目的 探讨PXR* 1B多态性对妇科手术患者芬太尼术后镇痛效应的影响.方法 择期全麻下行腹式子宫全切或子宫肌瘤剔除术患者102例,河南籍,汉族,年龄20 ~ 50岁,ASA Ⅰ或Ⅱ级,体重指数14.8~ 30.0 kg/m2,采用聚合酶链反应(PCR)-基因测序法检测PXR多态性位点,根据基因型分组:PXR* 1B单倍型携带组(PXR*1B组)、PXR* 1B单倍型非携带组(n-PXR* 1B组)及PXR* 1B/PXR*1B携带组(PXR* 1B/PXR* 1B组).术毕清醒后行视觉模拟评分(VAS评分),若VAS>3分,则间断静脉注射芬太尼20μg,直至VAS≤3分时接镇痛泵行芬太尼PCIA.PCIA药物:芬太尼1.0 mg、氟哌利多5 mg,生理盐水稀释至100 ml,背景输注速率0.5 ml/h,PCA剂量2 ml,锁定时间5min,每小时有效按压次数设定为7次,每小时芬太尼最大用量为145 μg,若超过此剂量患者VAS评分仍大于3,则采用非甾体类镇痛药物进行补救.记录术毕即刻VAS评分、术后24 h内芬太尼消耗量.全麻诱导时静脉注射咪达唑仑0.1 mg/kg,1h后,抽取静脉血,采用高效液相色谱法检测血浆1'-羟咪达唑仑与咪达唑仑的浓度,并计算两者比值,反映CYP3A4活性.结果 3组患者均未采用补救镇痛.PXR* 1B组27例,n-PXR* 1B组53例,PXR* 1B/PXR* 1B组22例.PXR* 1B等位基因突变率为37.2%.3组患者术毕即刻VAS评分、术后24 h芬太尼消耗量和CYP3A活性比较差异无统计学意义(P>0.05).结论 PXR* 1B多态性对妇科手术患者芬太尼术后镇痛效应无影响,不是其术后镇痛效应个体差异性的遗传因素.
Objective To investigate the effect of PXR* 1B polymorphism on postoperative analgesia with fentanyl in the patients undergoing gynecological operation.Methods A total of 102 female patients from Henan province, of Han nationality, aged 20-50 yr, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ , with body mass index of 14.8-30.0 kg/m2, scheduled for elective abdominal total hysterectomy or myomectomy under general anesthesia, were enrolled in this study.PXR genetic polymorphic sites were analyzed by polymerase chain reaction (PCR)-direct DNA sequencing.PXR* 1B haplotype was analyzed by the PHASE V.2.1 software.The patients were assigned into 3 groups according to their genotypes: PXR* 1B haplotype group (group PXR* 1B), non-PXR* 1B haplotype group (group n-PXR* 1B) and PXR* 1B/PXR * 1B group (group PXR* 1B/PXR* 1B).Postoperative pain was assessed with visual analogue scale (VAS) score.When VAS 〉 3, fentanyl 20 μg was injected intermittently until VAS ≤ 3, and then a pump was connected to perform patient-controlled intravenous analgesia (PCIA) with fentanyl.PCIA solution contained fentanyl 1.0 mg and droperidol 5 mg in 100 ml of normal saline.The PCA pump was set up with a 2 ml bolus dose, a 5 min lockout interval and background infusion at a rate of 0.5 ml/h.The number of successfully delivered doses was set at 7 times, and the maximal amount of fentanyl was 145 μg.If exceeding the maximal dose, the VAS score was still more than 3, nonsteroidal anti-inflammatory drugs were given as rescue medication.VAS score immediately after the end of operation, and the consumption of fentanyl within 24 h after operation were recorded.Midazolam 0.1 mg/kg was injected intravenously during induction of general anesthesia, and 1 h later venous blood samples were collected for determination of plasma 1'-hydroxymidazolam and midazolam concentrations.The ratio of 1'-hydroxymidazolam concentration to midazolam concentration was calculated to reflect the activ