基因多态性对腹腔镜术后舒芬太尼用量的预测效能

Efficacy of Gene Polymorphism in Predicting the Dosage of Sufentanil After Laparoscopic Surgery

目的探讨基因多态性用于早期评估患者腹腔镜术后舒芬太尼用量的价值。方法收集医院2021年4月至2023年3月收治的行腹腔镜手术患者围术期的临床资料,术前采用实时荧光定量聚合酶链反应法测定基因CYP3A4(rs2242480)、COMT(rs4680)、OPRM1(rs1799971)、ABCB1(rs1045642)的单核苷酸多态性(SNP);术后均予静脉自控镇痛泵(枸橼酸舒芬太尼注射液+盐酸托烷司琼注射液)镇痛,记录患者术后24 h舒芬太尼使用量。采用有序Logistic回归分析评估腹腔镜术后舒芬太尼用量的相关影响因素;采用R软件建立基于独立相关因素的列线图模型,绘制校正曲线、受试者操作特征(ROC)曲线评估模型早期预测价值。结果共纳入300例患者,术后中位舒芬太尼用量为30.35μg,按总用量四分位区间分为A组(总用量≤25%)、B组(总用量26%~50%)、C组(总用量51%~74%)、D组(总用量≥75%),各75例。4组患者手术时间、术前空腹血糖水平及CYP3A4(rs2242480)、ABCB1(rs1045642)、COMT(rs4680)、OPRM1(rs1799971)的基因型比例差异均有统计学意义(P<0.05)。有序Logistic回归分析显示,手术时间、术前空腹血糖水平、CYP3A4(rs2242480)的CT基因型是腹腔镜术后舒芬太尼用量的独立影响因素(P<0.05)。术后舒芬太尼用量的早期预测列线图模型的C-指数为0.915,且模型校准曲线与理想模型接近;ROC曲线分析显示,列线图模型在早期评估舒芬太尼用量的药-时曲线下面积(AUC)为0.909,敏感性为82.67%,特异性为86.67%。结论CYP3A4(rs2242480)的SNP是腹腔镜术后舒芬太尼用量的独立影响因素,术前检测患者CYP3A4(rs2242480)的SNP有助于指导临床个体化应用舒芬太尼镇痛。

Objective To investigate the value of gene polymorphism in early assessment of dosage of sufentanil in patients after laparoscopic surgery.Methods The clinical data of patients underwent laparoscopic surgery in the perioperative period admitted to the hospital from April 2021 to March 2023 were collected.Before surgery,the single nucleotide polymorphism(SNP)of genes CYP3A4(rs2242480),COMT(rs4680),OPRM1(rs1799971)and ABCB1(rs1045642)were detected by the real-time fluorescence quantitative polymerase chain reaction;after surgery,the intravenous patient-controlled analgesia(Sufentanil Citrate Injection+Tropisetron Hydrochloride Injection)was given,and the dosage of sufentanil used by the patients 24 h after surgery was recorded.The relevant factors affecting the dosage of sufentanil after laparoscopic surgery were evaluated by the ordinal Logistic regression analysis.The alignment diagram model based on the independent relevant factors was constructed by the R software,the calibration curve and receiver operating characteristic(ROC)curve were drawn to evaluate the early predictive value of the model.Results A total of 300 patients were included,the median postoperative dosage of sufentanil was 30.35μg.The patients were divided into the group A(total dosage≤25%),the group B(total dosage was in the range of 26%to 50%),the group C(total dosage was in the range of 51%to 74%)and the group D(total dosage≥75%)based on the the quartile interval of total dosage,with 75 cases in each group.The surgical time,preoperative fasting blood glucose(FBG)level,and the genotype proportions of CYP3A4(rs2242480),ABCB1(rs1045642),COMT(rs4680)and OPRM1(rs1799971)in the four groups were significantly different(P<0.05).The ordinal Logistic regression analysis showed that the surgical time,preoperative FBG level and CT genotype of CYP3A4(rs2242480)were the independent influencing factors of sufentanil dosage after laparoscopic surgery(P<0.05).The C-index of the alignment diagram model for early prediction of postoperative sufentanil dosage was 0.915,and the calibration curve of the model was similar to the ideal curve.The ROC curve analysis showed that the alignment diagram model had an area under the drug-time curve of 0.909,a sensitivity of 82.67%and a specificity of 86.67%in the early assessment of sufentanil dosage.Conclusion The SNP of CYP3A4(rs2242480)is an independent influencing factor on the dosage of sufentanil after laparoscopic surgery.Preoperative detection of the SNP of CYP3A4(rs2242480)in patients is helpful to guide the clinical individualized use of sufentanil for analgesia.