Anaesthesia 2012, 67, 377383

doi:10.1111/j.1365-2044.2011.07018.x

Original Article
A comparison of the Nexfin and transcardiopulmonary thermodilution
to estimate cardiac output during coronary artery surgery
O. Broch,1 J. Renner,2 M. Gruenewald,1 P. Meybohm,2 J. Schottler,3 A. Caliebe,4 M. Steinfath,5
M. Malbrain6 and B. Bein7
1 Staff member, 2 Associate Professor, 6 Professor and Chair, 7 Professor, Department of Anaesthesiology and Intensive
Care Medicine, 3 Staff member, Department of Cardiothoracic and Vascular Surgery, 4 Staff member, Institute of Medical
Informatics and Statistics, Christian-Albrechts University, Kiel, Germany
5 Associate Professor of Internal Medicine, ICU and High Care Burn Unit, ZNA Campus Stuivenberg, Antwerp, Belgium

Summary
The newly introduced Nexn device allows analysis of the blood pressure trace produced by a non-invasive nger cuff.
We compared the cardiac output derived from the Nexn and PiCCO, using transcardiopulmonary thermodilution,
during cardiac surgery. Forty patients with preserved left ventricular function undergoing elective coronary artery bypass
graft surgery were studied after induction of general anaesthesia and until discharge to the intensive care unit. There was
a signicant correlation between Nexn and PiCCO before (r2 = 0.81, p < 0.001) and after (r2 = 0.56, p < 0.001)
cardiopulmonary bypass. BlandAltman analysis demonstrated the mean bias of Nexn to be )0.1 (95% limits of
agreement )0.6 to +0.5, percentage error 23%) and )0.1 ()0.8 to +0.6, 26%) l.min)1.m)2, before and after
cardiopulmonary bypass, respectively. After a passive leg-raise was performed, there was also good correlation between
the two methods, both before (r2 = 0.72, p < 0.001) and after (r2 = 0.76, p < 0.001) cardiopulmonary bypass. We
conclude that the Nexn is a reliable method of measuring cardiac output during and after cardiac surgery.
. ..............................................................................................................................................................

Correspondence to: Dr O. Broch

Email: broch@anaesthesie.uni-kiel.de
Accepted: 19 November 2011

Monitoring of haemodynamic variables, such as cardiac

output and left ventricular stroke volume, is of
increasing interest, as it allows treatment to be tailored
to the individual patient. Recent studies have shown
that optimisation of left ventricular stroke volume or
cardiac output is associated with benecial effects on
both morbidity and length of stay on the intensive care
unit (ICU) [13]. The gold standard is the pulmonary
artery catheter; however, this is associated with a
number of complications and clinical limitations [4
6]. Therefore, investigators have examined the utility of
less invasive techniques such as transcardiopulmonary

Anaesthesia 2012 The Association of Anaesthetists of Great Britain and Ireland

thermodilution or continuous arterial waveform analysis [79].

The Nexn (BMEYE, Amsterdam, The Netherlands) has recently been introduced into clinical
practice. It consists of a model-based method that
provides beat-to-beat measurement of cardiac output by
analysis of the non-invasive nger arterial blood
pressure trace, which is measured continuously by the
use of an inatable nger cuff. Stroke volume is
determined by dividing the pulsatile systolic area of
each beat by impedance, which is estimated by the
device based on patient characteristics.
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Anaesthesia 2012, 67, 377383

We designed a study to compare the Nexn with

transcardiopulmonary thermodilution using the PiCCO
(Pulsion Medical Systems, Munich, Germany), looking
at the accuracy of cardiac output estimation and the
ability to track haemodynamic changes and trends.

