Journal of Cardiothoracic and Vascular Anesthesia 32 (2018) 901–914

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Journal of Cardiothoracic and Vascular Anesthesia

journal homepage: www.jcvaonline.com

Review Article

Assessment of Pulmonary Edema:

Principles and Practice
Sherif Assaad, MDn,1, Wolf B. Kratzert, MD, PhD†,
Benjamin Shelley, MD‡, Malcolm B. Friedman, MD§,
Albert Perrino Jr, MDn
n
Cardiothoracic Anesthesia Service, VA Connecticut Healthcare System, Yale University School of Medicine,
New Haven, CT
†
Department of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine at University of
California at Los Angeles, Los Angeles, CA
‡
Golden Jubilee National Hospital /West of Scotland Heart and Lung Centre, University of Glasgow, Glasgow,
Scotland
§
Department of Radiology and Biomedical Imaging, Yale University School of Medicine, VA Connecticut
Healthcare System, New Haven, CT

Pulmonary edema increasingly is recognized as a perioperative complication affecting outcome. Several risk factors have been identified,
including those of cardiogenic origin, such as heart failure or excessive fluid administration, and those related to increased pulmonary capillary
permeability secondary to inflammatory mediators.
Effective treatment requires prompt diagnosis and early intervention. Consequently, over the past 2 centuries a concentrated effort to develop
clinical tools to rapidly diagnose pulmonary edema and track response to treatment has occurred. The ideal properties of such a tool would
include high sensitivity and specificity, easy availability, and the ability to diagnose early accumulation of lung water before the development of
the full clinical presentation. In addition, clinicians highly value the ability to precisely quantify extravascular lung water accumulation and
differentiate hydrostatic from high permeability etiologies of pulmonary edema.
In this review, advances in understanding the physiology of extravascular lung water accumulation in health and in disease and the various
mechanisms that protect against the development of pulmonary edema under physiologic conditions are discussed. In addition, the various
bedside modalities available to diagnose early accumulation of extravascular lung water and pulmonary edema, including chest auscultation,
chest roentgenography, lung ultrasonography, and transpulmonary thermodilution, are examined. Furthermore, advantages and limitations of
these methods for the operating room and intensive care unit that are critical for proper modality selection in each individual case are explored.
Published by Elsevier Ltd.

Key Words: pulmonary edema; auscultation; chest radiography; lung ultrasound; transpulmonary thermodilution

THE LUNGS REPRESENT unique organs in which air and circulating in a permeable and pressurized capillary network.
blood are circulating efficiently, each in its own conduit Normally there is a balance between the net fluid filtered from
without mixing with one another. Air circulates in the lungs’ the pulmonary circulation and the fluid absorbed by the
bronchial and alveolar conduits that are surrounded by blood lymphatic system. This balance ensures that only a small
volume of fluid is present in the interstitial space. Excessive
1
accumulation of extravascular lung water (EVLW) is clinically
Address reprint requests to Sherif Assaad, MD, VA Healthcare System,
Department of Anesthesiology, 950 Campbell Avenue, West Haven, CT
manifested as pulmonary edema. This can result from an
06516. increase in the amount of filtered fluid secondary to marked
E-mail address: [email protected] (S. Assaad). increases in pulmonary hydrostatic pressure or an increase in

http://dx.doi.org/10.1053/j.jvca.2017.08.028
1053-0770/Published by Elsevier Ltd.
902 S. Assaad et al. / Journal of Cardiothoracic and Vascular Anesthesia 32 (2018) 901–914

