Perioperative Cognitive Function - Dexmedetomidine and Cognitive Reserve

Postoperative Delirium or PD and Postoperative Cognitive Dysfunction or POCD are syndromes of
central nervous system dysfunction that significantly complicate the recovery of a proportion
of elderly patients following surgery.

Delirium is typically a transient syndrome characterized by a de-novo appearance of several
pathognomonic behaviors, including disorientation, decreased attention span, sensory
misperceptions, a waxing-and-waning type of confusion, and disorganized thinking. PD
typically occurs on postoperative days 1 to 3 and is associated with prolonged hospital
stays, increased risks for morbidity and mortality and significant health care expenditures.

The neuroendocrine stress response to surgery, including the immediate postoperative period,
remains an important potential etiologic factor. In particular, our data suggests that stress
in the immediate postoperative period is poorly controlled by all anesthetic techniques and
the normal diurnal variation in cortisol is suppressed in subjects who develop POCD.

Dexmedetomidine is a highly selective alpha 2A agonist currently approved for sedation in the
ICU. Dexmedetomidine produces analgesia, sympatholysis, and a light sedation characterized by
easy arousal. Its action converges on the endogenous substrates for natural sleep to produce
their sedative action, an effect that could prove beneficial to elderly postoperative
patients.

We hypothesize that treatment with dexmedetomidine will diminish both PD and POCD. The
essential proposition is that modulation of perioperative stress can ameliorate perioperative
delirium and cognitive dysfunction.

Based on both the concept of cognitive reserve as well as clinical experience, there is
concern that patients with preoperative cognitive impairment are particularly vulnerable to
POCD. In general, such patients have been excluded from previous studies. This study is
unique in that we will assess all participants for mild cognitive impairment prior to
surgery. Assessment of the impact of preexisting cognitive impairment is a secondary aim. A
broad goal of this interdisciplinary project is to evaluate POCD, which is primarily an
anesthesia concept, in the more general context of dementing illness as explored by geriatric
psychiatry.

Inclusion Criteria:

- 68 and older

- elective major surgery under general anesthesia(major surgery is defined by a planned
2 day hospitalization)

- ASA physical status I-III

- capable and willing to consent

- MMSE > 20 (to exclude dementia)

Exclusion Criteria:

- Cardiac surgery

- Intracranial Surgery

- Emergency Surgery

- Patients with severe visual or auditory disorder/handicaps

- Illiteracy

- Patients with clinically significant Parkinson's Disease

- Patients not expected to be able to complete the 3 and 6 month postoperative tests

- Sick sinus syndrome without pacemaker

- Hypersensitivity to drug or class

- Current 2nd or 3rd degree AV block

- History of clinically significant bradycardia

- Contraindication to the use of an 2A-agonist

- Presence of a major psychiatric condition such as bipolar disorder, major depression,
schizophrenia, or dementia

- ASA physical status IV or V