What diagnostic tests should be performed on pleural (pleural space) fluid from a patient with a pleural effusion?

From the Guidelines

When evaluating pleural effusion fluid, the most critical tests to run include cytological analysis, microbiological studies, and basic tests such as appearance assessment, cell count with differential, protein, LDH, glucose, and pH. These tests are essential in distinguishing between transudates and exudates, identifying potential malignancies, and guiding appropriate management strategies 1. The British Thoracic Society guideline recommends submitting 25–50 mL of pleural fluid for cytological analysis in patients with suspected malignant pleural effusion (MPE) 1. Key tests to consider include:

• Cytological analysis to identify malignant cells
• Microbiological studies, including Gram stain and culture, to identify potential infections
• Basic tests such as:
  • Appearance assessment
  • Cell count with differential
  • Protein
  • LDH
  • Glucose
  • pH Additional specialized tests may be indicated based on clinical suspicion, such as:
• Amylase for pancreatic disease or esophageal rupture
• Triglycerides for chylothorax (>110 mg/dL suggests chylothorax)
• Tumor markers for malignancy
• Adenosine deaminase for tuberculosis
• Rheumatoid factor or antinuclear antibodies for autoimmune causes Molecular testing like PCR for tuberculosis or other pathogens may be useful in specific cases 1. It is crucial to prioritize these tests to determine the underlying cause of the effusion and guide appropriate management strategies, ultimately improving patient outcomes in terms of morbidity, mortality, and quality of life.

From the Research

Initial Testing

• The first step in evaluating a patient with an undiagnosed pleural effusion is to determine whether the patient has a transudate or an exudate, using Light's criteria 2.
• If the patient's pleural fluid meets exudative criteria, but the patient appears clinically to have a transudative effusion, then the serum-pleural fluid albumin gradient should be measured 2, 3.
• The gross appearance and the odour of the pleural fluid should be noted 2, 3.

Laboratory Tests

• Laboratory tests that are useful in the differential diagnosis of exudative pleural effusions include:
  • Differential white cell count of the pleural fluid 2, 3
  • Cytology of the pleural fluid 2, 3
  • Levels of adenosine deaminase, glucose, amylase, and lactate dehydrogenase in the pleural fluid 2, 3
  • Gram stain and cultures 3, 4
  • Protein and lactic acid dehydrogenase levels in the pleural fluid and serum 3
  • pH levels 4

Specialized Testing

• If pleural tuberculosis is suspected, a needle biopsy of the pleura is indicated 2.
• If malignant pleural effusion is suspected, a serum lactate dehydrogenase (LDH) to pleural fluid adenosine deaminase (ADA) ratio can be used, with a cut-off level of >20 being highly predictive of malignancy 5.
• Lactate dehydrogenase isoenzyme analysis may also be helpful in the differential diagnosis of pleural effusions 6.
• Point-of-care ultrasound can be used to guide thoracentesis and evaluate the pleural space 4.
• Computed tomography of the chest can be used to exclude other causes of dyspnea and suggest complicated parapneumonic or malignant effusion 4.