Trial Outcomes & Findings for Characterizing the Electroencephalogram Signature of Fentanyl During Induction of General Anesthesia (NCT NCT03866278)

Last Updated: 2023-12-18

Results Overview

We estimated the fentanyl effect site concentration (ESC) in (nanograms/mL) using pharmacokinetic/pharmacodynamic (PK/PD) modeling implemented in StanpumpR. We estimated EEG power using multitaper spectral analysis and calculated the power in decibels (dB) within the theta band (4 - 8 Hz). To quantify the relationship between the EEG and fentanyl concentration, we constructed a linear mixed-effects model representing fentanyl concentration as a function of theta power.

Recruitment status

COMPLETED

Target enrollment

31 participants

Primary outcome timeframe

Twenty minutes prior to surgery

Results posted on

2023-12-18

Participant Flow

Participant milestones

Participant milestones
Measure	Study Group Only arm of the study. Subjects received an anesthetic dose of fentanyl during induction to general anesthesia while having vitals and frontal electroencephalogram monitored.
Overall Study STARTED	31
Overall Study COMPLETED	28
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Two subjects were not studied because of scheduling conflicts, and one further was not studied due to withdrawal of consent. There were technical problems in three additional subjects that led to data loss: In one subject, we were unable to record the respiratory signals; in another, we were unable to obtain the behavioral responses; and in yet another, the EEG signal was too noisy to analyze.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Study Group n=25 Participants Only arm of the study. Subjects received an anesthetic dose of fentanyl during induction to general anesthesia while having vitals and frontal electroencephalogram monitored.
Age, Continuous	54 years STANDARD_DEVIATION 10.1 • n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants • Two subjects were not studied because of scheduling conflicts, and one further was not studied due to withdrawal of consent. There were technical problems in three additional subjects that led to data loss: In one subject, we were unable to record the respiratory signals; in another, we were unable to obtain the behavioral responses; and in yet another, the EEG signal was too noisy to analyze.
Sex: Female, Male Male	13 Participants n=5 Participants • Two subjects were not studied because of scheduling conflicts, and one further was not studied due to withdrawal of consent. There were technical problems in three additional subjects that led to data loss: In one subject, we were unable to record the respiratory signals; in another, we were unable to obtain the behavioral responses; and in yet another, the EEG signal was too noisy to analyze.
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants • Two subjects were not studied because of scheduling conflicts, and one further was not studied due to withdrawal of consent. There were technical problems in three additional subjects that led to data loss: In one subject, we were unable to record the respiratory signals; in another, we were unable to obtain the behavioral responses; and in yet another, the EEG signal was too noisy to analyze.
Ethnicity (NIH/OMB) Not Hispanic or Latino	22 Participants n=5 Participants • Two subjects were not studied because of scheduling conflicts, and one further was not studied due to withdrawal of consent. There were technical problems in three additional subjects that led to data loss: In one subject, we were unable to record the respiratory signals; in another, we were unable to obtain the behavioral responses; and in yet another, the EEG signal was too noisy to analyze.
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants • Two subjects were not studied because of scheduling conflicts, and one further was not studied due to withdrawal of consent. There were technical problems in three additional subjects that led to data loss: In one subject, we were unable to record the respiratory signals; in another, we were unable to obtain the behavioral responses; and in yet another, the EEG signal was too noisy to analyze.
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants • Two subjects were not studied because of scheduling conflicts, and one further was not studied due to withdrawal of consent. There were technical problems in three additional subjects that led to data loss: In one subject, we were unable to record the respiratory signals; in another, we were unable to obtain the behavioral responses; and in yet another, the EEG signal was too noisy to analyze.
Race (NIH/OMB) Asian	1 Participants n=5 Participants • Two subjects were not studied because of scheduling conflicts, and one further was not studied due to withdrawal of consent. There were technical problems in three additional subjects that led to data loss: In one subject, we were unable to record the respiratory signals; in another, we were unable to obtain the behavioral responses; and in yet another, the EEG signal was too noisy to analyze.
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants • Two subjects were not studied because of scheduling conflicts, and one further was not studied due to withdrawal of consent. There were technical problems in three additional subjects that led to data loss: In one subject, we were unable to record the respiratory signals; in another, we were unable to obtain the behavioral responses; and in yet another, the EEG signal was too noisy to analyze.
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants • Two subjects were not studied because of scheduling conflicts, and one further was not studied due to withdrawal of consent. There were technical problems in three additional subjects that led to data loss: In one subject, we were unable to record the respiratory signals; in another, we were unable to obtain the behavioral responses; and in yet another, the EEG signal was too noisy to analyze.
Race (NIH/OMB) White	23 Participants n=5 Participants • Two subjects were not studied because of scheduling conflicts, and one further was not studied due to withdrawal of consent. There were technical problems in three additional subjects that led to data loss: In one subject, we were unable to record the respiratory signals; in another, we were unable to obtain the behavioral responses; and in yet another, the EEG signal was too noisy to analyze.
Race (NIH/OMB) More than one race	0 Participants n=5 Participants • Two subjects were not studied because of scheduling conflicts, and one further was not studied due to withdrawal of consent. There were technical problems in three additional subjects that led to data loss: In one subject, we were unable to record the respiratory signals; in another, we were unable to obtain the behavioral responses; and in yet another, the EEG signal was too noisy to analyze.
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants • Two subjects were not studied because of scheduling conflicts, and one further was not studied due to withdrawal of consent. There were technical problems in three additional subjects that led to data loss: In one subject, we were unable to record the respiratory signals; in another, we were unable to obtain the behavioral responses; and in yet another, the EEG signal was too noisy to analyze.
Region of Enrollment United States	25 participants n=5 Participants • Two subjects were not studied because of scheduling conflicts, and one further was not studied due to withdrawal of consent. There were technical problems in three additional subjects that led to data loss: In one subject, we were unable to record the respiratory signals; in another, we were unable to obtain the behavioral responses; and in yet another, the EEG signal was too noisy to analyze.

