A 5-Fluorouracil-Induced Hyperammonemic EncephalopathyChallenged with Capecitabine

Cancer patients presenting with altered mental status demand a broad differential with early recognition of the etiology. Failure todo so is associated with increased morbidity and mortality. Causes that must be considered include organ involvement of thecancer, electrolytes abnormalities, and even chemotherapeutic agents. A 32-year-old female patient had been recently started onFOLFOX for metastatic colon cancer. Her initial treatments were uneventful, but she later developed encephalopathy during daythree of cyclefive. During her evaluation, she was found to have hyperammonemia (84 mcmol/L), without hepatic failure, thatresolved with stopping chemotherapy and supportive care. After a trial of home infusionfluorouracil, she developedhyperammonemic encephalopathy again. During both admissions, her symptoms resolved with IV hydration and cessation ofchemotherapy. She was then successfully challenged with capecitabine (1000 mg/m2daily), and additional hydration, andcontinued chemotherapy without recurrence of symptoms. Hyperammonemia is associated withfluorouracil though themechanism is unclear. Suspected etiologies include either elevated levels of the drug due to slower metabolism or accumulationof certain metabolites. Additionally, risk factors such urease-producing bacterial infections, dehydration, and increasedcatabolism are thought to increase the risk for hyperammonemia. This case demonstrates the need for greater awareness offluorouracil as a cause of hyperammonemic encephalopathy. Knowledge of this may allow for earlier recognition and reducedunnecessary testing