In a 50‑year‑old man with bulky diffuse large B‑cell lymphoma who develops tumor‑lysis syndrome 24 hours after the first R‑CHOP cycle (nausea, vomiting, oliguria, hyperkalemia, hyperphosphatemia, hypocalcemia, uric acid 570 µmol/L), what medication should be given in addition to aggressive intravenous hydration?

Rasburicase for Tumor Lysis Syndrome

Give rasburicase 0.2 mg/kg IV immediately in addition to aggressive hydration. 1, 2, 3, 4

Why Rasburicase is the Correct Answer

This patient has clinical tumor lysis syndrome (TLS) with all four metabolic derangements plus acute kidney injury manifesting as oliguria—a life-threatening emergency requiring immediate intervention. 1

• The American Society of Hematology and European Hematology Association explicitly recommend rasburicase for all patients with clinical TLS, which this patient clearly has (hyperkalemia K=6, hyperphosphatemia PO4=3, hypocalcemia Ca=1.2, hyperuricemia UA=570 µmol/L, plus decreased urine output). 1, 2

• Rasburicase converts uric acid to allantoin within 4 hours, achieving undetectable levels by 48 hours—far superior to allopurinol which only prevents new uric acid formation. 5, 6

• In randomized trials, rasburicase reduced mean uric acid area-under-curve from 329±129 to 128±70 mg/dL/hour (p<0.001) compared to allopurinol, with 97-100% response rates in achieving uric acid control. 1

• Even in anuric patients, rasburicase reduces metabolic burden and facilitates earlier renal recovery once dialysis begins. 3

Why the Other Options Are Wrong

Lasix (Furosemide) Alone is Inadequate

• Loop diuretics are contraindicated in established oliguria/anuria despite adequate hydration—they only work when residual renal function exists. 1, 3, 4

• Guidelines explicitly state loop diuretics should NOT be used in patients with anuria or oliguria despite adequate volume resuscitation. 3, 4

• Furosemide may be added AFTER rasburicase to maintain urine output ≥100 mL/hour, but only if the patient is adequately hydrated and still producing some urine. 1, 2

Allopurinol is Too Slow

• Allopurinol only prevents NEW uric acid formation by inhibiting xanthine oxidase—it does nothing about the existing massive uric acid burden already causing renal shutdown. 7, 8, 5

• This patient needs immediate uric acid clearance, not prevention of future production. 2, 4

• Allopurinol is appropriate for TLS prophylaxis 24-48 hours before chemotherapy, not for treating established clinical TLS. 3

Complete Management Algorithm

Immediate Actions (First 30 Minutes)

• Administer rasburicase 0.2 mg/kg IV over 30 minutes through central venous access immediately. 2, 3, 4

• Continue aggressive IV hydration at 150-200 mL/hour (approximately 4-5 L/m²/day) to maintain urine output ≥100 mL/hour. 1, 3

• Start continuous ECG monitoring for hyperkalemia-induced arrhythmias (K=6 is life-threatening). 1, 2, 3

Hyperkalemia Management (K=6 mmol/L)

• Give calcium gluconate 50-100 mg/kg IV over 2-5 minutes immediately to stabilize cardiac membrane. 1, 2, 3, 4

• Follow with insulin 0.1 units/kg IV plus 25% dextrose 2 mL/kg IV to shift potassium intracellularly (onset 15-30 minutes, duration 4-6 hours). 1, 2, 3

• Add sodium polystyrene sulfonate 1 g/kg orally or by enema for ongoing potassium removal. 1, 3, 4

Phosphate and Calcium Management

• Do NOT treat the hypocalcemia (Ca=1.2) beyond the initial calcium gluconate dose for cardiac stabilization—further calcium administration with hyperphosphatemia (PO4=3) will precipitate calcium-phosphate crystals and worsen renal injury. 1, 3, 4

• Only treat hypocalcemia if patient develops tetany, seizures, or prolonged QT interval. 1, 4

• For hyperphosphatemia, consider aluminum hydroxide 50-100 mg/kg/day divided in 4 doses if PO4 remains elevated. 1

Monitoring Parameters

• Recheck potassium every 2-4 hours after initial treatment. 2, 3, 4

• Monitor uric acid, electrolytes, phosphate, calcium every 4-6 hours for first 24 hours. 2, 3, 4

• Measure hourly urine output—target ≥100 mL/hour. 1, 2, 3

When to Add Loop Diuretics

• Only add furosemide 40-80 mg IV if:
  • Patient is adequately volume resuscitated (assess skin turgor, mucous membranes, blood pressure) 3
  • Urine output remains <100 mL/hour despite adequate hydration 1, 2
  • Patient is NOT anuric 3, 4
  • No obstructive uropathy present 1, 3

Urgent Dialysis Indications

Call nephrology immediately for hemodialysis if: 1, 2, 3, 4

• Anuria persists despite aggressive hydration and rasburicase 3, 4
• Severe refractory hyperkalemia ≥6 mmol/L unresponsive to medical management 2, 3, 4
• Progressive respiratory distress from fluid overload 3
• Symptomatic hypocalcemia refractory to treatment 3

Critical Pitfalls to Avoid

• Never use allopurinol concurrently with rasburicase—this causes xanthine accumulation and removes substrate for rasburicase. 2

• Never alkalize urine in patients receiving rasburicase—this increases calcium-phosphate precipitation risk without benefit since rasburicase rapidly degrades uric acid to allantoin. 4

• Never delay dialysis in anuric patients—waiting for medical management when kidneys have shut down increases mortality from hyperkalemia-induced cardiac arrest. 4

• Never give loop diuretics to anuric patients—they are ineffective in complete renal shutdown and delay appropriate dialysis. 3, 4

• Never treat asymptomatic hypocalcemia aggressively in the presence of hyperphosphatemia—this causes metastatic calcification and worsens renal function. 3, 4

Expected Outcomes with Rasburicase

• Uric acid levels drop significantly within 4 hours and reach undetectable levels by 48 hours. 5, 6

• Hemodialysis (if needed) provides uric acid clearance of 70-100 mL/min and lowers plasma uric acid by approximately 50% per 6-hour session while correcting hyperkalemia. 3

• Early rasburicase administration prevents progression to complete renal failure, cardiac arrhythmias, seizures, and death. 2, 9