右美托咪定对先天性心脏病儿童舒芬太尼药代动力学的影响

Effect of dexmedetomidine on pharmacokinetics of sufentanil in children with congenital heart disease

目的观察右美托咪定(DEX)对先天性心脏病儿童舒芬太尼(SUF)药代动力学和血流动力学的影响。方法纳入ASA分级Ⅱ级,月龄3~72个月全身麻醉下行心脏介入手术的儿童167例。麻醉诱导给予丙泊酚2 mg/kg、SUF 0.3μg/kg和苯磺顺阿曲库铵0.2 mg/kg。随机分为DEX组(D组)和丙泊酚组(P组)。麻醉维持:D组给予DEX首剂量1μg/kg和维持剂量0.7μg/(kg·h)静脉泵注;P组给予丙泊酚8 mg(/kg·h)静脉泵注。记录患儿术中血流动力学参数和不良反应。采用稀释采样法收集给予SUF后5、10、20、30、45、60、75、90、120 min的血液标本。用UHPLC-MS/MS法测定SUF血浆药物浓度,Phoenix WinNonlin^(TM)软件计算药代动力学参数。结果 P组20、60、120 min血药浓度显著高于D组(P <0.05)。D组清除率为(28.59±10.23)mL(/kg·min),明显高于P组[(20.78±10.45)mL(/kg·min)],差异有统计学意义(P <0.05);两组舒芬太尼消除半衰期、曲线下面积、表观分布容积和平均驻留时间差异均无统计学意义(P> 0.05)。D组和P组术中血流动力学不良反应的发生率为23.8%和19.3%,差异无统计学意义(P> 0.05)。结论在儿童心脏介入治疗手术中,DEX可加快SUF的清除率,但不增加血流动力学不良反应的发生率。

Objective To observe the effects of dexmedetomidine on pharmacokinetics and hemodynamics of sufentanil in children with congenital heart disease.Methods A total of 167 children,ASA classⅡ,aged 3 to 36 months,receiving general anesthesia for cardiac interventional surgery were enrolled.All the subjects received propofol of 2 mg/kg,sufentanil of 0.3μg/kg,and cisatracurium besilate of 0.2 mg/kg during anesthesia induction.In anesthesia maintenance,group D was intravenously given dexmedetomidine with the first dose of 1μg/kg followed by a maintenance dose of 0.7μg/(kg·h),and group P was given propofol of 8 mg/(kg·h).The intraoperative hemodynamic parameters and adverse reactions were recorded.Blood samples were collected at 5,10,20,30,45,60,75,and 90 min after SUF administration by dilution sampling method.Plasma concentration of SUF was determined by UHPLC-MS/MS method,and pharmacokinetic parameters were calculated by the Phoenix WinNonlinTMsoftware.Results The plasma concentration at 20,60,or 120 min was significantly higher in group P than in group D(P<0.05).The clearance rate was(28.59±10.23)mL/(kg·min)in group D,which was significantly higher than that in group P(20.78±10.45)mL/(kg·min)(P<0.05).There were no significant differences between the two groups in the elimination half-life,area under curve,apparent volume of distribution,and mean residence time of sufentanil(P>0.05).The incidence of intraoperative adverse hemodynamic reactions were 23.8%in group D and 19.2%in group P(P>0.05).Conclusion sDexmedetomidine accelerates the clearance rate of sufentanil but does not increase the incidence of adverse reactions in children with congenital heart disease.