What are the diagnostic criteria for pleural effusion in a patient with suspected excess fluid in the pleural space?

Diagnostic Criteria for Pleural Effusion

The diagnosis of pleural effusion requires thoracentesis with pleural fluid analysis to differentiate transudates from exudates using Light's criteria when protein levels are borderline (25-35 g/L), followed by comprehensive biochemical, microbiological, and cytological testing to establish the underlying etiology. 1, 2

Initial Classification: Transudate vs Exudate

Protein-Based Classification

• Pleural fluid protein <25 g/L = transudate 3
• Pleural fluid protein >35 g/L = exudate 3
• Pleural fluid protein 25-35 g/L = apply Light's criteria 1, 2, 3

Light's Criteria (for borderline cases)

An effusion is an exudate if it meets any one of the following:

• Pleural fluid protein/serum protein ratio >0.5 4
• Pleural fluid LDH/serum LDH ratio >0.6 4
• Pleural fluid LDH >2/3 the upper limit of normal serum LDH 4

Clinical Pearl: Transudates indicate normal pleural surfaces with hydrostatic/oncotic pressure imbalance (heart failure, cirrhosis, hypoalbuminemia), while exudates indicate altered pleural surface or capillary permeability (infection, malignancy, inflammation). 1

Mandatory Pleural Fluid Tests

Core Analysis (All Patients)

Every pleural fluid sample must be analyzed for: 1, 2

• Protein and LDH (for transudate/exudate differentiation) 1, 2
• pH (in all non-purulent effusions when infection suspected) 1, 2
• Cytology (25-50 mL required) 2
• Gram stain and microbiological culture 1, 2
• Acid-fast bacilli (AAFB) stain and TB culture 1, 2

Sample Collection Technique

• Send 5-10 mL in BOTH aerobic and anaerobic blood culture bottles AND sterile containers to maximize diagnostic yield 1, 2, 3
• Use fine-bore 21G needle with 50 mL syringe 1, 3
• Image guidance should ALWAYS be used to reduce complications 2

Specific Diagnostic Criteria by Etiology

Complicated Parapneumonic Effusion/Empyema

• pH ≤7.2 = high risk, requires chest tube drainage 1, 2
• pH >7.2 and <7.4 = intermediate risk; measure LDH 1
  • If LDH >900 IU/L, consider drainage especially with fever, high volume, glucose <4.0 mmol/L (72 mg/dL), pleural enhancement on CT, or septations on ultrasound 1
• pH ≥7.4 = low risk, no immediate drainage indicated 1
• Glucose <3.3 mmol/L can substitute for pH when immediate pH unavailable 1

Critical Pitfall: Avoid contaminating pH samples with local anesthetic or heparin (lowers pH); expel all heparin from arterial blood gas syringes. Air in syringe or delays increase pH falsely. 1

Tuberculous Pleural Effusion

• Adenosine deaminase (ADA) >35-45 U/L with >50% lymphocytes suggests TB in high prevalence areas 2, 5
• Interferon-gamma: 89% sensitivity, 97% specificity 2
• Tissue sampling (pleural biopsy) is strongly recommended as preferred diagnostic approach with 69-97% sensitivity 2

Malignant Effusion

• Cytology detects only 60% of malignant effusions 1, 2, 3
• Sensitivity varies by tumor type: highest for adenocarcinoma, lower for mesothelioma, squamous cell, lymphoma, sarcoma 1
• First specimen yields 65% of diagnoses, second adds 27%, third only 5% 1
• Negative cytology mandates further investigation with contrast-enhanced CT and pleural biopsy 1, 2

Chylothorax vs Pseudochylothorax

Chylothorax criteria: 1

• Triglyceride >1.24 mmol/L (110 mg/dL) = chylothorax
• Triglyceride <0.56 mmol/L (50 mg/dL) = excludes chylothorax
• Between these values: look for chylomicrons

Pseudochylothorax criteria: 1

• Cholesterol >5.18 mmol/L (200 mg/dL)
• Cholesterol crystals present on microscopy
• No chylomicrons

Hemothorax

• Pleural fluid hematocrit >50% of peripheral blood hematocrit = hemothorax 1, 2
• Hematocrit <1% = blood not clinically significant 1

Heart Failure

• Serum NT-proBNP should be measured to support diagnosis in unilateral effusions suspected of heart failure 1, 2
• Pleural fluid NT-proBNP not superior to serum levels and should not be ordered routinely 1, 2

Visual Inspection Criteria

Fluid Appearance 1, 2

• Turbid/milky fluid: Centrifuge to differentiate
  • Clear supernatant = empyema (cell debris)
  • Turbid supernatant = chylothorax (lipids)
• Frankly bloody: Usually malignancy, pulmonary embolism with infarction, trauma, benign asbestos effusion, or post-cardiac injury syndrome 1
• Purulent: Empyema, requires immediate drainage 1
• Odor: Unpleasant aroma suggests anaerobic infection 1

Diagnostic Algorithm

Step 1: Clinical Assessment

• Determine if clinical picture suggests transudate (heart failure with cardiomegaly, hypoalbuminemia, cirrhosis, dialysis) 1, 3, 6
• If bilateral effusions with clear systemic cause and patient asymptomatic, observation may be appropriate 3, 6

Step 2: Thoracentesis with Core Tests

• Perform all mandatory tests listed above 1, 2, 3
• Classify as transudate vs exudate using protein levels and Light's criteria 1, 2, 3

Step 3: Transudate Management

• Treat underlying cause (heart failure, cirrhosis, etc.) 1, 3
• Repeat thoracentesis only if atypical features or no response to treatment 3

Step 4: Exudate Without Diagnosis

• Order contrast-enhanced CT thorax (perform with fluid present for better pleural visualization) 1, 2, 3
• Obtain pleural tissue via: 1, 2, 3
  • Ultrasound/CT-guided biopsy
  • Thoracoscopy (preferred for suspected TB or malignancy)
  • Never perform blind (non-image-guided) pleural biopsies 1

Additional Specialized Tests

When to Order

• Triglycerides and cholesterol: Suspected chylothorax/pseudochylothorax 1, 2
• Creatinine: Suspected urinothorax (pleural fluid creatinine > serum creatinine) 1
• ADA: High TB prevalence areas or strong clinical suspicion 2, 5
• Hematocrit: Hemorrhagic fluid to confirm/exclude hemothorax 1, 2

Tests NOT Routinely Recommended

• Serum biomarkers should NOT be used routinely to diagnose secondary pleural malignancy, pleural infection, or autoimmune pleuritis 1, 2
• Pleural fluid NT-proBNP should NOT be ordered routinely 1, 2

Critical Pitfalls to Avoid

• Do not skip thoracentesis in bilateral effusions if heart size is normal (raises malignancy concern) or patient is symptomatic 3, 6
• Recognize alternative diagnoses that mimic parapneumonic effusion with low pH: rheumatoid effusion, advanced malignancy/mesothelioma 1
• If initial decision is not to drain, perform regular clinical reviews and consider repeat thoracentesis to avoid missing complicated parapneumonic effusion 1
• Cytology alone is insufficient for malignancy diagnosis given 40% false-negative rate; proceed to biopsy when suspicion remains high 1, 2