the pulmonary capillary permeability, which causes water and The mechanism controlling fluid exchange between the
proteins extravasation,1 or from interruption of the lymphatic microvascular and interstitial spaces proposed by Ernest
drainage, such as what occurs in lung resection surgery.2 Starling in 1896 shaped medical thinking for more than a
Regardless of the etiology, the resultant fluid accumulation in century. He concluded that the interplay of outward filtration
the lung impairs respiratory gas exchange, resulting in forces created by the capillary hydrostatic pressure and the
respiratory distress and the need for mechanical ventilation. inward reabsorption forces from plasma protein oncotic
Pulmonary edema increasingly is being recognized as a pressure determines fluid exchange, with the capillary
perioperative complication affecting outcome. Several factors endothelium acting as a semipermeable membrane.14
have been identified (eg, fluid overload, systemic inflammatory Although this model became widely adopted as doctrine, a
response to surgery, myocardial ischemia, blood product transfu- series of experimental data beginning in the 1940s raised doubts
sion), all of which contribute to increased fluid transudation and on its merit. The discovery that an endothelial surface layer
accumulation of EVLW.3 Management strategies directed at lining the luminal side of the capillary endothelium,
avoiding excessive fluid administration (eg, goal-directed fluid as first described by Danielli 1940,15 and the nonlinear relation-
therapy) or reducing inflammatory response (eg, protective lung ship between hydrostatic pressure and vascular permeability,
ventilation to avoid ventilator-induced lung injury) commonly which represents a deviation from the classic Starling relation-
are advocated in perioperative care protocols.1,4–7 ship, revolutionized the understanding of fluid dynamics.16–18
Furthermore, pulmonary edema represents a significant Electron microscopy shows that the endothelial surface
burden to the health care system. A review of 8,195 patients layer is lined with a complex network of glycosaminoglycans
who underwent major inpatient surgeries in two university and proteins, which creates a gel-like coating. The structure of
teaching hospitals revealed an incidence of pulmonary edema this endothelial surface layer is called the endothelial glyco-
of 7.6% with an associated in-hospital mortality rate of calyx (EG) (Fig 1).19 The EG recently has been discovered to
11.9%.8 Pulmonary edema is associated with higher morbidity play a critical role in capillary fluid dynamics, preventing
rates and prolonged intensive care unit (ICU) stay, in which excessive fluid extravasation. First, it acts as a molecular sieve
15% of those diagnosed with pulmonary edema will require limiting water and solute efflux across the intercellular
mechanical ventilation.9 Furthermore, the addition of mechan- junction. Second, it provides scaffolding on which serum
ical ventilation will extend the length of stay in the ICU.10 As plasma proteins accumulate and consequently a layer of
such this complication often results in a lose-lose proposition ultrafiltrate is created between the endothelium and the EG.
because it worsens patient outcomes while greatly increasing This layer of ultrafiltrate creates a powerful oncotic force,
health care costs.11 pulling fluid to the intravascular compartment. Breakdown of
For decades, chest auscultation and roentgenography played a this layer, such as after surgical trauma and ischemic/reperfu-
major role in the diagnosis of pulmonary edema and in sion injuries, results in markedly increased capillary perme-
monitoring response to therapy. The understanding of the ability (Fig 2).17 Lastly, the EG acts as a mechanosensor,
inherent limitations of these 2 methods has led to the develop- transmitting the shear stress from blood flow to the endothe-
ment of newer technologies that offer more sensitive detection of lium cytoskeleton and initiating intracellular signaling, which
lung water changes in real time to better aid diagnosis and guide increase capillary permeability.16,20 After a marked increase in
clinical interventions.12 Of these, both the lung ultrasound (LUS) capillary hydrostatic pressure, fluid extravasates out of the
and transpulmonary thermodilution (TPTD) methods have now capillaries and accumulates in the interstitial space.
entered the clinical arena. The aim of this review is to provide an The emerging role of the EG has reshaped the current
up-to-date examination of the recent advances in understanding understanding of the pathophysiology of pulmonary edema.
the physiology of lung water dynamics in health and disease and Either damage to this EG layer or marked increases in
to highlight the various bedside methods available to measure capillary hydrostatic pressure will lead to excessive fluid
EVLW and diagnose pulmonary edema. Special emphasis is transudation into the interstitial space.
placed on the emerging roles of LUS and TPTD as new tools to
quantitatively measure EVLW in the perioperative period and
provide early diagnosis of pulmonary edema.

Current Concepts in Pulmonary Fluid Dynamics

Extravascular Lung Water in Health and Disease

It is a remarkable feat of engineering that prevents the air-

filled alveoli and surrounding interstitium from being soaked
by the neighboring pulmonary vessels. Pressurized and highly
permeable, there is a strong motive force driving pulmonary
capillary fluids across the microvascular endothelium into the
interstitium and air sacs. Yet the interstitium is a relatively dry Fig 1. Electron microscopy reveals vascular capillary in cross-section and its
space with an EVLW of o10 mL/kg of ideal body weight.13 associated EG layer. Adapted from Rehm et al.19
 S. Assaad et al. / Journal of Cardiothoracic and Vascular Anesthesia 32 (2018) 901–914 903

Fig 2. (A) An intact EG covers the luminal endothelial surface and cell-cell junctions limiting water and electrolyte efflux. (B) Breakdown of the glycocalyx layer,
such as seen after surgery or ischemic/reperfusion injury, results in increased vascular permeability and pulmonary edema. Adapted from Collins et al.17

Role of Pulmonary Capillary Pressure and Hydrostatic Edema cuffs increased 70% when transpulmonary pressure was
increased to 20 cmH2O.26 Further accumulation of interstitial
The pulmonary capillary wedge pressure or left atrial fluid is limited by the low compliance of the interstitial
pressure are clinically used as indicators of the pressure in compartment. This protective mechanism is short-lived sec-
the pulmonary microvasculature, although they are not the ondary to fragmentation of interstitial proteoglycans causing
same as the pulmonary capillary hydrostatic pressure. The loss of matrix integrity.27
relationship between pulmonary microvascular hydrostatic
pressure and left atrial pressure can be estimated by the Progression to Pulmonary Edema
following equation:
Pmv ¼ PLa þ 0:4ðMPAP–PLa Þ Whether a result of increases in hydrostatic forces or
increases in permeability, fluid accumulation progresses in a
where Pmv is the pulmonary microvascular hydrostatic pres- defined sequence. In stage 1 (“compensated”), fluid accumula-
sure, PLa is left atrial pressure, and MPAP is mean pulmonary tion increases but is balanced by the increase in lymphatic flow
pressure.21 resulting in no net accumulation of fluids. Stage 2 (“perihilar
To mitigate EVLW accumulation after increases in capillary edema”) develops when the lymphatic flow is overwhelmed by
hydrostatic pressure and cardiac output, the pulmonary circu- the increase in fluid accumulation and edema starts to develop
lation exhibits several protective mechanisms, namely recruit- surrounding the bronchioles and lung vasculature, yielding the
ment and distention of the pulmonary capillaries.22 In an classic roentgenographic pattern of interstitial pulmonary
animal model, it was found that the EVLW accumulation did edema (Kerley B lines, indistinct vessels, peribronchial cuff-
not change significantly until microvascular hydrostatic pres- ing). Stage 3 (“alveolar edema”) develops after further accu-
sure more than doubled, supporting a wide safety margin mulation of interstitial fluid, which tracks first around the
against rises in microvascular hydrostatic pressure.21,23 How- periphery of the alveolar membrane (stage 3a) and finally
ever, conditions associated with further rise in hydrostatic disrupts the alveolar wall, causing alveolar flooding (stage 3b),
pressure, such as excessive fluid administration or heart which results in impairment in the gas exchange, yielding the
failure, can overwhelm these mechanisms, resulting in fluid roentgenographic image of alveolar pulmonary edema.28 The
extravasation and pulmonary edema. ability to track the progression of lung water accumulation and
to determine its causative etiology remain the Holy Grail for
Role of Lymphatics in Fluid Clearance clinical assessment of pulmonary edema.

