Respiratory Medicine 214 (2023) 107279

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Respiratory Medicine
journal homepage: www.elsevier.com/locate/rmed

A practical approach to pseudoexudative pleural effusions

Gaurav Mohan a, *, Poorva Bhide a, Abhinav Agrawal b, Viren Kaul c, Udit Chaddha d
a
Department of Internal Medicine, Rutgers-Monmouth Medical Center, Long Branch, NJ, USA
b
Division of Pulmonary, Critical Care & Sleep Medicine, Zucker School of Medicine at Hofstra/Northwell, New Hyde Park, NY, USA
c
Crouse Health/SUNY Upstate Medical University, Syracuse, NY, USA
d
Division of Pulmonary, Critical Care & Sleep Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA

A R T I C L E I N F O A B S T R A C T

Keywords: Light’s criteria falsely label a significant number of effusions as exudates. Such exudative effusions with tran­
Pseudoexudate sudative etiologies are referred to as “pseduoexudates”. In this review, we discuss a practical approach to
Exudate correctly classify an effusion that may be a pseudoexudate. A PubMed search yielded 1996 manuscripts between
Transudate
1990 and 2022. Abstracts were screened and 29 relevant studies were included in this review article. Common
Light’s criteria
Pleural effusion
etiologies for pseudoexudates include diuretic therapy, traumatic pleural taps, and coronary artery bypass
grafting. Here, we explore alternative diagnostic criteria. Concordant exudates (CE), defined as effusions where
proteins in pleural fluid/serum (PF/SPr) > 0.5 and pleural fluid LDH level of >160 IU/L (>2/3 upper limit of
normal) confer higher predictive value to the Light’s criteria. Serum-pleural effusion albumin gradient (SPAG) >
1.2 g/dL and serum-pleural effusion protein gradient (SPPG) > 3.1 g/dL together yielded a sensitivity of 100% in
heart failure and a sensitivity of 99% in hepatic hydrothorax whe n identifying pseudoexudates (Bielsa et al.,
2012) [5]. Pleural fluid N-Terminal Pro Brain Natriuretic Peptide (NTPBNP) offered a specificity and sensitivity
of 99% in identifying pseudoexudates when using a cut-off of >1714 pg/mL (Han et al., 2008) [24]. However, its
utility remains questionable. Additionally, we also looked at pleural fluid cholesterol and imaging modalities
such as ultrasound and CT scan to measure pleural thickness and nodularity. Finally, the diagnostic algorithm we
suggest involves using SPAG >1.2 g/dL and SPPG >3.1 g/dL in effusions classified as exudates when there is a
strong clinical suspicion for pseudoexudates.

3. Pleural fluid LDH more than 2/3rd of the upper limit of normal for
serum LDH
1. Introduction
Light’s criteria are designed to be exquisitely sensitive to exudates as
these effusions often need further diagnostic work-up, as they are usu­
Pleural effusions affect around 1.5 million patients in the United
ally secondary to an underlying inflammatory, infectious, or neoplastic
States (US) each year and contribute to a healthcare burden of about $5
etiology. This, however, compromises on the specificity of these criteria,
billion [1]. The management of pleural effusions is largely based on the
which implies that effusions that are commonly transudative, such as
underlying etiology. Based on fluid chemistry, pleural effusions are
those related to heart, renal or liver failure, can be misclassified as ex­
broadly classified as transudates or exudates. This dichotomization
udates by Light’s criteria [3,4]. This misclassification occurs in up to
helps guide further workup to determine the underlying etiology. The
20–30% of effusions associated with liver or heart failure [5,6]. Such
differentiation between transudates and exudates has been based pri­
effusions are referred to as “pseduoexudates” as their underlying etiol­
marily on the criteria put forward by Light et al. [2]. A pleural effusion is
ogy would usually cause an effusion that is transudative but they are
considered to be an exudate if it meets at least one of the following
classified as exudative based on the Light’s criteria. In this review, we
criteria.
discuss a practical approach to pleural effusions that have been labeled
as pseudoexudates.
1. Pleural fluid protein to serum protein ratio of more than 0.5
2. Pleural fluid lactate dehydrogenase (LDH) to serum LDH ratio of
more than 0.6

* Corresponding author. 735 Greens Ave Apt 22A, Long Branch, NJ, 07740, USA.
E-mail addresses: gm718@scarletmail.rutgers.edu, gaurav.mohan@rwjbh.org (G. Mohan).

https://doi.org/10.1016/j.rmed.2023.107279
Received 15 February 2023; Received in revised form 4 May 2023; Accepted 9 May 2023
Available online 10 May 2023
0954-6111/© 2023 Elsevier Ltd. All rights reserved.

