Background Information

Definitions

Pleural effusion:

• An abnormal accumulation of fluid in the pleural space

Aetiology and Classification

Causes of pleural effusion are classified as transudative or exudative based on the underlying pathophysiology and pleural fluid analysis.

• A pleural fluid protein concentration of <25–30 g/L is generally suggestive of a transudative effusion, but is NOT definitive, and should not be used alone to distinguish transudates from exudates.
• The Light’s criteria should be used to differentiate between exudative vs transudative.

 

The Light’s criteria states that an effusion is exudative if ANY of the following is present: ^[Ref]

• Pleural fluid protein/serum protein ratio > 0.5
• Pleural fluid LDH/serum LDH ratio > 0.6
• Pleural fluid LDH > 2/3 of the upper limit of normal for serum LDH

Exudative Effusions

Definition of exudative effusion: accumulation of fluid (typically protein-rich / cellular) in the pleural space due to increased pleural membrane permeability (usually from inflammation / infection / malignancy).

 

A non-exhaustive list of exudative effusion causes: ^[Ref1][Ref2]

Most common causes	Parapneumonic effusion (from underlying pneumonia) – most common cause Pulmonary tuberculosis Malignant pleural effusion – most commonly from metastatic lung and breast cancer Pulmonary embolism
Less common causes	Empyema Connective tissue disease – RA, SLE Haemothorax (most commonly due to trauma) Chylothorax Post-cardiac surgery (inc. CABG) Dressler’s syndrome (post-myocardial infarction) Benign asbestos pleural effusion
Rarer causes	Abdominal disease (e.g., pancreatitis / cholecystitis, hepatic / splenic abscess, oesophageal perforation) Gynaecologic Meig’s syndrome (triad of: ovarian fibroma, ascites, pleural effusion) Endometriosis Ovarian hyperstimulation (e.g. from infertility treatment) Ruptured ectopic pregnancy Drug-induced effusion (e.g., amiodarone, nitrofurantoin, methotrexate, dasatinib) Yellow nail syndrome (rare disorder with triad of yellow, thickened, slow-growing nails + lymphoedema + pleural effusions that are often recurrent) Amyloidosis Uraemia Cholesterol effusion (“pseudochylothorax”)

Transudative Effusions

Definition of transudative effusion: accumulation of fluid (typically low protein) in the pleural space caused by imbalance of hydrostatic and oncotic pressure across the pleural membrane (↑ hydrostatic pressure / ↓ oncotic pressure), WITHOUT increased permeability from inflammation / injury.

 

A non-exhaustive list of transudative effusion causes: ^[Ref1][Ref2]

Common causes	Mechanism: ↑ hydrostatic pressure	Congestive heart failure – leading cause Superior vena cava obstruction (e.g. from tumour) Pulmonary arterial hypertension
	Mechanism: ↓ hydrostatic pressure	Cirrhosis Nephrotic syndrome Hypoalbuminaemia
Less common causes	Mechanism: ↑ hydrostatic pressure	Pericardial disease Peritoneal dialysis Atelectasis
	Mechanism: ↓ hydrostatic pressure	Hypothyroidism (myxoedema effusion) Malnutrition Protein-losing enteropathy

Subtypes

Parapneumonic Effusion and Pleural Infection

The terminology is confusing, but the distinction is important as it guides management:

• Parapneumonic effusion is an exudative pleural effusion that occurs next to a pneumonia, which can be uncomplicated or complicated (see below for criteria)
• Complicated parapneumonic effusion falls under the category of pleural infection, together with empyema
• Uncomplicated parapneumonic effusion does NOT fall under the category of pleural infection.

Feature	Uncomplicated parapneumonic effusion	Complicated parapneumonic effusion	Empyema
Definition	Sterile exudative effusion (no bacterial invasion of pleural space)	Infected pleural fluid without gross pus	Collection of frank pus in the pleural space
Distinguishing / Clinical features	Typically mild Usually resolves with antibiotic therapy alone	Patient is more unwell CPPE may cause respiratory compromise and is less likely to resolve without drainage	More severe symptoms OR septic with marked respiratory compromise Risk of rapid clinical deterioration (without prompt drainage + antibiotics)
Imaging Findings	CXR: loss of costophrenic angle CT: simple, homogeneous fluid	CXR: larger effusion, may appear complex CT: loculations and septations possible, pleural thickening possible	CT with IV contrast shows split pleura sign Fluid is complex and purulent in nature
Pleural fluid analysis	Exudative BUT normal biochemistry pH >7.20 Normal glucose > 60 mg/dL LDH mildly elevated (but <1000 IU/L) Gram stain/culture → negative (sterile)	Biochemical features of infection are required to make the diagnosis: pH <7.20  Low glucose < 60 mg/dL High LDH >1000 IU/L Gram  stain/culture → may be positive	The presence of frank pus (usually visible on aspiration) is diagnostic of empyema Biochemical features of infection (same as CPPE), are often present but not required to make the diagnosis pH <7.20  Glucose <60 mg/dL LDH >1000 IU/L Gram stain/culture → frequently positive

