The Effects of Dexmedetomidine and Remifentanil on Carotid Patients

NCT ID: NCT00335972

Last Updated: 2017-08-11

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 142 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-06-30
• Study Completion Date: 2008-05-31

Brief Summary

We propose to test whether intraoperative administration of dexmedetomidine will reduce hemodynamic control in the intra- and post-operative periods and reduces PACU analgesic requirements in patients undergoing carotid endarterectomy.

Detailed Description

Remifentanil is an amidopiperidine derivative with unique pharmacokinetic properties. Its steady-state volume of distribution is 30 L (3). Its context-sensitive half life is consistently short (3.2 min), even after prolonged infusion(4). The pharmacokinetic profile of remifentanil is independent of the hepatic (5) and renal function (6). And finally, the recovery profile of remifentanil is excellent with a speedy anesthetic emergence time which is important for a quick and proper neurologic assessment in the early postoperative period.

Remifentanil produces good intraoperative hemodynamic control during intense noxious stimulation like laryngoscopy, endotracheal intubation, and during pinning of the head (8). However, side effects of remifentanil include hypotension and bradycardia (15) intraoperatively, along with apnea(16,17) and hyperalgesia(18) postoperatively which is caused by increasing sensitivity to noxious stimuli. Investigations demonstrate different mechanisms of opioid-induced post-infusion anti-analgesia and secondary hyperalgesia (9). Overall remifentanil is a versatile opioid that is being increasingly used in the operating room.

DEXMEDETOMIDINE (DEX), an alpha-2 adrenoreceptor agonist, is gaining popularity in neuroanesthesia. It has a desirable neurophysiologic profile including neuroprotective characteristics through its effect on α2A receptor subtypes (10). Its hypnotic effect is mediated through the α2 receptors in the locus ceruleus and its analgesic properties are mediated through an effect on the dorsal horn of the spinal cord (11,12). Since it has sympatholytic and antinociceptive properties, it may improve hemodynamic stability at critical moments of neurosurgical stimulation. Dexmedetomidine reduces anesthetic drug and opioid requirements in the perioperative period (13,14). In addition, dexmedetomidine does not affect evoked potential monitoring, (19) making it a favorable anesthetic adjunct in cases in which neurophysiologic monitoring is being used. In recent years, dexmedetomidine has emerged as an effective drug useful in a wide range of anesthesia related areas.

Study Questions We postulate that dexmedetomidine provides better hemodynamic control in the intra- and post-operative periods and reduces PACU analgesic requirements.

Primary Hypothesis 1: Intraoperative dexmedetomidine provides better postoperative analgesia than remifentanil, thus reducing PACU opioid requirements.

Primary Hypothesis 2: Dexmedetomidine causes fewer hemodynamic perturbations than remifentanil.

Conditions

Carotid Artery Stenosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

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

Group Type: ACTIVE_COMPARATOR

Remifentanil

Intervention Type: DRUG

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

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.

Group Type: ACTIVE_COMPARATOR

Dexmedetomidine

Intervention Type: DRUG

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.

Interventions

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

Intervention Type: 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.

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Cleveland Clinic

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ehab Farag, MD

Role: PRINCIPAL_INVESTIGATOR

The Cleveland Clinic

Locations

Cleveland Clinic

Cleveland, Ohio, United States

Countries

United States

Other Identifiers

10-27-05

Identifier Type: -

Identifier Source: org_study_id