Acute management for spontaneous pneumothorax

Optimal management after the resolution of a first episode of pneumothorax

Optimal management for spontaneous pneumothorax and ongoing air leak

Optimal surgical approach and surgical operation for pneumothorax management

Radiology for diagnosing unilateral pleural effusions of benign aetiology

Image-guided versus non-image-guided intervention for suspected unilateral pleural effusion

Optimal volume and container for pleural aspiration samples

Pleural fluid tests (biomarkers) for diagnosing unilateral pleural effusion

Serum biomarkers for diagnosing unilateral pleural effusion

Pleural biopsy for diagnosing unilateral pleural effusion

Predicting clinical outcomes of pleural infection

Pleural fluid, or radiology parameters for determining which patients can be treated with intercostal drainage

Optimal initial drainage strategy for established pleural infection

Intrapleural therapy for managing pleural infection

Optimal surgical approach and surgical method for managing pleural infection

Optimal imaging modality for diagnosing pleural malignancy

Systemic therapy for reducing the need for definitive pleural intervention for malignant pleural effusion

Managing malignant pleural effusion

Managing malignant pleural effusion and non-expandable lung

Managing malignant pleural effusion and septated effusion (on radiology)

Managing malignant pleural effusion treated with an indwelling pleural catheter

Evidence statements

Recommendations

• Conservative management can be considered for the treatment of minimally symptomatic (ie, no significant pain or breathlessness and no physiological compromise) or asymptomatic PSP in adults regardless of size. (Conditional—by consensus)

• Ambulatory management should be considered for the initial treatment of PSP in adults with good support, and in centres with available expertise and follow-up facilities. (Conditional)

• In patients not deemed suitable for conservative or ambulatory management, NA or tube drainage should be considered for the initial treatment of PSP in adults. (Conditional)

• Chemical pleurodesis can be considered for the prevention of recurrent SSP in adults (eg, patients with severe chronic obstructive pulmonary disease who significantly decompensated in the presence of a pneumothorax, even during/after the first episode). (Conditional)

• Thoracic surgery can be considered for the treatment of pneumothorax in adults at initial presentation if recurrence prevention is deemed important (eg, patients presenting with tension pneumothorax, or those in high-risk occupations). (Conditional)

Good practice points

• When establishing local ambulatory treatment pathways, planning and coordination between with the emergency department, general medicine and respiratory medicine is vital.

• When performing chemical pleurodesis for the treatment of pneumothorax in adults, adequate analgesia should be provided before and after treatment.

• All treatment options should be discussed with the patient to determine their main priority, with consideration for the least invasive option.

Evidence statement

There was no evidence relevant to the review.

Recommendations

Due to the lack of supporting evidence, no recommendations can be made on the role of elective surgery at an earlier stage to prevent recurrence.

Good practice points

• Elective surgery may be considered for patients in whom recurrence prevention is deemed important (eg, at-risk professionals (divers, airline pilots, military personnel), or those who developed a tension pneumothorax at first episode).

• Elective surgery should be considered for patients with a second ipsilateral or first contralateral pneumothorax.

• Discharge and activity advice should be given to all patients post pneumothorax.

Discharge advice, flying and activity

All patients discharged after active treatment or otherwise should be given verbal and written advice to return to the accident and emergency department immediately should they develop further breathlessness. It is recommended that all patients should be followed up by a respiratory physician to ensure resolution of the pneumothorax, to institute optimal care of any underlying lung disease, to explain the risk of recurrence and the possible later need for surgical intervention and to reinforce lifestyle advice on issues such as smoking and air travel. Those managed by observation alone or by NA should be advised to return for a follow-up chest X-ray (CXR) after 2–4 weeks to monitor resolution. Patients managed with an ambulatory device may need to be seen more frequently to monitor for complications and prompt removal at resolution.

Patients with a persistent closed pneumothorax (ie, no pleural breach or communication across the chest wall, and incompletely resolved on CXR) should not travel on commercial flights until complete radiological resolution. An exception to this is the very rare case of a loculated or chronic localised air collection which has been very carefully evaluated. In those with resolved pneumothorax confirmed radiologically (ie, at least CXR), patients can fly 7 days after the X-ray demonstrates full resolution (the rationale for waiting 7 days is to exclude early recurrence). The BTS Clinical Statement on air travel for passengers with respiratory disease (2022) addresses this with greater detail.22 After a pneumothorax, scuba diving (ie, with pressurised gas tanks) should be discouraged permanently unless a very secure definitive prevention strategy has been performed such as surgical pleurectomy. The BTS Guidelines on respiratory aspects of fitness for diving deal with this in greater detail.23 Smoking influences the risk of recurrence so cessation should be advised.

Evidence statements

• Length of hospital stay appears to be shorter following autologous blood pleurodesis treatment, regardless of delivery method, for pneumothorax and persistent air leak in adults when compared with chest drainage alone. (Ungraded)

• There was no evidence to suggest that the application of suction is beneficial to treat pneumothorax and persistent air leak in adults.

• Limited evidence suggests that endobronchial therapies may have the potential to treat pneumothorax and persistent air leak. (Ungraded)

Recommendations

There is insufficient evidence to make any recommendations on the best treatment method for pneumothorax and persistent air leak in adults.

Good practice point

• If a patient is not considered fit for surgery, autologous blood pleurodesis or endobronchial therapies should be considered for the treatment of pneumothorax with persistent air leak in adults (please refer to the BTS Clinical Statement on Pleural Procedures).1

Evidence statements

• The rate of pneumothorax recurrence after surgical intervention appears to be very low. However, pneumothorax recurrence rate and the need for further procedures appear to be slightly increased following VATS when compared with thoracotomy. (Very low)

• Length of hospital stay, postoperative pain and complications appear to be reduced following VATS when compared with thoracotomy. (Very low)

Recommendations

• Video-assisted thoracoscopy access can be considered for surgical pleurodesis in the general management of pneumothorax in adults. (Conditional)

• Thoracotomy access and surgical pleurodesis should be considered for the lowest level of recurrence risk required for specific (eg, high-risk) occupations. (Conditional)

There is no evidence on which to base the ideal timing for thoracic surgical intervention in cases of persistent air leak. The BTS 2010 pleural guidelines advised thoracic surgical opinion at 3–5 days to balance the risks of ongoing air leak and potentially unnecessary surgical procedures.5 Each case should be assessed individually on its own merit. Patients with pneumothoraces should be managed by a respiratory physician, and a thoracic surgical opinion will often form an early part of the management plan. Patient choice should inform the decision, weighing the benefits of a reduced recurrence risk against that of chronic pain and paraesthesia. Accepted indications for surgical advice are as follows:

• First pneumothorax presentation associated with tension and first secondary pneumothorax associated with significant physiological compromise;

• Second ipsilateral pneumothorax;

• First contralateral pneumothorax;

• Synchronous bilateral SP;

• Persistent air leak (despite 5–7 days of chest tube drainage) or failure of lung re-expansion;

• Spontaneous haemothorax;

• Professions at risk (eg, pilots, divers), even after a single episode of pneumothorax;

• Pregnancy.

