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出境医 / 临床实验 / Interest of the Study of Electroencephalogram and Peripheral Vegetative Markers for the Evaluation of Nociception Under General Anesthesia. (BRAIN)

Interest of the Study of Electroencephalogram and Peripheral Vegetative Markers for the Evaluation of Nociception Under General Anesthesia. (BRAIN)

Study Description
Brief Summary:

General anesthesia (GA) is a state of loss of consciousness induced by anesthetic products. In a GA, two classes of products are usually used: on the one hand, hypnotics that are responsible for the sleep component (hypnosis) and memory loss (amnesia), and on the other hand opioids that have an analgesic role.

The doses of hypnotic and morphine necessary to achieve this state of loss of consciousness and lack of response to painful stimulation vary from subject to subject, and during surgery depending on the intensity of the stimulus, requiring permanent adaptation to avoid overdose or underdosing, responsible for morbidity.

Several monitors of the hypnotic component have been developed in recent years, which can now be used routinely, such as the Bispectral Index (BIS) or Spectral Entropy.

However, there is currently no clinically validated technique for monitoring pain or the effect of opioids in the operating room.

Spectral analysis of the electroencephalogram (EEG) revealed a significant decrease (-30%) in alpha spectral power, observed specifically in painful experimental conditions in healthy awake subjects. On the other hand, a painful experience is accompanied by transient changes in various parameters under vegetative control, whether cardiovascular, cutaneous or pupillary, essentially underpinned by the activation of the sympathetic system.

The investigators hypothesize that a real-time dynamic analysis of the spectral power of EEG combined with that of cardiovascular vegetative parameters, cutaneous conductance and pupillary diameter is likely to be a marker of nociception under GA.


Condition or disease Intervention/treatment Phase
General Anesthesia Device: Experimental group Not Applicable

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: This is a monocentric and prospective observational study on the physiology of nociception under general anesthesia. The patient will be his own witness.
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Interest of the Study of Electroencephalogram and Peripheral Vegetative Markers for the Evaluation of Nociception Under General Anesthesia.
Estimated Study Start Date : May 2021
Estimated Primary Completion Date : March 2023
Estimated Study Completion Date : March 2023
Arms and Interventions
Arm Intervention/treatment
Experimental: Experimental group
Patients under general anesthesia will be included.
Device: Experimental group
EEG acquisition system BioSemi (Amsterdam, the Netherlands), enabling real-time measurement and continuous recording of EEG on up to 128 leads.

Outcome Measures
Primary Outcome Measures :
  1. ElectroEncephaloGram (EEG) Alpha spectral power [ Time Frame: 1 day ]
    variations of the EEG parameters (spectral power of the alpha rhythms), during nociceptive stimuli performed under AG at constant hypnosis depth (BIS between 50 and 60), without and after injection of a standardized dose of morphine (0.2 μg / kg of sufentanil based on the theoretical weight) of the patient).


Secondary Outcome Measures :
  1. Beta spectral power [ Time Frame: 1 day ]
    variations of the EEG parameters (spectral power of the beta rhythms), during nociceptive stimuli performed under AG at constant hypnosis depth (BIS between 50 and 60), without and after injection of a standardized dose of morphine (0.2 μg / kg of sufentanil based on the theoretical weight) of the patient).

  2. gamma spectral power [ Time Frame: 1 day ]
    variations of the EEG parameters (spectral power of the gamma rhythms), during nociceptive stimuli performed under AG at constant hypnosis depth (BIS between 50 and 60), without and after injection of a standardized dose of morphine (0.2 μg / kg of sufentanil based on the theoretical weight) of the patient).

  3. delta spectral power [ Time Frame: 1 day ]
    variations of the EEG parameters (spectral power of the delta rhythms), during nociceptive stimuli performed under AG at constant hypnosis depth (BIS between 50 and 60), without and after injection of a standardized dose of morphine (0.2 μg / kg of sufentanil based on the theoretical weight) of the patient).

  4. theta spectral power [ Time Frame: 1 day ]
    variations of the EEG parameters (spectral power of the tetha rhythms), during nociceptive stimuli performed under AG at constant hypnosis depth (BIS between 50 and 60), without and after injection of a standardized dose of morphine (0.2 μg / kg of sufentanil based on the theoretical weight) of the patient).


Other Outcome Measures:
  1. Low frequency spectral power [ Time Frame: 1 day ]
    Low Frequence : 0,04-0,15 Hz on EEG in nociceptive stimuli performed under GA at constant hypnosis depth, without and after injection of a standardized dose of morphine (0.2 µg/kg sufentanil based on the patient's theoretical weight)

  2. High frequency spectral power [ Time Frame: 1 day ]
    High frequency (HF : 0,15-0,4 Hz) on EEG in nociceptive stimuli performed under GA at constant hypnosis depth, without and after injection of a standardized dose of morphine (0.2 µg/kg sufentanil based on the patient's theoretical weight)

  3. Cutaneous conductance [ Time Frame: 1 day ]
    The cutaneous conductance will be given by the Nociception Level index (NoL®)

  4. Pupil dilation reflex [ Time Frame: 1 day ]
    The pupillary dilation reflex will be given by the AlgiScan® videopupillometer.


