Clinical Electrocardiography: A Simplified Approach, 7th Edition (2006)

Part II. CARDIAC RHYTHM DISTURBANCES

Chapter 18. Digitalis Toxicity

This chapter focuses on the arrhythmias and conduction disturbances caused by digitalis toxicity. This subject is included in an introductory textbook for several reasons. The most important is that digitalis glycosides (mainly digoxin) are still frequently prescribed and digitalis toxicity remains an important clinical problem. Furthermore, digitalis toxicity can cause fatal arrhythmias. Therefore, all clinicians should strive to prevent and recognize digitalis toxicity early. Finally, because digitalis toxicity can produce a wide variety of arrhythmias and all degrees of heart block, this topic provides a convenient review of material presented in previous chapters.

BASIC AND CLINICAL BACKGROUND

Digitalis refers to a class of cardioactive drugs called glycosides that have specific effects on the mechanical and electrical function of the heart. The most commonly used digitalis preparation in current practice is digoxin.

Digitalis is used in clinical practice for two major reasons. First, in selected patients with dilated hearts and congestive heart failure (CHF), it increases the strength of myocardial contractions. This effect is its mechanical action. Second, it affects the conductivity of certain heart tissues. This is its electrical action. Thus digitalis is useful for treating selected arrhythmias. Its antiarrhythmic action results primarily from its slowing of conduction through the atrioventricular (AV) junction (node) as the result of an increase in vagal tone. Consequently, digitalis is used for controlling the ventricular response in atrial fibrillation (AF) and atrial flutter, which are characterized by the excessive transmission of stimuli from the atria to the ventricles through the AV junction. In addition, it is sometimes still used in the treatment of certain reentrant types of paroxysmal supraventricular tachycardia (PSVT).

Although digitalis has continued indications in the treatment of heart failure and selected supraventricular arrhythmias, it also has a relatively low margin of safety. The difference between therapeutic and toxic concentrations is narrow.

The basic mechanisms involved in digitalis-related arrhythmias are complex and incompletely understood. Bradyarrhythmias may be due to excessive increases in vagal tone caused by digitalis. Increased automaticity and tachycardias may be due at least in part to activating effects of toxic doses of digitalis on the sympathetic nervous system. The automaticity of certain cardiac cells may also be directly increased by the calcium loading effects of digitalis.

 

SIGNS OF DIGITALIS TOXICITY

Digitalis toxicity can produce general systemic symptoms as well as specific cardiac arrhythmias and conduction disturbances. Common extracardiac symptoms include weakness, anorexia, nausea, and vomiting. Visual effects (altered color perception) and mental changes may occur. This section of the chapter concentrates on the arrhythmias and conduction disturbances produced by digitalis excess.

As a general clinical rule, virtually any arrhythmia and all degrees of AV heart block can be produced by digitalis intoxication. Of all the arrhythmias discussed in this book, AF and atrial flutter with a rapid ventricular response are the least likely to be caused by digitalis toxicity. A number of other arrhythmias and conduction disturbances, however, are commonly seen with digitalis toxicity ( Box 18-1).

BOX 18-1 

Arrhythmias and Conduction Disturbances Caused by Digitalis Toxicity

Bradycardias

Sinus bradycardia (including sinoatrial block)

Junctional (nodal) escape rhythms[*]

Atrioventricular (AV) heart block, including Mobitz type I (Wenckebach) AV block and complete heart block[*]

Tachycardias

Accelerated or junctional rhythm such as nonparoxysmal or junctional tachycardia[*]

Atrial tachycardia with block

Ventricular ectopy, including ventricular premature beats, monomorphic ventricular tachycardia, bidirectional ventricular tachycardia, and ventricular fibrillation

*  These arrhythmias and conduction disturbances may occur with underlying atrial fibrillation leading to slow or regularized ventricular response. AV dissociation without complete heart block may also occur.

VENTRICULAR ARRHYTHMIAS

Ventricular premature beats (VPBs) are often the first sign of digitalis toxicity. Isolated VPBs may occur at first. Ventricular bigeminy ( Fig. 18-1 ), with each normal beat followed by a VPB, is common. Ventricular tachycardia (VT) and fatal ventricular fibrillation (VF) may occur if digitalis toxicity is not recognized and treated (see Chapter 16 ).

