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.
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
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 organizing 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 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
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 tumor 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.
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.
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
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 dyspnea.
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).
Tumor 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 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
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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