AUTHOR INFORMATION

Section 1 of 12

Authored by Richard M Caggiano, MD, FACEP, Adjunct Faculty, Department of Medicine, University of Washington, School of Medicine; Director of Emergency Services, Medical Director of Employee Health, Assistant Director of Trauma Services, Pullman Regional Hospital

Richard M Caggiano, MD, FACEP, is a member of the following medical societies: American College of Emergency Physicians

Edited by Edward Bessman, MD, Chairman, Department of Emergency Medicine, John Hopkins Bayview Medical Center; Assistant Professor, Department of Emergency Medicine, Johns Hopkins University; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Gary Setnik, MD, Chair, Department of Emergency Medicine, Mount Auburn Hospital; Assistant Professor, Division of Emergency Medicine, Harvard Medical School; John Halamka, MD, Chief Information Officer, CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School; and Jonathan Adler, MD, Attending Physician, Department of Emergency Medicine, Massachusetts General Hospital; Division of Emergency Medicine, Harvard Medical School

Author's Email:	Richard M Caggiano, MD, FACEP
Editor's Email:	Edward Bessman, MD

eMedicine Journal, February 8 2007, VOLUME 8, Number 2

INTRODUCTION

Section 2 of 12

Background: Asystole is cardiac standstill with no cardiac output and no ventricular depolarization; it eventually occurs in all dying patients.

Pulseless electrical activity (PEA) is the term applied to a heterogenous group of dysrhythmias unaccompanied by a detectable pulse. Bradyasystolic rhythms are slow rhythms; they can have a wide or narrow complex, with or without a pulse, and often are interspersed with periods of asystole. When discussing PEA, ventricular fibrillation (VF) and ventricular tachycardia (VT) are excluded.

Pathophysiology: Asystole can be primary or secondary. Primary asystole occurs when the heart's electrical system intrinsically fails to generate a ventricular depolarization. This may result from ischemia or from degeneration (ie, sclerosis) of the sinoatrial (SA) node or atrioventricular (AV) conducting system. Primary asystole usually is preceded by a bradydysrhythmia due to sinus node block-arrest, complete heart block, or both.

Reflex bradyasystole/asystole can result from ocular surgery, retrobulbar block, eye trauma, direct pressure on the globe, maxillofacial surgery, hypersensitive carotid sinus syndrome, or glossopharyngeal neuralgia. Episodes of asystole and bradycardia have been documented as manifestations of left temporal lobe complex partial seizures. These patients experienced either dizziness or syncope. No sudden deaths were reported, but the possibility exists if asystole were to persist. The longest interval was 26 seconds.

Secondary asystole occurs when factors outside of the heart's electrical conduction system result in a failure to generate any electrical depolarization. In this case, the final common pathway is usually severe tissue hypoxia with metabolic acidosis. Asystole or bradyasystole follows untreated VF and commonly occurs after unsuccessful attempts at defibrillation. This forebodes a dismal outcome.

Frequency:

• In the US: The number of adults in cardiopulmonary arrest who had bradyasystole as the initial arrest rhythm is difficult to measure accurately. Reports vary and may be skewed by the patient population studied and/or by the method of reporting the initial rhythm. In a 1991 study of 185 patients in cardiopulmonary arrest at the time of arrival to the emergency department, 9% had survived to hospital admission and none were discharged alive (Gray, 1991). This study was not limited to patients with asystole.

• Internationally: In one study from Goteborg, Sweden, asystole was the presenting rhythm in the field in 35% of patients with cardiac arrest (Engdahl, 2000).

  When the incidence of coronary artery disease in the population of a country is relatively low, asystole is relatively more common as a manifestation of cardiopulmonary arrests. This is because cardiac ischemia more frequently results in VF. Asystole is most likely to be found in cardiopulmonary arrests occurring in children; this is usually secondary to another noncardiac event (ie, respiratory arrest due to sudden infant death syndrome, infection, choking, drowning, or poisoning).

Mortality/Morbidity: Asystole is associated with a poor outcome regardless of its initial cause. In the Goteborg study, 10% of 1,635 asystolic patients survived to hospital admission and 2% survived to hospital discharge.

