CLINICAL MEASUREMENT

Cardiac output
measurement

Learning objectives
After reading this article, you should be able to:
C
understand the relationship between cardiac output, stroke
volume, heart rate and arterial pressure
C
describe how estimates of cardiac output are derived from
other measured variables
C
outline additional information derived from each measurement
technique

Michael Gilbert

Abstract
Cardiac output measurement is used to guide uid and inotropic drug
therapy. Techniques employ modelling of the circulation to derive estimates of cardiac output from readily measured variables, including
thermodilution, analysis of arterial pressure waveforms, Doppler measurements of blood ow velocity, and electrical bioimpedance.

exponential pressure decline to an asymptote, during the prolonged diastole after a premature ventricular complex.3

Keywords Bioimpedance; cardiac output; oesophageal Doppler;

Measurement techniques

pulse contour analysis; thermodilution

The circulation is a complex system of branching vessels with

variable flow velocity, calibre and compliance, so pressure and
flow vary across measurement sites. Blood flow measurement
creates challenges, because of difficulty siting instruments in or
near blood vessels of interest. The relationships between arterial
pressure, blood flow, vascular resistance and vessel dimensions
are determined by Ohms Law and the Hagen-Poiseuille Law of
laminar flow. Haemodynamic monitors measure a spectrum of
variables, including arterial pressure, blood velocity, indicator
dilution, or electrical impedance to estimate cardiac output, and
other values reflecting haemodynamic status.

Royal College of Anaesthetists CPD Matrix: 1A03, 2A04

Cardiac output is the product of ventricular stroke volume and

heart rate, and estimates of it are used to guide fluid and
inotropic therapy in intraoperative and critical care settings, in an
attempt to improve clinical outcomes.

The pressureeow relationship

When the stroke volume is ejected from either the left or right
ventricle, pressure is generated in the aorta and pulmonary arteries by a combination volume change and the propagation and
reflection of waves generated by the energy of ejection. Arterial
pressure is the sum of these effects (Figure 1).

Measurement of indicator dilution

Indicator dilution employs the principle that a known volume
(V0) and concentration (C0) of an indicator is injected into the
circulation, diluting the indicator within a volume of distribution (V1). The indicator concentration (C1) is detected at a
remote site, where it initially increases and then decreases in a
non-stepwise manner. If V1 C0  V0/C1 and cardiac output (Q)
V1/t, then cardiac output is inversely related to the area under
the concentrationetime curve (Figure 2a).

Volume change: the great vessels are compliant, so during systole, more blood is ejected into them than actually leaves. In
diastole, they passively empty into smaller arteries, and return to
their original calibre, at a rate determined by arterial compliance
and vascular resistance.1 The volume of blood entering a vessel
or cardiac chamber must equal the volume of blood leaving,
during each cardiac cycle, or distension would occur. Stroke
volume therefore consists of systolic and diastolic components,
preventing systolic pressure overshoot during rapid ejection, and
allowing for it to be delivered to the arteries throughout the
cardiac cycle.2 Aortic pressure peaks during systole and declines
exponentially during diastole, determined by a time constant t.

Thermodilution uses the concept of a thermal indicator, where

cold crystalloid solution injected into the circulation produces a
blood temperature change at the measurement site.4,5 Cardiac
output is inversely proportional to the area under the blood
temperature changeetime curve.
The pulmonary artery catheter was developed as the route by
which boluses of cold crystalloid solution could be injected into
the right atrium, with proximal and distal thermistors to detect
injectate temperature and blood temperature in the pulmonary
artery. The catheter is inserted via a central vein and is floated
into the pulmonary artery using a small inflatable balloon on the
catheter tip. As the temperature change is measured across the
right ventricle, this technique estimates right ventricular stroke
volume.

Wave generation: the energy of stroke volume ejection generates compression and decompression waves in the arterial system, which rapidly propagate and are reflected at points of
branching and calibre change. Waves propagating through the
arterial system are the result of successive ventricular ejections,
rather than harmonic oscillation. This is demonstrated by the

Continuous cardiac output (CCO) monitors use an element in

the proximal part of the catheter to intermittently heat the surrounding blood, as it passes through the right atrium. The temperature change is much smaller than with cold crystalloid

Michael Gilbert MB ChB FRCA is a Consultant Cardiothoracic

Anaesthetist at Morriston Hospital, Swansea, UK. Conicts of
interest: none.

