Case Presentation: A 44 year old woman with a history of Roux-En-Y gastric bypass (RYGB), hypothyroidism, and morbid obesity, presented with one day of confusion and somnolence. In the emergency department, she was unresponsive to voice with an initial Glasgow Coma Score of 9. Her temperature was 94 F, pulse 94 beats per minute, blood pressure 145/90, and respiratory rate 24 breaths per minute. Laboratory evaluation revealed: ALT 34 U/L, AST 36 U/L, total bilirubin 0.6 mg/dL, glucose 167 mg/dL, lactate 2.37 mmol/L and venous ammonia 235 umol/L. Over the past two years, she had been admitted three times for encephalopathy associated with hyperammonemia. Prior liver imaging—including ultrasound and CT—showed no evidence of cirrhosis. She had no history of abnormal liver function testing. Serum amino acids were obtained at a prior admission and showed mild, non-specific elevations in citrulline and glutamine. A liver biopsy one year ago showed severe steatosis and moderate fibrosis. At this time, she was given the diagnosis of NASH and was started on lactulose and rifaximin.Her hospital course was uncomplicated and her mental status returned to baseline after 24 hours of increased lactulose frequency. Her zinc level was low at 41 mcg/dL and zinc sulfate 220 mg daily was initiated. Her recurrent hyperammonemia was thought to be secondary to her RYGB and she was discharged home in stable condition.
Discussion: Hyperammonemia occurs when the metabolic clearance of ammonia becomes imbalanced, which can occur from either enhanced production or inadequate elimination. Symptoms include irritability, emesis, ataxia, lethargy, altered consciousness, coma, and even death. Hyperammonemia is classically associated with advanced liver cirrhosis, with one study finding that 96.5% of ICU patients with hyperammonemia showed evidence of acute or chronic cirrhosis. Though rare, alternative etiologies of hyperammonemia can include medications (valproic acid, carbamazepine, iron, and cyanide), RYGB, urea cycle defects, chronic malnutrition, high tumor burden, and total parental nutrition. Following RYGB, multiple factors contribute to hyperammonemia. Decreased nutritive intake may lead to increased catabolic activity and subsequent ammonia production. It is also thought that the RYGB can interfere with intestinal citrulline synthesis, leading to a depletion of urea cycle components. Furthermore, bacterial overgrowth can occur in the blind pouch and lead to increased enterohepatic circulation reuptake of ammonia. Ornithine transcarbamylase and carbamoyl synthase type 1 deficiencies may also be unmasked following RYGB and should also be considered.
Conclusions: Non-cirrhotic hyperammonemic encephalopathy can occur following Roux-en-Y gastric bypass surgery. It remains a diagnosis of exclusion and diligent efforts should be made to rule-out underlying liver disease prior to pursuing alternative diagnoses. Conservative measures such as dietary protein restriction, lactulose, rifaximin, and zinc supplementation may be utilized. If unsuccessful, reversal of the RYGB should be considered.