RespiratoryTier 1Disease (DEADMAN)

Pleural effusion

Description

Abnormal fluid accumulation in the pleural space
- Normal volume ~10 mL; ~0.2 mL/kg/h turnover, cleared by parietal lymphatic stomata
- Lymphatic reserve capacity is ~20x normal - an effusion requires either massive production or blocked drainage

Mechanisms

Mechanism	Type	Example
inc hydrostatic pressure	Transudate	Heart failure
dec oncotic pressure	Transudate	Nephrotic, cirrhosis, malnutrition
inc capillary permeability	Exudate	Infection, malignancy, inflammation
dec lymphatic drainage	Exudate	Malignancy, mediastinal fibrosis
Transdiaphragmatic movement	Transudate	Hepatic hydrothorax, peritoneal dialysis
Thoracic duct disruption	Chylothorax	Lymphoma, surgery, trauma

Named effusions

Empyema - frank pus, or organisms on Gram stain/culture
Complicated parapneumonic - sterile but loculated/acidotic; requires drainage
Chylothorax - triglycerides >1.24 mmol/L (110 mg/dL) +/- chylomicrons; milky, not clearing on centrifugation
Pseudochylothorax - cholesterol >5.18 mmol/L, cholesterol crystals; chronic (TB, RA)
Haemothorax - pleural fluid Hct >50% of blood Hct
Trapped lung - visceral pleural peel prevents re-expansion; markedly negative pleural pressure

Epidemiology

~1-1.5 per 1000 population per year
Heart failure is the commonest cause overall (~80% of transudates)
Malignancy is the commonest cause of a large/massive unilateral effusion
Australia: mesothelioma incidence among the highest in the world - always ask about asbestos
~40% of pneumonias develop a parapneumonic effusion; ~10% become complicated

Aetiopathogenesis

Transudate

Cardiac failure (~80%) - usually bilateral, R>L
Hypoalbuminaemia - nephrotic syndrome, cirrhosis, protein-losing enteropathy, malnutrition
Hepatic hydrothorax - right-sided in ~85%, via diaphragmatic defects
Hypothyroidism (can be exudative)
Constrictive pericarditis, SVC obstruction, Fontan circulation
Peritoneal dialysis, urinothorax (the only effusion with pleural fluid creatinine > serum)
CSF leak via duro-pleural fistula
Atelectasis

Exudate

Infection - parapneumonic, empyema, TB, subphrenic/hepatic abscess, viral
Malignancy - lung, breast, lymphoma, ovary, GI; mesothelioma; metastatic
Pulmonary embolism/infarction (may be transudative or exudative - a classic trap)
Inflammatory - RA, SLE, pancreatitis, post-CABG, Dressler, sarcoid, IgG4
Drugs - methotrexate, amiodarone, nitrofurantoin, dasatinib, bromocriptine, phenytoin
Oesophageal rupture - very low pH (<6.0), high amylase (salivary)
Asbestos-related benign pleural effusion, yellow nail syndrome, ovarian hyperstimulation
Meigs syndrome - benign ovarian fibroma + ascites + pleural effusion (resolves with tumour removal)

Diagnosis

Clinical

Dyspnoea, pleuritic pain (implies pleural inflammation), dry cough
Stony dullness, absent breath sounds, dec vocal resonance, dec expansion
Bronchial breathing and egophony at the upper level (compressed lung)
Tracheal deviation away if massive; towards suggests concurrent collapse or trapped lung

Imaging

Erect CXR: blunted costophrenic angle needs ~200 mL; lateral film detects ~50 mL; meniscus sign
Ultrasound - use for every diagnostic and therapeutic tap
- Detects <20 mL; identifies septations, differentiates from consolidation, marks a safe site
- *Reduces pneumothorax and organ puncture; never tap by percussion alone*
- Echogenic/septated fluid or pleural thickening -> exudate; pleural nodularity or thickening >1 cm -> malignancy
CT with contrast (before full drainage) - pleural thickening, nodularity, mediastinal pleural involvement, circumferential rind -> malignancy or empyema

Pleural aspiration - send in every case

Protein, LDH (with paired serum), pH (blood-gas analyser, heparinised, anaerobic), glucose
Gram stain, culture (and inoculate blood culture bottles - raises yield ~20%), AFB, TB PCR
Cytology (large volume, at least 25-50 mL; repeat sample raises yield from ~60% to ~72%)
Selective: amylase, triglycerides, cholesterol, haematocrit, ADA, flow cytometry, NT-proBNP

