Trial Outcomes & Findings for Evaluation of Bispectral Index (BIS™) and Levels of Sedation With Common Inhalational Anesthetics in Healthy Volunteers (OLIVER) (NCT NCT04602546)

Last Updated: 2023-04-18

Results Overview

To determine BIS50, the BIS™ value (index score on a scale of 0-100 (0 being dead and 100 being fully awake/responsive) on the BIS™ monitor) at which 50% of patients will be unresponsive at a given drug concentration. Responsiveness is measured using the Modified Observer's Assessment of Alertness and Sedation (MOAAS) a 0-5 scale where 0 represents no response to deep stimulus and 5 represents fully awake).

Recruitment status

COMPLETED

Study phase

Target enrollment

211 participants

Primary outcome timeframe

duration of anesthesia administration, up to 2 hours

Results posted on

2023-04-18

Participant Flow

Subjects without a procedure (n=49) include screen failure (n=14), withdrawal by subject (n=11), informed consent passed 60 day limit (n=18), physician decision (n=1), sponsor request (n=2), and other (n=3)

Participant milestones

Participant milestones
Measure	Sevoflurane Alone Sevoflurane will be administered in steps to achieve a loss of consciousness via a tight-face mask by increasing the end-tidal concentration of Sevoflurane (ETSEVO). Targeted concentration for ETSEVO are 0.25, 0.5, 0.75, 1, 3, 4, 5% or higher until MOAA/S scales at values less than 2 is reached. The equilibration time for each targeted concentration will be approximately 12 minutes to maintain a constant ETSEVO. The BIS™ value, MOAA/S score and picture recall test will be assessed when the patient is awake and at the different ETSEVO concentrations. ETSEVO is decreased by the same steps until consciousness is regained. BIS Complete Monitoring System: The BIS™ EEG complete monitoring system is intended for use under the direct supervision of a licensed healthcare practitioner or by personnel trained in its proper use. The system and its associated parameters are intended for use on adult patients within a hospital or medical facility, providing patient care to monitor the state of the brain by data acquisition of EEG signals.	Sevoflurane With Remifentanil Group Two (2) minutes before starting sevoflurane, to attain an effect-site targeted concentration of remifentanil of 4 ng/ml, an initial IV bolus of remifentanil will be given followed by the start of an infusion. Approximately within 7 minutes, the infusion rate of remifentanil may be adjusted to maintain the effect-site concentration of remifentanil of 4 ng/ml. Sevoflurane will be administered via a tight-face mask in steps to achieve a loss of consciousness by increasing the end-tidal concentration of Sevoflurane (ETSEVO). Targeted concentration for ETSEVO are 0.25, 0.5, 0.75, 1, 3, 4, 5% or higher until an MOAA/S score of less than 2 is reached. ETSEVO is decreased by the same steps until consciousness is regained. BIS Complete Monitoring System: The BIS™ EEG complete monitoring system is intended for use under the direct supervision of a licensed healthcare practitioner or by personnel trained in its proper use. The system and its associated parameters are intended for use on adult patients within a hospital or medical facility, providing patient care to monitor the state of the brain by data acquisition of EEG signals.	Sevoflurane With Fentanyl Group Two (2) minutes before starting sevoflurane, to attain an effect-site targeted concentration of fentanyl of 2 ng/mL, an initial IV bolus of fentanyl will be given followed by the start of an infusion. Approximately within 10 minutes, the infusion rate of fentanyl may be adjusted to maintain the effect-site concentration of fentanyl of 2 ng/ml. Sevoflurane will be administered via a tight-face mask in steps to achieve a loss of consciousness by increasing the end-tidal concentration of Sevoflurane (ETSEVO). Targeted concentration for ETSEVO are 0.25, 0.5, 0.75, 1, 3, 4, 5% or higher until an MOAA/S score of equal to or less than 2 is reached. ETSEVO is decreased by the same steps until consciousness is regained. BIS Complete Monitoring System: The BIS™ EEG complete monitoring system is intended for use under the direct supervision of a licensed healthcare practitioner or by personnel trained in its proper use. The system and its associated parameters are intended for use on adult patients within a hospital or medical facility, providing patient care to monitor the state of the brain by data acquisition of EEG signals.	