Review Article

Cardiorenal Med 2022;12:141–154 Received: August 2, 2022

Accepted: August 26, 2022
DOI: 10.1159/000526902 Published online: September 12, 2022

Diagnosis of Fluid Overload: From

Conventional to Contemporary Concepts
Abhilash Koratala a Claudio Ronco b, c Amir Kazory d
aDivision
of Nephrology, Medical College of Wisconsin, Milwaukee, WI, USA; bDepartment of Nephrology,

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San Bortolo Hospital and International Renal Research Institute of Vicenza (IRRIV), Vicenza, Italy; cDepartment of
Medicine, University of Padova, Padova, Italy; dDivision of Nephrology, Hypertension, and Renal Transplantation,
University of Florida, Gainesville, FL, USA

Keywords Introduction
Fluid overload · Heart failure · Point-of-care
ultrasonography · Point-of-care ultrasound · Critical illness Recognizing and treating fluid overload (FO) is a key
component of managing patients with heart failure (HF).
The pathophysiology of FO is complex and involves an
Abstract interplay of absolute volume gain, fluid redistribution
Fluid overload has been associated with morbidity and mor- from venous capacitance beds to the central venous cir-
tality in various clinical scenarios including heart failure and culation, and inadequate elimination due to renal dys-
critical illness. It exerts pathologic sequelae in almost all the function, salt and water retention, and endothelial dys-
organ systems. Proper management of patients with fluid function. FO leads to hemodynamic congestion charac-
overload requires knowledge of the underlying pathophysi- terized by elevated cardiac filling pressures, which
ology, objective evaluation of volume status, selection of ap- subsequently results in clinical congestion manifested by
propriate therapeutic options, and maintenance and modu- signs and symptoms such as orthopnea, elevated jugular
lation of tissue perfusion. There are several methods to ap- venous pressure (JVP), peripheral edema, and rales [1]. It
praise volume status but none without limitations. In this is well recognized that in patients hospitalized for decom-
review, we discuss the diagnostic utility, prognostic signifi- pensated HF, persistent congestion at discharge portends
cance, and shortcomings of various bedside tools in the de- worse outcomes [2–5]. In the recent past, the deleterious
tection of fluid overload and evaluation of hemodynamic effects of FO are being increasingly recognized in other
status. These include clinical examination, biomarkers, blood clinical settings such as critical illness where empiric ad-
volume assessment, bioimpedance analysis, point-of-care ministration of intravenous fluid (IVF) is a common sce-
ultrasound, and remote pulmonary pressure monitoring. In nario. In a meta-analysis including 19,902 patients admit-
our opinion, clinicians must adopt a multiparametric ap- ted to the intensive care unit (ICU), the cumulative fluid
proach offsetting the limitations of individual methods to balance after 1 week of ICU stay in nonsurvivors was
formulate a management plan tailored to patients’ needs. found to be 4.4 L more than in survivors. Moreover, a re-
© 2022 The Author(s). strictive fluid management was associated with a lower
Published by S. Karger AG, Basel mortality compared to liberal fluid administration (24.7

[email protected] © 2022 The Author(s). Correspondence to:

www.karger.com/crm Published by S. Karger AG, Basel Abhilash Koratala, akoratala @ mcw.edu
This is an Open Access article licensed under the Creative Commons
Attribution-NonCommercial-4.0 International License (CC BY-NC)
(http://www.karger.com/Services/OpenAccessLicense), applicable to
the online version of the article only. Usage and distribution for com-
mercial purposes requires written permission.
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Fig. 1. Pathologic effects of fluid overload in various organs/organ systems. BioRender® was used to create the figure.

