Anesthesia
Conditions
Brief summary
To investigate the relationship between BIS™ and inhaled anesthetics across a wide range of anesthetic concentration and hypnotic states, and to provide evidence to support BIS™ performance in use with Isoflurane, Sevoflurane and Desflurane in combination with opioids.
Interventions
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.
Sponsors
Medtronic - MITG
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Intervention model description
Prospective, Randomized study to collect data to evaluate the relationship between BIS and inhaled anesthetics
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy (ASA physical status 1), male or female subjects between the ages of 18 to 60 years; 2. Completion of a health screening for a medical history by a licensed physician, nurse practitioner or physician assistant; 3. Vital signs must be within the following ranges to be included: Vital signs measured sitting after 3 minutes rest; heart rate: 45-90 bpm; systolic blood pressure: 110-140; diastolic blood pressure: 50-90. Out-of-range vital signs may be repeated once. \[Pre-dose vital signs will be assessed by the Principal Investigator or designee (e.g., a medically qualified sub-investigator) before study drug administration. The Principal Investigator or designee will verify the eligibility of each subject with out-of-range vital signs and document approval before dosing\].
Exclusion criteria
1. Has severe contact allergies that may cause a reaction to standard adhesive materials found in pulse oximetry sensors, ECG electrodes, respiration monitor electrodes, or other medical sensors \[self-reported\]; 2. Known neurological disorder (e.g., 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) \[self-reported and assessment by PI or delegate\]; 3. Known cardiovascular disease (e.g., hypertension, coronary artery disease, prior acute myocardial infarction, any valvular and/or myocardial disease involving a decrease in ejection fraction, arrhythmias, which are either symptomatic or require continuous medication/ pacemaker/ automatic internal cardioverter defibrillator), current implanted pacemaker or automatic internal cardioverter defibrillator \[self-reported and assessment by PI or delegate\]; 4. Has a clinically significant abnormal finding on medical history, physical examination, clinical laboratory tests, or ECG at the screening \[self-reported and assessment by PI or delegate\]; 5. Use of psychoactive medication within the past 60 days (e.g., benzodiazepines, antiepileptic drugs, Parkinson's medication, anti-depressant drugs, opioids) \[self-reported and assessment by PI or delegate\]; 6. Subjects with known gastric diseases \[self-reported and assessment by PI or delegate\]; 7. Has a positive urine cotinine test or urine drug screen or oral ethanol test \[Point of Care (POC) testing\]; 8. Known history of allergic or adverse response to drugs to be administered \[self-reported\]; 9. Known history of complications relating to previous general anesthesia or conscious sedation \[self-reported and assessment by PI or delegate\]; 10. Known history of malignant hyperthermia \[self-reported and assessment by PI or delegate\]; 11. Has a room air saturation less than 95% by pulse oximetry \[measurement by PI or delegate\]; 12. Has a clinically significant abnormal pulmonary function test via spirometry \[assessment by PI or delegate\]; 13. Pregnant or lactating women \[assessed by urine test and self-reported\]; 14. Subjects with tattooed skin specific to the sensor placement areas (forehead, fingers, chest) \[self-reported and assessment by PI or delegate\]; 15. The subject must not take any prescription medication, except female hormonal contraceptives or hormone replacement therapy, from 14 days before the dosing until the end-of-study visit without evaluation and approval by the Investigator. Subjects who participated in a previous clinical trial who received a required FDA approved concomitant medication, for example, naltrexone, but were not randomized may be considered for participation in this study if they meet the washout requirement \[assessment by PI or delegate\].
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| BIS 50 | duration of anesthesia administration, up to 2 hours | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| BIS 95 | 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). |
| Prediction Probability (PK) | 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). |
Countries
United States
Participant flow
Recruitment details
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)
Participants by arm
| Arm | Count |
|---|---|
| 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. | 29 |
| 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. | 27 |
| 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. | 29 |
| 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. | 28 |
| 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. | 30 |
| Total | 143 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Randomized with disqualified data | 2 | 0 | 2 | 5 | 3 |
| Overall Study | Training | 2 | 2 | 1 | 2 | 0 |
Baseline characteristics
| Characteristic | Sevoflurane Alone | Total | Isoflurane Group | Desflurane Group | Sevoflurane With Fentanyl Group | Sevoflurane With Remifentanil Group |
|---|---|---|---|---|---|---|
| Age, Continuous | 28.6 years STANDARD_DEVIATION 8.4 | 26.5 years STANDARD_DEVIATION 6.7 | 25.4 years STANDARD_DEVIATION 6.1 | 28.6 years STANDARD_DEVIATION 7.9 | 24.1 years STANDARD_DEVIATION 4.5 | 25.7 years STANDARD_DEVIATION 4.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 27 Participants | 3 Participants | 8 Participants | 5 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 114 Participants | 27 Participants | 20 Participants | 22 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 31 Participants | 6 Participants | 2 Participants | 9 Participants | 9 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 19 Participants | 6 Participants | 2 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 5 Participants | 0 Participants | 3 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 5 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 14 Participants | 80 Participants | 16 Participants | 20 Participants | 16 Participants | 14 Participants |
| Region of Enrollment United States | 29 participants | 143 participants | 30 participants | 28 participants | 29 participants | 27 participants |
| Sex: Female, Male Female | 11 Participants | 69 Participants | 14 Participants | 16 Participants | 13 Participants | 15 Participants |
| Sex: Female, Male Male | 18 Participants | 74 Participants | 16 Participants | 12 Participants | 16 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 33 | 0 / 29 | 0 / 32 | 0 / 35 | 0 / 33 |
| other Total, other adverse events | 13 / 33 | 24 / 29 | 29 / 32 | 14 / 35 | 18 / 33 |
| serious Total, serious adverse events | 0 / 33 | 0 / 29 | 0 / 32 | 0 / 35 | 0 / 33 |
Outcome results
Primary
BIS 50
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).
Time frame: duration of anesthesia administration, up to 2 hours
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Sevoflurane Alone | BIS 50 | 72.3 units on a scale 0-100 |
| Sevoflurane With Remifentanil Group | BIS 50 | 74.2 units on a scale 0-100 |
| Sevoflurane With Fentanyl Group | BIS 50 | 76.2 units on a scale 0-100 |
| Desflurane Group | BIS 50 | 67.5 units on a scale 0-100 |
| Isoflurane Group | BIS 50 | 72.2 units on a scale 0-100 |
Secondary
BIS 95
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).
Time frame: duration of anesthesia administration
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Sevoflurane Alone | BIS 95 | 58.4 units on a scale |
| Sevoflurane With Remifentanil Group | BIS 95 | 62.3 units on a scale |
| Sevoflurane With Fentanyl Group | BIS 95 | 60.6 units on a scale |
| Desflurane Group | BIS 95 | 49.1 units on a scale |
| Isoflurane Group | BIS 95 | 54.8 units on a scale |
Secondary
Prediction Probability (PK)
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).
Time frame: duration of anesthesia administration, up to 2 hours
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Sevoflurane Alone | Prediction Probability (PK) | 0.967 Prediction Probability |
| Sevoflurane With Remifentanil Group | Prediction Probability (PK) | 0.960 Prediction Probability |
| Sevoflurane With Fentanyl Group | Prediction Probability (PK) | 0.945 Prediction Probability |
| Desflurane Group | Prediction Probability (PK) | 0.977 Prediction Probability |
| Isoflurane Group | Prediction Probability (PK) | 0.957 Prediction Probability |