Pleural Effusion

Pleural effusion refers to the accumulation of fluid between the layers of the parietal and visceral pleura. Common causes of this condition include infection, malignancy, autoimmune disorders, or volume overload. Clinical manifestations include chest pain, cough, and dyspnea. Imaging can confirm the presence of a pleural effusion, and pleural fluid analysis can help in the evaluation of an etiology. Management is dependent on the underlying condition and whether the effusion is causing respiratory distress. Drainage of the effusion may provide symptomatic relief.

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Overview

Definition

Pleural effusion is an excessive accumulation of fluid within the pleural cavity (between the parietal and visceral pleura).

Classification

Light’s criteria are used to categorize effusions and to guide further workup.

An effusion is classified as exudative if any of these 3 criteria are met:

  • Pleural fluid protein:serum protein ratio > 0.5
  • Pleural fluid LDH:serum LDH ratio > 0.6
  • Pleural fluid LDH > ⅔ upper limit of normal for serum LDH

If these 3 criteria are not met, the pleural effusion is considered transudative.

Etiology

  • Common causes of transudate:
    • Congestive heart failure (CHF)
    • Liver cirrhosis
    • Hypoalbuminemia
    • Nephrotic syndrome
  • Common causes of exudate:
    • Pneumonia
    • TB
    • Malignancy (most commonly a primary lung cancer)
    • Connective tissue diseases
    • Pancreatitis
    • Hemothorax
    • Chylothorax (accumulation of lymphatic fluid)
    • Benign asbestos pleural effusion (BAPE)
  • Transudative or exudative: pulmonary embolism

Pathophysiology

Pleural effusions represent a disturbance between pleural fluid production and lymphatic resorption.

Normal physiology

Pleural fluid is a product of Starling forces within the capillary bed of the parietal pleura and is absorbed by lymph vessels in the diaphragmatic and mediastinal surfaces of the parietal pleura.

  • The normal mean rate of production and absorption of the pleural fluid is 0.2 mL/kg/hour.
  • The entire volume of pleural fluid normally turns over within 1 hour.
  • The lymphatic vessels can handle flow of up to approximately 20 times more than the normal production rate → lymphatic resorption has a large reserve capacity

Transudative effusions

A transudative pleural effusion may result from increased fluid entry into the pleural space due to:

  • ↑ Hydrostatic pressure in the vasculature (e.g., CHF)
  • ↓ Oncotic forces in the plasma (e.g., hypoalbuminemia)
  • Ascitic fluid movement through the diaphragm (e.g., hepatic hydrothorax)

Exudative effusions

An exudative pleural effusion may result from:

  • ↑ Capillary permeability → ↑ pleural levels of:
    • Proteins
    • Cells
    • Other plasma contents (depending on the etiology)
  • Impaired lymphatic drainage from:
    • Malignant infiltration or blockage of the lymphatics 
    • Inflammatory processes
    • Mechanical compression of the lymphatics 
    • Acute ↑ in systemic venous pressure

Clinical Presentation

Symptoms

Some pleural effusions may be asymptomatic. Symptoms may vary and can depend on the severity and cause of the effusion.

  • Dyspnea (most common)
  • Pleuritic chest pain:
    • Pain worsens with deep inspiration.
    • Indication of pleural inflammation
  • Fever
  • Cough

Clinical lung examination

  • Inspection:
    • An asymmetrical chest expansion (reduced expansion on the side of the effusion)
    • Fullness of intercostal spaces
  • Palpation:
    • ↓ or absent tactile fremitus
    • Tracheal deviation:
      • Trachea is shifted to the opposite side of the effusion.
      • Seen in large, severe effusions
  • Auscultation: 
    • ↓ or inaudible breath sounds over the effusion 
    • Bronchial breath sounds, bronchophony, and egophony:
      • Heard over the lung parts directly above the effusion
      • Due to consolidation of the lung in that area
    • Pleural friction rub
  • Percussion:
    • In the case of an effusion > 300 mL, chest examination will also be notable for dullness to percussion.
    • The upper border dullness follows a laterally ascending curve apexing at the midaxillary line (Ellis–Damoiseau line).
Ellis–Damoiseau line

Ellis–Damoiseau line:
This drawing depicts the shape that dullness to percussion will follow when assessing for a pleural effusion.

Image by Lecturio.

Indications of an underlying etiology

Parapneumonic effusions (adjacent to a pneumonia) can present with signs of sepsis or septic shock.

  • Fever
  • Tachycardia
  • Hypotension

Transudative effusions may be associated with:

  • Weight gain
  • Peripheral edema
  • Jugular venous distention

Malignant effusions may be associated with:

  • Weight loss
  • Early satiety
  • Night sweats

Diagnosis

Imaging studies

Pleural effusions are often easily detected on imaging.

