Chidambaran Vidya, Sadhasivam Senthilkumar, Mahmoud Mohamed
Department of Anesthesiology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, USA.
Curr Opin Anaesthesiol. 2017 Jun;30(3):349-356. doi: 10.1097/ACO.0000000000000455.
Use of perioperative opioids for surgical pain management of children presents clinical challenges because of concerns of serious adverse effects including life-threatening respiratory depression. This is especially true for children with history of obstructive sleep apnea. This review will explore current knowledge of clinically relevant factors and genetic polymorphisms that affect opioid metabolism and postoperative outcomes in children.
Within the past several years, an increasing number of case reports have illustrated clinically important respiratory depression, anoxic brain injuries and even death among children receiving appropriate weight-based dosages of codeine and other opioids for analgesia at home setting particularly following tonsillectomy. Several national and international organizations have issued advisories on use of codeine in pediatrics, based on cytochrome P450 family 2 subfamily D type 6 (CYP2D6) pharmacogenetics. We have discussed the pros and cons of alternatives to codeine for pain management.
Although routine preoperative genotyping to identify children at risk and personalized opioid use for pediatric perioperative pain management is still a distant reality, current known implications of CYP2D6 pharmacogenetics on codeine use shows that pharmacogenetics has the potential to guide anesthesia providers on perioperative opioid selection and dosing to maximize efficacy and safety.
围手术期使用阿片类药物来管理儿童手术疼痛存在临床挑战，因为担心其严重不良反应，包括危及生命的呼吸抑制。对于有阻塞性睡眠呼吸暂停病史的儿童尤其如此。本综述将探讨影响儿童阿片类药物代谢和术后结果的临床相关因素及基因多态性的现有知识。
在过去几年中，越来越多的病例报告表明，在家中接受基于适当体重剂量的可待因和其他阿片类药物镇痛的儿童，尤其是扁桃体切除术后，出现了具有临床重要性的呼吸抑制、缺氧性脑损伤甚至死亡。基于细胞色素P450 2D6（CYP2D6）药物遗传学，几个国家和国际组织已发布关于儿科使用可待因的建议。我们讨论了可待因替代药物用于疼痛管理的利弊。
虽然通过常规术前基因分型来识别有风险的儿童以及针对儿科围手术期疼痛管理进行个性化阿片类药物使用仍是遥远的现实，但目前已知的CYP2D6药物遗传学对可待因使用的影响表明，药物遗传学有潜力指导麻醉医生在围手术期选择阿片类药物和确定剂量，以实现疗效和安全性的最大化。
