Pleural Fluid Analysis for Pleural Effusion

Essential Initial Tests

The British Thoracic Society recommends that all pleural fluid samples should be analyzed for protein, LDH, pH, cytology, Gram stain, acid-fast bacilli (AAFB) stain, and microbiological culture, with samples sent in both sterile containers and blood culture bottles to maximize diagnostic yield 1, 2, 3
Measure pleural fluid protein to differentiate transudates from exudates, using Light's criteria when protein is borderline (25-35 g/L) 2, 3
Perform pH measurement in all non-purulent effusions when infection is suspected; pH <7.2 indicates complicated parapneumonic effusion requiring drainage 2, 3

Send 5-10 mL in aerobic and anaerobic blood culture bottles PLUS sterile containers for Gram stain, AAFB stain, and TB culture 1, 4, 3
When volume is limited (2-5 mL), prioritize blood culture bottles over plain containers 1, 4

Submit 25-50 mL for cytological analysis in suspected malignancy (strong recommendation by consensus) 1, 4
Use both direct smear and cell block preparation 1, 4
Cytology detects only 60% of malignant effusions; negative results should prompt further investigation 2, 3

Consider adenosine deaminase (ADA) in high prevalence populations (>35-45 U/L with >50% lymphocytes suggests TB); use as exclusion test in low prevalence areas 1, 4, 5
Interferon-gamma (IFN-γ) can be measured with 89% sensitivity and 97% specificity 5
Tissue sampling is strongly recommended as preferred diagnostic approach for all suspected TB cases (69-97% sensitivity) 1, 4, 5

Cytology sensitivity varies by tumor type: direct biopsies should be considered for tumors with low cytological yield (especially mesothelioma) 1, 4
Pleural fluid biomarkers should NOT be routinely used for diagnosing secondary pleural malignancy 1, 4

Serum NT-proBNP should be measured to support diagnosis in unilateral effusions suspected of heart failure (conditional recommendation) 1, 4
Pleural fluid NT-proBNP is not superior to serum levels and should not be ordered routinely 1, 4

Note appearance and odor: serous, blood-tinged, frankly bloody, or purulent 2, 3
Turbid/milky fluid: centrifuge to differentiate empyema (clear supernatant) from chylothorax (turbid supernatant due to lipids) 2, 3
Hemorrhagic fluid: measure hematocrit if hemothorax suspected; pleural fluid hematocrit >50% of peripheral blood confirms hemothorax 2, 3

Image guidance should ALWAYS be used to reduce complications (strong recommendation by consensus) 1, 4
Use fine-bore 21G needle with 50 mL syringe 2, 3

Determine if transudate likely (heart failure, hypoalbuminemia, dialysis) 2, 3, 6
If transudate suspected: treat underlying cause; perform thoracentesis only if atypical features or no response 6
Perform thoracentesis: send for all core tests listed above 2, 3
Classify as transudate vs exudate: use protein levels and Light's criteria when borderline 2, 3
If exudate without diagnosis: proceed to contrast-enhanced CT thorax and consider pleural biopsy (ultrasound/CT-guided, closed, or thoracoscopic) 2, 3, 6