Indian Journal of Cancer Medknow Publications on behalf of Indian Cancer Society ISSN: 0019-509X EISSN: 1998-4774 Vol. 46, Num. 1, 2009, pp. 76-77

Indian Journal of Cancer, Vol. 46, No. 1, January-March, 2009, pp. 76-77

Letter To Editor

Refractory hypokalemia due to conventional amphotericin B in patients with leukemia

Bamba AV, Jadhav MP, Prabhu R, Ray S, Gogtay NJ, Jijina FF, Kshirsagar NA

Department of Clinical Pharmacology, Seth G.S. Medical College and KEM, Hospital, Parel, Mumbai - 400 012
Correspondence Address:Department of Clinical Pharmacology, Seth G.S. Medical College and KEM, Hospital, Parel, Mumbai - 400 012
manojpjadhav@yahoo.com

Code Number: cn09018

Sir,

Amphotericin B (Amp B) is used in leukemia for treatment of febrile neutropenia and is known to cause nephrotoxicity and potassium depletion which is corrected by oral and parenteral supplements. ^[1],[2] We report two patients of acute leukemia with refractory hypokalemia following treatment with Amp B.

A 12-year-old boy, with B-ALL leukemia, developed febrile neutropenia. The absolute neutrophil count (ANC) was 440/mm ³ during induction chemotherapy. On the fifth day of fever he was started on empirical antifungal treatment with conventional Amp B (1 mg/kg/day) and potassium supplements. Baseline serum K ⁺ was 3.8 mEq/l. On day 5 of Amp B therapy, he developed hypokalemia (K ⁺ 2.8 mEq/l), vomiting, and diarrhea. Blood, urine, sputum, and stool culture for bacterial and fungal growth were negative; The ECG was normal. On days 9 and 12 serum K ⁺ was 2.9 and 1.6 mEq/l, respectively, and his ANC was 80/mm. ³ Based on these results, the K ⁺ correction was increased to 40 mEq/l t.i.d.; GCSF was also introduced. His vomiting and diarrhea continued. The patient was administered prednisolone and promethazine as he did not respond to granisetron. He developed odynophagia and epigastric pain and tenderness, and pancreatitis was ruled out on examination. On day 15, the ANC was 120/mm ³ with severe symptomatic hypokalemia (K ⁺ 0.9 mEq/l). Ultrasound abdomen showed bulky kidneys and multiple lesions at corticomedullary junction indicative of tubular dysfunction. He developed anasarca for which amiloride was initiated. A pleural and ascitic tap was negative for malignant cells. Later, he developed hematuria, oliguria, and the fever persisted. On day 18, K ⁺ was 1.9 mEq/l and ANC was 240 /mm ³ ; therefore, Amp B was stopped. By day 23, ANC counts recovered, the patient improved, and his bone marrow was in remission, but it took 45 days for K ⁺ levels to normalize.

Our second case was a 21-year-old female AML patient with an indwelling urinary catheter of one month duration for urinary retention. She developed febrile neutropenia following chemotherapy with ANC 00/mm. ³ After 96 hours of broad spectrum antibiotics, she was started on empirical antifungal treatment with Amp B (1 mg/kg/day). Baseline serum K ⁺ was 3.18 mEq/l, HRCT chest was normal, and sputum and urine were positive for Candidia paracoccus and Candida tropicalis , respectively. Despite routine K ⁺ supplements (60 mEq/l), serum K ⁺ continued to drop to 1.8, 2.1, and 1.4 mEq/l on days 3, 4, and 5 respectively. Since she developed severe vomiting, parenteral K ⁺ supplements were doubled. On day 6, the patient suffered a cardiac arrest. The drug was stopped. An ECG showed u waves, ultrasound abdomen revealed medical renal disease, and arterial blood gas analysis suggested metabolic acidosis. Serum Mg ⁺⁺ and renal function tests were normal. She was changed over to liposomal Amp B 1 mg/kg/day. On day 8, she again experienced cardiac arrest and liposomal Amp B was stopped. Ten days later her serum K ⁺ levels increased. The condition of the patient improved and her bone marrow was in remission.

Both reported cases developed severe refractory hypokalemia in spite of adequate correction due to which Amp B had to be stopped. Contributory factors could be Amp B, aminoglycosides, prednisolone, vomiting, and diarrhea. In leukemia, hypokalemia occurs as abnormal WBC′s take up large amounts of potassium and increased urinary loss accompanying blast cell waste. ^[3] In both patients, Naranjo′s probability scale scored the adverse drug reaction as probable association with Amp B. ^[4]

Acknowledgment

References

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