The patient in this vignette is starting digoxin for rate control in the setting of atrial fibrillation and congestive heart failure. Hypokalemia increases patient susceptibility to the toxic effects of digoxin.
Digoxin is used for rate control in atrial fibrillation due to its ability to decrease conduction at the AV node. Additionally, it exerts a positive inotropic effect, which can be of benefit in the treatment of CHF. Digoxin acts through direct inhibition of the Na+/K+ ATPase on cardiac myocytes. Digoxin normally competes with potassium ions for binding to this Na+/K+ ATPase. In hypokalemia, without the presence of the normal amount of competing potassium ions, digoxin can more freely bind this pump and exert its effects, thereby leading to toxic effects at typically normal plasma concentrations of this drug.
Chavey et al. discuss the pharmacologic management of systolic dysfunction heart failure. They conclude that digoxin can improve CHF symptoms and is useful for patients who also have atrial fibrillation in addition to CHF. However, they note that digoxin therapy has not been shown to improve cardiovascular or overall mortality in these patients. The authors also emphasize that serum digoxin levels should not exceed 1 ng/mL, so as to avoid toxicity; they note that this is especially true in female patients.
Whittbeck et al. discuss the results of a recent clinical investigation, the AFFIRM study, which found, after correcting for comorbities and clinical characteristics, increased all-cause mortality in patients with atrial fibrillation who were taking digoxin. This research questions the current widespread use of digoxin in the setting of atrial fibrillation. Of note, the findings of this study are currently being debated with a host of retorts and responses found in the literature.
Illustration A summarizes the mechanism of action of digoxin and its positive inotropic effect. Illustration B depicts potential electrocardiogram changes associated with digoxin toxicity; note the combination of supraventricular tachycardia and the slowed ventricular response, which is due to a decrease in AV conduction. Illustration C summarizes how to differentiate digoxin toxicity from toxicity of drugs commonly co-administered with digoxin.
Answer 1: Hyponatremia does not potentiate digoxin toxicity.
Answer 2: Digoxin is primarily metabolized and eliminated by the kidneys; therefore, alterations in liver function should not affect this patient's susceptibility.
Answer 4: While renal insufficiency is a risk factor for increased susceptibility to digoxin toxicity, a normal creatinine signifies adequate kidney function; digoxin has the potential to cause increased renal blood flow and thereby an increased GFR.
Answer 5: Hyperkalemia represents a potential side effect of digoxin therapy but does not increase one's risk for experiencing digoxin toxicity.
Chavey WE, Bleske BE, Van Harrison R, Hogikyan RV, Kesterson SK, Nicklas JM. Pharmacologic management of heart failure caused by systolic dysfunction. Am Fam Physician. 2008 Apr 1;77(7):957-64.
PMID:18441861 (Link to Abstract)
Whitbeck MG, Charnigo RJ, Khairy P, Ziada K, Bailey AL, Zegarra MM, Shah J, Morales G, Macaulay T, Sorrell VL, Campbell CL, Gurley J, Anaya P, Nasr H, Bai R, Di Biase L, Booth DC, Jondeau G, Natale A, Roy D, Smyth S, Moliterno DJ, Elayi CS. Increased mortality among patients taking digoxin--analysis from the AFFIRM study. Eur Heart J. 2013 May;34(20):1481-8.
PMID:23186806 (Link to Abstract)