Characterizing the Electroencephalogram Signature of Fentanyl During Induction of General Anesthesia

While historically anesthesiologists rely on pharmacokinetics to track the loss of consciousness, new research in anesthesiology has identified the salient features of the electroencephalogram (EEG) that correlate to states of sedation and unconsciousness induced by different anesthetic drugs. While the EEG features of many sedative-hypnotic anesthetics have been well- characterized, the opioid analgesic drugs have not been analyzed in detail in this way. A characterization of the EEG signatures of opioid analgesic drugs could be useful in monitoring and titrating the effects of these drugs.

Study Overview

• Status: Completed
• Conditions: Anesthesia

Detailed Description

Fentanyl is one of the most commonly used opioid analgesic drugs. Prior to induction of general anesthesia, fentanyl is frequently administered to blunt the nociceptive response to intubation. A typical scenario is to administer 2 to 4 mcg/kg of fentanyl first, followed by a sedative hypnotic drug such as propofol to induce general anesthesia. In this study, we propose to administer a total of 4 mcg/kg of fentanyl, administered in 2 boluses, before administering a sedative hypnotic drug. At this dose, fentanyl will serve to blunt nociception during intubation, but will also contribute to intraoperative pain management. During this time, we will record the EEG using standard EEG-based anesthetic monitors that are routinely used in the operating room. We will assess the patient's level of responsiveness using an auditory task and ulnar nerve stimulation. These measurements will allow us to identify the EEG signatures of fentanyl for future use in EEG-based anesthetic monitoring. During this study we will measure EEG and responses to auditory and ulnar nerve stimuli during induction of general anesthesia in surgical patients. The anesthetic will be administered according to a typical sequence in which fentanyl is first administered, followed by a sedative hypnotic drug for induction of general anesthesia. The primary difference is that, in this study, we will record the EEG and response data for a short period of time after initial administration of fentanyl and prior to administration of a sedative hypnotic drug to induce general anesthesia.

• Study Type: Observational
• Enrollment (Actual): 31

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Only those patients capable of giving their own consent will be considered for this study. All study subjects will be American Society of Anesthesiologists (ASA) physical status classification P1 to P3. That is, all study subjects will have at most mild to moderate systemic disease.

Description

Inclusion Criteria:

-Undergoing surgery anticipated to take 2 hours or longer

Exclusion Criteria:

• Craniofacial abnormalities
• Allergies to fentanyl, bisulfite, eggs or egg products, latex, soybeans, soybean oil BMI ≤ 30 (kg/m2)
• Known or suspected difficult intubation
• Known or suspected need for rapid sequence induction and intubation
• History of obstructive sleep apnea requiring CPAP
• History of uncontrolled gastroesophageal reflux disease (GERD)
• Opiate use within 24 hours
• History of opiate abuse within 3 years

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Slope of EEG Theta Band Power Over Fentanyl Effect Site Concentration (dB/ng/mL)	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.	Twenty minutes prior to surgery
Slope of Minute Ventilation Index Over Theta Band Power (Index/dB)	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.	Twenty minutes prior to surgery
Slope of Response Time Over Minute Ventilation Index (Milliseconds/Index)	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.	Twenty minutes prior to surgery
Changes in Reaction Time as a Function of Theta Power.	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).	Twenty minutes before the surgery.

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: National Institute on Drug Abuse (NIDA)

Study record dates

Study Major Dates

• Study Start (Actual): June 27, 2018
• Primary Completion (Actual): October 31, 2019
• Study Completion (Actual): August 30, 2022

Study Registration Dates

• First Submitted: August 14, 2018
• First Submitted That Met QC Criteria: March 6, 2019
• First Posted (Actual): March 7, 2019

Study Record Updates

• Last Update Posted (Actual): December 18, 2023
• Last Update Submitted That Met QC Criteria: November 30, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Opiate
• Other Study ID Numbers: 2018P000383; 5R21DA048323-02 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No