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Pleural Effusion

Author: Steven Crane, Chris Wearmouth / Editor: Jason B Lee / Reviewer: Chris Wearmouth / Codes: CAP6, HAP6 / Published: 01/05/2019 / Review Date: 01/05/2022

Context and Definition

A pleural effusion is an abnormal collection of fluid within the pleural space.

The annual incidence of pleural effusion in the developed world has been estimated at 320 per 100,000 population per year [1]. In the USA approximately 1.5 million people are diagnosed with a pleural effusion each year [2]. There are no reliable figures for the UK, however there are estimated to be 50,000 new cases of pleural effusions due to malignancy alone each year. [3]

Little data relating specifically to the frequency of pleural effusions presenting to ED exists. Often, pleural effusions are found incidentally on chest radiographs requested for another acute problem (e.g. heart failure, pneumonia) or a chronic condition already known to the patient (e.g. malignant effusion).

Mortality and morbidity for patients with pleural effusion is related more to the underlying cause than the size of the effusion. However, pleural effusions are not entirely innocuous. Patients with pneumonia have a poorer outcome if it is associated with a para-pneumonic effusion [4] and patients with a malignant pleural effusion (particularly those associated with carcinoma of the lung or gut) have a mean survival time of only a few months [5].

Mortality and morbidity is also related to the biochemical make-up of the pleural fluid (e.g. protein content, pH, cell content). This is because it reflects the underlying cause of the effusion (e.g. transudate in heart failure; exudate in pneumonia or malignancy).

Aetiology

Normal anatomy

The pleural space is walled by the parietal pleura which lines the inside of the chest wall, and the visceral pleura which lines the lung. Pleural fluid is produced by filtering from systemic capillaries within the parietal interstitium and production is greatest at the apex of the lung [5].

The fluid enters the pleural space down a small pressure gradient. In health, approximately 0.13 mls/kg bodyweight of pleural fluid lubricates the space between the parietal and visceral pleura [6]. The fluid allows for smooth movement of the lungs during normal ventilation.

Pleural fluid is absorbed and drained via parietal lymphatic vessels predominantly in the region of the mediastinum and diaphragm where lymphatic vessel numbers have been shown to be greatest. These vessels ultimately drain into mediastinal lymph nodes. The visceral pleura and its capillaries and lymphatic vessels, plays an insignificant part in pleural fluid production and turnover [7].

Normal fluid physiology

Pleural fluid volume is maintained by the balance of pulmonary capillary hydrostatic and oncotic pressure, lymphatic drainage and the integrity of the pleural and capillary membranes. Disturbances to any of these can lead to the formation of excess pleural fluid.

Normal pleural fluid is formed from the filtration of plasma by healthy parietal pleural membranes and has the following characteristics:

A glucose content similar to plasma
A low sodium content (1-2 g/dl)
A low white cell count (<1000 cells / mm3)
A low lactate dehydrogenase (LDH) level (<50% that of plasma)

Figure 1. Pleural anatomy

Pleural E CEM - 1

Pleural E CEM - 2

Transudates are associated with increased systemic or pulmonary capillary hydrostatic pressure or decreased colloid osmotic pressure. These factors often co-exist. The pleural membranes are intact and the permeability of pleural capillaries to proteins is normal.

  • Cardiac failure
  • Liver failure/cirrhosis
  • Renal failure, nephrotic syndrome
  • Constrictive pericarditis
  • Hypothyroidism
  • Meigs Syndrome (right pleural effusion with ovarian fibroma)

Exudates are associated with altered permeability of pleural membranes, increased capillary wall permeability to proteins or vascular disruption. They can also be associated with reduced or obstructed lymphatic drainage from the pleural space.

  • Pneumonia
  • Pulmonary embolism/infarction
  • Malignancy
  • Mesothelioma
  • Connective tissue disorders such as rheumatoid arthritis, systemic lupus erythematosus

Aortic dissection, oesophageal rupture, pancreatitis may also cause pleural effusions. An effusion in the context of trauma should be assumed to be a haemothorax until proved otherwise.

Malignant effusions

The tumours most commonly associated with malignant pleural effusions are:

  • Lung
  • Breast
  • Lymphoma
  • Tumours of the GI tract

Tumour cells migrate to the pleura by either haematogenous or lymphatic spread. This can occur from a primary site in the lung or via metastases from distant sites.

Tumour cells disrupt the network of lymphatic channels within the parietal pleura causing obstruction. Effusions associated with malignancy are therefore exudates.

Pathophysiology of pleural infections

There are three main stages in the development of pleural infection. This is shown in the diagram below.

