Pleural Effusion

Classification

Transudative Effusions

• Result from imbalances in oncotic and hydrostatic pressures.
• Common causes:
  • Congestive heart failure
  • Cirrhosis with hepatic hydrothorax
  • Nephrotic syndrome
  • Hypoalbuminemia
  • Peritoneal dialysis

Exudative Effusions

• Result from inflammation, increased vascular permeability, or impaired lymphatic drainage.
• Common causes:
  • Infections (e.g., pneumonia, tuberculosis)
  • Malignancies
  • Autoimmune diseases (e.g., lupus, rheumatoid arthritis)
  • Pancreatitis
  • Post-cardiac injury syndrome
  • Pulmonary embolism

Light’s Criteria

• Used to differentiate exudative from transudative effusions:
  • Pleural fluid protein/serum protein ratio > 0.5
  • Pleural fluid LDH/serum LDH ratio > 0.6
  • Pleural fluid LDH > two-thirds the upper limit of normal for serum LDH

Heffner’s Criteria

• Additional markers for exudative effusions:
  • Pleural fluid protein > 2.9 g/dL
  • Pleural fluid cholesterol > 45 mg/dL
  • Pleural LDH > two-thirds the upper limit of normal serum LDH

Mechanisms

• Altered permeability of pleural membranes (e.g., infections, malignancy)
• Increased capillary hydrostatic pressure (e.g., congestive heart failure)
• Decreased oncotic pressure (e.g., hypoalbuminemia)
• Impaired lymphatic drainage (e.g., malignancy, trauma)
• Diaphragmatic defects allowing peritoneal fluid migration (e.g., hepatic hydrothorax)
• Pulmonary edema fluid crossing visceral pleura

Drug-Related Causes

• Medications such as methotrexate, amiodarone, phenytoin, and tyrosine kinase inhibitors may induce exudative effusions

Uncommon Causes

• Gonadotrophin-induced ovarian hyperstimulation syndrome (OHSS)
• Oesophageal rupture
• Radiotherapy
• Hemothorax or chylothorax

Surgical Causes

• Post-thoracic surgery effusions due to mediastinal lymphatic interruption, pleuritis, or pericarditis

Mixed Aetiologies

• Some pleural effusions may exhibit both transudative and exudative features, reflecting multifactorial causes such as malignancy with associated hypoalbuminemia

Normal Pleural Fluid Dynamics

• The pleural space contains a small volume of fluid (approximately 0.1 to 0.3 mL/kg body weight), which ensures smooth gliding of the lung within the thoracic cavity during respiration.
• Fluid enters the pleural space via filtration from capillaries in the parietal pleura, driven by systemic hydrostatic pressure.
• It is removed through lymphatic vessels located primarily in the dependent portions of the pleural cavity, maintaining a thin layer of fluid (2–10 micrometers thick).

Mechanisms of Pleural Effusion Formation

Increased Fluid Production

• Increased Hydrostatic Pressure
  • Seen in conditions like heart failure and renal failure, leading to fluid accumulation due to elevated vascular pressure.
• Increased Capillary Permeability
  • Often a result of inflammation or infection (e.g., pneumonia), allowing protein-rich fluid (exudate) to enter the pleural space.

Decreased Fluid Removal

• Impaired Lymphatic Drainage
  • Common in malignancies that obstruct pleural lymphatics.
• Decreased Plasma Oncotic Pressure
  • Observed in hypoalbuminemia due to nephrotic syndrome, liver cirrhosis, or malnutrition.

Abnormal Fluid Migration

• From Adjacent Cavities
  • Examples include hepatic hydrothorax (fluid crossing diaphragmatic defects) or retroperitoneal fluid migration.
• From Thoracic Structures
  • Ruptured thoracic ducts or vessels can cause chylothorax or hemothorax.

Other Causes

• Decreased Intrapleural Pressure
  • Occurs in atelectasis due to bronchial obstruction or fibrotic contraction.
• Drug-Induced Effects
  • Certain medications disrupt pleural homeostasis (e.g., tyrosine kinase inhibitors, dantrolene).

Classification by Fluid Characteristics

Transudates

• Low protein and LDH content.
• Associated with systemic conditions (e.g., congestive heart failure, cirrhosis).

Exudates

• High protein and LDH content.
• Result from local pleural pathology (e.g., infections, malignancy).

Clinical Impact

• Excess fluid accumulation flattens the diaphragm, separates the visceral and parietal pleura, and can lead to restrictive lung defects detectable on pulmonary function tests.

Prevalence

• Pleural effusion is the most common pleural space disease, affecting approximately 1.5 million people annually in the United States.
• In industrialised countries, the prevalence is estimated at 320 cases per 100,000 individuals, largely reflecting the prevalence of causative conditions.

