Pleural Effusion - 10 Marker Notes

Definition

Classification: Transudate vs Exudate

• Causes: CHF (most common), cirrhosis, nephrotic syndrome, hypoalbuminemia, constrictive pericarditis, myxedema, peritoneal dialysis, SVC obstruction

• Causes: Bacterial pneumonia (parapneumonic), malignancy (lung, breast, lymphoma), TB, pulmonary embolism, rheumatoid arthritis, SLE, pancreatitis, esophageal rupture

Light's Criteria (1972)

1. Pleural fluid protein / serum protein > 0.5
2. Pleural fluid LDH / serum LDH > 0.6
3. Pleural fluid LDH > 2/3 the upper limit of normal serum LDH

• Sensitivity 98-99%, specificity 65-86%
• Misclassifies ~20% of transudates as "pseudo-exudates"
• Correction: serum-to-pleural albumin gradient > 1.2 g/dL = transudate

Clinical Features

• Symptoms: Dyspnea (usually not until >500 mL), pleuritic chest pain, cough; referred ipsilateral shoulder pain
• Signs:
  • Dullness to percussion
  • Diminished breath sounds
  • Decreased tactile fremitus
  • Egophony at upper border of effusion
  • Pleural friction rub (pleurisy without effusion)
• Massive effusion (>1.5-2 L): mediastinal shift, hemodynamic compromise (tension hydrothorax - rare)

Radiological Findings

• CXR: Blunting of costophrenic angle (needs ~200 mL); meniscus sign; mediastinal shift (large)
• Lateral decubitus: detects ~50 mL
• CT: Identifies septations, loculations, pleural masses, underlying cause; evaluate density (Hounsfield units)
• Ultrasound: Detects small effusions; fluid is anechoic/hypoechoic; guides thoracentesis; distinguishes free vs loculated

Pleural Fluid Analysis - Key Tests

Special Subtypes

• Parapneumonic effusion: associated with bacterial pneumonia/lung abscess; complicated = pus, bacteria, or pH <7.2
• Empyema (pyothorax): frank pus in pleural space
• Hepatic hydrothorax: cirrhosis; small diaphragmatic defects; 85% right-sided; transudate
• Malignant effusion: metastatic lung Ca (40%), breast Ca (2nd), NHL most common in <30 yrs
• Chylothorax: thoracic duct disruption; milky fluid; high triglycerides
• Loculated effusion: adhesions between pleura; unilocular or multilocular; infectious or malignant

Management

• Diagnostic: all unexplained/new effusions
• Therapeutic: symptomatic massive effusion
• Remove no more than 1-1.5 L at a time (re-expansion pulmonary edema risk)
• Ultrasound guidance reduces pneumothorax risk
• Contraindications: coagulopathy, pleurodesis history, chest wall infection

• Empyema: small-bore pigtail catheter (14 Fr) now first-line; large-bore (28-40 Fr) traditionally used
• Malignant recurrent effusion: pleurodesis (talc most effective) or indwelling pleural catheter (IPC)

• CHF/cirrhosis: diuretics ± TIPS (hepatic hydrothorax)
• TB: anti-tuberculous therapy
• Malignant: chemotherapy/pleurodesis

Complications of Thoracentesis

Sources: Fischer's Mastery of Surgery 8e, Rosen's Emergency Medicine, Murray & Nadel's Respiratory Medicine - Fischer's Mastery of Surgery, p. 2428-2430; Rosen's EM, p. 988-990

Pleural Effusion - Harrison's 22e Notes (10 Marker)

Anatomy & Normal Physiology

• Pleural space lies between lung and chest wall; normally contains a thin fluid layer that acts as a coupling system
• Maintained at -3 to -5 cmH₂O (balance between lung elastic recoil and chest wall counter-expansion)
• Fluid enters from parietal pleural capillaries and is removed by parietal pleural lymphatics
• Fluid can also enter from: lung interstitial spaces (via visceral pleura) or peritoneal cavity (via diaphragmatic holes)
• Lymphatics can absorb 20x more fluid than normally formed - effusion develops when this capacity is overwhelmed
• ~1.5 million Americans/year develop pleural effusion

Etiology (Harrison's Table 305-1)

• CHF (left ventricular failure) - most common cause overall
• Cirrhosis
• Nephrotic syndrome
• Peritoneal dialysis
• SVC obstruction
• Myxedema
• Urinothorax

• Neoplastic: Metastatic disease, Mesothelioma
• Infectious: Bacterial (parapneumonic), TB, Fungal, Viral, Parasitic
• Pulmonary embolism
• GI disease: Esophageal perforation, Pancreatitis, Intraabdominal abscesses, Diaphragmatic hernia, Post-abdominal surgery, Endoscopic variceal sclerotherapy, Post-liver transplant
• Collagen vascular: Rheumatoid pleuritis, SLE, Drug-induced lupus, Sjögren, Granulomatosis with polyangiitis (Wegener), Churg-Strauss
• Miscellaneous: Post-CABG, Asbestos exposure, Sarcoidosis, Uremia, Meigs' syndrome, Yellow nail syndrome, Radiation therapy, Post-cardiac injury syndrome, Ovarian hyperstimulation, Pericardial disease, Chylothorax, Trapped lung, Hemothorax, Iatrogenic
• Drugs: Nitrofurantoin, Dantrolene, Methysergide, Bromocriptine, Procarbazine, Amiodarone, Dasatinib

