Glioma
Conditions
Keywords
sedation, eloquent area glioma, neurologic function
Brief summary
Sedation in the operating room, the Post Anesthesia Care Unit and the Intensive Care Unit is common and often necessary for patients with intracranial brain tumor. Repeated neurological function assessments is needed in those locations, especially in patients with tumors in or near eloquent regions, this is to monitor their neurologic performance to determine if there are alterations that require treatment. Some slowly infiltrative low-grade gliomas near eloquent regions do not show any detectable neurologic deficits, perhaps from reorganization, but with sedation by some sedatives such as benzodiazepine midazolam and anesthetic hypnotic propofol, the disease may seem much worse resulting in inappropriately aggressive treatment. This may be especially problematic in patients undergoing awake craniotomy for tumors in eloquent regions. This is a single-center perspective study. Patients will be mildly sedated to keep them responsive and cooperative. Motor and sensory function will be evaluated before and after mild sedation. Specific benzodiazepine antagonist will be used if sedated by midazolam. The purpose of this study is to observe if commonly used benzodiazepine midazolam exacerbates or unmasks motor and sensory function in patients with intracranial eloquent area gliomas. Hypothesis: mild sedation can unmasks or exacerbate motor and sensory deficits in patients with eloquent area glioma but not in non-neurosurgical patients/healthy volunteers. If the neurologic deficits induced by benzodiazepine agonist, then can be reversed by flumazenil.
Interventions
DRUGMidazolam
specific benzodiazepine agonist midazolam will be used titrate to desired sedation level, its specific antagonist flumazenil will also be used
Sponsors
Beijing Tiantan Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Age between 18-60 year-old * American Society of Anesthesiology(ASA) status I\ II * Elective craniotomy patients with supratentorial eloquent glioma diagnosed by MRI (In control group: volunteers without neuro-diseases)
Exclusion criteria
* Unable to comprehend and cooperate with the neurologic examination * Impaired mental status * Taking sedative drugs in the past 24 hours * Taking pain reliever in the past 24 hours * Drug and/or alcohol abuse * Pregnant and/o lactating women * Recurrent brain tumors * Multiple brain tumors * Accepting radiotherapy or chemotherapy * Complicated with intracranial trauma and vascular diseases * Complicated with grand mal epilepsy ( in midazolam group) * Complicated with neuromuscular diseases * Complicated with cutaneous paresthesia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Task Completing Time Change Between Sedation and Baseline Measured by 9-hole Peg Test | after sedation | this is a focal neurologic deficits induced by sedatives, the outcome is the performing time changes after sedation as : sedation-baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With OAA/S=4 After Sedation | withing 1 hour | OAA/S is Observer Assessment of Sedation with 5 levels (5 = alert, 4 = lethargic, 3 = aroused by voice, 2 = aroused by shaking, 1 = deep sleep), all participants have to achieve OAA/S=4 after sedation. |
| Mean Arterial Blood Pressure (MAP) as a Measure of Physiological Change | 1 hour | The MAP was measured at three time points: baseline, sedation and sedation reversal. |
| Heart Rate as a Measure of Physiological Change | 1 hour | The HR was measured at three time points: baseline, sedation and sedation reversal. |
| Brain Glioma Pathological Diagnose as a Measure of Tumor Type | 2 weeks | the WHO grade and the type of glioma (WHO glioma grade I\ II is regarded as low grade glioma, WHO glioma grade III\ IV is regarded as high grade glioma) |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Glioma Group Patients in this group will be administered sedatives (midazolam or propofol or dexmedetomidine) titrating to mild sedation.
Midazolam: specific benzodiazepine agonist midazolam will be used titrate to desired sedation level, its specific antagonist flumazenil will also be used as a reversal | 15 |
| Non-neurosurgical Group patients in this group will be administered the same sedative midazolam as compared glioma group, and titrate to mild sedation.
Midazolam: specific benzodiazepine agonist midazolam will be used titrate to desired sedation level, its specific antagonist flumazenil will also be used as a reversal | 17 |
| Total | 32 |
Baseline characteristics
| Characteristic | Glioma Group | Non-neurosurgical Group | Total |
|---|---|---|---|
| Age, Continuous | 46 years old STANDARD_DEVIATION 9 | 35 years old STANDARD_DEVIATION 7 | 40 years old STANDARD_DEVIATION 9 |
| education college | 3 Participants | 10 Participants | 13 Participants |
| education high school | 8 Participants | 2 Participants | 10 Participants |
| education middle school | 2 Participants | 2 Participants | 4 Participants |
| education primary school | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 15 Participants | 17 Participants | 32 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment China | 15 participants | 17 participants | 32 participants |
| Sex: Female, Male Female | 8 Participants | 10 Participants | 18 Participants |
| Sex: Female, Male Male | 7 Participants | 7 Participants | 14 Participants |
| weight | 64.9 kg STANDARD_DEVIATION 14 | 75.8 kg STANDARD_DEVIATION 5.1 | 70.7 kg STANDARD_DEVIATION 21.1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 17 |
| other Total, other adverse events | 0 / 15 | 0 / 17 |
| serious Total, serious adverse events | 0 / 15 | 0 / 17 |
Outcome results
Primary
Task Completing Time Change Between Sedation and Baseline Measured by 9-hole Peg Test
this is a focal neurologic deficits induced by sedatives, the outcome is the performing time changes after sedation as : sedation-baseline.
