Methylene blue for management of ifosfamide-induced encephalopathy

OBJECTIVE: To evaluate the use of methylene blue for the treatment of ifosfamide-induced encephalopathy. DATA SOURCES: MEDLINE (1966-August 2005) and International Pharmaceutical Abstracts (1971-August 2005) were searched, using the terms methylene blue, ifosfamide, encephalopathy, and neurotoxicity. DATA SYNTHESIS: Several case reports and one retrospective chart review described the use of methylene blue for ifosfamide-induced encephalopathy, but no controlled clinical trials were found. Methylene blue appeared to aid in the resolution of encephalopathic symptoms as rapidly as within 10 minutes of administration in some patients, but it had modest efficacy in most patients. Symptoms in patients who did not receive methylene blue resolved in the same time frame; this indicates that ifosfamide-induced encephalopathy may resolve without treatment. CONCLUSIONS: Available data from case reports indicate that methylene blue is an option in the treatment of ifosfamide-induced encephalopathy, especially in patients with severe symptoms of toxicity. However, the lack of controlled clinical trials and the possibility of spontaneous resolution of encephalopathy make the usefulness of methylene blue unclear.