|
Journal of Zhejiang University SCIENCE B
ISSN 1673-1581(Print), 1862-1783(Online), Monthly
2014 Vol.15 No.8 P.743-749
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 At the time of LOC, the BIS was recorded and a blood sample was withdrawn for measurement of the concentration of MDZ.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
创新è¦ç‚¹ï¼šæ˜Žç¡®ä¸åŒè‚功能状æ€çš„患者对ä¸æž¢æŠ‘制è¯çš„æ•æ„Ÿæ€§ä»¥åŠBIS预测æ„识消失概率å‘生的æ•æ„Ÿæ€§ã€‚æŒ‡å¯¼ä¸´åºŠåŒ»ç”Ÿæ ¹æ®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。
ç ”ç©¶æ–¹æ³•ï¼šé€‰æ‹©æ„è¯†æ¶ˆå¤±ä½œä¸ºç ”ç©¶ç»ˆç‚¹ï¼Œä»¥50%患者æ„识消失时的咪唑安定的浓度以åŠBISå€¼ä½œä¸ºè§‚å¯ŸæŒ‡æ ‡ã€‚
é‡è¦ç»“论:终末期è‚病患者对ä¸æž¢é•‡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»„:
References:
[1]Cotreau, M.M., von Moltke, L.L., Greenblatt, D.J., 2005. The influence of age and sex on the clearance of cytochrome P450 3A substrates. Clin. Pharmacokinet., 44(1):33-60.
[2]Dahaba, A.A., Worm, H.C., Zhu, S.M., et al., 2008. Sensitivity and specificity of bispectral index for classification of overt hepatic encephalopathy: a multicentre, observer blinded, validation study. Gut, 57(1):77-83.
[3]Foley, J.M., Watson, C.W., Adams, R.D., 1950. Significance of the electroencephalographic changes in hepatic coma. Trans. Am. Neurol. Assoc., 51:161-165.
[4]Franks, N.P., Lieb, W.R., 1998. Which molecular targets are most relevant to general anaesthesia? Toxicol. Lett., 100-101:1-8.
[5]Gibbs, M.A., Hosea, N.A., 2003. Factors affecting the clinical development of cytochrome P450 3A substrates. Clin. Pharmacokinet., 42(11):969-984.
[6]Glass, P.S., Bloom, M., Kearse, L., et al., 1997. Bispectral analysis measures sedation and memory effects of propofol, midazolam, isoflurane, and alfentanil in healthy volunteers. Anesthesiology, 86(4):836-847.
[7]Greenblatt, D.J., Abernethy, D.R., Locniskar, A., et al., 1984. Effect of age, gender, and obesity on midazolam kinetics. Anesthesiology, 61(1):27-35.
[8]Heizmann, P., Ziegler, W.H., 1981. Excretion and metabolism of 14C-midazolam in humans following oral dosing. Arzneimittelforschung, 31(12a):2220-2223.
[9]Hunt, C.M., Westerkam, W.R., Stave, G.M., 1992. Effect of age and gender on the activity of human hepatic CYP3A. Biochem. Pharmacol., 44(2):275-283.
[10]Jenkins, A., Franks, N.P., Lieb, W.R., 1996. Actions of general anaesthetics on 5-HT3 receptors in N1E-115 neuroblastoma cells. Br. J. Pharmacol., 117(7):1507-1515.
[11]Kronbach, T., Mathys, D., Umeno, M., et al., 1989. Oxidation of midazolam and triazolam by human liver cytochrome P450IIIA4. Mol. Pharmacol., 36(1):89-96.
[12]Luo, N.F., Zhang, W.S., Jia, M.X., et al., 2006. Determination of midazolam in plasma by RP-HPLC. West China Pharm. J., 21(4):384-385 (in Chinese).
[13]MacGilchrist, A.J., Birnie, G.G., Cook, A., et al., 1986. Pharmacokinetics and pharmacodynamics of intravenous midazolam in patients with severe alcoholic cirrhosis. Gut, 27(2):190-195.
[14]Mennerick, S., Jevtovic-Todorovic, V., Todorovic, S.M., et al., 1998. Effects of nitrous oxide on excitatory and inhibitory synaptic transmission in hippocampal cultures. J. Neurosci., 18(23):9716-9726.
