> Table of Contents > Pleural Effusion
Pleural Effusion
Felix B. Chang, MD, DABMA, FAAMA
image BASICS
Abnormal accumulation of fluid in the pleural space
DESCRIPTION
Types: transudate, exudate
  • Congestive heart failure 40%: transudate
  • Pneumonia 25%, malignancy 15%, and pulmonary embolism (PE) 10% account for exudative effusions
  • Malignant: lung cancer and metastases of breast, ovary, and lymphoma
EPIDEMIOLOGY
Incidence
Estimated 1.5 million cases/year in the United States; CHF: 500,000; pneumonia: 300,000; malignancy: 150,000; PE: 150,000; cirrhosis: 150,000; TB: 2,500; pancreatitis: 20,000; collagen vascular disease: 6,000
Prevalence
  • Estimated 320 cases/100,000 people in industrialized countries; in hospitalized patients with AIDS, prevalence is 7-27%.
  • No gender predilection: ˜2/3 of malignant pleural effusions occurs in women.
ETIOLOGY AND PATHOPHYSIOLOGY
  • 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
  • Transudates
    • CHF: 40% of transudative effusions; 80% bilateral. Constrictive pericarditis, atelectasis; superior vena cava syndrome
    • Cirrhosis (hepatic hydrothorax); nephrotic syndrome, hypoalbuminemia; myxedema
    • Urinothorax, central line misplacement; peritoneal dialysis
  • Exudates
    • Lung parenchyma infection, bacterial (parapneumonic, tuberculous pleurisy), fungal, viral, parasitic (amebiasis, Echinococcus)
    • Cancer: lung cancer, metastases (breast, lymphoma, ovaries), mesothelioma
    • PE: 25% of PEs are transudate.
    • Collagen vascular disease: rheumatoid arthritis, systemic lupus erythematosus, Wegener granulomatosis, sarcoidosis, Churg-Strauss
    • 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 graft; Dressler syndrome; uremia, asbestos exposure, radiation; drug-induced: nitrofurantoin, bromocriptine, amiodarone, procarbazine, hydralazine, procainamide, quinidine, methotrexate, and methysergide
    • Meigs syndrome; yellow nail syndrome; ovarian stimulation syndrome; lymphangiomatosis; acute respiratory distress syndrome (ARDS)
    • Chylothorax: thoracic duct tear, malignancy, associated with lymphoma
RISK FACTORS
  • Occupational exposures/drugs
  • PE, TB, bacterial pneumonias
  • Opportunistic infections (in HIV patients when CD4 count is <150 cells/&mgr;L)
COMMONLY ASSOCIATED CONDITIONS
Hypoproteinemia, heart failure, cirrhosis
image DIAGNOSIS
Presumptive diagnosis in 50% of cases. Small pleural effusions, radiographic area <2 intercostal spaces (<300 mL) are asymptomatic.
PHYSICAL EXAM
  • Pleural effusion >300 mL: tachypnea, asymmetric expansion of the thoracic cage; decrease/absent tactile fremitus; dullness to percussion; decreased/inaudible breath sounds, egophony, pleural friction rub
  • Ascites suggest the following: hepatic hydrothorax, ovarian cancer, and Meigs syndrome.
  • If associated with unilateral swelling in lower extremity, consider DVT with PE.
DIFFERENTIAL DIAGNOSIS
Empyema, malignancy, inflammatory, fungal, tuberculosis
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
  • Pleural fluid: appearance, pH, WBC differential, total protein, lactate dehydrogenase (LDH), glucose, Gram stain and culture, and acid-fast bacilli staining. Consider polymerase chain reaction (PCR) for Mycobacterium tuberculosis and Streptococcus pneumoniae (1,2)[A].
