Brain hypoxanthine concentration correlates to lactate/pyruvate ratio but not intracranial pressure in patients with acute liver failure.
OBJECTIVE
The pathogenesis of cerebral edema in acute liver failure is suggested, in in vitro and animal studies, to involve a compromised oxidative metabolism with a decrease in cerebral ATP levels and an increase in purine concentrations. In this study we hypothesize that the cerebral concentrations of hypoxanthine, inosine, and lactate/pyruvate (LP) ratio are increased and correlated in patients with acute liver failure. Furthermore, we expect the purines and L/P ratio to correlate with intracranial pressure (ICP) (positively), and cerebral perfusion pressure (CPP) (negatively).


METHODS
In 17 patients (aged 18-60 years) with acute liver failure and severe hyperammonemia (182 ± 36 μM (mean ± SD)), cerebral microdialysis was performed, and ICP and CPP were monitored. Microdialysate concentrations of hypoxanthine, inosine, lactate, and pyruvate were measured.


RESULTS
The hypoxanthine concentration was 23.0 ± 12 μM in early samples and 11.7 ± 6.8 μM in late samples (normal level ~2.0 μM). The inosine concentration was 7.2 ± 7.1 μM and 2.8 ± 1.6 μM, and the LP ratio was 55.8 ± 21.6 and 45.6 ± 20.8, respectively (normal level ~18). Hypoxanthine correlated significantly to LP ratio (r(2)=0.40, p<0.01) while inosine did not. The purine levels and L/P ratio did not correlate to ICP or CPP, nor did they differ between patients with high ICP (>20 mmHg, n=9) and patients without (n=8).


CONCLUSIONS
This study shows that the high cerebral LP ratio correlates to the hypoxanthine level in patients with acute liver failure. However, these metabolic alterations were not related to the development of intracranial hypertension.
Bjerring
Peter Nissen
PN
Department of Hepatology, Rigshospitalet, University Hospital of Copenhagen, Denmark. peter.nissen.bjerring@rh.regionh.dk
Hauerberg
John
J
Jørgensen
Linda
L
Frederiksen
Hans-Jørgen
HJ
Tofteng
Flemming
F
Hansen
Bent Adel
BA
Larsen
Fin Stolze
FS
D000293:Adolescent; D000328:Adult; D001921:Brain / Q000378:metabolism*; D001929:Brain Edema / Q000209:etiology; D005260:Female; D006801:Humans; D022124:Hyperammonemia / Q000150:complications; D019271:Hypoxanthine / Q000378:metabolism*; D007288:Inosine / Q000378:metabolism; D019586:Intracranial Hypertension / Q000209:etiology; D007427:Intracranial Pressure; D019344:Lactic Acid / Q000378:metabolism*; D017114:Liver Failure, Acute / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D017551:Microdialysis; D008875:Middle Aged; D019289:Pyruvic Acid / Q000378:metabolism*; D055815:Young Adult
D019271:Hypoxanthine; D019344:Lactic Acid; D007288:Inosine; D019289:Pyruvic Acid