Tumor lysis syndrome

Definition

Massive release of intracellular products from malignant cells after antitumor rx or spontaneously, resulting in constellation of metabolic and subsequent clinical derangements (see Cairo-Bishop below):

1. Hyperuricemia
2. Hyperkalemia
3. Hyperphosphatemia
4. Hypocalcemia

Etiology

1. Usually occurs within 1-5 days of starting chemotherapy or radiation for rapidly growing tumors (esp leukemia/lymphoma)
2. Can present spontaneously in certain lymphoproliferative malignancies before they are diagnosed
3. Categorized according to tumor classification (heme v. solid tumor) and relationship to antitumor rx (spontaneous v. treatment-associated)

Epidemiology

1. Most common among non-Hodgkin lymphoma (esp. Burkitt lymphoma), acute and chronic leukemia
2. Solid tumors (rare): metastatic breast CA, small cell and NSC lung CA, seminoma, invasive thymoma, metastatic medulloblastoma, Merkel cell CA, ovarian CA, rhabdomyosarcoma, metastatic melanoma, vulvar CA

Pathophysiology

1. Lysed tumor cells release nucleic acid metabolites, phosphorus and potassium into circulation
2. Nucleic acids degrade into purine metabolites which are then processed by xanthine oxidase into uric acid (excreted in urine)
3. Phosphorus binds calcium leading to hypocalcemia

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

Signs/Symptoms

1. Hyperuricemia (nausea, vomiting, lethargy, renal failure)
2. Hyperkalemia (arrythmias)
3. Hyperphosphatemia (renal failure)
4. Hypocalcemia (anorexia, cramping, tetany, confusion, seizures, V tach/torsades)
5. Acute renal failure

Work Up

1. CBC, Chem (including phos, ionized Ca)
2. Uric Acid, LDH
3. UA
4. Lactate
5. ECG (hyperK, hypoCa)

Imaging

Avoid IV contrast

Management

1. Hypocalcemia (≤ 7mg/dL or 25% dec in baseline)
   1. Calcium gluconate 50-200mg IV (only if symptomatic)
2. Hyperphosphatemia (≥4.5 mg/dL or 25% increase; ≥ 6.5mg/dL in children)
   1. Aluminum hydroxide (50-150mg/kg PO q4-6h)
   2. Dialysis if refractory
3. Hyperuricemia (≥8mg/dL or 25% increase)
   1. Allopurinol 10mg/kg/d PO q8 OR 200-400 mg/m2 IV q12; renally dosed
      1. Inhibition of xanthine oxidase can last 18-30h
      2. Acts slowly and only against FUTURE production of uric acid
   2. Urate Oxidase Rx (eg Rasburicase 0.05-0.2mg/kg IV)
      1. uric acid final product of purine metabolism in humans; in mammals urate oxidase converts uric acid to allantoin (5-10x more soluble)
      2. Can be used for BOTH prevention and treatment
      3. Expensive
4. Hyperkalemia (see Hyperkalemia)

Diuretics (only if euvolemic)

Urine Alkalinization

1. NaHCO3 to urine pH >= 7.0
2. uric acid solubility increases in alkaline environment
3. no better than NS hydration
4. not currently recommended

Acute Kidney Injury (Cr > 1.5)

1. Hydration with NS: goal UO 3L/24h
   1. decreases uric acid concentration in serum and renal tubules and reduces uric acid precipitation
   2. if vol overload-->dialysis

Dialysis (criteria)

1. K > 6mEq/L
2. Significant renal insufficiency
3. Uric Acid > 10 mg/dl
4. Symptomatic hypocalcemia
5. Serum phosphorus > 10mg/dl

Disposition

Admission

Cairo-Bishop Definitions

1. Laboratory Tumor Lysis SyndromeUric acid level: ≥ 8 mg/dL or 25% increase from baseline
2. Potassium level: ≥ 6.0 mEq/L or 25% increase from baseline
3. Phosphorus: ≥ 6.5 mg/dL for children Phosphorus concentration: ≥ 4.5 mg/dL for adults or 25% increase from baseline
4. Calcium level: ≤ 7 mg/dL or 25% decrease from baseline
5. Clinical Tumor Lysis Syndrome: Laboratory tumor lysis syndrome plus 1 or more of the following criteria:
6. Creatinine > 1.5 times upper limit of age-adjusted reference range
7. Cardiac dysrhythmia or sudden death Seizure

Source

EM Practice March '10