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2016 Published by Elsevier Ltd.

Please cite this article in press as: Gilbert M, Cardiac output measurement, Anaesthesia and intensive care medicine (2016), http://dx.doi.org/
10.1016/j.mpaic.2015.11.005

CLINICAL MEASUREMENT

lithium concentration with an ion-sensitive electrode attached to

a peripheral arterial line. Lithium recirculation limits the ability
to repeat measurements at short time intervals.

ECG, aortic and radial artery pressure and

bioimpedance waveforms

Additional clinical data derived from indicator dilution

measurement
Global end-diastolic volume (GEDV) is a reflection of the adequacy of preload. It represents end-diastolic volume of all cardiac
chambers, and is calculated as the difference between ITTV and
PTV (Figure 2b). The normal range is 680e800 ml m2, which
is greater than the actual end-diastolic volume of the cardiac
chambers.
Extravascular lung water (EVLW) is a reflection of the severity
of pulmonary oedema. It is theoretically represented by the
volume of indicator sequestered in the lung during transit, and is
the difference between pulmonary thermal volume (PTV) and
pulmonary blood volume (PBV). Experimentally derived
formulae are used to calculate EVLW, which estimate the difference between ITTV and the sum of GEDV and PBV [Reuter,
Bendjelid]. One example is: EVLW (CO  MTTT)  (1.25 
GEDV).
There is controversy about EVLW and GEDV calculations.
Firstly, CO, MTTT and EDTT are all derived from the same
thermodilution curve, so any error in the detection of the indicator is multiplied. Secondly, there is conflict between the assumptions that the calculation of cardiac output should occur
with no loss of indicator while at the same time the calculation of
EVLW assumes that there is. Thirdly, GEDV is calculated from
cardiac output, assuming that they are invariably related, which
they are not.6

Pulse contour analysis

Early investigators discovered an empirical correlation between
central pulse pressure and stroke volume. Analysis of the peripheral arterial pressure waveform to derive estimates of stroke
volume and cardiac output necessitates accurate reproduction of
the central aortic pressure waveform and an estimation of arterial
resistance.
The time constant t of an exponential decay curve fitted to
the diastolic part of the central aortic pressure waveform provides a combined estimate of large vessel compliance (C) and
total arterial resistance (R) (Figure 1). To derive a value for
arterial resistance, compliance must be estimated. Current technology employs two main models:

Note systolic pressure augmentation and secondary, non-dicrotic peaks

caused by wave effects in the radial artery waveform. Ventricular
activation, Q, aortic valve opening, A, aortic valve closing, C, pulmonary valve opening, P, and mitral valve opening, M. LVET, left
ventricular ejection time; PEP, pre-ejection period. Bioimpedance, Z,
bioimpedance change, Z.

Figure 1

injection, making the measurement more prone to error from

thermal noise.

Windkessel model: so-called because the term was used by

Starling to describe the compliance chamber represented by the
distensible aorta (Figure 3a). This model attempts to fit the area
under the curve (AUC) of arterial waveforms measured over
several cardiac cycles to physiological models which predict the
central aortic pressure waveform. These approaches require
calibration against another method of CO measurement, such as
thermodilution or indicator dilution, to calculate a constant
which represents large vessel compliance. Derived values for
compliance and vascular resistance are then entered in a calculation of cardiac output, and subsequent changes in measured

Transpulmonary thermodilution (TPTD) employs temperature

measurement in a peripheral systemic artery (e.g. femoral artery)
following cold crystalloid injection into a central vein. This has
the advantage of not requiring catheterization of the pulmonary
artery. The indicator is diluted to a greater extent, producing a
smaller thermodilution curve. This technique estimates left
ventricular stroke volume.
Lithium dilution cardiac output (LiDCO) monitors employ the
injection of lithium into a central vein, and measurement of

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CLINICAL MEASUREMENT

Thermodilution curves
a
THERMODILUTION CURVE

ln T
EXTRAPOLATED DECLINE

MEAN TRANSIT TIME (MTTT)