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient affiliated or entitled to a social security scheme
  • Over 18 years old
  • To be operated on a regulated surgery allowing access to the head and to one eye, under AG, in the operating theater of the CHU of Saint-Etienne
  • And having given his free, informed, written and signed consent.

Exclusion Criteria:

  • Subject to a measure of legal protection (tutelage, guardianship)
  • Admitted for emergency surgery
  • With known allergy to any of the anesthetic agents used in the study
  • Having been asleep under general anesthesia in the 7 days preceding the intervention
  • A pacemaker or heart transplant patient
  • With a history of Parkinson's disease, insulin-dependent or non-insulin-dependent diabetes at a dysautonomic stage or chronic alcoholism at a dysautonomia stage
  • With psychiatric history or severe depression
  • Presenting a peripheral or central neurological pathology that may modify the physiological responses to nociceptive stimulation
  • With abnormal heart rhythm (atrial fibrillation or frequent extrasystoles)
  • Treated for arterial hypertension with angiotensin type 2 receptor antagonists
  • Treated with anti-arrhythmic, α- or β-blocking, which would make the interpretation of the results more difficult
  • With chronic pain
  • Treated with morphine or long-term neuroleptic
  • Consuming cannabis or another narcotic
  • Presenting bilateral ocular pathology that may interfere with pupillary dilatation
  • Or refusing to participate in the study.
Contacts and Locations

Contacts
Layout table for location contacts
Contact: DAVID CHARIER, MD (0)477828565 ext +33 david.charier@chu-st-etienne.fr
Contact: CARINE LABRUYERE, CRA (0)477120286 ext +33 carine.labruyere@chu-st-etinne.fr

Locations
Layout table for location information
France
Chu Saint-Etienne
Saint-etienne, France, 42055
Contact: DAVID CHARIER, MD    (0)477828565 ext +33    david.charier@chu-st-etienne.fr   
Principal Investigator: DAVID CHARIER, MD         
Sub-Investigator: SERGE MOLLIEX, PHD         
Sub-Investigator: FRANCOIS VASSAL, MD         
Sponsors and Collaborators
Centre Hospitalier Universitaire de Saint Etienne
Investigators
Layout table for investigator information
Principal Investigator: DAVID CHARIER, MD CHU DE ST ETIENNE
Tracking Information
First Submitted Date  ICMJE June 7, 2019
First Posted Date  ICMJE June 21, 2019
Last Update Posted Date May 3, 2021
Estimated Study Start Date  ICMJE May 2021
Estimated Primary Completion Date March 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 20, 2019)
ElectroEncephaloGram (EEG) Alpha spectral power [ Time Frame: 1 day ]
variations of the EEG parameters (spectral power of the alpha rhythms), during nociceptive stimuli performed under AG at constant hypnosis depth (BIS between 50 and 60), without and after injection of a standardized dose of morphine (0.2 μg / kg of sufentanil based on the theoretical weight) of the patient).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 20, 2019)
  • Beta spectral power [ Time Frame: 1 day ]
    variations of the EEG parameters (spectral power of the beta rhythms), during nociceptive stimuli performed under AG at constant hypnosis depth (BIS between 50 and 60), without and after injection of a standardized dose of morphine (0.2 μg / kg of sufentanil based on the theoretical weight) of the patient).
  • gamma spectral power [ Time Frame: 1 day ]
    variations of the EEG parameters (spectral power of the gamma rhythms), during nociceptive stimuli performed under AG at constant hypnosis depth (BIS between 50 and 60), without and after injection of a standardized dose of morphine (0.2 μg / kg of sufentanil based on the theoretical weight) of the patient).
  • delta spectral power [ Time Frame: 1 day ]
    variations of the EEG parameters (spectral power of the delta rhythms), during nociceptive stimuli performed under AG at constant hypnosis depth (BIS between 50 and 60), without and after injection of a standardized dose of morphine (0.2 μg / kg of sufentanil based on the theoretical weight) of the patient).
  • theta spectral power [ Time Frame: 1 day ]
    variations of the EEG parameters (spectral power of the tetha rhythms), during nociceptive stimuli performed under AG at constant hypnosis depth (BIS between 50 and 60), without and after injection of a standardized dose of morphine (0.2 μg / kg of sufentanil based on the theoretical weight) of the patient).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: June 20, 2019)
  • Low frequency spectral power [ Time Frame: 1 day ]
    Low Frequence : 0,04-0,15 Hz on EEG in nociceptive stimuli performed under GA at constant hypnosis depth, without and after injection of a standardized dose of morphine (0.2 µg/kg sufentanil based on the patient's theoretical weight)
  • High frequency spectral power [ Time Frame: 1 day ]
    High frequency (HF : 0,15-0,4 Hz) on EEG in nociceptive stimuli performed under GA at constant hypnosis depth, without and after injection of a standardized dose of morphine (0.2 µg/kg sufentanil based on the patient's theoretical weight)
  • Cutaneous conductance [ Time Frame: 1 day ]
    The cutaneous conductance will be given by the Nociception Level index (NoL®)
  • Pupil dilation reflex [ Time Frame: 1 day ]
    The pupillary dilation reflex will be given by the AlgiScan® videopupillometer.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Interest of the Study of Electroencephalogram and Peripheral Vegetative Markers for the Evaluation of Nociception Under General Anesthesia.
Official Title  ICMJE Interest of the Study of Electroencephalogram and Peripheral Vegetative Markers for the Evaluation of Nociception Under General Anesthesia.
Brief Summary