Figure 2. Stages of pleural infection

Pleural E CEM - 3

Key points to note: [4, 8, 9]

  • More than half of patients with pneumonia develop para-pneumonic effusions. If the fluid becomes infected an empyema results
  • Primary empyemas can also develop in patients without evidence of underlying pneumonia
  • Empyemas require drainage
  • The most commonly found bacteria in pleural infection are aerobic organisms (gram positive and gram negative)
  • Common gram positive bacteria include streptococcal and staphylococcal species
  • Common gram negatives include E. Coli, Pseudomonas spp, Haemophilus influenzae and Klebsiella spp
  • Staphylococcus aureus is a common pathogen in patients following surgery, trauma or chest drain insertion
  • The most common associated underlying disease processes present in patients with empyemas are:
    1. Diabetes mellitus (commonest)
    2. Malignancy
    3. COPD
    4. CNS disease
  • Approximately one-third of patients presenting with empyema have no underlying health problems.

 

Clinical Assessment

History

Symptoms due to effusion: Dyspnoea, chest pain that may be pleuritic, cough, shoulder pain, lethargy

Symptoms depending on the underlying cause: Weight loss, haemoptysis, fever, night sweats, swollen legs/abdomen

The following points should be specifically covered when taking a history from a patient with a pleural effusion:

  • History of heart, liver or renal disease
  • History of malignancy (however remote)
  • History of chest disease, especially recent pneumonia
  • History of pancreatic disease
  • History of connective disease such as rheumatoid arthritis
  • Previous cardiac surgery
  • Smoking history
  • Occupational history, especially any previous asbestos exposure
  • Previous tuberberculosis exposure and HIV status
  • Risk factors for venous thrombo-embolism
  • Recent trauma, especially if anticoagulated (suggesting haemothorax)
  • Accurate drug history

An accurate drug history is important, as certain drugs are known to sometimes cause pleural effusions. Some of the more common include:

  • Phenytoin
  • Methotrexate
  • Amiodarone
  • Nitrofurantoin
  • Beta-blockers

Further information may be found here.

Equally, a recent reduction in diuretics may precipitate fluid accumulation that leads to an effusion.

Examination

Signs due to pleural effusion: Respiratory distress, dyspnoea, hypoxia, asymmetrical lung expansion, reduced breath sounds, reduced tactile vocal fremitus, stony dull to percussion, tracheal deviation

Signs due to underlying cause: Clubbing, cachexia, lymphadenopathy, peripheral oedema, raised JVP, ascites, peripheral stigmata of cardiac/renal/liver disease, previous operative scars or radiotherapy marks, signs of DVT, nicotine staining, signs of connective tissue disease

Investigations

Investigations in patients presenting with pleural effusion will largely be guided by features elucidated from the patients history. Investigations are aimed at determining the size, nature (transudate or exudate) and underlying cause of the condition. Many of these investigations can be initiated in the ED:

Imaging

Chest X-ray

The most common first line imaging is a chest radiograph. Blunting of the costo-phrenic angle is visible after 250-500ml of fluid accumulation. If other imaging modalities are not available and there is doubt over the diagnosis, a lateral decubitus radiograph may help in demonstrating a shifting fluid level.

Learning bite: A pleural effusion should have a meniscus. If it is completely flat this may suggest a concurrent pneumothorax.

Ultrasound

Point of care ultrasound is being increasingly used in Emergency Departments to help guide diagnosis and treatment. It can provide a rapid diagnosis at the bedside and is particularly helpful in those patients who are acutely unwell. It is also recommended for use in all therapeutic aspirations and chest drain insertions [10]. It requires a suitably trained and competent user to be safe and effective.

CT Scan

CT can aid with the identification and quantification of effusions. It can also help with identifying a causative underlying pathology e.g. malignant tumour, pulmonary embolism, aortic dissection. It may also be used by interventional radiologists for difficult drainage procedures and planning biopsy procedures.

Bloods

  • Arterial Blood Gas (may be required if there are concerns about oxygenation/ventilation)
  • Full Blood Count and CRP (to assess inflammatory response suggesting infection)
  • U&Es, LFTs (identifying renal/liver disease)
  • Serum Protein, LDH and Glucose (for Lights criteria)
  • Serum Amylase (if pancreatitis or ruptured oesophagus are suspected)
  • D-Dimer (if PE suspected with a low risk Wells score)

Pleural Fluid

Appearance

The gross appearance of pleural fluid should be noted as this may suggest a specific diagnosis (see Table 1).

Table 1: Pleural fluid analysis
Appearance of Aspirate Suspected Disease
Putrid odour Anaerobic empyema
Food particles Ruptured oesophagus
Bile Stained Biliary Fistula (cholothorax)
Milky Chylothorax
‘Anchovy sauce’ Ruptured amoebic abscess

 

Analysis

When pleural fluid is aspirated it should be sent for the following:

  • Protein
  • LDH
  • Cytology, cell count and differential
  • Fluid pH
  • Fluid glucose
  • Gram staining and culture +/- Acid fast bacilli
  • Haematocrit (if there is uncertainty about the presence of a haemothorax)

Learning bite: A transudate contains less than 25 g/l of protein. An exudate contains more than 35 g/l of protein.