The pulmonary lymphatics are present along the peribronch- Clinical Techniques to Assess Extravascular Lung Water
ovascular, interlobular septa, and the pleural spaces. These
loose connective tissue spaces serve as a sump suction system, Auscultation
draining fluid away from the alveolar interstitium in early
stages of EVLW accumulation.24 The effectiveness of this Although symptoms and signs from the patient examination
lymphatic sump drainage was demonstrated by Zarins et al, (tachypnea, orthopnea) can suggest pulmonary edema, it was
who showed that the lymph flow is about 20 mL/h under not until the advent of chest auscultation, and later the
normal conditions and increases 5- to 10-fold with chronic development of the stethoscope, that clinicians had a more
elevations in interstitial pressure.25 Gee and Williams deter- objective means to assess for lung edema. Auscultation
mined that water content contained by the peribronchovascular remains a highly valued diagnostic tool that is in wide use
904 S. Assaad et al. / Journal of Cardiothoracic and Vascular Anesthesia 32 (2018) 901–914

Fig 3. Laënnec’s stethoscope. (A) 1, Instrument assembled; 2 and 3, two portions of the instrument in longitudinal section; 4, detachable chest piece; 5, earpiece
unscrewed; 6, transverse section. (B) Laennec and the Stethoscope, from "The History of Medicine" painting by Robert A. Thom [1915-1979], circa 1952,
University of Michigan Museum of Art, Ann Arbor, MI. A courtesy the US National Library of Medicine. B adapted from Roguin A.29

today despite the development of more sophisticated technol- nonmusical adventitious sounds normally heard in inspiration.
ogies. The ability to diagnose different lung diseases using They are classified according to their duration, loudness, and
chest auscultation initially was explored by Hippocrates, who timing in the respiratory cycle as fine or coarse crackles
placed his ears directly on the patient’s chest to hear (Fig 4).31 Importantly, fine crackles are produced within small
transmitted sounds and called this procedure “direct ausculta- airways often affected by interstitial edema, whereas coarse
tion.” The development of the stethoscope, first using a rolled crackles arise from large bronchi in processes such as
paper cone and later a hollow wooden tube, by the French pneumonia.32 The mechanism of production of fine crackles
physician René Laënnec in the 19th century brought ausculta- is the snap opening of small airways during inspiration after
tion into the focus of clinical practice (Fig 3).29 Laënnec, being collapsed during expiration. In cardiogenic pulmonary
through extensive medical practice, was the first to classify edema, crackles occur due to opening of the small airways
different breath sounds, which he then determined to be narrowed by peribronchial edema.33 They are detected as high-
pathognomonic of pulmonary pathologies, including pneumo- pitched, long duration sounds beginning in late inspiration.
nia, bronchiectasis, and pulmonary edema. In his landmark They typically are best appreciated in posterior basal regions
publication, A Treatise on the Diseases of the Chest and on in supine patients.
Mediate Auscultation, he described the classic auscultatory The stethoscope is an inexpensive, accessible, bedside tool
findings in pulmonary edema as deep crepitus inspiratory rales that has been in common practice for more than a century,
that convey the impression of air entering and distending dry despite significant limitations of its usefulness. These limita-
lungs.30 tions include wide interobserver variability, inadequate under-
Rales, a term that has been replaced by “crackles” in modern standing of the mechanism of sound production in different
practice, remain the key diagnostic feature of auscultation in pathologies, failure to detect lung water accumulation in its
pulmonary edema. These are discontinuous, explosive, and early phases, and difficulty in monitoring the progression of

Fig 4. Classification of pulmonary crackles. ‖Time in milliseconds from the onset of the crackle until the first deflection returns to the baseline. Adapted from
Andrews J, Badger T31 Cugel D, et al.,106 Murphy RLH Jr, et al.,107 VBenjamin Burrows,108 Forgacs P.109
 S. Assaad et al. / Journal of Cardiothoracic and Vascular Anesthesia 32 (2018) 901–914 905

