Bradyarrhythmias (2024)

Bradyarrhythmias
~ iEM Education Project Team

by Hassan M. Alshaqaq & Danya Khoujah

Authors
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An 80-year-old male patient was brought to the emergency department (ED) by ambulance from a long-term care facility with a chief complaint of altered mental state for 2 hours. On arrival, his vitals were as follows: heart rate= 42 beats/min, blood pressure (BP)=70/50 mmHg, SpO2=95% on room air, respiratory rate=23 breaths/min, temperature=37.6°C, glucocheck= 215 mg/dL. The patient was pale, diaphoretic, alert, and disoriented. Pupils were equal and reactive to light. No neurological deficits or lateralizing signs were identified. The patient has a history of diabetes mellitus, hypertension, and ischemic heart disease. There is no history of drug ingestion or recent symptoms of infection. The patient was given 1 liter of intravenous (IV) normal saline during transport. A 12-lead electrocardiogram (ECG) was obtained (Figure 1). What are your initial assessment steps? What are the ECG features? What is the most likely diagnosis? How will you stabilize this patient?

Figure 1. Courtesy of Dr. Ahmad Alsaif. Digitized using PMcardio app. 
Figure 1. Courtesy of Dr. Ahmad Alsaif. Digitized using PMcardio app. 

Importance and Epidemiology

Bradyarrhythmias are defined as rhythms with a ventricular rate lower than 60 beats/min in adults and lower than the age-appropriate rate in pediatrics. Bradycardia may cause symptoms at a rate of <50 beats/min, which is the functional definition that most guidelines use [1]. Bradyarrhythmias are categorized into bradycardias and atrioventricular (AV) blocks [2].

Bradycardias are characterized by a slow rate of both atria and ventricles and include sinus bradycardia, junctional rhythm, idioventricular rhythm, and hyperkalemia-related sinoventricular rhythm. Bradyarrhythmias due to AV blocks are characterized by ventricular beats slower than the atria and include second- and third-degree AV blocks. Uncommonly, atrial fibrillation or flutter may present with a slow ventricular rate secondary to either significant conduction disturbance or excessive nodal-blocking medications.

Patients with bradyarrhythmias can be either stable or unstable. Patients with hemodynamically unstable bradycardia are at a high risk of cardiovascular collapse [3]. On the other hand, stable asymptomatic bradycardia could be physiological in athletes and well-conditioned individuals [4,5].

Compromising bradycardia has an incidence of 6 per 10,000 patients presenting to the ED for any reason; 20% of those require temporary pacing and 50% require a permanent pacemaker [6]. One percent of admission to the intensive care units (ICUs) from the ED are patients with compromising bradycardia, and 10% of syncope can be attributed to bradycardia [6,7]. Due to the significant potential for instability in bradycardic patients [3], emergency clinicians play a critical role in their initial stabilization, identification of underlying etiology, and treatment.

Pathophysiology

Normal cardiac electrophysiology starts with an impulse generated in the sinoatrial (SA) node, traveling into the atria via interatrial conduction pathways leading to atrial contraction, which appears as a P wave on the ECG. The impulse is then conducted down to the AV node, then from the AV node into the bundle of His and bundle branches, and finally into the Purkinje system leading to a ventricular contraction. The AV conduction appears as the PR interval, whereas the ventricular depolarization appears as the QRS complex (Figure 2). Several electrolytes, such as potassium and calcium, play a crucial role in initiating and regulating the cardiac action potential.

Figure 2. Cardiac conduction system. Used with permission from OpenStax licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). Access for free at https://openstax.org/books/anatomy-and-physiology/pages/1-introduction
Figure 2. Cardiac conduction system. Used with permission from OpenStax licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). Access for free at https://openstax.org/books/anatomy-and-physiology/pages/1-introduction

There is an anatomical variance in the blood supply of the SA and AV nodes. The blood supply of the SA node arises from the right coronary artery in 63% and the left circumflex artery in 37% of the population [8]. The AV node is supplied by a branch of the right coronary artery in 90% and the left circumflex artery in 10% [8]. This is most relevant in acute myocardial infarction (MI), as different may arise from ischemia of the conduction system [9]. MI may also lead to ischemia through a vagal-mediated response.

Cardiac output is dependent on the heart rate and stroke volume. Initially, the reduced heart rate increases the diastolic filling leading to an augmentation in the stroke volume. This compensatory mechanism is eventually overwhelmed, leading to decreased cardiac output, hypoperfusion and potentially cardiogenic shock [2,10].

Blood pressure equals the cardiac output multiplied by the systemic vascular resistance. In patients with reduced cardiac output, endogenous sympathetic reflex leads to vasoconstriction and increased systemic vascular resistance. Therefore, patients could have hypoperfusion despite normal-appearing blood pressure.

The underlying cause of bradyarrhythmias could be either conditions affecting the automaticity of cardiac cells (i.e., their ability to generate impulses) or the conduction of impulses within the cardiac conduction system [11,12]. be intrinsic (due to an innate dysfunction of the heart) or extrinsic (Table 1). A practical mnemonic is DIE, which stands for Drugs, Ischemia, and Electrolytes. Half of the patients with compromising bradycardia have a treatable underlying etiology [6].

Table 1. Causes of bradyarrhythmias [7]

Intrinsic:

  • Myocardial ischemia/infarction
  • Cardiomyopathy
  • Congenital heart disease
  • Degenerative fibrosis (with aging)
  • Traumatic (e.g., Denervation post cardiac surgery, cardiac ablation)
  • Infectious/inflammatory (e.g., myocarditis, endocarditis, Lyme disease, syphilis, sarcoidosis, lupus)
  • Sepsis
  • Infiltrative disorders (amyloidosis, hemochromatosis)

Extrinsic:

  • Autonomic-mediated (e.g., athletes, carotid sinus hypersensitivity, situational)
  • Electrolyte disturbances (e.g., hyperkalemia, hypokalemia, hypocalcemia)
  • Hypothermia
  • Endocrinopathy (e.g., hypothyroidism)
  • Raised intracranial pressure
  • Medication overdose (e.g., β-Blockers, calcium channel blockers, digoxin, clonidine, opioids)
  • Toxicologic exposure (e.g., organophosphate)

Types of Bradycardia

Sinus Bradycardia

Sinus bradycardia is characterized by ECG findings of a P wave preceding each QRS, a fixed P-P interval equal to the R-R interval, and a ventricular rate lower than 60 beats/min (Figure. 3). Sinus bradycardia can be found in healthy individuals, particularly athletes with high resting vagal tone.

Figure 3. Sinus bradycardia. ECG shows sinus and regular rhythm, normal PR interval, and a rate of 46 beats/min. Courtesy of Dr. Ahmad Alsaif. ECG digitized using PMcardio app.
Figure 3. Sinus bradycardia. ECG shows sinus and regular rhythm, normal PR interval, and a rate of 46 beats/min. Courtesy of Dr Hassan Alshaqaq and Dr Danya Khoujah.

It could also be secondary to pathological conditions, such as acute MI (Figure 4) [9]. Patients with sinus bradycardia are usually asymptomatic and do not require any specific treatment. However, profound bradycardia causing hypoperfusion requires emergent treatment of the underlying cause. Atropine may be used, as well as cardiac pacing.

Figure 4. Sinus bradycardia with inferior STEMI. ECG shows sinus and regular rhythm, normal PR interval, and a rate of 58 beats/min combined with ST-segment elevation in the inferior leads (Leads III and aVF), hyperacute T waves in leads III and aVF with relative loss of R wave height, early Q-wave formation in leads II, III and aVF, and reciprocal ST depression and T wave inversion in leads I and aVL. Courtesy of Dr. Ahmad Alsaif. ECG digitized using PMcardio app.
Figure 4. Sinus bradycardia with inferior STEMI. ECG shows sinus and regular rhythm, normal PR interval, and a rate of 58 beats/min combined with ST-segment elevation in the inferior leads (Leads III and aVF), hyperacute T waves in leads III and aVF with relative loss of R wave height, early Q-wave formation in leads II, III and aVF, and reciprocal ST depression and T wave inversion in leads I and aVL. Courtesy of Dr. Hassan Alshaqaq and Dr. Danya Khoujah.

Junctional Rhythm

When the SA node fails to discharge or the discharge of the SA node fails to reach the AV node, the AV node generates “junctional escape beats” at a ventricular rate ranging between 40 and 60 beats/min (Figure. 5). These QRS complexes on the ECG are not usually preceded by P waves. However, in some cases, the junctional beats conduct in retrograde into the atria, producing a P wave before or after the QRS. If present before the QRS complex, the PR interval will be abnormally short (<120 msec).

Figure 5. Junctional rhythm. ECG shows an absence of sinus P waves, regular and narrow QRS complexes, and a ventricular rate of 54 beats/min. Also, there is evidence of 2 premature ventricular contractions (PVCs). Courtesy of Dr. Ahmad Alsaif. ECG digitized using PMcardio app.
Figure 5. Junctional rhythm. ECG shows an absence of sinus P waves, regular and narrow QRS complexes, and a ventricular rate of 54 beats/min. Also, there is evidence of 2 premature ventricular contractions (PVCs). Courtesy of Dr. Ahmad Alsaif. ECG digitized using PMcardio app.

Sustained junctional escape rhythm may be caused by inferior MI with right ventricle (RV) extension (Figure 6) [9], posterior MI, myocarditis, hypokalemia, and digitalis toxicity. Infrequent junctional escape beats do not require treatment. Treating the underlying etiology is the mainstay of treatment in symptomatic patients and atropine can be used as a bridge until then. Atropine enhances SA node discharge rate and AV nodal conduction, therefore suppressing slower pacemakers. In case of hemodynamic compromise, cardiac pacing might be necessary [9].

Figure 6. Junctional rhythm with inferior STEMI with posterior extension. ECG shows an absence of sinus P waves, regular and narrow QRS complexes, and ventricular rate of 43 beats/min combined with ST-segment elevation in the inferior leads (Leads II, III, and aVF), ST elevation in lead III > II, early Q-wave formation in lead III, horizontal ST segment depression and upright T waves in leads V2-V3 (posterior MI), and reciprocal ST depression in leads V4-V6, lead I, and aVL. Courtesy of Dr. Anas Halim. Digitized using PMcardio app.
Figure 6. Junctional rhythm with inferior STEMI with posterior extension. ECG shows an absence of sinus P waves, regular and narrow QRS complexes, and ventricular rate of 43 beats/min combined with ST-segment elevation in the inferior leads (Leads II, III, and aVF), ST elevation in lead III > II, early Q-wave formation in lead III, horizontal ST segment depression and upright T waves in leads V2-V3 (posterior MI), and reciprocal ST depression in leads V4-V6, lead I, and aVL. Courtesy of Dr. Anas Halim.

Idioventricular Rhythm

In idioventricular rhythm, beats originate from the ventricles with wide (>120 ms) and regular QRS complexes and a rate of 30-50 beats/min. In idioventricular rhythms, ECG shows no P waves (Figure 7). It is usually non-sustained; present for a short duration only. The significance of idioventricular rhythm is that it is most commonly seen in the setting of an ST-segment elevation MI (STEMI) [13].

Figure 7. Idioventricular rhythm. ECG shows regular and wide QRS complexes (>120 ms), absence of P wave, and ventricular rate of 49 beats/min. Courtesy of Dr. Anas Halim. ECG digitized using PMcardio app.
Figure 7. Idioventricular rhythm. ECG shows regular and wide QRS complexes (>120 ms), absence of P wave, and ventricular rate of 49 beats/min. Courtesy of Dr. Hassan Alshaqaq and Dr. Danya Khoujah.

Atropine may be utilized in symptomatic patients but is usually unsuccessful. If the rhythm persists and is compromising, cardiac pacing may be attempted. Antiarrhythmic agents are best avoided as these could lead to asystole by suppressing the rescue functioning pacemaker [9,14,15].