Methods
After approval from our institutional ethics committee,
patients with preserved left ventricular function undergoing elective coronary artery bypass surgery were
approached and consent for participation in the study
was sought. Exclusion criteria included age < 18 years,
left ventricular ejection fraction 0.5, emergency
surgery, haemodynamic instability, intracardiac shunt,
severe aortic, tricuspid or mitral stenosis or insufciency, and mechanical circulatory support.
Patients were prescribed midazolam 0.1 mg.kg)1
orally, 30 min before induction of anaesthesia. Routine
monitoring was established including peripheral oxygen
saturation and heart rate (S 5 monitor; GE Healthcare,
Helsinki, Finland).
The Nexn monitoring system was set up by
entering patient-specic data followed by attaching the
pneumatic nger cuff to the middle phalanx of the
third nger (on the opposite hand to the arterial line),
as recommended by the manufacturer. Finger arterial
pressure measurement is based on the volume clamp
method [1012] in combination with Physiocal calibration [13]. Continuous nger pressure is reconstructed to brachial artery levels using a generalised
waveform lter and a level correction formula, correcting for differences in wave shape and pressure values
between these sites. Once the brachial artery waveform
has been developed, the pulsatile systolic area (determined by the time integral of the pressure curve above
the diastolic pressure and between the upstroke and the
dicrotic notch) is calculated for each beat. Stroke
volume is then calculated using the estimated arterial
impedance. To that end, a patient-specic threeelement Windkessel model is produced using patient
characteristics (age, sex, height and weight). Moreover,
for each beat, mean arterial pressure is used to correct
the elements that are pressure-dependent in a nonlinear way [14]. Dividing the pulsatile systolic area by
the impedance gives beat-to-beat stroke volume. Heart
rate was calculated from the pulse interval, followed by
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Broch et al. | Nexfin vs PiCCO

cardiac output (stroke volume multiplied by heart rate);

variables were automatically indexed to body surface
area.
After administration of sufentanil (0.5 lg.kg)1),
propofol (1.5 mg.kg)1) and rocuronium (0.6 mg.kg)1),
the trachea was intubated. Anaesthesia was maintained
by administering a continuous infusion of both sufentanil (1 lg.kg)1.h)1) and propofol (3 mg.kg)1.h)1). The
patients lungs were ventilated with an oxygen air
mixture using a tidal volume of 8 ml.kg)1 ideal body
weight, and positive endexpiratory pressure was set at
5 cmH2O. Subsequently, a central venous catheter and a
transpulmonary thermodilution PiCCO catheter were
inserted into the right internal jugular vein and the
femoral artery, respectively. The thermodilution catheter
was connected to the PiCCO monitor (Software version
1.3.0.8).
After induction of anaesthesia, Nexn and PiCCO
measurements as well as other haemodynamic values
were recorded every 10 min, both before and after
cardiopulmonary bypass (CPB). These were only measured when the following conditions were met: stable
haemodynamics; an undamped arterial pressure trace;
and (with respect to the Nexn) a frequency of
physiological autocalibration > 30 heartbeats. Thermodilution measurements were made by injecting 15 ml cold
saline ( 8 C) through the central venous line at least
three times, at random points in the respiratory cycle. If
a difference of 15% was detected between the PiCCO
measurements, they were repeated. At the same time,
Nexn measurements were performed by collecting ve
numerical values over a period of 3 min and determining the mean value.
A passive leg-raising manoeuvre was performed
after induction of anaesthesia and after surgery (before
transfer to the ICU); this involved elevating the legs to
45 while the patient was in the horizontal position. This
manoeuvre causes blood to be shifted from the lower
part of the body to the intrathoracic compartment,
generating an increase in right and left ventricular
preload, and leads to well recognised haemodynamic
effects. All measurements were repeated before, during,
and after raising the legs.
Statistical comparisons were performed using commercially available statistics software (GraphPad Prism
5; GraphPad Software Inc., San Diego, CA, USA and
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Broch et al. | Nexfin vs PiCCO

MedCalc for Windows, version 11.6.1.0; MedCalc Software, Mariakerke, Belgium). To demonstrate the relationship between sample size and the width of the
condence interval of the estimated variable, we calculated the width of the 95% condence interval of the
limits of agreementqas
recommended by Bland and
Altman (as 1:96 n3
s, where s is the standard
deviation of the bias). To describe the agreement
between PiCCO and Nexn, BlandAltman plots for
repeated measures were calculated for each time period
(before and after CPB). Percentage error was calculated
as described by Critchley et al. [15], using the limits of
agreement (2 SD) of the bias divided by the mean values
of the two methods. BlandAltman plots for haemodynamic trends and paired t-tests followed by Bonferroni
correction for multiple comparisons were also performed.

