1

Pharmacologic treatment of arrhythmias

A. General comments
The rational choice of an antiarrhythmic agent is based on three considerations: (1) correct
clinical diagnosis of the arrhythmia, (2) an understanding of the electrophysiology of the
rhythm disturbance, and (3) an understanding of the mechanism of action and side effects of
antiarrhythmic agents.
B. Commonly used antiarrhythmic agents
1. Procainamide (Pronestyl)
a. Electrophysiologic properties. Procainamide raises the threshold of ventricular muscle to
electrical stimulation. It increases the effective refractory period and decreases conduction
velocity and automaticity. The major metabolite of procainamide is N-acetylprocainamide
(NAPA), which has different electrophysiologic properties than the parent compound. NAPA
does not prolong the effective refractory period but does prolong the action potential of
ventricular muscle and Purkinje fibers.
b. Absorption, excretion, and plasma levels. Gastrointestinal absorption of oral procainamide
is approximately 85%. Peak plasma levels are achieved within 60 minutes of ingestion. Its
half-life is 3.5 hours. Therapeutic plasma levels are 3-10 micro-g/ml. Excretion is 100% renal
(60% excreted unchanged, 40% metabolized and then excreted by kidneys).
c. Clinical uses and dosages. Procainamide may be effective in treatment of the following
arrhythmias: VT, VPCs, and supraventricular arrhythmias (quinidine is preferred in this
setting, if tolerated). Procainamide generally is given orally but may be given IM or IV to
achieve serum concentrations of 4-10 micro-g/ml and to achieve the desired antiarrhythmic
effect. Recommended dosage for oral procainamide is 2-6 gm/day; total dosage given in
divided doses of 3-4 hours. A sustained release form is available (Procan SR) that allows
dosing intervals of q6h. If a loading dose is given it should be twice the maintenance dose.
Doses of up to 1 gm orally of procainamide q4h may be required to control VT.
Blood pressure and ECG must be monitored continuously during intravenous administration.
Intravenous dosage is 20-50 mg/minute to a total dose of 1 gm, followed by a constant
infusion of 2-4 mg/minute.
d. Toxicity. Procainamide may cause gastrointestinal upset (nausea, vomiting, anorexia),
immunologic

disturbances

(positive antinuclear

antibody titer

[ANA] and lupus

erythematosus [LE] cell preparation develop in 50-70% of patients on the drug), rash, drug
fever, and agranulocytosis (rare). Procainamide has direct myocardial depressant action. It is
contraindicated in patients with second- or third-degree block and should be used with caution

in patients with intraventricular conduction defect. Hypotension may occur with intravenous
administration.
2. Quinidine
a. Electrophysiologic properties. The electrophysiologic properties of quinidine are similar to
those of procainamide. Its major effect is to depress the rate of spontaneous depolarization. It
increases the effective refractory period and decreases conduction velocity and automaticity.
b. Absorption, excretion, and plasma levels. The gastrointestinal absorption of oral quinidine
is greater than 95%; 60% of the drug is bound to serum albumin. Peak concentrations occur 24 hours after dosage. Therapeutic plasma levels are 2.5-9.0 micro-g/ml. Biologic half-life is
6.5 hours. The drug is metabolized in the liver and excreted in the urine.
c. Clinical uses and dosages. Quinidine is used to suppress a variety of atrial arrhythmias. It is
the drug of choice to suppress atrial premature contractions (APCs) and helpful in converting
atrial fibrillation and flutter to sinus rhythm. It is used to suppress ventricular arrhythmias
(both VPCs and VT). Quinidine increases both the atrial and the ventricular fibrillation
threshold.
Two preparations of quinidine are available: quinidine sulfate and quinidine gluconate
(Quinaglute). Quinaglute is said to allow doses to be given less frequently by sustaining
adequate blood levels longer. Recommended PO doses are quinidine sulfate 300-600 mg q6h
or quinidine gluconate 660 mg q6-8h. Using maintenance dosages a steady state will be
achieved in 24 hours. To achieve an earlier effective concentration a loading dose of 600-1000
mg may be given orally. When the therapeutic levels are needed quickly, a loading regimen-300 mg IM at 0, 3, and 6 hours--may be given, followed by the usual oral regimen. In
emergencies, quinidine may be given intravenously. This route is hazardous and must be
closely monitored. Severe hypotension secondary to vasodilatation is the most frequent and
dangerous adverse reaction. A test dose of 200 mg of quinidine gluconate IM should be given
before IV administration is attempted. Quinidine gluconate should be diluted--500 mg of the
drug in 50 ml of 5% D/W--and slowly injected (at a rate not to exceed 60 mg/hour), with
monitoring of ECG and blood pressure. Usually 300 mg is sufficient to terminate the
arrhythmia; no more than 500 mg of quinidine gluconate should be given by the intravenous
route.
d. Toxic effects and contraindications. Quinidine should not be administered to patients with
second- or third-degree AV block. Intraventricular block is a relative contraindication.
Quinidine should be avoided in individuals with prolonged Q-T interval. Previous adverse
reaction to quinidine is an absolute contraindication (quinidine syncope is a potentially fatal

