Pleural Effusion – Causes, Symptoms, Diagnosis, Treatment and Ongoing care
A pleural effusion is an abnormal accumulation of fluid in the pleural space.
- Pneumonia (25%), malignancy (15%), and pulmonary embolism (10%) account for most exudative effusions.
- Malignant: Primary carcinoma of the lung and metastases of breast, ovary, and lymphoma constitute ∼75–80% of malignant effusions.
Estimated 1.3 million cases/year in US; congestive heart failure (CHF), 500,000; pneumonia, 300,000; malignancy, 200,000; pulmonary embolus, 150,000; cirrhosis with ascites, 150,000; tuberculosis, 2,500; pancreatitis, 20,000; and collagen-vascular disease, 6,000 (1)
- Estimated 320 cases/1 million people in industrialized countries
- No gender predilection: About 2/3 of malignant pleural effusions occur in women.
- The prevalence of pleural effusion in hospitalized patients with AIDS is 7–27%.
- Occupational exposure
- Risk factors for pulmonary embolism (PE) and tuberculosis (TB)
- Opportunistic infections of the pleura should be considered in HIV patients when the CD4 count is <150 cells/µL.
- Pleural fluid formation exceeds pleural fluid absorption. Transudates result from imbalances in hydrostatic and oncotic forces.
- Increase in hydrostatic and/or low oncotic pressures
- Increase in pleural capillary permeability
- Lymphatic obstruction or impaired drainage
- Movement of fluid from the peritoneal or retroperitoneal space
- CHF: 40% of transudative effusions; 80% bilateral
- Constrictive pericarditis, atelectasis
- Cirrhosis (hepatic hydrothorax): 2/3 right side
- Nephrotic syndrome, hypoalbuminemia
- Trapped lung, peritoneal dialysis
- Myxedema, superior vena cava obstruction
- Urinothorax, central line misplacement
- Peritoneal dialysis
- Lung parenchyma infection, bacterial: Parapneumonic, tuberculous pleurisy, fungal, viral
- Parasitic (amebiasis, Echinococcus)
- Malignancy: Lung cancer, metastases (breast, lymphoma, ovaries), mesothelioma
- Pulmonary embolism (although 25% of PEs are transudate)
- Collagen-vascular disease: Rheumatoid arthritis, systemic lupus erythematosus (SLE), Wegener granulomatosis, sarcoidosis
- GI: Pancreatitis, esophageal rupture, abdominal abscess, after liver transplant
- Chylothorax: Thoracic duct tear, malignancy
- Hemothorax: Trauma, PE, malignancy, coagulopathy, aortic aneurysm
- Others: After coronary artery bypass grafting (CABG); Dressler syndrome: pericarditis and pleuritis after myocardial infarction (MI); uremia, asbestos exposure, radiation; drug-induced: nitrofurantoin, bromocriptine, amiodarone, procarbazine, methysergide, hydralazine, procainamide, quinidine, methotrexate, and methysergide; Meigs syndrome: benign ovarian tumor, ascites, and pleural effusion; yellow-nail syndrome: yellow nails, lymphedema, pleural effusion, and bronchiectasis; atelectasis, cholesterol effusion; ovarian stimulation syndrome; lymphangiomatosis; acute respiratory distress syndrome
Commonly Associated Conditions
Presumptive diagnosis based on clinical impression in 50%
Small pleural effusions are asymptomatic
- The degree of dyspnea is related to the associated lung disease, respiratory function, and the size of the pleural effusion.