Light's criteria - exudate if ANY one

Pleural protein : serum protein >0.5
Pleural LDH : serum LDH >0.6
Pleural LDH > 2/3 upper limit of normal serum LDH

Sensitivity ~98% for exudate; specificity poorer - misclassifies ~25% of transudates as exudates, especially after diuretics
*If clinically a transudate but Light's says exudate, use:*
- Serum-pleural albumin gradient >12 g/L -> transudate
- Serum-pleural protein gradient >31 g/L -> transudate
- Pleural NT-proBNP >1500 ng/L -> cardiac failure

Fluid pattern -> diagnosis

Finding	Suggests
pH <7.20	Complicated parapneumonic/empyema, TB, malignancy, RA, oesophageal rupture
Glucose <2.2 mmol/L	Empyema, RA (often <1.6), malignancy, TB
LDH >1000 IU/L	Complicated parapneumonic, empyema, RA, paragonimiasis
Amylase raised	Pancreatitis, oesophageal rupture (salivary isoenzyme), malignancy
Lymphocyte predominant	TB, malignancy, lymphoma, chylothorax, post-CABG, sarcoid, RA
Neutrophil predominant	Parapneumonic, PE, early TB, pancreatitis
Eosinophils >10%	Air or blood in the pleural space (commonest), drugs, parasites, Churg-Strauss, malignancy
RBC >5000/mL	PE/infarct, malignancy, trauma, asbestosis, TB
Haematocrit >50% of blood	Haemothorax
Milky, TG >1.24 mmol/L	Chylothorax - lymphoma, trauma, LAM, tuberous sclerosis

*Very low pleural glucose in a chronic lymphocytic effusion in a patient with deforming arthropathy = rheumatoid pleuritis*

Specific tests

Pleural fluid ADA for TB - sens ~92%, spec ~90%; validated in high-prevalence settings; false positives with empyema, RA, lymphoma
- Pleural fluid AFB microscopy yield <30%; pleural biopsy (culture + histology) yield >80%
Pleural fluid CRP >45 mg/L in a neutrophilic exudate -> parapneumonic; >100 performs as well as pH/glucose for complicated effusion
Cytology yield varies by primary: high in adenocarcinoma, low in mesothelioma (~<30%) and lymphoma - both usually need histology

When cytology is negative and malignancy still suspected

Local anaesthetic thoracoscopy (medical pleuroscopy) - diagnostic yield >90%; allows talc poudrage at the same sitting
Image-guided (CT/US) cutting-needle biopsy of pleural thickening - yield ~85%
Blind Abrams biopsy retains a role only for suspected TB

Undiagnosed effusion after full workup (~15%)

Observe with interval imaging; many are PE, TB or early mesothelioma that declares later
A persistently undiagnosed exudate in an asbestos-exposed patient is mesothelioma until proven otherwise

RAPID score - prognosis in pleural infection

Renal (urea), Age, Purulence, Infection source (hospital vs community), Dietary (albumin)
Stratifies 3-month mortality; identifies patients for early aggressive management

Management

1. Transudate - treat the cause, not the fluid

Diuresis for heart failure; albumin/TIPS for hepatic hydrothorax; thyroxine
Drainage only for symptomatic relief; repeated drainage of a hepatic hydrothorax depletes protein and risks infection - avoid IPC (high infection rate)

2. Parapneumonic effusion and empyema

The decision is: does it need a drain?

Drain if ANY of:
- Frank pus or positive Gram stain/culture
- pH <7.20 (or glucose <2.2 mmol/L / LDH >1000 if pH unavailable)
- Loculated or large effusion with ongoing sepsis
Antibiotics - cover anaerobes; prolonged course (2-6 weeks)
- Atypical organisms do not cause primary pleural infection (MIST1/MIST2) - do not target them
- Aspiration/oral flora predominate in community-acquired; MRSA and Gram-negatives in hospital-acquired
Small-bore (10-14F) chest drain with regular flushes = large-bore, less painful
Intrapleural tPA 10 mg + DNase 5 mg BD x 3 days if drainage fails
- MIST2: combination improved fluid drainage and reduced hospital stay and surgical referral; neither agent alone was effective (tPA alone reduced surgical referral but not the primary outcome)
- ~70% of pleural infection resolves with drain + antibiotics alone
Surgical referral (VATS decortication) if failing at 5-7 days
Nutritional support and VTE prophylaxis - these patients have long admissions and high mortality (~20% at 1 year)

3. Malignant pleural effusion

Palliative. Goal = dyspnoea relief with minimum hospital time.

