Intracranial Neurosurgery
Conditions
Keywords
dexmedetomidine, propofol, cerebral blood flow, brain oxygenation
Brief summary
The investigators will evaluate the effects of dexmedetomidine and propofol on cerebral blood flow and brain oxygenation during Deep Brain Stimulation (DBS) surgery. Specifically, the investigators will test the hypothesis that dexmedetomidine is non-inferior to propofol for cerebral blood flow as measured by transcranial Doppler and brain oxygenation as measured by near-infrared spectroscopy.
Interventions
DRUGdexmedetomidine
Patients assigned to dexmedetomidine will be given a mg/kg bolus over 10-20 minutes; subsequently, an infusion will be titrated to between 0.4-0.6 mcg/kg/hr to maintain an adequate level of sedation during the procedure.
DRUGpropofol
Patients assigned to propofol will be given an infusion dose of 50-75 µ/kg/min which will be titrated to the patient's response
Sponsors
The Cleveland Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* ASA I-III. * Scheduled for DBS.
Exclusion criteria
* History of dystonia. * Severe heart failure with ejection fraction less than 30%. * History of obstructive sleep apnea. * History of renal failure with creatinine level \> 2 mg/dl. * Allergies to α-2 agonists and propofol. * Current use of α-2 agonist medications such as clonidine.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cerebral Blood Flow | For patients randomized to dexmedetomidine: at the first peak of study drug (i.e., at peak dose of study drug during first infusion period); for patients randomized to propofol: when infusion of propofol stopped. | Cerebral blood flow was the average of right and left carotid velocities recorded by transcranial Doppler. |
| Brain Oxygen | during first (10-20 minutes) and second (throughout the procedure) study drug infusion periods | Brain oxygenation values were estimated by near-infrared spectroscopy and brain oxygenation was averaged across the first and second study drug infusion periods. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pulsatility Index | at the first peak during DBS surgery | Pulsatility index is a measure of the variability of blood velocity in a vessel, and was calculated as the difference between the peak systolic and minimum diastolic velocities divided by the mean velocity during the cardiac cycle. |
| Cerebral Perfusion Pressure | at the first peak during DBS surgery | — |
| Cerebral Blood Flow | after procedure, in post anesthesia care unit (PACU) | The investigator will test the hypothesis that dexmedetomidine is non-inferior to propofol for cerebral blood flow as measured by transcranial Doppler and brain oxygenation as measured by near-infrared spectroscopy. |
| Number of Apneic Episodes. | during DBS surgery | The number of antihypertensive interventions during Deep Brain Stimulation (DBS) surgery. |
| Number of Hypertensive Episodes | During DBS surgery | The number of hypertensive episodes during Deep Brain Stimulation (DBS) surgery. |
| Alertness/Sedation | at the first peak during DBS surgery | Modified observer's assessment of alertness /sedation (OAA/S) scale which ranges from 0 to 5 (0 = does not respond to noxious stimuli and 5 = responds to name spoken in normal tone) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Propofol Subjects will be sedated with propofol.
propofol: Patients assigned to propofol will be given an infusion dose of 50-75 µ/kg/min which will be titrated to the patient's response | 21 |
| Dexmedetomidine Subjects will be sedated with dexmedetomidine.
dexmedetomidine: Patients assigned to dexmedetomidine will be given a mg/kg bolus over 10-20 minutes; subsequently, an infusion will be titrated to between 0.4-0.6 mcg/kg/hr to maintain an adequate level of sedation during the procedure. | 23 |
| Total | 44 |
Baseline characteristics
| Characteristic | Propofol | Dexmedetomidine | Total |
|---|---|---|---|
| Age, Continuous | 63.5 years STANDARD_DEVIATION 10.5 | 65.4 years STANDARD_DEVIATION 6.8 | 64.5 years STANDARD_DEVIATION 8.7 |
| Gender Female | 3 Participants | 5 Participants | 8 Participants |
| Gender Male | 18 Participants | 18 Participants | 36 Participants |
| Race/Ethnicity, Customized Caucasian | 21 participants | 21 participants | 42 participants |
| Race/Ethnicity, Customized Others | 0 participants | 2 participants | 2 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 21 | 0 / 23 |
| serious Total, serious adverse events | 0 / 21 | 0 / 23 |
Outcome results
Primary
Brain Oxygen
Brain oxygenation values were estimated by near-infrared spectroscopy and brain oxygenation was averaged across the first and second study drug infusion periods.