complication). Gastrointestinal side effects (nausea, vomiting, diarrhea) are common. When
mild, they may be symptomatically controlled if quinidine is essential. Symptoms of
cinchonism may occur (tinnitus, vertigo, visual disturbances). Allergic responses (rash,
thrombocytopenia, hemolytic anemia) are less common. Idiosyncratic central nervous system
reactions (respiratory arrest, convulsions) have been reported but are rare. Quinidine also has
direct myocardial toxicity. Depressed myocardial contractility and peripheral vasodilatation
can occur. Specific signs of myocardial toxicity include a greater than 50% widening of the
QRS, AV block, and ventricular arrhythmias. Often toxicity is preceded by widening of the
QRS, but any of the above reactions can occur without prior ECG changes. Any signs of
toxicity (with the possible exception of mild gastrointestinal symptoms) are indication for
cessation of the drug.
3. Disopyramide
a. Electrophysiologic properties. Disopyramide has electrophysiologic effects resembling
quinidine and procainamide although its chemical structure is quite different. It prolongs the
refractory period and action potential duration and slows conduction time in the Purkinje
fibers. It decreases the slope of phase 4 depolarization and depresses the V max of phase 0.
b. Absorption, excretion and plasma levels. Disopyramide is absorbed 80-90%. Half-life is 89 hours in healthy volunteers and is prolonged to almost 10 hours in heart failure patients.
Renal, hepatic, or cardiac insufficiency all prolong elimination time and require that loading
and maintenance doses be adjusted downward. Peak blood levels after oral administration
occur in 1-2 hours. Bioavailability is > 80%.
c. Clinical uses and dosages. Typical doses are 100-200 mg orally every six hours. Daily
dosages range from 400-1200 mg. An intravenous form is under investigation and is
administered at a loading dose of 1-2 mg/kg given over 5-10 minutes followed by a
maintenance infusion of 1 mg/kg/hr.
Disopyramide is as effective as quinidine in reducing the number of VPBs. It is as effective as
quinidine in reducing the recurrence of atrial fibrillation following cardioversion. It may be
useful in terminating atrial flutter. In both atrial fibrillation and atrial flutter the ventricular
rate must be controlled before administration to prevent 1:1 conduction resulting from
disopyramide's vagolytic effects. It terminates and prevents recurrent episodes of PSVT and is
particularly effective in WPW, where it prolongs anterograde and retrograde refractory
periods of the accessory pathway.
d. Toxicity. Disopyramide has potent parasympatholytic effects that can lead to urinary
retention, constipation, blurred vision, and dry mouth. It is a myocardial depressant and

