Pleural Effusion

Definition



  • A pleural effusion is the abnormal accumulation of fluid in the pleural space between the parietal and visceral pleura.
  • This space normally contains a minimal amount of lubricating fluid to facilitate smooth lung movement during respiration.

Aetiology


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).
  • Esophageal 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.

Pathophysiology


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.

Epidemiology


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.

History


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 edema, indicate systemic fluid overload.
  • Hemoptysis 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 hemothorax 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, hemoptysis.
  • Tuberculosis: Night sweats, fever, chronic cough, recent travel to endemic regions.

Physical Examination


General Examination Findings

  • Physical findings in pleural effusion vary depending on the size of the effusion.
    • 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 edema, 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:
    • Uremia-related symptoms and edema in nephrotic syndrome.
  • Systemic Lupus Erythematosus (SLE):
    • Rash, joint pain, or pleuritis in SLE-associated pleural effusions.

Differentiating Features of Symptoms

  • Dyspnea:
    • 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

  • Hemodynamic 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.

Investigations


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 etiology, may require therapeutic drainage to relieve dyspnea and improve lung expansion.

Transudative Effusions

  1. Congestive Heart Failure:
    • Managed with diuretics (e.g., furosemide, bumetanide).
    • Refractory cases may require thoracentesis for symptomatic relief.
  2. 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.
  3. Nephrotic Syndrome and Hypoalbuminemia:
    • Address underlying renal or nutritional deficiencies.

Exudative Effusions

  1. 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.
  2. 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.
  3. 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

  1. Chylous Effusions:
    • Managed with dietary modifications (low-fat, medium-chain triglycerides) or somatostatin analogues.
    • Persistent cases may require thoracic duct ligation or pleuroperitoneal shunting.
  2. Drug-Induced Effusions:
    • Discontinuation of the offending medication is the primary treatment.
    • Common culprits include methotrexate, nitrofurantoin, and hydralazine.

Surgical Interventions

  1. Pleurodesis:
    • Indicated for recurrent malignant or refractory effusions.
    • Achieved using talc insufflation via VATS or bedside slurry instillation.
  2. Decortication:
    • Required for trapped lung or chronic organizing effusions with thick pleural peels.
  3. 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 edema.
  • 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.

Prognosis


General Prognostic Overview

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

Morbidity and Mortality

  1. 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.
  2. 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 tumor burden and worse prognosis.
  3. 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

  1. 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%.
  2. LENT Score (Malignant Pleural Effusion):
    • Factors: Pleural fluid LDH, ECOG performance status, neutrophil-to-lymphocyte ratio, and tumor type.
    • Risk categories for 6-month survival:
      • Low risk: 92% survival.
      • Intermediate risk: 57% survival.
      • High risk: 17% survival.
  3. PROMISE Score:
    • Predicts 3-month mortality in malignant pleural effusion.
    • Factors: Hemoglobin, C-reactive protein, white blood cell count, ECOG performance status, cancer type, TIMP1 concentrations, and prior chemotherapy/radiotherapy.
  4. 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).

Complications


Infectious Complications

  1. 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

  1. 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 dyspnea.
    • Management:
      • Observation for benign cases, as many resolve within six months.
      • Surgical decortication is indicated for persistent symptoms or trapped lung.
  2. Trapped Lung:
    • Fibrous bands or pleural peel formation restrict lung expansion.
    • Causes include:
      • Chronic infections (e.g., empyema).
      • Tumor encasement of the pleura.
    • Treatment involves decortication if lung function remains compromised after conservative management.
  3. 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

  1. 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.
  2. Re-expansion Pulmonary Edema:
    • 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, dyspnea, 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

  1. Compressive Atelectasis:
    • Caused by large effusions compressing lung parenchyma.
    • Resolves with fluid drainage, but rapid fluid removal may risk re-expansion pulmonary edema.

Risk Factors and Timeframes

  • Short-Term:
    • Pneumothorax, re-expansion pulmonary edema, and atelectasis.
  • Long-Term:
    • Pleural fibrosis, trapped lung, and pseudochylothorax.



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