AnesthesiaNCT03866278
Characterizing the Electroencephalogram Signature of Fentanyl During Induction of General Anesthesia
An observational study of Anesthesia, run by Massachusetts General Hospital at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Anesthesia
- How many people
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Jun 2018to 30 Aug 2022
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Adult, Older adult
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.
Who may be able to join
- -Undergoing surgery anticipated to take 2 hours or longer
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
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.
Read the 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.
- Conditions
- Anesthesia
- Keywords
- Opiate
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: Twenty minutes before the surgery.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2019
- Study start27 Jun 2018
- Primary completion31 Oct 2019
- Study completion30 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for AnesthesiaStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Principal investigator, Patrick L. Purdon, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03866278
- Sponsor's protocol ID
- 2018P000383
- Other IDs
- 5R21DA048323-02
- Status last verified
- Nov 2023
- First submitted
- 14 Aug 2018
- Last updated
- 18 Dec 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Characterizing the Electroencephalogram Signature of Fentanyl During Induction of General Anesthesia
- ClinicalTrials.gov ID
- NCT03866278
- Acronym / sponsor ID
- 2018P000383
- Conditions
- Anesthesia
- Keywords
- Opiate
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- 27 Jun 2018 (actual)
- Primary completion
- 31 Oct 2019 (actual)
- Study completion
- 30 Aug 2022 (actual)
- First posted
- 7 Mar 2019 (actual)
- Results
- Posted 18 Dec 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (1 listed)
- -Undergoing surgery anticipated to take 2 hours or longer
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Slope of EEG Theta Band Power Over Fentanyl Effect Site Concentration (dB/ng/mL)
Time frame: 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.
Slope of Minute Ventilation Index Over Theta Band Power (Index/dB)
Time frame: 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.
Slope of Response Time Over Minute Ventilation Index (Milliseconds/Index)
Time frame: 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.
Changes in Reaction Time as a Function of Theta Power.
Time frame: 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).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
Related trials for Anesthesia
Not yet recruitingObservational study
"Comparison of Oxygen Reserve Index (ORI), End-Tidal Oxygen, and Time-Based Preoxygenation Targets With Arterial Blood Gas During Preoxygenation
Preoxygenation Adequacy Assessed by Oxygen Reserve Index, End-tidal Oxygen and Arterial Blood Gas
RecruitingObservational study
Comparison of Hemodynamic Responses During Anesthesia Induction Using Eleveld and Schnider
Spinal (Fusion) Surgery, Total Intravenous Anesthesia
Not yet recruiting
A Randomized Controlled SaCo-VLM Trial
General Anaesthesia Using Supraglotic Airway
Not yet recruiting
Bispectral Index-Guided Propofol Sedation During Endoscopic Retrograde Cholangiopancreatography
Deep Sedation, Endoscopic Retrograde Cholangiopancreatography
RecruitingPhase 4
Comparison of Hemodynamics and Respiratory Function Between Ciprofol and Propofol in Elderly Patients Undergoing Non-intubated General Anesthesia
Comparison of Hemodynamics and Respiratory Function Between Ciprofol and Propofol in Elderly Patients Undergoing Non-intubated General Anesthesia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Anesthesia, run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Slope of EEG Theta Band Power Over Fentanyl Effect Site Concentration (dB/ng/mL) (time frame: Twenty minutes prior to surgery). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2023.