舒更葡糖钠用于婴幼儿日间手术拮抗罗库溴铵肌松残余的药代动力学

Pharmacokinetics of sugammadex in reversal of rocuronium-induced muscle relaxant residual in infants and young children undergoing daytime surgery

目的:探讨舒更葡糖钠用于婴幼儿日间手术拮抗罗库溴铵残余肌松的药代动力学。方法:腹腔镜下行日间手术的腹股沟斜疝和/或鞘膜积液患儿104例,年龄3~36个月,性别不限,ASA分级Ⅱ级,BMI 18.5~28.0 kg/m^(2)。使用TOF Guard监测仪以四个成串刺激法(TOF)透皮刺激腕部尺神经监测术中神经肌肉阻滞情况。静脉注射罗库溴铵0.9 mg/kg、丙泊酚3 mg/kg和舒芬太尼0.5 μg/kg诱导麻醉;静脉输注丙泊酚6~8 mg·kg^(-1)·h^(-1)维持麻醉。根据患儿术后神经肌肉阻滞程度分为2组:Ⅰ组,当TOF恢复到T_(2)重现时,静脉注射舒更葡糖钠2 mg/kg;Ⅱ组,当强直刺激后计数为1或2时,静脉注射舒更葡糖钠4 mg/kg。分别于给予罗库溴铵后2、10 min、手术结束即刻、给予舒更葡糖钠后2 、10 min和符合离开复苏室标准时采集静脉血标本,采用超高效液相色谱-质谱联用法检测血浆罗库溴铵和舒更葡糖钠浓度,采用Pheonix WinNonlin软件计算药代动力学参数。记录罗库溴铵起效时间和TOF比值恢复至90%的时间。 结果:舒更葡糖钠药代动力学符合混合效应非线性房室模型。2组舒更葡糖钠达峰浓度、药物浓度-时间曲线下面积、消除半衰期、表观清除率、表观分布容积、平均滞留时间和TOF比值恢复至90%的时间比较差异均无统计学意义( P>0.05)。 结论:舒更葡糖钠用于婴幼儿日间手术拮抗罗库溴铵肌松残余的药代动力学符合混合效应非线性房室模型,且2和4 mg/kg舒更葡糖钠药代动力学相似。

Objective To investigate the pharmacokinetics of sugammadex in reversal of rocuronium-induced muscle relaxant residual in infants and young children undergoing daytime surgery.Methods One hundred and four pediatric patients of either sex,aged 3-36 months,of American Society of Anesthesiologists Physical Status classification Ⅱ,with body mass index of 18.5-28.0 kg/m^(2),diagnosed with oblique inguinal hernia and/or hydrocele,scheduled for laparoscopic high ligation of hernia sac and/or high ligation of sphingoid surgery,were included in the study.Intraoperative neuromuscle relaxation was assessed by transdermal stimulation of the ulnar nerve in the wrist using a TOF Guard monitor.Rocuronium 0.9 mg/kg,propofol 3 mg/kg,and sufentanyl 0.5μg/kg were intravenously injected for anesthesia induction,and propofol 6-8 mg·kg^(-1)·h^(-1) was intravenously infused to maintain anesthesia.The pediatric patients were divided into Ⅰ group and Ⅱ group according to the degree of postoperative neuromuscular block.In group Ⅱ,sugammadex 2 mg/kg was intravenously injected when TOF returned to T_(2) recurrence.In group I,sugammadex 4 mg/kg was intravenously injected when the single stimulation count was 1 or 2 after tetanic stimulation.At 2 and 10 min after rocuronium administration,at the end of operation,2 and 10 min after sugammadex administration,and when the children met the standard of leaving the resuscitation room,venous blood samples were collected for determination of plasma concentrations of rocuronium and sugammadex using ultra-high performance liquid chromatography-mass spectrometry.Pharmacokinetic parameters were determined using the Pheonix WinNonlin software.The onset of rocuronium and time for recovery of TOF ratio to 90%were recorded.Results The pharmacokinetics of sugammadex was fitted to the nonlinear mixedeffect satrioventricular model.There was no significant difference in the peak concentration,area under the drug concentration-time curve,elimination half-life,apparent clearance,apparent volume of distribution,mean retention time,and time for TOF ratio returning to 90%between the two groups(P>0.05).Conclusions The pharmacokinetics of sugammadex in reversal of rocuronium-induced muscle relaxant residual is fitted to a nonlinear mixed-effect satrioventricular model,and sugammadex 2 and 4 mg/kg have similar pharmacokinetics in infarits and young children undergoing daytime surgery.