the disease.34 In a study on acute respiratory distress syndrome

(ARDS) patients, lung auscultation had a diagnostic accuracy
of 55% compared with thoracic computed tomography (CT).35
Lung auscultation also was shown to have a very low power to
discriminate mild and moderate pulmonary congestion com-
pared with LUS in patients with end-stage renal disease on
hemodialysis.36
A clinician’s hearing loss due to increasing age or disease is
an additional limitation of stethoscopy.37 Stethoscopes com-
patible with hearing aids and electronic stethoscopes using
sophisticated mathematical models have been introduced into
clinical practice in an attempt to overcome some of the
limitations and improve its sensitivity and specificity for lung
water detection.38,39
The stethoscope remains an important part of the physical Fig 6. Chest roentgenogram features of ARDS showing patchy opacities. The
indistinct vessels signify interstitial edema, whereas the airspace disease
examination, but because of its shortfalls, it is becoming a signifies alveolar edema.
decorative instrument for many practitioners, who increasingly
rely on more sensitive and reliable technologies.
be used as clues to the cause and severity of the pulmonary
edema. Table 1 highlights the radiographic findings associated
Chest Roentgenography with disease severity. For example, stage 2 pulmonary edema
appears as a perihilar process, whereas the more severe stage
The chest roentgenogram has been relied on to diagnose and 3 appears as a generalized flooding of the lung fields.40–43
follow the progression of pulmonary edema for decades. It Radiologists often seek out a pattern of chest roentgenogram
quickly established itself as the standard reference technique findings to differentiate between cardiogenic (eg, congestive
against which other methods to measure lung water content heart failure [CHF]), noncardiogenic (eg, ARDS), and fluid
were compared. It offers the advantages of being widely overload (eg, renal failure) causes of edema (Table 2).44,45
available, reproducible, noninvasive, portable, and relatively Using these chest roentgenogram features, Milne et al showed
low in cost. an average of 91% accuracy in distinguishing capillary
Standard imaging uses the posteroanterior and lateral views, permeability edema from other varieties and 81% accuracy
or in the case of portable examinations, the anteroposterior in distinguishing cardiogenic edema from that of renal
view. Interstitial features of pulmonary edema manifest radio- failure.44
graphically as peribronchial cuffing, indistinct vessels, and Gluecker et al offered further insight into radiographic
septal (Kerley) lines (Fig 5). In distinction, alveolar features patterns to allow for the differentiation between a myriad of
present with acinar opacities, ground glass opacities, and frank causes of pulmonary edema (eg, the bilateral perihilar alveolar
consolidations (Fig 6). The appearance of these features and edema “bat-wing” appearance in patients with acute severe
patterns of distribution and other accompanying findings can CHF or renal failure that can improve rapidly with aggressive
treatment).42 Septal lines, peribronchial cuffing and, if severe,
alveolar edema are markers for negative pressure or post-
obstructive edema. Kerley lines, peribronchial cuffing, and
patchy perihilar airspace consolidation are seen in near-
drowning cases. Bilateral homogenous airspace consolidation
favoring the upper lobes is typical of neurogenic edema.
Central interstitial edema (peribronchial cuffing, indistinct
vessels) and asymmetric patchy airspace consolidation are
findings in high-altitude edema. A spectrum from modest
interstitial (Kerley lines, peribronchial cuffing, and indistinct
vessels) to severe alveolar (consolidation) is seen in post-
pneumonectomy edema.42 Accordingly, the ability of chest
roentgenogram patterns to be used to differentiate pathology
and predict response to therapy is highly valued in the clinical
setting.
From a physiologic standpoint, radiographic features of
acute cardiogenic pulmonary edema generally correlate with
the pulmonary capillary wedge pressures. The chest roentgen-
ogram can be normal with mildly elevated pressures, but with
Fig 5. Chest roentgenogram features of cardiogenic pulmonary edema. increasing pressures and fluid transudation, various features
906 S. Assaad et al. / Journal of Cardiothoracic and Vascular Anesthesia 32 (2018) 901–914

Table 1
Chest Roentgenogram Findings in Acute Cardiogenic Pulmonary Edema

Pulmonary Edema Severity PCWP (mmHg) Radiographic Findings Normal Value Abnormal Value

Stage 1 Vascular pedicle width o53 mm 453 mm

Pulmonary vascular congestion 12-17 Cephalization (upper v lower lung vessel caliber) Lower 4 upper Upper 4 lower
Cardiothoracic ratio (heart width/thorax width) o0.5 40.5
Stage 2 17-20 Kerley B lines (thin horizontal lines to pleura) Absent Visible
Interstitial pulmonary edema 20-25 Vascular indistinctness (vessel to lung interface) Sharp Indistinct
Peribronchial cuffing (thickened end on bronchial walls) Pencil thin Thickened
Stage 3 425 Ground glass opacification Absent Present
Alveolar edema Lung consolidation Absent Present

Abbreviation: PCWP, pulmonary capillary wedge pressure.

