Clinical Pharmacodynamics Of Remifentanil In Different Age Patients Under General Anesthesia With Propofol

OBJECTIVE To investigate the influence of age on the clinical pharmacodynamic profiles of remifentanil, Analysed the relation between the effect and the concentration. Intergrated the HR and MAP to be a better comprehensive index that could better quantitate the drug effect of remifentanil.and provided evidences for the use of the close-loop TCI of remifentanil.METHODS Thirty-six ASAⅠ～Ⅲpatients were assigned to one of three age groups:group A:age ranged from 18～44 (n=12);group B:45～59 (n=14) and group C:60～80 (n=10).Weight between 49 and 75 kg , height between 149 and 175cm. BMI 20～29kg/m2. I.m luminal 1～2mg/kg and atropine 0.008～0.01mg/kg before entering the room. Established peripheral venous access after entering the room. Monitoring the heart rate, blood pressure, pulse oxygen saturation.Punctured Radial artery under region anesthesia. applied the pharmacokinetic parameters of propofol that Zhangxing An reported. Target control infusion propofol by TIAC-I with plasma concentration between3～4μg/mL.I.v cis-atracurium 0.15mg/kg after unconscious and intubated. Remifentanil were continuous infused at the speed of 0.50μg·kg^-1·min^-1 for twenty minutes.Drawed the blood of Radial artery during the infusion and 30minutes of withdraw period.and recorded the HR and MAP. calculated the pharmacodynamics parameters of remifentanil with the PK-PD model of DAS 3.0.Analysed the relation between the effect and the concentration.Intergrated the HR and MAP to be a better comprehensive index that could better quantitate the drug effect of remifentanil by programming solver and provided evidences for the use of the close-loop TCI of remifentanil.RESULTS1. Thirty-six ASAⅠ～Ⅲpatients, aged 18～80yr, weight 49～75 kg, height 149～175cm, body mass index 20～29 kg/m2,undergoing elective surgery were randomly divided into three groups.There were no statistically significant differences between gender,weight and height of three groups(P>0.05).the age had statistically significant differences(P<0.05).2. Under general anesthesia with propofol,using HR as measure of remifentanil drug effect, calculated the pharmacodynamics parameters of remifentanil with the PK-PD model of DAS 3.0.Group A :Ke0 0.532±0.189 min^-1,EC₅₀ 5.638±1.523μg/L,γ1.925±0.665,E_max (0.304±0.124)%,R 0.906±0.026.Group B: Ke0 0.493±0.057min^-1,EC₅₀ 4.869±1.081μg/L,γ2.078±0.742,E_max (0.328±0.157)%,R 0.921±0.022. Group C: Ke0 0.389±0.094 min^-1,EC₅₀ 3.641±1.298μg/L,γ2.022±0.765,E_max (0.314±0.172)%,R 0.918±0.039.3. Under general anesthesia with propofol,using MAP as measure of remifentanil drug effect, calculated the pharmacodynamics parameters of remifentanil with the PK-PD model of DAS 3.0.Group A : Ke0 0.538±0.109 min^-1,EC₅₀ 5.371±1.44μg/L,γ2.14±0.945,E_max(0.363±0.192)%.R 0.776±0.096.GroupB:Ke0 0.478±0.067min^-1, EC₅₀ 4.815±0.895μg/L,γ2.044±0.808, E_max(0.352±0.145 )% ,R 0.766±0.082.GroupC: Ke0 0.379±0.111 min^-1,EC₅₀ 3.672±1.384μg/L,γ2.034±0.663,E_max (0.368±0.146)%,R 0.789±0.062.4.Under general anesthesia with propofol, using HR or MAP as a measure of remifentanil drug effect,The Ke0 and EC₅₀ of elderly group was significantly lower than the other two groups( P<0.05). and had no statistically significant differences between the middle and young groups.There were no statistically significant differences between R,γ,E_max of three groups.5. The mean R of HR and MAP were 0.904 and 0.752 respectively. Integrated the HR and MAP as an comprehensive index,The best combination: Comprehensive index = 0.58* E(t)HR +0.42* E(t)MAP and the relevant index is 0.946 . CONCLUSION1. Under general anesthesia with propofol, using HR or MAP as a measure of remifentanil drug effect ,The EC50 of elderly group was significantly lower than the other two groups( P<0.05). and had no statistically significant differences between the middle and young groups. The elderly patients was more sensitive and the dosage should be reduce.2. The Ke0 decreased with the age. The Ke0 of elderly group was significantly lower than the other two groups( P<0.05).The effect compartment concentration of elderly rose slowly.and the peak concentration was lower, drug effects emerged later.3. The mean R of HR and MAP were 0.904 and 0.752 respectively.4. Under general anesthesia with propofol, using comprehensive index=0.58* E(t)HR +0.42* E(t)MAP as a measure of remifentanil drug effect, The comprehensive index could better quantitate the drug effect of remifentanil. The mean R was 0.946.we could provide evidences for the use of the close-loop TCI of remifentanil. KEYWORDS Age; remifentanil; propofol; pharmacodynamics; PK-PD modeling; close-loop...