摘要
目的：使用响应曲面模型,研究吸入性麻醉药七氟醚和舒芬太尼对喉镜置入反应的药效学相互作用。方法：全身麻醉下行择期手术的患者62例平行随机分为7组,每例患者随机选定吸入不同浓度的七氟醚,并在试验过程中保持七氟醚呼气末浓度恒定。靶控输注舒芬太尼的起始效应室浓度0.05 ng·mL^-1,达到预定靶浓度6 min后,开始吸入七氟醚。当患者的OAA/S评分达到0分时,置入喉镜,观察不同浓度组合时患者对置入喉镜刺激的反应。应用NONMEM软件,分别以Minto模型、Kleef＆Dahan模型、Greco模型及Logit模型为基础模型进行七氟烷-舒芬太尼联合应用的药效学模型拟合。结果：Logit模型的目标函数值（objective function value,OFV）明显小于Greco模型。NONMEM软件计算得到置入喉镜刺激的参数C50sevo和C50sufen分别为1.61%和4.24 ng·mL^-1,β3为9.18。诊断图显示,响应曲面与实际观测值的拟合度较好。结论：七氟醚（0.5%-3.5%）与舒芬太尼（0.1-0.5 ng·mL^-1）合用后对喉镜置入不发生体动反应时,二者相互作用性质是协同作用。
Objective：Applying response surface model to characterize the interactions between sufentanil and sevoflurane.Methods：Based on parallel slices design,62 patients were randomly assigned to 7 groups.Each patient randomly inhaled a specific end-tidal concentration of sevoflurane（0.5%-3.5%） and maintained at a certain end-tidal concentration during the trial process.Sufentanil was administered to a specific predicted effect site concentration from 0.05 to 0.5ng·mL^-1,6 minutes after achieving the targeted effect site concentration,sevoflurane was administered by a tight-fitting mask attached to an anesthetic machine.When patients got the Observer＇s Assessment of Alertness/Sedation score zero,the responses to the laryngoscopy stimulation were observed for each target concentration pair.Modeling of the anesthetic effect measured by laryngoscopy was performed with NONMEM using the Minto,Kleef Dahan,Greco model and Logit model.Results：The objective function value of Logit model was significantly lower than that of Greco model.The average of the model parameters for laryngoscopy of C50sevo,C50sufen were 1.61% and 4.24ng·mL^-1 respectively,β3 was 9.18.The respond surface could fit the observed values perfectly.Conclusion：Response surface analyses demonstrate a synergistic interaction between sufentanil and sevoflurane for the analgesic endpoint.
出处
《中国新药杂志》
CAS
CSCD
北大核心
2010年第22期2070-2075,共6页
Chinese Journal of New Drugs
