Persistent hyperammonemia is associated with complications and poor outcomes in patients with acute liver failure

Abstract

Background & aims: 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.