Tumor lysis syndrome is a life-threatening metabolic emergency frequently associated with certain types of neoplasms. Concentrations of intracellular electrolytes, those that are within the cell, differ from extracellular electrolytes, or those that are outside the cell and in the bloodstream. In tumor lysis syndrome, tumor cells lyse, or break apart, releasing their contents into the blood stream. The result is a dangerous alteration in the normal balance of serum electrolytes—potassium, phosphate and uric acid levels are elevated, while calcium levels are decreased. The changes occur so quickly and can be so dramatic, that immediate death can result.
Causes
Many factors contribute to the development of tumor lysis syndrome. Most of the research performed to date revolves around high-grade non-Hodgkin's lymphoma cases, 40% of which demonstrate laboratory evidence of tumor lysis syndrome. (An estimated 6% demonstrate clinical evidence of the syndrome.) Tumors that carry the highest risk of the development of tumor lysis syndrome are those that are large and bulky, usually greater than
eight to ten cm (3-4 in), and comprised of rapidly dividing cells. In addition, tumors that respond well to treatment are associated with tumor lysis syndrome because treatment results in rupture of a large number of cells.
Most often, the syndrome is associated with hemato-logic tumors, such as non-Hodgkin's lymphoma, particularly Burkitt's lymphoma, and acute leukemia. Though less likely because of lower rates of cell division, tumor lysis syndrome can also occur in solid tumors such as breast cancer. The Washington Manual of Medical Therapeutics associates the following cancer types with tumor lysis syndrome:
Usually, tumor lysis syndrome develops after the administration of combination chemotherapy regimens, but it may also occur spontaneously or as a result of radiation or corticosteroid therapy. Lactic acid dehydrogenase (LDH) is an enzyme found in cells of body tissues. An increase in the LDH level is considered a marker of bulky disease that correlates with the risk of tumor lysis syndrome.
Patients with underlying renal (kidney) dysfunction and/or decreased urine output are at a higher risk of developing tumor lysis syndrome. Without optimal kidney functioning, waste products that build up cannot be excreted in the urine at high enough rate. Patients with cancer may be predisposed to conditions that increase the risk of renal failure due to increased uric acid buildup. For example, a patient undergoing chemotherapy may experience nausea and vomiting, and may, as a result, be dehydrated, increasing the risk. The same patient may have decreased white blood cell counts, making him or her more susceptible to infections. Many antibiotics adversely affect the kidneys, also increasing the risk.
Treatments
Treatment is aimed at prevention and supportive care, with the main goals being to prevent renal failure and severe electrolyte imbalances. Patients at risk receive treatment on an inpatient basis to allow for close monitoring by medical personnel. At all times, patients should have reliable intravenous access. Prior to initiating treatment, a patient's hydration status and electrolyte levels are carefully evaluated. If there are abnormalities, a treatment delay may be considered, though this is not always an option.
Laboratory tests are done frequently to monitor levels of calcium, potassium, phosphate, magnesium and uric acid. A typical hospital protocol may require blood be drawn for these tests every two to six hours over the course of two to three days. Following are prevention and management strategies for each of the major electrolyte imbalances, hyperuricemia, hyperkalenia, hyperphosphatemia, and hypocalemia.
Hyperuricemia is a medical term used to describe an abnormal increase of uric acid levels in the blood that can lead to acute renal failure. There are several methods employed to prevent kidney damage—aggressive hydration being a major focus. Intravenous (IV) hydration is started before treatment and continues throughout to maintain a urine output of 100 to 200 milliliters per hour (ml/hr). Medications called diuretics, such as furosemide or acetazolamide, are given to help increase urine output when necessary.
Urine may be alkalized to prevent uric acid buildup. Alkalization can be accomplished by adding sodium bicarbonate to the patient's IV fluid. For example, the basic maintenance IV fluid may consist of 5% dextrose in 0.25 normal saline, to which sodium bicarbonate, in amounts ranging from 50 to 200 milliequivalents (mEq—the total number of charges of electrolytes in solution), may be added. Urine pH is routinely tested, and the sodium bicarbonate is periodically increased or decreased to maintain a pH level between 7 and 8.
