Pleural effusion is the accumulation of fluid in
the pleural space.
The pleural space lies between the lung and
chest wall and normally contains a very thin
layer of fluid, which serves as a coupling
A pleural effusion is present when there is an
excess quantity of fluid in the pleural space.
Normally, fluid enters the pleural space from
the capillaries in the parietal pleura and is
removed via the lymphatics situated in the
Fluid can also enter the pleural space from
the interstitial spaces of the lung via the
visceral pleura or from the peritoneal cavity
via small holes in the diaphragm.
Pleural fluid accumulates when pleural fluid formation
exceeds pleural fluid absorption.
The lymphatics have the capacity to absorb 20 times
more fluid than is normally formed. Accordingly, a
pleural effusion may develop when there is excess
pleural fluid formation (from the interstitial spaces of
the lung, the parietal pleura, or the peritoneal cavity)
or when there is decreased fluid removal by the
Transudative pleural effusions
result from alteration of hydrostatic and
oncotic factors that increase the formation or
decrease the absorption of pleural fluid (e.g.,
increased mean capillary pressure [heart
failure] or decreased oncotic pressure
[cirrhosis or nephrotic syndrome]).
Exudative pleural effusions
occur when damage or disruption of the
normal pleural membranes or vasculature
(e.g., tumor involvement of the pleural space,
infection, inflammatory conditions, or trauma)
leads to increased capillary permeability or
decreased lymphatic drainage.
The underlying cause of the effusion usually
dictates the symptoms, although patients may
Pleural inflammation, abnormal pulmonary
mechanics, and worsened alveolar gas
exchange produce symptoms and signs of
symptoms and signs
Inflammation of the parietal pleura leads to
pain in local (intercostal) involved areas or
referred (phrenic) distributions (shoulder).
Dyspnea is frequent and may be present
and out of proportion to the size of the
Cough can occur.
Chest examination is notable for
dullness to percussion, decreased or
absent tactile fremitus, and decreased
Tracheal shift to the contralateral side or
an ipsilateral pleural rub may be present.
The clinical setting is crucial to establishing a proper
diagnosis. A definitive diagnosis based solely upon
pleural fluid analysis is possible in the minority of
History or physical examination findings suggestive
of congestive heart failure, malignancy, pneumonia,
pulmonary embolism, myocardial infarction, surgery,
cirrhosis, or rheumatologic arthritis provide important
clues to the underlying diagnosis.
Pleural effusions are typically detected by
chest radiography as blunting of the
costophrenic angle or opacification of the
base of the hemithorax without loss of volume
of the hemithorax (which would suggest
atelectasis), and may be accompanied by air
bronchograms (which would suggest an
alveolar filling process such as pneumonia).
Prior to invasive diagnostic or therapeutic
procedures, the patient should undergo
imaging to confirm the presence and size of
the effusion. Preferred modalities include:
Decubitus chest radiography
Showing layering fluid will confirm the
presence of pleural effusion and
demonstrates that at least a portion of the
fluid is not loculated.
Is one of the best modalities to assess for
pleural fluid loculations.
Ultrasonography can also provide real-time
guidance for pleural procedures and can
reduce both the complication and failure rate
Computed tomography of the chest
With contrast helps differentiate pleural fluid
from lung masses and atelectatic lung, and
helps define the extent of pleural thickening,
pleural nodularity, and other associated
Pleural fluid analysis
Thoracentesis can be performed safely at the
bedside, in the absence of disorders of hemostasis,
on effusions that extend >10 mm from the inner chest
wall on a lateral decubitus film.
Loculated effusions can be localized with
ultrasonography or CT scan.
Proper technique and sonographic guidance
minimize the risk of pneumothorax and other
The first step is to determine whether the
effusion is a transudate or an exudate.
A transudative pleural effusion occurs when
systemic factors that influence the formation
and absorption of pleural fluid are altered.
The leading causes of transudative pleural
effusions are left ventricular failure and
An exudative pleural effusion occurs when
local factors that influence the formation and
absorption of pleural fluid are altered. The
leading causes of exudative pleural effusions
are bacterial pneumonia, malignancy, viral
infection, and pulmonary embolism.