EXP DECAY
TIME (EDTT)

b
INJECTION OF
COLD INDICATOR

RA

DETECTION OF INDICATOR
IN PULMONARY ARTERY

RV

PBV

TRANSPULMONARY
DETECTION OF INDICATOR

LA

LV

EVLW
(a) Upper graph: Temperature change plotted against time. Recirculation of the indicator causes the slope of
the curve to flatten out, diverging from the exponential decline. The dashed line shows extrapolation of the
curve to exclude the effect of recirculation.Lower graph: Semi-logarithmic plot of temperature change against
time, where extrapolation of the line of decline allows accurate calculation of the duration of indicator
detection. (b) Volume indices are calculations based on estimated cardiac output and specific time intervals
derived from the thermodilution curve: Intrathoracic thermal volume (ITTV) = CO MTTT. Pulmonary thermal
volume (PTV) = CO EDTT.

Figure 2

values are used to estimate cardiac output from the point of

calibration.7

of the data (Figure 3b). Stroke volume is given as the product of

sAP and the correction factor.8
There is a significant factor which confounds calculation of
stroke volume using the peripheral arterial waveform.
Forward-propagating and reflected waves distort the waveform
and, in particular, the exponential diastolic pressure decline.
These waves are also augmented by vasoconstriction and
blunted by vasodilatation, further distorting the waveform in
hypovolaemia and sepsis, precisely when the measurements are
most crucial.
Recent work on wave intensity analysis, has focussed on
modelling which separates reservoir (Windkessel) pressure, the

Empirical approach: this technique does not attempt to fit AUC

data to a physiological model, but works from the assumption
that stroke volume is related to the standard deviation of
measured arterial pressure data (sAP), which is proportional to
pulse pressure. This echoes the earliest techniques of estimating
stroke volume, but inaccuracies of the original assumption are
now corrected for by the application of a conversion factor. A
multivariate polynomial equation is used to calculate the conversion factor, including variables such as skewness and kurtosis

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CLINICAL MEASUREMENT

Figure 3 (a) Hydrodynamic and electrical models of the systemic circulation, showing the Windkessel (WK) representing the compliant large arteries and the parallel resistances of the branching peripheral arterial system (R), represented in the electrical models as capacitance and resistance respectively. The two-, three- and four-component models are renements which better describe ow and pressure changes in the
ascending aorta and the peripheral arteries. Reproduced under Creative Commons Licence from Westerhof N, Lankhaar J-W, Westerhof BE.7 (b)
Effect of vascular resistance: increased leftward skewness of pressure data is related to increased vascular resistance or vasoconstriction. (c)
Effect of large vessel compliance: increased kurtosis (broadness) indicates decreased aortic compliance.

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CLINICAL MEASUREMENT

Oesophageal Doppler waveform

The figure shows the measurement variables, peak blood flow velocity, velocity time integral, ejection time, interpeak
time.

Figure 4

component of arterial pressure related to volume change in the

aorta, from wave pressure, the component resulting from
augmentation and attenuation by these waves.3,9 The accurate
reproduction of the central aortic pressure waveform would
allow for more accurate calculation of systolic and pulse pressures, and the time constant of the exponential diastolic pressure
decline.

of insonation, which is the angle between the axis of the Doppler

beam and the axis of blood flow. At an angle of <20 the Doppler
shift is only reduced by 6% and can be corrected for, but at
angles beyond 20 , the calculation of velocity becomes increasingly inaccurate. At 90 (i.e. with the beam perpendicular to the
axis of blood flow) no Doppler shift is detected.
Cross-sectional area of the aorta is either measured using Mmode ultrasound, or is estimated using a nomogram.

Doppler measurement of velocity

Descending aortic blood velocity is measured by a probe in the
oesophagus, which emits a 4e5 Hz pulsed or continuous Doppler
signal at a shallow angle to the aorta. Ultrasound travels at a
speed of 1540 m s1 in blood, and is reflected by cellular components moving away from the ultrasound emitter. Rarefaction
of the reflected wave increases wavelength, lowering its frequency, which is measured by the probe (Figure 4).