FIGURE 18-1  Ventricular bigeminy caused by digitalis toxicity. Ventricular ectopy is one of the most common signs of digitalis toxicity. A, The underlying rhythm is atrial fibrillation. B, Each normal QRS complex is followed by a ventricular premature beat.

BIDIRECTIONAL VENTRICULAR TACHYCARDIA

Bidirectional VT ( Fig. 18-2 ) is a special type of VT in which each successive beat in any lead alternates in direction. This distinctive tachyarrhythmia should always raise the question of digitalis intoxication.

FIGURE 18-2  This digitalis-toxic arrhythmia is a special type of ventricular tachycardia with QRS complexes that alternate in direction from beat to beat. No P waves are present.

AV JUNCTIONAL (NODAL) RHYTHMS

AV junctional rhythms are frequently a sign of digitalis toxicity.[*] Most AV junctional rhythms resulting from excessive digitalis have a rate of less than 130 beats/min.

*  Two classes of junctional (nodal) rhythms may occur: (1) a typical junctional escape rhythm with a rate of 60 beats/min or less, and (2) an accelerated junctional rhythm (also called nonparoxysmal junctional tachycardia) at a rate of about 60 to 130 beats/min.
SINUS BRADYCARDIA AND SINOATRIAL BLOCK

Sinus bradycardia may be one of the earliest signs of digitalis excess. Sinoatrial (SA) block with sinus arrest may also occur.

ATRIAL TACHYCARDIA WITH AV BLOCK

Atrial tachycardia (AT) with AV block is another tachyarrhythmia that has not been discussed in earlier chapters (an example appears in Figure 18-3 ). This arrhythmia is usually characterized by regular, rapid P waves occurring at a rate between 150 and 250 beats/min and, because of the AV block, a slower ventricular rate. Not uncommonly, 2:1 AV block is present so that the ventricular rate is half the atrial rate. Mobitz type I (Wenckebach) AV block is also common. Digitalis toxicity is an important but not the only cause of these arrhythmias. Superficially, AT with block may resemble atrial flutter; however, in AT with block, the baseline between P waves is isoelectric. Furthermore, when atrial flutter is present, the atrial rate is faster (usually 250 to 350 beats/min).

FIGURE 18-3  This rhythm strip shows atrial tachycardia (about 200 beats/min) with 2:1 block, producing a ventricular rate of about 100 beats/min.

AV HEART BLOCK AND AV DISSOCIATION

Because digitalis slows conduction through the AV junction, it is not surprising that toxic doses can result in any degree of AV heart block.

First-Degree Block

With first-degree AV block, PR intervals are uniformly prolonged beyond 0.2 second. Some degree of PR lengthening may be expected with digitalis therapy. More marked widening of the PR interval suggests early digitalis toxicity.

Second-Degree Block

With higher doses of digitalis, PR prolongation may progress to second-degree block of the Mobitz type I (Wenckebach) variety.

Complete Heart Block

Third-degree, or complete, heart block may also occur with digitalis toxicity.

Digitalis toxicity can cause other types of AV dissociation as well (see Chapter 17 ).

ATRIAL FIBRILLATION OR FLUTTER WITH SLOW VENTRICULAR RATE

Rarely, digitalis causes AF and atrial flutter with a rapid ventricular response. In such cases, the toxicity is often shown by marked slowing of the ventricular rate to less than 50 beats/min ( Fig. 18-4 ) and/or the appearance of VPBs. In some cases, the earliest sign of digitalis toxicity in a patient with AF may be a subtle regularization of the ventricular rate. The need for potentially toxic doses of digoxin to control the ventricular rate in AF has been obviated by the availability of other drugs (beta blockers and calcium channel blockers) and AV nodal ablation procedures (see Chapter 15 ).

FIGURE 18-4  Atrial fibrillation with an excessively slow ventricular rate because of digitalis toxicity. Atrial fibrillation with a rapid ventricular rate is rarely caused by digitalis toxicity. In patients with underlying atrial fibrillation, however, digitalis toxicity is sometimes manifested by excessive slowing or regularization of the QRS rate.

