Department of Anaesthesia, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Primate Research Institute, Kyoto University, Inuyama, Aichi, Japan.
Br J Anaesth. 2017 Jun 1;118(6):901-909. doi: 10.1093/bja/aex134.
Models of propofol pharmacokinetics and pharmacodynamics developed in patients without brain pathology are widely used for target-controlled infusion (TCI) during brain tumour excision operations. The goal of this study was to determine if the presence of a frontal brain tumour influences propofol pharmacokinetics and pharmacodynamics and existing PK-PD model performance.
Twenty patients with a frontal brain tumour and 20 control patients received a propofol infusion to achieve an induction-emergence-induction anaesthetic sequence. Propofol plasma concentration was measured every 4 min and at each transition of the conscious state. Bispectral index (BIS) values were continuously recorded. We used non-linear mixed-effects modelling to analyse the effects of the presence of a brain tumour on the pharmacokinetics and pharmacodynamics of propofol. Subsequently we calculated the predictive performance of Marsh, Schnider, and Eleveld models in terms of median prediction error (MdPE) and median absolute prediction error (MdAPE).
Patients with brain tumours showed 40% higher propofol clearance than control patients. Performance of the Schnider model (MdPEpk -20.0%, MdAPEpk 23.4%) and Eleveld volunteer model (MdPEpk -8.58%, MdAPEpk 21.6%) were good. The Marsh model performed less well (MdPEpk -14.3%, MdAPEpk 41.4%), as did the Eleveld patient model (MdPEpk -30.8%, MdAPEpk 32.1%).
Brain tumours might alter the pharmacokinetics of propofol. Caution should be exerted when using propofol TCI in patients with frontal brain tumours due to higher clearance.
NCT01060631.
在没有脑病理的患者中开发的丙泊酚药代动力学和药效动力学模型广泛用于脑肿瘤切除手术中的靶控输注（TCI）。本研究的目的是确定额部脑肿瘤是否会影响丙泊酚的药代动力学和药效动力学以及现有的 PK-PD 模型性能。
20 例额部脑肿瘤患者和 20 例对照患者接受丙泊酚输注，以达到麻醉诱导-苏醒-诱导的麻醉顺序。每 4 分钟测量一次丙泊酚血浆浓度，并在意识状态每次转变时测量一次。连续记录脑电双频指数（BIS）值。我们使用非线性混合效应模型分析脑肿瘤对丙泊酚药代动力学和药效动力学的影响。随后，我们计算了 Marsh、Schnider 和 Eleveld 模型在中位预测误差（MdPE）和中位绝对预测误差（MdAPE）方面的预测性能。
脑肿瘤患者的丙泊酚清除率比对照组患者高 40%。Schnider 模型（MdPEpk -20.0%，MdAPEpk 23.4%）和 Eleveld 志愿者模型（MdPEpk -8.58%，MdAPEpk 21.6%）的性能良好。Marsh 模型的性能较差（MdPEpk -14.3%，MdAPEpk 41.4%），Eleveld 患者模型的性能也较差（MdPEpk -30.8%，MdAPEpk 32.1%）。
脑肿瘤可能改变丙泊酚的药代动力学。由于清除率较高，在有额部脑肿瘤的患者中使用丙泊酚 TCI 时应谨慎。
NCT01060631。