Evidence statements

• There appears to be no difference in pneumothorax recurrence (Very low), length of hospital stay (Very low), the need for further treatment (surgery, chest drain or conservative management) (Very low), duration of air leak (Very low), complications (Very low) or mortality (Very low) following bullectomy or surgical pleurodesis for the treatment of SP in adults.

• There is insufficient evidence to comment on pain and breathlessness and quality of life following bullectomy or surgical pleurodesis for the treatment of SP in adults.

Recommendation

• Surgical pleurodesis and/or bullectomy should be considered for the treatment of SP in adults. (Conditional)

Pregnancy

Pneumothorax in pregnancy can pose risks to the mother and foetus. Physiological changes during pregnancy increase the maternal oxygen consumption and the accelerated pattern of breathing in pregnant subjects may heighten the risk of further bleb rupture.24 Pneumothorax that occurs during pregnancy can be managed by simple observation if the mother is not dyspnoeic, there is no fetal distress and the pneumothorax is small (<2 cm). Otherwise, aspiration or chest tube drainage can be used.

Oxygen consumption can increase by 50% during labour and repeated Valsalva manoeuvres during spontaneous delivery may increase the intrathoracic pressures, increasing the size of the pneumothorax.24 Close cooperation between the respiratory physician, obstetrician and thoracic surgeon is essential. To avoid spontaneous delivery or caesarean section, both of which have been associated with an increased risk of recurrence, close liaison with the obstetric team is required on the safest approach for both mother and baby and may take the form of elective assisted delivery at or near term, with regional (epidural) anaesthesia. If caesarean section is unavoidable because of obstetric considerations, then a spinal anaesthetic is preferable to a general anaesthetic.

Catamenial pneumothorax

The typical combination of chest pain, dyspnoea and haemoptysis occurring within 72 hours before or after menstruation in young women should prompt consideration of catamenial pneumothorax. The true incidence is unknown among women undergoing routine surgical treatment for recurrent pneumothorax, catamenial pneumothorax has been diagnosed in as many as 25%.25 Thus, it may be relatively underdiagnosed, and should be suspected in female patients who have recurrent pneumothoraces.

The associated pneumothorax is usually right-sided and there is a heightened tendency to recurrence coinciding with the menstrual cycle. Patients have a history of pelvic endometriosis.26 Although the aetiology is not fully understood, inspection of the pleural diaphragmatic surface at thoracoscopy often reveals defects (termed fenestrations) as well as small endometrial deposits, which may be present on the visceral pleural surface. The most accepted theory to explain the phenomenon of catamenial pneumothorax is that of aspiration of air from the abdomen and genital tract via the diaphragmatic fenestrations, but the appearance of endometriosis deposits on the visceral pleural surface raises the possibility that erosion of the visceral pleura might be an alternative mechanism.

Management of catamenial pneumothorax should be multidisciplinary and include hormonal treatment or surgery by VATS. Medical therapy to achieve ovarian rest is often advocated in the postoperative period.27

Pneumothorax and cystic fibrosis

SSP remains a common complication of cystic fibrosis, occurring in 0.64% of patients per annum and 3.4% of patients overall.28 It occurs more commonly in older patients and those with more advanced lung disease, and is associated with a poor prognosis, the median survival being 30 months.29 Contralateral pneumothoraces occur in up to 40%.29 30 An increased morbidity also results, with increased hospitalisation and a measurable decline in lung function.28 While a small pneumothorax without symptoms can be observed or aspirated, larger pneumothoraces require a chest drain. The collapsed lung can be stiff and associated with sputum retention, thus requiring a longer time to re-expand. During this time other general measures, such as appropriate antibiotic treatment, are needed. Chest tube drainage alone has a recurrence rate of 50%, but interventions such as pleurectomy, pleural abrasion and pleurodesis reduce recurrence.31–33 Partial pleurectomy is generally regarded as the treatment of choice in patients with recurrent unilateral pneumothoraces or evidence of bilateral pneumothorax, with chemical pleurodesis an alternative strategy in those not deemed fit for surgery.29

Surgical emphysema

Please refer to the ‘Intercostal drain insertion, troubleshooting’ section in the BTS Clinical Statement on Pleural Procedures for information on surgical emphysema.1

Iatrogenic and traumatic pneumothorax

Traumatic pneumothorax is a distinct entity from SP, with its own considerations including diagnosis (often made on trauma CTs) and treatment requirements (patients may require positive pressure ventilation), and hence not specifically addressed in this guideline. The GDG are however aware of ongoing randomised trials which are addressing conservative management in this population. Iatrogenic pneumothorax (eg, post-CT-guided lung biopsy or pacemaker insertion) is also a different entity to SP. Good quality data on iatrogenic pneumothorax optimal management is required, but in general, these pneumothoraces tend to resolve more easily and intervention may not be required.

Familial pneumothorax

Around 10% of pneumothorax cases in some series have a family history of pneumothorax, and in such cases, clinicians should seek potential familial causes. These include Birt-Hogg-Dubé syndrome, tuberous sclerosis complex, lymphangioleiomyomatosis and connective tissue disorders such as Marfan syndrome and Ehlers-Danlos syndrome. If a familial pneumothorax is suspected, CT imaging would always be part of the standard workup and advice from specialists in this area, or specialist pneumothorax clinics, should be considered.

Diagnosing pleural effusion

Pleural effusion can be diagnosed using radiology, pleural aspiration or pleural biopsy, so the clinical questions in this section were focused on determining the optimal method(s) for diagnosing unilateral pleural effusion in adults:

• What is the diagnostic accuracy of radiology? (Question B1)

• Is image-guided intervention better than non-image-guided intervention? (Question B2)

• What is the optimal volume and container for a pleural aspiration sample? (Question B3)

• What is the diagnostic accuracy of pleural fluid tests (biomarkers)? (Question B4)

• What is the diagnostic accuracy of serum biomarkers? (Question B5)

• What is the diagnostic accuracy of pleural biopsy? (Question B6)

What is the diagnostic accuracy of radiology?

Radiological tests form a key role in the detection and diagnostic pathway of a unilateral pleural effusion in adults and may include CXR, CT, TUS, positron emission tomography-CT (PET-CT) and MRI. The first clinical question in the ‘Investigation of the undiagnosed unilateral pleural effusion’ section reviewed the diagnostic accuracy of radiology when investigating unilateral pleural effusions of benign aetiology:

B1 What is the diagnostic accuracy of radiology when diagnosing benign pleural disease as a cause of unilateral pleural effusion in adults?

Please note that the diagnostic accuracy of radiological tests for distinguishing benign from malignant disease is addressed in the ‘Pleural malignancy’ subsection ‘Which imaging modality is best for diagnosing adults with suspected pleural malignancy?’.