In summary, digitalis toxicity causes a number of important arrhythmias and conduction disturbances. Therefore, because of the frequency and potential lethality of digitalis toxicity, you should suspect this problem in any patient taking a digitalis preparation who has an unexplained arrhythmia, until you can prove otherwise.

 

FACTORS PREDISPOSING TO DIGITALIS TOXICITY

A number of factors significantly increase the hazard of digitalis intoxication ( Box 18-2 ). For example, a low serum potassium concentration increases the likelihood of certain digitalis-induced arrhythmias, particularly ventricular ectopy and AT with block. Hypokalemia is not uncommon in patients who are taking digitalis because these patients frequently receive diuretics for the treatment of heart failure and edema. The serum potassium concentration must be checked periodically in any patient taking digitalis and in every patient suspected of having digitalis toxicity.

BOX 18-2 

Predisposing Factors for Digitalis Toxicity

Cardiac amyloidosis

Chronic lung disease

Hypercalcemia

Hypertrophic cardiomyopathy (an inherited heart condition associated with excessive cardiac contractility)

Hypokalemia

Hypomagnesemia

Hypothyroidism

Hypoxemia

Myocardial infarction

Old age

Renal insufficiency

Wolff-Parkinson-White syndrome and atrial fibrillation

Hypomagnesemia occurs in a variety of settings, including alcoholism, intestinal malabsorption, and diuretic therapy. Hypercalcemia is seen with hyperparathyroidism and certain tumors, among other conditions. Both hypomagnesemia and hypercalcemia can be predisposing factors for digitalis toxicity.

Hypoxemia and chronic lung disease may also increase the risk of digitalis toxicity, probably because they are associated with increased sympathetic tone. Patients with acute myocardial infarction (MI) or ischemia appear to be more sensitive to digitalis. Patients with hypothyroidism appear to be more sensitive to the effects of digitalis.

Digoxin, the most widely used preparation of digitalis, is excreted primarily in the urine. Therefore, any degree of renal insufficiency, as measured by increased blood urea nitrogen (BUN) and creatinine concentrations, requires a lower maintenance dose of digoxin. Thus elderly patients may be more susceptible to digitalis toxicity, in part because of decreased renal excretion of the drug.

Even therapeutic levels of digoxin can be dangerous in certain special clinical settings. For example, digitalis may worsen the symptoms of patients with hypertrophic cardiomyopathy, an inherited heart condition associated with excessive cardiac contractility. Patients with heart failure due to amyloidosis are also extremely sensitive to digitalis. In patients with the Wolff-Parkinson-White syndrome and AF (see Chapter 20 ), digitalis may facilitate extremely rapid transmission of impulses down the atrioventricular bypass tract, leading to a potentially lethal tachycardia (see Fig. 20-10 A).

 

TREATMENT OF DIGITALIS TOXICITY

The first step in treatment is prevention. Before any patient is started on digoxin or a related drug, the indications should be carefully reviewed. Some patients continue to receive digoxin or related drugs for inappropriate reasons. The patient should have a baseline ECG, serum electrolytes, and BUN and creatinine measurements. Serum magnesium blood levels should also be considered, particularly if indicated by diuretic therapy and other factors. Additional considerations include the patient's age and pulmonary status, as well as whether the patient is having an acute MI. Early signs of digitalis toxicity (e.g., VPBs, sinus bradycardia, or increasing AV block) should be carefully checked. Furthermore, concomitant administration of a number of different drugs (including amiodarone, propafenone, quinidine, and verapamil) increases the digoxin level.

Definitive treatment of digitalis toxicity depends on the particular arrhythmia. With minor arrhythmias (e.g., isolated VPBs, sinus bradycardia, prolonged PR interval, Wenckebach AV block or AV junctional rhythms), discontinuation of digitalis and careful observation are usually adequate. More serious arrhythmias (e.g., prolonged VT) may require suppression with an intravenous drug such as lidocaine. For tachycardias with hypokalemia, potassium supplements should be given to raise the serum potassium level to well within normal limits.

Patients with complete heart block from digitalis toxicity may require a temporary pacemaker while the effect of the digitalis dissipates, particularly if they have symptoms of syncope, hypotension, or CHF. In other cases, complete heart block can be managed conservatively while the digitalis wears off.

