http://www.kidney-international.
org
& 2013 International Society of Nephrology
Assessment of intravascular volume status and
volume responsiveness in critically ill patients
Kambiz Kalantari1, Jamison N. Chang1, Claudio Ronco2 and Mitchell H. Rosner1
1
Division of Nephrology, University of Virginia Health System, Charlottesville, Virginia, USA and 2Department of Nephrology Dialysis and
Transplantation, International Renal Research Institute (IRRIV), San Bortolo Hospital, Vicenza, Italy
Accurate assessment of a patient’s volume status, as well
as whether they will respond to a fluid challenge with
an increase in cardiac output, is a critical task in the care of
critically ill patients. Despite this, most decisions regarding
fluid therapy are made either empirically or with limited and
poor data. Given recent data highlighting the negative
impact of either inadequate or overaggressive fluid therapy,
understanding the tools and techniques available for
accurate volume assessment is critical. This review highlights
both static and dynamic methods that can be utilized to help
in the assessment of volume status.
Kidney International (2013) 83, 1017–1028; doi:10.1038/ki.2012.424;
published online 9 January 2013
KEYWORDS: assessment; intravascular; techniques; volume
Correspondence: Mitchell H. Rosner, Division of Nephrology, University of
Virginia Health System, Box 800133, Charlottesville, Virginia 22908, USA.
E-mail: mhr9r@virginia.edu
Received 26 August 2012; revised 18 October 2012; accepted 26
October 2012; published online 9 January 2013
Kidney International (2013) 83, 1017–1028
review
Accurate assessment of intravascular volume remains one of
the most challenging and important tasks for clinicians.
Rivers et al.1 demonstrated that a protocol of early goal-
directed therapy, which included aggressive fluid
resuscitation targeted to central venous pressure (CVP) and
physiological variables, reduced organ failure and improved
survival in patients with severe sepsis and septic shock.
However, more recent studies in critically ill patients have
demonstrated that excessive fluid resuscitation and markedly
positive net fluid balance is associated with higher rates of
complications and increased mortality.2,3 In a European
multicenter observational study of patients admitted to the
intensive care unit (ICU), each 1 liter of positive fluid balance
during the first 72 h of ICU stay was associated with a 10%
increase in mortality after adjustments for other risk factors.2
Furthermore, in a landmark study of liberal versus
conservative fluid management of patients with acute lung
injury in the ICU, a more conservative fluid management
strategy improved lung function and shortened the ICU stay,
whereas there was no difference in the 60-day mortality
between the two groups.4 Thus, outcomes are clearly
influenced by fluid balance with either inadequate or overly
aggressive resuscitation associated with excess morbidity and
mortality (Figure 1). Despite this, most decisions regarding
fluid therapy are still made empirically.
When dosing intravenous fluids, two key clinical questions
are asked: (1) what is the current state of the patient’s
intravascular volume? and (2) if the patient receives
continued fluid resuscitation or a fluid bolus, will physiolo-
gical variables such as blood pressure, tissue perfusion, and
urine output improve? Fundamentally, the only reason to
give a patient a fluid challenge is to increase the stroke
volume (SV; by at least 10–15%) and improve organ
perfusion. It is therefore crucial during the resuscitation
phase of critically ill patients to determine not only the
volume status but also whether the patient is fluid-responsive
or not. In clinical practice, physical examination, radio-
graphy, laboratory parameters, and in case of the critically ill
patients in the ICU, monitoring of central pressures and
cardiac output are combined to assess the patient’s
intravascular volume and determine clinical interventions
such as fluid or diuretic administration. As with any
diagnostic tests, clinicians utilizing these volume assessment
1017
review
Assessment of
volume status and
fluid responsiveness
Optimum fluid balance
Volume depletion
• Hypotension
• Shock
• Organ hypoperfusion
• Acute kidney injury
Inadequate fluid therapy
Figure 1 | Volume assessment goals. Proper assessment of patients’ volume status and whether they will respond with an increase in cardiac
output, following a fluid challenge, are critical to avoid the consequences of either inadequate or overaggressive fluid therapy.
techniques need to understand their limitations and
diagnostic accuracy. The intent of this review is to survey
the literature and summarize the performance characteristics
of tests commonly used for the assessment of both
intravascular volume status and volume responsiveness in
critically ill patients. It is noteworthy that laboratory
assessments such as the mixed venous oxygen saturation,
blood lactate, and others are not discussed in this paper.
HISTORY AND PHYSICAL EXAMINATION
The earliest assessment of the patient is the history and
physical examination (Table 1). The majority of studies
assessing the utility of the history and physical examination
in clinical volume assessment are derived from either the
assessment of patients with heart failure (HF) or acute blood
loss.
Wang et al.5 performed a meta-analysis of 18 studies that
evaluated the utility of the history, physical examination,
and diagnostic tests in diagnosing HF and volume overload
in patients presenting to the emergency department with
dyspnea. Among all presenting symptoms, paroxysmal
nocturnal dyspnea was most helpful, if present (positive
likelihood ratio: 2.6), followed closely by orthopnea and
peripheral edema.
In a review on the value of physical examination findings
in the diagnosis of hypovolemia, it was shown that physical
examination findings are dependent on the type and amount
of fluid loss.6 The most useful physical findings are postural
dizziness (preventing measurement of upright vital signs)
or a postural pulse increment of 30 beats/min or more.
However, these findings had a high sensitivity for hypovolemia
caused only by large blood losses (approximately 1 liter) but
a poor sensitivity for moderate blood losses (approximately
500 ml). The authors point out that in states of volume
depletion produced by non–blood loss states, very few
findings have clinical utility, and ancillary lab/diagnostic
testing is required.6 This was confirmed in another study that
demonstrated that no single clinical sign was useful in
identifying a low circulating blood volume.7 Furthermore,
when clinicians were asked to predict hemodynamic
parameters based only on history and physical examination,
their performance was poor.8 In this study, pulmonary artery
occlusive (wedge) pressure was correctly predicted only 30%
1018
K Kalantari et al.: Volume assessment
Volume overload
• Impaired oxygenation
• Edema
• Hypertension
• Organ congestion
Overaggressive fluid therapy
Table 1 | Commonly used clinical and laboratory parameters
in the assessment of volume status
 Vital signs
J Blood pressure (mean arterial pressure)
J Pulse
J Orthostatic changes in blood pressure and pulse
 Physical examination
J Mentation
J Capillary refill
J Skin turgor/dryness
J Skin perfusion (color/mottling, temperature)
J Temperature of extremities
J Urine output
 Laboratory parameters
J Fractional excretion of sodium, urea
J Blood lactate
J Mixed venous oxygen saturation
of the time. Cardiac output, systemic vascular resistance, and
right atrial pressures were correctly predicted approximately
50% of the time.
CHEST RADIOGRAPHY
The daily chest X-ray (CXR) in the ICU is an established
diagnostic tool to complement history and physical exam-
ination findings, and is commonly used to assess volume
status. In a study of patients with systolic HF awaiting heart
transplantation, CXR findings were correlated with measure-
ment of pulmonary capillary wedge pressure (PCWP) as their
gold standard for volume overload.9 Although venous
redistribution and interstitial pulmonary edema were seen
more commonly among subjects with high PCWP readings,
there was a high degree of overlap among groups with
different PCWP values. In addition, the absence of radiologic
findings typically associated with volume overload did not
ensure lower PCWP.9 Other studies have confirmed that the
typical radiologic signs suggesting volume overload are
Kidney International (2013) 83, 1017–1028
K Kalantari et al.: Volume assessment
highly variable and insensitive and that CXR findings cannot
predict extravascular lung water.10–13
Another method derived from the CXR is to examine the
vascular pedicle width (VPW). The VPW is measured by1
dropping a perpendicular line from the point at which the
left subclavian artery exits the aortic arch and2 measuring
across to the point at which the superior vena cava (SVC)
crosses the right mainstem bronchus.14 Studies of critically
ill patients have demonstrated correlations between serial
changes in VPW and changes in volume status.15–18 Ely
et al.10 demonstrated that using a VPW cutoff value of
70 mm in addition to a cardiothoracic ratio (cardiac width
divided by thoracic width) greater than 0.55 significantly
improved the accuracy of CXR in determining volume status
(gold standard determined by PCWP). The VPW is best
utilized in a single patient on serial measurements, and
changes in VPW show a high correlation with changes in
volume status.19,20 In clinical practice, VPW is not widely
used by practitioners, owing to the fact that the position of
the patient, patient’s height and body build, technical
factors, diseases of mediastinum, and prior trauma, surgery,
or irradiation may all affect the validity of VPW
measurements.20
It is evident that both the physical examination and chest
radiography provide limited value in the determination of a
patient’s volume status and that other more sensitive and
specific techniques are needed.
STATIC PRESSURE MEASUREMENTS
In theory, fluid resuscitation in the hypovolemic patient
increases right ventricular end-diastolic volume, left ventri-
cular end-diastolic volume, and depending upon the position
on the Frank–Starling curve, SV and cardiac output (CO). If
this holds true, measuring such parameters would be a useful
tool in guiding decisions regarding fluid resuscitation. The
most common of these parameters are CVP, pulmonary
artery occlusion pressure, or PCWP, and right ventricular
end-diastolic volume.
Arguably, CVP is the most commonly used parameter for
guiding fluid management in ICUs. Surveys of intensivists
and anesthesiologists suggest that more than 90% use CVP to
guide fluid management.21,22 In addition, guidelines have
recommended the use of CVP in guiding fluid management
in critically ill septic patients.23 In a meta-analysis of five
studies, the pooled correlations between CVP and measured
blood volume or change in cardiac index (CI) or SV in
response to volume expansion were 0.16 and 0.18,
respectively, and the pooled area under the ROC curve was
only 0.56.24 Thus, the likelihood that CVP can accurately
predict fluid responsiveness is only 56% (slightly better than
flipping a coin). The same meta-analysis also investigated the
utility of changes in CVP after volume expansion in
predicting changes in CO or SV by including 19 additional
studies. Pooled correlation coefficient between the change in
CVP and changes in CI or SI were even worse at 0.11.24
Numerous other studies have come to similar
Kidney International (2013) 83, 1017–1028
review
conclusions.25–28 CVP is dependent on venous return (VR)
to the heart, right ventricular compliance, peripheral venous
tone, and posture, and the CVP is particularly unreliable in
pulmonary vascular disease, right ventricular disease, patients
with tense ascites, isolated left ventricular failure, and
valvular heart disease.24,29 In patients with an intact
sympathetic response to hypovolemia, the CVP may
actually fall in response to fluid, as compensatory
venoconstriction is reduced.29 Thus, it is possible to have a
low CVP and not be volume responsive, as well as have a high
CVP and be volume responsive.
Pulmonary artery occlusion pressure or PCWP has been
widely used to assess volume status and fluid responsiveness
in the ICU and operating room. Ideally, the PCWP is
proportional to left -ventricular end-diastolic volume/pre-
load and would seem to be an ideal parameter for monitoring
volume status. However, the vast majority of studies have
demonstrated a poor correlation between PCWP, volume
status, and responsiveness to fluid resuscitation.25,30–33
Michard and Teboul25 determined that seven out of nine
studies demonstrated no significant association between a
low starting PCWP and subsequent fluid responsiveness as
defined by either an increase in SV or CO after a bolus of
intravenous fluids. In one of the studies, responders (an
increase in SV of at least 15% in association with a fluid
challenge) had a higher baseline PCWP than
nonresponders.30 In two other studies, there was an
association between lower baseline PCWP and fluid
responsiveness, but the authors were unable to develop a
threshold that would differentiate responders from
nonresponders.31,32 In addition, in a study of 100 ICU
patients, Osman et al.33 determined that a baseline PCWP
cutoff value of o11 mm Hg was poor at determining fluid
responsiveness, defined as an increase of the cardiac index of
415%. The sensitivity of this cutoff value was 77%, with
a specificity of 51%. They further examined a combination
of CVPo8 mm Hg and PCWPo12 mm Hg in predicting
response to fluid challenge. This combination performed
poorly as well, with a sensitivity of 35% and specificity of
71%.33 Furthermore, several studies have demonstrated no
benefit of pulmonary artery catheters in improving ICU
outcomes and maybe even harmful for these patients.34–36
The weak relationship between surrogate indicators of
preload and volume responsiveness/intravascular volume
status is due to several factors. First, the relationship between
volume and pressure is not constant and is modified by
changes in vascular and cardiac compliance. Depending on
the compliance of a system, a given volume and volume
change may correspond to widely varying pressures. For
example, ventricular compliance is altered in critically ill
patients owing to processes such as sepsis and ischemia, and
cannot be easily predicted. Michard and Teboul25 highlighted
two additional issues: (1) changes in the cardiovascular
system depend on the proportional portioning of fluids
between the various compartments of the cardiovascular
system, and (2) the increase in SV with increased
1019
review
end-diastolic volume depends on preserved cardiac function,
which is often not the case in critically ill patients. Viewed
from this perspective, a patient may be a nonresponder to a
fluid challenge because of high venous compliance, low
ventricular function, and/or compliance or third-spacing of
administered fluids out of the vascular space. Unfortunately,
no current measure of cardiac preload can capture all this
information. Furthermore, a given preload does not correlate
with fluid responsiveness (Figure 2).37 This suggests a need
for caution in using these measures for assessing and
managing volume therapy in patients.
ECHOCARDIOGRAPHIC ASSESSMENT OF VOLUME STATUS
There are several two-dimensional and Doppler flow
measurements that can be obtained from trans-thoracic or
transesophageal echocardiography (TTE or TEE) that
provide cardiac chamber volume assessment.38 For
example, TEE has been used to measure left ventricular
dimensions in mechanically ventilated patients.38 Specifically,
Reuter et al.39 demonstrated that left ventricular end-diastolic
area (LVEDA) is a good predictor of volume responsiveness.
Other studies have failed to replicate this finding.40,41 One
major issue with this parameter is that in the absence of
baseline echocardiographic data absolute levels of LVEDA are
hard to interpret and vary from patient to patient, depending
upon baseline cardiac anatomy and physiology.38 Thus,
static, single echocardiographic measurements are of limited
value in the assessment of preload and volume
responsiveness.
DYNAMIC VARIABLES
Given the limited ability of static measures to predict volume
status in critically ill patients, research has targeted measures
that better discriminate those patients who increase SV with
fluid therapy (‘fluid responders’) from those who do not
(‘nonresponders’). As these measures look at changes in
cardiovascular parameters in real time, they have been
deemed ‘dynamic’ measures as opposed to the static or
snapshot measures discussed above.
The degree of variation in parameters such as SV (SV
variation, SVV), pulse pressure (pulse pressure variation,
PPV), changes in aortic flow velocity, and the diameter of
inferior vena cava (IVC) or SVC as a result of changes in
intrathoracic pressure induced by spontaneous respiration or
by positive pressure ventilation are among the tools to assess
volume responsiveness. Although in the normal breathing
cycle the VR and right heart preload increase during
inspiration and decrease at the end of inspiration, these
changes are reversed during positive pressure ventilation
(Figure 3).42 With mechanical insufflation, the rise in pleural
pressure leads to reduction of VR and RV preload. At the
same time, the RV afterload increases because of an increase
in transpulmonary pressure (Figure 3).43 Left ventricular
preload increases during mechanical inspiration due to the
increase in transpulmonary pressure. Left ventricular
afterload decreases during mechanical inspiration because
1020
K Kalantari et al.: Volume assessment
A
Stroke volume
Fluid
administration
B
Ventricular preload
Figure 2 | Preload does not predict volume responsiveness. For a
given fixed amount of fluid administration, the increase in stroke
volume will be greater for a patient with normal ventricular function
(A, preload-dependent and fluid-responsive) than for a patient with
impaired ventricular function (B, preload-independent and fluid-
nonresponsive). However, a static measurement of preload would be
the same in each patient.
Mechanically ventilated
patient inspiration
1. Reduction in venous return
2. Reduction in right ventricular preload
3. Increase in right ventricular afterload
Biventricular
dependence
Decrease in left ventricular output
occurs during expiration
Inspiration Expiration Inspiration
Arterial pressure
Figure 3 | Respiratory variations in cardiac hemodynamics in the
mechanically ventilated patient. Mechanical ventilation results in a
decrease in left ventricular output during the expiratory phase that
can be seen by changes in the arterial pressure wave form. These
changes form the basis of stroke volume variation and pulse pressure
variation.
the positive pleural pressure increases systolic extracardiac
pressure. Importantly, the codependence of the LV output
on RV output is seen because of the relatively long
(approximately 2 s) transit time of blood through the
alveolar capillary bed.44,45 Thus, the inspiratory decrease in
right ventricular output leads to a decrease in LV output a few
heartbeats later, which corresponds to the expiratory phase of
mechanical ventilation.
The changes in RV and LV SV with respiration/ventilation
are more pronounced on the steep (‘volume responsive’)
compared with the flat portion of the Frank–Starling curve
and are explained by at least four mechanisms: (1) the venous
Kidney International (2013) 83, 1017–1028
K Kalantari et al.: Volume assessment
system, particularly the SVC is more collapsible in hypovo-
lemic states; (2) the inspiratory increase in right atrial
pressure is greater in hypovolemic states secondary to the
greater transmission of pleural pressures to the more
compliant right atrium; (3) the effect of mechanical
inspiration on RV afterload is greater because of higher
transalveolar pressures in the setting of hypovolemia; and (4)
the ventricles are more sensitive to preload when they are
operating on the steep portion of the Frank–Starling
curves.46–51 These changes are reflected in biventricular
preload dependence and lead to a fall in LV output during
the expiratory phase of mechanical ventilation.44 In other
words, significant intravascular volume depletion results in
more pronounced changes in arterial pressure during the
respiratory cycle. In contrast, in hypervolemic states the
magnitude of respiratory variation in arterial pressure is low
because of the inspiratory increase in left ventricular
output.52–54 There are several techniques available at the
bedside that can be used to assess the variability in left
ventricular SV associated with mechanical ventilation that
include the following: respiratory variation in arterial pulse
pressure (PPV), respiratory variation in systolic pressure,
SVV with respiration, and aortic blood velocity variation
with ventilation.55–58 It is important to note that for all of
these measures, the patient must be in normal sinus rhythm,
have no spontaneous respirations, and have a closed chest.
Systolic pressure variation, PPV, and SVV
Rick and Burke59 first demonstrated that blood volume status
and the magnitude of arterial pressure variation were strongly
correlated. They defined hypovolemia using a combination
of variables including: PCWPo5 mm Hg, CVPo5 mm Hg,
tachycardia, signs of peripheral vasoconstriction, and a urine
output o0.5 ml/kg/h. Hypovolemic patients frequently
demonstrated systolic pressure variation (SPV)410 mm Hg,
whereas this was unusual in normovolemic or hypervolemic
patients. Further work has shown that SPV decreases with
increasing blood volume and increases with volume
depletion.60–62
For a given arterial compliance, the amplitude of the pulse
pressure is directly related to SV. This makes SVV and PPV
potentially more useful parameters over SPV as they are less
affected by changes in diastolic pressure that affect the
systolic pressure and could confound interpretation.63,64 PPV
is calculated by one of several techniques that calculate the
difference between maximum and minimum pulse pressures
during mechanical breaths, and SVV is computed through
pulse contour analysis and computation of the area under the
systolic portion of the arterial pressure curve.43,52,65–67 Several
studies have compared these values in an effort to refine the
best variables associated with fluid responsiveness.
In a study on 40 patients with sepsis on mechanical
ventilation, Michard et al.62 demonstrated higher variations
in systolic pressure (15% vs. 6%) and pulse pressure (24% vs.
7%) during respiration in the group of patients who
responded to volume expansion (defined as a rise of 15%
Kidney International (2013) 83, 1017–1028
review
in cardiac index) than those who were not volume
responsive. The responders demonstrated a reduction in
PPV after volume expansion. A cutoff value of 13% for PPV
had a sensitivity of 94% and specificity of 96% to
discriminate between fluid responders and nonresponders.
Variability in PP was superior to SPV in discriminating fluid
responders.62
Berkenstadt et al.68 studied the value of monitoring vital
signs, CVP, and SVV in predicting response to volume
expansion. In 15 mechanically ventilated patients undergoing
brain surgery, they infused 100 ml of a colloid solution in
multiple steps and monitored the response by measuring
changes in SV. Heart rate and CVP were similar in responders
and nonresponders to volume expansion. However, SVV was
significantly higher among responders than in nonresponders
(12.6% vs. 6.8%).65 Baseline SVV correlated strongly with the
changes in SV after volume expansion. The area under the
ROC curve in detecting responders was 0.87 for SVV and 0.49
for CVP in this study.68
Marik et al.69 performed a meta-analysis of 29 clinical
studies, including 685 patients, to evaluate the utility of PPV
and SVV in predicting responsiveness to volume expansion in
critically ill patients and undergoing mechanical ventilation.
The correlation coefficient for baseline PPV and SVV and
changes in CI or SV in response to volume expansion were
0.78 and 0.72, respectively. The area under the ROC curve
was 0.94 for PPV and 0.86 for SVV. In comparison, CVP,
global end-diastolic volume index and LVEDA index had
poor to marginal performances. Adding to the strength of
their conclusions, the included studies had a remarkably
consistent threshold PPV/SVV of 12–13% for defining fluid
responsiveness. As demonstrated in these studies, PPV is a
more reliable predictor of volume responsiveness than SVV,
and this probably relates to the fact that PPV is directly
measured and SVV relies on pulse contour analysis, which
makes a number of assumptions. An important caveat to the
use of PPV is that there is a ‘gray zone’ of PPV values
(between 9 and 13%) where fluid responsiveness cannot be
predicted reliably.70 Cannesson et al.70 demonstrated that this
‘gray zone’ may affect up to 25% of patients during general
anesthesia.
Edwards Lifesciences (Irvine, CA) manufactures a system
that calculates SVV (the Vigileo monitor and FloTrac sensor)
through the use of an arterial catheter and analysis of the
arterial pressure waveform. This system has been shown to be
effective in monitoring SV and fluid responsiveness in
mechanically ventilated patients.71–73 Several studies have
also shown improvements in outcomes utilizing intra-
operative fluid optimization strategies relying on
measurement of SVV.74,75
Another system for determining beat-to-beat measure-
ment of cardiac output along with the ability to ascertain
SVV, PPV, and SPV is the LiDCO Plus System (LiDCO,
Cambridge, UK).76,77 This calibrated system combines the
LiDCO system for the measurement of cardiac output using a
lithium-based indicator dilution method along with the
1021
review
PulseCO system, which calculates continuous beat-to-beat
analysis of cardiac output. Data derived from this system can
be used to derive SVV, PPV, and SPV.76,77 Clinical trials
utilizing such a system are underway to assess its impact on
clinical outcomes.78
A less invasive alternative to these techniques is pulse
pressure analysis during mechanical ventilation using dy-
namic changes in both the peak and amplitude of the pulse
oximeter plethysmographic wave form. These changes
measure volume changes as opposed to pressure changes in
arterial and venous vessels.79 These dynamic changes in the
pulse oximeter wave form have shown significant correlation
with PPV and accurately predicted fluid responsiveness.80–82
A commercially available monitor will assess these dynamic
changes in the pulse oximeter wave form and determine the
‘Pleth Variability Index’ (Masimo, Irvine, CA) and is helpful
in predicting fluid responsiveness.83,84 The Pleth Variability
Index is an automatic measure of the dynamic change in the
perfusion index (the ratio of nonpulsatile to pulsatile blood
flow) that occurs during the respiratory cycle. A Pleth
Variability Index414% before volume expansion is
predictive that a patient will respond to fluid administra-
tion with a sensitivity of 81%.
There are important limitations to these techniques. Most
importantly, the respiratory variation in SV and arterial
pressure has been best validated in mechanically ventilated
and heavily sedated patients.43 Both arrhythmias and
spontaneous respiration may influence the change in PPV/
SVV in response to volume loading.43 In addition, at any
given preload condition, the SVV/PPV varies according to
the set tidal volume and can also be influenced by chest wall
compliance and the level of positive end-expiratory
pressure.43 De Backer et al.85 further demonstrated that the
tidal volume must be at least 8 ml/kg to ensure accurate and
reproducible results when utilizing PPV. If smaller tidal
volumes are required (such as in a patient with acute
respiratory distress syndrome), the authors have suggested
increasing the tidal volumes transiently when a volume
challenge is given.85 Lansdorp et al.86 also recently
demonstrated that the predictive value of PPV, SPV, and
SVV was optimal in limited circumstances such as with tidal
volumes 47 ml/kg and with normal sinus rhythm.
Nevertheless, even given these limitations, the relative ease
of obtaining these measures, as well as their strong predictive
ability, makes them strong candidates for improving the
assessment of fluid responsiveness in the ICU and perhaps
improving outcomes.
Esophageal Doppler monitoring
By measuring the aortic blood flow in the descending
thoracic aorta, esophageal Doppler monitoring allows a
reliable estimation of cardiac output and SV.87–89 The
procedure requires placing a flexible Doppler probe into
the patient’s esophagus through the nose or mouth. The tip
of the probe contains a transducer, which transmits an
ultrasound signal toward the descending aorta, allowing
1022
K Kalantari et al.: Volume assessment
measurement of blood velocity using the shift in Doppler
frequency. Using the diameter of the aorta (measured or
calculated), the distribution of blood flow to the descending
aorta, and the aortic flow velocity, one can calculate an
estimate of the cardiac preload. The validity of this technique
was explored in a meta-analysis by Dark and Singer.88
Cardiac output was determined by thermodilution (gold
standard) and esophageal Doppler and changes in cardiac
output after an IV fluid bolus were assessed as well using
both techniques. Changes in cardiac output as determined by
Doppler agreed 86% of the time with thermodilution
methods and suggests that esophageal Doppler may be
useful in this regard. Further, like SVV/PVV, changes in aortic
blood flow velocity with the respiratory cycle, as assessed by
esophageal Doppler, correlate with fluid responsiveness in
patients on positive pressure ventilation.90
Sinclair et al.91 randomized patients undergoing operative
repair of a proximal femur fracture to volume optimization
based on esophageal Doppler or to usual care. The group
randomized to esophageal Doppler monitoring had a more
rapid post-operative recovery and shorter length of stay.
Chytra et al.92 also demonstrated that optimization of
volume using esophageal Doppler monitoring in the ICU
was associated with lower blood lactate levels, a lower
incidence of infections, and reduced ICU and hospital stay in
trauma patients. It is noteworthy that these studies did not
include respiratory variation in aortic blood flow as a
parameter. In 2009, the Health Technology Assessment
Program of the National Institute for Health Research in
the United Kingdom assessed the clinical and cost-
effectiveness of esophageal Doppler monitoring.93 This
assessment concluded that the addition of esophageal
Doppler monitor guided fluid therapy to CVP monitoring,
and conventional volume assessment during surgery resulted
in fewer major and total complications, shorter length of stay,
and possibly fewer deaths.93 However, for patients with
critical illness, the addition of esophageal Doppler
monitoring is of less clear benefit and further studies are
required.93 Limitations to this technique include the
following: (1) the probe is poorly tolerated in awake
patients and thus requires adequate sedation; (2) the probe
needs to be refocused before each measurement and thus it is
used to make frequent, repeated measurements rather than
for continuous monitoring.
As demonstrated by Feissel et al.,94 transesophageal
echocardiography offers potentially comparable data to
esophageal Doppler. Respiratory changes in aortic peak
velocity were calculated and these changes were higher in
fluid responders (defined as an increase in cardiac increase
415% in response to volume expansion) than in
nonresponders. Before volume expansion, a change in
peak aortic velocity with respiration 412% allowed
discrimination between responders and nonresponders with
a sensitivity of 100% and a specificity of 89%. This was not
confirmed in a study of mechanically ventilated
cardiovascular surgery patients that compared SVV and
Kidney International (2013) 83, 1017–1028
K Kalantari et al.: Volume assessment
PPV compared with the respiratory changes in
transesophageal echo-derived aortic blood velocity in
cardiac surgical patients.95 In this study, SVV was the best
predictor of fluid responsiveness, and changes in aortic peak
velocity did not correlate with fluid responsiveness. The
logistical barriers in performing a transesophageal
echocardiogram in unstable, critically ill patients make this
technique far from user-friendly.
Respiratory variation in vena cava diameter
The intrathoracic changes in pressure during the respirator
cycle affect VR and thus the diameter of the central veins
such as the IVC. Ultrasound-measured absolute diameter of
the IVC or the extent of change in its diameter with the
respiratory cycle has been used to assess volume status.
Yanagawa et al.96 measured IVC diameters in 35 trauma
patients, with 10 of them in shock and 25 in a stable
hemodynamic state, on arrival to the emergency department
and again at day 5. They found significantly smaller IVC
diameters in the group of patients in shock on arrival in
comparison with those not in shock (7.7 vs. 13.4 mm).96 The
same group of investigators demonstrated that the IVC
diameter is useful in predicting the response of patients in
shock states to fluid resuscitation.97 In this study, the IVC
diameter at the end of expiration was measured in trauma
patients with hemorrhagic shock at baseline and again after
what was believed to be adequate fluid resuscitation (defined
by the improvement of systolic blood pressure to a level
greater than 90 mm Hg). Individuals who were able to
maintain a stable blood pressure after fluid resuscitation
had a significant increase in end-expiratory IVC diameter,
whereas those who remained hemodynamically unstable did
not have a change in IVC diameter with resuscitation.97 The
authors concluded that changes in IVC diameter in response
to fluid resuscitation is a better indicator of adequate fluid
resuscitation than vital signs. Sefidbakht et al.98 also
demonstrated significantly smaller IVC diameters at the end
of expiration or inspiration in a group of patients in shock as
compared with controls (5.6 and 4.0 mm vs. 11.9 and
9.6 mm, respectively). In addition, they showed a higher vena
cava collapsibility (or pulsatility) index ((end-expiratory
diameter  end-inspiratory diameter)/end-expiratory
diameter) in the shock group.98 The vena cava collapsibility
index was shown to decline after volume expansion in a
group of patients in hypovolemic shock in another small
study.99 Among 39 patients in septic shock and on a
mechanical ventilator, volume expansion resulted in
significant drop in IVC collapsability index (13.8–5.2%),
which correlated with a rise in cardiac output.100 Those who
responded to volume expansion (defined as a 415% increase
in CO) as compared with those who did not respond, had
greater collapsability index at baseline (25 vs. 6%).
Viellard-Baron et al.101 studied the utility of the SVC
collapsibility index in identifying responders to volume
expansion using 10 ml/kg of a colloid solution among
individuals in septic shock on a ventilator. In that study, a
Kidney International (2013) 83, 1017–1028
review
threshold of 36% for SVC collapsibility had sensitivity of 90%
and specificity of 100% in detecting an 11% rise in cardiac
index after volume expansion.
Technically, the measurement of the IVC diameter can be
taken in the subxyphoid, lateral, and even suprailiac position.
However, body habitus can be a potential barrier in obtaining
accurate measurements. Although measurement of IVC
diameter can be taken transcutaneously, accurate SVC
measurements require TEE. Both of these measures cannot
be obtained on a continuous basis. In addition, the IVC
diameter is affected by high intra-abdominal pressure and
thus has limited use in patients post laparotomy or with
suspected high intra-abdominal pressures.98,99
Passive leg raising
A major limitation of the dynamic techniques is the
requirement for mechanical ventilation and sedation. In an
effort to determine volume responsiveness in spontaneously
breathing patients, passive leg raising (PLR) has been
developed.102 With PLR, there is gravitational transfer of
blood from the legs to the intrathoracic cavity with resultant
increases in PCWP and LV preload. The ability of PLR to
predict fluid responsiveness has been confirmed in several
studies with critically ill patients.103–106 Furthermore, a recent
meta-analysis determined that the area under the curve or
PLR for determining fluid responsiveness was 0.95 and
was not affected by spontaneous breathing or cardiac
dysrhythmias.107 Technically, PLR is best performed by
both elevating the lower limbs to 451, while at the same
time lowering the patient into the supine position from a 451
semi-recumbent position.108 This technique has the
advantage of both increasing cardiac preload from the shift
of venous blood from the legs as well as the abdominal
compartment.
PLR leads to rapid changes in VR, and thus, a rapid, real-
time method to assess changes in SV or CO must be available
to assess fluid responsiveness. In this regard, the FloTrac-
Vigleo (Edwards Lifesciences, Irvine, CA) system can be
used to measure SVV with PLR where a 10% or greater
increase in cardiac output in response to PLR predicts fluid
responsiveness.109 Transpulmonary thermodilution (PiCCO
system, Pulsion Medical Systems, Munich, Germany) can also
be utilized in this regard where the effects of PLR on cardiac
output can be assessed with pulse pressure analysis.110 An
alternative to these more invasive systems is the noninvasive
CO monitor (NICOM, Cheetah Medical, Portland, OR). This
system provides continuous, accurate, noninvasive hemody-
namic monitoring based on bioreactance (http://www.
cheetah-medical.com). The foundation of bioreactance is
that when an AC current is applied to the thorax, the
pulsatile blood flow taking place in the large thoracic arteries
causes the amplitude of the applied thoracic voltage to
change. In addition, it causes a time delay or phase shift
between the applied current and the measured voltage. These
phase shifts are tightly correlated with SV (http://www.
cheetah-medical.com). The CO measured by this technique
1023
review
has been correlated with thermodilution and arterial pulse
contour analysis (http://www.cheetah-medical.com).111–113
Benomar et al.114 have utilized the NICOM system to assess
fluid responsiveness in response to either PLR or a 500 ml IV
rapid colloid infusion and found that PLR had an 88%
sensitivity and 100% specificity for predicting fluid
responsiveness. Another study has also confirmed the
utility of this approach.115 Thus, measurement of
bioreactance with the NICOM system may provide a
noninvasive method for determining fluid responsiveness to
either PLR or IV fluid bolus.116
Bioreactance can also be utilized to determine thoracic
fluid content and evaluate its change with various therapeutic
maneuvers. Kossari et al.117 used the NICOM system to
evaluate changes in thoracic fluid content during
hemodialysis and demonstrated that fluid removal during a
dialysis session correlated with changes in thoracic fluid
content, suggesting that bioreactance monitoring may be of
use in dialysis session management.
Most recently, two studies have demonstrated that changes
in end-tidal carbon dioxide levels (X5%) reflect changes in
cardiac index induced by volume expansion or dynamic
measures such as PLR with a precision greater than changes
in arterial pulse pressure.118,119 This assessment tool may
prove extremely useful for the rapid, noninvasive
determination of fluid responsiveness.
Other dynamic measures
As described above, in patients receiving mechanical ventila-
tion, the increase in intrathoracic pressure leads to a series of
hemodynamic changes where the positive end-expiratory
pressure decreases the central blood volume, reduces the
cardiac output, and increases preload responsiveness. Given
this cyclical effect of tidal ventilation, a short end-expiratory
occlusion (as used to measure the intrinsic positive end-
expiratory pressure) can act like a fluid challenge and prevent
the cyclic changes in left ventricular preload. The hemody-
namic effects of this technique (using a 15-s end-expiratory
occlusion) were assessed in 34 patients with acute circulatory
failure, who were monitored with the PiCCOplus system.120
Fluid responsiveness was predicted by the end-expiratory
pressure occlusion with high degree of sensitivity and
specificity, including those patients with spontaneous
breathing activity and those with cardiac arrhythmias. This
technique will require further study, but holds promise as
another dynamic measure to assess fluid responsiveness.
BIOIMPEDANCE VECTOR ANALYSIS
Bioimpedance and bioimpedance vector analysis (BIVA) have
shown promise as noninvasive, real-time measures of static
volume status. A full description of the theoretical under-
pinnings of bioimpedance and BIVA is beyond the scope of
this review (see ref. 121 for an excellent review on this
subject). Bioimpedance can be understood in terms of Ohm’s
law, where the flow of current is equal to the voltage drop
between two ends of a circuit divided by the impedance,
1024
K Kalantari et al.: Volume assessment
E (voltage drop) ¼ I (current) * Z (impedance). If the current
stays constant, the voltage drop is proportional to changes
in the impedance to current flow. Considering that Z
(impedance) can be related to volume in the following
manner, Z ¼ r*(L^2/V) where L ¼ length, V ¼ volume, r ¼
resistivity, changes in impedance can thus be related to
changes in volume. This is the fundamental idea that enables
one to relate changes in cardiac output (volume) to changes
in impedance.122 In practice, a high-frequency current is
applied across the thoracic cavity and electrodes placed
elsewhere on the thorax measure the impedance. The average
thoracic impedance can be considered as an estimate of the
static volume of the thorax and dynamic changes in
impedance, when correlated with ECG-derived timing
measurements can be used to calculate hemodynamic
parameters.123 When compared with measures of cardiac
output obtained by thermodilution, a meta-analysis of over
200 studies revealed a positive correlation with bioimpedance
measurements (r ¼ 0.81).124 However, there are scant data on
clinical outcomes of critically ill patients managed exclusively
with methods using bioimpedance.
The concept of BIVA adds the principle of capacitance (the
time required to charge a circuit) to refine and optimize the
assessment of volume status.125,126 Whole-body impedance
can be broken down into resistance, Rc (opposition to flow of
current through the extra and intracellular environment) and
reactance Xc (the capacitance produced by tissue interfaces
and cell membranes).125,126 Conceptually, resistance is
inversely proportional to the amount of total body water
and reactance is more closely related to the structure and
function of cell membranes. The inclusion of Xc is thought to
result in a more accurate assessment of body fluid
volume.125,126 Once measured, both Rc and Xc are
standardized to height (H) and can be plotted as R/H
(ohms/meter, x axis) vs. X/H (ohms/meter, y axis) (Figure 4).
These data are indicative of total body water and not simply
Fluid depleted
Reactance/height (Xc /H)
7 0th
95 5th
5
B
th
Fluid overload
A
Phase angle
Resistance/height (Rz/H)
Figure 4 | Bioimpedance vector analysis. Shown here are the
ellipses of the standard vectors of the 50th, 75th, and 95th
percentiles of the normal population, as well as two vectors from
hypothetical patients. In patient A, the short vector represents total
body water excess, whereas the longer vector for patient B is
indicative of lower total body water and falls within the 95th
percentile of the normal population.
Kidney International (2013) 83, 1017–1028
K Kalantari et al.: Volume assessment
Table 2 | Summary of volume assessment tools
Method Invasive or noninvasive
Historical findings Noninvasive
Physical exam Noninvasive
Chest radiograph Noninvasive
Central venous pressure Invasive
Pulmonary capillary wedge Invasive
pressure
Echocardiogram Noninvasive
Stroke volume or pulse Invasive (pulse oximeter
pressure variation method in noninvasive)
Esophageal doppler Invasive
Vena cava diameter Noninvasive
Passive leg raising Noninvasive (bioreactance,
end-tidal CO2)
Invasive (FloTrac or PiCCO or
LiDOO)
End-expiratory occlusion Passive leg raising
Bioimpedance Noninvasive
intravascular volume. This information is used to construct a
vector (Figure 4), where a shorter length is associated with
greater degrees of fluid overload and longer lengths with
lower levels of total body water (relative to measurements
made in the general population as reflected by ellipses
representing the 50th, 75th, and 90th percentiles). The angle
of the vector measured from the x axis is referred to as a
phase angle. The exact biological meaning of the phase angle
is unclear though it can be thought of as describing the
distribution of water between the extracellular and intracel-
lular water, and may be a measure of cellular integrity.127
Changes in the phase angle (less than the mean average) seem
to have negative prognostic significance.128,129
BIVA has proven to be a useful tool in assessing the static
volume status of patients. When compared with deuterium
dilution in 22 HF patients, BIVA demonstrated excellent
correlations with total body water measurements
(r ¼ 0.93).130 BIVA has also been used in guiding HF
therapy. In a retrospective evaluation of approximately 186
acute HF patients undergoing both BIVA and brain-derived
natriuretic peptide-guided therapy, this strategy resulted in a
lower rate of a composite endpoint of death or readmission
to the hospital within 6 months.131 The combined use of
BIVA with other cardiac and renal biomarkers may be a
promising mode of determining and managing fluid overload
states including patient on dialysis.132–133
There are a few limitations of BIVA.121 The results can be
misinterpreted if body position is not correct (limb
abduction with arms separated from trunk by 30 degrees
and legs 45 degrees) or if the electrodes cannot be properly
placed (because of diaphoresis, skin wounds, etc.). In
addition, BIVA is unable to differentiate between
compartmentalized edema (pleural, pericardial, and
Kidney International (2013) 83, 1017–1028
review
Static or Assess fluid
dynamic responsiveness Comments
Static No Of limited value with poor correlation with invasive pressure
measurements
Static and Yes Of limited value but serial examinations may detect changes
dynamic in organ perfusion
Static No Requires use of standardized measures of vascular pedicle
width and cardiothoracic ratio. Serial chest X-ray may be
helpful in determining effects of fluid therapy
Static No Poor correlation with fluid responsiveness
Static No Poor correlation with fluid responsiveness
Static No Single measures of cardiac chamber volume hard to assess.
Serial measures may be helpful
Dynamic Yes Requires sedated, mechanically ventilated patient
Dynamic Yes Not useful for continuous measurements
Dynamic Yes Body habitus dependent
Dynamic Yes Unreliable with intra-abdominal hypertension
Dynamic Yes Requires 15-s end-expiratory occlusion
Static No Not able to assess intravascular volume
peritoneal) and increased total body water. Finally, this
technique is standardized to Western European
demographics and may not be accurate in other races.
Perhaps, most importantly, BIVA does not assess
intravascular volume and cannot be used to determine
fluid responsiveness. However, monitoring serial BIVA
studies and assessing vector migration to more normal
hydration states associated with therapies such as
ultrafiltration may be feasible and requires further study.
CONCLUSION
The assessment of intravascular volume status remains one of
the most challenging diagnostic problems faced by clinicians
on a daily basis. Errors in this assessment may lead to
inappropriate therapy and potentially worse outcomes in
both populations. As clinical experience and acumen can be
so valuable in the initial patients’ work-up, the history and
physical examination will always anchor the acute, rapid
diagnostic assessment of volume status. Nevertheless, few
clinicians would disagree with the need for additional
diagnostic tests to support or refute clinical assessments
(Table 2). Static pressure measurements such as the CVP and
PCWP have little utility and should not be routinely used to
assess volume status or fluid responsiveness. Newer dynamic
measurements hold great promise for determining fluid
status, and bioimpedance and bioreactance techniques allow
further refinement. Additional study of these methods is
required to determine whether their use can improve
morbidity and mortality in ICU patients.
Outside of the ICU, we need to improve our ability to
accurately assess the volume status of patients with chronic
disorders of volume, such as congestive HF and end-stage
renal disease, using noninvasive techniques. Data repeatedly
1025
review
suggest that poor control of volume in these patients is
associated with worse outcomes. There is reason to be
optimistic about our ability to do this, as the use of BIVA has
shown the ability to discriminate a patient’s static fluid status
in both populations.
DISCLOSURE
All the authors declared no competing interests.
REFERENCES
1. Rivers E, Nguyen B, Havstad S et al. Early goal-directed therapy in the
treatment of severe sepsis and septic shock. N Engl J Med 2001; 345:
1368–1377.
2. Vincent JL, Sakr Y, Sprung CL et al. Sepsis in European intensive care
units: results of the SOAP study. Crit Care Med 2006; 34: 344–353.
3. RENAL Replacement Therapy Study Investigators. Bellomo R, Cass A,
Cole L et al. An observational study fluid balance and patient outcomes
in the Randomized Evaluation of Normal vs. Augmented Level of
Replacement Therapy trial. Crit Care Med 2012; 12: 1753–1760.
4. Wiedemann HP, Wheeler AP, Bernard GR et al. Comparison of two fluid-
managemet strategies in acute lung injury. N Engl J Med 2006; 354:
2564–2575.
5. Wang CS, FitzGerald JM, Schulzer M et al. Does this dyspneic patient in
the emergency department have congestive heart failure? JAMA 2005;
294: 1944–1956.
6. McGee S, Abernethy WB III, Simel DL. The rational clinical examination. Is
this patient hypovolemic? JAMA 1999; 281: 1022–1029.
7. Stephan F, Flahault A, Dieudonne N et al. Clinical evaluation of
circulating blood volume in critically ill patients- contribution of a
clinical scoring system. Br J Anaesth 2001; 86: 754–762.
8. Eisenberg PR, Jaffe AS, Schuster DP. Clinical evaluation compared to
pulmonary artery catheterization in the hemodynamic assessment of
critically ill patients. Crit Care Med 1984; 12: 549–553.
9. Chakko S, Woska D, Martinez H et al. Clinical, radiographic, and
hemodynamic correlations in chronic congestive heart failure:
conflicting results may lead to inappropriate care. Am J Med 1991; 90:
353–359.
10. Ely EW, Smith AC, Chiles C et al. Radiologic determination of
intravascular volume status using portable, digital chest radiography: a
prospective investigation in 100 patients. Crit Care Med 2001; 29:
1502–1512.
11. Halperin BD, Feeley TW, Mihm FG et al. Evaluation of the portable chest
roentgenogram for quantitating extravascular lung water in critically ill
adults. Chest 1985; 88: 649–652.
12. Saugel B, Ringmaier S, Holzapfel K et al. Physical examination, central
venous pressure, and chest radiography for the prediction of
transpulmonary thermodilution-derived hemodynamic parameters in
critically ill patients: A prospective trial. J Crit Care 2011; 26: 402–410.
13. Baudendistel L, Shields JB, Kaminski DL. Comparison of double indicator
thermodilution measurements of extravascular lung water (EVLW) with
radiographic estimation of lung water in trauma patients. J Trauma
1982; 22: 983–988.
14. Miller RR, Ely EW. Radiographic measures of intravascular volume status:
the role of vascular pedicle width. Curr Opin Crit Care 2006; 12: 255–262.
15. Pistolesi M, Milne EN, Miniati M et al. The vascular pedicle of the heart
and the vena azygos. Part II: Acquired heart disease. Radiology 1984;
152: 9–17.
16. Haponik EF, Adelman M, Munster AM et al. Increased vascular pedicle
width preceding burn-related pulmonary edema. Chest 1986; 90:
649–655.
17. Don C, Burns KD, Levine DZ. Body fluid volume status in hemodialysis
patients: the value of the chest radiograph. Can Assoc Radiol J 1990; 41:
123–126.
18. Thomason JW, Ely EW, Chiles C et al. Appraising pulmonary edema using
supine chest roentgenograms in ventilated patients. Am J Resp Crit Care
Med 1998; 157: 1600–1608.
19. Pistolesi M, Milne EN, Miniati M et al. The vascular pedicle of the heart
and the vena azygous. Part II: Acquired heart disease. Radiology 1984;
152: 9–17.
20. Ely EW, Haponik EF. Using the chest radiograph to determine
intravascular volume status: the role of vascular pedicle width. Chest
2002; 121: 942–950.
1026
K Kalantari et al.: Volume assessment
21. Boldt J, Lenz M, Kumle B et al. Volume replacement strategies on
intensive care units: results from a postal survey. Intensive Care Med
1998; 24: 147–151.
22. Kastrup M, Markewitz A, Spies C et al. Current practice of hemodynamic
monitoring and vasopressor and inotropic therapy in post-operative
cardiac surgery patients in Germany: results from a postal survey. Acta
Anaes Scand 2007; 51: 347–358.
23. Dellinger RP, Carlet JM, Masur H et al. Surviving Sepsis Campaign
guidelines for management of severe sepsis and septic shock. Crit Care
Med 2004; 32: 858–873.
24. Marik PE, Baram M, Vahid B. Does central venous pressure predict fluid
responsiveness? A systematic review of the literature and the tale of
seven mares. Chest 2008; 134: 172–178.
25. Michard F, Teboul JL. Predicting fluid responsiveness in ICU patients: a
critical analysis of the evidence. Chest 2002; 121: 2000–2008.
26. Baek SM, Makabaki GG, Bryan-Brown CW et al. Plasma expansion in
surgical patients with high central venous pressure (CVP): the
relationship of blood volume to hematocrit, CVP, pulmonary wedge
pressure, and cardiorespiratory changes. Surgery 1975; 78: 304–315.
27. Hoeft A, Schorn B, Weyland A et al. Bedside assessment of intravascular
volume status in patients undergoing coronary bypass surgery.
Anesthesiology 1994; 81: 76–86.
28. Godje O, Peyerl M, Seebauer T et al. Central venous pressure, pulmonary
capillary wedge pressure and intrathoracic blood volumes as preload
indicators in cardiac surgery patients. Eur J Cardiothorac Surg 1998; 13:
533–539.
29. Marik PE, Baram M. Non-invasive hemodynamic monitoring in the
intensive care unit. Crit Care Clin 2007; 23: 383–400.
30. Diebel LN, Wilson RF, Tagett MG et al. End-diastolic volume: a
better indicator of pre-load in the critically ill. Arch Surg 1992; 127:
817–822.
31. Wagner JG, Leatherman JW. Right ventricular end-diastolic volume as a
predictor of the hemodynamic response to a fluid challenge. Chest 1998;
113: 1048–1054.
32. Tousignant CP, Walsh F, Mazer CD. The use of transesophageal
echocardiography for preload assessment in critically ill patients. Anesth
Analg 2000; 90: 351–355.
33. Osman D, Ridel C, Ray P et al. Cardiac Filling Pressures are not
appropriate to predict hemodynamic response to volume challenges.
Crit Care Med 2007; 35: 64–68.
34. Richard C, Warszawski J, Anquel N et al. Early use of pulmonary artery
catheters and outcomes in patients with ARDS and septic Shock: a
randomized controlled trial. JAMA 2003; 290: 2732–2734.
35. Shah MR, Hasselblad V, Stevenson LW et al. Impact of pulmonary artery
catheters in critically ill patients: meta-analysis of randomized controlled
trials. JAMA 2005; 294: 1664–1670.
36. Cheatham ML, Nelson LD, Chang MC et al. Right ventricular end-
diastolic volume index as a predictor of preload status in patients on
positive end-expiratory pressure. Crit Care Med 1998; 26: 1801–1811.
37. Pinsky MR, Teboul JL. Assessment of indices of preload and volume
responsiveness. Curr Opin Crit Care 2005; 11: 235–239.
38. Josephs S. The use of current hemodynamic monitors and
echocardiography in resuscitation of the critically ill or injured patient.
Int Anesth Clin 2007; 45: 31–59.
39. Reuter DA, Felbinger TW, Schmidt C et al. Stroke volume variations for
the assessment of cardiac responsiveness to volume loading in
mechanically ventilated patients. Intensive Care Med 2002; 28: 392–398.
40. Feissel M, Michard F, Mangin I et al. Respiratory changes in aortic blood
velocity as an indicator of fluid responsiveness in patients with septic
shock. Chest 2001; 119: 867–873.
41. Rex S, Brose S, Metzelder S et al. Prediction of fluid responsiveness
during cardiac surgery. Br J Anesth 2004; 93: 782–788.
42. Morgan BC, Martin WE, Hornbein TF et al. Hemodynamic effects on
intermittent positive pressure ventilation. Anesthesiology 1966; 27: 584–590.
43. Monnet X, Bleibtreu A, Ferre A et al. Passive leg raising and end-
expiratory occlusion tests perform better than pulse pressure variation
in patients with low respiratory system compliance. Crit Care Med 2012;
40: 152–157.
44. Jardin F, Farcot JC, Guerret P et al. Cyclic changes in arterial pulse during
respiratory support. Circulation 1983; 68: 266–274.
45. Michard F, Teboul JL. Using heart-lung interactions to assess fluid
responsiveness during mechanical ventilation. Crit Care 2000; 4:
282–289.
46. Viellard-Baron A, Chergui K, Rabillar A et al. Superior vena caval
collapsibility as a gauge of volume status in ventilated septic patients.
Intensive Care Med 2004; 30: 1734–1739.
Kidney International (2013) 83, 1017–1028
K Kalantari et al.: Volume assessment
47. Viellard-Baron A, Augarde R, Prin S et al. Influence of superior vena caval
zone conditions on cyclic changes in right ventricular outflow during
respiratory support. Anesthesiology 2001; 95: 1083–1088.
48. Feisel M, Michard F, Faller JP et al. The respiratory variation in inferior
vena cava diameter as a guide to fluid therapy. Intensive Care Med 2004;
30: 1834–1837.
49. Magder S, Georgiadis G, Cheong T. Respiratory variations in right atrial
prssure predict the response to fluid challenge. J Crit Care 1992; 7:
76–85.
50. Santamore WP, Amoore JN. Buffering of respiratory variations in venous
return by right ventricle: a theoretical analysis. Am J Physiol 1994; 267:
H2163–H2170.
51. West JB, Dollery CT, Naimark A. Distribution of blood flow in isolated
lung: relation to vascular and alveolar pressure. J Appl Physiol 1964; 19:
713–724.
52. Rooke GA, Schwid HA, Shapira Y. The effect of graded hemorrhage and
intravascular volume replacement on systolic pressure variation in
humans during mechanical and spontaneous ventilation. Anesth Analg
1995; 80: 925–932.
53. Szold A, Pizov R, Segal E et al. The effect of tidal volume and
intravascular volume state on systolic pressure variation in ventilated
dogs. Intensive Care Med 1989; 15: 368–371.
54. Preisman S, Pfeiffer U, Lieberman N et al. New monitors of intravascular
volume: a comparison of arterial pressure waveform analysis
and the intrathoracic blood volume. Intensive Care Med 1997; 23:
651–657.
55. Michard F, Chemla D, Richard C et al. Clinical use of respiratory change
in arterial pulse pressure to monitor the hemodynamic effects of PEEP.
Am J Resp Crit Care Med 1999; 159: 935–939.
56. Marx G, Cope T, McCrossan L et al. Assessing fluid responsiveness by
stroke volume variation in mechanically ventilated patients with severe
sepsis. Eur J Anesth 2004; 21: 132–138.
57. Dalibon N, Schlumberger S, Saada M et al. Hemodynamic assessment of
hypovolemia under general anesthesia in pigs submitted to graded
hemorrhage and retransfusion. Br J Anesth 1999; 82: 97–103.
58. Lai HY, Yang CCH, Huang FY et al. Respiratory-related arterial pressure
variability as an indicator of graded blood loss: Involvement of the
autonomic nervous system. Clin Sci 2003; 105: 491–497.
59. Rick JJ, Burke SS. Respiratory paradox. South Med J 1978; 71: 1376–1378.
60. Coriat P, Vrillon M, Perel A et al. A comparison of systolic blood pressure
variations and echocardiographic estimates of end-diastolic left
ventricular size in patients after aortic surgery. Anesth Analg 1994; 78:
46–53.
61. Tavernier B, Makhotine O, Lebuffe G et al. Systolic pressure variation as a
guide to fluid therapy in patients with sepsis-induced hypotension.
Anesthesiology 1998; 89: 1313–1321.
62. Michard F, Boussat S, Chemla D et al. Relation between respiratory
changes in arterial pulse pressure and fluid responsiveness in septic
patients with acute circulatory failure. Am J Resp Crit Care Med 2000;
162: 134–138.
63. Scharf SM, Brown R, Saunders N et al. Hemodynamic effects of positive-
pressure ventilation. J Appl Physiol 1980; 49: 124–131.
64. Robotham JL, Cherry D, Mitzner W et al. A re-evaluation of the
hemodynamic consequences of intermittent positive-pressure
ventilation. Crit Care Med 1983; 11: 783–793.
65. Perel A, Pizov R, Cotev S. Systolic blood pressure variation is a sensitive
indicator of hypovolemia in ventilated dogs subjected to graded
hemorrhage. Anesthesiology 1987; 67: 498–502.
66. Morelot-Panzini C, Lefort Y, Derenne JP et al. Simplified method to
measure respiratory-related changes in arterial pulse pressure in
patients receiving mechanical ventilation. Chest 2003; 124:
665–670.
67. Reuter DA, Kirchner A, Felbinger TW et al. Optimizing fluid therapy in
mechanically ventilated patients after cardiac surgery by on-line
monitoring of left ventricular stroke volume variations: a comparison to
aortic systolic pressure variations. Br J Anesth 2002; 88: 124–126.
68. Berkenstadt H, Margalit N, Hadani M et al. Stroke volume variation as a
predictor of fluid responsiveness in patients undergoing brain surgery.
Anesth Analg 2001; 92: 984–989.
69. Marik PE, Cavallazzi R, Vasu T et al. 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.
70. Cannesson M, Le MY, Hofer CK et al. Assessing the diagnostic accuracy
of pulse pressure variations for the prediction of fluid responsiveness: a
‘gray zone’ approach. Anesthesiol 2011; 115: 231–241.
Kidney International (2013) 83, 1017–1028
review
71. Zhang Z, Lu B, Sheng X et al. Accuracy of stroke volume variation in
predicting fluid responsiveness: a systematic review and meta-analysis.
J Anesth 2011; 25: 904–916.
72. McLean AS, Huang SJ, Kot M et al. Comparison of cardiac output
measurements in critically ill patients: FloTrac/Vigileo vs. transthoracic
Doppler echocardiography. Anesth Intensive Care 2011; 39: 590–598.
73. Cannesson M, Musard H, Desebbe O et al. The ability of stroke volume
variations obtained with Vigileo/FloTrac system to monitor fluid
responsiveness in mechanically ventilated patients. Anesth Analg 2009;
108: 513–517.
74. Benes J, Chityra I, Altmann P et al. Intraoperative fluid optimization
using stroke volume variation in high risk surgical patients: results of a
prospective randomized study. Crit Care 2010; 14: R118.
75. Cecconi M, Fasano N, Langiano M et al. Goal-directed hemodynamic
therapy during elective total hip arthroplasty under regional anesthesia.
Crit Care 2011; 15: R132.
76. Sundar S, Panzica P. LiDCO systems. Int Anesthesiol Clin 2010; 48:
87–100.
77. Pearse RM, Ikram K, Barry J. Equipment review: an appraisal of the LiDCO
plus method of measuring cardiac output. Crit Care 2004; 8: 190–195.
78. Wiles MD, Whiteley WJ, Moran CG et al. The use of LiDCO based fluid
management in patients undergoing hip fracture surgery under spinal
anesthesia: neck of femur optimisation therapy- targeted stroke volume
(NOTTS): study protocol for a randomized controlled trial. Trials 2011;
12: 213.
79. Desebbe O, Cannesson M. Using ventilation-induced plethysomographic
variations to optimize patient fluid status. Curr Opin Anesthesiol 2008; 21:
772–778.
80. Natalini G, Rosano A, Taranto M et al. Arterial versus plethysmographic
dynamic indices to test responsiveness for testing fluid administation in
hypotensive patients: a clinical trial. Anesth Analg 2006; 103: 1478–1484.
81. Cannesson M, Besnard C, Durand PG et al. Relation between respiratory
variations in pulse oximetry plethysmographic waveform amplitude and
arterial pulse pressure in ventilated patients. Crit Care 2005; 9:
R562–R568.
82. Feissel M, Teboul JL, Merlani P et al. Plethysmographic dynamic indices
predict fluid responsiveness in septic ventilated patients. Intensive Care
Med 2007; 33: 993–999.
83. Cannesson M, Desebbe O, Rosamel P et al. Pleth variability index to
monitor the respiratory variations in the pulse oximeter
plethysmographic waveform amplitude and predict fluid
responsiveness in the operating theatre. Br J Anesth 2008; 101: 200–206.
84. Cannesson M, Delannoy B, Morand A et al. Does the pleth variability
index indicate the respiratory-induced variation in the plethysmogram
and arterial pressure waveforms? Anesth Analg 2008; 106: 1189–1194.
85. De Backer D, Heenen S, Piagnerelli M et al. Pulse pressure variations to
predict fluid responsiveness: influence of tidal volume. Intensive Care
Med 2005; 31: 517–523.
86. Lansdorp B, Lemson J, van Putten MJ et al. Dynamic indices do not
predict volume responsiveness in routine clinical practice. Br J Anaesth
2012; 108: 395–401.
87. Bernadin G, Tiger F, Fouche R et al. Continuous non-invasive
measurement of aortic blood flow in critically ill patients with a new
esophageal echo-Doppler system. J Crit Care 1998; 13: 177–183.
88. Dark PM, Singer M. The validity of trans-esophageal Doppler
ultrasonography as a measure of cardiac output in critically ill adults.
Intensive Care Med 2004; 30: 2060–2066.
89. Valtier B, Cholley BP, Belot JP et al. Noninvasive monitoring of cardiac
output in critically ill patients using transesophageal Doppler. Am J Resp
Crit Care Med 1998; 158: 77–83.
90. Monnet X, Rienzo M, Osman D et al. Esophageal Doppler monitoring
predicts fluid responsiveness in critically ill ventilated patients. Intensive
Care Med 2005; 31: 1195–1201.