should be used with extreme caution in patients with preexistent LV dysfunction. It may
provoke ventricular tachyarrhythmias by prolonging the Q-T interval. It is contraindicated in
patients who have had previous torsades de pointes.
4. Moricizine
a. Electrophysiologic properties. Moricizine is a Class I antiarrhythmic with properties of 1A,
1B, and 1C subclasses. The FDA approved moricizine in 1990 to treat documented lifethreatening ventricular arrhythmias.
b. Absorption, excretion, and plasma levels. Moricizine is absorbed readily through the
gastrointestinal tract. Its systemic bioavailability is reduced to 30-40% due to significant firstpass metabolism in the liver. Peak plasma concentrations are achieved within 1-2 hours after
an oral dose. It is almost completely biotransformed by the liver. Less than 1% of moricizine
is excreted unchanged in the urine. Approximately 39% of moricizine and its metabolites are
eliminated in the urine, and 56% is excreted in the feces.
c. Clinical uses and dosages. A loading dose has not yet been established for moricizine.
Dosages required to produce antiarrhythmic effects may vary among patients. Most patients
can be adequately treated with 200-300 mg q8h. Initial dosage is 200 mg q8h, and this may be
gradually increased over 3-day intervals to 250 mg and then 350 mg q8h.
d. Toxicity. Moricizine may worsen cardiac performance in patients who have preexisting LV
dysfunction or a history of congestive heart failure. Moricizine may also exacerbate
ventricular arrhythmias.
5. Lidocaine (Xylocaine)
a. Electrophysiologic properties. Lidocaine shortens the effective refractory period and
decreases the duration of the action potential. It depresses the rate of spontaneous
depolarization, decreases automaticity (particularly in the bundle of His and Purkinje system),
and speeds conduction at Purkinje fiber-myocardial junctions. Lidocaine raises the threshold
for ventricular fibrillation.
b. Absorption, excretion, and plasma levels. Lidocaine is poorly absorbed through the
gastrointestinal tract. In most instances the preferred route of administration is intravenous,
although the intramuscular route also is acceptable. There are two phases of lidocaine washout
from the circulation. Half-life for the first phase is less than 20 minutes and for the second
phase approximately 2 hours (thus, toxic levels may accumulate with repeated bolus dosages).
Usual effective plasma concentration is 2-5 micro-g/ml. Effective levels are achieved within
5-15 minutes after intramuscular injection and immediately after intravenous administration.

More than 90% of lidocaine metabolism occurs in the liver, and the agent should be
administered cautiously in the presence of liver disease.
c. Clinical uses and dosages. Lidocaine has widespread utility in the treatment of ventricular
arrhythmias. It is the drug of choice for acute treatment of VT and also the preferred drug for
ventricular arrhythmias accompanying MI. It is of limited utility in supraventricular
arrhythmias. Recommended dosages are as follows: IV, 50-100 mg, followed by a constant
infusion of 1-4 mg/minute; IM, 300 mg (yields therapeutic levels for up to 2 hours).
d. Toxic effects and contraindications. Lidocaine offers the advantage of essentially no cardiac
toxicity at therapeutic levels. Hypotension may occur at high serum levels. At toxic levels
there may be CNS disturbances including confusion and occasionally coma or respiratory
arrest. Seizures may result from high serum concentrations. The treatment for symptoms of
toxicity is discontinuance of the drug. Seizures are controlled with diazepam, 5-10 mg IV.
6. Phenytoin (Dilantin)
a. Electrophysiologic properties. Phenytoin shortens the duration of the action potential and
the effective refractory period. It depresses the rate of spontaneous depolarization and
decreases automaticity. It enhances conduction in the AV node and ventricle.
b. Absorption, excretion, and plasma levels. Phenytoin is well absorbed from the
gastrointestinal tract. Half-life for oral phenytoin is 24-36 hours. Half-life for intravenous
phenytoin is 4-6 hours. The drug is metabolized in the liver and excreted in the urine. Drugs
that induce the hepatic microsomal enzymes (e.g., warfarin) accelerate its excretion.
Therapeutic levels are 5-20 micro-g/ml.
c. Clinical uses and dosages. Phenytoin is the drug of choice for atrial or ventricular
arrhythmias provoked by digitalis toxicity. It is also effective for supraventricular arrhythmias
associated with digitalis. It is occasionally effective in ventricular arrhythmias not associated
with digitalis but is not useful for other supraventricular arrhythmias. Phenytoin may be
administered either orally or intravenously. The intravenous route is preferable in emergency
situations. Intramuscular administration is not recommended because of unpredictable
absorption. Intravenous phenytoin may be given as rapidly as 100 mg every 5 minutes up to a
total dose of 700 mg. Oral regimens usually involve 100 mg q6h. On this schedule, peak
levels are not achieved for 6-12 days.
d. Toxic effects and contraindications. The most common side effects of phenytoin are CNS
disturbances (drowsiness, nystagmus, vertigo). These side effects are generally not observed
until plasma levels exceed 20 micro-g/ml. Other manifestations of toxicity include
gastrointestinal upset, gingival hyperplasia (only after long-term use), and "pseudolymphoma"