Leading Causes

Congestive Heart Failure (CHF)

• Accounts for about 500,000 cases annually in the US and is the most common cause.

Pneumonia and Parapneumonic Effusions

• Second most common, with 300,000 annual cases; 40% of hospitalised pneumonia patients develop associated effusions.

Malignancy

• Approximately 150,000 new cases of malignant pleural effusion (MPE) are diagnosed annually in the US. Lung and breast cancers contribute to over 60% of cases, with gastrointestinal and hematologic malignancies accounting for 11% each.

Geographical and Socioeconomic Variation

• In developing countries, tuberculosis is a significant cause of pleural effusion, particularly in high-incidence areas, among travelers returning from endemic regions, and in immunocompromised individuals.

Demographics

Sex-Related

• Incidence is generally equal between sexes for most causes.
• Malignant pleural effusions are more common in women, often linked to breast and gynecologic cancers.
• Rheumatoid effusions and those associated with chronic pancreatitis are more frequent in men, the latter often related to alcohol abuse.
• Systemic lupus erythematosus-associated effusions are more common in women.
• Mesothelioma-associated effusions occur predominantly in men due to occupational asbestos exposure.

Age-Related

• Most cases occur in adults, although incidence in children is rising, typically secondary to pneumonia.
• Fetal pleural effusions are rare but can be treated in utero in specific circumstances.

Race-Related

• Differences in incidence align with the racial prevalence of underlying diseases rather than intrinsic racial predispositions.

International Data

• Global incidence varies based on the distribution of causative conditions.
• For example, cirrhosis-associated effusions (hepatic hydrothorax) occur in approximately 5% of cirrhotic patients, while pulmonary embolism is associated with small effusions in up to 40% of cases.

General History

• A thorough medical history is critical to identify underlying causes of pleural effusion.
• Common comorbidities include congestive heart failure (CHF), pneumonia, malignancy, and chronic liver or kidney diseases.
• Chronic conditions such as hepatitis or cirrhosis may suggest hepatic hydrothorax.
• History of cancer, even remote, raises suspicion for malignant pleural effusion.
• Renal failure or nephrotic syndrome indicates risk for transudative effusions.

Respiratory Symptoms

Dyspnea

• Most common complaint, related to lung compression and diaphragm distortion.

Cough

• Often non-productive; productive cough may suggest pneumonia.

Pleuritic Chest Pain

• Suggests inflammation, infection, or malignancy.

Extrapulmonary Symptoms

• Night sweats, fever, and weight loss suggest tuberculosis or malignancy.
• Symptoms of CHF, such as orthopnea and lower extremity oedema, indicate systemic fluid overload.
• Haemoptysis may suggest malignancy, pulmonary embolism, or severe infection.

Occupational History

• Asbestos exposure may suggest mesothelioma or asbestos-related effusion.
• Exposure to beryllium, silica, or other hazardous materials should be noted.

Medication History

• Drugs such as nitrofurantoin, amiodarone, tyrosine kinase inhibitors, and others are associated with pleural effusions.

Trauma and Procedures

• Recent thoracic trauma or surgery may indicate haemothorax or procedure-related effusion (e.g., central line misplacement).

Specific Risk Factors

Congestive Heart Failure:

• Most common cause, recurrent with decompensations.

Pneumonia

• Second most common cause, often associated with parapneumonic effusions.

Malignancy

• A frequent cause, especially in older adults.

Systemic Lupus Erythematosus (SLE)

• Associated with lupus pleuritis and pulmonary embolism.

Rheumatoid Arthritis

• Can cause rheumatoid pleuritis with cholesterol effusions.

Ovarian Hyperstimulation Syndrome

•  Rare cause linked to fertility treatments.

Symptoms Based on Underlying Aetiology

Pneumonia

• Fever, purulent sputum, pleuritic pain.

Malignancy

• Weight loss, fatigue, haemoptysis.

Tuberculosis

• Night sweats, fever, chronic cough, recent travel to endemic regions.

General Examination Findings

Small Effusions (<300 mL)

• Often asymptomatic, with no discernible clinical signs.

Larger Effusions (>300 mL)

• Associated with more prominent physical signs, including:
  • Dullness to percussion: Reliable indicator over areas of effusion.
  • Decreased or absent tactile fremitus: Reduced sound wave transmission due to fluid barrier.
  • Asymmetrical chest expansion: Diminished or delayed expansion on the affected side.
  • Decreased or absent breath sounds: Most evident over the effusion.
  • Egophony: Notable "E-to-A" sound changes at the upper border of the effusion.
  • Pleural friction rub: Indicative of pleural inflammation; may mimic coarse crackles.

