Hyperammonemia and Fatal Cerebral Edema: A Complication of Gastric Bypass Surgery

Introduction: Hyperammonemia is characteristic of few disease processes including liver failure, urea cycle disorders, inborn errors of metabolism, drugs and infection with urea-splitting organisms in lung transplant.Renal replacement therapy(RRT) is indicated in acute liver failure with grade 2 or higher encephalopathy even in the absence of renal failure. We present a case of hyperammonemia in a patient with gastric bypass which resulted in fatal cerebral edema despite prompt initiation of continuous RRT(CRRT). Case Description: A 50-year-old woman with history of Protein C and S deficiency complicated by venous thromboembolism and gastric bypass surgery was brought to the emergency department due to confusion following a gastrointestinal illness. Laboratory studies revealed a large anion gap and hyperammonemia to 169 umol/L with normal liver tests. Patient was admitted to intensive care unit and intubated for progressive encephalopathy and ammonia levels rose to 478 umol/L. Nephrology was consulted, CRRT was initiated, and she was started on a high-caloric/low-protein enteral diet. On hospital day two she developed progressive cerebral edema and her family decided to transition to comfort care.Studies for Ureaplasma and Mycoplasma PCR were negative and Valproic acid levels were undetectable.Evaluation for inborn errors of the urea cycle revealed elevated levels of plasma glutamine and acylcarnitine species but low levels of free carnitine. Genetic studies for urea cycle defects and hyperammonemia revealed a heterozygote variant of uncertain significance in the CYC1 gene. Discussion: Hyperammonemia is an uncommon under-recognized complication of bariatric surgery. Bariatric surgery may unmask latent urea cycle enzyme deficiencies or impair citrulline synthesis in the intestinal wall which leads to depletion of urea cycle substrates. The associated weight loss, hyperinsulinemia and zinc deficiency may downregulate urea cycle enzymes and interfere with ornithine transcarbamylase function. Post-surgical proliferation of urea-splitting microbiota may also raise ammonia levels. Hemodialysis is effective in reducing ammonia levels and continuous dialysis strategy is often employed to avoid rebound hyperammonemia. This case illustrates a rare complication of bariatric surgery and highlights the role for renal replacement therapy in the management of cerebral edema.