Digoxin is derived from the purple foxglove plant (Figure 1), and was discovered 200 years ago (British Heart Foundation (BHF), 2019). It is not usually the first choice when prescribing for people with arrhythmia or heart failure, as it carries many risks owing to its narrow therapeutic range (BHF, 2019). Thus, its potential for toxicity—which often can have highly problematic effects, including dysrhythmia—may be fatal in cases of massive overdose.
Digoxin is a cardioactive corticosteroid and is used therapeutically to increase cardiac contractility and to control the heart rate (British Medical Journal (BMJ), 2019). Cardiac arrhythmias resulting from digoxin toxicity account for most digoxin toxicity-associated deaths (Kanji and MacLean, 2012).
Pincus (2016), a cardiologist, outlines how hyperkalaemia is often seen in digoxin toxicity; he notes that digoxin increases intracellular calcium in myocardial cells indirectly as a result of inhibiting the sodium-potassium pump in the cell membrane. This leads to an increase in cardiac contractility, thus resulting in risk of tachyarrhythmia, but also in hyperkalaemia. Another result of digoxin is an increase in vagal activity, reducing the activity seen in the sinus node and prolonging conduction in the atrioventricular (AV) node (Pincus, 2016)
The clinical features of toxicity commonly include lethargy, confusion and gastrointestinal symptoms (anorexia, nausea, vomiting, diarrhoea and abdominal pain), as well as rarer visual effects (blurred vision, colour disturbances, haloes and scotomas) (Pincus, 2016).
The best practice guidelines for digoxin overdose from the BMJ (2019) detail the toxicity as acute, chronic, intentional or accidental, usually presenting with gastrointestinal and/or cardiovascular symptoms (BMJ, 2019). Diagnosis of digoxin toxicity is based on symptoms and laboratory test results (BMJ, 2019). At therapeutic digoxin doses (0.6–1.2 nmol/litre [0.5–0.9 ng/ml]), the electrocardiogram (ECG) typically shows PR-interval prolongation and a scooped ST segment (BMJ, 2019). In cases of overdose, the ECG would also show signs of increased automaticity (premature ventricular contractions (PVCs)), AV nodal blockade, and slowed ventricular response (BMJ, 2019).
Digoxin toxicity can be treated in some cases with antibody fragments. The National Institute for Health and Care Excellence (NICE) (2019) recommends use of DigiFab for known or strongly suspected life-threatening digoxin toxicity associated with ventricular arrhythmias or bradyarrhythmias which are unresponsive to atropine and when measures beyond digoxin withdrawal and correction of electrolyte abnormalities are considered necessary. NICE (2019) recommends serious cases of digoxin toxicity be discussed with the National Poisons Information Service. DigiFab is given intravenously in adults intermittently in sodium chloride 0.9%. DigiFab needs to be reconstituted with water for injections (4 ml/vial), then diluted with infusion fluid and given over 30 minutes.
Lidocaine and phenytoin can be used for cardiac dysrhythmias when antibody fragments are unavailable (BMJ, 2019). There are no long-term complications of poisoning in patients treated appropriately for chronic digoxin toxicity, as long as anoxic brain injury, myocardial infarction, or terminal dysrhythmias have not occurred prior to treatment (BMJ, 2019).
Digoxin toxicity is a clinical diagnosis that depends partially on ECG findings such as signs of increased automaticity and AV node blockade (PVCs, slowed ventricular response) (BMJ, 2019).
In cases of digoxin toxicity, serum digoxin concentration is usually greater than the therapeutic range of 0.6–1.2 nmol/litre (0.5–0.9 ng/ml), but may not be elevated (BMJ, 2019). Toxicity can also occur as a result of exposure to various plants and animals containing cardioactive corticosteroids (BMJ, 2019).