Fatal 5-Fluorouracil Toxicity With Hyperammonemic Encephalopathy, Lactic Acidosis, and Pneumatosis Intestinalis Despite Uridine Triacetate Rescue: A Case Report.

5-Fluorouracil (5-FU) is among the most widely prescribed chemotherapeutic agents worldwide, yet severe toxicity can produce a life-threatening metabolic syndrome, most commonly associated with dihydropyrimidine dehydrogenase (DPD) deficiency. We report a fatal case of early-onset fluoropyrimidine toxicity characterized by severe metabolic derangements followed by severe myelosuppression. A 56-year-old male patient with stage III (primary tumor (T4), regional lymph nodes (cN2), distant metastasis (cM0), human papillomavirus (HPV)-16-positive) squamous cell carcinoma of the right tonsil developed intractable vomiting within 24 hours of initiating continuous 5-FU infusion as part of a TPF regimen (docetaxel, cisplatin, 5-FU). He presented with severe lactic acidosis (lactate 14.8 mmol/L, rising to >17), hyperammonemia (ammonia 462 µmol/L), high anion gap metabolic acidosis (anion gap 30 mmol/L), and acute kidney injury. DPYD genotyping was ordered on the day of treatment, but the results were not available during hospitalization. The 5-FU infusion was discontinued before the completion of the planned four-day course. The patient was intubated for airway protection and transferred to a tertiary care center, and uridine triacetate was initiated approximately 24 hours after the discontinuation of 5-FU. Over 48 hours, the metabolic derangements improved (lactate 4.2 mmol/L, ammonia <10 µmol/L), though acute kidney injury continued to worsen. Subsequent myelosuppression developed by hospital day 3, with profound cytopenia (absolute neutrophil count (ANC) 0.02 × 10³/µL, platelets 26 × 10³/µL). The patient developed