Pleural Effusion: Comprehensive Overview
Definition and Pathophysiology
Pleural effusion is an abnormal accumulation of fluid in the pleural space exceeding 15-20 mL, resulting from multiple mechanisms including increased pleural membrane permeability, elevated pulmonary capillary pressure, decreased intrapleural pressure, reduced oncotic pressure, and obstructed lymphatic drainage. 1
The condition affects approximately 1.5 million patients annually in the United States and represents 5-12% of emergency medical admissions. 2, 3
Major Causes
Transudative Effusions (Low Protein Content)
- Heart failure is the leading cause, accounting for 29% of all pleural effusions and over 80% of transudates 4
- Cirrhosis represents approximately 10% of transudates and 3% of all effusions 4
- End-stage renal failure causes effusions in 24.7% of ESRF patients, primarily through fluid overload (61.5%) rather than heart failure (9.6%) 1
- Other causes include hypoalbuminemia, nephrotic syndrome, and atelectasis 4
Exudative Effusions (High Protein Content)
- Malignancy accounts for 26% of all effusions, with lung cancer being the most common (25-52% of malignant effusions), followed by breast cancer (3-27%) and lymphomas (12-22%) 4, 5
- Pneumonia (parapneumonic effusions) represents 16% of all effusions 4
- Tuberculosis causes 6% of effusions 4
- Pulmonary embolism should be suspected when dyspnea is disproportionate to effusion size, with 75% of patients having pleuritic pain 1
Clinical Presentation
Symptoms
- Dyspnea is the most common symptom, initially on exertion, occurring in more than half of malignant effusion cases 4, 5, 6
- Pleuritic chest pain is characteristic, particularly in pulmonary embolism and mesothelioma 1, 5
- Dry cough is predominantly present 6
- Constitutional symptoms including weight loss, anorexia, and malaise suggest malignancy 5
- Up to 25% of malignant effusions are asymptomatic at presentation 5
Physical Examination Findings
Look for decreased breath sounds, dullness to percussion, and reduced tactile fremitus on the affected side. 6
Diagnostic Approach
Initial Imaging
Ultrasound guidance should be used for all pleural interventions as it significantly reduces pneumothorax risk (1.0% vs 8.9% without guidance) and improves success rates. 7
- Chest radiography detects moderate to large effusions and determines laterality 3
- Point-of-care ultrasound detects small effusions, identifies loculations, and guides thoracentesis 3
- CT chest identifies small effusions not visible on radiographs, mediastinal lymphadenopathy, underlying parenchymal disease, and pleural metastases 5
When to Perform Thoracentesis
Do NOT aspirate bilateral effusions in clinical settings strongly suggestive of transudate (heart failure, cirrhosis) unless atypical features exist or they fail to respond to therapy. 1
Perform thoracentesis for:
- New, unexplained unilateral effusions 1, 3
- Parapneumonic effusions with fever or infection symptoms 7
- Suspected malignancy 7
- Effusions not responding to treatment of underlying condition 1
Pleural Fluid Analysis
Use Light's criteria to differentiate exudates from transudates: 4
- Pleural fluid protein/serum protein >0.5
- Pleural fluid LDH/serum LDH >0.6
- Pleural fluid LDH >2/3 upper limit of normal serum LDH
Critical pitfall: Light's criteria misclassify 25-30% of cardiac and liver transudates as exudates. 4 When heart failure is suspected but Light's criteria suggest exudate, use serum-effusion albumin gradient >1.2 g/dL to reclassify as transudate. 4
Routine pleural fluid tests should include: 7, 3
- Cell count with differential
- Protein and LDH
- Gram stain and culture
- Cytology (positive in 31-60% of malignant effusions on first sample) 5
- pH (pH <7.2 indicates complicated parapneumonic effusion requiring drainage) 7, 3
- Glucose
Additional tests based on clinical suspicion:
- NT-BNP >1500 μg/mL confirms heart failure 4
- Tuberculosis testing in high-prevalence regions 3
- Amylase for pancreatitis or esophageal rupture 5
Advanced Diagnostic Procedures
If initial cytology is negative, repeat a second time as an additional 27% of malignant cases are diagnosed from the second specimen. 5
Pleural biopsy adds approximately 7% diagnostic yield when cytology is negative and should be performed for suspected tuberculosis or malignancy. 5, 6
Thoracoscopy should be considered when malignancy is suspected after routine tests fail, though minimize interventions in mesothelioma as 40% of needle incisions are invaded by tumor. 1, 4
Treatment Based on Effusion Type
Transudative Effusions
