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


Chapter 10. Drug Effects, Electrolyte Abnormalities, and Metabolic Factors

The ECG is importantly affected by a number of factors, including drug effects, certain electrolyte abnormalities, and a variety of other metabolic conditions. Indeed, the ECG may be the major initial indicator of a life-threatening abnormality such as hyperkalemia or tricyclic antidepressant toxicity. This chapter introduces these topics and provides a brief review of nonspecific versus more specific ST-T changes.



Numerous drugs can affect the ECG. Generally, the ECG changes are slight and nonspecific. Distinctive changes can be produced, however, by a number of commonly used classes of drugs, including digitalis glycosides, cardiac antiarrhythmic agents, and psychotropic agents.

Digitalis is used in the treatment of heart failure and certain arrhythmias. One of its effects is to shorten repolarization time in the ventricles. This shortens the QT interval and is associated with a characteristic scooping of the ST-T complex (digitalis effect), as shown in Figures 10-1 and 10-2 [1] [2]. Notice that when digitalis effect occurs, the ST segment and T wave are fused together and it is impossible to tell where one ends and the other begins. Digitalis effect can be seen in patients taking therapeutic or toxic doses of any digitalis preparation (e.g., digoxin). Digitalis effect must be distinguished from digitalis toxicity, which refers to arrhythmias, conduction disturbances, and systemic side effects produced by excessive amounts of digitalis (see Chapter 18 ).

FIGURE 10-1  Characteristic scooping of the ST-T complex produced by digitalis. (Not all patients taking digitalis exhibit these changes.)

FIGURE 10-2  The characteristic scooping of the ST-T complex produced by digitalis is best seen in leads V5 and V6. (Low voltage is also present, with total QRS amplitude of 5 mm or less in all six limb leads.)

Quinidine, procainamide, and disopyramide are antiarrhythmic drugs with similar properties. In contrast to digitalis, they prolong ventricular repolarization, due to blocking of a potassium channel. Therefore they may prolong the QT interval and flatten the T wave. In toxic doses, they may also prolong ventricular depolarization, leading to a widening of the QRS complexes. Occasionally, these agents produce prominent U waves resembling those seen with hypokalemia (discussed later in this chapter).

In selected cases, these drugs may actually cause sudden cardiac arrest due to the torsades de pointes type of ventricular tachycardia, as described in Chapter 16 . This proarrhythmic effect is most likely to occur with prolonged QT intervals and/or prominent U waves ( Fig. 10-3 ).

FIGURE 10-3  Lead V6 from the ECG of a patient with a quinidine blood level of 2.9 μg/mL (therapeutic range). Notice the prolonged repolarization with prominent T-U waves, similar to the pattern of hypokalemia. Patients in whom quinidine and other drugs causes marked repolarization (QT) prolongation (often with large U waves) are at increased risk for polymorphic ventricular tachycardia (torsades de pointes, see Chapter 16 ). This patient did, in fact, subsequently develop torsades de pointes.

Prolongation of the QT(U) interval with a risk of torsades de pointes can occur with other cardiac antiarrhythmic drugs, notably ibutilide, dofetilide, sotalol, and amiodarone ( Fig. 10-4 ). This effect is also related to blocking of potassium channel function with prolongation of myocardial cellular repolarization.

FIGURE 10-4  Effects of amiodarone (monitor lead). Note the prominent prolongation of repolarization (long QT) produced by a therapeutic dose of amiodarone in this patient as therapy for atrial fibrillation. The heart rate also slowed due to the beta-blocking effect of the drug.

Other drugs used to treat cardiac arrhythmias can have important effects on the ECG. Drugs such as flecainide and propafenone, used to treat atrial fibrillation and other supraventricular tachycardias, may produce widening of the QRS complex (intraventricular conduction delay). This effect is due to blocking of sodium channels in the ventricular conduction system and myocardium.


Psychotropic drugs (e.g., phenothiazines and tricyclic antidepressants) can markedly alter the ECG and, in toxic doses, can induce syncope or cardiac arrest due to a ventricular tachyarrhythmia or asystole. They may also prolong the QRS interval, causing a bundle branch block–like pattern, or they may lengthen repolarization (long QT-U intervals), predisposing patients to develop torsades de pointes. Figure 10-5 presents the typical ECG findings of tricyclic antidepressant overdose, in this case, in a young adult. Notice the prolonged QRS and QT intervals, as well as sinus tachycardia.

FIGURE 10-5  A, This ECG from a patient with tricyclic antidepressant overdose shows three major findings: sinus tachycardia (from anticholinergic and adrenergic effects), prolongation of the QRS complex (from slowed ventricular conduction), and prolongation of the QT interval (from delayed repolarization). B, A repeat ECG obtained 4 days later shows persistent sinus tachycardia but normalization of the QRS complex and QT interval.