Desflurane Group Due to desflurane being a volatile agent and not well tolerated as an induction agent, an initial IV bolus of 1% propofol provided at 2mg/kg, with supplemental boluses given at the investigators discretion in order to achieve LMA insertion, will be administered 15-20 minutes prior to desflurane. Once correct LMA placement has been confirmed, there will be an equilibrium time of approximately 15-20 minutes to allow the effect site concentration of propofol to reach a level consistent with a pharmacodynamic effect of consciousness as measured by a MOAA/S score of 2 or 3. Desflurane will then be administered via a tight-face mask at the targeted end-tidal concentration (ETDES) of 2, 5, 7, 8, 9, 10 %, or higher until an MOAA/S score of less than 2 is reached. The BIS™ value will be correlated with desflurane ETDES concentration. ETDES is decreased by the same steps until consciousness is regained. BIS Complete Monitoring System: The BIS™ EEG complete monitoring system is intended for use under the direct supervision of a licensed healthcare practitioner or by personnel trained in its proper use. The system and its associated parameters are intended for use on adult patients within a hospital or medical facility, providing patient care to monitor the state of the brain by data acquisition of EEG signals.	Isoflurane Group Due to isoflurane being a volatile agent and not well tolerated as an induction agent, an initial IV bolus of 1% propofol provided at 2mg/kg, with supplemental boluses given at the investigators discretion in order to achieve LMA insertion, will be administered 15-20 minutes prior to isoflurane.Isoflurane will be administered via a tight-face mask in steps to achieve a loss of consciousness (MOAA/S of 0,1) by increasing the end-tidal concentration of Isoflurane (ETISO). Targeted concentration for ETISO are 0.25, 0.5, 0.75, 1, 1.5% or higher until MOAA/S scales at values less than 2 is reached. The BIS™ value will be correlated with desflurane ETISO concentration. ETISO is decreased by the same steps until consciousness is regained. BIS Complete Monitoring System: The BIS™ EEG complete monitoring system is intended for use under the direct supervision of a licensed healthcare practitioner or by personnel trained in its proper use. The system and its associated parameters are intended for use on adult patients within a hospital or medical facility, providing patient care to monitor the state of the brain by data acquisition of EEG signals.
Overall Study STARTED	33	29	32	35	33
Overall Study COMPLETED	29	27	29	28	30
Overall Study NOT COMPLETED	4	2	3	7	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Sevoflurane Alone Sevoflurane will be administered in steps to achieve a loss of consciousness via a tight-face mask by increasing the end-tidal concentration of Sevoflurane (ETSEVO). Targeted concentration for ETSEVO are 0.25, 0.5, 0.75, 1, 3, 4, 5% or higher until MOAA/S scales at values less than 2 is reached. The equilibration time for each targeted concentration will be approximately 12 minutes to maintain a constant ETSEVO. The BIS™ value, MOAA/S score and picture recall test will be assessed when the patient is awake and at the different ETSEVO concentrations. ETSEVO is decreased by the same steps until consciousness is regained. BIS Complete Monitoring System: The BIS™ EEG complete monitoring system is intended for use under the direct supervision of a licensed healthcare practitioner or by personnel trained in its proper use. The system and its associated parameters are intended for use on adult patients within a hospital or medical facility, providing patient care to monitor the state of the brain by data acquisition of EEG signals.	