Severe Hyperammonemic Encephalopathy Associated With Gastrointestinal Bleeding During Capecitabine and Oxaliplatin Chemotherapy in a Patient With Rectal Adenocarcinoma

Hyperammonemic encephalopathy is a rare complication of fluoropyrimidine and platinum-based chemotherapy that can occur independently of hepatic dysfunction. While gastrointestinal bleeding is a well-established precipitant of hyperammonemia in cirrhosis, its role in patients treated with chemotherapy without liver disease has rarely been reported. An 87-year-old male with stage IIIA rectal adenocarcinoma, treated with capecitabine and oxaliplatin, presented with two episodes of acute altered mental status. The first, associated with mild melena and modest hemoglobin decline, resulted in moderate encephalopathy that resolved spontaneously. One week later, he presented with profound unresponsiveness requiring intubation. This episode was related to recurrent melena with a significant hemoglobin drop. Endoscopy revealed a Mallory-Weiss tear. Liver function tests and hepatic imaging were unremarkable. EEG showed diffuse slowing with triphasic waves, and ammonia was elevated at 128 µmol/L. Treatment with lactulose and rifaximin led to neurologic recovery and return to baseline. This case suggests a potential association between gastrointestinal bleeding and hyperammonemic encephalopathy in a non-cirrhotic patient receiving chemotherapy. Clinicians should consider hyperammonemia in the evaluation of acute altered mental status during or after these chemotherapy regimens, especially in patients with other possible predisposing factors such as gastrointestinal bleeding.