vs. 33.2%; p < 0.0001) [6]. Similarly, in a cohort of criti- quent impaired organ perfusion is gaining recognition
cally ill patients with cirrhosis, a higher median fluid bal- challenging the traditional forward flow-centric para-
ance 7 days post-ICU admission (+13.50 vs. +6.90 L; p = digm and shifting the focus from “fluid responsiveness”
0.036) was associated with an increased risk of in-hospital to “fluid tolerance” [23, 24]. Objective assessment of fluid
mortality [7]. Interestingly, a recent clinical trial demon- status is a critical step in timely detection of FO and titrat-
strated that restrictive fluid management strategy is safe ing therapy to optimize hemodynamics. Though accu-
in patients with septic shock compared to standard care rate, the utility of invasive modalities such as pulmonary
(i.e., liberal strategy); although the outcome was not su- artery catheterization is limited to a small subset of criti-
perior in the restrictive group, it is notable that the stan- cally ill patients and does not necessarily improve out-
dard care group received substantially less fluid com- comes [25]. In this review, we will provide an overview of
pared to prior studies (a median of 3.8 L) [8]. While a various bedside tools/laboratory tests in the evaluation of
direct causative relationship cannot be established be- FO and congestion focusing on but not limited to HF.
tween FO and mortality based on the current evidence, it
is a potentially preventable cause of iatrogenic morbidity;
there are data that suggest FO adversely affects almost all Clinical Examination
the organ systems [9, 10] (Fig. 1). For example, FO leads
to pulmonary edema, low lung compliance, increased Careful history taking and physical examination of the
work of breathing [11, 12]; delirium, raised intra-cranial cardiopulmonary system are the first steps in the manage-
pressure [13–15]; prolonged ileus, impaired hepatic syn- ment of patients with FO. These are intended to detect
thetic function, cholestasis, impaired drug absorption increased cardiac filling pressures and their consequenc-
[16, 17]; impaired cardiac contractility and conduction es. However, as mentioned, hemodynamic congestion
abnormalities [18, 19]; acute kidney injury (AKI) [20, 21]; may exist in the absence of clinical congestion. Therefore,
impaired wound healing [22]; and so forth. Furthermore, it is conceivable that the sensitivity of these findings is
the contribution of FO to venous congestion and conse- relatively low to detect ongoing congestion; sole reliance

142 Cardiorenal Med 2022;12:141–154 Koratala/Ronco/Kazory

DOI: 10.1159/000526902
on them to manage patients eventually leads to clinically <500 pg/mL) conferred a favorable outcome in one study
apparent FO and recurrent hospitalizations. For instance, [32]. Nevertheless, natriuretic peptide-guided therapy
in a study including 50 HF patients with severely reduced was not associated with superior cardiovascular outcome
ejection fraction (18%), the combined sensitivity of rales, compared to standard care in patients with HF with re-
edema, and elevated mean JVP was just 58% to detect an duced ejection fraction in two recent clinical trials [33,
elevated pulmonary capillary wedge pressure of ≥22 mm 34]. Moreover, approximately 20–35% of outpatients
Hg despite good specificity [26]. Similarly, in a meta- with HF with preserved ejection fraction may exhibit a
analysis of 22 studies including patients presenting with state of intermittent or chronic natriuretic peptide defi-
dyspnea [27], pooled sensitivities of orthopnea, periph- ciency despite coexisting hemodynamic congestion [35,
eral edema, JVP, third heart sound, and rales were only 36]. Additionally, the concentrations of natriuretic pep-
50%, 51%, 39%, 13%, and 60%, respectively, to diagnose tides are elevated in patients with renal dysfunction ow-
congestive HF. Only parameter among these with a posi- ing to impaired clearance limiting their utility [28].
tive likelihood ratio above 10 was the third heart sound
(S3 gallop), which ironically had the lowest sensitivity. In Lactate
summary, most of the conventional physical examination HF is classically described as a condition in which the

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findings are helpful when present, but their absence does cardiac pump is not able to support adequate oxygen de-
not exclude congestion. Patients’ weight is useful but lim- livery to the tissues [37]. Surprisingly however, blood lac-
ited by documentation errors, inaccurate calibration of tate, a marker of tissue hypoperfusion, is normal in ∼75%
the equipment, and inability to detect redistribution-re- of patients with advanced HF and a widened arterio-ve-
lated FO. nous oxygen difference [38]. On the other hand, the risk
of mortality is higher in patients with acute HF who have
elevated lactate levels on hospital admission [39]. Al-
Biomarkers though HF treatment may reduce lactate levels, it is un-
clear whether lactate-guided treatment translates into
Several biomarkers have been studied in patients with better clinical outcomes. This is even more vague in the
HF, which can be broadly classified into markers of in- context of septic shock where reduced lactate clearance
flammation (C-reactive protein, myeloperoxidase), fi- (as opposed to increased production) may prompt the cli-
brosis and extracellular remodeling (procollagen, galec- nician to administer IVF in the absence of tissue hypoper-
tin-3, ST2), mechanical strain/stretch (natriuretic pep- fusion, contributing to iatrogenic FO [40]. For instance,
tides, CD146, carbohydrate antigen 125 [CA125]), in the ANDROMEDA-SHOCK trial, lactate-guided re-
markers of hemodynamic homeostasis (adrenomedullin, suscitation group received an excess of 400 mL of IVF
copeptin), tissue perfusion (lactate), and cardiomyocyte within the first 8 h compared to the capillary refill time-
injury (troponins) [28, 29]. Herein, we discuss some of guided group while having more organ dysfunction at 72
the commonly tested biomarkers in clinical practice. In h [41].
the ICU setting, their utility is often limited because of
variable specificity and presence of multiple confounding Hemoglobin and Hematocrit
factors. Expansion of plasma volume (PV) leads to decreased
red blood cell concentration (hemodilution) and vice ver-
Natriuretic Peptides sa. Therefore, hemoconcentration or increasing hemato-
Natriuretic peptides are frequently used as an adjunct crit with fluid removal has been purported as a surrogate
to clinical assessment in patients presenting with symp- for evaluating decongestion and plasma refill rate [42]. In
toms suggestive of HF. In fact, B-type natriuretic peptide a study including 102 patients hospitalized for acute HF,
(BNP) levels have an excellent negative predictive value hemodilution during the first 3 days was associated with
(96% at levels ≤50 pg/mL) for HF diagnosis in such pa- a severe degree of pulmonary edema compared to those
tients [30]. In addition, they carry prognostic significance who had hemoconcentration (85 vs. 63%, p < 0.01). Ad-
with observational studies showing better outcomes in ditionally, HF-related readmission rate was higher in the
patients whose levels decrease in response to deconges- hemodilution group (34 vs. 9%, p < 0.01) [43]. Likewise,
tive therapy [28, 31]. Similar findings have been observed in the post hoc analysis of the PROTECT trial [44], a rap-
in critically ill patients with septic cardiomyopathy id increase in hemoglobin level during the first week was
though the data are sparse; a decline in BNP over time (to independently associated with a favorable outcome, de-

Fluid Overload Cardiorenal Med 2022;12:141–154 143

DOI: 10.1159/000526902
spite a slight decline in renal function in patients hospital- known volume (V) and its concentration (C) is measured.
ized with HF. Conversely, a subset of patients with HF Then, the unknown volume can be calculated by the for-
may have true polycythemia as a response to chronic low mula, V = q/C [46]. In the method that is commercially
cardiac output state, hypoxemic tissue perfusion, and tis- available currently (BVA-100 Blood Volume Analyzer;
sue acidosis; this may predispose to increased risk of Daxor Corp., New York, NY, USA), a standard dose of
thrombosis and myocardial work burden from blood hy- radioactive iodine-labeled albumin (I-131) is injected in-
perviscosity. In such cases, clinicians must exercise cau- travenously. A pre-injection blood sample is collected fol-
tion not to mistake dilution-related pseudo-anemia for lowed by a series of samples at timed intervals once the
true anemia, especially if contemplating erythropoietin tracer has fully circulated in the bloodstream. Plasma ra-
therapy [45, 46]. Quantitative analysis of PV may be help- dioactivity of each sample is then measured using a semi-
ful in some cases to titrate diuretic therapy based on ad- automated computerized counter which calculates pa-
justed red blood cell volume. tient’s PV by comparing the concentration of undiluted
tracer prior to injection to the tracer concentration di-
Carbohydrate Antigen 125 luted over time due to transudation of albumin into ex-
CA125 is a high molecular weight transmembrane gly- tracellular space (Fig. 2). Total BV is determined based on

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coprotein used in the diagnosis and prognostication of the measured PV and patient’s hematocrit [50]. Normal
ovarian cancer. In the recent past, there has been a re- total BV is generally defined as measured volumes within
newed interest in its role as a biomarker for congestion in ±8% (approximately 3 standard deviations) of the expect-
HF. It has been proposed that CA125 is shed from meso- ed normal for the patient, and red blood cell mass and PV
thelial cell surfaces in response to mechanical stress such as measured volumes within ±10% of expected normal.
as FO, and inflammatory stimuli. High CA125 levels are Mild to moderate total BV expansion is defined as >8%
associated with the presence of serosal fluid and positive- (>10% for red blood cell mass and PV) to <25%, and se-
ly correlate with inflammatory markers including serum vere expansion as ≥25% of the normal volume [51]. In a
TNF-α, IL-6, and IL-10 levels in patients with HF [47]. In cohort of 177 patients hospitalized for HF (mixed ejection
a systematic review and meta-analysis including 23 stud- fraction), decongestion strategy guided by admission
ies investigating its role in HF management, serum levels BVA was associated with lower 30-day mortality and re-
of CA125 were found to increase in parallel with decline admission rates compared to propensity-matched con-
in cardiac function from the New York Heart Association trols (2.0 vs. 11.1% and 12.2 vs. 27.7%, respectively; p <
(NYHA) class I/II to III and further from class III to IV. 0.001) [52]. In another study including 26 HF patients, 24
Further, HF patients with higher CA125 level had poorer of whom were hypervolemic at hospital admission (BV
outcomes [48]. In a recent prospective observational +39%), there was only marginal decrease (+30%) in BV at
study including 191 patients admitted with acute HF, discharge despite large reductions in body weight (−6.9
CA125 has demonstrated a positive and independent as- kg) [53]. This observation is in line with previously re-
sociation with the presence of peripheral edema, pleural ported data raising concerns about inadequate deconges-
effusion, and an increased diameter of the inferior vena tion when using conventional monitoring tools.
cava (IVC). On the other hand, NT-proBNP was associ- The utility of BVA is generally limited in critically ill
ated with pleural effusion and IVC diameter but not pe- patients with hemodynamic instability or those undergo-
ripheral edema. Notably, CA125 exhibited a better cor- ing acute volume transitions as the analysis presumes
relation with IVC diameter [49]. These findings have led steady-state conditions. Nevertheless, carefully selected
to the premise that CA125 is a better marker for right patients at increased risk for FO may benefit from this
heart dysfunction and venous congestion whereas NT- technique. In a clinical trial including 100 critically ill sur-
proBNP is more indicative of left-sided filling pressures gical patients, Yu et al. [54] have demonstrated that BVA-
and pulmonary congestion. guided fluid management strategy is associated with im-
proved outcome compared to control group managed ac-
cording to pulmonary artery catheter parameters
Quantitative Blood Volume Analysis (mortality rate 8 vs. 24%, p = 0.03) . As mentioned, BVA
can provide information about albumin transudation
Blood volume analysis (BVA) is based on the indica- rate based on the dilution of tracer over time. In an inter-
tor-dilution technique, in which a known quantity of a esting case series including 4 critically ill patients with
substance (q) is dissolved in a fluid compartment of un- COVID-19, Bakker et al. [55] leveraged this characteristic

144 Cardiorenal Med 2022;12:141–154 Koratala/Ronco/Kazory

DOI: 10.1159/000526902
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Fig. 2. Principle of blood volume assessment: a dose of albumin from the intravascular to the extravascular space (depicted as the
I-131 tracer is injected intravenously. Once the tracer has fully cir- pink dots moving outside the red vein), its quantity decreases in-
culated in the bloodstream, a series of small blood samples are travascularly implying a higher dilution factor and therefore high-
drawn. The blood volume analyzer automatically calculates pa- er blood volume. Red line represents the regression calculation of
tient’s blood volume by comparing the concentration of undiluted the analyzed draws to time 0 or time of injection, which indicates
tracer prior to injection to the tracer concentration diluted in the the level of true total intravascular blood volume. The red line is
patient blood samples. The human figures represent sequential also a measure of albumin transudation, a measure of capillary
calculated blood volumes at the recommended intervals for draw- permeability. Figure adapted from https://www.daxor.com/how-
ing blood samples after tracer injection. As the tracer transudates bva-100-works/ with kind permission of Daxor Corporation.

to assess capillary permeability . Larger studies are needed reveal alternative causes of dyspnea, coexisting thoracic
to understand how this information can be utilized to ti- diseases, and valvular or pericardial calcification. Notably,
trate therapy. a normal chest radiograph should not be used to exclude
the diagnosis of HF as up to 20% of the patients presenting
with acute HF do not demonstrate any radiographic ab-
Chest Radiography normalities. A supine chest radiograph further limits the
diagnostic utility [56, 57]. Having said that, residual pul-
Chest radiography is the most common modality used monary congestion at hospital discharge assessed by ra-
in the diagnosis of acute HF and FO. Key findings include diographic scoring has shown to predict worse outcome
central vascular congestion, interstitial edema with Kerley outperforming physical assessment, echocardiographic
B-lines, cardiomegaly, and pleural effusions. It may also parameters, and BNP [58]. In our practice, we prefer lung

Fluid Overload Cardiorenal Med 2022;12:141–154 145

DOI: 10.1159/000526902
ultrasonography over chest radiographs to diagnose and or narrow the differential or guide a procedure. Over the
monitor congestion. In addition to being radiation-free, past several years, multi-organ POCUS has evolved as an
ultrasound has better diagnostic accuracy for the detec- adjunct to physical examination in specialties such as
tion of cardiogenic pulmonary edema. For instance, in a emergency medicine, critical care, and nephrology [74,
recent meta-analysis, sensitivity and specificity for lung 75]. We previously proposed the pump-pipes-leaks ap-
ultrasound compared to chest radiography were 91.8% proach to conduct a goal-directed POCUS-assisted he-
versus 76.5% and 92.3% versus 87%, respectively [59]. modynamic evaluation in patients with HF and FO [76].
Pump represents focused cardiac ultrasound (FoCUS),
pipes represent IVC ultrasound and Doppler assessment
Bioimpedance Analysis of venous congestion, and leaks signify extravascular
lung and abdominal fluid. This allows assessment of both
Bioimpedance analysis (BIA) involves application of al- forward flow and effects of elevated cardiac filling pres-
ternating current to the body and measuring changes in im- sures.
pedance/resistance as it relates to changes in volume. It can
be used to quantify total body water, intracellular water, ex- Focused Cardiac Ultrasound

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tracellular water, protein, and fat levels. BIA has been suc- In patients presenting with symptoms and signs of FO,
cessfully employed in the assessment of peri-operative fluid a quick subjective assessment or “eyeballing” of the left
depletion, measuring body composition in chronic HF, liver ventricular (LV) size and motion provides a qualitative
disease, and kidney disease [60–63]. In patients undergoing estimate of EF, which is reasonably accurate when per-
maintenance dialysis, there are conflicting data on whether formed by noncardiologists with short training [77]. In
routine BIA-guided dry weight adjustment portends favor- addition, presence or absence of pericardial effusion,
able outcomes. For example, a single-center study showed gross valvular dysfunction, and chamber enlargement
BIA-guided ultrafiltration strategy confers mortality benefit can be evaluated. Volume overload and acute pressure
compared to routine care (hazard ratio [HR] 0.1, p = 0.03) overload are associated with right ventricular (RV) en-
[64]; these findings were not replicated in other clinical trials largement and interventricular septal flattening in dias-
in hemodialysis as well as peritoneal dialysis patients though tole (leading to a D-shaped LV assessed in the parasternal
there was a suggestion toward better FO control [65–67]. It short axis cardiac view), whereas chronic pressure over-
might still benefit a selected subset of these patients with dif- load causes flattening in both systole and diastole [78, 79].
ficult to manage fluid status as FO negatively impacts qual- RV enlargement is often associated with functional tri-
ity of life [68]. In patients with acute HF, BIA reliably reflects cuspid regurgitation, which further exacerbates RV over-
changes in hydration status, correlates with echocardio- load at end-diastole as well as causes increased right atri-
graphic parameters, natriuretic peptide levels, and predicts al pressure (RAP) and central venous congestion [80].
hospital length of stay. However, BIA-guided decongestive IVC ultrasound can be used to estimate RAP. Figure 3
therapy has not shown to be superior compared to standard shows FoCUS images obtained from a patient who pre-
care with respect to outcome [69–72]. In critically ill pa- sented with HF exacerbation and FO. There was near-
tients, the accuracy of BIA as a measure of hydration status complete resolution of the septal flattening and tricuspid
remains unclear at this time [73]. A key limitation of BIA is regurgitation after approximately 14 L fluid removal. Us-
its inability to detect the location of extracellular volume ex- ers trained in Doppler applications can assess stroke vol-
pansion (e.g., pleural effusion vs. pulmonary edema vs. asci- ume at the bedside by measuring LV outflow tract veloc-
tes vs. venous congestion). Further, misinterpretation of the ity time integral. This helps get an idea of the cardiac in-
results can occur if the patient’s body position is not correct, dex and also evaluate fluid responsiveness in selected
or electrodes cannot be appropriately placed due to chest patients, potentially avoiding iatrogenic FO [76]. Fur-
hair, diaphoresis, or skin lesions. thermore, ability to perform Doppler-enhanced FoCUS
allows assessment of LV filling pressures, which can be
used to titrate diuretic therapy in the outpatient setting.
Point-Of-Care Ultrasonography For example, in a study including 1,135 patients with HF
with reduced ejection fraction, the group in which man-
Point-of-care ultrasonography (POCUS) is a limited agement was guided by LV filling pressures and BNP lev-
bedside ultrasound examination performed by the clini- el had a lower incidence of death (HR 0.45, p < 0.0001),
cian to answer focused questions to confirm a diagnosis and death or worsening renal function (HR 0.49, p <

