应用脑电频谱熵建立七氟醚药代药效学模型

Pharmacokinetic-pharmacodynamic modeling using spectral entropy of electroencephalogram during sevoflurane anesthesia

目的研究七氟醚浓度与效应的关系,建立七氟醚药代药效学(PKPD)模型。方法选择23例ASAI或II级拟在全身麻醉下行择期手术的患者。吸入5%(v/v)七氟醚,观察频谱熵的变化过程。通过参数估计和优化建立PKPD模型,采用交叉验证进行模型准确性验证。结果患者意识消失时反应熵(RE)和状态熵(SE)的平均值是96和87,以RE、SE作为效应指标得到药代药效学参数:ke0=(0.32±0.12)/min,(0.33±0.14)/min;γ=3.40±1.12,3.62±1.19;EC50=1.22±0.21,1.25±0.20;七氟醚的效应位浓度与RE、SE之间的相关系数γRE=-0.77,γSE=-0.77(P<0.01)。结论应用脑电频谱熵建立的七氟醚药代药效学模型预测的准确性较好。七氟醚效应位浓度与脑电频谱熵具有显著的相关性。

Objective To establish a pharmacokinetic-pharmacodynamic （PKPD） model of the relationship between sevoflurane concentration and spectral entropy by studying the dose-response relation between the sevoflurane concentration and spectral entropy. Methods Twenty-three patients received anesthesia with sevoflurane inhalation. Two transitions between 0 and 5% inspired concentration were performed. Spectral entropy data were collected. An effect-site compartment and inhibitory Emax model described the relation between sevoflurane concentration and spectral entropy. PKPD parameters were derived from the full anesthetic cycle and separately from the first and second increase-decrease stages. Results The median response entropy （RE） and state entropy（SE） of loss of response to verbal command （LOC） are 96 and 87, respectively. Emax model accurately describes the relationship between sevoflurane concentration and spectral entropy, which are ke0 = （0. 32 ± 0.12）/ min and （0.33±0.14）/min, 7= 3.40± 1.12 and 3.62± 1.19,and EC30 = 1.22±0.21 and 1.25± 0.20. Conclusion The predictability of the PKPD model is good. The effect site concentration correlates with spectral entropy perfectly.