Stroke
Conditions
Brief summary
Controversy surrounds the use of regional cerebral oximetry (rSO2) as a measure of true cerebral oxygenation because of extracranial signal contamination and unmeasured confounding of cerebral a:v ratio. The measurement of brain tissue oxygen (PbrO2) has been used in routine neurosurgery and has been shown to reliably demonstrate cerebral hypoxia following severe head injury. It is the most direct measure of cerebral oxygenation. Here, we test the hypothesis that there is a correlation between PbrO2 and rSO2 under conditions of varying inspired oxygen fraction and the varying partial pressure of carbon dioxide in arterial blood in uninjured, normal human brain. Patients who are scheduled for elective removal of secondary cerebral metastases under general anesthesia will be recruited following written informed consent obtained by a study team member during their preoperative evaluation. BIS and rSO2 optodes will be applied, before induction of anesthesia, by a single researcher on both sides of the patient's forehead, as recommended by the manufacturer. General anesthesia will be maintained by total intravenous anesthesia (TIVA) with a combination of propofol (80-150 mcg/kg/min) and remifentanil (0.05-0.1 mcg/kg/min) targeted to a Bispectral Index range 40-60 (BIS; Covidien, Boulder, CO). Following craniotomy, the LICOX probe will be placed under direct vision into an area of normal brain within the tumor excision canal by the attending neurosurgeon. During a pause in surgery FIO2 and minute ventilation will be sequentially adjusted to achieve the following pairs of ventilation set points: 1) FIO2 0.3 and paCO2 30mmHg, 2) FIO2 1.0 and paCO2 40mmHg. After ≥5 minutes at each set point FIO2, PaCO2, rSO2 and PbrO2 will be recorded as a snap-shot. A sample size of 15 achieves an 80% power with a one-sided type I error of 5% to detect a positive correlation of 0.6 (from the null hypothesis of no correlation) between changes in PbrO2 and changes in rSO2 subsequent on alterations made in ventilation strategy. Correlation will be measured using Pearson's Correlation. P values \< 0.05 will be considered statistically significant.
Interventions
DEVICEIVOS cerebral oximeter
Measuring percutaneous cerebral oxygenation secondary to changing end tidal carbon dioxide and inspired oxygen fraction.
DEVICELicox cerebral oxygenation monitor
Measuring tissue cerebral oxygenation secondary to changing end tidal carbon dioxide and inspired oxygen fraction.
OTHERCerebral oxygenation
Measuring cerebral oxygenation with varying ventilation strategy
Sponsors
University of Michigan
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients who are scheduled for elective removal of secondary cerebral metastases under general anesthesia.
Exclusion criteria
* Patients will be excluded if they refuse to give consent, have evidence of elevated intracranial pressure on preoperative CT scan, have coagulopathy, are taking therapeutic agents known to increase bleeding risk, have a history of cardiovascular disease, cerebrovascular disease, suffer from respiratory failure, or are not fluent English speakers.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Correlation Between Regional Cerebral Oximetry (RSO2) and Cerebral Oxygen Tissue Tension (PbrO2). | Time required for cerebral oxygenation to reach equilibrium following a change in ventilation - typically less than 20 minutes | Correlation - correlation coefficient between cerebral oxygenation measured by Licox and INVOS oxygen measurement systems subsequent upon changes in ventilation strategy Spearman correlation describes the strength of the monotonic relationship between two measures and is bounded between -1 and 1. Negative values indicate an inverse relationship while positive values mean that the variables move in tandem. \[Example of correlation coefficient in CT.gov: NCT02318667\] |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in PbrO2 Resultant Upon Changes in End Tidal Carbon Dioxide and Inspired Oxygen Fraction | Time required for cerebral oxygenation to reach equilibrium following a change in ventilation - typically less than 20 minutes | PbrO2 - measured in millimeters of mercury(mmHg); Steady State PbrO2 Upon Changes in End Tidal Carbon Dioxide and Inspired Oxygen Fraction after Equilibration for each Set Point |
| Changes in rSO2 Resultant Upon Changes in End Tidal Carbon Dioxide and Inspired Oxygen Fraction | Time required for cerebral oxygenation to reach equilibrium following a change in ventilation - typically less than 20 minutes | rSO2 - %saturation; Steady State rSO2 Upon Changes in End Tidal Carbon Dioxide and Inspired Oxygen Fraction after Equilibration for each Set Point |
Countries
United States
Participant flow
Pre-assignment details
A total of 12 subjects were consented, two were excluded for logistical reasons prior to any data collection.
Participants by arm
| Arm | Count |
|---|---|
| Varying Cerebral Oxygenation With Varying Ventilation Compare oxygenation under conditions of varying ventilation strategy. Low end tidal CO2/Low inspired oxygen vs High end tidal CO2/high inspired oxygen
IVOS cerebral oximeter: Measuring percutaneous cerebral oxygenation secondary to changing end tidal carbon dioxide and inspired oxygen fraction.