Sevoflurane With Remifentanil Group Two (2) minutes before starting sevoflurane, to attain an effect-site targeted concentration of remifentanil of 4 ng/ml, an initial IV bolus of remifentanil will be given followed by the start of an infusion. Approximately within 7 minutes, the infusion rate of remifentanil may be adjusted to maintain the effect-site concentration of remifentanil of 4 ng/ml. Sevoflurane will be administered via a tight-face mask in steps to achieve a loss of consciousness by increasing the end-tidal concentration of Sevoflurane (ETSEVO). Targeted concentration for ETSEVO are 0.25, 0.5, 0.75, 1, 3, 4, 5% or higher until an MOAA/S score of less than 2 is reached. ETSEVO is decreased by the same steps until consciousness is regained. BIS Complete Monitoring System: The BIS™ EEG complete monitoring system is intended for use under the direct supervision of a licensed healthcare practitioner or by personnel trained in its proper use. The system and its associated parameters are intended for use on adult patients within a hospital or medical facility, providing patient care to monitor the state of the brain by data acquisition of EEG signals.	Sevoflurane With Fentanyl Group Two (2) minutes before starting sevoflurane, to attain an effect-site targeted concentration of fentanyl of 2 ng/mL, an initial IV bolus of fentanyl will be given followed by the start of an infusion. Approximately within 10 minutes, the infusion rate of fentanyl may be adjusted to maintain the effect-site concentration of fentanyl of 2 ng/ml. Sevoflurane will be administered via a tight-face mask in steps to achieve a loss of consciousness by increasing the end-tidal concentration of Sevoflurane (ETSEVO). Targeted concentration for ETSEVO are 0.25, 0.5, 0.75, 1, 3, 4, 5% or higher until an MOAA/S score of equal to or less than 2 is reached. ETSEVO is decreased by the same steps until consciousness is regained. BIS Complete Monitoring System: The BIS™ EEG complete monitoring system is intended for use under the direct supervision of a licensed healthcare practitioner or by personnel trained in its proper use. The system and its associated parameters are intended for use on adult patients within a hospital or medical facility, providing patient care to monitor the state of the brain by data acquisition of EEG signals.	Desflurane Group Due to desflurane being a volatile agent and not well tolerated as an induction agent, an initial IV bolus of 1% propofol provided at 2mg/kg, with supplemental boluses given at the investigators discretion in order to achieve LMA insertion, will be administered 15-20 minutes prior to desflurane. Once correct LMA placement has been confirmed, there will be an equilibrium time of approximately 15-20 minutes to allow the effect site concentration of propofol to reach a level consistent with a pharmacodynamic effect of consciousness as measured by a MOAA/S score of 2 or 3. Desflurane will then be administered via a tight-face mask at the targeted end-tidal concentration (ETDES) of 2, 5, 7, 8, 9, 10 %, or higher until an MOAA/S score of less than 2 is reached. The BIS™ value will be correlated with desflurane ETDES concentration. ETDES is decreased by the same steps until consciousness is regained. BIS Complete Monitoring System: The BIS™ EEG complete monitoring system is intended for use under the direct supervision of a licensed healthcare practitioner or by personnel trained in its proper use. The system and its associated parameters are intended for use on adult patients within a hospital or medical facility, providing patient care to monitor the state of the brain by data acquisition of EEG signals.	Isoflurane Group Due to isoflurane being a volatile agent and not well tolerated as an induction agent, an initial IV bolus of 1% propofol provided at 2mg/kg, with supplemental boluses given at the investigators discretion in order to achieve LMA insertion, will be administered 15-20 minutes prior to isoflurane.Isoflurane will be administered via a tight-face mask in steps to achieve a loss of consciousness (MOAA/S of 0,1) by increasing the end-tidal concentration of Isoflurane (ETISO). Targeted concentration for ETISO are 0.25, 0.5, 0.75, 1, 1.5% or higher until MOAA/S scales at values less than 2 is reached. The BIS™ value will be correlated with desflurane ETISO concentration. ETISO is decreased by the same steps until consciousness is regained. BIS Complete Monitoring System: The BIS™ EEG complete monitoring system is intended for use under the direct supervision of a licensed healthcare practitioner or by personnel trained in its proper use. The system and its associated parameters are intended for use on adult patients within a hospital or medical facility, providing patient care to monitor the state of the brain by data acquisition of EEG signals.
Overall Study Training	2	2	1	2	0
Overall Study Randomized with disqualified data	2	0	2	5	3