become evident.42,43 Early on, in cardiac compromise and/or roentgenogram lacked quantitative measurement of EVLW
volume overload, radiographic findings of enlarged heart, that can be advantageous to guide fluid management and was
engorged upper lobe vessels, or widened vascular pedicle are insensitive to the detection of small changes in EVLW and
considered “pre-edema” features. With progressive EVLW failed to predict mortality compared with TPTD.48 In an
accumulation, the chest roentgenogram typically begins to animal study, chest radiography did not detect EVLW until
show features associated with pulmonary edema (eg, Kerley lung water had increased 4 35%.49 Although chest roentgen-
lines, indistinct vessels, peribronchial cuffing, and airspace ogram was able to be used to distinguish temporal changes in
opacities). lung water in critically ill patients randomly assigned to
Despite these advantages, the clinical environment has receive a diuretic or placebo,50 it failed to accurately monitor
shown substantial limitations with chest roentgenographic modest changes in lung water.51
monitoring. For example, the well-described relationship The degree of interobserver variation in chest roentgenogra-
between pathology and imaging has a clinical correlation that phy represents another concern. In a study of 21 expert
is less than desired.46,47 In addition, there often is a time lag of radiologists selected to review 28 chest radiographs of ARDS
up to 12 hours after the clinical and physiologic manifestations patients on mechanical ventilation, the interobserver variability
of CHF to the appearance of radiographic findings due to the ranged from 36% to 71% in diagnosing ARDS according to
relatively slow movement of water through the widened the American-European Consensus Conference definition of
capillary endothelial cell junction. Similarly, with resolution ARDS.52 Many anesthesiologists practicing in ICUs make
of pulmonary edema, the radiographic findings will persist for important clinical decisions guided by radiographic interpreta-
1 to 4 days after physiologic and clinical improvement.46 tions. Given the challenges faced by radiologists, it is no
Limitations in accuracy also must be considered. In the surprise the radiographic interpretation in patients with sig-
diagnosis of alveolar-interstitial pulmonary edema, the accu- nificant pulmonary diseases can exceed the skills of many
racy of chest roentgenogram was shown to be only 72% anesthesiologists.53
compared with CT in a case-control study.35 In a study of The suboptimal quality of portable images is another
ARDS patients, chest roentgenogram correlated modestly with disadvantage, which particularly affects perioperative and
TPTD-measured EVLW. The authors noted that chest critical care clinicians. In portable, supine radiographs, the
evaluation of heart and vessel size is limited; however,
alveolar and interstitial edema and possibly pleural effusions
Table 2
still can be evaluated. Similarly, chest fluoroscopy is not
Common Chest Roentgenogram Features Differentiating Between Cardio-
genic, Noncardiogenic, and Hypervolemia Pulmonary Edema preferred to evaluate for pulmonary edema because its fidelity
for assessment of fluid accumulation is even inferior to that of
Cardiogenic Noncardiogenic Hypervolemia a portable chest radiograph (eg, evaluation of pulmonary
Heart size Enlarged Normal Enlarged
vessels, bronchial walls, interstitial lines).54 In current practice
Vascular pedicle Normal or Normal or reduced Enlarged the use of fluoroscopy is out of favor because the digital chest
width enlarged radiograph can be obtained portably and is almost instantly
Pulmonary blood Inverted Normal or balanced Balanced available for review.
flow (cephalization) Regardless of technique, chest roentgenography lacks the
Pulmonary blood Normal or Normal Increased
volume increased
fidelity obtained with CT in which the extent and character-
Kerley lines Not common Absent Not common ization of airspace disease (ground glass opacity and con-
Peribronchial Common Uncommon Common solidation) are more vividly portrayed, as are certain interstitial
cuffing features such as septal lines and pleural effusions. In addition,
Pleural diffusion Common Uncommon Common although the radiation exposure of a chest roentgenogram is far
Air bronchograms Uncommon Common Uncommon
less than that of CT, cumulative radiation exposure with
Adapted from Milne EN et al.44 repeated examinations remains a concern.
 S. Assaad et al. / Journal of Cardiothoracic and Vascular Anesthesia 32 (2018) 901–914 907

Despite these shortfalls, chest roentgenography continues to ARDS, or pulmonary fibrosis, and only identification of AIS
be widely used as a tool to monitor pulmonary edema in ICUs. on LUS in conjunction with other pathologic image patterns
However, clinical desire for more accurate and timely gui- enables the skilled sonographer to differentiate these etiologies
dance of fluid therapy and more sensitive detection of early (Table 3).60 AIS in the setting of left atrial hypertension and
lung water changes are leading to the adoption of newer increased hydrostatic pressure often shows a uniform distribu-
technologies. tion pattern of B-lines, with normal lung sliding and a high
incidence of homogenous-appearing pleural effusions. In
Lung Ultrasound contrast, ultrasound findings suggestive of ARDS include
increased amounts of B-lines seen in combination with pleural
LUS has become a valuable point-of-care (POC) tool in the line abnormalities, lack of lung sliding, uneven tissue patterns
assessment of acute pulmonary pathologies in the ICU, such as “spared areas” and consolidations, and consolidation-
emergency department, and operating room. Based on visua- associated findings such as “lung pulse” (which is defined as
lization of anatomic structures, pathologic findings, and the absence of lung sliding with the perception of heart activity
acoustic artifacts, specific image patterns can be identified at the pleural line) and air bronchograms (Fig 9).
for the differentiation of a variety of pulmonary disease and When pattern recognition is used in an algorithmic
pleural disease states.55 Whereas healthy lung tissue is poorly approach, like the Bedside Lung Ultrasound in Emergency
penetrated by ultrasound due to the high acoustic impedance protocol, LUS has a diagnostic accuracy of 495% sensitivity
of air, the presence of EVLW results in the occurrence of the and specificity for a broad variety of pulmonary and pleural
so-called B-lines, or lung comets, which are formed as a pathologies.61,62 This contrasts with chest roentgenogram or
result of acoustic reverberation artifacts arising from the clinical examination including auscultation, or both, that
air-fluid interface between collapsed, fluid-filled, and aerated showed a sensitivity of 7% to 14% in patients with documen-
alveoli.56,57 ted AIS using LUS in the perioperative period of cardiac
First described in 1982,58 specific characteristics distinguish surgery.63
B-lines from other artifacts seen on LUS, and they represent The correlation of B-line artifacts as a marker of increased
the core-imaging finding used in the evaluation of pulmonary EVLW shows similar high accuracy, with sensitivities and
edema. Sonographic appearance of normal lung tissue is specificities of 490% compared with multiple classic methods
defined by “black” lung with sliding movement of visceral of assessing EVLW, such as CT of the chest,62,64 chest
and parietal pleura against each other and horizontal reverbera- roentgenogram,35,65 pulmonary occlusion pressures,66,67 brain
tion artifact of the pleural line in equal distance—termed natriuretic peptide measurements,68 or TPTD method to measure
A-lines, as shown in Video 1. EVLW.66 In addition, the linear correlation between quantity of
B-lines are well-defined, hyperechoic artifacts arising from B-lines, amount of EVLW, and clinical pulmonary edema has
the pleural line fanning down into the far field of the screen been well-recognized, and application of quantitative algorithms,
without fading (Fig 7). Whereas healthy lung tissue may such as lung comet scores, may provide a useful clinical tool in
display 3 to 4 B-lines correlating with radiographic Kerley the daily POC assessment for pulmonary edema.65,66,69
B lines, the presence of more than 3 B-lines (also called lung Over the last decade multiple studies have established good
rockets) is indicative of interstitial edema. With further temporal correlation between the amount of EVLW and the
increase in EVLW, a rising number of B-lines are seen in onset and resolution of B-lines.65,66,70 In addition, Caltabeloti
narrower distance apart, and they can merge to display ground et al found that loss in lung aeration in patients with sepsis
glass rockets, also called “white lung,” seen in severe states of receiving fluid resuscitation could be detected using LUS
alveolar-interstitial syndrome (AIS) (Fig 8).59 Sonographic within 40 minutes, even before changes in oxygenation
appearance of AIS can be seen with multiple underlying determined with the partial pressure of arterial oxygen
pathologies such as cardiogenic acute pulmonary edema, to fraction of inspired oxygen ratio.71 Furthermore, the

