Tang J, Wu G, Peng L
Department of Anaesthesia & Critical Care Medicine, Fifth People's Hospital of Shanghai, Fudan University, China.
Anaesthesist. 2011 Sep;60(9):835-40. doi: 10.1007/s00101-011-1907-y. Epub 2011 Jun 19.
The aim of the study was to investigate the effects of acute hypervolemic hemodilution (HHD) on the pharmacokinetics of propofol in patients undergoing total hip replacement.
A total of 16 patients undergoing elective surgery for total hip replacement under general anesthesia in combination with epidural analgesia were randomly assigned to 2 groups: the control group (n = 8) or the HHD group (n = 8). All patients in both groups received lactated Ringer's solution before induction of general anesthesia. In the control group the conventional fluid replacement protocol was used. In the HHD group 4% succinylated gelatin was infused at the rate of 20 ml•kg(-1)BW•h(-1 )with a targeted hematocrit of 30. Anesthesia was induced with midazolam 0.04 mg•kg(-1), fentanyl 4 µg•kg(-1) and propofol 1.5 mg•kg(-1). Tracheal intubation was facilitated by infusion of succinylcholine 2 mg•kg(-1). Anesthesia was maintained with isoflurane, fentanyl, vecuronium and epidural analgesia. Electrocardiogram (ECG), blood pressure (BP), blood oxygen saturation (SpO(2)), partial pressure of end-tidal carbon dioxide (P(ET)CO(2)) and central venous pressure (CVP) were monitored continuously. Blood samples were taken at 1, 2, 4, 6, 10, 15, 30, 45, 60, 75, 90, 120, 150, 180, 240, 300 and 360 min after propofol administration to determine plasma concentrations of propofol by high performance liquid chromatography (HPLC).
Plasma propofol concentrations were significantly lower in the HHD group than in the control group at 1, 2, 4, 6 and 10 min after propofol administration (p < 0.01) while there were no significant differences in plasma propofol levels 15-360 min after administration of propofol (p > 0.05). In the HHD group the volume of distribution of the central compartment (V(C)) increased significantly, elimination half-life (T(1/2) (γ)) was significantly prolonged, the elimination rate constant (K(10)) and the whole-body clearance (CL) were significantly decreased compared with the control group (p < 0.01 or 0.05). There were no significant differences of the half-life of the fast distribution phase (T(1/2) (α)), half-life of the slower distribution phase (T(1/2) (β)), K(12), K(21), K(13), K(31) and the area under the curve (AUC) (p > 0.05). The pharmacokinetic profile of propofol is best described by a three-compartment model in both groups using minimal Akaike information criteria (AIC).
Acute HHD increases V(C), prolongs the T(1/2) (γ), and decreases K(10) and CL, which suggests that care must be taken when propofol is used in patients undergoing HHD. The induction dose should be increased, but the maintenance dose should be decreased. The time to emergency from anesthesia will likely be prolonged, especially in patients receiving prolonged continuous infusions.
本研究旨在探讨急性高容量血液稀释（HHD）对全髋关节置换术患者丙泊酚药代动力学的影响。
16例择期行全髋关节置换术且接受全身麻醉联合硬膜外镇痛的患者被随机分为2组：对照组（n = 8）和HHD组（n = 8）。两组所有患者在全身麻醉诱导前均输注乳酸林格氏液。对照组采用传统的液体补充方案。HHD组以20 ml•kg(-1)BW•h(-1)的速率输注4%琥珀酰明胶，目标血细胞比容为30。用咪达唑仑0.04 mg•kg(-1)、芬太尼4 μg•kg(-1)和丙泊酚1.5 mg•kg(-1)诱导麻醉。输注琥珀酰胆碱2 mg•kg(-1)以利于气管插管。用异氟烷、芬太尼、维库溴铵和硬膜外镇痛维持麻醉。持续监测心电图（ECG）、血压（BP）、血氧饱和度（SpO(2)）、呼气末二氧化碳分压（P(ET)CO(2)）和中心静脉压（CVP）。在丙泊酚给药后1、2、4、6、10、15、30、45、60、75、90、120、150、180、240、300和360分钟采集血样，用高效液相色谱法（HPLC）测定丙泊酚的血浆浓度。
丙泊酚给药后1、2、4、6和10分钟，HHD组的血浆丙泊酚浓度显著低于对照组（p < 0.01），而丙泊酚给药后15 - 360分钟血浆丙泊酚水平无显著差异（p > 0.05）。与对照组相比，HHD组中央室分布容积（V(C)）显著增加，消除半衰期（T(1/2) (γ)）显著延长，消除速率常数（K(10)）和全身清除率（CL）显著降低（p < 0.01或0.05）。快速分布相半衰期（T(1/2) (α)）、较慢分布相半衰期（T(1/2) (β)）、K(12)、K(21)、K(13)、K(31)和曲线下面积（AUC）无显著差异（p > 0.05）。两组使用最小赤池信息准则（AIC）时，丙泊酚的药代动力学特征均以三室模型最佳描述。
急性HHD增加V(C)，延长T(1/2) (γ)，降低K(10)和CL，这表明在HHD患者中使用丙泊酚时必须谨慎。诱导剂量应增加，但维持剂量应减少。麻醉苏醒时间可能延长，尤其是在接受长时间持续输注的患者中。
