Editing Pleural effusions

An increased (clinically significant) volume of fluid in the pleural space

== '''Epidemiology''' ==

* Breakdown according to Shields:
** 40% CCF
** 20% parapneumonic effusion
** 10% malignancy
** 8% PE
** 5% viral disease
** 2.5% post-cardiac surgery
** 1% GIT pathology
** 0.1% TB
** 0.1% malignant pleural mesothelioma
** 0.1% asbestos-related benign pleural diseases

== '''Aetiology''' ==

* Pleural infection (parapneumonic effusion - about 40%) and CCF (about 25%) are the most common causes, followed by things like chronic liver disease, renal disease, asbestosis, RA, SLE pleuritis, pancreatitis, PE and cardiac surgery.
* '''Transudative'''
** Left heart failure (marked increase in permeability of '''visceral''' pleura, and interstitial lung oedema - not seen commonly in RHF)
** Cirrhosis/hepatic failure
** Nephrotic syndrome/renal failure
** Hypoalbuminaemia
** Fluid retention/overload
** Pulmonary embolism (usually occupies less than one third of hemithorax and can be bilateral in 46% of cases, with dyspnoea out of proportion)
** Lobar collapse/trapped lung (pleural dead space is filled by effusion fluid)
** Meigs syndrome
* '''Exudative'''
** Malignant
*** Primary lung
*** Metastatic
*** Lymphoma
*** Mesothelioma
** Infectious
*** Bacterial (parapneumonic)/empyema (see separate topic)
*** TB
*** Fungal
*** Viral
*** Parasitic
** Collagen vascular disease related
*** RA
*** Wegener granulomatosis
*** SLE
*** Churg-Strauss syndrome
** Others
*** Chylothorax
*** Uraemia
*** Sarcoidosis
*** After CABG
*** Radiation/trauma
*** Dressler syndrome
*** PE with infarction
*** Asbestosis related
* Benign effusions (sometimes also called hydrothorax)
** Systemic disease
*** Generally cause bilateral effusions
** Local disease
*** Inflammation leads to both increased fluid filtration and decreased lymphatic drainage
*** Often causes unilateral moderate to large effusions

=== '''Causes of transudative pleural effusions''' ===
{| class="wikitable"
|'''Causes of transudative effusions'''
|'''Comment'''
|-
|'''Processes that ''always'' cause a transudative effusion'''
|
|-
|Atelectasis
|Caused by increased intrapleural negative pressure
|-
|Cerebrospinal fluid leak into pleural space
|Thoracic spinal surgery or trauma and ventriculopleural shunts
|-
|Heart failure
|Acute diuresis can result in borderline exudative features
|-
|Hepatic hydrothorax
|Rare without clinical ascites
|-
|Hypoalbuminemia
|Edema liquid rarely isolated to pleural space
|-
|Iatrogenic
|Misplaced intravenous catheter into the pleural space; post Fontan procedure
|-
|Nephrotic syndrome
|Usually subpulmonic and bilateral
|-
|Peritoneal dialysis
|Acute massive effusion develops within 48 hours of initiating dialysis
|-
|Urinothorax
|Caused by ipsilateral obstructive uropathy or by iatrogenic or traumatic GU injury
|-
|'''Processes that ''may'' cause a transudative effusion, but ''usually'' cause an exudative effusion'''
|
|-
|Amyloidosis
|Often exudative due to disruption of pleural surfaces
|-
|Chylothorax
|Most are exudative effusions 
|-
|Constrictive pericarditis
|Bilateral effusions
|-
|Hypothyroid pleural effusion
|From hypothyroid heart disease or hypothyroidism per se
|-
|Malignancy
|Usually exudative, but 3 to 10 percent transudative possibly due to early lymphatic obstruction, obstructive atelectasis, or concomitant disease (eg, heart failure)
|-
|Pulmonary embolism
|Most are exudative effusions
|-
|Sarcoidosis
|Stage II and III disease
|-
|Superior vena caval obstruction
|May be due to acute systemic venous hypertension or acute blockage of thoracic lymph flow
|-
|Coronavirus disease 2019 (COVID-19)
|Limited data profile the nature of pleural fluid in COVID-19-related pleural effusions, although transudative effusions have been reported 
|-
|Nonexpandable lung*
|A result of remote or chronic inflammation
|}

