Abstract
IntroductionAs a result of drug sequestration and increased volume of distribution, the extracorporeal membrane oxygenation (ECMO) procedure might lead to a decrease in drug concentrations during a patient’s treatment. The aim of this study was to evaluate sedative, antibiotic and immunosuppressive drug loss in ECMO circuit using ex-vivo and in-vitro experiments.MethodsBlood concentrations of propofol, midazolam, cyclosporine and vancomycin were measured in an ex-vivo ECMO circuit primed with whole human blood, and compared to controls stored in polypropylene tubes. In vitro experiments were also conducted to further explore the role of temperature, oxygen exposure and polyvinylchloride surfaces on propofol loss in the ECMO circuit.ResultsPropofol concentration decreased rapidly; 70% of its baseline concentration was lost after only 30 minutes, and only 11% remained after five hours (P <0.001 for the comparison with control polypropylene tube propofol concentration). Further experiments demonstrated that oxygen exposure and contact with polyvinylchloride tubing were respectively responsible for 70% and 85% of propofol loss after 45 minutes. Midazolam concentration also rapidly decreased in the ECMO circuit, with only 54% and 11% of baseline concentration being detected at 30 minutes and 24 hours respectively (P = 0.01 versus control). Alternatively, cyclosporine concentration remained stable for the five first hours, then decreased to 78% and 73% of the baseline value after 24 hours and 48 hours, (P = 0.35 versus control). Lastly, vancomycin concentration remained stable in the ECMO circuit for the 48-hour experimental protocol.ConclusionsWe observed important losses of propofol and midazolam, while cyclosporine concentration decreased slowly and moderately, and vancomycin concentration remained unchanged in the ex-vivo ECMO circuit primed with whole human blood. These data might help intensive care unit physicians planning clinical trials with a final objective to better adapt doses of these drugs while treating critically ill ECMO patients.
Highlights
As a result of drug sequestration and increased volume of distribution, the extracorporeal membrane oxygenation (ECMO) procedure might lead to a decrease in drug concentrations during a patient’s treatment
The objective of the present study was, to determine, in an ex vivo ECMO circuit primed with human whole blood, changes in the concentrations of propofol, midazolam, vancomycin and cyclosporine, which are frequently prescribed to ECMO patients
Changes in drug concentrations in ex vivo circuits primed with whole human blood Propofol, midazolam, cyclosporine and vancomycin concentrations remained stable over time in control polypropylene tubes
Summary
As a result of drug sequestration and increased volume of distribution, the extracorporeal membrane oxygenation (ECMO) procedure might lead to a decrease in drug concentrations during a patient’s treatment. The aim of this study was to evaluate sedative, antibiotic and immunosuppressive drug loss in ECMO circuit using ex-vivo and in-vitro experiments. Modern ECMO circuits consist of polyvinyl chloride (PVC) tubing, a polymethylpentene membrane oxygenator and a centrifugal pump [2]. Patients on ECMO require multiple medications including sedatives, analgesics, antibiotics and sometimes immunosuppressive drugs [3,4]. Pharmacokinetics of drugs administered during ECMO is complex notably due to a larger volume of distribution in ECMO-treated patients and to the adsorption of drugs on the PVC tubing and/or the membrane oxygenator leading to an increase in drug clearance [2,5]. Drug adsorption on the circuit may depend on circuit duration of use, since binding sites may become saturated after a few hours of operation [3,9]
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