- Fever, malaise, and weight loss with empyema; chest pain, either constant or pleuritic; nonproductive or purulent cough, hemoptysis
When pleural effusion >300 mL:
- General: No voice transmission; tachypnea; asymmetric expansion of the thoracic cage; mediastinal shift (>1,000 mL)
- Pulmonary: Decreased or inaudible breath sounds; dullness to percussion; decreased or absent tactile fremitus; egophony; pleural friction rub
Diagnostic Tests & Interpretation
Initial lab tests
- Pleural fluid: Appearance, pH, white blood cell (WBC) differential, total protein, lactate dehydrogenase (LDH), glucose, Gram stain and culture, acid-fast bacilli staining
- By clinical scenario: Amylase, triglycerides, cholesterol, LE cells, cytology, antinuclear antibodies (ANAs), adenosine deaminase, tumor markers, rheumatoid factor, cytology
- Transudate vs exudate:
- Light criteria for exudate: 98% sensitivity, 80% specificity (2)[B]:
- Ratio of pleural fluid/serum protein levels >0.5
- Ratio of pleural fluid/serum LDH levels >0.6
- Pleural fluid LDH level >2/3 the upper limit for serum LDH level
- Exudate criteria:
- Serum-effusion albumin gradient ≤1.2; sensitivity 87%, specificity 92% (3)[B]
- Cholesterol effusion >45 mg/dL and LDH effusion >200 mg/dL; sensitivity 90%, specificity 98%
- Light criteria for exudate: 98% sensitivity, 80% specificity (2)[B]:
Follow-Up & Special Considerations
- 75% of patients with exudative effusions have a non-CHF cause.
- 30% cases of pleural effusion in AIDS patients are due to bacterial pneumonia.
- Chest X-ray (CXR): Posteroanterior–anteroposterior (PA-AP) views
- A concave meniscus in the costophrenic angle on an upright CXR suggests >250 mL of pleural fluid; homogeneous opacity and diffuse haziness, visibility of pulmonary vessels through the haziness, and an absence of air bronchogram; 75 mL of fluid will obliterate the posterior costophrenic sulcus.
- Lateral X-rays show blunting of the posterior costophrenic angle and the posterior gutter when as little as 175–200 mL of fluid is present. Decubitus X-rays to exclude a loculated effusion and underlying pulmonary lesion or pulmonary thickening; can depict as little as 5–10 mL of fluid
- Supine X-rays show costophrenic blunting, haziness, obliteration of the diaphragmatic silhouette, decreased visibility of the lower lobe vasculature, widened minor fissure
- Ultrasonography (US): Detects as little as 5–50 mL of pleural fluid; identifies loculated effusions; useful to determine site for thoracocentesis, pleural biopsy, or pleural drainage
- Chest CT scan with contrast material in patients with undiagnosed pleural effusion: For early-stage pleural abnormalities, multiple loculations, pleural thickening, cystic vs solid lesions, nodules, masses, or round atelectasis, benign vs malignant pleural involvement or invasion
- CT pulmonary angiography if PE is suspected
- Positron-emission tomographic (PET)/CT scan: Focal increased uptake of 18-fluorodeoxyglugose (FDG) in the pleura and the presence of solid pleural abnormalities on CT scan are suggestive of malignant pleural disease. A negative PET/CT scan favors a benign cause.
Follow-Up & Special Considerations
Observation in uncomplicated asymptomatic patients (i.e., CHF, cirrhosis), viral pleurisy, thoracic or abdominal surgery
Diagnostic thoracentesis: Clinically significant pleural effusion (>10 mm thick on US or lateral decubitus x-ray with no known cause); CHF: Asymmetric effusion, fever, chest pain, or failure to resolve after diuretics; parapneumonic effusions
- Empyema: Pus, putrid odor; culture; a putrid odor suggest an anaerobic empyema: LDH levels >1,000 IU/L (normal serum = 200 IU/L); glucose <60 mg/dL; low pH
- Malignancy: Cytology, red, bloody; glucose normal to low depending of the tumor burden; red blood cells (RBCs) >100,000/mm3
- Lupus pleuritis: LE cells present; pleural fluid serum ANAs >1.0; glucose <60 mg/dL; pleural fluid/serum glucose ratio <0.5
- Fungal: Positive KOH, culture; peritoneal dialysis: protein <1 g/dL; glucose 300–400 mg/dL
- Urinothorax: Creatinine pleural/blood >0.5; high LDH pleural fluid with low protein levels
- Hemothorax: Hematocrit pleural/blood >0.5; benign asbestos effusion: unilateral, exudative; 1/3 have an elevated eosinophil count.
