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

Cerebral edema leading to cerebral herniation (CH) is a common cause of dea th in acute liver failure (ALF), Animal studies have related ammonia with t his complication. During liver failure, hepatic ammonia removal can be expe cted to determine the arterial ammonia level. In patients with ALF, we exam ined the hypotheses that high arterial ammonia is related to later death by CH, and that impaired removal in the hepatic circulation is related to hig h arterial ammonia. Twenty-two patients with ALF were studied retrospective ly. In addition, prospective studies with liver vein catheterization were p erformed after development of hepatic encephalopathy (HE) in 22 patients wi th ALF and 9 with acute on chronic liver disease (AOCLD), Cerebral arterial -venous ammonia difference was studied in 13 patients with ALE In all patie nts 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 m u mol/L; P < .001), In contrast, galactose elimination capacity, bilirubin, creatinine, and prothrombin time were not different (NS), Cerebral arteria l-venous differences increased with increasing arterial ammonia (P < .001), Arterial plasma ammonia was lower than hepatic venous in ALF (148 +/- 73 v s. 203 +/- 108 mu mol/L; P < .001). In contrast, arterial plasma ammonia wa s higher than hepatic venous in patients with AOCLD (91 +/- 26 vs. 66 +/- 1 8 mu mol/L; P < .05), Net ammonia release from the hepatic-splanchnic regio n was 6.5 +/- 6.4 mmol/h in ALF, and arterial ammonia increased with increa sing release. In contrast, there was a net hepatic-splanchnic removal of am monia (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, l eading to high arterial ammonia concentrations, which in turn is associated with increased cerebral ammonia uptake and CH.