Download Clinical monitoring of antiarrhythmics in critical care

CLINICAL MONITORING OF ANTIARRHYTHMICS
IN CRITICAL CARE
By Jean-Luc Beaumont, nurse-clinician specialized in cardiovascular and
respiratory nursing
Antiarrrhytmics are an important pharmacological class of drugs used in cardiology. The
objective of this article is in particular to provide a greater understanding of the
mechanisms of action of antiarrhythmics and, consequently, the clinical monitoring of
expected outcomes. This article is divided into two parts. The first part,
electrophysiology, illustrates the relationship between the action potential of the
myocardial fiber and the point of impact of antiarrythmics. The second half,
antiarrythmics, provides a classification of antiarrhythmics as well as the mechanisms
of action of each class of antiarrythmics and their particularities, including clinical
monitoring.
PART ONE: ELECTROPHYSIOLOGY
In the myocardium, there is a system of specialized fibers which differ from contractile
fibers. Those fibers make up the nodal tissue and are composed of two types of cell
populations. Automatic cells generate cardiac impulses (automaticity). Conductive cells
propagate impulses through the conduction system (conductivity). The set of cells reacts
to a stimulus (excitability). These three properties make up the core of the cardiac
intrinsic nervous system (CINS). In addition, certain afferent fibers (sensitive) connected
to the electrical conduction system of the heart have an influence over cardiac
electrophysiology. The sympathetic system, under the influence of adrenaline, and the
parasympathetic nervous system, activated by acetylcholine, make up the extrinsic
nervous system and allow it to regulate the functioning of the heart.
The electrical activity of the heart is generated by strong ionic concentrations
disseminated throughout the cell membrane. A significant disruption in transmembrane
ionic transfer is a precursor of arrhythmias. The electric potential, the work and rest
activity of the cell, is recorded using micro-electrodes placed across the cellular
membrane. The electric potential produces a typical image called an action potential
(Figure 1).
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Figure 1: Phases of the action potential and transmembrane ionic flow
Source: J.-L. Beaumont (2006)
The action potential is subdivided into five phases (Figure 1).
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Phase 0, the first phase, corresponds to cell activation or depolarization. The
impulse is propagated to neighbouring cells thanks to an avalanche of sodium ions
(Na+) which penetrate the cell and favour automaticity. Those ions rapidly
circulate along the Na+ rapid-response fibers through specific channels. This type
of fiber which emits a sodium current mainly serves to activate the functioning of
the atrium, the His-Pukinje system and the ventricular muscle fibers (Figure 2).
The medications which are likely to inhibit Na+ entry (phase 0) into the cell
belong to Class 1 antiarrythmics, also known as sodium channel blockers
(Table 1). Phase 0 corresponds to the QRS complex on the surface ECG (Figure
3).
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Phases 1 and 2, the second and third phases, of the action potential correspond to
the initial repolarization of the cell. Sodium inactivation leaves room for calcium
entry into the cell. During these phases, the speed at which repolarization occurs
diminishes because of the intracellular exit of potassium channelling outside the
cell. This calcium current influences in particular the functioning of slow response
fibers located in the sinoatrial node and in the atrioventicular node (Figure 2).
During supraventricular tachychardia, the calcium blockers are choice indicators
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because those arrhythmias arise along the boundaries of fibers whose calciumtype action potential significantly influences the heart rate for the sinoatrial node
and the atrioventicular (AV) conduction for the AV node. The medications which
are likely to inhibit Ca+ entry (phase 0) into the cell belong to Class 4
antiarrythmics, also known as calcium channel blockers (Table 1). Phases 1
and 2 of the action potential correspond to the ST segment on the surface ECG
(Figure 3).
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Phase 3, the fourth phase of the action potential, corresponds to the terminal
repolarization of the cell. This phase results from an outward potassium (K+)
current which increases the duration of the action potential. At this stage, the fiber
recovers its initial rest charge. This phase corresponds to the T wave on the
surface ECG (Figure 3). Certain conditions may occasionally require controlling
the exits of intracellulaar potassium. This has the effect of extending the duration
of the action potential and, consequently, of the QT interval on the surface ECG
(Figure 3). The medications which alleviate the exits of K+ in the cell make up
Class 3 antiarrythmics known as potassium blockers (Table 1).
