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Pleural effusion 

Pleural effusion
Pleural effusion

Stephen Chapman

, Grace Robinson

, John Stradling

, Sophie West

, and John Wrightson

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date: 26 October 2021

Clinical assessment

Pleural effusion is a common presentation of a wide range of different diseases. Commonest causes in the UK and USA (in order): cardiac failure, pneumonia, malignancy, PE.

Priority is to make a diagnosis and relieve symptoms, with minimum number of invasive procedures. The majority of patients do not require a chest drain and can be managed as outpatients. Procedures, such as therapeutic thoracentesis, may be performed readily on a day unit. Consider admission and chest drain insertion for:

  • Patients with malignant effusions who are candidates for pleurodesis

  • Empyema (pus) or complicated parapneumonic effusion (pleural fluid pH <7.2)—the majority of these effusions are unlikely to resolve without drainage and antibiotics

  • Patients who are unwell with an acute massive effusion.

Key steps in the management of the patient with a pleural effusion follow and are also detailed in the diagnostic algorithm in Fig. 8.1.

Fig. 8.1 Diagnostic algorithm for the patient with a pleural effusion.

Fig. 8.1 Diagnostic algorithm for the patient with a pleural effusion.

History, examination, CXR, and pleural USS

Including a drug history (see Pleural effusion

Does the patient have an obvious cause for transudative effusions?

(e.g. heart failure, hypoalbuminaemia, dialysis) If so, this should be treated, with no need for thoracentesis unless atypical features (such as very asymmetrical bilateral effusions, unilateral effusion, echogenicity/septations/nodularity on pleural USS, chest pain, or fever) or failure to respond to therapy.


(= ‘pleural tap’ or pleural fluid aspiration) may be diagnostic and/or therapeutic, depending on the volume of fluid removed. See Pleural effusion p. [link] for procedure details and Pleural effusion p. [link] for pleural fluid analysis. Following diagnostic tap:

  • Note pleural fluid appearance

  • Send sample to biochemistry for measurement of glucose, protein, and lactate dehydrogenase (LDH)

  • Send a fresh 20mL sample in sterile pot to cytology for examination for malignant cells (yield ~60% in malignancy) and differential cell count

  • Send samples in sterile pot to microbiology for Gram stain and microscopy, culture. For suspected pleural infection, also send pleural fluid in blood culture bottles. Low threshold for AFB stain and TB culture

  • Process non-purulent, heparinized samples in ABG analyser for pH

  • Consider measurement of cholesterol, triglycerides, chylomicrons, haematocrit, adenosine deaminase, and amylase, depending on the clinical circumstances.

If the patient is breathless, they may benefit from removal of a larger volume of fluid (therapeutic thoracentesis, see Pleural effusion p. [link]).

Is the pleural effusion a transudate or an exudate?

Helpful in narrowing the differential diagnosis. In patients with a normal serum protein, pleural fluid protein <30g/L = transudate, and protein >30g/L = exudate. In borderline cases (protein 25–35g/L) or in patients with abnormal serum protein, apply Light’s criteria—effusion is exudative if it meets one of following criteria.

  • Pleural fluid protein/serum protein ratio >0.5

  • Pleural fluid LDH/serum LDH ratio >0.6

  • Pleural fluid LDH > two-thirds the upper limit of normal serum LDH.

These criteria are very sensitive in the diagnosis of exudative effusions although may occasionally falsely identify transudates as being exudates, e.g. patients with partially treated heart failure on diuretics may be misidentified as exudates. N-terminal pro-brain natriuretic peptide (NT-proBNP) may be of use in these cases.

Further investigations

if the diagnosis remains unclear:

  • CT chest with pleural phase contrast (ideally scan prior to complete fluid drainage to improve images of pleural surfaces; useful in distinguishing benign and malignant pleural disease, see Pleural effusion p. [link])

  • Further pleural fluid analysis (see Pleural effusion pp. [link][link]), e.g. cholesterol, triglyceride, chylomicrons, haematocrit, adenosine deaminase, amylase, fungal stains

  • Pleural tissue biopsy for histology and TB culture using image-guided or thoracoscopic biopsies. These techniques are superior to Abrams’ closed pleural biopsy for malignant disease and TB (thoracoscopy has sensitivity of ~100% for TB and >90% for malignancy and allows therapeutic talc pleurodesis at the same time). Use Abrams’ biopsy only when TB is strongly suspected and thoracoscopy not available

  • Reconsider PE and TB.

Bronchoscopy has no role in investigating undiagnosed effusions, unless the patient has haemoptysis or a CXR/CT pulmonary abnormality. Pleural fluid may compress the airways and limit bronchoscopic views, and so, if bronchoscopy is indicated, it is best performed following drainage of the effusion.

Further information

Light RW. Pleural effusion. N Engl J Med 2002;346:1971–7.Find this resource:

Hooper C et al. Investigation of a unilateral pleural effusion in adults: British Thoracic Society pleural disease guideline 2010. Thorax 2010;65(Suppl. 2):ii4–17.Find this resource:

Transudative pleural effusions


involve either increased hydrostatic pressure or reduced osmotic pressure (due to hypoalbuminaemia) in the microvascular circulation.