Resuscitation is likely to be successful only if it is secondary to an event that can be corrected immediately, such as a cardiac arrest due to choking on food (a cafe coronary), and only if an airway can be established and the patient may be rapidly reoxygenated. Occasionally, primary asystole can be reversed if it is due to pacemaker failure, which could be either intrinsic or extrinsic, and this is corrected immediately by external pacing.

Sex: Frequency of asystole, as a percentage of all cardiopulmonary arrests, is higher in women than in men; however, the frequency of cardiac arrest in general is proportional to the underlying incidence of heart disease, which is more common in males until around 75 years of age.

Age: Prevalence of asystole as the presenting cardiac rhythm is lower in adults (25-56%) than in children (90-95%).

CLINICAL

Section 3 of 12

History: Immediate diagnosis of asystole requires the recognition of a full cardiac arrest and a confirmed flat-line rhythm in 2 perpendicular leads. Lightheadedness or syncope may precede asystole when it follows a bradyasystolic rhythm.

Physical: If the rhythm is truly asystole and has been present for more than several seconds, the patient will be unconscious and unresponsive. A few agonal (final gasping) breaths may be noted, but detectable heart sounds and palpable peripheral pulses are absent.

Causes:

• Examples of common conditions that can result in secondary asystole include suffocation, near drowning, stroke, massive pulmonary embolus, hyperkalemia, hypothermia, MI complicated by VF or VT that deteriorates to asystole, defibrillation, and sedative-hypnotic or narcotic overdoses leading to respiratory failure.

• Hypothermia is a special circumstance, since asystole can be tolerated for a longer period of time under such conditions and can be reversed with rapid rewarming while cardiopulmonary resuscitation (CPR) is being performed. If available, institute cardiopulmonary bypass immediately, because it can accomplish both of these goals. Most survivors have received cardiopulmonary bypass.

• Primary asystole develops when cellular metabolic functions are no longer intact and an electrical impulse cannot be generated. With severe ischemia, pacemaker cells cannot transport the ions necessary to effect the transmembrane action potential. Implantable pacemaker failure may also be a cause of primary asystole.

• Proximal occlusion of the right coronary artery can cause ischemia or infarction of both the SA and the AV nodes.

• Extensive infarction can cause bilateral bundle-branch block (ie, infranodal complete heart block).

• Idiopathic degeneration of the SA or AV node can result in sinus arrest-block and/or AV heart block, respectively. This process is slow and progressive, but the symptoms may be acute and asystole may result. An implantable pacemaker is usually required for these conditions.

• Occasionally, asystolic sudden death occurs from congenital heart block, local tumor, or cardiac trauma.

• Asystole can occur following an indirect lightning strike (ie, direct current [DC]) that depolarizes all the cardiac pacemakers. A rhythm may return spontaneously or shortly after CPR is initiated. These patients may survive intact if given immediate attention. Alternating current (AC) from man-made sources of electrical current usually results in VF.

DIFFERENTIALS

Section 4 of 12

Ventricular Fibrillation

Other Problems to be Considered:

ECG lead misplacement

WORKUP

Section 5 of 12

Lab Studies:

• A potassium level may be useful if deemed appropriate, and results are immediately available.

• Arterial blood gas (ABG) analysis may be used to obtain rapid reporting of potassium level in many institution's laboratories. ABG level may also help to evaluate the ventilatory and acid-base status of the patient as well as hemoglobin level. If the patient is in full arrest, a blood gas level does not accurately reflect the pH status of the tissues.

Imaging Studies:

• Asystole is generally a diagnosis made via ongoing cardiac monitoring or ECG and physical examination with pulselessness. Bedside ultrasonography may be useful to confirm cardiac standstill. The heart may be viewed via either a subxiphoid view or an intercostal view and wall motion, or lack thereof, observed.

• For documentation purposes, in addition to including rhythm strips from 2 separate leads identifying asystole, an image of 2-dimensional echocardiography taken over time in M-mode may be taken, saved, and included in the medical record. This will further document lack of heart wall motion.

Other Tests:

• Continuous cardiac monitoring is useful during attempts at resuscitation to determine rhythm and effects of intervention.

