What is the recommended diagnostic and treatment approach for a pleural effusion in an adult over 40 with risk factors such as heart failure, malignancy, infection, recent thoracic surgery, or chronic liver or kidney disease?

Diagnostic and Treatment Approach for Pleural Effusion

In adults over 40 with risk factors, begin by determining whether the clinical picture strongly suggests a transudate (heart failure, cirrhosis, nephrotic syndrome, dialysis) before performing thoracentesis—if bilateral effusions are present with classic heart failure features, treat the underlying condition without aspiration unless atypical features exist or the effusion fails to respond to therapy. 1

Initial Clinical Assessment

Key historical and examination findings to identify:

• Heart failure indicators: Bilateral effusions occur in 59% of cardiac cases, unilateral right-sided in 41%; heart failure accounts for 80% of all transudates and 29% of all pleural effusions 2
• Pulmonary embolism clues: Pleuritic pain (present in 75% of cases), dyspnea disproportionate to effusion size, effusion occupying less than one-third of hemithorax 1, 2
• Infection features: Fever, purulent appearance, foul odor suggesting anaerobic infection 1
• Malignancy red flags: Unilateral large effusion, unexplained weight loss, known cancer history 3
• Medication history: Document all drugs, as numerous medications cause exudative effusions 1

When to Perform Thoracentesis

Do NOT aspirate if:

• Bilateral effusions with clear clinical evidence of heart failure on chest radiograph, unless atypical features present or failure to respond to diuretics 1, 4

DO aspirate for:

• All unilateral effusions of unknown cause 4
• Any effusion with fever, pleuritic pain, or weight loss 4
• Bilateral effusions not responding to standard therapy 4

Thoracentesis Technique

Always use real-time ultrasound guidance to reduce pneumothorax risk 5, 4

• Use 21-gauge needle with 50 mL syringe 1, 5
• Obtain 25-50 mL for optimal diagnostic yield 5
• Record gross appearance (color, clarity) and odor at bedside 1, 5

Essential Laboratory Testing on Pleural Fluid

Send every sample for:

• Protein and LDH (to apply Light's criteria when protein is 25-35 g/L) 1, 5
• pH measurement in all non-purulent effusions when infection suspected 1, 5
• Gram stain and acid-fast bacilli (AAFB) stain 5
• Culture in both sterile vials AND blood culture bottles (blood culture bottles markedly increase pathogen detection) 5
• Cytology (detects only 60% of malignant effusions, so negative cytology does not exclude cancer) 1, 5
• Cell count with differential 3

Transudate vs Exudate Classification

Apply Light's criteria—effusion is exudative if ANY of the following:

• Pleural fluid-to-serum protein ratio >0.5
• Pleural fluid-to-serum LDH ratio >0.6
• Pleural fluid LDH >2/3 upper limit of normal for serum 2, 6

Critical pitfall: 25-30% of cardiac and hepatic transudates are misclassified as exudates by Light's criteria, especially in patients on diuretics 4, 2

To reclassify suspected cardiac transudates:

• Use serum-effusion albumin gradient >1.2 g/dL to confirm transudate 4, 2
• NT-proBNP ≥1,500 pg/mL (serum or pleural fluid) confirms heart failure as cause 4

Management Based on Classification

Transudative Effusions

Treat the underlying condition:

• Heart failure: diuretics 4, 7
• Cirrhosis: manage ascites 4, 7
• Nephrotic syndrome or dialysis: address systemic cause 2

Exudative Effusions—Specific Etiologies

Parapneumonic Effusion/Empyema (Most Common Exudate)

pH <7.2 indicates complicated parapneumonic effusion requiring immediate chest tube drainage 5, 3

Additional poor prognostic indicators requiring drainage:

• Frank pus on aspiration 7
• Positive Gram stain 7
• Glucose <2.2 mmol/L 7
• LDH >3 times upper limit of normal 7
• Pleural loculations on imaging 7

If fluid cannot be completely evacuated due to loculations, consider intrapleural thrombolytic therapy (tissue plasminogen activator/deoxyribonuclease); if ineffective, proceed to thoracoscopy or thoracotomy with decortication 3, 7

Tuberculosis

Suspect when:

• Lymphocyte-predominant effusion (>50% lymphocytes) with positive tuberculin skin test 1
• Adenosine deaminase (ADA) >40-47 U/L (sensitivity 97.1%, specificity 92.9% at cutoff 41.5 U/L) 2

Empirical antituberculous therapy is justified when exudative lymphocytic effusion plus positive tuberculin skin test are present 1

Tissue sampling via pleural biopsy is the preferred diagnostic approach (69-97% sensitivity), as AAFB stains are positive in only 10-20% of cases 5, 2

Malignancy

Lung cancer is the most frequent cause, followed by breast cancer 2

If initial cytology is non-diagnostic:

• Obtain second pleural fluid sample (increases diagnostic yield) 1, 5
• Perform contrast-enhanced CT thorax with fluid present to visualize pleura and identify best biopsy site 1, 5
• If routine tests fail, thoracoscopy is advised 1, 5

For symptomatic malignant effusions:

• If therapeutic thoracentesis relieves dyspnea, consider pleurodesis with tetracycline derivative 7
• Indwelling pleural catheter is alternative for recurrent effusions 8

Critical pitfall for mesothelioma: Minimize needle incisions, as 40% of needle tracts become invaded by tumor 1, 4

Pulmonary Embolism

No specific pleural fluid tests exist—if clinical suspicion present, proceed directly to imaging for embolism 1, 2

Special Populations

HIV-Infected Patients

Leading causes differ markedly from immunocompetent patients:

• Kaposi's sarcoma (33%)
• Parapneumonic effusions (28%)
• Tuberculosis (14%)
• Pneumocystis jirovecii pneumonia (10%)
• Lymphoma (7%) 1, 5, 2

End-Stage Renal Disease

Approximately 24.7% of dialysis patients develop pleural effusion 2

Management of Persistent Undiagnosed Effusions

When diagnosis remains unclear after initial workup (occurs in ~15% of cases):

1. Reconsider pulmonary embolism and tuberculosis, as both are treatable yet frequently missed 1, 5, 2

2. Obtain pleural tissue via:

   • Ultrasound/CT-guided core biopsy
   • Closed pleural biopsy (least expensive, minimal complications)
   • Medical thoracoscopy 1, 5, 9

3. Place biopsy specimens in both saline (for culture) and formalin (for histology) 1, 5

4. Many undiagnosed effusions eventually prove to be malignancy with sustained observation 1

Critical Pitfalls to Avoid

• Do NOT perform diagnostic bronchoscopy for undiagnosed effusion unless hemoptysis or bronchial obstruction features are present 1, 5, 4
• Do NOT perform blind thoracentesis without ultrasound guidance 5, 4
• Do NOT omit blood culture bottles when sending fluid for microbiology 5
• Do NOT rely solely on imaging to exclude infection, as malignancy can coexist with pleural infection in ~5% of cases 5

Fluid Appearance Interpretation

• Turbid/milky fluid: Centrifuge—if supernatant clears, diagnosis is empyema; if remains turbid, consider chylothorax 1, 5
• Foul odor: Suggests anaerobic infection, guides antibiotic selection 1
• Bloody: Check hematocrit to diagnose hemothorax 1