title: Persistent hyperammonemia is associated with complications and poor outcomes in patients with acute liver failure.
abstract: OBJECTIVE
  Patients admitted to the hospital with acute liver failure (ALF) and high arterial levels of ammonia are more likely to have complications and poor outcomes than patients with lower levels of ammonia. ALF is a dynamic process; ammonia levels can change over time. We investigated whether early changes (first 3 days after admission) in arterial levels of ammonia were associated with complications and outcomes and identified factors associated with persistent hyperammonemia.
  
  
  METHODS
  We performed a prospective observational study that measured arterial ammonia levels each day for 5 days in 295 consecutive patients with ALF. We analyzed associations of changes in ammonia levels during the first 3 days with complications and outcomes.
  
  
  RESULTS
  Patients with persistent arterial hyperammonemia (≥122 μmol/L for 3 consecutive days), compared with those with decreasing levels, had lower rates of survival (23% vs 72%; P < .001) and higher percentages of cerebral edema (71% vs 37%; P < .001), infection (67% vs 28%; P = .003), and seizures (41% vs 7.7%; P < .001). Patients with persistent hyperammonemia had greater mortality, with an odds ratio (OR) of 10.7, compared with patients with baseline levels of ammonia ≥122 μmol/L (OR, 2.4). Patients with persistent hyperammonemia were more likely to progress to and maintain advanced hepatic encephalopathy than those with decreasing levels. Patients with persistent, mild hyperammonemia (≥85 μmol/L for 3 days) were also more likely to have complications or die (P < .001) than patients with serial ammonia levels <85 μmol/L. Infections (OR, 4.17), renal failure (OR, 2.20), and decreased arterial pH (OR, 0.003) were independent predictors of persistent hyperammonemia.
  
  
  CONCLUSIONS
  Patients with ALF and persistent arterial hyperammonemia for 3 days after admission are more likely to develop complications and have greater mortality than patients with decreasing levels or high baseline levels. Infection, renal failure, and decreased arterial pH are independent predictors of persistent hyperammonemia.
authors.affiliation: Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Kumar
authors.lastname: Shalimar
authors.forename: Hanish
authors.initials: H
authors.lastname: Sharma
authors.forename: Shyam
authors.initials: S
authors.lastname: Prakash
authors.forename: Subrat Kumar
authors.initials: SK
authors.lastname: Panda
authors.forename: Shankar
authors.initials: S
authors.lastname: Khanal
authors.forename: Subrat Kumar
authors.initials: SK
authors.lastname: Acharya
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000641:Ammonia / Q000097:blood; D001774:Blood Chemical Analysis; D001929:Brain Edema / Q000453:epidemiology; D002648:Child; D003141:Communicable Diseases / Q000453:epidemiology; D005260:Female; D006801:Humans; D022124:Hyperammonemia / Q000150:complications* / Q000401:mortality*; D017114:Liver Failure, Acute / Q000150:complications* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D012640:Seizures / Q000453:epidemiology; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000641:Ammonia