Author: Jason B Lee / Editor: Jason B Lee / Codes: CAP6, HAP6 / Published: 01/06/2011 / Review Date: 01/06/2014
The annual incidence of pleural effusion in the developed world has been estimated at 320 per 100,000 population per year1. In the USA approximately 1.5 million people are diagnosed with a pleural effusion2 each year. Hospital Episode Statistics in England record around 21,000 hospital consultations annually for patients with pleural effusion, two-thirds of which require acute hospital admission3.
Pleural effusion is rarely the primary presenting complaint in patients attending Emergency Departments and it is perhaps no surprise that little data relating specifically to the frequency of pleural effusion as a problem within the ED exists. More commonly, 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 a pleural effusion related to pneumonia have a worse outcome than those with pneumonia alone4 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 months5.
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 the underlying cause of the effusion influences the content of the fluid (e.g. transudate in heart failure; exudate in pneumonia or malignancy).
Basic science and patho-physiology
A pleural effusion is an abnormal collection of fluid within the pleural space.
Pleural effusions are classified as either transudates or exudates and there are multiple underlying causes of each (see tables 1&2)
Congestive cardiac failure is the commonest cause of pleural effusion6
Normal anatomy and pleural fluid physiology
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 lung7. 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 pleura8. 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 turnover9.
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)
Transudates are associated with increased systemic or pulmonary capillary hydrostatic pressure (e.g. congestive cardiac failure) or decreased colloid osmotic pressure (e.g. hypoalbuminaemia, cirrhosis). These factors often co-exist.
In conditions resulting in the formation of transudates, the pleural membranes are intact and the permeability of pleural capillaries to proteins is normal. Neither is involved in the pathogenesis of fluid formation.
In the formation of transudates, the pleural membranes are intact and the permeability of pleural capillaries to proteins is normal
The formation of exudates is associated with altered permeability of pleural membranes, increased capillary wall permeability to proteins or vascular disruption. It can also be associated with reduced or obstructed lymphatic drainage from the pleural space.
Disease of the pleural membranes is involved in the formation of exudates and increased capillary permeability to protein results in elevated protein content of the fluid.
Disease of the pleural membranes is involved in the formation of exudates. Increased capillary permeability results in elevated protein content of the fluid
Pleural Infection pathophysiology4,10,11
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 no evidence of underlying pneumonia. 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.
Although anaerobic organisms can be found in pleural infection in up to 75% of cases this is mostly as part of a mixed culture (with aerobes). In only around 14% of empyemas are anaerobes solely implicated as the cause.
There are three main stages in the development of pleural infection4,10.
Stage 1 Simple para-pneumonic stage
- Increased capillary permeability
- Inflammation caused by cytokine release
- Fluid enters the pleural space as it is initially free flowing
- The fluid is clear, contains no organisms, and has a low white cell count, low LDH level, a normal pH and normal glucose levels.
Patients with such effusions can normally be treated with antibiotics alone.
Stage 2 Complex para-pneumonic stage
- Increasing fluid accumulation
- Bacteria are present within the fluid and there is increasing neutrophil activity and bacterial death
- The coagulation cascade is activated
- Decreased fibrinolysis leads to fibrin formation and loculation of the fluid
- The fluid becomes turbid
- Increased cell activity and bacterial death leads to increased lactate production, a fall in the fluid pH, a rise in fluid LDH levels and a fall in fluid glucose levels.
Stage 3 Empyema stage
- Accumulation of fibrin within the pleural space impairs lung function.
- The pleural space may be kept open and vulnerable to further infection.
- Fluid within the space is frank pus.
The most common associated underlying disease processes present in patients with empyemas in order of decreasing prevalence11 are:
- Diabetes mellitus (commonest)
- CNS disease
Alcohol dependent patients may also be at risk of empyema but only represent a small proportion of patients11. Approximately a third of patients presenting with empyema have no underlying health problems.
Pathophysiology of malignant pleural effusion7
- The tumours most commonly associated with pleural effusion are lung, breast, lymphoma and 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.
- Obstruction of lymph channels by tumour cells or involvement of the mediastinal lymph nodes results in pleural effusion.