An overview of the evidence review is shown in the ‘Pleural infection’ and ‘Non-infective causes of unilateral pleural effusions’ subsections below, followed by the evidence statements and GPPs. The full evidence review is available in online supplemental appendix B1.

Pleural infection

The absence of malignant radiological features (circumferential pleural thickening with nodularity involving the mediastinal surface) is suggestive of a benign pleural effusion, but there is overlap in the imaging features of malignancy and infection. On CT, features that are more common in pleural infection (parapneumonic, empyema and TB) than malignancy are34 35:

1. Lentiform configuration of pleural fluid;

2. Visceral pleural thickening (‘split pleura sign’);

3. Hypertrophy of extrapleural fat (>2 mm);

4. Increased density of the extrapleural fat;

5. Presence of pulmonary consolidation.

However, poor sensitivity of these features (0.20–0.48) highlights the need for diagnostic thoracentesis in unexplained pleural effusions to allow pleural fluid characterisation.

Malignancy can also co-exist with pleural infection, with synchronous disease processes found in approximately 5% of cases.36 37 In this context, the presence of a mass involving the extrapleural fat and mediastinal pleural thickening may be markers of co-existent malignancy,37 but common clinical practice is to perform follow-up imaging for up to 2 years to exclude occult disease if there are ongoing symptoms or other clinically concerning features.

TB pleuritis may mimic malignancy with circumferential pleural thickening >1 cm, involvement of the mediastinal surface and nodularity,35 but, unlike malignancy, is not associated with chest wall invasion.38 On ultrasound, tuberculous effusions tend to be highly complex with internal septations, unlike malignancy, and in lymphocyte-rich pleural effusions, the presence of complex internal septation is reported as predictive of TB.39

Non-infective causes of unilateral pleural effusions

Pleural effusions due to non-infective inflammatory causes, including rheumatoid arthritis, Dressler syndrome, organising pneumonia, pulmonary emboli and benign asbestos-related pleural effusion, are typically bland in appearance on CT, showing mild smooth thickening of the parietal pleura not involving the mediastinum.34 Chronic inflammatory effusions are commonly associated with the development of pleuroparenchymal bands and subsequently folded lung. In many cases, aetiology of pleural effusion may be inferred based on circumstantial findings (table 7).

Evidence statements

• CT features such as lentiform pleural collection, enhancement of the visceral pleura, adjacent hypertrophied extrapleural fat of increased density and an absence of malignant features may suggest pleural infection over malignancy. (Ungraded)

• TB may mimic malignancy on imaging. (Ungraded)

• Malignancy may co-exist with pleural infection. (Ungraded)

• In the context of pleural infection, PET-CT is not a useful test to identify pleural malignancy. (Ungraded)

• Assessment of extrathoracic structures on imaging may provide clues to underlying aetiology. (Ungraded)

Recommendations

There is not enough evidence to make any recommendations.

Good practice points

• Imaging findings of a unilateral pleural effusion should be interpreted in the context of clinical history and knowledge of pleural fluid characteristics.

• CT follow-up should be considered for patients presenting with pleural infection to exclude occult malignancy if there are ongoing symptoms, or other clinically concerning features.

• PET-CT should not be used in the assessment of pleural infection.

Evidence statements

• The use of ultrasound guidance immediately prior to thoracentesis appears to reduce the risk of pneumothorax when compared with non-image-guided thoracentesis. (Very low)

• Image-guided thoracentesis appears to reduce the risk of pneumothorax when compared with non-image-guided thoracentesis. (Very low)

• Image-guided thoracentesis appears to improve the rate of successful fluid sampling when compared with non-image-guided thoracentesis. (Very low)

• Length of hospital stay does not appear to be reduced if choosing image-guided thoracentesis over non-image-guided thoracentesis. (Ungraded)

Recommendation

• Image-guided thoracentesis should always be used to reduce the risk of complications. (Strong—by consensus)

Evidence statements

Based on a narrative review:

• The evidence does not support an optimal pleural fluid volume for initial cytological diagnosis but suggests that increasing pleural fluid volume above 50 mL provides no diagnostic benefit. (Ungraded)

• The evidence supports the use of aerobic blood culture bottles, anaerobic blood culture bottles and plain (‘white top’) containers when investigating suspected pleural infection. (Ungraded)

Recommendations

• 25–50 mL of pleural fluid should be submitted for cytological analysis in patients with suspected MPE. (Strong—by consensus)

• Pleural fluid should be sent in both plain and blood culture bottle tubes in patients with suspected pleural infection. (Strong—by consensus)

Good practice points

• At least 25 mL, and where possible 50 mL, of pleural fluid should be sent for initial cytological examination.

• If volumes of ≥25 mL cannot be achieved, smaller volumes should be sent, but clinicians should be aware of the reduced sensitivity.

• If small volume aspirate (<25 mL) has been non-diagnostic, a larger volume should be sent, if achievable, except when there is high suspicion of a tumour type associated with low pleural fluid cytology sensitivity (especially mesothelioma).

• Pleural fluid samples should be processed by direct smear and cell block preparation.

• In patients with an undiagnosed pleural effusion where pleural infection is possible and volume of fluid sample available allows, microbiological samples should be sent in both white top containers and volumes of 5–10 mL inoculated into (aerobic and anaerobic) blood culture bottles.

• In cases where volume available does not allow 5–10 mL inoculation, volumes of 2–5 mL should be prioritised to blood culture bottles rather than a plain, sterile container.

Secondary pleural malignancy

A summary of the diagnostic accuracies of cytology and pleural biomarkers carcinoembryonic antigen (CEA), fragment of cytokeratin 19 (CYFRA21-1), carbohydrate antigen 19-9 (CA19-9), cancer antigen 15-3 (CA15-3) and cancer antigen 72-4 (CA72-4) for diagnosing secondary pleural malignancy are shown in table 10.

Tuberculous pleural effusion

The point estimate diagnostic accuracies of pleural biomarkers adenosine deaminase (ADA) and interferon gamma (IFN-gamma) for diagnosing tuberculous pleural effusion are shown in table 11.

Heart failure

The point estimate diagnostic accuracy of pleural fluid N-terminal prohormone brain natriuretic peptide (NT-proBNP) for diagnosing heart failure pleural effusion is shown in table 12.

Pleural infection (complex parapneumonic effusion or empyema)

No studies directly investigated the diagnostic accuracy of pleural fluid tests for diagnosing pleural infection (complex parapneumonic effusion (CPPE) or empyema). This was primarily due to the use of inappropriate reference standards, failure to adequately describe reference standards used, discovery biomarker analyses without validation and the use of biomarkers for prognostic, not diagnostic, analyses.

Autoimmune pleuritis (lupus pleuritis)

The point estimate sensitivity and specificity of pleural fluid antinuclear antibody (ANA) for diagnosing lupus pleuritis is shown in table 13.

