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.
