The Neural Mechanisms of Anesthesia and Human Consciousness (Part 6)
Overview
- Phase
- Phase 4
- Intervention
- Placebo
- Conditions
- Anesthesia
- Sponsor
- University of Turku
- Enrollment
- 160
- Locations
- 1
- Primary Endpoint
- Regional cerebral metabolism of glucose
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
Positron Emission Tomography (PET), Magnetic Resonance Imaging (MRI) and electroencephalography (EEG) studies will be carried out to reveal the neural correlates of consciousness. Consciousness of the subjects will be manipulated with anesthetic agents dexmedetomidine, propofol, S-ketamine and sevoflurane. One-hundred-and-sixty (160) healthy male subjects will be recruited to receive EC50 concentration of the anesthetic (40 dexmedetomidine, 40 propofol, 20 S-ketamine, 40 sevoflurane) or placebo (20) while being imaged for cerebral metabolic rate of glucose (CMRglu). Also genetic, immunological and metabolomics samples will be taken and analysed to find possible genetic factors explaining the variability in drug response and to find chemical fingerprints of acute drug effect.
Detailed Description
The explanation of consciousness poses one of the greatest challenges to science and philosophy in the 21st century. It remains unclear what consciousness is and how it emerges from brain activity. Positron Emission Tomography (PET), Magnetic Resonance Imaging (MRI) and electroencephalography (EEG) studies will be carried out to reveal the neural correlates of consciousness. Consciousness of the subjects will be manipulated with anesthetic agents dexmedetomidine acting through α2-agonism, with propofol and sevoflurane both mainly acting through the enhancement of gamma-aminobutyric acid (GABA) system, and with S-ketamine acting through N-methyl-D-aspartate (NMDA) receptor antagonism. One-hundred-and-sixty (160) healthy male subjects will be recruited to receive EC50 concentration of either dexmedetomidine, propofol, S-ketamine or sevoflurane, or placebo while being imaged for cerebral metabolic rate of glucose (CMRglu). 40 subjects will receive dexmedetomidine, 40 subjects propofol, 20 subjects S-ketamine, 40 subjects sevoflurane and 20 subjects will receive placebo. Also genetic, immunological and metabolomics samples will be taken and analysed to find possible genetic factors explaining the variability in drug response and to find possible immunological and chemical fingerprints of acute drug effect.
Investigators
Harry Scheinin
Adjunct Professor
University of Turku
Eligibility Criteria
Inclusion Criteria
- •Age 18-30 years
- •Good general health i.e. American Society of Anesthesiologists (ASA) physical status I
- •Fluent in Finnish language
- •Right handedness
- •Written informed consent
- •Good sleep quality
Exclusion Criteria
- •Chronic medication
- •History of alcohol and/or drug abuse
- •Strong susceptibility for allergic reactions
- •Serious nausea in connection with previous anesthesia
- •Strong susceptibility for nausea
- •Any use of drugs or alcohol during the 48 hours preceding anesthesia
- •Use of caffeine products 10-12 hours prior the study
- •Clinically significant previous cardiac arrhythmia / cardiac conduction impairment
- •Clinically significant abnormality in prestudy laboratory tests
- •Positive result in the drug screening test
Arms & Interventions
Placebo
Intravenous saline.
Intervention: Placebo
Dexmedetomidine
Intravenous dexmedetomidine using target controlled infusion.
Intervention: Dexmedetomidine
Propofol
Intravenous propofol using target controlled infusion.
Intervention: Propofol
S-ketamine
Intravenous S-ketamine using target controlled infusion.
Intervention: S-ketamine
Sevoflurane
Inhalational sevoflurane using target controlled inhalation.
Intervention: Sevoflurane
Outcomes
Primary Outcomes
Regional cerebral metabolism of glucose
Time Frame: 40 min
Comparison of responsive and unresponsive subjects
Secondary Outcomes
- Immunological effects(2 hours)
- Gene expression(2 hours)
- Psychological well-being(2 hours)
- Dream report(1 hour)
- EEG(1 hour)
- Metabolomic effects(2 hours)