Anaesth Intensive Care 2012; 40: 393-409

Review
The PiCCO monitor: a review
E. Litton*, M. Morgan†
Department of Intensive Care Medicine, Royal Perth Hospital, Perth, Western Australia, Australia

Summary
Advanced haemodynamic monitoring remains a cornerstone in the management of the critically ill. While
rates of pulmonary artery catheter use have been declining, there has been an increase in the number of
alternatives for monitoring cardiac output as well as greater understanding of the methods and criteria
with which to compare devices. The PiCCO (Pulse index Continuous Cardiac Output) device is one such
alternative, integrating a wide array of both static and dynamic haemodynamic data through a combination
of trans-cardiopulmonary thermodilution and pulse contour analysis. The requirement for intra-arterial and
central venous catheterisation limits the use of PiCCO to those with evolving critical illness or at high risk
of complex and severe haemodynamic derangement. While the accuracy of trans-cardiopulmonary
thermodilution as a measure of cardiac output is well established, several other PiCCO measurements require
further validation within the context of their intended clinical use. As with all advanced haemodynamic
monitoring systems, efficacy in improving patient-centred outcomes has yet to be conclusively demonstrated.
The challenge with PiCCO is in improving the understanding of the many variables that can be measured
and integrating those that are clinically relevant and adequately validated with appropriate therapeutic
interventions.
Key Words: monitoring, haemodynamic, cardiac output, PiCCO monitor

Advanced haemodynamic monitoring has
remained a cornerstone in the management of the
critically ill since the introduction of the pulmonary
artery catheter into clinical practice in the 1970s1.
The pulmonary artery catheter is still to a large
extent the clinical reference standard for cardiac
output measurement, but its utility is increasingly
questioned and use appears to be declining2,3.
Technological advances coupled with both the
recognition of costs4, complications5 and a failure to
demonstrate mortality benefit6,7 with the pulmonary
artery catheter has driven the demand for less
invasive alternatives.
Despite a substantial increase in the number of
publications comparing haemodynamic monitoring
* MB, ChB, MSc, FCICM, Intensive Care Specialist, Royal Perth Hospital
and Clinical Senior Lecturer, School of Medicine and Pharmacology,
University of Western Australia.
† MB, BCh, BSc, FRCA, Clinical Lecturer, School of Medicine, Cardiff
University and Anaesthetic and Intensive Care Doctor, University Hospital
of Wales, Cardiff, UK.
Address for correspondence: Dr E. Litton; Email: ed.litton@health.
wa.gov.au
Accepted for publication on February 6, 2012.
Anaesthesia and Intensive Care, Vol. 40, No. 3, May 2012
devices8, there are several reasons why their
appropriate role in clinical practice remains
uncertain. First, cardiac output and other advanced
haemodynamic measurements can be derived
through a variety of unrelated methods, each
with important benefits and limitations requiring
consideration. Second, the aortic flow probe as
the accepted gold standard for cardiac output
measurement is impractical and highly invasive and
in the clinical setting is substituted for a reference
device with known but imperfect characteristics9.
Third, valid statistical methods with which to
compare devices and the relationship between
statistical significance and thresholds for clinical
decision-making remain the subject of debate,
although there appears to be agreement that the
majority of comparative studies to date are sub-
optimal8-11. Fourth, the ultimate aim of monitoring
a specific parameter is the belief that responding to
the measurements will lead to an improvement in
patient survival or function. However, evaluating
the effectiveness of a monitoring device is complex,
requiring a valid measurement to be coupled with
accurate clinical interpretation and initiation of a
beneficial therapeutic intervention in an appropriate
394 E. Litton, M. Morgan

patient population. Finally, no single device
currently fulfils all the criteria to be considered
an ideal advanced haemodynamic monitor as
summarised in Table 1 and by others elsewhere12.
The choice of most appropriate monitor may
vary, requiring consideration of its unique
characteristics and the circumstances in which it
will be used.
The PiCCO (Pulse index Continuous Cardiac
Output) monitor measures and integrates a wide
array of haemodynamic variables through intra-
arterial and central venous catheterisation alone.
As such it is considered a less invasive monitor
of cardiac output than the pulmonary artery
catheter, although the need for arterial and venous
catheterisation renders it more so than so-called
minimally or non-invasive devices (see Table 2
for a comparison of advanced haemodynamic
monitoring devices).
Having been in use for over 10 years, a substantial
number of studies of PiCCO exist, including
comparisons to a range of monitoring alternatives.
The aim of this review therefore was to provide
a summary of the current role of PiCCO in the
clinical context by describing its practical use, the
underlying physiological basis for the parameters
measured, and their validity and clinical utility.
A glossary of terms is provided in the Appendix.
PRACTICAL USAGE
The most established commercially available
complete PiCCO set is produced by Pulsion Medical
Systems, Germany. It consists of three main
components, an arterial catheter with a solid-state
thermistor 5 mm from its tip, an injection device that
connects to the distal lumen of a standard central
venous catheter and the user-interface monitor24.
The latest model is the PiCCO2 which includes a
13 inch colour liquid crystal display touchscreen
that can display all standard clinical parameters.
Alternatively, both Philips (PiCCO-Technology
Module, Andover, MA, USA) and Dräger (Infinity®
PiCCO SmartPod®, Lübeck, Germany) have
modular attachments for their monitor range to
allow use of a Pulsion PiCCO arterial catheter
and central venous catheter injectate device with
these monitors. More recently, an alternative
to the Pulsion system has been developed by
Edwards Lifescience (Irvine, CA, USA, EV1000
clinical platform and VolumeView sensor) although
comparative data are currently lacking25.
Patient selection
None of the large (and increasing) number of
devices currently available for measuring cardiac
output can be considered universally ideal (Table 1).
Given the lack of comprehensive criteria to
determine when invasive haemodynamic monitoring
should be initiated, PiCCO may be considered in
all patients in whom central venous and intra-
arterial cannulation is deemed necessary. Risks
associated with insertion of the PiCCO arterial
catheter appear to be low26, and although difficult
to quantify, a greater risk is likely to result from
therapy initiated on the basis of inaccurate data
measurement or its inappropriate interpretation
or contextualisation. While the benefit of PiCCO

Table 1
Features of an ideal advanced haemodynamic monitoring device

Relevance Measures parameters relevant to patient management.

Accuracy Measured parameter is equal to the true parameter as approximated by the reference standard.
Quantified in terms of bias
Precision Repeated measurements provide the same results under stable conditions. Quantified in terms
of the standard deviation of measurements. Depending on device, both intra- and inter-observer
variability may be relevant
Response time Continuously updates haemodynamic parameters to reflect current clinical status
Risk Non-invasive with application conferring no risk to the patient
Ease of use Quick and easy to set up and use with a minimal number of components and training required.
Ongoing data acquisition, processing and display fully automated
Transportability Suitable for inter- and intra-hospital transfer with a small footprint. Imaging-compatible
Cost Inexpensive acquisition, maintenance and disposables
Familiarity Similarity to established monitoring devices and parameters
Generalisability Utility to a broad range of specialties and wide spectrum of clinical conditions, and haemodynamic
states and patient groups
Efficacy Proven benefit in clinical trials with patient-centred outcomes

Anaesthesia and Intensive Care, Vol. 40, No. 3, May 2012


Monitor type
PiCCO
Lithium dilution,
e.g. LiDCO
Ultrasound dilution,
e.g. COstatus
Pulmonary artery
thermodilution, e.g.
Vigilence, OptiQ
Pulse contour analysis,
e.g. FlowTrac PRAM
Anaesthesia and Intensive Care, Vol. 40, No. 3, May 2012
The PiCCO monitor
Table 2
Comparison of PiCCO with other cardiac output monitoring devices
Advantages
Validated intermittent cardiac output measurement
by trans-cardiopulmonary thermodilution.
Accuracy comparable to pulmonary artery catheter
thermodilution13
Calibrated continuous cardiac output monitoring
by combination of trans-cardiopulmonary
thermodilution and pulse contour analysis
Potentially useful additional parameters including
extravascular lung water, global end-diastolic
volume and stroke volume variation
Central venous access not required
Calibrated continuous cardiac output monitoring
by combination of trans-cardiopulmonary
thermodilution and pulse contour analysis
Pulse power calculation (LiDCO) may be more
accurate than other waveform analysis for
continuous cardiac output
Studies of accuracy and precision compared with
pulmonary artery catheter generally small with
different patient groups and methodologies, Li+
dilution and LiDCO moderate and comparable
precision14
Minimal volume normothermic indicator suitable
for neonates
Potential to detect shunts through dilution curve
analysis
Clinical reference standard for cardiac output
measurement
Measures pulmonary artery pressures
Simple set-up using existing standard monitoring
Continuous measurement
395
Disadvantages
Requires intra-arterial and central venous access
Inability to measure pulmonary artery pressures
PCA unreliable in patients with arrhythmia (e.g. atrial
fibrillation), mechanical circulatory assist devices, aortic
valve pathology and possibly dependent on arterial line
site
Lithium indicator unreliable with chronic use of Li+,
recent benzylisoquinoline neuromuscular blockers and
where significant indicator is lost prior to measurement.
Calibration of pulse contour analysis for Li+ requires
input of haematocrit and serum Na+
Inability to measure pulmonary artery pressures or
extravascular lung water
Requires intra-arterial and central venous access
Inability to measure pulmonary artery pressures
No continuous cardiac output measurement
Invasive arterial pressure not recorded or displayed
while ultrasound cardiac output being measured
Risks associated with additional central venous access
and pulmonary artery catheter insertion, arrhythmia,
knotting and pulmonary embolism
Continuous cardiac output inaccurate when
hypothermic and signal averaging over several minutes
creates time lag in displaying sudden changes in cardiac
output
Moderate imprecision when compared with aortic flow
probe as gold standard. May be as much as 13% under
steady state conditions and 40% intraoperatively15
Intra-arterial catheter required for reliable trace
Inaccurate in patients with arrhythmia (e.g. atrial
fibrillation), aortic valve pathology, mechanical assist
device or line kinking or damping
Earlier versions have poor accuracy compared with
pulmonary artery catheter thermodilution studies
particularly when haemodynamics unstable and
unacceptably high percentage error of up to 58.8%16.
Insufficient data to assess accuracy, precision and
trending of most recent software versions (including
FlowTrac 3).
396 E. Litton, M. Morgan

