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体外膜肺氧合中右美托咪定的体外清除率

In vitro clearance of dexmedetomidine in extracorporeal membrane oxygenation.

作者信息

Wagner D, Pasko D, Phillips K, Waldvogel J, Annich G

机构信息

Pharmacy/Anesthesiology, University of Michigan Hospitals and Health Systems, Ann Arbor, MI, USA.

出版信息

Perfusion. 2013 Jan;28(1):40-6. doi: 10.1177/0267659112456894. Epub 2012 Aug 13.

Abstract

Dexmedetomidine (DMET) is a useful agent for sedation, both alone and in combination with other agents, in critically ill patients, including those on extracorporeal membrane oxygenation (ECMO) therapy. The drug is a clonidine-like derivative with an 8-fold greater specificity for the alpha 2-receptor while maintaining respiratory and cardiovascular stability. An in vitro ECMO circuit was used to study the effects of both "new" and "old" membrane oxygenators on the clearance of dexmedetomidine over the course of 24 hours. Once primed, the circuit was dosed with 840 μg of dexmedetomidine for a final concentration of 0.9 μg/ml. Serial samples, both pre- and post-oxygenator, were taken at 5, 60, 360, and 1440 minutes. Concentrations of the drug were expressed as a percentage of the original concentration remaining at each time point, both for new and old circuits. The new circuits were run at a standard flow for 24 hours, after which time the circuit was considered old and re-dosed with dexmedetomidine and the trial repeated. Results show that dexmedetomidine losses occur early in the circuits and then continue to decline. Initial losses in the first hour were 11+-65% and 59-73% pre- and post-oxygenator in the new circuit and 36-50% and 42-72% in the old circuit. The clearance of the drug through the membrane oxygenator exhibits no statistical difference between pre and post or new and old circuits. Dexmedetomidine can be expected to exhibit concentration changes during ECMO therapy. This effect appears to be more related to adsorption to the polyvinyl chloride (PVC) tubing rather than the membrane oxygenator. Dosage adjustments during dexmedetomidine administration during ECMO therapy may be warranted in order to maintain adequate serum concentrations and, hence, the desired degree of sedation.*(Lack of equilibrium).

摘要

右美托咪定(DMET)是一种用于危重病患者镇静的有效药物,可单独使用或与其他药物联合使用,包括接受体外膜肺氧合(ECMO)治疗的患者。该药物是一种可乐定样衍生物,对α2受体的特异性高8倍,同时保持呼吸和心血管稳定性。使用体外ECMO回路研究“新型”和“旧型”膜式氧合器在24小时内对右美托咪定清除率的影响。回路预充后,给予840μg右美托咪定,最终浓度为0.9μg/ml。在氧合器前后分别于5、60、360和1440分钟采集系列样本。药物浓度以每个时间点新回路和旧回路中剩余原始浓度的百分比表示。新回路以标准流量运行24小时,之后该回路被视为旧回路,重新给予右美托咪定并重复试验。结果表明,右美托咪定在回路中早期就会出现损失,然后持续下降。新回路中,氧合器前第一小时的初始损失为11±65%,氧合器后为59 - 73%;旧回路中分别为36 - 50%和42 - 72%。药物通过膜式氧合器的清除率在氧合器前后或新回路和旧回路之间无统计学差异。在ECMO治疗期间,右美托咪定的浓度可能会发生变化。这种效应似乎更多地与吸附到聚氯乙烯(PVC)管道上有关,而不是与膜式氧合器有关。在ECMO治疗期间给予右美托咪定时,可能需要调整剂量,以维持足够的血清浓度,从而达到所需的镇静程度。(缺乏平衡)

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