Cerebral microdialysis in patients with fulminant hepatic failure

Abstract

Fulminant hepatic failure (FHF) is often complicated by high intracranial pressure (ICP) and fatal brain damage. In this study, we determined if a rise in [glutamate]ec and [lactate]ec preceded surges of high ICP in patients with FHF (median age, 42; range, 20-55 years; 7 women; 3 men) by inserting a microdialysis catheter into the brain-cortex together with an ICP catheter. The microdialysis catheter was perfused with artificial cerebrospinal-fluid at a rate of 0.3 microL/min. Dialysate was collected approximately every 30 minutes or when ICP increased. A total of 352 microdialysis samples were collected during a median of 3 days and allowed for approximately 1,760 bedside analyses of the collected dialysate. In 5 patients that later developed surges of high ICP, the initial values of [glutamate]ec and [lactate]ec were 2 to 5 times higher compared with patients with normal ICP. [Glutamate]ec then tended to vanish with time in both groups of patients. An increase in [glutamate]ec did not precede high ICP in any of the cases. In contrast, [lactate]ec was high throughout the study in the high ICP group and increased further before surges of high ICP. We conclude that in patients with FHF, cerebral [glutamate]ec and [lactate]ec are elevated. However, the elevated [glutamate]ec is not correlated to high ICP. In contrast, elevations in [lactate]ec preceded surges of high ICP. In conclusion, accelerated glycolysis with lactate accumulation is implicated in vasodilatation and high ICP in patients with FHF. The data suggest that bedside cerebral microdialysis is a valuable tool in monitoring patients with FHF and severe hyperammonemia.

Brain edema in acute liver failure and chronic liver disease: Similarities and differences

“…An increase in extracellular glutamate has been documented to be associated with severe HE (Michalak et al, 1996, Oria et al, 2012, Rose et al, 2007and Tofteng et al, 2002, and has been described to occur as a result of decreased mRNA and protein expression of astrocytic glutamate transporters (Desjardins et al, 2001, Knecht et al, 1997, Norenberg et al, 1997and Suárez et al, 2000. Subsequently, this is accompanied by a decrease in GS activity, but the continuous presence of high glutamine levels (Desjardins et al, 1999 andRao et al, 2005).…”

Hypothermia in Acute Liver Failure

“…Chatauret et al (2001) found an increase in CSF lactate during severe encephalopathy and brain edema in rats with ALF. Clinically, extracellular brain lactate concentrations were found to increase in association with increased ICP in patients with ALF (Tofteng et al, 2002). It has also been demonstrated that alanine is elevated in the hyperammonemic brain (Hilgier et al, 1999;Mans et al, 1994;Swain et al, 1992) and more recently in rats with ALF using nuclear magnetic resonance (NMR) spectroscopy (Chatauret et al, 2003).…”

Keeping cool in acute liver failure: Rationale for the use of mild hypothermia

“…These observations may provide new insights into the pathogenesis of brain edema in ALF. Increased extracellular brain glutamate is a common finding in ALF [98], [99], [100] and [101]. Potential explanations include impairment of its clearance [102] and [103] and deregulation of calcium-dependent glutamate release from astrocytes [104].…”

“…Increased brain lactate is common in animal models [77], [93], [94] and [121], and peaks of lactate in brain microdialysate preceding surges of ICP have been described in patients with ALF [98]. Increased brain lactate correlated with worsening encephalopathy and intracranial hypertension in experimental models [92] and [121], and it was due to increased de novo synthesis from circulating glucose.…”