Slepchenko Gregory, Simon Nicolas, Goubaux Bernard, Levron Jean-Claude, Le Moing Jean-Pierre, Raucoules-Aimé Marc
Department of Anesthesiology, Centre Hospitalier Universitaire, Nice, France.
Anesthesiology. 2003 Jan;98(1):65-73. doi: 10.1097/00000542-200301000-00014.
Because obesity might affect pharmacokinetic parameters, the authors evaluated the accuracy of target-controlled sufentanil infusion in morbidly obese patients using a pharmacokinetic model usually applied to a normal-weight population.
Target-controlled propofol and sufentanil coinfusions were administered to 11 morbidly obese patients (body mass index: 45.0 +/- 6.5 kg/m2 ) undergoing laparoscopic gastroplasty. The target plasma propofol concentration was 3 micro g/ml. The effect-site sufentanil target concentration was initially 0.4 ng/ml but was modified during surgery as a function of blood pressure and heart rate. Plasma sufentanil concentrations were measured from the onset of infusion until 24 h after its termination. The predicted sufentanil target concentrations were calculated by STANPUMP software. Intrasubject data analyzed included calculation of performance error, median performance error, median absolute performance error, divergence, and wobble. Pharmacokinetic analysis was performed using a nonlinear mixed effect model.
Applied sufentanil target concentrations ranged from 0.3 to 0.65 ng/ml. The mean +/- SD plasma sufentanil concentration measured during spontaneous ventilation was 0.13 +/- 0.03 ng/ml. Median performance error (range) was -13% (-42 to 36%). Median absolute performance error was 26% (8-44%) during infusion and 17% (12-59%) for the 24 h after its completion. The pharmacokinetic sets used slightly overpredicted the concentrations, with a median divergence of -3.4% (-10.2 to 3.1%) during infusion. For body mass index greater than 40, the overestimation of plasma sufentanil concentrations was greater. A two-compartment model with proportional error for interindividual variability best fitted the data. The residual variability was modeled as an additive (0.016 ng/ml) or proportional error (23%). Clearance, central volume of distribution, intercompartmental clearance, and peripheral volume of distribution (coefficient of variation) were 1.27 l/min (23%), 37.1 l (20%), 0.87 l/min (44%), and 92.7 l (22%), respectively.
The pharmacokinetic parameter set derived from a normal-weight population accurately predicted plasma sufentanil concentrations in morbidly obese patients.
由于肥胖可能影响药代动力学参数,作者使用通常应用于正常体重人群的药代动力学模型,评估了目标控制舒芬太尼输注在病态肥胖患者中的准确性。
对11例接受腹腔镜胃成形术的病态肥胖患者(体重指数:45.0±6.5kg/m²)进行目标控制丙泊酚和舒芬太尼联合输注。目标血浆丙泊酚浓度为3μg/ml。效应室舒芬太尼目标浓度最初为0.4ng/ml,但在手术期间根据血压和心率进行调整。从输注开始至结束后24小时测量血浆舒芬太尼浓度。通过STANPUMP软件计算预测的舒芬太尼目标浓度。分析的个体内数据包括性能误差、中位性能误差、中位绝对性能误差、偏差和摆动的计算。使用非线性混合效应模型进行药代动力学分析。
应用的舒芬太尼目标浓度范围为0.3至0.65ng/ml。自主通气期间测量的平均±标准差血浆舒芬太尼浓度为0.13±0.03ng/ml。中位性能误差(范围)为-13%(-42%至36%)。输注期间中位绝对性能误差为26%(8%至44%),输注结束后24小时为17%(12%至59%)。使用的药代动力学模型略微高估了浓度,输注期间中位偏差为-3.4%(-10.2%至3.1%)。对于体重指数大于40的患者,血浆舒芬太尼浓度的高估更大。具有个体间变异性比例误差的二室模型最适合数据。残余变异性建模为加性误差(0.016ng/ml)或比例误差(23%)。清除率、中央分布容积、室间清除率和外周分布容积(变异系数)分别为1.27l/min(23%)、37.1l(20%)、0.87l/min(44%)和92.7l(22%)。
源自正常体重人群的药代动力学参数集准确预测了病态肥胖患者的血浆舒芬太尼浓度。