British Journal of Anaesthesia 93 (1): 86±94 (2004)

DOI: 10.1093/bja/aeh166 Advance Access publication May 14, 2004

Perioperative cardiac arrhythmias

A. Thompson1 and J. R. Balser1 2*
1
Department of Anesthesiology and 2Department of Pharmacology, D3300 Medical Center North,
Vanderbilt University School of Medicine, Nashville, TN 37232, USA
*Corresponding author. Department of Anesthesiology. E-mail: [email protected]

Br J Anaesth 2004; 93: 86±94

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Keywords: complications, arrhythmia; heart, arrhythmia

Cardiac arrhythmias are a signi®cant cause of morbidity and i.v. form.1 55 Although the molecular targets are distinctive,
mortality in the perioperative period. While literature on the drug receptor sites among the ion channel classes are
antiarrhythmic agent use in postoperative and non-surgical highly homologous, causing some of the `class overlap'
intensive care settings is expanding, randomized clinical (and clinical side-effects) associated with antiarrhythmic
trials examining the use of these agents in the perioperative therapy.
period are scarce. Nonetheless, as our understanding of the Drug effects on the surface ECG can be predicted from
relevant molecular targets for manipulating cardiac excit- their effects on the cardiac action potential, which in turn
ability grows, the range of options for treating arrhythmias result from activity towards molecular targets (Fig. 1). The
during surgery expands. In the sections that follow, these action potential represents the time-varying transmembrane
molecular targets are used as a basis for clinical manage- potential of the myocardial cell during the cardiac cycle. As
ment strategies for arrhythmias in adults during surgery and such, the ECG can be viewed as the ensemble average of the
anaesthesia. In addition, the controversy surrounding action potentials arising from all myocardial cells, and is
droperidol and its reported proarrhythmic effects will be biased toward the activity of the left ventricle because of its
addressed. Finally, since pacemakers and implantable greater overall mass. The trajectory of the cardiac action
cardioverter-de®brillators (ICD) have gained widespread potential is divided into ®ve distinct phases, which re¯ect
use in the treatment of tachyarrhythmias and bradyarrhyth- changes in the predominant ionic current ¯owing during the
mias, a basic understanding of their perioperative function cardiac cycle (Fig. 2). The current responsible for `phase 0',
and management is discussed. the initial period of the action potential, initiates impulse
conduction through the cardiac tissue. A critical feature of
arrhythmia management is the understanding that the
Basic science current responsible for impulse initiation in the atria and
ventricles differs from that of the sinoatrial (SA) and
Ion channel mechanisms atrioventricular (AV) nodes. In the atria and ventricles, the
Antiarrhythmic pharmacology is focused primarily on the impulse is initiated by Na+ current through Na+ channels.
cardiac ion channels and adrenergic receptors as drug Hence, drugs that suppress Na+ current (class I agents,
targets. The number of drug targets for antiarrhythmic Fig. 1) slow myocardial conduction and prolong the QRS
therapy is expanding exponentially, and detailed discussion complex (ventricle) and the P wave (atrium). In AV and SA
is provided in recent reviews.41 Recognizing this com- nodal cells, phase 0 is produced by Ca2+ current through
plexity, it is still useful to consider the ion channel targets in L-type Ca2+ channels. Drugs that suppress Ca2+ current
three general classes (based on the cation they conduct): therefore slow the atrial rate (by acting on the SA node), and
sodium (Na+), calcium (Ca2+) and potassium (K+) channels. also slow conduction through the AV node. The latter effect
Virtually all drugs that modulate the heart rhythm work prolongs the PR interval on the ECG, making the AV node a
through the adrenergic receptor/second-messenger systems, more ef®cient `®lter' for preventing rapid trains of atrial
through one or more of the ion channel classes, or both. The beats from passing into the ventricle (hence the rationale for
classi®cation scheme provided (Table 1) is not exhaustive, AV nodal blockade during supraventricular tachyarrhyth-
but lists the agents currently available for use in the US in mias (SVT), see below). Because Ca2+ currents do not

Ó The Board of Management and Trustees of the British Journal of Anaesthesia 2004
 Perioperative cardiac arrhythmias

Table 1 Antiarrhythmic agents principally used in anaesthesiology and critical

care, listed by their molecular targets. Classi®cation by functional effect
according to the Vaughan Williams scheme 2 is also provided. *Available
commercially in oral form only. (Modi®ed Balser JR. Perioperative management
of arrhythmias. In: Barash PG, Fleisher LA, Prough DS, eds. Problems in
Anaesthesia. Lippincott-Raven, Philadelphia, 1998; Vol 10(2): 199)

Receptor Class2 Drugs

Na+, K+ channels IA Procainamide, quinidine, amiodarone

Na+ channels IB Lidocaine, phenytoin, *mexiletine, *tocainide
Beta adrenoceptors II Esmolol, amiodarone, propranolol, atenolol,
*sotalol
K+ channels III Bretylium, ibutilide, *sotalol, *dofetilide
Ca2+ channels IV Verapamil, diltiazem, amiodarone