Table 2
Comparison of PiCCO with other cardiac output monitoring devices (continued)

Monitor type Advantages Disadvantages

Partial rebreathing, Non-invasive Multiple potential error sources especially in those with
e.g. NICO respiratory disease
Continuous measurement Inaccurate unless ventilated with no spontaneous
respiratory effort
Limited data but accuracy poor when compared with
pulmonary artery catheter-derived cardiac output and
unacceptably high percentage error of >40%17
Bioimpedence, Non-invasive Validity in the critically ill uncertain. Accuracy and
e.g. PhysioFlow precision of previous devices unacceptably poor, more
current versions remain unreliable18.
Continuous measurement Alterations in thoracic water and peripheral vascular
resistance reduce accuracy

Doppler Continuous real-time with beat-to-beat variability Risks associated with oesophageal probe insertion and
contraindicated in those with oesophageal pathology
Oesophageal, Additional parameters including measure of Makes assumptions about descending aortic flow as a
e.g. CardioQ , cardiac preload proportion of total cardiac output
HemoSonic
Some evidence to support oesophageal Doppler- Small window for acoustic signal may require frequent
guided therapy in improving surrogate repositioning
perioperative outcomes19
Data on accuracy and precision compared with
pulmonary artery catheter thermodilution generally
limited to small studies and variable dependent on
population studied and methodology used. Percentage
error reported to be as high as 65%20,21
Suprasternal, Non-invasive Difficulty in acquiring adequate acoustic window
e.g. USCOM
Easily transportable Requires user training
Intermittent measurement only
Limited data but accuracy appears poor when
compared with pulmonary artery catheter and
unacceptably high mean percentage error of up to
56%22
Echocardiography Global assessment of haemodynamic status and Significant training and experience required
diagnosis of potential underlying cardiac pathology

Non-invasive via transthoracic route Inter-observer variability

Well-validated measures of all haemodynamic Not continuous

parameters
Mean percentage error compared with pulmonary High start-up costs
artery catheter may be as small as 2% depending
on experience of operator, technique and onditions23
Time consuming

Procedural risks associated with TOE including

sedation if not intubated

PiCCO=pulse index continuous cardiac output, PCA=pulse contour analysis, PRAM=pulse recording analytical method, NICO=non-
invasive cardiac output, TOE=transoesophageal echocardiography.

is most likely to be apparent in those with
evolving critical illness or at high-risk of severe
haemodynamic derangement, in practice PiCCO is
generally employed in patients in one of three main
categories:
1. Intraoperative and early postoperative manage-
ment of patients in whom complex co-
morbidities are present or particular fluid
management strategies are considered to be
beneficial. For example, restricted fluid use
Anaesthesia and Intensive Care, Vol. 40, No. 3, May 2012
 The PiCCO monitor
following goal-directed administration according
to PiCCO parameters in major colonic resection27.
2. Intraoperative monitoring of patients during
cardiac surgery28.
3. Monitoring of the critically ill patient to help
direct fluid and vasoactive therapy29.
Contraindications to use fall into two categories.
First, contraindications to vascular device insertion
including severe peripheral vascular disease, arterial
grafting, overlying infection and coagulopathy.
Second, anatomical or physiological derangements
likely to render PiCCO-derived measurements
grossly inaccurate. These are further described in
the section on PiCCO parameters.
Site selection and catheter insertion
Clinically important differences may exist in both
the absolute values of arterial pressure measured
at more peripheral compared with more central
sites30 as well as the shape of the arterial pressure
wave-form. The femoral artery is the most common
site of cannulation, however radial, brachial and
axillary sites are potential alternatives. Removal
of the arterial catheter is recommended within
10 days of insertion and replacement of the arterial
line transduction kit and inline injectate sensor
housing is required every three to five days24.
The venous injectate port should be placed in
the central cardiopulmonary circulation, within or
directly proximal to the right atrium. Placement in
the femoral vein will result in significant over-
estimation of intrathoracic volumetric measure-
ments although trans-cardiopulmonary thermo-
dilution cardiac output measurement may still be
reliable31. In addition, cannulation of the ipsilateral
femoral artery should be avoided to reduce
temperature artefact from injection close to the
thermistor in the nearby artery32.
Performing a calibration
Following catheter insertion and monitor setup
with a mandatory data set, calibration is required
before data acquisition. The injectate solution
should ideally be 0.9% saline as both lipid and
dextrose compounds can damage the sensor’s
housing24. The recommended volume for injection is
directly proportional to the patient’s extravascular
thermal volume and therefore depends on both
patient’s weight and the amount of extravascular
lung water (EVLW). In practice between 15 and
30 ml per injection is normally used. The optimal
fluid temperature is below 8°C although room
temperature solutions are acceptable33. Three
separate injections within a five-minute period
Anaesthesia and Intensive Care, Vol. 40, No. 3, May 2012
397
performed by the same person at the same speed
and pressure should yield results with <20%
variation. Calibration should be repeated every
eight hours or following a major change in the
patient’s clinical condition34.
Goal-directed use
In an attempt to provide an appropriate response
to the values displayed, a decision tree model has
been proposed by the manufacturers of PiCCO24.
The clinical response to the data provided can be
divided into expectant, volume loading, volume
reduction and use of vasoactive medication. This
structured approach couples standardised inter-
ventions to specific data patterns but must only
be considered in the context of a global clinical
assessment and suffers from several shortcomings.
First, the presence of serious reversible pathology
should also be explored and corrected as a cause
of haemodynamic derangement. For example, the
decision tree does not direct a clinician to decompress
a pneumothorax or provide source control in the
event of sepsis. Second, it does not encompass
consideration of mechanical support devices such
as intra-aortic balloon counter-pulsation or veno-
arterial extracorporeal membrane oxygenation.
Whereas the vast majority of the literature
comparing cardiac output monitoring devices
provides a comparison between specific isolated
variables, clinical practice demands that all available
information be assimilated to guide decision-
making35. The particular attraction of goal-directed
use of PiCCO therefore, is in its capacity to
integrate a large number of haemodynamic
parameters. In this regard, few pragmatic studies of
the efficacy of PiCCO monitoring in representative
perioperative and intensive care settings exist.
Results in selected patient groups such as post-
operative cardiac surgery are preliminary but
encouraging36, and reflect similar benefit seen in
surrogate outcomes such as hospital length of stay
from perioperative studies of goal-directed therapy
using minimally invasive monitors37.
Estimates of the true accuracy and precision of
PiCCO compared with other cardiac output devices
are variable and currently unreliable. Issues include
differences in the patient groups studied, comparative
statistics, study methodology, timing of assessments
and imprecision of the pulmonary artery catheter
itself as the most common clinical reference. A broad
overview is provided in Table 2 with comparative
data where available.
398 E. Litton, M. Morgan

PICCO PARAMETERS volume (ITBV), cardiac function index and

The PiCCO device measures and displays a
wide array of haemodynamic data (see Table 3 for
a summary of the parameters and quantification
of their potential utility). These can be divided
into intermittent measurements based on trans-
cardiopulmonary thermodilution and continuous
measurements based on pulse contour analysis
of the arterial pressure waveform. A further
important distinction must be made between directly
measured values and those that have been
derived and susceptible to compounding of errors
(Table 3).
Interpretation of the trans-cardiopulmonary
thermodilution indicator-time curve allows
estimation of cardiac output, EVLW, global end-
diastolic volume (GEDV), intrathoracic blood
global ejection fraction. Pulse contour analysis
provides continuous estimation of stroke volume,
cardiac output, pulse pressure variation, stroke
volume variation and an index of left ventricular
contractility. PiCCO2 also allows continuous
monitoring of central venous oxygen saturation
(ScvO2) with the addition of a CeVOX fibreoptic
probe inserted through the distal lumen of the
central venous catheter.
Evaluation of the validity of these measures can
be approached using the framework proposed in
Table 4. Equally important is an understanding of
the underlying physiological principles from which
they are derived, for which much of the pioneering
work was undertaken as far back as the late 19th
century38,39.

