Investigation of Sleep

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PROJECT SUMMARY / ABSTRACT: Investigation of Sleep in the Intensive Care Unit (ICU-SLEEP) Sleep deprivation is among the most common complaints about the ICU experience. ICU sleep tends to be light and non-restorative (as opposed to deep / restorative sleep), severely fragmented, and distributed throughout the day and night rather than consolidated into nighttime hours. Sleep deprived patients suffer from sleep debt, a condition of impaired attention and memory, and cognitive slowing. Sleep disturbances in the ICU arise not only from light and noise pollution, but also from drugs that interfere with brain activity involved in restorative sleep. Sleep deprivation has also been suggested as a major modifiable risk factors for acute encephalopathy, also known as delirium. Delirium is an acute state of confusion that affects up to 80% of ICU patients, and is one of six leading causes of preventable morbidity and mortality in hospitalized elderly patients. Many patients who survive delirium experience long-term cognitive impairment and loss of independence. Current medications used in the ICU to treat sleep problems (e.g. benzodiazepines, antipsychotics) do not induce natural sleep and do not prevent delirium. In contrast, we have found that the α2-adrenoceptor agonist dexmedetomidine can induce biomimetic sleep, a brain state whose pattern of electroencephalogram (EEG) activity, cerebral blood flow, and functional connectivity approximates restorative sleep. Moreover, a recent large clinical trial in post-surgical patients suggests that low-dose dexmedetomidine given overnight substantially reduces the risk of delirium. It is unknown whether this benefit is linked to improved sleep, or whether patients with better sleep while in the ICU have better long-term cognitive outcomes. Our central hypothesis is that sleep deprivation substantially mediates both the short- and long-term cognitive impairments associated with delirium in critical illness. To test this hypothesis, our specific aims are designed to systematically determine 1) the impact of prophylactic dexmedetomidine on sleep quality, 2) the optimal way to give dexmedetomidine (all night vs at the beginning of the night only), 2) the impact of sleep deprivation on short-term cognitive function and delirium, and 3) the contribution of sleep deprivation to long-term neuropsychiatric outcome following critical illness. At the conclusion of these studies, we will have expanded our knowledge of sleep physiology in critical illness and relationship of sleep with delirium; evaluated a new preemptive therapeutic strategy to promote sleep and prevent delirium, and developed an understanding of how sleep impacts neuropsychological outcomes after critical illness. Our studies will thus will provide crucial guidance for individualized approaches to preserving long-term brain health in this vulnerable patient population.