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initiate impulse propagation in the atria and ventricles, these
agents only slow the ventricular response to atrial
tachycardia, and usually do not acutely terminate arrhyth- Fig 1 The action potential in ventricular muscle and its temporal
mias arising in either the atrium or the ventricle. relationship with the surface ECG. The QRS interval is related to the rate
The later phases of the action potential (phases 1, 2 and 3; of upstroke of the action potential, which partly determines the rate of
impulse conduction through the ventricular myocardium. The QT interval
Fig. 1) inscribe repolarization. The long plateau (phase 2) is
is related to the length of the action potential (the absolute refractory
maintained by Ca2+ current and is terminated (phase 3) by period). The phases of the action potential are indicated, as are the major
K+ current. Hence, the QT interval on the ECG re¯ects the ionic currents (I) that ¯ow during each phase. The dotted lines indicate
length of the action potential, and is determined by a anticipated effects on the action potential and ECG when drugs suppress
delicate balance between these and many other smaller either the sodium (Na+) current (class IA or IB) or potassium (K+)
current (class IA or III). ACh, acetylcholine; Ado, adenosine; Cl,
inward and outward currents. Drugs that reduce Ca2+ chloride; To, transient outward K+ current; Ks, slow component of
current, namely those with class II or class IV activity, recti®er K+ current; Kr, rapid component of recti®er K+ current.
abbreviate the action potential plateau, shorten the QT (Adapted from Balser JR. Perioperative management of arrhythmias. In:
interval and reduce the inward movement of Ca2+ into the Barash PG, Fleisher LA, Prough DS, eds. Problems in Anaesthesia.
Lippincott-Raven, Philadelphia, 1998; Vol 10(2): 199.)
cardiac cell. Hence, all agents that reduce Ca2+ current have
the clinical potential to act as negative inotropes.
Conversely, agents with class IA or III activity block
rate, but does not terminate. Similarly, atrial tachycardias
outward K+ current, prolonging the action potential and the
that result from enhanced phase 4 depolarization will
QT interval on the ECG. The electrophysiological mani-
transiently slow, but rarely cease. Atrial tachycardia due to
festations of QT prolongation may be either therapeutic or cAMP-mediated triggered activity in the SA node is a
arrhythmogenic, as discussed below (Re-entry, automaticity rare exception, where adenosine-mediated inhibition of
and arrhythmias). adenylate cyclase sometimes terminates the arrhythmia.16
During phase 4 (Fig. 1) the properties in SA and AV Conversely, SVTs that utilize the AV nodal tissue as a
nodal tissue are again distinctive from those in atrial and substrate for re-entry are terminated by bolus adenosine
ventricular muscle. Nodal cells spontaneously depolarize administration (Table 2). Junctional tachycardias, common
(`pace'), and activation of the adenosine A1 receptor during the surgical period, also sometimes convert to sinus
triggers outward K+ currents5 that hyperpolarize the nodal rhythm in response to adenosine. Ventricular arrhythmias
cell and oppose pacing. Since atrial and ventricular tissues exhibit no response to adenosine since these rhythms
are normally hyperpolarized, adenosine has little or no originate in tissues distal to the AV conduction pathway.
effect in these tissues. However, in SA and AV nodal tissue, The vasodilatory properties of adenosine, and all other AV
adenosine slows the SA node (reducing the sinus rate) and nodal blocking agents used for rate control in SVT, may be
blocks conduction through the AV node, creating `transient' harmful in patients with `stable' ventricular tachycardias
third-degree AV block. Adenosine also slows nodal con- (VT) because of their marginal haemodynamic stability.
duction by inhibiting Ca2+ current through reducing cyclic Hence, i.v. adenosine is no longer recommended as a means
AMP (cAMP). to distinguish wide-complex SVT from VT.2
These transient and speci®c effects make adenosine a
choice agent for terminating SVT that involves SA or AV
node re-entrant pathways, and it is therefore possible to Re-entry, automaticity and arrhythmias
classify supraventricular arrhythmias according to their
response to adenosine (Table 2).16 SVT due to re-entry in Re-entry
atrial tissue, such as atrial ¯utter or ®brillation, responds to Re-entry is a mechanism that may precipitate a wide variety
adenosine with transient slowing of the ventricular response of supraventricular and ventricular arrhythmias, and implies

87
 Thompson and Balser

Table 2 The response of common supraventricular tachyarrhythmias (SVT) to i.v. adenosine. AV, atrioventricular; WPW, Wolff±Parkinson±White. (Adapted
from Balser JR. Perioperative management of arrhythmias. In: Barash PG, Fleisher LA, Prough DS, eds. Problems in Anaesthesia. Lippincott-Raven,
Philadelphia, 1998; Vol 10(2): 201)

SVT Mechanism Adenosine response

AV nodal re-entry Re-entry within AV node Termination

AV reciprocating tachycardias Re-entry involving AV node and accessory pathway Termination
(orthodromic and antidromic) (WPW)
Intra-atrial re-entry Re-entry in the atrium Transiently slows ventricular response
Atrial ¯utter/®brillation Re-entry in the atrium Transiently slows ventricular response
Other atrial tachycardias 1 Abnormal automaticity 1 Transient suppression of the tachycardia
2 cAMP-mediated triggered activity 2 Termination
AV junctional rhythms Variable Variable

