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| CYP3A4*1G不同基因型对髋关节置换术后地佐辛复合舒芬太尼自控镇痛效应的影响 |
| Effects of CYP3A4*1G genotype status on patient-controlled analgesia of dezocine combined with sufentanil after hip replacement |
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| DOI：10.12089/jca.2020.03.006 |
| 中文关键词: CYP3A4*1G 基因多态性 地佐辛 舒芬太尼 自控镇痛效应 |
| 英文关键词: CYP3A4*1G Gene polymorphism Dezocine Sufentanil Patient-controlled analgesia |
| 基金项目:郑州市科技攻关项目(20150079) |
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| 中文摘要: |
目的 探讨CYP3A4*1G多态性对髋关节置换术后地佐辛复合舒芬太尼静脉镇痛效应的影响。方法选取在本院行关节置换术患者150例,男79例,女71例,年龄21～61岁,BMI 16～29 kg/m2,ASA Ⅰ 或 Ⅱ 级。根据患者CYP3A4*1G基因分型检测分为:野生型纯合子(CYP3A4*1/*1)基因型组(11组)、突变型杂合子(CYP3A4*1/*1G)基因型组(11G组)和突变型纯合子(CYP3A4*1G/*1G)基因型组(1G1G组)。所有患者在全麻下行髋关节置换术,术后行地佐辛复合舒芬太尼患者自控镇痛(PCIA)。记录三组患者苏醒即刻、术后12、24 和48 h 的视觉模拟疼痛(VAS)评分、镇静程度(Ramsay)评分,记录镇静过度的患者例数。记录三组术后0～24 和24～48 h 地佐辛+舒芬太尼使用量、手术时间和苏醒时间。采用PCR-RFLP对三组患者外周血单核细胞中CYP3A4 mRNA相对表达量进行检测。
结果 11组患者93例(62.0%)、11G组患者50例(33.3%)、1G1G组患者7例(4.7%),CYP3A4*1G 最小等位基因频率(MAF)为0.213,等位基因和基因型分布符合Hardy-Weinberg平衡(P=0.933)。三组不同时点VAS评分和Ramsay评分差异无统计学意义,三组均未见镇静过度者。术后0～24 h、24～48 h 1G1G组地佐辛+舒芬太尼使用量明显少于11组和11G组(P<0.05),11组和11G术后0~24 h、24~48 h地佐辛+舒芬太尼使用量差异无统计学意义。三组手术时间和苏醒时间差异无统计学意义。11G组和1G1G组外周血单核细胞中CYP3A4 mRNA相对表达量明显低于11组(P<0.05)。三组恶心呕吐、瘙痒等不良反应发生情况差异无统计学意义。
结论 与野生型纯合子比较,突变型杂合子和突变型纯合子基因型患者对地佐辛复合舒芬太尼耐受性更低,所需剂量更少。该基因型可作为疼痛个体化治疗的参考指标。 |
| 英文摘要: |
Objective To investigate the effect of CYP3A4*1G polymorphism on intravenous analgesia of dezocine combined with sufentanil after hip replacement.
Methods A total of 150 patients underwent arthroplasty in our hospital were selected, including 79 males and 71 females, aged 21-61 years, BMI 16-29 kg/m2, ASA physical status Ⅰ or Ⅱ. According to CYP3A4*1G genotyping, the patients were divided into wild type homozygote (CYP3A4*1/*1) genotype group (group 11), mutant heterozygote (CYP3A4*1/*1G) genotype group (group 11G) and mutant homozygote (CYP3A4*1G/*1G) genotype group (group 1G1G). Postoperative patient-controlled analgesia (PCIA) with dizocine and sufentanil was performed. All patients underwent hip arthroplasty under general anesthesia and patient-controlled analgesia (PCIA) with dezocine and sufentanil after operation. Visual analogue pain (VAS) score and sedation degree (Ramsay) score were recorded immediately after awakening, 12, 24 and 48 h after operation, and the number of patients with excessive sedation was recorded. The dosage of dezocine+sufentanil at 0-24 and 24-48 h after operation, operation time and recovery time were recorded. The relative expression of CYP3A4 in peripheral blood mononuclear cells of the three groups was detected by PCR-RFLP.
Results Among 150 patients, there are 93 patients (62%) in group 11, 50 patients (33.3%) in group 11G and 7 patients (4.7%) in group 1G1G. The minimum allele frequency (MAF) of CYP3A4*1G was 0.213. The distribution of alleles and genotypes conformed to Hardy-Weinberg equilibrium (P = 0.933). There was no significant difference in VAS score and Ramsay score at different time points in the three groups, and no sedation overdose was found in the three groups. The dosage of dezocine+sufentanil in group 1G1G at 0-24 h and 24-48 h after operation was significantly less than that in group 11 and group 11G (P < 0.05). There was no significant difference in the dosage of dezocine+sufentanil in group 11 and group 11G at 0-24 h and 24-48 h. There was no significant difference in operation time and recovery time among the three groups. The relative expression of CYP3A4 in peripheral blood mononuclear cells of group 11G and group 1G1G was significantly lower than that of group 11 (P < 0.05). There was no significant difference in the occurrence of nausea, vomiting, itching and other adverse reactions among the three groups.
Conclusion Compared with wild type homozygotes, patients with mutant heterozygotes and mutant homozygotes have lower tolerance to dezocine combined with sufentanil and require fewer doses. The genotype can be used as a reference index for individualized treatment of pain. |
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