Antiarrhythmic drugs and anaesthesia: part 1. mechanisms of cardiac arrhythmias

Learning objectives.

By reading this article you should be able to:

• •Describe the normal electrophysiology of the heart and heterogeneity of its electrical activity.
• •Explain the mechanisms of arrhythmogenesis.
• •Outline factors that increase the risk of developing perioperative arrhythmias.
• •Discuss the principles of the perioperative management of arrhythmias.

Key points.

• •The majority of perioperative arrhythmias do not require treatment with antiarrhythmic drugs.
• •There are three main mechanisms of arrhythmogenesis: automaticity, triggered rhythm and re-entry.
• •If possible, risk factors for arrhythmias should be corrected before surgery.
• •Many drugs used in anaesthesia are potentially arrhythmogenic.
• •Inappropriate use of antiarrhythmic drugs can increase morbidity and mortality.

Perioperative arrhythmias are extremely common, usually transient and typically require no intervention. Persistent arrhythmias with associated haemodynamic instability may reflect an underlying pathological process. Indeed, the clinical scenario outlined of a patient with sepsis who develops rapid atrial fibrillation describes a situation that anaesthetists and intensivists frequently encounter. In some situations, the primary cause of the arrhythmia may be evident. However, in many cases the cause is multifactorial, relating to coexisting disease, acute physiological disturbance, medications or the surgical procedure itself (e.g. cardiac or thoracic surgery).

Clinical scenario.

A 72-year-old man presented for an elective laparoscopic right hemicolectomy for adenocarcinoma of the colon. He had a history of ischaemic heart disease, with previous angioplasty and stenting to the left anterior descending coronary artery. His left ventricular function was mildly impaired and he was taking a loop diuretic and metoprolol for blood pressure control. Surgery was uneventful, except for occasional ventricular ectopic beats. On the fifth day after surgery, he developed atrial fibrillation with rapid ventricular response, which was associated with severe hypotension and required admission to the ICU. Further investigation revealed an anastomotic leak with peritoneal sepsis.

The principles of perioperative management are based on maintaining cardiovascular stability through restoration of sinus rhythm or controlling heart rate. Interventions include treating the underlying causes(s), haemodynamic support and electrical cardioversion. Antiarrhythmic drugs are sometimes – but not always – required to successfully manage patients with arrhythmias.

To understand the mechanism of action of antiarrhythmic drugs, it is necessary to understand normal cardiac electrophysiology and the pathophysiology of arrhythmogenesis. In part one of this two-part series, we focus on normal cardiac electrophysiology, arrhythmogenesis and how arrhythmias are triggered. We discuss the indications for pharmacological therapy and outline the factors to consider before initiating drug treatment. In a forthcoming article, we will discuss the classification and clinical pharmacology of antiarrhythmic drugs and provide an overview of managing perioperative arrhythmias.

Important concepts and terms are summarised in Table 1. The ion currents associated with cardiac action potentials are shown in Fig 1.

Table 1.

Terms and their meanings.

Term	Meaning
Resting membrane potential (RMP)	RMP is determined by equilibrium potentials and permeability of various ions across the cell membrane. K+ is the most important ion because of its high permeability at the resting state. The RMP is approximately –90 mV, close to the K+ equilibrium potential. The cell is fully excitable and capable of generating an action potential.
Hyperpolarisation	Repolarisation of cell membrane below the RMP making the potential more negative. This is mainly caused by efflux of K+.
Partial depolarisation	A state where the RMP is less negative. Usually associated with pathological conditions such as myocardial ischaemia.
Depolarisation	A change in membrane potential owing to influx of cations (e.g. Na+ and Ca2+) into the cell resulting in a less negative or even a positive membrane potential.
Repolarisation	A change in membrane potential caused by efflux of K+ into the cell resulting in a more negative membrane potential.
Absolute refractory period (ARP)	The interval between the beginning of the action potential and when the cell can generate another action potential. During this period, the cell is not excitable as all Na+ channels are in an inactivated state and no channels are available to generate a new action potential.
Relative refractory period (RRP)	The interval after the absolute refractory period where the cell regains partial excitability. An action potential can only be generated with a stimulus stronger than one that would normally elicit an action potential from RMP. Sufficient number of Na+ channels have recovered to generate an action potential, but not enough to regain full excitability.
Early after depolarisation (EAD)	A triggered activity that occurs at the end of the plateau (phase 2) of an action potential. EAD is associated with a prolonged action potential.
Delayed after depolarisation (DAD)	A triggered activity that occurs near the very end of repolarisation or just after full repolarisation. DAD is associated with increased intracellular Ca2+ concentration.
Transmural dispersion of repolarisation (TDR)	Dispersion of repolarisation is a phenomenon where repolarisation times are different in different parts of the heart. Epicardial cells, endocardial cells, and M-cells in the ventricular wall have different repolarisation time resulting in different action potential durations across the thickness of the ventricular wall – termed TDR. This results from different ion channel distribution and intrinsic differences in activity between different cell types.
Na+/K+ ATPase pump	ATP-dependent active transport found in the cell membrane. For every ATP molecule hydrolysed, three Na+ are exported out of the cell and two K+ are imported into the cell. This keeps intracellular K+ and extracellular Na+ concentrations high. The pump is also electrogenic as there is a net outward movement of a cation.