Lights Criteria

If the pleural fluid contains protein at levels between 25 g/l and 35 g/l then Lights Criteria should be used to decide whether the effusion is a transudate or an exudate.

Lights criteria state that the fluid is an exudate if one or more of the following criteria are met:

  • Pleural fluid : Serum protein ratio is greater than 0.5
  • Pleural fluid LDH : Serum LDH is greater than 0.6
  • Pleural fluid LDH is greater than two thirds the upper limit of normal serum LDH

Cytology

Malignant effusions can be diagnosed by pleural fluid cytology in about 60% of cases.

Cell count/differential

Pleural fluid cell count and differential may give important clues as to the underlying diagnosis [10] (Table 2).

Table 2: Fluid cell differentials
Fluid cell differential Common causes
High red cell count (>100,000 mm3) Malignancy
Pulmonary Infarction
Trauma
Neutrophilia Acute inflammatory effusion
Para-pneumonic
Lymphocytosis (>85% lymphocytes) Malignancy (e.g. lymphoma)
Tuberculosis
Rheumatoid
Sarcoid
Eosinophilia (>10% eosinophils) Malignancy
Some infections e.g. fungal, TB
Drug induced (e.g. sulfasalazine)
Churg-Strauss
Post CABG surgery

Pleural fluid pH

Pleural fluid pH should be measured on all non-purulent effusions:

  • It can be performed using a heparinised sample of fluid in a standard blood gas analyser
  • Low pH will be found in effusions caused by infection, malignancy, oesophageal rupture and rheumatoid disease.
  • A fluid pH of <7.2 in the setting of infection indicates that tube drainage is required and differentiates between simple and complex para-pneumonic effusion [8,10]

Learning bite: Frank pus should not be put in a blood gas analyser since it is an indication for chest drainage regardless of fluid pH and it may also damage the machine.

Pleural fluid glucose

Low pleural fluid glucose is found in the same conditions which give a low pH. The lowest levels of fluid glucose are found in rheumatoid arthritis and empyema.

Amylase

This is useful in suspected oesophageal rupture or pancreatitis where levels will be higher than normal serum amylase.

Triglyceride and cholesterol levels

These may be helpful when a chylothorax is suspected.

Management

Decision making in ED

Pleural effusions in the ED may vary from being an incidental finding in an otherwise asymptomatic patient, to being the cause of life-threatening cardiovascular compromise. There are comprehensive national guidelines from the British Thoracic Society outlining investigation and management strategies of pleural diseases, including effusions. However, there is no national consensus on which patients should undergo diagnostic aspiration, therapeutic aspiration or drainage in the ED. It is important to take into account local guidelines and the condition of the patient when deciding to intervene in ED or refer onto the appropriate specialty service.

The BTS guidelines state that aspiration should not be performed for bilateral effusions in a clinical setting strongly suggestive of a transudate unless there are atypical features or they fail to respond to therapy. If a transudate effusion if suspected, the focus should be on identifying and treating the underlying diagnosis [10].

The most common indication for drainage in ED is large effusion causing significant hypoxia or distress, particularly those associated with mediastinal shift.

If a patient requires aspiration or drainage [10]:

  • Unless the patient has significant cardiovascular or respiratory compromise, the procedure should not be performed overnight
  • Procedures should be carried out with full aseptic technique
  • Non-urgent interventions should be avoided in anticoagulated patients until the INR is <1.5 (note newer anticoagulants may still be effective despite a normal INR)
  • A recent chest radiograph should be reviewed prior to insertion
  • Bedside ultrasound should be used to increase likelihood of success and reduce risk of complications
  • A suitably trained practitioner should perform or directly supervise the procedure
  • Unless in an emergency, consent should be gained before any procedure. If a drain is being inserted, this should be in writing
  • There must be suitable and clearly organised follow up for investigations requested in the ED

Aspiration and Drainage

Anatomy

Figure 3. The “Triangle of Safety”

The preferred site for aspiration or drain insertion is usually within the triangle of safety (see Figure 2). It is bordered:

  • Anteriorly by the lateral edge of pectoralis major
  • Laterally by the lateral edge of latissimus dorsi
  • Inferiorly by the line of the fifth intercostal space
  • Superiorly by the base of the axilla

Sometimes a posterior lying effusion will be best approached with imaging guidance from the back with the patient sitting forward.

Diagnostic aspiration

A 21 G (green) needle attached to a 50ml syringe should be directed along the top of a rib to avoid damaging the neurovascular bundle. Medial sites (less than 5cm from the thoracic spine) should be avoided as the intercostal artery is in the middle of the intercostal space in this region. Local anaesthetic is not required if landmarks can be easily felt.

