Synchronous Effect of Anesthetics on fMRI, EEG and Clinical Responses

Sedative Overdose Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03928366
• Other study ID #: UNLOCK
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: June 13, 2017
• Est. completion date: June 30, 2021

Study information

• Verified date: September 2022
• Source: Parc de Salut Mar
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: June 30, 2021
• Est. primary completion date: January 9, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• Drug Overdose
• Sedative Overdose

Intervention

Drug:
• Propofol
sedation
• Remifentanil
remifentanil

Locations

Country	Name	City	State
Spain	Hospital del Mar	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
Parc de Salut Mar

Country where clinical trial is conducted

Spain, 

References & Publications (1)

Borrat X, Ubre M, Risco R, Gambús PL, Pedroso A, Iglesias A, Fernandez-Esparrach G, Ginés À, Balust J, Martínez-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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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