The primary reason to make this
differentiation is that additional diagnostic
procedures are indicated with exudative
effusions to define the cause of the local
While pleural effusion occurs in a vast array
of disease states, 90% of pleural effusions
are the result of only five diseases.
Congestive heart failure (36%)
Pulmonary embolism (11%)
Viral disease (7%)
Check pleural fluid for
lactate dehydrogenase (LDH),
Serum lactate dehydrogenase (LDH), protein,
pH, glucose and albumin should be
measured within hour of the thoracentesis to
allow appropriate comparison.
Pleural fluid appearance
Most transudates are clear, straw colored,
nonviscid, and without odor
Red-tinged pleural effusions indicate the
presence of blood.
In exudative pleural effusions,
serosanguineous fluid is usually not helpful in
narrowing the diagnosis.
Bloody pleural fluid
If the blood is due to thoracentesis, the
degree of discoloration should clear during
Bloody pleural fluid usually indicates the
presence of malignancy, pulmonary
embolism (PE), or trauma.
The presence of gross blood should lead to
the measurement of a pleural fluid
Hemothorax is defined as a pleural fluid to
blood hematocrit ratio of >0.5, and chest tube
drainage should be considered.
Exudative pleural effusions meet at least one
of the Light's criteria , whereas transudative
pleural effusions meet none:
(a) a pleural fluid-to-serum protein ratio of
(b) a pleural fluid-to-serum LDH ratio of >0.6,
(c) a pleural fluid LDH of more than two-thirds
of the upper limit of normal for serum LDH
The above criteria misidentify ~25% of
transudates as exudates.
If one or more of the exudative criteria are
met and the patient is clinically thought to
have a condition producing a transudative
effusion, like in whom clinical suspicion for
heart, liver, or kidney disease is high what
should be done?
The difference between the protein levels in the
serum and the pleural fluid should be measured.
If this gradient is greater than 31 g/L (3.1 g/dL), the
exudative categorization by the above criteria can be
ignored because almost all such patients have a
transudative pleural effusion.
In some texts a gradient of >1.2 g/dL suggests that
the pleural fluid is transudate.
If a patient has an exudative pleural
Description of the fluid,
Differential cell count,
The WBC differential is often not diagnostic,
although neutrophilia is suggestive of
Eosinophilia (>10% of total nucleated cell
count) is suggestive of air or blood in the
pleural space. If air or blood is not present in
the pleural space, consideration should be
given to fungal and parasitic infection, druginduced disease, PE, asbestos-related
disease, and Churg-Strauss syndrome.
Lymphocytosis (>50% of the total nucleated
cell count) is suggestive of malignancy or
Mesothelial cells argues against the
diagnosis of tuberculosis.
Plasma cells suggest a diagnosis of multiple
Exudative effusions with normal protein but
high LDH are likely to be parapneumonic or
secondary to malignancy.
LDH is an indicator of the degree of pleural
A glucose concentration of <60 mg/dL is
probably due to
rheumatoid arthritis, or
For parapneumonic pleural effusions with a
glucose of <60 mg/dL, tube thoracostomy
should be considered.
Pleural fluid with a low pH
A pH of <7.3 is seen with
collagen vascular disease, or
For parapneumonic pleural effusions with a pH of
<7.20, tube thoracostomy should be considered.
Pleural fluid for pH testing should be collected
anaerobically in a heparinized syringe and placed on
Pleural fluid with a low pH usually has a low glucose
and a high LDH; otherwise, the low pH may be due to
poor sample collection technique.
An elevation of amylase suggests that the
patient has pancreatic disease, malignancy,
or esophageal rupture.
Malignancy and esophageal rupture have
salivary amylase elevations and not
pancreatic amylase elevations.
Turbid or milky fluid
should be centrifuged.
If the supernatant clears, the cloudiness is likely due
to cells and debris.
If the supernatant remains turbid, pleural lipids should
be measured. Elevation of triglycerides (>110 mg/dL)
suggests that a chylothorax is present, usually due to
disruption of the thoracic duct from trauma, surgery,
or malignancy (i.e., lymphoma).
