Kazama T, Ikeda K, Morita K, Kikura M, Doi M, Ikeda T, Kurita T, Nakajima Y
Department of Anesthesiology and Intensive Care, Hamamatsu University School of Medicine, Japan.
Anesthesiology. 1999 Jun;90(6):1517-27. doi: 10.1097/00000542-199906000-00004.
Drug effect lags behind the blood concentration. The goal of this investigation was to determine the time course of plasma concentration and the effects of propofol demonstrated by electroencephalogram or blood pressure changes and to compare them between elderly and young or middle-aged patients.
A target-controlled infusion was used to rapidly attain and maintain four sequentially increasing, randomly selected plasma propofol concentrations from 1 to 12 microg/ml in 41 patients aged 20-85 yr. The target concentration was maintained for about 30 min. Bispectral index (BIS), spectral edge frequency, and systolic blood pressure (SBP) were used as measures of propofol effect. Because the time courses of these measures following the started drug infusion showed an exponential pattern, the first-order rate constant for equilibration of the effect site with the plasma concentration (k(eO)) was estimated by fitting a monoexponential model to the effect versus time data resulting from the pseudo-steady-state propofol plasma concentration profile.
The half-times for the plasma-effect-site equilibration for BIS were 2.31, 2.30, 2.29, and 2.37 min in patients aged 20-39, 40-59, 60-69, and 70-85 yr, respectively (n = 10 or 11 each). The half-times for SBP were 5.68, 5.92, 8.87, and 10.22 min in the respective age groups. All were significantly longer than for BIS (P < 0.05). The propofol concentration at half of the maximal decrease of SBP was significantly greater (P < 0.05) in the elderly than in the younger patients.
The effect of propofol on BIS occurs more rapidly than its effect on SBP. Age has no effect on the rate of BIS reduction with increasing propofol concentration, whereas with increasing age, SBP decreases to a greater degree but more slowly.
药物效应滞后于血药浓度。本研究的目的是确定血浆浓度的时间进程以及丙泊酚通过脑电图或血压变化所表现出的效应,并比较老年患者与年轻或中年患者之间的差异。
采用靶控输注,在41例年龄为20 - 85岁的患者中,快速达到并维持4个依次递增、随机选择的血浆丙泊酚浓度,范围为1至12μg/ml。每个靶浓度维持约30分钟。双谱指数(BIS)、谱边缘频率和收缩压(SBP)用作丙泊酚效应的指标。由于这些指标在开始药物输注后的时间进程呈指数模式,通过将单指数模型拟合到由伪稳态丙泊酚血浆浓度曲线产生的效应与时间数据,来估计效应部位与血浆浓度平衡的一级速率常数(k(eO))。
20 - 39岁、40 - 59岁、60 - 69岁和70 - 85岁患者中,BIS的血浆 - 效应部位平衡半衰期分别为2.31、2.30、2.29和2.37分钟(每组n = 10或11)。各年龄组SBP的半衰期分别为5.68、5.92、8.87和10.22分钟。所有这些均显著长于BIS的半衰期(P < 0.05)。老年患者中,SBP最大降幅一半时的丙泊酚浓度显著高于年轻患者(P < 0.05)。
丙泊酚对BIS的效应比对SBP的效应出现得更快。年龄对丙泊酚浓度增加时BIS降低的速率无影响,而随着年龄增加,SBP下降幅度更大但更缓慢。