• Asystole is best determined in 2 separate cardiac leads. This helps protect against reading a flat line due to lead malfunction incorrectly as asystole, as well as in differentiating fine VF, particularly in an isoelectric lead, from asystole.

• Eliminate a possible diagnosis of VF, which may masquerade as asystole, by checking 2 leads perpendicular to each other. In spite of this caveat, using a flat-line protocol based on a 3-lead check, occult VF was documented in only 3 (2.5%) of 118 asystolic patients, indicating that VF masquerading as asystole is uncommon. Technical problems were much more common, observed in 10 patients (8%).

• Exclude the possibility of lead misplacement by always checking for the presence of a pulse.

• Spurious asystole can be seen when using manual defibrillator paddles to monitor the rhythm. This is usually very brief, but nevertheless, can be avoided by switching to monitoring leads, especially after several successive shocks.

• Pulse oximetry may be used during resuscitation to monitor for effectiveness of forward flow or CPR; however, usually flow is too inadequate for the sensor to register any results.

Procedures:

• Endotracheal intubation is indicated with attempts at resuscitation.

• Central venous access or intraosseous access may be needed for vascular access.

TREATMENT

Section 6 of 12

Prehospital Care:

• The only 3 drugs recommended or acceptable by the American Heart Association (AHA) for adults in asystole are epinephrine, vasopressin, and atropine. In spite of full vagolytic doses of atropine (0.03 mg/kg) and high-dose epinephrine (0.20 mg/kg), or the use of vasopressin 40 units (U), few patients survive to leave the hospital neurologically intact. Atropine is no longer recommended in young children and infants in asystole but can be considered in adults with slow PEA rhythms.

• If spontaneous circulation has not been restored, administering vasopressin 40 U IV for the first 2 doses or followed by epinephrine given at the physician's discretion has recently showed superior results. A recent study showed that more patients survived to hospital discharge, although the neurologic status of the patients at discharge was not clearly stated. The number of patients with asystole in the study was 528. Of those, 12 patients in the vasopressin group survived to discharge compared with 4 in the standard therapy group. In this study, the odds ratio stated may not be statistically significant. The study also showed a nonstatistically significant trend toward worse results for VF and PEA (Wenzel, 2004). The advanced cardiac life support (ACLS) 2005 guidelines allow vasopressin 40 IU IV as a one-time dose treatment option in VF and asystole. It can be given either before epinephrine or after the first dose of epinephrine.

• Transcutaneous pacing (TCP), even when used immediately, has not altered meaningful survival (ie, functional lifestyle) significantly. When no metabolic deficit exists, such as in a cardiac arrest preceded by a conduction or impulse generation disorder (ie, primary asystole), immediate use of TCP may be lifesaving.

Emergency Department Care: Mainstays of ED treatment are providing oxygenation and ventilation via endotracheal intubation and circulation via CPR, attempts at transcutaneous or transvenous pacing (that have some small potential to be fruitful in primary asystole that has just occurred), and administration of pharmacologic agents.

• A case has been reported of a long but successful resuscitation from asystole of a patient who was hyperkalemic secondary to renal failure. The treatment included calcium chloride to reverse the physiologic effects of hyperkalemia and insulin and glucose to lower serum potassium levels. This cannot be recommended routinely for all cases of asystolic arrest.

• Electrical defibrillation should not be applied indiscriminately to the patient in asystole. This is not only fruitless, but also detrimental, eliminating any possibility of recovering a rhythm. Asystole following electrical defibrillation has an even worse outcome than that in a patient whose first documented rhythm was asystole. One caution is that following defibrillation, a brief spurious asystole can occur using manual monitoring through the defibrillator paddles. This does not occur with the rhythm monitoring leads or hands-off monitor pads. If not taken into consideration, it could lead to a delay in defibrillation, when indeed VF is present.

MEDICATION

Section 7 of 12

Parasympathetic influences during cardiopulmonary arrest have not been elucidated fully, and the clinical benefits of atropine have yet to be confirmed. Atropine can be used for asystole, but the AHA now states that its use should be considered. High-dose epinephrine (0.20 mg/kg) may improve the hemodynamics of CPR, thereby increasing the rate of return to spontaneous circulation; however, it has not been demonstrated to influence the final clinical outcome. Therefore, these doses no longer are recommended for children or adults. Adenosine antagonists, such as aminophylline, have been investigated but have not been shown to be clinically useful.