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the existence of a pathological circus movement of electical prolonging agents appear to be acquired manifestations of
impulses around either an anatomic (i.e. Wolff±Parkinson± the same molecular mechanisms involved in forms of the
White syndrome) or functional (i.e. myocardial ischaemia) congenital long-QT syndrome.47 To extend this connection
loop. Fibrillation, in either the atrium or ventricle, is further, `silent' mutations have been identi®ed in the protein
believed to involve multiple coexistent re-entrant circuits of substituents of K+ channels that do not cause excessive QT
the functional type. These re-entrant loops may result from prolongation unless patients are also exposed to K+-channel
disparities in either the repolarization rates or conduction blocking drugs.3 These mutations sensitize the cardiac cell
rates between normal and ischaemic myocardium, or even to K+-channel blockade, and provide a pharmacogenetic
from refractory period differences between epicardial and rationale for the `idiosyncratic' incidence of torsade upon
endocardial layers.32 Unfortunately, our understanding of exposure to QT-prolonging drugs.44 (See also Ventricular
re-entry and its pharmacological termination by ion channel arrhythmias below and Table 4.)
current suppression is incomplete. Drugs can terminate re-
entry through at least two mechanisms. Agents that suppress
currents responsible for phase 0 of the action potential (INa Supraventricular arrhythmias
in atrium and ventricle, ICa in the SA and AV node, Table 1)
may slow or block conduction in a re-entrant pathway, and Acute management of perioperative supraventricular
thus terminate an arrhythmia. Alternatively, by prolonging arrhythmias
the action potential, drugs with K+ channel blocking activity A cascade of adverse physiological phenomena can pre-
(Table 1) prolong the refractory period of cells in a re- cipitate SVT in critically ill or anaesthetized patients. The
entrant circuit, and thus `block' impulse propagation management of the surgical patient who suddenly develops
through the circuit. In clinical trials, agents operating SVT requires a thorough but rapid consideration of potential
through this latter mechanism have proven to be more aetiologies. Aetiology should be considered before therapy
successful in suppressing ®brillation.34 is instituted, except in cases of extreme haemodynamic
instability. SVT is among the clinician's most valuable
Automaticity warning signs, often foreshadowing life-threatening condi-
This refers to abnormal depolarization of atrial or tions that may be easily corrected (Table 3). Antiarrhythmic
ventricular muscle cells during periods of the action therapy should only be considered after these aetiologies
potential normally characterized by repolarization (phases have been excluded. Patients with narrow complex
2 or 3) or rest (phase 4). Studies over the last decade have tachycardias who are dangerously hypotensive (e.g. loss
identi®ed some of the key molecular substrates that underlie of consciousness, cardiac ischaemia, or a systolic pressure
triggered automaticity. Although K+ channel blockade is below 80 mm Hg) require immediate synchronous DC
highly effective for treating certain arrhythmias in the cardioversion in order to prevent the life-threatening
atrium and ventricle, delaying repolarization (manifest as complications of hypoperfusion, such as central nervous
prolongation of the QT interval) may at the same time system or cardiac ischaemia. While some patients may only
provoke ventricular arrhythmias in 2±10% of patients. Low respond transiently to cardioversion in this setting (or not at
serum potassium concentrations slow the heart rate, and K+- all), a brief period of sinus rhythm may provide valuable
channel blocking drugs (class IA or III) synergistically time for correcting the reversible causes of SVT (discussed
induce a polymorphic VT known as `torsades de pointes'.45 above), instituting pharmacological therapies, or both. In
Similarly, mutations in ion channels critical to repolariza- less urgent cases, adenosine may be administered as a 6 mg
tion have also been identi®ed in the genes of patients with i.v. bolus (repeated with 12 mg if no response). In practice,
inherited forms of the long-QT syndrome.41 Hence, the the SVTs most commonly seen in the perioperative period
proarrhythmic features of drug therapy with repolarization- (such as atrial ®brillation, Table 2) do not involve the AV

88
 Perioperative cardiac arrhythmias

Table 3 Reversible causes of supraventricular tachycardias and non- render it titratable on a minute-by-minute basis,9 allowing
sustained ventricular tachycardia. Listed are some of the most common
conditions in the operating room environment that predispose patients to meaningful dose adjustments during periods of surgery that
arrhythmias. These conditions are usually reversible, and should be treated provoke changes in haemodynamic status (i.e. bleeding,
before considering use of pharmacological antiarrhythmic therapies abdominal traction). While esmolol is largely b1-receptor
Hypoxaemia selective and is generally well tolerated by patients with
Hypercarbia chronic obstructive lung disease, the drug has obligatory
Acidosis
Hypotension
negative inotropic effects that may not be well tolerated in
Electrolyte imbalances patients with severe left ventricular dysfunction. Both i.v.
Mechanical irritation verapamil and i.v. diltiazem are calcium channel blockers
Pulmonary artery catheter
Chest tube
that are less easily titrated than esmolol but nonetheless
Hypothermia provide rapid slowing of the ventricular rate in SVT within
Adrenergic stimulation (light anaesthesia) minutes. The agents are therapeutically equivalent for
Proarrhythmic drugs
purposes of AV nodal blockade,46 but i.v. diltiazem has

