A pleural effusion results from the accumulation of abnormal volumes (>10–20mL) of fluid in the pleural space. Pleural effusions are common and are associated with many different diseases; see Chapter 8 for a step-by-step approach to the diagnosis of a patient with a pleural effusion, differential diagnosis of effusions, and details of pleural fluid analysis.
• May be asymptomatic or associated with breathlessness, dry cough, pleuritic chest pain (suggesting pleural inflammation), chest ‘heaviness’, and sometimes pain referred to the shoulder or abdomen
• Signs on examination include reduced chest expansion, reduced tactile vocal fremitus, a stony dull percussion note, quiet breath sounds, and sometimes a patch of bronchial breathing above the fluid level. A friction rub may be heard with pleural inflammation.
• Sequential blunting of posterior, lateral, and then anterior costophrenic angles are seen on radiographs as effusions increase in size
• PA CXR will usually detect effusion volumes of 200mL or more; lateral CXR is more sensitive and may detect as little as 50mL pleural fluid
• Classical CXR appearance is of basal opacity obscuring hemidiaphragm, with concave upper border. Massive effusion may result in a ‘white-out’ of the hemithorax, with mediastinal displacement away from the effusion; lack of mediastinal shift in such cases raises the possibility of associated volume loss due to bronchial obstruction from a lung cancer
• Other CXR appearances include rounded or lentiform shadowing in loculated interlobar effusions and diffuse shadowing throughout the hemithorax on supine films
• CXR appearance may suggest the underlying diagnosis, e.g. bilateral effusions with cardiomegaly in cardiac failure; massive effusions are most commonly seen due to malignancy.
(see p. [link]) has a much higher sensitivity than CXR at detecting and localizing pleural fluid and is useful for distinguishing pleural fluid from pleural masses or thickening. Sonographic appearances can be useful at predicting exudates (echogenic or septated fluid) and for predicting malignancy. Its use for pleural procedures increases success at fluid aspiration and reduces risk of complications.
chest with pleural contrast is useful in distinguishing benign and malignant pleural disease: nodular, mediastinal, or circumferential pleural thickening and parietal pleural thickening >1cm are all highly specific for malignant disease. Scans are best performed prior to complete drainage of fluid. CT may also reveal evidence of extrapleural disease, e.g. lymphadenopathy or parenchymal change, which may suggest, e.g. cancer or TB.
Commonest cause of exudative pleural effusion in patients older than 60y. About 40, 000 cases of malignant effusion each year in the UK.
Most malignant effusions are metastatic, with lung and breast the most common 1° sites (see Table 35.1).
Table 35.1 1° sites and frequency
Approximate frequency (%)
Other rarer tumours include sarcoma, melanoma, leukaemia, and myeloma; almost any malignant tumour may spread to the pleural cavity. Mesothelioma is an important cause of malignant effusions and is discussed on pp. [link]–[link].
Breathlessness is the main symptom; chest pain, cough, weight loss, and anorexia may also be present. A small proportion of patients are asymptomatic. Effusions may be unilateral or bilateral and are frequently large volume.
Consider other potential causes of pleural effusion in patients known to have cancer, e.g. due to pneumonia, PE, radiotherapy, pericardial disease, or drugs.
A strategy for investigating the patient with an undiagnosed pleural effusion is detailed on p. [link]. Key investigations in patients suspected to have a malignant effusion are:
Pleural fluid cytology
Sensitivity for malignancy is about 60%. Immunostaining of malignant cells may provide clues as to the likely primary site. Visualization of monoclonal cells in fluid on flow cytometry may support a diagnosis of lymphoma.
CT chest with pleural contrast
Nodular, mediastinal, or circumferential pleural thickening and parietal pleural thickening >1cm on CT are highly specific for malignant disease. May also demonstrate extrapleural disease, e.g. lymphadenopathy.