Lithium carbonate may cause nonspecific ST-T changes. Occasionally, especially in toxic doses, it may cause sinus node dysfunction and severe bradycardia.

A variety of noncardiac drugs can prolong the QT interval, predisposing the development of the torsades de pointes type of ventricular tachycardia. This topic is discussed further in Chapter 16 and is summarized in a review in Chapter 24 .



Abnormal serum concentrations of potassium and calcium can produce marked effects on the ECG. Hyperkalemia can, in fact, be lethal because of its cardiac toxicity.


As shown in Figure 10-6 , progressive hyperkalemia produces a distinctive sequence of ECG changes affecting both depolarization (QRS complex) and repolarization (ST-T segments). The normal serum potassium concentration is between 3.5 and 5 mEq/L. The first change seen with abnormal elevation of the serum potassium concentration is narrowing and peaking of the T waves. As Figure 10-6demonstrates, the T waves with hyperkalemia have a characteristic “tented” or “pinched” shape, and they may become quite tall. With further elevation of the serum potassium concentration, the PR intervals become prolonged and the P waves are smaller and may disappear entirely. Continued elevations produce an intraventricular conduction delay, with widening of the QRS complexes (see Figs. 10-6 and 10-7 [6] [7]). As the serum potassium concentration rises further, the QRS complexes continue to widen, leading eventually to a large undulating (sine-wave) pattern and asystole.

FIGURE 10-6  The earliest change with hyperkalemia is peaking (“tenting”) of the T waves. With progressive increases in the serum potassium concentration, the QRS complexes widen, the P waves decrease in amplitude and may disappear, and finally a sine-wave pattern leads to asystole unless emergency therapy is given.

FIGURE 10-7  ECG of a patient with a serum potassium concentration of 8.5 mEq/L. Notice the absence of P waves and the presence of bizarre wide QRS complexes.

Because hyperkalemia can be fatal, recognition of the earliest signs of T wave peaking may prove lifesaving. Hyperkalemia can be seen in several clinical settings. The most common is kidney failure, in which the excretion of potassium is reduced.


Hypokalemia produces distinctive changes in the ST-T complex. The most common pattern seen is ST depressions with prominent U waves and prolonged repolarization[*] (Figs. 10-8 and 10-9 [8] [9]). With hypokalemia, the U waves typically become enlarged and may even exceed the height of the T waves.

FIGURE 10-8  The ECG patterns that may be seen with hypokalemia range from slight T wave flattening to the appearance of prominent U waves, sometimes with ST depressions or T wave inversions. These patterns are not directly related to the specific level of serum potassium.

FIGURE 10-9  ECG leads from a patient with a markedly low serum potassium concentration of 2.2 mEq/L. Notice the prominent U waves, with flattened T waves.

*  Technically the QT interval with hypokalemia may remain normal, whereas repolarization is prolonged (as shown by the prominent U waves). Because the T waves and U waves often merge, the QT intervals cannot always be accurately measured.

Ventricular repolarization is shortened by hypercalcemia and lengthened by hypocalcemia ( Fig. 10-10 ). In hypercalcemia, the shortening of the QT interval is due to shortening of the ST segment. With marked hypercalcemia, the T wave appears to take off right from the end of the QRS complex. High serum calcium concentrations may lead to coma and death. A short QT interval in a patient with mental status changes is sometimes the first clue to the diagnosis of hypercalcemia. Hypocalcemia lengthens or prolongs the QT interval, usually by “stretching out” the ST segment. Note, however, that patients may have clinically significant hypocalcemia or hypercalcemia without diagnostic ECG changes.

FIGURE 10-10  Hypocalcemia prolongs the QT interval by stretching out the ST segment. Hypercalcemia decreases the QT interval by shortening the ST segment so that the T wave seems to take off directly from the end of the QRS complex.




Patients with systemic hypothermia may develop a distinctive ECG pattern in which a humplike elevation is usually localized to the junction of the end of the QRS complex and the beginning of the ST segment (J point) ( Fig. 10-11 ). These pathologic J waves are sometimes called Osborn waves. This pattern disappears with rewarming. The basic mechanism of these prominent J waves appears to be related to the differential effects of systemic cooling on epicardial and endocardial repolarization in the ventricles.

FIGURE 10-11  Systemic hypothermia is associated with a distinctive bulging of the J point (the very beginning of the ST segment). The prominent J waves (arrows) with hypothermia are referred to as Osborn waves.


Most endocrine disorders do not produces specific changes on the ECG. In some instances, however, the ECG may play an important role in the diagnosis and management of hormonal abnormalities. For example, hyperthyroidism (most commonly due to Graves disease) is often associated with an inappropriately high resting sinus heart rate. The finding of a high sinus rate at rest should always lead to suspicion of hyperthyroidism, as should the finding of atrial fibrillation (see Chapter 15 ).