General anesthesia (GA) is a state of loss of consciousness induced by anesthetic products. In a GA, two classes of products are usually used: on the one hand, hypnotics that are responsible for the sleep component (hypnosis) and memory loss (amnesia), and on the other hand opioids that have an analgesic role.

The doses of hypnotic and morphine necessary to achieve this state of loss of consciousness and lack of response to painful stimulation vary from subject to subject, and during surgery depending on the intensity of the stimulus, requiring permanent adaptation to avoid overdose or underdosing, responsible for morbidity.

Several monitors of the hypnotic component have been developed in recent years, which can now be used routinely, such as the Bispectral Index (BIS) or Spectral Entropy.

However, there is currently no clinically validated technique for monitoring pain or the effect of opioids in the operating room.

Spectral analysis of the electroencephalogram (EEG) revealed a significant decrease (-30%) in alpha spectral power, observed specifically in painful experimental conditions in healthy awake subjects. On the other hand, a painful experience is accompanied by transient changes in various parameters under vegetative control, whether cardiovascular, cutaneous or pupillary, essentially underpinned by the activation of the sympathetic system.

The investigators hypothesize that a real-time dynamic analysis of the spectral power of EEG combined with that of cardiovascular vegetative parameters, cutaneous conductance and pupillary diameter is likely to be a marker of nociception under GA.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
This is a monocentric and prospective observational study on the physiology of nociception under general anesthesia. The patient will be his own witness.
Masking: None (Open Label)
Primary Purpose: Diagnostic
Condition  ICMJE General Anesthesia
Intervention  ICMJE Device: Experimental group
EEG acquisition system BioSemi (Amsterdam, the Netherlands), enabling real-time measurement and continuous recording of EEG on up to 128 leads.
Study Arms  ICMJE Experimental: Experimental group
Patients under general anesthesia will be included.
Intervention: Device: Experimental group
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: June 20, 2019)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2023
Estimated Primary Completion Date March 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patient affiliated or entitled to a social security scheme
  • Over 18 years old
  • To be operated on a regulated surgery allowing access to the head and to one eye, under AG, in the operating theater of the CHU of Saint-Etienne
  • And having given his free, informed, written and signed consent.

Exclusion Criteria:

  • Subject to a measure of legal protection (tutelage, guardianship)
  • Admitted for emergency surgery
  • With known allergy to any of the anesthetic agents used in the study
  • Having been asleep under general anesthesia in the 7 days preceding the intervention
  • A pacemaker or heart transplant patient
  • With a history of Parkinson's disease, insulin-dependent or non-insulin-dependent diabetes at a dysautonomic stage or chronic alcoholism at a dysautonomia stage
  • With psychiatric history or severe depression
  • Presenting a peripheral or central neurological pathology that may modify the physiological responses to nociceptive stimulation
  • With abnormal heart rhythm (atrial fibrillation or frequent extrasystoles)
  • Treated for arterial hypertension with angiotensin type 2 receptor antagonists
  • Treated with anti-arrhythmic, α- or β-blocking, which would make the interpretation of the results more difficult
  • With chronic pain
  • Treated with morphine or long-term neuroleptic
  • Consuming cannabis or another narcotic
  • Presenting bilateral ocular pathology that may interfere with pupillary dilatation
  • Or refusing to participate in the study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: DAVID CHARIER, MD (0)477828565 ext +33 david.charier@chu-st-etienne.fr
Contact: CARINE LABRUYERE, CRA (0)477120286 ext +33 carine.labruyere@chu-st-etinne.fr
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03994887
Other Study ID Numbers  ICMJE 18CH168
2019-A00201-56 ( Other Identifier: ANSM )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Centre Hospitalier Universitaire de Saint Etienne
Study Sponsor  ICMJE Centre Hospitalier Universitaire de Saint Etienne
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: DAVID CHARIER, MD CHU DE ST ETIENNE
PRS Account Centre Hospitalier Universitaire de Saint Etienne
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP