Arousal Pathways and Emergence From Sedation
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|ClinicalTrials.gov Identifier: NCT02253758|
Recruitment Status : Unknown
Verified September 2014 by michal roll, Tel-Aviv Sourasky Medical Center.
Recruitment status was: Not yet recruiting
First Posted : October 1, 2014
Last Update Posted : October 1, 2014
Emergence from sedation involves an increase in both the level of consciousness and arousal. Some insight to the neural core of consciousness was gained in the recent past. Our research objective is to characterize for the first time the spatiotemporal mobilization of the ascending reticular activating system during emergence from sedation; stated otherwise - to capture the neural core of arousal.
To achieve this objective we plan to utilize the advanced imaging modality of EEG-fMRI. In short, volunteers will be placed in the MRI. Following baseline recordings they will be sedated with a continuous drip of propofol, titrated to deep sedation. Once in that sedation level, propofol administration will cease until emerging to an awake-calm/light sedation.
Continuous EEG recordings and fMRI scans will be taken, both task specific (auditory oddball) and resting-fMRI. Analyses will focus (but will not be restricted to) on constituents of the ascending reticular activating system.
The expected advances of this proposal are:
- Emergence from sedation (and anesthesia) is one of the critical stages and least elucidated area in the practice of anesthesia. Delayed awakening of varying degree is not uncommon after anesthesia and may have a number of different causes, individual or combined, which may be both drug or non-drug related, thus causing a diagnostic dilemma. Eventually - better insight into this subject will lead to better clinical practice and better understanding why patients emerge in such a diverse and sometimes unexpected manner.
- Knowledge of the internal structure underlying arousal from anesthesia will help develop / upgrade brain monitors that could tell the anesthesiologist the patient's level of consciousness and prediction of arousal.
- A detailed reproducible mapping of the arousal process may serve as the core of a drug screening platform for drugs that may expedite patient arousal.
- Elucidation of the arousal paradigm from sedation will enhance our knowledge of physiological sleep.
Return of consciousness is a complex phenomenon comprising of interplay between the cortex and deeper brain structures. We hypothesize that the activation signature is conserved and similar between subjects. Furthermore, we hypothesize that inter-subject variability will arise mainly in the time domain, as evident from the clinical observation of variable time to emergence in different patients.
|Condition or disease||Intervention/treatment||Phase|
|Anesthesia||Drug: Propofol||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||Arousal Pathways and Emergence From Sedation|
|Study Start Date :||October 2014|
|Estimated Primary Completion Date :||December 2015|
|Estimated Study Completion Date :||December 2016|
Volunteers will be sedated to Ramsay score 4-5 with propofol, and data will be recorded during arousal
Propofol will be injected as a continuous infusion by TCI intravenously
Other Name: Propofol Liporum 1%
- Characterization of brain network connectivity underlying arousal from anesthesia. [ Time Frame: Data collection time frame will not exceed one hour post propofol infusion cessation. ]Network connectivity of brain loci involved in arousal pathways will be evaluated for each patient at these time points: baseline, deep sedation and return to conscious state. The identification of these time points will be decided according to the Ramsay clinical scale for sedation depth. A score of 2 for baseline, 5 for deep sedation, and 2-3 for regaining consciousness. An external validation for these time points will derive from the oddball auditory test, in which the brain reaction to a sound in a different pitch is recorded. In the sedated state this reaction is perturbed.
- Characterization of the internal structure and temporal hierarchy underlying arousal from anesthesia. [ Time Frame: Data collection time frame will not exceed one hour post propofol infusion cessation. ]At the group level an attempt will be made to discern temporal hierarchy (which of the aforementioned nuclei is the first to regain activity within the network) between the different ROIs (in voxels and normalized to a standarized brain) involved in the arousal pathways. The basal forebrain, laterodorsal tegmental nuclei, pedunculupontine nuclei, the ventral hypothalamus and the thalamus will all be included in the putative connectivity map.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02253758
|Contact: Idit Matot, Prof. M.D.||firstname.lastname@example.org|
|Contact: Miri Davidovichemail@example.com|
|Whol Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center|
|Tel Aviv, Israel|
|Contact: Talma Hendler, M.D. PhD 97236973094 firstname.lastname@example.org|
|Sub-Investigator: Talma Hendler, M.D. PhD|
|Division of Anesthesia, Pain and Critical Care, Tel-Aviv Sourasky Medical Center|
|Contact: Idit Matot, Prof. M.D. 97236974758 email@example.com|
|Contact: Miri Davidovich 97236974758 firstname.lastname@example.org|
|Principal Investigator: Idit Matot, Prof. M.D.|
|Sub-Investigator: Tomer Nir, Resident|
|Principal Investigator:||Idit Matot, Prof. M.D.||Tel-Aviv Sourasky Medical Center|