Specific Findings for Large Effusions (>1000 mL)

Mediastinal shift

• Displacement of the trachea and mediastinum away from the effusion.
• If the shift is toward the effusion, it may suggest bronchial obstruction or atelectasis.

Intercostal space fullness

• Increased intercostal spacing due to fluid accumulation.

Extrapulmonary Clues to Aetiology

Congestive heart failure

• Peripheral oedema, distended neck veins, and an S3 gallop.

Liver disease

• Cutaneous changes (e.g., spider angiomas) and ascites.

Malignancy

• Lymphadenopathy or a palpable mass may suggest cancer.

Renal disease

• Uraemia-related symptoms and oedema in nephrotic syndrome.

Systemic lupus erythematosus (SLE)

• Rash, joint pain, or pleuritis in SLE-associated pleural effusions.

Differentiating Features of Symptoms

Dyspnoea

• Often correlates poorly with effusion volume; significant relief with thoracentesis despite minimal change in oxygenation.

Cough

• Usually non-productive; productive sputum may indicate pneumonia.

Chest pain

• Typically pleuritic, sharp, and exacerbated by breathing or coughing.
• Diminishes as effusion size increases and inflamed pleurae separate.

Rare Examination Findings

Haemodynamic changes

• Rarely, large effusions mimic tamponade physiology, causing hypotension and jugular venous distension.

Egophony and vocal fremitus

• Most pronounced at the superior edge of large effusions.

General Principles

• Management depends on the underlying cause and severity of symptoms.
• Transudative effusions are treated by addressing the primary condition (e.g., heart failure, cirrhosis).
• Symptomatic effusions, regardless of aetiology, may require therapeutic drainage to relieve dyspnoea and improve lung expansion.

Transudative Effusions

Congestive Heart Failure

• Managed with diuretics (e.g., furosemide, bumetanide).
• Refractory cases may require thoracentesis for symptomatic relief.

Hepatic Hydrothorax

• Treated with salt restriction, diuretics, and possibly transjugular intrahepatic portosystemic shunt (TIPS).
• Large symptomatic effusions may require therapeutic thoracentesis, though repeated drainage risks infection and recurrence.

Nephrotic Syndrome and Hypoalbuminemia

• Address underlying renal or nutritional deficiencies.

Exudative Effusions

Parapneumonic Effusions and Empyema

• Require prompt drainage to prevent fibrosing pleuritis.
• Indications for chest tube drainage include:
  • Frank pus in pleural fluid.
  • pH < 7.2.
  • Positive Gram stain or culture.
  • Loculated effusions on imaging.
• Intrapleural fibrinolytics combined with DNase may enhance drainage in loculated cases.
• Surgical options include video-assisted thoracoscopic surgery (VATS) or decortication for non-resolving effusions.

Malignant Pleural Effusions

• Commonly recur; management focuses on symptom palliation.
• Options include:
  • Therapeutic Thoracentesis: Effective for symptom relief but has a high recurrence rate.
  • Indwelling Pleural Catheters (IPC): Allow at-home fluid drainage; often induce spontaneous pleurodesis in ~45% of cases.
  • Pleurodesis: Achieved using talc, bleomycin, or doxycycline via chest tube or thoracoscopy. Contraindicated in cases of lung entrapment.

Tuberculous Pleural Effusions

• Empirical anti-TB therapy is initiated based on clinical suspicion.
• Adenosine deaminase (ADA) levels in pleural fluid aid in diagnosis.

Specialised Management

Chylous Effusions

• Managed with dietary modifications (low-fat, medium-chain triglycerides) or somatostatin analogues.
• Persistent cases may require thoracic duct ligation or pleuroperitoneal shunting.

Drug-Induced Effusions

• Discontinuation of the offending medication is the primary treatment.
• Common culprits include methotrexate, nitrofurantoin, and hydralazine.

Surgical Interventions

Pleurodesis

• Indicated for recurrent malignant or refractory effusions.
• Achieved using talc insufflation via VATS or bedside slurry instillation.

Decortication

• Required for trapped lung or chronic organising effusions with thick pleural peels.

Pleuroperitoneal Shunting

• Used for recurrent effusions resistant to other therapies, especially in malignancy or chylothorax.
• Shunts can malfunction and require revision.

Symptom Management and Monitoring

• Limit fluid removal to 1–1.5 L per session to prevent re-expansion pulmonary oedema.
• Oxygen therapy may benefit hypoxic patients with large effusions.
• Monitor post-drainage for complications (e.g., pneumothorax, infection).
• Reassess unresolved or recurrent effusions with imaging and additional diagnostics.

General Prognostic Overview

• The prognosis of pleural effusion is closely tied to the underlying aetiology, severity, and response to treatment.
• Prompt medical care and accurate diagnosis significantly reduce complications and improve outcomes.