Differential diagnosis

See Table 8.1.

Table 8.1 Causes of transudative pleural effusions





Investigate further if atypical features (very asymmetrical bilateral effusions, unilateral effusion, chest pain, fever); may be complicated by PE (up to 1/5 of cases at autopsy)


Common on ITU or post-operatively (also, hypoalbuminaemia); usually small effusion, may be bilateral; rarely needs investigation

Cirrhotic liver disease (‘hepatic hydrothorax’)

Ascites often, but not invariably, present; majority right-sided; remove ascites and treat hypoalbuminaemia (see Pleural effusion pp. [link][link])


Peritoneal dialysis

Pleural fluid analysis resembles dialysis fluid, with protein <10g/L and glucose >17mmol/L


10–20% are transudates (see Pleural effusion p. [link])

Nephrotic syndrome

Usually bilateral; consider 2° PE if atypical features

Less common

Constrictive pericarditis

May be unilateral or bilateral


May be transudate or exudate; pleural effusions occur most commonly in association with ascites, pericardial effusion, and cardiac failure, although may be an isolated finding


Up to 5% are transudates

Meigs’ syndrome

Unilateral (often right-sided) or bilateral pleural effusions and ascites; occurs in women with ovarian or other pelvic tumours; resolves following removal of tumour

Mitral stenosis


Effusion ipsilateral to obstructed kidney with retroperitoneal urine leak, resolves after treatment of obstruction; pleural fluid smells of urine, pH usually low; pleural fluid creatinine > serum creatinine is diagnostic


of transudative effusions is directed at the underlying cause; consider further investigation if fails to respond.

Exudative pleural effusions


involve an increase in capillary permeability and impaired pleural fluid resorption.

Differential diagnosis

See Table 8.2.

Table 8.2 Causes of exudative pleural effusions




Simple parapneumonic effusion (SPPE)

Occurs in 40% of bacterial pneumonias; commonest exudative effusion in young patients (see Pleural effusion p. [link])


Commonest exudative effusion in patients >60y (see Pleural effusion p. [link])


Typically lymphocytic effusion; pleural fluid AFB smear positive in <5% of cases, culture positive in 10–20%, thoracoscopic biopsy histology sensitivity ~100% (see Pleural effusion p. [link]). Adenosine deaminase may be a useful ‘rule out’ test.

Less common

Complicated parapneumonic effusion (CPPE) and empyema

CPPE defined by pleural fluid pH <7.2 and clinical features of infection, e.g. fever, sweats (see Pleural effusion pp. [link][link]); empyema defined by pleural pus

Other infections

Rare; include viral, parasitic, rickettsial, and fungal (e.g. Aspergillus, histoplasma, coccidioidomycosis)


80–90% are exudates (see Pleural effusion p. [link])


Typically low pleural fluid glucose, often <1.6mmol/L (see Pleural effusion pp. [link][link])


Lupus erythematosus cells in fluid are diagnostic; may respond quickly to prednisolone

Other autoimmune diseases

Eosinophilic granulomatosis with polyangiitis (Churg–Strauss syndrome; intensely eosinophilic fluid), Sjögren’s syndrome, scleroderma, dermatomyositis, GPA (Wegener’s)


Effusions uncommon

Hepatic, splenic, or subphrenic abscess

Oesophageal rupture

Initially sterile exudate, followed by empyema; pH <7.2, ↑ salivary amylase, often history of vomiting


Pleural fluid pancreatic amylase may be raised

Post-cardiac injury syndrome (Dressler’s syndrome) and post-CABG surgery

Pleural effusions common; may be bloodstained (see Pleural effusion p. [link])

Less common


May cause small, unilateral effusions up to 6 months after treatment


Effusions frequently resolve after starting dialysis


Presence of chylomicrons or pleural fluid triglyceride level >1.24mmol/L (see Pleural effusion pp. [link][link])

Benign asbestos-related pleural effusion

(See Pleural effusion pp. [link][link])


Drugs include amiodarone, β‎-blockers, bromocriptine, methotrexate, nitrofurantoin, and phenytoin; see Pleural effusion for full list; effusions usually resolve following discontinuation of drug

Other, rare causes

Include yellow nail syndrome, COP, amyloidosis, familial Mediterranean fever


of exudates involves treatment of the underlying cause, as well as measures to improve breathlessness and remove pleural fluid, e.g. therapeutic thoracentesis (see Pleural effusion p. [link]), intercostal drainage (see Pleural effusion p. [link]), and pleurodesis (see Pleural effusion p. [link]).