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Micro/macro shock
Cardiac ischaemia less negative inotropic action and is preferable in patients
with heart failure.7 57 Thus, for patients with congestive
heart failure, digitalis, diltiazem and amiodarone are all
recommended for rate control management of SVT.2 In a
node in a re-entrant pathway, and AV nodal block by prospective randomized study of 60 patients in a cardiology
adenosine will therefore produce only transient slowing of intensive care unit who had atrial arrhythmias and heart
the ventricular rate. According to the 2000 American Heart rates over 120 beats min±1, diltiazem was found to have
Association guidelines, adenosine is no longer recom- better heart rate control than amiodarone (load and load plus
mended to differentiate wide-complex SVT from ventricu- infusion); however, diltiazem was more frequently discon-
lar tachycardias because of its vasodilatory properties.2 tinued because of hypotension.10 I.V. digoxin slows the
Patients with underlying structural heart disease are at ventricular response during SVT through its vagotonic
greatest risk for developing either supraventricular or effects, but should be either substituted or temporarily
ventricular arrhythmias during the induction of anaesthesia supplemented with other agents because of its slow onset
secondary to hypotension, autonomic imbalance or airway (about 6 h).53
manipulation.56 In addition, during cardiac or major vascu- Paroxysmal SVT (PSVT) due to re-entrant circuits that
lar surgery, patients may experience SVT during dissection involve accessory pathways (congenital electrical connec-
of the pericardium, placement of atrial sutures or insertion tions between the atrium and ventricle that bypass the AV
of the venous canulae required for cardiopulmonary bypass. node, such as Wolff±Parkinson±White Syndrome) pose
If haemodynamically unstable SVT occurs during cardiac caveats in the management of SVT. A detailed discussion of
surgery, the surgeon will usually attempt open synchronous this interesting subgroup is beyond the scope of this review.
DC cardioversion. However, in patients with critical However, it should be noted that patients with accessory
coronary lesions or severe aortic stenosis, SVT may be pathways, in addition to PSVT, may also develop atrial
refractory to cardioversion and provoke a malignant cascade ®brillation, and in the latter situation are at increased risk for
of ischaemia and worsening arrhythmias that requires the developing ventricular ®brillation (VF) upon exposure to
institution of cardiopulmonary bypass. Hence, early prepar- classic AV-nodal blocking agents (digoxin, calcium channel
ation for cardiopulmonary bypass is recommended before blockers, beta blockers, adenosine) because these agents
inducing anaesthesia in cardiac surgery patients who are at reduce the accessory bundle refractory period. In such cases,
exceptionally high risk for SVT and consequent haemo- i.v. procainamide, which slows conduction over the acces-
dynamic deterioration. sory bundle, is an acceptable option. Flecainide and
The majority of patients who develop intraoperative SVT amiodarone should also be considered, and cardiology
remain haemodynamically stable and do not require consultation may be helpful.2
cardioversion. Ventricular rate control is the mainstay of
therapy for SVT that does not require immediate DC
cardioversion. The advantages of slowing the ventricular Chemical cardioversion of SVT
rate during SVT are twofold. First, lengthening diastole Efforts to chemically convert SVT to sinus rhythm using
serves to enhance left ventricular ®lling, thus enhancing antiarrhythmic agents in the operating room should be
stroke volume and improving haemodynamic stability. aimed at those patients who cannot tolerate (or do no
Second, slowing the ventricular rate reduces myocardial respond to) rate control therapy, or who fail DC cardio-
oxygen consumption and lowers the risk of cardiac version and remain haemodynamically unstable. For
ischaemia. Intraoperatively, rate control is readily achieved intraoperative patients who are stable and rate controlled
with one of a variety of AV nodal blockers (agents with in SVT, the wisdom of chemical cardioversion is question-
class II or IV activity, Table 1). Among the i.v. beta able. First, the 24 h rate of spontaneous conversion to sinus
blockers, esmolol has ultra-rapid elimination properties that rhythm for recent-onset perioperative SVT exceeds 50%,