Baseline Characteristics

Evaluation of Bispectral Index (BIS™) and Levels of Sedation With Common Inhalational Anesthetics in Healthy Volunteers (OLIVER)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sevoflurane Alone n=29 Participants Sevoflurane will be administered in steps to achieve a loss of consciousness via a tight-face mask by increasing the end-tidal concentration of Sevoflurane (ETSEVO). Targeted concentration for ETSEVO are 0.25, 0.5, 0.75, 1, 3, 4, 5% or higher until MOAA/S scales at values less than 2 is reached. The equilibration time for each targeted concentration will be approximately 12 minutes to maintain a constant ETSEVO. The BIS™ value, MOAA/S score and picture recall test will be assessed when the patient is awake and at the different ETSEVO concentrations. ETSEVO is decreased by the same steps until consciousness is regained. BIS Complete Monitoring System: The BIS™ EEG complete monitoring system is intended for use under the direct supervision of a licensed healthcare practitioner or by personnel trained in its proper use. The system and its associated parameters are intended for use on adult patients within a hospital or medical facility, providing patient care to monitor the state of the brain by data acquisition of EEG signals.	Sevoflurane With Remifentanil Group n=27 Participants Two (2) minutes before starting sevoflurane, to attain an effect-site targeted concentration of remifentanil of 4 ng/ml, an initial IV bolus of remifentanil will be given followed by the start of an infusion. Approximately within 7 minutes, the infusion rate of remifentanil may be adjusted to maintain the effect-site concentration of remifentanil of 4 ng/ml. Sevoflurane will be administered via a tight-face mask in steps to achieve a loss of consciousness by increasing the end-tidal concentration of Sevoflurane (ETSEVO). Targeted concentration for ETSEVO are 0.25, 0.5, 0.75, 1, 3, 4, 5% or higher until an MOAA/S score of less than 2 is reached. ETSEVO is decreased by the same steps until consciousness is regained. BIS Complete Monitoring System: The BIS™ EEG complete monitoring system is intended for use under the direct supervision of a licensed healthcare practitioner or by personnel trained in its proper use. The system and its associated parameters are intended for use on adult patients within a hospital or medical facility, providing patient care to monitor the state of the brain by data acquisition of EEG signals.	Sevoflurane With Fentanyl Group n=29 Participants Two (2) minutes before starting sevoflurane, to attain an effect-site targeted concentration of fentanyl of 2 ng/mL, an initial IV bolus of fentanyl will be given followed by the start of an infusion. Approximately within 10 minutes, the infusion rate of fentanyl may be adjusted to maintain the effect-site concentration of fentanyl of 2 ng/ml. Sevoflurane will be administered via a tight-face mask in steps to achieve a loss of consciousness by increasing the end-tidal concentration of Sevoflurane (ETSEVO). Targeted concentration for ETSEVO are 0.25, 0.5, 0.75, 1, 3, 4, 5% or higher until an MOAA/S score of equal to or less than 2 is reached. ETSEVO is decreased by the same steps until consciousness is regained. BIS Complete Monitoring System: The BIS™ EEG complete monitoring system is intended for use under the direct supervision of a licensed healthcare practitioner or by personnel trained in its proper use. The system and its associated parameters are intended for use on adult patients within a hospital or medical facility, providing patient care to monitor the state of the brain by data acquisition of EEG signals.	Desflurane Group n=28 Participants Due to desflurane being a volatile agent and not well tolerated as an induction agent, an initial IV bolus of 1% propofol provided at 2mg/kg, with supplemental boluses given at the investigators discretion in order to achieve LMA insertion, will be administered 15-20 minutes prior to desflurane. Once correct LMA placement has been confirmed, there will be an equilibrium time of approximately 15-20 minutes to allow the effect site concentration of propofol to reach a level consistent with a pharmacodynamic effect of consciousness as measured by a MOAA/S score of 2 or 3. Desflurane will then be administered via a tight-face mask