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G. Mohan et al. Respiratory Medicine 214 (2023) 107279

finally included 33 studies in our review (Fig. 1).

Abbreviations list
3. Etiologies
US United States
LDH lactate dehydrogenase Common causes of pseudoexudates include.
RBC red blood cell count
CABG coronary artery bypass grafting
3.1. Diuretic therapy
CE concordant exudates
PF/SPr ratio of protein in pleural fluid/serum
Diuretic therapy may convert an initially transudative effusion into
DE discordant exudates
an exudate [7]. The mechanism of this is thought to be an increase in the
LDEX lactate dehydrogenase discordant exudates
relative concentration of proteins by losing water from the pleural cavity
PDEX protein discordant exudates
[8]. Smaller molecules are absorbed faster as this can be done by the
PPV positive predictive value
visceral pleura which is supplied by the lower-pressure pulmonary cir­
SPAG serum-pleural effusion albumin gradient
culation. Lymphatic channels on the other hand remove larger protein
SPPG serum-pleural effusion protein gradient
molecules at a much slower rate [7]. Therefore, diuretics can increase
HF heart failure
pleural fluid protein concentrations [9].
HH hepatic hydrothorax
NTPBNP N-terminal pro-brain natriuretic peptide
BNP brain natriuretic peptide 3.2. Traumatic pleural taps

Traumatic pleural taps resulting in bleeding into the pleural fluid can
occur during a thoracentesis. Blood in the pleural fluid can raise pleural

Fig. 1. PRISMA representing literature review.

2. Methods and materials fluid LDH and hence tip the biochemical parameters into the exudative
territory [8]. The specificity of the Light’s criteria is significantly lower
A search was conducted across PubMed, Medline, Embase, Scopus, (~60%) when the pleural fluid red blood cell (RBC) count is > 106 per
and Web of Science. Our first search term “pseudoexudate” generated 5 mcL [10].
results. Our next search term “exudative pleural effusion” generated
5243 results. Manuscripts, including all case reports, review articles,
3.3. History of coronary artery bypass grafting
meta-analyses, and systematic reviews between 1990 and 2022 were
reviewed. We read through abstracts to identify articles that commented
After coronary artery bypass grafting (CABG), up to 50% of effusions
on the diagnosis of pleural effusions and on the discrepancies that exist
can be exudative, after ruling out causes such as infection, malignancy,
with transudates that have exudative biochemical parameters.
and uremia. Obstruction of lymphatic clearance of fluid from the pleural
Excluding manuscripts that we felt were not practically relevant, we
cavity is postulated as the cause of pseudoexudates in these patients with

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G. Mohan et al. Respiratory Medicine 214 (2023) 107279

Table 1 Table 2
Studies investigating SPAG. Study by Bielsa et al. analyzing the Light’s criteria, SPAG and SPPG in HF and
Study Sample Cut- Sensitivity Specificity Accuracy
HH.
size off Parameter HF HH, % (95% CI)
Sangsayunh 86 1.2 g/ 90.1% 33.3% 80.2% Sensitivity of lights criteria 71 (66–75); p = 82 (74–89); p =
et al. [16] dL 0.02 0.02
Gonlugur et al. 285 1.2 g/ 69.4% 92.4% 74.7% Sensitivity of SPPG >3.1 g/dL 82 (78–85); p = 93 (87–97); p =
[17] dL 0.01 0.01
Gonlugur et al. 285 1.3 g/ 80% 76.7% 90.9% Sensitivity of SPAG >1.2 g/dL 95 (91–98); p = 86 (76–92); p =
[17] dL 0.01 0.01
Roth et al. [14] 59 1.2 g/ 95% 100% NA Combined criteria – protein or 100 (97–100); p = 99 (93–100); p =
dL albumin gradient 0.82 0.19
Romero- 249 NA 88% 86% 87%
Canderia HF – heart failure.
et al. [15] HH – hepatic hydrothorax.
Beilsa et al. [5] 364 1.2 g/ 95% (p = NA NA
patients dL 0.01)
with HF Table 3
Beilsa et al. [5] 102 1.2 g/ 86% (p = NA NA
Effect of serial thoracentesis on SPAG and SPPG.
patients dL 0.01)
with HH Parameter Percentage of pseudoexudates correctly classified
Burgess et al. 393 1.2 g/ 87% 92% 89%
First Second Third
[18] dL
Thoracentesis Thoracentesis Thoracentesis
Burgess et al. 393 1.55 54% 92% 70%
[18] g/dL Serum-pleural fluid 7% 7% 20%
Sandeesha et al. 66 1.2 g/ 93.18% NA 92.42% albumin gradient
[19] dL (<12 g/L)
Serum pleural fluid 7% 7% 20%
HF – heart failure. proteins gradient
HH – hepatic hydrothorax. (<31 g/L)
Light’s criteria 7% 47% 67%
CABG [8].

