D e c i s i o n Ma k i n g a n d A l g o r i t h m

f o r th e M a n a g e m e n t o f P l e u r a l
E ff u s i o n s
Tam Quinn, MBBS, BMedSci, PGDipSurgAnata,b,
Naveed Alam, MD, FRCSC, FRACSc, Ali Aminazad, MD, FRACPd,
M. Blair Marshall, MDe,
Cliff K.C. Choong, MBBS, FRCS, FRACSf,g,*

KEYWORDS
 Pleural effusion  Management  Causes  Algorithm

KEY POINTS
 Multiple causes for pleural effusion ranging from cardiovascular disease to infection to neoplasm.
 History and examination can elicit cause. Radiological investigations are a useful adjunct to
diagnosis.
 Management varies depending on diagnosis, from treatment of underlying cause to symptomatic
treatment.

INTRODUCTION Part I: Pathogenesis and Causes of Pleural

Effusions
The pleural space, between the visceral and pari-
etal pleura, usually contains between 10 to 25 mL Pathogenesis
of fluid.1 This fluid is a filtrate created in the pleural The pathogenesis of pleural effusions can largely
capillaries and lymphatics and is largely reab- be classified as excess pleural fluid formation or
sorbed via the lymphatics of the parietal pleura.2 decreased fluid reabsorption. In greater detail,
In disease states, more than 3 L of fluid can accu- the mechanisms of the development of pleural
mulate within the pleural cavity. Pleural diseases effusions can be caused by the following2,4:
are common, and more than 3000 per 1 million
 Increased pulmonary capillary pressure (eg,
population develop a pleural effusion each year.
heart failure)
Considering that there are 60 different causes of
 Increased pulmonary capillary permeability
pleural effusions, establishing the diagnosis and
(eg, pneumonia)
subsequent management can be challenging.3
 Decreased intrapleural pressure (eg,
Left ventricular failure is the most common
atelectasis)
cause,1,2 and other causes are categorized and
 Decreased plasma oncotic pressure (eg,
listed later.
hypoalbuminemia)

a
Royal Australasian College of Surgeons (RACS), College of Surgeons’ Gardens, 250-290 Spring Street, East
Melbourne, VIC 3002, Australia; b Department of Cardiothoracic Surgery, Monash Medical Centre, 246 Clayton
Road, Clayton 3002, VIC, Australia; c Department of Thoracic Surgery, St Vincent’s Hospital, 55 Victoria Parade,
thoracic.theclinics.com

Suite 1, 5th Floor, Melbourne, Fitzroy 3065, VIC, Australia; d Eastern Health, Box Hill Hospital, Monash Univer-
sity, 51 Nelson Road, Box Hill 3128, Melbourne, VIC, Australia; e Department of Thoracic Surgery, Georgetown
University Hospital, 4PHC, 3800 Reservoir Road NW, Washington, DC 20007, USA; f Department of Surgery
(MMC), The Knox Hospital, Monash University, 262 Mountain Highway, Wantirna 3152, Melbourne, VIC,
Australia; g The Valley Hospital, Melbourne, VIC, Australia
* Corresponding author.
E-mail address: [email protected]

Thorac Surg Clin 23 (2013) 11–16

http://dx.doi.org/10.1016/j.thorsurg.2012.10.009
1547-4127/13/$ – see front matter Ó 2013 Published by Elsevier Inc.
12 Quinn et al

 Increased pleural permeability (eg, infection)  Medications

 Obstruction of pleural lymphatic drainage  Amiodarone (antiarrhythmic agent)
(eg, malignancy)  Bromocriptine (dopamine agonist)
 Fluid from other cavities or sites (eg, perito-  Dantrolene (muscle relaxant)
neal, retroperitoneal, or subarachnoid fluid)  Metronidazole (antibiotic)
 Rupture of thoracic vessels (eg, hemoth-  Nitrofurantoin (antibiotic)
orax, chylothorax)  Procarbazine (chemotherapeutic agent)
 Postoperative
Causes  Postcardiac surgery
Transudate (ultrafiltrates of plasma)  Lung transplantation (and also in rejec-
 Cardiovascular diseases tion states)
 Congestive cardiac failure  Abdominal surgery (including liver
 Pulmonary embolism (pulmonary embo- transplantation)
lism can also cause an exudative pleural  Other
effusion)  Hemothorax
 Infradiaphragmatic  Chylothorax
 Cirrhosis (caused by direct movement of  Benign asbestos-related effusion
peritoneal fluid through the diaphragm)  Trapped lung
 Peritoneal dialysis  Esophageal rupture
 Other  Yellow nail syndrome (lower limb lymphe-
 Nephrotic syndrome dema, nail discoloration, bronchiectasis,
 Hypoalbuminemia from other sources sinusitis, and pleural effusion)5
(eg, malnutrition, chronic hepatitis)  Amyloidosis

