Pleural Effusion: Transudate or Exudate, and What the Fluid Tells You

Introduction

The pleural space normally contains only 10 to 20 ml of fluid, continuously produced by the parietal pleura and reabsorbed by parietal pleural lymphatics. A pleural effusion develops when production exceeds reabsorption, and around 50,000 people are diagnosed with one in the UK each year.¹

An effusion is a sign, not a diagnosis, and the whole of its management is directed at answering one question: why is the fluid there? The single most useful step in reaching an answer is dividing effusions into transudates and exudates, because that division separates two entirely different lists of causes and two entirely different management approaches.

Transudate or exudate

• Transudate - the pleura is normal. Fluid moves out because of raised hydrostatic pressure or reduced oncotic pressure. Protein content is low (typically under 25 g/L), and the fluid is usually clear and straw-coloured. Transudates are commonly bilateral.
• Exudate - the pleura itself is diseased. Inflammation or malignancy increases capillary permeability, or lymphatic drainage is obstructed, allowing protein-rich fluid to leak into the space. Protein content is high (typically above 35 g/L), and the effusion is more often unilateral.

Clinical features

Symptoms

• Breathlessness - the dominant symptom, worsening as the effusion enlarges and often worse lying on the unaffected side
• Pleuritic chest pain - suggests pleural inflammation and therefore an exudate; transudates are typically painless
• Dry cough
• Symptoms of the underlying cause - orthopnoea and oedema in heart failure, fever and purulent sputum in pneumonia, weight loss and haemoptysis in malignancy, night sweats in tuberculosis
• Small effusions may be entirely asymptomatic and found incidentally

Signs

• Stony dull percussion note - the classic and most useful sign, and distinctly duller than the dullness of consolidation
• Reduced or absent breath sounds over the effusion
• Reduced vocal resonance and tactile vocal fremitus
• Reduced chest expansion on the affected side
• Bronchial breathing and egophony at the upper border of the effusion, where the underlying lung is compressed
• Tracheal and mediastinal deviation away from the side of the effusion if it is massive - a large effusion pushes, unlike collapse which pulls
• Signs of the cause - raised JVP and peripheral oedema in heart failure, clubbing and cachexia in malignancy, a rheumatoid hand, ascites and spider naevi in cirrhosis

Investigations

Imaging

• Erect chest radiograph - blunting of the costophrenic angle appears once around 200 ml has accumulated on a PA film (only 50 ml is needed on a lateral). Larger effusions show a meniscus curving upwards laterally, and a massive effusion produces a complete white-out with mediastinal shift away from the affected side.
• Thoracic ultrasound - more sensitive than radiography, distinguishes fluid from consolidation and pleural thickening, identifies septations that predict the need for drainage, and is used to select the safest site. It is mandatory before every pleural procedure.
• CT thorax with contrast - for undiagnosed exudative effusions. It should ideally be performed before complete drainage, since fluid provides contrast against which pleural nodularity, thickening and mediastinal pleural involvement - all features suggesting malignancy - are more easily seen.

Pleural fluid analysis

Aspirate 20 to 50 ml under ultrasound guidance and send it for the following, taking paired serum protein and LDH at the same time.

The undiagnosed exudative effusion

Around a quarter of exudative effusions remain undiagnosed after initial fluid analysis, and the concern in almost all of them is malignancy. The pathway is:

1. CT thorax with contrast, before full drainage
2. Repeat cytology on a second sample
3. Local anaesthetic thoracoscopy - the investigation of choice, giving a diagnostic yield above 90% and allowing talc pleurodesis at the same sitting
4. Image-guided pleural biopsy where thoracoscopy is not available or the patient is unfit
5. Blind (Abrams) pleural biopsy is now reserved for suspected tuberculosis, where the pleural involvement is diffuse

Other tests

• Bloods - FBC, U&Es, LFTs including albumin, CRP, clotting, serum protein and LDH, and NT-proBNP where heart failure is suspected
• Echocardiogram for suspected heart failure
• Thyroid function, and urine protein-creatinine ratio for nephrotic syndrome
• Autoimmune serology - rheumatoid factor, anti-CCP and ANA where a connective tissue disease is suspected
• Occupational history - a careful asbestos exposure history in every unexplained unilateral effusion