Fig. 1.

Action potentials and currents involved in (a) myocyte and (b) sinoatrial and atrioventricular. ARP, absolute refractory period; RRP, relative refractory period.

Electrophysiology of the heart

An electrical impulse is generated at the sinoatrial (SA) node at regular intervals with a normal frequency of 60–100 beats min⁻¹. The electrical impulse travels through the left and right atria to the atrioventricular (AV) node where the speed of conduction decreases, providing approximately 0.15 s for the atria to fill the ventricles with blood. The impulse then rapidly travels down the His-Purkinje fibre to depolarise the ventricles in a synchronised fashion, resulting in coordinated ventricular contraction.

Cardiac action potentials can be broadly classified into two distinct types: (i) myocyte action potentials (Fig 1A) and (ii) SA and AV node action potentials (Fig 1B).

Myocyte action potentials

The resting membrane potential (RMP), corresponding to phase 4 in Fig. 1A, is mainly established by the Na⁺/K⁺-ATPase pump and the high permeability of the cell membrane to K⁺. The cell membrane is much less permeable to Na⁺ and Ca²⁺ and, therefore, these ions contribute little to the RMP. The Na⁺/K⁺-ATPase pump moves 3 Na⁺ ions out of the cell and 2 K⁺ ions into the cell, resulting in the net outward movement of positive charge. Along with intracellular anionic proteins, the Na⁺/K⁺-ATPase pump generates a negative electrical potential inside the cell and maintains the high intracellular concentration of K⁺ and the high extracellular concentration of Na⁺.

In the resting state, specific K⁺ channels are open, allowing K⁺ to move down its electrochemical gradient. Movement of K⁺ into the cell down its electrical gradient is balanced by movement of K⁺ out of the cell down its chemical gradient. At the equilibrium potential for K⁺, these two opposing forces are balanced, which is quantified by the Nernst equation:

$${\mathrm{E}}_{\mathrm{K}}=\left(\frac{\text{RT}}{\text{zF}}\right){\log }_{\mathrm{e}}\left(\frac{\left[{\mathrm{K}}_{\text{out}}^{+}\right]}{\left[{\mathrm{K}}_{\text{in}}^{+}\right]}\right)$$ (1)

where E_K is the equilibrium potential for K⁺, R is the universal gas constant, T is the (absolute) temperature in degrees Kelvin, F is the Faraday constant, z is the valency (1 for K⁺), and log_e is the natural logarithm. E_K is approximately –90 mV, which is close to the RMP. At the RMP – which is slightly less negative than E_K – there is net outward movement of K⁺ and this current is called the inwardly rectifier current (I_K1). Owing to its relatively high membrane permeability, the extracellular K⁺ concentration is the main determinant of the RMP.

In the presence of cellular hypoxia, the Na⁺/K⁺-ATPase pump is unable to maintain the transmembrane potential and the Na⁺ and K⁺ concentration gradients across the cell membrane are reduced. Consequently, the intracellular K⁺ concentration decreases and the local extracellular K⁺ concentration increases (interstitial hyperkalaemia). In accordance with the Nernst equation, the RMP becomes less negative (i.e. partially depolarised). For instance, at an extracellular K⁺ concentration of 10 mmol L⁻¹, the RMP is about –70 mV.¹

When the cell membrane reaches the threshold potential, voltage-gated Na⁺ channels change from a ‘resting’ to an ‘open’ state, resulting in rapid inflow of Na⁺ (I_Na), depolarising the membrane to approximately +30 mV (phase 0). The rate of depolarisation largely determines the conduction velocity of the propagating action potential. Normally, depolarisation lasts approximately 1 ms, after which time Na⁺ channels assume an ‘inactivated’ state. Although inactivated, Na⁺ channels cannot reopen until the channels enter the ‘resting’ state when the membrane repolarises. In certain pathological conditions (e.g. myocardial ischaemia), a small number of Na⁺ channels remain open during the plateau (phase 2) of the action potential, providing a persistent inwards Na⁺ current (late Na⁺ current, I_NaL), prolonging the action potential.

