Cerebral microdialysis reflects the neuroprotective effect of fractionated plasma separation and adsorption in acute liver failure better and earlier than intracranial pressure: a controlled study in pigs

Abstract

BackgroundCerebral edema is a well-recognized and potentially fatal complication of acute liver failure (ALF). The effectiveness of treatments that address intracranial hypertension is generally assessed by measuring intracranial pressure (ICP). The aim of this study was to determine the role of cerebral microdialysis in monitoring the efficacy of fractionated plasma separation and adsorption (FPSA) treatment for ALF. We hypothesized that in ALF cerebral microdialysis reflects the benefits of FPSA treatment on cerebral edema before ICP.MethodsA surgical resection model of ALF was used in 21 pigs. We measured plasma ammonia concentration, brain concentrations of glucose, lactate, pyruvate, glutamate and glutamine, and ICP. Animals were randomized into three groups: in one group eight animals received 6 hours of FPSA treatment 2 hours after induction of ALF; in another group 10 animals received supportive treatment for ALF only; and in the final group three underwent sham surgery.ResultsThe ICP was significantly higher in the ALF group than in the FPSA group 9 hours after surgery. The lactate/pyruvate (L/P) ratio was significantly lower in the FPSA group than the ALF group 5 hours after surgery, before any significant difference in ICP was detected. Indeed, significant changes in the L/P ratio could be observed within 1 hour of treatment. Glutamine levels were significantly lower in the FPSA group than the ALF group between 6 hours and 10 hours after surgery.ConclusionsBrain lactate/pyruvate ratio and concentration of glutamine measured by cerebral microdialysis reflected the beneficial effects of FPSA treatment on cerebral metabolism more precisely and rapidly than ICP in pigs with fulminant ALF. The role of glutamine as a marker of the efficacy of FPSA treatment for ALF appears promising, but needs further evaluation.

Interstitial ion homeostasis and acid-base balance are maintained in oedematous brain of mice with acute toxic liver failure

“…Increased brain tissue or extracellular lactate content (or lactate/pyruvate ratio) is has been recorded, and considered to reflect impaired oxidative metabolism, in brain of comatose human ALF patients (Bjerring et al, 2010; Tofteng et al, 2002), of rats (Zwingmann et al, 2003) or guinea pigs in which ALF was induced by hepatic artery ligation (HAL) (Rose et al, 2007), and in pigs with surgically resected liver (Prazak et al, 2013). Here we found that extracellular lactate does not change in the brains of mice under conditions where ALF was induced by a hepatotoxin, AOM (Fig.…”

Establishment of a Novel Simplified Surgical Model of Acute Liver Failure in the Cynomolgus Monkey

“…Compared with hepatotoxic drug models, surgical models are preferred increasingly by some researchers, particularly in large animals [24, 25]. Generally, the primary surgical procedures used for modeling could be classified into three major categories: devascularization (total and partial), hepatectomy (total and partial), and a combination of both [26, 27].…”

Hepatocyte Transplantation Attenuates the Course of Acute Liver Failure Induced by Thioacetamide in Lewis Rats

“…Some meta-analyses (Kjaergard et al 2003, Struecker et al 2014) have reported no beneficial effects of application of artificial and bioartificial liver support systems on the mortality of patients with ALF. It was shown that while such support devices are safe for acute application and can improve biochemical markers (Prazak et al 2013, Ryska et al 2009, Struecker et al 2014, Stutchfield et al 2011), they do not generally improve survival rate of patients with ALF (Pless 2010, Struecker et al 2014, Stutchfield et al 2011 and, remarkably, no bioartificial liver support system has obtained approval from U.S. Food and Drug Administration for standard clinical uses (Arenas-Herrera et al 2013). It will be noted that the original notion that the critical "failed" function in ALF is detoxification, and thus approaches ensuring this are adequate for treatment of ALF, proved inaccurate (Banares et al 2013, Selden andHodgson 2004).…”