Management

General principles

• Treat the underlying cause. A transudative effusion from heart failure, cirrhosis or nephrotic syndrome should be managed by treating that condition - diuretics, albumin, sodium restriction - and does not usually need drainage.
• Therapeutic aspiration for symptomatic relief in a breathless patient
• Remove no more than 1.5 litres at a time, and stop earlier if the patient develops chest discomfort or persistent cough, to avoid re-expansion pulmonary oedema
• Repeat the chest radiograph after drainage to assess re-expansion and exclude a pneumothorax

Parapneumonic effusion

• Simple parapneumonic effusion - clear fluid, pH above 7.2, negative Gram stain and culture. Treat the pneumonia with antibiotics; the effusion resolves.
• Complicated parapneumonic effusion - pH below 7.2, low glucose, or a positive Gram stain or culture. Requires chest drain insertion in addition to antibiotics.
• Empyema - frank pus. Requires chest drainage, prolonged antibiotics and, if drainage fails, intrapleural fibrinolytics or surgical referral

Malignant pleural effusion

A malignant effusion indicates advanced disease, and treatment is directed at relieving breathlessness rather than at cure. The choice is guided by prognosis, whether the lung re-expands after drainage, and above all by patient preference.

• Therapeutic aspiration - simple and immediate, but the fluid usually recurs within days to weeks. Reasonable in patients with a very short prognosis.
• Chest drain with talc pleurodesis - instilling talc to obliterate the pleural space. Requires the lung to re-expand fully and an inpatient stay of several days. Success is around 70 to 80%.
• Indwelling pleural catheter - a tunnelled catheter drained at home by the patient or a carer, allowing outpatient management. This is the preferred option where the lung fails to re-expand (trapped lung), since pleurodesis cannot work in that situation, and is increasingly chosen by patients who wish to avoid admission.
• Thoracoscopy with talc poudrage - combines diagnosis and pleurodesis in one procedure
• Systemic anti-cancer therapy where the tumour is responsive - for example, effusions from small cell lung cancer or lymphoma may resolve with chemotherapy alone

Complications

• Empyema - infection of the pleural fluid, requiring drainage
• Trapped lung and pleural thickening - causing persistent breathlessness and restriction
• Respiratory failure from a large or bilateral effusion
• Re-expansion pulmonary oedema - after removing too much fluid too quickly, presenting with cough, breathlessness and unilateral pulmonary oedema
• Pneumothorax - from aspiration or drain insertion
• Haemothorax and organ injury - laceration of intercostal vessels, liver or spleen during a poorly sited procedure
• Tumour seeding along the needle or drain tract - a particular problem in mesothelioma, where prophylactic radiotherapy to the tract is sometimes considered
• Infection at the drain site, and catheter-related infection with indwelling catheters
• Recurrence - the norm in malignant effusions without definitive treatment

Red flags

Prognosis

Prognosis is entirely determined by the underlying cause. Transudative effusions from heart failure, cirrhosis or nephrotic syndrome resolve as the cause is treated, and their prognostic significance is that of the underlying organ failure rather than of the fluid itself.

Parapneumonic effusions resolve with adequate treatment of the pneumonia, though a complicated effusion or empyema carries a mortality of around 20% and much longer hospital stays.

Malignant pleural effusion indicates advanced disease, with a median survival of around 4 to 6 months, though this varies considerably by tumour type - measured in a few months for lung cancer and often much longer for breast cancer, ovarian cancer, lymphoma and mesothelioma. The LENT score (pleural fluid LDH, ECOG performance status, neutrophil-to-lymphocyte ratio and tumour type) is used to estimate survival and to guide whether an invasive definitive procedure or a simpler palliative approach is more appropriate. In practice, choosing between talc pleurodesis and an indwelling catheter is as much a conversation about how the patient wants to spend their remaining time as it is a technical decision.