How to measure and interpret volumetric measures of preload

Giorgio Della Rocca, Maria Gabriella Costa and Paolo Pietropaoli

Purpose of review Introduction

To update the situation over the past few years on the Restoration and maintenance of adequate circulating
clinical application of volumetric measures of preload blood volume are an essential goal in the proper manage-
in critically ill patients. ment of the critically ill patient [1,2]. Inadequate cardiac
Recent findings output and reduced organ perfusion may lead to multi-
Cardiac filling pressures monitoring is unreliable for organ dysfunction. According to the Frank–Starling
assessing cardiac preload in mechanically ventilated mechanism, cardiac preload is a major determinant of
critically ill patients. The transpulmonary dilution indicator cardiac performance.
technique was shown to better identify preload than
pulmonary arterial catheterization. Measuring static preload Transpulmonary double indicator dilution
index as intrathoracic blood volume or global end diastolic technique
volume provides a good preload index, either in Following discussion about pulmonary artery catheter
experimental or in different clinical settings. (PAC) utility, efficacy, either to guide fluid and drug
Summary therapy or to improve critically ill patients’ outcomes,
Volumetric measures of preload are good preload indexes. and invasiveness, there has been recent interest in less
These data are to be interpreted together with the clinical invasive alternatives – catheter-related, bedside-device
patient’s condition, conventional hemodynamic data and volume estimates, using thermodilution [3–6]. The
the course of illness in critically ill patients. In order to original transpulmonary indicator dilution (TPID) tech-
evaluate whether the application of a predefined therapy nique introduced is the double indicator dilution
algorithm based on volumetric monitoring can improve approach, which is based on two indicators injected
patients’ outcome, more studies are needed. simultaneously: a plasma-bound indicator (indocyanine
green dye) and a freely diffusible indicator (COLD
Keywords System, Pulsion Medical System, Munich, Germany)
critical illness, global end diastolic volume, hemodynamic [7,8]. The determination of flow and volume by this
monitoring, intrathoracic blood volume, preload method is based on the simultaneous application of the
two indicators: one that is diffusable into the extra-
Curr Opin Crit Care 13:297–302. ß 2007 Lippincott Williams & Wilkins. vascular pulmonary tissue compartments (temperature)
Department of Anesthesia and Intensive Care Medicine, University of Udine, Udine,
and the other that is not diffusible (dye).
Italy
Correspondence to Giorgio Della Rocca, MD, C.so Trieste 169/A, 00198 Rome, The accuracy of intrathoracic blood volume (ITBV) as a
Italy measure of preload has been prospectively assessed by
Tel: +39 0432 559500 1; fax: +39 0432 545526;
e-mail: giorgio.dellarocca@uniud.it Lichtwark-Aschoff et al. [7] in a group of ventilated
patients with acute respiratory failure. This study demon-
Current Opinion in Critical Care 2007, 13:297–302
strated a much tighter correlation between changes in
Abbreviations ITBV index (ITBVI) and cardiac index (CI) than between
CEDVI continuous end diastolic volume index changes in either central venous pressure (CVP) or pul-
CVP central venous pressure
EVLW extravascular lung water
monary artery occlusion pressure (PAOP) and cardiac
GEDV global end-diastolic volume index. The same investigators’ group, in an experimental
GEDVI global end-diastolic volume index
ITBV intrathoracic blood volume
study, tested the effects of an infusion of dobutamine
ITBVI intrathoracic blood volume index under normovolemia and hypovolemia. Under these
LVEDAI left ventricular end diastolic area index
PAC pulmonary artery catheter
experimental conditions, neither CVP, PAOP nor right
PAOP pulmonary artery occlusion pressure ventricular end diastolic volume (RVEDV) reliably indi-
SVI stroke volume index
TPID transpulmonary indicator dilution
cated changes in circulating blood volume, nor were they
linearly and tightly correlated with the resulting changes
ß 2007 Lippincott Williams & Wilkins
in stroke volume index (SVI) [8]. ITBV reflected both
1070-5295 changes in volume status and the resulting alteration in
cardiac output (Table 1, [9–26]).

