Adult Intracranial Tumor, Adult Solid Tumor
Conditions
Keywords
Craniotomy, pain relief, Adult solid neoplasm
Brief summary
This will be a randomized blinded clinical trial. Patients will be randomized to receive either a remifentanil or dexmedetomidine infusion for general anesthesia. The anesthesia team will know the result of randomization at induction. Data will be gathered by research personnel who will be blinded to the anesthetic method used. Patients will be blinded to the anesthetic they receive till they are discharged from the PACU when they will have the option to be unblinded. The Data Safety and -Toxicity Committee will review all serious adverse events and toxicity reports as well as annual reviews.
Detailed description
Anesthesia for craniotomy presents a unique challenge to the anesthesiologist. Anesthesia for neurosurgical procedures should provide optimal surgical conditions while maintaining appropriate cerebral oxygen supply and stable systemic hemodynamics. (1) It is important to prevent patient response to noxious stimuli during the procedure like pinning, drilling of the bone, opening and manipulation of the dura etc., avoid coughing and bucking during surgery and during extubation thus necessitating a deeper level of anesthesia and analgesia. At the same time it is desirable to have the patient fully awake toward the end of the surgery in order to facilitate neurologic evaluation. Management of the above presents a challenge during induction, maintenance and extubation and also during multiple critical stages of surgery Fear of the side effects of analgesic drugs frequently leads to the under-treatment of post-craniotomy pain. (2) Nevertheless, this pain continues to be commonly observed, is frequently severe, and, if unrelieved, may cause distress for the neurosurgical patient and serious complications for the operative brain. (2) There is a need for larger trials to delineate safety and efficacy of analgesic therapies with a focus on short- and long-term outcomes.
Interventions
DRUGRemifentanil
Remifentanil 0.08-0.15MCG/KG/MIN INFUSION THROUGHOUT PROCEDURE BASED ON HEMODYNAMICS
DRUGDexmedetomidine
a loading dose of dexmedetomidine was given at 0.5 to 1 micrograms/kg ideal body weight over 15 minutes, followed by an infusion at 0.2 to 0.7 micrograms/kg/hour.
Sponsors
The Cleveland Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Patients who undergo general anesthesia for elective surgical excision of a brain tumor with following specifications: * Age: Older than 18 * Primary and redo cases will be included * Duration of surgery not exceeding 6 hrs.
Exclusion criteria
* Patient refusal * Emergency craniotomy * Morbid obesity * Uncontrolled hypertension - DBP more than 110 * Cardiac conduction defects * Patients with chronic pain.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hemodynamics | 15, 30, 45, 60, and 90 minutes after extubation. | Hemodynamics were defined as mean arterial pressure (MAP), measured in milimeters of mercury (mmHg). This outcome was analyzed using a repeated measures ANOVA approach. In the outcome measure data table, mean ± standard deviation MAP was reported as the aggregate mean across time points. |
| Postoperative Pain | 15, 30, 45, 60, and 90 minutes after extubation. | Pain was measured using the visual analogue scale (VAS), where 0 is defined as no pain and 10 is defined as worst pain imaginable. This outcome was analyzed using a repeated measures ANOVA approach. In the outcome measure data table, mean ± standard deviation pain was reported as the aggregate mean across time points. |
| Total Opioid Consumption | Initial 90 minutes of recover after surgery | Total opioid consumption was defined as the sum of all opioid doses given within the first 90 minutes after surgery, converted to milligram morphine equivalents. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Nursing Workload Comparison | 90 minutes after extubation | To evaluate the nurses workload when either of the two drugs are given in terms Nursing Research Usage form's therapeutic index scoring system. This score ranges from 0 (minimal interventions and time spent by nurses on study patient) to 22 (maximum interventions and time spent by nurses on the study patient). |
| Drug Stop Time to Open Eyes | Anesthesia drug stop time to open eyes. Time is measured continuously until patients eyes open, regardless of how long it takes. | time until patient first opened their eyes, squeezed a hand, or wiggled their toes in response to verbal commands after surgery |
| Drug Stop Time to Recall | Time between extubation until patients could say their names. | Time between extubation until patients could say their names. |