Evidence statements

• Pleural fluid biomarkers do not provide improved sensitivity, when compared with cytology, for diagnosing secondary pleural malignancy. (Low)

• Pleural fluid ADA and IFN-gamma provide high sensitivity and specificity for diagnosing tuberculous pleural effusion. (Very low)

• Pleural fluid NT-proBNP provides high sensitivity and specificity for diagnosing heart failure in patients with unilateral pleural effusion. (Very low)

• Pleural fluid ANA provides high sensitivity and specificity for diagnosing lupus pleural effusion. (Low)

Recommendations

• Pleural fluid cytology should be used as an initial diagnostic test in patients with suspected secondary pleural malignancy, accepting that a negative cytology should lead to consideration of further investigation. (Conditional)

• Pleural fluid biomarkers should not be used for diagnosing secondary pleural malignancy. (Conditional)

• In high prevalence populations, pleural fluid ADA and/or IFN-gamma test(s) can be considered for diagnosing tuberculous pleural effusion. (Conditional)

• In low prevalence populations, pleural fluid ADA can be considered as an exclusion test for tuberculous pleural effusion. (Conditional)

• Tissue sampling for culture and sensitivity should be the preferred option for all patients with suspected tuberculous pleural effusion. (Strong—by consensus)

• Pleural fluid ANA should be considered to support a diagnosis of lupus pleuritis. (Conditional)

Good practice points

• The clinical utility of pleural fluid cytology varies by tumour subtype, including diagnostic sensitivity and predictive value for response to subsequent cancer therapies. This should be taken into consideration when planning the most suitable diagnostic strategy (eg, direct biopsies in those with a likely low cytological yield can be considered).

• Pleural fluid NT-proBNP is useful when considering heart failure as a cause in unilateral pleural effusions but not superior to serum NT-proBNP and therefore should not be ordered routinely.

Secondary pleural malignancy

The sensitivity and specificity of serum CA15-3, CEA, C reactive protein (CRP) and CYFRA21-1 for diagnosing secondary pleural malignancy is shown in table 14. Please note that all presented data are based on data from single studies.

Tuberculous pleural effusion

The diagnostic accuracies of serum biomarkers T-spot and TB antibody for diagnosing tuberculous pleural effusion are shown in table 15. Please note again that the presented data come from single studies.

Heart failure

The diagnostic accuracy of NT-proBNP as a diagnostic serum biomarker for diagnosing heart failure in patients with unilateral pleural effusion is shown in table 16.

Pleural infection (CPPE or empyema) and autoimmune pleuritis

No studies directly reported on the diagnostic accuracy of serum biomarkers to diagnose CPPE, empyema or autoimmune pleuritis in patients with unilateral pleural effusion.

Evidence statements

• Serum NT-proBNP provides high sensitivity and specificity for diagnosing heart failure in patients with unilateral pleural effusion. (Low)

• There is insufficient evidence to support the use of serum biomarkers to diagnose secondary pleural malignancy, pleural infection, tuberculous pleural effusion or autoimmune pleuritis in patients with unilateral pleural effusion.

Recommendation

• Serum NT-proBNP should be considered to support a diagnosis of heart failure in patients with unilateral pleural effusion suspected of having heart failure. (Conditional)

Good practice points

• Serum biomarkers should not currently be used to diagnose secondary pleural malignancy, pleural infection or autoimmune pleuritis.

• Serum biomarkers should not routinely be used to diagnose tuberculous pleural effusion, but may be considered in high prevalence areas.

• Serum biomarkers, including NT-proBNP, should not be used in isolation for diagnosing unilateral pleural effusion as multiple conditions may co-exist.

Evidence statements

• There is insufficient evidence to determine the diagnostic test performance comparing awake thoracoscopic pleural biopsy and video-assisted thoracoscopic pleural biopsy under general anaesthesia. (Ungraded)

• There is no difference in diagnostic yield when using rigid thoracoscopy or semi-rigid thoracoscopy to obtain a pleural biopsy. (Low)

• Definitive diagnosis is more likely with thoracoscopic pleural biopsy when compared with image-guided closed pleural biopsy. (Low)

• Diagnostic accuracy appears to be higher with thoracoscopic pleural biopsy when compared with image-guided closed pleural biopsy. (Ungraded)

• Definitive diagnosis is more likely with thoracoscopic pleural biopsy when compared with blind closed pleural biopsy. (Ungraded)

• Diagnostic yield appears to be higher with thoracoscopic pleural biopsy when compared with blind closed pleural biopsy. (Very low)

• There is no difference in diagnostic accuracy between CT-guided closed pleural biopsy and ultrasound-guided closed pleural biopsy. (Very low)

• Image-guided closed pleural biopsy may increase definitive diagnosis and diagnostic accuracy when compared with blind closed pleural biopsy (for malignant disease and tuberculous pleuritis). (Ungraded)

Recommendations

• Thoracoscopic or image-guided pleural biopsy may be used depending on the clinical indication and local availability of techniques (including need for control of pleural fluid). (Strong)

• Blind (non-image-guided) pleural biopsies should not be conducted. (Strong—by consensus)

Evidence statements

Clinical parameters

• Higher RAPID scores (table 18) appear to indicate an increased risk of mortality (Low) (figure 1) and may indicate an increased length of hospital stay. (Ungraded)

• The Charlson Comorbidity Index Score (CCIS) is associated with an increased risk of mortality with increased CCIS score. (Ungraded)

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Table 18

RAPID score*

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Figure 1

Comparison of the risk of mortality with low, medium and high RAPID scores (based on the meta-analysis results from online supplemental appendix C1, table C1d and figures C1a–C1f).

Recommendation

• RAPID scoring should be considered for risk stratifying adults with pleural infection and can be used to inform discussions with patients regarding potential outcome from infection. (Conditional)

Evidence statements

• Pleural fluid pH appears to have a high specificity and high sensitivity for identifying patients who will undergo a complicated clinical course (complicated parapneumonic effusion (CPPE)) and thus require intercostal drainage. (Ungraded)

• In the context of clinically suspected pleural infection:

• Pleural fluid pH >7.38 appears to indicate a very low risk of CPPE. (Ungraded)

• Pleural fluid pH ≤7.15 appears to indicate a high risk of CPPE. (Ungraded)

• Pleural fluid pH between 7.16 and 7.38 appears to indicate a decreasing risk of CPPE/pleural infection with increasing pH, especially with pH >7.22. (Ungraded)

• Pleural fluid LDH or glucose measurements appear to be less accurate than pH in initial, independent prediction of which patients should be treated with intercostal drainage. (Ungraded)

• Pleural fluid pH and glucose are highly correlated, and thus where immediate or accurate pH measurement is not possible, an initial glucose of 4.0 mmol/L (in the non-diabetic patient) indicates a moderate-to-high likelihood of CPPE. (Ungraded)

• CT pleural fluid contrast enhancement may improve detection of CPPE. (Ungraded)

Recommendations

• For patients with PPE or suspected pleural infection, where diagnostic aspiration does not yield frank pus, immediate pH analysis should be performed. (Strong—by consensus)

