What investigations should be sent for a patient undergoing pericardiocentesis (pericardial fluid aspiration)?

Pericardiocentesis: Investigations to Send on Pericardial Fluid

Send pericardial fluid for cell count with differential, biochemical analysis (protein, LDH, glucose), cytology with tumor markers, bacterial/fungal/mycobacterial cultures, and PCR for tuberculosis as the core diagnostic panel. 1

Essential Fluid Analyses

Routine Studies (Send in All Cases)

Biochemical Analysis:

• Protein level and LDH to characterize as exudate vs transudate (protein >3.0 g/dL, fluid/serum protein ratio >0.5, LDH >200 mg/dL, fluid/serum LDH ratio >0.6) 1
• Glucose level - critically important as low pericardial:serum glucose ratio (mean 0.3) differentiates purulent pericarditis from tuberculous (ratio 0.7) and neoplastic (ratio 0.8) causes 1
• Note: Pericardial fluid glucose ≤70 mg/dL with CT attenuation values >20 HU suggests malignancy 2

Cell Count and Differential:

• Total white cell count with differential - purulent effusions show mean 2.8/mL with 92% neutrophils, tuberculous show 1.7/mL with 50% neutrophils, and neoplastic show 3.3/mL with 55% neutrophils 1
• Monocyte predominance (79%) suggests malignancy or hypothyroidism, while neutrophil predominance (78%) indicates rheumatoid or bacterial causes 1

Microbiological Studies

Bacterial Cultures:

• At least three cultures for aerobic and anaerobic organisms - mandatory in all cases to exclude purulent pericarditis 1
• Send blood cultures simultaneously before starting antibiotics 1

Mycobacterial Studies:

• Acid-fast bacilli staining and mycobacterium culture with radiometric growth detection (e.g., BACTEC-460) 1
• PCR for tuberculosis (Xpert MTB/RIF) - more specific (100%) than ADA estimation (78%) though slightly less sensitive (75% vs 83%) 1
• Adenosine deaminase (ADA) - very high levels have prognostic value for pericardial constriction 1
• Unstimulated interferon-gamma (uIFN-γ) - offers superior accuracy for tuberculous pericarditis compared to ADA 1
• Pericardial lysozyme 1

Fungal Studies:

• Fungal cultures and staining - particularly important in immunocompromised patients 1

Cytological and Tumor Studies

Cytology:

• Centrifugation and rapid cytological analysis to improve diagnostic yield 1
• Essential for confirming malignant pericardial disease 1

Tumor Markers (if malignancy suspected):

• Carcinoembryonic antigen (CEA) - high CEA with low ADA virtually excludes tuberculosis and confirms malignancy 1
• CA 125, CA 72-4, CA 15-3, CA 19-9 1
• Alpha-fetoprotein (AFP) 1
• CD-30, CD-25 for lymphomas 1

Molecular Studies

PCR for Viruses (Class IIa indication):

• PCR for cardiotropic viruses discriminates viral from autoreactive pericarditis 1
• Consider genome search for enteroviruses, adenovirus, parvovirus B19, cytomegalovirus, herpes simplex, influenza, hepatitis C, HIV 1
• Note: PCR is preferred over serology for most viruses 1

Clinical Context-Specific Testing

Suspected Autoimmune Disease:

• Send blood for ANA, ENA, ANCA, ferritin (if Still disease suspected), ACE and 24-hour urinary calcium (if sarcoidosis suspected) 1

Suspected Tuberculosis in Endemic Areas:

• IGRA test (Quantiferon, ELISpot) on blood 1
• Pericardial score ≥6 (fever=1, night sweats=1, weight loss=2, globulin >40 g/L=3, peripheral leukocyte count <10×10⁹/L=3) highly suggestive 1

Chronic Pericardial Effusion:

• TSH and renal function tests on blood 1

Critical Pitfalls to Avoid

• Do not rely solely on exudate vs transudate classification - nearly all pericardial effusions (118 of 120 in one study) meet exudate criteria by Light's criteria, making this distinction less useful than in pleural effusions 3
• Do not skip glucose measurement - this is one of the most discriminating tests, particularly for purulent pericarditis which shows dramatically low glucose levels (mean 47.3 mg/dL vs 102.5 mg/dL in non-infectious effusions) 1
• Do not send only routine cultures - tuberculous and fungal cultures require specific media and prolonged incubation 1
• Do not forget simultaneous blood samples - pericardial:serum ratios are essential for interpretation of protein, LDH, and glucose levels 1
• In suspected malignancy, cytology alone may miss the diagnosis - in patients with documented malignancy, almost 2/3 of pericardial effusions are caused by non-malignant diseases (radiation pericarditis, opportunistic infections) 1