Pleural effusions

At a glance

1. A pleural effusion is an excess of fluid in the space between the lung and the chest wall. It is always a sign of another disease. The most common causes are heart failure, pneumonia, cancer, pulmonary embolism and tuberculosis.
2. It causes breathlessness, sometimes with pleuritic pain, and a stony dull percussion note with reduced breath sounds. The chest film shows a meniscus; ultrasound finds smaller collections and guides the needle.
3. Sampling the fluid is the key test. By Light's criteria an effusion is an exudate if the pleural to serum protein ratio is above 0.5, the LDH ratio above 0.6, or the pleural LDH above two thirds of the serum upper limit.
4. Transudates come from altered pressures (heart failure, cirrhosis, nephrotic syndrome) and treat the cause. Exudates come from disease of the pleura or its drainage (infection, cancer, embolism) and need a cause to be found.
5. In pneumonia, pus or a pH of 7.2 or below means drainage, and a pH between 7.2 and 7.4 needs a closer look. A recurring malignant effusion is managed with an indwelling pleural catheter or pleurodesis.

01Definition and overview

A pleural effusion is an abnormal accumulation of fluid in the pleural space. Normally a thin film, perhaps a few millilitres, lubricates the parietal and visceral pleura. It is detectable on the chest film when about 300 mL or more is present and clinically at around 500 mL, though ultrasound sees much less.

The effusion is classified by its fluid:

An effusion is a finding and not a diagnosis, so the work is to find the cause.

02Etiology and pathophysiology

Fluid enters the pleural space from the capillaries of the parietal pleura and is drained back by the lymphatics of the parietal pleura. An effusion forms when more enters than the lymphatics can clear. The mechanisms are:

• raised hydrostatic pressure, as in heart failure;
• lowered oncotic pressure, as in nephrotic syndrome, cirrhosis and malnutrition;
• increased capillary permeability from inflammation, infection or tumour;
• blocked lymphatic drainage, from a tumour in the parietal pleura or mediastinal nodes;
• fluid from the abdomen through the diaphragm: ascites in cirrhosis (hepatic hydrothorax), peritoneal dialysis, and ovarian tumours (Meigs syndrome, a right-sided effusion with a benign ovarian fibroma);
• injury to the thoracic duct (chylothorax), or bleeding (haemothorax).

Transudates

The protein is under 30 g/L, the LDH under 200 IU/L and the fluid to serum LDH ratio below 0.6. They may be bilateral, and are often larger on the right. The causes are:

• heart failure (the commonest);
• hypoproteinaemia (nephrotic syndrome, cirrhosis, protein-losing states);
• constrictive pericarditis; and
• hypothyroidism.

Exudates

The protein is over 30 g/L and the LDH over 200 IU/L. Causes include:

• bacterial pneumonia (the commonest exudate, a parapneumonic effusion);
• carcinoma of the bronchus, with fluid that may be bloodstained, and metastases from the breast and other primaries;
• pulmonary infarction from embolism;
• tuberculosis;
• mesothelioma and asbestos exposure;
• autoimmune rheumatic diseases (rheumatoid arthritis, lupus);
• post-myocardial infarction (Dressler) syndrome;
• acute pancreatitis (high amylase);
• sarcoidosis, yellow nail syndrome and familial Mediterranean fever (very rare);
• Meigs syndrome (some textbooks list it with the transudates, but most reported cases are exudates); and
• drugs such as amiodarone, nitrofurantoin and methotrexate.

The parapneumonic effusion (an effusion with pneumonia) passes through stages. It begins as a sterile exudate with a normal pH; if bacteria invade, the fluid becomes complicated, with a low pH and glucose and a high LDH, and fibrin forms loculations; and finally it is an empyema with pus, which thickens into a fibrous "peel" that traps the lung. An effusion is seen with a third to a half of community-acquired pneumonias, most of them small, and a minority become complicated.

03Clinical features

The commonest symptom is breathlessness, which depends on the size and the speed of the effusion and on the lung beneath it. Pleuritic chest pain is sharp and worse on inspiration; it comes from an inflamed pleura, and it can ease as fluid separates the layers. There may be a dry cough. The rest of the history points to the cause: fever and sputum in pneumonia; weight loss, haemoptysis and smoking in cancer; asbestos exposure in mesothelioma; orthopnoea and oedema in heart failure; night sweats in tuberculosis.

