Pleural Disease — Written Clinical Reasoning

SAQ 1 — Parapneumonic Effusion Progressing to Empyema: Diagnosis, Drainage, and tPA-DNase (20 marks, 30 minutes)

Prompt: Outline your diagnostic and management approach to this pleural effusion. Include the specific pleural fluid tests you would send, how you would interpret the pH and glucose, when you would drain, the role of intrapleural tPA and DNase, and the threshold for surgical referral. Include the evidence base for each major decision. [1]

Model Answer

Diagnostic thoracentesis and fluid panel (4 marks): [1]

This patient has a parapneumonic effusion that is loculated on ultrasound (echogenic strands and septation) in a patient who is not responding to 5 days of antibiotics — a complicated parapneumonic effusion or empyema until proven otherwise. I would perform an ultrasound-guided diagnostic thoracentesis and send pleural fluid for: [1]

• pH (in a heparinised blood gas syringe, analysed on a blood gas analyser — NOT in a plain tube, NOT contaminated with lidocaine which is acidic and falsely lowers pH)
• Glucose, protein, LDH (with simultaneous serum levels for Light's criteria)
• Cell count and differential
• Gram stain, culture, and culture for anaerobes
• Cytology (to exclude a malignant effusion masquerading as infection) [1]

The key decision-makers are the pH and glucose [1]:

• pH over 7.20 and glucose over 2.2 mmol/L — simple parapneumonic effusion; antibiotics alone suffice
• pH 7.0-7.20 or glucose under 2.2 — complicated parapneumonic effusion; requires chest tube drainage in addition to antibiotics
• pH under 7.0 or frank pus — empyema; urgent chest tube drainage, consider early surgical referral

Drainage decision (4 marks): [1]

Given the loculated, echogenic effusion in a patient failing antibiotic therapy, the probability of a complicated effusion or empyema is high. If the pH is under 7.20 (or under 7.2), I would insert a small-bore (8-14 Fr) Seldinger intercostal chest drain in the safe triangle under ultrasound guidance, and connect it to an underwater seal drainage system. I would NOT apply routine suction — the BTS guideline recommends against routine suction as it does not improve outcomes and may worsen pain. [1]

I would also broaden the antibiotic regimen to cover the likely organisms in pleural infection — Gram-positive streptococci and staphylococci (including MRSA in high-risk settings), anaerobes, and Gram-negative bacilli. A typical regimen is amoxicillin-clavulanate IV plus (if MRSA risk) vancomycin, or ceftriaxone plus metronidazole, adjusted to culture results. The BTS 2023 guideline recommends 4-6 weeks of antibiotic therapy for pleural infection [5].

Intrapleural tPA and DNase — the Rahman trial (5 marks): [1]

If the chest drain does not adequately drain the loculated collection (persistent fever, rising inflammatory markers, residual collection on ultrasound or CT after 24-72 hours), I would instil intrapleural tissue plasminogen activator (tPA) and DNase. The evidence comes from the Rahman et al. trial (NEJM 2011), a randomised, double-blind, 2-by-2 factorial trial of 210 patients with pleural infection [2].

The key findings:

• The combination of tPA (alteplase 10 mg) and DNase (dornase alfa 5 mg), each instilled intrapleurally daily for up to 3 days, significantly increased pleural fluid drainage (reduced radiographic pleural opacity on day 7 CT)
• Reduced the rate of surgical referral at 3 months from approximately 16% (placebo) to approximately 4% (combination)
• Shortened hospital stay by a mean of 6 days [1]

Critically, neither agent alone was effective. tPA alone increased drainage volume but did not improve clinical outcomes, and DNase alone actually worsened outcomes (possibly by increasing fluid viscosity). This is why the combination is used, not monotherapy. [1]

The regimen: alteplase 10 mg plus dornase alfa 5 mg, each diluted in 30-50 mL normal saline, instilled daily via the chest tube, clamped for one hour with the patient rolling position, then reopened. Repeat for up to 3 doses, assessing drainage and radiographic response between doses. [1]

Surgical referral (3 marks): [1]

I would refer for surgical drainage (VATS decortication) if:

• The patient has persistent sepsis or a residual collection despite chest tube drainage and tPA-DNase after 5-7 days
• There is a thick pleural peel (rind) on CT trapping the lung — this requires surgical decortication to release the lung
• The collection is multiloculated and not amenable to catheter drainage [1]

The window for VATS is best within the first 1-2 weeks of the empyema, before the pleural peel organises and fibroses. A patient who is not fit for surgery may need prolonged antibiotics, continued catheter drainage, or rib resection drainage. [1]

Communication and follow-up (4 marks): [1]

