Investigation of Sleep in the Intensive Care Unit

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, the
investigators 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. The investigator's 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, this study is 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, the investigators will have expanded 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. These
studies will thus will provide crucial guidance for individualized approaches to preserving
long-term brain health in this vulnerable patient population.

Inclusion Criteria:

In order to be eligible to participate in this study, an individual must meet all of the
following criteria:

1. Admitted to MGH Blake 7 or 12, or Elllison 4 ICU at Massachusetts General Hospital.

2. Male or female, aged >18 years

3. Provision of signed and dated informed consent form (by patient or LAR)

4. Stated willingness to comply with all study procedures and availability for the
duration of the study

5. No on mechanical ventilation at the time of enrollment.

6. Have not been in the ICU for more than 48 hours before enrollment.

7. Able to be enrolled before 7PM.

8. For females of reproductive potential: pregnancy test is negative.

Exclusion Criteria:

An individual who meets any of the following criteria will be excluded from participation
in this study:

1. Mechanical ventilation in the previous 2 months or >5 days in an ICU in the prior
month

2. Unable to be assessed for delirium (e.g. blindness or deafness)

3. Pregnancy or lactation

4. Known allergic reactions to components of dexmedetomidine

5. Follow-up would be difficult (e.g. active substance abuse, homelessness)

6. Severe dementia, as measured by a score of ≥3.3 on the Short Informant Questionnaire
on Cognitive Decline in the Elderly (IQCODE)

7. Known pre-existing neurologic disease or injury with focal neurologic or cognitive
deficits

8. Serious cardiac disease (e.g. sick sinus syndrome, sinus bradycardia)

9. Cardiac surgery <3 months ago

10. Severe liver dysfunction (Child-Pugh class C)

11. Severe renal dysfunction (receiving dialysis)

12. Low likelihood of survival >24 hours

13. Patient is receiving either of the anticholinergic drugs scopolamine or penehyclidine

14. Concomitant enrollment in another study protocol that may interfere with data
acquisition or reliability of measurements;

15. Deemed unsuitable for selection by the research team or ICU providers due to any
medical, legal, social, or interpersonal issues that would either compromise the study
or the routine care of patients.