We propose to test whether intraoperative administration of dexmedetomidine will reduce postoperative neurocognitive dysfunction in patients undergoing carotid endarterectomy.

Stroke is the third leading cause of death and the leading cause of severe long-term disability with serious physical and psychosocial effects. Each year about 700,000 people experience a new or recurrent stroke out of which 88% are ischemic. Atherosclerotic carotid artery disease is a major contributor to the incidence of stroke, particularly in the elderly. Carotid endarterectomy (CEA) is believed to reduce the risk of stroke in patients with symptomatic as well as non-symptomatic carotid artery stenosis and is the most frequently performed surgical procedure to prevent stroke.

However, CEA itself carries a risk of complications. Although the incidence of overt neurological injury associated with CEA is low, cognitive injuries not revealed in routine neurological examinations are believed to be as high as 20-30%.

The purpose of this study is to determine the neuro-protective (brain-protecting) effect of the Food and Drug Administration (FDA) approved drug, dexmedetomidine and desflurane in patients undergoing a carotid endarterectomy surgery. We will also determine if administering anesthetics by intravenous route (through blood) is brain-protecting as compared to inhaled anesthetics administered. It is expected that the action of these techniques on brain will decrease the neurological (brain) damage after a period of decreased blood supply to the brain that normally occurs during the procedure.

This neuroprotective action has already been demonstrated in animal studies.

The goals for intraoperative anesthetic management of CEA include protection of the brain from ischemic injury. Dexmedetomidine has been found to be neuroprotective in vivo and vitro models of hypoxic-ischemic injury. We therefore propose to test whether intraoperative administration of dexmedetomidine will reduce postoperative neurocognitive dysfunction in patients undergoing CEA.

Desflurane has been shown to be neuroprotective after incomplete cerebral ischemia. Desflurane not only attenuates the decrease but also increases brain tissue oxygenation and pH during ischemic injury and might improve neurological outcome. Neurocognitive outcomes may thus be superior with desflurane than with total intravenous anesthesia (TIVA). We thus also propose to test whether desflurane anesthesia reduces the incidence of postoperative neurocognitive dysfunction in patients undergoing carotid endarterectomy (CEA).

• Drug: Remifentanil
• Drug: Dexmedetomidine
• Drug: Remifentanil and Desflurane
• Drug: Desflurane
• Drug: Dexmedetomidine and Desflurane

• Active Comparator: Remifentanil will be infused throughout surgery at a rate of 0.1-0.2 µg/kg/min. Propofol will be titrated to maintain a BIS value as close to 45 as clinically practical
• Active Comparator: Dexmedetomidine, 0.5-1 µg/kg, will be infused over 20 minutes, immediately followed by an infusion at a rate of 0.2 µg/kg/hr until the end of surgery (For patients in renal failure, the loading dose will be 0.2 µg/kg). The infusion rate will be reduced as necessary to maintain acceptable blood pressure and heart rate. Propofol will be titrated to maintain BIS as close to 45 as clinically practical.
• Active Comparator: Remifentanil will be infused throughout the surgery at a rate of 01-0.2 µg/kg/min. Desflurane will be titrated to maintain BIS as close to 45 as clinically practical
• Active Comparator: Dexmedetomidine, 0.5-1 µg/kg, will be infused over 20 minutes, immediately followed by an infusion of 0.2 µg/kg/hr until the end of surgery (For patients in renal failure, the loading dose will be 0.2 µg/kg). The infusion rate will be reduced as necessary to maintain acceptable blood pressure and heart rate. Desflurane will be titrated to maintain BIS as close to 45 as clinically practical.

Inclusion Criteria:

• Consenting adult patients (age >50 years) undergoing carotid endarterectomy with general anesthesia.

Exclusion Criteria:

• Receiving another alpha 2-adrenoreceptor agonist;
• Contraindication to dexmedetomidine, including allergy;
• Current hepatic disease (liver function tests > twice upper limit of normal);
• Renal insufficiency, as defined by a creatinine > 2.0 mg/dL;
• Mentally impairment, including dementia or delirium;
• Heart block ;
• Sick sinus syndrome;
• Atrial fibrillation with a low ventricular response (< 50 bpm);
• Absolute or relative hypovolemia;
• Prior stroke;
• Severe left-ventricular dysfunction