Exudate (caused by increased capillary permeability, Part II: Approach to Patients with Pleural
usually containing protein and cellular debris) Effusion
 Infection (most common cause of exudative
pleural effusions) History and examination
 Bacterial (pneumonia or systemic The history should be targeted to find the cause of
infection) the pleural effusion. Common causes, such as
 Tuberculosis cardiac disease, risk factors for malignancy, and
 Fungal exposure to infection, should be elicited. Other
 Viral (respiratory, hepatic, cardiac) questions, such as the duration of symptoms,
 Parasitic whether or not the effusion is recurrent, and the
 Neoplastic effect of symptoms on patients, will suggest a diag-
 Primary lung cancer nosis and the appropriate course of management.
 Metastatic disease to pleura (most com- Clinical examination should similarly be per-
monly in lung and breast carcinomas) formed with causes of effusions in mind. The exam-
 Mesothelioma ination of patients will establish whether the effusion
 Infradiaphragmatic is unilateral or bilateral, further aiding diagnosis.
 Pancreatitis Investigations
 Peritonitis
Blood tests
 Bile duct obstruction
 Full blood count including white cell differ-
 Inflammatory bowel disease
entiation (can suggest infection or hemato-
 Intra-abdominal abscess
logical malignancy)
 Endoscopic esophageal variceal
 Biochemistry (eg, renal impairment)
sclerotherapy
 Liver function tests (for hepatic causes of
 Meigs syndrome (ascites and pleural
effusion)
effusion associated with pelvic tumors)
 Albumin
 Immune conditions
 Lipase
 Rheumatoid arthritis
 Lactate dehydrogenase (LDH)
 Systemic lupus erythematosus
 Blood cultures and serology
 Sjögren syndrome
 Investigations for autoimmune conditions
 Wegner granulomatosis
 Ankylosing spondylitis Radiological tests
 Churg-Strauss syndrome  Chest radiographs: Effusions of greater than
 Sarcoidosis 75 mL are visible on chest radiographs.
 Algorithm for the Management of Pleural Effusions 13

Effusions can be free flowing or loculated. effusions. If the pH is less than 7.2
Lateral decubitus views can confirm the in patients with parapneumonic effusion,
appearance of smaller effusions. A chest it indicates complicated parapneumonic
radiograph can also show lesions or abnor- effusion and necessitates fluid drainage by
malities in the lung parenchyma. Chest radio- intercostal catheter insertion or surgery.
graphs have limitations for diagnosis of  Cholesterol: In exudates, cholesterol is
pleural effusion. Xirouchaki and colleagues6 more than 1.16.
reported sensitivity and specificity of 65%  White blood cell and red blood cell count: can
and 81%, respectively, in critically ill patients indicate the presence of infection or blood,
when they compared chest X-ray with particulary if not visible macroscopically.
bedside ultrasound.6  Cultures: micro-organisms in the pleural
 Ultrasound: Chest ultrasonography is fluid can be cultured in the case of infection.
useful in locating small effusions, identifying  Cytology: The sensitivity for malignancy
areas of loculation, and guiding thoraco- varies between 40% and 87%.8
centesis and pleural biopsies.2 Bedside  Acid-fast bacilli (AFB): Consider tubercu-
ultrasound is becoming a routine part of losis polymerase chain reaction if there is
pleural effusion management because of lymphocytic pleural effusion.
its accuracy and convenience.
Fiberoptic bronchoscopy Bronchoscopy can be
 Computed tomography (CT): Chest CT
scans can further identify the causes of the useful if an endobronchial malignancy is sus-
pleural effusion, such as pulmonary, bron- pected4 (particularly if patients have symptoms,
chial, or pleural malignancy. It can also char- such as hemoptysis and stridor2) because biop-
acterize the effusion in terms of its size, sies can be taken at the time of the procedure.
location, and presence of loculations. Pleural biopsy Needle biopsy of the pleural is
 Positron emission tomography (PET): PET sometimes undertaken and can be performed
scans are useful in the investigation of under local anesthesia. At least 4 biopsy speci-
malignant pleural effusions.2 mens should be taken from the one site.2,8 A
Thoracocentesis The pleural fluid should always be diagnosis of tuberculosis (sensitivity >85%), malig-
sampled unless the underlying cause of the effu- nancy (sensitivity of 45%–60%), and amyloidosis
sion is known (eg, heart failure). The morbidity can be established.2 Contraindications include
associated with thoracocentesis is low if per- patients with low platelet counts (<50 000 m/L),
formed by an experienced operator.2 If there is skin infections at the site of incision, small effusions
any concern about damaging intradiaphragmatic or (caused by the risk of injury to infradiaphragmatic
adjacent structures, such as an enlarged heart, the viscera), and severe respiratory disease (because
procedure should be done under ultrasound guid- of the risk of pneumothorax). Complications in-
ance. Coagulation therapy should be considered clude bleeding, including hemothorax, pneumo-
in patients with platelets less than 50 000/mL or pro- thorax, superficial and pleural infection, and injury
longed clotting time. The most common complica- to the liver or spleen.
tions are vagal reactions and pneumothoraces.2 Thoracoscopy Thoracoscopy is typically per-
The macroscopic appearance of the fluid should formed under general anesthesia but can be
be analyzed: straw colored (normal, transudate), done using a local anesthetic and sedation. It
milky white (chylothorax), turbid (empyema), allows for direct visualization of the visceral
bloodstained (trauma, malignant, parapneu- and parietal pleural, and biopsy of the pleura can
monic), food particles (esophageal rupture),7 and be simultaneously performed. Pleurodesis can
bile in bilothorax. Smell can also be suggestive: also be performed for the management of pleural
putrid in infections caused by anaerobic bacteria effusions.
and ammoniac in urinothorax.4
Thoracotomy Thoracotomy should only be per-
Laboratory testing of pleural fluid formed if other diagnostic methods have failed.2
 Protein: In exudates, the ratio of pleural pro- Thoracotomy is discussed further in the manage-
tein to serum protein is greater than 0.5.1 ment of pleural effusions.
 LDH: In exudates, the ratio of pleural LDH to
serum LDH is greater than 0.6.1
Management
 pH: The pH is usually 7.45 to 7.55 for transu-
dates and 7.30 to 7.45 for exudates.2 Pleural An algorithm is provided in Fig. 1. In 15% of cases,
fluid pH is the most important laboratory test the cause of the effusion cannot be found despite
in the management of parapneumonic repeated cytology and pleural biopsy.8 In these
14 Quinn et al

