Tumor lysis syndrome

Background

• Associated w/ treatment of ALL, Burkitt lymphoma, NHL
  • Rarely observed in solid tumros or without prior therapy
• Rapid turnover of tumor cells (spontaneously or after Rx) leading to release of:
  • Potassium
  • Phosphate
    • Binds Ca > hypocalcemia
  • Uric acid (converted from nucleic acids)

Risk Factors

1. High cell proliferation rate
2. Large tumor burden (LDH) > 1500 IU/L, WBC ≥ 50 x 103 cells/L
3. Extensive BM involvement
4. Tumor infiltration of the kidney

Cairo-Bishop Definition

• Laboratory Tumor Lysis Syndrome
  • Abnormality in 2 or more of the following, occurring w/in 3d before or 7d after chemo:

1. Uric acid ≥ 8 mg/dL or 25% increase from baseline
2. Potassium ≥ 6mEq/L or 25% increase from baseline
3. Phosphate ≥ 4.5 mg/dL or 25% increase from baseline (≥ 6.5 for children)
4. Calcium ≤ 7 mg/dL or 25% decrease from baseline

• Clinical Tumor Lysis Syndrome
  • Laboratory tumor lysis syndrome plus 1 or more of the following:

1. Cr > 1.5 times upper limit of age-adjusted reference range
2. Cardiac dysrhythmia or sudden death
3. Seizure

Clinical Features

1. Hyperuricemia
   1. N/V, lethargy, renal failure
2. Hyperkalemia
   1. Most immediate life-threatening element (due to dysrrhythmias)
3. Hyperphosphatemia
   1. May combine w/ Ca to precipiate in renal tubules
4. Hypocalcemia
   1. Anorexia, cramping, tetany, confusion, seizures, V-tach/torsades
5. Acute renal failure
   1. Most common cause of morbidity
   2. Usually results from uric acid precipitation within renal tubules

Work Up

1. CBC
2. Chemistry
3. Calcium, phosphate
4. Uric Acid
5. LDH
6. UA
7. ECG
   1. HyperK, hypoCa

Imaging

• Avoid IV contrast

Management

1. Agressive hydration
   1. Goal UO = 3L in 24hr
2. Urine Alkalinization
   1. NaHCO3 to urine pH >= 7.0
   2. uric acid solubility increases in alkaline environment
   3. ?Efficacy

Hypocalcemia

• ≤7 or 25% dec in baseline
  • Treat only if symptomatic (increased Ca leads to increased Ca/phos deposition)
  • Calcium gluconate 50-200mg IV

Hyperphosphatemia

• ≥4.5 or 25% increase; ≥ 6.5mg/dL in children
  • Aluminum hydroxide (50-150mg/kg PO q4-6h)
  • Dialysis if refractory

Hyperuricemia

• ≥8 or 25% increase
  • Allopurinol
    • Acts slowly; only helpful for preventing future production of uric acid
    • 10mg/kg/d PO q8 OR 200-400 mg/m2 IV q12; renally dosed
    • Inhibition of xanthine oxidase can last 18-30h
  • Urate Oxidase Rx
    • Rasburicase 0.05-0.2mg/kg IV)
    • Can be used for BOTH prevention and treatment
    • Uric acid final product of purine metabolism
      • Urate oxidase converts uric acid to allantoin (5-10x more soluble)

Hyperkalemia

• Only give Ca for cardiovascular instability (e.g.ventricular arrhythmias, widened QRS)
  • Giving Ca leads to increased Ca/phos deposition which leads to renal failure
• See Hyperkalemia for treatment options

Dialysis (Criteria)

1. K >6
2. Significant renal insufficiency
3. Uric Acid >10
4. Symptomatic hypocalcemia
5. Serum phosphorus >10

Disposition

• Admit (often to ICU)

Source

• Tintinalli
• EM Practice March '10