Stroke volume (SV) is calculated by multiplying the crosssectional area by the integral of the blood velocity e ejection
time curve. Cardiac output is calculated as the product of SV and
heart rate, which is calculated using the time between adjacent
velocity peaks.

Additional clinical data derived from Doppler

measurement

Blood flow velocity is calculated using the Doppler equation,

which is proportional to the difference between the frequencies
of emitted and reflected waves. Two Doppler shifts occur, first
when ultrasound travels between the source and the blood, and a
second when the ultrasound is reflected back to the source. The
velocity calculation should only take account of the Doppler shift
of the reflected wave, so the total frequency change is halved.
The velocity calculation includes a correction factor for the angle

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Mean acceleration (MA) is the mean slope of the ascent of the

velocityetime curve. It is an indicator of contractility. Unlike
peak velocity, it is independent of afterload, so it is reproducible
independent of vascular tone.
Corrected flow time (CFT) is an indicator of preload. It is
calculated by indexing the duration of ejection against normal

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CLINICAL MEASUREMENT

A bioimpedance model of the thorax

THORACIC CROSS SECTIONAL AREA, A T

AORTIC CROSS SECTIONAL AREA, A A

THORACIC LENGTH, L

The blood within aorta and great vessels are represented by the inner cylinder, with impedance (B)
and cross-sectional area (AA). The thorax is represented by the by the outer cylinder, with impedance
(T) and cross-sectional area (AT).

Figure 5

heart rate of 60 beats min1. CFT <450 ms indicates that the

ventricular ejection ends prematurely, a marker of
hypovolaemia.

bioimpedance (DZ) during ventricular ejection (LVET) is proportional to left ventricular stroke volume.10 This is represented
by the DZ peak between aortic valve opening and closing
(Figure 1).
The calculation of stroke volume, requires estimation of the
contribution to conductivity from the different blood components, as these exhibit different impedances. Haematocrit, electrolyte concentrations, age, sex and weight are used as correction
factors in this calculation.

Bioimpedance
The human body is able to conduct electrical current because of
the presence of charged ions within blood and interstitial fluid.
Impedance (Z), a measure of resistance in alternating current
circuits, cannot be directly measured. In the presence of constant
current, bioimpedance is calculated by measurement of voltage,
using Ohms law. Current passes differentially through the body
along high impedance and low impedance pathways. The lowest
impedances are in blood (150 U cm1) and plasma (63 U cm1),
while the highest are in air (1275 U cm1) and cardiac muscle
(750 U cm1).
Thoracic bioimpedance systems apply low-amperage alternating current of 1.4e1.8 mA, at a frequency of 30e75 Hz between electrodes applied to the base of the neck (thoracic inlet)
and the costal margin (thoracic outlet). Thoracic baseline
impedance (Z0) is inversely proportional to the total currentconducting fluid content of the thorax (TFC). The individual
contributions to conductivity (the inverse of impedance) of the
intravascular, interstitial and alveolar fluids cannot be separated,
so the thorax is modelled as two concentric cylinders. The inner
cylinder represents the low impedance of blood and the outer
cylinder represents the high impedance components of the rest of
the thorax (Figure 5).
The blood volume of the thorax increases transiently during
systole, increasing the volume of the low impedance conduit,
relative to the rest of the thorax. The volume within venous
capacitance vessels and the pulmonary microcirculation varies
only slightly with respiration, so this change is mainly due to the
increase in the aorta and pulmonary arteries. The change in

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Additional clinical data derived from bioimpedance

measurement
Systolic time ratio is the ratio between the durations of electrical
and mechanical systole. Pre-ejection period (PEP) represents the
time between the beginning of electrical activation of the
ventricle (q-wave on ECG) and the beginning of ventricular
ejection, or mechanical systole (LVET). This ratio increases in
cardiac failure.
Velocity index is an indicator of the peak velocity of blood in the
aorta. This is affected by both myocardial contractility and
afterload, and can remain in the normal range even as myocardial contractility decreases.
Acceleration index represents the acceleration of blood into the
aorta in the first 10e20 ms of ventricular ejection, and is calculated from the steep ascent on the DZ-time waveform. It is an
indicator of myocardial contractility, with higher values indicating increased contractility.
A
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10.1016/j.mpaic.2015.11.005

CLINICAL MEASUREMENT

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