Table 3
Summary of the parameters measured by PiCCO

Parameter Description
Parameters measured intermittently by trans-cardiopulmonary thermodilution
Cardiac output Validated in appropriate clinical settings with an acceptable level of accuracy
May be of particular use as a pulmonary artery catheter substitute where cardiac output measurement likely to be
required for a prolonged period of time and/or pulmonary artery pressure measurement not required
Both trend and absolute values of clinical importance
Interpretation of absolute values requires indexing to body surface area
EVLW Water content outside of the pulmonary vasculature including the pulmonary interstitium plus any alveolar fluid
Normal range is 3-7 ml/kg but ideal cut-off yet to be established
Preliminary studies suggest potential diagnostic, therapeutic and prognostic utility
Definitive studies are lacking but utility may increase with increasing evidence of association between fluid
balance and outcome in the critically ill
GEDV Measure of the total volume in all four chambers of the heart at end-diastole
May be superior to cardiac filling pressures in determining volume responsiveness
Role uncertain and may be of greatest utility in situations where the more accurate dynamic measures such as
systolic pressure variation cannot be used. Definitive studies of benefit currently lacking
ITBV Derived from GEDV by simple multiplication although the relationship may not always be linear
Clinical utility equivalent to GEDV but with different reference range
No additional clinical utility compared with GEDV
CFI The ratio of CO to GEDV
Derived from other measures displayed by PiCCO providing uncertain additional utility
Additional caution required for all derived measurements. No clear benefit compared with clinician assessment of
the individual components
GEF Derived as the ratio of stroke volume to GEDV multiplied by a factor of 4
Similar to CFI, GEF is simply a ratio of other measures displayed by PiCCO. The additive value to clinical
decision-making is uncertain with caveats on derived measurements as stated for CFI
PVPI Derived from the ratio of EVLW to pulmonary blood volume (pulmonary blood volume=pulmonary thermal
volume EVLW)
May help to differentiate hydrostatic from inflammatory causes of pulmonary oedema
Additional caution is required for all derived values as risk of measurement error is compounded. Clinician
assessment of individual components may be preferable

Anaesthesia and Intensive Care, Vol. 40, No. 3, May 2012

 The PiCCO monitor 399

Table 3
Summary of the parameters measured by PiCCO (continued)

Parameter Description
Parameters measured continuously by pulse contour analysis
Cardiac output Derives cardiac output from heart rate and stroke volume by analysis of the area under the systolic portion of the
arterial waveform
Appears reasonably accurate during stable conditions however validity in conditions of significant haemodynamic
derangement not definitively proven
Requires calibration and measurement of aortic compliance using trans-cardiopulmonary thermodilution
Greatest clinical utility may be as a marker of need to re-calibrate with trans-cardiopulmonary cardiac output
after any significant change in value
Stroke volume Measures stroke volume by analysis of the area under the systolic portion of the arterial waveform
Requires calibration and measurement of aortic compliance using trans-cardiopulmonary thermodilution
Moderately accurate under stable conditions but clinical utility also lowest under such conditions
Systemic vascular Derived from mean arterial pressure and CO
resistance
No independent clinical utility likely compared with clinical assessment of the individual components.
Additionally, measurement errors may be compounded for derived values
Pulse pressure Dynamic measure of intravascular volume status measuring the variation in difference between systolic and
variation diastolic blood pressure
More accurate than either pressure or volume-based static measures of volume responsiveness during mechanical
ventilation, but with significant caveats
Proven accuracy in determining volume responsiveness however, predictive of volume responsiveness does
not indicate that additional fluid is necessarily required and clinical utility in improving outcomes is yet to be
demonstrated and will depend on synthesis of these two components
Stroke volume Dynamic measure of intravascular volume status measuring variation in area under the systolic portion of the
variation arterial waveform
More accurate than either pressure- or volume-based static measures of volume responsiveness during mechanical
ventilation but with significant caveats
LVCI More difficult to measure than PPV and uncertain whether diagnostic accuracy is superior. Additional caveats to
utility as per PPV
Derived measure of left ventricular performance derived from the maximum upslope of the arterial pressure-time
curve in systole
Very preliminary data only and validity and clinical utility yet to be established
Other parameters measured
Basic parameters Heart rate, systolic, diastolic and mean arterial blood pressure, central venous pressure
Central venous Surrogate marker of the overall balance between oxygen delivery and consumption
oxygen saturation
(ScvO2) Only takes into account the upper body drained by the superior vena cava and relationship with mixed venous
oxygen saturation is variable
Role of ScvO2 measurement in the critically ill is still uncertain. Although a single centre study has shown benefit
in early severe sepsis, generalisability of these findings is currently under investigation
EVLW=extravascular lung water, GEDV=global end-diastolic volume, ITBV=intrathoracic blood volume, CFI=cardiac function index,
CO=cardiac output, GEF=global ejection fraction, PiCCO=pulse index continuous cardiac output, PVPI=pulmonary vascular perme-
ability index, LVCI=left ventricular contractility index, PPV=positive pressure ventilation.

1. INTERMITTENT BOLUS TRANS- equation for a thermal indicator requires the

CARDIOPULMONARY THERMODILUTION addition of a constant (K) to correct for the
Cardiac output specific thermal mass of the injectate and blood
The measurement of cardiac output by (Equation 1).
thermodilution is based on the Stewart-Hamilton COtd=(Tb–Ti) Vi K/∫ΔTb dt
equation40, in which cardiac output is inversely Equation 1: Adaptation of the Stewart-Hamilton equation for
related to the concentration and total passage time a thermal indicator. COtd=cardiac output by thermodilution,
T b=blood temperature, Ti=injectate temperature,
of an indicator solution measured after its transit Vi=injectate volume, ∫ΔTb=area under the thermo-dilution
through the heart. Adaptation of the original curve, K=constant.
Anaesthesia and Intensive Care, Vol. 40, No. 3, May 2012
400 E. Litton, M. Morgan

Table 4
Evaluating validation studies of advanced haemodynamic monitoring

1. Is the study population appropriate?

a. The patients, therapeutic interventions and range of values for the parameters under investigation are representative of those
in which the monitor will be used
2. Is the choice and description of the reference method appropriate?
a. The accuracy* of the reference method is known and is clinically acceptable
b. The precision† of the reference method is reported for the study population
3. Is the comparison method assessed appropriately?
a. The physiological basis and limitations of the monitoring technique are understood and taken into account in the study design
b. The method and timeframe of data acquisition is described
c. The precision and accuracy of the device are reported
d. The relationship between proposed statistical analyses and thresholds for clinical decision-making are considered
* Accuracy refers to how closely the measured value represents the true value measured by the gold standard or the comparative value
measured by the reference standard. Quantitative measurement should describe both relative and absolute differences with limits
of clinical acceptability defined a priori. † Precision refers to the concurrence of repeated measurements under stable conditions.
‡ Correlation and regression are not appropriate measures of accuracy as they describe the extent to which changes in one
measurement device predict changes in the other, e.g. a change in measurement in one device may correlate perfectly with a
four times change in the other but provides no information on the absolute level of agreement between the two.

