Expert opinion - Understanding pleural effusions

Dr Nick Maskell and Dr Andrew Medford answer questions about causes, investigations and prescribing.

Pleural effusions are accumulations of fluid within the pleural space. They are usually discovered incidentally on examination or X-ray. There are various causes and effusions are generally classified as either transudates or exudates.

Q: What investigations should my patient with a new effusion expect when attending a respiratory specialist clinic?

Most patients will undergo diagnostic pleural sampling, possibly with aspiration to improve their symptoms if necessary.

If a pleural exudate is confirmed, then a pleural phase contrast CT scan of the thorax would be the next investigation of choice to demonstrate any pleural abnormalities for biopsy. Biopsy can be achieved either CT-guided or by thoracoscopy. Abrams closed pleural biopsy can also be performed in patients unsuitable for CT-guided biopsy or thoracoscopy.

Q: Which drugs are associated with pleural effusions?

The drugs most commonly implicated in pleural effusions are amiodarone, nitrofurantoin, phenytoin, penicillamine and cyclophosphamide. This is worth bearing in mind when initiating these prescriptions. There is an excellent resource at www.pneumotox.com which is freely accessible and contains reported drugs with lung side-effects including pleural disease, as well as giving an indication of frequency of reporting using a star system.

Q: Can I prescribe NSAIDs for my patient with persistent pain recently discharged following pleurodesis?

Yes. Traditional teaching is that NSAIDs interfere with pleurodesis. There is a relative lack of studies but a recent animal study using ketoprofen did not interfere with pleurodesis with talc or doxycycline.1

NSAIDs will block cyclo- oxygenase2 but have no impact on transforming growth factor-ss (TGF-ss) production, which is one of the key fibrogenic cytokines in the effector pathway of pleurodesis.3

Steroids should be stopped if possible as they have been shown in animal studies to attenuate the production of TGF-ss and interfere with pleurodesis.4

Q: How much fluid needs to be present to be detectable on chest X-ray and can imaging predict malignancy?

A posterior-anterior chest X-ray is relatively insensitive and often fails to detect effusions until they have approached 500ml.5

Image 1:Pleural ultrasound showing multiple septations

Pleural ultrasound is more accurate for estimating pleural fluid volume, aiding safe aspirations and showing septations and echogenicity (which correlates with being an exudate) and differentiating pleural fluid and thickening6 (see image 1).

Image 2: CT thorax showing a pleural effusion and nodular pleural thickening

CT can predict pleural malignancy, with the following suggestive of cancer: parietal pleural thickening of >1cm; nodular pleural thickening involving the mediastinal border and circumferential pleural thickening (see image 2).

Q: How do I manage my patient with a Pleurx catheter?

Pleurx tunnelled intrapleural catheters are commonly inserted for trapped lung with recurrent malignant pleural effusion, where the lung will not appose to the pleural surface to facilitate an effective pleurodesis, or where an attempted pleurodesis has been unsuccessful. The aim here is to facilitate management in the community and to reduce unscheduled primary and secondary care visits.

The catheters are much more comfortable than repeated intercostal drains with low infection and complication rates and do not need to be replaced for the expected lifetime of the patient. Typically, the patient's life expectancy should be at least eight weeks to derive significant benefit from the procedure. Carers can be trained to manage the vacuum drainage bottles and system (see image below).

Catheter in patient with malignant pleural effusion

Q: How important is it to differentiate an exudate from a transudate and are the methods perfect?

This is very important as the investigative pathway is entirely different. Traditional teaching used a pleural fluid protein level of 30g/l as the cut-off between transudate (<30) and exudate (>30). However, this is not accurate in low protein states as an exudate may be missed. Light's criteria are more accurate.7

Q: Is there anything new for my patient with suspected or confirmed mesothelioma?

Serum mesothelin (a 40kDa mesothelial cell glycoprotein) is a potential novel new diagnostic marker. In a blinded controlled study, 84 per cent of histologically-confirmed mesothelioma patients had increased mesothelin levels compared with 2 per cent of patients with other cancers or inflammatory pleural diseases and none of the healthy controls. None of the 33 asbestos-exposed patients with normal soluble mesothelin-related concentrations developed mesothelioma over eight years.8 It may therefore prove to have value as an adjunct to diagnosis and assessing tumour progression.

Non-surgical treatment options have been disappointing until recently. Pemetrexed, in combination with cisplatin, has now had a NICE recommendation as a chemotherapy treatment for patients with irresectable and advanced mesothelioma but of WHO performance status 0-1.

Q: Which antibiotics should we use to treat pleural infection?

