Rigby, Mark

Abstract Background Intracranial hypertension from cerebral edema is a feared complication in patients with acute liver failure. Diagnosing cerebral edema in critically ill patients can be challenging as it may be insidious in onset. We present a case of fulminant hyperammonemia-induced cerebral edema in a patient with newly diagnosed alpha-1-antitrypsin deficiency (A1AD) in the setting of intestinal ileus and ineffective lactulose therapy. Case A 48-year-old male with newly diagnosed A1AD-related cirrhosis, alcohol use, and obesity (BMI 48.9) presented at an outside facility with altered mental status. Physical exam showed waxing and waning mentation, and serum ammonia was 245 mcmol/L. Upon transfer to our facility, hemoglobin was 10.3 g/dL, creatinine 1.77 mg/dL, total bilirubin 1.5 mg/dL, INR 1.2, ALT 60 U/L, AST 107 U/L, ALP 173 U/L, and serum ammonia 138 mcmol/L. Serum alpha-1-antitrypsin returned at 41 mg/dL with SZ phenotype. Abdominal ultrasound showed cirrhosis with moderate ascites. Paracentesis demonstrated no acute peritonitis. After initiation of lactulose and rifaximin, his mental status improved initially. However, he experienced 2 episodes of coffee-ground emesis with hemoglobin dropping to 7.0 g/dL requiring blood transfusions. Urgent esophagogastroduodenoscopy, limited by large residual contents, found no active bleed. A nasogastric tube was placed. CT abdomen pelvis showed diffuse colonic and small bowel dilation consistent with adynamic ileus impairing lactulose administration. His mental status worsened, necessitating ICU transfer and intubation for airway protection. Serum ammonia peaked at 397 mcmol/L. Neostigmine did not restore any effective bowel movement, and continuous renal replacement therapy was initiated to control the hyperammonemia. A convulsive episode prompted imaging. Head CT showed diffuse cerebral edema, later confirmed on MRI (Figure 1). Continuous electroencephalogram showed diffuse slowing without epileptiform discharges. His protracted hospital course was marked by minimal neurological recovery requiring tracheostomy and ongoing supportive measures per family wishes. Discussion Cerebral edema is one of the leading causes of morbidity and mortality in patients with severe hyperammonemia, which can result in irreversible cortical and deep grey matter injury that typically spares perirolandic and medial occipital regions. Although the exact mechanism continues to be researched elevated serum ammonia plays a critical role in disrupting the innate cerebral autoregulation. Prompt diagnosis and early intracranial pressure control (head of the bed elevation, hyperventilation, mannitol, hypertonic saline) are paramount. Typical hyperammonemia treatment includes lactulose, rifaximin, or polyethylene glycol, and correction of any precipitating factors. Dialysis should be considered early to prevent cerebral toxicity in hyperammonemia refractory to conventional treatments.