Abstract：
Propofol and opioids are commonly used in anaesthesia, but are highly susceptible to haemodynamic instability, thereby threatening the patient\'s surgical safety and prognosis. The purpose of this study was to investigate the predictors of haemodynamic instability and establish its predictive model.
A total of 150 Chinese patients undergoing thyroid or breast surgery participated in the study, with target-controlled infusion concentrations of propofol, opioids dosage, heart rate (HR), mean arterial pressure (MAP) and Narcotrend Index recorded at key points throughout the procedure. The Agena MassARRAY system was used to genotype candidate single nucleotide polymorphisms related to pharmacodynamics and pharmacokinetics of propofol and opioids.
Among nongenetic factors, baseline HR (R = -.579, P < .001) and baseline MAP (R = -.725, P < .001) had a significant effect on the haemodynamic instability. Among genetic factors, the CT/CC genotype of GABRB1 rs4694846 (95% confidence interval [CI]: -11.309 to -3.155), AA/AG of OPRM1 rs1799971 (95%CI: 0.773 to 10.290), AA of CES2 rs8192925 (95%CI: 1.842 to 9.090) were associated with higher HR instability; the AA/GG genotype of NR1I2 rs6438550 (95%CI: 0.351 to 7.761), AA of BDNF rs2049046 (95%CI: -9.039 to -0.640) and GG of GABBR2 rs1167768 (95%CI: -10.146 to -1.740) were associated with higher MAP instability. The predictive models of HR and MAP fluctuations were developed, accounting for 45.0 and 59.2% of variations, respectively.
We found that cardiovascular fundamentals and genetic variants of GABRB1, GABBR2, OPRM1, BDNF, CES2 and NR1I2 are associated with cardiovascular susceptibility, which can provide a reference for haemodynamic management in clinical anaesthesia.
A total of 150 Chinese patients undergoing thyroid or breast surgery participated in the study, with target-controlled infusion concentrations of propofol, opioids dosage, heart rate (HR), mean arterial pressure (MAP) and Narcotrend Index recorded at key points throughout the procedure. The Agena MassARRAY system was used to genotype candidate single nucleotide polymorphisms related to pharmacodynamics and pharmacokinetics of propofol and opioids.
Among nongenetic factors, baseline HR (R = -.579, P < .001) and baseline MAP (R = -.725, P < .001) had a significant effect on the haemodynamic instability. Among genetic factors, the CT/CC genotype of GABRB1 rs4694846 (95% confidence interval [CI]: -11.309 to -3.155), AA/AG of OPRM1 rs1799971 (95%CI: 0.773 to 10.290), AA of CES2 rs8192925 (95%CI: 1.842 to 9.090) were associated with higher HR instability; the AA/GG genotype of NR1I2 rs6438550 (95%CI: 0.351 to 7.761), AA of BDNF rs2049046 (95%CI: -9.039 to -0.640) and GG of GABBR2 rs1167768 (95%CI: -10.146 to -1.740) were associated with higher MAP instability. The predictive models of HR and MAP fluctuations were developed, accounting for 45.0 and 59.2% of variations, respectively.
We found that cardiovascular fundamentals and genetic variants of GABRB1, GABBR2, OPRM1, BDNF, CES2 and NR1I2 are associated with cardiovascular susceptibility, which can provide a reference for haemodynamic management in clinical anaesthesia.
摘要：
目的：丙泊酚和阿片类药物常用于麻醉，但是极易受到血液动力学不稳定的影响，从而威胁到患者的手术安全和预后。目的探讨血流动力学不稳定的预测因素并建立其预测模型。
方法：共有150名接受甲状腺或乳腺手术的中国患者参加了这项研究，靶控输注丙泊酚浓度，阿片类药物剂量，心率(HR),在整个过程中记录的关键点的平均动脉压（MAP）和Narcotrend指数。AgenaMassARRAY系统用于对与异丙酚和阿片类药物的药效学和药代动力学相关的候选单核苷酸多态性进行基因分型。
结果：在非遗传因素中，基线HR(R=-.579,P<.001)和基线MAP(R=-.725,P<.001)对血流动力学不稳定有显著影响。在遗传因素中，GABRB1rs4694846的CT/CC基因型（95％置信区间[CI]：-11.309至-3.155），OPRM1的AA/AGrs1799971（95CI：0.773至10.290），CES2rs8192925的AA（95CI：1.842至9.090）与较高的HR不稳定性相关；NR1I2rs6438550的AA/GG基因型（95CI：0.351至7.761），BDNFrs2049046的AA（95CI：-9.039至-0.640）和GABBR2rs1167768的GG（95CI：-10.146至-1.740）与更高的MAP不稳定性相关。建立了HR和MAP波动的预测模型，占差异的45.0％和59.2％，分别。
结论：我们发现GABRB1，GABBR2，OPRM1，BDNF，CES2和NR1I2与心血管易感性相关，可为临床麻醉中的血流动力学管理提供参考。
方法：共有150名接受甲状腺或乳腺手术的中国患者参加了这项研究，靶控输注丙泊酚浓度，阿片类药物剂量，心率(HR),在整个过程中记录的关键点的平均动脉压（MAP）和Narcotrend指数。AgenaMassARRAY系统用于对与异丙酚和阿片类药物的药效学和药代动力学相关的候选单核苷酸多态性进行基因分型。
结果：在非遗传因素中，基线HR(R=-.579,P<.001)和基线MAP(R=-.725,P<.001)对血流动力学不稳定有显著影响。在遗传因素中，GABRB1rs4694846的CT/CC基因型（95％置信区间[CI]：-11.309至-3.155），OPRM1的AA/AGrs1799971（95CI：0.773至10.290），CES2rs8192925的AA（95CI：1.842至9.090）与较高的HR不稳定性相关；NR1I2rs6438550的AA/GG基因型（95CI：0.351至7.761），BDNFrs2049046的AA（95CI：-9.039至-0.640）和GABBR2rs1167768的GG（95CI：-10.146至-1.740）与更高的MAP不稳定性相关。建立了HR和MAP波动的预测模型，占差异的45.0％和59.2％，分别。
结论：我们发现GABRB1，GABBR2，OPRM1，BDNF，CES2和NR1I2与心血管易感性相关，可为临床麻醉中的血流动力学管理提供参考。
