9/7/2020 Pleural effusion- ClinicalKey

DISEASE OVERVIEW

Pleural effusion
Ferri's Clinical Advisor 2021 Conn's Current Therapy 2020

Ferri, Fred F., MD, FACP

Pleural Effusion
Definition

Etiology

Diagnosis

Differential Diagnosis

Imaging Studies

Treatment

Copyright © 2021 by Elsevier, Inc. All rights reserved.

Basic Information
Definition

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Pleural effusion is the pathologic accumulation of fluid in the pleural space, with a wide range of
etiologies.

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Etiology
Caused by a number of factors, including increased capillary permeability, increased vascular
hydrostatic pressure, decreased vascular oncotic pressure, inflammation of the pleurae,
traumatic/iatrogenic causes, and/or obstruction of normal pleural fluid efflux. Box 2 (b0015)
summarizes causes of pleural effusion.

BOX 2
Causes of Pleural Effusions
From Adams JG et al: Emergency medicine, clinical essentials , ed 2, Philadelphia, 2013, Elsevier.

Transudates

Atelectasis (early)

Congestive heart failure

Cirrhosis

Glomerulonephritis

Hypoalbuminemia

Myxedema

Nephrotic syndrome

Peritoneal dialysis

Pulmonary embolism

Superior vena cava syndrome

Exudates
Infectious

Bacterial infection

Bronchiectasis

Fungal infection

Lung abscess

Parasitic infection

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Traumatic hemothorax

Tuberculosis

Viral illness

Malignancies

Lymphoma

Mesothelioma

Primary lung cancer

Pulmonary metastasis

Connective Tissue Disease

Rheumatoid arthritis

Systemic lupus erythematosus

Abdominal/Gastrointestinal

Esophageal rupture

Pancreatic disorders

Subphrenic abscess

Other

Atelectasis (chronic)

Chylothorax

Drug reactions (amiodarone)

Postpartum state

Pulmonary infarction or embolism

Uremia

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Diagnosis
Differential Diagnosis
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Transudate (pleural to serum LDH ratio <0.6 or total protein ratio <0.5)

• Congestive heart failure

• Cirrhosis (hepatic hydrothorax)

• Chronic renal insufficiency

• Hypoalbuminemia

• Constrictive pericarditis

• Superior vena cava obstruction

• Urinothorax

Exudate (defined as pleural to serum LDH ratio ≥0.6 or total protein ratio ≥0.5)

• Malignancy (secondary to metastatic cancer or primary; e.g., mesothelioma)

• Infection

1. Uncomplicated parapneumonic effusion (pH >7.2)

2. Complicated parapneumonic effusion (pH ≤7.2)

3. Tuberculous effusion

4. Viral pleurisy

• Pulmonary embolism

• Hemothorax

• Chylothorax

• Esophageal perforation

• Pleuropancreatic fistula

• Connective tissue disease

Workup
The Light criteria for classification of pleural effusions is summarized in Box 3 (b0020) . Fig. 1 (f0010)
illustrates a diagnostic algorithm for pleural effusions. Fig. E2 (f0020) illustrates an approach to
malignant pleural effusions.

BOX 3
Light Criteria for Classification of Pleural Effusions
From Adams JG et al: Emergency medicine, clinical essentials , ed 2, Philadelphia, 2013, Elsevier.

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In 1972, Light et al developed the currently accepted benchmark for classifying pleural fluid, as
follows:

Pleural fluid protein to serum protein ratio >0.5:1

Pleural fluid lactate dehydrogenase (LDH) to serum LDH ratio >0.6:1

Pleural fluid LDH greater than two thirds the upper limit of normal for serum LDH (a
cutoff value of 200 IU/L was used previously)

Pleural fluid is classified as an exudate if it meets any of the aforementioned criteria. Conversely,
if all three characteristics are absent, the fluid is classified as a transudate. These researchers
achieved a diagnostic sensitivity of 99% and a specificity of 98% for classification of an exudate.

FIG. 1
Diagnostic algorithm.
ADA, Adenosine deaminase; Hct, hematocrit; LDH, lactate dehydrogenase.

FIG. E2
Evaluation of suspected malignant pleural effusion.

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From Niederhuber JE: Abeloff’s clinical oncology , ed 6, Philadelphia, 2020, Elsevier.

Laboratory Tests
See Table 1 (t0010) .