• For patients with suspected CPPE:

  • If pleural fluid pH is ≤7.2, this implies a high risk of CPPE or pleural infection and an ICD should be inserted if the volume of accessible pleural fluid on ultrasound makes it safe to do so. (Strong—by consensus)

  • If pleural fluid pH is >7.2 and <7.4, this implies an intermediate risk of CPPE or pleural infection. Pleural fluid LDH should be measured and if >900 IU/L ICD should be considered, especially if other clinical parameters support CPPE (specifically ongoing temperature, high pleural fluid volume, low pleural fluid glucose (72 mg/dL ≤4.0 mmol/L), pleural contrast enhancement on CT or septation on ultrasound. (Strong—by consensus)

  • If pleural fluid pH is ≥7.4, this implies a low risk of CPPE or pleural infection and there is no indication for immediate drainage. (Strong—by consensus)

• In the absence of readily available immediate pleural fluid pH measurement, an initial pleural fluid glucose <3.3 mmol/L may be used as an indicator of high probability of CPPE/pleural infection and can be used to inform decision to insert ICD in the appropriate clinical context. (Strong—by consensus)

Good practice points

• Clinicians should be mindful of alternative diagnoses that can mimic PPE with a low pH and potential for loculations (eg, rheumatoid effusion, effusions due to advanced malignancy/mesothelioma).

• Pleural fluid samples taken for pH measurement should not be contaminated with local anaesthetic or heparin (eg, by extruding all heparin from an arterial blood gas syringe) as this lowers pleural fluid pH. Delays in obtaining a pleural fluid pH will also increase pleural fluid pH.

• In patients where a clinical decision is made not to insert an ICD at initial diagnostic aspiration, regular clinical reviews should be performed and repeat thoracocentesis considered to ensure that CPPE is not missed.

The data derived from this question review have been integrated into an updated decision-making algorithm for the diagnosis of patients with pleural infection which includes both pleural fluid and radiological parameters—see Appendix 1, Suspected pleural infection, non-purulent fluid—initial decision tree.

Evidence statements

• Chest tube bore size appears to have no effect on mortality rate, the need for post-treatment thoracic surgery or the length of hospital stay following chest tube drainage to treat pleural infection in adults, but bore size >14 F may increase post-treatment pain. (Ungraded)

• Drainage under VATS or open thoracotomy appears to reduce the need for repeat intervention and the length of hospital stay when compared with standard chest tube drainage for the treatment of pleural infection in adults. (Ungraded)

Recommendation

• Initial drainage of pleural infection should be undertaken using a small bore chest tube (14 F or smaller). (Conditional—by consensus)

Good practice points

• Due to the lack of supporting evidence, early surgical drainage under VATS or thoracotomy should not be considered over chest tube (‘medical’) drainage for the initial treatment of pleural infection.

• Due to lack of supporting evidence, medical thoracoscopy should not be considered as initial treatment for pleural infection.

Conclusions from the evidence review (please see above and online supplemental appendix B3) have been integrated into the pleural infection treatment algorithm (see Appendix 1, Pleural infection treatment pathway).

Evidence statements

• Streptokinase appears to have no effect on mortality (Very low), length of hospital stay (Very low), the need for thoracic surgery (Very low) or radiographic resolution of effusion (Very low) for the treatment of pleural infection.

• Streptokinase increases post-treatment complications (Very low) when compared with chest drainage alone or placebo for the treatment of pleural infection.

• Urokinase appears to reduce the need for thoracic surgery (Low), hasten the time to resolution of fever (Very low) and reduce the length of hospital stay (Low) compared with placebo or standard care in adults with pleural infection.

• TPA plus DNAse appears to reduce the length of hospital stay (Ungraded), reduce the likelihood of persistent fevers (Ungraded) and increase improvements in CXR opacification (Ungraded), when compared with placebo in the treatment pleural infection, but TPA plus DNAse may increase the risk of post-treatment complications (serious and non-serious). (Ungraded)

• Single agent TPA or single agent DNAse do not appear to improve clinical outcomes when compared with placebo for treating pleural infection. (Ungraded)

• Saline irrigation (250 mL saline three times a day) may reduce the need for thoracic surgery (Ungraded) but appears to have no impact on mortality (Ungraded), length of hospital stay (Ungraded) or time to resolution of fever (Ungraded) when compared with saline flushes.

Recommendations

• Combination tissue plasminogen activator (TPA) and DNAse should be considered for the treatment of pleural infection, where initial chest tube drainage has ceased and leaves a residual pleural collection. (Conditional—by consensus)

• Saline irrigation can be considered for the treatment of pleural infection when intrapleural TPA and DNase therapy or surgery is not suitable. (Conditional—by consensus)

• Single agent TPA or DNAse should not be considered for treatment of pleural infection. (Conditional—by consensus)

• Streptokinase should not be considered for treatment of pleural infection. (Conditional)

Good practice points

• Patient consent should be taken when using TPA and DNase as there is a potential risk of bleeding.

• When administering TPA plus DNase, the regime of should be 10 mg TPA twice daily (10 mg two times per day)+5 mg DNase two times per day for 3 days, based on randomised controlled trial data. Based on retrospective case series data, 5 mg TPA two times per day+5 mg DNase two times per day for 3 days may be as effective, and can be used if considered necessary.

• Reduced doses of TPA may be considered in those with a potentially higher bleeding risk (eg, those on therapeutic anticoagulation which cannot be temporarily ceased).

• For details on administration of intrapleural treatments, please refer to the BTS Clinical Statement on Pleural Procedures.1

Conclusions from the evidence review (please see above and online supplemental appendix C4) have been integrated into the pleural infection treatment algorithm (see Appendix 1, Pleural infection treatment pathway).

Evidence statements

• Postoperative mortality and the need for repeat intervention are similar following VATS or thoracotomy for pleural infection. (Very low)

• Immediate postoperative pain appears to be less following VATS than thoracotomy for pleural infection. (Ungraded)

• Length of hospital stay appears to be shorter following VATS than thoracotomy for pleural infection. (Very low)

• VATS access appears to cause fewer postoperative complications than thoracotomy for pleural infection. (Very low)

Recommendation

• VATS access should be considered over thoracotomy for adults in the surgical management of pleural infection. (Conditional)

Good practice point

• When selecting a surgical access for the treatment of pleural infection in adults, it is important to ensure the technique can facilitate optimal clearance of infected material and achieve lung re-expansion where appropriate.

Evidence statement

• Based on very limited evidence, decortication surgery for pleural infection may be associated with a longer postoperative stay and higher mortality than surgery that does not involve decortication, but is associated with less breathlessness. (Ungraded)

Recommendations

No recommendations can be made based on the available evidence.

Good practice points

• Extent of surgery should be tailored according to patient and empyema stage when the lung is not completely trapped (drainage vs debridement).

• Decortication should be a decision that is individualised to the patient with a trapped lung based on assessment of patient fitness and empyema stage.