Fig 7. Normal LUS. (A) A-lines reverberation artifact in equal distance (arrows). (B) B-lines (stars) arising as a well-defined echogenic comet tail from the pleural
line throughout the entire ultrasound image.
908 S. Assaad et al. / Journal of Cardiothoracic and Vascular Anesthesia 32 (2018) 901–914

Fig 8. CXR and LUS of normal lung and AIS. (A) Normal AP-CXR. (B) CXR in mild AIS. (C) CXR in severe AIS. (D) Ultrasound findings of normal lung tissue
with A-lines (arrows) and B-line (star), smooth pleural interface, and homogenous lung tissue. (E) Ultrasound findings of mild interstitial pulmonary edema with
lung rockets (stars). (F) Ultrasound findings in severe AIS with ground glass rockets or “white lung,” with persistent smooth pleural line and homogenous lung
tissue suggestive of severe pulmonary edema secondary to APE. AP, anteroposterior; APE, acute cardiopulmonary edema; CXR, chest radiography.

immediate dynamic changes of B-lines in correlation to hemodialysis.72,73 These findings confirm the clinical advan-
volume removal in patients while undergoing hemo- tage of LUS in the immediate and dynamic feedback of
dialysis was shown in renal failure patients undergoing severity of pulmonary edema compared with chest radiograph.
The clinical use of LUS in evaluating increases in EVLW is
Table 3 ample. It ranges from initial POC diagnostic modality for
Sonographic Findings Used to Differentiate Etiology of AIS respiratory failure to guidance of patient care to, finally,
follow-up monitoring of performed clinical interventions.
Sonographic Findings Cardiogenic ALI/ARDS
Currently the overwhelming use remains in the diagnosis
Uniform distribution of AIS þ - and management of respiratory failure and guidance in volume
Pleural effusion þ þ /- resuscitation. Standardized algorithms used for the assessment
Pleural line abnormalities - þ of EVLW and lung pathologies optimize sensitivity and
Reduction/absence of lung sliding - þ
“Spared areas” - þ
specificity while making it a fast and practical tool in daily
Lung consolidations - þ clinical management.69,74,75 In a study of patients undergoing
Consolidation-associated findings cardiac surgery, the combined use of transthoracic echocardio-
Lung pulse - þ graphy and LUS was shown to change the clinical manage-
Air bronchogram - þ ment in 67% of patients. Furthermore, LUS was able to be
Abbreviations: AIS, alveolar-interstitial syndrome; ALI/ARDS, acute lung used to detect alveolar interstitial disease that was missed by
injury/acute respiratory distress syndrome. clinical examination and chest roentgenography.76
 S. Assaad et al. / Journal of Cardiothoracic and Vascular Anesthesia 32 (2018) 901–914 909

Fig 9. LUS of AIS. Acute cardiogenic edema versus ARDS. (A) LUS findings suggestive of AIS secondary to acute cardiogenic edema include ground glass
rockets or “white lung” with persistent smooth pleural line and homogenous lung tissue. (B) LUS findings suggestive of AIS secondary to severe ARDS include
“white lung” in combination with thickened and uneven pleural line, inhomogenous lung tissue, and air bronchograms (arrows).

Using 5-13 MHz linear array, or 1 to 6 MHz phased array Transpulmonary Thermodilution
ultrasound probes, multimodal scanning of the anterior and
lateral lung at different locations is applied to achieve a TPTD uses a cold indicator delivered into a central vein and
panoramic impression of the complete lung and pleura.77 Even detected by a thermistor tipped catheter in the aorta (either in
though most of the literature focuses on the advantages, the femoral or axillary artery), resulting in the recording of a
accuracy, and feasibility of LUS for the diagnosis of pulmon- thermodilution curve. A variety of physiologic parameters
ary edema and other pathologies, little data have been including cardiac output, intrathoracic volumes, and EVLW
published on outcomes when used to guide patient manage- are obtained from this curve. The presence of pulmonary
ment. One study by Frassi et al showed that LUS is a more edema results in a heat sink with increased indicator loss
powerful predictor for significant events in patients with (ie, warming of the fluid bolus) during pulmonary transit. This
symptoms of dyspnea or chest pain on hospital admission loss of indicator is used to quantify EVLW. The calculation of
than echocardiographic variables.78 In addition, Soummer et al EVLW using the TPTD method is beyond the scope of this
suggested a predictive value of LUS in the weaning process review. A detailed review of this technique is available in the
from mechanical ventilation. In their study, B-lines predomi- authors’ previous publication.3 As such, clinical measurement
nance was associated with increased respiratory failure after of EVLW reflects a morphologic correlate of pulmonary
extubation.79 edema.83
The advantages of LUS as an economic, fast, and real-time Compelling evidence supports the ability of TPTD to be
imaging modality for diagnosis and surveillance of clinical used to characterize progressive accumulation of pulmonary
relevant pathologies has positioned the technique at the center edema. In a porcine model of hydrostatic pulmonary edema,
of POC diagnostics in critical care medicine, emergency Bongard et al demonstrated the association between EVLW
medicine, and anesthesiology. Its high accuracy and absence and the classical histologic progression of pulmonary edema.83
of radiation exposure surpasses its confinements as a non- EVLW measurements have a strong linear association with
panoramic imaging modality compared with chest roentgen- increases in perivascular cuff width to vessel diameter ratio
ogram or CT in the daily management of patients. (r ¼ 0.87; p o 0.0001); interalveolar septal width (r ¼ 0.89;
Variability of practitioner knowledge and lack in standar- p o 0.001); and, once present, alveolar flooding (r ¼ 0.87;
dized training are challenges to the expanded use of LUS. To p o 0.001).83
address these concerns, the American College of Chest The sensitivity of TPTD to be used to detect early and small
Physicians and La Société de Réanimation de Langue Fran- changes in pulmonary edema is another strong asset to this
caise published a joint statement on competence in critical care modality. Fernandez-Mondejar et al examined the ability of
ultrasonography.80 TPTD EVLW measurement to detect “small changes” in
In anesthesiology and other medical disciplines, training EVLW in pigs both with and without pulmonary edema.84
programs are being initiated to ensure uniformity and con- By measuring EVLW immediately before and after intratra-
sistency in education and the evaluation of proficiency for the cheal administration of 50 mL of saline solution (so increasing
use of ultrasound.81,82 EVLW [alveolar fluid] by 50 mL), they demonstrated that
910 S. Assaad et al. / Journal of Cardiothoracic and Vascular Anesthesia 32 (2018) 901–914

