Tumour Lysis Syndrome

OVERVIEW

  • oncological emergency due to turnover of high cell mass malignancies resulting in severe metabolic derangement

HISTORY

  • lymphoproliferative malignancy + chemotherapy, radiotherapy or corticosteroids
  • can occur spontaneously
  • normally 12-72h hours post chemo
  • GI upset
  • oedema
  • fluid overload
  • haematuria
  • symptoms of metabolic derangements (see below)

RISK FACTORS

  • large tumour burden
  • LDH > 1500 IU
  • extensive marrow involvement
  • high tumour sensitivity to chemotherapeutic agents
  • ALL
  • Burkitt lymphoma
  • chemotherapy – cisplatin, etoposide, fludarabine, intrathecal methotrexate, paclitaxel, ritiuximab, radiation, interferon, corticosteroids, tamoxifen

Tumours that cause TLS include:

  • poorly differentiated lymphomas, e.g. Burkitt lymphoma and high-grade non-Hodgkin lymphomas
  • leukemia, e.g. acute myeloid leukemia (AML), transformed chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL)
  • some fast-growing solid tumours such as hepatocellular carcinoma, hepatoblastoma, testicular cancer, small cell lung cancer, breast cancer and neuroblastoma

Usually occurs 12-72 hours after chemotherapy but can occur spontaneously (usually less hyperphosphatemia in this case, presumably due to recycling of phosphate)

EXAMINATION

  • arrhythmias -> haemodynamically unstable
  • weakness
  • paraesthesia
  • tetany
  • renal failure

INVESTIGATIONS

Metabolic derangement

  • Hyperkalaemia
  • Hyperphosphataemia
  • Hypocalcaemia
  • Hyperuricaemia
  • High creatinine and urea consistent with renal impairment
  • Low HCO3 consistent with metabolic acidosis +/- hyperlactemia
  • High lactate dehydrogenase (LDH)

MANAGEMENT

Prevention

  • identify those at risk
  • hydration (pre chemotherapy)
  • monitoring of electrolytes
  • allopurinol

General Management of TLS

Establish severity using the Cairo-Bishop classification

1. hydration – aggressive +/- diuretics
2. metabolic correction
3. support of renal failure

Hyperuricemia

  • > 476 micromol/L or 25% increase from baseline
  • cell lysis -> increased purine nucleic acids into the circulation -> metabolized to uric acid -> renal failure

(1) inhibit the formation of uric acid -> hydration, xanthine oxidase inhibitors (allopurinol – up to 800mg/day), urate oxidase/rasburicase (catalyzes oxidation of uric acid to allantoin), no evidence for alkalinisation of urine
(2) increasing renal clearance -> dialysis

Hyperkalaemia

  • >6.0 mmol/L or increase in 25% from baseline
  • rapid expulsion of intracellular K+ into circulation -> ventricular arrhythmias, weakness, paraesthesia, GI upset

(1) membrane stabilisation -> calcium gluconate
(2) shift of K+ intracellularly -> insulin/glucose, sodium bicarbonate, beta-agonists
(3) reduction of K+ load -> resonium, diuretics, dialysis

Hyperphosphataemia

  • >1.45mmol/L or 25% increase
  • release of intracellular PO4- due to cell lysis
  • tumour cells can have up to 4x the normal levels
  • tubular transport mechanisms become overloaded

-> phosphate binders
-> dialysis

Hypocalcaemia

  • precipitation of calcium phosphate due to rapid increase in PO4
    -> muscle cramps, tetany, arrhythmias, seizures, renal failure from nephrocalcinosis

-> calcium gluconate only in symptomatic patients as there is a risk of precipitation with PO4-

Renal Failure

  • multi-factorial
  • volume depletion
  • cytokine mediated reduction in renal perfusion
  • ischaemic ATN
  • precipitation of uric acid crystals
  • calcium phosphate nephropathy

References and Links

LITFL

Journal articles and textbooks

  • Cammalleri L, Malaguarnera M. Rasburicase represents a new tool for hyperuricemia in tumor lysis syndrome and in gout. Int J Med Sci. 2007 Mar 2;4(2):83-93. PMC1838823.
  • McCurdy MT, Shanholtz CB. Oncologic emergencies. Crit Care Med 2012;40:2212-2222. PMID: 22584756

Social media and other web resources


CCC 700 6

Critical Care

Compendium

Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also the Innovation Lead for the Australian Centre for Health Innovation at Alfred Health and Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of two amazing children.

On Twitter, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

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