MEDizzy - A 68-year-old man with ischemic cardiomyopathy has been

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A 68-year-old man with ischemic cardiomyopathy has been treated with digoxin 250 μg daily for the past year. He has chronic kidney disease with a stable baseline creatinine of 2.1 mg/dL. He is initiated on an oral amiodarone load for new-onset atrial fibrillation with rapid ventricular response. Over 1 week, he develops increasing nausea, vomiting, and fatigue. On presentation to the emergency department, he is lethargic and difficult to arouse with a heart rate of 45 beats/min and a blood pressure of 88/50 mmHg. His laboratory values demonstrate a potassium of 5.2 meq/L, creatinine of 3.0 mg/dL, and a digoxin level of 13 ng/mL. His ECG shows complete heart block. What is the most appropriate treatment for this patient?

ExplanationDigitalis is a cardiac glycoside that exerts its effect via reversible inhibition of the sodium–potassium–ATPase pump. The cellular effect of this inhibition is to increase intracellular sodium and decrease extracellular potassium. The increase in intracellular sodium leads to a change in the membrane potential of the cell and an influx of calcium. This influx of calcium improves inotropy of the heart and leads to increased vagal tone with resultant decrease in heart rate through action at the sinoatrial and atrio - ventricular nodes. Digoxin is a drug with a narrow therapeutic window, meaning that the effective dose and the toxic dose are close to one another. Digoxin is a substrate for P-glycoprotein, which is an efflux pump that excretes drugs into the proximal tubule of the kidney. Caution must be taken when introducing a new medication that is an inhibitor of P-glycoprotein because these drugs can increase the serum concentration of digoxin. Examples of inhibitors of P-glycoprotein include amiodarone, clarithromycin, verapamil, and diltiazem. In this patient, initiation of an oral amiodarone load in the face of the patient’s known renal insufficiency was sufficient to cause digoxin toxicity. The typ - ical manifestations of digoxin toxicity in this patient with a subacute onset include lethargy, generalized weakness, and delirium. Gastrointestinal manifestations may be seen but are less pronounced that in acute overdoses. The cardiac manifestations of digoxin toxicity are of the greatest concern, and the electrocardiogram can demonstrate a wide range of abnormalities, including bradycardia, atrial tachyarrhythmias, atrioventricular block, and ventricular tachycardia or fibrillation. The ECG can evolve over time, so continu - ous cardiac monitoring is warranted. Electrolyte abnormalities are common, especially hyperkalemia caused by the effects on the sodium–potassium–ATPase pump. However, in chronic toxicity, hypokalemia can also be seen. Worsening renal function is also a fre - quent manifestation and is often the cause for the rise in digoxin levels. The therapeutic range of digoxin is between 0.8 and 2 ng/mL. However, the level may not correlate well with the development of toxicity. Levels greater than 10 ng/mL often require treatment with digoxin-specific antibody fragments (Fab). This patient has other indications for use of Fab fragments as well given the complete heart block on ECG. Thus, observation alone is not an appropriate choice in this patient. Fab fragments are highly effective in the management of cardiac arrhythmias and are given as a single intravenous dose. Given the large molecular weight of digoxin and large volume of distribution, neither hemodi - alysis nor hemoperfusion is effective in elimination of digoxin. There are case reports of combined use of Fab fragments and plasmapheresis in individuals with profound renal failure, but this is not a standard option.