at the targeted end-tidal concentration (ETDES) of 2, 5, 7, 8, 9, 10 %, or higher until an MOAA/S score of less than 2 is reached. The BIS™ value will be correlated with desflurane ETDES concentration. ETDES is decreased by the same steps until consciousness is regained. BIS Complete Monitoring System: The BIS™ EEG complete monitoring system is intended for use under the direct supervision of a licensed healthcare practitioner or by personnel trained in its proper use. The system and its associated parameters are intended for use on adult patients within a hospital or medical facility, providing patient care to monitor the state of the brain by data acquisition of EEG signals.	Isoflurane Group n=30 Participants Due to isoflurane being a volatile agent and not well tolerated as an induction agent, an initial IV bolus of 1% propofol provided at 2mg/kg, with supplemental boluses given at the investigators discretion in order to achieve LMA insertion, will be administered 15-20 minutes prior to isoflurane.Isoflurane will be administered via a tight-face mask in steps to achieve a loss of consciousness (MOAA/S of 0,1) by increasing the end-tidal concentration of Isoflurane (ETISO). Targeted concentration for ETISO are 0.25, 0.5, 0.75, 1, 1.5% or higher until MOAA/S scales at values less than 2 is reached. The BIS™ value will be correlated with desflurane ETISO concentration. ETISO is decreased by the same steps until consciousness is regained. BIS Complete Monitoring System: The BIS™ EEG complete monitoring system is intended for use under the direct supervision of a licensed healthcare practitioner or by personnel trained in its proper use. The system and its associated parameters are intended for use on adult patients within a hospital or medical facility, providing patient care to monitor the state of the brain by data acquisition of EEG signals.	Total n=143 Participants Total of all reporting groups
Age, Continuous	28.6 years STANDARD_DEVIATION 8.4 • n=5 Participants	25.7 years STANDARD_DEVIATION 4.6 • n=7 Participants	24.1 years STANDARD_DEVIATION 4.5 • n=5 Participants	28.6 years STANDARD_DEVIATION 7.9 • n=4 Participants	25.4 years STANDARD_DEVIATION 6.1 • n=21 Participants	26.5 years STANDARD_DEVIATION 6.7 • n=10 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	15 Participants n=7 Participants	13 Participants n=5 Participants	16 Participants n=4 Participants	14 Participants n=21 Participants	69 Participants n=10 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	12 Participants n=7 Participants	16 Participants n=5 Participants	12 Participants n=4 Participants	16 Participants n=21 Participants	74 Participants n=10 Participants
Race (NIH/OMB) Asian	5 Participants n=5 Participants	9 Participants n=7 Participants	9 Participants n=5 Participants	2 Participants n=4 Participants	6 Participants n=21 Participants	31 Participants n=10 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants	6 Participants n=7 Participants	5 Participants n=5 Participants	8 Participants n=4 Participants	3 Participants n=21 Participants	27 Participants n=10 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	24 Participants n=5 Participants	21 Participants n=7 Participants	22 Participants n=5 Participants	20 Participants n=4 Participants	27 Participants n=21 Participants	114 Participants n=10 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	2 Participants n=10 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	3 Participants n=10 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Black or African American	7 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	6 Participants n=21 Participants	19 Participants n=10 Participants
Race (NIH/OMB) White	14 Participants n=5 Participants	14 Participants n=7 Participants	16 Participants n=5 Participants	20 Participants n=4 Participants	16 Participants n=21 Participants	80 Participants n=10 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants	0 Participants n=21 Participants	5 Participants n=10 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants	5 Participants n=10 Participants
Region of Enrollment United States	29 participants n=5 Participants	27 participants n=7 Participants	29 participants n=5 Participants	28 participants n=4 Participants	30 participants n=21 Participants	143 participants n=10 Participants

