Cognitive Protection - Dexmedetomidine and Cognitive Reserve

This is a pilot study to evaluate the effect of dexmedetomidine in the prevention of delirium in non-cardiac surgical patients. The preliminary data regarding the effect of dexmedetomidine on delirium comes from a study underway at Stanford. We propose to randomize fifty patients into two different protocols, one using dexmedetomidine until PACU discharge (hip replacement) and the other using dexmedetomidine for 24 hours in a monitored setting.

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. The proposed is a pilot study for an NIH grant which was recently submitted. This is a randomized controlled trial of perioperative dexmedetomidine to prevent PD and, potentially, POCD. Fifty patients will be enrolled at Mount Sinai with two different surgeries, either hip replacement or vascular bypass. The patients undergoing hip replacement will receive dexmedetomidine until discharge from the PACU. Vascular surgery patients who are transferred from the PACU to a monitored step-sown unit will continue dexmedetomidine for 24 hours.Participants will be screened for Mild Cognitive Impairment (MCI), and undergo preoperative cognitive testing. Unlike the parent trial, we will test for but will not select for patients with MCI. Participants will be randomized to either dexmedetomidine or placebo which will be started prior to surgery and continued for 24 hours postoperatively. Follow up studies will include surveillance for delirium while in the hospital and cognitive testing at 3 months following surgery.

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.

Eligibility Criteria:
Inclusion Criteria:

* age 65 years and older
* elective major hip replacement or peripheral vascular (major surgery is defined by a planned 2 day hospitalization)
* ASA physical status I-III
* capable and willing to consent

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 month postoperative test
* 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