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).

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.

Volunteers receive propofol to the loss of consciousness. Then they receive remifentanil during 12 min (pain stimuli in their finger also)

Volunteers stop tightening pneumatic pear. We register time and dose of propofol when the volunteer stops tightening pneumatic pear.

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.

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.

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.

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.