Perioperative Cognitive Function - Dexmedetomidine and Cognitive Reserve

• Delirium Battery [ Time Frame: post surgery ] [ Designated as safety issue: Yes ]
  Occurrence of Post-Operative Delirium in PACU
• Delirium Battery [ Time Frame: postoperative day 1 ] [ Designated as safety issue: Yes ]
  Occurrence of Post-Operative Delirium in PACU
• Delirium Battery [ Time Frame: postoperative day 2 ] [ Designated as safety issue: Yes ]
  Occurrence of Post-Operative Delirium in PACU
• Delirium Battery [ Time Frame: postoperative day 3 if possible ] [ Designated as safety issue: Yes ]
  Occurrence of Post-Operative Delirium in PACU
• Delirium Battery [ Time Frame: postoperative day 4 if possible ] [ Designated as safety issue: Yes ]
  Occurrence of Post-Operative Delirium in PACU
• Delirium Battery [ Time Frame: postoperative day 5 if possible ] [ Designated as safety issue: Yes ]
  Occurrence of Post-Operative Delirium in PACU
• Delirium Battery [ Time Frame: at 3 months postoperatively ] [ Designated as safety issue: Yes ]
  Occurrence of Post-Operative Delirium in PACU
• Delirium Battery [ Time Frame: at 6 months postoperatively ] [ Designated as safety issue: Yes ]
  Occurrence of Post-Operative Delirium in PACU

• Neuropsychological testing [ Time Frame: at 3 months postoperatively ] [ Designated as safety issue: No ]
  Rate of change of cognitive function
• Neuropsychological testing [ Time Frame: at 6 months postoperatively ] [ Designated as safety issue: No ]
  Rate of change of cognitive function

Elderly patients who undergo anesthesia and non-cardiac surgery are subject to deterioration of brain function including the development of postoperative delirium (PD) and postoperative cognitive dysfunction (POCD). These disorders cause disability, distress for both patients and their families, are associated with other medical complications and account for significant additional health care costs. We currently use relatively primitive approaches to preventing and treating PD and POCD.

Dexmedetomidine is a drug used for sedation in critically ill patients that provides some pain relief and controls the bodies response to stress. The sedation produced by dexmedetomidine appears more similar to natural sleep than any other drug used for anesthesia and postoperative sedation. Data suggesting that dexmedetomidine can prevent delirium following cardiac surgery and the developing understanding of the causes of PD and POCD suggest that dexmedetomidine will be particularly effective.

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.

• Postoperative Delirium
• PD
• Postoperative Cognitive Dysfunction
• POCD

• Drug: Precedex (Dexmedetomidine)
  0.5/ug/kg/hr Dexmedetomidine infusions will begin prior to the surgery (no loading dose), and will be maintained at 0.5 mcg/kg/hour throughout surgery and titrated postoperatively for 2 hours postoperatively.
  Other Name: Dexmedetomidine
• Drug: Placebo
  0.5/ug/kg/hr Placebo infusions will begin prior to the surgery (no loading dose), and will be maintained at 0.5 mcg/kg/hour throughout surgery and titrated postoperatively for 2 hours postoperatively.
  Other Name: Normal Saline

• Experimental: Precedex
  Precedex (Dexmedetomidine)
  Intervention: Drug: Precedex (Dexmedetomidine)
• Placebo Comparator: Placebo
  Placebo - normal saline
  Intervention: Drug: Placebo

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