  • If comorbidities implying risk, consider amylase, triglycerides, cholesterol, lupus erythematosus (LE) cells, cytology, antinuclear antibodies (ANAs), adenosine deaminase, tumor markers, rheumatoid factor, cytology, creatinine (2)[A]
  • Light criteria, transudate versus exudate (98% sensitivity; 80% specificity); fluid is considered an exudate if any of the following (2)[A]:
    • Ratio of pleural fluid-to-serum protein levels >0.5; ratio of pleural fluid-to-serum LDH levels >0.6; pleural fluid LDH level >2/3 the upper limit for serum LDH level (1,3)[A]
  • Other exudate criteria (4)[A]:
    • Serum-effusion albumin gradient ≤1.2 (sensitivity 87%; specificity 92%); cholesterol effusion >45 mg/dL and LDH effusion >200 mg/dL (sensitivity 90%; specificity 98%)
  • Empyema: pus, putrid odor; culture. A putrid odor suggests 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 on the tumor burden; RBCs, >100,000/mm3
  • Lupus pleuritis: LE cells present; pleural fluid-to-serum ANAs ratio >1; glucose <60 mg/dL; pleural fluid-to-serum glucose ratio <0.5
  • Fungal: positive KOH, culture; peritoneal dialysis: protein, <1 g/dL; glucose, 300 to 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; have elevated eosinophil count
  • TB pleuritis: lymphocytes >80% predominance effusion; elevated levels of adenosine deaminase >50 U/L and interferon-&ggr; >140 pg/mL; positive acid-fast bacillus (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; amylase-rich: acute pancreatitis, chronic pancreatic pleural effusion, malignancy, esophageal rupture; rheumatoid pleurisy: glucose <60 mg/dL; pleural fluid/serum glucose <0.5
  • Lymphocytosis: tuberculous pleurisy, lymphoma, sarcoidosis, chronic rheumatoid pleurisy, yellow nail syndrome, or chylothorax (80-95% of the nucleated cells). Carcinomatosis in half of cases (50-70% are lymphocytes)
  • Pleural fluid eosinophilia (>10% of total nucleated cells): pneumothorax, hemothorax, malignancy, drugs, pulmonary infarction, fungal (coccidiomycosis, cryptococcosis, histoplasmosis), benign asbestos pleural effusion
  • Low glucose (<60 mg/dL): TB, malignancy, rheumatoid pleurisy, parapneumonic, 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 >5% of mesothelial cells.
  • Streptococcus pneumoniae accounts for 50% of cases of parapneumonic effusions in AIDS patients, followed by Staphylococcus aureus, Haemophilus influenzae, Mycoplasma pneumoniae, Legionella, Nocardia, and Bordetella bronchiseptica. Exudate with low count of nucleated cells
  • Pneumocystis jirovecii is an uncommon cause in HIV. Usually it is a small effusion, unilateral or bilateral, and serous to bloody in appearance. Demonstration of the trophozoite or cyst is mandatory.
  • P.809

  • Cancer-related HIV pleural effusion: Kaposi sarcoma, Castleman disease, and primary effusion lymphoma. Kaposi sarcoma: mononuclear predominance, exudate, pH >7.4; LDH, 111 to 330 IU/L; glucose >60 mg/dL.
  • Chest x-ray (CXR): posteroanterior-anteroposterior views
    • Upright x-rays show a concave meniscus in the costophrenic angle that suggests >250 mL of pleural fluid; homogeneous opacity, with visibility of pulmonary vessels through diffuse haziness and 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; decubitus x-rays to exclude a loculated effusion and underlying pulmonary lesion or pulmonary thickening
    • Supine x-rays show costophrenic blunting, haziness, obliteration of the diaphragmatic silhouette, decreased visibility of the lower lobe vasculature, and widened minor fissure.
  • Ultrasonography (US): detects as 5 to 50 mL of pleural fluid; identifies loculated effusions; site for thoracocentesis, pleural biopsy, or pleural drainage
  • Chest CT scan with contrast for patients with undiagnosed pleural effusion. CT pulmonary angiography if PE is suspected.
Follow-Up Tests & Special Considerations
  • 75% of patients with exudative effusions have a non-CHF cause.
    • NT-ProBNP: biomarker of CHF-associated effusion; >1,500 pg/mL; sensitivity and specificity 94% (2)[A]
    • Observation in uncomplicated asymptomatic patients (i.e., CHF, cirrhosis), viral pleurisy, thoracic or abdominal surgery
Diagnostic Procedures/Other
Diagnostic thoracentesis indicated for the following:
  • 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
image TREATMENT
Oxygen support
GENERAL MEASURES
  • Therapeutic thoracentesis, if symptomatic
  • Chest tube thoracostomy drainage: >1/2 hemithorax; complicated parapneumonic effusion (positive Gram stain or culture, pH <7.2, or glucose <60 mg/dL); empyema; hemothorax. Recommended limit is 1,000 to 1,500 mL in a single thoracentesis procedure (5)[B].
MEDICATION
First Line
CHF: diuretics (75% clearing in 48 hours); parapneumonic effusion: antibiotics; rheumatologic conditions/inflammation: steroids and NSAIDs
Second Line
Symptomatic nonmalignant effusions that are refractory to treatment may be managed with repeated therapeutic thoracentesis or pleurodesis.
