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Bradycardia is the vital sign change that most likely indicates digoxin toxicity. Digoxin is a cardiac glycoside used to treat various heart conditions, primarily atrial fibrillation and heart failure. It works by increasing the force of myocardial contraction and controlling heart rate. However, one of the key effects of digoxin is its ability to influence the conduction system of the heart, particularly by increasing vagal tone. This increased vagal activity can result in a slower heart rate, or bradycardia, which is often a hallmark sign of digoxin toxicity.

Digoxin toxicity can occur when blood levels of the medication become too high, leading to adverse effects on the heart's rhythm and rate. Clinicians closely monitor heart rate in patients receiving digoxin, and bradycardia—defined as a heart rate of less than 60 beats per minute—serves as an important indicator that the patient may be experiencing toxic effects from the drug.

In contrast, other vital sign changes, such as increased respiratory rate, hypotension, and hyperthermia, may be associated with various conditions or reactions but are not specific indicators of digoxin toxicity. Thus, bradycardia is the vital sign change that directly correlates with the potential adverse