Prevention and management

• Monitor daily weight bd, urine output, fluid balance, renal function, serum potassium, phosphate, calcium, uric acid and ECG for 72h after initiation of chemotherapy; monitor parameters at least three times daily in patients with TLS.

• Ensure aggressive intravenous hydration:

- Aim for urine output >100mL/h (>3L/d) and total input >4Ld (3L/m2/d) from 24-48h prior to chemotherapy and in high risk patients, until 48-72h after completion of chemotherapy.

- Frusemide (20mg IV) may be given cautiously to maintain adequate diuresis in well hydrated patients; may be used to treat hyperkalaemia or fluid overload but may cause uric acid or calcium deposition in dehydrated patients; no proven benefit in initial treatment of TLS.

• Prevent hyperuricaemia:

- Allopurinol: xanthine oxidase inhibitor; 300-600mg/d PO for prophylaxis if renal function normal (100mg/d if creatinine >100mmol/L) up to max 500mg/m2/d for treatment of TLS; may be given IV if necessary (max 600mg/d); side effects: rash, xanthine urolithiasis; reduce dose in renal impairment or mercaptopurine, 6-thioguanine or azathioprine therapy.

- Rasburicase: recombinant urate oxidase; converts uric acid to water soluble metabolites without increasing excretion of xanthine and other purine metabolites; very rapidly 5 uric acid levels and simplifies management of high risk patients; dose 200mg/kg/d IVI over 30 mins for 5-7d; recommended in Burkitt lymphoma, high count leukaemia and as rescue treatment in hyperuricaemia plus rapidly rising creatinine, oliguria, phosphate > 2mmol/L or K+ >5.5mmol/L; side effects: fever, nausea, vomiting; less common: haemolysis, allergic reactions or anaphylaxis; contraindicated in G-6-PD deficiency and pregnancy.

• Alkalinisation of urine:

- Not routine; administer NaHCO3 PO (3g every 2h) or IV through central line (500mL 1.26% NaHCO3 over 1h; 1L 5% dextrose over 4h; 500mL 0.9% NaCl over 1h, repeated 6 hourly) to increase urinary pH to 7.0 and maximise uric acid solubility.

- Risk of more severe symptoms or hypocalcaemia and increased calcium phosphate precipitation in tubules.

- Requires close monitoring of urinary pH (test all urine passed), serum bicarbonate and uric acid; withdraw IV sodium bicarbonate when serum bicarbonate >30 mmol/L, urinary pH>7.5 or serum uric acid normalised.

• Control of electrolytes

- Hyperkalemia: treat aggressively:

1 Restrict dietary K+ intake and eliminate K+ from IV fluids.

2 Use K+-wasting diuretics with caution.

3 Measure arterial blood gases (correction more difficult if acidosis).

4 K+ >5mmol/L, start calcium resonium 15g PO qds and increase hydration; recheck K+ after 2h. 561

5 K+ >6mmol/L, check ECG; commence IVI of 50mL 50% dextrose with 20 U actrapid insulin over 1h.

6 ECG changes or K+ >6.5mmol/L, give 10mL calcium gluconate 10% or calcium chloride 10% IV cardioprotection.

- Hyperphosphataemia:

1 Commence oral phosphate binding agent, e.g. aluminium hydroxide 20-100mL or 4-20 capsules daily or Sevelamer 2.4-4.8g/d in divided doses; adjust dose according to serum phosphate.

2 Infuse 50mL 50% dextrose with 20 U actrapid insulin IV over 1h.

- Seek renal and critical care consultations early if initial measures fail to control electrolyte abnormalities or renal failure.

- Dialysis indicated if persistent hyperkalaemia (>6mmol/L) or hyperphosphataemia (>3.33mmol/L) despite treatment, fluid overload, rising urea or creatinine (>880mmol/L), hyperuricaemia (>0.6mmol/L) or symptomatic hypocalcaemia.

- Haemodialysis achieves better phosphate and uric acid clearance than peritoneal dialysis.

0 0

Post a comment