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 membranebased 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

CHAPTER 59

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.

CLINICAL PRESENTATION

� History

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.

� Physical Examination

Obtain a complete set of vital signs and carefully monitor

for any evidence of hemodynamic instability. Although

bradydysrhythrnias 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.

DIAGNOSTIC STUDIES

� Laboratory

Obtain a STAT metabolic panel as serum electrolytes play

an extremely important role in digoxin toxicity. Serum

hyperkalemia (K+ >5.5 mEq/L) indicates significant toxicity with acute overdoses and is associated with increased

fatality. Serum hypokalemia (K+ <3.5 mEq/L) is far more

common with chronic toxicity and inhibits the function of

the cellular sodium-potassium pumps, thereby increasing

myocardial susceptibility to digoxin-related dysrhythrnias.

Serum hypomagnesemia may further predispose to this

increased cardiac toxicity. Finally, any decline in renal

function will intensify toxicity, as digoxin is primarily

eliminated via the kidneys.

Obtain a serum digoxin level, as this will guide the

dosing of digoxin Fab fragments. Therapeutic digoxin

levels range from 0.5 to 2.0 ng/mL. Interpret the digoxin

level carefully within the clinical context. The distributive

phase of digoxin lasts for -6 hours after an ingestion, and

serum levels obtained within this period may be falsely

elevated.

� Electrocardiogram

Obtain an emergent electrocardiogram (ECG) in all

patients with potential digoxin toxicity. Prolongation of

the PR interval and shortening of the QT segment are not

uncommon with therapeutic digoxin concentrations.

Upward "scooping" of the ST segment is also fairly

common. These changes taken as a whole are referred to as

the digitalis effect. In addition, excesses in intracellular

calcium may produce frequent premature ventricular

complexes (PVCs) and occasional U waves.

Digoxin poisoning can induce nearly every form of

dysrhythmia or conduction disturbance. Classic ECG

fmdings include supraventricular tachydysrhythmias

(atrial flutter or fibrillation) combined with variable AV

nodal blockade resulting in slow ventricular rates

(Figure 59- 1). Bidirectional ventricular tachycardia is

nearly pathognomonic for serious digoxin toxicity.

Additional ECG findings include sinus bradycardia,

ventricular bigeminy, and ventricular fibrillation.

PROCEDURES

Cardioversion or defibrillation may be performed following Advanced Cardiovascular Life Support protocols in

digoxin-poisoned patients exhibiting significant toxicity

and unstable rhythms (ventricular tachycardia or

.A Figure 59·1 . Digitalis toxicity: Atrial fibril lation with

slow ventricular rate and "scooped" ST-segment

depression. Reproduced with permission from Ritchie JV,

Juliano ML, Thurman RJ. Chapter 23. ECG Abnormal ities.

In: Knoop KJ, Stack LB, Storrow AB, Thurman RJ, eds. The

Atlas of Emergency Medicine. 3rd ed. New York:

McGraw-Hill, 201 0. Photo contributor: JV Ritchie, MD.

fibrillation). Transcutaneous or transvenous pacing often

fails to correct digoxin-associated bradydysrhythmias and

may actually lower the threshold for life-threatening ventricular dysrhythmias.

MEDICAL DECISION MAKING

The differential diagnosis of digoxin toxicity includes any

disease process or toxin capable of inducing cardiac

dysrhythmias. Specific toxins include calcium channel

blockers, beta-blockers, clonidine, organophosphate

insecticides, class lA antidysrhythmics, and cardiotoxic

plants (eg, rhododendron, monkshood). Medical conditions

include underlying cardiac pathologies such as sick sinus syndrome and AV nodal blocks as well as systemic conditions

such as sepsis, myxedema coma, and adrenal crisis.

The toxicologic differential of any hypotensive and/or

bradycardic patient includes beta-blockers, calcium

channel blockers, digoxin, and clonidine. Obtaining a

thorough history frequently aids in establishing the

appropriate diagnosis. The most common current presen ­

tation of digoxin toxicity is an elderly patient with an

underlying cardiac history on multiple medications who

experiences either significant drug-drug interactions or

dehydration with secondary renal insufficiency and

decreased digoxin clearance despite therapeutic usage.

DIGOXIN

The physical exam combined with appropriate

ancillary testing is invaluable for identifying the correct

toxidrome. Clonidine poisoning typically presents similar

to an opioid toxidrome. A significantly elevated capillary

blood glucose in a nondiabetic patient may indicate serious calcium channel blocker toxicity. Taken in context of

the history and physical exam, classic ECG findings and

abnormal serum digoxin levels may be used to direct further treatment (Figure 59-2).

TREATMENT

After addressing and stabilizing the patient's airway,

breathing, and circulation status, pursue gastrointestinal

(GI) decontamination with activated charcoal (AC) for

cases of acute overdose. Do not give AC to patients with

depressed levels of consciousness without first securing the

airway to prevent aspiration. Initiate volume resuscitation

in dehydrated patients but be wary of those with a history

of congestive heart failure (CHF). Treat severe hyperkale ­