| Drug Stop Time to Fitness to Discharge | Anesthesia drug stop time to fitness to discharge. Time is measured continuously until fitness for discharge is reached, regardless of how long it takes. | — |
| Heart Rate | 15, 30, 45, 60, and 90 minutes after extubation. | Heart rate was determined from the arterial catheter and measured as beats per minute. This outcome was analyzed using a repeated measures ANOVA approach. |
| Postoperative Nausea | Whether patients had nausea or not, from anesthesia stop time until hospital discharge. | Indicator of whether patients had nausea or not |
| Postoperative Vomitting | Whether patients had vomiting or not, from anesthesia stop time until hospital discharge. | Indicator of whether patients had postoperative vomiting. |
| Postoperative Shivering | Whether patients had postoperative or not, from anesthesia stop time until hospital discharge. | Indicator of whether patients had postoperative shivering. |
| End Case to Post Anesthesia Care Unit (PACU) Discharge | End case to post anesthesia care unit (PACU) discharge. Time is measured continuously until PACU discharge, regardless of how long it takes. | Post Anesthesia Care Unit (PACU) Discharge time is the timing at which patients are discharged from the PACU. This outcome is the amount of time (minutes) from end case to PACU discharge. |
| Modified Short Orientation Memory Concentration Test (SOMCT) | 15, 30, 45, 60, and 90 minutes after extubation. | The Modified Short Orientation Memory Concentration Test (SOMCT) is a validated questionnaire that discriminates among mild, moderate, and severe cognitive deficits. SOMCT is based on 6 questions and produces a total score ranging from 0 (worst possible function) to 28 (best possible function). Scores \> 20 are considered normal. This outcome was analyzed using a repeated measures ANOVA approach. |
| Aldrete Score | 15, 30, 45, 60, and 90 minutes after extubation. | The Aldrete score measured level of sedation and fitness and is used to assess the appropriate departure time from the post anesthesia care unit. The score ranges from 0 to 10, where 0 indicates poor fitness (and such patients are transferred to the ICU), while 10 indicates good fitness. This outcome was analyzed using a repeated measures ANOVA approach. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Remifentanil Remifentanil 0.08-0.15MCG/KG/MIN INFUSION THROUGHOUT PROCEDURE BASED ON HEMODYNAMICS
Remifentanil: Remifentanil 0.08-0.15MCG/KG/MIN INFUSION THROUGHOUT PROCEDURE BASED ON HEMODYNAMICS | 71 |
| Dexmedetomidine a loading dose of dexmedetomidine was given at 0.5 to 1 micrograms/kg ideal body weight over 15 minutes, followed by an infusion at 0.2 to 0.7 micrograms/kg/hour.
Dexmedetomidine: a loading dose of dexmedetomidine was given at 0.5 to 1 micrograms/kg ideal body weight over 15 minutes, followed by an infusion at 0.2 to 0.7 micrograms/kg/hour. | 68 |
| Total | 139 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Did not receive study drug | 0 | 3 |
Baseline characteristics
| Characteristic | Remifentanil | Dexmedetomidine | Total |
|---|---|---|---|
| Age, Continuous | 55 years STANDARD_DEVIATION 14 | 56 years STANDARD_DEVIATION 14 | 56 years STANDARD_DEVIATION 14 |
| Gender Female | 37 Participants | 33 Participants | 70 Participants |
| Gender Male | 34 Participants | 35 Participants | 69 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 71 | 0 / 68 |
| serious Total, serious adverse events | 0 / 71 | 0 / 68 |
Outcome results
Primary
Hemodynamics
Hemodynamics were defined as mean arterial pressure (MAP), measured in milimeters of mercury (mmHg). This outcome was analyzed using a repeated measures ANOVA approach. In the outcome measure data table, mean ± standard deviation MAP was reported as the aggregate mean across time points.
Time frame: 15, 30, 45, 60, and 90 minutes after extubation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Remifentanil | Hemodynamics | 98 mmHg | Standard Deviation 11 |
| Dexmedetomidine | Hemodynamics | 88 mmHg | Standard Deviation 12 |
Comparison: Dexmedetomidine versus remifentanyl on MAP collapsed over time was estimated using a 1-tailed t test from a repeated measures ANOVA model.p-value: <0.00195% CI: [-13, -5]t-test, 1 sided
Comparison: Dexmedetomidine versus remifentanyl on MAP collapsed over time was estimated using a 1-tailed t test from a repeated measures ANOVA model.p-value: <0.00197.5% CI: [-13, -4]t-test, 1 sided
Primary
Postoperative Pain
Pain was measured using the visual analogue scale (VAS), where 0 is defined as no pain and 10 is defined as worst pain imaginable. This outcome was analyzed using a repeated measures ANOVA approach. In the outcome measure data table, mean ± standard deviation pain was reported as the aggregate mean across time points.
