What is the evidence-based treatment algorithm for tumor lysis syndrome?

Evidence-Based Treatment Algorithm for Tumor Lysis Syndrome

Aggressive hydration and rasburicase should be administered to all patients with clinical TLS, laboratory TLS, or those at high risk for developing TLS. 1

Risk Assessment and Classification

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

Laboratory TLS Definition:

• At least 2 biochemical alterations among:
  • Hyperkalemia
  • Hyperphosphatemia
  • Hypocalcemia
  • Hyperuricemia

Clinical TLS Definition:

• Laboratory TLS plus at least one clinical complication:
  • Elevated creatinine (>1.5 × ULN)
  • Cardiac arrhythmia
  • Seizure

Treatment Algorithm

Step 1: Initial Management

• Aggressive IV hydration:
  • Begin 48 hours before chemotherapy when possible
  • Target urine output ≥100 mL/hour in adults (3 mL/kg/hour in children <10 kg)
  • Use central venous access 1, 2

Step 2: Hyperuricemia Management

• Administer rasburicase 0.20 mg/kg/day IV 2
  • Contraindications: G6PD deficiency, metahemoglobinemia, or other metabolic disorders that can cause hemolytic anemia
  • Rapidly degrades uric acid, allowing earlier chemotherapy if needed 1, 3

Step 3: Electrolyte Management

• Hyperkalemia:

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

• Hyperphosphatemia:

  • Mild (<1.62 mmol/L): No treatment or aluminum hydroxide 50-100 mg/kg/day divided in 4 doses 1

• Hypocalcemia:

  • Asymptomatic: No treatment (avoid routine calcium replacement)
  • Symptomatic (tetany, seizures): Calcium gluconate 50-100 mg/kg as single dose, cautiously repeated if necessary 1, 2

Step 4: Monitoring

• High-risk patients:
  • Monitor LDH, uric acid, sodium, potassium, creatinine, BUN, phosphorus, and calcium every 12 hours during first 3 days, then every 24 hours 2
  • Monitor vital signs, uric acid, electrolytes, and renal function every 6 hours during first 24 hours 2
  • Daily assessment of blood cell count, serum LDH, albumin, serum osmolality, blood gases, acid-base equilibrium, ECG, and body weight 2

Step 5: Indications for Dialysis

• Acute renal failure
• Severe electrolyte disturbances unresponsive to medical treatment
• Refractory volume overload
• Excessively elevated uric acid or phosphorus levels
• Severe metabolic acidosis 1, 2

Important Considerations

Avoid:

• Urine alkalinization when using rasburicase (provides no benefit and may worsen calcium phosphate precipitation) 2
• Calcium administration for asymptomatic hypocalcemia (increases risk of calcium phosphate tissue deposition) 2
• Loop diuretics in patients with hypovolemia or obstructive uropathy 1

Special Situations:

• Hemodialysis reduces uric acid levels by approximately 50% with each 6-hour treatment 1
• Uric acid clearance with hemodialysis is approximately 70-100 mL/min 1
• Oliguria due to acute uric acid nephropathy often responds to hemodialysis when plasma uric acid falls to 10 mg/dL 1

Clinical Pitfalls to Avoid

• Delaying treatment in high-risk patients
• Inadequate hydration
• Failure to monitor electrolytes frequently
• Administering calcium for asymptomatic hypocalcemia
• Alkalinizing urine when using rasburicase
• Overlooking the need for dialysis when indicated

This algorithm provides a systematic approach to managing TLS, focusing on prevention and early intervention to reduce morbidity and mortality associated with this oncologic emergency.