PDF(Pubmed)
Abstract：
OBJECTIVE: Liver function of intensive care patients is routinely monitored by static blood pathology. For specific indications, liver specific cytochrome activity may be measured by the commercially available maximum liver function capacity (LiMAx) test via quantification of the cytochrome P450 1A2 (CYP1A2) dependent C-methacetin metabolism. Sedation with the volatile anesthetic isoflurane was suspected to abrogate the correlation of LiMAx test with global liver function. We hypothesized that isoflurane has a CYP1A2-activity and LiMAx test result decreasing effect.
METHODS: In this monocentric, observational clinical study previously liver healthy intensive care patients, scheduled to be changed from propofol to isoflurane sedation, were enrolled. LiMAx testing was done before, during and after termination of isoflurane sedation.
RESULTS: The mean LiMAx value decreased during isoflurane sedation. Septic patients (n = 11) exhibited lower LiMAx values compared to non-septic patients (n = 11) at all time points. LiMAx values decreased with isoflurane from 140 ± 82 to 30 ± 34 µg kg-1 h-1 in the septic group and from 253 ± 92 to 147 ± 131 µg kg-1 h-1 in the non-septic group while laboratory markers did not imply significant hepatic impairment. Lactate increased during isoflurane inhalation without clinical consequence.
CONCLUSIONS: Sepsis and isoflurane have independently demonstrated an effect on reducing the hepatic CYP1A2-activity. A network model was constructed that could explain the mechanism through the influence of isoflurane on hypoxia inducible factor (HIF-1α) by upregulation of the hypoxia-inducible pathway and the downregulation of CYP1A2-activity via the ligand-inducible pathway. Thus, the increased anaerobic metabolism may result in lactate accumulation. The influence of isoflurane sedation on the validated correlation of global liver function with CYP1A2-activity measured by LiMAx testing needs to be investigated in more detail.
METHODS: In this monocentric, observational clinical study previously liver healthy intensive care patients, scheduled to be changed from propofol to isoflurane sedation, were enrolled. LiMAx testing was done before, during and after termination of isoflurane sedation.
RESULTS: The mean LiMAx value decreased during isoflurane sedation. Septic patients (n = 11) exhibited lower LiMAx values compared to non-septic patients (n = 11) at all time points. LiMAx values decreased with isoflurane from 140 ± 82 to 30 ± 34 µg kg-1 h-1 in the septic group and from 253 ± 92 to 147 ± 131 µg kg-1 h-1 in the non-septic group while laboratory markers did not imply significant hepatic impairment. Lactate increased during isoflurane inhalation without clinical consequence.
CONCLUSIONS: Sepsis and isoflurane have independently demonstrated an effect on reducing the hepatic CYP1A2-activity. A network model was constructed that could explain the mechanism through the influence of isoflurane on hypoxia inducible factor (HIF-1α) by upregulation of the hypoxia-inducible pathway and the downregulation of CYP1A2-activity via the ligand-inducible pathway. Thus, the increased anaerobic metabolism may result in lactate accumulation. The influence of isoflurane sedation on the validated correlation of global liver function with CYP1A2-activity measured by LiMAx testing needs to be investigated in more detail.
摘要：
目的：重症监护患者的肝功能常规通过静态血液病理学监测。对于特定的适应症，肝脏特异性细胞色素活性可以通过对细胞色素P4501A2（CYP1A2）依赖性C-美沙西丁代谢的定量，通过市售的最大肝功能容量（LiMAx）测试来测量。怀疑使用挥发性麻醉剂异氟烷镇静消除了LiMAx试验与整体肝功能的相关性。我们假设异氟烷具有CYP1A2活性和LiMAx试验结果降低作用。
方法：在这个单中心，观察性临床研究以前的肝脏健康重症监护患者，计划从异丙酚改为异氟烷镇静，已注册。LiMAx测试是以前做的，异氟烷镇静期间和之后。
结果：异氟烷镇静期间平均LiMAx值降低。败血症患者(n=11)在所有时间点表现出比非败血症患者(n=11)更低的LiMAx值。在脓毒症组中，异氟烷的LiMAx值从140±82降至30±34µgkg-1h-1，在非脓毒症组中从253±92降至147±131µgkg-1h-1，而实验室标志物并不意味着明显的肝功能损害。吸入异氟烷期间乳酸增加，无临床后果。
结论：脓毒症和异氟烷独立地显示了降低肝CYP1A2活性的作用。构建了一个网络模型，该模型可以解释异氟烷通过上调缺氧诱导途径对缺氧诱导因子（HIF-1α）的影响以及通过配体诱导途径对CYP1A2活性的下调。因此，厌氧代谢的增加可能导致乳酸积累。需要更详细地研究异氟烷镇静作用对通过LiMAx测试测量的整体肝功能与CYP1A2活性的有效相关性的影响。
方法：在这个单中心，观察性临床研究以前的肝脏健康重症监护患者，计划从异丙酚改为异氟烷镇静，已注册。LiMAx测试是以前做的，异氟烷镇静期间和之后。
结果：异氟烷镇静期间平均LiMAx值降低。败血症患者(n=11)在所有时间点表现出比非败血症患者(n=11)更低的LiMAx值。在脓毒症组中，异氟烷的LiMAx值从140±82降至30±34µgkg-1h-1，在非脓毒症组中从253±92降至147±131µgkg-1h-1，而实验室标志物并不意味着明显的肝功能损害。吸入异氟烷期间乳酸增加，无临床后果。
结论：脓毒症和异氟烷独立地显示了降低肝CYP1A2活性的作用。构建了一个网络模型，该模型可以解释异氟烷通过上调缺氧诱导途径对缺氧诱导因子（HIF-1α）的影响以及通过配体诱导途径对CYP1A2活性的下调。因此，厌氧代谢的增加可能导致乳酸积累。需要更详细地研究异氟烷镇静作用对通过LiMAx测试测量的整体肝功能与CYP1A2活性的有效相关性的影响。