PRIMARY outcome

Timeframe: duration of anesthesia administration, up to 2 hours

Outcome measures

Outcome measures
Measure	Sevoflurane Alone n=29 Participants Sevoflurane will be administered in steps to achieve a loss of consciousness via a tight-face mask by increasing the end-tidal concentration of Sevoflurane (ETSEVO). Targeted concentration for ETSEVO are 0.25, 0.5, 0.75, 1, 3, 4, 5% or higher until MOAA/S scales at values less than 2 is reached. The equilibration time for each targeted concentration will be approximately 12 minutes to maintain a constant ETSEVO. The BIS™ value, MOAA/S score and picture recall test will be assessed when the patient is awake and at the different ETSEVO concentrations. ETSEVO is decreased by the same steps until consciousness is regained. BIS Complete Monitoring System: The BIS™ EEG complete monitoring system is intended for use under the direct supervision of a licensed healthcare practitioner or by personnel trained in its proper use. The system and its associated parameters are intended for use on adult patients within a hospital or medical facility, providing patient care to monitor the state of the brain by data acquisition of EEG signals.	Sevoflurane With Remifentanil Group n=27 Participants Two (2) minutes before starting sevoflurane, to attain an effect-site targeted concentration of remifentanil of 4 ng/ml, an initial IV bolus of remifentanil will be given followed by the start of an infusion. Approximately within 7 minutes, the infusion rate of remifentanil may be adjusted to maintain the effect-site concentration of remifentanil of 4 ng/ml. Sevoflurane will be administered via a tight-face mask in steps to achieve a loss of consciousness by increasing the end-tidal concentration of Sevoflurane (ETSEVO). Targeted concentration for ETSEVO are 0.25, 0.5, 0.75, 1, 3, 4, 5% or higher until an MOAA/S score of less than 2 is reached. ETSEVO is decreased by the same steps until consciousness is regained. BIS Complete Monitoring System: The BIS™ EEG complete monitoring system is intended for use under the direct supervision of a licensed healthcare practitioner or by personnel trained in its proper use. The system and its associated parameters are intended for use on adult patients within a hospital or medical facility, providing patient care to monitor the state of the brain by data acquisition of EEG signals.	Sevoflurane With Fentanyl Group n=29 Participants Two (2) minutes before starting sevoflurane, to attain an effect-site targeted concentration of fentanyl of 2 ng/mL, an initial IV bolus of fentanyl will be given followed by the start of an infusion. Approximately within 10 minutes, the infusion rate of fentanyl may be adjusted to maintain the effect-site concentration of fentanyl of 2 ng/ml. Sevoflurane will be administered via a tight-face mask in steps to achieve a loss of consciousness by increasing the end-tidal concentration of Sevoflurane (ETSEVO). Targeted concentration for ETSEVO are 0.25, 0.5, 0.75, 1, 3, 4, 5% or higher until an MOAA/S score of equal to or less than 2 is reached. ETSEVO is decreased by the same steps until consciousness is regained. BIS Complete Monitoring System: The BIS™ EEG complete monitoring system is intended for use under the direct supervision of a licensed healthcare practitioner or by personnel trained in its proper use. The system and its associated parameters are intended for use on adult patients within a hospital or medical facility, providing patient care to monitor the state of the brain by data acquisition of EEG signals.	Desflurane Group n=28 Participants Due to desflurane being a volatile agent and not well tolerated as an induction agent, an initial IV bolus of 1% propofol provided at 2mg/kg, with supplemental boluses given at the investigators discretion in order to achieve LMA insertion, will be administered 15-20 minutes prior to desflurane. Once correct LMA placement has been confirmed, there will be an equilibrium time of approximately 15-20 minutes to allow the effect site concentration of propofol to reach a level consistent with a pharmacodynamic effect of consciousness as measured by a MOAA/S score of 2 or 3. Desflurane will then be administered via a tight-face mask at the targeted end-tidal concentration (ETDES) of 2, 5, 7, 8, 9, 10 %, or higher until an MOAA/S score of less than 2 is reached. The BIS™ value will be correlated with desflurane ETDES concentration. ETDES is decreased by the same steps until consciousness is regained. BIS Complete Monitoring System: The BIS™ EEG complete monitoring system is intended for use under the direct supervision of a licensed healthcare practitioner or by personnel trained in its proper use. The system and its associated parameters are intended for use on adult patients within a hospital or medical facility, providing patient care to monitor the state of the brain by data acquisition of EEG signals.	Isoflurane Group n=30 Participants Due to isoflurane being a volatile agent and not well tolerated as an induction agent, an initial IV bolus of 1% propofol provided at 2mg/kg, with supplemental boluses given at the investigators discretion in order to achieve LMA insertion, will be administered 15-20 minutes prior to isoflurane.Isoflurane will be administered via a tight-face mask in steps to achieve a loss of consciousness (MOAA/S of 0,1) by increasing the end-tidal concentration of Isoflurane (ETISO). Targeted concentration for ETISO are 0.25, 0.5, 0.75, 1, 1.5% or higher until MOAA/S scales at values less than 2 is reached. The BIS™ value will be correlated with desflurane ETISO concentration. ETISO is decreased by the same steps until consciousness is regained. BIS Complete Monitoring System: The BIS™ EEG complete monitoring system is intended for use under the direct supervision of a licensed healthcare practitioner or by personnel trained in its proper use. The system and its associated parameters are intended for use on adult patients within a hospital or medical facility, providing patient care to monitor the state of the brain by data acquisition of EEG signals.
BIS 50	72.3 units on a scale 0-100 Interval 70.1 to 74.3	74.2 units on a scale 0-100 Interval 72.6 to 75.7	76.2 units on a scale 0-100 Interval 74.3 to 78.0	67.5 units on a scale 0-100 Interval 63.5 to 71.7	72.2 units on a scale 0-100 Interval 69.5 to 74.8