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Phase 4, the fifth phase of the action potential, is the time interval between two
action potentials. At this stage, the cell has recovered its rest potential or
membrane potential linked to the role of sodium and potassium. Enzymes help
provide the cell with the necessary energy for transmembrane ion exchanges.
Schematically, a heart beat can be superimposed over an action potential. Phase 4
of the action potential determines the heart rate. The shorter a phase 4 action
potential, the greater the action potential in a minute and the greater the number of
heart beats per minute. By comparing the action potentials of pacemakers
(sinoatrial node, bundle of His and the Purkinje fibers), the phase 4 of the
sinoatrial node is the shortest, which explains the dominance of the sinoatrial
node, hence the expression sinusal rhythm. Phase 4 corresponds to the end of the
T-wave and the beginning of the QRS complex on the surface ECG (Figure 3).
The sympathetic and parasympathetic systems interfere directly on the heart rate
and on AV conduction. Medications acting on phase 4 of the action potential
make up class 2 antiarrythmics, known as beta-adrenergic receptor blockers or
beta blockers (Figure 1).
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Figure 2: Electrical conduction system of the heart
Figure 3: Correlation among transmembrane ion movements, the action potential
and the surface ECG
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PART TWO: ANTIARRYTHMICS
Antiarrythmics act one way or another on the phases of the action potential by modifying
the permeability of the myocardial membrane to sodium, calcium and potassium ions.
They are subdivided into four classes according to the Vaughan Williams classification
(Table 1). Even though digitalis and adenosine have antiarrythmic properties, they will be
the subject of a complementary presentation.
Class I: Sodium Channel Blockers
Sodium current fibers activate the depolarization of the atrial fibers, of the His-Purkinje
system and of the ventricular fibers. The substances which are likely to reduce the
depolarization of those fibers are the key elements of this pharmacological class. The
common substances belonging to this class include procainamide (Pronestyl®) and
flecainide (Tombocor®).
Procainamide (Pronestyl®) is a choice indication for the pre-excitation syndrome which
is symptomatic of types such Wolff-Parkinson-White (WPW). During this syndrome, the
pulse circumvents the nodohisian pathway (His node) to reach the ventricles via
abnormal/accessory pathways which may favour major ventricular arrhythmias.
Procainamide slows depolarization down and, consequently, the conduction of accessory
pathways, which protects the ventricles. Clinical monitoring of the intravenous
administration principally aims to detect any reduction in the heart output, checking the
vital signs, and monitoring arrhythmias for emergency treatments. The effect on cell
repolarization can lead to an increase in the intervals of the QRS complex and the QT
interval. Any duration of the QRS complex that is superior to its initial value by 25% and
any duration of the QT interval which is superior by 0.44 seconds must be reported.
Flecainide (Tambocor®) is the most powerful antiarrhythmic of this class. Its effects are
an extension of cell depolarization time (phase 0) of the atrium, Purkinje network and
ventricle. A reduction in intraventricular conduction velocity can be observed. Flecainide
is particularly efficient in the absence of coronary artery disease for treating frequent
premature ventricular contractions (PVC) Clinical monitoring involves the checking of
vital signs, detecting the extension of the QRS interval on the ECG, and monitoring
major arrhythmia events. Increased surveillance is required when a bundle branch block
occurs. Flecainide is counter-indicated among people suffering from coronary disease
because it favours PVCs and ventricular tachycardia.
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Class II: Beta-Adrenergic Receptor Blockers or Beta-Blockers
These substances are an efficient competitor of catecholamines (noradrenaline,
epinephrine, adrenaline) because they occupy the receptor sites of these chemical
mediators. These receptors are subcategorized into Beta-1 and Beta-2. The Beta-1
adrenergic receptors are found in significant numbers in the heart; consequently, they
have a positive influence on automaticity, conductibility, excitability and contractility.
Beta-2 are predominant in the airway smooth muscle whose dominant effect is
bronchodilation.
