Management of Tumor Lysis Syndrome in Children
Immediate Management Approach
All children with clinical TLS or laboratory TLS with rapidly worsening parameters should receive aggressive intravenous hydration through central venous access plus rasburicase immediately. 1
The cornerstone of TLS management is prevention through risk stratification, but once TLS develops, rapid intervention is critical to prevent mortality (which reaches 83% in untreated clinical TLS). 2
Risk Stratification and Prophylaxis
High-Risk Patients
High-risk children include those with:
- Burkitt's lymphoma or B-cell ALL (26.4% TLS rate) 2
- Stage III/IV non-Hodgkin lymphoma 1
- Acute leukemia with WBC >100,000/mm³ 2
- Elevated LDH >2 times upper normal limit 2
- Pre-existing renal dysfunction or hyperuricemia 3, 2
High-risk patients require hydration plus rasburicase 0.20 mg/kg/day IV over 30 minutes in an inpatient setting. 1, 3, 2
Intermediate-Risk Patients
Intermediate-risk patients should receive aggressive hydration plus either allopurinol (100 mg/m² three times daily, max 800 mg/day) or rasburicase. 1, 3
Low-Risk Patients
Low-risk patients require hydration (≥2 L/m²/day) plus oral allopurinol with close monitoring. 3, 2
Hydration Protocol
Target urine output of ≥100 mL/hour in adults or 3 mL/kg/hour in children <10 kg body weight. 1, 4
- Start hydration 48 hours before chemotherapy when possible 1, 4
- Administer 3 L/m²/day of IV fluids 4, 2
- Loop diuretics (furosemide) may be required to maintain urine output, but only after confirming adequate hydration and ruling out obstructive uropathy or hypovolemia 1, 4
Critical pitfall: Administering diuretics to hypovolemic patients worsens renal perfusion and increases TLS complications. 4 Always verify hydration status by checking urine osmolality and fractional excretion of sodium before giving furosemides. 4
Pharmacologic Management
Rasburicase (Preferred for High-Risk)
Rasburicase 0.20 mg/kg/day IV over 30 minutes for 3-5 days is the treatment of choice for established TLS and high-risk prophylaxis. 1, 2, 5
- Converts existing uric acid to allantoin (5-10 times more soluble than uric acid) 1, 3
- Achieves 100% response rate in treatment groups and 93% in prophylaxis groups within 24 hours 1
- Mean uric acid decreases from 15.1 to 0.4 mg/dL in hyperuricemic children 1
- Contraindicated in G6PD deficiency (causes severe hemolysis) 5
Never administer rasburicase concurrently with allopurinol - this causes xanthine accumulation and removes substrate for rasburicase. 4, 2
Allopurinol (For Low-Intermediate Risk)
Allopurinol 100 mg/m² three times daily (maximum 800 mg/day) blocks xanthine oxidase, preventing new uric acid formation. 4, 2
- Does not reduce existing uric acid levels 2
- Less effective than rasburicase in randomized trials (mean uric acid AUC 329±129 vs 128±70 mg/dL/hour, p<0.001) 1
Urine Alkalinization: NOT Recommended
Do not alkalinize urine - this increases calcium phosphate precipitation risk without improving outcomes. 1, 4
Electrolyte Management
Hyperkalemia
Mild hyperkalemia (<6 mmol/L) asymptomatic: Correct with hydration, loop diuretics, and sodium polystyrene 1 g/kg orally or by enema. 1
Severe hyperkalemia (≥6 mmol/L):
- Rapid insulin 0.1 units/kg plus 25% dextrose 2 mL/kg 1
- Calcium carbonate 100-200 mg/kg/dose to stabilize myocardial membranes 1
- Sodium bicarbonate to correct acidosis 1
- Continuous ECG monitoring is mandatory 1
Hyperphosphatemia
Mild hyperphosphatemia (<1.62 mmol/L): No treatment required or aluminum hydroxide 50-100 mg/kg/day divided in 4 doses. 1
Hypocalcemia
Asymptomatic hypocalcemia requires no treatment. 1
Symptomatic hypocalcemia (tetany, seizures): Single dose of calcium gluconate 50-100 mg/kg infused slowly, repeated cautiously if necessary. 1
Critical pitfall: Avoid calcium administration in hyperphosphatemia unless symptomatic, as it promotes calcium phosphate precipitation in renal tubules. 1
Monitoring Protocol
High-Risk Patients
Monitor every 12 hours for first 3 days, then every 24 hours: 3, 2
- Vital signs
- Serum uric acid, potassium, phosphorus, calcium, creatinine, BUN, LDH
- Urine output
Established TLS
Monitor every 6 hours for first 24 hours, then daily. 2
Special sample handling for uric acid: Blood must be collected in prechilled heparin tubes, immediately immersed in ice water bath, centrifuged at 4°C, and analyzed within 4 hours to prevent ex vivo uric acid degradation by rasburicase. 5
Indications for Renal Replacement Therapy
Initiate dialysis for: 2
- 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
Hemodialysis effectively removes uric acid (clearance 70-100 mL/min) with plasma uric acid falling approximately 50% per 6-hour treatment. 2 Continuous veno-venous hemofiltration (CVVH) can prevent renal failure in very high-risk patients (LDH >10 times normal) when started before chemotherapy. 6
Common Pitfalls to Avoid
Fluid overload: Severe fluid overload (≥10%) occurs in 35.7% of pediatric TLS patients and significantly increases PICU admission (35% vs 8.3%), hypoxemia (30% vs 5.6%), and pulmonary edema (25% vs 2.8%). 7 Monitor closely for respiratory distress.
Premature diuretic use: Never give diuretics before confirming adequate hydration status. 4
Concurrent allopurinol and rasburicase: This combination is contraindicated. 4, 2
Urine alkalinization: Abandoned practice that increases complications. 1, 4
Delayed recognition in younger children: Children <2 years have lower rates of achieving normal uric acid by 48 hours (83% vs 93%) and require closer monitoring. 5