After depolarisation, transient outwards K⁺ channels open, creating an outwards repolarising K⁺ current (I_t0) and forming a notch on the action potential (phase 1). The plateau of the action potential (phase 2) is generated by a balance of opposing currents: an inwards Ca²⁺ current (I_CaL) via L-type Ca²⁺ channels and outwards K⁺ currents (rapid and slow delayed rectifier currents, I_Kr and I_Ks, respectively). I_CaL slowly diminishes during phase 2, whereas I_Kr and I_Ks increase, leading to repolarisation. Phase 3 is characterised by a continual decline of I_CaL, increase in I_Kr and I_Ks, and recovery of I_K1, leading to repolarisation, returning the membrane to the resting state (phase 4).

Although the membrane is depolarised during phase 2 and the early part of stage of phase 3, Na⁺ channels are unavailable to generate new action potentials. This period is termed the absolute refractory period. Once Na⁺ channels begin to recover to a ‘resting’ state, a premature action potential may be generated when a strong enough stimulus occurs during phase 3. This period is termed the ‘relative refractory period’. The number of Na⁺ channels available during the relative refractory period is substantially reduced, resulting in reduction of the magnitude and rate of depolarisation and, therefore, speed of conduction.

Sinoatrial and atrioventricular node action potentials

The SA node exhibits pacemaker activity resulting from spontaneous diastolic depolarisation (phase 4). Under normal circumstances, the rate of spontaneous depolarisation in the SA node is higher than in other pacemaker cells (e.g. AV node, Purkinje fibres), resulting in overdrive suppression of latent pacemaker cells. When the SA node fails to initiate an impulse, latent pacemaker cells take over the pacemaker function of the heart. The intrinsic rate of spontaneous depolarisation of the SA node and other pacemaker cells is affected by neurohumoral responses, drugs and physiological disturbances (e.g. hypoxaemia).

Spontaneous depolarisation results from inwards current of Na⁺ and K⁺ (referred to as the funny current, I_f), via hyperpolarisation-activated cyclic nucleotide-gated (HCN) channels.¹ At approximately –50 mV, voltage-gated T-type Ca²⁺ channels allow the influx of Ca²⁺ (I_CaT current), which brings the membrane to the threshold potential. L-type Ca²⁺ channels then open, resulting in an increase in I_CaL (phase 0). L-type Ca²⁺ channels open slowly, resulting in a slow rate of depolarisation and low conduction velocity. Finally, repolarisation occurs as a consequence of the inactivation of Ca²⁺ channels and opening of delayed rectifier K⁺ channels (phase 3).

Physiological heterogeneity of action potentials

There is heterogeneity of action potentials across different parts of the heart because of variable expression of ion channels.^2,3 This heterogeneity has two main consequences. First, atrial cells generally have shorter action potentials than ventricular myocytes because of their larger transient outward K⁺ current (I_t0). Second, repolarisation times in different parts of the heart vary. Within the ventricles, there are three electrophysiologically distinct cell types: epicardial, endocardial and mid-myocardial cells (M-cells). The action potential is longer in the Purkinje fibres and M-cells, resulting from decreased K⁺ currents and increased late Na⁺ current (I_NaL).⁴ Differences in ion channel expression cause variability in repolarisation times, which is responsible for a phenomenon termed transmural dispersion of repolarisation (TDR). It is important to understand action potential heterogeneity in order to appreciate the aetiology of arrhythmias and the targets for pharmacological treatment.

Mechanism of arrhythmogenesis

Arrhythmias are caused by disturbances in impulse generation and conduction. Bradyarrhythmia occurs with failure of impulse generation from the SA node or failure of action potential propagation from the atria to the ventricles resulting from AV block or abnormalities in the His-Purkinje conduction system. Tachyarrhythmias arise via three distinct mechanisms: (i) enhanced automaticity, (ii) triggered automaticity and (iii) re-entry.

