Minimizing ICU Neurological Dysfunction With Dexmedetomidine-induced Sleep

Delirium is an acute brain dysfunction characterized by disturbances in attention, awareness,
and cognition not explained by a preexisting neurocognitive disorder. Although the increased
mortality rates ascribed to delirium remain debatable, delirium remains a leading cause of
preventable morbidity in hospitalized elderly patients. It is also associated with prolonged
hospitalization, prolonged institutionalization, and long-term cognitive deficits. Patients
with pre-existing dementia, such as Alzheimer's disease, are especially vulnerable to
developing delirium. The total healthcare cost attributable to delirium is estimated between
$143 and $152 billion annually. In the United States, delirium occurs in approximately 80% of
critically ill patients admitted to medical/surgical intensive care units (ICU), and 15% of
patients admitted to cardiac surgical (CS) ICU. Most patients diagnosed with delirium also
present with multiple comorbidities (sepsis, multi-organ failure) that significantly confound
our understanding of this disease. Thus, to date, no pharmacological intervention to treat
delirium has been identified.

There is mounting evidence to suggest that sleep deprivation may be a modifiable risk factor
for the development of delirium. Presently, pharmacological treatment with no current
medication (benzodiazepines, antipsychotics) induces natural sleep or reliably reduces the
incidence of delirium. The investigators have found that biomimetic sleep, defined here as
pharmacological induction of rapid eye movement sleep (REM) and non-REM (N1, N2, N3) sleep
states using dexmedetomidine, can now be achieved in humans. The overall objective of this
study is to evaluate the efficacy of biomimetic sleep in reducing the incidence and severity
of delirium in extubated CSICU patients. The investigators will also assess for
peri-operative electroencephalogram biomarkers of delirium, and the association between
delirium and chronic neuroinflammation using positron emission tomography. The MINDDS study
is poised to enable therapeutic and diagnostic discoveries to aid the care of elderly
patients who are at risk for developing postoperative delirium.

Inclusion Criteria:

- Age ≥ 60

- Scheduled for a cardiac surgical procedure with planned post-operative admission to
the CSICU for ≥ 24 hours

- Scheduled same day surgical admission

Exclusion Criteria:

- Blind, deafness or the inability to speak English

- Greater than 2 days of ICU admission in the month preceding the current surgical
procedure

- Renal and liver failure requiring dialysis or Child-Pugh score > 5

- Follow-up difficulties (i.e. active substance abuse, psychotic disorder, homelessness)

- Previous cardiac surgery within 1 year of surgical procedure

- Allergy to dexmedetomidine

- Chronic therapy with benzodiazepines and/or antipsychotics

- Severe deficit due to structural or anoxic brain damage

- Surgical procedure requiring total circulatory arrest

Objective Drop Criteria

- Scheduled for a second surgical procedure during hospital stay

- Post-operative intubation > 12 hours