Microbiology

The microbiology of pleural infection is a large topic in itself, and not specifically covered by this guideline. However, knowledge of likely microbiological cause will influence the required antibiotic therapy which in a significant proportion of patients will be empirical throughout the treatment course. Large-scale studies have demonstrated that conventional microbiological tests (culture of pleural fluid in plain tubes) results in a sensitivity of 50%–60% at best, with blood cultures having a yield of <10%. There is now good evidence that microbiological yield can be increased by inoculating pleural fluid into blood culture bottle media, and by the use of image-guided parietal pleural biopsy for microbiological assessment (covered in the ‘Investigation of the undiagnosed unilateral pleural effusion, What is the optimal volume and container for a pleural aspiration sample?’ section of this guideline).

Data on likely microbiological cause in pleural infection are little changed compared with the 2010 Guideline,7 and it remains the case that the majority of community-acquired pleural infection is caused by Gram-positive aerobic organisms, especially streptococcal species including the anginosus group and Staphylococcus aureus. Gram-negative bacteria are less commonly cultured in community-acquired disease, but anaerobic bacteria are commonly seen both in isolation and as co-infection with aerobic organisms. In contrast, hospital-acquired pleural infection is dominated by resistant Gram-positive organisms (including methicillin-resistant Staphylococcus aureus (MRSA)) and Gram-negative organisms such as Escherichia coli, Enterobacter and Pseudomonas, with significant anaerobic involvement. Polymicrobial infection is commonly seen in both community-acquired and hospital-acquired disease, especially when molecular diagnostic techniques are used.

Fungal pleural infection is rare (<1% of cases overall),50 and usually seen in immunosuppressed individuals, associated with a very high mortality.51 The diagnosis of fungal pleural infection (especially in those without known immunocompromise) should prompt investigation for other sources of potential infection including oesophageal leak.

Antibiotics

Initial antibiotic treatment for suspected or confirmed pleural infection should commence before results of culture tests are available and will be dictated by the likely source of infection (community-acquired or hospital-acquired disease) as per the likely microbiological cause. Local audit and assessment of likely bacteria is encouraged, as there are geographic differences in microbiological pattern. Initial treatment should include cover of likely organisms including anaerobes, and discussion with local microbiological services should occur. An example of empirical initial antibiotic choice in community-acquired pleural infection is a combination of a second-generation cephalosprin with anaerobic cover (cefuroxime+metronidazole) which covers all likely organisms, whereas empirical treatment for hospital-acquired pleural infection should cover resistant Gram-negative organisms and potentially MRSA (eg, vancomycin+meropenem). A positive culture test from pleural fluid or blood culture may allow narrowing of empirical antibiotics, specifically if pneumococcus is detected, as this is usually a monomicrobial disease.

In general, between 2 and 6 weeks of antibiotic therapy is used according to clinical response, as shorter courses may result in earlier clinical relapse. However, there has not, to date, been an adequately powered study addressing shorter antibiotic duration for pleural infection, and the optimal length of treatment therefore remains unknown. Similarly, direct comparative studies of the use of intravenous or oral antibiotics for pleural infection are lacking, and it is therefore usual practise to treat with intravenous antibiotics initially while patients are in hospital, transitioning to suitable oral therapy according to clinical response and on discharge from hospital. Where oral therapy is not possible (due to bacterial sensitivities or drug allergies), consideration should be given to ambulatory services providing home intravenous treatment.

Diagnosis

When a patient presents with MPE breathlessness is a common symptom,53 although up to a quarter of those presenting may not be breathless.54 Constitutional symptoms, such as fever, chills, fatigue, weakness and weight loss, may be prominent and other symptoms, such as chest pain, are usually because of malignant infiltration of structures in the chest wall.

MPE can be diagnosed by radiology, pleural aspiration under ultrasound guidance or image-guided pleural biopsy. The diagnostic accuracy of various imaging modalities used for diagnosing MPE are explored in the first clinical question and provide an understanding of the relative merits of each technique (see the ‘Which imaging modality is best for diagnosing adults with suspected pleural malignancy?’ section below).

Diagnostic pleural aspiration under ultrasound guidance also remains an important first intervention and may lead to a diagnosis in many cases. Since the widespread adoption of medical thoracoscopy, diagnosis and management of MPE may be combined. This provides a ‘one-stop’ intervention for patients and may significantly shorten the patient pathway. Image-guided pleural biopsy may also be useful where there is significant volume of disease, but little pleural fluid or limited availability of medical thoracoscopy (please see the ‘Ultasound-guided pleural biopsy’ section in the BTS Clinical Statement on Pleural Procedures for further details1). Both of these techniques are discussed in the ‘Investigation of the undiagnosed unilateral pleural effusion, Is image guided intervention better than non-image guided intervention?’ section.

Treatment

For patients with a known MPE, management options now include ambulatory intermittent intervention with recurrent aspiration, home-based management with indwelling pleural catheters (IPCs) (also combined with pleurodesis) and traditional inpatient admission with a chest tube and talc slurry pleurodesis. In this guideline, the relative merits of each approach are explored, but it is important to stress that in most cases there is not a ‘right’ answer as to the best approach. Patient preference is always important and various online tools and documents have been developed to help patients navigate the various options. The presented evidence will allow clinicians and patients to make the right decision, including the relative value of pleurodesis and optimum drainage strategies (see ‘Is pleural aspiration with no pleurodesis agent better than talc slurry?’, ‘Is an indwelling pleural catheter better than talc slurry pleurodesis?’, ‘Is thoracoscopy and talc poudrage pleurodesis better than chest drain and talc slurry pleurodesis?’, ‘Is surgical pleurodesis or surgical decortication better than talc slurry pleurodesis?’, ‘Is symptom-based/conservative drainage better than daily drainage?’ and ‘Do intrapleural agents (talc or other pleurodesis agents) improve clinical outcomes in patients with MPE treated with an indwelling pleural catheter?’ sections below). Please note that all procedural techniques are covered separately in the BTS Clinical Statement on Pleural Procedures.1

For patients with complex malignant pleural disease, the management of trapped lung is an important question, and the guideline has addressed this in the ‘Is pleural aspiration, talc slurry pleurodesis, talc poudrage pleurodesis or decortication surgery better than using an indwelling pleural catheter to treat malignant pleural effusion and non-expandable lung?’ section below. The use of fibrinolytics for complex pleural effusions has also been explored in the ‘Is intrapleural chemotherapy better than systemic treatment for treating pleural malignancy?’ section.

Finally, the value of systemic anticancer treatment (SACT) or intrapleural chemotherapy for the treatment of MPE are investigated in the ‘Does systemic therapy avoid the need for definitive pleural intervention?’ and ‘Is intrapleural chemotherapy better than systemic treatment for treating pleural malignancy?’ sections, respectively.

Prognosis

Prognosis is a question that is frequently asked, but one which can be difficult to answer. The final clinical question aimed to address if prognostic or predictive scores could provide patients wih MPE with important information about their prognosis (‘Does the use of prognostic or predictive scores provide important prognostic information for the patient?’, Question D12).

