In a 50-year-old man with bulky diffuse large B-cell lymphoma who develops tumor lysis syndrome (hyperkalemia, hyperphosphatemia, hypocalcemia, uric acid 570 µmol/L) and oliguria after his first R-CHOP cycle, what medication should be added to vigorous intravenous hydration?

Management of Tumor Lysis Syndrome After R-CHOP

In addition to aggressive IV hydration, you should give rasburicase 0.2 mg/kg IV immediately to this patient with clinical tumor lysis syndrome (TLS) manifesting as anuria, severe hyperkalemia (K 6 mmol/L), hyperphosphatemia (PO₄ 3 mmol/L), hypocalcemia (Ca 1.2 mmol/L), and severe hyperuricemia (uric acid 570 µmol/L ≈ 9.6 mg/dL). 1

Why Rasburicase Is the Correct Choice

• Rasburicase rapidly converts uric acid to allantoin, a highly soluble metabolite that provides uric acid clearance far faster than any other intervention, with randomized trials demonstrating mean uric acid area-under-curve of 128 ± 70 mg/dL·h versus 329 ± 129 mg/dL·h with allopurinol (p < 0.001) and response rates of 97–100% for uric acid control. 1

• The European Society for Medical Oncology and American Society of Hematology strongly recommend rasburicase for all patients who meet criteria for clinical TLS, defined by the presence of all four metabolic abnormalities (hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia) plus acute kidney injury such as oliguria or anuria. 1

• Even in anuric patients, rasburicase reduces the metabolic burden of uric acid and may aid earlier renal recovery once dialysis is started, making it essential therapy regardless of current urine output. 1

Why Allopurinol Is Incorrect in This Setting

• Allopurinol is a prophylactic agent that prevents formation of new uric acid by inhibiting xanthine oxidase, but it does nothing to clear the massive uric acid burden already present in established TLS. 2, 3

• Allopurinol should have been started 24–48 hours before chemotherapy at 300 mg orally once daily as part of TLS prophylaxis in this patient with bulky DLBCL, but once clinical TLS has developed, it is too late for allopurinol to be effective. 1

• The plasma half-life of allopurinol is only 1–2 hours, and while its active metabolite oxipurinol has a 15-hour half-life, this still provides no mechanism for rapid clearance of existing uric acid. 2

Why Furosemide (Lasix) Is Contraindicated

• Loop diuretics are contraindicated in established oliguria or anuria despite adequate hydration because they require residual renal function to work—this patient has had decreased urine output for 24 hours despite presumed hydration in the ER. 1

• Furosemide may only be added after rasburicase and only if the patient is adequately volume-resuscitated, still producing urine, and not anuric, with the goal of maintaining urine output ≥100 mL/hour. 1

• In this anuric patient, furosemide will be ineffective and may delay the urgent nephrology consultation for hemodialysis that is clearly indicated. 1

Complete Management Algorithm

Immediate interventions (within minutes):

• Administer rasburicase 0.2 mg/kg IV over 30 minutes through a central line if available. 1

• Give calcium gluconate 50–100 mg/kg IV over 2–5 minutes to stabilize the myocardial membrane against the severe hyperkalemia (K 6 mmol/L), with effects beginning within 1–3 minutes. 1, 4

• Administer rapid-acting insulin 0.1 units/kg IV plus 25% dextrose 2 mL/kg IV to shift potassium intracellularly, with onset within 15–30 minutes and duration 4–6 hours. 1, 4

• Start continuous ECG monitoring to detect arrhythmias from severe hyperkalemia. 1, 4

Concurrent interventions:

• Increase IV hydration to 150–200 mL/hour (approximately 4–5 L/m²/day) to achieve urine output ≥100 mL/hour if renal function recovers. 1

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

• Consult nephrology immediately for urgent hemodialysis, as this patient meets absolute indications: persistent anuria despite aggressive hydration plus severe refractory hyperkalemia (≥6 mmol/L). 1

Critical pitfalls to avoid:

• Do NOT treat the asymptomatic hypocalcemia beyond the initial calcium gluconate dose used for cardiac membrane stabilization, because additional calcium administration can precipitate calcium-phosphate crystals and worsen renal injury when hyperphosphatemia is present (PO₄ 3 mmol/L). 1, 4

• Do NOT add furosemide in this anuric patient—it will be ineffective and may create false reassurance. 1

• Do NOT rely on allopurinol to manage established TLS—it prevents new uric acid formation but does not clear existing uric acid. 1, 2

Monitoring Requirements

• Measure urine output hourly, targeting ≥100 mL/hour once renal function recovers. 1

• Recheck potassium every 2–4 hours after initial treatment to assess response. 1, 4

• Recheck electrolytes, uric acid, phosphate, and calcium every 4–6 hours during the first 24 hours. 1

• Continue continuous ECG monitoring throughout the acute management period. 1, 4

Expected Outcomes With Rasburicase

• Significant uric acid reduction occurs within 4 hours, with undetectable levels by 48 hours in most patients, preventing progression to irreversible renal failure, cardiac arrhythmias, seizures, and death. 1

• Hemodialysis provides uric acid clearance of approximately 70–100 mL/min and can lower plasma uric acid by about 50% with each 6-hour session while simultaneously correcting life-threatening hyperkalemia. 1

Why This Patient Developed TLS Despite R-CHOP

• This patient with bulky DLBCL should have received prephase treatment with prednisone 100 mg orally daily for 5–7 days before starting R-CHOP to prevent TLS, as recommended by the European Society for Medical Oncology for patients with high tumor burden. 5

• Prophylactic allopurinol 300 mg daily should have been started 24–48 hours before chemotherapy in this high-risk patient with bulky disease. 1

• The absence of these prophylactic measures likely contributed to the development of this severe, life-threatening TLS. 5