CAJ | 학술논문

目的以脑电双频谱指数(BIS)为效应指标,建立患儿七氟醚药效学模型.方法选择行非心脏手术患儿13例,年龄4-9岁,体重12～39 kg,ASA分级Ⅰ或Ⅱ级.患儿经面罩顺序吸入七氟醚1％、5％和1％,每个浓度维持15 min.每间隔10 s自动记录BIS值、HR、BP、SpO2.基于非线性混合效应模型、采用NONMEM软件建立群体药效学模型,依据向前选择和向后消除法分析年龄对药效学参数的影响.模型改善的判断标准:目标函数值减少大于3.84.结果 12名患儿纳入研究,年龄4.0～8.5岁、体重12.8～ 38.0 kg、身高92～ 135 cm,纳入数据共2964个有效浓度-时间-BIS数据点.将协变量(年龄、身高、体重)引入药效学模型,模型拟合后差异无统计学意义(P＞0.05).最终建立的七氟醚药效学模型参数为:效应位消除速率常数0.516/min; EC5o=2.11％;浓度-效应关系曲线的斜率2.46,无药物作用时的基础值74.6,药物作用的最大效应11.2.结论以BIS作为效应指标,成功建立了患儿七氟醚药效学模型,从模型的各项参数分析提示,与成人比较,患儿对七氟醚的敏感性较低,但药物的血脑平衡时间短,起效和恢复更为迅速.
목적 이뇌전쌍빈보지수(BIS)위효응지표,건립환인칠불미약효학모형.방법 선택행비심장수술환인13례,년령4-9세,체중12～39 kg,ASA분급Ⅰ혹Ⅱ급.환인경면조순서흡입칠불미1％、5％화1％,매개농도유지15 min.매간격10 s자동기록BIS치、HR、BP、SpO2.기우비선성혼합효응모형、채용NONMEM연건건립군체약효학모형,의거향전선택화향후소제법분석년령대약효학삼수적영향.모형개선적판단표준:목표함수치감소대우3.84.결과 12명환인납입연구,년령4.0～8.5세、체중12.8～ 38.0 kg、신고92～ 135 cm,납입수거공2964개유효농도-시간-BIS수거점.장협변량(년령、신고、체중)인입약효학모형,모형의합후차이무통계학의의(P＞0.05).최종건립적칠불미약효학모형삼수위:효응위소제속솔상수0.516/min; EC5o=2.11％;농도-효응관계곡선적사솔2.46,무약물작용시적기출치74.6,약물작용적최대효응11.2.결론 이BIS작위효응지표,성공건립료환인칠불미약효학모형,종모형적각항삼수분석제시,여성인비교,환인대칠불미적민감성교저,단약물적혈뇌평형시간단,기효화회복경위신속.
Objective To establish the pharmacodynamic model of sevoflurane with bispectral index (BIS) as the effective index in pediatric patients.Methods Thirteen ASA physical status Ⅰ or Ⅱ pediatric patients,aged 4-9 yr,weighing 12-39 kg,undergoing non-cardiac surgery,were selected in the study.The pediatric patients sequentially inhaled 1％,5 ％ and 1％ sevoflurane via a face mask and each concentration was inhaled for 15 min.BIS value,HR,BP and SpO2 were automatically recorded every 10 s.Based on nonlinear mixed effect modeling,the population pharmacodynamic model of sevoflurane was established using NONMEM software.The effect of age on the pharmacodynamic parameters was evaluated using a stepwise forward addition then backward elimination modeling approach.The standard for model improvement was defined as a decrease in the value of the objective function by more than 3.84.Results Twelve pediatric patients,aged 4.0-8.5 yr,weighing 12.8-38.0 kg,with body height of 92-135 cm,were enrolled in this study and the data which were enrolled comprised 2964 effective concentration-time-BIS points.The model was not improved significantly with any covariates (age,body height,and body weight) introduced (P ＞ 0.05).The estimated parameters of the final pharmacodynamic model of sevoflurane were as follows:ke0 =O.516/min ; EC50 (BIS50) =2.11％ ; γ =2.46 ; E0 =74.6 ; EMAx =11.2.Conclusion The pharmacodynamic model of sevoflurane is successfully established with BIS as the effective index in pediatric patients,and the analysis for each parameter of the model indicates that the sensitivity to sevoflurane is lower,but the blood-brain equilibration time of the drug is shorter and the onset and recovery are faster in children than in adults.