Time frame: 15, 30, 45, 60, and 90 minutes after extubation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Remifentanil | Postoperative Pain | 5.1 units on a scale | Standard Deviation 2.4 |
| Dexmedetomidine | Postoperative Pain | 2.9 units on a scale | Standard Deviation 2.6 |
Comparison: Dexmedetomidine versus remifentanyl on VAS pain score estimated from a 1-tailed t test from a repeated measures ANOVA model.p-value: <0.00195% CI: [-2.7, -1.1]t-test, 1 sided
Comparison: Dexmedetomidine versus remifentanyl on VAS pain score estimated from a 1-tailed t test from a repeated measures ANOVA model.p-value: <0.00197.5% CI: [-2.8, -0.9]t-test, 1 sided
Primary
Total Opioid Consumption
Total opioid consumption was defined as the sum of all opioid doses given within the first 90 minutes after surgery, converted to milligram morphine equivalents.
Time frame: Initial 90 minutes of recover after surgery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Remifentanil | Total Opioid Consumption | 10 mg morphine equivalents |
| Dexmedetomidine | Total Opioid Consumption | 5 mg morphine equivalents |
Comparison: Dexmedetomidine versus remifentanyl on opioid consumption estimated from a Wilcoxon rank sum testp-value: <0.00195% CI: [-10, -5]Wilcoxon (Mann-Whitney)
Comparison: Dexmedetomidine versus remifentanyl on opioid consumption estimated from a Wilcoxon rank sum testp-value: <0.00197.5% CI: [-10, -3]Wilcoxon (Mann-Whitney)
Secondary
Aldrete Score
The Aldrete score measured level of sedation and fitness and is used to assess the appropriate departure time from the post anesthesia care unit. The score ranges from 0 to 10, where 0 indicates poor fitness (and such patients are transferred to the ICU), while 10 indicates good fitness. This outcome was analyzed using a repeated measures ANOVA approach.
Time frame: 15, 30, 45, 60, and 90 minutes after extubation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Remifentanil | Aldrete Score | Aldrete score at 15 minutes after extubation | 8.4 units on a scale | Standard Deviation 1 |
| Remifentanil | Aldrete Score | Aldrete score at 45 minutes after extubation | 9.0 units on a scale | Standard Deviation 1 |
| Remifentanil | Aldrete Score | Aldrete score at 60 minutes after extubation | 9.2 units on a scale | Standard Deviation 0.9 |
| Remifentanil | Aldrete Score | Aldrete score at 30 minutes after extubation | 8.7 units on a scale | Standard Deviation 1 |
| Remifentanil | Aldrete Score | Aldrete score at 90 minutes after extubation | 9.4 units on a scale | Standard Deviation 0.8 |
| Dexmedetomidine | Aldrete Score | Aldrete score at 90 minutes after extubation | 9.1 units on a scale | Standard Deviation 1.1 |
| Dexmedetomidine | Aldrete Score | Aldrete score at 15 minutes after extubation | 8 units on a scale | Standard Deviation 1.4 |
| Dexmedetomidine | Aldrete Score | Aldrete score at 30 minutes after extubation | 8.3 units on a scale | Standard Deviation 1.4 |
| Dexmedetomidine | Aldrete Score | Aldrete score at 45 minutes after extubation | 8.7 units on a scale | Standard Deviation 1.1 |
| Dexmedetomidine | Aldrete Score | Aldrete score at 60 minutes after extubation | 8.9 units on a scale | Standard Deviation 1.1 |
Comparison: Dexmedetomidine versus remifentanyl on Aldrete score estimated using a linear mixed effects model adjusting for baseline Aldrete score.p-value: 0.0795% CI: [-0.6, 0.03]Mixed Models Analysis
Secondary
Drug Stop Time to Fitness to Discharge
Time frame: Anesthesia drug stop time to fitness to discharge. Time is measured continuously until fitness for discharge is reached, regardless of how long it takes.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Remifentanil | Drug Stop Time to Fitness to Discharge | 150 minutes |
| Dexmedetomidine | Drug Stop Time to Fitness to Discharge | 172 minutes |
Comparison: Remifentanyl versus Dexmedetomidine on time to fitness discharge estimated using Cox regression.p-value: 0.02295% CI: [0.48, 0.95]Regression, Cox
Secondary
Drug Stop Time to Open Eyes
time until patient first opened their eyes, squeezed a hand, or wiggled their toes in response to verbal commands after surgery
Time frame: Anesthesia drug stop time to open eyes. Time is measured continuously until patients eyes open, regardless of how long it takes.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Remifentanil | Drug Stop Time to Open Eyes | 8 minutes |
| Dexmedetomidine | Drug Stop Time to Open Eyes | 38 minutes |
Comparison: Remifentanyl versus Dexmedetomidine on time to open eyes estimated using Cox regression.p-value: <0.00195% CI: [0.07, 0.18]Regression, Cox
Secondary
Drug Stop Time to Recall
Time between extubation until patients could say their names.
