Pericardial Fluid Analysis

The pericardial sac normally contains 15 to 50 mL of plasma ultrafiltrate that lubricates the heart. A pericardial effusion forms from inflammation, infection, malignancy, haemorrhage, impaired lymphatic drainage or systemic fluid retention.

The speed of accumulation matters more than the volume: 100 to 200 mL appearing within minutes (haemorrhage, aortic dissection, rupture) can cause tamponade, while 1 to 2 L accumulating over weeks may be tolerated. Pericardiocentesis, done with echocardiography, relieves tamponade and gives fluid for analysis. Surgical drainage with pericardial biopsy gives a better diagnosis for recurrent or unexplained effusions.

The fluid is analysed for appearance, protein, LDH, glucose, cell count, microbiology, cytology and specific markers. This separates transudate from exudate and identifies the cause: idiopathic or viral pericarditis, tuberculosis, bacterial (purulent) pericarditis, malignancy, uraemia, autoimmune disease, hypothyroidism, myocardial infarction (including Dressler syndrome), cardiac surgery, trauma and aortic dissection.

Pericardial effusion is found in 3 to 6% of echocardiograms. In high income countries, idiopathic and viral causes (about 50 to 60%), malignancy (10 to 25%) and iatrogenic causes predominate. In sub-Saharan Africa, tuberculosis is the commonest cause (60 to 70% of large effusions in HIV-infected patients). Cardiac tamponade carries a high mortality if not drained.

Indications. Tamponade (therapeutic and diagnostic), large effusion (over 20 mm of echo free space) of unknown cause, effusion not resolving after 3 weeks of treatment, suspected purulent pericarditis, suspected tuberculosis or malignancy, and effusion with fever or evidence of systemic illness. Small effusions with a known cause (uraemia, hypothyroidism, heart failure) are not tapped.

Specimen. Fluid collected under sterile conditions, at least 20 to 50 mL. Plain tube for protein, LDH, glucose and adenosine deaminase. EDTA tube for cell count and differential. Sterile pots for Gram stain, bacterial, mycobacterial and fungal culture, and Xpert MTB/RIF. A large volume (at least 50 mL) for cytology.

Pericardial biopsy is sent for histology, culture and PCR. Send a paired serum for protein, LDH and glucose. Haematocrit is measured when the fluid is bloody.

Appearance. Normal fluid is clear and straw coloured, under 50 mL. Serous: transudate or viral. Serosanguinous: tuberculosis, malignancy, uraemia, post-pericardiotomy. Bloody: haemorrhage, malignancy, tuberculosis, aortic dissection, ventricular rupture, trauma (a fluid haematocrit close to the blood value suggests frank haemorrhage). Purulent: bacterial infection. Milky: chylopericardium (triglycerides over 5.65 mmol/L, or 500 mg/dL).

Exudate and transudate. Light's ratios (protein over 0.5, LDH over 0.6 of serum, LDH over two thirds of the upper limit) distinguish exudate from transudate, with a fluid protein over 30 g/L usually an exudate. Almost all pericardial effusions that need drainage are exudates. A transudate suggests heart failure, hypoalbuminaemia, nephrotic syndrome, liver disease or hypothyroidism.

Specific findings.