89
 Thompson and Balser

and many patients who develop SVT under anaesthesia will exceeding 100 beats min±1 and last 30 s or less without
remit spontaneously before or during emergence. Moreover, haemodynamic compromise. These arrhythmias are
most of the antiarrhythmic agents with long-term activity routinely seen in the absence of cardiac disease, and may
against atrial arrhythmias have limited ef®cacy when not require drug therapy in the perioperative period.
utilized for rapid chemical cardioversion. While 50±80% Conversely, in patients with structural heart disease, these
ef®cacy rates are cited for many i.v. antiarrhythmics in non-sustained rhythms do predict subsequent life-threaten-
uncontrolled studies, these ®ndings are largely an artifact of ing ventricular arrhythmias.29 However, particular anti-
high placebo rates of conversion. For example, the ef®cacy arrhythmic drug therapies in patients with structural heart
of i.v. procainamide for conversion of SVT has not been disease and NSVT may either worsen (encainide, ¯ecai-
established in placebo-controlled trials.43 Moreover, a nide)13 or improve (amiodarone)49 survival.
placebo-controlled trial of patients with atrial ®brillation NSVT occurs in nearly 50% of patients during and after
recently found a 60% 24 h conversion rate for patients in the cardiac and major vascular surgery, but does not in¯uence
placebo arm, statistically indistinguishable from that of early or late mortality in patients with preserved left

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patients treated with i.v. amiodarone (68%).18 Although ventricular function.4 39 50 These patients usually do not
improved rates of chemical cardioversion are seen with high require antiarrhythmic drug therapy; however, their arrhyth-
doses of i.v. amiodarone (approximately 2 g per day),27 the mias, like SVT, may signal reversible aetiologies that
potential for undesirable side-effects in the operating room should be treated (Table 3). Conversely, nearly 2% of
requires further study. patients experience sustained VT or VF after cardiac
While the most effective agents for converting atrial surgery,4 28 54 and low cardiac output following CABG
®brillation are K+ channel blockers that prolong atrial (requiring pressor support) has been identi®ed as an
repolarization, the use of these agents is hampered by the independent predictor of life-threatening VT/VF within
proarrhythmic risk inherent in coexistent prolongation of 72 h of surgery.14 In most cases, symptoms of postoperative
ventricular repolarization (manifest as QT prolongation and ischaemia are not apparent, although one trial did identify
torsades de pointes). Ibutilide, a rapid-acting antiarrhyth- saphenous vein graft failure at angiography in three out of
mic, produced a 31% rate of conversion in non-surgical seven patients experiencing unanticipated VT/VF, suggest-
patients with atrial ®brillation, with a mean time from ing that subclinical graft occlusion is a frequent aetiology of
treatment to conversion of only 27 min.51 Unfortunately, postoperative VT/VF.54 After aortic valve replacement, a
rates of torsades de pointes as high as 8% have been retrospective analysis found that patients who died un-
reported, and the risk/bene®t ratio for i.v. ibutilide use in expectedly had an elevated incidence of NSVT on their
periopertive SVT remains questionable. Intraoperative postoperative ECG (44%) compared with survivors (10%,
elective DC cardioversion in an otherwise stable patient P<0.05).48 Nonetheless, the incidence of NSVT after aortic
with SVT also carries risks (VF, asystole, stroke). valve replacement approaches 50%,36 and the role for
Moreover, the underlying factors provoking SVT during electrophysiological diagnostic evaluation in this popula-
or shortly after surgery are likely to persist beyond the time tion has not been clari®ed.
of cardioversion, inviting recurrence.56 A recent trial of There are few studies available to guide therapeutic
patients with SVT (mainly atrial ®brillation) who had decision-making for patients with ventricular arrhythmias in
undergone coronary artery bypass grafting (CABG) did ®nd the early postoperative period. While NSVT has not been
that low-energy DC cardioversion (utilizing indwelling linked to increased morbidity or mortality after cardiopul-
atrial pacing leads) was 80% effective and minimized monary bypass, unstable patients with marginal perfusion
sedation requirements, but the rate of recurrence within may deteriorate with recurrent episodes of NSVT (problem-
1 min was nearly 50%.31 Hence, when elective DC atic ventricular pacing or intra-aortic balloon counter-
cardioversion is considered, it may be prudent to ®rst pulsation) and may bene®t from suppression with
establish a therapeutic level of an antiarrhythmic agent that lidocaine26or beta blockade.4 50 In addition, repletion of
maintains sinus rhythm (i.e. procainamide, amiodarone) in post-bypass hypomagnesaemia (MgCl2 2 g i.v.) reduces the
order to minimize the risk of SVT recurrence following incidence of NSVT after cardiac surgery,17 and is now
electrical cardioversion. standard at most centres. A retrospective evaluation has
suggested a survival bene®t with electrophysiological-
guided prophylaxis in post-CABG patients with low ejec-
Ventricular arrhythmias tion fraction who survive an episode of sudden cardiac
death,25 although a de®nitive role for prophylactic anti-
Non-sustained ventricular arrhythmias
arrhythmic drug therapy in this setting has not been
Ventricular arrhythmias can be subdivided according to evaluated prospectively. A multicentre trial (CABG Patch)
their morphology (monomorphic vs polymorphic) and their found no survival advantage with implantation of a cardiac
duration (sustained vs non-sustained). Non-sustained ven- de®brillator in high-risk patients (those with low ejection
tricular tachycardia (NSVT) is de®ned as three or more fractions) at the time of elective cardiac surgery.6 Hence,
premature ventricular contractions that occur at a rate identi®cation of effective strategies for preventing ventri-

