Aim: Hyperammonemia causes brain edema and high intracranial pressure (ICP) in acute liver failure (ALF) by accumulation of glutamine in brain. Since a high-level glutamine may compromise mitochondrial function, the aim of this study was to determine if the lactate-pyruvate ratio is associated with a rise in the glutamine concentration and ICP.
Patients and methods: In 13 patients with ALF (8F/5M; median age 46 (range 18-66) years) the cerebral extracellular concentrations of glutamine, lactate, and pyruvate were measured by in vivo brain microdialysis together with ICP and cerebral perfusion pressure (CPP).
Results: The cerebral glutamine concentration was 4,396 (1,011-9,712) microM, lactate 2.15 (1.1-4.45) mM, and pyruvate 101 (43-255) microM. The lactate-pyruvate ratio was 21 (16-40), ICP 20 (2-28) mmHg, and CPP 72 (56-115) mmHg. Cerebral glutamine concentration correlated with the lactate-pyruvate ratio (r = 0.89, P < 0.05). Also the ICP, but not CPP, correlated to the lactate-pyruvate ratio (r = 0.64, P < 0.05).
Conclusion: ICP and the cerebral glutamine concentration in patients with ALF correlate to the lactate-pyruvate ratio. Since CPP was sufficient in all patients the rise in lactate-pyruvate ratio indicates that accumulation of glutamine compromises mitochondrial function and causes intracranial hypertension.