Characterizing the Electroencephalogram Signature of Fentanyl During Induction of General Anesthesia

NCT03866278 | Completed Results DMC

• 2 other identifiers: 2018P0003835R21DA048323-02
• Study Type: observational
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Anesthesia

Keywords

Opiate

Outcome Measures

Primary Outcomes (4)

• 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.

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• Undergoing surgery anticipated to take 2 hours or longer

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Limitations and Caveats

We report these findings from a moderate-sized sample of subjects undergoing a structured protocol prior to general anesthesia. The sample size however is comparable and exceeds previous studies of fentanyl EEG effects. The EEG is commonly regarded as being noisy and prone to artifact, but in this clinical setting and with appropriate analyses methods we observed clear EEG signatures that correlated with predicted fentanyl effect site concentrations and with physiological and behavioral changes.

Results Point of Contact

• Title: Principal investigator
• Organization: Massachusetts General Hospital

patrick.purdon@MGH.HARVARD.EDU

6176709739

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Anesthesia

Study Record Dates

• First Submitted: August 14, 2018
• First Posted: March 7, 2019
• Study Start: June 27, 2018
• Primary Completion: October 31, 2019
• Study Completion: August 30, 2022
• Last Updated: December 18, 2023
• Results First Posted: December 18, 2023

Record last verified: 2023-11

Locations

US (1)