See p. [link]. Required in cytology-negative cases. Options:
• CT-guided cutting needle biopsy has been demonstrated to be a more effective diagnostic test for malignant pleural disease than Abrams’ pleural biopsy (sensitivity 87% in CT-guided biopsy group vs 47% in Abrams’ group)
• US-guided needle biopsies are also effective and relatively straightforward to perform
• Thoracoscopy (see p. [link]) is an extremely useful investigation allowing direct visualization of the pleural space, with a high sensitivity (>92%) for biopsies. Therapeutic talc poudrage (talc is ‘puffed’ directly on to the pleural surfaces) may be performed at same time, with a pleurodesis success rate >80%. Usually performed using conscious sedation and local anaesthesia. Complications (such as empyema) are rare.
Serum/pleural fluid tumour markers
(e.g. CEA, CA19-9, CA15-3, CA125, PSA) should not be routinely used for investigation of pleural effusions, having a poor combined sensitivity for malignant disease. Mesothelin has a low sensitivity of 48–84% and specificity 70–100% for mesothelioma and is therefore not routinely recommended.
Roberts ME et al. Management of a malignant pleural effusion: British Thoracic Society pleural disease guideline 2010. Thorax 2010;65(Suppl. 2):ii32–40.Find this resource:
Maskell NA et al. Standard pleural biopsy vs CT-guided cutting-needle biopsy for diagnosis of malignant disease in pleural effusions: a randomised controlled trial. Lancet 2003;361:1326–31.Find this resource:
Key points influencing the management of malignant effusions are:
• Symptoms, performance status, and wishes of the patient
• Sensitivity of the 1° tumour to chemotherapy, e.g. small cell lung carcinoma, lymphoma, ovarian and breast carcinoma may respond to chemotherapy, although, in some cases, pleural effusions remain problematic and require additional treatment
• Extent of lung re-expansion following effusion drainage.
Therapeutic pleural aspiration
of 1–1.5L pleural fluid to improve breathlessness (see p. [link]). Can be performed at the bedside as a day-case procedure, avoiding hospital admission. Useful in the palliation of breathlessness in patients with a poor prognosis and in rare cases where effusion reaccumulates very slowly. Most effusions recur within 1 month of aspiration, and these patients should be considered for pleurodesis or insertion of an IPC; repeated aspiration may be inconvenient and uncomfortable for the patient and carries a risk of complications such as empyema, pneumothorax, and tumour seeding (in mesothelioma).
If the breathlessness does not improve following fluid aspiration, then there is little to be gained by repeated aspiration, and other causes of breathlessness should be considered, e.g. lymphangitis carcinomatosis, PE.
Intercostal chest drainage and pleurodesis
The aim of pleurodesis is to seal the visceral pleura to the parietal pleura with adhesions to prevent pleural fluid accumulating. The success of pleurodesis depends on the degree of apposition of the visceral and parietal pleura, which depends on the degree of lung re-expansion following drainage of the effusion. ‘Trapped lung’ occurs when tumour encases the visceral pleura and prevents lung expansion. Lung expansion may also be inhibited by a proximal airway obstruction or by a persistent air leak (e.g. after tearing of a friable tumour-infiltrated lung on re-expansion). Trapped lung may also be caused by non-malignant, fibrotic processes, e.g. rheumatoid pleuritis, haemothorax, TB.
The patient should be admitted and the effusion drained with a small-bore (10–14F) intercostal tube. If lung fully re-expands on CXR, proceed to pleurodesis (see p. [link]). If lung fails to re-expand fully (trapped lung; CXR shows a pneumothorax or hydropneumothorax), consider chest drain suction, which may encourage lung expansion and allow pleurodesis.