Urine alkalinization is somewhat controversial. If urine is too alkaline, calcium phosphate crystal formation may occur, increasing the likelihood of renal failure. However, it is generally believed that if urine output levels are appropriately maintained, calcium phosphate will be diluted, and the possibility of crystal formation will diminish.
Patients at risk for tumor lysis syndrome may also be given allopurinol prophylactically. One dose of 600 milligrams (mg) may be given the day before treatment, followed by 300 mg once a day for the remainder of treatment days. Allopurinol is effective because it inhibits the formation of uric acid.
Hyperkalemia is a medical term used to describe an abnormal increase of potassium levels in the blood that can cause dangerous abnormalities in heart rhythms, heart attack, and muscle weakness. Frequent monitoring
with electrocardiography (EKG) is recommended in patients at risk for tumor lysis syndrome so that alterations in the electrical activity of the heart can be caught early. Potassium-rich foods may also be restricted to prevent already elevated levels from increasing. Sometimes, medications such as Kayexalate are administered to help reduce potassium levels.
Hyperphosphatemia is a medical term used to describe an abnormal increase on phosphate levels in the blood that can cause neuromuscular irritability and worsen kidney function. Malignant cells may contain up to four times as much phosphate as non-malignant cells. Patients experiencing acute tumor lysis syndrome may be instructed to reduce their dietary intake of phosphate. In addition, they may be given medications that bind to phosphate, thereby inhibiting its absorption in the intestines.
Hypocalemia is a medical term used to describe an abnormal decrease in calcium levels in the blood that can cause tetany, muscle cramps, and seizures. A calcium supplement may be required.
Dialysis is a procedure used to normalize electrolyte imbalances through the diffusion and ultrafiltration of fluid. Potassium, for example, can be separated and filtered from fluid, bringing levels back to a safer range. Hemodialysis is a procedure that removes waste products through the blood. Dialysis can alternatively be performed through the peritoneum, the tissue that lines the abdominal area and surrounds the organs in what is called peritoneal dialysis. Because peritoneal dialysis does not clear phosphate and urate as efficiently, and because it is not feasible in patients with abdominal tumors, hemodialysis is the preferred method. A doctor who specializes in nephrology will generally examine a high-risk patient before cancer treatment begins, to prepare for the possibility of dialysis treatment. In some cases, dialysis is started as a preventative measure, either before or during chemotherapy treatment.
Resources
BOOKS
Abeloff, A. Clinical Oncology, 2nd Ed. New York: Churchill Livingstone, Inc., 2000.
Goldman, L. Cecil Textbook of Medicine, 21st Ed. St Louis, MO: W.B. Saunders Company, 2000.
Lee, G., et al.(Eds.) Wintrobe's Clinical Hematology Baltimore, MD: Williams & Wilkins Publishing, 1999.
Carey, C., Hans, L. & Woeltje, K. (Eds.) Washington Manual of Medical Therapeutics, 29th Ed. Philadelphia, PA: Lippincott-Raven Publishers, 1998.
PERIODICALS
Kelly, K. and Lange, B. "Oncologic Emergencies." Pediatric Clinics of North America (Aug 1997): 809-30
Meyer, M. "Renal Replacement Therapies." Critical Care Clin ics (Jan 2000): 29-58.
Tamara Brown, R.N.
Dialysis
—A medical procedure that uses a special machine to filter waste products from the blood and restore it. It is a life-sustaining procedure in end-stage kidney failure.
Electrolytes
—Substances or particles that dissolve into ions, (atoms with a positive or negative charge) such as potassium or sodium, and carry water molecules across cell membranes, regulating electric charge in order to maintain the proper oxygen flow of body fluids.
Metabolic
—Pertaining to the physical and chemical process of synthesis and breakdown of substances necessary to sustain life.
Nephrology
—The study of the kidneys—their structure and function.
pH
—A measure of the alkalinity or acidity of a substance.