Table 2 compares ECG features of bradycardic rhythms.

Sinus bradycardia

Junctional rhythm

Idioventricular rhythm

 
  • Sinus P waves present.
  • PR interval 120-200 msec (normal).
  • Rate < 60 beats/min.
  • Absence of normal sinus P waves (may be retrograde).
  • Ventricular rate 40-60 beats/min.
  • Narrow QRS complexes.
  • Absence of P waves.
  • Ventricular rate 30-50 beats/min.
  • Regular and wide QRS complexes.
 
 
 
 

Sinus Node Dysfunction

Sinus node dysfunction is caused by the failure of the sinus node to generate or conduct appropriate cardiac potentials. It can be associated with various supraventricular rhythms, including tachycardia and bradycardia, as well as prolonged pauses (>3 secs). It is most often due to age-dependent fibrosis of the nodal tissue [16,17] or post-cardiac transplantation [18], and might also be seen in patients with myocardial ischemia [19,20], myocarditis [19], and cardiomyopathy [7, 21, 22]. On ECG, it is characterized by episodes of bradycardia and/or sinus arrest with episodes of supraventricular tachycardia (Figure 8).

Figure 8. Sinus node dysfunction. ECG shows tachycardia interspersed with long sinus pauses (absence of any electrical activity). Courtesy of Dr. Anas Halim. ECG digitized using PMcardio app.
Figure 8. Sinus node dysfunction. ECG shows tachycardia interspersed with long sinus pauses (absence of any electrical activity). Courtesy of Dr. Hassan Alshaqaq and Dr. Danya Khoujah.

First-Degree AV Block

First-degree AV block (more accurately described as AV delay) is characterized by delayed AV conduction of all atrial impulses to the ventricles at the level of the atria, AV node, or His-Purkinje system. There is no blocked atrial conduction. Therefore, the ECG reveals a 1:1 atrioventricular conduction (P wave for each QRS complex) and prolonged PR interval (>200 milliseconds) (Figure 9).

Figure 9. First-degree AV block. ECG shows sinus rhythm, 1:1 atrioventricular conduction, with a fixed prolonged PR interval (PR interval = 203 ms). Courtesy of Dr. Anas Halim. ECG digitized using PMcardio app.
Figure 9. First-degree AV block. ECG shows sinus rhythm, 1:1 atrioventricular conduction, with a fixed prolonged PR interval (PR interval = 203 ms). Courtesy of Dr. Hassan Alshaqaq and Dr. Danya Khoujah.

Table 3 illustrates a comparison between ECG features of the AV block types.

 

Type of Block

 

First-degree AV block

Second-degree AV block Mobitz type I

Second-degree AV block Mobitz type II

Third-degree AV block

PQRS

 

Sinus rhythm (P wave for each QRS complex)

 

Nonconducted atrial impulse (P wave not followed by QRS complex)

Cycle repeats after a dropped beat (atrial impulse is completely blocked)

Nonconducted atrial impulse (P wave not followed by QRS complex)

PR interval remains constant after the non-conducted atrial impulse

No association between P waves and QRS complexes (complete dissociation)

Atrial rate higher than ventricular rate

 

PR interval

PR interval >200 msec

Progressively prolonged PR interval

Fixed prolonged PR interval

PR interval remains constant after the non-conducted atrial impulse

Variable PR interval

QRS

Narrow

Regular

Narrow

Narrow

Wide

Regular

First-degree AV block could be found as a normal variant or may be secondary to increased vagal tone, medication toxicity, inferior MI (Figure 10) [9], or myocarditis [15]. Those with a new-onset first-degree AV block in the setting of ACS may be at a higher risk of progression to complete heart block [9,15]. Patients with first-degree AV block usually do not require specific treatment,1 especially if asymptomatic. Symptomatic patients should have their management focused on the underlying cause. Agents with AV nodal blocking effect (Table 4) should be avoided as they would worsen the conduction delay [23].

Figure 10. First-degree AV block with inferolateral STEMI. ECG shows sinus rhythm, 1:1 atrioventricular conduction, with a fixed prolonged PR interval (PR interval = 205 ms) combined with ST-segment elevation in the inferior leads (Leads II, III, and aVF) and lateral leads (V5-V6), ST depression in V1-V2 is suggestive of associated posterior infarction, and reciprocal ST depression in leads I and aVL. Courtesy of Dr. Anas Halim. ECG digitized using PMcardio app.
Figure 10. First-degree AV block with inferolateral STEMI. ECG shows sinus rhythm, 1:1 atrioventricular conduction, with a fixed prolonged PR interval (PR interval = 205 ms) combined with ST-segment elevation in the inferior leads (Leads II, III, and aVF) and lateral leads (V5-V6), ST depression in V1-V2 is suggestive of associated posterior infarction, and reciprocal ST depression in leads I and aVL. Courtesy of Dr. Hassan Alshaqaq and Dr. Danya Khoujah.

Table 4. List of agents with AV nodal blocking/slowing activity [24].

Agents with potent AV nodal blocking activity:

  • Beta-blockers (e.g., Esmolol, Metoprolol)
  • Calcium channel blockers (e.g., Diltiazem, Verapamil)
  • Digoxin
  • Adenosine
  • Sotalol

Other cardiovascular agents with AV nodal blocking/slowing activity:

  • Amiodarone
  • Procainamide
  • Quinidine
  • Lidocaine
  • Flecainide
  • Propafenone
  • Disopyramide
  • Dronedarone

Second-Degree AV Block

Second-degree AV block is characterized by intermittent conduction failure, where one or more atrial impulses are not conducted; some conduction is still present. The atrial rate (P waves) is <100 bpm. The ECG shows P waves that are not followed by a ventricular contraction (QRS complex). It is classified into two types based on the pathophysiology and ECG features.

Second-Degree Mobitz Type I AV Block

Mobitz type I (also known as Wenckebach’s block) is characterized by a progressive prolongation of the AV conduction with a nonconducted atrial impulse. The ECG shows progressive prolongation of the PR interval until an atrial impulse is blocked (not followed by a QRS complex) (Figure 11). These cyclic features lead to a grouped beating in a rhythm strip.  Mobitz Type I could be identified in healthy individuals and might also be seen in patients with acute or chronic heart disease such as inferior MI [9], medication toxicity, myocarditis, or in patients after cardiac surgery. In most cases, specific treatment is not required unless hypoperfusion is present, in which case atropine is the first-line therapy [9].

Figure 11. Second-degree Mobitz type I AV Block. ECG shows progressive prolongation of PR interval with a subsequent nonconducted P wave, then the cycle repeats after the dropped beat. Courtesy of Dr. Harry Patterson, FACEM. Used with permission from Life in the Fast Lane licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License (CC BY-NC-SA 4.0). Source: https://litfl.com/. ECG digitized using PMcardio app.
Figure 11. Second-degree Mobitz type I AV Block. ECG shows progressive prolongation of PR interval with a subsequent nonconducted P wave, then the cycle repeats after the dropped beat. Courtesy of Dr. Harry Patterson, FACEM. Used with permission from Life in the Fast Lane licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License (CC BY-NC-SA 4.0). Source: https://litfl.com/.
Second-Degree Mobitz Type II AV Block

Mobitz type II block is characterized by a fixed AV conduction delay followed by a nonconducted atrial beat. ECG shows a fixed prolonged PR interval, each P wave is followed by a QRS complex until a nonconducted P wave is noted without a QRS complex (Figure 12). If 2 or more P waves are not conducted, it is called a high-grade AV block (Figure 13). Mobitz type II block represents electrical intranodal conducting system structural damage. In acute MI (most commonly anterior), it could progress into a complete heart block [9].

Figure 12. Second-degree Mobitz II AV block. The rhythm strip shows non-conducted P waves (arrows), with constant PR interval, constant P-P interval, and the RR interval surrounding the dropped beat is multiple the preceding RR interval. Used with permission from Life in the Fast Lane licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License (CC BY-NC-SA 4.0). Source: https://litfl.com/
Figure 12. Second-degree Mobitz II AV block. The rhythm strip shows non-conducted P waves (arrows), with constant PR interval, constant P-P interval, and the RR interval surrounding the dropped beat is multiple the preceding RR interval. Used with permission from Life in the Fast Lane licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License (CC BY-NC-SA 4.0). Source: https://litfl.com/
Figure 13. Second-degree “high-grade” AV block. ECG shows a 4:1 conduction ratio, atrial rate is approximately 140 beats/min, and ventricular rate is approximately 35 beats/min. Used with permission from Life in the Fast Lane licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License (CC BY-NC-SA 4.0). Source: https://litfl.com/
Figure 13. Second-degree “high-grade” AV block. ECG shows a 4:1 conduction ratio, atrial rate is approximately 140 beats/min, and ventricular rate is approximately 35 beats/min. Used with permission from Life in the Fast Lane licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License (CC BY-NC-SA 4.0). Source: https://litfl.com/

These patients should be placed on transcutaneous pacing pads in anticipation of clinical deterioration. Although atropine is usually ineffective, it may be utilized during preparation for pacing as it is not harmful. Patients with second-degree Mobitz type II AV block and features of hypoperfusion require emergent cardiac pacing. Eventually, these patients require transvenous cardiac pacing, especially those with underlying acute MI [9].

Third-Degree AV Block

Third-degree (complete) heart block is characterized by the lack of any AV conduction between atria and ventricles, leading to AV dissociation. Atrial impulses are not conducted at all, and an escape pacemaker arises to pace the ventricles with a rate of 40-60 beats/min or lower for the intranodal level. The ECG features no association between the P waves and QRS complexes, an atrial rate higher than the ventricular rate, and wide QRS complexes (Figure 14).

Figure 14. Third-degree AV block. ECG shows complete dissociation between P waves and QRS complexes, wide QRS complexes (QRS duration=154 ms), atrial rate of ~100 beats/min, Ventricular rate of ~30 beats/min, and the rhythm is maintained by a junctional escape rhythm. Courtesy of Dr. Ahmad Alsaif. Digitized using PMcardio app.
Figure 14. Third-degree AV block. ECG shows complete dissociation between P waves and QRS complexes, wide QRS complexes (QRS duration=154 ms), atrial rate of ~100 beats/min, Ventricular rate of ~30 beats/min, and the rhythm is maintained by a junctional escape rhythm. Courtesy of Dr. Ahmad Alsaif. Digitized using PMcardio app.

Depending on the block’s location, it may be termed “nodal” (such as in inferior MI) or “infranodal” (such as in anterior MI) [9]. Patients with third-degree AV block are usually unstable due to the inadequate cardiac output generated by the ventricular escape pacemaker. Atropine might work in cases of nodal blockade; however, it is unlikely to be effective in infranodal blockade. If the response to atropine is inadequate, transcutaneous cardiac pacing should be started. In those patients, consider beta-adrenergic medications (epinephrine or dopamine). Eventually, transvenous pacing is necessary in the majority of cases.

Atrial Fibrillation With a Slow Ventricular Response

Patients with atrial fibrillation may present with a slow ventricular response in the setting of an overdose of nodal-blocking medications (e.g., beta-blockers, calcium channel antagonists, digoxin) or significant conduction disease [25]. A very low ventricular rate may lead to hemodynamic compromise [26]. The hallmark ECG feature in these patients is an irregularly irregular ventricular rhythm without discernible P waves, either chaotic or flat isoelectric baseline (Figure 15). Patients with an irreversible cause of slow ventricular response (such as those with intrinsic conduction system disease) may require a permanent pacemaker [27].