[15]Milne, S.E., Troy, A., Irwin, M.G., et al., 2003. Relationship between bispectral index, auditory evoked potential index and effect-site EC50 for propofol at two clinical end-points. Br. J. Anaesth., 90(2):127-131.
[16]Nordt, S.P., Clark, R.F.J., 1997. Midazolam: a review of therapeutic uses and toxicity. J. Emerg. Med., 15(3):357-365.
[17]Pentikäinen, P.J., Välisalmi, L., Himberg, J.J., et al., 1989. Pharmacokinetics of midazolam following intravenous and oral administration in patients with chronic liver disease and in healthy subjects. J. Clin. Pharmacol., 29(3):272-277.
[18]Rosow, C., Manberg, P.J., 2001. Bispectral index monitoring. Anesthesiol. Clin. N. Amer., 19(4):947-966.
[19]Sandin, M., Thörn, S.E., Dahlqvist, A., et al., 2008. Effects of pain stimulation on bispectral index, heart rate and blood pressure at different minimal alveolar concentration values of sevoflurane. Acta Anaesthesiol. Scand., 52(3):420-426.
[20]Shafer, S.L., Gregg, K.M., 1992. Algorithms to rapidly achieve and maintain stable drug concentrations at the site of drug effect with a computer-controlled infusion pump. J. Pharmacokinet. Biopharm., 20(2):147-169.
[21]Smith, C., McEwan, A.I., Jhaveri, R., et al., 1994. The interaction of fentanyl on the Cp50 of propofol for loss of consciousness and skin incision. Anesthesiology, 81(4):820-828.
[22]Song, J.C., Zhang, M.Z., Lu, Z.J., et al., 2009. The effects of obstructive jaundice on the pharmacodynamics of propofol: does the sensitivity of intravenous anesthetics change among icteric patients? Acta Anesthesiol. Scand., 53(6):1329-1335.
[23]Song, J.G., Cao, Y.F., Yang, L.Q., et al., 2005. Awakening concentration of desflurane is decreased in patients with obstructive jaundice. Anesthesiology, 102(3):562-565.
[24]von Moltke, L.L., Greenblatt, D.J., Schmider, J., et al., 1996. Midazolam hydroxylation by human liver microsomes in vitro: inhibition by fluoxetine, norfluoxetine, and by azole antifungal agents. J. Clin. Pharmacol., 36(9):783-791.
[25]White, M., Kenny, G.N., 1990. Intravenous propofol anesthesia using a computerized infusion system. Anaesthesia, 45(3):204-209.
[26]Wojnowski, L., 2004. Genetics of the variable expression of CYP3A in humans. Ther. Drug Monit., 26(2):192-199.
[27]Wu, J., Huang, S.Q., Chen, Q.L., et al., 2013. The influence of the severity of chronic virus-related liver disease on propofol requirements during propofol-remifentanil anesthesia. Yonsei Med. J., 54(1):231-237.
[28]Yamakura, T., Harris, R.A., 2000. Effects of gaseous anesthetic nitrous oxide and xenon on ligand-gated ion channels. Comparison with isoflurane and ethanol. Anesthesiology, 93(4):1095-1101.
[29]Yang, L.Q., Song, J.C., Irwin, M.G., et al., 2010. A clinical prospective comparison of anesthetics sensitivity and hemodynamic effect among patients with or without obstructive jaundice. Acta Anaesthesiol. Scand., 54(7):871-877.
[30]Zbinden, A.M., Maggiorini, M., Petersen-Felix, S., et al., 1994. Anesthetic depth defined using multiple noxious stimuli during isoflurane/oxygen anesthesia. I. Motor reactions. Anesthesiology, 80(2):253-260.
Open peer comments: Debate/Discuss/Question/Opinion
<1>
DOI:
10.1631/jzus.B1300242
CLC number:
R452
Download Full Text:
Downloaded:
2637
Download summary:
<Click Here>Downloaded:
1964Clicked:
5292
Cited:
3
On-line Access:
2014-08-05
Received:
2013-09-08
Revision Accepted:
2014-05-06
Crosschecked:
2014-07-11