Chylous Pleural Effusion

Milky pleural fluid containing chylomicrons from leakage of lymph (chyle) from the thoracic duct or its tributaries (chylothorax). Pleural fluid triglycerides greater than 1.24 mmol/L (110 mg/dL) with chylomicrons confirm it; a level less than 0.56 mmol/L (50 mg/dL) makes it very unlikely.

• Causes in adults: traumatic (about 50%; oesophagectomy in about 1 to 4%, cardiothoracic and neck surgery, penetrating injury, central venous catheter thrombosis) and non-traumatic (about 50%; lymphoma in about 50 to 70% of non-traumatic cases, other malignancies, sarcoidosis, tuberculosis, lymphangioleiomyomatosis, filariasis in endemic coastal areas, mediastinal fibrosis, superior vena cava thrombosis, yellow nail syndrome, amyloidosis, Gorham disease, and idiopathic). In neonates it is the commonest cause of pleural effusion (congenital thoracic duct malformation or birth trauma).
• Anatomy: the thoracic duct enters the chest at the aortic hiatus (T10 to T12), runs to the right of the vertebral column, crosses to the left at about T5, and drains into the left subclavian and internal jugular vein junction. A leak at or caudal to the fifth thoracic vertebra causes a right sided effusion, and a leak cranial to it causes a left sided effusion.
• Consequences: loss of up to 1.5 to 2.5 L of chyle per day, with protein, fat, fat soluble vitamins, electrolytes and lymphocytes, leading to malnutrition, dehydration, immunosuppression (lymphopenia, low immunoglobulins) and infection. Mortality was historically about 50% untreated and is now about 10% with modern care.
• Pseudochylothorax is a long standing effusion (tuberculosis, rheumatoid arthritis) with cholesterol greater than 5.18 mmol/L (200 mg/dL) and cholesterol crystals; triglycerides are usually normal or only mildly raised.

• Progressive breathlessness, cough, chest tightness, fatigue; fever is usually absent (chyle is bacteriostatic). Weight loss, muscle wasting and oedema with long leaks. Chylous ascites in some.
• Signs: dullness, reduced breath sounds, and the features of the cause (lymphadenopathy, splenomegaly, hepatomegaly, yellow nails, lymphoedema).
• Differential diagnosis: empyema and parapneumonic effusion (turbid fluid), pseudochylothorax, malignant effusion, tuberculous effusion, haemothorax, and effusion from lipid rich total parenteral nutrition misplaced into the pleura.
• Complications: malnutrition, lymphopenia, infection, respiratory failure, fibrothorax, thrombosis, and vitamin deficiency.

• Chest X-ray and ultrasound: unilateral (about two thirds on the right) or bilateral effusion. CT chest and abdomen: lymphoma, masses, thoracic duct injury, lymphangioleiomyomatosis cysts.
• Pleural fluid: milky or turbid (may be clear in fasting patients), triglycerides greater than 1.24 mmol/L, lipoprotein electrophoresis for chylomicrons, cholesterol, cell count (lymphocyte predominance), protein, LDH, glucose, cytology, flow cytometry, Xpert MTB/RIF and culture, adenosine deaminase. If triglycerides are 0.56 to 1.24 mmol/L, send lipoprotein analysis. Fat globules stain with Sudan III.
• Blood tests: full blood count with lymphocytes, albumin, triglycerides, immunoglobulins, vitamins A, D, E and K, zinc, HIV test, creatinine, and serology for filariasis (antigen test or microfilariae on night blood film in endemic coastal areas).
• Lymphoscintigraphy, magnetic resonance lymphangiography or intranodal lymphangiography to locate the leak before intervention; biopsy of nodes or pleura when malignancy is suspected.

