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):

-Hyperuricemia

-Hyperkalemia

-Hyperphosphatemia

-Hypocalcemia

Etiology

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

Epidemiology

-Most common among non-Hodgkin lymphoma (esp. Burkitt lymphoma), acute and chronic leukemia

-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

-Lysed tumor cells release nucleic acid metabolites, phosphorus and potassium into circulation

-Nucleic acids degrade into purine metabolites which are then processed by xanthine oxidase into uric acid (excreted in urine)

-Phosphorus binds calcium leading to hypocalcemia

Risk Factors

-High cell proliferation rate

-Large tumor burden (LDH) > 1500 IU/L, WBC ≥ 50 x 103 cells/L

-Extensive BM involvement

-Tumor infiltration of the kidney

Signs/Symptoms

• -Hyperuricemia (nausea, vomiting, lethargy, renal failure)
• -Hyperkalemia (arrythmias)
• -Hyperphosphatemia (renal failure)
• -Hypocalcemia (anorexia, cramping, tetany, confusion, seizures, V tach/torsades)
• Acute renal failure

Work Up

• CBC, Chem (including phos, ionized Ca)
• Uric Acid, LDH
• UA
• Lactate
• ECG (hyperK, hypoCa)

Imaging

• Avoid IV contrast

Management

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

Diuretics (only if euvolemic)

Urine Alkalinization

-NaHCO3 to urine pH >= 7.0

-uric acid solubility increases in alkaline environment

-no better than NS hydration

-not currently recommended

Acute Kidney Injury (Cr > 1.5):

-Hydration with NS: goal UO 3L/24h

--decreases uric acid concentration in serum and renal tubules and reduces uric acid precipitation

--if vol overload-->dialysis

Dialysis (criteria)

K > 6mEq/L

Significant renal insufficiency

Uric Acid > 10 mg/dl

Symptomatic hypocalcemia

Serum phosphorus > 10mg/dl

Disposition

Admission

*Cairo-Bishop Definitions

Laboratory Tumor Lysis SyndromeUric acid level: ≥ 8 mg/dL or 25% increase from baseline

Potassium level: ≥ 6.0 mEq/L or 25% increase from baseline

Phosphorus: ≥ 6.5 mg/dL for children Phosphorus concentration: ≥ 4.5 mg/dL for adults or 25% increase from baseline

Calcium level: ≤ 7 mg/dL or 25% decrease from baseline

Clinical Tumor Lysis SyndromeLaboratory tumor lysis syndrome plus 1 or more of the following criteria:

Creatinine > 1.5 times upper limit of age-adjusted reference range

Cardiac dysrhythmia or sudden death Seizure

Source

EM Practice March '10