The general anesthetic potency of propofol and its dependence on hydrostatic pressure.
The general anesthetic potency of propofol and its dependence on hydrostatic pressure.
复制标题
异丙酚的全身麻醉效力及其对静水压的依赖性。
DOI：
10.1097/00000542-199211000-00015
复制
发表时间：
1992
期刊：
影响因子：
8.8
通讯作者：
Miller,KW
中科院分区：
文献类型：
--
作者：
Tonner,PH;Poppers,DM;Miller,KW
尽管麻醉期间异丙酚的血浆浓度是众所周知的，但由于血浆蛋白结合、与其他蛋白结合物质的相互作用、与其脂质载体的结合水平以及佐剂的使用的不确定性，游离浓度仍然未知。在周围压力升高的情况下，所有全身麻醉剂都需要更高的浓度才能达到足够的麻醉水平。为了确定平衡条件下异丙酚的麻醉效力并研究压力对异丙酚诱导麻醉的影响，将林蛙蝌蚪暴露于不同浓度的纯非乳化异丙酚水溶液中。麻醉被定义为翻正反射丧失。每个浓度使用十只动物，每个实验进行两次。以非麻醉蝌蚪和聚氨酯麻醉蝌蚪作为对照组进行压力实验。通过分光光度法测量异丙酚浓度。在 1 个绝对大气压 (atm abs) 下，获得半对数 S 形浓度-反应曲线，丙泊酚在 2.2+/-0.22 microM 下具有半最大效应（EC50；平均值+/-SE）。增加的压力使浓度-反应曲线向右移动。 EC50 随着压力增加而线性增加，直至 121 atm 绝对值（121 atm 绝对值时的 EC50= 4.1+/-0.41 microM）。当压力大于 121 atm 绝对值时，蝌蚪的兴奋性增加，使得难以区分翻正反射和不自主运动。发现丙泊酚在水溶液中的饱和溶解度为1.0+/-0.02mM(平均值+/-SD)，辛醇/水分配系数为4,300+/-280。异丙酚遵循其他全身麻醉药所表现出的麻醉效力与辛醇/水分配系数之间的相关性。（摘要截断为 250 字）
Although plasma concentrations of propofol during anesthesia are well known, the free concentration remains unknown because of uncertainties regarding plasma protein binding, interaction with other protein-bound substances, the level of binding to its lipid carrier, and the use of adjuvants. At elevated surrounding pressure, all general anesthetics require higher concentrations to reach adequate levels of anesthesia. To determine the anesthetic potency of propofol at equilibrium conditions and to study the effects of pressure on propofol-induced anesthesia, Rana pipiens tadpoles were exposed to different concentrations of pure, not emulsified, propofol in aqueous solution. Anesthesia was defined as loss of the righting reflex. Ten animals per concentration were used, and each experiment was conducted twice. Pressure experiments were performed with nonanesthetized tadpoles and urethane-anesthetized tadpoles as control groups. Propofol concentrations were measured spectrophotometrically. At 1 atmosphere absolute (atm abs), a semilogarithmic sigmoidal concentration-response curve was obtained with a half-maximal effect of propofol at 2.2+/-0.22 microM (EC50; mean+/-SE). Increased pressure shifted the concentration-response curve to the right. The EC50 increased linearly with increasing pressure up to 121 atm abs (EC50 at 121 atm abs= 4.1+/-0.41 microM). For pressure greater than 121 atm abs, an increased excitability of the tadpoles made it difficult to distinguish the righting reflex from involuntary movements. The saturated solubility of propofol in aqueous solution was found to be 1.0+/-0.02 mM (mean+/-SD), and the octanol/water partition coefficient was 4,300+/-280. Propofol adhered to the correlation between anesthetic potency and octanol/water partition coefficient exhibited by other general anesthetics.(ABSTRACT TRUNCATED AT 250 WORDS)