The principal action mechanism of beta blockers consists in inhibiting the cardiac
stimulation of the beta-adrenergic receptors (sympatholytic effect) This action is carried
out by an extension of the phase 4 of the action potential. The sympatholytic effect on
the heart leads to a decrease in the heart rate (negative chronotropic effect), an extension
of the conduction time (negative dromotropic effect), a lower contraction force (negative
inotropic effect). In addition, automaticity is also altered (negative bathmotropic effect).
All beta blockers are essentially identical as regards cardiovascular therapeutic effects.
Certain beta blockers are cardioselective, meaning that they specifically act on Beta-1
receptors while inhibiting as little as possible the Beta-2 receptors, an important
advantage for clients suffering from bronchopneumopathies. The following beta blockers
share this property: acebutolol (Sectral®), atenolol (Tenormin®), bisoprolol (Monocor®),
metoprolol (Lopressor®). Considering the depression effect on the sinus, the AV node
and the ventricular functioning, the side effects of beta blockers could be exacerbated
when combined with substances whose negative bathmotropic, chronotropic and
dromotropic effects are similar such as: amiodarone (Cordarone®), diltiazem
(Cardizem®), flecainide (Tambocor™) and verapamil (Isoptin®).
Clinical monitoring is mainly based upon detecting symptomatic bradycardia, signs and
symptoms of low output syndrome and the extension of the PR interval. It remains
essential to check the vital signs. Concomitant medication deserves special attention
because it favours excessive bradycardia.
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Class III: Potassium Channel Blockers
Pharmacological substances belonging to this class block the intracellular exits of
potassium during phase 3 of the action potential. Repolarization thereby being extended,
certain re-entry arrhythmias associated with scar tissue can be inhibited because the
refractory or protection period is increased (Figure 3). The outcome of this action
mechanism leads to an increase in the QT interval. Substances belonging to this class
include: amiodarone (Cordarone®) and sotalol (Sotacor®).
Amiodarone (Cordarone®) is a powerful antiarrhythmic which prolongs the refractory
period and the repolarization of all cardiac tissues including the accessory pathways
during the pre-excitation syndrome. Because this substance groups together four classes
of antiarrhythmics, amiodarone indeed is the star of antiarrhythmics. It is the drug of
choice for ventricular tachychardia in cardiac emergencies.
The decrease in the heart rate (Class IV); the extension of the PR (Class II) QRS (Class I)
and, especially, QT (Class III) intervals are predictable electrocardiographic effects of
amiodarone. Sinus bradycardia conjugated with the extension of the QT interval make up
the pro-arrhythmic factors which are likely to favour torsades de pointes (lit. “twisting of
the points”).
Clinical monitoring consists of checking the vital signs and detecting any extension of
the PR, QRS and QT intervals. Amiodarone potentializes the effect of warfarin
(Coumadin®) and doubles the plasmatic concentration of digoxin. By its iodine content, it
can affect the functioning of the (hypo – hyper) thyroid gland. Potentially significant side
effects include liver damage, the formation of corneal micro-deposits (perception of halos
around lights), photosensitivity and a risk of developing pulmonary fibrosis.
Sotalol (Sotacor®) also has the properties of a non-selective beta-blocker. It is
administered orally in the treatment of supra-ventricular and ventricular arrhythmias
without heart injury. The torsade de pointes effect is reported in the range of 4%.
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Class IV: Calcium Channel Blockers
Phase 2 of the action potential corresponds to the plateau of the action potential. During
this phase, the calcium current leaves its mark in particular on the fibers of the sinoatrial
node and of the AV node by inhibiting the entry of calcium ions, which slows down
depolarization. The most dominant effects are a reduction in the heart rate and in AV
conduction; furthermore, the calcium blockers are cardiodepressive.
Antiarrhythmics belonging to this class include diltiazem (Cardizem®) and verapamil
(Isotopin®). These medications are used in the symptomatic treatment and/or diagnosis of
symptomatic supra-ventricular tachycardia. The negative chronotropic and dromotropic
effect of these substances is desirable. Hypotension arises from the relaxation of the
smooth musculation of vessels.