Figure 15. Atrial fibrillation with a slow ventricular response. ECG shows irregular rhythm with no evidence of organized atrial activity, fine fibrillatory waves, with a ventricular rate of 60 beats/min. Courtesy of Dr. Ahmad Alsaif. ECG digitized using PMcardio app.
Figure 15. Atrial fibrillation with a slow ventricular response. ECG shows irregular rhythm with no evidence of organized atrial activity, fine fibrillatory waves, with a ventricular rate of 60 beats/min. Courtesy of Dr. Hassan Alshaqaq and Dr. Danya Khoujah.

Hyperkalemia-induced Bradycardia

Patients with hyperkalemia demonstrate several features on the ECG, including peaked T waves, PR prolongation, QRS widening, and sine-wave morphology [28]. Junctional rhythm is the most common bradycardic rhythm in patients with severe hyperkalemia [29], and patients may show other types of bradydysrhythmias [29]. Obtaining a serum potassium level is critical in any bradydysrhythmia, even without other ECG changes suggestive of hyperkalemia [29].

BRASH Syndrome

BRASH syndrome (Bradycardia, Renal failure, AV blockade, Shock, and Hyperkalemia) is caused by a synergistic effect of hyperkalemia and AV-blocking medications that produce dramatic bradycardia [30]. The marked bradycardia leads to poor renal perfusion, exacerbating hyperkalemia and leading to a vicious cycle, with resulting hemodynamic instability and multiorgan failure [30]. Precipitating factors identified include nephrotoxins, potassium-sparing diuretics, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, and digitalis [30].

Medical History

After stabilizing the patient, a comprehensive medical history often helps identify the underlying etiology. In patients unable to provide history (e.g., altered mentation), collateral history from family, emergency medical service (EMS) personnel, or nursing facility staff can be helpful.

Determining the stability of patients starts with their medical history. Symptoms of end-organ hypoperfusion, such as ischemic chest pain, dyspnea, altered mental state, and syncope,  may indicate hemodynamic instability [3,6]. Lack of symptoms, or only mild symptoms such as palpitations, lightheadedness, nausea, generalized fatigability, or mild anxiety [31], may indicate hemodynamic stability. It is essential to determine whether the presenting symptoms in patients with bradycardia are secondary to the bradycardia itself or whether the presence of bradycardia is coincidental.

Analyzing the characteristics of presenting symptoms is vital, including onset, progression (gradual vs. abrupt), duration, precipitating factors, preceding events, and any associated symptoms. Specific precipitating events include emotional distress, positional changes, urination, defecation, cough, prolonged standing, shaving, and head-turning [7]. Additionally, ask about symptoms of ACS, infectious diseases, and hypothyroidism.

A past medical history of rhythm disturbance, ischemic heart disease, structural heart disease, pacemaker placement, or coronary artery bypass graft (CABG) is relevant. Patients post transcatheter aortic valve replacement are at high risk for conduction system abnormalities [7]. A history of renal failure increases the risk of hyperkalemia.

Reviewing the medication list, as well as herbal substances and recreational drugs, including timing, doses, recent changes in patterns, compliance, and the possibility of overdose, is essential.

Travel history to areas endemic for infectious diseases, such as Chagas or Lyme, is relevant. Sexual history, specifically for history of or risk factor for syphilis, is relevant. Occupational history and chemical exposures (e.g., organophosphate) may offer clues for a toxicologic etiology.

Physical Examination

Physical examination of patients with rhythm disturbance primarily focuses on clues of end-organ hypoperfusion and underlying etiology. Assess the level of consciousness, and confirm adequate perfusion by examining the capillary refill, peripheral pulses, and temperature of extremities; cool extremities and delayed capillary refill (>3 sec) indicate hypoperfusion.

The cardiovascular examination includes palpating the radial pulse to determine the rate and rhythm, auscultating the heart sounds for the presence of murmurs, as well as looking for signs of heart failure (jugular venous distention, rales, edema of the extremities). Chest wall inspection for a midline sternotomy scar adds important information regarding the medical history. Palpating the skin overlying an implanted pacemaker may uncover lead abnormalities [32].

Look for signs of underlying pathology, including toxidromes (e.g., cholinergic, opioid-like), an arteriovenous fistula or dialysis catheter (indicates renal failure), head trauma, and signs of hypothyroidism. Core temperature measurement is vital in patients suspected to have hypothermia. In patients with head trauma, look for Cushing’s triad (hypertension, bradycardia, and irregular respirations). Table 5 illustrates a constellation of signs and symptoms indicating a possible underlying cause.

Table 5. Signs and symptoms suggestive of the underlying cause of bradycardia.

Possible underlying etiology

History

Physical examination

Myocardial infarction

  • Chest pain
  • Dyspnea
  • Anginal equivalent symptoms
  • Hypotension
  • Rales
  • New murmur

Myopericarditis

  • Fever
  • Dyspnea
  • Pleuritic chest pain
  • Recent respiratory or gastrointestinal infection
  • Malaise
  • Myalgias
  • Pericardial friction rub

Hyperkalemia

  • History of renal failure / dialysis
  • Arteriovenous fistula or dialysis catheter

Pacemaker malfunction

  • History of implanted cardiac device
  • History of cardiac conduction abnormality
  • Pacemaker identification card
  • Obvious device or lead abnormalities by palpation of the overlying skin

Increased ICP

  • History of head trauma
  • Headache
  • Vomiting
  • Decreased level of consciousness
  • Signs of basilar fracture
  • Depressed skull fracture
  • Focal neurologic deficit
  • Decreased level of consciousness

Beta blocker toxicity

  • Confusion
  • History of seizure
  • History of drug ingestion
  • History of underlying cardiac disease
  • Presence of cardioactive agents at home
  • Empty medication bottles
  • Depressed mental state
  • Hypoglycemia
  • Bronchospasm
  • Hypotension
  • Shock

Calcium channel blocker toxicity

  • History of drug ingestion
  • History of underlying cardiac disease
  • Presence of cardioactive agents at home
  • Empty medication bottles
  • Hyperglycemia
  • Hypotension
  • Shock

Digoxin toxicity

  • GI symptoms (abdominal pain, nausea, vomiting, anorexia)
  • Fatigue
  • Visual disturbance
  • Lethargy
  • Confusion
  • History of drug ingestion
  • History of underlying cardiac disease
  • Presence of cardioactive agents at home
  • Empty medication bottles
  • Altered mental status
  • Seizures
  • Hypotension
  • Shock

Local anesthetics toxicity

  • Perioral numbness
  • Visual disturbance
  • Confusion
  • Dizziness
  • Seizure
  • History of regional or topical anesthesia procedure
  • Altered mental status (ranging from agitation to unresponsiveness)
  • Weakness
  • Slurred speech

Clonidine overdose

  • History of drug ingestion
  • Miosis
  • Respiratory depression

Hypothyroidism

  • History of thyroid disease
  • Cold intolerance
  • Weight gain
  • Fatigability
  • Hypothermia
  • Constipation
  • Skin and hair changes
  • Thyroidectomy scar
  • Goiter
  • Pretibial myxedema
  • Coarse skin
  • Muscle hypertrophy
  • Hypothermia
  • Delayed relaxation phase of reflexes

Acing Diagnostic Testing

A 12-lead ECG is diagnostic for bradyarrhythmia. A single lead, most commonly lead II, is often adequate to make the diagnosis. ECG reading requires noting the rate, regularity, P waves, P-R interval, the relation between P waves and QRS complexes, and QRS width.

Furthermore, ECG may identify the underlying cause, such as acute ischemic changes (e.g., hyperacute T waves, ST-segment elevation/depression, T waves inversions, Q-waves), hyperkalemic changes (e.g., peaked T waves, P wave flattening, PR prolongation, wide QRS), cerebral T-waves (i.e., deep, symmetric, inverted T waves) in elevated intracranial pressure (ICP), downsloping ST depression in digoxin toxicity, and Osborn wave (i.e., positive deflection at the J point) in severe hypothermia (<32˚C). In patients with a malfunctioning implanted pacemaker, the ECG may show pacing spikes not followed by a QRS complex (electrical non-capture).

Given the intermittent nature of some bradyarrhythmia, a normal ECG does not exclude the diagnosis, especially in asymptomatic patients. Moreover, bradyarrhythmia may evolve; therefore, serial ECGs are advisable [2]. 

Point-of-care ultrasound (POCUS) helps in the assessment of volume status (inferior vena cava [IVC] assessment) and pulmonary edema (B-lines: vertical comet tail artifact).

Laboratory work-up to uncover the underlying etiology should be tailored to the clinical assessment. It may include the following:

  • Cardiac biomarkers (e.g., troponin) for identifying acute MI.
  • Electrolytes profile for identifying electrolyte abnormalities (particularly potassium and calcium).
  • Creatinine and blood urea nitrogen (BUN) can help diagnose acute and chronic renal failure.
  • Brain natriuretic peptide (BNP) elevation may indicate fluid overload and heart failure in the appropriate context.
  • Infectious work-up: 3 sets of peripheral cultures for infective endocarditis, serologic testing for syphilis, Lyme serology for Lyme disease, and thick and thin blood smear for Chagas disease.
  • Thyroid function test (TSH and free T4) for suspected hypothyroidism or myxedema coma.
  • Drug levels such as digoxin.

As for imaging, a chest X-ray may show evidence of pulmonary edema in patients with heart failure. In patients with pacemakers, it can identify lead fracture and migration.

Transthoracic echocardiography is essential in evaluating patients with newly identified Mobitz type II or third-degree AV block for cardiac wall motion abnormalities (indicative of an MI), valvular abnormalities, and structural heart disease. However, in patients with asymptomatic bradycardia or first-degree AV block, routine echocardiography is usually not indicated [7].

In patients with signs of a head injury and suspected increased ICP, obtain a head computed tomography (CT) scan.

Risk Stratification

Stability of Patient

Determining the hemodynamic stability of patients with bradyarrhythmia critical to management. Unstable patients require immediate treatment. Instability indicators include hypotension (defined as systolic BP [SBP] of <90 mm Hg), signs of shock (cold and moist skin, pale skin, delayed capillary refill time), ischemic chest pain, altered mental state, and dyspnea secondary to pulmonary edema (Table 6). Patients’ condition may change during treatment or ED stay, necessitating frequent reassessment to recognize impending clinical deterioration.

Table 6. Indicators of instability in patients with bradydysrhythmias

  1. Hypotension (SBP <90 mm Hg)
  2. Signs of shock
  3. Altered mental status
  4. Ischemic chest pain
  5. Dyspnea secondary to pulmonary edema

Symptomatic versus Asymptomatic

The presence of symptoms guides management. Generally, asymptomatic patients do not require treatment and may need monitoring only. In symptomatic patients, it is important to determine whether symptoms are caused by bradycardia or if the bradycardia is incidental to the actual cause of the presenting complaint.

Management

Pre-hospital care considerations

Stabilization might be started by EMS personnel, such as administration of atropine, epinephrine/dopamine infusion, and transcutaneous cardiac pacing [11,33-37], depending on their capabilities and local protocols. Transportation to a PCI-capable center is optimal for patients suspected to have an underlying ischemic pathology.

Initial Stabilization

Initial stabilization must start with a rapid assessment of the circulation, airway, and breathing “the CABs”), as well as the vital signs and signs of instability (Table 6). Patients with symptomatic bradyarrhythmia require a monitored bed with flat positioning [7]. Perform fingerstick glucose, establish two large-bore IVs, attach the patient to a continuous cardiac rhythm monitor, obtain a 12-lead ECG, and prepare for drug and electrical therapy simultaneously. If IV access cannot be obtained, attempt intraosseous (IO) access or a central line. Patients with significant symptomatic bradyarrhythmia, those with advanced heart block, and those predicted to deteriorate should be placed on pacer pads, irrespective of stability.

