Why does digoxin cause arrhythmias

Furthermore, digoxin therapy was associated with a significantly greater number of prolonged attacks of atrial fibrillation defined as those lasting more than 30 minutes. Most studies of digoxin in atrial fibrillation or flutter have either enrolled patients with atrial fibrillation only, or have combined patients with atrial fibrillation and atrial flutter. There is certainly no reason to believe that digoxin has any role for either pharmacological cardioversion or prophylaxis for atrial flutter any more than it does for atrial fibrillation , and common observation supports the widely-held belief that digoxin is less effective at rate control in patients with atrial flutter than it is in those with atrial fibrillation E4.

In , there is little or no role for digoxin in managing arrhythmias other than atrial fibrillation or flutter. It has been widely used in the past to treat re-entrant supraventricular tachycardia in adults and children, but newer agents have superseded it for treating these arrhythmias. It has occasionally been recommended for use in multifocal atrial tachycardia, and there are occasional observational reports of efficacy for this, but its use for this indication is limited by the fact that these patients commonly have pulmonary hypertension and hypoxia, which renders them more liable to digitalis toxicity.

There is no evidence for efficacy of digoxin in suppressing ventricular arrhythmias and every reason to suspect that the agent should be avoided in this situation. It is of course occasionally observed that patients treated with digoxin for left ventricular dysfunction show reduced ventricular ectopy concomitant with improvement in their underlying condition. In patients who lead a predominantly sedentary lifestyle, particularly the elderly, digoxin alone may be the agent of choice for chronic atrial fibrillation E4.

Certainly, digoxin carries a potential advantage over the other agents in that it is very unlikely to precipitate worsening ventricular function in patients whose ventricular function is either depressed or unknown. Other than this, there is no role for digoxin in pharmacological reversion of atrial fibrillation, and little or no support for the use of digoxin in the management of other arrhythmias.

Increases vagal tone central effect , leading to slowed ventricular response in atrial fibrillation. Reduces sympathetic tone, especially when this is abnormally high, as in heart failure.

This is probably mediated partly via vagotonic actions and partly via direct effects. Cardiotoxicity is most serious and may manifest as ventricular or supraventricular arrhythmias, including sudden increased prevalence of cardiac death this was almost exactly balanced in Digitalis Investigation Group trial by reduction in "pump failure" deaths.

Also, vagotonic actions can produce bradyarrhythmias, including prolonged PR interval and high-grade heart block. Non-cardiac toxicity includes nausea, vomiting, diarrhoea, visual effects, including "yellow" vision, and gynaecomastia. Greater decline in exercise tolerance and higher rate of worsening CHF in digoxin-withdrawal group. Higher rate of worsening CHF and greater decline in exercise tolerance in digoxin-withdrawal group. Evidence for the statements made in this article is graded according to the NHMRC system 13 for assessing the level of evidence.

E1 Level I: Evidence obtained from a systematic review of all relevant randomised controlled trials. E2 Level II: Evidence obtained from at least one properly designed randomised controlled trial. E3 1 Level III Evidence obtained from well-designed pseudo-randomised controlled trials alternate allocation or some other method. E3 2 Level III Evidence obtained from comparative studies with concurrent controls and allocation not randomised cohort studies , case—control studies, or interrupted time series with a parallel control group.

E3 3 Level III Evidence obtained from comparative studies with historical control, two or more single-arm studies, or interrupted time series without a parallel control group. E4 Level IV: Evidence obtained from case series, either post-test, or pre-test and post-test.

Digoxin is a useful drug, but taking the correct dose is critical, and side effects do occur. Digoxin should be taken exactly as prescribed, and any possible side effects, such as unexplained nausea, vomiting or visual changes, should be reported at once to your doctor. Publication of your online response is subject to the Medical Journal of Australia 's editorial discretion. You will be notified by email within five working days should your response be accepted. Basic Search Advanced search search.

Use the Advanced search for more specific terms. Title contains. Body contains. Date range from. Date range to. Article type. Author's surname. First page. Issues by year. Article types. Research letters. Guidelines and statements. Narrative reviews. Ethics and law. Medical education. New Drugs, Old Drugs. Volume Issue 2. Digoxin in heart failure and cardiac arrhythmias. Med J Aust ; 2 : Topics Cardiovascular diseases. Abstract Heart failure. Digoxin therapy has no effect on mortality in heart failure.

