The Effects of DexMed and Desflurane on Carotid Patients - Full Text View

Sponsored by:	Outcomes Research Consortium
Information provided by:	Outcomes Research Consortium
ClinicalTrials.gov Identifier:	NCT00335972

Purpose

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

Condition	Intervention	Phase
Carotid Artery Stenosis	Drug: Remifentanil Drug: Dexmedetomidine Drug: Remifentanil and Desflurane Drug: Desflurane Drug: Dexmedetomidine and Desflurane	Phase IV

Drug Information available for: I 653 Dexmedetomidine Remifentanil hydrochloride Remifentanil Dexmedetomidine hydrochloride

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator), Active Control, Factorial Assignment, Efficacy Study
Official Title:	Phase 4: The Effects of Dexmedetomidine and Desflurane on Postoperative Cognitive Dysfunction in Patients Undergoing Carotid Endarterectomy

Further study details as provided by Outcomes Research Consortium:

Primary Outcome Measures:

Neurocognition [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]

Enrollment:	400
Study Start Date:	June 2006
Estimated Study Completion Date:	June 2008
Estimated Primary Completion Date:	June 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: 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	Drug: Remifentanil 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
2: 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.	Drug: Dexmedetomidine 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.
3: 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	Drug: Remifentanil and Desflurane 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 Drug: Desflurane 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.
4: 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.	Drug: Dexmedetomidine and Desflurane 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.

Detailed Description:

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).

Eligibility

Ages Eligible for Study:	50 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00335972

Locations

United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195

Sponsors and Collaborators

Outcomes Research Consortium

Investigators

Principal Investigator:

Ehab Farag, MD

Cleveland Clinic

More Information

No publications provided

Responsible Party:	Cleveland Clinic ( Ehab Farag, MD )
Study ID Numbers:	10-27-05
Study First Received:	June 8, 2006
Last Updated:	May 22, 2008
ClinicalTrials.gov Identifier:	NCT00335972 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Outcomes Research Consortium:

Carotid Endarterectomy patients

Study placed in the following topic categories:

Neurotransmitter Agents
Adrenergic Agents
Benzocaine
Anesthetics
Constriction, Pathologic
Brain Diseases
Cerebrovascular Disorders
Adrenergic Agonists
Desflurane
Hypnotics and Sedatives
Dexmedetomidine
Analgesics
Propofol
Analgesics, Opioid

Anesthetics, Intravenous
Arterial Occlusive Diseases
Adrenergic alpha-Agonists
Remifentanil
Vascular Diseases
Central Nervous System Diseases
Central Nervous System Depressants
Carotid Stenosis
Anesthetics, Inhalation
Anesthetics, General
Analgesics, Non-Narcotic
Peripheral Nervous System Agents
Carotid Artery Diseases

Additional relevant MeSH terms:

Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Adrenergic Agents
Physiological Effects of Drugs
Anesthetics
Brain Diseases
Cerebrovascular Disorders
Adrenergic Agonists
Desflurane
Sensory System Agents
Therapeutic Uses
Hypnotics and Sedatives
Cardiovascular Diseases
Dexmedetomidine
Analgesics

Analgesics, Opioid
Anesthetics, Intravenous
Arterial Occlusive Diseases
Adrenergic alpha-Agonists
Remifentanil
Nervous System Diseases
Vascular Diseases
Central Nervous System Diseases
Central Nervous System Depressants
Pharmacologic Actions
Anesthetics, Inhalation
Carotid Stenosis
Anesthetics, General
Analgesics, Non-Narcotic
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on May 06, 2009