Although electrical cardiac pacing is immediately indicated in unstable patients, medical management may be more immediately available, making it reasonable to administer both while simultaneously identifying and treating the underlying cause [1,11]. However, atropine administration should never delay the initiation of transcutaneous pacing in unstable patients.1

A resuscitation cart, transvenous pacer kit, and airway equipment should be available at the bedside in anticipation of deterioration of critically ill patients with bradyarrhythmia. Oxygen is indicated to target SpO2 ≥94%. In select patients with hypotension (SBP < 90 mmHg), crystalloid fluids may improve blood pressure; caution must be taken in patients with decompensated heart failure. Hypotension refractory to fluid resuscitation may require inotropic and/or vasopressor support (e.g., epinephrine).

For unstable Mobitz Type II or third-degree AV block, initiate transcutaneous pacing, as well as atropine, if immediately available.  If ineffective, administer epinephrine 2-10 µg/min IV infusion. Although atropine is considered the first line of medical therapy, epinephrine may be preferred in critically unstable patients [38,39], and may be administered short-term through a peripheral IV access [40].

In patients with a wide QRS complex, atropine is unlikely to be effective due to a block at the distal conduction system; therefore, proceed immediately to epinephrine and transcutaneous pacing [1,41].

Patients with symptomatic bradycardia, or second- or third-degree AV block should be placed on continuous ECG monitoring (Class I recommendation) [42].

Figure 16 illustrates emergency approach and management of acute bradyarrhythmia in the ED.

Figure 16. Emergency management approach of patients with bradydysrhythmia. *Atropine should not be given to patients after heart transplantation. Abbreviations: BP, blood pressure; ECG, electrocardiogram; HR, heart rate; ICP, intracranial pressure; IV, intravenous; kg, kilogram; mA, milliampere; mg, milligram; mcg, microgram; MI, myocardial infarction; PCI, percutaneous coronary intervention; RR, respiratory rate; SpO2, oxygen saturation.
Figure 16. Emergency management approach of patients with bradydyarrhythmia. *Atropine should not be given to patients after heart transplantation. Abbreviations: BP, blood pressure; ECG, electrocardiogram; HR, heart rate; ICP, intracranial pressure; IV, intravenous; kg, kilogram; mA, milliampere; mg, milligram; mcg, microgram; MI, myocardial infarction; PCI, percutaneous coronary intervention; RR, respiratory rate; SpO2, oxygen saturation. Courtesy of Dr. Hassan Alshaqaq and Dr. Danya Khoujah.

Treatment Considerations

The anatomical location causing the bradycardia may predict the management and outcomes of bradyarrhythmia. Narrow QRS complex bradycardia indicates dysfunction at the level of the SA or AV node, usually requires minimal intervention, and is rarely life-threatening. On the other hand, wide QRS complex bradycardia indicates dysfunction at the level of distal His-Purkinje, usually requires aggressive management, is unlikely to respond to atropine, may require electrical pacing, and is associated with an elevated mortality rate [3].

Medications

Atropine

Atropine is the first-line treatment to increase the heart rate in patients with symptomatic bradycardia [1,2]. Atropine is an antimuscarinic medication with direct vagolytic activity, increasing the SA node’s automaticity and potentiating the AV node’s conduction. Atropine is most effective in sinus bradycardia and junctional rhythm. It is usually not useful in infranodal blocks presenting with wide QRS bradyarrhythmia. Atropine should be used cautiously in the setting of ACS due to the potential risk of exacerbating ischemia and infarct size from the resulting tachycardia [43-48]. Additionally, atropine should not be used in patients who have undergone heart transplants due to the lack of vagal innervation, as atropine may cause paradoxical AV block and asystole [1,7,49,50]. The dose of atropine is 0.5-1 mg IV every 3-5 min until resolution or maximum dose is reached (3 mg) [1,7].

Epinephrine

Epinephrine is an alternative medical therapy for bradyarrhythmia, and is the preferred adjunct medical management to electrical therapy in unstable patients, particularly those with Mobitz Type II and third-degree AV block [7]. Epinephrine acts on β1- and β2-receptors, working on the entire myocardium to increase the heart rate (inotropic and chronotropic effects), as well as enhancing the AV nodal conduction [51-52]. The dose of epinephrine is 2-10 mcg/min IV infusion, titrated to desired heart rate [7].

In peri-arrest bradycardia, some experts recommend a temporizing bolus dose of 20-50 mcg of epinephrine as an IV push, followed by infusion and electrical pacing [38,39,53,54], despite the lack of supporting data [53,54].

Dopamine

Dopamine may be used in bradyarrhythmia refractory to atropine (Class IIb) [7]. It acts on dopaminergic α1-, β1-, and β2-receptors. Higher doses (>10 mcg/kg/min) have a vasoconstrictive effect, while lower doses (1-2 mcg/kg/min) have a selective inotropic effect on the heart rate [1]. The dose of dopamine is 2 to 20 mcg/kg/min IV infusion titrated by 5 mcg/kg/min every 2 minutes to the desired heart rate [7,33], monitoring peripheral perfusion to avoid profound vasoconstriction [7].

Dobutamine

Dobutamine is a β-agonist agent with a weak α-adrenergic activity that may be used in symptomatic bradycardia; its predominant effect is inotropic via stimulation of β1-receptors [55]. Dobutamine can lead to vasodilation (via β2-receptors) and hypotension, thus, it should not be used in hypotensive patients. It can be used in cases of bradycardia resistant to standard therapy with normal or elevated blood pressure [7,38]. Dobutamine is administered as a 2-20 µg/kg/min IV infusion, titrated to desired heart rate.

Isoproterenol

Isoproterenol infusion is indicated in post-heart transplant patients with unstable bradycardia [7]. It can also be used in refractory bradyarrhythmia and AV blocks not responding to epinephrine [38]. It is a non-selective β-agonist stimulating β1– and β2-receptors, speeding up the SA and AV nodes and enhancing cardiac contractility (chronotropic and inotropic) [56]. It does not have any vasopressor effects.  Isoproterenol is given as a 2-10 mcg/min IV infusion, titrated to effect, or can be administered as an IV bolus of 1-2 mcg [1]. Isoproterenol is contraindicated in patients with angina/active ischemia due to concerns about increasing myocardial oxygen demand (β1 effect) and decreasing coronary perfusion (β2 effect), as well as in digoxin toxicity [7,57-60].

Aminophylline and Theophylline

Aminophylline and theophylline are methylxanthines, which exert positive chronotropic effects on the myocardium, likely by inhibiting the suppression effect of the adenosine on the SA node [7]. Both are reasonable to use if clinically indicated in symptomatic post-cardiac transplant patients [7,61-63] and sinus node dysfunction secondary to spinal cord injury, based on a limited case series [7,64-67].

In addition, aminophylline (250 mg IV bolus) has been used in treating second- and third-degree AV block associated with acute inferior MI, despite the limited direct evidence [7,68-70]. Aminophylline is administered with a dose of 6 mg/kg over 20-30 minutes, followed by an infusion of 0.3-0.5 mg/kg/hour [7]. Theophylline is administered as a bolus dose of 300 mg IV, followed by an oral dose of 5–10 mg/kg/day titrated to effect [7]. Although recommended by the guidelines, evidence for the use of methylxanthines is limited [7].

Table 7. Present bradyarrhythmia medications’ mechanism of action, dosing, pharmacokinetics, contraindications, and adverse events. 

Table created by authors

Electrical Cardiac Pacing

Electrical cardiac pacing is a procedure that aims to stimulate effective cardiac depolarization. Cardiac pacing is the mainstay management of acutely symptomatic patients with bradyarrhythmia, particularly unstable bradyarrhythmia or stable symptomatic bradyarrhythmia refractory to medical therapy, including type II second-degree and third-degree AV blocks [7]. It is of little value in toxin-induced bradyarrhythmia [32]. Cardiac pacing is performed using either a transcutaneous or transvenous approach. Transcutaneous cardiac pacing is a temporary bridging treatment until transvenous pacing or resolution of symptoms [7,32,38,39]. Transvenous pacing is also temporary until the resolution of the underlying cause or placement of a permanent pacemaker [7]. 

In crashing bradycardia, transcutaneous pacing should be started immediately. It is minimally invasive, instituted rapidly, and effectively treats hemodynamically unstable bradydysrhythmia [32]. The pacing pads are placed on the patient’s chest using one of two positions, an anterolateral or anteroposterior (Figure 17); positioning placement is selected based on the patient’s habitus and clinician’s preference [32]. Sedation and analgesia should be initiated as soon as possible utilizing hemodynamically stable agents such as low-dose fentanyl and/or ketamine, keeping in mind that most patients requiring electrical pacing are hemodynamically unstable.

Figure 17. Correct placement of transcutaneous pacing pads. A, anterolateral position; the anterior adhesive pad is placed inferior to the right clavicle, and the lateral adhesive pad is placed on the left fifth intercostal space at the anterior axillary line. B, anteroposterior position; the anterior adhesive pad is placed on the sternum, and the posterior adhesive pad is placed on the left infrascapular area. “Illustration by Malak Alraygi / re-designed Arif Alper Cevik”
Figure 17. Correct placement of transcutaneous pacing pads. A, anterolateral position; the anterior adhesive pad is placed inferior to the right clavicle, and the lateral adhesive pad is placed on the left fifth intercostal space at the anterior axillary line. B, anteroposterior position; the anterior adhesive pad is placed on the sternum, and the posterior adhesive pad is placed on the left infrascapular area. “Illustration by Malak Alraygi / re-designed by Arif Alper Cevik”

Adjust the pacing setting targeting a rate of 80-100 beats/min (start at 80 mA and reduce to the lowest energy) [2,39]. If the pacing is successful, the ECG will show electrical capture, which are pacing spikes followed by wide QRS complexes. Mechanical capture is demonstrated by a palpable pulse corresponding to each paced QRS complex on the cardiac monitor, preferably the femoral pulse to avoid the muscular contractions triggered by the pacer near the carotid artery, which may be confused with a pulse [32]. POCUS may be used to confirm myocardial contractions corresponding to each pacing spike and in confirming femoral pulse. In cases of cardiac arrest during transcutaneous pacing, chest compressions can be safely performed over the pacing pads [32].

Transvenous pacing has a high success rate (>95%) and is preserved for unstable bradyarrhythmias refractory to medications and transcutaneous pacing [6]. Transvenous pacing is contraindicated in patients with severe hypothermia [32]. Transvenous pacing is performed by introducing a transvenous pacing catheter into the right ventricle through a central venous catheterization (either right internal jugular or left subclavian central line). Pacemaker wire may be advanced into the endocardial wall of the right ventricle either blindly, or under the guidance of ECG or ultrasound (four-chamber view) [32]. Observe the cardiac monitor during the advancement of the wire [32]. Capture is confirmed by pacer spikes followed by QRS and ST-segment elevation, which indicates proper positioning [32]. Set the pacer generator on full-demand mode, with an output of 5 mA and a rate of 80 beats/min or at least 10 beats/min faster than the underlying ventricular rhythm [32]. Afterward, confirm electrical and mechanical capture. Continuous electrocardiographic monitoring is recommended for all patients on pacing (both transcutaneous and transvenous) until pacing is discontinued (class I) [42].

Patients with structural or electrophysiological conduction abnormalities often require definitive management with permanent pacemaker implantation. Class I recommendations have been issued for the implantation of permanent pacemakers in patients with acquired Mobitz type II AV block, high-grade AV block, and third-degree AV block not caused by reversible or physiologic causes, irrelevant of the presence of symptoms, due to the high risk of decompensation [7]. The decision to place a permanent pacemaker in patients with symptomatic sinus node dysfunction, persistent and symptomatic sinus bradycardia, and atrial fibrillation with symptomatic bradycardia in the absence of nodal blocking medications is dependent on the presence of symptoms and its correlation with the block itself [7].

Treatment of underlying etiology

Ischemia-related bradycardia

Patients with symptomatic bradyarrhythmia secondary to acute MI require stabilization and immediate reperfusion therapy, either PCI or thrombolysis, depending on feasibility.

