The low-dose monoethylglycinexylidide test: Assessment of liver function with fewer side effects

Abstract

tients with chronic active hepatitis and cirrhosis. [4][5][6][7] Other The hepatic metabolism of lidocaine (1 mg/kg intravestudies have speculated that the test could replace histology nously) to its metabolite monoethylglycinexylidide for the diagnosis of cirrhosis. [8][9][10] However, in addition to the (MEG-X) is the basis of the standard MEG-X test. To retest's diagnostic value, its side effects must be considered. duce the lidocaine-induced side effects, we evaluated the The majority of authors have reported a low preva-MEG-X formation after 0.5 and 1 mg/kg lidocaine intravelence. 3,4,8,10,11 Only one study reported side effects in almost nously in subjects with normal (n Å 5) and severely imall tested individuals. 9 Surprisingly, the symptoms following paired liver function (n Å 7) (study I). From this study, lidocaine injection were not related to the degree of hepatic a low-dose test (MEG-X concentration 30 minutes after histological changes or to the Child class. 9 Because of these 50 mg lidocaine intravenously [MEG-X 30min ] normalized contradictory findings, the safety of the MEG-X test has been to standard MEG-X test results) was developed. Sensory questioned, and further studies were recommended. 12,13 Most side effects from this low dose and from the standard lidocaine-induced side effects are dose-dependent. In con-MEG-X test were compared in a double-blind, randomtrast, lidocaine clearance and the MEG-X formation rate are ized, cross-over study (study II) comprising 15 individudose-independent. 14 To date, it has not been evaluated als with normal liver function and 45 patients with cirwhether this first-order kinetic model holds true for patients rhosis (15 Child A, 15 Child B, and 15 Child C). In study I, with advanced cirrhosis. If this were the case, it should be MEG-X formation rate was dose-independent in patients possible to reduce side effects by extrapolating MEG-X values with severely impaired liver function. In study II, norobtained with lower lidocaine doses to standard MEG-X test malized MEG-X test results (ranging from°4 to 120 mg/ results. Therefore, we studied (study I) the dose-dependent L) were virtually identical to the standard test results pharmacokinetics of lidocaine in patients with severely im-(mean difference: 01.9 mg/L; 95% confidence interval paired liver function. In a second double-blind randomized [CI]: 05.3; 1.5 mg/L). Fewer individuals experienced side controlled study (study II), we assessed the sensory quality effects (30% vs. 53%) with the low-dose test (P Å .0013).and intensity of patients' side effects with the aim of finding In a multivariate analysis, the Child-Pugh score was intheir relationship to lidocaine dosage and liver function. and 0.5 mg/kg body weight to individuals with normal (n Å 5) and severely impaired liver function (n Å 7). To compare the low-dose versus the standard MEG-X test (study II: double-blind, randomized, Lidocaine is metabolized to its principal metabolite, monocross-over design), we injected 1 mg/kg body weight lidocaine and 50 ...

Elevated Soluble Tumour Necrosis Factor Receptor Serum Concentrations and Short-Term Mortality in Liver Cirrhosis without Acute Infections

“…A possible biologic explanation for this correlation could be that reduced MEGX test results in patients with liver cirrhosis may reflect depression of CYP3A4 activity by endotoxin which has been demonstrated by Shedlosfsky et al [40]. However, MEGX test results may not only reflect CYP3A4 activity [19, 41]but may also be related to impaired liver cell function, increased portovenous shunting, hypoperfusion of the hepatic parenchyma and to an increased volume of distribution [27, 42]. It is noteworthy that sTNF-R 75 serum concentrations were also found to be elevated in other clinical situations with hepatic hypoperfusion and an increased volume of distribution such as chronic heart failure [5].…”

“…Ten healthy individuals with normal liver function served as controls (table 1). All individuals had participated in a previously reported study [27]. However, none of the patients with liver cirrhosis was included into other long-term treatment trials during the study period.…”

Plasma hydroxy-metronidazole/ metronidazole ratio in hepatitis C virus-induced liver disease

“…The formation of monoethylglycinexylidide (MEGX), the main lidocaine metabolite, has been suggested as a simple and valuable liver function test (22)(23)(24). However, the administration of lidocaine may produce side effects in a high percentage of individuals tested (22), the formation of MEGX may be influenced by age and gender (24,25), and the lidocaine dose to be administered and the time point for measuring the MEGX concentration are still controversial (26)(27)(28). The MEGX test has also failed to discriminate between healthy volunteers and patients with chronic hepatitis (10,29).…”

Effect of erythromycin and rifampicin on monoethylglycinexylidide test

“…A power analysis, based on the coefficients of variation previously obtained for the 30-60 min MEGX concentrations,[7] indicated that ten subjects should be sufficient to detect differences of 20% with a significance level of 0.05 and power of 80%, in both, rifampicin and erythromycin studies. MEGX concentration values from 30-60 min were tested for normal distribution using the method of Kolmogorov and Smirnov.…”