What is the management of tumor lysis syndrome?

Management of Tumor Lysis Syndrome

Aggressive IV hydration, electrolyte management, and rasburicase should be administered to high-risk patients and those with established tumor lysis syndrome. 1

Risk Stratification and Initial Management

Tumor lysis syndrome (TLS) is a potentially life-threatening complication of massive cellular lysis in rapidly proliferating, bulky, or highly chemo-radiosensitive cancers. Proper management begins with risk assessment:

High-Risk Patients:

• Hematologic malignancies with high tumor burden (ALL, Burkitt's lymphoma, AML)
• Solid tumors with large tumor burden
• Pre-existing renal dysfunction
• Elevated baseline uric acid levels

Management Algorithm:

1. Hydration (Start 48 hours before chemotherapy when possible):

   • Administer 2-3 L/m²/day (200 mL/kg/day if <10 kg)
   • Use one-quarter normal saline/5% dextrose
   • Target urine output: 80-100 mL/m²/hour (4-6 mL/kg/hour if <10 kg) 1
   • Initially withhold potassium, calcium, and phosphate from hydration fluids

2. Hypouricemic Therapy:

   • High-risk patients: Rasburicase 0.20 mg/kg/day IV 1, 2
   • Low to intermediate-risk patients: Oral allopurinol 100 mg/m²/dose every 8 hours (maximum 800 mg/day) 1
   • Rasburicase is highly effective, with 96% of patients achieving uric acid levels ≤2 mg/dL within 4 hours of administration 2

3. Diuretic Use:

   • Loop diuretics may be used to maintain target urine output
   • Contraindicated in patients with obstructive uropathy or hypovolemia 1

Management of Specific Electrolyte Abnormalities

Hyperkalemia:

• Mild (<6 mmol/L): Hydration, loop diuretics, sodium polystyrene 1 g/kg orally or by enema
• Severe: Insulin (0.1 units/kg) plus glucose (25% dextrose 2 mL/kg), calcium carbonate 100-200 mg/kg/dose, sodium bicarbonate with continuous ECG monitoring 1

Hyperphosphatemia:

• Mild (<1.62 mmol/L): Aluminum hydroxide 50-100 mg/kg/day divided in 4 doses 1
• Severe: Consider renal replacement therapy

Hypocalcemia:

• Symptomatic (tetany, seizures): Calcium gluconate 50-100 mg/kg as a single dose
• Asymptomatic: No routine calcium replacement recommended 1

Renal Replacement Therapy

Consider renal replacement therapy for:

• Volume overload unresponsive to diuretics
• Persistent hyperkalemia
• Severe metabolic acidosis
• Overt uremic symptoms
• Excessively elevated uric acid or phosphorus levels 1

Hemodialysis reduces uric acid levels by approximately 50% with each 6-hour treatment 1.

Monitoring

• Monitor vital signs, uric acid, electrolytes, and renal function every 6 hours during the first 24 hours
• Every 24 hours assess: blood cell count, serum LDH, albumin, serum osmolality, blood gases, acid-base equilibrium, ECG, and body weight 1

Important Considerations

• Alkalinization controversy: Currently not routinely recommended due to lack of evidence and potential risk of calcium phosphate precipitation 1
• Rasburicase limitations: Contraindicated in patients with G6PD deficiency, metahemoglobinemia, or other metabolic disorders that can cause hemolytic anemia 1
• Single course treatment: Rasburicase is indicated only for a single course of treatment 2

Clinical Pearls

• Early recognition and prophylaxis in high-risk patients is crucial for preventing complications 3
• Rasburicase acts rapidly by converting existing uric acid to allantoin, which is 5-10 times more soluble in urine than uric acid 3
• Allopurinol prevents formation of new uric acid but does not reduce existing levels 3
• Careful attention to fluid balance is essential to prevent volume overload while maintaining adequate urine output

By following this structured approach to TLS management, clinicians can effectively prevent and treat this potentially fatal oncologic emergency.