S4138 Hyperammonemia Following Roux-en-Y Gastric Bypass: A Life-Threatening Complication

Introduction: Hyperammonemia is a rare but potentially fatal complication following Roux-en-Y gastric bypass (RYGB), often presenting with altered mental status (AMS) and rapid neurological decline. Early recognition is critical, as delayed diagnosis can result in cerebral edema, coma, and death. Although mechanisms remain unclear, proposed contributors include altered gut microbiota, nutritional deficiencies, and unmasked or acquired urea cycle disorders. Case Description: A 55-year-old woman with a history of obesity, chronic back pain, depression and prior RYGB 19 years ago with revision and distalization 3 years ago presented with subacute weakness, anorexia, and depressed mental status. On presentation, she had anasarca, hypoalbuminemia (1.3 g/dL) and hepatic steatosis without cirrhosis. Initial work up for AMS was unrevealing, without evidence of infection, stroke or significant metabolic derangement. She developed worsening encephalopathy with myoclonus and asterixis. Additional labs revealed zinc deficiency (26 µg/dL), elevated ammonia (initially 84.9 µmol/L, peaking at 220 µmol/L), normal glutamine (379 µmol/L), and citrulline (19.6 µmol/L). Despite rectal lactulose, encephalopathy progressed, with development of acute hypoxic respiratory failure leading to intensive care unit admission. Magnetic resonance imaging was consistent with hepatic encephalopathy; video electroencephalogram revealed diffuse cortical hyperexcitability. She was treated with lactulose, rifaximin, L-carnitine, continuous venovenous hemofiltration, and aggressive nutritional repletion including zinc. Her course was complicated by acute respiratory distress syndrome, ventilator-associated pneumonia, and suspected cerebral edema requiring hypertonic saline. She eventually improved, was weaned to tracheostomy collar, and discharged to subacute rehabilitation. Discussion: Post-RYGB–related hyperammonemia is under-recognized, with less than 30 cases reported. Onset ranges from 1 month to 28 years post-operation, with a reported 50% mortality. Common features include AMS, signs of severe malnutrition, elevated ammonia, and often glutamine, hypoalbuminemia, and zinc deficiency. Management includes ammonia-lowering therapies, acute protein restriction with adequate caloric support, and nutritional repletion, especially zinc, to restore urea cycle function. This case highlights the need to consider hyperammonemia in the differential for AMS in post-RYGB patients and underscores the importance of early recognition and intervention in this potentially reversible condition.