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 mol/L; P F .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 F .001). Arterial plasma ammonia was lower than hepatic venous in ALF (148 ؎ 73 vs. 203 ؎ 108 mol/L; P F .001). In contrast, arterial plasma ammonia was higher than hepatic venous in patients with AOCLD (91 ؎ 26 vs. 66 ؎ 18 mol/L; P F .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. (HEPATOL-OGY 1999;29:648-653.)
Background and Purpose This study validates transcranial Doppler sonography (TCD) for determination of the lower limit of cerebral blood flow (CBF) autoregulation and establishes a relation between global CBF and mean flow velocity (V mean ) in the middle cerebral artery.Methods Relative changes in CBF and in V mean were compared in 12 normal volunteers (2 women and 10 men; median age, 30 years [range, 21 to 61 years]). Catheters was placed in the left radial artery and in the bulb of the right internal jugular vein, respectively. Baseline CBF was measured by single-photon emission computed tomography scanning; concomitantly, blood samples were drawn for calculation of the cerebral arteriovenous oxygen difference. Then changes in mean arterial pressure (MAP) were induced, and relative changes in global CBF were calculated according to Fick's principle assuming a constant cerebral oxygen metabolism. MAP was increased 30 mm Hg by norepinephrine infusion and was decreased by lower body negative pressure. V raean was
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