Feasibility study to measure Thermal Indicator Dilution Curves with a photonic sensor in human volunteers

In current clinical practice, measurement of Cardiac Output (CO) is performed
by injecting a cold volume intravenously and recording the corresponding
downstream temperature change. This results in a so-called thermal Indicator
Dilution Curve (IDC) of which the area under the curve is inversely
proportional to CO. With conventional electronic temperature sensors, the IDC
is measured once, because - after passing through the microvascular system of
the body, temperature has dropped below the detection-limit. However, using
photonic Fiber Bragg Grating (FBG) sensors, the detection limit and dynamic
range of the sensor have increased. This results in detecting the IDC that has
passed through the microvasculature of the body for a second and possibly third
time. The measurement of these recirculation curves permits measurement of the
Circulating Thermal Volume (CTV), which is closely related to Circulating
Blood- or Plasma Volume. In addition, the Ejection Fraction (EF) of the heart
can be measured.

Proof of Principle: to assess feasibility to measure; (1) a reproducible 1st
thermal IDC, (2) at least 1 recirculation IDC using the FBG photonic sensor
both peripheral and nasal.

- to compare the acquired Stroke Volume (SV) and Cardiac Output (CO) from the
thermal Indicator Dilution Curve (IDC) measured by the FBG photonic sensor,
with a validated non-invasive measurement in three positions of the Tilt-Table
Test.

- to evaluate the impact of external temperature differences (of inhaled air)
on the thermal IDC measured by the FBG photonic sensor

- to evaluate whether respiratory and pulse rate signals can be derived from
the 1st thermal Indicator Dilution Curve (IDC) measured by the FBG photonic
sensor.

In this feasibility study with human volunteers, the FBG photonic sensor is
used to perform measurements on the skin overlying the radial artery, and in
the nose. Measurements are performed by breathing air of body temperature and
air of room temperature, and with the human volunteer lying in three different
positions (neutral, Trendelenburg and anti-Trendelenburg). In total, 15
measurements will be performed; each time after intravenous injection of a
bolus of 10 ml cold (4 °C) 0,9% NaCl in the (contra-lateral) arm. The objective
of this study is to assess feasibility to measure; (1) an accurate thermal IDC,
(2) at least 1 recirculation IDC using the FBG photonic sensor both peripheral
and nasal. A Clearsight hemodynamic monitoring device will be used for
non-invasive continuous finger cuff reference measurements (Standard of Care).

Anticipated clinical benefits:
The results of this study may be important for future patients who need to
undergo hemodynamic measurements. If results are positive, a less invasive and
better quantification of cardiac output and ejection fraction of the left and
right ventricle could be provided in comparison with the current standard of
care which includes intra-arterial hemodynamic measurements.

Anticipated adverse device effects:
There are no anticipated adverse events related to the use of the
investigational device on itself. This includes the use of the FBG photonic
sensor on the skin overlying the radial artery. However, for the nasal
measurements performed by the photonic sensor, there is a small risk that nasal
tissue injury, pain and/or inflammation could occur.

Residual risks associated with investigational device, as identified in risk
analysis report:
None

Risks associated with participation in clinical study:
There is a small, anticipated risk for study participants (with a risk
classification of negligible risk) associated with the administration of
intravenous cold bolus injections of 10 ml 0.9% saline. However, adverse events
appear to be transient, mild, and rare. These mostly consist of inflammation of
the vein (phlebitis), local pain and/or bruising at the injection site.

Possible interactions with concomitant medical treatments:
None

Steps that will be taken to control or mitigate risks:
In case there are any adverse events resulting from participation in this
study, the study participants can be directly taken care of in the Catharina
Hospital Eindhoven since the study will be performed in this hospital.

Risk-to-benefit rationale:
There have been no direct benefits identified for any of the volunteers.
However, the results of this study may be important for future patients who
need to undergo hemodynamic measurements. Positive results could eventually
lead to a less invasive method and better quantification of these measurements,
in comparison to current clinical practice.

Moreover, the burden of the investigation is low and acceptable. As a result,
the benefits of the use of the investigational device outweigh the risks.