What are the indications, contraindications, standard dosing, and notable facts about atropine?

Atropine Reference Sheet

Indications

Atropine is a muscarinic antagonist indicated for temporary blockade of severe or life-threatening muscarinic effects, including symptomatic bradycardia, organophosphate poisoning, and specific cardiac arrest scenarios. 1

Cardiac Indications

• Symptomatic sinus bradycardia (heart rate <50 bpm with hypotension, ischemia, or escape ventricular arrhythmias) 2, 3
• Ventricular asystole during cardiac arrest 2, 3
• Symptomatic AV block at the AV nodal level (second-degree type I or third-degree with narrow-complex escape rhythm) 2, 3
• Bradycardia with hemodynamic compromise (hypotension, altered mental status, chest pain, acute heart failure, or shock) 3

Toxicological Indications

• Organophosphate poisoning (nerve agents, insecticides) 2
• Carbamate poisoning 2
• Digoxin toxicity 2
• Beta-blocker overdose 2
• Calcium channel blocker overdose 2
• Local anesthetic toxicity 2

Other Indications

• Antisialagogue (reduction of secretions) 1
• Antivagal effects during procedures 1

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Contraindications

Absolute Contraindications (FDA Label)

• Hypersensitivity to atropine 4
• Narrow-angle glaucoma 4
• Adhesions between iris and lens (synechiae) 4
• Tachycardia 4
• Unstable cardiovascular status in acute hemorrhage 4
• Obstructive GI disease (achalasia, pyloroduodenal stenosis, pyloric obstruction) 4
• Paralytic ileus 4
• Severe ulcerative colitis or toxic megacolon 4
• Obstructive uropathy (bladder neck obstruction from prostatic hypertrophy) 4
• Myasthenia gravis 4

Clinical Contraindications (Guideline-Based)

• Infranodal AV block (third-degree heart block with wide-complex escape rhythm or Mobitz II second-degree block) - atropine can paradoxically worsen bradycardia and precipitate ventricular asystole 2, 5, 3
• Heart transplant patients - may cause paradoxical slowing 5, 3

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Standard Dosing

Cardiac Indications

For symptomatic bradycardia or AV nodal block:

• Initial dose: 0.5 mg IV 2, 3, 1
• Repeat every 3-5 minutes as needed 2, 3
• Maximum total dose: 3 mg (complete vagal blockade) 2, 3
• Alternative maximum: 2-2.5 mg per some guidelines 2

Critical dosing caveat: Doses <0.5 mg can cause paradoxical bradycardia through central vagal stimulation - always use at least 0.5 mg IV 2, 3, 6

For patients with coronary artery disease:

• Limit total dose to 0.03-0.04 mg/kg to minimize tachycardia-induced ischemia 1
• Titrate to minimally effective heart rate (approximately 60 bpm) rather than maximal dosing 2

For cardiac arrest (ventricular asystole):

• 1 mg IV 2
• Repeat every 3-5 minutes if asystole persists 2

Toxicological Indications

For organophosphate/carbamate poisoning:

• Initial dose: 1-2 mg IV (adults) 2
• Double the dose every 5 minutes until muscarinic symptoms resolve 2
• Pediatric: 0.02 mg/kg, doubled every 5 minutes 2
• Maintenance infusion: 10-20% of total loading dose per hour (up to 2 mg/h in adults) 2
• Titrate to reversal of: bronchorrhea, bronchospasm, bradycardia, and hypotension 2
• Aggressive dosing required: 10-20 mg in first 2-3 hours is typical; up to 50 mg in 24 hours may be needed 2

For beta-blockers, calcium channel blockers, digoxin, local anesthetics:

• 0.5-1.0 mg IV every 3-5 minutes 2
• Maximum: 3 mg 2

Antisialagogue/Antivagal Effects

• Initial single dose: 0.5-1 mg IV 1

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Administration Considerations