90
 Perioperative cardiac arrhythmias

cular arrhythmias after thoracic surgery is an ongoing Drug selection for acute management of unstable VT
challenge. and VF
Sustained VT generally falls into one of two categories: The necessity to treat life-threatening arrhythmias in the
monomorphic and polymorphic. In monomorphic VT, the
operating room is self-evident, and in this setting the risks of
amplitude of the QRS complex remains constant, while in
drug therapy would appear to be small. However, objective
polymorphic ventricular tachycardia the QRS morphology
evidence to support the notion that i.v. antiarrhythmic
continually changes. The best understood mechanism for
therapy improves survival during cardiac arrest has
monomorphic VT is formation of a re-entrant pathway
developed only recently. The most important ®rst
around scar tissue from a healed myocardial infarction.33
manoeuvres in patients who experience VF intraoperatively
Although lidocaine has traditionally been the primary drug
are non-pharmacological and are nearly the same as those
therapy for all sustained ventricular arrhythmias, a recent
utilized in haemodynamically destabilizing SVT: rapid
study of 29 patients with haemodynamically stable mono-
de®brillation (as opposed to synchronous cardioversion in
morphic VT found termination within 24 h was more

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SVT), and correction of reversible aetiologies (Table 3).
common with i.v. procainamide therapy (12 out of 15
In the realm of pharmacological intervention, there are no
patients) than with i.v. lidocaine (3 out of 14; P<0.01).19
human clinical studies available to suggest that i.v.
I.V. amiodarone is also recommended for management of
lidocaine, the putative Na+-channel blocker most often
monomorphic VT.2
used during intraoperative cardiac arrest, promotes the
In contrast, the therapeutic approach for polymorphic VT
conversion of sustained VT or VF to sinus rhythm in any
depends critically on whether the QT interval during a prior
interval of sinus rhythm was prolonged. Polymorphic VT in setting. Recent evidence-based recommendations by the
the setting of a normal QT interval usually occurs in a American Heart Association have therefore changed the
setting of ischaemia or structural heart disease, although recommendation for lidocaine to `indeterminate', below
idiopathic cases are seen.15 The rhythm degenerates into amiodarone and procainamide. In support of this change, a
VF; pharmacological management is discussed in the recent prospective trial in Seattle, WA, USA (ARREST)
section below. Conversely, polymorphic VT in the setting examined the ef®cacy of i.v. amiodarone compared with
of a prolonged QT interval (torsades de pointes) is focused placebo (the amiodarone carrier) in patients experiencing
at reversal of the QT prolongation. As discussed above, a out-of-hospital cardiac arrest due to pulseless VT or VF
predisposition to torsades may be inherited and usually refractory to DC cardioversion.30 Of the 504 patients
manifests as an acquired complication of therapy with drugs enrolled, those who received amiodarone had a higher
that prolong the QT interval. In addition to QT-prolonging survival to hospital admission (44% vs 34%, P=0.03). These
antiarrhythmic drugs (class IA or III), a number of other were the ®rst randomized prospective data to show a short-
medications used in the perioperative period may evoke QT term survival advantage to the use of an antiarrhythmic
prolongation and torsades de pointes (see, for example, agent during cardiac arrest. A more recent comparable study
www.Torsades.org/druglist.cfm for a current on-line in Toronto (ALIVE) compared amiodarone with lido-
summary). caine.11 Enrollment required VF resistant to three shocks,
The management of torsades de pointes differs markedly epinephrine and a fourth shock, or alternatively recurrent
from other forms of VT, and includes i.v. magnesium sulfate VF after initially successful de®brillation. The lidocaine
(2±4 g), repleting potassium, and manoeuvres aimed at group was treated with lidocaine 1.5 mg kg±1 and placebo
increasing the heart rate (atropine, isoprenolol or temporary amiodarone, followed by a second dose of lidocaine 1.5 mg
atrial or ventricular pacing). Haemodynamic collapse with kg±1 if de®brillation was not successful. The amiodarone
torsades requires asynchronous DC countershocks. When group received amiodarone 5 mg kg±1 and placebo
antiarrhythmic therapy is deemed necessary, agents devoid lidocaine, followed by amiodarone 3.5 mg kg±1 if the
of K+-channel blocking properties such as lidocaine or de®brillation was not successful. Of the 347 patients
phenytoin (Table 1) are usually chosen to avoid further enrolled, 22.8% in the amiodarone-treated group survived
prolongation of the QT interval.42 In practice, it may be to hospital admission, compared with 12% of the lidocaine
relatively unclear whether an observed episode of poly- group (P=0.0083).
morphic VT is related to QT-interval prolongation. In such There was no signi®cant advantage to amiodarone
cases, magnesium and Na+-channel blocking agents may be therapy in survival to hospital discharge in either
administered empirically. Among the antiarrhythmic agents ARREST or ALIVE. At the same time, neither study
that prolong the QT interval, the incidence of torsades de controlled the elements of patient management after
pointes is lowest with amiodarone;35 hence, i.v. amiodarone emergency room admission, and both trials were under-
may be a rational alternative therapy for refractory powered for detecting longer-term survival differences. In
polymorphic VT of unclear aetiology. The risk of pro- ALIVE, the time between cardiac arrest and administration
arrhythmic events may be increased by the simultaneous use of drug also in¯uenced survival to hospital admission. In the
of more than one antiarrhythmic agent, and should be amiodarone group, short-term survival for those treated
avoided if possible. within 24 min was 28%, vs only 18% for those receiving

