Clinical Pharmacodynamics Of The Electroencephalogram Effect Of Alfentanil Using The Narcotrend Monitors

ObjectiveTo investigate the clinical pharmacodynamics of alfentanil under general anesthesia with propofol by the a wave,β wave,δ wave,θ wave spectral power of Narcotrend,in order to explore the methods of guiding administrated clinical analgesics.Materials and methods24 patients were selected for elective surgery,ASA class Ⅰ-Ⅱ,aged 19-65 years old.All patients were routinely forbidden to drink and eat before surgery and no preoperative medication was administered.After the patients entered the operating room,the ECG,NIBP and SpO₂ were routinely monitored,the center of the patient’s frontal hair and on both sides of the patient’s forehead are pasted with electrods to connect the Narcotrend monitors（the single resistor resistance<6KΩ,difference in impedance between any two electrodes<2.5KΩ）.The maximum proportion of a wave spectral power was recorded when the patients were in resting state.The arterial blood pressure（ABP）was measured by radial artery puncture and tube insertion.According to weight of the patients,target-controlled infusion of propofol（Marsh model）with effect chamber concentration of 3～5μg/ml,when the patient’s NTI was<46,0.15～0.20mg/kg cisatracurium was given,and tracheal intubation was performed 2 minutes later.When the anesthesia was stable,target-controlled infusion of alfentanil（Hudson model）at a plasma target concentration of 500 ng/ml was administered until the appearance of maximum α wave spectral power.If the maximum of a wave spectral power was not reached,the plasma concentration could be increased sequentially by 50ng/ml.When δ arousal or α dropout was occurred,the administration was stopped.Arterial blood samples were collected by radial artery immediately before and every minute after administration until it appears δ arousal or α dropout.Radial artery blood was taken intermittently after withdrawal until brain waves returned to the level before administration of afentanil.The operation was started after the observation was completed.Used ULC-MS/MS to determine the plasma concentration of alfentanil and the Main Window serial program was applied to record the proportional changes of EEG spectral power.The pharmacokinetic parameters of alfentanil were calculated by DAS2.0 software,and the PK/PD model parameters were calculated by Phoenix WinNonlin 8.3 software.Result1.Under total intravenous anesthesia with propofol,the chance of a spectral power was used as the pharmacodynamic effect measure of alfentanil,the main PD parameters were as follow:K_e0（α）=（0.86±0.58）/min,t_1/2,ke0（α）=0.83（0.61,1.92）min,EC₅₀（α）=（135.92±85.46）ng/mL,γ（α）=9.40±6.21,Emax（α）=（0.363±0.192）%,R（a）=0.81,the coefficient of variation of γ and EC₅₀ respectively was 66.1%and 50.6%.The correlation and the accuracy of the fitting model was good.2.Under total intravenous anesthesia with propofol,the chance of δ spectral power was used as the pharmacodynamic effect measure of alfentanil,the main PD parameters were as follow:K_e0（δ）=（0.41±0.13）/min,t_1/2,ke0（δ）=2.37±0.61min,EC₅₀（δ）=（316.56±84.41）ng/mL,γ（δ）=6.44±2.33,Emax（δ）=（0.17±0.05）%,R（δ）=0.69,the coefficient of variation of γ and EC₅₀ respectively was 36.2%and 26.7%.It indicated that the fitting model had lower correlation and accuracy than the a wave fitting model.3.The θ spectral power was used as the pharmacodynamic effect measure of alfentanil,with the effect of suppression on alfentanil concentration,the main PD parameters were as follow::K_e0（θ）=（0.34±0.18）/min,t_1/2,ke0（θ）=（2.04±0.26）min,EC₅₀（θ）=（134.80±52.46）ng/mL,γ（θ）=3.26±1.03,Emax（θ）=（0.79±0.22）%,R（θ）=0.53,the coefficient of variation of γ and EC₅₀ respectively is 31.6%and 38.9%.It indicates that the fitting model has better correlation and accuracy than the a wave fitting model.The fitting model had poor correlation and low accuracy.4.The β spectral power was used as the pharmacodynamic effect measure of alfentanil,with the effect of suppression on alfentanil concentration,the main PD parameters were as follow:K_e0（β）=（0.08±0.03）/min,tir2,ke0（β）=（8.66±4.26）min,EC₅₀（β）=（307.59±162.88）ng/mL,γ（β）=3.24±1.63,Emax（β）=（53.60±17.84）%,R（β）=0.33,the coefficient of variation of γ and EC₅₀ respectively is 31.6%and 38.9%.It indicates that the fitting model had poor correlation and lower accuracy.5.When the appropriate depth of anesthesia was maintained（20<NI<46）and no opioids were used for endotracheal intubation,a wave spectral power decreased and δwave spectral power increased compared to preintubation power,which was correlated with the inj urious stimulation.Conclusions1.Under intravenous anesthesia with propofol,using the a wave spectral power of Narcotrend monitors as the pharmacodynamic indexes of afentanil,it showed good correlation between the fitting model and the measured values,and the fastest equilibrium rate of afentanil effect compartment,which can reflect the pharmacodynamic changes of afentanil in time;2.The fitting model of 8 wave spectral power in Narcotrend monitors had good correlation with the actual values,with less variation and higher precision than the fitting models of α wave.3.The fitting values of θ and β wave spectral power in Narcotrend monitors were not recommended to be used to quantify the effect of afentanil.