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中华移植杂志(电子版)

中华移植杂志(电子版) ›› 2018, Vol. 12 ›› Issue (02) : 75 -79. doi: 10.3877/cma.j.issn.1674-3903.2018.02.007

所属专题： 文献；

综述

肝移植受者围手术期镇痛药物的选择与合理应用
饶跃峰1, 张晅2, 王融溶1, 冯智英3, 卢晓阳1, 王伟林4,†()   
  1. 1. 310003　杭州，浙江大学医学院附属第一医院药学部
    2. 310003　杭州，浙江大学医学院附属第一医院药学部；225001　扬州，江苏省苏北人民医院药学部
    3. 310003　杭州，浙江大学医学院附属第一医院疼痛科
    4. 310003　杭州，浙江大学医学院附属第一医院肝胆胰外科
  • 收稿日期:2017-06-13 出版日期:2018-05-25
  • 通信作者: 王伟林
  • 基金资助:
    浙江省自然科学基金(LY17H310002)

Selection and rational use of analgesics in perioperative period of liver transplantation

Yuefeng Rao1, Xuan Zhang2, Rongrong Wang1, Zhiying Feng3, Xiaoyang Lu1, Weilin Wang4,†()   

  1. 1. Department of Pharmacy, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
    2. Department of Pharmacy, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China; Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
    3. Department of Pharmacy, Northern Jiangsu People′s Hospital, Yangzhou 225001, China
    4. Department of Pain Medicine, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
  • Received:2017-06-13 Published:2018-05-25
  • Corresponding author: Weilin Wang
  • About author:
    Corresponding author: Wang Weilin, Email:
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饶跃峰, 张晅, 王融溶, 冯智英, 卢晓阳, 王伟林. 肝移植受者围手术期镇痛药物的选择与合理应用[J]. 中华移植杂志(电子版), 2018, 12(02): 75-79.

Yuefeng Rao, Xuan Zhang, Rongrong Wang, Zhiying Feng, Xiaoyang Lu, Weilin Wang. Selection and rational use of analgesics in perioperative period of liver transplantation[J]. Chinese Journal of Transplantation(Electronic Edition), 2018, 12(02): 75-79.

肝移植已成为现代医学中治疗终末期肝病的常规手术，近年来在国内外均有长足进步和发展。与肝功能正常的其他经腹手术患者相比，肝移植受者围手术期阿片类药物的需求量更低。术前肝功能水平和手术过程、术后一过性障碍以及手术创伤等均会影响镇痛药物的药物代谢动力学和药物效应动力学。选择合适的药物和剂量有助于获得适宜的麻醉深度及疼痛控制，同时避免过度镇静延长术后机械通气时间的风险，有利于肝移植受者的快速康复。本文对目前肝移植中常用镇痛药物的药物代谢动力学、药物效应动力学及其在肝移植受者中的合理应用及安全性作一综述，为肝移植围手术期疼痛管理提供参考。

关键词: 肝移植, 终末期肝病, 围手术期, 肝功能障碍, 疼痛管理, 镇痛药物

Liver transplantation has become a routine surgery for the treatment of end-stage liver disease in modern medicine, great progress and development of surgical techniques have been made world-wide in recent years. Liver transplantation recipients have been reported to have decreased demand for opioid during perioperative period compared with patients who underwent other types of abdominal surgeries without liver disease. Preoperative liver function, process of transplantation, transient hepatic dysfunction after surgery and surgical trauma may alter the pharmacokinetic and pharmacodynamic of different analgesic. Proper medication and dosage selection can help to obtain adequate anesthetic depth and pain control, and reduce the risk of prolongation of mechanical ventilation caused by over-sedation, and is also conducive to rehabilitation of patients. This review mainly focuses on the pharmacokinetics, pharmacodynamics of commonly used analgesics in liver transplantation, and its reasonable application and safety in liver transplantation recipients, hoping to provide reference for pain management in perioperative of liver transplantation.

Key words: Liver transplantation, End-stage liver disease, Perioperative period, Liver dysfunction, Pain management, Analgesic
表1 基于药物代谢动力学参数的镇痛药物分类
分类 CLH影响因素 代表药物
ERH≥0.7 QH 芬太尼、舒芬太尼
0.3<ERH<0.7 PB、酶活性、QH 可待因、哌替啶
ERH≤0.3, PB<85% 酶活性 对乙酰氨基酚
ERH≤0.3, PB≥85% PB、酶活性 吲哚美辛
表2 阿片类药物代谢动力学参数和代谢途径
药物 血浆蛋白结合率(%) 肝摄取率 消除半衰期 主要代谢途径
可待因 7.0 0.52 3.0 h CYP2D6、葡萄糖醛酸结合
哌替啶 70.0 0.52 3.0～4.5 h CYP2B6、CYP3A4
吗啡 30.0～40.0 0.70 2.0～4.0 h 葡萄糖醛酸结合、去甲基
氢吗啡酮 15.0 0.51 2.3 h 葡萄糖醛酸结合
羟考酮 40.0～45.0 <0.70 3.0～5.0 h CYP2D6、CYP3A4
芬太尼 80.0～85.0 0.80 2.5～6.0 h CYP3A4
舒芬太尼 92.5 0.70～0.90 164.0 min CYP3A4/5
瑞芬太尼 92.0 － 3.0～10.0 min 非特异性血液和组织酯酶水解
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