Morbidity and Mortality

Parapneumonic Effusions and Empyema

• Morbidity and mortality rates are higher in pneumonia complicated by pleural effusion compared to pneumonia alone.
• Prompt treatment usually results in resolution without long-term sequelae.
• Delayed or inadequate treatment can lead to empyema, fibrosis, or trapped lung, causing restrictive lung defects.

Malignant Pleural Effusions

• Associated with poor prognosis; median survival is 3–12 months, depending on the malignancy.
• Effusions due to cancers responsive to therapy (e.g., lymphoma, breast cancer) have better outcomes compared to lung cancer or mesothelioma.
• Lower pleural fluid pH is linked to a higher tumour burden and worse prognosis.

Nonmalignant Pleural Effusions (NMPEs)

• Prognosis varies widely based on the underlying cause.
• One-year mortality rates:
  • Cardiac failure: ~50%.
  • Kidney failure: ~46%.
  • Hepatic failure: ~25%.
• Bilateral effusions are associated with higher mortality compared to unilateral effusions.

Prognostic Scores

RAPID Score (Empyema)

• Factors: Renal function, age, purulence, infection source, and albumin level.
• Risk categories for 3-month mortality:
  • Low risk: 3%.
  • Intermediate risk: 9%.
  • High risk: 31%.

LENT Score (Malignant Pleural Effusion)

• Factors: Pleural fluid LDH, ECOG performance status, neutrophil-to-lymphocyte ratio, and tumour type.
• Risk categories for 6-month survival:
  • Low risk: 92% survival.
  • Intermediate risk: 57% survival.
  • High risk: 17% survival.

PROMISE Score

• Predicts 3-month mortality in malignant pleural effusion.
• Factors: Haemoglobin, C-reactive protein, white blood cell count, ECOG performance status, cancer type, TIMP1 concentrations, and prior chemotherapy/radiotherapy.

Brims’ Decision Tree (Mesothelioma)

• Categorises mesothelioma patients into four prognostic groups with 94.5% sensitivity for predicting death at 18 months.

Impact of Bilateral Effusions

• Bilateral effusions are associated with worse outcomes:
  • Higher 30-day mortality (47% vs. 17% for unilateral effusions).
  • Higher one-year mortality (69% vs. 36% for unilateral effusions).

Infectious Complications

Empyema

• Accumulation of infected pleural fluid leading to systemic infection, sepsis, and respiratory compromise.
• Prompt management includes:
  • Antibiotics targeting suspected pathogens.
  • Drainage using thoracentesis, chest tube thoracostomy (CTT), or surgical intervention in refractory cases.
• Delay in treatment may result in pleural thickening and fibrous adhesions, requiring decortication.

Structural Complications

Pleural Thickening and Fibrosis

• Occurs due to chronic inflammation, untreated infections, or asbestos exposure.
• Can result in decreased lung expansion, restrictive lung disease, and long-term dyspnoea.
• Management:
  • Observation for benign cases, as many resolve within six months.
  • Surgical decortication is indicated for persistent symptoms or trapped lung.

Trapped Lung

• Fibrous bands or pleural peel formation restrict lung expansion.
• Causes include:
  • Chronic infections (e.g., empyema).
  • Tumour encasement of the pleura.
• Treatment involves decortication if lung function remains compromised after conservative management.

Pseudochylothorax

• Long-standing effusions (>5 years) can lead to cholesterol-rich fluid accumulation.
• Often asymptomatic but may require therapeutic thoracentesis if symptomatic.

Complications from Management

Pneumothorax

• Occurs in ~6% of thoracentesis procedures.
• Managed based on severity:
  • Small pneumothoraces: Observation with serial chest X-rays.
  • Symptomatic or large pneumothoraces: Needle aspiration or insertion of a small-bore chest tube.
• Use of real-time ultrasound guidance reduces the risk of pneumothorax.

Re-expansion Pulmonary Oedema

• A rare but severe complication resulting from rapid re-expansion of a collapsed lung after large-volume fluid drainage.
• Symptoms include unilateral pulmonary oedema, chest pain, dyspnoea, and hypoxia.
• Prevention:
  • Limit fluid drainage to ≤1.5 L per session.
  • Monitor patient closely for the first hour post-procedure.
• Management:
  • Conservative treatment with oxygen therapy.
  • Persistent hypoxia may require continuous positive airway pressure (CPAP).

Atelectasis

Compressive Atelectasis

• Caused by large effusions compressing lung parenchyma.
• Resolves with fluid drainage, but rapid fluid removal may risk re-expansion pulmonary oedema.

Risk Factors and Timeframes

Short-Term

• Pneumothorax, re-expansion pulmonary oedema, and atelectasis.

Long-Term

• Pleural fibrosis, trapped lung, and pseudochylothorax.

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