细胞色素P4502D6^＊10基因多态性对曲马多术后病人自控镇痛效果的影响

Effects of cytochrome P-450 2D6^ ＊ 10 genetic polymorphism on the postoperative patient-controlled analgesia with tramadol

目的探讨细胞色素P4502D6^＊10（CYP2D6^＊10）基因多态性对曲马多术后病人自控镇痛（PCA）效果的影响。方法全麻病人212例，年龄20～64岁，ASAⅠ或Ⅱ级。按基因型分为野生型纯合子（w／w）组、杂合子（m／w）组和突变型纯合子（m／m）组。手术结束前30min静脉注射曲马多1．5mg／kg。清醒时VAS评分〉4分则静脉注射曲马多，若用量超过3mg／kg则静脉注射芬太尼，至VAS评分≤4分后开始PCA，记录曲马多负荷量。曲马多PCA背景输注速率18mg／h、16h后降为12mg／h、32h后降为9mg／h，PCA剂量22．5mg。记录术后6、12、24及48h（T1-4）时曲马多累积用量。分别于T1、T3和T4时采用视觉模拟评分法（VAS）评价疼痛程度。于T4后行PCA镇痛效果评价。结果与w／w组相比，m／m组曲马多负荷量、T1-3时曲马多累积用量均升高，清醒和T1时VAS评分升高（P〈0．05）；与m／w组相比，m／m组曲马多负荷量、T3时曲马多累积用量均升高，L时VAS评分升高（P〈0．05）。结论CYP2D6^＊10基因多态性为曲马多术后镇痛药效学个体差异的因素之一。

Objective To investigate the effects of cytochrome P-450 2D6 ^＊ 10 （CYP2D6^＊10） genetic polymorphism on the postoperative patient-controlled analgesia （PCA） with tramadol. Methods Two hundred and twelve ASA Ⅰ or Ⅱ patients aged 20-64 yr undergoing elective operation under general anesthesia were assigned to one of 3 groups according to their genotypes： group Ⅰ wild homozygote （w/w） ; groupⅡ heterozygote （m/w） and group Ⅲ mutation homozygote （m/m）. The patients＇pain was assessed using visual analogue scale （VAS）. Each patient received a loading dose of tramadol 1.5 mg/kg at 30 min before the end of surgery. In the recovery room when the patients were awake if VAS score was 〉 4 the patients were given tramadol 30 mg every 10 min until VAS score was decreased to 〈 4. If analgesia remained insufficient when the total dose of tramadol reached 3 mg/kg, fentanyl 50μg was administered every 10 min until VAS score ~〈 4. PCA with tramadol was then started. The background infusion rate of tramadol was 18 mg/h for the 1st 16 h, 12 mg/h for the 2nd 16 h and 9 mg/h for the 3rd 16 h. The PCA device was programmed to deliver a bolus dose of tramadol 22.5 mg. The cumulative dose of tramadol was recorded at 6 h （T1）, 12 h （T2）, 24 h （T3） and 48 h （T4） after operation, vAs scores were recorded at T1 , T3 and T4 The patients were asked to filled in a questionnaire on the patients＇ evaluation of the effectiveness of PCA they received. Results Two hundred and seven patients completed the study. Their genotypes were w/w 44; m/w 112; m/m 51. The loading dose and the cumulative dose at T1-3 and the VAS scores right after emergence from general anesthesia and at T1 were significantly higher in m/m group than in w/w group. The loading dose and the cumulative dose at T3 and the VAS scores at T1 were significantly higher in m/m group than in m/w group （ P 〈 0.05）. There was no significant difference in the VAS scores at T3 and T4 among the 3 groups. There were no significant differences in the ratio of the patients who were satisfied with the postoperative PCA they received. Conclusion CYP2D6^＊ 10 genetic polymorphism is one of the factors contributing to the individual variation in patient＇s response to postoperative PCA with tramadol.