Pleural Effusion – Causes, Symptoms, Diagnosis, Treatment and Ongoing care

Basics

A pleural effusion is an abnormal accumulation of fluid in the pleural space.

Description

  • 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.

Epidemiology

Incidence

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)

Prevalence

  • 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%.

Risk Factors

  • Occupational exposure
  • Drugs
  • 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.

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

Etiology

  • Transudates:
    • 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
  • Exudates:
    • 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

Hypoproteinemia

Diagnosis

Presumptive diagnosis based on clinical impression in 50%

Small pleural effusions are asymptomatic

History

  • 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

Physical Exam

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

Lab

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%

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.

Imaging

Initial approach

  • 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 Procedures/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

Differential Diagnosis

  • 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 aureusHaemophilus influenzae,Mycoplasma pneumoniaeLegionellaNocardia 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 MycobacteriumToxoplasmaHistoplasma capsulatumCryptococcus, 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

Treatment

Support with oxygen and arterial blood gas determinations (ABCs).

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Medication

Therapy for breast, lymphoma, ovarian, prostate, and small cell lung cancer may control the effusion.

First Line

  • CHF: Diuretics (75% clearing in 48 h)
  • Parapneumonic effusion: Antibiotics
  • For rheumatologic and inflammatory causes: Steroids and nonsteroidal anti-inflammatory drugs (NSAIDs)

Second Line

Symptomatic nonmalignant effusions that are refractory to treatment may be managed with repeated therapeutic thoracentesis or pleurodesis.

Additional Treatment

General Measures

  • 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

Additional Therapies

  • 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].

Surgery/Other Procedures

  • 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

In-Patient Considerations

Initial Stabilization

Treat underlying medical disorder.

Ongoing Care

Follow-Up Recommendations

Patient Monitoring

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.

Diet

Cardiac diet in patients with heart failure; correct hypoproteinemia.

Prognosis

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

Complications

  • 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)

References

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.

Codes

ICD9

  • 511.1 Pleurisy with effusion, with mention of a bacterial cause other than tuberculosis
  • 511.9 Unspecified pleural effusion
  • 511.81 Malignant pleural effusion

Snomed

  • 60046008 pleural effusion (disorder)
  • 85426002 bacterial pleurisy with effusion (disorder)
  • 83270006 neoplastic pleural effusion (disorder)

Clinical Pearls

  • A complicated parapneumonic effusion requires urgent drainage.
  • Outpatient therapeutic thoracentesis is preferred for patients with a short life expectancy (<3 months).

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