Indian J Pediatr DOI 10.1007/s12098-014-1459-7
SCIENTIFIC LETTER
Green Urine Secondary to Methylene Blue Ghasem Miri-Aliabad
Received: 11 January 2014 / Accepted: 10 April 2014 # Dr. K C Chaudhuri Foundation 2014
To the Editor: An 11-y-old boy with relapsed T-cell Acute lymphoblastic leukemia resistant to multiple chemotherapy regimens, was finally exposed to chemotherapy with ifosfamide 3 g/m2/d and etoposide 100 mg/m2/d for five consecutive days. On fourth day of the treatment, he was diagnosed with drowsiness, confusion, agitation, dysarthria, hallucinations, incontinence of urine and feces, and asterixis. Chemotherapy was stopped. Laboratory studies, including electrolytes, liver and renal function tests, and serum albumin were all normal. Diagnosed with ifosfamide-induced encephalopathy (IIE), he was exposed to a treatment with intravenous infusion of 30 mg methylene blue over a 5 min period. Two hours later, neurological symptoms, except drowsiness, completely improved. Urine output was normal except for dark green color 48 h after the treatment (Fig. 1). IIE is caused by a metabolite called chloroacetaldehyde. Its manifestations vary from confusion and drowsiness to coma and death [1]. Most cases of neurotoxicity occur during the first course of treatment and often, following oral administration of ifosfamide [2]. Although most cases are reversible within 1–3 d after ceasing ifosfamide administration, the reported treatments for severe, irreversible and fatal cases include methylene blue, albumin, thiamine, glucose and hemodialysis [2, 3]. Mechanism of action and efficacy of methylene blue in the treatment of IIE are not known accurately, however improvement of neurologic function was reported from 10 min to 8 d succeeding methylene blue administration. Without using this
Fig. 1 Green urine discoloration following methylene blue administration
drug, recovery from encephalopathy varies from 2 to 29 d [1, 3]. Metylene blue is filtered by the kidneys and may cause greenish or bluish urine that returns to the normal color after it is passed [4]. Neurologic evaluation should be carried out frequently during treatment with high doses of ifosfamide. In patients with suspected IIE, the ifosfamide infusion must be stopped immediately and treatment with methylene blue should commence as soon as possible. Conflict of Interest None. Role of Funding Source None.
G. Miri-Aliabad Department of Pediatric Hematology-Oncology, Children and Adolescent Health Research Center, Zahedan University of Medical Sciences, Zahedan, Iran
References
G. Miri-Aliabad (*) Department of Pediatrics, Second Floor, Ali-ebne-Abitaleb Hospital, Khalije Fars Highway, P. O. BOX: +9816743111, Zahedan, Iran e-mail: [email protected]
1. Ames B, Lewis LD, Chaffee S, Kim J, Morse R. Ifosfamide induced encephalopathy and movement disorder. Pediatr Blood Cancer. 2010;54:624–6.
Indian J Pediatr 2. Tajino T, Kikuchi SI, Yamada H, Takeda A, Konno SI. Ifosfamide encephalopathy associated with chemotherapy for musculoskeletal sarcomas: incidence, severity, and risk factors. J Orthop Sci. 2010;15:104–11.
3. Ajithkumar T, Parkinson C, Shamshad F, Murray P. Ifosfamide encephalopathy. Clin Oncol (R Coll Radiol). 2007;19:108–14. 4. Stratta P, Barbe MC. Images in clinical medicine. Green urine. N Engl J Med. 2008;358:e12.
SCIENTIFIC LETTER
Green Urine Secondary to Methylene Blue Ghasem Miri-Aliabad
Received: 11 January 2014 / Accepted: 10 April 2014 # Dr. K C Chaudhuri Foundation 2014
To the Editor: An 11-y-old boy with relapsed T-cell Acute lymphoblastic leukemia resistant to multiple chemotherapy regimens, was finally exposed to chemotherapy with ifosfamide 3 g/m2/d and etoposide 100 mg/m2/d for five consecutive days. On fourth day of the treatment, he was diagnosed with drowsiness, confusion, agitation, dysarthria, hallucinations, incontinence of urine and feces, and asterixis. Chemotherapy was stopped. Laboratory studies, including electrolytes, liver and renal function tests, and serum albumin were all normal. Diagnosed with ifosfamide-induced encephalopathy (IIE), he was exposed to a treatment with intravenous infusion of 30 mg methylene blue over a 5 min period. Two hours later, neurological symptoms, except drowsiness, completely improved. Urine output was normal except for dark green color 48 h after the treatment (Fig. 1). IIE is caused by a metabolite called chloroacetaldehyde. Its manifestations vary from confusion and drowsiness to coma and death [1]. Most cases of neurotoxicity occur during the first course of treatment and often, following oral administration of ifosfamide [2]. Although most cases are reversible within 1–3 d after ceasing ifosfamide administration, the reported treatments for severe, irreversible and fatal cases include methylene blue, albumin, thiamine, glucose and hemodialysis [2, 3]. Mechanism of action and efficacy of methylene blue in the treatment of IIE are not known accurately, however improvement of neurologic function was reported from 10 min to 8 d succeeding methylene blue administration. Without using this
Fig. 1 Green urine discoloration following methylene blue administration
drug, recovery from encephalopathy varies from 2 to 29 d [1, 3]. Metylene blue is filtered by the kidneys and may cause greenish or bluish urine that returns to the normal color after it is passed [4]. Neurologic evaluation should be carried out frequently during treatment with high doses of ifosfamide. In patients with suspected IIE, the ifosfamide infusion must be stopped immediately and treatment with methylene blue should commence as soon as possible. Conflict of Interest None. Role of Funding Source None.
G. Miri-Aliabad Department of Pediatric Hematology-Oncology, Children and Adolescent Health Research Center, Zahedan University of Medical Sciences, Zahedan, Iran
References
G. Miri-Aliabad (*) Department of Pediatrics, Second Floor, Ali-ebne-Abitaleb Hospital, Khalije Fars Highway, P. O. BOX: +9816743111, Zahedan, Iran e-mail: [email protected]
1. Ames B, Lewis LD, Chaffee S, Kim J, Morse R. Ifosfamide induced encephalopathy and movement disorder. Pediatr Blood Cancer. 2010;54:624–6.
Indian J Pediatr 2. Tajino T, Kikuchi SI, Yamada H, Takeda A, Konno SI. Ifosfamide encephalopathy associated with chemotherapy for musculoskeletal sarcomas: incidence, severity, and risk factors. J Orthop Sci. 2010;15:104–11.
3. Ajithkumar T, Parkinson C, Shamshad F, Murray P. Ifosfamide encephalopathy. Clin Oncol (R Coll Radiol). 2007;19:108–14. 4. Stratta P, Barbe MC. Images in clinical medicine. Green urine. N Engl J Med. 2008;358:e12.
