Division of Pediatric Critical Care, Department of Pediatrics, University of Utah, Salt Lake City, UT 84132, USA.
Division of Clinical Pharmacology, Department of Pediatrics, University of Utah, Salt Lake City, UT 84132, USA.
J Extra Corpor Technol. 2024 Sep;56(3):101-107. doi: 10.1051/ject/2024016. Epub 2024 Sep 20.
Patients supported with extracorporeal life support (ECLS) circuits such as ECMO and CRRT often require high doses of sedatives and analgesics, including ketamine and dexmedetomidine. Concentrations of many medications are affected by ECLS circuits through adsorption to the circuit components, dialysis, as well as the large volume of blood used to prime the circuits. However, the impact of ECLS circuits on ketamine and dexmedetomidine pharmacokinetics has not been well described. This study determined ketamine and dexmedetomidine extraction by extracorporeal circuits in an ex-vivo system.
Medication was administered at therapeutic concentration to blood-primed, closed-loop ex-vivo ECMO and CRRT circuits. Drug concentrations were measured in plasma, hemofiltrate, and control samples at multiple time points throughout the experiments. At each sample time point, the percentage of drug recovery was calculated.
Ketamine plasma concentration in the ECMO and CRRT circuits decreased rapidly, with 43.8% recovery (SD = 0.6%) from ECMO circuits after 8 h and 3.3% (SD = 1.8%) recovery from CRRT circuits after 6 h. Dexmedetomidine was also cleared from CRRT circuits, with 20.3% recovery (SD = 1.8%) after 6 h. Concentrations of both medications were very stable in the control experiments, with approximately 100% drug recovery of both ketamine and dexmedetomidine after 6 h.
Ketamine and dexmedetomidine concentrations are significantly affected by ECLS circuits, indicating that dosing adjustments are needed for patients supported with ECMO and CRRT.
接受体外生命支持（ECLS）回路（如 ECMO 和 CRRT）支持的患者通常需要大剂量的镇静剂和镇痛药，包括氯胺酮和右美托咪定。许多药物的浓度会受到 ECLS 回路的影响，包括吸附在回路组件上、透析以及用于预充回路的大量血液。然而，ECLS 回路对氯胺酮和右美托咪定药代动力学的影响尚未得到很好的描述。本研究在离体系统中确定了体外回路对氯胺酮和右美托咪定的提取作用。
在充满血液的闭环体外 ECMO 和 CRRT 回路中，以治疗浓度给予药物。在整个实验过程中的多个时间点测量血浆、血液滤过液和对照样品中的药物浓度。在每个采样时间点，计算药物回收率。
ECMO 和 CRRT 回路中的氯胺酮血浆浓度迅速下降，ECMO 回路 8 小时后回收率为 43.8%（SD=0.6%），CRRT 回路 6 小时后回收率为 3.3%（SD=1.8%）。右美托咪定也从 CRRT 回路中清除，6 小时后回收率为 20.3%（SD=1.8%）。在对照实验中，两种药物的浓度都非常稳定，6 小时后氯胺酮和右美托咪定的药物回收率均约为 100%。
氯胺酮和右美托咪定的浓度受到 ECLS 回路的显著影响，这表明需要对接受 ECMO 和 CRRT 支持的患者进行剂量调整。
