NCT03866278

Characterizing the Electroencephalogram Signature of Fentanyl During Induction of General Anesthesia

Completed Results posted Last updated 18 December 2023

What this trial tests

trial in Anesthesia in 31 participants. Completed in 30 August 2022.

Timeline

27 June 2018

Primary endpoint
31 October 2019

30 August 2022

Quick facts

Lead sponsor	Massachusetts General Hospital
Status	Completed
Study type	OBSERVATIONAL
Enrollment	31
Start date	27 June 2018
Primary completion	31 October 2019
Estimated completion	30 August 2022
Sites	1 location across United States

Conditions studied

• Anesthesia — all drugs for Anesthesia →

Sponsor

Massachusetts General Hospital

Who can join

Adults 18 to 65, any sex, with Anesthesia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Slope of EEG Theta Band Power Over Fentanyl Effect Site Concentration (dB/ng/mL) Primary · Twenty minutes prior to surgery

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.

Group	Value	95% CI
Study Group	0.55	0.25 – 0.8

Slope of Minute Ventilation Index Over Theta Band Power (Index/dB) Primary · 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

Group	Value	95% CI
Study Group	-1.62	-2.51 – 0.73

Slope of Response Time Over Minute Ventilation Index (Milliseconds/Index) Primary · 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.

Group	Value	95% CI
Study Group	-1.94

Changes in Reaction Time as a Function of Theta Power. Primary · 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).

Group	Value	95% CI
Study Group	30.11

Adverse events — posted to ClinicalTrials.gov

Time frame: twenty minutes. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Study Group

Serious: 0/28 (0%)

Deaths: 0/28

Other adverse events (1 terms — click to expand)

Reaction	System	Study Group
Clinically significant respiratory depression	Respiratory, thoracic and mediastinal disorders	—

Data from ClinicalTrials.gov NCT03866278 adverse events section.

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. An electroencephalogram biomarker of fentanyl drug effects.
   Balanza GA, Bharadwaj KM, Mullen AC, Beck AM, et al · · 2022 · cited 8× · PMID 36329725 · DOI 10.1093/pnasnexus/pgac158