Treatment options for trapped lung or failed pleurodesis
• Pleurodesis may be successful, despite only partial lung re-expansion, and should still be considered if there is >50% apposition of lung against chest wall on CXR. It may be repeated if unsuccessful initially
• Insertion of a long-term IPC is likely to be the preferred treatment for patients with significantly trapped lung and avoids the need for recurrent pleural aspiration (see p. [link]). The most frequent complications are symptomatic loculations, catheter blockage, and soft tissue/pleural infection. Can be inserted as a day-case procedure. Needs additional outpatient support (e.g. trained district nurse or respiratory specialist nurse), although most patients perform the drainage themselves after education
• Repeated therapeutic pleural aspiration should be avoided, unless prognosis is particularly limited (<1 month)
• Intrapleural fibrinolytics (e.g. streptokinase 250, 000IU) may be of benefit in the management of multiloculated effusions resistant to drainage and pleurodesis, encouraging free fluid drainage and, in some cases, enabling successful pleurodesis. Haemorrhage is a theoretical complication, although it appears to be uncommon
• Thoracoscopy enables the disruption of pleural adhesions and may have a role in facilitating pleurodesis in select patients with trapped lung
• Pleuroperitoneal shunts are effective in patients with trapped lung or failed pleurodesis, in the absence of multiple loculations. Shunting of fluid may occur spontaneously, at high pressures, or may require manipulation of a percutaneous pump chamber, inserted at thoracoscopy or mini-thoracotomy. Main problem is shunt occlusion, which occurs in at least 10% of cases, and necessitates shunt removal. Malignant spread may also occur
• Surgical parietal pleurectomy may be performed as VATS. The procedure is effective in the management of refractory malignant effusions. May be useful in a minority of patients with good performance status and prognosis. Not suitable for patients with heavily diseased visceral pleura and trapped lung; consider in patients who have failed pleurodesis
• Palliative care team involvement should also be considered.
Definition and pathophysiology
Pleural effusions occur in up to 57% of patients with pneumonia. An initial sterile exudate (simple parapneumonic effusion) may, in some cases, progress to a complicated parapneumonic effusion and eventually empyema (see Fig. 35.1).
Pleural infection may also occur in the absence of a preceding pneumonic illness (‘1° empyema’).
• Consider the diagnosis particularly in cases of ‘slow-to-respond’ pneumonia (e.g. failure of CRP to fall ≥50% in first 3 days), pleural effusion with fever, or high-risk groups with non-specific symptoms such as weight loss
• Similar to clinical presentation of pneumonia: fever, sputum production, chest pain, breathlessness
• Anaerobic empyema may present less acutely, often with weight loss and without fever.
• Infected pleural fluid may spontaneously drain through the chest wall (empyema necessitatis) or into the lung, leading to a bronchopleural fistula and severe pneumonia
• History of atypical chest pain, vomiting, or oesophageal instrumentation suggests possible underlying oesophageal rupture (measure pleural fluid amylase)
• History of a recent sore throat may suggest Lemierre’s syndrome (acute oropharyngeal infection with Fusobacterium species leads to septic thrombophlebitis of the internal jugular vein and subsequent metastatic infection and abscess formation, commonly in the lungs and pleura; consider US of internal jugular vein if suspected); see p. [link].
for developing empyema include diabetes, alcohol abuse, gastro-oesophageal reflux, and IV drug abuse. Anaerobic infection is associated particularly with aspiration or poor dental hygiene. Empyema may rarely occur following bronchial obstruction from a tumour or foreign body. Many patients, however, have no apparent risk factors. One study identified clinical variables associated with development of pleural infection in those with pneumonia: albumin <30g/L, CRP >100mg/L, platelets >400 × 109/L, sodium <130mmol/L, IVDU, and chronic alcohol use.
includes malignancy, TB (when the pleural fluid is usually lymphocytic), and rheumatoid pleuritis.
Davies HE et al. Management of pleural infection in adults: British Thoracic Society pleural disease guideline 2010. Thorax 2010;65(Suppl. 2):ii41–ii53.Find this resource:
Maskell NA et al. UK controlled trial of intrapleural streptokinase for pleural infection. N Engl J Med 2005;352:865–74.Find this resource:
Rahman NM et al. Intrapleural use of tissue plasminogen activator and DNase in pleural infection. N Engl J Med 2011;365:518–26.Find this resource:
• Community-acquired infection (% of cases):
• Streptococcus ‘milleri’ group (~30%)
• Anaerobes (~15–30%)
• Streptococcus pneumoniae (~15%)
• Staphylococcus aureus (~10%)
• Other less common organisms include other streptococci, enterobacteriaceae, H. influenzae, Pseudomonas, TB, and Nocardia
• Hospital-acquired infection (% of cases):
• MRSA (~25–30%)
• Staphylococcus aureus (~10–20%)
• Enterobacteriaceae (~20%)
• Enterococci (~10%)
• Others include streptococci, Pseudomonas, and anaerobes.