The full list of clinical questions in relation to the management of malignant pleural disease in adults were:

• Which imaging modality is best for diagnosing adults with suspected pleural malignancy? (Question D1)

• Does systemic therapy avoid the need for definitive pleural intervention? (Question D2)

• Is pleural aspiration with no pleurodesis agent better than talc slurry? (Question D3)

• Is an indwelling pleural catheter better than talc slurry pleurodesis? (Question D4)

• Is thoracoscopy and talc poudrage pleurodesis better than chest drain and talc slurry pleurodesis? (Question D5)

• Is surgical pleurodesis or surgical decortication better than talc slurry pleurodesis? (Question D6)

• Is pleural aspiration, talc slurry pleurodesis, talc poudrage pleurodesis or decortication surgery better than using an indwelling pleural catheter to treat malignant pleural effusion and non-expandable lung? (Question D7)

• Are intrapleural enzymes better than surgery, or no treatment, for treating malignant pleural effusion and septated effusion (on radiology)? (Question D8)

• Is symptom-based/conservative drainage better than daily drainage? (Question D9)

• Do intrapleural agents (talc or other pleurodesis agents) improve clinical outcomes in patients with MPE treated with an indwelling pleural catheter? (Question 10)

• Is intrapleural chemotherapy better than systemic treatment for treating pleural malignancy? (Question D11)

• Does the use of prognostic or predictive scores provide important prognostic information for the patient? (Question D12)

Evidence statements

• Ultrasound allows detailed evaluation of the peripheral pleura in the presence of a pleural effusion and has a moderate sensitivity and high specificity for diagnosing pleural malignancy. (Moderate)

• CT has a moderate sensitivity and specificity for the diagnosis of pleural malignancy. (Low)

• PET-CT has a high sensitivity and specificity for the diagnosis of pleural malignancy. (Low)

• MRI, using different techniques, appears to show high sensitivity and specificity for the diagnosis of pleural malignancy. (Ungraded)

Recommendations

• Ultrasound may be a useful tool at presentation to support a diagnosis of pleural malignancy, particularly in the context of a pleural effusion, where appropriate sonographic skills are present. (Conditional)

• CT allows assessment of the entire thorax, and positive findings may support a clinical diagnosis of pleural malignancy when biopsy is not an option (Conditional), however a negative CT does not exclude malignancy. (Strong—by consensus)

• PET-CT can be considered to support a diagnosis of pleural malignancy in adults when there are suspicious CT or clinical features and negative histological results, or when invasive sampling is not an option. (Conditional)

Good practice points

• Imaging can play an important role in the assessment of pleural malignancy, but results should be interpreted in the context of clinical, histological and biochemical markers.

• Features of malignancy may not be present on imaging at presentation. Unless a clear diagnosis is reached by other means (eg, biopsy), monitoring with follow-up imaging of patients presenting with pleural thickening and unexplained unilateral pleural effusion should be considered to exclude occult malignancy.

• MRI has potential as a diagnostic tool in pleural malignancy. Its clinical value has yet to be determined and its use should be limited to highly selected cases and research studies at the present time.

Evidence statements

• There was no evidence to support the use of SACT to reduce the need for definitive pleural procedures in adults with MPE.

• Systemic anti-angiogenesis agents may improve pleural effusion control in non-small-cell lung carcinoma, but methodological constraints limit the interpretation of the results.

Recommendation

• Definitive pleural intervention should not be deferred until after SACT. (Conditional—by consensus)

Evidence statements

Based on very limited evidence:

• Talc slurry pleurodesis may be associated with a longer hospital stay than pleural aspiration. (Ungraded)

• Talc slurry pleurodesis appears to reduce the need for re-intervention and reduces the overall number of complications compared with pleural aspiration alone. (Ungraded)

• Patients undergoing pleural aspiration as the first intervention will often require a second procedure, with approximately one-third requiring this within 2 weeks. (Ungraded)

• Pleural aspiration appears to improve breathlessness. (Ungraded)

Recommendation

• Management of MPE using talc pleurodesis (or another method) is recommended in preference to repeated aspiration especially in those with a better prognosis, but the relative risks and benefits should be discussed with the patient. (Conditional—by consensus)

Good practice points

• Decisions on the best treatment modality should be based on patient choice.

• Informed decision-making should include the role of inpatient versus ambulatory management and the potential risk of requiring further pleural interventions.

Evidence statements

• Talc slurry pleurodesis and IPCs appear to improve dyspnoea and quality of life scores, but there are no observable differences between the two treatments. (Ungraded)

• IPC insertion appears to be associated with a shorter length of initial hospital stay at the time of intervention and fewer subsequent inpatient days. (Ungraded)

• IPCs appear to be associated with a reduced need for further pleural intervention (defined as requirement for a further pleural procedure) when compared with talc slurry pleurodesis. (Moderate)

• There appears to be no difference in adverse events for patients treated with talc slurry pleurodesis or IPC. (Very low)

Recommendation

• Patients without known non-expandable lung (for a definition of non-expandable lung please see the ‘Is pleural aspiration, talc slurry pleurodesis, talc poudrage pleurodesis or decortication surgery better than using an indwelling pleural catheter to treat malignant pleural effusion and non-expandable lung?’ section) should be offered a choice of IPC or pleurodesis as first-line intervention in the management of MPE. The relative risks and benefits should be discussed with patients to individualise treatment choice. (Conditional)

Good practice points

• The psychological implications and potential altered body image aspects of having a semi-permanent tube drain in situ should not be underestimated and must be considered prior to insertion.

• All patients who have had an IPC inserted should be referred to the community nursing team on discharge for an early assessment of the wound site, symptom control, support with IPC drainage and removal of sutures.

• Patients and their relatives should be supported to perform community drainage and complete a drainage diary if they feel able to do so, to promote independence and self-management.

• Complications such as infection refractory to community management, suspected drain fracture, loculations or blockage with persistent breathlessness should be referred back to the primary pleural team for further assessment.

Evidence statements

• There appears to be no difference in health-related quality of life, length of hospital stay, chest pain or breathlessness in adults with MPE treated with chest drain and talc slurry, or thoracoscopy and talc poudrage. (Ungraded)

• Pleurodesis failure rate may be lower in adults who have thoracoscopy and talc poudrage for the treatment of MPE when compared with chest drain and talc slurry. (Low)

• There appears to be no difference in the occurrence of one or more complications following treatment with chest drain and talc slurry or thoracoscopy and talc poudrage in adults with MPE (Very low), but thoracoscopy and talc poudrage may cause an increased number of complications per patient. (Ungraded)

Recommendation

• Talc slurry or talc poudrage may be offered to patients with MPE to control fluid and reduce the need for repeated procedures. (Conditional)

Good practice point

• Where a diagnostic procedure is being conducted at thoracoscopy (pleural biopsies), if talc pleurodesis is reasonable, this should be conducted during the same procedure via poudrage.

