The effect of hyperventilation upon cerebral blood flow and metabolism in patients with fulminant hepatic failure.

Patients with FHF have a high risk of cerebral edema and intracranial hypertension. The pathophysiological background for this phenomenon is not completely settled, but alteration in CBF as well as cerebral metabolism seems to be of importance. Mechanical hyperventilation has a prompt effect on intracranial pressure. This effect is assumed to be caused by the hypocapnia induced alkalosis which produces vasoconstriction and thereby a decrease in CBF and cerebral blood volume. It has been stated that hyperventilation may be harmful to patients with FHF, but only few studies have addressed the effect of hyperventilation upon cerebral metabolism. In the present clinical studies we evaluated the effect of short-term mechanical hyperventilation upon cerebral circulation and metabolism in patients with FHF. Although global CBF was reduced in patients with FHF it tightly matched the cerebral oxidative requirements. Already in the early phase of FHF there was a prominent cerebral efflux of glutamine that could not be accounted for by cerebral ammonia uptake. Moderate hyperventilation reduced global CBF without compromising cerebral oxidative metabolism. In addition, moderate hyperventilation restored cerebral autoregulation in most patients with FHF, and normalised the cerebral nitrogen balance during short-term interventions. Studies of global and regional cerebral carbon dioxide reactivity showed normal global as well as regional cerebral carbon dioxide reactivity in almost all patients with FHF. However, cerebral perfusion in frontal brain regions as well as basal ganglia is low in FHF as compared to healthy subjects, which may make these regions at risk of hypoperfusion during pronounced hyperventilation. It is concluded that moderate short-term hyperventilation does not compromise cerebral oxidative metabolism. Recommendation of its prolonged use in FHF awaits further studies. Furthermore, the data of this thesis demonstrates that alterations in cerebral glutamine and ammonia metabolism precedes increases of CBF, which seems to be a phenomenon that takes place later during the disease course, i.e., immediately before intracranial pressure is rising.