• Route: Intravenous preferred for rapid effect 1
• Intramuscular administration: Feasible for mass casualty scenarios with organophosphate exposure, especially when using high-concentration formulations (2 mg/mL) 7
• Titration: Adjust according to heart rate, PR interval, blood pressure, and symptom resolution 1
• Non-IV or low-dose (<0.5 mg) administration: Can worsen bradycardia and depress AV conduction 6

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Warnings and Precautions

Cardiovascular

• Tachycardia risk: Atropine-induced tachycardia increases myocardial oxygen demand and can worsen ischemia or extend infarct size in acute MI 2, 3, 6, 1
• Use with extreme caution in acute coronary syndromes 2, 3
• Rare but serious: Ventricular tachycardia and ventricular fibrillation can occur 2, 6

Paradoxical Effects

• Low doses (<0.5 mg): Can paradoxically worsen bradycardia and depress AV conduction through central vagal stimulation 2, 6
• Infranodal block: May worsen block and precipitate asystole 5

Other Organ Systems

• Glaucoma: Can precipitate acute angle-closure glaucoma 1, 4
• Urinary retention: Can worsen obstructive uropathy 1, 4
• Respiratory: May cause viscid bronchial plugs 1
• GI: Can worsen pyloric obstruction 1, 4

CNS Toxicity

• Anticholinergic syndrome: Fever, confusion, hallucinations with repeated or high-dose administration 6
• Monitor for: Delirium, agitation, hyperthermia 6

Allergic Reactions

• Rare but documented: Anaphylaxis can occur 8
• Alternative agents for proven allergy: Glycopyrrolate (peripheral effects) combined with benzodiazepines or scopolamine (central effects) 8

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Fun Facts and Clinical Pearls

Historical and Pharmacological

• FDA approval: 1960 - one of the oldest continuously used emergency medications 1
• Mechanism: Competitive antagonist at muscarinic acetylcholine receptors 1
• Complete vagal blockade: Achieved at 3 mg total dose 2, 3

Organophosphate Poisoning Pearls

• Aggressive dosing is the norm: The American College of Cardiology notes that 10-20 mg in the first 2-3 hours is typical, with some patients requiring up to 50 mg in 24 hours 2
• Rapid incremental dosing superior: A 2012 randomized trial showed that doubling doses every few minutes followed by infusion reduced mortality from 22.5% to 8% compared to conventional bolus dosing 9
• Time to atropinization matters: Modern recommendations achieve therapeutic doses within 30 minutes, compared to >18 hours with older regimens 10
• Atropine addresses muscarinic effects only: Does not reverse nicotinic receptor paralysis - oximes (pralidoxime, obidoxime) are needed for respiratory muscle paralysis 2
• "Aging" phenomenon: Organophosphate-AChE bonds become irreversible within minutes, making early oxime administration critical 2

Cardiac Pearls

• Most effective within 6 hours: Atropine works best for sinus bradycardia occurring within 6 hours of acute MI symptom onset 2
• Bezold-Jarisch reflex: Atropine reverses bradycardia from reperfusion or right coronary artery thrombolysis 2
• Protective parasympathetic tone: The American College of Cardiology warns that parasympathetic activity protects against VF and infarct extension, so use cautiously in MI 2

Practical Considerations

• Mass casualty preparation: Existing 0.4-1 mg/mL atropine stocks can be fortified with pharmaceutical-grade powder to 2 mg/mL concentration, stable for 8 weeks refrigerated or 4 weeks at room temperature 7
• Compounding time: Approximately 1 hour to prepare high-concentration formulations 7
• Hospital stockpile inadequacy: Many hospitals lack sufficient atropine for mass organophosphate exposure scenarios 7

Dosing Evolution

• Consensus emerging: While WHO recommendations remain slow, most current authorities recommend rapid atropinization with dose-doubling strategies 10
• Evidence gap: Despite decades of use, controlled trials comparing atropine regimens remain scarce 10, 9