- TABLE OF CONTENTS
- Superior vena cava syndrome
- Venous thromboembolic complications
- Spinal cord compression
- Signs and symptoms
- Tumor lysis syndrome
- Signs and symptoms
- Suggested reading
- Lambert-Eaton syndrome
Compared with hypercalcemia, hyperuricemia is a less common metabolic emergency in adult cancer patients.
Hyperuricemia occurs most often in patients with hematologic disorders, particularly leukemias, high-grade lymphomas, and myeloproliferative diseases (polycythemia vera). It may occur secondary to treatment of the malignancy.
Hyperuricemia is also associated with certain cytotoxic agents (eg, tiazofurin and aminothiadiazoles). Various other drugs can contribute to hyperuricemia by increasing uric acid production or decreasing its excretion. Diuretics (thiazides, furosemide(Drug information on furosemide), and ethacrynic acid [Edecrin]) cause acute uricosuria, and hyperuricemia may occur secondary to volume contraction. Antituberculous drugs, such as pyrazinamide(Drug information on pyrazinamide) and ethambutol, as well as nicotinic acid(Drug information on nicotinic acid) (niacin) are also associated with hyperuricemia.
Extensive or aggressive tumors
Patients with extensive, anaplastic, or rapidly proliferating tumors are at greatest risk for hyperuricemia. These include patients with bulky lymphomas and sarcomas, those with chronic myelocytic leukemia or chronic lymphocytic leukemia and extreme leukocytosis, and those undergoing remission-induction chemotherapy for acute leukemia.
Individuals with preexisting renal impairment are also at risk of becoming hyperuricemic.
Patients with clinical syndromes caused by hyperuricemia present with significant elevations of serum uric acid. Gouty arthritis may be seen occasionally, but the most significant complication is renal dysfunction, particularly acute renal failure. Clinical symptoms associated with renal dysfunction vary depending on the degree of dysfunction and the timing of its development. In patients with acute renal failure, clinical symptoms may include abnormal mental status, nausea and vomiting, fluid overload, pericarditis, and seizures.
The diagnosis of hyperuricemia is based on laboratory findings of high serum uric acid levels, hyperuricosuria, and increased serum creatinine and urea(Drug information on urea) nitrogen levels.
Prognosis often depends on the etiology of the hyperuricemia.
Prophylactic measures against the development of hyperuricemia should be undertaken prior to initiation of chemotherapy. Drugs that increase serum urate levels or produce acidic urine (eg, thiazides and salicylates) should be discontinued if possible. Alkalinization of the urine should be initiated to maintain a urine pH > 7.0. Usually, sodium bicarbonate(Drug information on sodium bicarbonate) solution (50–100 mmol/L) is added to IV fluids and then adjusted so that an alkaline urinary pH is maintained. The carbonic anhydrase inhibitor acetazolamide(Drug information on acetazolamide) may be used to increase the effects of alkalinization. It is important to remember that alkalinization is secondary to the overall goal of decreasing urinary uric acid concentration by increasing urinary volume.
This xanthine oxidase inhibitor is the mainstay of drug treatment and may be started 1 to 2 days prior to cytotoxic treatment. Dosages range from 300 to 600 mg/d, and therapy is usually continued for 1 to 2 weeks or until the danger of hyperuricemia has passed.
Rasburicase(Drug information on rasburicase) (Elitek) is an antihyperuricemia drug. It has been approved by the FDA for malignancy-associated hyperuricemia in pediatric patients but is also used in adults. The usual pediatric dose is 0.15 or 0.2 mg/kg IV over 30 minutes for 5 days. The usual adult dosage is 0.15 to 0.2 mg/kg/d, based on limited studies.
In patients who develop acute oliguria, ureteral obstruction by urate calculi should be considered. This condition should be evaluated by ultrasonography or CT. Administration of IV contrast agents for pyelography should be avoided, as they may increase the risk of acute tubular necrosis.
Patients with advancing renal insufficiency and subsequent renal failure may benefit from peritoneal dialysis or hemodialysis. Dialysis has been shown to be effective in reversing renal failure caused by urate deposition.
Tumor lysis syndrome occurs due to the rapid release of intracellular contents into the bloodstream, leading to life-threatening concentrations. If the resulting metabolic abnormalities remain uncorrected, patients may develop renal failure and sudden death.
Tumor lysis syndrome most commonly develops during the rapid growth phase of high-grade lymphomas and leukemia in patients with high leukocyte counts; it is less common in patients with solid tumors. The syndrome is often iatrogenic, caused by cytotoxic chemotherapy. Because of clinicians' increased awareness of the tumor lysis syndrome during the past decade and the use of adequate prophylaxis prior to initiation of chemotherapy, there are fewer cases currently. Occasionally, the syndrome occurs following treatment with irradiation, glucocorticosteroids, tamoxifen(Drug information on tamoxifen), or interferon.
The typical patient at risk for tumor lysis syndrome tends to be young (< 25 years of age) and male and has an advanced disease stage (often with abdominal disease) and a markedly elevated lactate dehydrogenase level.
Other predisposing factors include volume depletion, concentrated acidic urine pH, and excessive urinary uric acid excretion rates.
The syndrome is characterized by hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia, and often, oliguric renal failure.
The diagnosis of tumor lysis syndrome is based on the development of increased levels of serum uric acid, phosphorus, and potassium; decreased levels of serum calcium; and renal dysfunction following chemotherapy.
The prognosis varies depending on the adequate correction of metabolic abnormalities and the underlying etiology of tumor lysis.
Patients at risk for tumor lysis syndrome should be identified before the initiation of chemotherapy and should be adequately hydrated and given agents to alkalinize the urine. Treatment with allopurinol (IV or oral) may be instituted to minimize hyperuricemia. The recommended dosage of IV allopurinol ranges from 200 to 400 mg/m2/d. This regimen should be started 24 to 48 hours before the initiation of cytotoxic treatment. The dose may be equally divided into 6-, 8-, or 12-hour increments, but the final concentration should not exceed 6 mg/mL. (For oral dosages of allopurinol and IV doses of rasburicase, see the section on hyperuricemia treatment earlier in this chapter.)
Serum electrolytes, uric acid, phosphorus, calcium, and creatinine levels should be checked repeatedly for 3 to 4 days after chemotherapy is initiated, with the frequency of monitoring dependent upon the clinical condition and the risk profile of the patient.
Established tumor lysis
Once tumor lysis is established, treatment is directed at vigorous correction of electrolyte abnormalities, hydration, and hemodialysis (as appropriate in patients with renal failure).
Cortes J, Moore JO, Maziarz RT, et al: Control of plasma uric acid in adults at risk for tumor lysis syndrome: Efficacy and safety of rasburicase alone and rasburicase followed by allopurinol compared with allopurinol alone--results of a multicenter phase III study. J Clin Oncol 28:4207-4213, 2010.
Cheuk DK, Chiang AK, Chan GC, et al: Urate oxidase for the prevention and treatment of tumor lysis syndrome in children with cancer. Cochrane Database Syst Rev 6:CD006945, 2010.