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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 At the time of LOC, the BIS was recorded and a blood sample was withdrawn for measurement of the concentration of MDZ.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  <22> 肝功能对意识消失时咪达唑仑血浆浓度和脑电双频谱指数的影响

研究目的:探索不同肝功能指数对镇静药咪达唑仑的敏感性以及脑电双频谱指数(BIS)的预测意识消失的影响。
创新要点:明确不同肝功能状态的患者对中枢抑制药的敏感性以及BIS预测意识消失概率发生的敏感性。指导临床医生根据患者的肝功能状态合理使用中枢抑制药以及正确利用BIS预测镇定深度。
研究方法:选择意识消失作为研究终点,以50%患者意识消失时的咪唑安定的浓度以及BIS值作为观察指标。
重要结论:终末期肝病患者对中枢镇静药咪唑安定更敏感,该类患者在BIS预测意识消失概率发生的敏感性存在差异。

关键词组:咪达唑仑;脑电双频谱指数;肝功能;意识消失;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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