Chest X-ray:

  • Best initial test
  • Findings:
    • Abnormal blunting of costophrenic angles
    • Fluid within horizontal or oblique fissures
    • Some effusions may demonstrate a meniscus
    •  Massive effusions
      • Complete opacification of a hemithorax
      • Tracheal deviation away from the affected side
      • Mediastinal shift
  • Lateral decubitus films
    • Most sensitive
    • Can demonstrate fluid layering (free-flowing pleural effusion)

CT of the chest:

  • Can detect small amounts of pleural fluid
  • Able to evaluate the entire lung parenchyma and mediastinum for potential etiologies

Ultrasonography: 

  • High sensitivity for diagnosis of pleural effusions 
  • Can detect small amounts of pleural fluid that may be missed on X-ray examination
  • Often used to visualize the effusion for thoracentesis or chest tube placement

Imaging considerations

Some imaging findings may help narrow the list of potential causes of the pleural effusion.

  • Bilateral pleural effusions:
    • Most commonly seen in volume overload states (e.g., CHF)
    • Differential diagnosis should also include malignancy, lupus, and constrictive pericarditis.
  • Massive effusions may occur in:
    • Malignancy
    • Complicated parapneumonic effusion or empyema
    • TB
  • Loculated effusions:
    • Caused by adhesions between contiguous pleural surfaces
    • Most commonly associated with higher inflammatory states (e.g., empyema, hemothorax, TB)

Pleural fluid analysis

Once a pleural effusion is found, the next step is to sample the pleural fluid by performing thoracentesis.

Routine investigations include: 

  • Pleural fluid should be sent for:
    • Cultures and microscopy
      • Bacteria
      • Acid-fast bacilli
      • Fungi
    • Cytology 
    • Cell count with differential
    • pH
    • LDH
    • Protein
    • Albumin
    • Glucose
  • Serum studies to order for Light’s criteria:
    • LDH
    • Protein
    • Albumin

Additional investigations include (based on clinical suspicion):

  • Amylase → pancreatitis, esophageal rupture
  • Triglycerides → chylothorax
  • Rheumatoid factor and antinuclear antibodies → autoimmune disorders
  • Acid-fast bacilli smear and adenosine deaminase → TB
Common pleural fluid investigations and associated diagnoses
Fluid analysisFindingsAssociated diagnosis
Fluid appearanceStraw colorTransudate
PusEmpyema
Bloody
  • Hemothorax
  • Malignancy
  • Pulmonary embolism
MilkyChylothorax
pH> 7.55Normal pleural fluid
< 7.2
  • Complex parapneumonic effusion
  • Empyema
Glucose< 60 mg/dL
  • Complicated parapneumonic effusion
  • Empyema
  • Autoimmune conditions
  • Malignant effusion
Cell countWBC > 10,000 cells/µL
  • Parapneumonic effusion
  • Empyema
  • Autoimmune conditions
  • Pulmonary embolism
Neutrophil predominanceBacterial infection
Lymphocytic predominance
  • Tuberculosis
  • Malignancy
  • Chylothorax
RBC > 5000 cells/µL
  • Hemothorax
  • Malignancy
Adenosine deaminase> 50 µg/LTuberculosis
Amylase> 200 µg/dL
  • Pancreatitis
  • Esophageal rupture
Triglycerides> 110 mg/dLChylothorax
Cultures
  • Bacterial
  • Fungal
  • Acid-fast bacilli
Parapneumonic effusion
CytologyCell analysisMalignancy

Advanced procedures

The following may be considered in the workup if the history, physical exam, imaging, and pleural fluid analysis do not reveal a diagnosis and the patient has worrisome symptoms (e.g., weight loss, persistent fever).

  • Bronchoscopy: can aid in diagnosis of associated malignancy or infectious causes
  • Pleural biopsy:
    • May be performed if there is clinical suspicion for malignancy or TB 
    • Options:
      • Percutaneous needle biopsy
      • Video-assisted thoracoscopic surgery (VATS)

Related videos

Special Forms of Pleural Effusion

Chylothorax

  • Lymphatic fluid in the pleural cavity
  • Etiology: 
    • Trauma (e.g., postsurgical)
    • Malignancy
    • Congenital anomalies
  • Pleural fluid analysis will reveal:
    • Cloudy and milky fluid
    • Exudate
    • Lymphocytic predominance 
    • High concentrations of lipids
Chyle removed from a chylothorax

A large amount of cloudy, milky fluid removed during a thoracentesis for a chylothorax

Image: “600 cubic centimeters of chyle removed from a chylothorax” by Matani S, Pierce JR. License: CC BY 3.0

Parapneumonic effusion

  • Exudative, neutrophilic pleural fluid associated with pneumonia
  • Classification:
    • Uncomplicated 
      • No bacterial invasion of the pleura
      • Will resolve with management of the pneumonia
    • Complicated
      • Bacterial invasion of the pleura
      • Bacteria are rapidly cleared from the pleural space → cultures are usually negative
    • Empyema
      • Bacterial infection of the pleura
      • Pleural fluid will be thick, viscous, and opaque (pus).
      • Can lead to fibrin deposition and restriction of lung movement

Hemothorax

  • Accumulation of blood within the pleural cavity 
  • Etiology:
    • Traumatic
    • Nontraumatic: 
      • Malignancy
      • Coagulopathy
      • Connective tissue or vascular disease
  • Pleural analysis will reveal:
    • Frank blood
    • ↑ RBC count