• Drain the pleural space and correct nutrition, then reduce chyle flow; start definitive treatment early for high output.
• Initial care:
  • Chest drain (small bore 12 to 14 French, or 20 to 28 French for high output) to expand the lung and measure output.
  • Avoid repeated thoracentesis without nutritional support, since it depletes protein and lymphocytes.
• Dietary and drug management of chyle flow (conservative treatment succeeds in about 50% of traumatic cases over 1 to 2 weeks):
  • Fat free enteral diet or medium chain triglyceride formula (absorbed directly into the portal vein, bypassing the thoracic duct), with protein 1.5 to 2 g/kg/day and fat soluble vitamin supplements; if output remains more than 1 L/day after 3 to 5 days, stop oral intake and use total parenteral nutrition.
  • Octreotide 50 to 100 micrograms SC every 8 hours (or 25 to 50 micrograms/h IV infusion), continued for 1 to 2 weeks (evidence is limited); somatostatin 250 micrograms/h IV is an alternative.
  • Midodrine 10 mg orally three times daily or etilefrine 5 to 10 mg three times daily to reduce lymph flow by vasoconstriction (evidence is limited).
  • Replace protein and fluids as needed (albumin 20% 100 mL daily for hypoalbuminaemia).
• Intervention for failure of conservative care:
  • Traumatic leak with output more than 1 L/day for 5 to 7 days, or more than 500 mL/day persisting for 2 weeks (or nutritional or metabolic deterioration): thoracic duct embolisation by percutaneous lymphangiography with coils or glue (success about 70 to 90%, less invasive and now first line where available) or video assisted thoracoscopic thoracic duct ligation (mass ligation of tissue at the diaphragm, with success about 90%, usually done on the right side), with fat containing food or cream (30 to 50 mL) given 2 to 3 hours before surgery to show the leak.
  • Pleurodesis with talc slurry 4 to 5 g (after intrapleural lidocaine 3 mg/kg, maximum 250 mg), or pleuroperitoneal shunt, for refractory leak in patients unfit for surgery.
• Treat the cause (non-traumatic):
  • Lymphoma: systemic chemotherapy (rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2 with a maximum of 2 mg on day 1, and prednisolone 100 mg daily for 5 days, every 21 days for 6 cycles) usually controls the effusion; low dose mediastinal radiotherapy (20 to 30 Gy in 10 to 15 fractions) for residual disease (evidence is limited).
  • Tuberculosis: rifampicin 10 mg/kg (maximum 600 mg), isoniazid 5 mg/kg (maximum 300 mg), pyrazinamide 25 mg/kg (maximum 2 g), 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.
  • Lymphangioleiomyomatosis: sirolimus 1 to 2 mg daily (trough 5 to 15 ng/mL).
  • Filariasis: albendazole 400 mg plus diethylcarbamazine 6 mg/kg as a single dose (avoid diethylcarbamazine if onchocerciasis or loiasis is possible), or doxycycline 200 mg daily for 4 to 6 weeks (evidence is limited for chylothorax); hygiene and lymphoedema care.
  • Catheter related thrombosis: remove the catheter and give anticoagulation (apixaban 10 mg twice daily for 7 days then 5 mg twice daily).
  • Yellow nail syndrome: treat the lymphoedema and respiratory disease; vitamin E 600 to 1200 units daily has been tried (evidence is limited).
• Neonates and infants: medium chain triglyceride formula for 3 to 6 weeks, octreotide 1 to 10 micrograms/kg/h IV infusion (or 1 to 10 micrograms/kg every 8 hours SC) and chest drainage; surgery for persistent leak after 4 weeks.
• Monitoring: weight, albumin, lymphocyte count, immunoglobulins, electrolytes and vitamin levels weekly; watch for infection.
• Special groups:
  • Pregnancy: drainage, medium chain triglyceride diet and nutritional support; avoid sirolimus and doxycycline; surgery only for refractory leak.
  • Children: weight based octreotide; early ligation or embolisation.
  • Immunosuppressed and HIV: test for tuberculosis and lymphoma; antiretroviral therapy.
  • Renal impairment: adjust octreotide and midodrine.
• Red flags: output more than 1 L/day, falling albumin or lymphocytes, fever (infection), rising oxygen need, bilateral effusions with chylous ascites.
• Follow up: chest X-ray weekly during treatment, remove drains when output is less than 100 mL/day for 3 days on a regular diet; review at 2 and 6 weeks; yearly imaging for lymphoma and cyst disease; dietitian and oncology follow up.