Xu Chuan-ya, Wu Xin-min, Jiang Jian-yu, Lu Wei
Department of Anesthesiology, Peking University Third Hospital, and Department of Pharmaceutics, Peking University School of Pharmaceutical Science, Beijing 100191, China.
Beijing Da Xue Xue Bao Yi Xue Ban. 2010 Dec 18;42(6):734-8.
To investigate the effects of remifentanil administered by target-controlled infusion (TCI) with different plasma concentration and time on pharmacokinetics of propofol in elderly patients.
Thirty-two ASA I-II patients (65-82 years old) undergoing elective lower abdominal operations were divided into 4 groups randomly: TCI propofol combined with epidural block (group A, n=8); TCI remifentanil with plasma concentration 4 μg/L and propofol (group B, n=8); TCI remifentanil with plasma concentration 7 μg/L and propofol (group C, n=8); and TCI propofol and remifentanil (plasma concentration 4 μg/L) with infusion time longer than 4 hours (group D, n=8). Propofol was infused by target-controlled infusion with plasma concentration 3 mg/L in the 4 groups. bispetral index (BIS), heart rate (HR), blood pressure (BP) were recorded during operation. Blood samples were collection from radial arterial catheter. Samples of 2 mL of arterial blood were taken at 0, 1, 3, 5, 10, 15, 30 min and then every 30 min after the start of the infusion of propofol, and at 0, 2, 4, 6, 8, 10, 15, 30, 45, 60, 120, 240, 360, 480, 720, 1440 min after the termination of the infusion of propofol. Propofol concentrations in blood were measured by reversed-phase high-performance liquid chromatography (HPLC). The pharmacokinetics analyses were performed using the nonlinear mixed-effects model approach implemented in NONMEM computer program. After obtaining the best NONMEM model with covariates, the influence of coadministered remifentanil on the model was examined.
In all the patients, the depth of anesthesia was enough (BIS value=40-60), and the circulatory system function was stable during operation. The final model of propofol pharmacokinetics in the three groups (A+B, A+C, and A+D groups) was best described by a three-compartment mammillary model. The values of objective function (OFV) were -810.1, -714.4, and -896.4. Addition of remifentanil covariate effects to the final model resulted in no improvement in the objective function.
target-controlled infusion of propofol combined with different plasma concentration of remifentanil or remifentanil infusing more than 4 hours had no effect on pharmacokinetics of propofol in elderly patients.
探讨不同血浆浓度和时间的瑞芬太尼靶控输注（TCI）对老年患者丙泊酚药代动力学的影响。
32例年龄65 - 82岁、拟行择期下腹部手术的ASA I-II级患者随机分为4组：丙泊酚TCI联合硬膜外阻滞组（A组，n = 8）；血浆浓度4μg/L瑞芬太尼与丙泊酚TCI组（B组，n = 8）；血浆浓度7μg/L瑞芬太尼与丙泊酚TCI组（C组，n = 8）；丙泊酚和瑞芬太尼（血浆浓度4μg/L）TCI且输注时间超过4小时组（D组，n = 8）。4组均采用血浆浓度3mg/L的丙泊酚靶控输注。术中记录脑电双频指数（BIS）、心率（HR）、血压（BP）。经桡动脉导管采集血样。在丙泊酚输注开始后0、1、3、5、10、15、30分钟，然后每隔30分钟采集2mL动脉血样本，在丙泊酚输注结束后0、2、4、6、8、10、15、30、45、60、120、240、360、480、720、1440分钟采集血样。采用反相高效液相色谱法（HPLC）测定血中丙泊酚浓度。使用NONMEM计算机程序中的非线性混合效应模型方法进行药代动力学分析。在获得含协变量的最佳NONMEM模型后，考察联合应用瑞芬太尼对该模型的影响。
所有患者麻醉深度足够（BIS值 = 40 - 60），术中循环系统功能稳定。三组（A + B、A + C和A + D组）丙泊酚药代动力学的最终模型以三室乳突模型最佳描述。目标函数（OFV）值分别为 - 810.1、 - 714.4和 - 896.4。将瑞芬太尼协变量效应加入最终模型后目标函数无改善。
不同血浆浓度瑞芬太尼的TCI或瑞芬太尼输注超过4小时对老年患者丙泊酚药代动力学无影响。
