Cerebral herniation in patients with acute liver failure is correlated with arterial ammonia concentration

Hepatology. 1999 Mar;29(3):648-53. doi: 10.1002/hep.510290309.


Cerebral edema leading to cerebral herniation (CH) is a common cause of death in acute liver failure (ALF). Animal studies have related ammonia with this complication. During liver failure, hepatic ammonia removal can be expected to determine the arterial ammonia level. In patients with ALF, we examined the hypotheses that high arterial ammonia is related to later death by CH, and that impaired removal in the hepatic circulation is related to high arterial ammonia. Twenty-two patients with ALF were studied retrospectively. In addition, prospective studies with liver vein catheterization were performed after development of hepatic encephalopathy (HE) in 22 patients with ALF and 9 with acute on chronic liver disease (AOCLD). Cerebral arterial-venous ammonia difference was studied in 13 patients with ALF. In all patients with ALF (n = 44), those who developed CH (n = 14) had higher arterial plasma ammonia than the non-CH (n = 30) patients (230 +/- 58 vs. 118 +/- 48 micromol/L; P <. 001). In contrast, galactose elimination capacity, bilirubin, creatinine, and prothrombin time were not different (NS). Cerebral arterial-venous differences increased with increasing arterial ammonia (P <.001). Arterial plasma ammonia was lower than hepatic venous in ALF (148 +/- 73 vs. 203 +/- 108 micromol/L; P <.001). In contrast, arterial plasma ammonia was higher than hepatic venous in patients with AOCLD (91 +/- 26 vs. 66 +/- 18 micromol/L; P <.05). Net ammonia release from the hepatic-splanchnic region was 6.5 +/- 6. 4 mmol/h in ALF, and arterial ammonia increased with increasing release. In contrast, there was a net hepatic-splanchnic removal of ammonia (2.8 +/- 3.3 mmol/h) in patients with AOCLD. We interpret these data that in ALF in humans, vast amounts of ammonia escape hepatic metabolism, leading to high arterial ammonia concentrations, which in turn is associated with increased cerebral ammonia uptake and CH.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Ammonia / blood*
  • Arteries
  • Encephalocele / etiology*
  • Encephalocele / mortality
  • Female
  • Hepatic Encephalopathy / blood
  • Hepatic Encephalopathy / physiopathology
  • Humans
  • Liver Circulation / physiology
  • Liver Failure / blood*
  • Liver Failure / complications*
  • Liver Failure / physiopathology
  • Male
  • Middle Aged
  • Osmolar Concentration
  • Prospective Studies
  • Retrospective Studies
  • Veins


  • Ammonia