Oellerich M, Armstrong V W
Department of Clinical Chemistry, Georg-August University, Göttingen, Germany.
Ther Drug Monit. 2001 Apr;23(2):81-92. doi: 10.1097/00007691-200104000-00001.
The dynamic liver function test based on the hepatic conversion of lidocaine to monoethylglycinexylidide (MEGX) can complement established static liver function tests if prognostic information is of particular interest. Because of its ease of use and rapid turnaround, the MEGX test has found widespread application for realtime assessment of hepatic function in transplantation, critical care medicine, and various experimental models. Lidocaine is metabolized primarily by the liver cytochrome P450 system through sequential oxidative N-dealkylation, the major initial metabolite in humans being MEGX. Because of the relatively high extraction ratio of lidocaine, this liver function test depends not only on hepatic metabolic capacity but also on hepatic blood flow. For the determination of MEGX in serum, an immunoassay based on the fluorescence polarization immunoassay technique high-performance liquid chromatography and gas liquid chromatography methods have been described. Whereas high-performance liquid chromatography and gas liquid chromatography are specific for MEGX, the fluorescence polarization immunoassay also cross-reacts with 3-OH-MEGX. Although this is not a problem in humans, some species, such as the rat, produce significant amounts of this metabolite. The findings of most studies published so far suggest that the MEGX test is a useful tool that can improve our decision-making process with respect to the selection of transplant candidates. Patients with a MEGX 15- or 30-minute test value <10 microg/L have a particularly poor 1-year survival rate. Serial monitoring of liver graft recipients early after transplantation with the MEGX test may initially alert the clinician to a major change in liver function; if used with other tests, such as serum hyaluronic acid concentrations, it may become more discriminatory. In critically ill patients, several studies have shown that an initially rapid decrease in MEGX test values is associated with an enhanced risk for the development of multiple organ dysfunction syndrome and a poor outcome. Further, this decrease appears to be associated with an enhanced systemic inflammatory response. The MEGX test has potential for investigating the pathogenesis of multiple organ dysfunction syndrome with regard to early hepatic functional impairment in critically ill patients after polytrauma or sepsis.
基于利多卡因在肝脏中转化为单乙基甘氨酰二甲苯胺(MEGX)的动态肝功能试验,如果对预后信息特别感兴趣,可补充已有的静态肝功能试验。由于其使用方便且周转迅速,MEGX试验已在移植、重症医学和各种实验模型中广泛应用于肝功能的实时评估。利多卡因主要通过肝脏细胞色素P450系统经连续的氧化N-脱烷基作用进行代谢,在人类中主要的初始代谢产物是MEGX。由于利多卡因的提取率相对较高,该肝功能试验不仅取决于肝脏代谢能力,还取决于肝血流量。对于血清中MEGX的测定,已描述了基于荧光偏振免疫分析技术、高效液相色谱法和气液色谱法的免疫分析方法。虽然高效液相色谱法和气液色谱法对MEGX具有特异性,但荧光偏振免疫分析也与3-OH-MEGX发生交叉反应。虽然这在人类中不是问题,但一些物种,如大鼠,会产生大量这种代谢产物。迄今为止发表的大多数研究结果表明,MEGX试验是一种有用的工具,可改善我们在选择移植候选者方面的决策过程。MEGX 15分钟或30分钟试验值<10μg/L的患者1年生存率特别低。移植后早期对肝移植受者进行MEGX试验的连续监测,可能最初会提醒临床医生肝功能发生重大变化;如果与其他试验,如血清透明质酸浓度一起使用,可能会更具鉴别力。在重症患者中,多项研究表明,MEGX试验值最初迅速下降与发生多器官功能障碍综合征的风险增加及不良预后相关。此外,这种下降似乎与全身炎症反应增强有关。MEGX试验有潜力研究多器官功能障碍综合征的发病机制,涉及多发伤或脓毒症后重症患者的早期肝功能损害。