What toxins can cause bradycardia?

Toxins That Cause Bradycardia

Beta blockers, calcium channel blockers, digoxin, organophosphates, and nerve agents are the primary toxins that cause bradycardia, with each requiring specific treatment approaches based on their mechanism of action. 1

Common Toxins Causing Bradycardia

Medication-Related Causes

• Beta blockers: Cause bradycardia through direct effects on the β1-adrenergic receptor, leading to reduced heart rate and cardiac contractility 1
• Non-dihydropyridine calcium channel blockers (e.g., diltiazem, verapamil): Cause pronounced effects on cardiac tissue, including sinoatrial and atrioventricular nodes, resulting in negative chronotropy 1
• Digoxin and related cardiac glycosides: Can cause severe bradycardia, AV nodal blockade, and life-threatening ventricular arrhythmias 1
• Antiarrhythmic drugs: Particularly Class IA (quinidine, procainamide), Class IC (flecainide, propafenone), and Class III (amiodarone, sotalol) 1
• Other medications: Lithium, methyldopa, risperidone, cisplatin, interferon 1

Chemical and Environmental Toxins

• Organophosphates: Cause bradycardia through cholinergic overstimulation 1, 2
• Carbamates: Similar mechanism to organophosphates 1, 2
• Nerve agents: Cause severe cardiac depression manifested as bradycardia and hypotension through parasympathetic overstimulation 1
• Tetrodotoxin: Blocks sodium channels leading to bradycardia 1
• Toluene: Industrial solvent that can cause bradycardia 1
• Cocaine: Can paradoxically cause bradycardia in certain circumstances 1

Pathophysiological Mechanisms

• Cholinergic/Muscarinic overstimulation: Organophosphates, carbamates, and nerve agents inhibit acetylcholinesterase, leading to excess acetylcholine and parasympathetic overstimulation 1, 2, 3
• Direct cardiac suppression: Beta blockers directly suppress sinoatrial node function 1
• Ion channel blockade: Calcium channel blockers block L-type calcium channels; some toxins affect sodium or potassium channels 1
• Combined mechanisms: BRASH syndrome (Bradycardia, Renal failure, AV nodal blockade, Shock, and Hyperkalemia) represents a dangerous cycle where hyperkalemia worsens bradycardia from medications like beta blockers 4

Clinical Manifestations

• Electrocardiographic changes: Sinus bradycardia (18.9-30.8% of organophosphate poisonings), prolonged QT interval, ST-T changes, and conduction defects 2, 3
• Hemodynamic effects: Hypotension, cardiogenic shock 1
• Rhythm disturbances: Can progress from bradycardia to more serious arrhythmias including ventricular tachycardia and ventricular fibrillation 3, 5

Management Approaches by Toxin Type

Beta Blocker Toxicity

1. First-line interventions:

   • Vasopressors for hypotension (Class I recommendation) 1
   • High-dose insulin for hypotension refractory to vasopressors (Class I recommendation) 1

2. Second-line interventions:

   • Glucagon bolus followed by continuous infusion (Class IIa recommendation) 1
   • Atropine for bradycardia (Class IIb recommendation) 1
   • Electrical pacing for bradycardia (Class IIb recommendation) 1
   • VA-ECMO for refractory cardiogenic shock (Class IIa recommendation) 1
   • Hemodialysis for atenolol or sotalol poisoning (Class IIb recommendation) 1

Calcium Channel Blocker Toxicity

• Calcium administration (20 mg/kg of 10% calcium chloride IV over 5-10 minutes) 1
• Vasopressors and inotropes such as norepinephrine or epinephrine 1
• Consider insulin-glucose infusion 1

Organophosphate and Nerve Agent Toxicity

• Atropine in large doses to counteract cholinergic effects 1, 2
• For severe cases, atropine dosing may need to be doubled every 10-20 minutes until pulmonary secretions are controlled 1
• Pralidoxime as an adjunct to atropine for organophosphate poisoning 1
• Beta-agonists (albuterol) for bronchospasm 1
• Mechanical ventilation for respiratory support 1

Digoxin Toxicity

• Antidigoxin Fab antibodies for severe cardiac glycoside toxicity (Class I recommendation) 1
• Avoid medications that can worsen AV block 1

Special Considerations

• Monitoring: ECG monitoring is essential in all cases of suspected toxin-induced bradycardia, as progression to more serious arrhythmias can occur 3, 5
• Refractory cases: Consider extracorporeal life support techniques for life-threatening toxicity unresponsive to pharmacological interventions 1
• Combined toxicity: When multiple toxins or mechanisms are involved (e.g., BRASH syndrome), addressing all components is critical 4
• Heart transplant patients: Atropine should not be used to treat sinus bradycardia in patients who have undergone heart transplant without evidence of autonomic reinnervation (Class III: Harm) 1

Pitfalls and Caveats

• Isolated benzodiazepine poisoning rarely causes significant bradycardia; consider concomitant toxins if bradycardia is present 1
• Intravenous lipid emulsion therapy is not likely to be beneficial for life-threatening beta-blocker poisoning (Class III: No Benefit) 1
• Atropine may be ineffective for severe beta-blocker induced bradycardia and should not delay implementation of more definitive therapies 1
• Electrocardiographic abnormalities in organophosphate poisoning can persist beyond the acute phase, requiring extended cardiac monitoring 3, 5