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. leukemias and 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
Si/Sy
-Hyperuricemia (nausea, vomiting, lethargy, renal failure)
-Hyperkalemia (arrythmias)
-Hyperphosphatemia (renal failure)
-Hypocalcemia (anorexia, cramping, tetany, confusion, seizures, v tach/torsades)
- Acute Renal Failure usually accompanies the above
Work Up
-CBC c dif and peripheral smear
-Chem -7, Mg, Phos, ionized Ca
-UA
-Uric Acid
-LDH
-Lactate
-EKG (hyperK, hypoCa)
Imaging
Avoid IV contrast
Management
Hypocalcemia (≤ 7mg/dL or 25% dec in baseline)
-Ca 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
--$$$
Hyperkalemia (see hyperK page)
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