Toxicity-related bradycardia

Patients with toxic or metabolic causes of bradycardia respond poorly to atropine and electrical pacing, and those patients require immediate treatment of the underlying cause, by eliminating the offending agent, utilizing supportive care, and administering an agent-specific antidote, if available [7]. Consulting toxicology and/or the local poison center early is paramount. Table 8 presents specific treatment strategies for toxicities related to bradycardia. In cardiac arrest secondary to an overdose, extracorporeal membrane oxygenation (ECMO) might be indicated to maintain perfusion until the underlying agent level is reduced or eliminated [6].

Table 8. Management of toxicologic causes of bradycardia.

Toxicity

Treatment

Beta-blocker toxicity

  • High-dose insulin 1 unit/kg IV bolus, followed by an infusion of 0.5 units/kg/h co-administered with dextrose 7,24,111
  • Glucagon 3-10 mg IV bolus over 3-5 min, followed by an IV infusion of 1-5 mg/h 7,96
  • Intravenous lipid emulsion112

Calcium channel blockers toxicity

  • 10% Calcium chloride 1-2 g IV bolus every 10-20 min or an infusion of 0.2-0.4 mL/kg/h7,113]
  • 10% calcium gluconate 3-6 g IV every 10-20 min or an infusion at 0.6-1.2 mL/kg/h7
  • High-dose insulin 1 unit/kg bolus, followed by an infusion of 0.5 units/kg/h co-administered with dextrose7,24,113
  • Glucagon 3-10 mg IV bolus over 3-5 min, followed by an IV infusion of 1-5 mg/h7,96
  • Intravenous lipid emulsion113

Digoxin toxicity

  • Digoxin-specific antibody fragments (dosage is dependent on amount of ingestion or serum level and whether acute or chronic toxicity)7. It is indicated in unstable bradydysrhythmias or K+ >5.0.

Organophosphate poisoning

  • Decontamination.
  • Atropine 1-3 mg IV every 5 min (0.01-0.04 mg/kg IV in children) with doubling the dose each time, followed by IV maintenance of 0.4-4 mg/hr.
  • Pralidoxime 1-2 g IM (20-40 mg/kg in children) with normal saline infused over 5-10 min followed by IV infusion of 500 mg/h (5-10 mg/kg/h in children).

Local anesthetic systemic toxicity

  • Intravenous lipid emulsion, initial bolus of 100 mL IV over 2–3 min, followed by an infusion of 200–250 mL IV over 15–20 min (for those <70 kg, the bolus dose is 1.5 mL/kg IV over 2–3 min, followed by 0.25 mL/kg/min IV infusion)114,115

Opioids toxicity

  • Naloxone 0.4-2 mg IV/IM/SC bolus repeated every 3 min (pediatrics: 0.1 mg/kg IV/IO/ET75).

Abbreviations: ET, endotracheal; ; g, gram; h, hour; IM, intramuscular; IO, intraosseous;  IV, intravenous; kg, kilogram; mg, milligram; min, minutes; mL, milliliter; mcg, microgram; SC, subcutaneous.

Hyperkalemia-related bradycardia treatment
Hyperkalemia may lead to profound bradycardia and mimic AV blocks [116]. Treatment should include the administration of 2 g calcium gluconate IV or 1 g calcium chloride IV to stabilize the cardiac membrane, in addition to treatments that shift the potassium across the cellular membrane and enhance its elimination.
BRASH syndrome treatment

Treating patients with BRASH syndrome involves a simultaneous approach that targets all associated conditions. The treatment strategy includes usual care of bradycardia (medications [such as epinephrine infusion] and/or pacing), hyperkalemia therapy (IV calcium, IV insulin and dextrose, and/or emergent dialysis), and fluid resuscitation [30]. In addition, it may include further advanced therapies in refractory cases or patients with AV-nodal blocking medication toxicity (e.g., lipid emulsion, glucagon, high-dose insulin, and digoxin-specific antibody) [30].

Hypothermia-related bradycardia treatment

In hypothermia, the first management line is rewarming, even before pacing. Due to the arrhythmogenic effect of hypothermia, pacing severely hypothermic patients has not been recommended due to concerns of precipitating ventricular fibrillation [23, 117]; however, case reports of successful pacing have been reported [118]. ECMO might be considered for severe hypothermia (<32 °C) and cardiac instability [119,120].

Myxedema coma-related bradycardia treatment

Patients with bradycardia secondary to myxedema coma require emergent thyroid hormone replacement (Levothyroxine [T4] 200-400 mcg IV, lower dose in geriatric patients) [121,122]. Adjunctive therapy includes hydrocortisone (100 mg IV), correction of hypoglycemia and electrolyte abnormalities (such as hyponatremia) and supportive care [121,122]. Moreover, identify and treat triggers causing decompensated hypothyroidism (e.g., infection, medications, MI, heart failure, and GI bleeding) [121]. 

Elevated ICP-related bradycardia treatment
For patients with bradycardia secondary to head trauma and increased ICP, treatment should be directed to lower the ICP, such as head elevation, hyperventilation, and mannitol or hypertonic saline.

Special Patient Groups

Considerations of bradycardia in pediatrics

The initial assessment of children is unique. The Pediatric Assessment Triangle is a rapid assessment tool to identify patients with respiratory or circulatory compromise who require immediate stabilization, and stands for appearance, breathing, and circulatory status [123, 124]. This is followed by a primary assessment using the ABCDE approach, similar to adults.

Clinically significant bradycardia in pediatric patients is defined as a heart rate less than the age-appropriate rate with impaired systemic perfusion [125]. The heart rate definition of pediatrics differs based on age, and in infants, an asleep heart rate has a different cut-off than an awake heart rate [126].

In pediatrics, always consider bradycardia as secondary to a reversible cause until proven otherwise. Bradycardia in the pediatric age group is usually associated with hypoxia (the most common cause), hypotension, acidosis, hypothermia, and medications, whereas primarily cardiac causes are rare [74,126].

Bradyarrhythmia in pediatrics is commonly a pre-arrest rhythm125; therefore, an early aggressive approach in children with bradycardia with poor perfusion has been recommended [127]. Immediate evaluation of adequate oxygenation and ventilation is necessary. In patients with a persistent heart rate of <60 and poor perfusion despite adequate oxygenation and ventilation, start chest compressions and follow the pediatric advanced life support (PALS) bradycardia algorithm [74,127], even if there is a detectable pulse.

Considerations for bradycardia in geriatrics

Older adults have a relatively high incidence of symptomatic bradycardia (6%), admission rate for symptomatic bradycardia (39%), rate of unstable bradycardia (16%), and mortality (5%) [128]. In older adults, ischemia tends to present atypically; thus, clinicians should have a high index of suspicion for an underlying ischemic cause. Moreover, polypharmacy is more common in older adults, thereby increasing the risk of drug-induced bradycardia and drug interactions.

Considerations of bradycardia in pregnancy

In critically ill pregnant patients, no medication should be withheld due to concerns of fetal teratogenicity [129,130]. Atropine crosses the placenta and risks and benefits of its use in stable patients should carefully weighed [131]. In unstable patients, atropine or epinephrine may be administered [132]. Epinephrine is preferred over dopamine in pregnancy [133].

Pregnant patients with symptomatic bradycardia necessitating atropine or vasoactive agents (e.g., epinephrine or dopamine) or those with advanced heart block require a multidisciplinary team, including obstetricians and neonatologists for maternal–fetal intensive monitoring [129], which may require transfer.

Bradycardia in patients with a heart transplant

Resting heart rate in heart transplant recipients ranges from 80-110 beats/min [134,135]. Therefore, bradycardia in these patients is defined as a heart rate persistently <70-80 beats/min [7,18,136]. Post-transplant bradycardia could be attributed to several mechanisms, including sympathetic denervation, SA ischemic injury, graft ischemia, and drug-induced [137-139].

Atropine is contraindicated due to the potential risk of paradoxical AV block and asystole [7,49]. Medications used to increase the heart rate include isoproterenol, aminophylline, and theophylline [7,61,140]. Target heart rate for temporary pacing, if indicated, is over 90 beats/min [140].

Following stabilization, those patients may require transport to an advanced heart transplant center for monitoring. It is recommended (Class I) to treat sinus node dysfunction medically in the postoperative period (1-6 weeks) and observe for resolution before attempting pacemaker implantation [21], which is eventually required in 7-24% of patients [136,141,144].

Disposition

All patients with symptomatic bradyarrhythmias require cardiology consultation [23]. Patients presenting with unstable or symptomatic bradyarrhythmias, particularly Mobitz type II or third-degree heart block, require admission to a cardiac ICU for monitoring.  Patients with secondary bradycardia often require admission for definitive treatment of the underlying etiology, either to the ICU or an intermediate care unit (i.e., stepdown). On the other hand, asymptomatic patients with benign ECG features and a normal ED work-up may be followed by cardiology on an outpatient basis; ambulatory electrocardiography monitoring and/or electrophysiology studies may be considered.

Revisiting your patient

The patient was rushed into a monitored bed. IV lines were established. The patient was placed on pacer pads. Atropine 1 mg IV was given with no response. ECG confirmed evidence of third-degree heart block (complete dissociation between P waves and QRS complexes, wide QRS complexes [QRS=154 ms], atrial rate of ~100 beats/min, Ventricular rate of ~30 beats/min, rhythm is maintained by a junctional escape rhythm). Epinephrine and transcutaneous pacing were initiated. Electrical capture was demonstrated on the ECG. The pacing rate was 85 beats/min.

The patient returned to his baseline mental state. Capillary refill improved, extremities became warm, the peripheral pulse became strong, and lactate clearance was appropriate.  Central line access was obtained to transition the patient into transvenous pacing. Cardiac biomarkers resulted, revealing a significantly elevated troponin level at seven times the upper limit of normal. The patient was diagnosed with non-ST elevation occlusive MI. Cardiology was consulted, and they admitted the patient to the cardiac ICU. The patient was taken to the cardiac catheterization laboratory for PCI the following day.

Authors

Picture of Hassan M. Alshaqaq, MBBS

Hassan M. Alshaqaq, MBBS

Hassan Alshaqaq is an Emergency Medicine PGY1 Resident at King Saud University Medical City. He is passionate about EM, research, medical education, resuscitation, and critical care. His research work has appeared in various medical journals and has been awarded by EM and critical care societies. He has been involved with several medical societies in different leadership and educational roles. He is interested in developing clinical practice guidelines and has contributed to the Saudi Critical Care Society guidelines. He is the student club president of the Saudi Society of EM. He is an enthusiast in contributing to EM education, particularly FOAMed.

Picture of Danya Khoujah, MBBS, MEHP

Danya Khoujah, MBBS, MEHP

Dr. Danya Khoujah is an American board-certified Emergency Physician with a keen interest in medical education. She completed her emergency medicine residency and faculty development fellowship at the University of Maryland in Baltimore and a Master of Education in Health Professions from Johns Hopkins University. She has developed over 120 lectures, 75 podcasts, and 50 publications on various emergency medicine and medical education topics that have been well received. She is most passionate about simplifying the science to allow healthcare practitioners to better care for their patients, whether seasoned physicians, resident physicians-in-training, medical students, or allied health professionals.