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 Thompson and Balser

Table 4 Droperidol black box warning, issued by the US Food and Drug Administration in December 2001. http://www.fda.gov/medwatch/safety/2001/
safety01.htminapsi

WARNING
Cases of QT prolongation and/or torsade de pointes have been reported in patients receiving INAPSINE at doses at or below recommended doses. Some cases have
occurred in patients with no known risk factors for QT prolongation and some cases have been fatal.
Due to its potential for serious proarrhythmic effects and death, INAPSINE should be reserved for use in the treatment of patients who fail to show an acceptable
response to other adequate treatments, either because of insuf®cient effectiveness or the inability to achieve an effective dose due to intolerable adverse effects
from those drugs (see WARNINGS, ADVERSE REACTIONS, CONTRAINDICATIONS, AND PRECAUTIONS).

Cases of QT prolongation and serious arrhythmias (e.g., torsade de pointes) have been reported in patients treated with INAPSINE. Based on these reports, all
patients should undergo a 12-lead ECG prior to administration of INAPSINE to determine if a prolonged QT interval (i.e., QTc greater than 440 msec for males or
450 msec for females) is present. If there is a prolonged QT interval, INAPSINE should NOT be administered. For patients in whom the potential bene®t of
INAPSINE treatment is felt to outweigh the risks of potentially serious arrhythmias, ECG monitoring should be performed prior to treatment and continued for 2±3
hours after completing treatment to monitor for arrhythmias.
INAPSINE is contraindicated in patients with known or suspected QT prolongation, including patients with congenital long QT syndrome. INAPSINE should be

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administered with extreme caution to patients who may be at risk for development of prolonged QT syndrome (e.g., congestive heart failure, bradycardia, use of a
diuretic, cardiac hypertrophy, hypokalemia, hypomagnesemia, or administration of other drugs known to increase the QT interval). Other risk factors may include
age over 65 years, alcohol abuse, and use of agents such as benzodiazepines, volatile anaesthetics, and i.v. opiates. Droperidol should be initiated at a low dose and
adjusted upward, with caution, as needed to achieve the desired effect.

later therapy (P=0.001). In the surgical venue, successful association between droperidol, QT prolongation and
use of i.v. amiodarone in ventricular arrhythmia manage- malignant arrhythmias such as torsades de pointes.24
ment has been reported,23 40 although placebo-controlled While the relative risk of arrhythmia from droperidol,
trials are not yet available (for any antiarrhythmic agent). It compared with other antiemetics or placebo, has not been
should be recognized that amiodarone has non-competitive clearly established, the labelling for droperidol now recom-
alpha- and beta-blocking effects, so that rapid i.v. loading mends a 12-lead ECG before administration, with con-
may exacerbate haemodynamic instability during the initial tinuous ECG monitoring for 2±3 h after administration. If
(rapid) loading phase in patients with severe left ventricular the corrected QT interval is prolonged on the baseline
dysfunction. In these cases, systemic perfusion may be ECG, droperidol administration is not recommended.
maintained during the initial bolus with additional pressors, Additionally, extreme caution is recommended when
and occasionally intra-aortic balloon counterpulsation.23 If droperidol is used in patients with risk factors for develop-
time permits, the negative inotropic effects of i.v. ing a prolonged QT interval, such as congestive heart
amiodarone are also mitigated by slowing the loading failure, bradycardia, diuretic use, ventricular hypertrophy,
infusion. hypokalaemia, hypomagnesaemia, or use of drugs known to
increase the QT interval (Table 4).

Droperidol and ventricular arrhythmias

A recent controversy surrounds the association between I.V. pacemakers and implantable
ventricular arrhythmias and droperidol, and has caused a cardioverter de®brillators
`black box' warning to be issued by the US Food and Drug Pacemaker and ICD placement has risen tremendously over
Administration (FDA) (Table 4). Droperidol, a butyro- the past few years, partly because of the expanded
phenone, is a dopamine subtype-2 receptor antagonist which indications for insertion of these devices. Worldwide, the
exhibits mild alpha-adrenergic receptor blockade and peri- number of pacemakers implanted has risen from 780 000 in
pheral vasodilation. Since its approval by the FDA in 1970, 2000 to more than 900 000 in 2003. The increase in
droperidol has been used as a ®rst-line agent in the de®brillator implantation is even more impressive, rising
prevention and treatment of postoperative nausea and from 80 000 in 2000 to more than 160 000 in 2003. The
vomiting. Its properties as a cost-effective antiemetic have ACC/AHA/NASPE Guidelines for implantation of pace-
been well established in large-scale randomized makers and ICDs have been updated recently, with some
trials.21 22 52 Droperidol was widely used for three decades important additions to the indications for placement,
in the ®elds of psychiatry, emergency medicine and particularly regarding ICD insertion. According to the
anaesthesia; therefore, many physicians were surprised updated guidelines, ICD insertion is a class IIa indication
when the FDA issued a `black box' warning for droperidol (weight of evidence/opinion in favour of usefulness/
in December 2001. ef®cacy) for patients with an ejection fraction of 30% or
The decision to recommend caution with droperidol lower for whom it is at least 1 month since myocardial
administration was based on several reports of adverse infarction and 3 months since coronary artery revascular-
cardiac events associated with less-than-maximal doses of ization surgery.20 This recommendation was based on a
droperidol. The cases reported to the FDA suggest an published study where 1232 patients with a prior myocardial