=== '''Causes of exudative pleural effusions''' ===
{| class="wikitable"
|
{| class="wikitable"
|'''Infectious'''
|-
|Bacterial pneumonia
|-
|Tuberculous pleurisy
|-
|Parasites
|-
|Fungal disease
|-
|Viral pneumonias (eg, influenza, coronavirus disease 2019 [COVID-19])
|-
|Nocardia, Actinomyces
|-
|Subphrenic abscess
|-
|Hepatic abscess
|-
|Splenic abscess
|-
|Hepatitis
|-
|Spontaneous esophageal rupture
|-
|Cholecystitis
|-
|'''Iatrogenic or trauma'''
|-
|Central venous catheter misplacement/migration
|-
|Drug-induced (eg, nitrofurantoin, dantrolene, methysergide, dasatinib, amiodarone, interleukin-2, procarbazine, methotrexate, clozapine, phenytoin, beta blocker, ergot drugs)
|-
|Esophageal perforation
|-
|Esophageal sclerotherapy
|-
|Enteral feeding tube in pleural space
|-
|Radiofrequency ablation of pulmonary neoplasms
|-
|Hemothorax
|-
|Chylothorax
|-
|'''Malignancy-related'''
|-
|Carcinoma
|-
|Lymphoma
|-
|Mesothelioma
|-
|Leukemia
|-
|Chylothorax
|-
|Paraproteinemia (multiple myeloma, Waldenstrom's macroglobulinemia)
|-
|Paramalignant effusions
|-
|'''Other inflammatory disorders'''
|-
|Pancreatitis (acute, chronic)
|-
|Benign asbestos pleural effusion
|-
|Pulmonary embolism
|-
|Radiation therapy
|-
|Uremic pleurisy
|-
|Sarcoidosis
|-
|Postcardiac injury syndrome
|-
|Acute respiratory distress syndrome (ARDS)
|-
|Immunoglobulin G4-related disease (fibroinflammatory)
|}
|
{| class="wikitable"
|'''Increased negative intrapleural pressure with accompanying pleural malignancy or inflammation'''
|-
|Lung entrapment
|-
|Cholesterol effusion (eg, due to tuberculosis, rheumatoid arthritis)
|-
|'''Connective tissue disease'''
|-
|Lupus pleuritis
|-
|Rheumatoid pleurisy
|-
|Mixed connective tissue disease
|-
|Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)
|-
|Granulomatosis with polyangiitis (Wegener's)
|-
|Familial Mediterranean fever
|-
|'''Endocrine dysfunction'''
|-
|Hypothyroidism
|-
|Ovarian hyperstimulation syndrome
|-
|'''Lymphatic abnormalities'''
|-
|Malignancy
|-
|Chylothorax (eg, yellow nail syndrome, lymphangioleiomyomatosis, lymphangiectasia)
|-
|'''Movement of liquid from abdomen to pleural space'''
|-
|Pancreatitis
|-
|Pancreatic pseudocyst
|-
|Meigs' syndrome
|-
|Chylous ascites
|-
|Malignant ascites
|-
|Subphrenic abscess
|-
|Hepatic abscess (bacterial, amebic)
|-
|Splenic abscess, infarction
|-
|'''Miscellaneous'''
|-
|Endometriosis
|-
|Drowning
|-
|Electrical burns
|-
|Capillary leak syndromes
|-
|Extramedullary hematopoiesis
|}
|}


== '''Pathophysiology''' ==

* Disrupted balance between fluid production and absorption
** The amount of pleural fluid is controlled by a balance of oncotic and hydrostatic pressure within the pleural space and pleural capillaries
** Under normal circumstances, the net pressure moves fluid from the parietal pleura into the pleural space
** Pleural space normally contains 0.3mL/kg of fluid
** Normal turnover is about 0.15mL/kg/hour
** Most pleural fluid is reabsorbed through lymphatics of the parietal pleura - protein cannot re-enter the relatively impermeable visceral pleura
* Causative factors:
** Increased input:
*** Increased hydrostatic pressure
*** Increased negative intra-pleural pressure
*** Increased capillary permeability
*** Decreased plasma oncotic pressure
** Decreased output:
*** Strong reduction in lymphatic drainage
* A pleural effusion represents a new equilibrium point between pressures acting across compartments - hence a larger imbalance will lead to a larger effusion
* Characterise as transudate or exudate
** Transudates are protein-poor and result in change in fluid balance in the pleural space
** Exudates are protein-rich and may be related to disruption of pleural or lymphatic reabsorption
* Volume
** 300mL of fluid causes blunting of costophrenic angle on upright CXR
** 500mL of fluid can be detected clinically