Injectate syringe

PiCCO thermistor-tipped
Injectate sensor cable arterial catheter

Central line

Injection of indicator
Sensed by PATD
Sensed by TCPTD

Δ Temperature

Recirculation
Time

Mean transit time

Exponential decay time

In Δ temperature

Time
Figure 1: Comparison of thermodilution curve with PAC and TCPTD. PC=pulmonary circulation, PiCCO=pulse index continuous
cardiac output, RA=right atrium, RV=right ventricle, LA=left atrium, LV=left ventricle, PATD=pulmonary artery thermodilution,
TCPTD=trans-cardiopulmonary thermodilution.
Anaesthesia and Intensive Care, Vol. 40, No. 3, May 2012
 The PiCCO monitor
The pulmonary artery catheter is based on indicator
transit through only the right side of the heart with
a sensor placed in the pulmonary artery. In contrast,
in trans-cardiopulmonary thermodilution a known
quantity of cold injectate is delivered via a central
venous catheter and mixing of the thermal indicator
occurs as it passes through the right atrium and
ventricle, pulmonary circulation, left atrium, ventricle
and aorta. A thermistor-tipped arterial line quantifies
the change in temperature over time in a large
proximal artery, most commonly the femoral artery.
A mono-exponential transformation of the curve
with extrapolation of a truncated descending limb
back to baseline allows calculation of area under
the curve for cardiac output measurement. A
comparison of trans-cardiopulmonary thermo-
dilution with pulmonary artery thermodilution and
the qualitatively similar resultant curves is shown
in Figure 1.
Compared with the measurement of cardiac
output by pulmonary artery thermodilution, trans-
cardiopulmonary thermodilution has been shown
to demonstrate a level of accuracy that is within a
clinically acceptable range in a number of different
patient populations and a recent summary of the
comparative studies is provided by Reuter et al41.
Potential sources of error common to both include
loss of injectate prior to delivery, regurgitant valve
lesions42, intra-cardiac shunts, extracorporeal
circulations, rapid changes in body temperature43,
conductive rewarming of the injectate during transit
and the cyclical change in cardiac output that
occurs with respiration44. Compared with pulmonary
artery thermodilution, the greater transit time and
distance between injectate delivery and measure-
ment with trans-cardiopulmonary thermodilution
will tend to increase the error associated with
conductive loss and recirculation while reducing
the potential for the measured cardiac output to be
unrepresentative of its true value over the entire
respiratory cycle44,45. Specific to PiCCO, a large aortic
aneurysm will result in overestimation of ITBV and
GEDV if femoral artery cannulation is used, while
intra-aortic balloon pumps reduces the accuracy
of pulse contour analysis measurement of cardiac
output but not when derived from trans-
cardiopulmonary thermodilution46.
Despite the limitations of thermodilution as
a measurement technique and a failure of large
randomised trials of pulmonary artery catheter use
to demonstrate mortality benefit, enthusiasm for
cardiac output monitoring appears undiminished.
Although one advantage of PiCCO over pulmonary
artery catheter is in dispensing with the need for
Anaesthesia and Intensive Care, Vol. 40, No. 3, May 2012
401
right heart catheterisation, significant adverse events
directly attributable to pulmonary artery catheter
insertion are low6,47. The greater potential for PiCCO
to demonstrate benefit where the pulmonary artery
catheter failed is in the integration of reliable
cardiac output measurement with other potentially
useful haemodynamic parameters. Demonstration
of efficacy will require a greater understanding of
the relationship between haemodynamic measure-
ments and patient outcome, allowing monitoring
results to be coupled with beneficial therapeutic
interventions.
Derivation of additional measures by trans-cardiopul-
monary thermodilution
Further analysis of the slope and duration of
the thermal indicator dilution curve after passage
through both sides of the heart and pulmonary
circulation enables estimation of additional
haemodynamic parameters including measures
of intrathoracic volumes and cardiac function
(Figures 1 and 2). The extrapolated and log-
transformed slope of the indicator time-
concentration curve as it returns to baseline
is represented by the exponential decay time.
Assuming a model of the circulation in which the
indicator solution has undergone mixing in a series
of chambers, the exponential decay time is pro-
portional to the volume of distribution of the largest
chamber, represented by the pulmonary circulation
in the case of trans-cardiopulmonary thermo-
dilution. The mean transit time of the indicator
solution is the time taken for half the indicator to
pass the arterial detection point and is proportional
to the total intrathoracic volume of distribution48.
These measurements are used to calculate EVLW
and GEDV which like cardiac output may be
indexed to body surface area (Figure 2). Derived
measurements indexed to body surface area may
be misleading in the morbidly obese if calculations
are based on actual weight49. In the latest PiCCO
system however, indexed measurements are derived
from ideal weight estimated from measured
height, adding a different potential source of error.
Additionally, there are a considerable number of
paediatric studies evaluating PiCCO use50-52. The
accuracy of trans-cardiopulmonary thermodilution
as a method of estimating cardiac output appears
similar to that of the adult population although
conclusive safety data is lacking and the validity
of some of the additional trans-cardiopulmonary
thermodilution-derived parameters, such as EVLW,
are uncertain53.
402 E. Litton, M. Morgan
1. ITTV=CO×MTT
2. PTV=CO×EDT
3. GEDV=ITTV-PTV
4. ITBV=GEDV×1.25
5. EVLW=ITTV-ITBV
Figure 2: Mixing chamber model and derivation of global
end-diastolic volume and extravascular lung water by single
indicator thermodilution. ITTV=intrathoracic thermal volume,
CO=cardiac output, MTT=mean transit time, PTV=pulmonary
thermal volume, EDT=exponential decay time, GEDV=global
end-diastolic volume, ITBV=intrathoracic blood volume,
EVLW=extravascular lung water, RA=right atrium, RV=right
ventricle, PV=pulmonary volume, LA=left atrium, LV left
ventricle.
Extravascular lung water
EVLW is the water content outside of the
pulmonary vasculature including the pulmonary
interstitium plus any alveolar fluid. The normal
range is 3 to 7 ml/kg54. Imaging modalities such as
computer tomography, magnetic resonance imaging
and positron emission tomography have all been
used to quantify EVLW however gravimetry is
considered to be the gold standard55,56.
The calculation of EVLW by trans-cardio-
pulmonary thermodilution was initially based on
a double indicator method whereby the volume of
distribution of an indicator contained within the
ITBV (e.g. an inert chemical such as indocyanine
green) was subtracted from the volume of
distribution of an indicator such as cold water
distributing to the total intrathoracic thermal
volume. The difference between the intrathoracic
thermal volume and the ITBV is equal to the
EVLW. Double-indicator trans-cardiopulmonary
thermodilution is able to detect changes in EVLW
of 20% or more with good correlation to
gravimetry57.
An eloquent sequence of calculations allows the
use of thermal injectate as a single indicator to
estimate EVLW with reasonably good correlation
to both the double indicator technique (Figure 2)58
and the gold standard gravimetry technique,
albeit with a slight bias of overestimation due to
thermal redistribution in extra-pulmonary tissue59.
Calculation of the ITBV is based on the extrapolation
of GEDV and assumes a linear relationship
between the two58,60. For both methods, there is
also the assumption that the extravascular water
content of the myocardium and non-pulmonary
vessels is insignificant in comparison to the total
EVLW48. Potential sources of error include those
common to trans-cardiopulmonary thermodilution
calculation of cardiac output. In addition, lung
resection, obstruction of major pulmonary vessels
and potentially also large increases in positive
end-expiratory pressure may lead to unreliable
measurement of EVLW61.
Trans-cardiopulmonary thermodilution calculation
of EVLW has been proposed as a diagnostic tool
both to measure sub-clinical pulmonary oedema
not apparent on clinical examination or plain
radiography and to differentiate hydrostatic and
inflammatory aetiologies of pulmonary oedema on
the basis of the pulmonary vascular permeability
index, the ratio of EVLW to PBV62,63. Several
small studies demonstrate the ability of trans-
cardiopulmonary thermodilution to measure
different changes in fluid compartment distribution
in inflammatory and non-inflammatory conditions;
further work is required in order to ascertain
whether this will translate into clinically meaningful
results63.
As well as its diagnostic utility, EVLW
measurement may have utility both prognostically in
predicting survival in those admitted to ICU64, and
therapeutically by providing a measurement against
which to titrate fluid balance. There is increasing
evidence of the association between fluid balance
