Sarah Klemencic, MD; Jack Perkins, MD

Disclosures

Western J Emerg Med. 2019;20(2):316-322. 

In This Article

Tumor Lysis Syndrome

Tumor lysis syndrome (TLS) is a rare but potentially deadly metabolic crisis with an estimated mortality of 29–79%.[32–35] With early and aggressive intervention, the mortality rate in TLS can be impacted significantly. TLS is the most frequently encountered metabolic complication of hematologic malignancy by an EP.[32–37] Tumor lysis syndrome occurs due to the liberation of intracellular components into the circulation.32 It rises in incidence with malignancies that have rapid cell turnover (e.g., hematologic malignancies).[33] While TLS most commonly occurs subsequent to chemotherapy, it may occur spontaneously in patients with hematologic malignancies (especially acute leukemias).[34,35] Patients with solid tumors rarely develop TLS after chemotherapy.[34] Those with baseline renal dysfunction, elderly patients with comorbidities, and patients taking multiple medications are at greater risk of developing TLS.[32–35] Presenting symptoms can include fatigue, signs of dehydration, seizures, cardiac dysrhythmia, nausea and vomiting.[36–37]

The predominant intracellular contents released systemically include potassium, phosphate, and uric acid. Consequently, laboratory values may reflect hyperkalemia, hyperphosphatemia, hypocalcemia, and hyperuricemia.[36] Initial testing should include CBC with differential, CMP, lactate dehydrogenase, uric acid, phosphate, total and ionized calcium levels, and urinalysis. An electrocardiogram (ECG) should also be obtained given the potential for electrolyte derangements.[32–39] Hyperkalemia poses the most immediate threat to the patient and is secondary to massive cellular breakdown, which overwhelms the kidneys. Hyperkalemia may be worsened by patient use of potassium-sparing medication, metabolic acidosis or prior renal insufficiency or failure. Phosphorous is present in malignant cells fourfold compared to normal cells; therefore, lysis of malignant cells releases large quantities of phosphate into the circulation, which ultimately binds with calcium to form calcium phosphate crystals.[39] The crystals deposit into soft tissue and can contribute to complications such as urinary obstruction, iritis, and skin lesions.[36–38] Hypocalcemia secondary to phosphate binding may cause symptoms of anorexia, vomiting, seizures or cardiac arrest.[41] The Cairo-Bishop criteria are preferred to diagnose TLS (Table 5). The diagnosis of TLS can be made before the development of acute kidney injury (AKI) and this is the best time for intervention.[36–40] Patients with TLS who develop AKI have a higher rate of mortality.[41]

Once TLS is identified, initial interventions consist of aggressive intravenous fluid (IVF) administration and correction of electrolyte abnormalities.[39–43] Isotonic fluid resuscitation is recommended with a goal of at least 2000–3000 L/m2/day (liters per meters squared per day) for adults and children. (Use goal of 200 milliters per kilogram [kg] per day for children less than 10 kg)[39–43] Hyperkalemia secondary to TLS should be a treatment priority and should proceed similarly as with other hyperkalemic patients.[39–43] Ultimately, dialysis may be required for severe or refractory cases of TLS to treat renal failure as well as severely elevated uric acid, potassium or phosphate levels.[39–42] Phosphate binders such as aluminum hydroxide (300-600 mg [milligram] oral dose) may be used to treat excess phosphorus in stable patients who have a phosphate level ≥ 6.0 mg per deciliter (dl).[40] Symptomatic hypocalcemia (e.g., seizures, tetany or cardiac dysrhythmias) should be treated with calcium gluconate one gram intravenously.[40–41] This dose may be repeated as required for symptom management. It is important to emphasize that asymptomatic hypocalcemia should not be treated as the additional calcium may cause calcium phosphate precipitation and acute obstructive uropathy.[39–41]

Additionally, hyperuricemia should be addressed to prevent uric acid nephropathy as it may lead to decreased filtration rate and crystal obstruction.[44] Allopurinol is effective in the prevention of uric acid production; however, it does not decrease uric acid already present, and so is less effective in treating TLS.[44–45] Rasburicase, a recombinant urate oxidase, has shown good promise when used for hyperuricemia.[44–47] Humans lack urate oxidase, which metabolizes uric acid to the more soluble allantoin, which can then be renally excreted.[44–45] Studies have shown rasburicase is more effective in lowering serum uric acid levels in patients with TLS compared to allopurinol, is well tolerated by patients, and does not require adjustment for changes in creatinine.[45–46] The recommended dose is 0.2 mg/kg by IV therapy. Of note, rasburicase is contraindicated in patients with history of glucose-6-phosphate dehydrogenase deficiency.[47] Management of TLS requires coordination with the patient's oncologist and frequent laboratory testing and intensive nursing care, which is often why these patients necessitate an intensive care unit (ICU) admission.[32]

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