Results
We enrolled 40 patients, 29 (73%) of whom were men;
mean (SD) age was 64 (4) years, body mass index was 28
(3) kg.m)2 and left ventricular ejection fraction was 0.6
(0.1). A total of 404 data pairs (213 before and 191 after

Anaesthesia 2012, 67, 377383

CPB) were obtained. There was a signicant difference

(p < 0.05) between mean arterial pressure, systemic
vascular resistance index, heart rate and cardiac index
using both measurement devices before and after CPB.
There was a signicant correlation between Nexn and
thermodilution before and after CPB (Fig. 1). The bias,
limits of agreement and percentage error were within the
acceptable range (Table 1).
The passive leg-raise manoeuvre was performed in
37 40 patients before and 32 40 patients after CPB
(Table 2). Patients who increased their stroke volume
index by > 15% were dened as responders. We
observed 19 responders both before (51%) and after
(59%) CPB. Again, the measurements obtained by the
Nexn and PiCCO were correlated, with acceptable bias
and limits of agreement.
Changes in values displayed by both devices are
illustrated in Fig. 2. Again, they were well correlated,
with limits of agreement from )31% to +23%; after CPB,
limits of agreement ranged from )12% to +13%.
There was no signicant correlation between mean
arterial pressure and Nexn before (r2 = 0.01, p = 0.08)
and after (r2 = 0.009, p = 0.72) CPB; however, there was

Figure 1 Correlation plots (left) and BlandAltman plots (right) showing correlation and agreement between the
cardiac index measured by the Nexn and by PiCCO in 40 patients undergoing coronary artery surgery, before and after
cardiopulmonary bypass. CI, cardiac index; CPB, cardiopulmonary bypass; PE, percentage error.
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Broch et al. | Nexfin vs PiCCO

Anaesthesia 2012, 67, 377383

Table 1 Comparison of Nexn and PiCCO in 40 patients undergoing coronary artery surgery. Values are mean (SD) or
percentage.
Cardiac index; l.min)1.m)2
Bias; l.min)1.m)2
95% limits of agreement; l.min)1.m)2
Percentage error

Before CPB (213 measurements)

After CPB (191 measurements)

2.4 (0.6)
0.06 (0.27)
)0.60 to +0.49
23%

2.8 (0.6)
0.09 (0.37)
)0.81 to +0.63
26%

CPB, cardiopulmonary bypass.

Table 2 Comparison of Nexn and PiCCO in patients

undergoing coronary artery surgery in whom a passive
leg-raise manoeuvre was performed. Values are mean
(SD) or percentage. CPB, cardiopulmonary bypass.

r2
Bias; l.min)1.m)2
95% limits of
agreement;
l.min)1.m)2
Percentage error

Before CPB
(n = 37)

After CPB
(n = 32)

r2 = 0.72
(p < 0.001)
0.14 (0.43)
)0.98 to +0.70

r2 = 0.76
(p < 0.001)
0.07 (0.26)
)0.59 to +0.44

39%

18%

some correlation between the Nexn and systemic

vascular resistance index before (r2 = 0.31, p < 0.0001)
and after (r2 = 0.16, p < 0.0001) CPB.

Discussion
We have shown that the haemodynamic values and
indices measured by the Nexn and the PiCCO in
patients with preserved left ventricular function who do
not require inotropic support are well correlated. Such a
comparison has not been described before. The Nexn
was able to track haemodynamic changes and trends
before and after CPB however values were inuenced by
systemic vascular resistance.
The recently introduced Nexn monitoring system
is completely non-invasive in that it requires only the
use of a pneumatic nger cuff, without the insertion of
any intravascular lines. We have shown that the values
of cardiac output that it displays are well correlated with
the more invasive PiCCO system that requires the
insertion of both a central venous line and a femoral