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References

  1. Neumar RW, Otto CW, Link MS, et al. Part 8: Adult Advanced Cardiovascular Life Support. Circulation. 2010;122(18_suppl_3). doi:10.1161/CIRCULATIONAHA.110.970988
  2. Deal N. Evaluation and management of bradydysrhythmias in the emergency department. Emerg Med Pract. 2013;15(9):1-15.
  3. Schwartz B, Vermeulen MJ, Idestrup C, Datta P. Clinical variables associated with mortality in out-of-hospital patients with hemodynamically significant bradycardia. Academic emergency medicine. 2004;11(6):656-661.
  4. Northcote RJ, Canning GP, Ballantyne D. Electrocardiographic findings in male veteran endurance athletes. Heart. 1989;61(2):155-160. doi:10.1136/hrt.61.2.155
  5. Talan DA, Bauernfeind RA, Ashley WW, Kanakis C, Rosen KM. Twenty-Four Hour Continuous ECG Recordings in Long-Distance Runners. Chest. 1982;82(1):19-24. doi:10.1378/chest.82.1.19
  6. Sodeck GH, Domanovits H, Meron G, et al. Compromising bradycardia: Management in the emergency department. Resuscitation. 2007;73(1):96-102. doi:10.1016/j.resuscitation.2006.08.006
  7. Kusumoto FM, Schoenfeld MH, Barrett C, et al. 2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation. 2019;140(8):382-482. doi:10.1161/CIR.0000000000000628
  8. Pejković B, Krajnc I, Anderhuber F, Košutić D. Anatomical Aspects of the Arterial Blood Supply to the Sinoatrial and Atrioventricular Nodes of the Human Heart. Journal of International Medical Research. 2008;36(4):691-698. doi:10.1177/147323000803600410
  9. Perron AD, Sweeney T. Arrhythmic Complications of Acute Coronary Syndromes. Emerg Med Clin North Am. 2005;23(4):1065-1082. doi:10.1016/j.emc.2005.07.002
  10. Wung SF. Bradyarrhythmias. Crit Care Nurs Clin North Am. 2016;28(3):297-308. doi:10.1016/j.cnc.2016.04.003
  11. Brady WJ, Swart G, DeBehnke DJ, Ma OJ, Aufderheide TP. The efficacy of atropine in the treatment of hemodynamically unstable bradycardia and atrioventricular block: prehospital and emergency department considerations. Resuscitation. 1999;41(1):47-55. doi:10.1016/S0300-9572(99)00032-5
  12. Swart G, Brady WJ, DeBehnke DJ, John O, Aufderheide TP. Acute myocardial infarction complicated by hemodynamically unstable bradyarrhythmia: Prehospital and ED treatment with atropine. Am J Emerg Med. 1999;17(7):647-652. doi:10.1016/S0735-6757(99)90151-1
  13. Norris RM, Mercer CJ. Significance of idioventricular rhythms in acute myocardial infarction. Prog Cardiovasc Dis. 1974;16(5):455-468. doi:10.1016/0033-0620(74)90006-1
  14. Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction—Executive Summary. Circulation. 2004;110(5):588-636. doi:10.1161/01.CIR.0000134791.68010.FA
  15. Tintinalli JE, Ma OJ, Yealy DM, et al. Tintinalli’s Emergency Medicine. Ninth. McGraw-Hill Education; 2019.
  16. Song Y, Laaksonen H, Saukko P, Toivonen S, Zhu J. Histopathological findings of cardiac conduction system of 150 Finns. Forensic Sci Int. 2001;119(3):310-317. doi:10.1016/S0379-0738(00)00457-6
  17. Bharati S, Lev M. The pathologic changes in the conduction system beyond the age of ninety. Am Heart J. 1992;124(2):486-496. doi:10.1016/0002-8703(92)90615-3
  18. HEINZ G, HIRSCHL M, BUXBAUM P, LAUFER G, GASIC S, LACZKOVICS A. Sinus Node Dysfunction After Orthotopic Cardiac Transplantation: Postoperative Incidence and Long-Term Implications. Pacing and Clinical Electrophysiology. 1992;15(5):731-737. doi:10.1111/j.1540-8159.1992.tb06838.x
  19. Demoulin JC, Kulbertus HE. Histopathological correlates of sinoatrial disease. Heart. 1978;40(12):1384-1389. doi:10.1136/hrt.40.12.1384
  20. Shaw DB, Linker NJ, Heaver PA, Evans R. Chronic sinoatrial disorder (sick sinus syndrome): a possible result of cardiac ischaemia. Heart. 1987;58(6):598-607. doi:10.1136/hrt.58.6.598
  21. Brignole M, Auricchio A, Baron-Esquivias G, et al. 2013 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy: The Task Force on cardiac pacing and resynchronization therapy of the European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA). Europace. 2013;15(8):1070-1118. doi:10.1093/europace/eut206
  22. Sathnur N, Ebin E, Benditt DG. Sinus Node Dysfunction. Card Electrophysiol Clin. 2021;13(4):641-659. doi:10.1016/j.ccep.2021.06.006
  23. Walls RM, Hockberger RS, Gausche-Hill M, Erickson TB, Wilcox SR. Rosen’s Emergency Medicine. Tenth. Philadelphia: Elsevier; 2022.
  24. Tisdale JE, Chung MK, Campbell KB, et al. Drug-Induced Arrhythmias: A Scientific Statement From the American Heart Association. Circulation. 2020;142(15):214-233. doi:10.1161/CIR.0000000000000905
  25. Fuster V, Rydén LE, Asinger RW, et al. ACC/AHA/ESC Guidelines for the Management of Patients With Atrial Fibrillation: Executive Summary A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to Develop Guidelines for the Management of Patients With Atrial Fibrillation) Developed in Collaboration With the North American Society of Pacing and Electrophysiology.Circulation. 2001;104(17):2118-2150.
  26. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation. J Am Coll Cardiol. 2014;64(21):e1-e76. doi:10.1016/j.jacc.2014.03.022
  27. Gilligan DM, Ellenbogen KA, Epstein AE. The management of atrial fibrillation. Am J Med. 1996;101(4):413-421. doi:10.1016/S0002-9343(96)00194-5
  28. Littmann L, Gibbs MA. Electrocardiographic manifestations of severe hyperkalemia. J Electrocardiol. 2018;51(5):814-817. doi:10.1016/j.jelectrocard.2018.06.018
  29. Drumheller BC, Tuffy E, Gibney F, Stallard S, Siewers C, Korvek S. Severe bradycardia from severe hyperkalemia: Patient characteristics, outcomes and factors associated with hemodynamic support. Am J Emerg Med. 2022;55:117-125. doi:10.1016/j.ajem.2022.03.007
  30. Farkas JD, Long B, Koyfman A, Menson K. BRASH Syndrome: Bradycardia, Renal Failure, AV Blockade, Shock, and Hyperkalemia. J Emerg Med. 2020;59(2):216-223. doi:10.1016/j.jemermed.2020.05.001
  31. Brady WJ, Harrigan RA. Evaluation and management of bradyarrhythmias in the emergency department. Emerg Med Clin North Am. 1998;16(2):361-388. doi:10.1016/S0733-8627(05)70007-9
  32. Roberts JR. Roberts and Hedges’ Clinical Procedures in Emergency Medicine and Acute Care. Seventh. Philadelphia: Elsevier; 2018.
  33. Morrison LJ, Long J, Vermeulen M, et al. A randomized controlled feasibility trial comparing safety and effectiveness of prehospital pacing versus conventional treatment: ‘PrePACE.’ Resuscitation. 2008;76(3):341-349. doi:10.1016/j.resuscitation.2007.08.008
  34. Sherbino J, Verbeek PR, MacDonald RD, Sawadsky B V., McDonald AC, Morrison LJ. Prehospital transcutaneous cardiac pacing for symptomatic bradycardia or bradyasystolic cardiac arrest: A systematic review. Resuscitation. 2006;70(2):193-200. doi:10.1016/j.resuscitation.2005.11.019
  35. Barthell E, Troiano P, Olson D, Stueven HA, Hendley G. Prehospital external cardiac pacing: A prospective, controlled clinical trial. Ann Emerg Med. 1988;17(11):1221-1226. doi:10.1016/S0196-0644(88)80074-X
  36. Hedges JR, Feero S, Shultz B, Easter R, Syverud SA, Dalsey WC. Prehospital Transcutaneous Cardiac Pacing for Symptomatic Bradycardia. Pacing and Clinical Electrophysiology. 1991;14(10):1473-1478. doi:10.1111/j.1540-8159.1991.tb04068.x
  37. Hedges JR, Syverud SA, Dalsey WC, Feero S, Easter R, Shultz B. Prehospital trial of emergency transcutaneous cardiac pacing. Circulation. 1987;76(6):1337-1343. doi:10.1161/01.CIR.76.6.1337
  38. Farkas J. Bradycardia. EMCrit. https://emcrit.org/ibcc/bradycardia/. Published November 20, 2021. Accessed April 1, 2023.
  39. Alblaihed L, Tewelde S. Bradydysrhythmias. CorePendium. https://www.emrap.org/corependium/chapter/recSdHpVvdD2oAbVe/Bradydysrhythmias. Published July 14, 2021. Accessed April 1, 2023.
  40. Tian DH, Smyth C, Keijzers G, et al. Safety of peripheral administration of vasopressor medications: A systematic review. Emergency Medicine Australasia. 2020;32(2):220-227. doi:10.1111/1742-6723.13406
  41. Helman A, Hedayati T, Dorian P. 4-Step Approach to Bradycardia and Bradydysrhythmias. Emergency Medicine Cases. https://emergencymedicinecases.com/approach-bradycardia-bradydysrhythmias/. Published 2018. Accessed April 1, 2023.
  42. Sandau KE, Funk M, Auerbach A, et al. Update to Practice Standards for Electrocardiographic Monitoring in Hospital Settings: A Scientific Statement From the American Heart Association. Circulation. 2017;136(19):e273-e344. doi:10.1161/CIR.0000000000000527
  43. Scheinman MM, Thorburn D, Abbott JA. Use of atropine in patients with acute myocardial infarction and sinus bradycardia. Circulation. 1975;52(4):627-633. doi:10.1161/01.CIR.52.4.627
  44. Richman S. Adverse effect of atropine during myocardial infarction. Enchancement of ischemia following intravenously administered atropine. JAMA. 1974;228(11):1414-1416.
  45. Dauchot P, Gravenstein JS. Bradycardia after Myocardial Ischemia and Its Treatment with Atropine. Anesthesiology. 1976;44(6):501-518. doi:10.1097/00000542-197606000-00008
  46. Massumi RA, Mason DT, Amsterdam EA, et al. Ventricular Fibrillation and Tachycardia after Intravenous Atropine for Treatment of Bradycardias. New England Journal of Medicine. 1972;287(7):336-338. doi:10.1056/NEJM197208172870706
  47. Pentecost BL, Bennett MA, George CF. Bradyarrhythmia Complicating Myocardial Infarction. The Lancet. 1968;292(7581):1300-1301. doi:10.1016/S0140-6736(68)91793-5
  48. Maroko PR, Kjekshus JK, Sobel BE, et al. Factors Influencing Infarct Size Following Experimental Coronary Artery Occlusions. Circulation. 1971;43(1):67-82. doi:10.1161/01.CIR.43.1.67
  49. Bernheim A, Fatio R, Kiowski W, Weilenmann D, Rickli H, Rocca HPBL. Atropine often results in complete atrioventricular block or sinus arrest after cardiac transplantation: an unpredictable and dose-independent phenomenon. Transplantation. 2004;77(8):1181-1185. doi:10.1097/01.TP.0000122416.70287.D9
  50. Rocca HPBL, Kiowski W, Bracht C, Weilenmann D, Follath F. Atrioventricular block after administration of atropine in patients following cardiac transplantation. Transplantation. 1997;63(12):1838-1839. doi:10.1097/00007890-199706270-00023
