Change of dexmedetomidine and midazolam concentrations by simultaneous injection in an in vitro extracorporeal circuit

Abstract

Purpose

Patient sedation and analgesia are vital for safety and comfort during extracorporeal membrane oxygenation (ECMO). However, adsorption by the circuit may alter drug pharmaco-kinetics and remains poorly characterized. This study is the first to examine the concentrations of DEX and MDZ in the presence of drug–drug interactions using an in vitro extracorporeal circuit system that incorporates a polymer-coated polyvinyl chloride tube, but not a membrane oxygenator.

Methods and Results

Nine in vitro extracorporeal circuits were prepared using polymer-coated PVC tubing. Once the circuits were primed and running, either a single drug or two drugs were injected as boluses into the circuit with three circuits per drug. Drug samples were drawn following injection at 2, 5, 15, 30, 60, and 120 min and at 4, 12, and 24 h. They were then analyzed using high-performance liquid chromatography with mass spectrometry. When compared with an injection of DEX alone, the combination of DEX and MDZ is highly changed, with DEX and MDZ affecting the availability of free drugs in the circuit.

Conclusions

The change of DEX and MDZ concentrations was confirmed by a combination of both drugs as compared with either single-infusion DEX or MDZ in an in vitro extracorporeal circuit. Drug–drug interactions developed between DEX and MDZ through albumin in an extracorporeal circuit; as a result, the unbounded drugs might change in the circuit.