How should atropine be diluted and dosed for acute organophosphate poisoning in adults and children?

Atropine Dilution and Dosing for Organophosphate Poisoning

Atropine should be administered undiluted as a direct IV bolus in organophosphate poisoning—dilution is unnecessary and delays life-saving therapy. 1, 2, 3

Immediate Administration Protocol

Adults

• Give 1–2 mg IV push immediately for severe manifestations (bronchospasm, bronchorrhea, seizures, significant bradycardia), using the commercially available 0.4 mg/mL or 1 mg/mL concentration without dilution. 1, 3
• Double the dose every 5 minutes (not every 20–30 minutes) until full atropinization is achieved—this aggressive escalation is critical and differs from older protocols. 1
• Expect to use 10–20 mg in the first 2–3 hours; some patients require up to 50 mg over 24 hours before muscarinic symptoms resolve. 1, 2, 4, 5

Children

• Give 0.02 mg/kg IV/IO immediately (minimum 0.1 mg, maximum 0.5 mg per dose for children; 1.0 mg for adolescents >40 kg). 1, 6
• Double the dose every 5 minutes until atropinization endpoints are met—standard pediatric bradycardia dosing is dangerously inadequate for organophosphate poisoning. 1, 6
• Higher cumulative doses are required in children compared to standard resuscitation; do not cap doses arbitrarily. 6

Atropinization Endpoints (When to Stop Escalating)

Monitor continuously and stop doubling doses only when all four criteria are met: 1, 2

• Clear lungs on auscultation (dry bronchi, no bronchorrhea)
• Heart rate >80 beats/min
• Systolic blood pressure >80 mm Hg
• Dry skin and mucous membranes with mydriasis (dilated pupils)

Maintenance Infusion After Initial Boluses

• Once atropinization is achieved, start a continuous infusion at 10–20% of the total loading dose per hour (maximum 2 mg/h in adults). 1
• This prevents the need for repeated boluses and maintains therapeutic levels during prolonged organophosphate absorption from lipid stores. 1

Mandatory Concurrent Therapies

Pralidoxime (2-PAM)

• Give pralidoxime 1–2 g IV over 15–30 minutes for adults (25–50 mg/kg for children, maximum 2 g) immediately after starting atropine. 1
• Follow with continuous infusion of 400–600 mg/h for adults (10–20 mg/kg/h for children) to maintain plasma levels above 4 µg/mL. 1
• Atropine reverses only muscarinic effects; pralidoxime is essential to reverse nicotinic effects (muscle paralysis, respiratory failure) that atropine cannot address. 1, 7

Benzodiazepines

• Administer diazepam 0.2 mg/kg IV or midazolam 0.05–0.1 mg/kg IV for seizures or severe agitation. 1, 6

Critical Pitfalls to Avoid

• Never dilute atropine for organophosphate poisoning—the FDA-approved formulations (0.4 mg/mL or 1 mg/mL) are ready for immediate IV push without dilution. 2, 3
• Never use doses below 0.5 mg in adults—paradoxical bradycardia from central vagal stimulation can occur with subtherapeutic doses. 2
• Never confuse cardiac bradycardia dosing (maximum 3 mg total) with toxicological dosing—organophosphate poisoning requires 10–50× higher cumulative doses without arbitrary limits. 1, 2
• Never stop atropine escalation due to tachycardia—tachycardia is an expected pharmacologic effect and is NOT a contraindication; the therapeutic endpoint is control of life-threatening muscarinic symptoms, not heart rate. 1
• Never delay pralidoxime while awaiting laboratory confirmation—the organophosphate–acetylcholinesterase bond "ages" irreversibly within minutes to hours, rendering oxime therapy ineffective. 1
• Never use succinylcholine or mivacurium for intubation—these neuromuscular blockers are metabolized by cholinesterase and are absolutely contraindicated. 1, 6

Practical Dosing Example: 13 kg Child

• Initial atropine dose: 0.26 mg IV (0.02 mg/kg × 13 kg), given undiluted as IV push. 1
• If inadequate response after 5 minutes: 0.52 mg IV (double the previous dose). 1
• Continue doubling every 5 minutes (1.04 mg → 2.08 mg → 4.16 mg) until all atropinization endpoints are met. 1
• Concurrent pralidoxime: 325–650 mg IV over 15–30 minutes (25–50 mg/kg), followed by 130–260 mg/h infusion (10–20 mg/kg/h). 1

Evidence Quality

The American Heart Association assigns atropine a Class 1 recommendation with Level A evidence for severe organophosphate poisoning, and pralidoxime a Class 2a recommendation with Level A evidence—both are supported by high-quality data and decades of clinical experience. 1 The aggressive 5-minute doubling protocol and undiluted administration represent current best practice based on pharmacokinetic studies showing rapid redistribution and the need for sustained therapeutic levels. 1, 7, 4