91. Sinclair S, James S, Singer M. Intraoperative intravascular optimization
and length of hospital stay after repair of proximal femur fracture repair:
a Randomized Controlled Trial. BMJ 1997; 315: 909–912.
92. Chytra I, Pradi R, Bosman R et al. Esophageal Doppler guided fluid
management decreases blood lactate levels in multiple trauma patients:
a randomized controlled trial. Crit Care 2007; 11: R24.
93. Mowatt G, Houston G, Hernandez R et al. Systematic review of the
clinical and cost-effectiveness of esophageal Doppler monitoring in
critically ill and high-risk surgical patients. Health Technol Assess 2009;
13: 1–95.
94. Feissel M, Michard F, Mangin I et al. Respiratory changes in aortic
velocity as an indicator of fluid responsiveness in ventilated patients
with septic shock. Chest 2001; 119: 867–873.
1027
review
95. Wiesenack C, Fiegl C, Keyser A et al. Assessment of fluid responsiveness
in mechanically ventilated cardiac surgical patients. Eur J Anest 2005; 22:
658–665.
96. Yanagawa Y, Nishi K, Sakamoto T et al. Early diagnosis of hypovolemic
shock by sonographic measurement of inferior vena cava in trauma
patients. J Trauma 2005; 58: 825–829.
97. Yanagawa Y, Sakamoto T, Okada Y. Hypovolemic shock evaluated by
sonographic measurement of the inferior vena cava during resuscitation
in trauma patients. J Trauma 2007; 63: 1245–1248.
98. Sefidbakht S, Assadsangabi R, Abbasi HR et al. Sonographic
measurement of the inferior vena cava as a predictor of shock in trauma
patients. Emer Radiol 2007; 14: 181–185.
99. Weekes AJ, Tassone HM, Babcock A et al. Comparison of serial
qualitative and quantitative assessments of caval index and left
ventricular systolic function during early fluid resuscitation of
hypotensive emergency department patients. Acad Emerg Med 2011; 18:
912–921.
100. Feissel M, Michard F, Faller JP et al. The respiratory variation in inferior
vena cava diameter as a guide to fluid therapy. Intensive Care Med 2004;
30: 1834–1837.
101. Vieillard-Baron A, Chergui K, Rabiller A et al. Superior vena caval
collapsibility as a gauge of volume status in ventilated septic patients.
Intensive Care Med 2004; 30: 1734–1739.
102. Monnet X, Teboul JL. Passive leg raising. Intensive Care 2008; 34:
659–663.
103. Monnet X, Rienzo M, Osman D et al. Passive leg raising predicts fluid
responsiveness in the critically ill. Crit Care Med 2006; 34: 1402–1407.
104. Boulain T, Achard JM, Teboul JL et al. Changes in BP induced by passive
leg raising prdict response to fluid leading in critically ill patients. Chest
2002; 121: 1245–1252.
105. Teboul JL, Monnet X. Prediction of volume responsiveness in critically ill
patients with spontaneous breathing activity. Curr Opin Crit Care 2008;
14: 334–339.
106. Lafanechere A, Pene F, Goulenok C et al. Changes in aortic blood flow
induced by passive leg raising predicts fluid responsiveness in critically
ill patients. Crit Care 2006; 10: R132.
107. Cavallaro F, Sandroni C, Marano C et al. Diagnostic accuracy of passive
leg raising for prediction of fluid responsiveness in adults: systematic
review and meta-analysis of clinical studies. Intensive Care Med 2010; 36:
1475–1483.
108. Marik PE, Monnet X, Teboul JL. Hemodynamic parameters to guide fluid
therapy. Ann Intensive Care 2011; 1: 1–9.
109. Biais M, Vidl L, Sarraby P et al. Changes in stroke volume induced by
passive leg raising in spontaneously breathing patients: comparison
between echocardiography and Vigileo/FloTrac device. Crit Care 2009;
13: R195.
110. Squara P, Denjean D, Estagnasie P et al. Noninvasive cardiac output
monitoring (NICOM): a clinical validation. Intensive Care Med 2007; 33:
1191–1194.
111. Marque S, Cariou A, Chiche JD et al. Comparison between Flotrac-
Vigileo, and Bioreactance, a totally noninvasive method for cardiac
output monitoring. Crit Care 2009; 13: R73.
112. Squara P, Cecconi M, Rhodes A et al. Tracking changes in cardiac output:
methodological considerations for the validation of monitoring devices.
Intensive Care Med 2009; 35: 1801–1808.
113. Benomar B, Ouattara A, Estagnasie P et al. Fluid responsiveness
predicted by noninvasive bioreactance-based passive leg raise test.
Intensive Care Med 2010; 36: 1875–1881.
1028
K Kalantari et al.: Volume assessment
114. Lamia B, Cuvelier A, Declercq PL et al. Response of NICOM stroke volume
to passive leg raising to predict fluid responsiveness in critically ill
patients with spontaneous breathing activity. Crit Care 2010; 14
(suppl 1): R13.
115. Marik PE. Non-invasive cardiac output monitors. A state-of-the-art
review. J Cardiothorac Vasc Anesth 2012; e-pub ahead of print 18 May 2012.
116. Kossari N, Hufnagel G, Squara P. Bioreactance: a new tool for cardiac
output and thoracic fluid content monitoring during hemodialysis.
Hemodial Int 2009; 13: 512–517.
117. Monnet X, Bataille A, Magalhaes E et al. End-tidal carbon dioxide is
better than arterial pressure for predicting volume responsiveness by
the passive leg raising test. Intensive Care Med 2013; 39: 93–100.
118. Monge Garcia MI, Gil Cano A, Gracia Romero M et al. Non-invasive
assessment of fluid responsiveness by changes in partial end-tidal CO2
pressure during a passive leg maneuver. Ann Intensive Care 2012; 2: 9.
119. Monnet X, Osman D, Ridel C et al. Predicting volume responsiveness by
using the end-expiratory occlusion in mechanically ventilated intensive
care patients. Crit Care Med 2009; 37: 951–956.
120. Kuhlmann MK, Zhu F, Seibert E et al. Bioimpedance, dry weight, and
blood pressure control: new methods and consequences. Curr Opin
Nephrol Hypertens 2005; 14: 543–549.
121. Peacock WF. Use of bioimpedance vector analysis in critically ill and
cardiorenal patients. Contrib Nephrol 2010; 165: 226–235.
122. Jaffrin MY, Morel H. Body fluid volumes measurements by impedance: a
review of bioimpedance spectroscopy (BIS) and bioimpedance analysis
(BIA) methods. Med Eng Phys 2008; 30: 1257–1269.
123. Peyton PJ, Chong SW. Minimally invasive measurement of cardiac
output during surgery and critical care: a meta-analysis accuracy and
precision. Anesthesiology 2010; 113: 1220–1235.
124. Piccoli A, Pillon L, Dumler F. Impedance vector distribution by sex, race,
body mass index and age in the United States: standard reference
intervals as bivariate Z scores. Nutrition 2002; 18: 153–167.
125. Piccoli A. Whole body-single frequency bioimpedance. Contrib Nephrol
2005; 149: 150–161.
126. Kyle UG, Zhang FF, Morabia A et al. Longitudinal study of body
composition changes associated with weight change and physical
activity. Nutrition 2006; 22: 1103–1111.
127. Colı́n-Ramı́rez E, Castillo-Martı́nez L, Orea-Tejeda A et al. Bioelectrical
impedance phase angle as a prognostic factor in chronic heart failure.
Nutrition 2012; 28: 901–905.
128. Barbosa–Silva MC, Barros AJ. Bioelectric impedance and individual
characteristics as prognostic factors for post-operative complications.
Clin Nutr 2005; 24: 830–838.
129. Uzko-Lencer NH. Measuring body composition in chronic heart failure: a
comparison of methods. Eur J Heart Fail 2006; 8: 208–214.
130. Valle R, Aspromonte N, Giovinazzo P et al. B-type natriuretic peptide
guided treatment for predicting outcomes in patients hospitalized in sub-
intensive care unit with acute heart failure. J Card Fail 2008; 14: 219–224.
131. Ronco C, Kaushik M, Valle R et al. Diagnosis and management of fluid
overload in heart failure and cardio-renal syndrome: the ‘5B Approach.’.
Semin Nephrol 2012; 32: 129–141.
132. Picolli A. for the Italian Hemodialysis-Bioimpedance Analysis (HD-BIA)
Study Group. Identification of operational clues to dry weight
prescription in hemodialysis patients use bioimpedance vector analysis.
Kidney Int 1998; 53: 1036–1043.
133. Pillon L, Piccoli A, Lowrie EG et al. Vector length as a proxy for the
adequacy of ultrafiltration in hemodialysis patients. Kidney Int 2004; 66:
1266–1271.
Kidney International (2013) 83, 1017–1028