No Sequestration of Commonly Used Anti-Infectives in the Extracorporeal Membrane Oxygenation (ECMO) Circuit-An Ex Vivo Study

Abstract

Patients undergoing extracorporeal membrane oxygenation (ECMO) often require therapy with anti-infective drugs. The pharmacokinetics of these drugs may be altered during ECMO treatment due to pathophysiological changes in the drug metabolism of the critically ill and/or the ECMO therapy itself. This study investigates the latter aspect for commonly used anti-infective drugs in an ex vivo setting. A fully functional ECMO device circulated an albumin-electrolyte solution through the ECMO tubes and oxygenator. The antibiotic agents cefazolin, cefuroxim, cefepime, cefiderocol, linezolid and daptomycin and the antifungal agent anidulafungin were added. Blood samples were taken over a period of four hours and drug concentrations were measured via high-pressure liquid chromatography (HPLC) with UV detection. Subsequently, the study analyzed the time course of anti-infective concentrations. The results showed no significant changes in the concentration of any tested anti-infectives throughout the study period. This ex vivo study demonstrates that the ECMO device itself has no impact on the concentration of commonly used anti-infectives. These findings suggest that ECMO therapy does not contribute to alterations in the concentrations of anti-infective medications in severely ill patients.

Keywords: ECMO; antibiotics; critical illness; pharmacokinetics.

Figure 1

Each diagram shows the change in concentration over time for the substance tested. The x-axis shows the time at which the probes were taken. The y-axis shows the mean percentage (±SD) of drug recovery relative to the baseline concentration at each time point. The baseline concentration is the starting point of each graph. The continuous graph represents the change in concentration of the ECMO circuit, while the dotted graph is the change in concentration of the control. min: minutes.

Figure 2

High-performance liquid chromatography result for cephalosporins and linezolid. The x-axis shows the retention time in minutes and the y-axis shows the adsorption of detection light at 260 nm wavelength. (A) Result of the probe with the internal standard without antibiotics added. Two spikes are displayed. The left spike is the internal standard metronidazole and the right spike is N-acetyl-DL-tryptophan, which is used as a stabilizer added to human albumin. (B) Result from an exemplary sample of the ex vivo study. The internal standard, N-acetyl-DL-tryptophan and cephalosporin and linezolid adsorption at 260 nm wavelength are displayed.

Figure 3

High-performance liquid chromatography result for daptomycin. The x-axis shows the retention time in minutes and the y-axis shows the adsorption of light at a 350 nm wavelength. Three spikes are shown: metronidazol (A; internal standard), N-acetyl-DL-tryptophan (B; human albumin stabilizer) and daptomycin (C).

Figure 4

High-performance liquid chromatography result for anidulafungin. The x-axis shows the retention time in minutes and the y-axis shows the adsorption of light at a 330 nm (A) and 260 nm (B) wavelength. (A) Result of an exemplary probe of the ex vivo study. The spike to the right shows the adsorption of light for anidulafungin at 330 nm, whereas the left spike at 260 nm represents the internal standard (midazolam). (B) Result of a probe without anidulafungin. Only the spike for the internal standard midazolam is shown.