Cytology is positive in approximately 60% of
Priming the fluid collection bag with
unfractionated heparin (UFH; e.g., 1,000
International Units) may increase the yield.
The volume of pleural fluid analyzed does not
impact the yield of cytologic diagnosis.
Repeat thoracentesis increases the
Closed pleural biopsy
Closed pleural biopsy adds little to the diagnostic
yield of thoracentesis, except in the diagnosis of
For tuberculous effusions, pleural fluid cultures alone
are positive in only 20% to 25% of cases. However,
the combination of pleural fluid studies and pleural
biopsy (demonstrating granulomas or organisms) is
90% sensitive in establishing tuberculosis as the
etiology of the effusion.
Diagnostic thoracoscopy has largely
replaced closed pleural biopsy. Thoracoscopy
allows directed biopsies that increase the
diagnostic yield for malignancy while
maintaining the high diagnostic yield of
closed pleural biopsy for TB.
Indications for diagnostic
Pleural effusion of unknown etiology
Other benign pleural disorders
Pulmonary parenchymal disease
Other diagnostic procedures that are useful in
establishing the etiology of a pleural effusion
when the aforementioned tests are
Evaluation of liver function
Biopsy of other abnormal sites (e.g., a
mediastinal or lung mass), and
Evaluation of PE.
Exudative Pleural Effusions
1. Neoplastic diseases
a. Metastatic disease
2. Infectious diseases
a. Bacterial infections
c. Fungal infections
d. Viral infections
e. Parasitic infections
3. Pulmonary embolization
4. Gastrointestinal disease
a. Esophageal perforation
b. Pancreatic disease
c. Intraabdominal abscesses
d. Diaphragmatic hernia
e. After abdominal surgery
f. Endoscopic variceal sclerotherapy
g. After liver transplant
5. Collagen-vascular diseases
a. Rheumatoid pleuritis
b. Systemic lupus erythematosus
c. Drug-induced lupus
d. Immunoblastic lymphadenopathy
e. Sjögren's syndrome
f. Wegener's granulomatosis
g. Churg-Strauss syndrome
"Classic" exudates that can be
Due to early lymphatic obstruction, obstructive
atelectasis, or concomitant disease (CHF).
23 percent incidence; due to atelectasis.
Stage II and III disease.
Hypothyroid pleural effusion:
From hypothyroid heart disease or hypothyroidism per
Transudates resolve with treatment of the
underlying heart, kidney, or liver disease.
Uncommonly, more aggressive approaches
including pleurodesis and shunts are
Parapneumonic effusions and empyema
should be managed with tube drainage when
indicated based on the size, gross
appearance, or biochemical analysis of the
pleural fluid or the presence of loculations
Multiple tubes are sometimes required to
adequately drain the pleural space.
Failure to adequately and quickly drain a
complicated parapneumonic effusion can
lead to organization of the pleural fluid and
formation of a thick pleural adhesions which
may necessitate surgical removal known as
Indications for Tube
Pleural fluid loculations
Effusion filling more than half the hemithorax
Air fluid level
Pus in the pleural space
Positive stain for microorganisms
Positive pleural fluid cultures
There are no absolute contraindications to
tube thoracostomy, particularly if the patient is
in respiratory distress.
Anticoagulation or a bleeding diathesis is a
relative contraindication in a patient
undergoing elective chest tube placement for
pleurodesis. Blind insertion of a chest tube is
dangerous in a patient with adhesions from
infection, previous pleurodesis, or a lung
transplant; guidance by CT scan without
contrast is preferred in these patients.
Type of tube
Silastic® tubes are preferred because older
rubber tubes have fewer drainage holes, are
not well visualized on chest radiographs, and
produce more pleural inflammation. Silastic
chest tubes contain a radiopaque strip with a
gap that serves to mark the most proximal
Size of tube
A chest tube's internal diameter and length
are the critical determinants of flow.
Select the appropriate chest tube size to
account for the viscosity and accumulation
rate of the pleural material to be drained.