PRIMARY outcome

Timeframe: Twenty minutes prior to surgery

Outcome measures

Outcome measures
Measure	Study Group n=25 Participants Only arm of the study. Subjects received an anesthetic dose of fentanyl during induction to general anesthesia while having vitals and frontal electroencephalogram monitored.
Slope of EEG Theta Band Power Over Fentanyl Effect Site Concentration (dB/ng/mL)	0.55 dB / nano gram / mL Interval 0.25 to 0.8

PRIMARY outcome

Timeframe: Twenty minutes prior to surgery

Minute ventilation is a physiological term that refers to the total volume of air a person breathes in and out of their lungs in one minute. To calculate this we measured the chest and abdominal expansion and contraction and estimated the instantaneous frequency and instantaneous amplitude. This measure is relative to a baseline minute ventilation defined as "tidal volume" and is therefore a dimensionless number between 0 and 1 where 1 is equivalent to the baseline tidal volume. We estimated the EEG power in decibels (dB) within the theta band range (4-8 Hz). To characterize the relationship between "theta band power" and respiratory changes (Minute Ventilation Index) we constructed a mixed-effects model.

Outcome measures

Outcome measures
Measure	Study Group n=25 Participants Only arm of the study. Subjects received an anesthetic dose of fentanyl during induction to general anesthesia while having vitals and frontal electroencephalogram monitored.
Slope of Minute Ventilation Index Over Theta Band Power (Index/dB)	-1.62 index/dB Interval -2.51 to 0.73

PRIMARY outcome

Timeframe: Twenty minutes prior to surgery

We measured the response time to auditory stimuli in milliseconds. We measured the changes in Minute Ventilation by estimating the instantaneous frequency and instantaneous amplitude of respiratory inductance bands. This measure is relative to a baseline minute ventilation defined as "tidal volume" and is therefore a dimensionless number between 0 and 1 where 1 is equivalent to the baseline tidal volume. We used a linear mixed-effects models to characterize reaction time as a function of minute ventilation index.

Outcome measures

Outcome measures
Measure	Study Group n=25 Participants Only arm of the study. Subjects received an anesthetic dose of fentanyl during induction to general anesthesia while having vitals and frontal electroencephalogram monitored.
Slope of Response Time Over Minute Ventilation Index (Milliseconds/Index)	-1.94 milliseconds/index

PRIMARY outcome

Timeframe: Twenty minutes before the surgery.

We measured the response time to auditory stimuli in milliseconds. We estimated EEG power using multitaper spectral analysis and calculated the power in decibels (dB) within the theta band (4 - 8 Hz).

Outcome measures

Outcome measures
Measure	Study Group n=25 Participants Only arm of the study. Subjects received an anesthetic dose of fentanyl during induction to general anesthesia while having vitals and frontal electroencephalogram monitored.
Changes in Reaction Time as a Function of Theta Power.	30.11 milliseconds/decibels

Adverse Events

Study Group

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Study Group n=28 participants at risk Only arm of the study. Subjects received an anesthetic dose of fentanyl during induction to general anesthesia while having vitals and frontal electroencephalogram monitored.
Respiratory, thoracic and mediastinal disorders Clinically significant respiratory depression	3.6% 1/28 • Number of events 1 • twenty minutes Adverse events are "any untoward or unfavorable medical occurrence including any abnormal sign, symptom or disease,...whether or not associated with the subject's participation in the research". Internal adverse events that are unexpected and related/possibly related to the research and external adverse events that are serious, unexpected and related/possibly related must be reported to the IRB within 5 working days/7 calendar days of the date the investigator first become aware of them.

Additional Information

Principal investigator

Massachusetts General Hospital

Phone: 6176709739

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place