(405) Profound Hyperammonemia Leading to Refractory Seizures

Introduction: Hyperammonemia can result from hepatic insufficiency, sepsis, renal failure, drugs, gastrointestinal bleeding (GIB), and inherent metabolic disorders. It may precipitate seizures via increased extracellular glutamate and cerebral edema. This signifies severe metabolic imbalance, frequently associated with multi-organ failure, and forecasts a grim prognosis. We present a case of profound hyperammonemia in the setting of partial hepatectomy, cirrhosis with GIB, and shock.

Description: A 69-year-old male with a history of cirrhosis due to NASH, hepatocellular carcinoma post partial hepatectomy, and squamous cell carcinoma of larynx presented after being found unresponsive. He was hemodynamically stable but had a negative gag reflex requiring intubation. Laboratory studies showed leukocytosis to 16,500 cells/mm3, Hb 11 g/dl (baseline 12.5 g/dl), lactic acid of 6.5 mmol/L, and ammonia level of 840 µmol(previously normal). Coagulation profile, liver, and renal function tests were normal. CT head did not reveal acute abnormality. For hepatic encephalopathy, he was started on lactulose, rifaximin, and enemas. Later, he developed melena accompanied by hypotension, hyperkalemia and anuria, requiring vasopressors and continuous renal replacement therapy (CRRT) initiation. Follow-up ammonia was 1454 µmol/L. EGD was scheduled, he was noted to have ongoing tonic-clonic seizures that remained refractory to high-dose propofol, midazolam infusions and levetiracetam. Repeat neuroimaging did not reveal cerebral edema. Given high suspicion for cerebral edema with associated high ammonia levels, he was referred to a liver transplant center, for Molecular Adsorbent Recirculating System (MARS) consideration, but due to refractory shock, he did not survive.

Discussion: This case highlights the impact of profound hyperammonemia in the setting of multiple risk factors, including hepatectomy, liver cirrhosis, renal failure, and concurrent shock with GIB. Profound hyperammonemia is an independent prognostic factor, with ongoing seizure likely indicative of cerebral edema and raised intracranial pressure. Ammonia being a water-soluble molecule though theoretically could be removed by CRRT, but in our case, worsen outlines the potential role of MARS that has limited regional access.