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Monoethylglycinexylidide (MEGX) as an early predictor of liver dysfunction in severe sepsis

The development of demonstrable liver dysfunction in severe sepsis is associated with high rates of mortality. Lidocaine metabolite MEGX has proven to be a highly sensitive indicator of hepatic dysfunction, especially in the field of liver transplantation. The present study aimed to assess the prognostic value of MEGX formation kinetics in predicting liver dysfunction in patients with severe sepsis, and compared it with other oxygenation indices as well as gastric mucosal pH (pHi).

Twenty-seven patients meeting the criteria for severe sepsis as defined by Bone et al were prospectively evaluated. Patients with hemodynamic instability, high liver enzymes (> 2 × normal) and bilirubin levels (> 3 mg/dl), coagulation disorders, and gastrointestinal bleeding were not included. A gastric tonometer (TRIP, Tonometrics, Worchester, MA) was introduced in all patients in place of a standard nasogastric tube. Gastric pHi was calculated as previously described. Oxygen delivery (DO2) was calculated by the simplified formula DO2 = CI × CaO2, and oxygen consumption (VO2) was determined by indirect calculation of the product of CI and arteriovenous oxygen content difference. Plasma aspartate aminotransferase, alanine aminotransferase, bilirubin and arterial lactate levels were determined by using enzymatic method. The serum MEGX concentrations were determined using an automated fluorescence polarization immunoassay (TDX, Abbott, Chicago) before and 15 min after an iv injection of 1 mg/kg lidocaine. Liver dysfunction indices (bilirubin > 3 mg/dl, liver enzymes > 2 × normal) were recorded until discharge or death. Effectiveness in predicting liver dysfunction was compared by calculating the sensitivity and specificity for each variable (lactate, pHi, MEGX). To evaluate the accuracy with which of these variables were able to discriminate between those %. In ROC curves constructed to compare the ability of the variables to discriminate two patient groups, MEGX displayed the greatest predictability of liver failure development in regard to lactate and pHi. Relating these variables to survival patients who developed clinically demonstrable liver dysfunction (LD+) and those who did not (LD-), receiver operating characteristics (ROC) curves were constructed. Values of the measurements given as median (25th per cent, 75th per cent) were compared by the Mann-Whitney U test.

MEGX values were the only parameter that showed a significant difference when comparing the two groups (LD+, LD-), Sixty-three per cent of the patients had MEGX values below 90 μg/1 which is a limit indicated as an impaired liver function. MEGX cut-off at 60 μg/l had a prognostic sensitivity of 84% and a specificity of 100, no significancy was determined in any of the parameters. No correlation was found between MEGX or pHi and oxygen derived variables, and there was also no significant difference in hemodynamics and oxygen derived variables either between LD+ and LD- groups, or in survivors and non-survivors.

Our data demonstrated that MEGX formation kinetics is an early bedside procedure to dynamically assess hepatic functions. This test might be an early sign showing the hepatic insult in severe sepsis when the global circulatory and splanchnic circulation indices are in normal range. More research is essential in order to see whether this parameter can guide therapeutic strategies for preventing liver hypoxia or metabolic impairment in the very early phase of sepsis.

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Esen, F., Erdem, T., Frieß, U. et al. Monoethylglycinexylidide (MEGX) as an early predictor of liver dysfunction in severe sepsis. Crit Care 1 (Suppl 1), P083 (1997).

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