Enlund Mats
Dept of Anaesthesia & Intensive Care, and Centre for Clinical Research, Central Hospital, Västerås, Sweden.
Ups J Med Sci. 2008;113(2):161-70. doi: 10.3109/2000-1967-222.
Different pharmacokinetic models for target controlled infusion (TCI) of propofol are available in the recently launched open TCI systems. There is also a compelling choice to work with either plasma- or effect-site targets. Knowledge about the clinical consequences of different alternatives is of importance. We aimed to illustrate the potential differences in the actual drug delivery/output between three present commercially available and clinically used pharmacokinetic models: the original Marsh model, which is also implemented in the Diprifusor, the "modified Marsh-" and the Schnider models. Simulations were made in the TivaTrainer program (eurosiva.com). Firstly, our standard plasma target regimen was simulated, and secondly an effect-site target of 3.5 microg/mL was chosen. Thirdly, real infusors were used for measuring the time to reach defined predicted effect-site concentrations when aiming at a plasma target of 6 microg/mL. Identical patient characteristics were used in all simulations: male, 170 cm, 70 kg, 40 years of age. Resulting predicted effect-site peak concentrations, and used bolus doses were recorded, as were the resulting plasma over-shoot, and time frames. The plasma target regimen gave predicted effect-site peaks in the different models ranging from 3.6 to 7.2 microg/mL, reached after 2(3/4) to 4 minutes. To reach the same effect-site target, the three models used bolus doses ranging from 68 to 150 mg given during 22 to 46 seconds. The predicted plasma concentration over-shoots varied from 5.0 to 13.4 microg/mL. There were obvious differences between the models in the time taken to reach defined effect-site concentrations. We observed clinically significant different results between the models. The choice of model will make a difference for the patient. To eliminate confusion - not necessarily to improve precision - we call for an optimised population based pharmacokinetic model for propofol - a consensus model!
在最近推出的开放式靶控输注（TCI）系统中，有多种用于丙泊酚靶控输注的药代动力学模型。在血浆靶标或效应室靶标之间进行选择也很有必要。了解不同选择的临床后果非常重要。我们旨在说明三种目前市售且临床使用的药代动力学模型在实际药物输送/输出方面的潜在差异：原始的Marsh模型（也应用于得普利麻输注泵）、“改良Marsh-”模型和Schnider模型。在TivaTrainer程序（eurosiva.com）中进行了模拟。首先，模拟了我们的标准血浆靶标方案，其次选择了3.5微克/毫升的效应室靶标。第三，使用实际的输注泵来测量在以6微克/毫升的血浆靶标为目标时达到规定的预测效应室浓度所需的时间。在所有模拟中使用了相同的患者特征：男性，身高170厘米，体重70千克，年龄40岁。记录了产生的预测效应室峰值浓度、使用的推注剂量、产生的血浆过冲以及时间范围。血浆靶标方案在不同模型中产生的预测效应室峰值范围为3.6至7.2微克/毫升，在2（3/4）至4分钟后达到。为了达到相同的效应室靶标，三种模型使用的推注剂量范围为68至150毫克，推注时间为22至46秒。预测的血浆浓度过冲范围为5.0至13.4微克/毫升。各模型在达到规定效应室浓度所需的时间上存在明显差异。我们观察到各模型之间存在具有临床意义的不同结果。模型的选择会对患者产生影响。为了消除混淆——不一定是为了提高精确度——我们呼吁建立一个优化的基于群体的丙泊酚药代动力学模型——一个共识模型！