Gödje et al. [9] compared filling pressures with ITBV and

global end-diastolic volume (GEDV) in 30 patients after
297

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 298 Cardiopulmonary monitoring

coronary artery by-pass grafting (CABG). The linear
regression analysis was computed between changes in
preload-dependent left ventricular SVI and cardiac index
and the corresponding, presumably preload-indicating,
parameters CVP, PAOP, ITBV and GEDV. No corre-
lation was found between DCVP compared with DSVI
(r ¼ 0.09) or DCI (r ¼ 0.00), and DPAOP compared with
DSVI (r ¼ 0.02) or DCI (r ¼ 0.01). DITBVI correlated
well with DSVI and DCI: coefficients were 0.76 and 0.83,
respectively. Correlation coefficients of DGEDVI
(GEDV index) compared with DSVI/DCI were 0.82
and 0.87, respectively. Gödje and co-workers [11] per-
formed a study focused on preload in heart-transplanted
patients in whom ITBVI and GEDVI were significantly
correlated with changes in SVI (r ¼ 0.65 and r ¼ 73,
respectively), while CVP and PAOP failed (r ¼ 0.23
and r ¼ 0.06, respectively).
Sakka and colleagues [10], comparing each preload vari-
able (CVP, PAOP and ITBVI) under clinical routine
conditions, in the early phase of hemodynamic stabiliz-
ation of 57 critically ill patients with sepsis or septic
shock, found a significant correlation between ITBVI
and SVI, while CVP and PAOP did not correlate. The
authors, confirming results obtained by Lichtwarck-
Aschoff and co-workers under controlled conditions,
concluded that ITBVI is also a more reliable preload
indicator than cardiac filling pressures in critically ill
patients with sepsis or septic shock. Holm and colleagues
[15,27,28] observed that, using ITBV as an endpoint for
resuscitation, larger volumes of crystalloids were admi-
nistered than predicted by the Parkland formula but the
efficacy of burn resuscitation to fixed endpoints on sur-
vival and multiple organ failure have to be evaluated.
Schiffmann and co-workers [21] demonstrated that the
TPID technique enables the measurement of cardiac
output and intravascular volume status in critically ill
neonates and infants at the bedside, whereas CVP was
not indicative of changes in intravascular volume status.
Many authors [17,22,29] described their experience with
the TPID technique in cardiac surgical patients, both
intra and postoperatively. Other studies on the PiCCO
System were performed during neurosurgery [12], laparo-
scopic procedures [20] and major abdominal surgery [30]
and in critically ill patients [13,31]. In all these studies,
ITBV was confirmed as a better cardiac preload index
when compared with conventional pressure-derived
preload indicators (Table 1).

Table 1 Intrathoracic blood volume and global end-diastolic volume correlations compared with cardiac index or stroke volume index
Authors Year Setting Patients R

Gödje et al. [9] 1998 CABG 30 GEDVI vs SVI 0.82

Sakka et al. [10] 1999 ICU (sepsis, septic shock) 57 DITBVI vs DSVI 0.67
Godje et al. [11] 2000 Cardiac surgery 40 ITBVI vs SVI 0.65
GEDVI vs SVI 0.73
Buhre et al. [12] 2000 Sitting position Neurosurg 10 DITBVI vs DSVI 0.78
Bindels et al. [13] 2000 Critically ill patients 45 DITBVI vs DSVI 0.81
Sakka et al. [14] 2000 ICU (sepsis, septic shock) 57 ITBV ¼ 1.25 GEDV
ITBVItherm vs ITBVIdye 0.97