4. Alternate diagnostic criteria Table 4

Various studies that evaluated NTBNP cut-off values.
4.1. Discordant exudates Study Sample Pleural fluid NTBNP cut Sensitivity Specificity
size offs (pg/mL)
Exudates can be divided into concordant and discordant exudates. Porcel et al. 117 >1500 91% 93%
Concordant exudates (CE) demonstrate both, the ratio of protein in [23]
pleural fluid/serum (PF/SPr) of >0.5 and LDH level of >160 IU/L (>2/3 Han et al. 240 >1714 99% 99%
upper limit of normal). Discordant exudates (DE) are sub-classified as [24]
Liao et al. 40 100% 96.7%
LDH discordant exudates (LDEX) when PF/SPr is </ = 0.50 and LDH
>2220
[25]
concentration is > 160 IU/L in the pleural fluid, and protein discordant Cincin et al. 66 >2300 70.8% 97.6%
exudates (PDEX) when PF/SPr is > 0.50 and LDH concentration is </ = [26]
160 IU/L in pleural fluid. In one study, 99% of CE were finally diagnosed Kolditz et al. 101 >4000 92% 91%
[27]
as exudates as compared to only 81.5% of DE. A higher positive pre­
Bayram et al. 162 >925 94% 95%
dictive value (PPV) and positivity likelihood ratio were observed when [28]
using Light’s criteria for LDEX and CE. This might be because LDH Bayram et al. 162 >1040 94% 98%
presence in pleural fluid is more consistent with inflammation as [28]
compared to protein concentration, which is dependent on capillary Valdes et al. 398 >894 85.1% 79.9%
[29]
permeability. Hence making LDH a strong predictive maker [4,11]. In
this study, 22% of transudates were classified as DE; among these 6% NTPBNP - N-terminal pro-brain natriuretic peptide.
were LDEX and 16% were PDEX [12].
only 62% of the samples correctly. Using both, SPAG and SPPG, yielded
4.2. Serum-pleural effusion albumin gradient (SPAG) and serum-pleural a sensitivity of 100% in heart failure and a sensitivity of 99% in hepatic
effusion protein gradient (SPPG) hydrothorax [5].
The low albumin state that malnutrition or cirrhosis leads to, lowers
After diuresis, the gradient (difference) between serum and pleural absolute values, therefore, reducing the accuracy of a SPAG. In these
fluid protein and albumin increases lesser than the ratio between them scenarios, the SPPG may perform better in correctly identifying exudates
[13]. as seen in Table 2.
SPAG <1.2 g/dL has a sensitivity of 70–95% to identify exudates [5, In addition, with repeat thoracenteses, the protein and albumin
14,16–19]. In those who have received diuretics, the accuracy of SPAG is gradient were more immune to misclassification than Light’s criteria as
higher than Light’s criteria [15]. Studies investigating the SPAG are seen in Table 3 [13].
listed in Table 1 below.
A 2012 study by Bielsa et al. demonstrated that overall, the SPAG 4.3. Pleural fluid N-Terminal Pro Brain Natriuretic Peptide (NTPBNP)
performs better than the SPPG. Combining data from 6 other studies, the
authors analyzed 857 transudative effusions including exudates from NTPBNP is predominantly secreted by the ventricles in response to
heart failure (HF) and hepatic hydrothorax (HH). Of the transudates, volume and pressure overload. It is an inactive byproduct of the
27.5% were misclassified, and using SPAG >1.2 g/dL helped classify biochemical pathway that produces brain natriuretic peptide (BNP). In a
80.5% of the samples correctly whereas the SPPG >3.1 g/dL identified 2010 meta-analysis of 10 studies, the effectiveness of NTPBNP in

