What is the management of uric acid emergency in chemotherapy patients?

Management of Uric Acid Emergency (Tumor Lysis Syndrome) in Chemotherapy Patients

Immediately administer rasburicase 0.20 mg/kg IV over 30 minutes along with aggressive hydration (3 L/m²/day) to maintain urine output ≥100 mL/hour in adults, while closely monitoring electrolytes every 6 hours for the first 24 hours. 1, 2

Immediate Recognition and Risk Assessment

Clinical TLS presents with the classic tetrad of hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia, often accompanied by acute renal failure, cardiac arrhythmias, or seizures. 1, 3 High-risk patients include those with:

• Bulky disease with rapid tumor response to therapy 1
• Pre-existing renal impairment or obstructive uropathy 1
• Baseline hyperuricemia (>8 mg/dL in children, >10 mg/dL in adults) 1
• Elevated LDH levels indicating high tumor burden 4
• Hematologic malignancies (70% of children with malignancies develop TLS) 1

Critical pitfall: TLS can occur with solid tumors and even after radiation therapy, not just hematologic malignancies—failure to recognize this leads to delayed treatment and increased mortality. 5, 4

Immediate Pharmacologic Management

Rasburicase Administration (First-Line)

Rasburicase is the preferred agent for established TLS because it rapidly converts existing uric acid to allantoin (5-10 times more soluble than uric acid), achieving 86% reduction in uric acid within 4 hours. 1, 6

Dosing protocol:

• 0.20 mg/kg IV infused over 30 minutes daily 2, 6
• Continue for 3-5 days 2
• First dose should be given at least 4 hours before chemotherapy when possible 2
• Administer through a separate line or flush with ≥15 mL normal saline before and after 6

Absolute contraindications to rasburicase: 6

• G6PD deficiency (screen patients of African or Mediterranean ancestry before use)
• History of severe hypersensitivity, hemolysis, or methemoglobinemia with rasburicase
• Pregnancy (may cause fetal harm)

Do not administer allopurinol concurrently with rasburicase—this causes xanthine accumulation and defeats the purpose of rasburicase therapy. 7, 2

Aggressive Hydration Protocol

Start hydration at least 48 hours before chemotherapy when possible: 1, 2

• Target: 3 L/m²/day (≥2 L/m²/day minimum) 1
• Maintain urine output ≥100 mL/hour in adults (3 mL/kg/hour in children <10 kg) 1, 2
• Use loop diuretics (or mannitol) if needed to achieve target urine output 1
• Avoid diuretics in patients with obstructive uropathy or hypovolemia 1, 2

Do not alkalinize urine in patients receiving rasburicase—this is unnecessary and can worsen calcium-phosphate precipitation. 2

Electrolyte Management

Hyperkalemia Management (Stepwise Approach)

Mild hyperkalemia (<6 mmol/L, asymptomatic): 1

• Hydration and loop diuretics
• Sodium polystyrene 1 g/kg orally or by enema

Severe hyperkalemia (≥6 mmol/L or symptomatic): 1, 5

• Continuous ECG monitoring is mandatory
• Calcium gluconate 100-200 mg/kg/dose to stabilize myocardial membranes
• Insulin 0.1 units/kg + 25% dextrose 2 mL/kg for rapid intracellular shift
• Sodium bicarbonate to correct acidosis
• Prepare for emergent dialysis if refractory

Hyperphosphatemia Management

Mild hyperphosphatemia (<1.62 mmol/L): 1

• May not require treatment
• If treatment needed: aluminum hydroxide 50-100 mg/kg/day divided in 4 doses (oral or nasogastric)

Severe hyperphosphatemia: Consider dialysis 1

Hypocalcemia Management

Asymptomatic hypocalcemia does not require treatment. 1

Symptomatic hypocalcemia (tetany, seizures): 1

• Calcium gluconate 50-100 mg/kg as single IV dose
• Repeat cautiously if necessary
• Critical pitfall: Avoid calcium supplementation for mild hypocalcemia—this increases calcium-phosphate precipitation in renal tubules and worsens renal failure 2

Monitoring Protocol

First 24 hours—monitor every 6 hours: 1, 2

• Uric acid, potassium, phosphate, calcium, creatinine, BUN
• Vital signs (heart rate, blood pressure, urine output, respiratory rate)
• Continuous ECG monitoring if hyperkalemic

Days 2-3—monitor every 12 hours: 2

• Same parameters as above
• LDH levels

After day 3—monitor daily until stable: 1, 2

Critical laboratory collection technique: Blood samples for uric acid must be collected in pre-chilled heparin tubes and immediately placed in ice water bath, then assayed within 4 hours—rasburicase enzymatically degrades uric acid in samples left at room temperature, causing falsely low readings. 6

Indications for Dialysis

Initiate dialysis immediately for: 1, 5

• Persistent severe hyperkalemia despite medical management
• Severe renal impairment with creatinine >6× upper normal limit or creatinine clearance <10 mL/min 1
• Symptomatic uremia
• Severe metabolic acidosis (pH <7.0) 7
• Fluid overload unresponsive to diuretics

Consider frequent dialysis sessions because metabolites continue releasing from ongoing tumor lysis. 5, 8 In the highest reported uric acid level (71.3 mg/dL), sequential hemodialysis sessions were required for effective treatment. 8

Transition and Follow-Up

After completing rasburicase (3-5 days): 2

• Transition to oral allopurinol for continued prophylaxis
• Ensure uric acid <8 mg/dL before resuming chemotherapy 7
• Normalize all electrolytes before next chemotherapy cycle 7

For subsequent chemotherapy cycles: 7

• Obtain nephrology consultation for all patients with previous clinical TLS 7
• Implement prophylactic rasburicase for all future cycles—these patients remain at high risk for recurrence 7
• Restart aggressive hydration 48 hours before chemotherapy 7

Comparative Efficacy: Rasburicase vs. Allopurinol

In a randomized trial, rasburicase demonstrated 2.6-fold lower uric acid exposure compared to allopurinol, with 86% reduction in uric acid within 4 hours versus only 12% with allopurinol. 1 A retrospective analysis showed only 2.6% of children receiving urate oxidase required dialysis compared to 16% receiving allopurinol. 1 This evidence strongly supports rasburicase as first-line therapy for established TLS.