(only after long-term use). A variety of toxic effects on the myocardium may be observed
after-too rapid intravenous administration: AV block, hypotension, asystole, and ventricular
fibrillation.
7. Propranolol (Inderal)
a. Electrophysiologic properties. Propranolol shortens the effective refractory period and the
action potential. It decreases automaticity. It has little effect on His-Purkinje system or
ventricular conduction, although it slows conduction through the AV node. Propranolol also
causes beta-adrenergic blockade.
b. Absorption, excretion, and plasma levels. Gastrointestinal absorption of propranolol
generally is good, although considerable differences exist among individuals. Intramuscular
administration of the drug is not recommended. Intravenous administration may be hazardous
and is reserved for emergency situations. Plasma half-life of propranolol is 3-6 hours. The
drug is metabolized in the liver (> 90%), and metabolites are excreted in the urine.
c. Clinical uses and dosages. Propranolol is effective in the treatment of both supraventricular
and ventricular arrhythmias. It may be employed as prophylaxis against atrial arrhythmias. It
is effective in the conversion of atrial flutter and paroxysmal atrial tachycardia (PAT) to sinus
rhythm. Propranolol is useful for slowing ventricular response to atrial fibrillation. It is
effective for ventricular arrhythmias caused by digitalis toxicity (second choice after
phenytoin) and may also be helpful in treating ventricular arrhythmias from other causes.
d. Toxic effects and contraindications. The beta-adrenergic blockade caused by propranolol
may precipitate excessive sinus bradycardia. The drug also has a direct depressant effect on
the myocardium and may precipitate or exacerbate congestive heart failure. It is
contraindicated in patients with bronchial asthma because of its tendency to produce
bronchospasm in these individuals. Other manifestations of toxicity include gastrointestinal
distress (nausea, vomiting), rash, drowsiness, lightheadedness, and mental depression.
8. Verapamil
a. Electrophysiologic properties. Verapamil is one of three "calcium" antagonists approved for
use in the United States. Of the others, nifedipine has little electrophysiologic activity.
Diltiazem can also be employed to control ventricular rate in atrial arrhythmias. Verapamil
blocks the slow inward current of depolarization (calcium-mediated). It suppresses normal
sinus and AV node activity by depressing the slope of diastolic depolarization. In most clinical
settings this action will not slow sinus rhythm because it is counterbalanced by sympathetic
stimulation caused by peripheral dilatation.

b. Absorption, excretion, and plasma levels. After intravenous administration effects on AV

node conduction are observed in 1-2 minutes. After oral dose measurable effects on AV
conduction begin to occur in 30 minutes and last as long as 6 hours. Effective plasma
concentrations to terminate SVT are approximately 125 ng/ml. Absorption is essentially 100%
following oral administration; however, bioavailability is only 35%, suggesting extensive
first-pass metabolism in the liver. Seventy percent of the drug is excreted by the kidneys with
an elimination half-life of 3-8 hours.
c. Clinical uses and dosages. Verapamil is the pharmacologic agent of choice for terminating
SVTs if vagal maneuvers fail. More than 90% of SVTs will be terminated in 2 minutes.
Verapamil will occasionally terminate AF or atrial flutter; it will slow ventricular response in
these rhythms. It is less effective for ventricular arrhythmias. Verapamil is administered 5-10
mg IV over 1-2 minutes. A second 10-mg dose may be given in 30 minutes. Constant infusion
may be maintained at 0.005 mg/kg/minute. Oral dosage is 80-120 mg given tid or qid.
d. Toxic effects and contraindications. Verapamil should be used cautiously in patients with
left ventricular dysfunction or sinus node disease and in patients being treated with beta
blockers. Contraindications include advanced heart failure, significant sinus node dysfunction,
cardiogenic shock, or second- or third-degree AV block. Verapamil may decrease digoxin
excretion by as much as 30%.
9. Bretylium tosylate (Bretylol)
a. Electrophysiologic properties. Bretylium causes an initial release of norepinephrine
followed by subsequent prevention of norepinephrine release. It causes significant increase in
VF thresholds and lengthens the action potential of proximal cells in the myocardial
conduction system.
b. Absorption, excretion, and plasma levels. Bretylium is approved only for parenteral use.
Gastrointestinal absorption is erratic, and bioavailability is less than 50%. Elimination is
100% by renal excretion. Elimination half-life is 5-10 hours.
c. Clinical uses and dosages. Bretylium is the fourth-line drug for life-threatening recurrent
tachyarrhythmias in the intensive care setting that do not respond to lidocaine, procainamide,
or quinidine. It may be more useful than lidocaine in helping to restore rhythm in VF but this
remains controversial. It is approved for parenteral use only. Bretylium is administered in
doses of 5-10 mg/kg diluted in 50-100 ml of 5% D/W and administered slowly over 10-20
minutes. During a cardiac arrest this dosage may be administered as an intravenous bolus over
2-3 minutes in an attempt to convert VF. Maintenance infusion is 0.5-2.0 mg/minute.

