CYP3A4基因多态性对羟考酮抑制腰椎手术后疼痛的影响-东南大学学报医学版

CYP3A4基因多态性对羟考酮抑制腰椎手术后疼痛的影响

单位：1. 大连医科大学研究生院, 辽宁大连 116044;
2. 南京医科大学附属常州市第二人民医院麻醉科, 江苏常州 213003

分类号：R681.57;R971.2

出版年·卷·期（页码）：2021·40·第六期（790-795）

摘要：

目的: 观察细胞色素P450 3A4酶(CYP3A4)基因多态性对羟考酮抑制腰椎手术后疼痛的影响。方法: 静吸复合全身麻醉下行腰椎手术患者150例, ASAⅠ或Ⅱ级, 按照术前CYP3A4基因型检测结果分成3组: 野生型纯合子(CYP3A4*1/*1, n=80)标记为AA组, 突变杂合子(CYP3A4*1/*1G, n=60)标记为GA组, 突变纯合子(CYP3A4*1G/*1G, n=10)标记为GG组。所有患者均于手术完成前30 min静脉推注羟考酮5 mg, 同时予以静脉泵镇痛。于术后10 min(T₀)、6 h(T₁)、12 h(T₂)和24 h(T₃)进行疼痛强度数字评估量表(NRS)评分, 同时抽取静脉血2 ml测定血浆皮质醇(Cor), 记录术后24 h羟考酮的使用剂量、患者自控静脉镇痛(PCIA)按压次数、无效按压次数和不良反应(恶心、呕吐和呼吸抑制)的发生情况, 同时计算术后24 h内时间加权平均动脉压(TWA-MAP)和时间加权平均心率(TWA-HR)。结果: (1) 与AA组比较, GA和GG组患者在各时间点的疼痛强度NRS评分降低, 在T₁、T₂、T₃时间点血浆Cor水平也降低(P < 0.05)。(2) 与AA组比较, GA和GG组PCIA按压次数和无效按压次数减少(P < 0.05), 羟考酮的总使用量也减少(P < 0.05), 恶心呕吐的发生率也明显降低(P < 0.05);但3组间呼吸抑制的发生率差异无统计学意义(P > 0.05)。(3) 与AA组比较, GA和GG组TWA-MAP和TWA-HR明显降低(P < 0.05)。结论: CYP3A4基因多态性是影响羟考酮镇痛效果的遗传因素。

Objective: To observe the effects of CYP3A4 gene polymorphism on inhibiting the postoperative pain of oxycodone in lumbar surgery.Methods: 150 patients undergoing selective lumbar surgery with general anesthesia were divided into three groups according to genotype: Wild-type homozygous (CYP3A4*1/*1, n=80) named AA group, Mutant heterozygous (CYP3A4*1/*1G, n=60) named GA group, Mutant homozygous (CYP3A4*1G/*1, n=10) named GG group. All patients received intravenous injection of 5 mg oxycodone 30 min before the end of the surgery, and continuous analgesia with intravenous analgesia pump. Numerical rating scales (NRS) were evaluated and venous blood was drawn to detect plasma cortisol at 10 min (T0), 6 h (T1), 12 h (T2), and 24 h (T3) after surgery. In addition, the total dose of oxycodone, the number of patient controlled intravenous analgesia(PCIA) compression and the ratio of adverse reactions (nausea, vomiting, and respiratory depression) were recorded, and the time-weighted mean arterial pressure (TWA-MAP) and time-weighted mean heart rate (TWA-HR) within 24 hours after surgery were calculated.Results: (1) Compared with the AA group, the NRS score in GA and AA groups decreased at all time points, and the level of Cor declined at T₁, T₂ and T₃(P < 0.05). (2) Compared with the AA group, the number of PCIA compression and the total dose of oxycodone in GA and GG groups were all reduced, therefore the ratio of nausea and vomiting was declined accordingly, but there was no significant difference in incidence of respiratory depression among the three groups(P > 0.05). (3) Compared with the AA group, the TWA-MAP and TWA-HR in GA and AA groups decreased significantly(P < 0.05).Conclusion: CYP3A4 gene polymorphism is a genetic factor affecting the analgesic effect of oxycodone.

参考文献：

[1] VAN DER SCHIER R, ROOZEKRANS M, VAN VELZEN M, et al. Opioid-induced respiratory depression: reversal by non-opioid drugs[J]. F1000Prime Reports, 2014, 6: 79.
[2] 徐建国. 盐酸羟考酮的药理学和临床应用[J]. 临床麻醉学杂志, 2014, 30(5): 511-513.
[3] 刘金玉, 刘东, 张程亮, 等. 基因多态性与羟考酮个体差异相关性的研究进展[J]. 中国疼痛医学杂志, 2017, 23(9): 686-690.
[4] ZHANG W, CHANG Y Z, KAN Q C, et al. CYP3A4*1G genetic polymorphism influences CYP3A activity and response to fentanyl in Chinese gynecologic patients[J]. Eur J Clin Pharmacol, 2010, 66(1): 61-66.
[5] 张啟维, 薛庆云, 王强, 等. 帕瑞昔布在后路腰椎融合术后多模式镇痛中的临床应用[J]. 中国脊柱脊髓杂志, 2010(10): 69-73.
[6] 何磊, 王志杰. 腰椎后路手术三种术后镇痛方式的比较分析[J]. 颈腰痛杂志, 2016, 37(6): 511-514.
[7] KIM K M, KIM H S, LIM S H, et al. Effects of genetic polymorphisms of OPRM1, ABCB1, CYP3A4/5 on postoperative fentanyl consumption in Korean gynecologic patients[J]. Int J Clin Pharmacol Ther, 2013, 51(5): 383-392.
[8] 许幸, 吴新民, 薛张纲, 等. 盐酸羟考酮注射液用于全麻患者术后镇痛的有效性和安全性: 前瞻性、随机、盲法、多中心、阳性对照临床研究[J]. 中华麻醉学杂志, 2013, 33(3): 269-274.
[9] SILVASTI M, ROSENBERG P, SEPPALA T, et al. Comparison of analgesic efficacy of oxycodone and morphine in postoperative intravenous patient-controlled analgesia[J]. Acta Anaesthesiologica Scandinavica, 1998, 42(5): 576-580.
[10] PEDERSEN K V, OLESEN A E, DREWES A M, et al. Morphine versus oxycodone analgesia after percutaneous kidney stone surgery[J]. Urolithiasis, 2013, 41(5): 423-430.
[11] 孙乃会. 羟考酮临床镇痛个体化与基因多态性相关性研究[D]. 沈阳: 中国医科大学, 2016.
[12] LIUKAS A, HAGELBERG N M, KUUSNIEMI K, et al. Inhibition of cytochrome P450 3A by clarithromycin uniformly affects the pharmacokinetics and pharmacodynamics of oxycodone in young and elderly volunteers[J]. J Clin Psychopharmacol, 2011, 31(3): 302-308.
[13] REN Z Y, XU X Q, BAO Y P, et al. The impact of genetic variation on sensitivity to opioid analgesics in patients with postoperative pain: a systematic review and meta-analysis[J]. Pain Physician, 2015, 18: 131-152.

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