and outcomes in critical illness65,66 and preliminary
studies suggest EVLW measurement may have a
role in the management of volume status in a variety
of patient groups including lung transplantation67,
acute lung injury68 and coronary artery bypass
grafting69. Whether titration of volume status to
EVLW measurements will lead to generalised
improvements in patient outcomes remains to be
determined.
Global end-diastolic volume and intrathoracic blood
volume
Accurate determination of intravascular
volume status is important as inappropriate fluid
administration is associated with an increased risk
of adverse outcomes in critical illness66,70. Central
venous pressure, a widely used endpoint for
volume resuscitation in the critically ill71, and
other pressure-based surrogate measures of
preload including pulmonary artery occlusion
pressure are dependent on several factors other
than mean circulatory filling pressure72,73 and their
utility in predicting volume responsiveness is
questionable74-76.
Anaesthesia and Intensive Care, Vol. 40, No. 3, May 2012
 The PiCCO monitor
Compared with pressure-based measures, GEDV
and ITBV or their indexed equivalents GEDVI
and ITBVI are volumetric measures of preload
derived from features of the trans-cardiopulmonary
thermodilution curve using the PiCCO device
(Figure 2). GEDV is a measure of the total volume
in all four chambers of the heart at end-diastole,
whereas ITBV also includes the volume in the
pulmonary circulation. Although their reference
ranges are different and their relationship under
varying haemodynamic conditions may not be linear,
from the point of view of clinical interpretation they
have equivalent utility. ITBV is simply extrapolated
from GEDV when derived by PiCCO using a single
thermal indicator58.
One-off baseline measures of preload, whether
pressure- or volume-based appear equally poor
in predicting volume responsiveness77,78. The
relationship between stroke volume and change
in preload measurement in response to fluid
bolus appears stronger for volumetric measures
than central venous pressure or pulmonary artery
occlusion pressure but still with only moderate
correlation60,79. Furthermore, few studies evaluate
whether the information from invasive monitoring
provides additional benefit over clinical judgement
and most involving trans-cardiopulmonary thermo-
dilution are also limited by the potential for
mathematical coupling between calculation of
cardiac output and volumetric indices80.
Compared with both static pressure- and volume-
based measures of preload, dynamic measures
such as stroke volume variation, pulse pressure
variation and systolic pressure variation, have
greater accuracy in predicting volume status in
mechanically ventilated patients and are described
in the section below81.
Cardiac function index and global ejection fraction
The PiCCO device calculates two specific
measures of cardiac performance based on the
trans-cardiopulmonary thermodilution curve.
Cardiac function index (the ratio of cardiac output
to GEDV) and global ejection fraction (the ratio
of stroke volume to GEDV multiplied by a factor
of 4) are simply derived as ratios of cardiac output
and volumetric measurements. Given the known
accuracy of trans-cardiopulmonary thermodilution
in estimating cardiac output and GEDV it is
perhaps unsurprising that cardiac function index
and global ejection fraction correlate with cardiac
function82-84. In general however, derived indices
should be avoided as a basis for decision-making
as measurement errors are simply compounded and
the individual components are already available.
Anaesthesia and Intensive Care, Vol. 40, No. 3, May 2012
403
2. PULSE CONTOUR ANALYSIS
Cardiac output
Pulse contour analysis allows continuous but
indirect measurement of cardiac output using a
variety of characteristics of the pressure waveform
of an arterial line trace to calculate beat-to-beat
stroke volume. Estimating cardiac output from
the arterial pressure waveform is complex as the
waveform is dependent not only on stroke volume
but also on aortic impedance that varies both
between individuals and within individuals in a non-
linear manner (see Equation 2).
CO=HR.SV where SV=Asys/Zao
Equation 2: Basic elements required for cardiac output calculation
by pulse contour analysis. CO=cardiac output, HR=heart rate,
SV=stroke volume, Asys=area under systolic portion of arterial
waveform trace, Zao=aortic impedance.
Although non-linear, aortic impedance and its
relationship to flow can be estimated mathematically
using the three-element Windkessel model of the
circulation described by Wesseling85, comprising
of: 1) opposition to pulsatile flow (characteristic
impedance); 2) change in aortic volume for a
given change in distending pressure (Windkessel
compliance); and 3) peripheral arterial resistance.
The Windkessel model is the basis for several
commercially available uncalibrated pulse contour
analysis devices that derive cardiac output by
assuming values for the three model elements based
on age, heart rate, mean arterial pressure and the
aortic pressure waveform86,87. Although algorithms
are becoming more complex88, inaccuracy may
still be a significant problem. An inability to
independently calibrate measured cardiac output
prevents change in aortic impedance over time
being taken into account when analysing the
pressure waveform. The extent of this inaccuracy will
depend both on the nature and severity of any
haemodynamic derangement. This limits clinical
utility, particularly where large variations could be
expected89.
The PiCCO pulse contour analysis algorithm
overcomes some of these limitations by using trans-
cardiopulmonary thermodilution to calibrate cardiac
output and measure aortic compliance. Systemic
vascular resistance is calculated from the mean
arterial pressure and the trans-cardiopulmonary
thermodilution-derived cardiac output. The
exponential decay time of the arterial pressure
curve during the passive diastolic arterial phase
is then measured and the aortic compliance (Ca)
calculated (Ca=exponential decay time/systemic
vascular resistance). Pulse contour analysis for
404 E. Litton, M. Morgan
stroke volume estimation includes both area under
the systolic portion of the arterial waveform and
analysis of the shape of the arterial waveform (dP/
dt). Pulse contour analysis-derived cardiac output
estimation is then calibrated against a simultaneous
trans-cardiopulmonary thermodilution measurement
providing a calibration factor (K) for continuous
cardiac output by pulse contour analysis (Figure 3)90.
Despite the ability to calibrate measurements,
the primary limitation of PiCCO pulse contour
analysis remains the potential for inaccuracy due to
the multitude of input variables required and the
assumptions inherent in the derived components
of the equation. Pulse contour analysis is also
inaccurate in those with arrhythmia, undergoing
intra-aortic balloon counterpulsation or other forms
of mechanical circulatory assist. Practical limitations
include intermittent inaccuracy due to kinking,
damping and insufficient zeroing of the arterial line.
The site of sampling also has the potential to affect
waveform interpretation as acoustic reflections and
alterations in vasomotor tone both increase with
increasing distance from the aorta although the
magnitude of effect may be small enough to still
allow reasonable accuracy91.
The optimal interval for trans-cardiopulmonary
thermodilution recalibration of pulse contour
analysis-derived cardiac output is uncertain but is
likely to be required more frequently the greater the
haemodynamic instability92,93. A novel method for
timing recalibration relying on changes in the ratio
of stroke volume to pulse pressure as an indicator
of alteration in vascular compliance has also
recently been proposed34.
A number of studies have compared PiCCO
pulse contour analysis with pulmonary artery
catheter-derived cardiac output and demonstrated
PCCO = cal • HR • ∫ ) SVR
P(t)
+ C(p) •
dP
dt
) dt
Systole
{
{
{
{
{
Patient-specific Heart Area Aortic Shape of
calibration rate under compli- pressure
factor pressure ance curve
(determined by curve
thermodilution)
Figure 3: Calculation of cardiac output by PiCCO pulse contour
analysis. PCCO=pulse contour cardiac output, cal=calibration
factor derived from trans-cardiopulmonary thermodilution,
HR=heart rate, ∫systole=systolic portion of curve, P(t)=change
in pressure over time, SVR=systemic vascular resistance, P(t)/
SVR=represents the area under the arterial pressure curve
in systole where SVR is derived from mean arterial pressure/
cardiac output, C(p)=aortic compliance, dP/dt=shape of the
arterial pressure waveform
variable comparative accuracy89,94-98. Irrespective
of the reference technique chosen, understanding
trending reliability and response to sudden changes
in haemodynamic conditions in the clinical setting
is arguably of greater utility than precision and
accuracy of absolute values but to date has not been
adequately assessed10,99. Assuming an acceptable
level of performance is found to exist, demonstrating
efficacy is likely to depend more on the choice of
treatment goals and patient population than the
specific pulse contour analysis monitor100.
Stoke volume variation and pulse pressure variation
