A 48-year-old man receiving ifosfamide for soft tissue sarcoma becomes confused and hallucinating on day 2 of therapy. He is disoriented with asterixis on examination. Which agent is the accepted treatment for this complication?

• A Naloxone
• B Physostigmine
• C Flumazenil
• D Methylene blue ✓

Explanation

Ifosfamide encephalopathy results from chloroacetaldehyde, a neurotoxic metabolite generated by hepatic CYP enzymes. It presents within days of dosing with somnolence, confusion, hallucinations and extrapyramidal signs. Intravenous methylene blue is the established antidote, believed to restore mitochondrial electron transport and monoamine synthesis impaired by the metabolite. Mesna protects the bladder against hemorrhagic cystitis but has no role in the encephalopathy, and supportive measures alone delay recovery.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.