Arousal Pathways and Emergence From Sedation
试验速览
- 阶段
- 不适用
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Characterization of brain network connectivity underlying arousal from anesthesia.
研究概览
简要总结
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.
Research hypothesis
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.
详细描述
Sedation and general anesthesia are at the hub of modern medicine. The practice of the administration of anesthesia and sedation has evolved considerably and is now considered safe and reproducible. Still, one of the critical parts of anesthesia practice is the emergence: with the phenomenological variability of the clinical presentations of emergence, and its increased inherent risks of airway patency, insufficient respiratory mechanics, hyperreflexia and altered mental state.
Our understanding of the underlying mechanisms of sedation and anesthesia is still somewhat lacking: The body of evidence concerning induction and maintenance is more evolved[1-4], whereas the most profound gaps of knowledge concern emergence.
While anesthetic agent exert a global effect on the brain, it is clear that some foci are more sensitive[5] and more relevant to the achievement of the anesthetic goals of hypnosis, amnesia, and reduced responsiveness.
Mechanisms of unconsciousness induced by general anesthesia[1] can be broadly dissected to two elements: consciousness and arousal: Current consciousness theories[6,7] ascribe to consciousness the ability to experience. To achieve that goal, information complexity and information integration are paramount. These faculties reside mainly in the neocortex. Arousal on the other hand, resides mainly in the thalamus, hypothalamus, midbrain and pons with the neural machinery of physiological sleep[8,9]. We tend to associate consciousness with arousability. Dreaming however - is a straightforward example of consciousness without arousal.
A given level of arousal is the output of the balance of the mutual inhibition between the sleep promoting locus - the ventrolateral preoptic nucleus - and the multiple arousal loci, commonly known as the ARAS (Ascending Reticular Activating System)[10,11]. Shortly, this dispersed system is comprised of multiple nuclei with different neurotransmitters. Some of the nuclei have thalamic projections and some are extra-thalamic with direct and diverse cortical projections. The transition between sleep and wakefulness is further enhanced by the Orexigenic neurons in the hypothalamus[12,13], which serve as a flip flop mechanism.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 40 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy males (ASA scale 1-2), volunteers only
排除标准
- •Use of chronic medications or illicit drugs
- •Metallic implants
- •Previous brain injury
- •General anaesthesia up to a week earlier to research examination
- •Known drug sensitivity to Propofol, soybean oil or peanuts
研究组 & 干预措施
Sedation
Volunteers will be sedated to Ramsay score 4-5 with propofol, and data will be recorded during arousal
干预措施: Propofol (Drug)
结局指标
主要结局
Characterization of brain network connectivity underlying arousal from anesthesia.
时间窗: 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.
次要结局
- Characterization of the internal structure and temporal hierarchy underlying arousal from anesthesia.(Data collection time frame will not exceed one hour post propofol infusion cessation.)
研究者
michal roll
Dr. Michal Roll
Tel-Aviv Sourasky Medical Center