Attempt to distinguish between acute versus chronic ingestions, as the symptoms and treatments differ.
Electrocardiogram changes are common and include downward-sloping (scooped) ST-segment depressions, premature ventricular complexes, supraventricular dysrhythmias with slow ventricular rates, and bidirectional ventricular tachycardia.
Although hyperkalemia can be a marker of significant digoxin poisoning, standard treatment with intravenous calcium should typically be avoided.
Empirically administer digoxin-specific antibodies (5 vials for chronic toxicity, 10–20 vials for acute ingestions) to all patients with life-threatening dysrhythmias or hemodynamic instability.
Digoxin, a commonly prescribed agent derived from the foxglove plant, belongs to a class of medications known as cardiac glycosides. These agents function to increase myocardial contractility and slow AV nodal conduction and are commonly used for the treatment of congestive heart failure and various cardiac dysrhythmias including atrial fibrillation. Of interest, cardiac glycosides are frequently encountered in the natural world as a predatory deterrent in both plant and animal species, including oleander, lily of the valley, red squill, and bufo toads. The relative potency of digoxin lends to a very narrow therapeutic window, and life-threatening toxicity can develop with both acute overdoses and chronic excessive exposures. Poisoned patients generally present with variable symptoms and must be viewed in light of acute versus chronic versus acute on chronic exposures. If left untreated, death will invariably result secondary to cardiac instability and hemodynamic compromise.
As a whole, cardiac glycosides were responsible for nearly 2,500 poisonings reported to the National Poison Data System in the year 2010. They were the third most common cardiovascular agent implicated in patient toxicity and were the primary agent responsible for 17 patient deaths. Of note, clinically significant toxicity is far more common in pediatric and geriatric populations. Pediatric overdoses arise from iatrogenic dosing errors or accidental ingestions of adult medications, whereas geriatric toxicity generally results from either drug–drug interactions or alterations in metabolic clearance. Intentional overdoses are most common in adult patients and can be of both the acute and chronic variety.
Orally administered digoxin begins to exhibit clinical effects within 90 minutes of ingestion and typically reaches maximal effect within 4–6 hours. Digoxin is primarily eliminated by the kidneys with a usual half-life of 36–48 hours. Although normal therapeutic concentrations generally range between 0.5 and 2 ng/mL, given the significant toxicity and narrow therapeutic window, the safest suggested concentration with maximal therapeutic benefit is between 0.5 and 1 ng/mL.
At the cellular level, digoxin inhibits the membrane-based sodium-potassium pumps, causing an increase in intracellular sodium concentrations. This rise in intracellular sodium inhibits the membrane-based sodium-calcium exchanger, causing a secondary elevation in intracellular calcium levels. The increased intracellular calcium concentration augments myocardial contractility and increases cardiac inotropy. It is this increase in cardiac inotropy that makes digoxin an attractive agent for the management of congestive heart failure. Additionally, digoxin increases the overall vagal tone of the heart and thereby decreases the electrical conduction velocity through both the SA and AV nodes. This property allows digoxin to be used as a rate-controlling agent in patients with supraventricular tachydysrhythmias (eg, atrial fibrillation). That said, this global slowing of myocardial signal conduction combined with a secondary shortening of the myocyte refractory period can potentially increase overall cardiac automaticity and excitability. Given these phenomena, toxic exposures typically present with a multitude of cardiovascular manifestations.
Ascertaining the time of exposure is extremely important with potential digoxin toxicity. As with all potential poisonings, it is extremely important to determine the total amount ingested. Elucidate the number and frequency of exposures to distinguish between acute versus chronic versus acute on chronic toxicity. Carefully clarify the circumstances of the overdose to differentiate between accidental versus more insidious etiologies. Inquire about the presence of any gastrointestinal symptoms, such as nausea, vomiting, and abdominal pain, which typically accompany most acute overdoses. Central nervous system (CNS) effects include mood changes, headache, altered mental status, lethargy, and hallucinations. Visual disturbances are common and include blurry vision, photophobia, and chromatopsia (a change of color vision), in which visualized objects are classically surrounded by yellowish-green halos.
Obtain a complete set of vital signs and carefully monitor for any evidence of hemodynamic instability. Although bradydysrhythmias and systemic hypotension are most common, patients may present with any number of cardiac manifestations, including life-threatening tachycardias. Additional physical exam findings are variable and nonspecific and typically lag up to several hours after ingestion. CNS effects including confusion, generalized weakness, altered mental status, and lethargy may be present, and generalized seizures may accompany severe overdoses.
