Department of Anesthesia, Stanford University, Stanford, California USA.
BMC Anesthesiol. 2009 Jul 27;9:5. doi: 10.1186/1471-2253-9-5.
The aim of this study was to provide a model-based analysis of the pharmacokinetics of remifentanil in infants and children undergoing cardiac surgery with cardiopulmonary bypass (CPB).
We studied nine patients aged 0.5 to 4 years who received a continuous remifentanil infusion via a computer-controlled infusion pump during cardiac surgery with mildly hypothermic CPB were studied. Arterial blood samples taken prior to, during and after CPB were analyzed for remifentanil concentrations using a validated gas-chromatographic mass-spectrophotometric assay. We used population mixed-effects modeling to characterize remifentanil pharmacokinetics. The final model was evaluated by its predictive performance.
The pharmacokinetics of remifentanil was described by a 1-compartment model with adjustments for CPB. Population mean parameter estimates were 1.41 L for volume of distribution (V) and 0.244 L/min for clearance. V was increased during CPB and post-CPB to 2.41 times the pre-CPB value. The median prediction error and the median of individual median absolute prediction error were 2.44% and 21.6%, respectively.
Remifentanil dosage adjustments are required during and after CPB due to marked changes in the V of the drug. Simulations indicate that a targeted blood concentration of 14 ng/mL is achieved and maintained in 50% of typical patients by administration of an initial dose of 18 mug remifentanil followed by an infusion of 3.7 mug/min before, during and post-CPB, supplemented with a bolus dose of 25 mug given at the start of CPB.
本研究旨在为体外循环（CPB）下心内直视手术患儿的雷米芬太尼药代动力学提供模型分析。
我们研究了 9 名年龄在 0.5 至 4 岁的患者，这些患者在 CPB 下接受心内直视手术时接受了计算机控制的输注泵持续输注瑞芬太尼。CPB 前后和期间采集动脉血样，使用经过验证的气相色谱-质谱联用分析瑞芬太尼浓度。我们使用群体混合效应模型来描述瑞芬太尼的药代动力学。最后，通过预测性能来评估模型。
瑞芬太尼的药代动力学用 1 室模型描述，并对 CPB 进行了调整。群体平均参数估计值为 1.41 L 的分布容积（V）和 0.244 L/min 的清除率。CPB 期间和 CPB 后 V 增加到 CPB 前值的 2.41 倍。中位数预测误差和中位数个体中位数绝对预测误差分别为 2.44%和 21.6%。
由于药物 V 发生明显变化，CPB 期间和之后需要调整瑞芬太尼的剂量。模拟表明，初始剂量为 18 微克瑞芬太尼，然后在 CPB 前、期间和后以 3.7 微克/分钟的速度输注，CPB 开始时给予 25 微克的推注剂量，可使 50%的典型患者达到并维持 14 纳克/毫升的目标血药浓度。