Time frame: during first (10-20 minutes) and second (throughout the procedure) study drug infusion periods
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Propofol | Brain Oxygen | 73.5 % oxygenation |
| Dexmedetomidine | Brain Oxygen | 72.7 % oxygenation |
p-value: <0.00190% CI: [0.96, 1.02]t-test, 1 sided
Primary
Cerebral Blood Flow
Cerebral blood flow was the average of right and left carotid velocities recorded by transcranial Doppler.
Time frame: For patients randomized to dexmedetomidine: at the first peak of study drug (i.e., at peak dose of study drug during first infusion period); for patients randomized to propofol: when infusion of propofol stopped.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Propofol | Cerebral Blood Flow | 45.4 cm/sec |
| Dexmedetomidine | Cerebral Blood Flow | 39.9 cm/sec |
p-value: 0.01190% CI: [0.84, 1.05]t-test, 1 sided
Secondary
Alertness/Sedation
Modified observer's assessment of alertness /sedation (OAA/S) scale which ranges from 0 to 5 (0 = does not respond to noxious stimuli and 5 = responds to name spoken in normal tone)
Time frame: at the first peak during DBS surgery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Propofol | Alertness/Sedation | 2 units on a scale |
| Dexmedetomidine | Alertness/Sedation | 3 units on a scale |
p-value: <0.00199% CI: [0, 2]Wilcoxon (Mann-Whitney)
Secondary
Cerebral Blood Flow
The investigator will test the hypothesis that dexmedetomidine is non-inferior to propofol for cerebral blood flow as measured by transcranial Doppler and brain oxygenation as measured by near-infrared spectroscopy.
Time frame: after procedure, in post anesthesia care unit (PACU)
Population: The cerebral flow at PACU was not planned as a primary outcome. The primary outcome was cerebral flow at the first peak of study drug. The data was collect for information purpose only. No test was done for cerebral blood flow at PACU.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Propofol | Cerebral Blood Flow | 55 cm/sec | Standard Deviation 18.1 |
| Dexmedetomidine | Cerebral Blood Flow | 46.7 cm/sec | Standard Deviation 10.5 |
Secondary
Cerebral Perfusion Pressure
Time frame: at the first peak during DBS surgery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Propofol | Cerebral Perfusion Pressure | 53.9 mmHg |
| Dexmedetomidine | Cerebral Perfusion Pressure | 54.6 mmHg |
Secondary
Number of Apneic Episodes.
The number of antihypertensive interventions during Deep Brain Stimulation (DBS) surgery.
Time frame: during DBS surgery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Propofol | Number of Apneic Episodes. | 0 number of episodes |
| Dexmedetomidine | Number of Apneic Episodes. | 0 number of episodes |
p-value: >0.9999% CI: [0, 0]Wilcoxon (Mann-Whitney)
Secondary
Number of Hypertensive Episodes
The number of hypertensive episodes during Deep Brain Stimulation (DBS) surgery.
Time frame: During DBS surgery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Propofol | Number of Hypertensive Episodes | 4.9 number of episodes | Standard Deviation 2.7 |
| Dexmedetomidine | Number of Hypertensive Episodes | 2.9 number of episodes | Standard Deviation 2.5 |
p-value: 0.0299% CI: [-4.1, 0.2]Wilcoxon (Mann-Whitney)
Secondary
Pulsatility Index
Pulsatility index is a measure of the variability of blood velocity in a vessel, and was calculated as the difference between the peak systolic and minimum diastolic velocities divided by the mean velocity during the cardiac cycle.
Time frame: at the first peak during DBS surgery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Propofol | Pulsatility Index | 1 units on a scale |
| Dexmedetomidine | Pulsatility Index | 1 units on a scale |
p-value: 0.9199% CI: [0.86, 1.18]Wilcoxon (Mann-Whitney)