Diagnostic Approach

• CXR with lateral decubitus films (standard)
• Ultrasound and CT: invaluable for characterizing effusion and guiding drainage

1. Pleural fluid protein / serum protein > 0.5
2. Pleural fluid LDH / serum LDH > 0.6
3. Pleural fluid LDH > 2/3 upper limit of normal serum LDH

Key Harrison's caveat: These criteria misidentify ~25% of transudates as exudates ("pseudoexudates" - most common in heart failure patients on diuretics)

Correction: If Light's criteria suggest exudate but clinical suspicion is transudate:

• Serum protein - pleural protein > 3.1 g/dL, OR
• Serum albumin - pleural albumin > 1.2 g/dL → identifies pseudoexudate with 100% sensitivity in CHF and 99% sensitivity in hepatothorax
• Elevated pleural cholesterol + elevated LDH also favors true exudate

Pleural Fluid Tests (Standard + Disease-Specific)

• Protein, LDH, Albumin
• Glucose
• Differential cell count
• Microbiologic studies (Gram stain, culture)
• Cytology

Key Individual Effusions (Harrison's)

CHF (most common cause)

• Elevated left atrial pressure → elevated pulmonary venous pressure → fluid in lung interstitium exits across visceral pleura → overwhelms lymphatic absorption (classic increased hydrostatic mechanism)
• Do thoracentesis if: effusions not bilateral + comparable in size, patient is febrile, or patient has pleuritic chest pain
• Otherwise treat heart failure first; if effusion persists despite therapy - then thoracentesis
• NT-proBNP > 1500 pg/mL in pleural fluid = suggestive of CHF effusion

Parapneumonic Effusion (PPE)

• Seen in up to 50% of community-acquired pneumonia - most common cause of exudative effusion in USA
• Usually reactive (no organisms on culture)
• 10% of PPE → complicated PPE or empyema (fibrinopurulent or grossly purulent)
• Aerobic bacterial: acute febrile illness, pleuritic chest pain, sputum production, leukocytosis
• Anaerobic: subacute illness, weight loss, mild anemia, predisposition to aspiration; minimal parenchymal infiltrates with large effusion
• Thoracentesis indicated if significant pleural fluid present (to exclude infected space)
• Indications for tube thoracostomy (drain):
  • Gross pus (empyema)
  • Organisms on Gram stain/culture
  • Glucose < 3.3 mmol/L (60 mg/dL)
  • pH < 7.20 (obtain if pH is <7.3)
  • Loculated fluid

Malignant Effusion

• Most common causes: lung > breast > lymphoma; lymphoma is most common in young adults
• Cytology: sensitivity ~60% (up to 3 samples may be needed)
• If cytology negative but strong suspicion → thoracoscopy (sensitivity >90%)
• Treatment: Observe if asymptomatic. If symptomatic:
  • Therapeutic thoracentesis (first line)
  • Pleurodesis (talc most effective) for recurrent effusions
  • Indwelling pleural catheter (IPC) - especially for trapped lung

TB Pleuritis

• Common in immunocompromised, endemic areas
• Exudate with lymphocyte predominance
• Pleural fluid AFB smear: low sensitivity (~10-40%)
• ADA (adenosine deaminase) elevated - useful screening test
• Pleural biopsy: most diagnostic (granulomas ± AFB)
• Treat with standard anti-TB therapy; effusion usually resolves

Hemothorax

• Pleural fluid hematocrit > 50% of peripheral blood hematocrit = hemothorax (by definition)
• Most common causes: trauma, iatrogenic, spontaneous (vessel/tumor rupture)
• Management: drainage; surgery if ongoing hemorrhage

Chylothorax

• Disruption of thoracic duct (trauma, malignancy, surgery)
• Milky appearance; triglycerides > 110 mg/dL (1.24 mmol/L) confirms diagnosis
• Chylomicrons on lipoprotein analysis are diagnostic

Clinical Features

• Symptoms: dyspnea (most common presentation), occasional chest pain
• Physical signs: dullness to percussion, decreased breath sounds, decreased tactile fremitus, egophony at upper effusion border, pleural friction rub

Treatment Principles (Harrison's)

• Transudate: treat the underlying cause
• Exudate (parapneumonic/empyema): drain if meets criteria above
• Malignant: thoracentesis → pleurodesis or IPC for recurrence
• Post-CABG: left-sided early (bloody exudate, resolves spontaneously) vs late (lymphocytic exudate; treat with NSAIDs/steroids)
• Asbestos-related benign effusion: diagnosis of exclusion after ruling out mesothelioma

Source: Harrison's Principles of Internal Medicine, 22nd Edition (2025) - Chapter 305, by Rebecca M. Baron