d. Toxic effects and contraindications. Hypotension (either orthostatic or in the supine patient)
is the most serious side effect. Transient hypertension caused by initial norepinephrine release
may occur. Nausea, vomiting, and parotid pain and swelling have been reported.
10. Amiodarone
a. Electrophysiologic properties. Amiodarone, when given orally, prolongs the refractory
period and action potential of all cardiac fibers. It prolongs the Q-T interval and may change
the contour of the T wave and produce U waves. Sinus rate is typically slowed 20-30%.
Intravenous administration results in less prolongation of conduction time (except in AV node)
and less prolongation of refractory periods.
b. Absorption, excretion, and plasma levels. Amiodarone is metabolized almost exclusively by
the liver with minimal plasma clearance and renal excretion. It is absorbed slowly and
incompletely with a bioavailability of 35-65%. It is accumulated in liver, fat, and lungs. Onset
of action following intravenous administration is typically 1-2 hours; following oral
administration, onset of action may not occur until 2-3 days or even 1-2 weeks. Loading doses
may decrease the period to onset of action. Since there is considerable variability among
patients in these pharmacokinetic parameters, close patient monitoring is essential.
c. Clinical uses and dosages. Some debate remains concerning optimal dosing schedules. One
commonly employed oral loading regimen starts with 800-1600 mg daily (in divided doses)
for 1-3 weeks followed by 800 mg daily for 2-4 weeks, then 600 mg daily for 4-8 weeks,
followed by a maintenance dose of 400 mg/day. Intravenous loading and dosage regimens are
under investigation and often involve a loading dose of 5-10 mg/kg over 20-30 minutes
followed by 1 gm/24 hours for several days. Amiodarone has been used to treat a wide
spectrum of supraventricular and ventricular tachyarrhythmias. It is typically successful in 6080% of PSVTs and 40-60% of VTs. Because of its long half-life, unpredictable absorption,
and the difficulty in starting another drug, amiodarone should be one of the last
antiarrhythmic agents tried for suppression of arrhythmias. It is often the final antiarrhythmic
tried when others have failed to control life-threatening ventricular arrhythmias.
d. Toxicity. Adverse effects occur in about 75% of patients receiving chronic amiodarone
therapy and require its discontinuance in 10-20% of patients. Pulmonary toxicity is the most
serious noncardiac toxicity and typically occurs within 30 months of initiation of therapy. It is
manifested by dyspnea, nonproductive cough, and infiltrates on chest radiography. It requires
cessation of the drug. The incidence of pulmonary toxicity is 5-15%. Asymptomatic
elevations in liver enzymes occur in most patients. The drug should be stopped if these
elevations exceed three times normal. Photosensitivity, hyperthyroidism and hypothyroidism,