How does digoxin work? Digoxin in heart failure Randomised controlled trials The role of digoxin in the management of heart failure was clarified by a number of well-designed randomised placebo-controlled clinical trials in the s Box 2. What is the optimal dose of digoxin? Digoxin in diastolic heart failure Diastolic heart failure has been increasingly recognised as a clinical entity, particularly in the elderly and in women.

Recommendations Digoxin is indicated for the management of heart failure. Digoxin for arrhythmia While there is little doubt that appropriate doses of digoxin see above will slow the resting ventricular rate in most patients with chronic atrial fibrillation E1 , it has been known for many years that digoxin is far less successful in controlling exercise-induced or stress-induced tachycardia in atrial fibrillation in many patients, even when plasma drug concentrations are near the upper end of the accepted therapeutic range.

When the calcium levels are high, in the setting of digoxin toxicity, the result is an increase in calcium influx and enhanced toxicity.

As mentioned above, digoxin toxicity can cause hyperkalemia. Recall that the treatment for hyperkalemia causing ECG changes is usually intravenous calcium administration; however, in the setting of digoxin toxicity and hyperkalemia, giving IV calcium may be potentially fatal. Digoxin administration should be discontinued immediately. Arrhythmia should be treated according to Advanced Cardiac Life Support ACLS protocols, with the exception of administering calcium intravenously, which can be fatal as this can potentiate the effects of digoxin as described above.

Intravenous fluids are given for hypotension. If hemodynamic compromise is present, or serious arrhythmia manifests from digoxin toxicity, then the mainstay of treatment is digoxin specific antibody Fab. References: 1. Cardiovascular Drugs: Digitalis. Levine M, et al. J Emerg Med. Chapter contents Show Digoxin effects on cardiac function and ECG Adverse effects of digoxin Hypokalemia potentiates the digoxin effect Arrhythmias caused by digoxin.

Digoxin may be used in patients with heart failure, atrial fibrillation, atrial flutter and in selected cases of paroxysmal supraventricular tachycardia. Due to its profound pro-arrhythmic effects and lack of compelling data regarding morbidity and mortality benefit , digoxin has been expelled repeatedly from the treatment arsenal.

However, it has kept coming back and it is still used in patients who do not achieve satisfactory effect by first line therapies. Moreover, digoxin is used frequently in the emergency setting to slow ventricular rate during supraventricular tachycardia e.

Because digoxin may cause life-threatening arrhythmias, every health care provider must be able to recognize common digoxin ECG changes and arrhythmias. Digoxin has a positive inotropic effect and negative chronotropic effect, meaning that it enhances ventricular contractility but lowers heart rate. The positive inotropic effect is due to inhibition of the sodium-potassium adenosine triphosphatase NaK-ATPase in ventricular myocardium.

Inhibition of Na-K-ATPase leads to increased intracellular concentration of sodium, which affects the sodium-calcium exchanger such that ultimately intracellular calcium concentration increases. This makes more calcium available to the contractile proteins which therefore produce stronger contractions.

Lowering of the heart rate is due to increased Vagus nerve activity caused by digoxin. Increased Vagus activity diminishes the automaticity in the sinoatrial node which lowers heart rate and also slows conduction over the atrioventricular AV node.

Refer to Figure 1. The incidence of adverse drug reactions is high, owing to the narrow therapeutic index of the drug. Digoxin is very pro-arrhythmic, meaning that it increases the probability of arrhythmias occurring. This is explained by the increase in intracellular calcium levels, which causes a shortening of the action potential.

Digoxin shortens the action potential in all cardiac cells, both in the atria and the ventricles. This increases the automaticity in cells with natural automaticity but it may also provoke abnormal automaticity in cells that normally do not exhibit automaticity.

The effect on automaticity should be distinguished from the effect on impulse conduction because digoxin slows impulse conduction. It is important to note that the association between ECG changes and the risk of arrhythmia is weak. Hence, arrhythmias may occur in the absence of ECG changes and vice versa i. Thus, digoxin is rather unpredictable in terms of arrhythmia risk. Hypokalemia always potentiates the pro-arrhythmic effects of digoxin.

Potassium levels must always be assessed in patients using digoxin whenever they seek medical attention.