Diltiazem has an elimination half-life of 3 to 7 hours and a reduction in the heart rate
appears within 2 to 7 minutes following bolus administration. The elimination half-life of
verapamil may vary from 3 to 7 hours and the negative dromotropic effect occurs within
2 minutes following the bolus administration of the medication and lasts for 15 to 20
minutes. The bolus administration of these medications must be made at the proximal site
and followed by a bolus of 20 ml of NaCl. Clinical monitoring consists of checking the
vital signs and monitoring cardiac arrhythmias which are predictable owing to the
bradycardia and the extension of the PR interval. The detection of cerebral hypoperfusion
signs and symptoms must be reported.
Other Antiarrhythmics: Digoxin (Lanoxin®) and Adenosine (Adenocard®)
Even though digitalis is known for its antiarrhythmic properties and its sympatholytic
activity, it is a cardiotonic agent which is primarily indicated for heart failure.
Adenosine exists in every cell of the organism and is not related to the antiarrhythmics
presented herein. Intravenous administration increases potassium currents which also
impede the entry of calcium into the heart muscle. Adenosine is an antagonist of the
sympathetic system as regards the action potential of the ventricular myocardium. The
negative chronotropic and dromotropic effects on AV conduction are the major effects of
this medication.
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Adenosine is a primary choice of intervention for symptomatic surpraventricular
tachycardia. The post-administration therapeutic response can be evaluated within 30
seconds. The elimination half-life inferior to 10 seconds and the complete excretion of
the medication within 30 seconds are among the significant advantages of this
medication. Adenosine is counter-indicated among asthmatic patients.
Clinical monitoring requires rapid administration, 1 to 2 seconds, because a slower
administration may trigger reflex tachycardia. The bolus administration of this
medication must be made at the proximal site and followed by a bolus of 20 ml of NaCl
with the member elevated. The checking of vital signs and the detection of arrhythmias,
in particular pauses and conduction anomalies consecutive to sinoatrial node depression
and the extension of AV conduction, are essential. The heart rate and PR interval must be
recorded as well as any medicine-related post-administration symptom such as: hot
flashes, histamine flush, dyspnea and tightness of the chest. These symptoms generally
do not exceed one per minute.
Understanding, on the one hand, the action mechanisms which regulate the action
potential of the cardiac fiber and, on the other, the impact points of antiarrhythmics
justifies an optimal clinical monitoring of the clientele which responds to the indications
of this pharmacological class which is widely used in cardiology.
References
Beaumont, J.L. (2006). Les arythmies cardiaques un guide clinique et thérapeutique (5e
édition). Montréal : Chenelière Éducation.
* We hereby thank Dr. Marcel Gilbert, cardiologist and rhythmologist, of the Institute de
cardiologie de Québec, for supervising this article.
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FIGURE 4: CLASSIFICATION OF ANTIARRHYTHMICS
CLASS
ACTION MECHANISMS
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CLASS I
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Sodium channel
blockers
CLASS II
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Beta-adrenergic
receptor
blockers or beta
ƒ
blockers
CLASS III
Potassium
blockers
CLASS IV
Calcium
channel
blockers
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ƒ
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ƒ
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ƒ
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Blocks the rapid entry of sodium
Acts on phase 0 of the action
potential
Slows down the depolarization and
amplitude of the action potential in
rapid-conduction cells:
ƒ Atrium, His-Purkinje system
and ventricular muscle
Raises the equilibrium potential
Sympatholytic effect
Extends:
ƒ phase 4 of the action
potential
ƒ the refractory period of the
AV node
Decreases:
ƒ Sinusoidal rate
ƒ AV conduction
Blocks the potassium current
Acts on phase 3 of the action
potential
Prolongs repolarization
Potential pro-arrhythmic effect
Blocks the entry of calcium
Acts on phase 2 of the action
potential, in particular on the
sinoatrial node and the AV node
Reduces the conduction velocity in
the AV node
Slows down the heart rate
MEDICATIONS
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Procainamide:
Pronestyl®
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Flecainide: Tambocor®
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Acebutolol: Sectral®
Atenolol: Tenormin®
Bisoprolol: Monocor®
Metoprolol:
Lopressor®
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Amiodarone:
Cordarone®
Sotalol: Sotacor®
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Diltiazen: Cardizen®
Verapamil: Isoptin®
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