- Effusions associated with malignancy are therefore exudates.
There are a number of signs which may be present in patients with pleural effusions.
Classical symptoms and signs
Dyspnoea, stony dullness to chest percussion, reduced breath sounds, reduced tactile fremitus, asymmetric chest expansion12.
Chest pain, upper abdominal pain, shoulder tip pain, peripheral oedema, haemoptysis, evidence of malignancy.
Patients with chest pain and pleural effusion are more likely to have an exudative aetiology such as pleural infection, pulmonary infarction (PE) or malignancy13
The following points should be specifically covered when taking a history from a patient with a pleural effusion:
- History of heart disease, especially congestive heart failure
- History of liver disease
- History of renal disease
- History of malignancy (however remote)
- History of chest disease, especially pneumonia
- History of pancreatitis
- Accurate drug history
- Risks for venous thrombo-embolism
- Drug History
An accurate drug history is important as certain drugs are known to be associated with pleural effusion occurrence. There are more than 100 cases in the medical literature implicating the following drugs:
Further information may be found on the Pneumotox website: http://www.pneumotox.com/
Emergency Department Patient Classification and Management
Patients presenting to the Emergency Department with pleural effusion may be physiologically stable or unstable and may have unilateral or bilateral effusions. They may be presenting for the first time or have previously documented and investigated pleural effusion. There are no Emergency Department studies which quantify the approximate distribution of these groups but most patients will be physiologically stable on arrival in the ED.
All patients with a new diagnosis of pleural effusion should undergo a thorough clinical assessment with investigations if necessary in order to determine the underlying cause and start appropriate treatment. Such clinical assessment and investigation should happen urgently. Depending on local policy, investigations may be started in the ED, as an inpatient or arranged via local out patient facilities.
Emergency Management of the Unstable Patient
Patients with pleural effusions do not classically present with sudden breathlessness or cardiac instability. Unless signs consistent with a massive pleural effusion are present then other co-existent pathologies should be considered. Pulmonary embolism or infarction cause dyspnoea out of all proportion to the size of any pleural effusion and Emergency physicians should have a high index of suspicion for this diagnosis in this setting14.
Massive Pleural Effusion with midline shift
Any evidence of physiological instability should prompt early involvement of a senior ED physician. Such patients may have midline tracheal shift secondary to a massive pleural effusion. As much as 3 litres of fluid can be contained within each side of the thorax. In this setting, the following treatment should be instituted:
- Sit the patient upright to improve their ventilation
- Administer high flow oxygen
- Support the circulation as indicated (e.g. intravenous crystalloid bolus)
- In patients with likely transudates or bilateral effusions treat the underlying cause aggressively (such patients rarely need therapeutic aspiration of the pleural fluid)14.
- In patients with unilateral massive pleural effusion +/- midline shift, urgent therapeutic drainage of the fluid is required.
- No more than 1.5 litres of fluid should be drained in the first hour as re-expansion pulmonary oedema (which as a significant mortality risk) can result when greater volumes are drained7,15.
- A small bore chest drain is usually all that is necessary. There is no evidence to suggest than larger bore chest drains are more effective in settings other than traumatic haemothorax7.
- Send fluid for laboratory analysis.
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.
- Chest radiograph (to identifying the size and location of the effusion and any underlying aetiology)
- Arterial Blood Gas (quantifying the extent of respiratory compromise)
- Urea & Electrolytes (identifying renal disease)
- Full Blood Count (evidence of elevated white cell count in infection)
- Serum Protein (evidence of hypoalbuminaemia; to compare with pleural fluid protein levels)
- Serum LDH (to compare with pleural fluid LDH levels)
- Serum Glucose (to compare with pleural fluid glucose levels)
- Serum Amylase (only of use if pancreatic disease is known or suspected)
Diagnostic pleural fluid aspiration is an important step in the investigation of many unilateral pleural effusions. However, it is invasive and is not routinely recommended for patients in whom the fluid is likely to be a transudate (e.g. congestive cardiac failure, hypoalbuminaemia). In these cases the underlying cause should be treated first as this will often resolve the effusion without the need for aspiration14
Routine pleural aspiration is not advocated for patients with unilateral pleural effusions that are likely to be transudates since they often resolve following successful treatment of the underlying condition
Pleural fluid analysis
When pleural fluid is aspirated it should be sent for the following analyses:
- Protein content
- LDH level
- Cytology, cell count and differential
- Fluid pH
- Fluid glucose
- Gram staining and culture
The gross appearance of the fluid should be noted as this may suggest a specific diagnosis (see table 3).