Pleural infection is frequently polymicrobial.
• Diagnostic pleural tap using US is essential if pleural infection is possible and fluid depth is >10mm (smaller effusions can usually be monitored). Frankly purulent or turbid/cloudy pleural fluid, organisms on pleural fluid Gram stain or culture, or pleural fluid pH <7.2 are all indications for chest tube drainage. 40% of pleural infections are culture-negative. Identification of anaerobes is improved following inoculation of blood culture bottles with pleural fluid. Ultrasound typically shows an echogenic effusion that may be septated, but absence of these features does not rule out pleural infection
• Contrast-enhanced pleural-phase CT may be useful both in supporting the diagnosis and visualizing the distribution of fluid, although CT is poor at demonstrating septations. Empyema is associated with pleural enhancement and increased attenuation of extrapleural subcostal fat. The displacement of adjacent lung by empyema may help to distinguish from a parenchymal lung abscess. Empyemas frequently appear lenticular and may exhibit the ‘split pleura’ sign of enhancing separated visceral and parietal pleura. Absence of pleural thickening on CT is unusual in empyema. CT may also sometimes identify a proximal endobronchial obstructing lesion
• Blood cultures positive in only 14% of cases, but, in these cases, they are often the only positive microbiology
• Bronchoscopy is only indicated if a bronchial obstructing lesion is suspected.
All patients with pleural infection should be treated with antibiotics; refer to local hospital prescribing guidelines. Typical choices:
• Community-acquired empyema—β-lactam/β-lactamase inhibitor (e.g. co-amoxiclav) or second-generation cephalosporin (e.g. cefuroxime), combined with metronidazole for anaerobic cover. Ciprofloxacin and clindamycin together may be appropriate
• Hospital-acquired empyema—cover Gram-positive and Gram-negative organisms and anaerobes. MRSA infection is common. Consult with microbiology team. One option is meropenem and vancomycin.
Rationalize with culture and sensitivity results (although note that anaerobes are frequently difficult to culture and may coexist with other organisms). Avoid aminoglycosides, which penetrate the pleural space poorly.
Switch to oral antibiotics when apyrexial and improving clinically. Co-amoxiclav is a useful single agent with anaerobic cover (not if penicillin-allergic). Optimal duration of antibiotic treatment unclear, although likely to be at least 3 weeks.
Indications for chest tube drainage
• Purulent pleural fluid
• Organisms on pleural fluid Gram stain or culture
• Pleural fluid pH <7.2.*
Drain insertion should be carried out under US or CT guidance. Ideal chest tube size remains subject to debate. Small (10–14F), flexible tubes are more comfortable and have been demonstrated to be as effective as large drains in the management of empyema. Usually apply suction (–20cmH2O), and flush regularly (e.g. 20mL normal saline every 6h) to prevent occlusion. Consider drain removal when clinical improvement occurs. If there is no indication for drainage, give antibiotics and monitor closely. If slow to improve or deteriorate, re-sample the effusion and consider chest drain.
A 2011 RCT (MIST2) showed that the combination of intrapleural alteplase (tPA) and dornase alfa (DNase) significantly improved CXR appearances for patients with pleural infection (1° outcome) and reduced surgical referral and hospital stay with a similar adverse event profile (2° outcomes). Lone tPA or DNase did not confer such benefits (and there was an increased rate of surgical referral for DNase alone). The effects of tPA/DNase combination treatment need further investigation to determine the appropriate circumstances for its use. The 2005 MIST1 RCT showed that intrapleural streptokinase had no effect on mortality and need for surgery or hospital stay, and is therefore not recommended.
