Synchronous Effect of Anesthetics on fMRI, EEG and Clinical Responses

Sedative Overdose

Propofol, remifentanil, hypnosis, EEG, fMRI,

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.

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