Silva-Filho Carlos R, Barbosa Ricardo Antonio G, Silva Carlindo V, Malbouisson Luiz M S, Carmona Maria José C, Jorge-Santos Silvia Regina C
Faculdade de Ciencias Farmaceuticas, Universidade de São Paulo, Sao Paulo, SP, BR.
Servico de Anestesiologia e Terapia Intensiva Cirurgica Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP Faculdade de Medicina, Universidade de São Paulo, Sao Paulo, SP, BR.
Clinics (Sao Paulo). 2018;73:e178. doi: 10.6061/clinics/2018/e178. Epub 2018 Feb 15.
The objective of this study was to apply a pharmacokinetics-pharmacodynamics approach to investigate the free propofol plasma levels in patients undergoing coronary artery bypass grafting under hypothermic conditions compared with the off-pump procedure.
Nineteen patients scheduled for on-pump coronary artery bypass grafting under hypothermic conditions (n=10) or the equivalent off-pump surgery (n=9) were anesthetized with sufentanil and propofol target-controlled infusion (2 μg/mL) during surgery. The propofol concentration was then reduced to 1 μg/mL, and a pharmacokinetics-pharmacodynamics analysis using the maximum-effect-sigmoid model obtained by plotting the bispectral index values against the free propofol plasma levels was performed.
Significant increases (two- to five-fold) in the free propofol plasma levels were observed in the patients subjected to coronary artery bypass grafting under hypothermic conditions. The pharmacokinetics of propofol varied according to the free drug levels in the hypothermic on-pump group versus the off-pump group. After hypothermic coronary artery bypass was initiated, the distribution volume increased, and the distribution half-life was prolonged. Propofol target-controlled infusion was discontinued when orotracheal extubation was indicated, and the time to patient extubation was significantly higher in the hypothermic on-pump group than in the off-pump group (459 versus 273 min, p=0.0048).
The orotracheal intubation time was significantly longer in the hypothermic on-pump group than in the off-pump group. Additionally, residual hypnosis was identified through the pharmacokinetics-pharmacodynamics approach based on decreases in drug plasma protein binding in the hypothermic on-pump group, which could explain the increased hypnosis observed with this drug in this group of patients.
本研究的目的是应用药代动力学 - 药效学方法，比较低温体外循环冠状动脉搭桥术患者与非体外循环手术患者的游离丙泊酚血浆水平。
19例计划接受低温体外循环冠状动脉搭桥术（n = 10）或等效非体外循环手术（n = 9）的患者在手术期间用舒芬太尼和丙泊酚靶控输注（2μg/mL）麻醉。然后将丙泊酚浓度降至1μg/mL，并使用通过将脑电双频指数值与游离丙泊酚血浆水平作图获得的最大效应 - sigmoid模型进行药代动力学 - 药效学分析。
在低温体外循环冠状动脉搭桥术患者中观察到游离丙泊酚血浆水平显著升高（两到五倍）。低温体外循环组与非体外循环组中丙泊酚的药代动力学根据游离药物水平而变化。低温冠状动脉搭桥术开始后，分布容积增加，分布半衰期延长。当指示进行气管插管时停止丙泊酚靶控输注，低温体外循环组患者拔管时间显著高于非体外循环组（459对273分钟，p = 0.0048）。
低温体外循环组气管插管时间显著长于非体外循环组。此外，通过药代动力学 - 药效学方法，基于低温体外循环组药物血浆蛋白结合的降低，发现了残余催眠作用，这可以解释该组患者中观察到的该药物催眠作用增强的现象。