Fig. 1. Algorithm for the diagnosis and management of pleural effusions. Abbreviations: PE, pulmonary embo-
lism; Prot, Protein; VATS, video-assisted thoracic surgery.

cases, treatable causes, such as pulmonary em- Benign pleural effusion

bolism, fungal infection, and tuberculosis, should Management will depend on the cause of the
be considered. With continued observation, pleu- effusion. Symptomatic relief and diagnosis can
ral malignancy will prove to be the cause in many be achieved with drainage. In severely loculated
previously undiagnosed effusions.8 effusions or empyema whereby drainage by
 Algorithm for the Management of Pleural Effusions 15

thoracocentesis is not possible, either thoraco- study found smaller catheters cause less patient
scopy or thoracotomy maybe required. Thora- discomfort and provide equal efficacy.15
cotomy should be performed if there are dense In order for pleurodesis to be effective, there
adhesions and/or a trapped lung seen on thoraco- needs to be apposition of the visceral and parietal
scopy and whereby it is deemed unsafe by the pleura. Incomplete lung expansion can be caused
surgeon to proceed without an open procedure. by a trapped lung, pleural loculations, or a per-
sistent air leak and needs to be appropriately
Malignant pleural effusion managed.12 Suction drainage may be required to
Malignant cells in pleural fluid (seen on cytology) or promote pleural apposition. A lack of response
the parietal pleura (histopathology from biopsies) following pleurodesis is associated with incom-
indicate disseminated or advanced disease. Sur- plete lung expansion.16 Increased pleural fibrino-
vival following diagnosis depends on the type of lytic activity,17 extensive pleural disease,18 acidic
the underlying malignancy.9 Metastatic pleural pleural effusion,19 and the use of corticosteroids20
disease is most commonly secondary to lung at the time of the pleurodesis can also be associ-
cancer in men and breast cancer in women.9 ated with failure of pleurodesis.
Most patients presenting with malignant effu- Pleurodesis can be done either by introducing
sions are symptomatic. Dyspnea and pleuritic a talc slurry through an intercostal catheter, or by
chest pain are the most common presenting using aerosolised talc during VATS. The introduc-
symptoms. Patients will often have other systemic tion of sclerosing agents can be painful and
symptoms, such as weight loss, anorexia, and discomfort can be reduced by administering local
malaise. Symptomatic patients should be dis- anesthetic via the drain before the pleurodesis12
cussed within a respiratory multidisciplinary team followed by parenteral narcotics. The authors
to determine the best management. If patients advise against the use of nonsteroidal antiinflam-
are asymptomatic with minimal pleural effusion matory drugs because of the prevention of an
and the tumor type is known, observation may inflammatory response, which is necessary for
be an appropriate course of action. successful pleurodesis.
Alternatively, pleurodesis can be performed with
Therapeutic thoracocentesis Malignant pleural
effusions can be symptomatically managed with aerosolized talc, which can be used during thora-
thoracocentesis aspiration and drainage of the coscopy when patients are sedated or under
general anesthetic. The advantage of thoraco-
effusion. However, many of these effusions are
likely to recur within weeks of drainage; pleurodesis scopy is that loculations or adhesions can be
or indwelling pleural catheter insertion is generally visualized and divided, thus aiding in lung reexpan-
recommended if life expectancy exceeds this time- sion. Also, aerosolized talc can be distributed as it
frame.10 Thoracocentesis may be appropriate in is sprayed throughout the pleural cavity under
vision. Pleurodesis during thoracoscopy has a
patients who are too frail for pleurodesis. Indwelling
