Carotid Artery Stenosis
Conditions
Keywords
Carotid Endarterectomy patients
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.
Interventions
DRUGRemifentanil
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
DRUGDexmedetomidine
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.
Sponsors
The Cleveland Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Arterial Pressure | mean arterial pressure at 15, 30, 45, 60, and 90 minutes after extubation | — |
| Visual Analogue Scale (VAS) Pain Score | pain score measured at 15, 30, 45, 60, and 90 minutes after extubation | Using a ruler, the score is determined by measuring the distance on the 10-cm line between the no pain anchor and the patient's mark, providing a range of scores from 0-10. 0 = no pain and 10 = worst |
| Intravenous Morphine Equivalents During Post-anesthesia Care Unit (PACU) After Surgery | During Post-anesthesia care unit after surgery,an average of 4 hours | intravenous morphine equivalents (mg) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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
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 | 71 |
| 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.
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. | 68 |
| Total | 139 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | not given treatments | 0 | 3 |
Baseline characteristics
| Characteristic | Remifentanil | Dexmedetomidine | Total |
|---|---|---|---|
| Age, Continuous | 55 years STANDARD_DEVIATION 14 | 56 years STANDARD_DEVIATION 14 | 55 years STANDARD_DEVIATION 14 |
| Race/Ethnicity, Customized Race-other | 6 Participants | 11 Participants | 17 Participants |
| Race/Ethnicity, Customized Race-white | 65 Participants | 57 Participants | 122 Participants |
| Sex: Female, Male Female | 37 Participants | 33 Participants | 70 Participants |
| Sex: Female, Male Male | 34 Participants | 35 Participants | 69 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 71 | 0 / 68 |
| other Total, other adverse events | 0 / 71 | 0 / 68 |
| serious Total, serious adverse events | 0 / 71 | 0 / 68 |
Outcome results
Primary
Intravenous Morphine Equivalents During Post-anesthesia Care Unit (PACU) After Surgery
intravenous morphine equivalents (mg)
Time frame: During Post-anesthesia care unit after surgery,an average of 4 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Remifentanil | Intravenous Morphine Equivalents During Post-anesthesia Care Unit (PACU) After Surgery | 10 mg |
| Dexmedetomidine | Intravenous Morphine Equivalents During Post-anesthesia Care Unit (PACU) After Surgery | 5 mg |
p-value: <0.00195% CI: [-10, -5]Wilcoxon (Mann-Whitney)
Comparison: superiorityp-value: <0.00197.5% CI: [-10, -3]repeated measures ANOVA model
Primary
Mean Arterial Pressure
Time frame: mean arterial pressure at 15, 30, 45, 60, and 90 minutes after extubation
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Remifentanil | Mean Arterial Pressure | at 30 minutes after extubation | 98 mmHg | Standard Deviation 12 |
| Remifentanil | Mean Arterial Pressure | at 60 minutes after extubation | 96 mmHg | Standard Deviation 12 |
| Remifentanil | Mean Arterial Pressure | at 45 minutes after extubation | 98 mmHg | Standard Deviation 13 |
| Remifentanil | Mean Arterial Pressure | at 90 minutes after extubation | 94 mmHg | Standard Deviation 12 |
| Remifentanil | Mean Arterial Pressure | at 15 minutes after extubation | 99 mmHg | Standard Deviation 12 |
| Dexmedetomidine | Mean Arterial Pressure | at 90 minutes after extubation | 88 mmHg | Standard Deviation 13 |
| Dexmedetomidine | Mean Arterial Pressure | at 15 minutes after extubation | 86 mmHg | Standard Deviation 13 |
| Dexmedetomidine | Mean Arterial Pressure | at 30 minutes after extubation | 87 mmHg | Standard Deviation 13 |
| Dexmedetomidine | Mean Arterial Pressure | at 45 minutes after extubation | 86 mmHg | Standard Deviation 13 |
| Dexmedetomidine | Mean Arterial Pressure | at 60 minutes after extubation | 89 mmHg | Standard Deviation 15 |
p-value: <0.00195% CI: [-13, -5]repeated measures ANOVA
Comparison: superiority testp-value: <0.00197.5% CI: [-13, -4]repeated measures ANOVA model
Primary
Visual Analogue Scale (VAS) Pain Score
Using a ruler, the score is determined by measuring the distance on the 10-cm line between the no pain anchor and the patient's mark, providing a range of scores from 0-10. 0 = no pain and 10 = worst
Time frame: pain score measured at 15, 30, 45, 60, and 90 minutes after extubation
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Remifentanil | Visual Analogue Scale (VAS) Pain Score | at 60 minutes after extubation | 4.9 cm | Standard Deviation 2.6 |
| Remifentanil | Visual Analogue Scale (VAS) Pain Score | at 15 minutes after extubation | 5.4 cm | Standard Deviation 3.4 |
| Remifentanil | Visual Analogue Scale (VAS) Pain Score | at 30 minutes after extubation | 5.3 cm | Standard Deviation 2.8 |
| Remifentanil | Visual Analogue Scale (VAS) Pain Score | at 45 minutes after extubation | 5.0 cm | Standard Deviation 2.4 |
| Remifentanil | Visual Analogue Scale (VAS) Pain Score | at 90 minutes after extubation | 4.8 cm | Standard Deviation 2.4 |
| Dexmedetomidine | Visual Analogue Scale (VAS) Pain Score | at 90 minutes after extubation | 2.9 cm | Standard Deviation 2.8 |
| Dexmedetomidine | Visual Analogue Scale (VAS) Pain Score | at 45 minutes after extubation | 3.1 cm | Standard Deviation 3 |
| Dexmedetomidine | Visual Analogue Scale (VAS) Pain Score | at 15 minutes after extubation | 2.6 cm | Standard Deviation 3.4 |
| Dexmedetomidine | Visual Analogue Scale (VAS) Pain Score | at 60 minutes after extubation | 2.9 cm | Standard Deviation 2.7 |
| Dexmedetomidine | Visual Analogue Scale (VAS) Pain Score | at 30 minutes after extubation | 2.8 cm | Standard Deviation 3.2 |
p-value: <0.00195% CI: [-2.7, -1.1]repeated measures ANOVA model
Comparison: superiority testp-value: <0.00197.5% CI: [-2.8, -0.9]repeated measures ANOVA model