SECONDARY outcome

Timeframe: duration of anesthesia administration

To determine BIS95, the BIS™ value (index score on a scale of 0-100 (0 being dead and 100 being fully awake/responsive) on the BIS™ monitor) at which 95% of patients will be unresponsive at a given drug concentration. Responsiveness is measured using the Modified Observer's Assessment of Alertness and Sedation (MOAAS) a 0-5 scale where 0 represents no response to deep stimulus and 5 represents fully awake).

Outcome measures

Outcome measures
Measure	Sevoflurane Alone n=29 Participants Sevoflurane will be administered in steps to achieve a loss of consciousness via a tight-face mask by increasing the end-tidal concentration of Sevoflurane (ETSEVO). Targeted concentration for ETSEVO are 0.25, 0.5, 0.75, 1, 3, 4, 5% or higher until MOAA/S scales at values less than 2 is reached. The equilibration time for each targeted concentration will be approximately 12 minutes to maintain a constant ETSEVO. The BIS™ value, MOAA/S score and picture recall test will be assessed when the patient is awake and at the different ETSEVO concentrations. ETSEVO is decreased by the same steps until consciousness is regained. BIS Complete Monitoring System: The BIS™ EEG complete monitoring system is intended for use under the direct supervision of a licensed healthcare practitioner or by personnel trained in its proper use. The system and its associated parameters are intended for use on adult patients within a hospital or medical facility, providing patient care to monitor the state of the brain by data acquisition of EEG signals.	Sevoflurane With Remifentanil Group n=27 Participants Two (2) minutes before starting sevoflurane, to attain an effect-site targeted concentration of remifentanil of 4 ng/ml, an initial IV bolus of remifentanil will be given followed by the start of an infusion. Approximately within 7 minutes, the infusion rate of remifentanil may be adjusted to maintain the effect-site concentration of remifentanil of 4 ng/ml. Sevoflurane will be administered via a tight-face mask in steps to achieve a loss of consciousness by increasing the end-tidal concentration of Sevoflurane (ETSEVO). Targeted concentration for ETSEVO are 0.25, 0.5, 0.75, 1, 3, 4, 5% or higher until an MOAA/S score of less than 2 is reached. ETSEVO is decreased by the same steps until consciousness is regained. BIS Complete Monitoring System: The BIS™ EEG complete monitoring system is intended for use under the direct supervision of a licensed healthcare practitioner or by personnel trained in its proper use. The system and its associated parameters are intended for use on adult patients within a hospital or medical facility, providing patient care to monitor the state of the brain by data acquisition of EEG signals.	Sevoflurane With Fentanyl Group n=29 Participants Two (2) minutes before starting sevoflurane, to attain an effect-site targeted concentration of fentanyl of 2 ng/mL, an initial IV bolus of fentanyl will be given followed by the start of an infusion. Approximately within 10 minutes, the infusion rate of fentanyl may be adjusted to maintain the effect-site concentration of fentanyl of 2 ng/ml. Sevoflurane will be administered via a tight-face mask in steps to achieve a loss of consciousness by increasing the end-tidal concentration of Sevoflurane (ETSEVO). Targeted concentration for ETSEVO are 0.25, 0.5, 0.75, 1, 3, 4, 5% or higher until an MOAA/S score of equal to or less than 2 is reached. ETSEVO is decreased by the same steps until consciousness is regained. BIS Complete Monitoring System: The BIS™ EEG complete monitoring system is intended for use under the direct supervision of a licensed healthcare practitioner or by personnel trained in its proper use. The system and its associated parameters are intended for use on adult patients within a hospital or medical facility, providing patient care to monitor the state of the brain by data acquisition of EEG signals.	