Cognitive Protection - Dexmedetomidine and Cognitive Reserve

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
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.

Official Title
-----------------
Cognitive Protection - Dexmedetomidine and Cognitive Reserve

Conditions
-----------------
Postoperative Delirium, PD, Postoperative Cognitive Dysfunction, POCD

Intervention / Treatment
-----------------
* Drug: Precedex (Dexmedetomidine)
* Drug: Placebo


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dexmedetomidine<br>Participants will be randomized to either dexmedetomidine or placebo which will be started prior to surgery and continued for 24 hours postoperatively. Patients will receive dexmedetomidine until discharge from the PACU. | Drug: Precedex (Dexmedetomidine)<br>* Dexmedetomidine started prior to surgery and continued for 24 hours postoperatively. Patients will receive dexmedetomidine until discharge from the PACU.<br>* Other names: Dexmedetomidine;|
| Placebo Comparator: Placebo<br>Participants will be randomized to either dexmedetomidine or placebo which will be started prior to surgery and continued for 24 hours postoperatively or until discharge from the PACU. | Drug: Placebo<br>* Matching placebo given prior to surgery and continued for 24 hours postoperatively<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional Recovery |  | 3 months post surgery | 
| Functional Recovery |  | 6 months post surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive Testing |  | prior to surgery | 
| Cognitive Testing |  | 3 months post surgery | 
| Cognitive Testing |  | 6 months post surgery | 
| Delirium Assessments |  | prior to surgery | 
| Delirium Assessments |  | duration of PACU stay, up to 4 days post-op | 
| Delirium Assessments |  | 3 months post surgery | 
| Delirium Assessments |  | 6 months post surgery | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Postoperative delirium, PD, Postoperative cognitive dysfunction, POCD