Given a high risk for developing VTE, all patients should receive LMWH unless contraindicated.
Consult with thoracic surgeon if there are ongoing features of sepsis and residual pleural collection after 5–7 days despite tube drainage and treatment with antibiotics. Surgical techniques include:
• VATS allows the breakdown of adhesions and drainage of residual collection, but it is frequently unsuccessful in chronic empyema with very thickened visceral pleura
• Thoracotomy and decortication Removal of fibrinous and infected tissue from the pleural space—a major surgical procedure
• Open thoracic drainage Resection of segments of several ribs adjacent to the empyema and insertion of large-bore drains into the cavity: a more minor procedure that can be performed under local anaesthesia but results in open chest wound for long period (typically around 5 months).
Difficulties in management
Chest drainage ceases despite residual pleural collection
• Attempt to flush drain with normal saline
• Ensure that drain is not kinked at skin insertion site or lying subcutaneously
• Consider CT to assess extent of residual collection and drain position
• Remove drain if persistently blocked
• Consider further image-guided chest drain(s), surgery
• If there has been significant clinical improvement, with falling CRP and WCC, further drains may not be warranted despite residual fluid.
Failure to clinically improve despite antibiotics and chest drain
• Review microbiology results, and ensure appropriate antibiotics
• CT to assess extent of residual collection and drain position
• Surgical referral (at days 5–7)
• Options if unfit for surgery:
• Further image-guided small-bore drains into loculated effusions
• Large-bore drain
• Surgical rib resection and open drainage under local anaesthesia.
About 15% of patients require surgery. Empyema 1y mortality is about 15%. Increased age, renal impairment, low serum albumin, hypotension, and hospital-acquired infection are associated with a poor outcome. CXR may remain abnormal despite successful treatment of empyema, with evidence of calcification or pleural scarring or thickening.
Definition and epidemiology
Tuberculous pleural effusion usually develops from a delayed hypersensitivity reaction to mycobacteria released into the pleural space. It is a common manifestation of 1° TB in regions with a high prevalence, affecting children and young adults; it may also be associated with reactivation of TB in older individuals. May occur more commonly in the setting of HIV co-infection.
Rarely, TB may present as pseudochylothorax or tuberculous empyema.
• Clinical features are similar to those of pulmonary TB, i.e. fever, sweats, weight loss, and dyspnoea, although it may present acutely with pleuritic chest pain and fever, mimicking pneumonia
• Effusions are typically small to moderate in volume although can be massive.
• Associated parenchymal infiltrate on CXR in less than one-third of cases
• Tuberculin skin tests positive in two-thirds of cases
• Interferon γ release assays (IGRAs) reported to have high sensitivity (~90%) but fail to distinguish between latent and active TB
• Pleural fluid Lymphocytosis, exudative effusion, pH and glucose moderately depressed, mesothelial cells rare. Pleural fluid AFB smears are positive in around 5–10% of cases; pleural fluid cultures are positive in 25% of cases and take 2–6 weeks
• Blind Abrams’ pleural biopsy alone has a sensitivity of 79%
• Thoracoscopic biopsies have a sensitivity of nearly 100%
• Measurement of adenosine deaminase (an enzyme released by macrophages after phagocytosis of mycobacteria) in pleural fluid may be of benefit in regions where TB is highly prevalent; a raised value is very sensitive for pleural TB but is non-specific and may also occur in empyema and malignancy. May have a role as a ‘rule-out’ test
• PCR for mycobacterial DNA in the pleural fluid may be useful diagnostically but is not widely available
• Induced sputum for AFB may have a diagnostic role in high-risk patients with lymphocytic effusions, even in the absence of parenchymal disease on CXR.
Treatment and outcome
• Tuberculous pleural effusions resolve spontaneously in the majority of cases, but two-thirds of untreated patients go on to develop pulmonary TB within 5y, and so treatment is recommended
• Pleural fluid volumes may increase during effective treatment, and therapeutic thoracentesis may be required
• Steroids may reduce fluid volume but do not affect long-term outcome
• Pleural thickening and calcification are common long-term consequences of tuberculous pleural effusion.
