Evaluation of digoxin dosing and therapeutic drug monitoring in adult patients receiving continuous venovenous hemodiafiltration.

BACKGROUND: Digoxin dosing guidance during continuous renal replacement therapy (CRRT) is scarce, relying on two case reports with pharmacokinetic modeling not subsequently validated by TDM and expert opinion. OBJECTIVE: To examine varying digoxin dosing regimen effects on serum digoxin concentrations (SDCs) in patients receiving continuous venovenous hemodiafiltration (CVVHDF). DESIGN: Retrospective, multicenter, single-health-system case series. METHODS: Adult patients admitted to an intensive care unit over a 3.5-year period who received digoxin, with concurrent SDC monitoring and CVVHDF were included. The primary outcome of this study was to describe digoxin dosing and associated SDCs in adult patients receiving CVVHDF. Secondary outcomes aimed to determine the safety and tolerability of digoxin for patients receiving CVVHDF, including the incidence of bradycardia, digoxin immune fab administration, and in-hospital mortality. RESULTS: Six patients met criteria for inclusion, yielding fourteen digoxin levels drawn during CVVHDF. The median CRRT effluent rate was 30.7 mL/kg/hr with a median digoxin level of 0.9 (IQR 0.7-1.1) ng/mL. Both levels ≥ 1.2 ng/mL (above the safety-oriented upper threshold) occurred in patients following a loading dose exceeding 8 mcg/kg ideal body weight. Ten total SDC were drawn in 4 patients receiving 125 mcg every 48-hours maintenance regimens and all resulted in pre-steady state levels < 1.2 ng/mL. Two patients (33.3%) experienced bradycardia, both of whom were receiving concomitant amiodarone. No patients received digoxin immune fab, and two patients (33.3%) experienced in-hospital mortality. CONCLUSION: A maintenance regimen of 125 mcg every 48 hours during CVVHDF achieved levels below the safety SDCs, although notably all levels reflect the first several doses during CVVHDF and may not reflect steady state monitoring. These data help address the current gap in data describing digoxin dosing during CRRT. Although this adds limited insight for digoxin dosing during CRRT, standard dosing and monitoring recommendations remain unconfirmed.