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Journal of Zhejiang University SCIENCE B

ISSN 1673-1581(Print), 1862-1783(Online), Monthly

Effect of hepatic function on the EC50 of midazolam and the BIS50 at the time of loss of consciousness

Abstract: Objective: To explore the effect of hepatic function on loss of consciousness (LOC) and bispectral index (BIS) during sedation with midazolam (MDZ). Methods: Forty-five patients were assigned to three groups according to their liver function. Thirty of these patients with diagnoses of cholelithiasis were scheduled laparoscopic cholecystectomy, including 15 patients with normal liver function (normal group), and 15 patients with moderately abnormal liver function based on the results of ultrasonic diagnosis of a moderately fatty liver and elevated alanine transaminase levels of less than three times normal (moderate group). The other 15 patients with end-stage liver disease (severe group) underwent liver transplantation. Each patient was administered MDZ by way of target-controlled infusion to increase the concentration gradually. At the time of LOC, the BIS was recorded and a blood sample was withdrawn for measurement of the concentration of MDZ. The concentration of MDZ (EC50) and the BIS value (BIS50) at which 50% of patients lose consciousness were calculated using logistic regression. Results: At the time of LOC, the EC50 of MDZ and the BIS50 were similar in the normal and moderate groups (P>0.05). LOC occurred at a lower EC50 of MDZ and at a higher BIS50 in the severe group, compared with the normal and moderate groups (P<0.01). Conclusions: Patients with end-stage liver disease were more sensitive to MDZ and this affected the prediction of their time of LOC following MDZ administration. There were no changes in response in patients with moderately abnormal hepatic function.

Key words: Midazolam, Hepatic function, EC50, Bispectral index (BIS), Loss of consciousness

Chinese Summary  <23> è‚功能对æ„识消失时咪达唑仑血浆浓度和脑电åŒé¢‘谱指数的影å“

研究目的:探索ä¸åŒè‚功能指数对镇é™è¯å’ªè¾¾å”‘仑的æ•æ„Ÿæ€§ä»¥åŠè„‘电åŒé¢‘谱指数(BIS)的预测æ„识消失的影å“。
创新è¦ç‚¹ï¼šæ˜Žç¡®ä¸åŒè‚功能状æ€çš„患者对中枢抑制è¯çš„æ•æ„Ÿæ€§ä»¥åŠBIS预测æ„识消失概率å‘生的æ•æ„Ÿæ€§ã€‚指导临床医生根æ®æ‚£è€…çš„è‚功能状æ€åˆç†ä½¿ç”¨ä¸­æž¢æŠ‘制è¯ä»¥åŠæ­£ç¡®åˆ©ç”¨BIS预测镇定深度。
研究方法:选择æ„识消失作为研究终点,以50%患者æ„识消失时的咪唑安定的浓度以åŠBIS值作为观察指标。
é‡è¦ç»“论:终末期è‚病患者对中枢镇é™è¯å’ªå”‘安定更æ•æ„Ÿï¼Œè¯¥ç±»æ‚£è€…在BIS预测æ„识消失概率å‘生的æ•æ„Ÿæ€§å­˜åœ¨å·®å¼‚。

关键è¯ç»„:咪达唑仑;脑电åŒé¢‘谱指数;è‚功能;æ„识消失;CYP3A4


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DOI:

10.1631/jzus.B1300242

CLC number:

R452

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On-line Access:

2014-08-05

Received:

2013-09-08

Revision Accepted:

2014-05-06

Crosschecked:

2014-07-11

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