Pharmacokinetics of fentanyl in extracorporeal membrane oxygenation

ABSTRACT

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) is used to treat patients with refractory circulatory or respiratory failure as a bridge to recovery, long-term support device (e.g., ventricular assist device), or transplant. Patients on ECMO commonly receive large doses of analgesia and sedation, and prior in vitro studies have been equivocal when evaluating the effect of ECMO therapy on blood concentrations of these medications. Because dose escalations may result in excessive drug exposure, over-sedation, and drug side effects, we seek to quantify the impact of ECMO initiation on plasma concentrations of fentanyl. METHODS: This is preliminary data from a single-center, prospective trial of patients treated with ECMO to evaluate the effects of ECMO therapy on systemic fentanyl levels. Patients ≥ 18 years of age who were cannulated for ECMO and already receiving a continuous fentanyl infusion were considered for enrollment, while patients younger than 18 years of age, pregnant, and/or cannulated at another hospital prior to arrival at our institution were excluded. Whole blood samples were collected within 30 minutes of ECMO cannulation, at the time of initiating ECMO flow, and after initiating flow at 15-, 30-, and 60-minutes. RESULTS: Three patients (two male, one female) were included in this preliminary sample, and all were placed on VV-ECMO for refractory respiratory failure due to COVID-19 pneumonia. Mean fentanyl concentrations were reduced by 13% after 30 minutes and 5% after 60 minutes. However, one of the three patients received a bolus dose of fentanyl during the study period. When assessing fentanyl concentrations from the two patients not receiving an additional fentanyl bolus, mean fentanyl concentrations were reduced by 18% after 30 minutes and 19% after 60 minutes. CONCLUSIONS: In this preliminary data from three patients treated with ECMO for refractory respiratory failure, systemic fentanyl concentrations were reduced after 30- and 60-minutes. While this data is limited to three patients and a greater number of patients are needed to ascertain statistical significance, these data may provide quantitative evidence to support why patients on ECMO require increased doses of fentanyl to maintain adequate analgesia. This study is currently ongoing and enrolling additional patients.