Can Tumor lysis syndrome be prevented in those who are at high risk?
• Hydration: The amount of hydration a patient requires is based on a clinical evaluation of volume status and should take into account comorbidities. Vigorous hydration is ideal, but it should be avoided in patients with impaired cardiac function or those with preexisting hypervolemia. In general, patients should receive at least 2 L/m 2 per day beginning 24 hours prior to the administration of chemotherapy, with a goal urine output of greater than 100 mL/h. Increased hydration increases tubular flow, thus enhancing uric acid and phosphate excretion and decreasing intratubular concentrations.
• Alkalinization: Acidic urine promotes the crystallization of uric acid. By contrast, in alkaline environments, uric acid is converted to urate salts, which are more soluble. In theory, the administration of bicarbonate would increase the solubility of uric acid and diminish crystal-induced injury. Maximal uric acid solubility occurs at a urine pH greater than 7.0. However, it should be noted that calcium phosphate crystals precipitate readily in alkaline environments and that xanthine and hypoxanthine crystals also precipitate at a higher urine pH. Thus the role of alkalinization in TLS is controversial and it is not routinely used.
• Allopurinol: Allopurinol and its metabolite oxypurinol are competitive inhibitors of xanthine oxidase. Xanthine oxidase is an enzyme found predominantly in the liver, which converts xanthine and hypoxanthine to uric acid. The blocking of xanthine oxidase decreases the production of uric acid. Allopurinol does not decrease the amount of uric acid already present; it only prevents the generation of additional uric acid and therefore should be started 48 to 72 hours prior to the initiation of chemotherapy.
• Rasburicase: This recombinant urate oxidase enzyme converts uric acid to allantoin, replacing the deficient enzyme in humans. Allantoin is 5 to 10 times more soluble than uric acid and is easily excreted by the kidneys. In high-risk patients, the drug should be given at least 4 hours prior to chemotherapy and continued for 3 to 5 days following initiation of chemotherapy. Rasburicase is very expensive; lower-dose and shorter-duration protocols are also used. Rasburicase will lower serum uric acid levels dramatically within 24 hours, and clinical studies have shown it to be effective in the prevention of TLS.
