What does a very high Lactate Dehydrogenase (LDH) level in pleural fluid indicate?

Very High LDH in Pleural Fluid: Diagnostic Significance

A very high lactate dehydrogenase (LDH) level in pleural fluid strongly indicates an exudative effusion, most commonly associated with malignancy, empyema, or complicated parapneumonic effusion. 1, 2 The magnitude of LDH elevation can provide valuable diagnostic clues to the underlying pathology and guide management decisions.

Diagnostic Significance of Elevated Pleural Fluid LDH

Classification of Pleural Effusions

• LDH is a key component of Light's criteria, which remain the gold standard for distinguishing exudates from transudates 2
• Light's criteria define an exudate as meeting at least one of the following:
  • Pleural fluid/serum protein ratio > 0.5
  • Pleural fluid/serum LDH ratio > 0.6
  • Pleural fluid LDH > 2/3 upper limit of normal serum LDH 1, 2

Common Causes of Very High Pleural Fluid LDH

1. Malignancy:

   • Particularly adenocarcinoma and mesothelioma
   • Often associated with very high LDH levels
   • Pleural fluid cytology can diagnose approximately 60% of malignant effusions 1
   • A serum LDH:pleural fluid ADA ratio >20 is highly predictive of malignancy (sensitivity 98%, specificity 94%) 3

2. Pleural Infection:

   • Empyema and complicated parapneumonic effusions
   • Extremely high LDH levels, often >1000 U/L
   • Associated with low glucose (<3.3 mmol/L) and low pH (<7.2) 1, 2

3. Rheumatoid Arthritis:

   • Characterized by very low glucose levels and high LDH
   • Typically has glucose <1.6 mmol/L 1

4. Other Causes:

   • Tuberculosis (elevated LDH with high ADA >40 U/L) 2
   • Esophageal rupture (high LDH with elevated salivary amylase) 1
   • Lupus pleuritis 1

Clinical Implications and Management Approach

Diagnostic Algorithm for Very High LDH

1. Confirm exudative nature using complete Light's criteria

2. Evaluate additional pleural fluid parameters:

   • pH: <7.2 suggests infection, rheumatoid disease, or advanced malignancy 1
   • Glucose: <3.3 mmol/L suggests empyema, rheumatoid disease, TB, malignancy 1
   • Amylase: Elevated in pancreatic disease, esophageal rupture, malignancy 1, 2
   • Cell count and differential: Predominance of neutrophils suggests infection 2
   • Cytology: Essential for diagnosing malignancy (60% sensitivity) 1
   • ADA: >40 U/L suggests TB 2

3. Management based on suspected etiology:

   • Malignancy: Consider thoracoscopy if cytology negative but suspicion high; pleurodesis for recurrent effusions 4
   • Infection: Immediate chest tube drainage if purulent fluid, pH <7.2, or positive Gram stain/culture; appropriate antibiotics 2
   • Rheumatoid/Autoimmune: Treat underlying disease 4

Prognostic Significance

• In malignant effusions, pleural fluid pH <7.3 predicts poor survival (median 2.1 months vs 9.8 months for pH >7.3) 1, 2
• Very high LDH (>3 times upper limit of normal) in infected pleural fluid indicates poor prognosis 4

Important Clinical Pearls

• Repeat cytology if first sample is negative but malignancy suspected; second sample increases yield by approximately 27% 1
• LDH isoenzyme analysis can provide additional diagnostic information - increased isoLDH 4 and 5 in exudates, with >30% rise in isoLDH 2 suggesting malignancy 5, 6
• Thoracoscopy should be considered if diagnosis remains unclear after initial testing 2
• The pattern of LDH elevation, rather than absolute value alone, should be interpreted in context with other pleural fluid parameters 6

Pitfalls to Avoid

• Don't rely solely on LDH for diagnosis; always correlate with clinical picture and other pleural fluid parameters
• Don't assume all exudates with high LDH are infectious - malignancy is a common cause
• Don't forget to measure serum LDH simultaneously to calculate ratios for Light's criteria 1, 2
• Don't delay drainage in suspected infection with very high LDH and low pH 2