General Approach to Treatment

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Prevention of TLS is generally achieved by increasing the urine output and preventing accumulation of uric acid. Prophylactic strategies should begin immediately upon presentation, preferably 48 hours prior to cytotoxic therapy. Treatment modalities primarily increase uric acid solubility, maintain electrolyte balance, and support renal output.

Nonpharmacologic Therapy

Vigorous IV hydration with dextrose 5% in water with normal saline at 3 L/m /day to maintain a urine output greater than or equal to 100 mL/m2/hour is necessary, unless the patient presents with acute renal dysfunction. Alkalinization of the urine to a pH greater than or equal to 7.0 with 50 to 100 mEq/L of sodium bicarbonate has been used to promote uric acid solubility for excretion. This measure is controversial because xanthine and hypoxanthine are less soluble at alkaline pH potentially leading to crystallization, especially during and after allopurinol therapy (Fig. 99-6).54 Medications that increase serum potassium (angiotensin-converting enzyme [ACE] inhibitors, spironolactone) or block tubular resorption of uric acid (probenecid, thiazides) should be discontinued. Nephrotoxic agents such as amphotericin B or aminoglycos-ides should also be avoided. Hemodialysis may be required in patients who develop anuria or uncontrolled hyperkalemia, hyperphosphatemia, hypocalcemia, acidosis or volume overload.

Low Risk

• Normal une acid luvti flflss inan 10 mij'dL)

• Solid tumor, KodgKin disease, chronic niyfilwj HHJkflTii.l

• WBC lass than or aqua) lo-SO.OCKVmiw1

• LDH less Mian cr equal to 2 limes normal ' r.-i id cyido«ic therapy intensity

• No tumor inMttJliafi in kidn&ys

High Risk

■ Elevated uric acid leva) (giHlsftnn or equal to 10 mg/dL)

• W6C grails Hian 5&.0iKYmm3

* LDH grealer man 2 limes normal

* Aggressiv chemotherapy

■ Xidniy 1uiw(y iniiUrabon

Orel allapunnol (IV ¿1 uns&fe to loferflte or take oral medi)

Daily monitoring of li iK acid



Continue mrough (ytolaxic therapy

Uric atid Ibvöj increase

RUSDurirjaSSi iijCt- prcijr 10 cytotoxic Iherapy

Mtiniltir uric acid every 6 hours


Uric aod levefe increase

Adminislet daily until normalized

Ufte normal

Do not continue

FIGURE 99-7. Prophylaxis and treatment of hyperuricemia associated with TLS. (ALL, acute lymphoblastic leukemia; AML, acute myelogenous leukemia.) (From Refs 35, 36.)

Pharmacologic Therapy

Pharmacologic prevention strategies for TLS are aimed at low- and high-risk patients (Fig. 99-7). Allopurinol is a xanthine oxidase inhibitor that is used for prevention only because it has no effect on pre-existing elevated uric acid. Rasburicase is a recombinant form of urate oxidase that is useful for both prevention and treatment, but is extremely expensive (Table 99-15). Although the approved dose is 0.2 mg/kg/day for 5 days, recent studies using abbreviated courses (1-3 days) and/or lower doses (0.05-0.1 mg/kg/day) may be equally efficacious with significantly reduced cost.54 Because uric acid levels generally fall within 4 hours of the first dose, one dose may be administered with frequent, serial monitoring of the uric acid level for repeat dosing if necessary (Fig. 99-7). Of note, rasburicase continues to break down uric acid in blood samples drawn from patients. This can be avoided by immediately placing the sample in an ice bath for processing to avoid falsely lowered uric acid levels.

Electrolyte disturbances that develop in patients with TLS should be aggressively managed to avoid renal failure and cardiac sequelae. One exception pertains to the use of IV calcium for hypocalcemia. Adding calcium may cause further calcium phosphate precipitation in the presence of hyperphosphatemia and should be used cautiously.

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