The Effect of Sedation on Restorative Sleep

镇静对恢复性睡眠的影响

• 批准号: 6911478
• 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 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6911478
• 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.

睡眠剥夺在重症监护室（ICU）中很常见，可能会使结果恶化。最近将丙泊酚作为ICU镇静剂的引入允许广泛使用连续的镇静剂，而不会延迟出现。这种策略被提倡促进睡眠。尽管连续的镇静剂与睡眠具有行为相似性，但尚不知道镇静是否有效地治疗了睡眠不足的状态。原则上，镇静的生理和行为影响可能会增强或损害睡眠能力扭转睡眠剥夺后果的能力。镇静时期本身可能会改变ICU中睡眠剥夺的发作和强度。我们试图表征连续镇静剂对睡眠的影响，其长期目标是理解睡眠不足状态的神经生物学基础。申请人以前在大鼠中证明了延长的镇静剂不会导致睡眠剥夺，而下丘脑丙泊酚可以增加睡眠。这些发现表明，镇静期与从睡眠剥夺中恢复相兼容，这意味着丙泊酚可能通过在下丘脑部位作用增加睡眠。我们假设在长时间使用连续镇静期间，睡眠剥夺的生理后果会逆转。为了检验这一假设，我们将1）评估镇静剂防止环境破坏引起的睡眠剥夺的能力，2）将连续镇静剂与不同因素对与睡眠相关的修复过程的影响进行比较，3）确定连续镇静剂在睡眠剥夺后是否改变了恢复睡眠。我们将在镇静，睡眠剥夺和恢复大鼠模型中获取EEG/EMG和行为数据。使用微透析，我们还将在镇静之前，期间和之后测量基底前脑中的细胞外腺苷浓度。基底前脑腺苷水平随着长时间的清醒而升高，并且随着恢复睡眠而下降。从历史上看，几乎没有战略重要性被分配给ICU中的睡眠剥夺，部分原因是没有可靠的治疗睡眠剥夺的方法。该提案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镇静剂的临床使用更有效。