Time frame: after sedation
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Glioma Group | Task Completing Time Change Between Sedation and Baseline Measured by 9-hole Peg Test | baseline for contralesional hand | 27.8 seconds | Standard Deviation 15.9 |
| Glioma Group | Task Completing Time Change Between Sedation and Baseline Measured by 9-hole Peg Test | after sedation for contralesional hand | 54.3 seconds | Standard Deviation 32.4 |
| Glioma Group | Task Completing Time Change Between Sedation and Baseline Measured by 9-hole Peg Test | baseline for ipsilesional hand | 21.8 seconds | Standard Deviation 7.1 |
| Glioma Group | Task Completing Time Change Between Sedation and Baseline Measured by 9-hole Peg Test | after sedation for ipsilesional hand | 35.5 seconds | Standard Deviation 16.6 |
| Non-neurosurgical Group | Task Completing Time Change Between Sedation and Baseline Measured by 9-hole Peg Test | after sedation for ipsilesional hand | 21.4 seconds | Standard Deviation 3.41 |
| Non-neurosurgical Group | Task Completing Time Change Between Sedation and Baseline Measured by 9-hole Peg Test | baseline for contralesional hand | 19.1 seconds | Standard Deviation 3.2 |
| Non-neurosurgical Group | Task Completing Time Change Between Sedation and Baseline Measured by 9-hole Peg Test | baseline for ipsilesional hand | 19.1 seconds | Standard Deviation 3.2 |
| Non-neurosurgical Group | Task Completing Time Change Between Sedation and Baseline Measured by 9-hole Peg Test | after sedation for contralesional hand | 21.4 seconds | Standard Deviation 3.41 |
p-value: <0.0195% CI: [14.16, 32.87]t-test, 2 sided
Secondary
Brain Glioma Pathological Diagnose as a Measure of Tumor Type
the WHO grade and the type of glioma (WHO glioma grade I\ II is regarded as low grade glioma, WHO glioma grade III\ IV is regarded as high grade glioma)
Time frame: 2 weeks
Population: In non-neurosurgical group, patients were not diagnosed as glioma, so the belowed outcome measure data table could not indicate the number of glioma grade.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Glioma Group | Brain Glioma Pathological Diagnose as a Measure of Tumor Type | high grade glioma | 9 Participants |
| Glioma Group | Brain Glioma Pathological Diagnose as a Measure of Tumor Type | low grade glioma | 6 Participants |
Secondary
Heart Rate as a Measure of Physiological Change
The HR was measured at three time points: baseline, sedation and sedation reversal.
Time frame: 1 hour
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Glioma Group | Heart Rate as a Measure of Physiological Change | baseline | 78.1 bpm | Standard Deviation 15.6 |
| Glioma Group | Heart Rate as a Measure of Physiological Change | sedation | 84.3 bpm | Standard Deviation 14.3 |
| Glioma Group | Heart Rate as a Measure of Physiological Change | sedation reversal | 81.5 bpm | Standard Deviation 17.7 |
| Non-neurosurgical Group | Heart Rate as a Measure of Physiological Change | baseline | 79.0 bpm | Standard Deviation 9.1 |
| Non-neurosurgical Group | Heart Rate as a Measure of Physiological Change | sedation | 79.0 bpm | Standard Deviation 9.4 |
| Non-neurosurgical Group | Heart Rate as a Measure of Physiological Change | sedation reversal | 71.5 bpm | Standard Deviation 8.9 |
Secondary
Mean Arterial Blood Pressure (MAP) as a Measure of Physiological Change
The MAP was measured at three time points: baseline, sedation and sedation reversal.
Time frame: 1 hour
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Glioma Group | Mean Arterial Blood Pressure (MAP) as a Measure of Physiological Change | baseline MAP | 96.5 mmHg | Standard Deviation 13.5 |
| Glioma Group | Mean Arterial Blood Pressure (MAP) as a Measure of Physiological Change | sedation MAP | 96.2 mmHg | Standard Deviation 9.5 |
| Glioma Group | Mean Arterial Blood Pressure (MAP) as a Measure of Physiological Change | sedation reversal MAP | 95.4 mmHg | Standard Deviation 13.6 |
| Non-neurosurgical Group | Mean Arterial Blood Pressure (MAP) as a Measure of Physiological Change | baseline MAP | 95.7 mmHg | Standard Deviation 14.7 |
| Non-neurosurgical Group | Mean Arterial Blood Pressure (MAP) as a Measure of Physiological Change | sedation MAP | 91.2 mmHg | Standard Deviation 12.2 |
| Non-neurosurgical Group | Mean Arterial Blood Pressure (MAP) as a Measure of Physiological Change | sedation reversal MAP | 88.2 mmHg | Standard Deviation 14.1 |
Secondary
Number of Participants With OAA/S=4 After Sedation
OAA/S is Observer Assessment of Sedation with 5 levels (5 = alert, 4 = lethargic, 3 = aroused by voice, 2 = aroused by shaking, 1 = deep sleep), all participants have to achieve OAA/S=4 after sedation.
Time frame: withing 1 hour
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Glioma Group | Number of Participants With OAA/S=4 After Sedation | 15 Participants |
| Non-neurosurgical Group | Number of Participants With OAA/S=4 After Sedation | 17 Participants |