A Single-Center, Prospective Study in Healthy Volunteers for Validation of the O3 Regional Somatic Tissue Oxygenation Monitor

In perioperative medicine, maintenance of tissue oxygenation is of paramount
importance to prevent organ damage and development of (post-operative)
complications. The Masimo O3 regional oximeter allows measurement of regional
tissue oxygenation (rSO2) using near-infrared spectroscopy, allowing continuous
monitoring of rSO2 of the tissue(s) of interest. The absolute and trend
accuracy of the O3 oximeter at baseline and hypoxic states revealed acceptable
results for cerebral tissue when compared to the reference gold standard (blood
samples). However, during hypoxia, the absolute accuracy of somatic rSO2 values
with invasive reference values is unknown.

The objective of this study is to assess the performance of the Masimo O3
regional oximeter on somatic tissue oxygenation, under controlled hypoxia.
Somatic rSO2 values will be compared with combined arterial and venous blood
gas measurements from vessels draining the blood from the respective
measurement sites.

This study is a prospective, single-center healthy volunteer validation study.

In all volunteers, a radial artery catheter will be inserted, as well as a
femoral venous catheter via a sheath, so that blood can be drawn from the tip
of the catheter (located in the renal vein) and from the femoral vein. O3
sensors will be placed bilaterally (when possible) on the flank superficial to
the kidney, and quadriceps muscles, the latter preferably at a high muscle
density location. rSO2 sensors will be placed on the forehead as well.
During interventions, volunteers will be allowed to breathe standardized oxygen
concentrations using a tight-sitting facemask or mouth-piece. Each volunteer
will undergo the *stepped hypoxia plateau sequence protocol*: Breathing
mixtures of N2 in air via a tight-fitting facemask or mouth-piece, as
determined by the preference of the volunteer. The FiO2 will be set at 0.21
(room air, baseline) and will be reduced in a stepwise fashion to achieve SpO2
values of 95%, 90%, 85%, 80%, 75% and 70%.
During baseline and during all subsequent SpO2 plateau intervals, paired whole
blood reference samples from the arterial and femoral venous access points will
be drawn.

Non-invasive measurement risks: The risk from non-invasive devices is minimal
since the measurement is non-invasive and uses optical technology.

Sensor risks: As with all optical sensors, the investigational device has the
theoretical risk of thermal burn. The design includes safeguards, and this risk
is believed to be very low. Sensors will be attached with adhesive, and may be
secured by a supplemental headband. Pressure damage may occur to the tissue if
the sensor is placed too tightly. This risk is believed to be low. Optical
exposure is minimized by procedure and low power. This risk is believed to be
low.

Stepped Hypoxia Plateau Sequence Protocol: The risks of the brief exposures to
hypoxia include feeling short of breath, headache, and dizziness. Brief loss of
consciousness may occur, but is not expected at the levels of oxygen targeted
for these tests given the magnitude of comparable studies, in which none of
these events occurred.

Femoral venous catheter placement: ultrasound-guided insertion of a femoral
venous sheath and sampling catheter is regarded safe for short-term use. It is
associated with a low incidence of serious complications, such as renal
thrombosis. To prevent renal thrombosis, a low dose of heparin will be
administered locally via the tip of the catheter. The most common complication
of the femoral venous cathether placement is local hematoma.
Catheterization is performed by experienced and qualified interventional
radiologists. Correct positioning of the proximal tip of the catheter (at the
level of the renal vein) will be ensured by x-ray or fluoroscopy, which has a
negligible long-time carcinogenic risk, and low-dose intravenous contrast
medium, which is safe in volunteers with no history of allergy.

Radial artery line placement: Arterial catheters have been found to be
relatively safe with a low incidence of serious complications. Typical
complications include temporary radial artery occlusion and hematoma. (Very)
rare complications (less than 1% of procedures) include localized catheter site
infection, hemorrhage, sepsis, permanent ischemic damage and pseudo-aneurysm
formation.

Both the use of the femoral venous catheter, as well as the stepped hypoxia
plateau sequence protocol methods is similar to the standard protocols
recommended by the FDA and ISO Standards for testing pulse oximeters with mild
hypoxia steps and blood drawn from arterial catheters (ISO 80601-2-61:2011).