Synchronous Effect of Anesthetics on fMRI, EEG and Clinical Responses

Synchronous Effect of Anesthetics on fMRI, EEG and Clinical Responses. Development of a More Precise System for Monitoring Anesthetic Effect.

Background: The mechanisms of action of intravenous anesthetics are unclear and the current monitors have limitations.

This signifies difficulties when assessing the correct dosage due to the considerable inter-individual variability of the patients, particularly in the elderly or seriously ill. It is necessary to customize the administration of anesthetics as underdosage can lead to the patient awareness during aggressive procedures, and over-dosage can cause serious complications and even augment mortality.

Objective: To design a new monitoring system of the levels of consciousness and analgesia in anesthetized subjects which is more accurate than those currently employed. It will be based on the synchronic changes of functional magnetic resonance (fMR) and electroencephalograph (EEG) readings, and clinical responses.

Methodology: Thirty healthy volunteers will be given propofol and remifentanil in different combinations, and painful stimuli will be also applied. The principal variable will be fMR images obtained by echo-planar imaging sequences. Real time will be correlated with cortical connectivity maps, EEG parameters (qCON, qNOX), clinical responses, and concentrations of anesthetics measured by pharmacokinetic and pharmacodynamic models (TCI).

Study Overview

• Status: Completed
• Conditions: Sedative Overdose
• Intervention / Treatment: Drug: Propofol; Drug: Remifentanil

Detailed Description

Main goal:

Develop a system for monitoring the effect of anesthetics on consciousness and pain, based on synchronous changes in functional neuroimaging, EEG and clinical responses.

Secondary objectives:

• Analyze the changes produced in the cortical connectivity map during the induction of anesthesia to understand the process of "advancement".
• Know more accurately the neuronal circuits involved in propofol-induced sleep.
• Study if the application of a known painful stimulus modifies in any way (clinical, EEG or by RMf) the LOC that has just been reached.
• Establish propofol dosing guidelines adjusted to each patient, studying if they reach the LOC at "sedative" or "hypnotic" doses.
• Establish remifentanil dosing guidelines, adjusted to each patient, studying the concentration of remifentanil to which the pain response in neuroimaging is inhibited (activation deactivation neuronal in fMRI).
• Validate existing mathematical models in relation to plasma and brain concentrations of propofol and remifentanil.
• Validate the value of clinical signs to predict whether a patient feels the painful stimulus received.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08026
    • Hospital del Mar

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy adult volunteers (ASA 1 physical state) who agree to participate voluntarily in the study, previous information about it by the Principal Investigators (IP).

Exclusion Criteria:

• Psychological, psychiatric or neurological disorders. Consumption of drugs. Alterations cutaneous or anatomical cranial. Idiomatic or communication barrier. Allergy to propofol, remifentanil or to some of its excipients. Body mass index (BMI) <18 or> 30 kg / m2. Pregnancy. Airway or ventilation criteria hard. Absence of accompanying adult at the end of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NA
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Volunteers receiving propofol and remifentanil; Volunteers receive propofol to the loss of consciousness. Then they receive remifentanil during 12 min (pain stimuli in their finger also)	Drug: Propofol; sedation; Other Names: remifentanil; Drug: Remifentanil; remifentanil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time and dose of propofol at loss of consciousness(LOC)	Volunteers stop tightening pneumatic pear. We register time and dose of propofol when the volunteer stops tightening pneumatic pear.	10-15 min
Register EEG and neuroimage during remifentanil administration.	After LOC, volunteers receive increasing doses of remifentanil and painful stimuli in the nail bed. If apnea, stop infusion remifentanil Volunteers receive increasing doses of remifentanil and painful stimuli in the nail bed. If apnea, stop infusion remifentanil. We registered time, dose, saturation and breathing frequency in every volunteer.	10-15 min

Collaborators and Investigators

• Sponsor: Parc de Salut Mar

Publications and helpful links

General Publications

• Borrat X, Ubre M, Risco R, Gambus PL, Pedroso A, Iglesias A, Fernandez-Esparrach G, Gines A, Balust J, Martinez-Palli G. Computerized tests to evaluate recovery of cognitive function after deep sedation with propofol and remifentanil for colonoscopy. J Clin Monit Comput. 2019 Feb;33(1):107-113. doi: 10.1007/s10877-018-0134-3. Epub 2018 Mar 27.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 13, 2017
• Primary Completion (ACTUAL): January 9, 2019
• Study Completion (ACTUAL): June 30, 2021

Study Registration Dates

• First Submitted: April 11, 2019
• First Submitted That Met QC Criteria: April 25, 2019
• First Posted (ACTUAL): April 26, 2019

Study Record Updates

• Last Update Posted (ACTUAL): September 30, 2022
• Last Update Submitted That Met QC Criteria: September 27, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Propofol, remifentanil, hypnosis, EEG, fMRI,
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Substance-Related Disorders; Drug Overdose; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Opioid; Narcotics; Hypnotics and Sedatives; Remifentanil; Propofol
• Other Study ID Numbers: UNLOCK

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Participants will be introduced to the fMRI The head will be set to try to prevent involuntary movements associated with the LOC. Routine by pulse oximetry, non-invasive blood pressure and electrocardiogram (ECG). It will be administered oxygen at 2 liters / min by nasal cannula with capnography line and transcutaneous carbon dioxide will be monitored. Volunteers will not be premedicated.

EEG activity and fMRI images, as detailed in the section "Study variables". Each series of acquisitions will consist of a "resting state" (rs-fMRI), in which the subject will be asked to close their eyes and leave the mind ramble without further slogans, and also a series of tasks in which the participant will be exposed to a sequence of perceptive and nociceptive stimuli in order to objectify the effect of the drug on the nervous system central. The signal extracted from the RMf images will allow to study the dynamics of the metabolic changes and neurons in the brain with a temporal resolution.

• IPD Sharing Time Frame: 3 years
• IPD Sharing Access Criteria: volunteers without exclusion criteria
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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