== '''Symptoms:''' ==

* Dyspnoea (effusion causes compression and collapse of adjacent lung - most commonly lower lobe)
** Volume of effusion
** Degree of compression and collapse
** Underlying lung function
* Chest pain
* Cough
* Massive pleural effusion can cause tension effusion - mediastinal shift and tension physiology (requires 1-3L)

== '''Examination''' ==

* Asymmetrical decreased expansion
* Dullness to percussion
* Diminished or inaudible breath sounds
* Effusions <300mL will not show on physical exam

== '''Diagnosis''' ==

* Pleural fluid only 3-test combination (favoured by UTD)
** Any one of the following means exudate:
*** Pleural fluid protein >30g/L
*** Pleural fluid cholesterol >1.42mmol/L
*** Pleural fluid LDH >0.67 * serum LDH ULN ''(LDH ULN is typically ~280U/L)''
* Light's criteria
** Any one of the following means exudate:
*** Pleural fluid to serum protein ratio >0.5
*** Pleural fluid to serum LDH ratio > 0.6
*** Pleural fluid LDH > 0.67 * serum LDH ULN ''(LDH ULN is typically ~280U/L)''
** High sensitivity but only moderate specificity for exudates
** 25% of transudates are incorrectly classified as exudates, particularly those due to heart failure when diuretics are given, or where erythrocytes are present in pleural fluid, which release LDH
* Visual characteristics
** Serous
** Bloody
** Milky
** Turbid
** Frankly purulent
* Cytology (sensitivity and specificity 65-90%)
* Cell counts
* Gram stain and MCS
* TB testing
* Pleural and serum protein, glucose, LDH and pH

== Other investigations ==

* Exclude medical conditions
** BNP
** eGFR
** LFTs
** TTE
* CT chest

== Management: ==

* Treat the underlying disorder
* Drainage for symptomatic effusions
* Drainage for diagnostic purposes if complication is suspected

== Treatment ==

* Benign effusions
** Most benign pleural effusions are transudates, free-flowing, without loculation
** Treat underlying cause (CCF, ascites, malnutrition)
** Completely drain for diagnosis and treatment (14Fr or smaller if leaving a drain in)
** CXR to confirm complete drainage
** 'Trapped lung' may require decortication, especially if remaining symptomatic
** If no improvement in symptoms, look for alternative causes
** Recurrences
*** Consider repeat thoracentesis, tube thoracostomy or pleurodesis (mechanical vs chemical)
*** Don't need to continuously drain unless significant respiratory compromise is present
* Unilateral effusions
** Parapneumonic, empyema, inflamed parietal pleura, chylothorax, haemothorax, pleural infection
** Drain effusion and correct consequences
** Indications for VATS:
*** Recurrent effusion following earlier drainage
*** Trapped lung (lack of re-expansion following drainage)
*** Loculated or multiloculated effusions
*** Parietal pleural tissue biopsies are required for diagnosis
*** Very large unilateral effusion (consider VATS vs drainage - higher recurrence rate and malignancy rate)
** Role for VATS
*** Complete drainage of effusion
*** Parietal pleural biopsies
*** Re-expansion of lung and de-cortication if necessary
*** Pleurodesis
* Malignant pleural effusions
** An effusion with positive cytopathology
** Median survival 90 days (5 months in breast cancer, and longer in lymphoma)
** Not all effusions associated with malignancy are caused by direct or metastatic pleural involvement (consider bronchial or lymphatic obstruction, hypoproteinaemia, and accumulation from infra-diaphragmatic involvement)
** Consider pleurX catheter or pleurodesis
* Tension pleural effusion
** Drain immediately
* Drainage
** Need CT or USS prior to drainage, since CXR can get it wrong
** Typically needle thoracocentesis under USS-guidance, with a catheter sometimes being left in 
** Dogma states don't remove more than 1-1.5L in one sitting to prevent re-expansion pulmonary oedema, however the veracity of this is unknown. Larger volumes can be removed if the benefits of symptom improvement are thought to outweigh the risks.
** Those who respond well to drainage should also respond well for drainage of reaccumulations
** Drain on the larger side, or the right side if both are equal