Holm et al. [15] 2000 Burn patients 24 ITBVI vs CI 0.45

Della Rocca et al. [16] 2001 Cirrhotic patients 56 ITBVI vs CI (PiCCO) 0.378

ITBVI vs CI (COLD) 0.453

Brock et al. [17] 2002 ICU postcardiac surgery 14 DITBVI vs DSVI 0.67

Della Rocca et al. [18] 2002 OLTx 60 ITBVI vs CI 0.47

ITBVI vs SVI 0.55

D1ITBVI vs D1SVI 0.60

D2ITBVI vs D2SVI 0.47

Della Rocca et al. [19] 2002 Lung tx 50 ITBVI vs SVI 0.41
Hofer et al. [20] 2002 Pneumoperitoneum 30 ITBVI vs SVI 0.79
Schiffmann et al. [21] 2002 Pediatric ICU 10 GEDVI vs SVI 0.76
ITBVI vs SVI 0.56
Reuter et al. [22] 2002 ICU postcardiac surgery 19 ITBVItherm vs ITBVIdye 0.94
DITBVItherm vs DITBVIdye 0.90
DITBVItherm vs DSVI 0.85
DITBVI dye vs DSVI 0.76
Michard et al. [23] 2003 Septic shock 36 DGEDVI vs DSVI 0.72
Kuntscher et al. [24] 2003 Burn patients 18 ITBVItherm vs ITBVIdye 0.77
ITBVI vs CI 0.74
DITBVI vs DCI 0.80

Neumann et al. [25] 2005 Postop major surgery SB patients 15 DGEDVI vs DSVI 0.34

Hofer et al. [26] 2005 CABG 20 GEDVI vs LVEDAI 0.658

CEDVI vs LVEDAI 0.161

DGEDVI vs DSVI 0.576
DCEDVI vs DSVI 0.267

Means r2. CABG, coronary artery bypass graft; CEDVI, continuous end diastolic volume index; CI, cardiac index; GEDVI, global end-diastolic volume
index; ICU, intensive care unit; ITBVI, intrathoracic blood volume index; LVEDAI, left ventricular end diastolic area index; OLTx, orthotopic liver
transplantation; SB, spontaneous breathing; SVI, stroke volume index.

Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

Although effective at the bedside due to the preparation
of the indocyanine green solution, the transpulmonary
double indicator dilution technique is relatively time-
consuming, cumbersome and expensive.
Transpulmonary single indicator dilution
technique: global end diastolic volume and
intrathoracic blood volume
To simplify and reduce the practicalities of monitor
application, research led to the development of a
device based on the transpulmonary thermodilution
technique with a single thermal indicator – the PiCCO
system (PiCCO System, Pulsion Medical System,
Munich, Germany). The PiCCO system requires the
placement of central venous and modified arterial
catheters with a thermistor embedded into the wall.
The system provides intermittent (transpulmonary
thermodilution-derived, cardiac output) and continu-
ous (‘pulse contour’-derived, PCCO) assessment of
cardiac output and estimations of intrathoracic volumes
[GEDV, ITBV and extravascular lung water (EVLW)].
Experimental and clinical data [14,32 –34] demon-
strated that single arterial thermodilution-derived
ITBV correlates well with the respective values
measured by the double indicator technique (Table 1).
The commercially available device currently using this
technology uses a linear equation with a coefficient of 1.25
and an intercept of 0 to estimate ITBV from measured
GEDV values:
ITBV ¼ 1.25  GEDV.
Della Rocca et al. [18] described their experience with
volumetric monitoring during anesthesia in patients
undergoing double lung transplantation. The main find-
ings of this study showed a fairly good correlation
between ITBVI and SVI (r2 ¼ 0.41, P < 0.0001), while
PAOP correlated poorly with SVI (r2 ¼ 0.01, not sig-
nificant). The same investigators [16,19] demonstrated
that ITBV better reflected preload in hyperdynamic
patients receiving liver transplantation as well (ITBVI
vs SVI, r2 ¼ 0.55).
Michard and co-workers [23] studied 36 patients with
septic shock-evaluated GEDV and preload indicator
after volume infusion and dobutamine infusion.
GEDV, CVP, SVI and cardiac index significantly
increased after volume loading and changes in GEDVI
were correlated with changes in SVI (r ¼ 0.72,
P < 0.001), while changes in CVP were not. Dobuta-
mine infusion induced an increase in SVI and cardiac
index but no significant changes in CVP and GEDVI.
The authors concluded that in patients with septic
shock, in contrast to CVP, the transpulmonary thermo-
dilution GEDVI behaves as an indicator of cardiac
preload.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Volumetric measures of preload Della Rocca et al. 299
Hofer and colleagues [26] compared volume preload
monitoring using two different thermodilution tech-
niques with left ventricular preload assessment by trans-
esophageal echocardiography (TEE). They studied 20
patients undergoing elective cardiac surgery with pre-
served left–right ventricular function after induction of
anesthesia. GEDVI, continuous end diastolic volume
index (CEDVI), left ventricular end diastolic area index
(LVEDAI) and SVI significantly increased after fluid
loading. The correlation coefficient for DGEDVI and
DSVI was stronger (r2 ¼ 0.576) than between DCEDVI
and DSVI (r2 ¼ 0.267). The authors concluded that
GEDVI assessed by the PiCCO system gives a better
reflection of echocardiographic changes in left ventricular
preload, in response to fluid replacement therapy, than
CEDVI measured by a modified PAC.
The same authors [35] studied the new volumetric ejection
fraction monitoring system (VoLEF) combined with the
PiCCO system for measurements of left and right heart
end-diastolic volume by thermodilution in 20 cardiac
surgical patients. In this study, both LVEDAI and GEDVI
significantly increased after fluid administration, while left
heart end-diastolic volume index (LHEDI) failed to cor-
relate. The authors concluded that only GEDVI can be
recommended as an estimate of left ventricular preload.
Neumann and colleagues [25] demonstrated that changes
in GEDV were also linearly correlated with changes in
cardiac index in spontaneously breathing patients.
Thirty-four per cent of the changes in cardiac index
are explained by changes in the GEDV.
Recently, Uchino and colleagues [36] conducted a
prospective multicenter, multinational study in a cohort
of 331 critically ill patients who received hemodynamic
monitoring by PAC or PiCCO, according to physician
preference, in intensive care units of eight hospitals in
four countries. Direct comparison showed that the use of
PiCCO was associated with a greater positive fluid bal-
ance and fewer ventilator-free days. After correcting for
confounding factors, the choice of monitoring did not
influence major outcomes, while a positive fluid balance
was a significant independent predictor of outcome.
Future studies may best be targeted to understand the
effect of pursuing different fluid balance regimens rather
than monitoring technique.
Lopez-Herce and colleagues [37] evaluated the response
to acute hypovolemia, rapid blood volume expansion and
epinephrine administration in an infant animal model.
Also in this study, ITBVI and GEDVI were more sensi-
tive to changes in blood volume than CVP or PAOP.
Some concerns need to be investigated further in the
burns population. Even though Holm and colleagues [15]
 300 Cardiopulmonary monitoring
have introduced ITBVI as a possible endpoint to guide
major burn fluid resuscitation, Kuntscher and co-workers
[24,38] found that the TPID technique performed with
the single indicator is not suitable to assess ITBV and
EVLW in burn shock, although the method is suitable for
assessing cardiac output and its derived parameters in
burn resuscitation.
How to interpret global end-diastolic volume and
intrathoracic blood volume
As ‘to monitor’ means ‘to warn’ (derived from the Latin
‘monere’), when we are talking about hemodynamic
monitoring, we want to identify a device that allows us
