Correlating Brain Tissue Oxygen and Regional Cerebral Oximetry

Correlating Brain Tissue Oxygen Tension (PbrO2) and Regional Cerebral Oximetry (rSO2) in Normal Human Brain Under the Conditions of Changing Ventilation Strategy

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.

Study Overview

• Status: Completed
• Conditions: Stroke
• Intervention / Treatment: Device: IVOS cerebral oximeter; Device: Licox cerebral oxygenation monitor; Other: Cerebral oxygenation

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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

Device: IVOS cerebral oximeter; Measuring percutaneous cerebral oxygenation secondary to changing end tidal carbon dioxide and inspired oxygen fraction.; Device: Licox cerebral oxygenation monitor; Measuring tissue cerebral oxygenation secondary to changing end tidal carbon dioxide and inspired oxygen fraction.; Other: Cerebral oxygenation; Measuring cerebral oxygenation with varying ventilation strategy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 required for cerebral oxygenation to reach equilibrium following a change in ventilation - typically less than 20 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 required for cerebral oxygenation to reach equilibrium following a change in ventilation - typically less than 20 minutes
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 required for cerebral oxygenation to reach equilibrium following a change in ventilation - typically less than 20 minutes

Collaborators and Investigators

• Sponsor: University of Michigan
• Investigators: Principal Investigator: Paul Picton, MB ChB, University of Michigan

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2017
• Primary Completion (Actual): June 22, 2021
• Study Completion (Actual): June 22, 2021

Study Registration Dates

• First Submitted: April 14, 2017
• First Submitted That Met QC Criteria: April 20, 2017
• First Posted (Actual): April 25, 2017

Study Record Updates

• Last Update Posted (Actual): September 1, 2022
• Last Update Submitted That Met QC Criteria: August 10, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: HUM00105648

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No