APC-trial: Accuracy, Precison and Concordance of Ventricular Field Recognition in patients after open Abdominal Aortic Aneurysm Repair.

Cardiac output measurement
Hemodynamic monitoring and therapy in the operating room (OR) and intensive
care unit (ICU) is aimed at maintaining adequate oxygen delivery to the tissues
(1). Oxygen delivery depends on adequate oxygenation, presence of sufficient
haemoglobin concentration and cardiac output (CO). Measurement of CO in the OR
and ICU is therefore important, but its widespread use in these settings is
hindered by safety considerations and technical limitations.
An ideal CO monitor should be non-invasive, operator-independent,
cost-effective, reliable, and providing continuous measurement with a short
response time (2). Various efforts have been made to develop this ideal
instrument: echocardiography, bioimpedance, transpulmonary thermodilution, and
arterial waveform analysis (2). Until now, no single commercially available CO
monitor fulfils all these requirements, and question remains which CO monitor
technique should be used when CO measurement is indicated.

Ventricular Field Recognition
Recently, a new, non-invasive, continuous CO monitoring technique has been
developed by researchers of the Department of Medical Technology and Clinical
Physics of the University Medical Centre in Utrecht: Ventricular Field
Recognition (VFR) (3, 4). VFR is based on the finding that, if a weak electric
current is applied over the thorax, emptying and filling of the ventricles
during the cardiac cycle give rise to two-dimensional spatial patterns of
voltage changes on the thoracic skin, which are different from patterns
obtained during filling and emptying of the atria (4). Atria and ventricles are
differently located inside the human thorax, and hence the atrial epicentre
locates differently compared to the ventricular epicentre.
Moreover, a predecessor of this technique was previously investigated in the
University Medical Centre under protocol number 00/203. That technique used an
identical positioning of the current injecting electrodes, but a different
positioning of voltages sensing electrodes. The underlying stroke volume
algorithm was quite different. That investigation resulted in a publication in
Intensive Care Medicine concluding that a more robust approach for estimating
stroke volume index may exclude inconsistencies in the underlying algorithms
for estimating stroke volume (5). Therefore, VFR was developed.

Recently, VFR was used in six Dalland pigs, and CO measured with this device
(VFRCO) was compared to CO obtained with an invasive ultrasonic flow-probe
(FPCO) around the ascending aorta. Variations in CO were achieved by a change
in ventricular loading conditions, cardiac pacing and dobutamine administration
(3). The results demonstrate that VFRCO was comparable to FPCO in that specific
animal model in a wide range of CO measurements. It was postulated that VFR has
the potential to become a clinical applicable CO monitor.
In addition, VFR was compared to CO measured at the LVOT with TTE in 7 healthy
volunteers, using G-suit inflation and deflation to provoke stroke volume
changes (4). In this study, VFR was able to track changes in stroke volume
reliably in an in-vitro study and in healthy volunteers.

Aim of the study
In this prospective, observational trial, we aim to investigate the accuracy,
precision and concordance of VFR in patients after open abdominal aortic
aneurysm (AAA) repair during their stay in the ICU. CO measurements obtained
with VFR (continuous) are compared to two reference techniques: 1) intermittend
thermodilution with a pulmonary artery catheter (TDCO) and 2) continuous
arterial waveform analysis CO measured with ProAQT/Pulsioflex (PCO).

We designed a single-centre, prospective observational trial in 27 patients
scheduled for open Abdominal Aortic Aneurysm repair.
In the OR, before induction of anesthesia, a peripheral infusion line (16G) and
a radial arterial line (20G) are routinely placed under local anesthesia in
these patients. After induction of anesthesia, a pulmonary artery catheter
(PAC, 7.5F, CCOmbo CCO/SvO2 catheter, type 744HF75, Edwards Lifesciences,
Irvine, CA) is routinely placed for advanced hemodynamic monitoring: cardiac
output (TDCO) and central venous oxygen saturation (SvO2). The radial arterial
line is routinely placed to monitor arterial blood pressure continuously.
Moreover, the arterial line is connected to the ProAQT transducer and the
Pulsioflex system (Pulsion, Munich, Germany) providing continuous CO monitoring
(PCO). As a result, TDCO and PCO are obtained without the need for additional
catheters or deviation from routine care.
After the operation, at arrival in the intensive care unit, current-injecting
electrodes will be attached on the neck and on each leg. A set of fourteen
voltage-sensing electrodes in a fixed scheme of electrode positions will be
attached to the thorax. A continuous harmless, electrical current (2,83 mArms,
55-91 kHz) will be administered inducing voltage changes over the thorax due to
cardiac filling and emptying during the cardiac cycle. With these voltage
changes, cardiac stroke volume (SV) and hence VFRCO is measured and compared to
TDCO and PCO.