Enhanced automaticity – normal and abnormal

Enhanced normal automaticity refers to a rapid regular heartbeat originating from the SA node (i.e. sinus tachycardia). Enhanced normal automaticity occurs with β-adrenergic or vagolytic stimulation, hypokalaemia or mechanical stretch, causing an increased slope of the phase 4 pacemaker action potential and, therefore, an increased pacemaker rate.²

Enhanced abnormal automaticity refers to a situation where the heartbeat originates from sites other than the SA node. Myocyte injury can lead to partial depolarisation of the membrane. Myocytes with a RMP of –60 to –40 mV have an increased tendency to spontaneously depolarise, producing ectopic atrial and ventricular tachycardias.^2,5

Triggered automaticity

Triggered arrhythmia describes the occurrence of a premature action potential occurring before the previous beat is complete (Fig 2A). There are two main types of triggered automaticity: delayed afterdepolarisations (DADs) and early afterdepolarisations (EADs).

Fig. 2.

(a) Triggered automaticity. Black solid and dotted lines represent the normal action potential. Red lines represent action potentials triggered by delayed afterdepolarisations (DADs) and early afterdepolarisations (EADs). Note the reduction in the rate of depolarisation of triggered action potentials with reduced slope. (b) Re-entry. In the presence of a region where conduction is slowed, antegrade conduction is blocked from insufficient Na⁺ channel recovery. Retrograde conduction occurs when the antegrade conduction reaches the area from downstream, causing re-entry.

Delayed afterdepolarisations occur during the early stage of phase 4 and are caused by intracellular Ca²⁺ overload, such as occurs in myocardial ischaemia, adrenergic stimulation, or digoxin toxicity.² Intracellular Ca²⁺ overload upregulates activity of the electrogenic 3Na⁺/Ca²⁺ exchanger, bringing the membrane to the threshold potential and ‘triggering’ a premature action potential.

Early afterdepolarisations occur during phase 3 when the action potential is prolonged. Prolongation of the action potential involves an increase in the inwards I_NaL and I_CaL currents and reduction in the outwards K⁺ currents. Any pathology (e.g. myocardial ischaemia) or use of pharmacological agents that inhibit K⁺ channels also prolong the action potential, which manifests as QT prolongation on the ECG. An important clinical consequence of EADs is torsade de pointes ventricular tachycardia. Purkinje and M cells inherently have a long action potential and EADs are more frequently observed in these regions.²

Re-entry

Re-entry arrhythmia arises in regions with functional or structural conduction delay resulting in unidirectional block (Fig 2B). After propagation of an action potential in the diseased region, the next antegrade conduction is blocked, as Na⁺ channels remain inactivated from the previous action potential. The impulse eventually enters the diseased region from downstream, propagating retrogradely if sufficient Na⁺ channels have recovered. The abnormal electrical region may be anatomical (e.g. pre-excitation syndrome with an accessory pathway) or functional, where the membrane is partially depolarised (e.g. because of ischaemia), resulting in a region of slow conduction. Tachycardia caused by re-entry can be transient or sustained, depending on the number of round trips the circuit makes. Multiple re-entry circuits predispose to atrial or ventricular fibrillation.

Influence of heterogeneity of electrical activity on arrhythmia

Another important contributor to arrhythmia is increased TDR resulting from exaggerated heterogeneity. Drugs that prolong the QT interval or the presence of localised abnormal cells, preferentially prolong the action potential in M-cells – where the action potential is already longer than that in epicardial or endocardial cells – increasing TDR.⁶ Increased TDR predisposes to arrhythmia because of triggered automaticity (via EADs) and re-entry (Fig 3). Increased TDR is a precondition for torsade de pointes ventricular tachycardia in patients with long QT syndrome.^7,8

Fig. 3.

Arrhythmia caused by heterogeneity of electrical activity. Repolarisation is delayed owing to a reduction in the net repolarisation current (outwards I_Kr, I_Ks and I_K1) and an increase in the net depolarising current (inwards I_CaL and I_NaL) resulting in preferential increase in action potential duration (APD) in M-cells. Exaggerated transmural dispersion of repolarisation (TDR) results in the generation of torsade de pointes. EAD, early afterdepolarisation.

Arrhythmia in the perioperative period

If possible, factors that increase the risk of developing arrhythmia should be corrected before surgery. Modifiable causes of arrhythmia include physiological or biochemical disturbances and acute pathological conditions, such as sepsis and myocardial ischaemia (Fig. 4). Surgery-related oxidative stress, systemic inflammation, autonomic dysfunction and damage to autonomic fibres are also proposed risk factors.⁹

Fig. 4.

Patient-related factors that increase risk of arrhythmia and their mechanisms.

Patient-related factors

Increased sympathetic activity

Any insult to physiological homeostasis, such as hypoxaemia, hypercarbia, acidosis or pathological processes, can lead to increased sympathetic nervous system activity. Anaesthesia (e.g. laryngoscopy) and surgical (e.g. skin incision) procedures can induce an intense sympathetic response. Drugs with sympathomimetic effects (e.g. ketamine, ephedrine, adrenaline [epinephrine]) can have similar consequences.

Stimulation of β₁ receptors leads to the opening of HCN channels with the increased inwards I_f current steepening the slope of phase 4 of pacemaker cells. Simultaneously, Ca²⁺ entry via I_CaL also increases, leading to Ca²⁺ release from the sarcoplasmic reticulum, which results in Ca²⁺ overload, predisposing to arrythmia caused by DADs (triggered automaticity).

Severe bradycardia

Bradycardia or heart block results from depressed SA node activity or severe AV conduction delay, which can occur with intense vagal stimulation (e.g. during laparoscopic surgery). Latent pacemaker cells within the AV node, ventricular myocytes or Purkinje fibres then take over impulse generation. Impulses arising in latent pacemaker cells have a prolonged action potential duration relative to the SA node, which enhances TDR. Bradycardia exacerbates action potential heterogeneity between neighbouring cells, creating an electrical gradient that facilitates ventricular ectopic beats and re-entry arrhythmia.¹⁰

Myocardial ischaemia and infarction

Ischaemic myocardial cells become partially depolarised. In this state, Ca²⁺ may be spontaneously released from the sarcoplasmic reticulum, which indirectly triggers increased activity of the 3Na⁺/Ca²⁺ exchanger. The electrogenic inflow of Na⁺ causes pacemaker-like activity, increasing the risk of DADs. In addition, partial membrane depolarisation slows the rate of depolarisation during phase 0, creating an area of slow conduction, predisposing to re-entry.

Electrolyte disturbances

Electrolyte disturbances are an important cause of perioperative arrythmia. Hypokalaemia with serum K⁺ <3.5 mmol L⁻¹ (e.g. from diuretic therapy) hyperpolarises the RMP, causing depressed automaticity and AV block. Severe hypokalaemia (<2.5 mmol L⁻¹) inhibits delayed rectifier K⁺ channels, prolonging the action potential and increasing the risk of developing EADs and DADs. Atrial fibrillation and flutter are the most common perioperative arrhythmia associated with hypokalaemia and serum K⁺ <3.5 mmol L⁻¹ is an indication for K⁺ replacement.¹¹

Hyperkalaemia (>5.0–6.0 mmol L⁻¹) initially shortens the action potential duration and the absolute refractory period. However, as hyperkalaemia worsens (>7.0 mmol L⁻¹), the RMP becomes partially depolarised, inducing postrepolarisation refractoriness and prolonging the absolute refractory period. As the number of Na⁺ channels available for depolarisation is reduced, the rate of phase 0 depolarisation decreases along with the conduction velocity. Severe hyperkalaemia is associated with conduction block (e.g. left bundle branch block, right bundle branch block, AV block), asystole, ventricular tachycardia and ventricular fibrillation.¹²

Hypocalcaemia (ionised Ca²⁺ <1.17 mmol L⁻¹) prolongs the action potential and is associated with EADs, predisposing to torsade de pointes ventricular tachycardia. Hypocalcaemia also exacerbates the pro-arrhythmia effect of hyperkalaemia.¹³ Hypercalcaemia (ionised Ca²⁺ >1.4 mmol L⁻¹) shortens the action potential but is not associated with clinically important arrhythmia.

Hypomagnesaemia (<0.74 mmol L⁻¹) commonly coexists with hypokalaemia and hypocalcaemia, as a consequence of diuretic therapy.¹⁴ Reduced Mg²⁺ concentration leads to a decrease in Na⁺/K⁺-ATPase activity, rendering the RMP less negative. This in turn slows the rate of depolarisation and decreases the outwards K⁺ current, prolonging the QT interval, thereby increasing the risk of ventricular ectopic beats and torsade de pointes ventricular tachycardia. Although moderate hypermagnesaemia has no known clinically important effects on cardiac rhythm, severe hypermagnesaemia (>4 mmol L⁻¹) exerts a calcium antagonist effect and may cause conduction defects, bradycardia and hypotension.

When combined with other risk factors, electrolyte disturbances substantially increase the risk of developing clinically important arrhythmias.

Metabolic and respiratory abnormalities

Metabolic and respiratory abnormalities, such as hypoxaemia, hypercarbia and acid–base disturbances, can increase sympathetic nervous system activity, leading to arrhythmia.

Pharmacological factors

Intravenous anaesthetic agents

Most agents used for inducing general anaesthesia reduce sympathetic nervous system activity, potentially leading to myocardial depression and bradycardia. The baroreceptor reflex is also attenuated, reducing the compensatory responses to hypotension. Propofol is the i.v. Anaesthetic agent used most frequently, and has a significant cardiovascular depressant effect in susceptible patients. Ketamine increases sympathetic activity and prolongs the QT interval (see below), both of which predispose to arrhythmia.

Opioids

Opioids rarely cause marked haemodynamic instability. However, large boluses, especially of alfentanil and remifentanil, are associated with severe sinus bradycardia caused by a direct parasympathetic effect and blunting of sympathetic tone.^15,16 Methadone prolongs the QT interval (see below).

Anticholinesterases

Anticholinesterases (e.g. neostigmine) increase acetylcholine concentration and stimulate muscarinic receptors. Activation of M₂ receptors within the heart causes bradycardia and AV conduction delay. To prevent severe bradycardia, anticholinergic drugs (atropine, glycopyrrolate) should be given together with neostigmine.

Vasoconstrictors

Vasoconstrictors (phenylephrine, metaraminol, noradrenaline [norepinephrine]) have no direct proarrhythmic effects. However, these agents can cause hypertension, which in turn activate carotid baroreceptors, leading to reflex bradycardia. The effect is typically short-lived and does not usually require intervention.

Drugs that prolong the QT interval

Several drugs commonly given during the perioperative period can prolong the QT interval (Table 2). It is postulated that drugs that cause torsade de pointes ventricular tachycardia preferentially prolong the QT interval of M-cells and Purkinje fibres, thereby worsening TDR and increasing the risk of ventricular arrhythmia.

Table 2.

Drugs that increase the QT interval and the risk of inducing torsade de pointes.^7,8 ∗Adrenergic drugs should be avoided unless necessary; metaraminol and phenylephrine can be used safely. ^†Neostigmine-glycopyrrolate prolongs the QT interval and thus should be avoided if possible. ^‡Although 5HT₃ antagonists should be avoided, ondansetron has been used without any issues. ^¶Ketamine should be avoided because of the increased sympathetic activity. Other intravenous anaesthetic agents are safe.

Adrenergic drugs∗	Adrenaline Dobutamine Dopamine Ephedrine Noradrenaline Salbutamol
Antiarrhythmic agents	Class Ia and class III drugs
Antibiotics	Azithromycin Clarithromycin Erythromycin
Anticholinergic agents†	Atropine Glycopyrrolate
Antiemetic agents	Chlorpromazine Droperidol Domperidone Metoclopramide Ondansetron‡
Intravenous anaesthetic agents¶	Ketamine
Neuromuscular blocking agents	Pancuronium Suxamethonium
Opioids	Methadone Sufentanil
Oxytocic agents	Oxytocin

Numerous anaesthetic drugs increase the QT interval but do not increase the risk of torsade de pointes ventricular tachycardia owing to their limited effect on TDR. Such agents include volatile anaesthetics, thiopentone, midazolam and etomidate. Therefore, these drugs are safe for use in patients with a prolonged QT interval. However, ketamine and methadone do increase TDR and are associated with torsade de pointes ventricular tachycardia and should be avoided in patients with a prolonged QT interval.

Patients with a corrected QT (QTc) >450 ms (males) and >460 ms (females) are at risk of developing ventricular arrhythmia.

Management of perioperative arrhythmia

Assessment before surgery

An ECG should be obtained in all patients with known cardiovascular disease. The following abnormalities should be specifically sought: ischaemia, previous myocardial infarction, ventricular hypertrophy or strain, prolonged QTc, bundle branch block and arrhythmias. Acute or unexpected abnormalities should be evaluated with an echocardiogram to identify functional or structural heart disease. Accurate diagnosis of arrhythmia and its cause can be difficult in the short window before surgery and an opinion from a cardiologist can be useful when unexpected arrhythmias are identified. Arrhythmias that may warrant postponing surgery include trifascicular block, second degree heart block, complete heart block, or new onset left bundle branch block, atrial fibrillation, atrial flutter, supraventricular tachycardia or sustained ventricular arrhythmia.

Indications for antiarrhythmic drug therapy

Antiarrhythmic drugs may be indicated in the following settings: alleviation of symptoms, to improve cardiac function when dysfunction is a result of tachycardia or dyssynchrony, to prevent progression into a life-threatening arrhythmia, and to reduce the need for electrical cardioversion.¹⁷

The benefit of symptom relief in patients with chronic arrhythmia is controversial, as adverse effects may negate any benefit from symptomatic relief. Many antiarrhythmic drugs have a narrow therapeutic window and exhibit inter-patient variability in efficacy. Several trials, including the Cardiac Arrhythmia Suppression Trial (CAST), Survival with Oral d-sotalol (SWORD), and Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM),¹⁸ have demonstrated an association between the use of antiarrhythmic drugs and mortality in patients with structural heart disease, myocardial infarction or both.¹⁹

Once the causes are treated, perioperative arrhythmia typically resolve without the need for antiarrhythmic drugs. In situations where an antiarrhythmic drug is required, patients should be closely monitored for drug-induced proarrhythmias.

Intraoperative management

When arrhythmia is encountered, the following general steps should be considered before starting pharmacological therapy:

• •Identify and eliminate the cause(s).
• •Establish an accurate diagnosis.
• •Evaluate the presence of underlying structural or functional heart disease, especially congestive heart failure or ischaemic heart disease. Few antiarrhythmic drugs have an established safety profile in these settings.¹⁷
• •Once the decision is made to use an antiarrhythmic drug, the adverse effect profile and patient-specific contraindications should be considered. For example, amiodarone in patients with severe pulmonary disease, β-blockers in patients with asthma, and calcium channel blockers in patients with acute decompensated heart failure.^5,10

Management after surgery

Patients with arrhythmias that are self-limiting can usually follow a routine postoperative care pathway. Arrhythmias such as sinus bradycardia, first-degree heart block, junctional rhythm, sinus tachycardia and premature ventricular contractions are common and rarely require further management.

Clinically significant arrhythmias, such as new onset atrial fibrillation, second-degree or complete AV block and persistent ventricular arrhythmias, require continuous ECG monitoring and evaluation by a cardiologist. If there is haemodynamic instability, admission to the high dependency unit or ICU is appropriate.

Conclusions

Perioperative arrhythmias are common and are attributable to a multitude of factors including the drugs used for anaesthesia, electrolyte disorders and patient pathologies (sepsis, myocardial ischaemia). The majority of perioperative cardiac arrhythmias do not require intervention other than general supportive care. Treatment of the underlying cause of the arrhythmia is crucial. Before an antiarrhythmic drug is given, the potential benefits and risks should be considered carefully, as inappropriate use can lead to increased morbidity and mortality.

Declaration of Interest

The authors declare that they have no conflicts of interest.

Biographies

Chang Joon Kim FANZCA is a consultant anaesthetist at Auckland City Hospital, Health New Zealand. He routinely provides anaesthesia care for patients requiring cardiac, thoracic, interventional cardiology procedures including TAVI, catheter ablations and PCIs and non-cardiac procedures. He is a primary examiner for Australian and New Zealand College of Anaesthetists.

Nigel Lever FRACP FCSANZ is a consultant cardiologist at Auckland City Hospital and associate professor at the University of Auckland, with clinical expertise in cardiac rhythm disorders and cardiac ablation procedures. He is involved in translational research with cardiac mapping, heart failure, and novel pacing therapies; and is also an examiner for the Royal Australasian College of Physicians.

Jeremy Ormond Cooper FANZCA is a consultant anaesthetist at Auckland City Hospital. He has expertise in preoperative patient assessment, cardiothoracic anaesthesia and an extensive interest and involvement in education.

Matrix codes: 1A01, 1A02, 2A03, 3I00

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