Clinical trial NCT03928366: Synchronous Effect of Anesthetics on fMRI, EEG and Clinical Responses
Official title: Synchronous Effect of Anesthetics on fMRI, EEG and Clinical Responses. Development of a More Precise System for Monitoring Anesthetic Effect.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Sedative Overdose
Keywords: Propofol, remifentanil, hypnosis, EEG, fMRI,
Lead sponsor: Parc de Salut Mar
Sponsor class: OTHER
First posted: 2019-04-26
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: Volunteers receiving propofol and then remifentanil.
Primary purpose: BASIC_SCIENCE

Brief summary: 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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Time and dose of propofol at loss of consciousness(LOC)
timeFrame: 10-15 min
measure: Register EEG and neuroimage during remifentanil administration.
timeFrame: 10-15 min
Secondary outcomes:
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital del Mar
Study officials:
References:
citation: 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.