Changes in pleural pressure associated with
respiration alter the loading conditions of the right
and left ventricle and are the major determinant
of cyclical variations in stroke volume101. During
mechanical ventilation, initiation of a positive
pressure breath will transiently increase left
ventricular stroke volume as the pulmonary veins
are compressed increasing blood return to the left
side of the heart. Reduced right ventricular stroke
volume resulting from a decrease in the pressure
gradient for systemic venous return then leads to a
reduction in left ventricular stroke volume, albeit
with a lag of two to three heartbeats. The extent
of the variation over the course of the respiratory
cycle is inversely proportional to the mean systemic
filling pressure and is exaggerated by absolute or
relative hypovolaemia.
Pulse pressure, the difference between the systolic
and diastolic blood pressure during a single cardiac
cycle, is proportional to the left ventricular stroke
volume. Pulse pressure variation, defined as the
difference between the maximum and minimum
pulse pressure as a proportion of the mean over a
defined time period, is therefore also a measure
of stroke volume variation. Both pulse pressure
variation and stroke volume variation are measured
by pulse contour analysis in the PiCCO system.
Whether stroke volume variation measured using
area under the systolic pressure waveform curve is
more accurate in predicting volume responsiveness
over the more simple measures of pulse pressure
variation and systolic pressure variation is
uncertain81. Although systolic pressure variation,
pulse pressure variation and stroke volume variation
of >10 to 13% predict an increase in cardiac output
in response to fluid challenge, in clinical practice
the generalisability of these finding is limited as
they cannot be applied to those with spontaneous
ventilatory effort, low airway driving pressures102,
variable diastolic filling time due to arrhythmia, or
in open-chest conditions103. Furthermore, under
Anaesthesia and Intensive Care, Vol. 40, No. 3, May 2012
 The PiCCO monitor
normal physiological conditions the human cardio-
vascular system is in a volume-responsive state104,105.
A measurement that accurately predicts an increase
in cardiac output in response to a fluid challenge
provides no information on whether additional
fluid will be associated with benefit or harm.
Measurement of central venous oxygen saturation
Continuous monitoring of central venous oxygen
saturation (ScvO2) monitoring is available with
PiCCO2 through the addition of a CeVOX catheter.
The fibreoptic catheter is inserted through the distal
lumen of the central venous catheter with the tip
placed in the superior vena cava or right atrium.
ScvO2 is a surrogate marker of the overall balance
between oxygen delivery and consumption taking
into account only the upper body drained by the
superior vena cava. The relationship between
ScvO2 and the more established global measure of
mixed venous oxygen saturation (SVO2) may be
unpredictable during haemodynamic instability,
however the two trends appear to move in parallel106.
The potential utility of ScvO2 monitoring arises
from the theory that occult tissue hypoxia may persist
despite the restoration of arterial pressure and
adequate venous filling107. As part of an algorithm of
early and quantitative resuscitation, ScvO2-directed
therapy was found to be associated with a significant
mortality benefit in a single-centre study of severe
sepsis108 and is a recommendation of the Surviving
Sepsis Guidelines71. The role of ScvO2 measurement
in the critically ill is still uncertain. Localised
imbalance in oxygen utilisation may still exist without
an apparent global abnormality and monitoring
lactate clearance may provide a viable systemic
alternative without the need for more invasive
monitoring109. Furthermore, both high and low ScvO2
may be associated with worse outcome, complicating
interpretation110.
CONCLUSION
There is considerable variation in the utilisation
of advanced haemodynamic monitoring devices
resulting from the lack of definitive efficacy data to
support their use. The choice of monitor requires
an understanding of its underlying physiological
basis, risks associated with insertion and ongoing
use, and the range and validity of the data provided.
These factors must be considered within the clinical
circumstances of proposed use and should take into
account the extent to which the data will be directly
relied upon to guide therapeutic decision-making
Anaesthesia and Intensive Care, Vol. 40, No. 3, May 2012
405
as well as the potential implications of those
decisions.
The requirement for intra-arterial and central
venous catheterisation limits the use of PiCCO to
those with evolving critical illness or at high risk of
complex and severe haemodynamic derangement,
however these are also the patients most likely to
benefit from advanced haemodynamic monitoring.
Although the PiCCO monitor has been available
for over 10 years and numerous comparative
studies have been published, the validity and utility
of some of its parameters remains to be established
in the settings of its intended use.
The greatest potential advantage of PiCCO in
comparison to many other cardiac output monitors
is in its ability to measure and integrate a wide
array of haemodynamic data. Given the potential
for harm from many of the interventions initiated
on the basis of the results of advanced haemo-
dynamic measurements, conclusive studies designed
to demonstrate efficacy are required. In the case
of PiCCO, benefit is most likely to results when
definitive studies provide validated parameters
in the population of interest that can then be
integrated into clinical decision-making. Continued
technological advances and increased understanding
of the appropriate methods with which to compare
monitors coupled with evaluation of clinically
important endpoints will lead to a greater strength
in the evidence base for device selection in the
coming years.
ACKNOWLEDGEMENT
The authors would like to thank the Medical
Illustration Department at Royal Perth Hospital
for their help in preparing this manuscript and
Dr Andy Chapman for his review of the manuscript.
References
  1. Ganz W, Donoso R, Marcus HS, Forrester JS, Swan HJ. A new
technique for measurement of cardiac output by thermodilu-
tion in man. Am J Cardiol 1971; 27:392-396.
  2. Koo KKY, Sun JCJ, Zhou Q, Guyatt G, Cook DJ, Walter SD
et al. Pulmonary artery catheters: evolving rates and reasons
for use. Crit Care Med 2011; 39:1613-1618.
  3. Cowie BS. Does the pulmonary artery catheter still have a role
in the perioperative period? Anaesth Intensive Care 2011;
39:345-355.
  4. Stevens K, McCabe C, Jones C, Ashcroft J, Harvey S, Rowan
K. The incremental cost effectiveness of withdrawing pulmo-
nary artery catheters from routine use in critical care. Appl
Health Econ Health Policy 2005; 4:257-264.
  5. Balk E. For the Agency for Healthcare Research and Quality:
Evaluation of the evidence on benefits and harms of pulmo-
nary artery catheter use in the critical care setting. Technology
Assessment 2008; 28:17-19.
406 E. Litton, M. Morgan
 6. Harvey S, Harrison DA, Singer M, Ashcroft J, Jones CM,
Elbourne D et al. Assessment of the clinical effectiveness
of pulmonary artery catheters in management of patients in
intensive care (PAC-Man): a randomised controlled trial.
Lancet 2005; 366:472-477.
  7. Sandham JD, Hull RD, Brant RF, Knox L, Pineo GF, Doig CJ
et al. A randomized, controlled trial of the use of pulmonary-
artery catheters in high-risk surgical patients. N Engl J Med
2003; 348:5-14.
  8. Critchley LA, Lee A, Ho AM-H. A critical review of the ability
of continuous cardiac output monitors to measure trends in
cardiac output. Anesth Analg 2010; 111:1180-1192.
  9. Cecconi M, Rhodes A, Poloniecki J, Della RG, Grounds RM.
Bench-to-bedside review: the importance of the precision of
the reference technique in method comparison studies--with
specific reference to the measurement of cardiac output. Crit
Care 2009; 13:201.
10. Myles PS, Cui J. Using the Bland-Altman method to meas-
ure agreement with repeated measures. Br J Anaesth 2007;
99:309-311.
11. Squara P, Cecconi M, Rhodes A, Singer M, Chiche J-D.
Tracking changes in cardiac output: methodological considera-
tions for the validation of monitoring devices. Intensive Care
Med 2009; 35:1801-1808.
12. Vincent J-L, Rhodes A, Perel A, Martin GS, Della RG, Vallet
B et al. Clinical review: update on hemodynamic monitoring –
a consensus of 16. Crit Care 2011; 15:229.
13. Chakravarthy M, Patil TA, Jayaprakash K, Kalligudd P,
Prabhakumar D, Jawali V. Comparison of simultaneous esti-
mation of cardiac output by four techniques in patients under-
going off-pump coronary artery bypass surgery – a prospective
observational study. Ann Card Anaesth 2007; 10:121-126.
14. Costa MG, Della RG, Chiarandini P, Mattelig S, Pompei L,
Barriga MS et al. Continuous and intermittent cardiac output
measurement in hyperdynamic conditions: pulmonary artery
catheter vs. lithium dilution technique. Intensive Care Med
2008; 34:257-263.
15. Stetz CW, Miller RG, Kelly GE, Raffin TA. Reliability of the
thermodilution method in the determination of cardiac output