  51. Morady F, Nelson SD, Kou WH, et al. Electrophysiologic effects of epinephrine in humans. J Am Coll Cardiol. 1988;11(6):1235-1244. doi:10.1016/0735-1097(88)90287-2
  52. Tisdale JE, Patel R V., Webb CR, Borzak S, Zarowitz BJ. Proarrhythmic Effects of Intravenous Vasopressors. Annals of Pharmacotherapy. 1995;29(3):269-281. doi:10.1177/106002809502900309
  53. Panchal AR, Bartos JA, Cabañas JG, et al. Part 3: Adult Basic and Advanced Life Support: 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.Circulation. 2020;142(16_suppl_2):S366-S468. doi:10.1161/CIR.0000000000000916
  54. Holden D, Ramich J, Timm E, Pauze D, Lesar T. Safety Considerations and Guideline-Based Safe Use Recommendations for “Bolus-Dose” Vasopressors in the Emergency Department. Ann Emerg Med. 2018;71(1):83-92. doi:10.1016/j.annemergmed.2017.04.021
  55. Hollenberg SM. Vasoactive Drugs in Circulatory Shock. Am J Respir Crit Care Med. 2011;183(7):847-855. doi:10.1164/rccm.201006-0972CI
  56. Cossú SF, Rothman SA, Chmielewski IL, et al. The Effects of Isoproterenol on the Cardiac Conduction System. J Cardiovasc Electrophysiol. 1997;8(8):847-853. doi:10.1111/j.1540-8167.1997.tb00845.x
  57. Duong H, Masarweh OM, Campbell G, Win TT, Joolhar F. Isoproterenol Causing Coronary Vasospasm and ST Elevations During Tilt Table Testing. J Investig Med High Impact Case Rep. 2020;8. doi:10.1177/2324709620966862
  58. Ferrans VJ, Hibbs RG, Black WC, Weilbaecher DG. Isoproterenol-induced myocardial necrosis. A histochemical and electron microscopic study. Am Heart J. 1964;68(1):71-90. doi:10.1016/0002-8703(64)90242-X
  59. Kurland G, Williams J, Lewiston N. Fatal myocardial toxicity during continuous infusion intravenous isoproterenol therapy of asthma. Journal of Allergy and Clinical Immunology. 1979;63(6):407-411. doi:10.1016/0091-6749(79)90214-8
  60. Becker DJ, Nonkin PM, Bennett LD, Kimball SG, Sternberg MS, Wasserman F. Effect of isoproterenol in digitalis cardiotoxicity. Am J Cardiol. 1962;10(2):242-247. doi:10.1016/0002-9149(62)90302-8
  61. Bertolet BD, Eagle DA, Conti JB, Mills RM, Belardinelli L. Bradycardia after heart transplantation: Reversal with theophylline. J Am Coll Cardiol. 1996;28(2):396-399. doi:10.1016/0735-1097(96)00162-3
  62. Heinz G, Kratochwill C, Buxbaum P, et al. Immediate normalization of profound sinus node dysfunction by aminophylline after cardiac transplantation. Am J Cardiol. 1993;71(4):346-349. doi:10.1016/0002-9149(93)90805-M
  63. Redmond JM, Zehr KJ, Gillinov MA, et al. Use of theophylline for treatment of prolonged sinus node dysfunction in human orthotopic heart transplantation. J Heart Lung Transplant. 1993;12(1):133-139.
  64. Sadaka F, Naydenov SK, Ponzillo JJ. Theophylline for Bradycardia Secondary to Cervical Spinal Cord Injury. Neurocrit Care. 2010;13(3):389-392. doi:10.1007/s12028-010-9454-y
  65. Sakamoto T, Sadanaga T, Okazaki T. Sequential use of aminophylline and theophylline for the treatment of atropine-resistant bradycardia after spinal cord injury: a case report. J Cardiol. 2007;49(2):91-96.
  66. Pasnoori VR, Leesar MA. Use of Aminophylline in the Treatment of Severe Symptomatic Bradycardia Resistant to Atropine. Cardiol Rev. 2004;12(2):65-68. doi:10.1097/01.crd.0000096418.72821.fa
  67. Weant KA, Kilpatrick M, Jaikumar S. Aminophylline for the treatment of symptomatic bradycardia and asystole secondary to cervical spine injury. Neurocrit Care. 2007;7(3):250-252. doi:10.1007/s12028-007-0067-z
  68. Bertolet BD, McMurtrie E, Hill J, Belardinelli L. Theophylline for the Treatment of Atrioventricular Block after Myocardial Infarction. Ann Intern Med. 1995;123(7):509-511. doi:10.7326/0003-4819-123-7-199510010-00006
  69. Goodfellow J, Walker PR. Reversal of atropine-resistant atrioventricular block with intravenous aminophylline in the early phase of inferior wall acute myocardial infarction following treatment with streptokinase. Eur Heart J. 1995;16(6):862-865. doi:10.1093/oxfordjournals.eurheartj.a061008
  70. Altun A, Kirdar C, Özbay G. Effect of aminophylline in patients with atropine-resistant late advanced atrioventricular block during acute inferior myocardial infarction. Clin Cardiol. 1998;21(10):759-762. doi:10.1002/clc.4960211012
  71. Gorten R, Gunnells JC, Weissler AM, Stead EA. Effects of Atropine and Isoproterenol on Cardiac Output, Central Venous Pressure, and Mean Transit Time of Indicators Placed at Three Different Sites in the Venous System. Circ Res. 1961;9(5):979-983. doi:10.1161/01.RES.9.5.979
  72. Hinderling PH, Gundert-Remy U, Schmidliny O, Heinzel G. Integrated Pharmacokinetics and Pharmacodynamics of Atropine in Healthy Humans II: Pharmacodynamics. J Pharm Sci. 1985;74(7):711-717. doi:10.1002/jps.2600740703
  73. Berry JN, Thompson HK, Miller DE, McIntosh HD. Changes in cardiac output, stroke volume, and central venous pressure induced by atropine in man. Am Heart J. 1959;58(2):204-213. doi:10.1016/0002-8703(59)90337-0
  74. Topjian AA, Raymond TT, Atkins D, et al. Part 4: Pediatric Basic and Advanced Life Support: 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2020;142(16_suppl_2):S469-S523. doi:10.1161/CIR.0000000000000901
  75. Kleinman ME, Chameides L, Schexnayder SM, et al. Part 14: Pediatric Advanced Life Support. Circulation. 2010;122(18_suppl_3):S876-908. doi:10.1161/CIRCULATIONAHA.110.971101
  76. Lönnerholm G, Widerlöv E. Effect of intravenous atropine and methylatropine on heart rate and secretion of saliva in man. Eur J Clin Pharmacol. 1975;8(3-4):233-240. doi:10.1007/BF00567121
  77. Santini M, Ammirati F, Colivicchi F, Gentilucci G, Guido V. The effect of atropine in vasovagal syncope induced by head-up tilt testing. Eur Heart J. 1999;20(23):1745-1751. doi:10.1053/euhj.1999.1697
  78. Kentala E, Kaila T, Iisalo E, Kanto J. Intramuscular atropine in healthy volunteers: a pharmacokinetic and pharmacodynamic study. Int J Clin Pharmacol. 1990;28(9):399-404.
  79. Volz-Zang C, Waldhäuser T, Schulte B, Palm D. Comparison of the effects of atropine in vivo and ex vivo (radioreceptor assay) after oral and intramuscular administration to man. Eur J Clin Pharmacol. 1995;49(1-2):45-49. doi:10.1007/BF00192357
  80. Hinderling PH, Gundert-Remy U, Schmidlin O. Integrated pharmacokinetics and pharmacodynamics of atropine in healthy humans. I: Pharmacokinetics. J Pharm Sci. 1985;74(7):703-710. doi:10.1002/jps.2600740702
  81. Adams RG, Verma P, Jackson AJ, Miller RL. Plasma pharmacokinetics of intravenously administered atropine in normal human subjects. J Clin Pharmacol. 1982;22(10):477-481. doi:10.1002/j.1552-4604.1982.tb02638.x
  82. Van der Meer MJ, Hundt HK, Müller FO. The metabolism of atropine in man. J Pharm Pharmacol. 1986;38(10):781-784. doi:10.1111/j.2042-7158.1986.tb04494.x
  83. Kalser SC, McLain PL. Atropine metabolism in man. Clin Pharmacol Ther. 1970;11(2):214-227. doi:10.1002/cpt1970112214
  84. MacGregor DA, Smith TE, Prielipp RC, Butterworth JF, James RL, Scuderi PE. Pharmacokinetics of dopamine in healthy male subjects. Anesthesiology. 2000;92(2):338-346. doi:10.1097/00000542-200002000-00013
  85. Horwitz D, SM FD, Goldberg L. Effects of Dopamine in man. Circ Res. 1962;10:237-243. doi:10.1161/01.res.10.2.237
  86. Gundert-Remy U, Penzien J, Hildebrandt R, Mäurer W, Weber E. Correlation between the pharmacokinetics and pharmacodynamics of dopamine in healthy subjects. Eur J Clin Pharmacol. 1984;26(2):163-169. doi:10.1007/BF00630281
  87. Mueller HS, Evans R, Ayres SM. Effect of dopamine on hemodynamics and myocardial metabolism in shock following acute myocardial infarction in man. Circulation. 1978;57(2):361-365. doi:10.1161/01.cir.57.2.361
  88. Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Part 6: advanced cardiovascular life support: section 6: pharmacology II: agents to optimize cardiac output and blood pressure. The American Heart Association in collaboration with the International Liaison Committee on Resuscitation. Circulation. 2000;102(8 Suppl):I129-135.
  89. Juste RN, Moran L, Hooper J, Soni N. Dopamine clearance in critically ill patients. Intensive Care Med. 1998;24(11):1217-1220. doi:10.1007/S001340050747
  90. Borne P, Oren R, Somers VK. Dopamine depresses minute ventilation in patients with heart failure. Circulation. 1998;98(2):126-131. doi:10.1161/01.cir.98.2.126
  91. Fellows IW, Bennett T, MacDonald IA. The effect of adrenaline upon cardiovascular and metabolic functions in man. Clin Sci (Lond). 1985;69(2):215-222. doi:10.1042/cs0690215
  92. Stratton JR, Pfeifer MA, Ritchie JL, Halter JB. Hemodynamic effects of epinephrine: concentration-effect study in humans. J Appl Physiol (1985). 1985;58(4):1199-1206. doi:10.1152/jappl.1985.58.4.1199
  93. Abboud I, Lerolle N, Urien S, et al. Pharmacokinetics of epinephrine in patients with septic shock: modelization and interaction with endogenous neurohormonal status. Crit Care. 2009;13(4):R120. doi:10.1186/cc7972
  94. Parmley WW, Glick G, Sonnenblick EH. Cardiovascular effects of glucagon in man. N Engl J Med. 1968;279(1):12-17. doi:10.1056/NEJM196807042790103
  95. Murtagh JG, Binnion PF, Lal S, Hutchison KJ, Fletcher E. Haemodynamic effects of glucagon. Br Heart J. 1970;32(3):307-315. doi:10.1136/hrt.32.3.307
  96. Bailey B. Glucagon in beta-blocker and calcium channel blocker overdoses: a systematic review. J Toxicol Clin Toxicol. 2003;41(5):595-602. doi:10.1081/clt-120023761
  97. Lavonas EJ, Drennan IR, Gabrielli A, et al. Part 10: Special Circumstances of Resuscitation: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2015;132(18 Suppl 2):S501-18. doi:10.1161/CIR.0000000000000264
  98. Lvoff R, Wilcken DE. Glucagon in heart failure and in cardiogenic shock. Experience in 50 patients. Circulation. 1972;45(3):534-542. doi:10.1161/01.cir.45.3.534
  99. Love JN, Howell JM. Glucagon therapy in the treatment of symptomatic bradycardia. Ann Emerg Med. 1997;29(1):181-183. doi:10.1016/s0196-0644(97)70327-5
  100. Mansell PI, Fellows IW, Birmingham AT, Macdonald IA. Metabolic and cardiovascular effects of infusions of low doses of isoprenaline in man. Clin Sci (Lond). 1988;75(3):285-291. doi:10.1042/cs0750285
