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

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.

Study Overview

• Status: Withdrawn
• Conditions: General Anesthesia
• Intervention / Treatment: Device: Experimental group

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Saint-etienne, France, 42055
    • CHU Saint-Etienne

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ElectroEncephaloGram (EEG) Alpha spectral power	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).	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Beta spectral power	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).	1 day
gamma spectral power	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).	1 day
delta spectral power	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).	1 day
theta spectral power	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).	1 day

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Low frequency spectral power	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)	1 day
High frequency spectral power	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)	1 day
Cutaneous conductance	The cutaneous conductance will be given by the Nociception Level index (NoL®)	1 day
Pupil dilation reflex	The pupillary dilation reflex will be given by the AlgiScan® videopupillometer.	1 day

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Saint Etienne
• Investigators: Principal Investigator: DAVID CHARIER, MD, CHU de St Etienne

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2023
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: June 7, 2019
• First Submitted That Met QC Criteria: June 20, 2019
• First Posted (Actual): June 21, 2019

Study Record Updates

• Last Update Posted (Estimated): November 22, 2023
• Last Update Submitted That Met QC Criteria: November 20, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Surgery; General anesthesia; Free Head
• Other Study ID Numbers: 18CH168; 2019-A00201-56 (Other Identifier: ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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