to recognize quickly the patient’s functional hemody-
namic status. Nowadays, it is possible to observe and
obtain a ‘single picture’ or a ‘movie’ of the hemodynamic
conditions, better known as the ‘static’ or ‘dynamic’
index, respectively.
The fact that the relationship between GEDV and ITBV
may be influenced by overall volume status and cardiac
output has been argued. Furthermore, compensatory
venous/arteriolar vasoconstriction in the pulmonary,
systemic and splanchnic circulations and the consequent
redistribution of blood from the peripheral compartments
to more central compartments may alter the numerical
relationship between GEDV and ITBV. In patients
receiving vasoconstrictors, it is possible to detect a rela-
tively ‘normal’ ITBV due to blood volume centralization
misleading a relative general hypovolemic status. Hemo-
dynamic monitoring should also be considered within the
context of the patient, pathophysiology and time point in
the disease process at which it is used. With volumetric
monitoring, and particularly with GEDV and ITBV
measurements, we can quantify a static preload index,
as demonstrated in different experimental and clinical
settings. A static preload index ‘per se’ can fail to identify
the global hemodynamic condition, particularly in cases
of critically ill patients receiving vasoconstrictors, or with
dilatative myocardiopathy, or in pump failure. It would
be better that with normal, low or high ITBV or GEDV
values, we have to identify whether the preload index is
‘adequate’ to the metabolic demand in the peculiar
hemodynamic condition. As blood flow varies to match
metabolic requirements, there is no one specific value of
cardiac output or oxygen delivery that can be defined as
‘normal’. Based on this concern, we have to identify in
which part of the Frank–Starling curve the patient’s heart
is working and then try to optimize cardiac output working
on preload, inotropism or afterload. Optimizing preload is a
challenge in critically ill patients avoiding fluid overload
with pulmonary edema. The PiCCO system allows us to
observe not only ‘one picture’ as cardiac preload (ITBV or
GEDV), but also an effective functional answer
(intermittent and continuous cardiac output) together with
a pulmonary edema quantification (EVLW).
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Volumetric measures limitations
As calculation of ITBV mathematically relies on cardiac
output, concerns have been raised as to the validity of
these measurements based on mathematical coupling of
data. No evidence of such a coupling was found, however, in
recent studies in which cardiac output was either decreased
by esmolol [39] or increased by dobutamine [40].
The TPID method is not suitable for patients with severe
peripheral vascular disease, those who undergo vascular
surgery, or those that have other contraindications for
femoral artery cannulation. A known alternative site for
cannulation is the axillary artery, which is a large artery, is
readily palpable, has a rich collateral circulation and has a
pressure waveform that resembles the aortic profile.
The fact that uniform pulmonary perfusion is an essential
prerequisite for the estimation of EVLW using the dye-
dilution principles is widely acknowledged. Schreiber
and co-workers [41], using an experimental model
of regional pulmonary hypoperfusion, have shown that
estimates of GEDV and ITBV may also be perfusion-
dependent and they suggested that an increase in mean
pulmonary transit velocity due to vasoconstriction may
lead to a reduction in transit time and, consequently,
underestimation of GEDV and ITBV. Nirmalan and
co-workers [42], in 2004, demonstrated that in the face
of pulmonary hypertension and small deficits in total
blood volume, ITBV may be estimated with reasonable
certainty by the single thermodilution technique. The
errors inherent in estimating ITBV (and therefore
EVLW) in the presence of an acute lung injury and
associated pulmonary hypertension were small. These
conclusions, however, cannot be extended to situations in
which a greater deficit in circulatory volume or regional
perfusion defects may be present. The same group [43]
demonstrated that the linear relationship between
GEDV and ITBV is also maintained in hypovolemic
shock. In this setting, even though the relationship
between GEDV and ITBV is influenced by circulatory
volume and cardiac output, the mean errors in predicting
ITBV were small and within clinically tolerable limits.
The correlation coefficient of 1.25 and an intercept of
0 used in the PiCCO algorithm overcome some of the
variations related to cardiac output and circulatory
volume and, consequently, provide a relatively useful
clinical measure of ITBV and EVLW.
Conclusion
During the last 7 years, some invasive hemodynamic
devices have become available. Hemodynamic volu-
metric monitoring allows us to obtain a ‘single picture’
(‘static’ measure) and a ‘movie’ (‘dynamic’ measure) of a
patient’s clinical status. Interpretation of volumetric
measures of preload has to be performed in view of
the peculiar, singular, unique ‘picture’ of a patient’s

clinical condition integrated with other conventional
hemodynamic data. Neither PAC nor volumetric
monitoring, however, has been shown to improve out-
come in critically ill patients. Probably not the device
‘per se’, but the application of predefined therapeutic
strategy based on volumetric measures of preload
together with clinical examination and other conven-
tional hemodynamic data may improve outcome in
critically ill patients. Further studies are needed to
investigate this crucial point on the application of
different hemodynamic tools in critically ill patients.
References and recommended reading
Papers of particular interest, published within the annual period of review, have
been highlighted as:
 of special interest
 of outstanding interest
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