TABLE 1
Selected Laboratory Tests Used to Diagnose Pleural Effusion

Test Diagnostic Utility Comments

Adenosine Values >72 IU/L highly specific for

>40 IU/L suggestive of tuberculous
deaminase tuberculosis, with improved yield with
pleurisy
(ADA) pleural biopsy and PCR

Pleural: serum albumin ratio <0.83 Can be used to corroborate mixed

Albumin
more consistent with transudate findings from LDH and protein ratios

Amylase Esophageal perforation, pancreatitis

Lymphocyte predominance
suggestive of tuberculosis, lymphoma,
other pleural malignancy, pulmonary
Helpful in distinguishing causes of
Cell count embolism
exudative effusions
Neutrophil predominant effusions
seen with bacterial infection,
occasionally with malignancy (20%)

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Test Diagnostic Utility Comments

Positive finding adds to specificity of

Consider thoracic duct defect (due to
Chylomicrons triglycerides for establishing
malignancy, trauma or iatrogenic)
chylothorax

Pleural:serum creatinine >1 suggests

Creatinine
urinothorax

Should be sent from every suspected

Positive findings used to narrow
Culture parapneumonic effusion to guide
therapy
antimicrobial selection

Modest increment in diagnostic yield

Cytology Sensitivity for malignancy of ∼65%
with up to three serial samples

<60 mg/dl suggests complicated

parapneumonic effusion, malignancy,
Glucose
tuberculous pleurisy or rheumatoid
effusion

Pleural fluid with relatively low

Pleural fluid hematocrit >50%
hematocrit can appear bloody on gross
Hematocrit peripheral blood hematocrit consistent
exam, does not necessarily represent
with hemothorax
hemothorax

Lactate Pleural to serum LDH ratio >0.6 or

dehydrogenase pleural LDH >2/3 the upper limit of
(LDH) normal serum LDH suggests exudate

>1500 pg/ml suggests heart failure Chronic pleural effusions related to heart
NT-proBNP even if effusion meets criteria for failure in patients on diuretic therapy
exudate may appear exudative

≤7.2 with clinical suspicion highly Can also have low pH with malignant
pH suggestive of complicated pleural effusions and esophageal
parapneumonic effusion perforation

Absent triglycerides w/high suspicion for

Triglycerides >110mg/dl seen with
Triglycerides chylothorax can be confirmed with
chylothorax
pleural chylomicrons

NT-proBNP, N-terminal pro b-type natriuretic peptide; PCR, polymerase chain reaction.

Imaging Studies
Chest radiography ( Fig. 3 (f0015) ) : Blunting of the costophrenic angle, ipsilateral atelectasis,
contralateral shift of the mediastinum with large effusions, elevated hemidiaphragm with
subpulmonic effusions, “spine sign” on lateral chest x-ray, may be free-flowing or fixed on lateral
decubitus film depending on etiology.

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FIG. 3
Pleural effusions.
A, Posterior-anterior upright view in which a pleural effusion is most evident on this patient’s left side. Both costophrenic angles are
blunted. The pleural effusion forms a meniscus against the left lateral chest wall. B, Lateral upright view shows two meniscus densities,
suggesting bilateral pleural effusions. The posterior diaphragmatic recess is filled with pleural fluid, which forms a meniscus with the
posterior chest wall.
From Broder JS: Diagnostic imaging for the emergency physician , Philadelphia, 2011, Saunders.

Ultrasonography ( Fig. E4 (f0025) ): Can demonstrate size/location of effusion relative to chest

wall, lung, and diaphragm. Can be used to assess for loculations, septations/adhesions, and
parietal/visceral pleural implants.

Computed tomography ( Fig. E5 (f0030) ): Useful to identify loculated effusions and to assess
underlying lung parenchyma to aid in establishing a diagnosis. In empyema, can demonstrate
heterogeneity and gas bubbles.

FIG. E4
Ultrasound examination of a multiloculated pleural effusion.
Pleural fluid with a pH of less than 7.20 in such patients with multiple loculations should be treated with early chest tube drainage.
From Parrillo JE, Dellinger RP: Critical care medicine, principles of diagnosis and management in the adult, ed 5, Philadelphia, 2019,
Elsevier.

FIG. E5
Chest computed tomography scan showing a left pleural effusion.

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With the patient supine, the fluid lies posteriorly against the chest wall in the dependent portion of the left hemithorax.
From Weinberger SE : Principles of pulmonary medicine , ed 7, Philadelphia, 2019, Elsevier.