146 Cardiorenal Med 2022;12:141–154 Koratala/Ronco/Kazory

DOI: 10.1159/000526902
 a b

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c d

Fig. 3. Cardiac ultrasound images obtained from a patient with head] on the apical 4-chamber view (c); images at hospital dis-
heart failure exacerbation: at presentation, diastolic interventricu- charge (b–d) demonstrate near-complete resolution of these ab-
lar septal flattening is seen on the parasternal long axis view (a), normalities. RV, right ventricle; LV, left ventricle.
qualitatively moderate to severe tricuspid regurgitation [arrow-

0.0001) compared to standard care group over a median IVC Ultrasound

follow-up of 37.4 months [81]. In critically ill patients, the IVC size and collapsibility are used to estimate RAP
diagnostic utility of FoCUS is well established, particu- and are standard components of comprehensive echo-
larly in the context of undifferentiated hypotension and cardiography. However, the correlation between IVC pa-
acute respiratory failure [82–85]. With respect to prog- rameters and right heart catheterization-derived RAP is
nostication, echocardiographic markers of both LV and modest at best [88–90] and not valid in mechanically
RV dysfunction have shown to be associated with in- ventilated patients [91]. In addition, IVC POCUS is sub-
creased morality in these patients [86, 87]. Currently, ject to numerous technical pitfalls limiting its practical
there are no randomized controlled trials that have exam- utility, especially when interpreted in isolation [24]. Hav-
ined the effect of FoCUS on improving outcomes in crit- ing said that, IVC is a good indicator of fluid tolerance as
ical illness. It is unlikely that such a trial will ever be per- a plethoric IVC almost always indicates elevated RAP in
formed owing to difficulty of defining outcome variables patients with high pretest probability of FO; in other
beyond mortality, the difficulty of recruiting ICU teams words, such patients have elevated right-sided filling
with clinical equipoise, and developing standardized pressures and are intolerant to IVF administration. In
treatment protocols based on FoCUS findings in hetero- patients with HF, an elevated IVC diameter has shown to
geneous groups [82]. be associated with adverse outcomes. For example, in a

Fluid Overload Cardiorenal Med 2022;12:141–154 147

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Fig. 4. Venous excess ultrasound (VExUS) grading: when the di- is considered mildly abnormal when the pulsatility is 30–50%, and
ameter of IVC is >2 cm, three grades of congestion are defined severely abnormal when it is ≥50%. Asterisks represent points of
based on the severity of abnormalities on hepatic, portal, and renal pulsatility measurement. Renal parenchymal vein Doppler is mild-
parenchymal venous Doppler. Hepatic vein Doppler is considered ly abnormal when it is pulsatile with distinct S, D components, and
mildly abnormal when the systolic (S) wave is smaller than the severely abnormal when it is monophasic with D-only pattern. Fig-
diastolic (D) wave, but still below the baseline; it is considered se- ure adapted from NephroPOCUS.com with permission.
verely abnormal when the S-wave is reversed. Portal vein Doppler

