(1179) Efficacy of Ivabradine in Improving Oxygenation in Venovenous Extracorporeal Membrane Oxygenation

Introduction: Utilizing beta blockers to lower cardiac output and improve oxygenation is safe and effective during venovenous (VV) extracorporeal membrane oxygenation (ECMO) support; however, ivabradine has never been studied in this setting. The purpose of this study is to determine safety, efficacy, and optimal dosing of ivabradine in patients receiving VV ECMO.

Methods: This was a single-center, retrospective cohort study conducted at a tertiary academic hospital from January 1, 2020 to July 1, 2022. Patients were included if they were 18 years or older and initiated ivabradine while on VV ECMO. Patients who received concomitant vasopressors or inotropes during baseline evaluation or ivabradine dose titration were excluded, as well as patients in atrial fibrillation within 24 hours prior to baseline evaluation. Efficacy in HR reduction and improvement of oxygenation compared to baseline at each ivabradine dose titration period were assessed, as were the incidence of bradycardia and pertinent drug interactions.

Results: Nineteen patients were included in the analysis with 31 dose titration periods. The majority were initiated on 5 mg twice daily (47%) or 10 mg twice daily (42%). Eleven (60%) patients were titrated to maximum dose of 10 mg twice daily. A significant decrease in HR [(median absolute change (25th, 75th percentiles)] was observed in patients receiving 5 mg twice daily [-8 (-17, -2), p=0.005] and 10 mg twice daily [-20 (-25, -12), p=0.008]. No significant changes were observed in PaO2 at the various dose titrations. A total of 9 (47%) patients experienced bradycardia (HR < 50 bpm) and 1 (5%) patient experienced severe bradycardia (HR < 40 bpm). Four (44%) patients receiving 10 mg twice daily were co-administered CYP3A4 inhibitors.

Conclusions: Ivabradine did not significantly improve PaO2 in VV ECMO patients and an adequately powered study is needed to further assess efficacy. Approximately half of patients experienced bradycardia while on ivabradine but severe bradycardia was rare. Careful titration of ivabradine is recommended to minimize the risk of bradycardia. While higher than the standard 5 mg twice daily dosing may be appropriate due to potential sequestration of ivabradine in the circuit, concomitant use with CYP3A4 inhibitors should be avoided.