Clinical trial NCT00335972: The Effects of Dexmedetomidine and Remifentanil on Carotid Patients
Official title: Phase 4: The Effects of Dexmedetomidine and Remifentanil on Postoperative Hemodynamics and Pain/Opioids in Patients Undergoing Carotid Endarterectomy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Carotid Artery Stenosis
Keywords: Carotid Endarterectomy patients
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
First posted: 2006-06-12
Enrollment: 142
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Mean Arterial Pressure
timeFrame: mean arterial pressure at 15, 30, 45, 60, and 90 minutes after extubation
measure: Visual Analogue Scale (VAS) Pain Score
timeFrame: pain score measured at 15, 30, 45, 60, and 90 minutes after extubation
measure: Intravenous Morphine Equivalents During Post-anesthesia Care Unit (PACU) After Surgery
timeFrame: During Post-anesthesia care unit after surgery,an average of 4 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
Study officials:
affiliation: The Cleveland Clinic
name: Ehab Farag, MD
role: PRINCIPAL_INVESTIGATOR
References: