Asystole is the total cessation of any electrical activity in the heart (Walthall, 2008). It results in the myocardium not contracting (Tortora and Derrickson, 2009), leading to a lack of circulating oxygenated blood being supplied to the brain, causing irreversible brain damage and death (Ballinger and Patchett, 2007).
Transient versus terminal asystole
Transient asystole differs from terminal asystole in that it is not a total failure of electrical activity (Bashian and Wazni, 2009). The period of asystole is brief or temporary, and ends when another pacemaker site initiates an escape beat or rhythm (Winters, 2009). Without this, ventricular standstill and death would follow (Walthall, 2008). Some specific cells of the heart have the ability to generate their own impulse, albeit at a slower rate (see next section), when the rate initiated by the sinoatrial (SA) node is too slow or impaired (Rolls et al, 2007).
Cardiac muscle cells have four specialized properties: automaticity—the ability to spontaneously initiate an impulse; excitability—the ability to respond to an impulse; conductivity—the ability to conduct impulses; and refractoriness—the
extent to which the cells are able to respond to a stimulus (Winters, 2009). These properties allow the cardiac conduction system to initiate an action potentially spontaneously, resulting in the heart muscle contracting and the expulsion of blood to the pulmonary and systemic circulation (Winters, 2009). Common aetiologies of transient asystole are sick sinus syndrome (Keller and Lemberg, 2006), sinus arrest (Winters, 2009) and Stoke-Adams syndrome/ attacks (Khan, 2002).
Conduction system of the heart
The electrical impulses that cause the heart to contract are initiated by the SA node. The SA node is shaped like a spindle and is made up of specialized autorhythmic fibres (Tortora and Derrickson, 2009) set in a fibrous tissue matrix that merges into the surrounding atrial tissues (Dobrzynski et al, 2007). The function of the SA node is the initiation of an impulse (Figure 1). It does this by spontaneous and rhythmic depolarization that causes the atria to contract (Tortora and Derrickson, 2009).
The rate of impulses it generates is controlled by the sympathetic and parasympathetic branches of the autonomic nervous system. The parasympathetic nervous system slows the heart rate via the vagus nerve (Porth and Matfin, 2009). The sympathetic nervous system accelerates the heart by sending messages from the reticular formation in the brain stem. The neuron axons exit the spinal cord in the thoracic segments and synapse with postganglionic neurons that innervate the heart (Porth and Matfin, 2009).
The SA node is commonly known as the pacemaker of the heart as it is the main generator of impulses. It fires impulses at 60–100 beats per minute (Winters, 2009), a faster rate than any other heart tissue. Without a properly functioning SA node, the intrinsic heart rate is much slower as it is initiated by the atrioventricular (AV) node, which can only produce impulses at 40–60 beats per minute (Winters, 2009).
Impulses from the SA node spread rapidly across the atria via intermodal pathways towards the AV node (Winters, 2009) causing the atria to contract (Tortora and Derrickson, 2009). This appears on the standard electrocardiogram (ECG) as the p wave (Tortora and Derrickson, 2009).
The impulse waves are held at the AV node for 0.1 seconds, which allows the atria to contract (Tortora and Derrickson, 2009), before travelling through the bundle of His, the bundle branches and the Purkinje fibres, resulting in contraction of the ventricles and completing the formation of the standard ECG (Tortora and Derrickson, 2009).
As discussed, should the SA node fail to produce an impulse, other areas of the heart will take over the pacemaker function. The AV node has the ability to initiate impulses at a rate of 40–60 beats per minute and is the first pacemaker area to take over responsibility for generating impulses should the SA node fail. Should the AV node also fail, then the Purkinje system would initiate an impulse, but at a rate of only 15–40 beats per minute (Winters, 2009).
Intrinsic causes of transient asystole
Sick sinus syndrome; sinus block and arrest: the first two causes of intrinsic transient asystole
In sick sinus syndrome (SSS), the atrial heart rate is inadequate for the body's needs (Dobrzynski et al, 2007). It is caused by dysfunction of the sinoatrial (SA) node, resulting in it not being able to generate and conduct impulses (Da Costa et al, 2002).
It is thought that 0.03% of the population are affected by SSS (National Institute for Clinical Excellence (NICE), 2005). The average age of onset is 68 years (Adán and Crown, 2003), although it can occur in children following cardiac surgery to correct abnormalities (Winters, 2009).
Sick sinus syndrome (SSS) has no single aetiology (Adán and Crown, 2003). Literature searches uncover much research into genes surrounding this syndrome such as that by Holm et al (2011); this research shows how complex this syndrome is.
The pathophysiology behind this syndrome is dysfunction of the SA node through idiopathic causes such as degeneration of the nodal tissue by fbrosis (Adán and Crown, 2003; NICE, 2005) or coronary heart disease, or by blockage of the sinus node artery (Winters, 2009). Blockage of the sinus node artery may occur as a result of a right coronary artery myocardial infarct because the sinus node artery originates from the right coronary artery in around 70% of people (Iyer et al, 2007).
It may also result from degeneration of the nerves and ganglia surrounding the SA node (Winters, 2009). This can affect the action potential of cells, by changing the amount of time they take to reach their threshold level and produce the stimulus for the cardiac muscle to contract (Winters, 2009).
The action potential of a cell is the step-by-step change of electrical charge caused by movement of ions across the cell membrane (Winters, 2009). In a resting state, the cell membrane is almost impermeable to sodium but permeable to potassium. As a result, potassium ions slowly diffuse out of the cell, leaving the inside of the cell with a negative charge compared with the outside of the cell. This change opens the sodium channels in the cell membrane, allowing a rapid influx of sodium and a change back to a positive charge. This is the depolarization phase and allows the cell to reach its threshold level (Winters, 2009).
SSS typically manifests as a severe sinus bradycardia or sinoatrial block (Adán and Crown, 2003). Sinoatrial block is a failure of conduction from the SA node across the atria and shows as intermittent pauses, appearing as the length of two or more p-p intervals on an ECG (Da Costa et al, 2002).
Failure of the SA node to produce a stimulus is known as sinus arrest (Figure 2). This could potentially lead to transient asystole if it is prolonged (Winters, 2009). The SA node fails to produce an impulse for a longer time than in sinoatrial block and the pause is not related to the length of the p-p interval (Da Costa et al, 2002). Potential causes of sinus arrest are disease of the SA node itself, myocardial infarction, excessive vagal tone, digitalis toxicity and metabolic disorders (Winters, 2009).
SSS may also cause a bradycardia-tachycardia syndrome where there are alternating periods of slow and fast heart rates (Winters, 2009). The slow heart rate is the result of the diseased SA node failing to produce an adequate impulse rate (Winters, 2009). The tachycardia is the result of paroxysmal atrial or junctional arrhythmias such as atrial fibrillation (Rolls et al, 2007; Winters, 2009).
Stoke-Adams syndrome and complete heart block: the third common cause of intrinsic transient asystole
Stoke-Adams syndrome is a disorder associated with complete AV block and is commonly known as third-degree or complete heart block (Harbison et al, 2002). It is a term classically used to describe a syncope happening without warning lasting a few seconds which may be accompanied by seizure-like activity (Harbison et al, 2002) caused by hypoxia (Da Costa et al, 2002). It can be caused by the body's inability to tolerate a severe ventricular bradycardia of less than 40 beats per minute (Da Costa et al, 2002); this bradycardia can be caused by heightened vagal tone slowing the firing rate of the SA node (Winters, 2009) or complete heart block. During this syncope, a period of transient asystole can occur (Harbison et al, 2002).
Stoke-Adams syndrome is generally a redundant term among specialist doctors as a better understanding of cardiovascular physiology has led to more specific diagnostic terms (Harbison et al, 2002).
In complete heart block, the impulses generated by the SA node are blocked and do not reach the AV node, resulting in complete disassociation between atrial and ventricular activity (Walthall, 2008). The SA node continues to generate impulses but they are blocked from reaching the AV node. The block can occur anywhere from the AV node downwards, particularly at the bundle of His (Khan 2002; Kanjwal et al, 2010). This results in a delay in conduction to the lower bundle branches and Purkinje fibres.
As the ventricular myocardium does not receive an impulse to contract, an ectopic pacemaker site is initiated. As mentioned above, pacemaker sites below the SA node are able to generate impulses at a rate of only 15–60 beats per minute. There is therefore a delay in the contraction of the myocardium (NICE, 2005), resulting in a decrease in cardiac output (Winters, 2009), which could lead to a period of transient asystole (Figure 3) (Khan, 2002). Intrinsic causes of complete AV block include myocardial ischaemia or infarction, degeneration of the conduction pathways through aging, surgery or congenital or immune disorders (Da Costa et al, 2002).
Extrinsic causes of transient asystole
Transient asystole has been known to be caused by drug toxicity (Rolls et al, 2007) and is an effect of some anti-arrhythmic drugs, especially calcium channel blockers, cardiac glycosides, beta-blockers and other antiarrhythmic drugs (Keller et al, 2006).
Calcium channel blockers or antagonists are used in the control of angina symptoms, hypertension and cardiac arrhythmias (Galbraith et al, 2007). Typical examples are amlodipine (Galbraith et al, 2007) and verapamil (Thompson, 2010). They work by controlling the flow of calcium into the myocardial muscle cells. Calcium is required by the myocardium to facilitate contraction and, by blocking the flow, the muscle tone is reduced. This reduces the myocardium's demand for oxygen and increases blood flow to the myocardium by dilating blood vessels and reducing spasm (Galbraith et al, 2007).
Verapamil is frequently prescribed as an anti-arrhythmic drug. It suppresses the SA and AV nodes (depolarization of the AV node requires calcium influx), and thereby slows the rate of impulse conduction (Galbraith et al, 2007).
Adverse effects of calcium channel blockers are bradycardia and AV blocks. If undiagnosed SSS is present, there is the possibility of transient asystole occurring (Simonsen et al, 2006; Galbraith et al, 2007; Thompson, 2011).
Beta-blockers are used in the treatment of hypertension, angina and tachyarrhythmia. Common examples are atenolol, bisoprolol and propranolol (Galbraith et al, 2007). They work by blocking the effects of epinephrine and norepinephrine, which innervate beta receptors (Carroll and Curtis, 2009). Beta receptors are adrenergic receptors in the autonomic nervous system; if they are stimulated, cardiac contraction increases in force and rate, which raises cardiac output and blood pressure (Galbraith et al, 2007). Beta antagonists block this effect and reduce heart rate (Ko, 2004) and the force of contraction (Simonsen et al, 2006) so reduce blood pressure.
If a patient with undiagnosed SSS is prescribed beta-blockers, it may cause further sinus bradycardia, sinus arrest or heart block (Galbraith et al, 2007), which may lead to transient asystole. Beta-blockers alone can cause sinus arrest and significant bradycardia (Kováts et al, 2006; Pelter and Carey, 2009).
Digoxin, from the digitalis plant, is an antiarrhythmic drug that is part of the cardiac glycoside group. It is used to treat conditions such as atrial fibrillation and heart failure (Galbraith et al, 2007). Cardiac glycosides exert their effect by altering the movement of sodium, calcium and potassium across myocardial cell walls (Galbraith et al, 2007). They inhibit the coenzyme adenosine triphosphate (ATP), the energy source behind the sodium-potassium pump, which leads to an increase in sodium inside the myocardial cells (Simonsen et al, 2006; Galbraith et al, 2007). Alongside this is the sodium-calcium pump, which removes the increased intracellular sodium out of the cell in exchange for calcium. Increased intracellular calcium enhances the force of contraction of the myocardium (Simonsen et al, 2006). Therefore, inhibiting ATP in turn inhibits the sodium-potassium pump, leading to a greater build-up of calcium inside the cell (Simonsen et al, 2006). This leads to an increased force of contraction (Katz et al, 2010) and improves cardiac efficiency (Galbraith et al, 2007).
However, cardiac glycosides also affect SA node impulse generation by increasing the parasympathetic nervous system's stimulation of the heart (Simonsen et al, 2006; Galbraith et al, 2007). This decreases heart rate. This is a positive effect in the treatment of atrial fibrillation but, in a patient with undiagnosed SSS, it could lead to sinus pause or arrest and transient asystole. Cardiac glycosides also delay the conduction of impulses through the AV node (Galbraith et al, 2007). The positive effect of this is that the ventricles have longer to fll; the negative effect could be AV block and transient asystole.
Other extrinsic causes of SSS are endocrine-metabolic disorders such as hypothyroidism, imbalances of electrolytes such as potassium and calcium, carotid sinus sensitivity (Yang and Batres, 2011) and toxins such as those found in sepsis (Adán and Crown, 2003).
Use of analgesic agents such as fentanyl or lidocaine, anaesthetics such as propofol and anaesthetic induction agents such as vecuronium (Ishida et al, 2007; Kim et al, 2011), also produce bradycardia which could unmask SSS and result in transient asystole. This would not normally be witnessed by paramedics in the UK unless these medications were being administered by a doctor in a pre-hospital emergency (Greaves and Porter, 2007). However, these drugs, with the exception of propofol, are used in many emergency medical services protocols around the world.
Treatment
Two forms of treatment are available to paramedics. These are pharmacological intervention in the form of atropine sulphate and external transcutaneous cardiac pacing; the latter can only be administered by staff trained in its use.
Paramedics must first decide whether any intervention is actually required. If a patient is stable and not displaying any adverse symptoms such as absolute bradycardia, low blood pressure or signs of inadequate perfusion (Joint Royal Colleges Ambulance Liaison Committee guidelines (JRCALC, 2006b) (see Appendix 1), it may be in the patient's best interests to be conveyed directly to hospital with intravenous access gained en route.
Atropine sulphate
Paramedics can use the anti-arrhythmic drug atropine sulphate to treat bradycardia caused by SSS and AV block. Paramedics are licensed to use certain drugs without prescription under part III schedule 5 of The Prescription Only Medicines (Human Use) Order 1997 (UK Parliament, 1997). Atropine can be used for the purpose of saving life by certain groups of people including paramedics (Davies, 2011).
Like all drugs, atropine is licensed for use by the Medicines and Healthcare products Regulatory Authority (MHRA). Paramedics are guided in its use by the Joint Royal Colleges Ambulance Liaison Committee guidelines (JRCALC, 2006a) (see Appendix 1). They can administer atropine to patients with bradycardia and low blood pressure (JRCALC, 2006b), which are possible signs of SSS or Stoke-Adams syndrome; other symptoms include light-headedness, syncope and confusion (Rolls et al, 2007; Winters, 2009). Its use is advocated by the Resuscitation Council (Pitcher and Perkins, 2010) in their guidelines for bradycardia. It is recommended that a minimum dose of 500 mcg is used to avoid paradoxical reduction in heart rate (Pitcher and Perkins, 2010).
Atropine sulphate is an anticholinergic drug (Simonsen et al, 2006). Anticholinergic drugs are more commonly classified as muscarinic antagonists (Galbraith et al, 2007) or antimuscarinics. It works by blocking the effects of the neurotransmitter acetylcholine in the central and peripheral nervous systems by competitive antagonism (MHRA, 2010).
Acetylcholine is the parasympathetic neurotransmitter of the autonomic nervous system. It stimulates muscarinic M2 receptors in the myocardium which results in a reduction in the force of contraction and a decrease in the rate of contraction (Galbraith et al, 2007). Atropine binds to muscarinic receptors thereby blocking the effect of acetylcholine (Klabunde, 2007). Therefore, by administering atropine to bradycardic patients, paramedics can expect to see an increase in the heart rate and force of contraction. This is because the acetylcholine effect on the vagus nerve of the parasympathetic nervous system is blocked (Deakin et al, 2010).
While this effect is the intended outcome of treatment, consideration should be given to possible unwanted effects that may be detrimental to the patient. As previously discussed, a major cause of SSS and AV block is blockage of the SA nodal artery, particularly in conjunction with right coronary artery myocardial infarction. When the body experiences stress, such as myocardial ischaemia, the adrenal medulla stimulates production of catecholamines, such as epinephrine and norepinephrine, in higher quantities (Kunert, 2009). These catecholamines produce the fight-or-fight response associated with raised heart rate and increased blood pressure (Kunert, 2009). If paramedics administer atropine in these circumstances and block the parasympathetic vagal effects, the outcome could be that the catecholamines enhance the sympathetic response and the heart rate may be dangerously increased.
Large-scale studies into this area have not been undertaken in recent years and literature regarding the effects of atropine date back many years. Scheinman et al (1975) reported that seven patients out of 56 developed adverse effects such as tachycardia in a study of atropine use in patients with bradycardia coupled with myocardial infarct. Chadda et al (1975) reported a 17% incidence rate of myocardial infarct complicated by bradycardia and hypotension. When atropine was administered, it benefited 61 out of 68 patients and they advocated its safe use. Klein et al (1975) undertook a study of atropine dosage in the presence of myocardial infarct and reported that, in low doses of 0.008 mg/kg, atropine was safe and effective; this represents 0.6 mg in a 75 kg person. Current guidelines indicate an initial dose below this amount (JRCALC 2006a).
