Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Changhai Road No. 225, Shanghai, China.
Acta Anaesthesiol Scand. 2009 Nov;53(10):1329-35. doi: 10.1111/j.1399-6576.2009.02079.x. Epub 2009 Aug 13.
Some studies suggest that certain clinical symptoms of cholestasis, such as fatigue and pruritus, result from altered neurotransmission. Patients with obstructive jaundice also have labile blood pressure and heart rate. In the present study, the authors investigated whether obstructive jaundice affects a patient's sensitivity to hypnotics and the haemodynamic profile of propofol.
Thirty-six ASA physical status I/II/III patients with serum total bilirubin (TBL) from 7.8 to 362.7 micromol/l scheduled for bile duct surgery were recruited. A computer-controlled propofol infusion programmed for effect site target was used to rapidly attain and maintain sequential increase of the compartment concentration (from 1 to 3 microg/ml). Each target-controlled concentration was maintained for about 12 min, and arterial blood samples were drawn for propofol concentration determination. The bispectral index (BIS) and mean arterial pressures (MAP) were used as indices of the propofol effect. The relation between the concentration and the effects was described by the Hill equation. The pharmacodynamic parameters were optimized using a nonlinear mixed-effect model.
TBL was not a significant covariate of EC(50) for the pharmacodynamic model. For BIS and MAP, the parameters of the pharmacodynamic model were E(max)=75.77%, EC(50)=2.34 microg/ml, and gamma=1.82, and E(max)=47.83%, EC(50)=1.49 microg/ml, and gamma=1.88, respectively.
We demonstrated that obstructive jaundice with serum TBL from 7.8 to 362.7 micromol/l had no effect on propofol pharmacodynamics observed by BIS and MAP.
一些研究表明，胆流阻滞的某些临床症状，如疲劳和瘙痒，是由于神经递质改变所致。阻塞性黄疸患者的血压和心率也不稳定。在本研究中，作者研究了阻塞性黄疸是否影响患者对催眠药的敏感性以及丙泊酚的血液动力学特征。
招募了 36 名 ASA 身体状况 I/II/III 级、血清总胆红素（TBL）为 7.8 至 362.7μmol/l 的患者，他们计划接受胆管手术。采用计算机控制的丙泊酚输注，编程为效应部位目标，以快速达到并维持连续增加隔室浓度（从 1 至 3μg/ml）。每个目标控制浓度维持约 12 分钟，并抽取动脉血样以确定丙泊酚浓度。双频谱指数（BIS）和平均动脉压（MAP）被用作丙泊酚作用的指标。浓度与效应之间的关系用 Hill 方程描述。使用非线性混合效应模型优化药效动力学参数。
TBL 不是药效动力学模型中 EC（50）的显著协变量。对于 BIS 和 MAP，药效动力学模型的参数为 E(max)=75.77%、EC(50)=2.34μg/ml 和γ=1.82，以及 E(max)=47.83%、EC(50)=1.49μg/ml 和γ=1.88。
我们证明了血清 TBL 为 7.8 至 362.7μmol/l 的阻塞性黄疸对 BIS 和 MAP 观察到的丙泊酚药效动力学无影响。
