Kurita Tadayoshi, Takata Kotaro, Morita Koji, Morishima Yoriko, Uraoka Masahiro, Katoh Takasumi, Sato Shigehito
Departments of Anesthesiology and Intensive Care, Hamamatsu University School of Medicine, Handayama, Hamamatsu, Japan.
Anesth Analg. 2009 Aug;109(2):398-404. doi: 10.1213/ane.0b013e3181a96f9a.
Hemorrhagic shock increases the hypnotic effect of propofol, but the influence of hemorrhagic shock on the immobilizing effect of propofol is not fully defined.
Twenty-four swine (30.3 +/- 3.6 kg) were anesthetized by inhalation of isoflurane and randomly assigned to either a control (n = 12) or a hemorrhagic shock (n = 12) group. Animals in the shock group were bled to a mean arterial blood pressure of 50 mm Hg and maintained at this level for 60 min. After isoflurane inhalation was stopped, propofol was infused at 50 mg x kg(-1) x h(-1) until no movement was observed after application of a dewclaw clamp every 2 min. Arterial samples for measurement of the propofol concentration were collected just before each use of the dewclaw clamp and the Bispectral Index (BIS) was also recorded. Analysis of the pharmacodynamics was performed using a sigmoidal inhibitory maximal effect model for BIS versus effect-site concentration and a logistic regression analysis for the probability of movement versus effect-site concentration.
The propofol doses needed to reach a 50% decrease from baseline BIS, and no movement after noxious stimuli were reduced by hemorrhagic shock by 54% and 38%, respectively. Hemorrhagic shock decreased the effect-site concentration that produced 50% of the maximal BIS effect from 11.6 +/- 3.8 to 9.1 +/- 1.7 microg/mL and that producing a 50% probability of movement from 26.8 +/- 1.0 to 20.6 +/- 1.0 microg/mL.
The results show that hemorrhagic shock increases both the hypnotic and immobilizing effects of propofol due to pharmacokinetic and pharmacodynamic alterations, with the changes in pharmacodynamics occurring to a similar extent for both effects.
失血性休克会增强丙泊酚的催眠作用,但失血性休克对丙泊酚制动作用的影响尚未完全明确。
24头猪(体重30.3±3.6千克)通过吸入异氟烷进行麻醉,并随机分为对照组(n = 12)和失血性休克组(n = 12)。休克组动物放血至平均动脉血压为50毫米汞柱,并维持此水平60分钟。停止吸入异氟烷后,以50毫克·千克⁻¹·小时⁻¹的速度输注丙泊酚,每2分钟应用一次爪钳,直至观察不到活动。在每次使用爪钳之前采集用于测量丙泊酚浓度的动脉样本,并记录脑电双频指数(BIS)。使用BIS与效应室浓度的S形抑制最大效应模型以及活动概率与效应室浓度的逻辑回归分析进行药效学分析。
失血性休克使丙泊酚剂量分别减少54%和38%,从而使BIS从基线降低50%,且在有害刺激后无活动。失血性休克使产生最大BIS效应50%的效应室浓度从11.6±3.8降至9.1±1.7微克/毫升,使产生50%活动概率的效应室浓度从26.8±1.0降至20.6±1.0微克/毫升。
结果表明,由于药代动力学和药效学改变,失血性休克增强了丙泊酚的催眠和制动作用,两种作用的药效学变化程度相似。