Malignant Pleural Effusion

Definition	Pleural effusion due to the presence of malignant cells in the pleural space
Causes	Involvement of the pleural cavity by malignant cells: [Ref] Most commonly → metastatic disease (often from lung and breast cancer) Less commonly → primary pleural tumours (e.g., mesothelioma)
Features	Features of underlying malignancy (e.g., fatigue, weight loss, mass effects) Malignant effusions are usually large and unilateral
Pleural fluid analysis	Exudative (by Light’s criteria) Often haemorrhagic Lymphocyte predominance Biochemistry ↑ Protein, LDH ↓ Glucose (<60 mg/dL) Low pH (pH <7.20 if tumour burden is high) Low ADA (helps differentiate from Tb – where high ADA) Cytology (microscopy – diagnostic in 55-60%) – identification of abnormal malignant cells Tumour markers (supportive, esp. if cytology negative) Most widely used marker → CEA (high specificity for malignant pleural effusion)

Diagnosis

Clinical Features

Symptoms

Patients may be asymptomatic (esp. in small or chronic effusions)

Potential symptoms include:

• Dyspnoea → most common; often disproportionate to effusion size
• Cough → usually nonproductive
• Pleuritic chest pain → sharp, localised, worsens with inspiration
• Hypoxia-related symptoms (esp. if large effusion)
• Systemic/underlying disease features
  • Fever, leukocytosis → parapneumonic effusion/empyema
  • Cachexia, weight loss → malignancy
  • Peripheral oedema, ↑ JVP → heart failure

Signs

Typical respiratory examination findings:

Examination aspect	Typical findings
Chest expansion	↓ on the affected side (asymmetric chest expansion)
Percussion	Stony dullness (most specific sign)
Tactile fremitus	↓
Auscultation	↓ or absent breath sounds over the effusion Pleural friction rub (if pleura is inflamed)

Investigation and Diagnosis

Step 1 – Confirm Pleural Effusion

To confirm pleural effusion:

• 1st line: chest X-ray or thoracic ultrasound
• Gold standard: CT chest

Step 2 – Investigation Underlying Cause

Perform an ultrasound-guided thoracentesis and send pleural fluid for

• Biochemistry: protein, LDH, glucose, pH
• Microbiology: gram stain, culture
• Cytology

 

Apply the Light’s criteria to distinguish between exudative and transudative causes of pleural effusion.

Exudative cause of pleural effusion is likely if at least 1 of the following:

• Pleural fluid: serum protein ratio >0.5
• Pleural fluid: serum LDH ratio >0.6
• Pleural fluid LDH >2/3 the upper limit of serum LDH normal value

Table summarising diagnostic clues to the underlying cause of pleural effusion based on pleural fluid analysis: ^[Ref1][Ref2]

Pleural effusion cause	Light’s criteria	Pleural fluid findings
Most transudative causes (including heart failure, cirrhosis, nephrotic syndrome)	Transudative	Low protein Low LDH Acellular fluid (low cell counts, i.e. leukocytes, mesothelial cells) Typically clear, straw-coloured fluid appearance
Parapneumonic effusion / empyema	Exudative	ALL the following are possible, but depends on the type of parapneumonic effusion or empyema (see section on subtypes below for more details): Neutrophil predominant Low glucose High LDH +ve Gram stain / culture Low pH
Tuberculosis		Lymphocyte predominant Low glucose +ve Acid-fast bacilli stain High ADA
Malignancy		Lymphocyte predominant High protein and LDH Low glucose +ve Cytology (abnormal malignant cells) Low ADA (helps differentiate from TB – which has high ADA)
Pulmonary embolism / pulmonary infarction		Grossly bloody appearance (possible) Neutrophil predominant High LDH Cytology: presence of mesothelial cells
Haemothorax		Grossly bloody appearance Pleural fluid haematocrit >50% of peripheral blood haematocrit
Chylothorax		Milky appearance High triglycerides Low cholesterol
Rheumatoid arthritis		Lymphocyte predominant Low glucose High cholesterol (pseudochylothorax)
Pancreatitis / oesophageal rupture		High amylase

Management

Treatment is indicated if symptomatic:

• 1st line: pleural fluid aspiration (thoracentesis)
• 2nd line: chest drain insertion

Pleural infection and malignant pleural effusion have distinctive management approaches.

Pleural Infection

Treatment is indicated in ALL patients with pleural infection:

• 1st line (all patients): antibiotics + chest drain insertion
• 2nd line: intrapleural enzyme therapy (thrombolytic therapy + DNase)
• 3rd line: surgical intervention
  • VATS is generally preferred
  • Open thoracotomy is typically reserved for advanced disease or failed VATS

Malignant Pleural Effusion

Treatment is only indicated if symptomatic:

• Expandable lung: indwelling pleural catheter or chemical pleurodesis 
• Non-expandable lung: indwelling pleural catheter

References