Evaluation of digoxin concentration after loading dose in patients with renal dysfunction.

BACKGROUND Loading dose recommendations for digoxin are based on the volume of distribution, which is proportional to lean body weight, whereas maintenance dose recommendations depend on renal function. The volume of distribution of this drug is demonstrably reduced in severe renal dysfunction, but the threshold at which a reduction in loading dose is warranted remains unknown. OBJECTIVES To describe the practice of digoxin loading at The Ottawa Hospital and to determine the proportion of patients, categorized by degree of renal function, who experienced digoxin toxicity after a loading dose. METHODS Data were collected retrospectively from charts of patients who had received a digoxin loading dose between May 2008 and January 2012, with a blood sample drawn for determination of digoxin concentration 6 to 24 h later. Patients were categorized into 4 groups according to creatinine clearance. RESULTS The mean loading dose of digoxin (± standard deviation) was 9.8 ± 4.1 μg/kg among patients with creatinine clearance below 15 mL/min, 14.4 ± 5.4 μg/kg for those with creatinine clearance between 15 and 29 mL/min, 16.0 ± 5.6 μg/kg for those with creatinine clearance between 30 and 59 mL/min, and 14.0 ± 3.7 μg/kg for those with creatinine clearance 60 mL/min or above. Degree of renal dysfunction, particularly creatinine clearance below 60 mL/min, predicted the likelihood of experiencing a toxic serum concentration of digoxin after the loading dose, after adjustment for dose and weight (odds ratio 2.60, 95% confidence interval 1.55-4.39). CONCLUSIONS Patients with creatinine clearance below 60 mL/min were more likely than those with creatinine clearance of 60 mL/min or greater to experience toxic serum digoxin concentrations with current loading dose strategies. It is recommended that loading doses be reduced (to 6-10 μg/kg) for these patients. Prospective trials are required to determine the clinical implications of these findings and to determine if greater reductions in loading dose are required for patients with severe renal dysfunction (i.e., creatinine clearance below 30 mL/min).