Management

Initial management

Asymptomatic patients do not generally require treatment, and many will have spontaneous resorption of the effusion. However, the following should be done in patients with symptoms:

  • Assess airway, breathing, and circulation.
  • Provide supplemental oxygen.
  • Urgent drainage if:
    • Severe respiratory distress or respiratory failure
    • Evidence of obstructive shock

Interventions

  • Thoracentesis:
    • Needle aspiration of pleural fluid
    • Diagnostic and therapeutic
    • Can be repeated if there is reaccumulation
  • Chest tube placement (tube thoracostomy):
    • Placement of a surgical tube into the pleural space
    • Critical in empyema and hemothorax
  • Indwelling pleural catheter:
    • Catheter that tunnels into the pleural space
    • Allows intermittent drainage of pleural fluid
    • Used in refractory pleural effusions (requiring frequent thoracentesis for recurrence, such as in malignancy) 
  • Pleurodesis:
    • Obliteration of the pleural space by way of inducing inflammation and fibrosis
    • May be performed with chemicals (e.g., talc) or with manual abrasion
    • Used for refractory pleural effusions
  • Pleurectomy and decortication: 
    • Surgical option if all the above measures fail
    • Used as a last resort in advanced cases
Thoracentesis

Image depicting the basic technique for thoracentesis, which allows for aspiration of a pleural effusion

Image by Lecturio.

Management of the underlying cause

The management of pleural effusions hinges on finding and treating the underlying etiology.

  • Parapneumonic effusion and empyema:
    • Antibiotics
    • Thoracentesis or chest tube drainage
  • Malignant pleural effusion:
    • Appropriate management of the primary malignancy
      • Chemotherapy
      • Radiation
    • May require frequent drainage or an advanced intervention (e.g., pleurodesis, pleural catheter)
  • Hemothorax:
    • Chest tube placement 
    • Identify and stop the source of bleeding:
      • Surgical exploration
      • Interventional radiology
    • Blood transfusion, as needed
  • Transudative effusions:
    • CHF: diuresis
    • Hepatic hydrothorax:
      • Diuresis
      • Transjugular portosystemic shunt
    • Renal failure with fluid overload: hemodialysis

Complications

Complications of pleural effusions

  • Respiratory failure:
    • Worsening hypoxia
    • Respiratory distress
  • Loculated pleural effusions:
    • Compartmentalization of a pleural effusion into smaller spaces by fibrous layers
    • Classically seen in empyema, hemothorax, and TB
    • Treated with intrapleural fibrinolytic agents
  • Lung entrapment:
    • Lung unable to expand because of formation of a pleural peel on visceral pleura 
    • Secondary to active pleural inflammation, infection, or malignancy
  • Shock:
    • Obstructive shock: compressive mediastinal effect causing impairment of cardiac output
    • Septic shock: result of infection causing hemodynamic instability and end-organ dysfunction
    • Hemorrhagic shock: seen in traumatic hemothorax

Complications of thoracentesis

  • Pneumothorax
  • Vascular injury → hemothorax
  • Re-expansion pulmonary edema

References

  1. Na M. (2014). Diagnostic tools of pleural effusion. Tuberculosis and Respiratory Diseases 76(5):199–210.
  2. Jany B, Welte T. (2019). Pleural effusion in adults—etiology, diagnosis, and treatment. Deutsches Aerzteblatt Online 116(21):377–386.
  3. Karkhanis V, Joshi J. (2012). Pleural effusion: diagnosis, treatment, and management. Open Access Emergency Medicine 4:31–52.
  4. Broaddus VC. (2020). Mechanisms of pleural liquid accumulation in disease. In Finlay G. (Ed.), UpToDate. Retrieved March 8, 2021, from https://www.uptodate.com/contents/mechanisms-of-pleural-liquid-accumulation-in-disease
  5. Heffner JE. (2020). Diagnostic evaluation of a pleural effusion in adults: initial testing. In Finlay G. (Ed.), UpToDate. Retrieved March 8, 2021, from https://www.uptodate.com/contents/diagnostic-evaluation-of-a-pleural-effusion-in-adults-initial-testing
  6. Lee YCG. (2020). Diagnostic evaluation of pleural effusion in adults: additional tests for undetermined etiology. In Finlay G. (Ed.), UpToDate. Retrieved March 8, 2021, from https://www.uptodate.com/contents/diagnostic-evaluation-of-pleural-effusion-in-adults-additional-tests-for-undetermined-etiology
  7. Stark P. (2019). Imaging of pleural effusions in adults. In Finlay G. (Ed.), UpToDate. Retrieved March 8, 2021, from https://www.uptodate.com/contents/imaging-of-pleural-effusions-in-adults
  8. Light RW. (2021). Pleural effusion. MSD Manual Professional Version. Retrieved March 8, 2021, from https://www.msdmanuals.com/professional/pulmonary-disorders/mediastinal-and-pleural-disorders/pleural-effusion
  9. Krishna R, Rudrappa M. (2020). Pleural effusion. StatPearls. Retrieved March 8, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK448189/

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