Pleural Fluid Analysis Approach
Begin with diagnostic thoracentesis using a 21G needle to obtain pleural fluid for protein, LDH, pH, Gram stain, AAFB stain, cytology, and microbiological culture, then apply Light's criteria to differentiate exudate from transudate, using albumin gradient or cholesterol when Light's criteria are borderline or when serum samples are unavailable. 1
Initial Fluid Collection and Gross Examination
Obtain pleural fluid with a 21G needle and 50 mL syringe, placing samples in both sterile vials and blood culture bottles to maximize diagnostic yield for microbiological examination. 1
Document the appearance (serous, blood-tinged, frankly bloody, or purulent) and odor of the fluid immediately. 1
If the fluid appears turbid or milky, centrifuge it: clear supernatant indicates empyema (cell debris), while persistent turbidity suggests chylothorax or pseudochylothorax (high lipid content). 1
For bloody fluid, obtain a pleural fluid hematocrit: >50% of peripheral blood hematocrit confirms hemothorax, while <1% indicates insignificant blood contamination. 1
Transudate vs Exudate Differentiation
Primary Approach: Light's Criteria
Apply Light's criteria when pleural fluid protein is between 25-35 g/L or when serum protein is abnormal. 1 The effusion is an exudate if it meets ANY of the following:
- Pleural fluid protein/serum protein ratio >0.5 1, 2
- Pleural fluid LDH/serum LDH ratio >0.6 1, 2
- Pleural fluid LDH >2/3 upper limit of normal serum LDH 1, 2
When Serum Sample is Unavailable
Measure pleural fluid cholesterol: >55 mg/dL indicates exudate with diagnostic accuracy equivalent to Light's criteria. 1, 3 This represents a practical, cost-effective alternative for initial evaluation. 3
Correcting Light's Criteria Misclassification
Light's criteria misclassify 25-30% of cardiac and hepatic transudates as exudates, particularly in patients receiving diuretics. 1, 3, 4
When Light's criteria suggest exudate BUT clinical picture strongly suggests heart failure or cirrhosis:
Calculate serum-to-pleural fluid albumin gradient (serum albumin minus pleural fluid albumin): >1.2 g/dL reclassifies the effusion as transudate. 1, 4
Alternative: Pleural fluid-to-serum albumin ratio <0.6 identifies cardiac transudates with 78% accuracy. 1, 4
Measure NT-proBNP (pleural fluid or serum): >1500 pg/mL indicates heart failure with 93% sensitivity and 93% specificity. 1
Apply the cardiac effusion scoring system if exudate criteria are met but heart failure is suspected: age ≥75 years (3 points), albumin gradient >1.2 g/dL (3 points), pleural fluid LDH <250 U/L (2 points), bilateral effusion (2 points), protein gradient >2.5 g/dL (1 point); score ≥7 suggests cardiac origin. 1
Additional Diagnostic Tests for Exudates
pH Measurement
Measure pleural fluid pH in all non-purulent effusions when infection is suspected. 1
pH <7.2 with normal blood pH indicates complicated parapneumonic effusion/empyema, requiring urgent chest tube drainage. 1, 5
pH <7.2 also occurs in rheumatoid arthritis, esophageal rupture, and malignancy. 1
Cell Count and Differential
Elevated nucleated cell count (>5,000 cells/μL) with neutrophil predominance suggests parapneumonic effusion or empyema. 5
Lymphocyte predominance suggests tuberculosis or malignancy. 5, 6
Specialized Biomarkers
In high tuberculosis prevalence populations, measure pleural fluid adenosine deaminase (ADA) and/or interferon-gamma: ADA has 91% sensitivity and 88% specificity, while interferon-gamma has 95% sensitivity and 96% specificity. 1
In low prevalence populations, use ADA as an exclusion test, but prioritize tissue sampling for culture and sensitivity. 1
For suspected lupus pleuritis, measure pleural fluid ANA to support diagnosis. 1
Cytology
Send pleural fluid for cytology in suspected malignancy, recognizing that only 60% of malignant effusions are diagnosed by cytological examination alone. 1
Negative cytology should prompt consideration of contrast-enhanced CT thorax (performed with fluid present) to identify pleural nodules/thickening and guide biopsy site selection. 1
Clinical Pitfalls and Caveats
In renal failure, pleural fluid may be transudative or exudative, and cholesterol can be elevated even in transudates through alternative mechanisms. 3
In nephrotic syndrome, fluid may be exudative despite transudate mechanisms due to oncotic and hydrostatic alterations. 3
Ultrasound echogenicity alone is unreliable for transudate-exudate discrimination (anechoic pattern has only 63% specificity for transudates), though pleural nodularity on ultrasound strongly suggests malignancy (96.9% specificity). 1
CT attenuation values (Hounsfield units) show significant overlap between transudates and exudates and should not be used for discrimination. 1