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Pleural Effusion

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Pleural Effusion

BASICS

DESCRIPTION

Abnormal accumulation of fluid in the pleural space

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

Presumptive diagnosis in 50% of cases. Small pleural effusions, radiographic area <2 intercostal spaces (<300 mL) are asymptomatic.

Dyspnea, fever, malaise, and weight loss; chest pain, cough, hemoptysis, and dull pain

Initial Tests (lab, imaging)

CHF: diuretics (75% clearing in 48 hours); parapneumonic effusion: antibiotics; rheumatologic conditions/inflammation: steroids and NSAIDs

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

Admission Criteria/Initial Stabilization

Treat any underlying medical disorder.

Cardiac diet in patients with heart failure; correct hypoproteinemia.

11 Sahn SA, Huggins JT, San Jose E, et al. The art of pleural fluid analysis. Clin Pulm Med. 2013;20(2):77 " 96.22 Saquil A, Wyrick K, Hallgren J. Diagnostic approach to pleural effusion. Am Fam Physician. 2014;90(2):99 " 104.33 Light RW. Pleural effusions. Med Clin North Am. 2011;95(6):1055 " 1070.44 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 " 2431.55 Mahmood K, Wahidi MM. Straightening out chest tubes: what size, what type, and when. Clin Chest Med. 2013;34(1):63 " 71.

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.

  • 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

  • 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
  • TransudatesCHF: 40% of transudative effusions; 80% bilateral. Constrictive pericarditis, atelectasis; superior vena cava syndromeCirrhosis (hepatic hydrothorax); nephrotic syndrome, hypoalbuminemia; myxedemaUrinothorax, central line misplacement; peritoneal dialysis
  • ExudatesLung parenchyma infection, bacterial (parapneumonic, tuberculous pleurisy), fungal, viral, parasitic (amebiasis, Echinococcus)Cancer: lung cancer, metastases (breast, lymphoma, ovaries), mesotheliomaPE: 25% of PEs are transudate.Collagen vascular disease: rheumatoid arthritis, systemic lupus erythematosus, Wegener granulomatosis, sarcoidosis, Churg-StraussGI: pancreatitis, esophageal rupture, abdominal abscess, after liver transplant. Chylothorax: thoracic duct tear, malignancyHemothorax: trauma, PE, malignancy, coagulopathy, aortic aneurysmOthers: after coronary artery bypass graft; Dressler syndrome; uremia, asbestos exposure, radiation; drug-induced: nitrofurantoin, bromocriptine, amiodarone, procarbazine, hydralazine, procainamide, quinidine, methotrexate, and methysergideMeigs syndrome; yellow nail syndrome; ovarian stimulation syndrome; lymphangiomatosis; acute respiratory distress syndrome (ARDS)Chylothorax: thoracic duct tear, malignancy, associated with lymphoma
  • 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; superior vena cava syndrome
  • Cirrhosis (hepatic hydrothorax); nephrotic syndrome, hypoalbuminemia; myxedema
  • Urinothorax, central line misplacement; peritoneal dialysis
  • 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/ Ž ΌL)

COMMONLY ASSOCIATED CONDITIONS

DIAGNOSIS

HISTORY

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

DIAGNOSTIC TESTS & INTERPRETATION

  • 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 > ’ ”; 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- Ž ³ >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; Waldenstr ƒ Άm 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.
  • 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 viewsUpright 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 thickeningSupine 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.
  • Ratio of pleural fluid-to-serum protein levels >0.5; ratio of pleural fluid-to-serum LDH levels >0.6; pleural fluid LDH level > ’ ”; the upper limit for serum LDH level (1,3)[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%)
  • 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.
  • 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
  • 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
  • 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

TREATMENT

GENERAL MEASURES

  • Therapeutic thoracentesis, if symptomatic
  • Chest tube thoracostomy drainage: > ‚ ½; 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

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 thoracentesisClose 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
  • 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.

INPATIENT CONSIDERATIONS

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

  • 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

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

COMPLICATIONS

  • Pleural effusion: constrictive fibrosis, pleurocutaneous fistula
  • Thoracentesis: pneumothorax (5 " “10%); hemothorax (~1%); empyema; spleen/liver laceration; reexpansion pulmonary edema (if >1.5 L is removed)

REFERENCES

ADDITIONAL READING

CODES

ICD10

  • J90 Pleural effusion, not elsewhere classified
  • J91.0 Malignant pleural effusion
  • J94.0 Chylous effusion
  • A15.6 Tuberculous pleurisy
  • J91.8 Pleural effusion in other conditions classified elsewhere

ICD9

  • 511.9 Unspecified pleural effusion
  • 511.81 Malignant pleural effusion
  • 511.1 Pleurisy with effusion, with mention of a bacterial cause other than tuberculosis
  • 511.89 Other specified forms of effusion, except tuberculous

SNOMED

  • 60046008 Pleural effusion (disorder)
  • 83270006 Neoplastic pleural effusion (disorder)
  • 85426002 Bacterial pleurisy with effusion (disorder)
  • 83035003 Chylothorax
  • 90727007 Pleural effusion due to congestive heart failure
  • 31892009 Hemothorax (disorder)
  • 13841000119107 Exudative pleural effusion (disorder)
  • 425802001 Bilateral pleural effusion (disorder)

CLINICAL PEARLS

  • 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.