ABC Medical Notes.com

About

• A metabolic complication that can occur during chemotherapy or radiotherapy for certain haematological malignancies and very occasionally solid tumours.

Aetiology

• Rapid tumour cell turnover leads to metabolic derangements

Risk Factors

• High tumour burden, High grade tumours with rapid cell turnover
• Pre-existing renal impairment or renal involvement by tumour
• Increased age, Treatment with highly active, cell-cycle specific agents
• Avoid Concomitant use of drugs that increase uric acid levels including

Drugs to avoid that increase Uric acid

• Alcohol, ascorbic acid, aspirin, caffeine, cisplatin, diazoxide, thiazide diuretics
• Adrenaline (epinephrine), ethambutol, levodopa, methyldopa, nicotinic acid
• Pyrazinamide, phenothiazines and theophylline

High-risk patients

• Burkitt's or Burkitt's-like Lymphoma
• Lymphoblastic Lymphoma
• ALL WCC > 100 x 10⁹/l
• AML WCC > 100 x 10⁹/l
• CML in blast crisis WCC > 100 x 10⁹/l
• High-grade Lymphoma with bulky disease defined by LDH more than twice upper limit of normal or tumour bulk >10 cm in diameter

Clinical

• Patients may experience symptoms of chemotherapy and underlying tumour. Correlation with lab results needed.
• Low calcium : cramps and spasms, paraesthesias, tetany, arrhythmias, heart block, hypotension, prolonged QT interval) and confusion, delirium, hallucinations and seizures
• High phosphate :nausea, vomiting, diarrhoea, lethargy and seizures
• High urate: acute gout, AKI

Investigations

• Raised urea and creatinine progressing to AKI
• High uric acid, High Potassium, High Phosphate, High LDH
• Low calcium, Reduced eGFR

Pathology

• Tissue breakdown and release of cell contents

Prevention

• Optimise hydration before chemotherapy aiming for 2-3 litres. If given IV then do not add potassium must not be added to the hydration fluid.
• Allopurinol should be considered for up to 7 days. Usually, 300 mg/day is effective but it may be prudent to increase the dose of allopurinol. Rasburicase may be preferred in the presence of deteriorating biochemical or clinical markers or high-risk patients.
• Start 24-48 hours prior to chemotherapy if possible. The dose should be reduced when creatinine clearance is < 20ml/min.
• Rasburicase prophylaxis alongside hydration is recommended for high-risk patients as detailed above.

Management

• Ensure well hydrated and good diuresis with IV fluids such as 3-4 litres/day or more to ensure a good urine output. Monitor urine output hourly. Maintain a strict fluid balance chart and place the urinary catheter. Reassess fluid balance formally every 4 hrs.
• Weigh twice daily. Any fluid retention may be treated with IV Furosemide or mannitol especially if weight gain is > 3 kg. In the event of severe oliguria or anuria, a single dose of furosemide may be considered to improve or initiate urinary output
• Rasburicase: Consider for 3-7 days depending on clinical and biochemical parameters: No dose adjustment is necessary in renal or hepatic impairment. Side effects: commonly fever, vomiting and nausea. Less commonly diarrhoea, headache, allergic reactions and haemolytic anaemia (in those with G6PD deficiency)
• Obtain biochemistry samples 4 hourly for the first 24 hours after chemotherapy these should include: Potassium, phosphate, calcium, magnesium, urea, creatinine and urate
• Vital signs (T, BP, RR, HR, O2 sats) 4-6 hourly minimum, including CVP as clinically indicated. Hourly urine output measurements. ECG as a baseline and continuous monitoring as indicated ( see Hyperkalemia)
• Hypocalcaemia: Avoid treatment of asymptomatic hypocalcaemia as the risk of precipitating metastatic calcification is high, especially in the setting of hyperphosphataemia. Symptomatic hypocalcaemia should be treated with IV calcium gluconate with the aim to treat the symptoms but not to normalize the biochemical parameters
• Hyperphosphataemia: If hydration and timely administration of rasburicase do not prevent significant hyperphosphataemia, it can be hard to control phosphate levels other than by dialysis. Avoid calcium supplements except in neuromuscular irritability.

References

• Management of the Prevention and Treatment of Tumour Lysis Syndrome in Adults