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 ?2-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.

Public Health Relevance

Investigation of Sleep in the Intensive Care Unit (ICU-SLEEP) RELEVANCE: Sleep deprivation is common and severe in critically ill patients cared for in intensive care units (ICUs), and is hypothesized to be a key modifiable risk factor for delirium and long-term cognitive disability. Dexmedetomidine reduces the incidence of delirium in ICU patients by unknown mechanisms. This project will determine whether dexmedetomidine reduces delirium by improving sleep, whether bolus dosing vs continuous infusion is better, and the relationship of sleep quality to long-term cognitive outcomes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS102190-02
Application #
9673789
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
He, Janet
Project Start
2018-04-01
Project End
2023-03-31
Budget Start
2019-04-01
Budget End
2020-03-31
Support Year
2
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02114
Amorim, Edilberto; Ghassemi, Mohammad M; Lee, Jong W et al. (2018) Estimating the False Positive Rate of Absent Somatosensory Evoked Potentials in Cardiac Arrest Prognostication. Crit Care Med 46:e1213-e1221