Department of Anesthesia, The University of Iowa Hospitals and Clinics, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, USA.
Burns. 2010 Dec;36(8):1215-21. doi: 10.1016/j.burns.2010.03.003. Epub 2010 May 26.
In operating theaters and burn units, propofol is commonly used for sedation and anesthesia in patients with major burns. This study determined the population pharmacokinetics of propofol in burns and identified clinically significant covariates.
Seventeen adults, age 42±10 (mean±SD) years, with 41±19% total body surface area burns, were enrolled at 16±14 days after-burn. Non-burn adults (n=19) served as controls. After an intravenous bolus of 2mg/kg propofol, the plasma concentration was determined at designated times for up to 4.5h. Concentration-time profiles were analyzed using nonlinear mixed-effect modeling.
A three-compartment model gave the best fit. The volume of distribution of the central compartment (V(1)) was considerably greater in the burned than non-burned group (48.4 L vs. 27.6 L, respectively). The clearances of the central (CL(1)) and slow peripheral (CL(3)) compartments were higher in burn patients (4.2 L/min vs. 1.7 L/min and 3.6 L/min vs. 1.1 L/min, respectively). Adding the covariates BURN to V(1), CL(1), and CL(3) and WT (weight) to CL(1) significantly improved the model performance.
The pharmacokinetic characteristics of a propofol bolus administered in patients with major burns were enhanced clearance and expanded volume of distribution. BURN and WT were the important covariates. For sedation or anesthesia induction, a higher than recommended dose of propofol may be required to maintain therapeutic plasma drug concentrations in patients with severe burns. Vigilance regarding the burned individual and careful titration of hypnotics to the desired effect cannot be overemphasized.
在手术室和烧伤病房中，丙泊酚常用于大面积烧伤患者的镇静和麻醉。本研究旨在确定烧伤患者中丙泊酚的群体药代动力学，并确定具有临床意义的协变量。
17 名年龄 42±10（均数±标准差）岁、烧伤面积 41±19%的成年烧伤患者在烧伤后 16±14 天入组。非烧伤成年患者（n=19）作为对照组。给予患者静脉推注 2mg/kg 丙泊酚后，在指定时间内测定血浆浓度，时间长达 4.5 小时。采用非线性混合效应模型分析浓度-时间曲线。
三室模型拟合度最佳。烧伤患者的中央室分布容积（V1）明显大于非烧伤患者（分别为 48.4 L 和 27.6 L）。中央室（CL1）和缓慢外周室（CL3）清除率在烧伤患者中较高（分别为 4.2 L/min、3.6 L/min 和 1.7 L/min、1.1 L/min）。将协变量 BURN 加入到 V1、CL1 和 CL3 中，将 WT（体重）加入到 CL1 中，可显著提高模型性能。
大面积烧伤患者给予丙泊酚负荷剂量后，其药代动力学特征表现为清除率增加和分布容积扩大。BURN 和 WT 是重要的协变量。对于镇静或麻醉诱导，严重烧伤患者可能需要高于推荐剂量的丙泊酚，以维持治疗性血浆药物浓度。需要特别注意烧伤患者，并根据所需的催眠效果仔细滴定催眠药物。
