S4671 Bleeding the Brain Dry: A Hidden Gastrointestinal Source of Metabolic Encephalopathy

Introduction: Hyperammonemia is a rare but serious metabolic disturbance caused by the accumulation of ammonia, a byproduct of protein metabolism. In healthy individuals, ammonia is converted to urea in the liver and excreted by the kidneys. When this process is impaired—whether due to liver dysfunction, increased production, or other factors—ammonia accumulates and crosses the blood-brain barrier, causing astrocyte swelling, which can lead to neurological dysfunction, cerebral edema, and potentially death. Although most cases are associated with hepatic pathology, non-hepatic triggers can also result in elevated ammonia levels. This case highlights an unusual presentation of hyperammonemia in a patient with gastrointestinal bleeding. Case Description/Methods: A 70-year-old man with heart failure with reduced ejection fraction, coronary artery disease status post CABG, atrial fibrillation, chronic kidney disease, and prior strokes presented with acute heart failure and was started on diuretics. During the hospitalization, he developed confusion and lethargy. Labs showed ammonia of 205 µmol/L and hemoglobin drop from 12 to 8.4 with dark stools. Anticoagulation with apixaban was discontinued, vitamin K was administered to address the elevated international normalized ratio and lactulose therapy was initiated. Due to poor oral intake and worsening mental status, he was transferred to the intensive care unit. He became unresponsive, with ammonia still elevated at 124 µmol/L. Neurological evaluation and electroencephalogram findings showing generalized periodic discharges were consistent with hepatic encephalopathy, while computed tomography head was negative. Workup for other causes of encephalopathy was unrevealing, and ultrasound ruled out cirrhosis. The presumed cause for severe encephalopathy was hyperammonemia due to gastrointestinal bleeding. Lactulose was continued and rifaximin was added, leading to significant clinical improvement. No invasive interventions were required, as hemoglobin stabilized and mental status improved. Discussion: Hyperammonemia, defined as ammonia >50 µmol/L, is uncommon but associated with significant morbidity. While most cases are related to liver disease, non-hepatic causes—such as GI bleeding, infection, renal failure, and total parenteral nutrition—must also be considered. Timely treatment with lactulose and rifaximin is essential. Considering the poor correlation between ammonia levels and the severity of encephalopathy, clinical judgment and early recognition are crucial. This case highlights the need to evaluate non-cirrhotic causes of hyperammonemia as a potential contributor to metabolic encephalopathy.