92
 Perioperative cardiac arrhythmias

infarction and reduced left ventricular ejection fraction Cardiovascular Care. Part 6: advanced cardiovascular life
(<30%) were randomized to receive an implantable support: 7D: the tachycardia algorithms. Circulation 2000; 102:
I158±65
de®brillator or conventional medical therapy. No electro-
3 Abbott GW, Sesti F, Splawski I, et al. MiRP1 forms IKr potassium
physiological testing was required before randomization. channels with HERG and is associated with cardiac arrhythmia.
There was a 31% reduction in the risk of death in patients Cell 1999; 97: 175±87
receiving de®brillators compared with those receiving 4 Abedin Z, Soares J, Phillips DF, Sheldon WC. Ventricular
conventional medical therapy.37 This study is signi®cant tachyarrhythmias following surgery for myocardial
because in the US alone, 3±4 million patients have coronary revascularization. Chest 1977; 72: 426±8
artery disease and advanced left ventricular dysfunction, 5 Belardinelli L, Isenberg G. Isolated atrial myoctes: adenosine and
acetylcholine increase potassium conductance. Am J Physiol 1983;
with 400 000 new cases annually.8 38 With the increase in
244: H737±47
patients who may bene®t from de®brillator placement, the 6 Bigger JT, Jr. Prophylactic use of implanted cardiac de®brillators
likelihood that these patients will present for non-cardiac in patients at high risk for ventricular arrhythmias after
surgery also increases. Therefore, anaesthetists will require coronary-artery bypass graft surgery. Coronary Artery Bypass

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a basic understanding of these devices in order to safely, Graft (CABG) Patch Trial Investigators [see comments]. N Engl J
effectively and expeditiously manage patients with pace- Med 1997; 337: 1569±75
makers and de®brillators. 7 Chew C, Hecht H, Colett J, McCallister R, Singh B. In¯uence of
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The major perioperative issue regarding pacemakers and
to intravenously administered verapamil in ischemic heart
ICDs is the risk of electromagnetic interference (EMI) from disease. Am J Cardiol 1981; 47: 927±32
electrocautery or cardioversion. EMI can result in inhibition 8 Cohn JN, Bristow MR, Chien KR, et al. Report of the National
of pacemaker output, activation of rate-responsive sensor Heart, Lung, and Blood Institute Special Emphasis Panel on Heart
resulting in increased pacing rate, ICD ®ring and myocar- Failure Research. Circulation 1997; 95: 766±70
dial injury at the lead tip resulting in failure to sense or 9 Das G, Ferris J. Esmolol in the treatment of supraventricular
capture, or both.12 Improved pacemaker and ICD design, tachyarrhythmias. Can J Cardiol 1988; 4: 177±80
10 DelleKarth G, Geppert A, Neunteu¯ T, et al. Amiodarone versus
including the nearly universal use of bipolar leads and better
diltiazem for rate control in critically ill patients with atrial
shielding from EMI, has greatly reduced the probability of tachyarrhythmias. Crit Care Med 2001; 29: 1149±53
the aforementioned adverse interactions. Except in urgent or 11 Dorian P, Cass D, Schwartz B, Cooper R, Gelaznikas R, Barr A.
emergent situations, management of pacemakers and ICDs Amiodarone as compared with lidocaine for shock-resistant
in the perioperative setting begins with the preoperative ventricular ®brillation. N Engl J Med 2002; 346: 884±90
visit, which should include documentation of the patient's 12 Eagle KA, Berger PB, Calkins H, et al. ACC/AHA Guideline
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Noncardiac Surgery ± Executive Summary. A report of the
date of device implantation. Since pacemakers and ICDs are
American College of Cardiology/American Heart Association
programmable, obtaining the most recent interrogation Task Force on Practice Guidelines (Committee to Update the
report can be helpful in determining magnet response, and 1996 Guidelines on Perioperative Cardiovascular Evaluation for
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14 Elami A, Merin G, Flugelman MY, et al. Usefulness of late
sion of arrhythmia detection can also be used with most
potentials on the immediate postoperative signal-averaged
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the pacemaker function of some ICDs unaffected. All of the early after isolated coronary artery bypass grafting. Am J Cardiol
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