What are the recommended tests and management for pleural fluid testing in patients with pleural effusions?

Pleural Fluid Testing: Recommended Tests and Management

Initial Diagnostic Approach

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. 1

Clinical Assessment Before Thoracentesis

• Determine if the clinical picture suggests a transudate (heart failure, hypoalbuminemia, dialysis) before performing thoracentesis 2, 1
• If transudate is clinically evident with confirmatory chest radiograph, thoracentesis is not needed unless atypical features exist or the effusion fails to respond to treatment 2
• Approximately 75% of pulmonary embolism cases with effusion present with pleuritic pain and dyspnea out of proportion to effusion size 2

Thoracentesis Technique

• Image guidance (ultrasound) should ALWAYS be used to reduce complications 1, 3
• Use a fine-bore 21G needle with 50 mL syringe for diagnostic sampling 2, 1
• Obtain 25-50 mL for optimal diagnostic yield, though 25 mL minimum is acceptable 1, 4

Essential Laboratory Tests

Core Biochemical Analysis

• Measure pleural fluid protein and LDH to differentiate transudates from exudates using Light's criteria when protein is borderline (25-35 g/L) 1, 5
• Light's criteria: effusion is exudative if any one of the following is met: pleural fluid protein/serum protein >0.5, pleural fluid LDH/serum LDH >0.6, or pleural fluid LDH >2/3 upper limit of normal serum LDH 5, 6
• If Light's criteria suggest exudate but clinical picture suggests transudate, measure serum-pleural fluid albumin gradient; if >1.2 g/dL, the effusion is likely transudative 5

pH Measurement

• Perform pH measurement in all non-purulent effusions when infection is suspected 1
• pH <7.2 indicates complicated parapneumonic effusion requiring drainage 1
• pH <7.0 is an indicator of poor prognosis in parapneumonic effusions 7

Microbiological Studies

• Send 5-10 mL in both aerobic and anaerobic blood culture bottles PLUS sterile containers for Gram stain, AAFB stain, and TB culture 1
• When volume is limited (2-5 mL), prioritize blood culture bottles over plain containers 1
• Blood culture bottles increase diagnostic yield compared to sterile containers alone 2, 1

Cytological Examination

• Submit 25-50 mL for cytological analysis in suspected malignancy 1, 4
• Use both direct smear and cell block preparation 1, 4
• If first cytology is non-diagnostic, obtain a second sample to increase diagnostic yield 2
• Cytology detects only 60% of malignant effusions; negative results require further investigation 2, 1

Specialized Testing Based on Clinical Context

Suspected Tuberculosis

• Consider adenosine deaminase (ADA) in high prevalence populations; levels >35-45 U/L with >50% lymphocytes suggest TB 1
• Interferon-gamma can be measured with 89% sensitivity and 97% specificity 1
• Tissue sampling via pleural biopsy is strongly recommended as the preferred diagnostic approach (69-97% sensitivity) 1
• A positive tuberculin skin test combined with exudative lymphocyte-predominant effusion is sufficient to justify empirical antituberculous therapy 2

Suspected Malignancy

• Cytology sensitivity varies by tumor type; direct biopsies should be considered for tumors with low cytological yield, especially mesothelioma 1
• Pleural fluid biomarkers should NOT be routinely used for diagnosing secondary pleural malignancy 1
• If routine tests fail to diagnose suspected malignancy, thoracoscopy is advised 2
• Contrast-enhanced CT thorax should be performed with fluid present to better visualize pleura and identify optimal biopsy sites 2

Suspected Parapneumonic Effusion/Empyema

• Measure pleural fluid glucose, LDH, and pH in addition to microbiological studies 7
• Poor prognostic indicators requiring drainage: frank pus, positive Gram stain, glucose <2.2 mmol/L, pH <7.0, pleural loculations, or LDH >3 times upper limit of normal 7
• If fluid cannot be completely evacuated due to loculations, consider intrapleural thrombolytic therapy 7

Suspected Heart Failure

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

Fluid Appearance Assessment

Visual Inspection

• Always record gross appearance and odor of pleural fluid 2, 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

Management of Persistent Undiagnosed Effusions

• Reconsider pulmonary embolism and tuberculosis since these disorders are amenable to specific treatment 2
• Approximately 15% of effusions remain undiagnosed after repeated cytology and pleural biopsy 2
• Many undiagnosed effusions are eventually proved to be malignancy with sustained observation 2
• If pulmonary embolism is suspected clinically, proceed with imaging for embolism as there are no specific pleural fluid tests 2
• Obtain pleural tissue via ultrasound/CT-guided biopsy, closed pleural biopsy, or thoracoscopy 2, 1
• Send tissue for histology and TB culture together with repeat pleural aspiration for cytology 2

Special Populations

HIV-Infected Patients

• Differential diagnosis differs significantly from immunocompetent patients 2
• Leading causes: Kaposi's sarcoma (33%), parapneumonic effusions (28%), tuberculosis (14%), Pneumocystis carinii pneumonia (10%), and lymphoma (7%) 2

Critical Pitfalls to Avoid

• Diagnostic bronchoscopy is NOT indicated in undiagnosed effusion assessment unless the patient has hemoptysis or features suggestive of bronchial obstruction 2
• Do not perform blind thoracentesis without image guidance 1, 3
• Do not rely solely on clinical judgment or Light's criteria alone; both have limitations and occasional errors 8
• Do not send less than 25 mL for cytology unless unavoidable, as sensitivity drops substantially 1, 4
• Pleural biopsy specimens should be placed in both saline and formalin and sent for histological examination and culture 2