- TB pleuritis: Lymphocytes >80% predominance effusion; elevated levels of adenosine deaminase >50 units/L and interferon-γ >140 pg/mL; positive AFB stain, culture; total protein >4 g/dL
- Chylothorax: Milky; triglycerides >110 mg/dL; lipoprotein electrophoresis (chylomicrons)
- Amebic liver abscess: Anchovy paste effusion; Waldenström macroglobulinemia and multiple myeloma: protein >7 g/dL
- Esophageal rupture: High salivary amylase; pleural fluid acidosis, pH <6.0; amylase-rich: acute pancreatitis, chronic pancreatic pleural effusion, malignancy, esophageal rupture; rheumatoid pleurisy: glucose <60 mg/dL; pleural fluid/serum glucose <0.5
- Pleural fluid lymphocytosis: Tuberculous pleurisy, lymphoma, sarcoidosis, chronic rheumatoid pleurisy, yellow-nail syndrome, or chylothorax (80–95% of the nucleated cells):
- Carcinomatosis in 1/2 of cases (50–70% lymphocyte percentage)
- Pleural fluid eosinophilia (>10% of total nucleated cells): Pneumothorax, hemothorax, malignancy (carcinoma, lymphoma), drugs, fungal (coccidiomycosis, cryptococcosis, histoplasmosis), benign asbestos pleural effusion, pulmonary infarction
- Low glucose (<60 mg/dL): TB, malignancy, rheumatoid pleurisy, complicated parapneumonic effusion, empyema, hemothorax, paragonimiasis, Churg-Strauss syndrome
- RBC count >100,000/mm3: Trauma, malignancy, PE, injury after cardiac surgery, asbestos pleurisy, pancreatitis, TB
- Pleural fluid LDH >1,000 IU/L: Suggests empyema, malignant effusion, rheumatoid effusion, or pleural paragonimiasis
- pH >7.3: Rheumatoid pleurisy, empyema, malignant effusion, TB, esophageal rupture, or lupus nephritis
- Mesothelial cells in exudates: TB is unlikely if there are more than 5% of mesothelial cells.
- Streptococcus pneumoniae accounts for 50% of cases of parapneumonic effusions in AIDS patients, follow by Staphylococcus aureus, Haemophilus influenzae,Mycoplasma pneumoniae, Legionella, Nocardia asteroides, and Bordetella bronchiseptica. The fluid is usually an exudate with a low count of nucleated cells.
- Pneumocystis jiroveci is an uncommon cause of pleural effusion in HIV patients. Usually it is a small effusion, unilateral or bilateral, that is serous to bloody in appearance. Demonstration of the trophozoite or cyst is mandatory.
- Less common pathogens involved in HIV pleural effusion patients are Mycobacterium, Toxoplasma, Histoplasma capsulatum, Cryptococcus, and Leishmania.
- Cancer-related HIV pleural effusion: Kaposi sarcoma, multicentric Castleman disease, and primary effusion lymphoma.
- Kaposi sarcoma: Mononuclear predominance, exudate, pH >7.4, LDH 111–330 IU/L, glucose >60 mg/dL
Support with oxygen and arterial blood gas determinations (ABCs).
Therapy for breast, lymphoma, ovarian, prostate, and small cell lung cancer may control the effusion.
- CHF: Diuretics (75% clearing in 48 h)
- Parapneumonic effusion: Antibiotics
- For rheumatologic and inflammatory causes: Steroids and nonsteroidal anti-inflammatory drugs (NSAIDs)
Symptomatic nonmalignant effusions that are refractory to treatment may be managed with repeated therapeutic thoracentesis or pleurodesis.
