The Effect of Sedation on Restorative Sleep

镇静对恢复性睡眠的影响

• 批准号: 6635757
• 负责人: AVERY TUNG
• 金额: $ 11.89万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-05 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6635757
• 关键词: adenosine; anesthetics; auditory stimulus; behavioral /social science research tag; drug adverse effect; drug screening /evaluation; electroencephalography; electromyography; isoflurane; laboratory rat; microdialysis; midazolam; neurobiology; neurochemistry; neuropsychology; prosencephalon; psychopharmacology; sedative /hypnotic; sensory depression; sleep; sleep deprivation

Sleep deprivation is common in the Intensive Care Unit (ICU) and can worsen outcomes. Recent introduction of propofol as an ICU sedative has allowed the widespread use of continuous sedation without delayed emergence. Such a strategy has been advocated to promote sleep. Although continuous sedation shares behavioral similarities with sleep, it is not known whether sedation effectively treats the sleep-deprived state. In principle, physiological and behavioral effects of sedation may either enhance or impair the ability of sleep to reverse the consequences of sleep deprivation. A period of sedation may itself alter the onset and intensity of sleep deprivation in the ICU. We seek to characterize the effects of continuous sedation on sleep with the long-term goal of understanding the neurobiological basis for the sleep-deprived state. The applicant has previously demonstrated in rats that prolonged sedation does not result in sleep deprivation, and that hypothalamic administration of propofol increases sleep. These findings suggest that a period of sedation is compatible with recovery from sleep deprivation, and imply that propofol may increase sleep by acting at a hypothalamic site. We hypothesize that the physiological consequences of sleep deprivation are reversed during prolonged use of continuous sedation. To test this hypothesis, we will 1) assess the ability of sedation to prevent sleep deprivation induced by environmental disruption, 2) compare the effects of continuous sedation with different agents on the restorative process associated with sleep, and 3) determine whether continuous sedation alters recovery sleep following sleep deprivation. We will acquire EEG/EMG and behavioral data in a rat model of sedation, sleep deprivation, and recovery. Using microdialysis, we will also measure extracellular adenosine concentrations in the basal forebrain before, during, and after sedation. Basal forebrain adenosine levels rise with prolonged wakefulness, and fall with recovery sleep. Little strategic importance has historically been assigned to preventing sleep deprivation in the ICU, partly because no proven method for treating sleep deprivation exists. Knowledge from this proposal will provide scientific insight into the relationships between anesthesia and sleep, and may lead to more effective clinical use of ICU sedatives.

睡眠不足在重症监护病房 (ICU) 中很常见，并且可能会使结果恶化。最近引入异丙酚作为 ICU 镇静剂，使得连续镇静得以广泛使用，而不会延迟苏醒。人们提倡采用这样的策略来促进睡眠。尽管持续镇静与睡眠在行为上有相似之处，但尚不清楚镇静是否能有效治疗睡眠不足状态。原则上，镇静的生理和行为影响可能会增强或削弱睡眠的能力，从而扭转睡眠不足的后果。一段时间的镇静本身可能会改变 ICU 睡眠剥夺的发生时间和强度。我们试图描述持续镇静对睡眠的影响，长期目标是了解睡眠剥夺状态的神经生物学基础。申请人先前已在大鼠中证明，长时间镇静不会导致睡眠剥夺，并且下丘脑施用异丙酚可增加睡眠。这些发现表明，一段时间的镇静与从睡眠剥夺中恢复是相容的，并意味着异丙酚可能通过作用于下丘脑部位来增加睡眠。我们假设，长期使用持续镇静剂会逆转睡眠不足的生理后果。为了检验这一假设，我们将 1) 评估镇静预防环境破坏引起的睡眠剥夺的能力，2) 比较不同药物的持续镇静对与睡眠相关的恢复过程的影响，以及 3) 确定持续镇静是否会改变睡眠剥夺后的恢复睡眠。我们将在镇静、睡眠剥夺和恢复的大鼠模型中获取脑电图/肌电图和行为数据。使用微透析，我们还将测量镇静前、镇静期间和镇静后基底前脑的细胞外腺苷浓度。基础前脑腺苷水平随着长时间清醒而上升，并随着恢复性睡眠而下降。历史上，在 ICU 中预防睡眠剥夺几乎没有被赋予战略重要性，部分原因是没有经过验证的治疗睡眠剥夺的方法。该提案中的知识将为麻醉与睡眠之间的关系提供科学见解，并可能导致 ICU 镇静剂在临床上更有效的使用。