and corneal microdeposits may also occur. Cardiac side effects include symptomatic
bradycardias in about 2% of patients and exacerbation of ventricular tachyarrhythmias in
about 2-3%. Drug interactions of amiodarone with other antiarrhythmics, warfarin, and
digoxin require monitoring and adjustment of doses of these other drugs.
11. Mexiletene
a. Electrophysiologic properties. Many of the electrophysiologic properties of mexiletene are
similar to lidocaine. It shortens the duration of the refractory period and action potential of
Purkinje fibers and depresses the automaticity of these fibers. It does not appear to alter the
refractory period of either atrial or ventricular muscle.
b. Absorption, excretion, and plasma levels. Peak plasma levels occur 2-4 hours after oral
administration. The bioavailability of the drug is approximately 90%. Mexiletene is
metabolized in the liver. Less than 10% is excreted unchanged in the urine. Therapeutic
plasma levels are 1-2 micro-g/ml.
c. Clinical uses and dosages. Recommended starting dose is 200 mg orally every 8 hours.
Dosage may be increased or decreased 50-100 mg every 2-3 days. Typical dosages are 200300 mg every 6-8 hours. Total daily dose should not exceed 1200 mg. Rapid loading may be
accomplished with an initial dose of 400 mg orally followed in 8 hours by 200 mg.
Mexiletene is effective for both acute and chronic ventricular tachyarrhythmias. It has had
widely variable reported success ranging from 6-60%. Its most important role may be as an
adjunct to other antiarrhythmics. It may also be an excellent choice for controlling ventricular
arrhythmias in patients with baseline prolonged Q-T intervals. It is often effective in
combination with quinidine or procainamide.
d. Toxicity. Adverse effects severe enough to warrant discontinuation of the drug may occur in
30-40% of patients. Most troublesome noncardiac effects are tremors, paresthesias, dizziness,
and dysarthria. Cardiac side effects include hypotension and bradycardia (seen most often
after intravenous administration) and exacerbation of ventricular arrhythmias.
12. Tocainide
a. Electrophysiologic properties. Tocainide is a primary amine analog of lidocaine with
electrophysiologic properties almost identical to lidocaine and mexiletene.
b. Absorption, excretion, and plasma levels. Peak plasma concentrations occur between 0.52.0 hours after oral administration. It is essentially 100% bioavailable. Approximately 40% of
the drug is excreted unchanged in the urine. Half-life is 11 hours.
c. Clinical usages and dosages. The fact that tocainide is an amine analog of lidocaine protects
it from first-pass elimination in the liver, making it an effective oral medication. It is slightly

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less effective than quinidine in suppressing VPBs. The response to intravenous lidocaine helps
predict the response to tocainide. If lidocaine has been ineffective, tocainide will be effective
in about 15% of patients. If lidocaine was effective, the success rate of tocainide increases to
60%. Typical oral regimens are 400-600 mg every 8 hours. Therapeutic plasma concentrations
range from 4-10 micro-g/ml. Dosage should be decreased in patients with renal, hepatic, or
cardiac insufficiency.
d. Toxicity. Side effects are similar to lidocaine, with gastrointestinal upset, memory
impairment, and tremors most prominent. Pulmonary fibrosis and aggravation of arrhythmia
have been reported in a small number of patients. Serious hematologic side effects including
agranulocytosis and bone marrow suppression have been reported in a small number of
patients.
13. Sotalol
a. Electrophysiologic properties. Sotalol hydrochloride has unique electrophysiologic
properties. It is indicated for treatment of a wide spectrum of ventricular arrhythmias. It also
has been shown to be of benefit in the treatment of supraventricular arrhythmias, although it
lacks official indication for this use. It possess two distinct properties -- a combination of
Class II and Class III antiarrhythmic activity, which distinguishes it from other antiarrhythmic
agents. Its Class II activity is characterized by beta-blocking properties. Its Class III activity is
characterized by selective lengthening of the effective refractory period and action potential
duration.
b. Absorption, excretion, and plasma levels. Sotalol is absorbed rapidly (2-3 hours) and
completely (>90%) through the gastrointestinal tract and has an oral bioavailability of almost
100%. It is eliminated primarily through the kidney. Approximately 75% of a single dose is
detected unchanged in the urine within 72 hours.
c. Clinical usage and dosages. No loading dose is necessary. Therapy is begun with 80 mg
twice a day. Most patients require maintenance doses of 240-300 mg/day. Occasional patients
require dosages as high as 480-640 mg/day. Maximum dose should not exceed 640 mg/day.
d. Toxicity. Sotalol may worsen preexisting diminished cardiovascular performance. It may
also prolong the acute QT interval and result in torsade de pointes.
C. Other antiarrhythmic agents
A variety of new antiarrhythmic agents have been introduced in the past 5 years. Some
possess properties similar to those of the drugs just discussed. Others operate by
fundamentally different mechanisms.