Therapeutic aspiration first to confirm symptoms improve and the lung re-expands
- Stop at ~1.5 L or if chest tightness/cough develops - re-expansion pulmonary oedema**
BTS 2023: indwelling pleural catheter (IPC) is a first-line option, not a salvage one

Situation	Option
Expandable lung, pleurodesis desired	Talc pleurodesis (slurry or thoracoscopic poudrage), or IPC
Expandable lung, wants fewer hospital visits	IPC (outpatient, drains at home)
Trapped lung / failed pleurodesis	IPC - pleurodesis cannot work if the lung will not appose
Both goals	Talc via IPC - achieves pleurodesis and allows catheter removal

IPC: ~50% spontaneous pleurodesis with daily drainage; risks infection (~5%), catheter tract metastasis (mesothelioma - consider prophylactic radiotherapy), blockage
Do not use pleurodesis in chemo-sensitive tumours (lymphoma, SCLC, germ cell) before a trial of systemic therapy
Treat the underlying malignancy; involve palliative care early

4. Chylothorax

Low-fat diet with medium-chain triglycerides or TPN with nil orally
Treat the cause (lymphoma responds to chemotherapy)
Octreotide, thoracic duct embolisation or ligation, pleurodesis if refractory
*Prolonged drainage causes immunodeficiency and malnutrition (loss of lymphocytes, protein, fat) - do not just leave a drain in*

5. Procedural safety

Ultrasound guidance for every tap; posterior/lateral approach above the rib
Correct coagulopathy where feasible; routine reversal is not required for small-bore drainage in most guidelines
Complications: pneumothorax, haemothorax (intercostal artery - tortuous in the elderly), organ puncture, re-expansion pulmonary oedema, tract seeding, infection

Associations

Heart failure - bilateral, R>L
Pneumonia - ~40% develop an effusion
Malignancy - lung, breast, lymphoma, ovary, mesothelioma
Asbestos exposure - benign asbestos pleural effusion, plaques, mesothelioma
RA - chronic, very low glucose and pH, high LDH, in men with nodular disease
SLE - bilateral, pleuritic pain, positive ANA in fluid
Cirrhosis - hepatic hydrothorax; can occur without clinical ascites
Nephrotic syndrome - bilateral; consider concurrent renal vein thrombosis and PE
Pancreatitis - left-sided, high amylase; pancreaticopleural fistula in chronic disease
Post-cardiac injury (Dressler) syndrome, post-CABG effusion
Yellow nail syndrome - lymphoedema, yellow nails, effusion, bronchiectasis
Ovarian hyperstimulation, Meigs syndrome
Lymphangioleiomyomatosis - chylothorax + cysts + pneumothorax in a young woman

Natural history & complications

Determined entirely by the cause
Transudative - resolves with treatment of the underlying disorder
Parapneumonic - progresses through stages if not drained

1. Exudative (free-flowing, sterile) -> simple drainage or none

2. Fibrinopurulent (loculation, fibrin deposition, falling pH) -> drain +/- fibrinolytics

3. Organising (pleural peel, trapped lung) -> surgical decortication

The window between stages is days, not weeks - delay in drainage is the main determinant of surgery
Empyema mortality ~10-20% at 1 year; higher with hospital-acquired infection, age, comorbidity, low albumin (the RAPID variables)
Malignant effusion - median survival 3-12 months from diagnosis
- Shortest in lung cancer and mesothelioma, longest in breast and ovarian
- LENT score (LDH, ECOG, Neutrophil-lymphocyte ratio, Tumour type) stratifies survival

Complications

Trapped lung and fibrothorax -> permanent restrictive defect
Empyema necessitans, bronchopleural fistula
Re-expansion pulmonary oedema after rapid large-volume drainage
Catheter tract metastasis (mesothelioma)
Chronic pain, recurrent hospitalisation

6 more sections, plus exam facts

Premium unlocks every note across every specialty, and the full exam fact library behind it.

Get premium access