In contrast, hypothyroidism is often associated with a slow resting heart (sinus bradycardia). Severe hypothyroidism (myxedema) may lead to pericardial effusion, thereby causing low-voltage QRS complexes. Low QRS voltage is said to be present when the total amplitude of the QRS complexes in each of the six limb leads is 5 mm or less, or 10 mm or less in the chest leads. Low QRS voltage is not a specific finding but can be related to a variety of mechanisms and causes (see Chapter 24 ). These include increased insulation of the heart by air (chronic obstructive pulmonary disease) or adipose tissue (obesity); replacement of myocardium, for example, by fibrous tissue (in cardiomyopathy), amyloid, or tumor; or due to the abnormal accumulation of extracellular fluid (as with anasarca, or with pericardial or pleural effusions).



The concluding topic of this chapter is a brief review of the major factors that cause ST-T (repolarization) changes. The term nonspecific ST-T change (defined in Chapter 9 ) is commonly used in clinical electrocardiography. Many factors (e.g., drugs, ischemia, electrolyte imbalances, infections, and pulmonary disease) can affect the ECG. As already mentioned, the repolarization phase (ST-T complex) is particularly sensitive to such effects and can show a variety of nonspecific changes as a result of multiple factors (Figs. 10-12 and 10-13 [12] [13]). These changes include slight ST depressions, T wave flattening, and slight T wave inversions (see Fig. 10-12 ).

FIGURE 10-12  Flattening of the T wave (bottom left and middle) and slight T wave inversion (bottom right) are abnormal but relatively nonspecific ECG changes that may be caused by numerous factors.

FIGURE 10-13  ECG showing nonspecific ST-T changes. Notice the diffuse T wave flattening.

In contrast to these nonspecific ST-T changes, certain fairly specific changes are associated with particular conditions (e.g., the tall tented T waves of hyperkalemia). Some of these relatively specific ST-T changes are shown in Figure 10-14 . Even such apparently specific changes can be misleading, however. For example, ST elevations are characteristic of acute transmural ischemia, but they are also seen in ventricular aneurysms, pericarditis, and benign (normal) early repolarization. Similarly, deep T wave inversions are most characteristic of ischemia but may occur in other conditions as well (seeChapters 9 and 24 ).

FIGURE 10-14  Examples of relatively specific ST-T changes. Note, however, that the changes are not absolutely specific for the abnormalities shown.

In summary, repolarization abnormalities can be grouped into two general categories. Nonspecific ST-T changes include slight ST segment deviation and flattening or inversion of the T wave. These changes are not diagnostic of any particular condition but must always be interpreted in clinical context. The relatively specific ST-T changes are more strongly but not always definitively diagnostic of some particular underlying cause (e.g., hyperkalemia or myocardial ischemia).



The ECG can be influenced by numerous factors, including many drugs. Digitalis effect refers to the characteristic scooped-out depression of the ST segment produced by therapeutic doses of digitalis. (Digitalis toxicity refers to the arrhythmias and conduction disturbances produced by excessive doses of digitalis.) Quinidine, procainamide, disopyramide, ibutilide, dofetilidesotalol, and certainpsychotropic drugs can prolong the QT interval and may also induce a potentially lethal type of ventricular tachycardia called torsades de pointes (see Chapter 16 ). Patients likely to develop this complication usually show prominently prolonged QT intervals and/or large U waves. Amiodarone is an antiarrhythmic drug that typically prolongs the QT interval, even at therapeutic doses.

Electrolyte disturbances can also affect the ECG:



Hyperkalemia typically produces a sequence of changes. First the T wave narrows and peaks (“tents”). Further elevation of the serum potassium concentration leads to prolongation of the PR interval and then to loss of P waves and widening of the QRS complex, followed by a sine-wave pattern and asystole.



Hypokalemia may produce ST depressions and prominent U waves. The QT interval becomes prolonged. (In some cases, you are actually measuring the QU interval, and not the QT interval, because it may be impossible to tell where the T wave ends and the U wave begins.)



Hypercalcemia may shorten the QT interval, and hypocalcemia may prolong it.

With systemic hypothermia, the ECG shows a humplike elevation located at the junction (J point) of the end of the QRS complex and the beginning of the ST segment. The pattern disappears with rewarming.





Which of the following factors can produce ST segment elevations?






Early repolarization pattern



Digitalis effect



Ventricular aneurysm






Right bundle branch block






Match ECGs A, B, and C with the following causes:




Digitalis effect









Prominent U waves are characteristic of which one of the following:















Digitalis effect

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