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G. Mohan et al.
Fig. 2. Diagnostic algorithm.
identifying misclassified exudates in cardiac pleural effusions and its
superiority over BNP was demonstrated [20]. Table 4 shows various
studies that looked at NTPBNP at different cut-offs, with their associated
sensitivity and specificity. However, the clinical utility of measuring
pleural fluid NTPBNP remains questionable, as it is unlikely to add value
to serum BNP measurements [21]. In addition, it may be falsely elevated
in critically ill patients with septic shock or acute kidney injury, and in
patients with parapneumonic or malignant effusions [22].
4.4. Pleural fluid cholesterol
Pleural fluid cholesterol is considered a measure of vascular leak
from increased permeability. Measurement of pleural fluid cholesterol
and LDH, using a cut-off of cholesterol>40 mg/dL and an LDH of >0.6
times the upper limit of normal was found to be as diagnostically ac­
curate as Light’s criteria [30]. A systematic review revealed that
exudative effusions were best diagnosed when the pleural fluid choles­
terol was >55 mg/dL (sensitivity 85%–94%), LDH >200U/L (specificity
98%), or the ratio of pleural cholesterol to serum cholesterol was greater
than 0.3 (sensitivity 93%, specificity 94%) [31]. However, the exact role
of these combination assessments to reclassify pseudoexudates as tran­
sudates is still unclear.
4.5. Imaging modalities to differentiate between exudative and
transudative effusions
Chest radiography or computerized tomography may assist in clas­
sifying effusions as transudates or exudates. Parietal pleural thickness or
nodularity, attenuation of extrapleural fat, and the presence of loculated
pleural effusions are highly accurate for diagnosing pleural exudates
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Respiratory Medicine 214 (2023) 107279
[32]. In a recent study looking at the accuracy of thoracic ultrasound to
classify 300 effusions, there was some value in predicting that a complex
effusion would be an exudate (PPV 90%). However, an anechoic effusion
did not have a good predictive value for classifying the effusion as a
transudate or an exudate [33].
5. Diagnostic approach in patients with pseudoexudates –
Light’s criteria misclassify some transudates as exudates. In scenarios
wherein a transudate is suspected, such as a patient with heart, renal, or
liver failure on diuretics, confirmation of these being pseudoexudates
helps avoid unnecessary further workup that a truly exudative effusion
would warrant. The SPAG >1.2 g/dL best helps classify effusions as
transudates in these situations. However, if the albumin level in the
pleural fluid was not checked during the initial thoracentesis, and it
cannot be added on to the specimen in the laboratory, we calculate an
SPPG. An SPPG cut-off>3.1 g/dL, while imperfect, will still help identify
most true transudates. When fluid needs to be resent, such as when a
second thoracentesis is required for either diagnostic or therapeutic
purposes, in addition to checking a pleural fluid albumin level (if not
checked the first time), we also check a pleural fluid cholesterol level to
better help accurately dichotomize effusions as transudates or exudates.
In clinical scenarios, wherein a transudate is strongly suspected (e.g.,
new bilateral effusions in a patient who is volume overloaded), we
manage the effusions as such even if the SPAG or SPPG may be low or
fluid cholesterol high as none of these parameters are 100% accurate.
When the clinical scenario is less certain (e.g., an isolated left-sided
effusion in a patient with known heart failure) then if a suspected
pseudoexudate is still classified as an exudate after reviewing the SPAG,
SPPG, and cholesterol levels, we proceed with workup as we would for
G. Mohan et al.
any other truly exudative effusion (especially when these effusions are
concordant exudates). Fig. 2 depicts our suggested diagnostic algorithm.
6. Conclusion
Light’s criteria misidentify 20–30% of effusions as exudates. This
occurs commonly in patients with heart, liver, or renal failure on di­
uretics. These pseudoexudates present a diagnostic conundrum that
carries a significant impact on how we approach these effusions.
Checking a SPAG and SPPG can help correctly classify effusions in these
scenarios.
Funding
This research did not receive any specific grant from funding
agencies in the public, commercial, or not-for-profit sectors.
Declaration of competing interest
All authors declare that they have no conflicts of interest.
Acknowledgments
None.
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