Pleural infection is common and there have been no significant advances in its treatment over the past decade.9

Most community pleural infections are secondary to anaerobic, streptococcal and staphylococcal infections and will require formal drainage if pleural fluid pH is <7.2. The actual organism may be unidentified in 42 per cent.

In reality, local antibiotic protocols will take account of local resistance, epidemiology and Clostridium difficile problems. With these provisos, an example of a typical regimen for a community-acquired pleural infection would be oral or IV co-amoxiclav or clindamycin in penicillin-allergic patients.

Q: I have a frail elderly patient with a lymphocytic pleural effusion. What are the treatable causes and what tests should I offer?

If the effusion is lymphocytic, TB must be considered as a potentially treatable cause, although malignancy is the most likely diagnosis. In this respect, a T-spot (blood T-cell gamma interferon assay) may be of use.

Pulmonary embolic disease can result in small bilateral or unilateral pleural effusions in 40 per cent of cases that are often haemorrhagic.10 It is important to have a high index of suspicion as these effusions have no distinguishing features.

Congestive cardiac failure can present as a unilateral pleural effusion and, if chronic following diuretic treatment, can be a lymphocytic. If available locally, a BNP test or echocardiogram may aid diagnosis.

The incidence of primary pleural lymphoma is increasing, and can present as an isolated pleural effusion.11 This can be diagnosed in most cases by flow cytometry on the pleural fluid.

Q: When can I avoid referring patients with a pleural effusion on a chest X-ray?

All patients with new, unexplained and not previously investigated unilateral pleural effusions (where a pleural exudate is suspected) should be referred. It is recommended to try to avoid inpatient admission for such cases if possible as the investigation pathway as an inpatient is often not as streamlined as that for urgent outpatient pleural investigation when co-ordinated by the respiratory team.

Sampling the pleural fluid will narrow the differential diagnosis down prior to the next investigation and if the patient is very symptomatic a therapeutic withdrawal of 1-1.5 litres will ease symptoms and often allow the patient to continue with outpatient investigations.

However, those with small bilateral effusions thought to relate to heart failure could be managed in the community with an empirical trial of a diuretic and a follow-up chest X-ray.

It may not be necessary to refer patients with previously thoroughly investigated known effusions that have not changed in character or severity.

  • Dr Maskell is a consultant chest physician and Dr Medford is a respiratory SpR at the North Bristol Lung Centre, Southmead Hospital, Bristol

Learning points

  • Refer patients with unexplained/new pleural effusions for specialist assessment.
  • NSAIDs can be given to post-pleurodesis patients but avoid steroids if possible.
  • Heart failure can occasionally cause unilateral effusions.
  • Pleurx catheters can be managed safely in the community and reduce patient admissions.
  • Empirical community pleural infection antibiotic therapy should cover anaerobes, streptococci and staphylococci.

Useful websites

References

1. Liao H, Guo Y, Jun Na M et al. The short-term administration of ketoprofen does not decrease the effect of pleurodesis induced by talc or doxycycline in rabbits. Respir Med 2007; 101(5): 9638.

2. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol 1971; 231(25): 232-5.

3. Lee YCG, Lane K. The many faces of transforming growth factor-ss in pleural disease. Curr Opin Pulm Med 2001; 7: 173-79.

4. Xie C, Teixeira LR, McGovern JP et al. Systemic corticosteroids decrease the effectiveness of talc pleurodesis. Am J Respir Crit Care Med 1998; 157: 1,441-4.

5. Blackmore C, Black W, Dallas R et al. Pleural fluid volume estimation: a chest radiograph prediction rule. Acad Radiol 1996; 3: 103-9.

6. Eibenberger K, Dock W, Ammann M et al. Quantification of pleural effusions: sonography versus radiography. Radiology 1994; 191: 681-4.

7. Light R, Macgregor M, Luchsinger P, et al. Pleural effusions: the diagnostic separation of transudates and exudates. Ann Intern Med 1972; 77: 507-13.

8. Robinson B, Creaney J, Lake R et al. Mesothelin-family proteins and diagnosis of mesothelioma. Lancet 2003; 362: 1,612-6.

9. Davies C, Gleeson F, Davies R et al. BTS guidelines for the management of pleural infection. Thorax 2003; 58 Suppl 2: ii18-28.

10. Ansari T, Idell S. Management of undiagnosed persistent pleural effusions. Clin Chest Med 1998; 19: 407-17.

11. Alexandrakis M, Passam F, Kyriakou D et al. Pleural effusions in haematologic malignancies. Chest 2004; 125(4): 1,546-55.

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