Pleural fluid analysis 1

‘Routine’ pleural fluid analysis comprises assessment of:

  • Pleural fluid appearance and other characteristics (see Table 8.3)

  • Biochemistry (glucose, protein, and LDH)

  • pH measured using a heparinized syringe in a blood gas analyser

  • Cytology (for malignant cells and differential cell count (see Table 8.4); ideally fresh 20mL sample)

  • Microbiology (Gram stain and culture). Also send blood culture bottles, each inoculated with 5mL of pleural fluid, if pleural infection likely (increases yield). Low threshold for AFB stain and TB culture

Table 8.3 Relevance of pleural fluid characteristics


Possible causes


Trauma, malignancy, pulmonary infarction, pneumonia, post-cardiac injury syndrome, pneumothorax, benign asbestos-related pleural effusion, aortic dissection/rupture; defined as haemothorax if pleural fluid haematocrit >50% of peripheral blood haematocrit (see Pleural effusion pp. [link][link])

Turbid or milky

Empyema, chylothorax, pseudochylothorax (clear supernatant after centrifuging favours empyema; cloudy after centrifuging suggests chylothorax or pseudochylothorax, see Pleural effusion p. [link])



Food particles

Oesophageal rupture


Cholothorax (biliary fistula)


Aspergillus infection

Brown, ‘anchovy sauce’

Amoebic liver abscess draining into pleural space

Urine odour


Putrid odour

Anaerobic empyema

Table 8.4 Relevance of pleural fluid differential cell count

Predominant cell type

Possible causes


Any acute effusion, e.g. parapneumonic, PE

Mononuclear cells

Any chronic effusion, e.g. malignancy, TB


TB, especially if >80%; other causes include cardiac failure, malignancy, sarcoidosis, lymphoma, rheumatoid pleurisy, post-CABG, chylothorax


Often unhelpful; associations include air or blood in pleural space (haemothorax, pulmonary infarct, pneumothorax, previous tap), malignancy, infection (parapneumonic, tuberculous, fungal, parasitic), drug- and asbestos-induced effusions, Churg–Strauss syndrome, or idiopathic

Mesothelial cells

Predominate in transudates; variable numbers in exudates, typically suppressed in inflammatory conditions, e.g. TB

Lupus erythematosus cells

Diagnostic of SLE

Although considered routine, some of these investigations may be unnecessary, and even misleading, depending on the clinical picture (e.g. microbiological analysis on patients suspected as having transudates).

Additional pleural fluid investigations, such as measurement of cholesterol and triglycerides, haematocrit, glucose, adenosine deaminase, and amylase, may be helpful in certain clinical circumstances.

Pleural fluid analysis 2

Pleural fluid pH and glucose

Pleural fluid pH may be measured using an arterial blood pH analyser. The sample should be appropriately heparinized, e.g. aspirate a few mL of pleural fluid into a pre-heparinized blood gas syringe. Pleural fluid pH is affected by exposure to air (increases pH) or local anaesthetic (decreases pH). Frankly purulent samples should not be analysed—it is unnecessary and might damage the machine.

Normal pleural fluid pH is about 7.6. An abnormally low pH (<7.3) suggests pleural inflammation and is often associated with a low pleural fluid glucose (<3.3mmol/L or pleural fluid/serum glucose ratio <0.5). The mechanism probably involves increased neutrophil phagocytosis and bacterial or tumour cell breakdown, resulting in the accumulation of lactate and CO2.

Causes of low pH and low glucose effusions

  • CPPE and empyema (pH <7.2 indication for drainage of pleural space, as unlikely to resolve spontaneously; this is not an absolute cut-off—values can vary in each locule of a multiloculated effusion)

  • Rheumatoid pleuritis (glucose <1.7mmol/L in 66% and <2.8mmol/L in 80% of cases)

  • Malignant pleural effusion (associated with advanced disease and poor survival, higher sensitivity of pleural fluid cytological analysis, and failure of pleurodesis)

  • Tuberculous pleural effusion

  • Oesophageal rupture

  • Lupus pleuritis.

Urinothorax is the only transudative effusion that can cause a pH <7.3. An abnormally high (alkaline) pH may rarely occur in the setting of Proteus pleural infection.

Pleural fluid triglyceride and cholesterol

Measure in turbid or milky effusions or where chylothorax is suspected.

Chylothorax occurs following disruption of the thoracic duct, and pleural fluid may appear turbid, milky, serous, or bloodstained. The presence of pleural fluid chylomicrons or a pleural fluid triglyceride level >1.24mmol/L confirms the diagnosis. Causes of chylothorax:

  • Trauma or following thoracotomy

  • Malignancy (particularly lymphoma)

  • Pulmonary LAM

  • TB.


occurs due to cholesterol crystal deposition in chronic effusions, most commonly due to rheumatoid pleurisy or TB, and may cause a milky effusion; raised pleural fluid cholesterol (>5.17mmol/L) and cholesterol crystals at microscopy distinguish it from chylothorax.

Pleural fluid amylase

Abnormal if pleural fluid amylase > upper normal limit for serum amylase, or if amylase pleural fluid/serum ratio >1.0. Causes include:

  • Pleural malignancy and oesophageal rupture (both associated with raised salivary amylase)

  • Pancreatic disease (acute and chronic pancreatitis, pancreatic pseudocyst; associated with raised pancreatic amylase).

Note—may be normal early in the course of acute pancreatitis or oesophageal rupture.