胃肠手术患者瑞芬太尼相关基因位点检测在术中麻醉药物剂量评估中的应用

Application of Remifentanil Related Genes Detection in Anesthetic Dose Assessment of Patients Undergoing Gastrointestinal Surgery

目的通过检测麻醉药物瑞芬太尼(remifentanil,REM)体内代谢和转运相关基因位点,探讨其与术中瑞芬太尼使用剂量的关系,为患者提供精准的麻醉药物个体化用药指导。方法收集5249例胃肠手术患者血液样本,应用荧光探针原位杂交技术检测瑞芬太尼相关基因位点OPRM1(118A>G),CYP3A4*1G(25343C>T),ABCB1(3435T>C),CYP3A4*18B(A>G)并进行分析,评估不同基因型患者麻醉药物的使用剂量。结果OPRM1(118A>G)位点AA/AG基因型4636例(88.32%),GG基因型613例(11.68%),CYP3A4*1G(25343C>T)位点CC/CT基因型4922例(93.77%),TT基因型327例(6.23%),ABCB1(3435T>C)位点TT基因型1842例(35.09%),TC/CC基因型3407例(64.91%),CYP3A4*18B(A>G)位点AA基因型5149例(98.09%),AG/GG基因型100例(1.91%)。54例OPRM1 AA/AG,CYP3A4*1G TT,ABCB1 TT基因型患者麻醉诱导及术中维持中应减低瑞芬太尼剂量,严格控制静脉泵注速度;118例OPRM1 GG,CYP3A4*1G CC和ABCB1 CC基因型患者,术中麻醉维持应根据其麻醉程度适当提高瑞芬太尼剂量和泵注速度;100例CYP3A4*18B AG/GG基因型患者适当减少瑞芬太尼剂量,降低静脉泵注速度。结论不同患者应根据其瑞芬太尼基因型别合理用药,为麻醉药物使用的患者提供精准的用药指导。

Objective By detecting the metabolism and transportation of remifentanil related genes,the relationship between the genes and the dosage was discussed,so as to provide accurate guidance for the individual use of anesthetic drugs.Methods Collected blood samples of 5249 patients undergoing gastrointestinal surgery,detected remifentanil related genes OPRM1(118A>G),CYP3A4*1G(25343C>T),ABCB1(3435T>C)and CYP3A4*18B(A>G)by fluorescence probe in situ hybridization,ssessed the dosage of anesthetic drugs used in patients with different enotypes.Results The cases of OPRM1(118A>G)AA/AG were 4636(88.32%),GG were 613(11.68%),and the cases of CYP3A4*1G(25343C>T)CC/CT were 4922(93.77%),TT were 327(6.23%).The cases of ABCB1(3435T>C)TT were 1842(35.09%),TC/CC were 3407(64.91%),and the cases of CYP3A4*18B(A>G)AA were 5149(98.09%),AG/GG were 100(1.91%).The dosage of remifentanil should be reduced and the speed of intravenous pump should be strictly controlled during anesthesia maintenance in 54 patients with OPRM1 AA/AG,CYP3A4*1G TT and ABCB1 TT genotype.In 757 patients with OPRM1 AA/AG,CYP3A4*1G CC/CT and ABCB1 TT genotype,remifentanil dosage and intravenous pump speed should be reduced appropriately according to the response during anesthesia maintenance.In 100 CYP3A4*18B AG/GG genotype patients,the dosage of remifentanil and the speed of intravenous pump should be properly reduced.Conclusion Different patients should use remifentanil reasonably according to their genotype,so as to provide accurate medication guidance for patients who use anesthetic drugs.