success rate of 77% to 100%,12 with talc being
pleural catheter is indicated in patients who are not
suitable candidates for video-assisted thoraco- the preferred agent for this purpose. Thoracoscopy
scopic surgery procedures or have been diag- is a safe procedure, with a perioperative mortality
nosed with a trapped lung whereby decortication of less than 0.5% in several studies.12 Another
substantial advantage with this approach is the
is considered unsuitable.11 The amount of fluid
drained should be guided by the patient’s symp- decreased risk of pulmonary edema caused by re-
toms, and if cough or chest discomfort develops, expansion being performed with positive pressure
aspiration should be ceased.12 The rate of drainage under general anesthesia rather than negative
pressure if patients are being drained while awake.
of large effusions should be controlled to reduce
the risk of reexpansion pulmonary edema.13
Long-term indwelling pleural catheters As briefly
Pleurodesis Other than patients who are too frail, mentioned earlier, insertion of a long-term catheter
have a trapped lung, or have a very short life can be useful in controlling recurrent pleural
expectancy, pleurodesis is preferable to recurrent effusions in patients for whom thoracoscopy or
thoracocentesis. A sclerosing agent, such as pleurodesis is not an appropriate option (eg, frail
sterile talc, tetracycline, bleomycin, or doxycy- patients or patients with a trapped lung). The
cline, can be used.12 A diffuse inflammatory reac- presence of a foreign body within the pleural
tion and fibrin deposition within the pleural space cavity can stimulate an inflammatory reaction
are elicited. In some studies, smaller catheters and, thus, encourage spontaneous pleurodesis
(10F–14F) have been found to be as effective as in some patients.21 In some patients, drains can
conventional large-bore catheters (24F–32F) in be removed after a relatively short period.12
the drainage of effusion and pleurodesis.14 One Patients with indwelling pleural catheters were
16 Quinn et al

found to have a shorter length of stay than those 8. Maskell NA, Butland RJ, A on behalf of the
who underwent pleurodesis11,21; therefore, it may British Thoracic Society Pleural Disease Group.
be appropriate for patients for whom hospitaliza- BTS guidelines for the investigation of a unilateral
tion should be minimized (eg, those with shorter pleural effusion in adults. Thorax 2003;58(Suppl ii):
life expectancies). Indwelling catheters should ii8–17.
only be used where appropriate expertise and 9. Roberts ME, Neville E, Berrisford RG, et al, on behalf
facilities are available. of the BTS Pleural Disease Guideline Group.
Management of a malignant pleural effusion: British
Parapneumonic effusions and empyema It is cru- Thoracic Society pleural disease guideline 2010.
cial to differentiate between simple parapneu- Thorax 2010;65(Suppl 2):ii32–40.
monic effusions and complex parapneumonic 10. Light R. Should thoracoscopic talc pleurodesis be
effusions or empyema because the latter needs the first choice management for malignant effusion?
drainage with thoracentesis or thoracic surgery. No. Chest 2012;142(1):17–9.
Empyema is defined by frankly purulent fluid or 11. Edward TH, Fysh E. Indwelling pleural catheters
positive gram stain or culture. Complicated para- reduce inpatient days over pleurodesis for malig-
pneumonic effusion is defined by the presence of nant pleural effusion. Chest 2012;142(2):394–400.
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or pH less than 7.2. These effusions typically occur relationship of pleural pressure to symptom devel-
in patients who have continued fever and sepsis opment during therapeutic thoracocentesis. Chest
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to thoracentesis alone. Intrapleural enzyme treat- sion pulmonary edema. J Thorac Imaging 1996;11:
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