Intensive Care and Department of Paediatric Surgery, Sophia Children's Hospital, Erasmus MC, Dr Molewaterplein 60, 3000 CB, Rotterdam, The Netherlands.
Intensive Care Med. 2010 Dec;36(12):2109-16. doi: 10.1007/s00134-010-2041-z. Epub 2010 Sep 23.
The aim of this in vitro study was to evaluate potential determinants of drug loss in different ECMO circuits.
Midazolam, morphine, fentanyl, paracetamol, cefazolin, meropenem and vancomycin were injected into three neonatal roller pump, two paediatric roller pump and two clinically used neonatal roller pump circuits, all with a silicone membrane, and two neonatal centrifugal pump circuits with polypropylene hollow-fibre membranes. Serial blood samples were taken from a post-oxygenator site. Drug recovery was calculated as the ratio between the determined and the theoretical maximum concentration. The latter was obtained by dividing dose by theoretical circuit volume.
Average drug recoveries at 180 min in three neonatal silicone membrane roller pump circuits were midazolam 0.62%, morphine 23.9%, fentanyl 0.35%, paracetamol 34.0%, cefazolin 84.3%, meropenem 82.9% and vancomycin 67.8%. There was a significant correlation between the lipophilicity of the drug expressed as log P and the extent of drug absorption, p < 0.001. The recovery of midazolam and fentanyl in centrifugal pump circuits with hollow-fibre membrane oxygenator was significantly higher compared to neonatal roller pump circuits with silicone membranes: midazolam 63.4 versus 0.62%, fentanyl 33.8 versus 0.35%, p < 0.001. Oxygenator size and used circuits do not significantly affect drug losses.
Significant absorption of drugs occurs in the ECMO circuit, correlating with increased lipophilicity of the drug. Centrifugal pump circuits with hollow-fibre membrane oxygenators show less absorption for all drugs, most pronounced for lipophilic drugs. These results suggest that pharmacokinetics and hence optimal doses of these drugs may be altered during ECMO.
本体外研究旨在评估不同 ECMO 回路中药物损失的潜在决定因素。
咪达唑仑、吗啡、芬太尼、对乙酰氨基酚、头孢唑林、美罗培南和万古霉素分别注入三种新生儿滚压泵、两种儿科滚压泵和两种临床使用的新生儿滚压泵回路（均带有硅橡胶膜）以及两种带有聚丙稀空心纤维膜的新生儿离心泵回路。从后置氧合器部位抽取系列血样。药物回收率计算为测定的与理论最大浓度之比。后者通过剂量除以理论回路体积获得。
三种新生儿硅橡胶膜滚压泵回路中，180 分钟时药物的平均回收率为咪达唑仑 0.62%、吗啡 23.9%、芬太尼 0.35%、对乙酰氨基酚 34.0%、头孢唑林 84.3%、美罗培南 82.9%和万古霉素 67.8%。药物的亲脂性（以 log P 表示）与药物吸收程度呈显著相关性，p<0.001。带有空心纤维膜氧合器的离心泵回路中咪达唑仑和芬太尼的回收率明显高于带有硅橡胶膜的新生儿滚压泵回路：咪达唑仑 63.4 比 0.62%，芬太尼 33.8 比 0.35%，p<0.001。氧合器大小和所用回路对药物损失没有显著影响。
药物在 ECMO 回路中发生明显吸收，与药物的亲脂性增加相关。带有空心纤维膜氧合器的离心泵回路对所有药物的吸收均较少，对亲脂性药物更为明显。这些结果表明，这些药物的药代动力学，因此在 ECMO 期间，可能会改变这些药物的最佳剂量。