Evidence statements

There was insufficient evidence to accurately address the question and published evidence was in highly selected, non-randomised patients.

• Surgical and non-surgical treatments for MPE may improve quality of life and reduce breathlessness. (Ungraded)

• Surgical MPE treatments may require a longer stay in hospital compared with talc slurry pleurodesis. (Ungraded)

• VATS with talc pleurodesis may reduce the need for early postsurgery re-intervention. (Ungraded)

• Pleurodesis failure rates may increase in patients wih MPE with non-expandable lung if thoracoscopic decortication is not performed. (Ungraded)

Recommendation

• In selected patients considered fit enough for surgery, either surgical talc pleurodesis or medical talc slurry can be considered for the management of patients with MPE. The relative risks, benefits and availability of both techniques should be discussed with patients to individualise treatment choice. (Conditional—by consensus)

Good practice points

• Informed decision-making should include the role of surgery versus ambulatory management with an IPC for the management of MPE in selected patients.

• Decortication surgery may improve pleurodesis success in patients with MPE with non-expandable lung, but the risks and benefits of IPC and surgical treatment should be discussed with patients, and treatment individualised according to circumstances (eg, fitness to undergo thoracic surgery).

Evidence statements

• IPCs may improve quality of life and breathlessness in patients with MPE and non-expandable lung but may result in the IPC remaining in situ for a prolonged period (>100 days). IPC carries a small risk of pleural infection in patients with MPE and non-expandable lung. (Ungraded)

• There is no direct evidence to support the use of talc slurry pleurodesis over IPC, but talc slurry pleurodesis may improve quality of life, symptoms and pleurodesis rate in patients with MPE and <25% lung non-expandable lung. (Ungraded)

• There is no direct evidence to support the use of talc poudrage pleurodesis over IPC in patients with MPE and non-expandable lung. (Ungraded)

• Pleurodesis failure rates may increase in patients with MPE and non-expandable lung if thoracoscopic decortication is not performed. (Ungraded)

Recommendations

No recommendations can be made on the use of pleural aspiration, talc slurry pleurodesis, talc poudrage pleurodesis or decortication surgery versus an IPC to control symptoms in patients with MPE and non-expandable lung.

Good practice points

• Decisions on treatment modality for MPE and non-expandable lung should be based on patient choice, with the relative risks and benefits of each modality discussed with the patient, but patients should be made aware of the limited evidence base regarding treatment options for non-expandable lung.

• IPCs are effective at controlling symptoms in non-expandable lung and should be considered, but it may be appropriate to undertake pleural aspiration first to assess symptomatic response.

• Pleural aspiration may result in a need for multiple procedures so alternatives should be discussed with the patient.

• In patients with radiologically significant (>25%) non-expandable lung requiring intervention for a symptomatic MPE, current evidence suggests the use of an IPC rather than talc pleurodesis.

• In patients with MPE and <25% non-expandable lung, talc slurry pleurodesis may improve quality of life, chest pain, breathlessness and pleurodesis rates.

• Decortication surgery may improve pleurodesis success in selected patients with MPE and non-expandable lung, but the risks and benefits of IPC and surgical treatment should be discussed with patients, and treatment individualised according to circumstances (eg, fitness to undergo thoracic surgery).

Evidence statements

There was insufficient evidence to determine if intrapleural enzymes are better than surgery at improving clinical outcomes in adults with MPE and septated effusion (on radiology).

Recommendations

Due to the lack of supporting evidence, no recommendations can be made on the use of intrapleural enzymes or surgery for treating adults with MPE and septated effusion (on radiology).

Good practice points

• Intrapleural fibrinolytics can be considered in highly selected symptomatic patients with MPE and septated effusion to try to improve breathlessness.

• Intrapleural fibrinolytics may be used in patients with MPE and septated effusion and an IPC to improve drainage if flushing the IPC with normal saline or heparinised saline does not improve drainage.

• Surgery can be considered for palliation of symptoms in a minority of patients with significantly septated MPE and associated symptoms and otherwise good prognosis and performance status.

Evidence statements

• Symptoms (breathlessness and chest pain), complications and length of hospital stay appear to be the same for daily drainage, symptom-guided drainage or alternate daily drainage. (Ungraded)

• There appear to be no differences in the occurrence of complications between daily drainage and symptom-based/conservative drainage regimes. (Low)

• Daily drainage increases pleurodesis rates when compared with alternate drainage or symptom-based drainage regimes. (Low)

• Daily drainage may improve quality of life when compared with a symptom-based/conservative drainage approach, but there is no current evidence that daily drainage improves quality of life when compared with alternate daily drainages. (Ungraded)

Recommendations

• Where IPC removal is a priority, daily IPC drainages are recommended to offer increased rates of pleurodesis when compared with less frequent drainages of symptom-guided or alternate drainage regimes. (Conditional)

• Patients should be advised that they do not require daily drainage to control symptoms of breathlessness and chest pain if they wish to opt for a less intensive regime. (Strong—by consensus)

Good practice points

• Decisions on the optimal drainage frequency should be based on patient choice.

• Informed decision-making should include the explanation of the effect of drainage regimes on the patient-centred outcomes such as breathlessness and the possibility of autopleurodesis during the disease course.

• Although daily drainage may result in earlier removal of IPC, there may be an associated cost associated with the increased number of drainage events (both to the healthcare system, and to the patient). This has been addressed in a modelling study2 and should be considered.

Evidence statements

Based on one paper:

• Pleurodesis rates and quality of life may be improved in patients with MPE and expandable lung (defined as >75% of hemithorax) who have talc instilled via an IPC. (Ungraded)

• Chest pain and breathlessness may be reduced in patients with MPE and expandable lung (defined as >75% of hemithorax) who have talc instilled via an IPC. (Ungraded)

• Complication rates do not appear to differ between patients with MPE treated with an IPC and talc or placebo. (Ungraded)

Recommendation

• Instillation of talc via an IPC should be offered to patients with expandable lung where the clinician or patient deems achieving pleurodesis and IPC removal to be important. (Conditional—by consensus)

Evidence statements

There was no direct evidence to support this question; and based on very limited evidence:

• Intrapleural combination therapies (chemotherapy plus VEGF inhibitor or angiogenesis inhibitor) may improve effusion control and increase quality of life, progression-free survival and survival time when compared with chemotherapy alone.

Recommendation

• Intrapleural chemotherapy should not be routinely used for the treatment of MPE. (Conditional—by consensus)

Evidence statements

• LENT and PROMISE provide estimates of survival for patients with MPE, but neither have been assessed in their ability to improve outcomes. (Ungraded)

Recommendations

No recommendation can be made from the presented evidence.

Good practice points

• Clinicians may consider using a validated risk score for MPE, if the information is of use in planning treatments or in discussion with patients.

• Patients with pleural malignancy should be managed in a multidisciplinary way, including referral to specialist palliative care services where appropriate.