Mehta Nilesh M, Halwick David R, Dodson Brenda L, Thompson John E, Arnold John H
Children's Hospital, Farley 517, Division of Critical Care Medicine, 300 Longwood Avenue, Boston 02115, MA, USA.
Intensive Care Med. 2007 Jun;33(6):1018-24. doi: 10.1007/s00134-007-0606-2. Epub 2007 Apr 3.
Using an ex vivo simulation model we set out to estimate the amount of drug lost due to sequestration within the extracorporeal circuit over time.
Simulated closed-loop extracorporeal membrane oxygenation (ECMO) circuits were prepared using a 1.5-m2 silicone membrane oxygenator. Group A consisted of heparin, dopamine, ampicillin, vancomycin, phenobarbital and fentanyl. Group B consisted of epinephrine, cefazolin, hydrocortisone, fosphenytoin and morphine. Drugs were tested in crystalloid and blood-primed circuits. After administration of a one-time dose of drugs in the priming fluid, baseline drug concentrations were obtained (P0). A simultaneous specimen was stored for stability testing at 24 h (P4). Serial post-membrane drug concentrations were then obtained at 30 min (P1), 3 h (P2) and 24 h (P3) from circuit fluid.
One hundred and one samples were analyzed. At the end of 24 h in crystalloid-primed circuits, 71.8% of ampicillin, 96.7% of epinephrine, 17.6% of fosphenytoin, 33.3% of heparin, 17.5% of morphine and 87% of fentanyl was lost. At the end of 24 h in blood-primed extracorporeal circuits, 15.4% of ampicillin, 21% of cefazolin, 71% of voriconazole, 31.4% of fosphenytoin, 53.3% of heparin and 100% of fentanyl was lost. There was a significant decrease in overall drug concentrations from 30 min to 24 h for both crystalloid-primed circuits (p = 0.023) and blood-primed circuits (p = 0.04).
Our ex vivo study demonstrates serial losses of several drugs commonly used during ECMO therapy. Therapeutic concentrations of fentanyl, voriconazole, antimicrobials and heparin cannot be guaranteed in patients on ECMO.
我们使用体外模拟模型来估计随着时间推移，体外循环中因隔离作用而损失的药物量。
使用一个1.5平方米的硅膜氧合器制备模拟闭环体外膜肺氧合（ECMO）回路。A组包括肝素、多巴胺、氨苄西林、万古霉素、苯巴比妥和芬太尼。B组包括肾上腺素、头孢唑林、氢化可的松、磷苯妥英和吗啡。药物在晶体预充回路和血液预充回路中进行测试。在预充液中一次性给药后，获取基线药物浓度（P0）。同时保存一份标本用于24小时稳定性测试（P4）。然后从回路液体中在30分钟（P1）、3小时（P2）和24小时（P3）获取膜后药物浓度系列值。
分析了101个样本。在晶体预充回路24小时结束时，71.8%的氨苄西林、96.7%的肾上腺素、17.6%的磷苯妥英、33.3%的肝素、17.5%的吗啡和87%的芬太尼损失。在血液预充体外回路24小时结束时，15.4%的氨苄西林、21%的头孢唑林、71%的伏立康唑、31.4%的磷苯妥英、53.3%的肝素和100%的芬太尼损失。对于晶体预充回路（p = 0.023）和血液预充回路（p = 0.04），从30分钟到24小时总体药物浓度均有显著下降。
我们的体外研究表明ECMO治疗期间常用的几种药物会出现系列性损失。ECMO患者无法保证芬太尼、伏立康唑、抗菌药物和肝素的治疗浓度。
