What is the recommended atropine (antimuscarinic agent) dose titration for organophosphate (OP) poisoning?

Atropine Dose Titration in Organophosphate Poisoning

For organophosphate poisoning, start with 1-2 mg IV atropine in adults (0.02 mg/kg in children), then double the dose every 5 minutes until bronchorrhea, bronchospasm, bradycardia, and hypotension resolve, followed by a maintenance infusion of 10-20% of the total loading dose per hour (up to 2 mg/h in adults). 1

Initial Bolus Dosing Algorithm

Adult Dosing

• Initial dose: 1-2 mg IV, administered immediately for severe manifestations (bronchospasm, bronchorrhea, seizures, or significant bradycardia) 1, 2
• Escalation protocol: Double the dose every 5 minutes until therapeutic endpoints are achieved 1, 2
• Example progression: 1-2 mg → 2-4 mg → 4-8 mg → 8-16 mg, continuing as needed 1

Pediatric Dosing

• Initial dose: 0.02 mg/kg IV/IO (minimum 0.1 mg, maximum single dose 0.5 mg for standard resuscitation) 2
• Escalation protocol: Double the dose every 5 minutes, same as adults 1
• Critical caveat: Children require relatively higher atropine doses than standard pediatric resuscitation protocols—do not underdose 2

Therapeutic Endpoints for Atropinization

Titrate atropine to reversal of life-threatening muscarinic symptoms, NOT to heart rate or pupil size. 1, 2 The specific endpoints include:

• Respiratory: Dry lungs with resolution of bronchorrhea and bronchospasm, adequate oxygenation 2, 3
• Cardiovascular: Resolution of bradycardia and hypotension 1
• Secretions: Dry skin and mucous membranes 2
• Pupils: Mydriasis (but this is a secondary sign, not a primary endpoint) 2

Maintenance Infusion Protocol

Once adequate atropinization is achieved with bolus dosing:

• Adult maintenance: 10-20% of the total loading dose per hour, up to 2 mg/h 1
• Pediatric maintenance: 10-20 mg/kg/hour 2
• Duration: Continue until muscarinic symptoms are controlled, which may require days of therapy (mean duration 9.6 days in severe cases) 4

Critical Management Principles

Aggressive Dosing is Essential

Very high doses of atropine are often required and should not be feared. 2, 5 Case reports document successful use of:

• Up to 100 mg IV bolus on admission 5
• Up to 100 mg/hour during follow-up 5
• Total cumulative doses exceeding 11.6 grams over 12 days 5
• Mean first-day doses of 178.9 mg (range 60-480 mg) 4

Tachycardia is NOT a Contraindication

Do not stop or reduce atropine due to tachycardia—this is an expected pharmacologic effect and NOT a reason to withhold therapy. 2 The tachycardia may actually result from:

• Nicotinic receptor overstimulation from the organophosphate itself 2
• Expected antimuscarinic effects of atropine 2, 3
• Mixed clinical picture from both muscarinic and nicotinic effects 2

The therapeutic endpoint is control of life-threatening muscarinic symptoms (bronchorrhea, bronchospasm, bradycardia, hypotension), not heart rate normalization. 1, 2

Concurrent Essential Therapies

Always administer pralidoxime concurrently with atropine (Class 2a recommendation, Level A evidence), as atropine alone is insufficient to manage respiratory depression and does not address nicotinic effects like muscle weakness. 2

• Pralidoxime dosing: 1-2 g IV initially for adults (10-20 mg/kg for children), followed by 400-600 mg/hour maintenance infusion for adults (10-20 mg/kg/hour for children) 2
• Timing: Administer early, before "aging" of the phosphorylated enzyme occurs 2

Benzodiazepines should be administered for seizures and agitation. 2

Common Pitfalls to Avoid

Underdosing Atropine

The most dangerous error is inadequate atropinization, which leads to respiratory failure and death. 2 The risk of undertreating organophosphate poisoning far exceeds the risk of atropine toxicity. 2

Stopping for Fever

Never withhold or prematurely discontinue atropine due to fever. 2 Atropine-induced fever is an expected adverse effect with high-dose therapy and does not indicate treatment failure. 2 Fever may also result from:

• Nicotinic effects causing muscle fasciculations and increased metabolic activity 2
• Aspiration pneumonia from bronchorrhea 2

Titrated vs. Ad Hoc Dosing

Evidence suggests that structured titration protocols based on clinical response are superior to ad hoc high-dose regimens. 6 Titrated dosing results in:

• Less atropine toxicity (delirium 1% vs. 17%, hallucinations 1% vs. 35%) 6
• No difference in mortality or ventilation rates 6
• More appropriate use of atropine with better monitoring 6

Monitoring Strategy

• Continuous cardiac monitoring for dysrhythmias 2
• Serial respiratory assessments to auscultate for bronchorrhea resolution 2
• Close monitoring for at least 48-72 hours after initial stabilization 2
• Use structured monitoring sheets to guide titration and prevent both under- and over-dosing 6

Airway Management Considerations

Early endotracheal intubation is recommended for life-threatening organophosphate poisoning. 2 When intubating:

• Avoid succinylcholine and mivacurium (metabolized by cholinesterase) 2
• Continue aggressive atropinization even after intubation 2