in clinical practice. Am Rev Respir Dis 1982; 126:1001-1004.
16. Compton FD, Zukunft B, Hoffmann C, Zidek W, Schaefer
J-H. Performance of a minimally invasive uncalibrated cardiac
output monitoring system (Flotrac/Vigileo) in haemodynami-
cally unstable patients. Br J Anaesth 2008; 100:451-456.
17. Nilsson LB, Eldrup N, Berthelsen PG. Lack of agreement
between thermodilution and carbon dioxide-rebreathing car-
diac output. Acta Anaesthesiol Scand 2001; 45:680-685.
18. de Waal EEC, Konings MK, Kalkman CJ, Buhre WF.
Assessment of stroke volume index with three different bio-
impedance algorithms: lack of agreement compared to ther-
modilution. Intensive Care Med 2008; 34:735-739.
19. Wakeling HG, McFall MR, Jenkins CS, Woods WGA,
Miles WFA, Barclay GR et al. Intraoperative oesophageal
Doppler guided fluid management shortens postoperative
hospital stay after major bowel surgery. Br J Anaesth 2005;
95:634-642.
20. Phan TD, Kluger R, Wan C, Wong D, Padayachee A. A com-
parison of three minimally invasive cardiac output devices with
thermodilution in elective cardiac surgery. Anaesth Intensive
Care 2011; 39:1014-1021.
21. Critchley LA, Critchley JA. A meta-analysis of studies using
bias and precision statistics to compare cardiac output
measurement techniques. J Clin Monit Comput 1999; 15:85-
91.
22. Boyle M, Steel L, Flynn GM, Murgo M, Nicholson L, O’Brien
M et al. Assessment of the clinical utility of an ultrasonic
monitor of cardiac output (the USCOM) and agreement with
thermodilution measurement. Crit Care Resusc 2009; 11:198-
203.
23. Feinberg MS, Hopkins WE, Davila-Roman VG, Barzilai B.
Multiplane transesophageal echocardiographic doppler imag-
ing accurately determines cardiac output measurements in
critically ill patients. Chest 1995; 107:769-773.
24. Pulsion Medical Systems, PiCCO2 Technical Datasheet ref:
MPI850305_R05. 2011.
25. Edwards. From http://www.Edwards.com/EV1000. Accessed
December 2011.
26. Belda FJ, Aguilar G, Teboul JL, Pestana D, Redondo FJ,
Malbrain M et al. Complications related to less-invasive
haemodynamic monitoring. Br J Anaesth 2011; 106:482-486.
27. Mayer J, Boldt J, Mengistu AM, Rohm KD, Suttner S. Goal-
directed intraoperative therapy based on autocalibrated arte-
rial pressure waveform analysis reduces hospital stay in high-
risk surgical patients: a randomized, controlled trial. Crit Care
2010; 14:R18.
28. de Wilde RBP, Schreuder JJ, van den Berg PCM, Jansen JRC.
An evaluation of cardiac output by five arterial pulse contour
techniques during cardiac surgery. Anaesthesia 2007; 62:760-
768.
29. Haller M, Zollner C, Briegel J, Forst H. Evaluation of a new
continuous thermodilution cardiac output monitor in critically
ill patients: a prospective criterion standard study. Crit Care
Med 1995; 23:860-866.
30. Galluccio ST, Chapman MJ, Finnis ME. Femoral-radial
arterial pressure gradients in critically ill patients. Crit Care
Resusc 2009; 11:34-38.
31. Schmidt S, Westhoff TH, Hofmann C, Schaefer J-H, Zidek
W, Compton F et al. Effect of the venous catheter site on
transpulmonary thermodilution measurement variables. Crit
Care Med 2007; 35:783-786.
32. Schramm S, Albrecht E, Frascarolo P, Chassot P-G, Spahn
DR. Validity of an arterial pressure waveform analysis device:
does the puncture site play a role in the agreement with inter-
mittent pulmonary artery catheter thermodilution measure-
ments? J Cardiothorac Vasc Anesth 2010; 24:250-256.
33. Renner LE, Morton MJ, Sakuma GY. Indicator amount, tem-
perature, and intrinsic cardiac output affect thermodilution
cardiac output accuracy and reproducibility. Crit Care Med
1993; 21:586-597.
34. Bendjelid K. When to recalibrate the PiCCO? From a physi-
ological point of view, the answer is simple. Acta Anaesthesiol
Scand 2009; 53:689-690.
35. Feldman JM. Is it a bird? Is it a plane? The role of patient
monitors in medical decision making. Anesth Analg 2009;
108:707-710.
36. Goepfert MSG, Reuter DA, Akyol D, Lamm P, Kilger E,
Goetz AE. Goal-directed fluid management reduces vaso-
pressor and catecholamine use in cardiac surgery patients.
Intensive Care Med 2007; 33:96-103.
37. Funk DJ, Moretti EW, Gan TJ. Minimally invasive cardiac
output monitoring in the perioperative setting. Anesth Analg
2009; 108:887-897.
38. Stewart GN. Researches on the circulation time and on the
influences which affect it. J Physiol 1897; 22:159-183.
39. Otto F. Die Grundform des arteriellen Pulses. Zeitung Fur
Biologie 1899; 37:483-586.
40. Hamilton W. Simultaneous determination of the pulmonary
and systemic circulation times in man and of a figure related
to the cardiac output. Am J Physiol 1928; 84:338-344.
Anaesthesia and Intensive Care, Vol. 40, No. 3, May 2012
 The PiCCO monitor
41. Reuter DA, Huang C, Edrich T, Shernan SK, Eltzschig HK.
Cardiac output monitoring using indicator-dilution tech-
niques: basics, limits, and perspectives. Anesth Analg 2010;
110:799-811.
42. Heerdt PM, Blessios GA, Beach ML, Hogue CW. Flow
dependency of error in thermodilution measurement of cardi-
ac output during acute tricuspid regurgitation. J Cardiothorac
Vasc Anesth 2001; 15:183-187.
43. Sami A, Sami A, Rochdil N, Hatem K, Salah BL. PiCCO
monitoring accuracy in low body temperature. Am J Emerg
Med 2007; 25:845-846.
44. Stevens JH, Raffin TA, Mihm FG, Rosenthal MH, Stetz CW.
Thermodilution cardiac output measurement. Effects of the res-
piratory cycle on its reproducibility. JAMA 1985; 253:2240-2242.
45. Bock J, Deuflhard P, Hoeft A, Korb H, Wolpers HG,
Steinmann J et al. Thermal recovery after passage of the pul-
monary circulation assessed by deconvolution. J Appl Physiol
1988; 64:1210-1216.
46. Baulig W, Schuett P, Goedje O, Schmid ER. Accuracy of a
novel approach to measuring arterial thermodilution car-
diac output during intra-aortic counterpulsation. J Clin Monit
Comput 2007; 21:147-153.
47. Wheeler AP, Bernard GR, Thompson BT, Schoenfeld D,
Wiedemann HP, deBoisblanc B et al. Pulmonary-artery ver-
sus central venous catheter to guide treatment of acute lung
injury. N Engl J Med 2006; 354:2213-2224.
48. Effros RM. Lung water measurements with the mean transit
time approach. J Appl Physiol 1985; 59:673-683.
49. Stelfox HT, Ahmed SB, Ribeiro RA, Gettings EM, Pomerantsev
E, Schmidt U. Hemodynamic monitoring in obese patients:
the impact of body mass index on cardiac output and stroke
volume. Crit Care Med 2006; 34:1243-1246.
50. McLuckie A, Murdoch IA, Marsh MJ, Anderson D. A com-
parison of pulmonary and femoral artery thermodilution car-
diac indices in paediatric intensive care patients. Acta Paediatr
1996; 85:336-338.
51. Linton RA, Jonas MM, Tibby SM, Murdoch IA, O’Brien TK,
Linton NW et al. Cardiac output measured by lithium dilution
and transpulmonary thermodilution in patients in a paediatric
intensive care unit. Intensive Care Med 2000; 26:1507-1511.
52. Schiffmann H, Erdlenbruch B, Singer D, Singer S, Herting
E, Hoeft A et al. Assessment of cardiac output, intravascular
volume status, and extravascular lung water by transpulmo-
nary indicator dilution in critically ill neonates and infants. J
Cardiothorac Vasc Anesth 2002; 16:592-597.
53. Proulx F, Lemson J, Choker G, Tibby SM. Hemodynamic
monitoring by transpulmonary thermodilution and pulse con-
tour analysis in critically ill children. Pediatr Crit Care Med
2011; 12:459-466.
54. Lewis FR, Elings VB, Hill SL, Christensen JM. The measure-
ment of extravascular lung water by thermal-green dye indica-
tor dilution. Ann N Y Acad Sci 1982; 384:394-410.
55. Lange NR, Schuster DP. The measurement of lung water. Crit
Care 1999; 3:R19-24.
56. Pearce ML, Yamashita J, Beazell J. Measurement of pulmo-
nary edema. Circ Res 1965; 16:482-488.
57. Mihm FG, Feeley TW, Jamieson SW. Thermal dye double
indicator dilution measurement of lung water in man: com-
parison with gravimetric measurements. Thorax 1987; 42:72-
76.
58. Sakka SG, Ruhl CC, Pfeiffer UJ, Beale R, McLuckie A,
Reinhart K et al. Assessment of cardiac preload and extravas-
cular lung water by single transpulmonary thermodilution.
Intensive Care Med 2000; 26:180-187.
Anaesthesia and Intensive Care, Vol. 40, No. 3, May 2012
407
59. Katzenelson R, Perel A, Berkenstadt H, Preisman S, Kogan
S, Sternik L et al. Accuracy of transpulmonary thermodilution
versus gravimetric measurement of extravascular lung water.
Crit Care Med 2004; 32:1550-1554.
60. Nirmalan M, Willard TM, Edwards DJ, Little RA, Dark
PM. Estimation of errors in determining intrathoracic blood
volume using the single transpulmonary thermal dilution tech-
nique in hypovolemic shock. Anesthesiology 2005; 103:805-
812.
61. Michard F, Schachtrupp A, Toens C. Factors influencing the
estimation of extravascular lung water by transpulmonary
thermodilution in critically ill patients. Crit Care Med 2005;
33:1243-1247.
62. Michard F. Bedside assessment of extravascular lung water
by dilution methods: temptations and pitfalls. Crit Care Med
2007; 35:1186-1192.
63. Monnet X, Anguel N, Osman D, Hamzaoui O, Richard C,
Teboul J-L. Assessing pulmonary permeability by transpulmo-
nary thermodilution allows differentiation of hydrostatic pul-
monary edema from ALI/ARDS. Intensive Care Med 2007;
33:448-453.
64. Sakka SG, Klein M, Reinhart K, Meier-Hellmann A.
Prognostic value of extravascular lung water in critically ill
