How is pleural fluid analysis performed and interpreted?

Pleural Fluid Analysis: Procedure and Interpretation

Pleural fluid analysis should be performed using a fine bore (21G) needle and 50 ml syringe, with samples sent in both sterile vials and blood culture bottles for comprehensive testing including protein, LDH, pH, cytology, and microbiological studies to accurately diagnose the underlying cause of the effusion. 1, 2

Procedure for Pleural Fluid Collection

• Perform thoracentesis using ultrasound guidance to improve success rates and reduce the risk of pneumothorax (0% vs 29% when performed without ultrasound) 1
• Use a fine bore (21G) needle and a 50 ml syringe for diagnostic thoracentesis 1, 3
• Collect approximately 50 ml of fluid for diagnostic purposes (larger volumes do not increase diagnostic yield) 1
• Place samples in both sterile vials and blood culture bottles to increase microbiological diagnostic yield 1, 2
• For suspected infections, send samples in blood culture bottles in addition to sterile tubes 1

Initial Assessment of Pleural Fluid

• Note the appearance and odor of the fluid immediately after collection 1
• Categorize appearance as serous, blood-tinged, frankly bloody, or purulent 1, 4
• For turbid or milky fluid, centrifuge the sample:
  • If supernatant is clear: likely empyema (cell debris) 1
  • If supernatant remains turbid: likely chylothorax or pseudochylothorax (high lipid content) 1
• For bloody fluid, measure pleural fluid hematocrit:
  • If >50% of peripheral blood hematocrit: confirms hemothorax 1
  • If <1%: blood is not clinically significant 1
  • Bloody appearance increases probability of malignancy (OR 1.73) 4

Laboratory Analysis

• Send fluid for the following tests:
  • Protein and LDH (to differentiate transudate from exudate) 1, 2
  • pH (especially if infection is suspected) 1, 2
  • Gram stain and microbiological cultures 1
  • Acid-fast bacilli stain and TB culture 1, 2
  • Cytological examination 1
  • Additional tests based on clinical suspicion (e.g., amylase, glucose, triglycerides) 5

Interpretation of Results

Transudate vs. Exudate Classification

• If pleural protein <25 g/L: transudate 1, 2
• If pleural protein >35 g/L: exudate 1, 2
• If pleural protein is between 25-35 g/L, apply Light's criteria 1:
  • Pleural fluid protein/serum protein ratio >0.5
  • Pleural fluid LDH/serum LDH ratio >0.6
  • Pleural fluid LDH >2/3 the upper limit of normal serum LDH

Specific Diagnostic Indicators

• Neutrophil predominance (>50%) with elevated C-reactive protein: suggests parapneumonic effusion 5
• pH <7.20 in parapneumonic effusion: indicates complicated pleural effusion requiring drainage 5
• Lymphocyte predominance (>50%) with adenosine deaminase >45 U/L: suggestive of tuberculosis 5
• Positive cytology: confirms malignant effusion (sensitivity ~60-72% with two samples) 1
• Elevated N-terminal pro-brain natriuretic peptide: highly suggestive of heart failure 5

Diagnostic Algorithm

1. Evaluate if clinical picture suggests a transudate (heart failure, hypoalbuminemia, dialysis) 1, 2
2. If transudate is suspected and bilateral effusions are present in a clear clinical context (e.g., heart failure), thoracentesis may be deferred unless there are atypical features 2
3. If not clearly a transudate or there are any doubts, proceed to diagnostic thoracentesis 1
4. Classify as transudate or exudate based on fluid analysis 1
5. For transudates: treat the underlying cause 1
6. For exudates: continue investigation based on fluid characteristics 1, 2
7. If initial analysis is non-diagnostic:
   • Consider a second thoracentesis (yields diagnosis in ~25-28% of malignant cases) 1
   • Proceed to contrast-enhanced CT scan (with fluid present for better pleural visualization) 1, 2
   • Consider pleural biopsy (ultrasound/CT-guided, closed, or thoracoscopic) 1, 2

Common Pitfalls and Caveats

• Performing thoracentesis without ultrasound guidance increases pneumothorax risk 1
• Submitting more than two pleural fluid specimens rarely increases diagnostic yield (only 5% additional yield from third sample) 1
• Relying solely on cytology for malignancy diagnosis misses ~40% of cases; pleural biopsy may be necessary 1, 2
• Bloody appearance is not specific for malignancy (only 11% of malignant effusions appear bloody) 4
• Technical problems occur in ~23% of thoracentesis, with blood contamination (11%) and dry tap (7%) being most common 6
• Patient discomfort is often underestimated by operators; anxiety (21%) and site pain (20%) are common 6