Time frame: Time between extubation until patients could say their names.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Remifentanil | Drug Stop Time to Recall | 13 minutes |
| Dexmedetomidine | Drug Stop Time to Recall | 42 minutes |
Comparison: Remifentanyl versus dexmedetomidine on time to recall assessed using Cox regression.p-value: <0.00195% CI: [0.07, 0.19]Regression, Cox
Secondary
End Case to Post Anesthesia Care Unit (PACU) Discharge
Post Anesthesia Care Unit (PACU) Discharge time is the timing at which patients are discharged from the PACU. This outcome is the amount of time (minutes) from end case to PACU discharge.
Time frame: End case to post anesthesia care unit (PACU) discharge. Time is measured continuously until PACU discharge, regardless of how long it takes.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Remifentanil | End Case to Post Anesthesia Care Unit (PACU) Discharge | 211 minutes |
| Dexmedetomidine | End Case to Post Anesthesia Care Unit (PACU) Discharge | 215 minutes |
Comparison: Remifentanyl versus Dexmedetomidine on time to PACU discharge estimated using Cox proportional hazard regressionp-value: 0.4595% CI: [0.81, 1.62]Regression, Cox
Secondary
Heart Rate
Heart rate was determined from the arterial catheter and measured as beats per minute. This outcome was analyzed using a repeated measures ANOVA approach.
Time frame: 15, 30, 45, 60, and 90 minutes after extubation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Remifentanil | Heart Rate | Heart rate 90 minutes after extubation | 75 beats per minute | Standard Deviation 13 |
| Remifentanil | Heart Rate | Heart rate 15 minutes after extubation | 76 beats per minute | Standard Deviation 15 |
| Remifentanil | Heart Rate | Heart rate 30 minutes after extubation | 72 beats per minute | Standard Deviation 14 |
| Remifentanil | Heart Rate | Heart rate 45 minutes after extubation | 73 beats per minute | Standard Deviation 14 |
| Remifentanil | Heart Rate | Heart rate 60 minutes after extubation | 73 beats per minute | Standard Deviation 13 |
| Dexmedetomidine | Heart Rate | Heart rate 60 minutes after extubation | 66 beats per minute | Standard Deviation 12 |
| Dexmedetomidine | Heart Rate | Heart rate 45 minutes after extubation | 66 beats per minute | Standard Deviation 13 |
| Dexmedetomidine | Heart Rate | Heart rate 15 minutes after extubation | 68 beats per minute | Standard Deviation 13 |
| Dexmedetomidine | Heart Rate | Heart rate 90 minutes after extubation | 69 beats per minute | Standard Deviation 14 |
| Dexmedetomidine | Heart Rate | Heart rate 30 minutes after extubation | 67 beats per minute | Standard Deviation 13 |
Comparison: Dexmedetomidine versus remifentanyl on heart rate was assessed using a linear mixed effects model adjusting for baseline heart rate.p-value: <0.00195% CI: [-10, 3]Mixed Models Analysis
Secondary
Modified Short Orientation Memory Concentration Test (SOMCT)
The Modified Short Orientation Memory Concentration Test (SOMCT) is a validated questionnaire that discriminates among mild, moderate, and severe cognitive deficits. SOMCT is based on 6 questions and produces a total score ranging from 0 (worst possible function) to 28 (best possible function). Scores \> 20 are considered normal. This outcome was analyzed using a repeated measures ANOVA approach.
