Koren G, Crean P, Klein J, Goresky G, Villamater J, MacLeod S M
Eur J Clin Pharmacol. 1984;27(1):51-6. doi: 10.1007/BF00553154.
Immediately following the connection of pediatric patients to cardiopulmonary bypass we have consistently observed a steep decrease in fentanyl plasma concentration (74 +/- 8.7%) (mean +/- SD), much greater than would have been expected from hemodilution alone (50.6% +/- 12.0%) (p less than 0.0001). Priming of the pump with 20 ng/ml of fentanyl before connection to the patients did not prevent this phenomenon. In order to study the possibility that fentanyl is sequestered by the bypass, levels of the primed drug in the bypass were assessed before connecting the pump to the children and a steep fall from 20 ng/ml to zero was shown before initiation of bypass. Pharmacokinetic assessment of fentanyl in a closed pump circuit showed that levels of 120 ng/ml fall to 2 ng/ml within 3 min and remain stable at the lower concentration for at least 30 min. Further studies have identified the membrane oxygenator as the major site of fentanyl sequestration. Concentrations across the membrane fall from 120 ng/ml to 10 ng/ml. The attached siliconized tubing is associated with a minor binding effect sufficient to reduce concentrations from 110 to 84 ng/ml. The pvc tubing, aluminium heat exchanger and plastic reservoir had no binding effect on fentanyl. The possibility that a decrease in fentanyl protein binding caused the fall in serum concentration was checked in 5 patients undergoing open heart surgery. After initiation of the cardiopulmonary bypass, there was a significant decrease in albumin serum concentrations from 32.0 +/- 2.3 mM to 15.0 +/- 1.6 mM (p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
在儿科患者连接到体外循环后,我们一直观察到芬太尼血浆浓度急剧下降(74±8.7%)(平均值±标准差),远大于仅因血液稀释所预期的下降幅度(50.6%±12.0%)(p<0.0001)。在连接患者之前用20 ng/ml的芬太尼预充泵并不能防止这种现象。为了研究芬太尼被体外循环截留的可能性,在将泵连接到儿童之前评估了体外循环中预充药物的水平,结果显示在体外循环开始前,芬太尼水平从20 ng/ml急剧降至零。对封闭泵回路中芬太尼的药代动力学评估表明,120 ng/ml的水平在3分钟内降至2 ng/ml,并在较低浓度下至少稳定30分钟。进一步的研究已确定膜式氧合器是芬太尼截留的主要部位。跨膜浓度从120 ng/ml降至10 ng/ml。连接的硅化管具有较小的结合作用,足以使浓度从110 ng/ml降至84 ng/ml。聚氯乙烯管、铝制热交换器和塑料储液器对芬太尼没有结合作用。对5例接受心脏直视手术的患者检查了芬太尼蛋白结合减少导致血清浓度下降的可能性。体外循环开始后,血清白蛋白浓度从32.0±2.3 mM显著降至15.0±1.6 mM(p<0.0001)。(摘要截短于250字)