TPTD could be used to detect these modest increases in to aid the clinician in determining the etiology of edema.
EVLW. Putting these results in context with the observations Measurement of EVLW in the context of cardiac preload92
of Bongard et al,83 who suggested that increases in EVLW in (ie, calculation of the ratio of EVLW to cardiopulmonary
excess of 100% are required before the onset of hypoxemia or blood volume) can provide a means to estimate pulmonary
histologic changes, is exciting because EVLW measurement vascular permeability. Intrathoracic blood volume,92–94 global
may be able to be used to sensitively detect subclinical end-diastolic volume,93,95 and pulmonary blood volume93–95
increases in EVLW, potentially facilitating early intervention. are indices of cardiac preload derived from TPTD to which
Several authors have demonstrated modest association EVLW has been indexed in the derivation of “pulmonary
between chest roentgenogram scores and TPTD-derived vascular permeability indices.” The concept is intuitive;
EVLW.48,85,86 The existence of only modest association a high EVLW in a hypovolemic patient (therefore an elevated
between the 2 modalities, ostensibly measuring the same ratio) suggests increased capillary permeability as the
thing, may reflect the superior sensitivity and specificity of primary pathology, whereas a high EVLW in a patient with
EVLW measurement; increased chest roentgenogram opacity elevated preload (normal ratio) suggests increased hydrostatic
is not specific to the existence of pulmonary edema, whereas forces.
the superior sensitivity of TPTD for small increases in EVLW TPTD methods for measuring EVLW can only measure
means that EVLW may exist, be measureable by TPTD, but lung water in perfused areas of lung and therefore rely on a
undetectable by chest roentgenogram. homogenous distribution of pulmonary perfusion to accurately
Another major advantage of the TPTD technique for determine EVLW. A large perfusion deficit will lead to
measuring pulmonary edema over imaging modalities is its underestimation of EVLW. Regional pulmonary perfusion is
inherent reproducibility. Both TPTD monitors available for influenced by many factors pertinent to the perioperative
clinical use (Fig 10)87,88 achieve values for the coefficient of critically ill population. Hypoxic pulmonary vasoconstric-
variation of EVLW ranging from 4.8% to 8%,89,90 which is tion,96 lung injury,97 vascular obstruction,98 positive end-
well within the 15% threshold of coefficient of variation that expiratory pressure,99,100 spontaneous breathing,101 and lung
has been suggested as a cutoff for clinical acceptability.91 In resection102 all can influence ventilation-perfusion relation-
practice, manual inspection of thermodilution curves at the ships and lead to errors in the estimation of EVLW.
time of measurement allows for clearly spurious measurements It is plausible that the presence of pleural or pericardial
to be discarded and adds further increased reliability. effusions could provide an additional extravascular fluid
TPTD requires central venous and arterial cannulation, volume into which cold indicator could distribute, leading to
limiting hospital-wide application of the technique. In patients an artifactual overestimation of the EVLW volume. Blomqvist
in intensive care or during the perioperative period in which et al systematically evaluated the effects of incremental
invasive monitoring is commonplace, however, TPTD-derived increases in pleural fluid volume (warmed normal saline
EVLW measurement has many benefits. Once TPTD monitor- introduced bilaterally via intercostal catheters) on EVLW in
ing is established, junior medical or nonmedical staff with otherwise healthy dog lungs. They reported a slight, but not
minimum training may easily and rapidly perform a series of statistically significant, rise in EVLW, and even though “a
thermodilution measurements. This ease of use and the minor, and for practical purposes negligible loss of thermal
absence of ionizing radiation mean that EVLW can be indicator to the pleural fluid could not be excluded,” they
determined repeatedly multiple times a day, allowing for ultimately concluded that installation of up to 20 mL/kg of
trends to be observed and for continuous monitoring of an fluid into the pleural cavity has no effect on EVLW.103
evaluation of response to therapy. Similarly, several clinical studies in medical intensive care
In addition to providing an index of the presence and patients undergoing thoracentesis have demonstrated no effect
severity of pulmonary edema, TPTD also offers the potential of pleural effusion on EVLW measurement.104,105

