What is the appropriate hospital workup for a patient presenting with a new large pleural effusion?

Hospital Workup for New Large Pleural Effusion

For a new large pleural effusion in a hospitalized patient, perform diagnostic thoracentesis immediately to differentiate transudate from exudate, obtain pleural fluid for comprehensive laboratory analysis including protein, LDH, pH, cell count with differential, Gram stain, culture (including blood culture bottles), and cytology, followed by contrast-enhanced CT chest if the diagnosis remains unclear. 1, 2

Initial Clinical Assessment

Determine if the clinical picture suggests a transudate:

• Look specifically for heart failure, hypoalbuminemia, cirrhosis, or renal failure as these account for most transudative effusions 1
• If transudate is clinically obvious (bilateral effusions with normal-sized heart on imaging suggests alternative diagnosis), treat the underlying cause first and reassess 1
• Critical caveat: Unilateral effusions or bilateral effusions with normal heart size mandate thoracentesis regardless of suspected etiology 1

Diagnostic Thoracentesis - The Cornerstone

Perform thoracentesis in virtually all patients with new large pleural effusions unless transudate is clinically certain: 1

Technique and Safety

• Use ultrasound guidance to reduce complications - this is now standard of care 2, 3
• Use a fine bore (21G) needle with 50 ml syringe for diagnostic sampling 1
• Place fluid in both sterile vials AND blood culture bottles to increase microbiological diagnostic yield 1

Essential Pleural Fluid Tests (Order All)

• Protein and LDH - to apply Light's criteria for transudate vs exudate differentiation 1, 3
• pH - critical for identifying complicated parapneumonic effusions (pH <7.2 requires drainage) 1, 3
• Cell count with differential - helps distinguish inflammatory from malignant processes 1, 3
• Gram stain and culture - send in blood culture bottles to maximize yield 1
• Acid-fast bacilli (AFB) stain and TB culture - essential in appropriate clinical contexts 1, 2
• Cytology - diagnoses approximately 60% of malignant effusions 1
• Glucose - low levels suggest complicated parapneumonic effusion, rheumatoid pleurisy, or malignancy 1

Interpreting Results

Apply Light's Criteria when protein is 25-35 g/L (borderline range): 1

• Exudate if any of: pleural fluid protein/serum protein >0.5, pleural fluid LDH/serum LDH >0.6, or pleural fluid LDH >2/3 upper limit of normal for serum

Common pitfall: 25-30% of cardiac and hepatic transudates are misclassified as exudates by Light's criteria 2

• If heart failure is suspected but fluid meets exudate criteria, calculate serum-effusion albumin gradient
• Gradient >1.2 g/dL reclassifies the effusion as transudate 2

Imaging Strategy

Obtain contrast-enhanced CT chest with IV contrast when: 1, 2

• Etiology remains unclear after initial thoracentesis 1, 2
• Malignancy is suspected (most important indication) 1, 4
• Parapneumonic effusion is present to assess for loculations and pleural thickening 1, 2

Timing of CT acquisition matters: Obtain images 60 seconds after IV contrast bolus to optimize pleural visualization 1, 2

Look for specific CT findings: 2

• Pleural enhancement and thickening suggest malignancy or infection
• Pleural nodularity strongly suggests malignancy
• Loculations indicate complicated parapneumonic effusion
• Absence of contralateral mediastinal shift with large effusion suggests mainstem bronchus obstruction, trapped lung, or mesothelioma 1

Therapeutic Thoracentesis Considerations

Before attempting any definitive therapy, perform therapeutic thoracentesis to: 1

• Determine if dyspnea improves with fluid removal (guides need for definitive intervention)
• Assess rate and degree of recurrence
• Confirm complete lung re-expansion (failure suggests trapped lung or endobronchial obstruction)

Measure pleural fluid pressure during initial drainage: 1

• Initial pressure <10 cm H₂O suggests trapped lung
• Pressure >19 cm H₂O after removing 500 mL predicts trapped lung
• Pressure >20 cm H₂O after removing 1 L predicts trapped lung

Specific Clinical Scenarios

If Infection is Suspected (Parapneumonic Effusion)

• pH <7.2 in non-purulent fluid mandates immediate chest tube drainage - this is a medical emergency 3
• Consider tissue plasminogen activator/DNase therapy or thoracoscopy for complicated effusions 3
• Purulent fluid (empyema) requires immediate drainage regardless of pH 1

If Malignancy is Suspected

• Cytology identifies only 60% of malignant effusions on first tap 1
• If cytology is negative but suspicion remains high, proceed to pleural biopsy (ultrasound-guided, CT-guided, or thoracoscopic) 1, 2
• CT chest with contrast should be performed with fluid present to better visualize pleural abnormalities 1

If Tuberculosis is Suspected

• Send pleural fluid for AFB stain and TB culture 1, 2
• Consider adenosine deaminase (ADA) levels in pleural fluid 2
• Pleural biopsy for histology and TB culture increases diagnostic yield to ~90% 2

If Pulmonary Embolism is Suspected

• Maintain high suspicion - up to 40% of PE cases have small effusions 2
• 80% of PE-related effusions are exudates and 80% are bloodstained 2
• May require CTA chest if clinical suspicion is high 1

Critical Pitfalls to Avoid

• Never skip ultrasound guidance for thoracentesis - it significantly reduces complications 2, 3
• Don't forget to check drug history - many medications cause pleural effusions (tyrosine kinase inhibitors, methotrexate, amiodarone) 1, 2
• Don't assume bilateral effusions are always transudates - malignancy and infection can be bilateral 1
• Don't delay drainage of pH <7.2 parapneumonic effusions - outcomes worsen with delay 3
• Don't perform pleurodesis without confirming complete lung re-expansion - it will fail if lung is trapped 1