Pleural effusion due to PE
• Fourth commonest cause of pleural effusion in the USA
• Consider in all patients with undiagnosed pleural effusion, particularly if there is a history of pleuritic chest pain or of breathlessness/hypoxia out of proportion to the size of the effusion
• Frequently complicates other disease processes, e.g. occurs in 1/5 of patients with cardiac failure and pleural effusions
• Effusions are usually small (<1/3 of hemithorax) and unilateral although may be bilateral
• Pleural fluid analysis is non-diagnostic; appearance varies from clear to bloody; 80% are exudates and 20% transudates. Bloodstained pleural fluid is not a contraindication to anticoagulation
• Imaging investigations, such as CTPA, are required to make the diagnosis; these should be performed prior to thoracentesis if PE is strongly suspected.
RA-associated pleural effusion
• Pulmonary changes may be the first manifestation of RA
• Rheumatoid pleurisy is more common in men (70% are in men)
• Pleural fluid may be yellow-green, serous, turbid, or bloody
• Unilateral or bilateral
• Pleural fluid glucose level frequently low (<1.6mmol/L) and progressively falls in chronic effusions
• Pleural fluid pH commonly reduced (<7.3)
• Low pleural fluid complement levels (C4 <0.04g/L) may also favour the diagnosis
• Pleural fluid RhF titre is not more diagnostically helpful than serum RhF
• Typically persist for months to years, although duration may be several weeks
• Some cases may respond to treatment with steroids.
• Haemothorax is defined as a pleural effusion with a haematocrit >50% of peripheral blood haematocrit
• Causes include trauma, iatrogenic, malignancy, pulmonary infarction, pneumothorax, thoracic endometriosis, and aortic rupture
• Massive haemothorax defined as >1, 500cm3 of blood in hemithorax and is most commonly due to trauma. Traumatic haemothorax requires a chest drain and sometimes thoracotomy; all cases should be discussed immediately with the cardiothoracic surgical team
• Large volumes of residual blood in the pleural space will clot and may lead to pleural thickening, empyema, or trapped lung. Tube drainage may be ineffective, and thoracoscopy or thoracotomy with decortication is often needed.
• Small, typically left-sided pleural effusions occur in the majority of patients post-CABG, and most resolve spontaneously
• Larger (>25% of hemithorax) effusions can be subdivided:
• Pleural effusions occurring within 30 days of surgery. Classically bloody and eosinophilic exudate, with high LDH; probably related to post-operative bleeding into pleural space
• Pleural effusions >30 days after surgery. Typically clear and lymphocytic exudate; cause unknown, perhaps immunological or a form of post-cardiac injury syndrome
• Main symptom in each case is breathlessness; chest pain and fever are unusual
• Management consists of repeated therapeutic thoracentesis to alleviate breathlessness. Recurrent effusions after 1y are rare and may be difficult to treat; NSAIDs, prednisolone, or thoracoscopy and pleurodesis may be considered
• Differential diagnosis of pleural effusion post-CABG includes PE, cardiac failure, pleural infection, post-cardiac injury syndrome, chylothorax.
Pleural effusion following asbestos exposure
• Pleural fibrosis and thickening may follow previous episodes of pleural inflammation. Causes include previous empyema, tuberculous pleuritis, rheumatoid pleuritis, haemothorax, thoracotomy, and asbestos exposure (diffuse pleural thickening; see p. [link])
• May be asymptomatic or cause breathlessness
• CXR features include blunting of the costophrenic angle or apices, sometimes with associated calcification
• Ultrasound or CT may be required to distinguish from a pleural effusion
• Treatment is difficult and usually unnecessary; decortication may be considered.
* This is not an absolute cut-off, as pH values vary between pockets of a multiseptated effusion and drainage may be still indicated for higher pH values. Also note that Proteus spp. infection gives pH >7.6.