ISSUES FOR REFERRAL
  • Uncertain etiology; malignant effusion; high-risk diagnostic thoracentesis; decortication
  • Video-assisted thoracoscopy for sclerosis; peritoneal shunts for symptomatic recurrence
ADDITIONAL THERAPIES
  • Pleurodesis for symptomatic patients whose pleural effusion reaccumulates too quickly for repeat therapeutic thoracentesis
  • Tunneled pleural catheter is the preferred treatment for patients with malignant pleural effusion and limited survival.
  • Sclerosing agents for malignant effusions: doxycycline, bleomycin, talc, and minocycline; talc is more efficacious. The relative risk of nonrecurrent effusion was 1.34 (95% CI 1.16-1.55) in favor of talc compared with bleomycin, tetracycline, or mustine.
SURGERY/OTHER PROCEDURES
  • Percutaneous pleural biopsy if a cause is not clear after thoracentesis
    • Close pleural biopsy: Pleura is diffusely involved (TB pleuritis, noncaseating granuloma 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.
  • Parapneumonic effusion should be sampled if free-flowing, but layer is >10 mm on a lateral decubitus film. Loculated, thickened pleura on a contrast-enhanced CT scan, clearly delineated by US open pleural biopsy by thoracotomy
  • Contraindications for thoracocentesis: anticoagulation, bleeding diathesis, thrombocytopenia <20,000/mm3, mechanical ventilation
  • Bronchoscopy: when malignancy is suspected (pulmonary infiltrate or mass on CXR or CT scan, hemoptysis, massive pleural effusion, or shift of the mediastinum toward the side of effusion)
  • Thoracoscopy
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
Treat any underlying medical disorder.
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
  • Check for the amount and quality of fluid drained, air leak (bubbling), and oscillation.
  • Repeat a CXR when drainage decreases to <100 mL/day to evaluate complete clearing.
  • For a large effusion, reevaluate catheter position; if positioned appropriately, consider fibrinolytics.
DIET
Cardiac diet in patients with heart failure; correct hypoproteinemia.
PROGNOSIS
  • Malignant effusion: poor
  • Low-pH malignant effusions have shorter survival and poorer response to chemical pleurodesis than those with pH >7.3.
  • Low pleural fluid pH (≤7.15): high likelihood of pleural space drainage
REFERENCES
1. Sahn SA, Huggins JT, San Jose E, et al. The art of pleural fluid analysis. Clin Pulm Med. 2013;20(2): 77-96.
2. Saguil A, Wyrick K, Hallgren J. Diagnostic approach to pleural effusion. Am Fam Physician. 2014;90(2): 99-104.
3. Light RW. Pleural effusions. Med Clin North Am. 2011;95(6):1055-1070.
4. Wilcox ME, Chong CA, Stanbrook MB, et al. Does this patient have an exudative pleural effusion? The rational clinical examination systematic review. JAMA. 2014;311(23):2422-2431.
5. Mahmood K, Wahidi MM. Straightening out chest tubes: what size, what type, and when. Clin Chest Med. 2013;34(1):63-71.
Additional Reading
&NA;
Bielsa S, Porcel JM, Castellote J, et al. Solving the Light's criteria misclassification rate of cardiac and hepatic transudates. Respirology. 2012;17(4): 721-726.
Codes
&NA;
ICD10
  • J90 Pleural effusion, not elsewhere classified
  • J91.0 Malignant pleural effusion
  • J94.0 Chylous effusion
Clinical Pearls
&NA;
  • Clinical presentation and pleural fluid analysis allow to diagnose the cause of effusion in 75% of patients at first evaluation.
  • Bilateral pleural effusion suggest heart failure, malignancy in absence of cardiomegaly, and tuberculosis or parasitic infection in children.
  • Loculation suggest pleural inflammation and may occur with the following: empyema, hemothorax, and TB.
  • Parapneumonic effusion should be tapped ASAP.
  • Ascites and pleural effusion suggest hepatic hydrothorax, ovarian cancer, or Meig syndrome
  • Consider diagnostic thoracocentesis in patient with heart failure: fever, pleuritic chest pain, unilateral effusion or effusion of markedly disparate size, effusion not associated with cardiomegaly, effusion fails to respond to management of heart failure
  • Most common cause of exudative effusion are pneumonia, neoplasms, and thromboembolism.