Brain hypoxanthine concentration correlates to lactate/pyruvate ratio but not intracranial pressure in patients with acute liver failure

Background & Aims 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 mu M (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 mu M in early samples and 11 7 6 8 mu M in late samples (normal level similar to 2 0 mu M) The inosine concentration was 7 2 +/- 7 1 mu M and 2 8 +/- 1 6 mu M and the LP ratio was 55 8 21 6 and 45 6 208 respectively (normal level similar to 18) Hypoxanthine correlated significantly to LP ratio (r(2) = 040 p <001) 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 (C) 2010 European Association for the Study of the Liver Published by Elsevier B V All rights reserved