Cerebral Oximetry in Single Lung Ventilation Thoracic Surgery

Study Rationale The use of bi-frontal, near infrared spectrophotometry (NIRS) based cerebral
oximetry monitoring has been demonstrated to result in improved clinical outcomes in both
general surgery patients and cardiac surgical patients using prospective, randomized
controlled trial methodology. Elderly thoracic surgical patients undergoing procedures that
involve single lung ventilation may also stand to benefit from the application of
intraoperative and early postoperative NIRS cerebral oximetry monitoring. Cerebral oximetry
has not been established as a standard of care monitoring modality in this patient
population, thus permitting the application of randomized, controlled testing methodology to
assess the potential impact of this monitoring modality upon these patients.

Hypothesis and Objectives:

The primary hypothesis in this pilot study of elderly thoracic surgical patients undergoing
procedures involving single lung ventilation (SLV) is that there will be a measurable and
significant clinical benefit (as assessed by a broad range of postoperative clinical outcome
measures) to the subjects randomized to the intervention cohort (open bi-frontal NIRS based
cerebral oximetry monitoring with a standardized intervention protocol) vs. the control
cohort (blinded bi-frontal NIRS based cerebral oximetry monitoring).

The primary objective of this pilot study is to identify the most relevant clinical outcome
variables which significantly diverge as a result of being randomized to the intervention
cohort vs. the control cohort so that a larger, multicenter, prospective, randomized
controlled clinical trial can be designed to further test the primary hypothesis as stated
in the preceding section. The subsequent larger, multicenter trial will be conducted to
definitively demonstrate the ability of INVOS® 5100 guided NIRS-based bi-frontal monitoring
to improve clinical outcomes in this surgical patient group and potentially establish a new
U.S. Food and Drug Administration cleared indication for this monitoring modality. The
clinical outcome variables being assessed as the primary objective are many and a detailed
list of these variables can be found in the OUTCOME MEASURES - Primary Outcome Measure
Section of this submission.

Secondary objectives of this pilot study include the following:

1. Assess the frequency of cerebral desaturations in both the intervention and control
cohorts by examining both the total number of patients experiencing any cerebral
desaturation as well as the total number of events among patients experiencing any
cerebral desaturation (of at least 5% below baseline and progressively larger
desaturations). These analyses will be conducted on the entire study population as well
as upon each cohort. The Area Under the Curve (AUC) analysis technique [incremental
desaturation categories will be assessed based upon 5 to 50% decreases, measured in 5%
increments, from established room air pre-incision baseline as well as oxygen
supplemented pre-incision baseline as well as desaturations below absolute measured
rSO2 values] will be employed to conduct these analyses.

2. Assess the frequency of adverse clinical events and serious adverse events overall and
in each cohort.

3. Perform a comprehensive assessment of the frequency and efficacy of predefined rSO2
desaturation mitigation interventions and their collective ability to affect the
observed cerebral oximetry values.

4. Assess the interventional cohort's preoperative demographics and collected covariates
for association with the ease or difficulty of mitigating observed cerebral
desaturation events.

Exploratory analyses will include performing all possible comparisons of the two groups
based upon all collected perioperative variables to examine the potentially significant
relationships between the collected clinical variables representing surrogates of organ
perfusion/function and cerebral oximetry desaturations (AUCrSO2). The following exploratory
endpoints will be assessed:

1. Logistic regression analysis to determine the most relevant AUCrSO2 desaturation
value(s) associated with any detrimental clinical outcome(s) monitored in this study

2. Logistic regression analysis to determine the most relevant AUC blood pressure values
associated with any detrimental clinical outcome(s) monitored in this study

3. Comparison of baseline rSO2 values (room air and oxygen supplemented) to all collected
clinical variables to assess for possibly significant associations

4. Explore the potential impact of rSO2 monitoring on changing the surgical conduct of the
procedure Methodology: Single center, prospective, randomized, controlled clinical
pilot study Number of Subjects: 100 subjects with balanced randomization (1:1) to
control (blinded NIRS data) or intervention (open NIRS data) cohorts Main Criteria for
Inclusion: Elderly patients (> 65 years of age) scheduled for a thoracic surgical
procedure at UHCMC that will involve SLV.

Duration of Treatment: Cerebral oximetry monitoring will begin with an assessment of both
room air and oxygen supplemented bi-frontal baseline NIRS values and continue through the
surgery to either PACU discharge or the initial 12 hours of post surgical ICU treatment.
Mini Mental Status exam testing and Delirium testing with the Confusion Assessment Method
will occur preoperatively and postoperatively through post-operative day (POD) #3 (or
discharge if that occurs sooner than POD #3). Enrolled subjects will be followed during the
index hospitalization and will undergo a 30 day follow up telephone interview to assess
their progress following hospital discharge.

Criteria for Evaluation:

A large number of intraoperative and postoperative clinical variables that include cerebral
oximetry, pulse oximetry, blood pressure, a composite outcome measure and clinical variables
representing organ function will be assessed with the primary endpoint being the
determination of which clinical variables are improved, if any, as a result of being
randomized to open NIRS data monitoring with a predefined desaturation intervention
algorithm guideline. The Mini Mental Status exam and Confusion Assessment Method test will
be used to determine if any measured clinical variables have an effect upon
neuropsychological outcomes. The frequency and effectiveness of the various cerebral
desaturation mitigating interventions will be assessed in the intervention cohort.

Additional Safety Observations:

The frequency and severity of adverse clinical events and serious adverse clinical events
will be assessed to determine if the use of open NIRS data bi-frontal cerebral monitoring is
associated with any significant change in the observation of such events.

Statistical Methods:

Preoperative demographics and clinical variables will be compared in the two groups to
assess for significant differences using the independent t-test. Differences in the observed
clinical data between groups will be determined with the Wilcoxon rank-sum test. Stepwise,
forward, multivariable logistic regression analysis will be performed to assess for
relationships between cerebral desaturations and any of the measured clinical variables with
a p value < 0.05 being considered significant

Inclusion Criteria:

1. Any male or female patient ≥ 65 years of age and able to provide informed consent (or
consent may be provided by a legally authorized representative) who is scheduled for
a thoracic surgical procedure that is expected to involve the use of intraoperative
single lung ventilation (SLV)

2. Able to adequately complete a baseline mini-mental status examination (MMSE)

3. Able to complete a baseline confusion assessment method (CAM) examination

4. Able to obtain bi-frontal baseline rSO2 values prior to induction of anesthesia

Exclusion Criteria:

1. Any patient who has participated in a clinical study of an investigational drug or
device in the past 30 days

2. Any patient who the principal investigator feels at any time or for any reason should
not participate in this clinical study

3. Withdrawal of informed consent for any reason