The signs over a moderate to large effusion are:

• reduced chest expansion on that side;
• a stony dull percussion note;
• reduced or absent breath sounds, and reduced vocal resonance and fremitus;
• bronchial breathing just above the fluid, where the lung is compressed; and
• with a massive effusion, shift of the trachea and mediastinum away from the effusion.

A trachea pulled towards the dull side means collapse of the lung, from an obstructing tumour, rather than fluid alone. A pleural rub may be heard when the amount of fluid is small. Clubbing and lymph nodes suggest cancer.

An empyema shows as a swinging fever, malaise and a rising CRP despite appropriate antibiotics.

04Diagnosis and management

Diagnosis

1. Chest X-ray. Blunting of the costophrenic angle, then a curved upper border (the meniscus), then dense homogeneous opacity of part or all of the hemithorax, with a shift of the mediastinum away from a massive effusion. Fluid under the lung (subpulmonary) can look like a raised diaphragm, and fluid in a fissure like a mass.
2. Ultrasound is the next step: it confirms fluid, shows septations and the pleural surface, estimates volume, and marks a safe site. Every pleural aspiration is done under ultrasound.
3. CT with contrast shows pleural thickening and nodularity, the lung beneath, lymph nodes and the primary tumour.
4. Pleural aspiration (thoracentesis). Look at the fluid, which can be straw-coloured, bloody, cloudy, pus or milky (a chylothorax). Send it for:

Light's criteria (1972): an effusion is an exudate if any one of these is met:

• pleural fluid protein to serum protein ratio above 0.5;
• pleural fluid LDH to serum LDH ratio above 0.6; or
• pleural fluid LDH above two thirds of the upper limit of normal for serum.

They are very sensitive for exudates, but about one in four transudates is wrongly labelled an exudate, particularly in patients on diuretics. When a heart-failure effusion looks like an exudate, a serum to pleural fluid albumin gradient above 12 g/L or a high serum NT-proBNP supports heart failure.

5. Pleural biopsy. If the fluid does not give the diagnosis in a patient with an exudate, image-guided needle biopsy or thoracoscopy (medical or surgical) gives histology with a high yield for malignancy and tuberculosis. Further tests (bronchoscopy, CT of the abdomen) follow the suspicion.

When an effusion is clearly caused by heart failure, with bilateral effusions and the right clinical picture, aspiration may be deferred, and the effusion treated with diuretics. Aspirate if the effusions are unilateral or unequal, the patient has pleuritic pain or a fever, or the effusion does not respond.

Management

Treat the cause. Heart failure responds to diuretics; cirrhosis to salt restriction and diuretics (and an intervention for refractory cases); nephrotic syndrome to treatment of the kidney disease; pulmonary embolism to anticoagulation; tuberculosis to antituberculous therapy; and autoimmune disease with immunosuppression.

Therapeutic thoracentesis relieves breathlessness. Drain slowly, and no more than about 1.5 litres at one time; stop if the patient develops chest tightness, cough or discomfort. Rapid removal of large volumes can cause re-expansion pulmonary oedema, usually within the first hour. Use a catheter and not a needle for therapeutic drainage of more than a small volume, and no vacuum bottles or wall suction.

Pleural infection is the term for a complicated parapneumonic effusion and empyema together. If the aspirate is not frank pus, measure the pH at once. A pH of 7.2 or below is high risk, and a drain is inserted if there is enough fluid to do so safely. With a pH above 7.2 and below 7.4 the risk is intermediate: measure the LDH, and consider a drain if it is above 900 IU/L, especially with a continuing fever, a large volume, a glucose of 4.0 mmol/L or less, septation on ultrasound or pleural enhancement on CT. At 7.4 or above there is no reason to drain at once, but review regularly and repeat the aspiration if the picture changes. If the pH is not quickly available, a glucose below 3.3 mmol/L suggests infection. Pus, or organisms on stain or culture, also mean pleural infection. A rheumatoid effusion, and advanced malignancy or mesothelioma, can give a low pH too.

Treatment is empirical antibiotics that cover anaerobes (cefuroxime with metronidazole, for example, in community-acquired disease), and a small-bore chest drain (14 Fr or smaller) under ultrasound guidance, flushed with saline. If drainage has stopped but a residual collection remains, intrapleural alteplase (tPA) 10 mg with DNase 5 mg twice a day for 3 days improved drainage and cut surgical referral from 16 to 4 per cent in a randomised trial; bleeding is part of the consent, and neither drug is given alone, nor is streptokinase. Surgery (video-assisted thoracoscopic decortication) is for persisting sepsis with a residual collection despite drainage, antibiotics and, where suitable, tPA with DNase; the timing is a matter of judgement. Antibiotics continue for several weeks, guided by cultures (see the treatment of pneumonias).

