, Baseline and Emax PR, PSI-1 (Emax)	63.1 index Standard Error 1.9
Patient State Index (PSI) Comparison, Baseline and Emax S, PSI-1 (Emax)	0.152 index Standard Error 17.1
Patient State Index (PSI) Comparison, Baseline and Emax SR, PSI-1 (Emax)	0.152 index Standard Error 17.1

OTHER_PRE_SPECIFIED outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Healthy Volunteers n=36 Participants 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).
Patient State Index (PSI) Comparison, C50 (Sevoflurane, Sevoflurane+Remifentanil) S, PSI-2 (C50)	1.22 %vol Standard Error 3.1
Patient State Index (PSI) Comparison, C50 (Sevoflurane, Sevoflurane+Remifentanil) SR, PSI-2 (C50)	1.22 %vol Standard Error 3.1
Patient State Index (PSI) Comparison, C50 (Sevoflurane, Sevoflurane+Remifentanil) S, PSI-1 (C50)	1.22 %vol Standard Error 3.1
Patient State Index (PSI) Comparison, C50 (Sevoflurane, Sevoflurane+Remifentanil) SR, PSI-1 (C50)	1.22 %vol Standard Error 3.1

OTHER_PRE_SPECIFIED outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Healthy Volunteers n=36 Participants 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).
Patient State Index (PSI) Comparison, C50 (Propofol, Propofol+Remifentanil) P, PSI-2 (C50)	1.63 ug/mL Standard Error 3.7
Patient State Index (PSI) Comparison, C50 (Propofol, Propofol+Remifentanil) PR, PSI-2 (C50)	1.63 ug/mL Standard Error 3.7
Patient State Index (PSI) Comparison, C50 (Propofol, Propofol+Remifentanil) P, PSI-1 (C50)	1.63 ug/mL Standard Error 3.7
Patient State Index (PSI) Comparison, C50 (Propofol, Propofol+Remifentanil) PR, PSI-1 (C50)	1.63 ug/mL Standard Error 3.7

OTHER_PRE_SPECIFIED outcome

Timeframe: 6 weeks

Population: 18 participants experienced the remifentanil 2 ng/mL intervention, and 18 participants experienced the remifentanil 4 ng/mL intervention.

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.

Outcome measures

Outcome measures
Measure	Healthy Volunteers n=36 Participants 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).
Propofol, Sevoflurane, and Remifentanil Interaction. Theta1, PSI-2 (P)	0 Index Standard Error 0
Propofol, Sevoflurane, and Remifentanil Interaction. Theta1, PSI-2 (S)	0 Index Standard Error 0
Propofol, Sevoflurane, and Remifentanil Interaction. Theta1, PSI-2 (PR 2ng/mL)	-0.135 Index Standard Error 20.8
Propofol, Sevoflurane, and Remifentanil Interaction. Theta1, PSI-2 (SR 2ng/mL)	-0.135 Index Standard Error 20.8
Propofol, Sevoflurane, and Remifentanil Interaction. Theta1, PSI-1 (P)	0 Index Standard Error 0
Propofol, Sevoflurane, and Remifentanil Interaction. Theta1, PSI-1 (S)	0 Index Standard Error 0
Propofol, Sevoflurane, and Remifentanil Interaction. Theta1, PSI-1 (PR 2ng/mL)	-0.135 Index Standard Error 20.8
Propofol, Sevoflurane, and Remifentanil Interaction. Theta1, PSI-1 (SR 2ng/mL)	-0.135 Index Standard Error 20.8
Propofol, Sevoflurane, and Remifentanil Interaction. Theta2, PSI-2 (P)	0 Index Standard Error 0
Propofol, Sevoflurane, and Remifentanil Interaction. Theta2, PSI-2 (S)	0 Index Standard Error 0
Propofol, Sevoflurane, and Remifentanil Interaction. Theta2, PSI-2 (PR 4ng/mL)	0.816 Index Standard Error 62.3
Propofol, Sevoflurane, and Remifentanil Interaction. Theta2, PSI-2 (SR 4ng/mL)	0.816 Index Standard Error 62.3
Propofol, Sevoflurane, and Remifentanil Interaction. Theta2, PSI-1 (P)	0 Index Standard Error 0
Propofol, Sevoflurane, and Remifentanil Interaction. Theta2, PSI-1 (S)	0 Index Standard Error 0
Propofol, Sevoflurane, and Remifentanil Interaction. Theta2, PSI-1 (PR 4ng/mL)	0.816 Index Standard Error 62.3
Propofol, Sevoflurane, and Remifentanil Interaction. Theta2, PSI-1 (SR 4ng/mL)	0.816 Index Standard Error 62.3

Adverse Events

Healthy Volunteers, Propofol (P)

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Healthy Volunteers, Sevoflurane (S)

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Healthy Volunteers, Propofol With Remifentanil (PR)

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Healthy Volunteers, Sevoflurane With Remifentanil (SR)

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Healthy Volunteers, Propofol (P) n=36 participants at risk 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).	Healthy Volunteers, Sevoflurane (S) n=36 participants at risk 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).	Healthy Volunteers, Propofol With Remifentanil (PR) n=36 participants at risk 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).	Healthy Volunteers, Sevoflurane With Remifentanil (SR) n=36 participants at risk 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).
General disorders Vomiting	0.00% 0/36	5.6% 2/36 • Number of events 2	0.00% 0/36	5.6% 2/36 • Number of events 2
Vascular disorders Hypotension	0.00% 0/36	0.00% 0/36	0.00% 0/36	2.8% 1/36 • Number of events 1
Renal and urinary disorders Urine tract infection	0.00% 0/36	0.00% 0/36	2.8% 1/36 • Number of events 1	5.6% 2/36 • Number of events 2
Injury, poisoning and procedural complications Pain at arterial line site	0.00% 0/36	0.00% 0/36	0.00% 0/36	2.8% 1/36 • Number of events 1
General disorders Temporary numb sensation in hand	2.8% 1/36 • Number of events 1	0.00% 0/36	0.00% 0/36	0.00% 0/36
Cardiac disorders Short phase of nodale ECG rhythm	0.00% 0/36	0.00% 0/36	0.00% 0/36	2.8% 1/36 • Number of events 1

Additional Information

Vikram Ramakanth

Masimo

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60