Tumour Lysis Syndrome

Life-threatening metabolic syndrome that occurs due to rapid destruction of a large number of tumour cells leading to toxic changes in ECF composition, namely:

Epidemiology and Risk Factors

Pathophysiology

Chemotherapy causes death of large number of tumour cells causes a release of cellular contents:

  • Potassium
    The dominant intracellular cation.
  • Phosphate
  • Purines
    Metabolised to uric acid by metabolic pathways. Uric acid is:
    • Renally cleared by a saturatable pathway
      Production of uric acid occurs much more rapidly than excretion, so in situations of purine excess a high amount of uric acid builds up.
    • Weakly soluble
      Precipitates in fluids, namely:
      • Renal tubules
      • Joints

Notably, primates are relatively unique in the animal kingdom in their inability to natively convert uric acid to the fairly harmless allantoin.

Aetiology

TLS occurs most commonly:

  • In high-volume malignancies:
    • Bulky solid tumours
    • Haematological malignancies
  • Following treatment
    • Chemotherapy
    • Radiotherapy

TLS may occasionally occur in absence of chemotherapy.

Clinical Features

Assessment

History:

Exam:

Investigations

Bedside:

  • ECG
    Hyperkalaemic changes.

Laboratory:

  • Blood
    • UEC
      • AKI
      • Potassium
      • Calcium
      • Magnesium
    • LDH
    • Urate

Imaging:

Other:

Diagnostic Approach and DDx

Management

  • Prevent with uric acid suppression
  • Cease nephrotoxins
  • Fluid resuscitation
  • Consider urinary alkalinisation
  • RRT if refractory

Resuscitation:

  • C
    • Arrhythmia
      Secondary to hyperkalaemia. Standard treatment applies.

Specific therapy:

  • Pharmacological
    • Cease nephrotoxins
    • Urinary alkalinisation
      Target serum HCO3- >28mmol/L; aiming to prevent urate crystallisation.
  • Procedural
    • RRT
      May be required for hyperkalaemia or hyperphosphataemia.

Supportive care:

Disposition:

Preventative:

The pathology of methaemoglobinaemia is covered under Methaemoglobinaemia.

  • Intravenous hydration
  • Uric acid suppression
    • Rasburicase
      Recombinant enzyme that catalyses metabolism of uric acid to allantoin, preventing uric acid buildup.
      • May cause methaemoglobinaemia
      • 15% develop an antibody response to rasburicase
    • Allopurinol
      ↓ Uric acid formation by inhibiting xanthine oxidase.
      • Leads to formation of xanthine
      • Less preferred to rasburicase as xanthine is accumulated, which can itself cause renal failure
      • Ineffective once uric acid is already ↑

Marginal and Ineffective Therapies

Anaesthetic Considerations

Complications

Prognosis

Key Studies

References