The management of cardiac arrhythmias requires familiarity with both the arrhythmia mechanism and the available pharmacologic and device approaches. Rhythm disturbances are related to abnormalities in the electrical impulse generation or conduction at the ion channel level of the cardiac pacemaker cells (native or ectopic). The Advanced Cardiac Life Support (ACLS) protocols provide a basic approach to the management of lifethreatening rhythm disturbances, but broader understanding is required for providing day-to-day patient care.1
The aim of this chapter is to overview the main pharmacologic options that are available in the management of rhythm disturbances.
In general, arrhythmias are divided into two broad categories: tachyarrhythmias (heart rate >100 beats per minute [bpm]) and bradyarrhythmias (heart rate <60 bpm). Tachyarrhythmias are broadly categorized as either supraventricular or ventricular tachycardias. The three main pathophysiologic mechanisms that explain tachyarrhythmias are reentry, increased automaticity, and triggered activity. Bradyarrhythmias are classified according to the anatomic level of abnormality in the conduction system (sinus node, atrioventricular [AV] node, or His-Purkinje system). Knowledge of the mechanism of action and the target tissue specificity (sinus node, atrial, AV node, ventricular) for each medication is pivotal in the management of the specific arrhythmia.
The Vaughan Williams classification3
of antiarrhythmic drugs designates four groups of drugs according to the predominant electrophysiologic mechanism of action:
Class I Sodium channel blockage and slowing of conduction velocity
Ia—Quinidine, procainamide, and disopyramide
Ib—Mexiletine, phenytoin, and lidocaine
Ic—Flecainide and propafenone
Class II β-Adrenergic receptor blocking medications that decrease catecholaminergic effect (e.g., propranolol, metoprolol)
Class III Potassium channel blockage with prolongation of repolarization (e.g., sotalol, amiodarone, bretylium)
TABLE 22.1 Medications for the Treatment of Bradyarrhythmias
Onset of Action
Acute Adverse Effects
0.5 mg every 3-5 min; maximum 3 mg
Blurry vision, palpitations, arrhythmias
0.02-0.06 mg bolus
Angina, palpitations, dyspnea
Class IV Calcium channel blockage with prolongation of conduction and refractory time (e.g., verapamil, diltiazem)
Of note, the classification does not account for the fact that some medications exhibit more than one mechanism of action (e.g., amiodarone blocks potassium, calcium, α- and β-adrenergic receptors). The classification also does not include several commonly used drugs such as atropine (muscarinic receptor blocker), adenosine (A1-receptor blocker), or digoxin (neurally mediated effects).
Treatment strategies in the management of rhythm disturbances depend on the patient’s presentation including history and the ECG tracing of the arrhythmia (preferably compared with a previous tracing) as well as his/her hemodynamic status. An aggressive approach is mandated if the patient is hemodynamically unstable including ventricular pacing for bradyarrhythmias and direct current (DC) cardioversion for tachyarrhythmias in conjunction with pharmacologic therapy.
MEDICATIONS FOR THE TREATMENT OF BRADYARRHYTHMIAS
Bradyarrhythmias may arise from dysfunction in the initiation or conduction of an electrical impulse as well as an increase in parasympathetic tone. The dysfunction may originate at the level of the sinus node, AV node, or His-Purkinje system. Cardiac Care Unit (CCU)admissions for symptomatic bradycardia commonly include high-degree AV blocks requiring ventricular pacing as a result of inherent conduction system disease (commonly degenerative), ischemia, or drug effect (overdose or decreased elimination). Other etiologies that may lead to bradycardia include increased vagal tone (vasovagal, increased intracranial pressure), infective endocarditis involving the aortic valve, Lyme disease, and infiltrative diseases. The most common medications used for the treatment of bradyarrhythmias are outlined in Table 22.1
. According to ACLS guidelines, atropine is the first-line agent used for symptomatic
bradycardia with certain exceptions (e.g., infranodal AV block) when it may be ineffective or even harmful. In those situations, chronotropic agents or temporary pacing is advised.4
Electrophysiologic actions: Atropine sulfate is an anticholinergic and parasympatholytic alkaloid agent that competitively antagonizes the muscarinic receptors. It is derived from the deadly nightshade plant (Atropa belladonna).
Pharmacokinetics: The onset of action after intravenous (IV) administration begins after 2 to 4 minutes and has a half-life of 2 to 3 hours. It is metabolized mainly in the liver and excreted in the urine.
: According to the ACLS guidelines,1
doses are 0.5 mg every 3 to 5 minutes, up to a total of 3 mg or 0.04 mg per kg. Dosages of <0.5 mg may be associated with paradoxical bradycardia.
Atropine is indicated for the treatment of acute symptomatic bradycardia (class IIa, level of evidence B) when the dysfunction is suspected to arise from the sinus node or the AV node. Atropine use in the setting of infranodal block, manifested with a wide QRS complex (e.g., Mobitz II AV block), may paradoxically increase the degree of block. The increase of the firing rate in the AV node “strains” the conduction system distally and prevents transmission of impulses. Atropine was frequently used during cardiac resuscitation but had been removed from the ACLS 2010 guidelines because of the lack of evidence.1
Heart transplant patients may not have any effect of the drug because of the lack of parasympathetic innervation.
Adverse effects: Anticholinergic side effects of atropine include flushing, dry mouth, decreased sweating, blurred vision, delirium, hallucination, as well as tachyarrhythmias.
Contraindication: Patients with glaucoma may develop acute angle closure glaucoma, and those with benign prostatic hypertrophy may develop urinary retention.
Electrophysiologic actions: Isoproterenol is not a commonly used drug nowadays as it is mainly used as a chronotropic agent in the electrophysiology lab and the CCU setting. It acts on the β1 – and β2-receptors, conveying chronotropic and inotropic effect. It may also cause peripheral vasodilatation because of β2 effect.
TABLE 22.2 Medications for the Treatment of Supraventricular Tachyarrhthmias
Onset of Action
Acute Adverse Effects
6 mg followed by 12 mg if needed
Dyspnea, flushing, chest pressure
0.5 mg followed by 0.25 mg × 2 every 6 hr
Conduction abnormalities, dizziness, nausea
15-20 mg over 2 min, second dose of 25 mg in 15 min if needed
Hypotension, bradycardia, AV block
2.5-5 mg over 2 min, second dose of 5-10 mg in 15 min if needed
Hypotension, bradycardia, dizziness
500 µ/kg bolus over 1 min, up to three boluses
2.5-5 mg every 2-5 min (maximum of 15 mg over 10-15 minutes)
Hypotension, bradycardia, worsening of heart failure
150 mg bolus over 10 min
1 mg/min for 6 hr, then 0.5 mg/min for 18 hr
Hypotension, bradycardia, heart block
Pharmacokinetics: The onset of action after IV administration begins after 1 to 2 minutes, has a half-life of 2.5 to 5 minutes, and is mainly metabolized by conjugation in the liver and lungs and excreted through the urine.
Dosage: Initial bolus of 0.02 to 0.06 mg, followed by continuous IV infusion, dose range: 2 to 10 µg per minute; titrate until response is achieved.
Indications: The drug is indicated for the treatment of bradyarrhythmias and refractory torsade de point VT storm (by decreasing the QT interval). The use of isoproterenol during cardiac resuscitation was replaced by epinephrine and dopamine.
Dopamine, epinephrine, and dobutamine are chronotropic agents that may be used to treat the bradyarrhythmias—they are discussed in length in Chapter 14