Pleural Fluid Analysis for Pleural Effusion
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
Essential Initial Tests
Core Biochemical Analysis
- Protein and LDH: Measure pleural fluid protein to differentiate transudates from exudates, using Light's criteria when protein is borderline (25-35 g/L) 1
- pH measurement: Perform in all non-purulent effusions when infection is suspected; pH <7.2 indicates complicated parapneumonic effusion requiring drainage 1, 2
- Glucose: Levels <60 mg/dL help identify complicated parapneumonic effusions 2
Microbiological Studies
- Sample collection: Send 5-10 mL in aerobic and anaerobic blood culture bottles PLUS sterile containers for Gram stain, AAFB stain, and TB culture 1
- Prioritization: When volume is limited (2-5 mL), prioritize blood culture bottles over plain containers 1
Cytological Examination
- Volume requirements: Submit 25-50 mL for cytological analysis in suspected malignancy (strong recommendation by consensus) 1
- Processing: Use both direct smear and cell block preparation 1
- Limitations: Cytology detects only 60% of malignant effusions; negative results should prompt further investigation 1
Specialized Tests Based on Clinical Context
For Suspected Tuberculosis
- Adenosine deaminase (ADA): Consider in high prevalence populations (>35-45 U/L with >50% lymphocytes suggests TB); use as exclusion test in low prevalence areas 1, 3, 2, 4
- Interferon-gamma (IFN-γ): Can be measured with 89% sensitivity and 97% specificity 3
- Tissue sampling: Strongly recommended as preferred diagnostic approach for all suspected TB cases (69-97% sensitivity) 1, 3
Critical caveat: ADA may be falsely elevated in empyema, parapneumonic effusions, and rheumatoid pleurisy, and may be falsely negative in HIV-positive patients 3
For Suspected Malignancy
- Cytology sensitivity varies by tumor type: Direct biopsies should be considered for tumors with low cytological yield (especially mesothelioma) 1
- Biomarkers: Pleural fluid biomarkers should NOT be routinely used for diagnosing secondary pleural malignancy 1
For Suspected Heart Failure
- Serum NT-proBNP: Should be measured to support diagnosis in unilateral effusions suspected of heart failure (conditional recommendation) 1
- Pleural fluid NT-proBNP: Not superior to serum levels and should not be ordered routinely 1
For Suspected Lupus Pleuritis
- Pleural fluid ANA: Should be considered to support diagnosis 1
Fluid Appearance Assessment
Visual Inspection
- Note appearance and odor: Serous, blood-tinged, frankly bloody, or purulent 1
- Turbid/milky fluid: Centrifuge to differentiate empyema (clear supernatant) from chylothorax (turbid supernatant due to lipids) 1
- Hemorrhagic fluid: Measure hematocrit if hemothorax suspected; pleural fluid hematocrit >50% of peripheral blood confirms hemothorax 1
Procedural Recommendations
Thoracentesis Technique
- Image guidance: Should ALWAYS be used to reduce complications (strong recommendation by consensus) 1
- Needle size: Use fine-bore 21G needle with 50 mL syringe 1
Diagnostic Algorithm
- Clinical assessment: Determine if transudate likely (heart failure, hypoalbuminemia, dialysis) 1, 5
- If transudate suspected: Treat underlying cause; perform thoracentesis only if atypical features or no response 5
- Perform thoracentesis: Send for all core tests listed above 1
- Classify as transudate vs exudate: Use protein levels and Light's criteria when borderline 1
- If exudate without diagnosis: Proceed to contrast-enhanced CT thorax and consider pleural biopsy (ultrasound/CT-guided, closed, or thoracoscopic) 1, 5
Common pitfall: Light's criteria occasionally misidentify transudates as exudates; if clinical picture suggests transudate but criteria indicate exudate, measure serum-pleural fluid albumin gradient (>1.2 g/dL confirms transudate) 6