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.

Cerebral blood flow and oxidative metabolism during human endotoxemia.

The proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), has been suggested to mediate septic encephalopathy through an effect on cerebral blood flow (CBF) and metabolism. The effect of an intravenous bolus of endotoxin on global CBF, metabolism, and net flux of cytokines and catecholamines was investigated in eight healthy young volunteers. Cerebral blood flow was measured by the Kety-Schmidt technique at baseline (during normocapnia and voluntary hyperventilation for calculation of subject-specific cerebrovascular CO reactivity), and 90 minutes after an intravenous bolus of a reference endotoxin. Arterial TNF-alpha peaked at 90 minutes, coinciding with a peak in subjective symptoms. At this time, CBF and Paco were significantly reduced compared to baseline; the CBF decrease was readily explained by hypocapnia. The cerebral metabolic rate of oxygen remained unchanged, and the net cerebral flux of TNF-alpha, interleukin (IL)-1beta, and IL-6 did not differ significantly from zero. Thus, high circulating levels of TNF-alpha during human endotoxemia do not induce a direct reduction in cerebral oxidative metabolism.

Circulating levels of vasoactive peptides in patients with acute bacterial meningitis.

PURPOSE: The underlying mechanisms for cerebral blood flow (CBF) abnormalities in acute bacterial meningitis (ABM) are largely unknown. Putative mediators include vasoactive peptides, e.g. calcitonin-gene related peptide (CGRP), vasoactive intestinal peptide (VIP), and endothelin-1 (ET-1), all of which may be affected by therapeutic interventions used in the intensive care unit. We measured arterial levels as well as the net cerebral flux of these peptides in patients with ABM, and in healthy volunteers undergoing interventions relevant to intensive care. METHODS: Seven patients with severe ABM and sepsis and fifteen healthy volunteers were included after informed consent. The net cerebral fluxes of vasoactive peptides were measured by the Kety-Schmidt technique in ABM patients (baseline study only), as well as in volunteers at baseline, during voluntary hyperventilation, after an intravenous injection of lipopolysaccharide (LPS), and during norepinephrine infusion. RESULTS: The arterial levels of CGRP, but not of VIP or ET-1, were elevated in patients with ABM, but no net cerebral flux was present. CGRP levels decreased during hyperventilation and after LPS injection. No net cerebral flux of VIP occurred in any group at any time. A cerebral efflux of ET-1, which occurred in volunteers at baseline, was neither present in volunteers after LPS injection nor in patients with ABM. CONCLUSION: The arterial concentration of the vasodilatory peptide, CGRP, but of neither VIP nor the vasoconstrictor ET-1, is elevated in patients with ABM and sepsis. A constitutive cerebral output of ET-1 appears to be present in healthy humans, but is abolished after LPS injection.

Cerebral glucose and oxygen metabolism in patients with fulminant hepatic failure.

Hyperammonemia and hyperventilation are consistent findings in patients with fulminant hepatic failure (FHF), which may interfere with cerebral glucose and oxygen metabolism. The aim of the present study is to evaluate whether cerebral oxidative metabolism is preserved early in the course of FHF and whether hyperventilation has an influence on this. We included 16 patients with FHF, 5 patients with cirrhosis of the liver, and 8 healthy subjects. Concomitant blood sampling from an arterial catheter and a catheter in the jugular bulb and measurement of cerebral blood flow by the xenon 133 wash-out technique allowed calculation of cerebral uptake of glucose (CMRgluc) and oxygen (CMRO2). Both CMRgluc and CMRO2 were reduced in patients with FHF compared with those with cirrhosis and healthy subjects, i.e., 11.8 +/- 2.7 v 18.3 +/- 5.5 and 28.5 +/- 6.6 micromol/100 g/min (P <.05) and 86 +/- 18 v 164 +/- 42 and 174 +/- 27 micromol/100 g/min (P <.05). Arteriovenous difference in oxygen and oxygen-glucose index were normal in patients with FHF. Institution of mechanical hyperventilation did not affect glucose and oxygen uptake and hyperventilation did not affect lactate-pyruvate ratio or lactate-oxygen index. In conclusion, we found that cerebral glucose and oxygen consumption are proportionally decreased in patients with FHF investigated before clinical signs of cerebral edema. Our data suggest that cerebral oxidative metabolism is retained at this stage of the disease without being compromised by hyperventilation.