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Abstract

Cerebral edema leading to cerebral herniation CHis 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 encephalopathyHEin 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-CHn = 30patients 230 ± 58 vs. 118 ± 48 μmol/L;P< .001. In contrast, galactose elimination capacity, bilirubin, creatinine, and prothrombin time were not differentNS. 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 μmol/L;P< .001. In contrast, arterial plasma ammonia was higher than hepatic venous in patients with AOCLD91 ± 26 vs. 66 ± 18 μmol/L;P lt; .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/hn 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.