What is the management of tumor lysis syndrome?

Management of Tumor Lysis Syndrome

All patients with clinical TLS require immediate aggressive hydration through central venous access plus rasburicase, not allopurinol, as the primary therapeutic agent. 1, 2

Immediate Interventions for Established TLS

Hydration Protocol

• Initiate aggressive IV hydration at 3 L/m²/day (or ≥2 L/m²/day) through central venous access to maintain urine output ≥100 mL/hour in adults (3 mL/kg/hour in children <10 kg). 1, 2, 3
• Start hydration 48 hours before tumor-specific therapy when possible, though rasburicase allows earlier chemotherapy initiation if needed. 1, 2
• Add loop diuretics (furosemide 40-80 mg IV) or mannitol if target urine output cannot be achieved, except in patients with obstructive uropathy or hypovolemia. 1, 2, 4

Rasburicase Administration

• Administer rasburicase 0.20 mg/kg/day IV infused over 30 minutes for 3-5 days as the primary uric acid-lowering agent. 1, 2, 3, 5
• Rasburicase is superior to allopurinol because it converts existing uric acid to allantoin, providing immediate reduction of pre-existing hyperuricemia rather than merely preventing new uric acid formation. 2, 5
• Never administer allopurinol concurrently with rasburicase to avoid xanthine accumulation and lack of substrate for rasburicase. 2, 3
• Rasburicase achieves plasma uric acid ≤2 mg/dL in 96% of patients within 4 hours of the first dose. 5

Management of Electrolyte Abnormalities

Hyperkalemia Management

• For mild hyperkalemia (<6 mmol/L): treat with hydration, loop diuretics, and sodium polystyrene 1 g/kg either orally or by enema. 1, 4
• For severe hyperkalemia (≥6 mmol/L): administer rapid insulin 0.1 units/kg IV plus 25% dextrose 2 mL/kg, with onset within 15-30 minutes and duration 4-6 hours. 1, 2, 4
• Add calcium carbonate 100-200 mg/kg/dose and sodium bicarbonate to stabilize myocardial cell membrane and correct acidosis. 1, 2
• Calcium gluconate 10% at 50-100 mg/kg IV over 2-5 minutes should be given immediately if ECG changes are present (peaked T waves, widened QRS, prolonged PR interval), with effects beginning within 1-3 minutes. 1, 4
• Perform continuous ECG monitoring for all hyperkalemic patients. 1, 2, 4

Hyperphosphatemia Management

• Mild hyperphosphatemia (<1.62 mmol/L) does not require treatment. 1, 2
• For hyperphosphatemia ≥1.62 mmol/L: administer aluminum hydroxide 50-100 mg/kg/day divided in 4 doses orally or by nasogastric tube. 1, 2, 4

Hypocalcemia Management

• Asymptomatic hypocalcemia does not require treatment. 1, 2
• Do not treat mild hypocalcemia with calcium gluconate as it may lead to increased tissue and renal precipitation of calcium phosphate. 2
• For symptomatic hypocalcemia (tetany, seizures): administer calcium gluconate 50-100 mg/kg as a single IV dose, cautiously repeated if necessary. 1, 2

Monitoring Protocol

High-Risk Patients

• Monitor every 12 hours for the first 3 days, then every 24 hours for: LDH, uric acid, sodium, potassium, creatinine, BUN, phosphorus, and calcium. 2, 3

Patients with Established TLS

• Monitor every 6 hours for the first 24 hours, then daily for: vital signs, serum uric acid, electrolytes, creatinine, and BUN. 2, 3
• Continuous ECG monitoring is mandatory for hyperkalemic patients. 1, 2, 4

Indications for Renal Replacement Therapy

Initiate hemodialysis for any of the following: 1, 2, 3

• Severe oliguria or anuria unresponsive to medical management
• Persistent hyperkalemia despite medical therapy
• Hyperphosphatemia with symptomatic hypocalcemia
• Hyperuricemia not responding to rasburicase
• Severe volume overload
• Symptomatic uremia

Dialysis Efficacy

• Hemodialysis achieves uric acid clearance of approximately 70-100 mL/min and reduces plasma uric acid levels by approximately 50% with each 6-hour treatment. 1, 3
• Intermittent hemodialysis effectively removes uric acid and phosphate by diffusive therapy. 1
• Continuous renal replacement therapies (CRRT) provide greater improvement in hemodynamic instability, azotemia, and fluid overload control compared to intermittent hemodialysis. 1

Critical Pitfalls to Avoid

• Do not use urine alkalinization in patients receiving rasburicase therapy. 2
• Do not delay chemotherapy without addressing TLS risk first, as mortality for clinical TLS in high-risk malignancies can reach 83% versus 24% in those without TLS. 3
• Do not administer calcium for mild asymptomatic hypocalcemia, as this increases the risk of calcium phosphate precipitation in renal tubules. 2
• Loop diuretics should not be used in patients with concomitant obstructive uropathy or hypovolemia. 1, 2