Digoxin is a semisynthetic steroid glycoside derived from the plant Digitalis lanata (common name: Grecian foxglove). It is used for the treatment of systolic dysfunction and some arrhythmias. By reversibly inhibiting the Na-K ATPase pump, digoxin increases the availability of intracellular calcium and subsequently increases cardiac contractility. This increase shifts the Frank-Starling curve to the left in both healthy and failing myocardium. Digoxin also reduces circulating levels of norepinephrine and thus increases parasympathetic tone. This in turn reduces sinoatrial nodal automaticity and atrioventricular nodal conduction. With its neurohumoral-modulating effects, digoxin has been used to treat some re-entrant paroxysmal supraventricular tachycardias.

Digoxin toxicity develops when there is an overload of intracellular calcium in both systolic and diastolic states, and this may cause significant arrhythmias. According to Mahdyoon et al., digoxin toxicity occurred in 0.8% and possible toxicity occurred in another 4% of the population. Factors that increase the risk of digitalis intoxication are renal insufficiency, electrolyte abnormalities (hypokalemia, hypomagnesemia, and hypercalcemia), acute myocardial ischemia, advanced age, hypothyroidism, and pulmonary disease. Pharmacokinetic interactions with other drugs can also affect digoxin levels. Remember that digoxin is a substrate of the P-glycoprotein transporter, so inhibitors and inducers of this transporter will raise and lower serum digoxin levels respectively (see Chapter 47).

Signs of digoxin toxicity may appear at a level of 2 ng/mL, and the incidence of toxicity increases with plasma concentration. Plasma concentration reaches steady state between 6 and 12 hours after the last dose, and thus digoxin levels are best measured within this time. Signs of digoxin toxicity may be very nonspecific. Patients may present with confusion, dizziness, ventricular ectopy, tachycardia, visual disturbances, depression, anxiety, apathy, gynecomastia, or simply a rash.

Dangerous signs of digoxin toxicity include atrioventricular (AV) nodal block, bradycardia, ventricular arrhythmia, thrombocytopenia, delirium,
and hallucinations. For patients under general anesthesia, the main warning signs of toxicity are electrocardiogram (EKG) changes. Digoxin toxicity can cause many types of dysrhythmias but does not usually cause atrial flutter, atrial fibrillation, or Mobitz type II second-degree AV block. However, digoxin toxicity can superimpose on the underlying cardiac pathology. For example, digoxin may create an unusually slow ventricular response to atrial fibrillation. Digoxin can also increase both atrial and ventricular ectopic activity and induce junctional tachycardia. Premature ventricular contraction is often the first sign of digoxin toxicity, progressing to ventricular bigeminy, fascicular tachycardia, ventricular tachycardia, and fatal ventricular fibrillation.

One arrhythmia that is almost pathognomonic for digoxin toxicity is bidirectional ventricular tachycardia (Fig. 58.1). The pattern resembles bigeminy except that the R-R interval is regular because all of the beats arise from a single ventricular focus. Patients with the rare disorder of familial catecholaminergic polymorphic ventricular tachycardia may also show this EKG pattern. Digoxin toxicity may cause AV junctional rhythms with escape rates of 30 to 50 beats/min. When the patient’s heart rate is 50 to 60 beats/min, an escape rhythm may be in play. With an accelerated junctional rhythm of 60 to 120 beats/min, nonparoxysmal junctional tachycardia is seen. The enhanced vagal tone created by digoxin may generate first-degree, second-degree type I, and third-degree heart blocks.