A chest x-ray after a simple pleural aspiration is not required unless air is withdrawn, the procedure is difficult, multiple attempts are required or the patient becomes symptomatic

Therapeutic aspiration

1% lignocaine is infiltrated to the skin and particularly the pleura (fluid aspiration confirms the depth of the chest wall). A cannula should be attached to three way tap and tubing/syringe. It is recommended to use a cannula of 20G or smaller where feasible as there is weak evidence that a large bore needle is more likely to cause a pneumothorax. However, in some patients with thick chest walls a larger needle may be required.

The procedure should be stopped when no more fluid or air can be aspirated, the patient develops symptoms of cough or chest discomfort or 1.5litres has been withdrawn. After the cannula is removed a simple dressing should be applied.

When the cause is unclear and the effusion large, a post-procedure chest radiograph may be requested to view the underlying lung.

Chest drainage

  • Antibiotic prophylaxis is not recommended for non-trauma patients requiring a chest drain.
  • Local anaesthetic should be used and analgesia given
  • Procedural sedation should be considered
  • Needle aspiration (following local anaesthetic infiltration) should confirm the presence of fluid before proceeding to drain insertion
  • Drains should never be inserted using substantial force
  • Tract dilators should not be inserted more than 1cm deep to the skin
  • Small drains (8-14 Fr) should be inserted for free flowing effusions or infections
  • The drain should be secured using sutures and an omental tag of tape (see Figure 3)
  • The chest drain should be connected to an underwater drainage system and no more than 1.5 litres of fluid allowed to drain in the first hour after insertion
  • A repeat chest radiograph should be requested post procedure.
  • A chest drain may be withdrawn to correct a malposition, but should never be pushed further in due to the risk of infection.

Figure 4. Omental tag

Para-pneumonic effusions

Patients with simple para-pneumonic effusions usually respond to antibiotics alone and do not require drainage. An effusion is deemed to be complex, therefore requiring drainage, if on aspiration they have either;

  • Low fluid pH and glucose or
  • Elevated WCC +/- organisms

Para-pneumonic effusions that do not respond to drainage may require intra-pleural fibrinolytic drugs. If these fail, the patient should be referred for surgical intervention.

Malignant effusions

Patients that require drainage are usually treated with pleurodesis (e.g. with intrapleural tetracyclines, talc or bleomycin) to reduce the likelihood of recurrence. Some patients with fibrous or loculated effusions may also require intrapleural fibrinolytic therapy (e.g. with urokinase).

Other approaches to subsequent management include thoracoscopy, intermittent therapeutic drainage (usually those with short life expectancy), long term indwelling pleural catheter and pleuro-peritoneal shunting.

References

  1. Boka K. Pleural Effusion. E-medicine. 2018. [Accessed May 2019].
  2. Sahn SA. The value of pleural fluid analysis. Am J Med Sci. 2008;335(1):7-15
  3. Rahman NM. et al. Local anaesthetic thoracoscopy: British Thoracic Society pleural disease guideline 2010
  4. Light RW. Parapneumonic Effusions and Empyema. Proc Am Thorac Soc 2006;3:75-80
  5. Robert ME, Neville E, Berrisford RG et al. BTS Guidelines for the Management of Malignant Pleural Effusions. Thorax 2010;65:ii32-ii40
  6. Noppen M. Normal volume and cellular contents of pleural fluid. Curr. Opin. Pulm. Med. 2001;7(4):180-2
  7. Miserocchi G. Physiology and Pathophysiology of Pleural Fluid Turnover. Eur Respir J.1997;10:219-25
  8. Davies HE, Davies CWH, Davies RJO et al. Management of pleural Infection in adults: British Thoracic Society guidelines 2010. Thorax 2010;65:ii45-ii53
  9. Chen KY, Hsueh PR, Liaw YS et al. A 10-Year Experience with Bacteriology of Acute Thoracic Empyema: Emphasis on Klebsiella pneumoniae in Patients with Diabetes Mellitus. Chest 2000;117:1685-1689
  10. Hooper C, Lee GYC, Maskell N. Investigation of a Unilateral Pleural Effusion in Adults: British Thoracic Society guidelines 2010. Thorax 20010;65:ii4-ii17
  11. Havelock T, Teoh R, Laws D et al. Pleural Procedures and Thoracic Ultrasound. British Thoracic Society pleural disease guidelines 2010. Thorax 2010;65:i61-i76
  12. BTS Pleural Disease Guideline 2010, British Thoracic Society, 2010

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4 Comments

  1. josephs5943 says:

    Thank you, excellent revision guide.

  2. Kalakoti says:

    Thanks for this good review.

  3. perrinth says:

    Good overview

  4. Jarno Holopainen says:

    Good revision guide

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