Malignant effusions are drained to relieve breathlessness and to show whether the lung re-expands. If they come back and cause breathlessness, a definitive procedure is preferred to repeated aspiration, and is not deferred until after systemic anticancer treatment. The options are:

• talc pleurodesis, in which a sclerosing agent (talc) sticks the pleura together after the fluid is drained and the lung has re-expanded; or
• an indwelling pleural catheter, which the patient drains at home. In a randomised trial (106 patients) the catheter relieved breathlessness as well as talc in the first 6 weeks and better at 6 months, with a shorter first hospital stay (a median of 0 days against 4) and fewer further pleural procedures (6 against 22 per cent), but it had more adverse events (21 of 52 patients against 7 of 54) and needs more care.

Chemotherapy or targeted therapy may help in sensitive tumours such as small-cell lung cancer, lymphoma and breast cancer. A trapped lung, in which a good part of the lung cannot re-expand, makes talc pleurodesis unreliable, and an indwelling catheter is then preferred.

Chylothorax is managed by a low-fat diet with medium-chain triglycerides, drainage, and ligation or embolisation of the duct; haemothorax by drainage; hepatic hydrothorax by treating the ascites, with a chest drain avoided if possible.

05Epidemiology

Pleural effusion is common: an often-quoted estimate is 1.5 million cases a year in the United States, and in the UK pleural infection alone is diagnosed in 11.2 per 100 000 people a year and is becoming commoner. It is one of the commonest reasons for a respiratory referral. In industrialised countries, heart failure, pneumonia and malignancy account for most effusions; pulmonary embolism, cirrhosis and surgery (after cardiac or abdominal operations) come next. In countries with a high burden of tuberculosis, TB is a leading cause of exudative effusion, in young adults in particular. Lung and breast cancer are the commonest causes of a malignant effusion. Asbestos-related disease, including mesothelioma, is related to occupational exposure, which was decades ago.

06Prognosis

The outlook is that of the cause.

• Transudates from heart failure or cirrhosis mark advanced disease, but the effusion itself responds to treatment.
• Parapneumonic effusions settle with antibiotics if they are simple. In empyema, delay in drainage leads to a thick fibrous peel, a trapped lung, and surgery; up to one in five patients with pleural infection die within a year, and about 15 per cent need surgery, the risk being highest in the elderly and in those with comorbidity. The RAPID score (urea, age, purulence of the fluid, source of infection and albumin; 0 to 2 low, 3 to 4 medium, 5 to 7 high risk) stratifies it.
• Malignant effusions signal advanced cancer. Median survival is measured in months (about 3 to 12 months, shorter for lung cancer and longer for breast and ovarian cancer), and scores such as the LENT score (LDH, performance status, neutrophil to lymphocyte ratio and tumour type) estimate it. Treatment aims at comfort.
• Tuberculous effusion usually resolves with treatment, though pleural thickening may remain, and many patients later develop active TB if untreated.

After an effusion, follow up the cause; if no cause is found after a full work-up, watch for the later emergence of cancer or TB.

Check yourselfAnswer, then say how sure you were: a lucky guess still counts as a weak point.

1Which result classifies a pleural effusion as an exudate by Light's criteria?

Pleural fluid protein below 30 g/L, with a normal LDHFluid to serum LDH ratio below 0.6Fluid to serum protein ratio above 0.5Fluid glucose above 3.3 mmol/L with a pH above 7.4

2A patient with pneumonia has a pleural effusion. The fluid is clear with a pH of 7.05. What is the next step?

Insert a chest drainRepeat the aspiration in 48 hoursAdd a diureticStop the antibiotic

3A 75-year-old with orthopnoea, ankle swelling and small bilateral pleural effusions on the chest film. What is the usual first approach?

Pleural biopsy by thoracoscopyTalc pleurodesis at onceAntibiotics for an empyemaDiuretics for the heart failure

4A 28-year-old from a country with a high incidence of TB has a fever, a unilateral effusion, a lymphocyte-rich exudate and an ADA of 65 U/L. What is the likely cause?

Pulmonary embolismTuberculous pleurisyHeart failureMalignant mesothelioma

5What limit is generally put on the volume of fluid removed at one therapeutic thoracentesis?

No limit, provided the patient is comfortable throughoutNo more than 300 mL, to avoid shockAbout 1.5 litres, less if symptoms ariseUp to 5 litres, in a single session to save time