- Therapeutic thoracentesis if symptomatic
- Chest tube thoracostomy drainage: Indications: >1/2 hemithorax; complicated parapneumonic effusion (positive Gram stain or culture, pH <7.2, or glucose <60 mg/dL); empyema; hemothorax
- The recommended limit is 1,000–1,500 mL in a single thoracentesis procedure.
Issues for Referral
- Uncertain etiology; thoracentesis technically difficult; high-risk diagnostic thoracentesis; malignant effusion; decortication
- Video-assisted thoracoscopy for sclerosis
- Peritoneal shunts for symptomatic recurrence
- Pleurodesis for symptomatic patients whose pleural effusion reaccumulates too quickly for repeat therapeutic thoracentesis (4)
- Sclerosing agents for malignant effusions: Doxycycline, bleomycin, talc, and minocycline; talc is more efficacious. The relative risk (RR) of nonrecurrent effusion was 1.34 (95% confidence interval 1.16–1.55) in favor of talc compared with bleomycin, tetracycline, or mustine (4)[A].
- Percutaneous pleural biopsy if cause is not clear after thoracentesis:
- Close pleural biopsy: When the pleura is diffusely involved (TB pleuritis, noncaseating granulomata in rheumatoid pleuritis)
- CT-guided needle biopsy: Pleural mass
- Video-assisted thoracoscopic pleural biopsy: Negative percutaneous biopsy, patchy disease, or CT scan does not show obvious mass
- Open pleural biopsy by thoracotomy
- Contraindications for thoracocentesis: Anticoagulation, bleeding diathesis, thrombocytopenia <20,000/mm3, mechanical ventilation
- Bronchoscopy: When endobronchial malignancy is likely; suggested by a pulmonary infiltrate or a mass on the CXR or CT scan, hemoptysis, massive pleural effusion, or shift of the mediastinum toward the side of the effusion
Treat underlying medical disorder.
Record the amount and quality of fluid drained, and monitor for an air leak (bubbling). Repeat CXR when drainage decreases to <100 mL/d to evaluate complete clearing. For a large effusion, reevaluate catheter position; if positioned appropriately, consider fibrinolytics (e.g., urokinase, streptokinase, alteplase) through the chest tube to break up clots that may be obstructing drainage.
Cardiac diet in patients with heart failure; correct hypoproteinemia.
Varies according to underlying condition:
- Malignant effusion: Poor prognosis; parapneumonic effusions may lead to constrictive fibrosis.
- Patients with low-pH malignant effusion have a shorter survival and poorer response to chemical pleurodesis than those with a pH >7.3.
- Parapneumonic effusion with a low pleural fluid pH (≤7.15): High likelihood of necessity for pleural space drainage
- Of effusions: Constrictive fibrosis, pleurocutaneous fistula
- Of thoracentesis: Pneumothorax (5–10%); hemothorax (∼1%); empyema; spleen/liver laceration; reexpansion pulmonary edema (if >1.5 L is removed)
1. Light RW. Clinical practice. Pleural effusion. N Engl J Med. 2002;346:1971–7.
2. Light RW, Macgregor MI, Luchsinger PC, et al. Pleural effusions: the diagnostic separation of transudates and exudates. Ann Intern Med. 1972;77:507–13.
3. Roth BJ, O’Meara TF, Cragun WH. The serum-effusion albumin gradient in the evaluation of pleural effusions. Chest. 1990;98:546–9.
4. Shaw P, Aganwal R. Pleurodesis for malignant pleural effusion. Cochrane Database of Systemtic Reviews. 2009;1:CO002916.
- 511.1 Pleurisy with effusion, with mention of a bacterial cause other than tuberculosis
- 511.9 Unspecified pleural effusion
- 511.81 Malignant pleural effusion
- 60046008 pleural effusion (disorder)
- 85426002 bacterial pleurisy with effusion (disorder)
- 83270006 neoplastic pleural effusion (disorder)
- A complicated parapneumonic effusion requires urgent drainage.
- Outpatient therapeutic thoracentesis is preferred for patients with a short life expectancy (<3 months).