study involving 80 patients hospitalized for acute HF, an pressure (RAP) impairs perfusion and leads to organ
admission IVC diameter ≥1.9 cm was associated with a dysfunction (e.g., AKI). A protocol to quantify system-
higher mortality at 90 days (25.4 vs. 3.4%; p = 0.009) and ic venous congestion called venous excess ultrasound
180 days (29.3 vs. 3.4%; p = 0.003) [92]. Similarly, in a (VExUS) has been recently validated in cardiac surgery
large cohort of HF patients (N = 355) managed in the patients and is rapidly gaining acceptance in various
ambulatory care clinic, every 0.5 cm increase in the IVC clinical settings including HF and critical illness [94].
diameter was associated with a 38% increase in risk of HF In a nutshell, VExUS involves assessing flow patterns in
admission (risk ratio [RR] 1.38, p < 0.01). The risk of HF hepatic, portal, and renal parenchymal veins and as-
admission increased proportionately in those with IVC signing a score based on the severity of flow alteration.
diameter 2–2.49 cm (RR 1.79, p < 0.01) versus ≥2.5 cm Figure 4 depicts the VExUS scoring system, and Figure
(RR 2.39, p < 0.01) compared to patients with diameter 5 illustrates waveforms obtained from a patient with se-
<2 cm [93]. vere congestion. Notably, neither IVC nor components
of VExUS can differentiate between pressure overload
Venous Congestion Assessment by Doppler Ultrasound (e.g., pulmonary hypertension) and volume overload,
Doppler evaluation of the systemic veins allows us to and hence, the findings must be interpreted in the ap-
gauge the downstream effects of elevated RAP. This is propriate clinical context. Regardless of the cause, a
important as the organ perfusion depends on both in- high VExUS score still indicates end organ congestion.
flow and outflow pressures; increase in the outflow In the original study [94], presence of severe flow ab-

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DOI: 10.1159/000526902
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Fig. 5. Left panel: Plethoric IVC (arrowhead), diastolic (D)-only pattern on hepatic vein Doppler, pulsatile portal
vein Doppler, and D-only or monophasic renal parenchymal vein Doppler obtained from a patient with fluid
overload and severe venous congestion; right panel: normal-appearing IVC with <2 cm diameter (arrowhead)
and normal venous waveforms.

normalities in two or more of the abovementioned diovascular morbidity and death [97, 98]. A key advan-
veins together with a dilated IVC (≥2 cm) has shown to tage of these Doppler waveforms is that they are dy-
predict the risk of AKI (HR 3.69, p = 0.001), outper- namic and allow monitoring the response to deconges-
forming isolated central venous pressure measurement. tive therapy in real time [99–105]. Clinical trials are in
Several other studies demonstrated prognostic signifi- progress to study the effect of waveform-guided thera-
cance of individual components of VExUS. For exam- py on patient outcomes [24].
ple, in another cardiac surgery cohort, portal vein pul-
satility and altered intra-renal venous flow were associ- Lung POCUS
ated with AKI (HR 2.09, p = 0.02, and HR 2.81, p = Lung POCUS can detect extravascular lung water be-
0.003, respectively) [95]. A prospective observational fore the onset of symptoms, even outperforming chest
study evaluated the prognostic utility of VExUS in 114 radiography in diagnosing cardiogenic pulmonary ede-
patients admitted to medical ICU [96]; abnormal he- ma [59, 106]. In normal state, the lung tissue is not vi-
patic vein Doppler flow has shown to predict 30-day sualized on ultrasound as the underlying air scatters the
risk of kidney events with an odds ratio of 4; however, ultrasound beam. Instead, a bright shimmering pleural
portal and renal parenchymal venous abnormalities did line followed by equidistant hyperechoic horizontal ar-
not share this association. The heterogenous nature of tifacts called the A-lines is seen. B-lines, which are ver-
AKI in an unselected cohort of critically ill patients tical hyperechoic artifacts, occur when the air content
could have contributed to the discrepancy. In the con- in the lung decreases due to interstitial thickening (typ-
text of HF, flow alterations in renal parenchymal veins ically from fluid). The number of B-lines correlates with
have shown to confer worse prognosis in terms of car- the degree of pulmonary edema and dynamically re-

Fluid Overload Cardiorenal Med 2022;12:141–154 149

DOI: 10.1159/000526902
 a b c

Fig. 6. Common lung ultrasound findings: A-lines (arrows; a); B-lines (arrows; b); right pleural effusion (asterisk;
c). IVC, inferior vena cava.