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1. Encainide. Encainide decreases action potential duration and phase 4 depolarization in

Purkinje fibers. It also decreases propagation velocity in atrial, ventricular, and Purkinje fibers
and prolongs atrial, accessory pathway, and ventricular refractory periods. It has minimal
myocardial depressant activity. Encainide is particularly useful for SVTs associated with AV
nodal reentry and WPW syndrome. It is effective in controlling VT in 25-30% of cases
refractory to conventional agents; however, its use is associated with torsades de pointes and
VF. It is only used for supraventricular arrhythmias. It is administered orally in a daily dose of
100-300 mg in four divided doses. It has a half-life of 3-4 hours. The most significant adverse
side effect is exacerbation of VT in approximately 10% of patients. Other adverse effects
include a metallic taste in the mouth, dizziness, paresthesias, diplopia, and vertigo.
2. Propafenone. The primary action of propafenone is to block the fast sodium channel. It
depresses sinus node automaticity and leads to A-H, H-V, P-R and QRS prolongation. It
increases the refractoriness of atrial, ventricular, and accessory pathway tissue. Dosages are
150-300 mg every 8-12 hours. It is 95% bioavailable. It is useful in both atrial and ventricular
arrhythmia suppression and WPW syndrome.
V. Electrical therapy of arrhythmias
A. Cardioversion
1. Theory and technique. The use of electrical cardioversion for the treatment of cardiac
arrhythmias is based on several theoretical considerations. First, although a variety of
mechanisms may be responsible for initiating a rhythm disturbance, once the disorder has
begun, it is frequently self-sustaining. Second, if the abnormal rhythm can be temporarily
interrupted, the sinus node, which has the highest intrinsic automaticity in the cardiac
conduction system, will have the opportunity to recapture the depolarization process.
Initial trials of electrical cardioversion in animals were attempted with alternating current.
Although this technique often successfully terminated arrhythmias, it resulted in an
unacceptably high risk of ventricular fibrillation and cardiac arrest. Modern defibrillation
equipment consists of a capacitor-discharge unit that delivers a direct-current electrical pulse
synchronized with the ECG at the most efficacious and least dangerous time during the
cardiac cycle.
Various protocols exist for performing cardioversion. It may be performed as an outpatient
procedure; however, many cardiologists prefer a brief hospitalization. If cardioversion is
being carried out on a patient with atrial fibrillation or flutter, quinidine, 300 mg q6h, is
administered 24-48 hours before the procedure. Premedication usually consists of IV

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diazepam (10-30 mg) administered in divided doses until the patient is asleep. The electrical
discharge is delivered by means of two paddles applied to the patient's chest. Initial electrical
setting is generally 5-10 watt-seconds. If reversion is not accomplished at this setting,
progressively higher energy levels are employed (25, 50, 100, 200, 300, and then 400 wattseconds).
2. Clinical uses
a. Atrial fibrillation. Atrial fibrillation is the most common indication for cardioversion.
Successful reversion to sinus rhythm (at least temporarily) can be expected in more than 90%
of cases. Patients who cannot be reverted generally have mitral valvular disease and
massively dilated atria. A left atrial diameter > 50 mm suggests that reversion to sinus rhythm
following cardioversion is less likely. Patients who have been in atrial fibrillation for more
than 5 years usually cannot be converted to sinus rhythm. Only one-third to one-half of
patients converted from atrial fibrillation to sinus rhythm will remain in sinus rhythm as long
as 1 year.
b. Ventricular tachycardia. VT is a medical emergency. Electrical cardioversion is the
treatment of choice and should be undertaken immediately, particularly if the arrhythmia is
accompanied by hypotension or pulmonary edema. The patient may be given a 50- to 100-mg
bolus of lidocaine IV while preparations for cardioversion are being made. Occasionally sinus
rhythm is restored by administration of this drug. Cardioversion is not indicated for short,
repetitive bursts of ventricular tachycardia, which respond better to treatment with lidocaine.
The implantable defibrillator (AICD) has been successfully employed in patients with
medically refractory ventricular tachycardia.
c. Atrial flutter. Cardioversion is highly effective in the treatment of atrial flutter. This
arrhythmia is easy to convert, often requiring less than 50 watt-seconds. A 24-hour trial of
quinidine may be attempted before cardioversion and frequently results in reversion to sinus
rhythm.
d. Supraventricular tachycardia. Supraventricular tachycardias require electrical conversion
only if they produce hemodynamic compromise. Otherwise, pharmacologic treatment should
be initially attempted. Arrhythmias resulting from digitalis toxicity generally do not respond
to cardioversion, and its application may be potentially dangerous in this setting. If the
possibility of digitalis toxicity exists, low-energy (5 watt-seconds) cardioversion should be
tried first, with subsequent cautious increases in energy. Some authors recommend
pretreatment with a bolus of lidocaine (50-100 mg IV) followed by a continuous infusion (2-3