'''Survival with malignant pleural effusions according to cancer type'''
{| class="wikitable"
|'''Cell type'''
|'''Median survival in days (95% CI)'''
|'''n'''
|-
|Mesothelioma
|339 (267 to 422)
|170
|-
|Hematological malignancy
|218 (160 to 484)
|35
|-
|Gynecological malignancy
|230 (97 to 279)
|59
|-
|Breast cancer
|192 (133 to 271)
|140
|-
|Renal cell carcinoma
|114 (33 to 334)
|22
|-
|Adenocarcinoma of unknown primary
|87 (13 to 286)
|11
|-
|Lung cancer
|74 (60 to 92)
|215
|-
|Other
|71 (46 to 102)
|33
|-
|Gastrointestinal cancer
|61 (44 to 73)
|61
|-
|Sarcoma
|44 (19 to 76)
|12
|-
|Melanoma
|43 (23 to 72)
|23
|-
|Urological cancer (bladder, prostate, testis, penile)
|33 (22 to 168)
|8
|-
|Overall
|136 (119 to 167)
|789
|}


'''LENT score'''
{| class="wikitable"
| 
|'''Variable'''
|'''Score'''
|-
|'''L'''
|'''LDH level in pleural fluid (IU/L)'''
|
|-
|
|<1500
|0
|-
|
|>1500
|1
|-
|'''E'''
|'''ECOG PS'''
|
|-
|
|0
|0
|-
|
|1
|1
|-
|
|2
|2
|-
|
|3 to 4
|3
|-
|'''N'''
|'''NLR'''
|
|-
|
|<9
|0
|-
|
|>9
|1
|-
|'''T'''
|'''Tumor type'''
|
|-
|
|Lowest risk tumor types

** Mesothelioma
** Hematological malignancy
|0
|-
|
|Moderate risk tumor types

** Breast cancer
** Gynecological cancer
** Renal cell carcinoma
|1
|-
|
|Highest risk tumor types

** Lung cancer
** Other tumor types
|2
|-
| 
|'''Risk categories'''
|'''Total score (median survival in days)'''
|-
|
|Low risk
|0 to 1 (319)
|-
|
|Moderate risk
|2 to 4 (130)
|-
|
|High risk
|5 to 7 (44)
|}
LDH: lactate dehydrogenase; ECOG PS: Eastern Cooperative Oncology Group performance score; NLR: neutrophil to lymphocyte ratio.


== '''Management of malignant and paramalignant pleural effusions''' ==
{| class="wikitable"
|'''Option'''
|'''Comment'''
|-
|Observation
|For asymptomatic effusions; most will progress and require therapy
|-
|Therapeutic thoracentesis
|Prompt relief of dyspnea; most effusions recur unless underlying tumor responds to chemo- or radiotherapy
|-
|Chest catheter drainage only
|Most effusions will recur after catheter removal
|-
|Chest catheter drainage with chemical pleurodesis (eg, talc slurry)
|Variable response rate with 60 to 90 percent of patients responding to talc pleurodesis
|-
|Thoracoscopy with talc insufflation
|Control of effusion with similar frequency as chest catheter drainage with talc pleurodesis
|-
|Long-term indwelling pleural catheter
|Control of effusion and improved symptoms in most patients. Some patients may experience pleurodesis after two weeks (median 11 weeks) of catheter drainage, which allows catheter removal.
|-
|Long-term indwelling pleural catheter with talc instillation
|Control of effusion and symptoms with successful pleurodesis in 43 percent of patients without hospitalization
|-
|Pleural abrasion or pleurectomy
|Requires thoracoscopy or thoracotomy. Effectively controls effusions in nearly all patients.
|-
|Pleuroperitoneal shunt
|When other options have failed or are not indicated; may be useful for chylothorax
|-
|Chemotherapy
|May be effective in some tumor types, such as breast cancer, lymphoma, and small cell lung cancer
|-
|Radiotherapy
|Mediastinal radiation therapy may be effective in lymphoma and lymphomatous chylothorax
|}



Traditional criteria for indwelling pleural catheter removal - <50mL drainage for three consecutive days

[[Category:Thoracics]]
[[Category:Intern education]]