Cerebral glutamine concentration and lactate-pyruvate ratio in patients with acute liver failure.
OBJECTIVE
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.


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).


CONCLUSIONS
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.
Bjerring
Peter Nissen
PN
Department of Hepatology, section A-2121, Rigshospitalet, University Hospital of Copenhagen, Blegdamsvej 9, 2100, Copenhagen O, Denmark.
Hauerberg
John
J
Frederiksen
Hans-Jorgen
HJ
Jorgensen
Linda
L
Hansen
Bent Adel
BA
Tofteng
Flemming
F
Larsen
Fin Stolze
FS
D000293:Adolescent; D000328:Adult; D000368:Aged; D001253:Astrocytes / Q000473:pathology; D001921:Brain / Q000378:metabolism; D001929:Brain Edema / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D003422:Critical Care; D005260:Female; D005973:Glutamine / Q000378:metabolism*; D006801:Humans; D022124:Hyperammonemia / Q000209:etiology / Q000378:metabolism; D019586:Intracranial Hypertension / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D019344:Lactic Acid / Q000378:metabolism*; D017114:Liver Failure, Acute / Q000150:complications / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D019289:Pyruvic Acid / Q000378:metabolism*; D012720:Severity of Illness Index
D005973:Glutamine; D019344:Lactic Acid; D019289:Pyruvic Acid