Pleural fluid laboratory analysis
- A transudate contains less than 25 g/l of protein
- An exudate contains more than 35 g/l of protein
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 exudate14,16.
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.
Pleural fluid cell count and differential may give important clues as to the underlying diagnosis14 (see table 4).
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 effusion10,14.
Frank pus should not be put in a blood gas analyser since it is an indication for chest drainage10 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.
This is useful in suspected oesophageal rupture or pancreatitis where levels will be higher than normal serum amylase.
Rheumatoid factor/ANA levels
These will be elevated to levels similar to those in the serum of patients with connective tissue disorders. They provide little additional information.
Triglyceride and cholesterol levels
These may be helpful when a chylothorax is suspected.
Advanced Imaging Studies
- The BTS strongly recommends the use of ultrasound to guide pleural aspiration wherever possible since it is associated with a lower failure and complication rate17,18 (dry taps, pneumothorax, organ puncture).
- If ultrasound is not employed and the aspiration fails, no subsequent attempts should be made until imaging has been performed.
- Ultrasound is far superior to clinical guided aspiration in the following settings:
- Small effusions
- Loculated effusions
- Unilateral white out on chest radiograph (with no mediastinal shift). One prospective study reported that 9 out of 50 patients with such radiographic appearances did not have a pleural effusion present on ultrasound.
- Although very large pleural effusions with a definite fluid level would seem simple enough to drain blindly ultrasound may identify adherent lung or raised hemi-diaphragm.
- In skilled hands ultrasound has a sensitivity approaching 100% for fluid volumes of 100 mls or more, but it may miss smaller effusions.
- Ultrasound can better visualise fibrous septa in malignant or para-pneumonic effusions than CT scanning.
- Contrast enhanced CT scanning is a useful in differentiating benign from malignant pleural effusion.
- Like ultrasound, CT can be used to delineate the size and position of small or loculated effusions, and aid difficult drainage procedures.
Pleural Fluid Aspiration
A recent chest radiograph should be reviewed and written consent obtained prior to a trained operator performing this procedure. The potential complications (dry tap, pneumothorax, visceral injury, haemothorax, infection) should be mentioned and listed on the consent form. An aseptic technique should be employed and ultrasound used to confirm the presence of fluid beneath the intended insertion point.
The preferred site for aspiration (see figure1) should either be within the triangle of safety bordered by:
- The anterior border of latissimus dorsi
- The lateral border of pectoralis major
- The superior border of the 6th rib
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. The BTS guidelines advocate the use of a green needle (21G) for a diagnostic aspiration of 50mls and do not consider local anaesthetic necessary where landmarks can be easily felt (thin patients).
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 (2010 BTS guidelines)
1% lignocaine is infiltrated to the skin and particularly the pleura (fluid aspiration confirms the depth of the chest wall). There is weak evidence that a large bore cannula is more likely to cause a pneumothorax than a small cannula and the BTS guidelines recommend using a cannula of 20G or smaller where feasible. However, in some patients with thick chest walls a larger cannula may be required. The cannula should be attached to a 3 way tap and up to 1.5 litres of fluid drained before it is removed and a simple dressing applied. When the cause is unclear and the effusion large, a post-procedure chest radiograph may be requested to view the underlying lung.
The procedure involved in pleural aspiration is described in more detail in the 2010 BTS pleural procedures guideline.18
Due to the increased incidence of complications overnight the BTS recommends that pleural procedures are deferred until the next morning unless the patient has significant cardiovascular or respiratory compromise
Chest Drain Insertion
The optimal approach to chest drain insertion is described in the BTS guidelines for insertion of a chest drain18, which include the following recommendations.
