Digoxin loading doses for atrial fibrillation in critically Ill patients
Authors: Ahuja T , Saadi R , Papadopoulos J , Pashun R A , Bernard S , Yuriditsky E , Horowitz J , Merchan C 
Published: October 2024

Abstract

Introduction
The use of digoxin, a cardiac glycoside, for inotropic effects and electrophysiologic actions date back as far as the 18th century. Loading doses (LD) of digoxin are recommended when used for rate control in the setting of atrial fibrillation or atrial flutter (AF/AFL), though the optimal serum drug concentration (SDC) remains unknown. Pharmacokinetic based formulas used to calculate a LD target a SDC of 0.8-1.2 ng/mL. Still, digoxin pharmacokinetics remain unpredictable and are influenced by age, weight, renal impairment, and critical illness.

Purpose
The purpose of this study was to assess the safety and efficacy of digoxin LD used in critically ill patients to rate control AF/AFL and to assess the SDC achieved after a LD.

Methods
We conducted an Institutional Review Board approved retrospective cohort study at New York University Langone Health between January 2013 and March 2018. Adult patients (18 years of age or older) were included if they received an intravenous digoxin LD for AF/AFL in any intensive care unit and had a digoxin SDC measured between 6 and 24 hours after the LD. Patients were excluded if they received the LD orally. The primary endpoint was the SDC achieved after the LD. Secondary safety endpoints were the incidence of supratherapeutic digoxin SDC (&gt; 1.2 ng/mL). Secondary efficacy endpoints included the incidence of rate control success, defined as a heart rate (HR) less than 110 beats per minute (bpm) within 24 hours of the digoxin LD.

Results
A total of 92 patients were included in the final analysis. The cohort was 53% male with a median age of 72 years, median BMI of 27, a median creatinine clearance (CrCL) of 47 mL/min at the time of IV digoxin LD and 66% of the cohort had AF. The highest HR associated with the AF/AFL 24 hours prior to digoxin was 133 (121, 145) bpm. The median total LD of digoxin for the entire cohort was 11 mcg/kg (750 mcg). In those with impaired renal function (CrCl &lt; 30 mL/min), the median LD of digoxin was 8.3 mcg/kg. For 61% of the cohort, the LD was distributed over 6-hour intervals. The median SDC after completion of the IV digoxin LD was 1.3 ng/mL (0.9, 1.7), with a range of 0.4-4.1 ng/mL. A SDC &gt; 1.2 ng/mL was observed in 51% of the cohort. Secondary outcomes of rate control success occurred in 60% of the cohort. No patients experienced any digoxin associated dysrhythmias or required reversal.

Conclusion
We found a SDC of 1.3 ng/mL post a digoxin LD in critically ill patients with AF/AFL to be successful in achieving rate control in 60% of our cohort. Despite 51% of the cohort achieving a SDC &gt; 1.2 ng/mL, digoxin related adverse events were uncommon. Our analysis support previous data suggesting dose adjustment of digoxin in patients with impaired renal function but suggest a higher SDC may be acceptable in the acute setting when used for rate control. Our sample size is limited, and future studies should confirm our findings in critically ill patients.