Licox cerebral oxygenation monitor: Measuring tissue cerebral oxygenation secondary to changing end tidal carbon dioxide and inspired oxygen fraction.
Cerebral oxygenation: Measuring cerebral oxygenation with varying ventilation strategy | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Varying Cerebral Oxygenation With Varying Ventilation |
|---|---|
| Age, Continuous | 61.4 years STANDARD_DEVIATION 9.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Region of Enrollment United States | 10 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
Correlation Between Regional Cerebral Oximetry (RSO2) and Cerebral Oxygen Tissue Tension (PbrO2).
Correlation - correlation coefficient between cerebral oxygenation measured by Licox and INVOS oxygen measurement systems subsequent upon changes in ventilation strategy Spearman correlation describes the strength of the monotonic relationship between two measures and is bounded between -1 and 1. Negative values indicate an inverse relationship while positive values mean that the variables move in tandem. \[Example of correlation coefficient in CT.gov: NCT02318667\]
Time frame: Time required for cerebral oxygenation to reach equilibrium following a change in ventilation - typically less than 20 minutes
Population: One subject's data was identified as an extreme value using the Tuckey Fences approach and was excluded from primary analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Varying Cerebral Oxygenation With Varying Ventilation | Correlation Between Regional Cerebral Oximetry (RSO2) and Cerebral Oxygen Tissue Tension (PbrO2). | .5 Spearman Correlation (rs) Coefficient |
Comparison: Non-parametric covariance adjusted Spearman's correlation ρ\_s. To test the Null that Ho: ρ\_s.=0 vs alternative that Ha: ρ\_s.≠0, we used a method that calculates the probability that it would be greater than or equal to the observed ρ ̂, given the null hypothesis, by using a permutation test. An advantage of this approach is that it automatically takes into account the number of tied data values in the sample and the way they are treated in computing the rank correlation.p-value: 0.036permutation test
Secondary
Changes in PbrO2 Resultant Upon Changes in End Tidal Carbon Dioxide and Inspired Oxygen Fraction
PbrO2 - measured in millimeters of mercury(mmHg); Steady State PbrO2 Upon Changes in End Tidal Carbon Dioxide and Inspired Oxygen Fraction after Equilibration for each Set Point
Time frame: Time required for cerebral oxygenation to reach equilibrium following a change in ventilation - typically less than 20 minutes
Population: One participant was identified as an extreme value using the Tuckey Fences approach and was excluded from final analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Varying Cerebral Oxygenation With Varying Ventilation | Changes in PbrO2 Resultant Upon Changes in End Tidal Carbon Dioxide and Inspired Oxygen Fraction | Set point 1 (FiO2 0.3 and PaCO2 30 mmHg) | 6.0 mmHg |
| Varying Cerebral Oxygenation With Varying Ventilation | Changes in PbrO2 Resultant Upon Changes in End Tidal Carbon Dioxide and Inspired Oxygen Fraction | Set point 2 (FiO2 1.0 and PaCO2 40 mmHg) | 22.5 mmHg |
Comparison: Set point 1 (FiO2 0.3 and PaCO2 30 mmHg) compared to set point 2 (FiO2 1.0 and PaCO2 40 mmHg)p-value: 0.015Kruskal-Wallis
Secondary
Changes in rSO2 Resultant Upon Changes in End Tidal Carbon Dioxide and Inspired Oxygen Fraction
rSO2 - %saturation; Steady State rSO2 Upon Changes in End Tidal Carbon Dioxide and Inspired Oxygen Fraction after Equilibration for each Set Point
Time frame: Time required for cerebral oxygenation to reach equilibrium following a change in ventilation - typically less than 20 minutes
Population: One subject was identified as an extreme value using the Tuckey Fences approach and was excluded from final analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Varying Cerebral Oxygenation With Varying Ventilation | Changes in rSO2 Resultant Upon Changes in End Tidal Carbon Dioxide and Inspired Oxygen Fraction | Set Point 1 (FiO2 0.3 and PaCO2 30 mmHg) | 68.0 percentage saturation |
| Varying Cerebral Oxygenation With Varying Ventilation | Changes in rSO2 Resultant Upon Changes in End Tidal Carbon Dioxide and Inspired Oxygen Fraction | Set Point 2 (FiO2 1.0 and PaCO2 40 mmHg) | 83.0 percentage saturation |
Comparison: Set point 1 (FiO2 0.3 and PaCO2 30 mmHg) compared to set point 2 (FiO2 1.0 and PaCO2 40 mmHg)p-value: 0.047Kruskal-Wallis