• I would explain to the patient that the pneumonia has caused an infection in the pleural space, that drainage is needed, and that the recovery may take several weeks
• I would arrange follow-up spirometry at 3-6 months to check for residual restrictive defect from pleural thickening
• I would review the CXR at 6 weeks to confirm radiographic resolution and exclude an underlying cause (bronchial obstruction, malignancy)
• I would address smoking cessation and pneumococcal and influenza vaccination [1]

SAQ 2 — Malignant Pleural Effusion and Mesothelioma: Diagnosis, Pleural Control, and Chemotherapy (15 marks, 25 minutes)

Prompt: A 68-year-old former shipyard worker presents with a 6-week history of progressive exertional dyspnoea, right chest wall pain, and 8 kg weight loss. CT chest shows a large right pleural effusion with circumferential right pleural thickening and a pleural rind. Pleural fluid cytology is negative on two samples but the clinical suspicion for mesothelioma is high. Outline your diagnostic approach, how you would establish definitive pleural control, and the systemic treatment options. Include the evidence for each decision. [1]

Model Answer

Diagnostic approach (4 marks): [1]

The clinical and radiological picture — asbestos exposure, chest wall pain, weight loss, circumferential pleural thickening with a rind — is highly suggestive of malignant pleural mesothelioma. Negative cytology on two samples does not exclude the diagnosis (cytology is positive in only approximately 30-50% of mesothelioma). I would proceed to: [1]

1. CT-guided cutting-needle pleural biopsy (Abrams or Tru-cut) with immunohistochemistry, OR
2. Medical thoracoscopy (local anaesthetic, semi-rigid) — the preferred approach because it allows direct visualisation of the pleura, targeted biopsy of nodular areas, and talc poudrage pleurodesis in a single procedure [1]

The biopsy must include immunohistochemistry to distinguish mesothelioma from metastatic adenocarcinoma:

• Mesothelioma: calretinin positive, WT-1 positive, D2-40 positive, CK5/6 positive; TTF-1 negative, CEA negative, Ber-EP4 negative
• Adenocarcinoma: TTF-1 positive (if lung primary), CEA positive, Ber-EP4 positive; calretinin negative, WT-1 negative [1]

I would also send serum mesothelin as a supportive biomarker (elevated in approximately 50-60% of mesothelioma). [1]

Definitive pleural control (5 marks): [1]

The effusion is symptomatic and will recur. The approach depends on whether the lung re-expands after drainage: [1]

1. Assess lung re-expansion — perform a therapeutic thoracentesis (limit 1.5 L to avoid re-expansion pulmonary oedema) and repeat the CT. If the lung fully re-expands, pleurodesis is feasible. If the lung is trapped (visceral pleural tumour preventing re-expansion), pleurodesis will fail and an indwelling pleural catheter is needed. [1]

2. If the lung re-expands — pleurodesis: either talc slurry via chest tube or talc poudrage at thoracoscopy/VATS. Success rate approximately 70-90%. [1]

3. If the lung is trapped — indwelling pleural catheter (IPC): a tunneled catheter (PleurX) for outpatient drainage, which is the only effective option for trapped lung. [1]

The TIME2 trial (Davies et al., JAMA 2012) showed that IPC and talc pleurodesis produce equivalent dyspnoea relief, but IPC reduces hospital days and has a higher cellulitis rate [4]. The choice depends on lung re-expansion, prognosis, and patient preference.

Systemic treatment — pemetrexed plus cisplatin (4 marks): [1]

If the diagnosis is confirmed mesothelioma and the patient has good performance status (ECOG 0-1) and adequate organ function, I would refer to the medical oncology MDT for pemetrexed plus cisplatin chemotherapy. The Vogelzang et al. trial (JCO 2003) established this regimen as first-line: median survival improved from 9.3 months (cisplatin alone) to 12.1 months, with response rate 41% versus 17% [3].

The regimen: pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 every 21 days for up to 6 cycles, with folic acid and vitamin B12 supplementation (mandatory to reduce myelosuppression, mucositis, and transaminitis). Carboplatin is substituted for cisplatin in patients with poorer renal function or performance status. [1]

Surgery (extrapleural pneumonectomy or pleurectomy/decortication) is not standard of care outside specialist centres and clinical trials — the MARS trial cast doubt on the benefit of radical surgery. Radiotherapy has a role for pain control and possibly tract metastasis prevention. [1]

Compensation and holistic care (2 marks): [1]

• Document the occupational asbestos exposure meticulously and refer to the dust diseases service (icare/Dust Diseases Board in NSW, equivalent in other states) for compensation
• Involve palliative care early for pain management (opioids, nerve blocks, palliative radiotherapy), nutritional support, and advance care planning
• Discuss prognosis honestly: median survival 8-12 months; epithelioid subtype fares better
• Provide information about legal compensation and refer to a specialist asbestos lawyer [1]