Heith Catherine S, Hansen Lizbeth A, Bakken Rhonda M, Ritter Sharon L, Long Breeanna R, Hume Janet R, Zhang Lei, Amundsen Danielle B, Steiner Marie E, Fischer Gwenyth A
J Pediatr Pharmacol Ther. 2019 Jul-Aug;24(4):290-295. doi: 10.5863/1551-6776-24.4.290.
With the expanding use of extracorporeal membrane oxygenation (ECMO), understanding drug pharmacokinetics has become increasingly important, particularly in pediatric patients. This study examines the effect of a pediatric Quadrox-iD ECMO circuit on the sequestration and binding of mycophenolate mofetil (MMF), tacrolimus, and hydromorphone hydrochloride, which have not been extensively studied to date in pediatric ECMO circuits. Fentanyl, which has been well studied, was used as a comparator.
ECMO circuits were set up using Quadrox-iD pediatric oxygenators and centrifugal pumps. The circuit was primed with whole blood and a reservoir was attached to represent a 5-kg patient. Fourteen French venous and 12 French arterial ECMO cannulas were inserted into the sealed reservoir. Temperature, pH, PO, and PCO were monitored and corrected. MMF, tacrolimus, hydromorphone, and fentanyl were injected into the ECMO circuit. Serial blood samples were taken from a postoxygenator site at intervals over 12 hours, and levels were measured.
Hydromorphone hydrochloride was not as significantly sequestered by the pediatric ECMO circuit when compared with fentanyl. Both mycophenolic acid and tacrolimus serum concentrations were stable in the circuit over 12 hours.
Hydromorphone may represent a useful medication for pain control for pediatric patients on ECMO due to its minimal sequestration. Mycophenolic acid and tacrolimus also did not show significant sequestration in the circuit, which was unexpected given their lipophilicity and protein-binding characteristics, but may provide insight into unexplored pharmacokinetics of particular medications in ECMO circuits.
随着体外膜肺氧合（ECMO）的使用不断增加，了解药物的药代动力学变得越来越重要，尤其是在儿科患者中。本研究考察了小儿Quadrox-iD ECMO回路对霉酚酸酯（MMF）、他克莫司和盐酸氢吗啡酮的隔离和结合作用，这些药物目前在儿科ECMO回路中尚未得到广泛研究。已得到充分研究的芬太尼用作对照。
使用Quadrox-iD小儿氧合器和离心泵设置ECMO回路。用全血预充回路，并连接一个储液器以模拟一名5公斤重的患者。将14号法国规格的静脉ECMO插管和12号法国规格的动脉ECMO插管插入密封的储液器中。监测并校正温度、pH值、氧分压和二氧化碳分压。将MMF、他克莫司、氢吗啡酮和芬太尼注入ECMO回路。在12小时内每隔一段时间从氧合器后的部位采集系列血样，并测定血药浓度。
与芬太尼相比，小儿ECMO回路对盐酸氢吗啡酮的隔离作用不明显。在12小时内，回路中的霉酚酸和他克莫司血清浓度均保持稳定。
由于盐酸氢吗啡酮的隔离作用最小，它可能是用于ECMO治疗的儿科患者疼痛控制的一种有效药物。霉酚酸和他克莫司在回路中也未显示出明显的隔离作用，鉴于它们的亲脂性和蛋白结合特性，这是出乎意料的，但可能为深入了解ECMO回路中特定药物未被探索的药代动力学提供线索。