• White cells: over 10 000 per microL with a neutrophil predominance suggests bacterial infection (purulent pericarditis) and often exceeds 50 000 per microL. A lymphocyte predominant exudate suggests tuberculosis, malignancy, viral infection, autoimmune disease or uraemia.
• Glucose: under 3.3 mmol/L (60 mg/dL), or fluid to serum ratio under 0.5, suggests purulent infection, tuberculosis, rheumatoid arthritis or malignancy.
• pH: low in bacterial infection and rheumatoid pericarditis.
• LDH: high (over 1000 U/L) in malignancy, tuberculosis, rheumatoid disease and empyema.
• Adenosine deaminase: over 40 U/L has sensitivity of 85 to 90% and specificity of 85 to 95% for tuberculous pericarditis. Interferon gamma is similar.
• Gram stain: positive in about 30 to 50% of purulent pericarditis, with Staphylococcus aureus, Streptococcus pneumoniae and Gram negative bacilli the leading organisms.
• Mycobacterium tuberculosis: smear sensitivity under 10%, culture 50 to 70%, Xpert MTB/RIF about 60 to 65% (higher with a high load), and pericardial biopsy or PCR adds yield. Pericardial biopsy shows caseating granulomas.
• Cytology: sensitivity about 70 to 90% for malignant effusions in the first sample (less in lymphoma). Carcinoembryonic antigen over 5 microg/L in the fluid supports malignancy. Lung, breast, lymphoma, melanoma and mesothelioma are the commonest tumours.
• Cholesterol: over 1.6 g/L suggests chronic effusions of myxoedema, rheumatoid disease or cholesterol pericarditis.
• Triglycerides over 5.65 mmol/L (500 mg/dL): chylopericardium after thoracic surgery or thoracic duct injury.
• Urea and creatinine: ratio near 1 to serum in uraemic effusion.
• Viral PCR (enterovirus, adenovirus, parvovirus B19, herpesviruses) has a low yield and rarely changes management.
• Autoimmune markers (ANA, rheumatoid factor) have little diagnostic value in fluid.

Critical values and findings needing immediate action.

• Tamponade (Beck triad of hypotension, raised venous pressure and muffled heart sounds, pulsus paradoxus over 10 mmHg, echocardiographic chamber collapse): immediate pericardiocentesis or surgical drainage.
• Purulent fluid or positive Gram stain: urgent surgical drainage and intravenous antibiotics.
• Bloody effusion with haemodynamic instability after trauma, cardiac procedure or aortic dissection: surgical exploration.
• Tuberculous pericarditis suspected (lymphocytic exudate, adenosine deaminase over 40 U/L, or positive Xpert): start antituberculous treatment, and consider corticosteroids in HIV-negative patients.
• Malignant cells: oncology review and a pericardial window or sclerosis for recurrence.

Interferences and pitfalls.

• Failure to distinguish blood in the pericardium from a traumatic tap: blood from the cardiac chamber clots and has the same haematocrit as venous blood, whereas pericardial blood does not clot because of defibrination and has a lower haematocrit.
• Cytology is negative in up to 30% of malignant effusions, and a biopsy adds yield.
• Tuberculous pericarditis is often culture negative, and the diagnosis rests on adenosine deaminase, biopsy and response to treatment in an endemic area.
• Adenosine deaminase can be raised in malignancy, bacterial infection and lymphoma, and is lower in HIV-infected patients with low CD4 counts.
• Pericardiocentesis risks: coronary or chamber laceration, pneumothorax, arrhythmia and bleeding. Doing the procedure with echocardiography reduces risk to about 1 to 2%.
• Large chronic effusions without tamponade may be observed. Rapid drainage of chronic effusions can cause pulmonary oedema and ventricular dysfunction.
• Pericardial fluid is not routinely tested in idiopathic effusions responding to treatment.

Special groups.

• Children: viral and bacterial causes predominate, with Haemophilus influenzae and Staphylococcus aureus, and rheumatic fever.
• Pregnancy: small physiological effusions occur, and tamponade is rare.
• Older adults: malignancy and renal disease are common, and tamponade may present with subtle signs.
• Patients with HIV: tuberculosis, Kaposi sarcoma, lymphoma and cryptococcus.
• Regions: tuberculous pericarditis and constrictive disease are common in Africa and South Asia, and late presentation is frequent.

Follow up tests. Echocardiography, ECG, chest radiograph, CT or MRI of the chest and pericardium, troponin and inflammatory markers, sputum and blood cultures, tuberculosis tests (Xpert, culture, interferon gamma release assay).

HIV test, thyroid function, urea and creatinine, autoimmune screen, tumour markers, pericardial biopsy with histology and PCR, and thoracoscopic or surgical window.