Reference CO: the thermodilution technique and ProAQT/Pulsioflex system
TDCO measurement via a PAC is performed in the ICU by five bolus injections of
10 ml of saline 0.9% (7) at room temperature. Each value of TD-CO represents
the average of five measurements. Injections will be randomly spread over the
respiratory cycle. PCO is continuously measured by connecting the ProAQT sensor
to the arterial line. The sensor is fixed at the right atrial level in the
intensive care unit.

Measurement of CO: Ventricular Field Recognition
On the neck and each leg, a total of 4 current-feeding electrodes will be
attached and connected to a weak and harmless high-frequency AC current source.
Furthermore, a set of fourteen voltage-sensing electrodes in a fixed scheme of
electrode positions will be attached to the human thorax. A small, harmless,
electrical current (2.83 mArms, 55-91 kHz) will be administered continuously,
and because of cardiac filling and emptying during the cardiac cycle, voltage
changes are measured over the thoracic skin. The voltage differences are
processed by the VFR electronics (filters and amplifiers) and digitized using
AD-converters. The digital voltage data are then fed into a computer that uses
the VFR algorithm (4) to compute Stroke Volume, Cardiac Output and ventricular
volume-time curves continuously. The Department of Medical Technology and
Clinical Physics of the UMC-Utrecht is the official department within the
UMC-Utrecht, which is responsible for the safety of medical equipment. On the
basis of this responsibility, the Department of Medical Technology and Clinical
Physics of the UMC-Utrecht has performed safety tests on the VFR equipment, and
has produced a safety analysis report of the VFR.

Measurement of CO: timing in the intensive care
After the operation, CO is continuously measured with VFR and the ProAQT
system. Data of VFR and the ProAQT are automatically stored in a digital
patient database. Moreover, at four time points after the operation, CO is
additionally measured with the thermodilution technique:
- after arrival in the ICU
- after achieving normothermia in the patient ( rectal temperature >36.5º)
- 15-30 minutes after extubation
- the next morning after the operation.
In addition, when the hemodynamic status of the patient desires a fluid
challenge, pulmonary artery thermodilution CO will be measured before and
immediately after the fluid challenge.

Data collection
A continuous registration of CO measured with VFR is obtained by storing the
calculated SV, CO and ventricular volume-time curve data on the hard disk of
the on-board computer of the VFR system. A continuous registration of CO
measured with Pulsioflex is obtained by connecting the ProAQT sensor to an
arterial catheter. This registration is automatically saved in a database. All
TDCO measurements required for the study are registered in the digital patient
data registry and on a special study record form. The time, at which a TDCO
measurement takes place, is registered to allow comparison with the
corresponding VFR-derived CO values.
Moreover, continuous measurements of the VFR-system are compared with the
continuous measurements obtained with the ProAQT-system.
Data of patients will be anonymously stored according to their sequence in
participating in the study: APC1, APC2, *. to APC27.

POTENTIAL RISKS: There are no risks known associated with the weak high
frequency electric current that is imposed on the patient using non-invasive
skin electrodes in VFR. The skin electrodes (commercially available) however
are known to potentially cause a light form of irritation of the skin in a
small number of patients.

BENEFITS: The measurement of left ventricular stroke volume (SV) and cardiac
output (CO) is important in the hemodynamic management of peri-operative and
critically ill patients. Pulmonary artery thermodilution CO monitoring using
the pulmonary artery catheter has major disadvantages, because pulmonary artery
catheterization is time-consuming, and associated with a risk of morbidity and
mortality.
Noninvasive ultrasound Doppler techniques to determine CO have been developed,
but require skilled operators, and therefore are not suitable for monitoring
CO continuously. More recently, esophageal Doppler, Fick principle applied to
carbon dioxide, and pulse contour analysis have been identified as key
technologies for cardiac output monitoring. Furthermore, recent advances in MRI
show promising results in measuring cardiac output. However, MRI is obviously
not suitable for continuous bed-side monitoring.
Thoracic impedance cardiography (ICG) is a non-invasive technique, but
conflicting results concerning the validity and reliability of ICG have been
reported, varying from satisfactory correlations to poor correlations in
comparison to thermodilution CO measurements.
The new VFR technique combines the advantages of ICG (non-invasive, continuous
monitoring of stroke volume) with a higher number of independent skin
electrodes, advanced electrode placement and improved algorithm for calculating
the stroke volume and ventricular volume-time curves.