Figure 2 Correlation plots (left) and BlandAltman plots (right) showing correlation and agreement of percentage
change in cardiac index measured by the Nexn and PiCCO in 40 patients undergoing coronary artery surgery before
and after cardiopulmonary bypass. CI, cardiac index; CPB, cardiopulmonary bypass.
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Broch et al. | Nexfin vs PiCCO

arterial line. The PiCCO is, however, in our opinion, less

invasive again than the pulmonary artery catheter, to
which many more complications are attributed [16].
As we have demonstrated, the Nexn does not
appear to need calibration before use. Its accuracy
depends on correct estimation of impedance, compliance and resistance [17], which are calculated using the
patient-specic data entered before connecting to the
patient. Aortic diameter and arterial pressure are then
estimated [1820], before cardiac output index is calculated.
Apart from the non-invasive nature and good
correlation of the device, we have shown that it is
easy and rapid to set up and use, meaning that we
can recommend use in similar settings. However, we
have not yet shown that its accuracy can be relied on
during haemodynamic instability or when inotropic or
vasoactive drugs are in use, meaning that further
studies in these areas must be carried out before more
widespread use can be recommended.
Other studies have also shown non-invasive measurement of nger arterial pressure to be quite accurate
[10, 21]. However, up to now, studies looking at their
use to estimate stroke volume and cardiac index have
been limited, with equivocal results [11, 2225].
Although in the study applying the Modelow algorithm
to the nger-derived arterial pressure curve, the device
showed less accuracy compared with pulmonary thermodilution, other investigations using the Nexn found
good correlation with pulmonary thermodilution and
echocardiography-derived cardiac output, respectively.
As recommended by Critchley et al. [26], we used
30% as our cut-off for limits of agreement, and we have
shown that the Nexn and PiCCO are adequately
correlated at varying times during coronary surgery, and
also before and after rapid intravascular volume expansion, as estimated using the passive leg-raise manoeuvre.
However, at the time of the passive leg-raise the Nexn
results did differ from the PiCCO by a small amount;
this nding has also been shown in a previous similar
study carried out in the ICU [27]. A number of previous
studies have also shown that other devices that rely on
pulse contour analysis are also not as accurate during
marked intravascular volume changes [2831].
Of interest, the mean arterial pressure was not
correlated with the cardiac output measured by the
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Anaesthesia 2012, 67, 377383

Nexn during the study period, but it was related to

the systemic vascular resistance. This has also been
shown in a number of other studies using pulse
contour analysis with other devices [7, 3235]. It must
be emphasised, however, that the relationship that we
have shown is based on only a few data points from a
small number of patients. However, from a physiological standpoint, cardiac index will be higher for a
given mean arterial pressure if systemic vascular
resistance index is low, which may explain some of
our ndings.
As suggested by a recent study [36], we have shown
that the Nexn and PiCCO are precise during stable
haemodynamic conditions, with no rapid changes
during data collection. This was also demonstrated
during the passive leg-raise test. This means both
systems are able to track such haemodynamic changes
and trends with acceptable accuracy.
Some limitations of our study should be noted. Our
data were derived from patients with preserved left
ventricular function undergoing elective coronary surgery under stable haemodynamic conditions and without ongoing pharmacologic support. Therefore, our
results cannot automatically be transferred to other
patient groups. Furthermore, we used PiCCO instead of
a pulmonary artery catheter as our gold standard. We
feel that this was justied because the PiCCO has been
shown to be interchangeable with the pulmonary artery
catheter in a number of other studies [7, 8, 37, 38].
However, the PiCCO has some limitations, particularly
after weaning from CPB, with transient thermal changes
leading to increased bias [35].
From the point of view of clinical relevance,
individualised intra-operative goal directed therapy has
been shown to lead to reduced morbidity [2]. Noninvasive and continuous estimation of stroke volume
and cardiac output is required for this to be carried out,
and we have demonstrated that the Nexn is a good
candidate for such a monitor.

Acknowledgements
The authors are indebted to Volkmar Hensel-Bringmann and Bernd Kuhr for excellent technical assistance
and logistic support. BB and MM are members of the
medical advisory board of Pulsion Medical Systems, the
manufacturer of the PiCCO device, and have received
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Anaesthesia 2012, 67, 377383

honoraria for consulting and giving lectures. The other

authors have no competing interests to declare.

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