Minimizing ICU Neurological Dysfunction With Dexmedetomidine-induced Sleep

This study aims to determine whether, compared with placebo, the nighttime administration of a intravenous dexmedetomidine is effective at inducing sleep and preventing postoperative delirium in extubated post-cardiac surgical patients.

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.

Eligibility Criteria:
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