Occasionally, patients present with a large overdose of digitalis taken inadvertently or in a suicide attempt. In such cases, the serum digoxin level is markedly elevated, and severe brady- or tachyarrhythmias may develop. In addition, massive digitalis toxicity may cause life-threatening hyperkalemia because the drug blocks the cell membrane mechanism that pumps potassium into the cells in exchange for sodium. Patients with a potentially lethal overdose of digitalis can be treated with a special digitalis-binding antibody given intravenously (digoxin immune Fab [antigen-binding fragment; Digibind]).

Finally, direct-current electrical cardioversion of arrhythmias in patients who have digitalis toxicity is extremely hazardous and may precipitate fatal ventricular tachycardia and fibrillation. Therefore, you should not electrically cardiovert any patient who has atrial tachycardia with block, AF, or atrial flutter and is suspected of having digitalis toxicity.

 

SERUM DIGOXIN LEVELS

The concentration of digoxin in the serum can be measured by means of radioimmunoassay. “Therapeutic concentrations” are reported to range from about 0.5 to 2 ng/mL in most laboratories. Concentrations exceeding 2 ng/mL are associated with a very high incidence of digitalis toxicity. In ordering a test of digoxin level in a patient, you must be aware that “therapeutic levels” do not rule out the possibility of digitalis toxicity. As previously mentioned, some patients are more sensitive to digitalis and may show signs of toxicity with “therapeutic” levels. For most patients being treated for systolic heart failure or atrial fibrillation, it is safest to keep the digoxin levels at the low end of the therapeutic range.

In other patients, factors such as hypokalemia or hypomagnesemia may potentiate digitalis toxicity despite a therapeutic serum level. Although a “high” digoxin level does not necessarily indicate overt digitalis toxicity, these patients should be examined for early evidence of digitalis excess, including extracardiac symptoms (e.g., gastrointestinal symptoms) and all cardiac effects that have been discussed. Efforts should be made to keep the digoxin level well within therapeutic bounds; lower levels appear to be as efficacious as (and safer than) higher ones in the treatment of heart failure. (A spuriously high digoxin level may be obtained if blood is drawn within a few hours of the administration of digoxin.)

 

DIGITALIS TOXICITY VS. DIGITALIS EFFECT

Digitalis toxicity, which refers to the arrhythmias and conduction disturbances produced by this drug, should not be confused with digitalis effect. Digitalis effect (see Fig. 10-1 ) refers to the distinct scooping of the ST-T complex (associated with shortening of the QT) typically seen in patients taking digitalis glycosides. The presence of digitalis effect by itself does not imply digitalis toxicity and may be seen at therapeutic doses.

 

REVIEW

Digitalis toxicity can produce almost any arrhythmia and all degrees of AV heart block.

Atrial fibrillation or atrial flutter with a rapid ventricular response rarely occurs as a result of digitalis toxicity. Furthermore, digitalis toxicity does not produce bundle branch blocks.

Factors such as renal failure, hypokalemia, hypercalcemia, hypomagnesemia, hypoxemia, old age, and acute myocardial infarction are predisposing factors for digitalis toxicity. The concomitant administration of certain drugs (e.g., quinidine, verapamil, amiodarone, propafenone) also increases serum digoxin levels.

Digitalis toxicity should not be confused with digitalis effect. Digitalis effect refers to the shortening of the QT interval and scooping of the ST-T complex produced by therapeutic doses of digitalis.

 

QUESTIONS

 

1.   

Name three factors that can potentiate digitalis toxicity. True or false (2 to 7):

 

2.   

Ventricular premature beats are a frequent manifestation of digitalis toxicity.

 

3.   

Atrial fibrillation with a rapid ventricular response is a common manifestation of digitalis toxicity.

 

4.   

Left bundle branch block may result from digitalis toxicity.

 

5.   

Mobitz type I (Wenckebach) AV block may be caused by digitalis toxicity.

 

6.   

A therapeutic digoxin level indicates that digitalis toxicity is not present.

 

7.   

DC cardioversion is very hazardous in the presence of digitalis toxicity and may lead to ventricular fibrillation.