What is the recommended fluid management and treatment approach for a patient with Tumor Lysis Syndrome (TLS), including the use of hydration, rasburicase (uric acid oxidase) and allopurinol (xanthine oxidase inhibitor), and what are the key parameters to monitor?

Management of Tumor Lysis Syndrome (TLS)

For patients with Tumor Lysis Syndrome (TLS), aggressive hydration with 3L/m² of fluid should be administered to maintain urine output of at least 100 mL/hour in adults, along with rasburicase for high-risk patients and appropriate electrolyte monitoring every 6 hours. 1

Fluid Management

• Hydration should start at least 48 hours before tumor-specific therapy when possible, with urine output maintained at ≥100 mL/hour in adults (3 mL/kg/hour in children <10 kg) 1
• Measurement of urine osmolality and fractional excretion of sodium can help define hydration status 1
• Loop diuretics may be required to maintain adequate urine output, but should be avoided in patients with obstructive uropathy or hypovolemia 1
• Hemodynamic status and hydration level should be assessed before using loop diuretics 1

Pharmacological Management

High-Risk Patients:

• Rasburicase (0.20 mg/kg/day, infused over 30 minutes) should be administered, with the first dose at least four hours before starting tumor-specific therapy 1
• Continue rasburicase for at least 3-5 days 1
• After completing rasburicase treatment, patients should transition to oral allopurinol 1
• Avoid concurrent administration of allopurinol with rasburicase to prevent xanthine accumulation 1, 2

Low-Risk Patients:

• Oral allopurinol (100 mg/m² three times daily, maximum 800 mg/day), hydration, and urine alkalinization 1, 3
• Allopurinol should be started at a low dose (100 mg daily) and increased weekly by 100 mg until serum uric acid level ≤6 mg/dL is attained 3

Special Considerations:

• Rasburicase is contraindicated in patients with metahemoglobinemia, G6PDH deficiency, or other metabolic disorders that can cause hemolytic anemia 1, 2
• Urine alkalinization is not recommended for patients receiving rasburicase therapy unless other clinical conditions require it 1
• Calcium gluconate should not be used to correct mild hypocalcemia as it can increase tissue and renal precipitation of calcium phosphate 1

Monitoring Parameters

For High-Risk Patients:

• Monitor LDH, uric acid, sodium, potassium, creatinine, BUN, phosphorus, and calcium every 12 hours for the first three days, then every 24 hours 1

For Patients with TLS:

• Every 6 hours for the first 24 hours and daily thereafter: vital parameters (heart rate, blood pressure, urine output, respiratory rate), serum uric acid, electrolytes (phosphate, calcium, potassium), and renal function (creatinine, BUN, urine pH and osmolality, specific gravity) 1
• Every 24 hours: CBC, LDH, albumin, serum osmolality, blood gases, acid-base equilibrium, ECG, and body weight 1

Criteria for Safe Resumption of Chemotherapy

• Uric acid level should be <8 mg/dL 4
• Creatinine level should be <141 μmol/L 4
• pH should be ≥7.0 4
• Nephrology consultation is recommended before restarting therapy in patients with previous clinical TLS 4

Common Pitfalls to Avoid

• Premature resumption of chemotherapy before metabolic abnormalities are corrected can lead to recurrent TLS 4, 5
• Inadequate hydration increases risk of renal injury 4, 6
• Simultaneous administration of allopurinol and rasburicase reduces efficacy 1, 2
• Urine alkalinization can increase calcium phosphate precipitation and reduce xanthine solubility 1, 7
• Calcium gluconate administration for mild hypocalcemia can worsen calcium phosphate precipitation 1

Indications for Hemodialysis

• Excessively elevated uric acid, phosphate, and/or potassium levels 6
• Acute renal failure with uremia 6, 5
• Severe fluid overload unresponsive to diuretics 5