Paramedics should use their clinical judgement when considering treatment for individual patients. This can be effectively achieved by careful review of the evidence surrounding atropine and an insight into possible adverse effects. By taking all evidence into account and following up-to-date clinical guidelines in its use, paramedics can administer atropine as a safe and effective first-line treatment for symptomatic bradycardia.
Effcacy of atropine sulphate
In complete heart block, the block can present anywhere from the AV node down to beyond the bundle of His. As atropine works by enhancing SA and AV node conduction (Brady et al, 1999) by blocking the vagal influences of the autonomic nervous system (as described above), it may have no effect on lower-region blocks (Budzikowski, 2011).
In complete heart block with a narrow QRS complex (Figure 4) the normal QRS indicates that impulses below the AV node are conducting normally so the block is above the bundle of His. In this case atropine may be effective in enhancing conduction through the SA and AV nodal pathways. However, in wide complex QRS (Figure 5) the level of block is below the bundle of His, so conduction through the AV node would be relatively normal, so atropine may have no effect (Budzikowski, 2011).
In a study by Brady et al (1999), only half of patients treated with atropine before arriving at hospital had some form of response. Bradycardic patients showed a greater response than those with AV block (Brady et al 1999). Budzikowski et al (2011) advocate administering atropine with caution to blocks at the bundle of His due to the possibility of increasing the atrial rate which can widen the degree of block. However, despite these limitations, atropine remains the drug of choice for symptomatic bradycardia (Sodeck et al, 2006).
External transcutaneous cardiac pacing
If atropine lacks efficacy in complete heart block or intravenous access cannot be established, paramedics need another form of treatment for emergency management.
In hospital, after emergency administration of atropine, the most favoured treatment is external transcutaneous cardiac pacing (Sodeck et al, 2006; Pitcher and Perkins, 2010; Budzikowski, 2011). This involves placing pads on the patient's chest and passing electrical currents through to the heart to stimulate cardiac depolarization and contraction of the myocardium (Gibson, 2008).
Modern monitor/defbrillator equipment incorporates an external pacing mode so it is possible for paramedics, with training, to initiate pacing. The decision to use this form of treatment is well within the remit of a properly trained paramedic as it is non-invasive and has low complication rates (Abate et al, 2008). Bocka (2011) reports a 50–100% survival to discharge rate for transcutaneous pacing in bradycardia but does not indicate the percentage initiated in pre-hospital phase. There appears to be little evidence or research on the pre-hospital implementation of transcutaneous pacing (Sherbino et al, 2006), despite its extensive use in hospital. The studies published are too small to be of great significance (Morrison, 2008) so its pre-hospital efficacy is yet to be established.
The main consideration for implementation of pre-hospital pacing appears to be the pain associated with its use (Bocka, 2011). A form of analgesia/ sedation (Pitcher and Perkins, 2010), such as midazolam (Bocka, 2011), is recommended but none are licensed for use by paramedics. Positioning of pads can help to minimize skeletal pain as can using the lowest current possible to achieve capture (Bocka, 2011).
Midazolam, a benzodiazepine, could be an ideal drug for use with transcutaneous pacing as it has sedative effects and produces amnesia (Galbraith et al, 2007). However, midazolam can cause respiratory and cardiac depression and lower blood pressure (Joint Formulary Committee, 2011) which could prove catastrophic for a patient already portraying a significant lowered heart rate and blood pressure. If the patient is haemodynamically unstable and obtunded, they may well cope with the discomfort of transcutaneous pacing without the need for pain relief if it is initiated slowly and considerately.
Discussion
This article has described causes of transient asystole caused by bradycardia or complete heart block developing due to sick sinus syndrome and atrioventricular block.
To enable paramedics to treat these patients effectively, they need to be trained in external cardiac pacing as atropine is not always effective. Despite the lack of pre-hospital research, the extensive use of transcutaneous pacing in emergency departments of hospitals is good reason for its use in the pre-hospital field. It would be particularly beneficial in rural areas where there may be long transport times as it may enable paramedics to support the patient's conduction system more effectively. Research into suitable sedation or analgesia will need to be implemented if paramedics are to manage the discomfort effectively.
Paramedics require a more thorough understanding of the pharmacology of drugs to enable them to recognize extrinsic causes of transient asytole. They should then be able to recognize when atropine may not be effective and initiate swift transfer to hospital rather than remaining on scene performing possibly ineffective treatment. This could help reduce mortality and morbidity in these types of patients.