What is the preferred method of atropine (antimuscarinic agent) administration, bolus versus infusion, in the treatment of organophosphorus poisoning in patients of various ages and with different medical histories, including those with pre-existing respiratory conditions?

Atropine Administration in Organophosphate Poisoning: Bolus vs Infusion

Use rapid incremental bolus dosing to achieve initial atropinization, followed by continuous infusion for maintenance therapy—this approach reduces mortality, shortens time to atropinization, and decreases complications compared to conventional intermittent bolus dosing alone. 1

Initial Atropinization: Rapid Incremental Bolus Protocol

The loading phase must use aggressive bolus dosing with rapid escalation:

• Start with 1-2 mg IV for adults (0.02 mg/kg for children, minimum 0.1 mg, maximum single dose 0.5 mg in pediatrics) 2, 3, 4
• Double the dose every 5 minutes until full atropinization is achieved 2, 3, 4
• This doubling strategy is critical and differs fundamentally from fixed-dose repetition 3

The FDA label recommends 2-4 mg initially, repeated at 5-10 minute intervals, which represents a more conservative approach 5. However, the American Heart Association's more aggressive 1-2 mg with doubling every 5 minutes has stronger guideline support 2, 3.

Endpoints of Atropinization

Stop escalation only when ALL of the following are achieved 3, 4:

• Clear chest on auscultation (resolution of bronchorrhea)
• Heart rate >80 beats/min
• Systolic blood pressure >80 mm Hg
• Dry skin and mucous membranes
• Mydriasis (pupil dilation)

Continue escalation regardless of heart rate—tachycardia is NOT a contraindication to continued dosing 3, 4. The tachycardia may originate from nicotinic receptor overstimulation by the organophosphate itself, not from atropine 4.

Maintenance Phase: Continuous Infusion is Superior

Once atropinization is achieved, switch to continuous infusion rather than intermittent boluses 3:

• Administer 10-20% of the total loading dose per hour, up to 2 mg/h in adults 2, 3
• Continuous infusion is preferred over intermittent boluses for maintenance 3

Evidence Supporting Infusion Over Bolus Maintenance

A randomized clinical trial in Bangladesh (n=156) demonstrated that rapid incremental bolus dosing followed by continuous infusion versus conventional intermittent bolus dosing resulted in 1:

• Mortality: 8% (infusion group) vs 22.5% (bolus-only group), p<0.05
• Time to atropinization: 23.9 minutes vs 151.7 minutes, p<0.001
• Atropine toxicity: 12% vs 28.4%, p<0.05
• Intermediate syndrome: 4% vs 13.6%, p<0.05
• Need for respiratory support: 8% vs 24.7%, p<0.05

This is the highest quality and most recent study directly comparing these approaches, and it clearly demonstrates superiority of the bolus-then-infusion strategy 1.

Dosing Considerations Based on Severity

Atropine requirements vary dramatically based on acetylcholinesterase inhibition 6:

• When RBC-AChE activity is 10-30%: approximately 0.005 mg/kg/h maintains adequate S-hyoscyamine levels
• When RBC-AChE is completely inhibited: doses up to 0.06 mg/kg/h may be required
• Cumulative doses may reach 10-20 mg in the first 2-3 hours, with some patients requiring up to 50 mg in 24 hours 3

Critical Management Principles

Never delay atropine administration—it is the immediate life-saving intervention with Class 1, Level A evidence 3, 7. The risk of undertreating organophosphate poisoning far exceeds the risk of atropine-induced complications 4.

Common Pitfalls to Avoid

• Underdosing: The therapeutic endpoint is control of muscarinic symptoms, not heart rate normalization 3, 4
• Stopping for tachycardia: Atropine-induced tachycardia is an expected pharmacologic effect representing adequate muscarinic receptor blockade 4
• Premature discontinuation: Maintain atropinization for at least 48-72 hours, as delayed complications and relapses can occur, especially with ingested organophosphates due to continued GI absorption 4, 8

Essential Concurrent Therapies

Atropine alone is insufficient 7, 4:

• Pralidoxime: 1-2 g IV over 15-30 minutes, then 400-600 mg/h for adults (10-20 mg/kg/h for children) 7, 4
• Benzodiazepines: Diazepam or midazolam for seizures and agitation 7, 4
• Early intubation: For life-threatening poisoning, avoiding succinylcholine and mivacurium 7, 4

Monitoring Strategy

• Continuous cardiac monitoring for dysrhythmias, not to limit atropine dosing 4
• Serial respiratory assessments every 5-10 minutes during escalation 4
• Observe for at least 48-72 hours for delayed complications 4, 8
• Monitor for malignant arrhythmias, which can occur when S-hyoscyamine concentrations fall below 2.5 nmol/L 6