Bonnardot J P, Levron J C, Deslauriers M, Brule M L, Flaisler B, Deligne P
Département d'Anesthésie-Réanimation, Hôpital Tenon, Paris.
Ann Fr Anesth Reanim. 1991;10(5):443-9. doi: 10.1016/s0750-7658(05)80847-0.
The pharmacokinetics of etomidate were studied in 9 control subjects (with normal liver function) and in 5 patients with cirrhosis scheduled for gastro-intestinal surgery. Anaesthetic induction included an initial bolus of etomidate 0.3 mg.kg-1, together with fentanyl 2 micrograms.kg-1, and pancuronium 60 micrograms.kg-1. An etomidate infusion was then started according to one of two following schemes: a (0.03 mg.kg-1.min-1 for 10 min, and then 0.01 mg.kg-1.min-1), or B (0.1 mg.kg-1.min-1 for 10 min, followed by 0.02 mg.kg-1.min-1 for a further 110 min, and 0.01 mg.kg-1.min-1 thereafter). Plasma concentrations of etomidate were determined at regular intervals throughout anaesthesia, and up to four hours afterwards, using inverse phase high pressure liquid chromatography. The infusion was given for 273 +/- 87 min in controls, and for 259 +/- 56 min in the cirrhotic group. Scheme A, only used in 3 controls and 1 cirrhotic in a preliminary study, resulted in very low plasma concentrations: 0.2 to 0.4 micrograms.ml-1. Those measured during the apparent plateau phase (steady state) of infusion protocol B were close to predicted values (0.5 to 0.6 micrograms.ml-1) in controls, whereas higher concentrations (approximately 1.5 micrograms.ml-1) were reached in cirrhotic patients. For all the patients the time interval to spontaneous recovery was 41 +/- 27 min; plasma levels were then 0.199 +/- 0.092 micrograms.ml-1. There were significant alterations in pharmacokinetic parameters in the cirrhotic patients.(ABSTRACT TRUNCATED AT 250 WORDS)
在9名对照受试者(肝功能正常)和5名计划接受胃肠手术的肝硬化患者中研究了依托咪酯的药代动力学。麻醉诱导包括初始静脉推注0.3 mg·kg-1依托咪酯,以及2 μg·kg-1芬太尼和60 μg·kg-1潘库溴铵。然后根据以下两种方案之一开始输注依托咪酯:方案A(0.03 mg·kg-1·min-1持续10分钟,然后0.01 mg·kg-1·min-1),或方案B(0.1 mg·kg-1·min-1持续10分钟,随后0.02 mg·kg-1·min-1再持续110分钟,之后为0.01 mg·kg-1·min-1)。在整个麻醉期间及之后长达4小时,定期使用反相高压液相色谱法测定依托咪酯的血浆浓度。对照组输注时间为273±87分钟,肝硬化组为259±56分钟。方案A仅在一项初步研究中的3名对照者和1名肝硬化患者中使用,导致血浆浓度非常低:0.2至0.4 μg·ml-1。在输注方案B的明显平台期(稳态)测得的浓度在对照组中接近预测值(0.5至0.6 μg·ml-1),而肝硬化患者中达到的浓度更高(约1.5 μg·ml-1)。所有患者自主恢复的时间间隔为41±27分钟;此时血浆水平为0.199±0.092 μg·ml-1。肝硬化患者的药代动力学参数有显著改变。(摘要截断于250字)