Arterial ammonia and clinical risk factors for encephalopathy and intracranial hypertension in acute liver failure

High circulating ammonia concentrations are common in patients with acute liver failure (ALF) and are associated with hepatic encephalopathy (HE) and intracranial hypertension (ICH). Other risk factors are poorly characterized. We evaluated the relation of the admission arterial ammonia concentration and other clinical variables with the development of HE and ICH. Arterial ammonia was measured on admission to the intensive care unit in 257 patients; 165 had ALF and severe HE, and there were 3 control groups: acute hepatic dysfunction without severe HE (n = 50), chronic liver disease (n = 33), and elective surgery (n = 9). Variables associated with ICH and HE were investigated with regression analysis. Ammonia was higher in ALF patients than controls. An independent risk factor for the development of severe HE and ICH, a level greater than 100 mu mol/L predicted the onset of severe HE with 70% accuracy. The model for end-stage liver disease (MELD) score was also independently predictive of HE, and its combination with ammonia increased specificity and accuracy. ICH developed in 55% of ALF patients with a level greater than 200 mu mol/L, although this threshold failed to identify most cases. After admission, ammonia levels remained high in those developing ICH and fell in those who did not. Youth, a requirement for vasopressors, and renal replacement therapy were additional independent risk factors. Conclusion: Ammonia is an independent risk factor for the development of both HE and ICH. Additional MELD scoring improved the prediction of HE. Factors other than ammonia also appear important in the pathogenesis of ICH. Ammonia measurements could form part of risk stratification for HE and ICH, identifying patients for ammonia-lowering therapies and invasive monitoring.