Time frame: 15, 30, 45, 60, and 90 minutes after extubation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Remifentanil | Modified Short Orientation Memory Concentration Test (SOMCT) | SOMCT 30 minutes after extubation | 25 units on a scale | Standard Deviation 7 |
| Remifentanil | Modified Short Orientation Memory Concentration Test (SOMCT) | SOMCT 45 minutes after extubation | 25 units on a scale | Standard Deviation 6 |
| Remifentanil | Modified Short Orientation Memory Concentration Test (SOMCT) | SOMCT 60 minutes after extubation | 26 units on a scale | Standard Deviation 5 |
| Remifentanil | Modified Short Orientation Memory Concentration Test (SOMCT) | SOMCT 90 minutes after extubation | 26 units on a scale | Standard Deviation 5 |
| Remifentanil | Modified Short Orientation Memory Concentration Test (SOMCT) | SOMCT 15 minutes after extubation | 22 units on a scale | Standard Deviation 9 |
| Dexmedetomidine | Modified Short Orientation Memory Concentration Test (SOMCT) | SOMCT 15 minutes after extubation | 18 units on a scale | Standard Deviation 11 |
| Dexmedetomidine | Modified Short Orientation Memory Concentration Test (SOMCT) | SOMCT 30 minutes after extubation | 20 units on a scale | Standard Deviation 11 |
| Dexmedetomidine | Modified Short Orientation Memory Concentration Test (SOMCT) | SOMCT 90 minutes after extubation | 25 units on a scale | Standard Deviation 7 |
| Dexmedetomidine | Modified Short Orientation Memory Concentration Test (SOMCT) | SOMCT 45 minutes after extubation | 23 units on a scale | Standard Deviation 9 |
| Dexmedetomidine | Modified Short Orientation Memory Concentration Test (SOMCT) | SOMCT 60 minutes after extubation | 24 units on a scale | Standard Deviation 7 |
Comparison: Dexmedetomidine versus remifentanyl on SOMCT estimated using a linear mixed effects model adjusting for baseline SOMCT score.p-value: 0.1695% CI: [-2.6, 0.5]Mixed Models Analysis
Secondary
Nursing Workload Comparison
To evaluate the nurses workload when either of the two drugs are given in terms Nursing Research Usage form's therapeutic index scoring system. This score ranges from 0 (minimal interventions and time spent by nurses on study patient) to 22 (maximum interventions and time spent by nurses on the study patient).
Time frame: 90 minutes after extubation
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Remifentanil | Nursing Workload Comparison | 6 units on a scale |
| Dexmedetomidine | Nursing Workload Comparison | 5.5 units on a scale |
Comparison: Dexmedetomidine versus remifentanyl on Nursing workload comparison estimated using a Wilcoxon rank sum test.p-value: 0.00995% CI: [-1, -0.001]Wilcoxon (Mann-Whitney)
Secondary
Postoperative Nausea
Indicator of whether patients had nausea or not
Time frame: Whether patients had nausea or not, from anesthesia stop time until hospital discharge.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Remifentanil | Postoperative Nausea | 12 participants |
| Dexmedetomidine | Postoperative Nausea | 12 participants |
Comparison: Dexmedetomidine versus remifentanyl on postoperative nausea estimated from chi squared test.p-value: 0.9195% CI: [0.5, 2.2]Chi-squared
Secondary
Postoperative Shivering
Indicator of whether patients had postoperative shivering.
Time frame: Whether patients had postoperative or not, from anesthesia stop time until hospital discharge.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Remifentanil | Postoperative Shivering | 7 participants |
| Dexmedetomidine | Postoperative Shivering | 3 participants |
Comparison: Dexmedetomidine versus remifentanyl on incidence of shivering estimated from a chi square test.p-value: 0.2195% CI: [0.1, 1.7]Chi-squared
Secondary
Postoperative Vomitting
Indicator of whether patients had postoperative vomiting.
Time frame: Whether patients had vomiting or not, from anesthesia stop time until hospital discharge.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Remifentanil | Postoperative Vomitting | 6 participants |
| Dexmedetomidine | Postoperative Vomitting | 2 participants |
Comparison: Dexmedetomidine versus remifentanyl on postoperative vomiting estimated from a chi square test.p-value: 0.1695% CI: [0.07, 1.7]Chi-squared