As an example, drainage of viscous fluids
requires a larger bore chest tube than that
required for drainage of a similar volume of
Malignant effusion— A small-bore catheter (8
to 14 Fr) placed under ultrasound or CT
guidance is usually adequate to drain a
malignant pleural effusion and achieve
Empyema — For a complicated
parapneumonic effusion or empyema that is
amenable to drainage with a single catheter.
Prefer initial image-guided placement of
small-bore catheters (10 to 14 Fr), with or
without intrapleural fibrinolytic agents.
It is preferred to use the smaller tube size as
this is generally more comfortable for
patients, particularly if more than one tube is
needed. Alternatively, when the fluid appears
viscous, a larger bore tube (16-24 Fr) may be
Unsuccessful drainage with a small-bore
catheter either indicates the presence of
multiple loculations or very viscous material.
Multiple small-bore catheters may be used in
multiloculated effusions or large bore
catheters in case of very viscous material.
Failure to drain with a single small-bore tube
should also lead to thoracic surgery
consultation to avoid delays in case video
assisted thoracoscopy (VATS) becomes
Hemothorax — The goals of tube
thoracostomy in acute hemothorax are
drainage of fresh blood, quantification of the
rate of bleeding, evacuation of any coexisting
pneumothorax, and tamponade of the
bleeding site. Large bore catheters (32 to 40
Fr) are required to reliably achieve these
Once a hemothorax is defibrinated in situ,
that is after the acute phase, success of
drainage is less dependent on the size of the
tube, than on the degree and mode of clot
formation. Large amounts of clotted blood
should be evacuated via video assisted
Occasionally, a hemothorax may result in a
sonographically complex septate pattern and
may be treated with small-bore catheters.
Treatment of hemothorax should be
individualized and done in consultation with
Malignant pleural effusions
Observation without invasive interventions
may be appropriate for some patients with
malignant pleural effusions.
Therapeutic thoracentesis may improve
patient comfort and relieve dyspnea. The
rapid removal of more than 1 L of pleural fluid
may rarely result in re-expansion pulmonary
edema, especially if the lung is unable to reexpand.
Repeated thoracenteses are reasonable if
they achieve symptomatic relief and if fluid
reaccumulation is slow. Unfortunately, 95% of
malignant effusions will recur with a median
time to recurrence of less than a week. When
frequent or repeated thoracentesis is required
for effusions that reaccumulate, early
consideration should be given to tube
drainage with pleurodesis or placement of a
chronic indwelling pleural catheter.
Chemical pleurodesis is an effective therapy
for recurrent effusions. This treatment is
recommended in patients whose symptoms
are relieved with initial drainage but who have
rapid reaccumulation of fluid.
Effective and inexpensive.
Fever and hypoxia are common following
instillation of talc into the pleural space, and
respiratory failure has been described on
Overall efficacy is similar for talc slurry
delivered via chest tube versus dry talc
insufflated during thoracoscopy.
Doxycycline or minocycline
Doxycycline or minocycline can also be
instilled into the pleural space via a chest
Pain is more prevalent and severe following
doxycycline and minocycline than following
Bleomycin appears to be less effective and
more expensive than other drugs.
Systemic analgesics and the administration of
lidocaine in the sclerosing agent solution help
to decrease the appreciable discomfort
associated with the procedure.
If the chest tube drainage remains high (>100
mL/d) more than 2 days after the initial
pleurodesis, a second dose of the sclerosing
agent can be administered.
Chronic indwelling pleural catheters
Provide good control of effusion-related
symptoms via intermittent drainage.
The Pleurx catheter is better at controlling
symptoms than doxycycline administered via a
chest tube. Furthermore, repeated drainage via
a Pleurx catheter leads to pleurodesis in roughly
50% of patients, allowing the catheter to be
Pleurectomy or pleural abrasion
Requires thoracic surgery and should be
reserved for patients with a good prognosis who
have had ineffective pleurodesis or inadequate
response to chronic pleural drainage.
Chemotherapy and mediastinal
May control effusions in responsive tumors, such
as lymphoma or small-cell bronchogenic
carcinoma, although it has poor efficacy in