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least four multicenter trials that have demonstrated that digoxin withdrawal is associated with worsening symptoms and signs of heart failure, more frequent hospitalizations for decompensation, and reduced exercise tolerance This was also seen in the 6800-patient Digitalis Investigators Group (DIG) trial, though that study found no benefit (or harm) with regard to survival A reduction in deaths due to progressive heart failure was balanced by an increase in deaths due to ischemic and arrhythmic events Based on these results, digoxin should be used for patients who remain symptomatic when taking diuretics and ACE inhibitors as well as for patients with heart failure who are in atrial fibrillation and require rate control Digoxin, the only widely used digitalis preparation, has a half-life of 24 36 hours and is eliminated almost entirely by the kidneys The oral maintenance dose may range from 0125 mg three times weekly to 05 mg daily It is lower in patients with renal dysfunction, in older patients, and in those with smaller lean body mass Although a loading dose of 075 125 mg (depending primarily on lean body size) over 24 48 hours may be given if an early effect is desired, in most patients with chronic heart failure it is sufficient to begin with the expected maintenance dose (usually 0125 025 mg daily) Amiodarone, quinidine, propafenone, and verapamil are among the drugs that may increase digoxin levels up to 100% It is prudent to measure a blood level after 7 14 days (and at least 6 hours after the last dose was administered) Most of the positive inotropic effect is apparent with serum digoxin levels between 07 ng/mL and 12 ng/mL, and levels above this range may be associated with a higher risk of arrhythmias and lower survival rates, though clinically evident toxicity is rare with levels below 18 ng/mL Once an appropriate maintenance dose is established, subsequent levels are usually not indicated unless there is a change in renal function or medications that affects digoxin levels or a significant deterioration in cardiac status that may be associated with reduced clearance Digoxin toxicity has become less frequent as there has been a better appreciation of its pharmacology, but the therapeutic-to-toxic ratio is quite narrow Symptoms of digitalis toxicity include anorexia, nausea, headache, blurring or yellowing of vision, and disorientation Cardiac toxicity may take the form of AV conduction or sinus node depression; junctional, atrial, or ventricular premature beats or tachycardias; or ventricular fibrillation Potassium administration (following serum potassium measurement, since severe toxicity may be associated with hyperkalemia) is usually indicated for the tachyarrhythmias even when levels are in the normal range, but may worsen conduction disturbances Lidocaine or phenytoin may be useful for ventricular arrhythmias, as is overdrive pacing, but quinidine, amiodarone, and propafenone should be avoided because they will increase digoxin levels Electrical cardioversion should be avoided if possible, as it may cause intractable ventricular fibrillation or cardiac standstill Pacing is indicated for third-degree AV block (complete heart block) and symptomatic or severe block (heart rate < 40 beats/min) if they persist after treatment with atropine Digoxin immune fab (ovine) is available for life-threaten-.

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