  101. Matsubara S, Morimatsu Y, Shiraishi H, et al. Fetus with heart failure due to congenital atrioventricular block treated by maternally administered ritodrine. Arch Gynecol Obstet. 2008;278(1):85-88. doi:10.1007/s00404-007-0516-0
  102. Castilla M, Jerez M, Llácer M, Martinez S. Anaesthetic management in a neonate with congenital complete heart block. Paediatr Anaesth. 2004;14(2):172-175. doi:10.1046/j.1460-9592.2003.01180.x
  103. Kadar D, Tang HY, Conn AW. Isoproterenol metabolism in children after intravenous administration. Clin Pharmacol Ther. 1974;16(5 Part 1):789-795. doi:10.1002/cpt1974165part1789
  104. Reyes G, Schwartz PH, Newth CJ, Eldadah MK. The pharmacokinetics of isoproterenol in critically ill pediatric patients. J Clin Pharmacol. 1993;33(1):29-34. doi:10.1002/j.1552-4604.1993.tb03899.x
  105. Okuya Y, Park JY, Garg A, Moussa I. Coronary Artery Spasm During Catheter Ablation Caused by the Intravenous Infusion of Isoproterenol. Intern Med. 2021;60(8):1221-1224. doi:10.2169/internalmedicine.6130-20
  106. McMurray JJ V, Adamopoulos S, Anker SD, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2012;33(14):1787-1847. doi:10.1093/eurheartj/ehs104
  107. Ahonen J, Aranko K, Iivanainen A, Maunuksela EL, Paloheimo M, Olkkola KT. Pharmacokinetic-pharmacodynamic relationship of dobutamine and heart rate, stroke volume and cardiac output in healthy volunteers. Clin Drug Investig. 2008;28(2):121-127. doi:10.2165/00044011-200828020-00006
  108. Pentel P, Benowitz N. Pharmacokinetic and pharmacodynamic considerations in drug therapy of cardiac emergencies. Clin Pharmacokinet. 1984;9(4):273-308. doi:10.2165/00003088-198409040-00001
  109. Dellinger RP, Levy MM, Rhodes A, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41(2):580-637. doi:10.1097/CCM.0b013e31827e83af
  110. Tisdale JE, Patel R, Webb CR, Borzak S, Zarowitz BJ. Electrophysiologic and proarrhythmic effects of intravenous inotropic agents. Prog Cardiovasc Dis. 1995;38(2):167-180. doi:10.1016/s0033-0620(05)80005-2
  111. Dalsey WC, Syverud SA, Hedges JR. Emergency department use of transcutaneous pacing for cardiac arrests. Crit Care Med. 1985;13(5):399-401. doi:10.1097/00003246-198505000-00006
  112. Rotella JA, Greene SL, Koutsogiannis Z, et al. Treatment for beta-blocker poisoning: a systematic review. Clin Toxicol (Phila). 2020;58(10):943-983. doi:10.1080/15563650.2020.1752918
  113. St-Onge M, Anseeuw K, Cantrell FL, et al. Experts Consensus Recommendations for the Management of Calcium Channel Blocker Poisoning in Adults. Crit Care Med. 2017;45(3):e306-e315. doi:10.1097/CCM.0000000000002087
  114. Neal JM, Neal EJ, Weinberg GL. American Society of Regional Anesthesia and Pain Medicine Local Anesthetic Systemic Toxicity checklist: 2020 version. Reg Anesth Pain Med. 2021;46(1):81-82. doi:10.1136/rapm-2020-101986
  115. Long B, Chavez S, Gottlieb M, Montrief T, Brady WJ. Local anesthetic systemic toxicity: A narrative review for emergency clinicians. Am J Emerg Med. 2022;59:42-48. doi:10.1016/j.ajem.2022.06.017
  116. Noble K, Isles C. Hyperkalaemia causing profound bradycardia. Heart. 2006;92(8):1063. doi:10.1136/hrt.2005.071803
  117. Helman A, Dorian P, Hedayati T. Treatment of Bradycardia and Bradydysrhythmias. Emergency Medicine Cases. https://emergencymedicinecases.com/treatment-bradycardia-bradydysrhythmias/. Published 2021. Accessed April 1, 2023.
  118. Ho JD, Heegaard WG, Brunette DD. Successful transcutaneous pacing in 2 severely hypothermic patients. Ann Emerg Med. 2007;49(5):678-681. doi:10.1016/j.annemergmed.2006.05.014
  119. Brugger H, Durrer B, Elsensohn F, et al. Resuscitation of avalanche victims: Evidence-based guidelines of the international commission for mountain emergency medicine (ICAR MEDCOM): intended for physicians and other advanced life support personnel. Resuscitation. 2013;84(5):539-546. doi:10.1016/j.resuscitation.2012.10.020
  120. Truhlář A, Deakin CD, Soar J, et al. European Resuscitation Council Guidelines for Resuscitation 2015: Section 4. Cardiac arrest in special circumstances. Resuscitation. 2015;95:148-201. doi:10.1016/j.resuscitation.2015.07.017
  121. Bridwell RE, Willis GC, Gottlieb M, Koyfman A, Long B. Decompensated hypothyroidism: A review for the emergency clinician. Am J Emerg Med. 2021;39:207-212. doi:10.1016/j.ajem.2020.09.062
  122. Jonklaas J, Bianco AC, Bauer AJ, et al. Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement. Thyroid. 2014;24(12):1670-1751. doi:10.1089/thy.2014.0028
  123. Dieckmann RA, Brownstein D, Gausche-Hill M. The pediatric assessment triangle: a novel approach for the rapid evaluation of children. Pediatr Emerg Care. 2010;26(4):312-315. doi:10.1097/PEC.0b013e3181d6db37
  124. Fernández A, Ares MI, Garcia S, Martinez-Indart L, Mintegi S, Benito J. The Validity of the Pediatric Assessment Triangle as the First Step in the Triage Process in a Pediatric Emergency Department. Pediatr Emerg Care. 2017;33(4):234-238. doi:10.1097/PEC.0000000000000717
  125. Jat KR, Lodha R, Kabra SK. Arrhythmias in children. Indian J Pediatr. 2011;78(2):211-218. doi:10.1007/s12098-010-0276-x
  126. Baruteau AE, Perry JC, Sanatani S, Horie M, Dubin AM. Evaluation and management of bradycardia in neonates and children. Eur J Pediatr. 2016;175(2):151-161. doi:10.1007/s00431-015-2689-z
  127. Van de Voorde P, Turner NM, Djakow J, et al. European Resuscitation Council Guidelines 2021: Paediatric Life Support. Resuscitation. 2021;161:327-387. doi:10.1016/j.resuscitation.2021.02.015
  128. Rujichanuntagul S, Sri-On J, Traiwanatham M, et al. Bradycardia in Older Patients in a Single-Center Emergency Department: Incidence, Characteristics and Outcomes. Open Access Emerg Med. 2022;14:147-153. doi:10.2147/OAEM.S351548
  129. ACOG Practice Bulletin No. 211: Critical Care in Pregnancy. Obstetrics and gynecology. 2019;133(5):e303-e319. doi:10.1097/AOG.0000000000003241
  130. Jeejeebhoy FM, Zelop CM, Lipman S, et al. Cardiac Arrest in Pregnancy: A Scientific Statement From the American Heart Association. Circulation. 2015;132(18):1747-1773. doi:10.1161/CIR.0000000000000300
  131. Bailey B. Are there teratogenic risks associated with antidotes used in the acute management of poisoned pregnant women? Birth Defects Res A Clin Mol Teratol. 2003;67(2):133-140. doi:10.1002/bdra.10007
  132. SANDLER M, RUTHREN CR, WOOD C. METABOLISM OF C14-NOREPINEPHRINE AND C14-EPINEPHRINE AND THEIR TRANSMISSION ACROSS THE HUMAN PLACENTA. Int J Neuropharmacol. 1964;3:123-128. doi:10.1016/0028-3908(64)90055-3
  133. Newell J. Dopamine. CorePendium. https://www.emrap.org/corependium/drug/recZPuXuOq4bUMquk/Dopamine#h.t44uk7at4g7p. Published May 12, 2023. Accessed April 1, 2023.
  134. Alexopoulos D, Yusuf S, Johnston JA, Bostock J, Sleight P, Yacoub MH. The 24-hour heart rate behavior in long-term survivors of cardiac transplantation. Am J Cardiol. 1988;61(11):880-884. doi:10.1016/0002-9149(88)90363-3
  135. Banner NR, Patel N, Cox AP, Patton HE, Lachno DR, Yacoub MH. Altered sympathoadrenal response to dynamic exercise in cardiac transplant recipients. Cardiovasc Res. 1989;23(11):965-972. doi:10.1093/cvr/23.11.965
  136. Woo GW, Schofield RS, Pauly DF, et al. Incidence, predictors, and outcomes of cardiac pacing after cardiac transplantation: an 11-year retrospective analysis. Transplantation. 2008;85(8):1216-1218. doi:10.1097/TP.0b013e31816b677c
  137. Thajudeen A, Stecker EC, Shehata M, et al. Arrhythmias after heart transplantation: mechanisms and management. J Am Heart Assoc. 2012;1(2):e001461. doi:10.1161/JAHA.112.001461
  138. Jacquet L, Ziady G, Stein K, et al. Cardiac rhythm disturbances early after orthotopic heart transplantation: prevalence and clinical importance of the observed abnormalities. J Am Coll Cardiol. 1990;16(4):832-837. doi:10.1016/s0735-1097(10)80330-4
  139. DiBiase A, Tse TM, Schnittger I, Wexler L, Stinson EB, Valantine HA. Frequency and mechanism of bradycardia in cardiac transplant recipients and need for pacemakers. Am J Cardiol. 1991;67(16):1385-1389. doi:10.1016/0002-9149(91)90469-2
  140. Costanzo MR, Dipchand A, Starling R, et al. The International Society of Heart and Lung Transplantation Guidelines for the care of heart transplant recipients. J Heart Lung Transplant. 2010;29(8):914-956. doi:10.1016/j.healun.2010.05.034
  141. Cantillon DJ, Tarakji KG, Hu T, et al. Long-term outcomes and clinical predictors for pacemaker-requiring bradyarrhythmias after cardiac transplantation: analysis of the UNOS/OPTN cardiac transplant database. Heart Rhythm. 2010;7(11):1567-1571. doi:10.1016/j.hrthm.2010.06.026
  142. Cantillon DJ, Gorodeski EZ, Caccamo M, et al. Long-term outcomes and clinical predictors for pacing after cardiac transplantation. J Heart Lung Transplant. 2009;28(8):791-798. doi:10.1016/J.HEALUN.2009.04.034
  143. Jones DG, Mortsell DH, Rajaruthnam D, et al. Permanent pacemaker implantation early and late after heart transplantation: clinical indication, risk factors and prognostic implications. J Heart Lung Transplant. 2011;30(11):1257-1265. doi:10.1016/j.healun.2011.05.010
  144. Wellmann P, Herrmann FEM, Hagl C, Juchem G. A Single Center Study of 1,179 Heart Transplant Patients-Factors Affecting Pacemaker Implantation. Pacing Clin Electrophysiol. 2017;40(3):247-254. doi:10.1111/pace.13021

Reviewed By

Picture of Arif Alper Cevik, MD, FEMAT, FIFEM

Arif Alper Cevik, MD, FEMAT, FIFEM

Prof Cevik is an Emergency Medicine academician at United Arab Emirates University, interested in international emergency medicine, emergency medicine education, medical education, point of care ultrasound and trauma. He is the founder and director of the International Emergency Medicine Education Project – iem-student.org, chair of the International Federation for Emergency Medicine (IFEM) core curriculum and education committee and board member of the Asian Society for Emergency Medicine and Emirati Board of Emergency Medicine.

Published by iEM Education Project Team

International collaboration to promote emergency medicine and provide free educational resources for undergraduate trainees and teachers/educators.

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