Why hypocalcemia in tumor lysis syndrome

Published online July 15, Purpose : Tumor lysis syndrome is characterized by hyperuricemia, hyperphosphatemia, hyperkalemia and hypocalcemia due to destruction of tumor cells. The purpose of this study is to estimate in children the incidence, onset time, differences in outcomes between hemodialysis and conservative therapy, and predictive factor of tumor lysis syndrome before treatment with chemotherapy.

Methods : Subjects were children who had received induction chemotherapy from January to December We reviewed 12 patients who developed tumor lysis syndrome, and retrospectively analyzed their data on WBC, Hb, platelet, LDH, uric acid, phosphorus, potassium, calcium, BUN and creatinine. Co CS et al.

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Eur J Nucl Med 11 : 33— Jankovic M et al. Am J Pediatr Hematol Oncol 7 : — Masera G et al. Navolanic PM et al. Overall, studies confirm that it is a relatively safe drug with minimal incidence of side effects.

However, one aspect of this agent that precludes its use in many institutions, is its high cost. Alkalinization promotes the conversion of uric acid to a more soluble urate salt, which in turn decreases the potential for urate crystal precipitation.

Agents such as sodium bicarbonate 50 to mEq per liter of IV fluid with intravenous fluids or acetazolamide to IV daily to stimulate an alkaline diuresis have been used for this purpose.

However, some studies suggest that hydration with intravenous fluids alone may be just as effective at minimizing uric acid precipitation. And a TLS expert panel recommends alkalinization of the urine only in patients with metabolic acidosis. The role of dialysis in the prevention of tumor lysis syndrome in adults is unclear. However, two studies have shown beneficial prophylactic effects in the pediatric population. TLS, when clinically evident, is an emergency that can obviate the possibility of using chemotherapy and can even result in death.

Once TLS has developed, parameters such as heart rate, blood pressure, urine output, respiration rate, serum uric acid level, serum electrolyte levels, and renal function should be monitored every 6 hours for the first 24 hours.

Other parameters-such as blood cell count, serum lactate dehydrogenase level, serum osmolality, blood gases, acid-base equilibrium, cardiac function via electrocardiogram , and body weight-should be assessed every 24 hours.

This monitoring can be achieved most efficiently in an ICU or on a medical oncology floor with well-trained staff. If prophylaxis has failed, then therapy centers on correction of the metabolic disturbances. Loop diuretics or mannitol may be used in conjunction with aggressive fluid-loading to promote aggressive diuresis.

Hyperkalemia must be treated rapidly and aggressively because of its potential for causing lethal cardiac arrhythmias. This shifts potassium into the intracellular space. Loop diuretics can also be used to promote potassium excretion. Phosphate binders can also be given to decrease the gut absorption of phosphate, but these agents may be of minimal benefit acutely. Aluminum hydroxide is one such agent and can be given orally 30 to 60 mL every 4 to 6 hours ; this will bind any free phosphate in the intestine and prevent its absorption.

Correcting hypocalcemia via replacement is discouraged because of the risk of metastatic precipitation of calcium deposits the calcium-phosphate product will already be increased. In the event that prevention fails, therapy is similar to prevention methods. This abnormality is one potential cause of acute renal failure associated with TLS. Role of urinary alkalinization.

Urinary alkalinization is often used as a prophylactic measure. However, it is not a universal recommendation for the management of established TLS.

Allopurinol is a key agent in the management of TLS. Allopurinol acts by competitively inhibiting xanthine oxidase, thereby preventing the conversion of xanthine to uric acid. When used for treatment, allopurinol is used in dosages similar to prophylactic dosages. One potential downside of this therapy is that in rare cases, treatment with allopurinol can still result in acute renal failure.

Because allopurinol, via its metabolite oxipurinol, prevents the metabolism of xanthine to uric acid, xanthine accumulates. Build-up of xanthine has been shown to be a rare cause of renal failure. This complication may be avoided with good hydration.

Another downside of this therapy is that allopurinol does not degrade the uric acid already present; thus, lower levels are not realized for at least 1 to 2 days. Urate oxidase rasburicase. This agent is not only used for the prophylaxis of TLS, but is also indicated for its treatment. The superior efficacy of rasburicase in the treatment of hyperuricemia associated with TLS has been demonstrated in many reports.

In fact, hyperuricemia can be reversed by the use of rasburicase after allopurinol failure. If the tumor lysis is massive, an increase of the dosage to twice daily may be needed. Recent data suggest that a single dose of 1. Patients being considered for rasburicase who potentially have glucosephosphate dehydrogenase deficiency G6PD , as indicated by the medical history, should be screened for G6PD; hydrogen peroxide, a product of uric acid breakdown, can cause severe hemolysis in patients with G6PD deficiency.

Brand names are listed in parentheses only if a drug is not available generically and is marketed as no more than two trademarked or registered products.

More familiar alternative generic designations may also be included parenthetically. Dialysis should be initiated early in patients with worsening renal failure despite optimal medical therapy. Dialysis should also be considered in those patients who cannot establish sufficient diuresis on their own after a trial of aggressive fluid-loading and the use of loop diuretics. In general, standard, intermittent hemodialysis is preferred to peritoneal dialysis because of its better efficacy in removing uric acid and phophorus.

Intermittent hemodialysis has the drawback of poor control of serum phosphorus and rebound hyperkalemia. Continuous arteriovenous hemodialysis CAVHD , continuous arteriovenous hemofiltration CAVH , and continuous venovenous hemofiltration CVVH have demonstrated effectiveness in those patients who cannot tolerate conventional intermittent hemodialysis. TLS is a major cause of morbidity and mortality in cancer patients worldwide and can be an economic burden to healthcare centers. Risk factor identification and prevention are the ideal modalities with which to approach this condition.

Prevention of TLS will reduce mortality in already fragile patients. In cases where prevention fails, prompt and aggressive treatment of the various metabolic derangements associated with this syndrome is essential. Acute renal failure, seizures, and cardiac arrhythmias are the most lethal consequences of TLS.

Effective prophylaxis and prompt, appropriate treatment should TLS develop can reduce healthcare costs by decreasing the number of intensive care days and by delaying dialysis.

Financial Disclosure: The authors have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article. Acute tumor lysis syndrome in patients with high-grade non-Hodgkin's lymphoma. Am J Med. Renal and metabolic complications of undifferentiated and lymphoblastic lymphomas. Medicine Baltimore. Acute tumor lysis syndrome. A review of 37 patients with Burkitt's lymphoma.

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