13

mg/min) when attempting to cardiovert rhythm disturbances thought to be caused by digitalis

toxicity.
3. Complications and contraindications. Although the incidence of serious complications
resulting from cardioversion is low (3%), a variety of complications have been described, and
some well-defined contraindications to cardioversion exist. Difficulties with the technique can
be minimized by careful patient selection and cautious application of the technique.
Electrolyte abnormalities should be corrected before cardioversion. Patients suspected of
having digitalis toxicity should not be subjected to cardioversion. Patients should be
euthyroid. Cardioversion is contraindicated in the presence of third-degree AV block.
Intolerance to quinidine and failure to remain in sinus rhythm after previous cardioversion are
also contraindications. Some arrhythmias, including sinus tachycardia and multifocal atrial
tachycardia, respond poorly to cardioversion.
Incidence of embolic phenomena after cardioversion from atrial fibrillation is estimated at 12%. It has been argued that, whenever possible, patients with atrial fibrillation should be
anticoagulated before cardioversion.
B. Pacemaker therapy
Pacemaker therapy has assumed increasing importance since its introduction in 1960.
Technologic advances have occurred both in power sources and in electronic circuitry. Longlasting lithium batteries (6 years or more) are employed in most current pacemakers. Demand
pacemakers have largely supplanted earlier fixed-rate models. A new generation of AV
pacemakers and pacemakers that will track atrial contractions has made physiologic pacing
possible. Dual-chamber pacing is now often preferable to ventricular pacing. The clinical
criteria for permanent pacemaker therapy differ somewhat from those for temporary pacing,
and the two topics are discussed separately.
1. Permanent pacing
a. Clinical uses. The criteria for implantation of a permanent pacemaker are not rigid and
should be individualized. Symptoms such as syncope and hypotension accompanying certain
arrhythmias and conduction disturbances generally indicate the need for definitive therapy.
Permanent pacing may be indicated with third-degree AV block, second-degree AV block with
slow ventricular response, sinus bradycardia (if symptomatic), sick sinus syndrome, atrial
fibrillation with slow ventricular response, and persistent bifascicular or trifascicular block
after myocardial infarction.
b. Complications. The most common complication of permanent pacing is power source
failure. This is often heralded by 3-5 beat/minute slowing of the pacemaker rate. Other

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complications include broken pacing wires, infection, electrode displacement, and myocardial
perfusion.
2. Temporary pacing
a. Clinical uses. Temporary pacing may be indicated until a permanent pacemaker can be
implanted in any of the settings discussed in the previous section. Temporary pacing may also
be indicated (and lifesaving) in acute myocardial infarction. In anterior myocardial infarction,
emergency temporary pacing may be indicated in a variety of conditions.
In inferior MI, AV block generally reflects temporary ischemia of the AV node. Temporary
pacing may be indicated for extreme bradycardia or hypotension, since AV block in this
setting is likely to be transient. Temporary pacing can be performed in an emergency by
electrical energy delivered to the chest wall by a device known as the external pacemaker.
Dual-chamber pacing appears preferable to single-chamber pacing in any condition where
ventricular compliance is diminished. Such conditions include hypertension, hypertrophic
obstructive cardiomyopathy (HOCM), acute myocardial infarction, and right ventricular
infarction.