Establishment of pharmacodynamic model of sevoflurane in pediatric patients: bispectral index / 中华麻醉学杂志

ABSTRACT

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 followske0 =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.