- Written consent should be obtained and tube malposition should be added to the complication list described for needle aspiration
- Aseptic technique with full gowning
- Ultrasound use to guide insertion
- Antibiotic prophylaxis is not recommended
- 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
- Tract dilators should not be inserted more than 1cm deep to the skin
- Small drains(8-14FG) should be inserted for free flowing effusions or infections
- The drain should be secured using sutures and an omental tag
- 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 or re-inserted due to the risk of infection
Emergency Department Management of the Stable Patient
The stable patient with a likely pleural transudate14
The underlying disease eg congestive cardiac failure, cirrhosis of the liver, hypoalbuminaemia and hypothyroidism should be treated aggressively.
Diagnostic aspiration of pleural fluid is not required in most cases. Therapeutic drainage of the fluid may be needed for patients that remain symptomatic despite treatment of the underlying cause.
The stable patient with pleural infection10
More than half the patients admitted to hospital with pneumonia will have associated pleural fluid. The nature of the pleural fluid associated with pneumonia is key to guiding subsequent treatment. In particular a low pH (<7.2) found in pleural fluid is an indication for chest drainage.
All patients with signs of pneumonia and a pleural effusion should have diagnostic aspiration of pleural fluid with fluid analysis as described above, unless their condition makes this an inappropriate intervention. This may be performed in the ED or arranged via in-patient specialties.
In patients with poor respiratory reserve or with small or loculated collections ultrasound guidance should be used.
Patients with simple para-pneumonic effusions (see below) rarely require therapeutic drainage.
- Normal fluid pH and glucose
- Low WCC and no organisms
- Can be treated with antibiotics alone
Patients with complex para-pneumonic effusions (see below) require therapeutic drainage.
- Low fluid pH and glucose
- Elevated WCC +/- organisms
Small bore chest drains are recommended in the first instance. If patient fails to respond intra-pleural fibrinolytic drugs (e.g. urokinase) may be required. Patients who do not respond to drainage and intra-pleural fibrinolytic drugs should be referred for surgical intervention.
The stable patient with malignant effusion7
Most patients will be symptomatic with a malignant effusion. However, 25% or so will have the effusion detected on a routine exam/investigation. Stable patients should be discussed with the medical team and may be discharged from the ED for urgent out-patient follow up.
Symptomatic patients will require therapeutic pleural drainage.
- No more than 1.5 litres should be drained at any one time as this may result in re-expansion pulmonary oedema or haemodynamic instability.
- Except for patients with very short life expectancy, pleural drainage should be combined with pleurodesis (e.g. with intrapleural tetracyclines, talc or bleomycin) as there is a high recurrence rate without this.
- Chest drains used to drain pleural fluid in the ED should therefore be left in place to allow pleurodesis later on. 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.
- Crawford Mechem C. Pleural Effusion. E-medicine 2009, available from http://emedicine.medscape.com/article/807375-overview
- Sahn SA. The value of pleural fluid analysis. Am J Med Sci. 2008;335(1):7-15.
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- Robert ME, Neville E, Berrisford RG et al. BTS Guidelines for the Management of Malignant Pleural Effusions. Thorax 2010;65:ii32-ii40.
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- 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.
- Wong CL, Holroyd-Leduc J, Straus SE. Does this patient have a Pleural Effusion? JAMA 2009;301(3):309-317.
- Froudarakis ME. Diagnostic Work-Up of Pleural Effusions. Respiration. 2008;75(1):4-13.
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- Tarver RD, Broderick LS, Conces DJ. Reexpansion Pulmonary Oedema. J Thorac Imag 1996;11:198-209.
- Light RW, MacGregor MI, Luchsinger PC et al. Pleural Effusions: The Diagnostic Separation of Transudates and Exudates. Arch Intern Med. 1972;77:507-513.
- Tayal VS, Nicks BA, Norton HJ. Emergency ultrasound evaluation of symptomatic nontraumatic pleural effusions. Am J Emerg Med. Nov 2006;24(7):782-6.
- 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