Fig 10. Screenshots from 2 proprietary TPTD systems commercially available. (A) The PiCCO2 system (Maquet, Rastatt, Germany) and (B) the VolumeView/
EV1000 system (Edwards Lifesciences, Irvine, CA). CI, cardiac index; GEDI, global end diastolic index; PCCI, pulse contour cardiac index; ScvO2, mixed venous
oxygen saturation; SVI, stroke volume index; SVV, stroke volume variation.
 S. Assaad et al. / Journal of Cardiothoracic and Vascular Anesthesia 32 (2018) 901–914 911

In summary, EVLW with other TPTD-derived parameters of pulmonary edema and its resolution. Despite these limita-
offer an insight for clinicians to explore and portray a patient’s tions, resource availability and the wealth of information
hemodynamic instability in depth. provided by chest roentgenograms and the availability of
TPTD-derived EVLW offers a unique means to quantify expert radiologists for interpretation continue to support its
and diagnose pulmonary edema early, track the progression widespread use in current practice.
and response to therapy, and help differentiate its etiology. Its LUS is a recent advance that addresses many of the
relative invasive nature limits its use to hemodynamically limitations inherent in chest auscultation and chest roentgen-
unstable patients in the ICU or to the operating room for ogram. It has the advantage of being able to be used to detect
patients undergoing surgeries that carry a high risk for lung early phases of EVLW accumulation before clinical manifes-
injury (eg, major cardiothoracic and vascular surgeries). tations, allowing the clinician to implement clinical interven-
tions before overt clinical manifestations. Its property of higher
Modality Selection specificity and sensitivity than that seen with prior techniques
promotes its use both as an initial screening and monitoring
In current practice the practitioner’s selection among auscul- modality. One of its most useful applications is in the
tation, chest roentgenogram, LUS, or TPTD to assess for perioperative period for early detection of acute interstitial
pulmonary edema is influenced by clinical and institutional pulmonary edema, especially in patients who present for
factors. The demands of the case at hand, along with the surgery without any preoperative respiratory symptoms. Its
expertise and resources available in the clinical setting, noninvasiveness, including no ionizing radiation, has led to
dictate the modality to be used. To aid in this selection process, LUS frequently being used in conjunction with or as a
the advantages and limitations of the various modalities in the replacement to chest roentgenograms. However, in contrast
clinician’s armamentarium are summarized in Table 4. to chest radiography that is supported by specialized radiology
Stethoscopy remains an important component of the initial technicians and physicians, the lack of available personnel
clinical examination. As a tool, it shows high specificity but at with skill in performance and interpretation of LUS limits its
the cost of low sensitivity, lacking in the ability to be used for use in many institutions. This remains an educational chal-
early detection of pulmonary congestion with a limited ability lenge for training institutions.
to inform on the severity of pulmonary edema. As such it is Invasive hemodynamic monitors are frequently required
recommended primarily as a readily available and inexpensive during major surgical procedures, such as cardiac, major
screening tool. vascular, or thoracic surgery, or in clinical conditions, such as
Chest roentgenography remains the modality of choice in septic shock, that carry a high risk for lung injury. In these
postanesthesia care units and ICUs to initially diagnose, profile patients, TPTD offers unique advantages. It provides several
the etiology, and subsequently monitor patients with pulmon- hemodynamic indices to guide therapeutic management. In
ary edema. Its panoramic view of the chest helps clinicians in addition, the ability to quantitatively measure EVLW accumula-
the identification of additional pulmonary pathologies coexist- tion at its earliest phase and assess its progression or improve-
ing with pulmonary edema. ment is particularly advantageous to these patient groups. As
To avoid clinical errors, clinicians must remain cognizant of such, TPTD monitoring offers a combination of benefits not
the limited accuracy of chest roentgenogram for both early obtainable with other modalities. Recognizing that its invasive-
detection and grading of the severity of EVLW accumulation. ness limits its use to select patients, the information provided by
As such, chest roentgenogram is another modality with high TPTD currently is unrivaled by competing technologies.
specificity and low sensitivity. Furthermore, the temporal
changes in the radiographic evidence of pulmonary congestion Conclusion
lag the clinical manifestations both in its detection of the onset
Pulmonary edema is a long-recognized morbid condition. In
Table 4 response, during the past 2 centuries the development of a
Comparison of Methods Used to Detect Pulmonary Edema on a Scale of Worst series of technologic approaches for its detection and monitor-
( þ) to Best ( þ þ þ þ) ing have occurred. Today’s clinician benefits from an arma-
mentarium of devices to assess lung water, each of which is
Auscultation CXR LUS TPTD
best suited to a particular application. The selection of
Availability þþþþ þþþ þþ þþ modality for the case at hand requires not only an under-
Ease of use þþþþ þþþ þþ þþþ standing of the unique advantages and limitations of these
Low cost þþþþ þþþ þþ þþ approaches but also the availability of expertise in each
Freedom from radiation þþþþ þ þþþþ þþþþ
Lack of invasiveness þþþþ þþþþ þþþþ þ
modality’s application and interpretation.
Early detection of EVLW þ þ þþþþ þþþþ
Etiology detection þ þþ þþþ þþþ Appendix A. Supplementary Material
Sensitivity for small þ þþ þþþ þþþþ
changes in EVLW Supplementary data associated with this article can be found
Abbreviations: CXR, chest roentgenography; EVLW, extravascular lung in the online version at http://dx.doi.org/10.1053/j.jvca.2017.
water; LUS, lung ultrasound; TPTD, transpulmonary thermodilution. 08.028.
912 S. Assaad et al. / Journal of Cardiothoracic and Vascular Anesthesia 32 (2018) 901–914

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