Synchronous Effect of Anesthetics on fMRI, EEG and Clinical Responses
Condition: Sedative Overdose
MeSH terms: Drug Overdose
Study type: Interventional
Phase: Phase 1/Phase 2

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.
    

Intervention name(s): Propofol; Remifentanil
Intervention type(s): Drug; Drug
Intervention description(s): sedation; remifentanil
Other intervention name(s): remifentanil
Intervention MeSH terms: Remifentanil; Propofol
Intervention model: Sequential Assignment
Intervention model description: Volunteers receiving propofol and then remifentanil.
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Propofol, remifentanil, hypnosis, EEG, fMRI,