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Differential Diagnosis
Transudate (pleural to serum LDH ratio <0.6 or total protein ratio <0.5)

• Congestive heart failure

• Cirrhosis (hepatic hydrothorax)

• Chronic renal insufficiency

• Hypoalbuminemia

• Constrictive pericarditis

• Superior vena cava obstruction

• Urinothorax

Exudate (defined as pleural to serum LDH ratio ≥0.6 or total protein ratio ≥0.5)

• Malignancy (secondary to metastatic cancer or primary; e.g., mesothelioma)

• Infection

1. Uncomplicated parapneumonic effusion (pH >7.2)

2. Complicated parapneumonic effusion (pH ≤7.2)

3. Tuberculous effusion

4. Viral pleurisy

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• Pulmonary embolism

• Hemothorax

• Chylothorax

• Esophageal perforation

• Pleuropancreatic fistula

• Connective tissue disease

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Imaging Studies
Chest radiography ( Fig. 3 (f0015) ) : Blunting of the costophrenic angle, ipsilateral atelectasis,
contralateral shift of the mediastinum with large effusions, elevated hemidiaphragm with
subpulmonic effusions, “spine sign” on lateral chest x-ray, may be free-flowing or fixed on lateral
decubitus film depending on etiology.

FIG. 3
Pleural effusions.
A, Posterior-anterior upright view in which a pleural effusion is most evident on this patient’s left side. Both costophrenic angles are
blunted. The pleural effusion forms a meniscus against the left lateral chest wall. B, Lateral upright view shows two meniscus densities,
suggesting bilateral pleural effusions. The posterior diaphragmatic recess is filled with pleural fluid, which forms a meniscus with the
posterior chest wall.
From Broder JS: Diagnostic imaging for the emergency physician , Philadelphia, 2011, Saunders.

Ultrasonography ( Fig. E4 (f0025) ): Can demonstrate size/location of effusion relative to chest

wall, lung, and diaphragm. Can be used to assess for loculations, septations/adhesions, and
parietal/visceral pleural implants.

Computed tomography ( Fig. E5 (f0030) ): Useful to identify loculated effusions and to assess
underlying lung parenchyma to aid in establishing a diagnosis. In empyema, can demonstrate
heterogeneity and gas bubbles.

FIG. E4

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Ultrasound examination of a multiloculated pleural effusion.

Pleural fluid with a pH of less than 7.20 in such patients with multiple loculations should be treated with early chest tube drainage.
From Parrillo JE, Dellinger RP: Critical care medicine, principles of diagnosis and management in the adult, ed 5, Philadelphia, 2019,
Elsevier.

FIG. E5
Chest computed tomography scan showing a left pleural effusion.
With the patient supine, the fluid lies posteriorly against the chest wall in the dependent portion of the left hemithorax.
From Weinberger SE : Principles of pulmonary medicine , ed 7, Philadelphia, 2019, Elsevier.

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Treatment
• Table 2 (t0015) summarizes treatment options for pleural effusions.
TABLE 2
Treatment Options for Pleural Effusion

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Site selection should be guided by ultrasonography whenever possible;

evacuation of pleural fluid can be limited when the lung cannot fully re-
Thoracentesis expand, including central airway obstruction, chronic atelectasis, and
the presence of extensive pleural adhesions; aspiration in these
circumstances can lead to pneumothorax ex vacuo

Tube Consider when ongoing drainage will be needed, especially for

thoracostomy empyema or hemothorax

Indwelling A cuffed pleural drainage catheter tunneled through subcutaneous

tunneled pleural tissue, drained regularly on an outpatient basis, most commonly used
catheter to manage malignant pleural effusions

Instillation of a chemical irritant under direct thoracoscopic visualization

Pleurodesis (e.g., talc poudrage) or via tube thoracostomy to adhere the visceral
and parietal pleurae

Based on underlying etiology (e.g., diuretics, antimicrobials,

Pharmacotherapy
chemotherapy)

• Fig. E6 (f0035) describes a treatment approach to malignant pleural effusions.

FIG. E6
Treatment approach algorithm to malignant pleural effusions.

From Niederhuber JE: Abeloff’s clinical oncology , ed 6, Philadelphia, 2020, Elsevier.

Referral
Negative diagnostic workup after initial pleural fluid sampling should be followed by referral to a
pulmonologist for further evaluation (including consideration for thoracoscopy for pleural biopsy).

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Copyright © 2020 Elsevier, Inc. All rights reserved.

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