Cerebral metabolism of ammonia and amino acids in patients with fulminant hepatic failure

Background & Aims: High circulating levels of ammonia have been suggested t o be involved in the development of cerebral edema and herniation in fulmin ant hepatic failure (FHF). The aim of this study was to measure cerebral me tabolism of ammonia and amino acids, with special emphasis on glutamine met abolism. Methods: The study consisted of patients with FHF (n = 16) or cirr hosis (n = 5), and healthy subjects (n = 8). Cerebral blood flow was measur ed by the Xe-133 washout technique. Blood samples for determination of ammo nia and amino acids were drawn simultaneously from the radial artery and th e internal jugular bulb. Results: A net cerebral ammonia uptake was only fo und in patients with FHF (1.62 +/- 0.79 mu mol . 100 g(-1) . min(-1)). The cerebral glutamine efflux was higher in patients with FHF than in the healt hy subjects and cirrhotics, -6.11 +/- 5.19 vs. -1.93 +/- 1.17 and -1.50 +/- 0.29 mu mol . 100 g(-1) . min(-1), respectively (P < 0.05). Patients with FHF who subsequently died of cerebral herniation (n = 6) had higher arteria l ammonia concentrations, higher cerebral ammonia uptake, and higher cerebr al glutamine efflux than survivors. Intervention with short-term mechanical hyperventilation in FHF reduced the net cerebral glutamine efflux, despite an unchanged net cerebral ammonia uptake. Conclusions: Patients with FHF h ave an increased cerebral glutamine efflux, and shortterm hyperventilation reduces this eff lux. A high cerebral ammonia uptake and cerebral glutamine efflux in patients with FHF were associated with an increased risk of subs equent fatal intracranial hypertension.