Drug Category: Anticholinergic agents -- The goal in using these agents is to enhance sinoatrial activity and to improve conduction through the SA or AV node by reducing vagal tone via muscarinic receptor blockade. This is effective only if the site of block is within the SA or AV node. For patients with infranodal block, this therapy is ineffective. It may increase a Mobitz II second-degree block to a higher degree of block or a third-degree block.

Drug Name	Atropine (Atropair, Isopto, Atropisol) -- Parasympatholytic agent used to eliminate vagal influence on SA and AV nodes. Not effective for infranodal third-degree heart block.
Adult Dose	1 mg IV/IO, may repeat dose up to 3 mg total, or 0.03 mg/kg, which is completely vagolytic If no IV/IO access is available, administer 2 or 2.5 mg via an endotracheal tube (ET); this is a less reliable method and should only be used as a last resort; dose should be followed (a "flush") with 5 mL of normal saline flush and 5 ventilations should be provided; a minimum dose of 0.1 mg IV/IO should be given to avoid centrally mediated paradoxical parasympathomimetic effect
Pediatric Dose	Pediatric bradyasystolic arrest: Not recommended. Symptomatic bradycardia with a pulse unresponsive to oxygen and fluids: 0.02 mg/kg IV/IO Children: 0.1 mg IV minimum dose; not to exceed 0.5 mg; maximum total dose 1 mg Adolescents: 0.1 mg IV minimum dose; not to exceed 1 mg; maximum total dose 2 mg If no IV or IO access exists, give 0.03 mg/kg ET; the same holds for this route as stated above when applied to pediatrics
Contraindications	None when indicated for symptomatic sinus bradycardia or Mobitz type I second-degree heart block; contraindicated in Mobitz type II second-degree heart block; generally not effective for infranodal third-degree heart block
Interactions	None for this indication
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Adds to tachydysrhythmia if a rhythm resumes, especially when used with sympathomimetic agents; may potentially lower the VF threshold (This is theoretical and only an issue if perfusing rhythm present.)

Drug Category: Adrenergic agonists -- These agents can produce constriction of skeletal and vascular muscle.

Drug Name	Epinephrine (Adrenaline) -- Considered the single most useful drug in cardiac arrest. Used to increase coronary and cerebral blood flow during CPR. May enhance automaticity during asystole. Can be used for bradycardia in adult and pediatric patients.
Adult Dose	1 mg IV/IO; 2-2.5 mg ET if not given IV/IO; range was 0.01-0.20 mg/kg depending on standard-dose or high-dose epinephrine protocols (High doses are no longer recommended by AHA.)
Pediatric Dose	0.01 mg/kg IV/IO; alternative, 0.10 mg/kg ET if no IV/IO access (High-dose epinephrine [0.20 mg/kg] is no longer recommended by AHA.)
Contraindications	None for this indication
Interactions	None for this indication
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	May result in tachydysrhythmia if rhythm resumes; this is additive to effects of atropine or other sympathomimetic agents

Drug Name	Vasopressin (Pitressin) -- Has vasopressor and ADH activity. Increases water resorption at distal renal tubular epithelium (ADH effect) and promotes smooth muscle contraction throughout vascular bed (vasopressor effects). Vasoconstriction is increased in splanchnic, portal, coronary, cerebral, peripheral, pulmonary, and intrahepatic vessels.
Adult Dose	40 IU IV once, although some studies suggest a repeat dose of 40 IU (not an AHA recommendation)
Pediatric Dose	Not established
Contraindications	None for this indication
Interactions	None for this indication
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	May result in tachydysrhythmia if rhythm resumes

FOLLOW-UP

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Further Inpatient Care:

• The intensive care unit is the appropriate disposition for the occasional patient who survives asystolic cardiopulmonary arrest and requires further treatment and diagnostic evaluation.

Deterrence/Prevention:

• Primary asystole may be prevented by the appropriate use of a permanent pacemaker in those patients who have high-grade heart block or sinus arrest.

• Preventing secondary asystole requires early recognition and treatment of the preceding event.

Complications:

• Complications include permanent neurologic impairment and complications from CPR or invasive procedures (eg, liver laceration, fractured ribs, pneumothorax, hemothorax, air embolus, aspiration, gastric/esophageal rupture).

• Death often occurs.

Prognosis:

• Prognosis depends on the etiology of the asystolic rhythm, timing of interventions, and success or failure of advanced cardiac life support. Generally, the prognosis is dismal and postcountershock asystole in particular has an even worse survival rate.

Patient Education:

• Advice about electrical storm safety and prevention of hypothermia is appropriate for those likely to be exposed to these conditions.

• For excellent patient education resources, visit eMedicine's Public Health Center. Also, see eMedicine's patient education article Cardiopulmonary Resuscitation (CPR).

MISCELLANEOUS

Section 9 of 12

Medical/Legal Pitfalls:

• Failure to anticipate impending asystolic arrest

• Failure to recognize esophageal intubation

• Withholding specific therapy for patients with hypothermia

TEST QUESTIONS

Section 10 of 12

CME Question 1: Acute cardiac ischemia can result in an asystolic arrest through which of the following mechanisms?

A: Autonomic disturbances
B: Failure of cardiac pacemaker generation and/or propagation
C: Pulmonary edema
D: Cardiogenic shock
E: All of the above

The correct answer is E: A bradyasystolic or asystolic arrest may be primary or secondary in a patient experiencing a myocardial infarction. It may be due to a failure of pacemaker generation or propagation directly because of ischemia to the sinoatrial (SA) node or the atrioventricular (AV) conducting system. Many patients with myocardial infarction have some degree of autonomic disturbance, ie, high parasympathetic tone, resulting indirectly in bradydysrhythmias or heart block. A lack of responsiveness to sympathetic stimulation may also be present. Hypoxemia from pulmonary edema and/or poor tissue perfusion from cardiogenic shock could also lead to a secondary asystolic arrest.

CME Question 2: Asystole as the initial presenting rhythm in a cardiopulmonary arrest is approached differently in which of the following circumstances?

A: Respiratory failure
B: Indirect lightning strike
C: Acute myocardial infarction
D: Environmental hypothermia
E: Septic shock

The correct answer is D: All of the above conditions, except hypothermia, would be treated by using standard cardiopulmonary resuscitation (CPR) and drug therapy with epinephrine and atropine. In the hypothermic patient, immediate core rewarming should be initiated, preferably using cardiopulmonary bypass. Atropine and epinephrine are not effective in patients with severe hypothermia (30°C or 86°F) until core rewarming has been effected.

Pearl Question 1 (T/F): A 20-year-old woman is found asystolic after injecting heroin. Respiratory arrest with secondary asystole is the most likely cause of her arrest.

The correct answer is True: Primary respiratory arrest with secondary asystole due to tissue hypoxia is the most probable explanation.

Pearl Question 2 (T/F): A 60-year-old man in cardiac arrest is conclusively asystolic only after checking lead II on the monitor.

The correct answer is False: Two perpendicular leads should be checked to rule out fine ventricular fibrillation.

Pearl Question 3 (T/F): If a patient with a pacemaker has a bradyasystolic arrest preceded by several minutes of lightheadedness, a transcutaneous pacemaker could be lifesaving if applied immediately.

The correct answer is True: The application of a transcutaneous pacemaker could be lifesaving in patients with primary asystole due to sinus arrest, heart block, or in this case pacemaker failure.

Pearl Question 4 (T/F): A 12-year-old boy is struck by lightning. Respiratory arrest and a stroke are two explanations for the asystolic cardiopulmonary arrest that followed.

The correct answer is False: Primary asystole occurs in lightning strikes from direct current (DC) depolarizing the entire myocardium, or the brain stem is depolarized resulting in respiratory arrest with secondary asystole. A stroke may result from a lightning strike in a survivor, but it would not be a likely cause of asystole.

PICTURES

Section 11 of 12

Caption: Picture 1. Rhythm strip showing asystole.
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Caption: Picture 2. Rhythm strip showing ventricular fibrillation.
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BIBLIOGRAPHY

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