Metz C, Göbel L, Gruber M, Hoerauf K H, Taeger K
Department of Anesthesiology, University Hospital Regensburg, Regensburg, Germany.
Anesthesiology. 2000 Jun;92(6):1559-67. doi: 10.1097/00000542-200006000-00012.
The pharmacodynamic differences in time to onset and dissipation of effect of sufentanil, fentanyl, and alfentanil probably result from different rates of blood-brain equilibration. The authors investigated this hypothesis in humans.
After simultaneous central venous bolus application of sufentanil (10 microg), fentanyl (100 microg), and alfentanil (1,000 microg), arterial and jugular bulb blood samples were drawn simultaneously at 20, 30, 45, 60, 75, 90, 105, 120, 140, 160, 180, 210, 240, 300, 360, and 420 s from 19 patients during the postacute stage of head injury with normal intracranial pressure, cerebral perfusion pressure, and cerebral oxygen metabolism during normocapnia.
Peak brain concentration, indicated by equilibrium between arterial and jugular bulb opioid concentrations, was achieved for alfentanil at 45 s, for sufentanil at 5 min, and for fentanyl at 6 min. The corresponding median time intervals (fifth and ninety-fifth percentiles) to reach 50% of peak brain concentration were 15 (14-18), 25 (18-38) and 35 (25-45) s, respectively. Uptake was highest 20 s after bolus and decreased continuously for fentanyl and sufentanil, whereas alfentanil uptake was biphasic. The ratio of the relative amounts of sufentanil, fentanyl, and alfentanil retained in the brain at peak brain concentration was 1x:x6x:x90.
The differences in the time lag between changes in serum concentrations and drug effect after bolus application of nearly equipotent doses of sufentanil, fentanyl, and alfentanil originate from the different times required to reach blood-brain equilibration, mainly depending on different levels and different time profiles of arterial blood concentrations caused by the different tissue distribution volumes.
舒芬太尼、芬太尼和阿芬太尼起效时间和效应消散的药效学差异可能源于血脑平衡速率不同。作者在人体中研究了这一假设。
对19例颅脑损伤急性期后患者在正常颅内压、脑灌注压和正常碳酸血症下脑氧代谢的情况下，同时经中心静脉推注舒芬太尼（10微克）、芬太尼（100微克）和阿芬太尼（1000微克）后，于20、30、45、60、75、90、105、120、140、160、180、210、240、300、360和420秒同时采集动脉和颈静脉球部血样。
以动脉和颈静脉球部阿片类药物浓度平衡表示的脑内峰值浓度，阿芬太尼在45秒达到，舒芬太尼在第5分钟达到，芬太尼在第6分钟达到。达到脑内峰值浓度50%的相应中位时间间隔（第5和第95百分位数）分别为15（14 - 18）秒、25（18 - 38）秒和35（25 - 45）秒。推注后20秒摄取最高，芬太尼和舒芬太尼摄取持续下降，而阿芬太尼摄取呈双相性。脑内峰值浓度时脑内保留的舒芬太尼、芬太尼和阿芬太尼相对量之比为1:6:90。
在推注近等效剂量的舒芬太尼、芬太尼和阿芬太尼后，血清浓度变化与药物效应之间的时间滞后差异源于达到血脑平衡所需的不同时间，这主要取决于不同组织分布容积导致的动脉血浓度的不同水平和不同时间曲线。