Primary treatment focuses on addressing the underlying medical condition (heart failure, cirrhosis, nephrotic syndrome) to reduce fluid accumulation. 7
Therapeutic thoracentesis may provide temporary symptomatic relief while treating the underlying condition, but remove no more than 1.5L during a single procedure to prevent re-expansion pulmonary edema. 7
Exudative Effusions
A. Parapneumonic Effusion/Empyema
All patients with parapneumonic effusion should be hospitalized for monitoring and treatment with intravenous antibiotics covering common respiratory pathogens. 7
Drainage is required when: 7, 3
- Pleural fluid pH <7.2
- Low glucose levels
- Positive Gram stain or culture
- Purulent appearance
Use small-bore chest tube (14F or smaller) for initial drainage to reduce complications. 7
Remove chest tube when 24-hour drainage is less than 100-150 mL. 7
B. Malignant Pleural Effusion
Treatment algorithm depends on tumor type, symptoms, lung expandability, and prognosis (median survival 3-12 months after diagnosis). 5
For Chemotherapy-Responsive Tumors:
Small-cell lung cancer requires systemic chemotherapy as primary treatment, with pleurodesis reserved only when chemotherapy is contraindicated or has failed. 7
Breast cancer should receive hormonal therapy or cytotoxic chemotherapy first, as these effusions respond better to systemic treatment than other tumor types. 7
Lymphoma warrants systemic chemotherapy as primary treatment, with local interventions only for symptomatic relief in recurrent effusions. 7
For Symptomatic Patients with Expandable Lung:
Perform therapeutic thoracentesis first (removing ≤1.5L) to assess symptom relief and confirm lung expandability on post-procedure chest radiograph. 7
Never attempt pleurodesis without confirming lung expandability—check for mediastinal shift and complete lung expansion on post-thoracentesis imaging. 7
Either indwelling pleural catheter (IPC) or chemical pleurodesis can be used as first-line definitive intervention, with similar efficacy. 7
For talc pleurodesis: 7
- Use 4-5g of talc in 50 mL normal saline
- Can be administered as slurry through chest tube or as poudrage via thoracoscopy
- Administer intrapleural lignocaine (3 mg/kg; maximum 250mg) for analgesia 7
- Clamp chest tube for 1 hour after instillation
- Remove tube when 24-hour drainage is 100-150 mL
- Avoid corticosteroids as they reduce pleural inflammation and prevent successful pleurodesis 7
For Non-Expandable Lung, Failed Pleurodesis, or Loculated Effusion:
IPCs are recommended over chemical pleurodesis. 7 Non-expandable lung occurs in at least 30% of malignant effusions and is a contraindication for pleurodesis. 7
For Asymptomatic Malignant Effusions:
Do not perform therapeutic pleural interventions to avoid unnecessary procedure risks—observation with close monitoring is appropriate. 7
For Limited Survival Expectancy:
Repeated therapeutic pleural aspiration for palliation is appropriate, though recurrence rate at 1 month approaches 100%. 7
Special Tumor Considerations:
Mesothelioma requires multimodality therapy, as single-modality treatments have been disappointing. 7
If bronchoscopy reveals central airway obstruction causing the effusion, remove the obstruction first to permit lung re-expansion. 7
Critical Pitfalls to Avoid
- Do not perform intercostal tube drainage without pleurodesis, as this has nearly 100% recurrence rate and offers no advantage over simple aspiration 7
- Never remove more than 1.5L during single thoracentesis to prevent re-expansion pulmonary edema 7
- Do not delay systemic therapy in chemotherapy-responsive tumors (small-cell lung cancer, breast cancer, lymphoma) in favor of local treatment 7
- Pleurodesis will fail if there is incomplete lung expansion—always confirm expandability before attempting 7
- Do not miss pulmonary embolism—maintain high index of suspicion when dyspnea is disproportionate to effusion size, as pleural fluid tests are unhelpful for this diagnosis 1
- Reconsider tuberculosis in persistent undiagnosed effusions, as it is amenable to specific treatment 4
- IPC-associated infections can usually be treated with antibiotics without removing the catheter; consider removal only if infection fails to improve 7
Special Populations
End-Stage Renal Failure
Causes include fluid overload (most common at 61.5%), heart failure (9.6%), uraemic pleuritis (16%), and unusual causes like urinothorax and peritoneal dialysis-associated pleuro-peritoneal leak. 1 Treatment involves intensifying renal replacement therapy and addressing specific underlying mechanisms. 1
HIV Patients
Leading causes are Kaposi's sarcoma, parapneumonic effusions, and tuberculosis. 4