patients. Chest 2002; 122:2080-2086.
65. Boyd JH, Forbes J, Nakada TA, Walley KR, Russell JA. Fluid
resuscitation in septic shock: a positive fluid balance and
elevated central venous pressure are associated with increased
mortality. Crit Care Med 2011; 39:259-265.
66. Wiedemann HP, Wheeler AP, Bernard GR, Thompson BT,
Hayden D, deBoisblanc B et al. Comparison of two fluid-
management strategies in acute lung injury. N Engl J Med
2006; 354:2564-2575.
67. Venkateswaran RV, Patchell VB, Wilson IC, Mascaro JG,
Thompson RD, Quinn DW et al. Early donor management
increases the retrieval rate of lungs for transplantation. Ann
Thorac Surg 2008; 85:278-286; discussion 286.
68. Perkins GD, McAuley DF, Thickett DR, Gao F. The beta-
agonist lung injury trial (BALTI): a randomized placebo-
controlled clinical trial. Am J Respir Crit Care Med 2006;
173:281-287.
69. von Spiegel T, Giannaris S, Wietasch GJK, Schroeder S,
Buhre W, Schorn B et al. Effects of dexamethasone on intra-
vascular and extravascular fluid balance in patients undergo-
ing coronary bypass surgery with cardiopulmonary bypass.
Anesthesiology 2002; 96:827-834.
70. Maitland K, Kiguli S, Opoka RO, Engoru C, Olupot-Olupot
P, Akech SO et al. Mortality after fluid bolus in African
children with severe infection. N Engl J Med 2011; 364:2483-
2495.
71. Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM,
Jaeschke R et al. Surviving Sepsis Campaign: international
guidelines for management of severe sepsis and septic shock:
2008. Crit Care Med 2008; 36:296-327.
72. Gelman S. Venous function and central venous pressure: a
physiologic story. Anesthesiology 2008; 108:735-748.
73. Osman D, Ridel C, Ray P, Monnet X, Anguel N, Richard C
et al. Cardiac filling pressures are not appropriate to predict
hemodynamic response to volume challenge. Crit Care Med
2007; 35:64-68.
74. Marik PE, Baram M, Vahid B. Does central venous pressure
predict fluid responsiveness? A systematic review of the litera-
ture and the tale of seven mares. Chest 2008; 134:172-178.
75. Kumar A, Anel R, Bunnell E, Habet K, Zanotti S, Marshall S
et al. Pulmonary artery occlusion pressure and central venous
pressure fail to predict ventricular filling volume, cardiac
performance, or the response to volume infusion in normal
subjects. Crit Care Med 2004; 32:691-699.
408 E. Litton, M. Morgan
76. Godje O, Peyerl M, Seebauer T, Lamm P, Mair H, Reichart B.
Central venous pressure, pulmonary capillary wedge pressure
and intrathoracic blood volumes as preload indicators in car-
diac surgery patients. Eur J Cardiothorac Surg 1998; 13:533-
539; discussion 539-540.
77. Muller L, Louart G, Bengler C, Fabbro-Peray P, Carr J, Ripart
J et al. The intrathoracic blood volume index as an indicator
of fluid responsiveness in critically ill patients with acute cir-
culatory failure: a comparison with central venous pressure.
Anesth Analg 2008; 107:607-613.
78. Reuse C, Vincent JL, Pinsky MR. Measurements of right ven-
tricular volumes during fluid challenge. Chest 1990; 98:1450-
1454.
79. Della RG, Costa MG, Pietropaoli P. How to measure and
interpret volumetric measures of preload. Curr Opin Crit
Care 2007; 13:297-302.
80. Breukers R-MBGE, de Wilde RBP, van den Berg PCM, Jansen
JRC, Faes TJC, Twisk JWR et al. Assessing fluid responses
after coronary surgery: role of mathematical coupling of
global end-diastolic volume to cardiac output measured by
transpulmonary thermodilution. Eur J Anaesthesiol 2009;
26:954-960.
81. Marik PE, Cavallazzi R, Vasu T, Hirani A. Dynamic changes in
arterial waveform derived variables and fluid responsiveness
in mechanically ventilated patients: a systematic review of the
literature. Crit Care Med 2009; 37:2642-2647.
82. Meybohm P, Gruenewald M, Renner J, Maracke M, Rossee S,
Hocker J et al. Assessment of left ventricular systolic function
during acute myocardial ischemia: a comparison of transpul-
monary thermodilution and transesophageal echocardiogra-
phy. Minerva Anestesiol 2011; 77:132-141.
83. Ritter S, Rudiger A, Maggiorini M. Transpulmonary ther-
modilution-derived cardiac function index identifies car-
diac dysfunction in acute heart failure and septic patients: an
observational study. Crit Care 2009; 13:R133.
84. Jabot J, Monnet X, Bouchra L, Chemla D, Richard C, Teboul
J-L. Cardiac function index provided by transpulmonary ther-
modilution behaves as an indicator of left ventricular systolic
function. Crit Care Med 2009; 37:2913-2918.
85. Wesseling KH, Jansen JR, Settels JJ, Schreuder JJ.
Computation of aortic flow from pressure in humans using a
nonlinear, three-element model. J Appl Physiol 1993; 74:2566-
2573.
86. Franchi F, Silvestri R, Cubattoli L, Taccone FS, Donadello
K, Romano SM et al. Comparison between an uncalibrated
pulse contour method and thermodilution technique for car-
diac output estimation in septic patients. Br J Anaesth 2011;
107:202-208.
87. Hashim B, Lerner AB. The FloTrac system – measurement of
stroke volume and the assessment of dynamic fluid loading.
Int Anesthesiol Clin 2010; 48:45-56.
88. De Backer D, Marx G, Tan A, Junker C, Van Nuffelen
M, Huter L et al. Arterial pressure-based cardiac output
monitoring: a multicenter validation of the third-generation
software in septic patients. Intensive Care Med 2011; 37:233-
240.
89. Monnet X, Anguel N, Naudin B, Jabot J, Richard C, Teboul
J-L. Arterial pressure-based cardiac output in septic patients:
different accuracy of pulse contour and uncalibrated pressure
waveform devices. Crit Care 2010; 14:R109.
90. Godje O, Hoke K, Goetz AE, Felbinger TW, Reuter DA,
Reichart B et al. Reliability of a new algorithm for continu-
ous cardiac output determination by pulse-contour analysis
during hemodynamic instability. Crit Care Med 2002; 30:52-
58.
91. de Wilde RBP, Breukers RBGE, van den Berg PCM, Jansen
JRC. Monitoring cardiac output using the femoral and radial
arterial pressure waveform. Anaesthesia 2006; 61:743-746.
92. Hamzaoui O, Monnet X, Richard C, Osman D, Chemla D,
Teboul J-L. Effects of changes in vascular tone on the agree-
ment between pulse contour and transpulmonary thermodi-
lution cardiac output measurements within an up to 6-hour
calibration-free period. Crit Care Med 2008; 36:434-440.
93. Gruenewald M, Meybohm P, Renner J, Broch O, Caliebe A,
Weiler N et al. Effect of norepinephrine dosage and calibra-
tion frequency on accuracy of pulse contour-derived cardiac
output. Crit Care 2011; 15:R22.
94. Goedje O, Hoeke K, Lichtwarck-Aschoff M, Faltchauser A,
Lamm P, Reichart B. Continuous cardiac output by femoral
arterial thermodilution calibrated pulse contour analysis:
comparison with pulmonary arterial thermodilution. Crit Care
Med 1999; 27:2407-2412.
95. Della Rocca G, Costa MG, Coccia C, Pompei L, Di Marco P,
Vilardi Vi et al. Cardiac output monitoring: aortic transpul-
monary thermodilution and pulse contour analysis agree with
standard thermodilution methods in patients undergoing lung
transplantation. Can J Anaesth 2003; 50:707-711.
96. Ostergaard M, Nielsen J, Rasmussen JP, Berthelsen PG.
Cardiac output – pulse contour analysis vs. pulmonary artery
thermodilution. Acta Anaesthesiol Scand 2006; 50:1044-1049.
97. Rodig G, Prasser C, Keyl C, Liebold A, Hobbhahn J.
Continuous cardiac output measurement: pulse contour analy-
sis vs thermodilution technique in cardiac surgical patients. Br
J Anaesth 1999; 82:525-530.
98. Muller L, Candela D, Nyonzyma L, Mattatia L, Suehs C,
Fabbro-Peray P et al. Disagreement between pulse contour
analysis and transpulmonary thermodilution for cardiac out-
put monitoring after routine therapeutic interventions in ICU
patients with acute circulatory failure. Eur J Anaesthesiol
2011; 28:664-669.
99. Critchley LAH. Pulse contour analysis: is it able to reliably
detect changes in cardiac output in the haemodynamically
unstable patient? Crit Care 2011; 15:106.
100. Uchino S, Bellomo R, Morimatsu H, Sugihara M, French C,
Stephens D et al. Pulmonary artery catheter versus pulse con-
tour analysis: a prospective epidemiological study. Crit Care
2006; 10:R174.
101. Magder S. Clinical usefulness of respiratory variations in arte-
rial pressure. Am J Respir Crit Care Med 2004; 169:151-155.
102. Muller L, Louart G, Bousquet P-J, Candela D, Zoric L, de
La Coussaye J-E et al. The influence of the airway driving
pressure on pulsed pressure variation as a predictor of fluid
responsiveness. Intensive Care Med 2010; 36:496-503.
103. de Waal EEC, Rex S, Kruitwagen CLJJ, Kalkman CJ, Buhre
WF. Dynamic preload indicators fail to predict fluid respon-
siveness in open-chest conditions. Crit Care Med 2009; 37:510-
515.
104. Robotham JL, Lixfeld W, Holland L, MacGregor D, Bryan
AC, Rabson J. Effects of respiration on cardiac performance.
J Appl Physiol 1978; 44:703-709.
105. Cournand A, Motley HL. Physiological studies of the effects
of intermittent positive pressure breathing on cardiac output
in man. Am J Physiol 1948; 152:162-174.
106. Marx G, Reinhart K. Venous oximetry. Curr Opin Crit Care
2006; 12:263-268.
107. Rady MY, Rivers EP, Nowak RM. Resuscitation of the
critically ill in the ED: responses of blood pressure, heart rate,
shock index, central venous oxygen saturation, and lactate.
Am J Emerg Med 1996; 14:218-225.
Anaesthesia and Intensive Care, Vol. 40, No. 3, May 2012