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duces with decongestive therapy [107]. Caution must Other POCUS Applications
be exercised as B-lines are not specific to cardiogenic In patients with FO, POCUS helps identify ascites,
pulmonary edema and can be seen in conditions such bowel wall edema, and ileus [76]. POCUS can also aid in
as acute respiratory distress syndrome, pneumonia, the assessment of JVP in cases where the vein is difficult
lung fibrosis, and contusion. A pleural effusion appears to visualize. JVP can be estimated by measuring the height
as an anechoic area above the diaphragm, around the of the collapse point (analogous to highest point of ve-
atelectatic lung (Fig. 6). Prognostic significance of lung nous pulsation in the inspection method) or change in the
ultrasound-detected pulmonary congestion has been vein diameter with respiration/head positioning or as-
well established in multiple clinical settings including sessing change in the cross-sectional area with Valsalva
HF, hemodialysis, and critical illness [108]. For exam- maneuver in spontaneously breathing patients [117, 118].
ple, in a cohort of 185 HF patients who underwent lung Jugular vein POCUS has shown to correlate well with
POCUS in the outpatient clinic, those who had ≥3 B- congestion parameters as well as mortality in patients
lines on an 8-zone scanning protocol had 4-fold higher with HF [119, 120]. However, it is prone to misinterpreta-
risk of the primary outcome, i.e., a composite of HF tion due to inadvertent excess transducer pressure, inap-
hospitalization or all-cause mortality (adjusted HR propriate patient positioning, restricted access to the neck
4.08, p < 0.001) [109]. Notably, auscultation was normal because of the presence of catheters, tracheostomy col-
in 81% of these patients, highlighting the poor sensitiv- lars, braces, etc. Requirement of additional instruments
ity of conventional physical examination. Likewise, in a such as a ruler and a card to accurately measure the height
cohort of 349 patients admitted for acute HF, the risk of the collapse point is another limitation, especially in
of HF hospitalization or all-cause mortality was signifi- the acute care settings [121, 122].
cantly higher in patients with a greater number of B-
lines at discharge (HR 3.3 at 60 days, p = 0.002; 2.94 at Remote Pulmonary Pressure Monitoring
90 days, p = 0.003; 2.01 at 180 days, p = 0.021) [110]. In Wireless implantable hemodynamic monitoring sys-
patients with end-stage kidney disease undergoing he- tems (e.g., CardioMEMS HF System [Abbott Medical,
modialysis, those with severe congestion, defined as Inc., Abbott Park, IL, USA]) allow remote monitoring of
>60 B-lines on a 28-zone lung POCUS, had a 4.2-fold the pulmonary artery pressures and titrate decongestive
risk of death and 3.2-fold risk of cardiac events adjusted therapy. In a prospective multi-center study, ambulatory
for NYHA class and other risk factors [111]. While lung patients managed using CardioMEMS had a 39% reduc-
POCUS-guided therapy has not shown to have mortal- tion in HF-related hospitalization compared with the
ity benefit, favorable outcomes have been demonstrated control group (HR 0.64, p < 0.0001) during a mean fol-
in terms of reduced hospital admissions in HF patients low-up of 15 months [123]. Due to its partially invasive
[112, 113]; improved ambulatory blood pressure and nature (right heart catheterization is needed to implant
LV filling pressures in hemodialysis patients [114, 115]; the sensor) and the need for trained personnel to manage
and improved lung aeration scores in critically ill pa- therapy based on the readings, patients who might ben-
tients on mechanical ventilation [116]. efit from this modality must be carefully selected. Fur-

150 Cardiorenal Med 2022;12:141–154 Koratala/Ronco/Kazory

DOI: 10.1159/000526902
thermore, pressure-based assessment of congestion in Conflict of Interest Statement
ambulatory HF patients does not accurately represent in-
Amir Kazory received consultancy fee from Baxter Inc. The
travascular volume and diuretic titration may not always other authors have no conflicts of interest to declare.
be the appropriate therapeutic choice [124].

Funding Sources
Conclusions and Future Directions
No specific financial support was obtained for preparation of
It is well recognized that FO has detrimental effects on this article.
organ function and portends worse patient outcomes.
While several bedside tools and techniques are available
for objective assessment of fluid status, each suffers from Author Contributions
inherent limitations. Physicians must be aware of these
Abhilash Koratala drafted the initial version of the manuscript.
limitations and adopt a multiparametric approach to for- Amir Kazory and Claudio Ronco reviewed and revised the manu-
mulate individualized management plan for their pa- script for critical intellectual content. Abhilash Koratala, Claudio

Downloaded from http://karger.com/crm/article-pdf/12/4/141/3709411/000526902.pdf by guest on 21 February 2024

tients. Such an approach eventually needs standardiza- Ronco, and Amir Kazory have approved the final version for sub-
tion, independent validation with a randomized con- mission.
trolled trial design to demonstrate precision, and
reproducibility of the findings as well as impact on the
measurable outcomes.

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