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 18–60years) with acute liver failure and severe hyperammonemia (182±36μM (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±12μM in early samples and 11.7±6.8μM in late samples (normal level ∼2.0μM). The inosine concentration was 7.2±7.1μM and 2.8±1.6μM, 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 20mmHg, 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.