Desflurane Group n=28 Participants Due to desflurane being a volatile agent and not well tolerated as an induction agent, an initial IV bolus of 1% propofol provided at 2mg/kg, with supplemental boluses given at the investigators discretion in order to achieve LMA insertion, will be administered 15-20 minutes prior to desflurane. Once correct LMA placement has been confirmed, there will be an equilibrium time of approximately 15-20 minutes to allow the effect site concentration of propofol to reach a level consistent with a pharmacodynamic effect of consciousness as measured by a MOAA/S score of 2 or 3. Desflurane will then be administered via a tight-face mask at the targeted end-tidal concentration (ETDES) of 2, 5, 7, 8, 9, 10 %, or higher until an MOAA/S score of less than 2 is reached. The BIS™ value will be correlated with desflurane ETDES concentration. ETDES is decreased by the same steps until consciousness is regained. BIS Complete Monitoring System: The BIS™ EEG complete monitoring system is intended for use under the direct supervision of a licensed healthcare practitioner or by personnel trained in its proper use. The system and its associated parameters are intended for use on adult patients within a hospital or medical facility, providing patient care to monitor the state of the brain by data acquisition of EEG signals.	Isoflurane Group n=30 Participants Due to isoflurane being a volatile agent and not well tolerated as an induction agent, an initial IV bolus of 1% propofol provided at 2mg/kg, with supplemental boluses given at the investigators discretion in order to achieve LMA insertion, will be administered 15-20 minutes prior to isoflurane.Isoflurane will be administered via a tight-face mask in steps to achieve a loss of consciousness (MOAA/S of 0,1) by increasing the end-tidal concentration of Isoflurane (ETISO). Targeted concentration for ETISO are 0.25, 0.5, 0.75, 1, 1.5% or higher until MOAA/S scales at values less than 2 is reached. The BIS™ value will be correlated with desflurane ETISO concentration. ETISO is decreased by the same steps until consciousness is regained. BIS Complete Monitoring System: The BIS™ EEG complete monitoring system is intended for use under the direct supervision of a licensed healthcare practitioner or by personnel trained in its proper use. The system and its associated parameters are intended for use on adult patients within a hospital or medical facility, providing patient care to monitor the state of the brain by data acquisition of EEG signals.
BIS 95	58.4 units on a scale Interval 52.9 to 61.9	62.3 units on a scale Interval 58.5 to 64.9	60.6 units on a scale Interval 55.8 to 63.9	49.1 units on a scale Interval 41.0 to 54.3	54.8 units on a scale Interval 48.2 to 59.2

SECONDARY outcome

Timeframe: duration of anesthesia administration, up to 2 hours

To determine if the value on the BIS™ monitor (index score on a scale of 0-100 (0 being dead and 100 being fully awake/responsive) on the BIS™ monitor) can predict the subject's responsiveness at a given drug concentration. Responsiveness is measured using the Modified Observer's Assessment of Alertness and Sedation (MOAAS) a 0-5 scale where 0 represents no response to deep stimulus and 5 represents fully awake).