Superior Vena Cava Syndrome

Obstruction of blood flow through the superior vena cava (by compression, invasion or thrombosis), causing venous hypertension in the head, neck and arms. Collateral veins (azygos, internal mammary, lateral thoracic and vertebral) develop over weeks.

• Malignancy causes about 60 to 85%: lung cancer (small cell and squamous, about half of cases), non-Hodgkin lymphoma (about 10 to 15%), metastatic disease (breast), thymoma and germ cell tumours. Benign causes (about 15 to 40%): thrombosis from central venous catheters, pacemaker and defibrillator leads; fibrosing mediastinitis (histoplasmosis, tuberculosis, sarcoidosis); retrosternal goitre; aortic aneurysm; constrictive pericarditis; Behçet disease. In sub-Saharan Africa, mediastinal tuberculosis, lymphoma and Kaposi sarcoma are important causes.
• About 2 to 4% of patients with lung cancer develop the syndrome. It is seldom an immediate emergency; the true emergencies are stridor from airway obstruction and cerebral oedema with confusion or coma. Prognosis depends on the cause: median survival is about 6 to 9 months when due to non-small cell lung cancer, but lymphoma, germ cell tumour and benign causes can be cured.

• Facial and neck swelling (worse on bending forward or lying flat, and in the morning), arm swelling, dyspnoea (about 60%), cough, orthopnoea, headache, dizziness, visual disturbance, hoarseness, dysphagia, and syncope.
• Signs: dilated neck and chest wall veins (about two thirds), facial plethora or oedema, conjunctival oedema, cyanosis, Pemberton sign (facial plethora and raised jugular venous pressure on raising both arms over the head), papilloedema, stridor with laryngeal or tracheal compromise, and arm swelling.
• Differential diagnosis: cardiac tamponade, constrictive pericarditis, heart failure, bilateral subclavian or axillary vein thrombosis, goitre, angioedema, nephrotic syndrome, drug flushing, and thoracic inlet masses.
• Complications: airway obstruction, cerebral oedema, catheter or device occlusion, thrombosis extending into the cava, pleural and pericardial effusion, and death.

• Chest X-ray: mediastinal widening, right hilar or paratracheal mass, pleural effusion. CT chest with IV contrast (preferred) shows the level of obstruction, collaterals, mass, nodes and thrombus. Venography or MR venography when intervention is planned.
• Tissue diagnosis is needed before radiotherapy or chemotherapy where possible: sputum cytology, pleural fluid cytology, biopsy of a palpable node (supraclavicular), CT-guided core biopsy, bronchoscopy with endobronchial ultrasound guided sampling, or mediastinoscopy. Avoid steroids before biopsy unless there is airway compromise, because they can obscure lymphoma.
• Blood tests: full blood count, LDH, urea, creatinine, calcium, HIV test, alpha fetoprotein and beta-hCG in young men, Xpert MTB/RIF on sputum or aspirate, and histoplasma or fungal serology when relevant. Echocardiography for pericardial effusion and right atrial thrombus.

• Supportive care:
  • Sit the patient upright with the head elevated to 30 to 45 degrees; oxygen; avoid IV lines and venepuncture in the arms (use the lower limb).
  • Furosemide 20 to 40 mg IV once may give temporary relief (evidence is limited); avoid over diuresis.
  • Dexamethasone 8 mg IV or orally twice daily for airway oedema, lymphoma, thymoma or cerebral oedema, ideally after tissue sampling unless there is stridor or neurological compromise.
  • Manage airway: intubation in stridor; avoid sedation and lying flat before the airway is secured.
• Endovascular stenting is the fastest way to relieve symptoms (relief within 24 to 72 hours in about 90 to 95%), and is indicated for stridor, cerebral oedema, severe symptoms, chemotherapy resistant tumours, recurrence after radiotherapy, and benign obstruction:
  • Self-expanding covered or bare metal stent (typically 14 to 20 mm diameter) placed through a femoral or jugular approach, after pre-dilatation when needed.
  • After stenting give anticoagulation or antiplatelet therapy (enoxaparin 1 mg/kg SC twice daily then warfarin to INR 2.0 to 3.0 or a direct oral anticoagulant for 3 to 6 months; some centres use aspirin 75 to 100 mg daily with clopidogrel 75 mg daily for 1 to 3 months).
  • Complications: stent migration, thrombosis, restenosis (about 10%), pulmonary oedema, cardiac tamponade or perforation, and infection.
• Treat the cause:
  • Small cell lung cancer: chemotherapy with cisplatin 75 mg/m2 on day 1 plus etoposide 100 mg/m2 on days 1 to 3 every 21 days for 4 to 6 cycles (carboplatin AUC 5 in place of cisplatin when needed), with thoracic radiotherapy; symptom relief occurs in about 70 to 80% within 1 to 2 weeks.
  • Non-small cell lung cancer: radiotherapy (for example 20 Gy in 5 fractions or 30 Gy in 10 fractions) with or without systemic therapy chosen by histology and mutation status.
  • Lymphoma: dexamethasone then chemotherapy such as rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2 (maximum 2 mg) on day 1 with prednisolone 100 mg daily for 5 days, every 21 days for 6 cycles; high grade lymphoma needs urgent specialist directed therapy.
  • Germ cell tumour: cisplatin based chemotherapy (bleomycin, etoposide and cisplatin) by oncology; thymoma: surgery with or without chemotherapy and radiotherapy.
  • Kaposi sarcoma: antiretroviral therapy plus liposomal doxorubicin 20 mg/m2 every 3 weeks or paclitaxel.
  • Catheter or lead related thrombosis: leave the catheter if it works and is needed; therapeutic anticoagulation with enoxaparin 1 mg/kg twice daily then warfarin to INR 2.0 to 3.0 or a direct oral anticoagulant for at least 3 months (longer while the catheter stays); catheter directed thrombolysis with alteplase 0.5 to 1 mg/h for acute thrombosis (symptoms less than 14 days); stenting for residual obstruction.
  • Mediastinal tuberculosis: rifampicin 10 mg/kg (maximum 600 mg), isoniazid 5 mg/kg (maximum 300 mg), pyrazinamide 25 mg/kg (maximum 2 g) and ethambutol 15 mg/kg (maximum 1.2 g) daily for 2 months, then rifampicin and isoniazid for 4 months, with pyridoxine 25 to 50 mg daily; stenting for persistent obstruction.
  • Fibrosing mediastinitis: stenting; itraconazole 200 mg twice daily for 6 to 12 months for histoplasmosis (evidence is limited).
• Special groups:
  • Children: lymphoma is the commonest cause, with airway collapse risk under sedation or anaesthesia; avoid lying flat and general anaesthesia, use local anaesthesia and upright positioning, and start steroids and chemotherapy urgently.
  • Pregnancy: treat the cause with shielding for imaging; stenting is possible with abdominal shielding; avoid cytotoxic therapy in the first trimester if the diagnosis allows.
  • Elderly: stenting offers quick relief with lower risk than prolonged radiotherapy.
  • Renal impairment: reduce contrast volume; adjust cisplatin (use carboplatin) and enoxaparin.
  • HIV: antiretroviral therapy and prophylaxis for opportunistic infection.
• Red flags: stridor, confusion, seizures, syncope, rapidly progressive swelling, coma, haemoptysis.
• Follow up: symptom review at 1 to 2 weeks and CT at 1 to 3 months; stent patency check and anticoagulation review at 1, 3 and 6 months; oncology follow up by tumour type.