PXR＊ 1B多态性对妇科手术患者芬太尼术后镇痛效应的影响

Effect of PXR＊ 1B polymorphism on postoperative analgesia with fentanyl in patients undergoing gynecological operation

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 activity of CYP3A4.Results No patients required rescue anesthetics in the three groups.There were 27 cases in group PXR ＊ 1B, 53 cases in group n-PXR＊ 1B, and 22 cases in group PXR＊ 1B/PXR＊ 1B.PXR＊ 1B allele frequency was 37.2%.There was no significant difference in VAS score immediately after the end of operation, consumption of fentanyl within 24 h after operation, and activity of CYP3A4 between the three groups （P〉0.05）.Conclusion PXR＊ 1B polymorphism has no effect on postoperative analgesia with fentanyl in the patients undergoing gynecological operation, and is not one of the genetic factors producing individual variation in postoperative analgesia.