Acetylcholinesterase Inhibitor Poisoning: Treatment Guidelines
Primary Antidotes and Immediate Management
For life-threatening organophosphate or carbamate poisoning, immediately administer atropine to reverse muscarinic effects (bronchorrhea, bradycardia, bronchospasm) and pralidoxime for organophosphate poisoning to reactivate acetylcholinesterase and reverse nicotinic effects (muscle weakness, respiratory failure). 1
Atropine Administration
Atropine is the first-line antidote and must be given immediately for severe cholinergic poisoning. 1
- Initial dose: 2-4 mg IV for adults, repeated every 5-10 minutes until full atropinization is achieved 1, 2
- Atropinization endpoints: Clear chest on auscultation, heart rate >80/min, systolic blood pressure >80 mm Hg, cessation of secretions 1
- Dosing strategy: Double the dose every 5 minutes until atropinization occurs 1
- Maintenance: Continue atropine infusion to maintain atropinization for at least 48-72 hours 1, 2
- Total doses required: May need massive cumulative doses (far exceeding the typical 3 mg maximum used for bradycardia) 1, 2
Critical distinction: The atropine dosing for organophosphate poisoning is fundamentally different from bradycardia treatment—there is no 3 mg maximum limit in poisoning cases. 1, 2
Pralidoxime (Oxime) Administration
Pralidoxime should be administered for organophosphate poisoning, ideally within 36 hours of exposure and before "aging" of the acetylcholinesterase enzyme occurs. 1, 2
- Adult dosing: 1000-2000 mg IV infusion over 15-30 minutes, repeated after 1 hour if muscle weakness persists 2
- Maintenance: Additional doses every 10-12 hours as needed for persistent muscle weakness 2
- Alternative regimen: Continuous infusion at 500 mg/hour may be more effective for prolonged nicotinic symptoms 3
- Infusion rate caution: Do not exceed 200 mg/minute to avoid temporary worsening of cholinergic manifestations including cardiac arrest 2
Mechanism: Pralidoxime reactivates acetylcholinesterase by breaking the organophosphate-enzyme bond, specifically reversing nicotinic effects (muscle paralysis, respiratory failure) that atropine cannot address. 1
Carbamate Poisoning Considerations
For carbamate poisoning, atropine remains essential, but pralidoxime use is controversial. 1
- Carbamates spontaneously dissociate from acetylcholinesterase (self-limiting inhibition), unlike organophosphates which form permanent bonds 1
- Guideline recommendation: Do not withhold pralidoxime when the specific poison class is unknown 1
- Animal studies suggest appropriately dosed pralidoxime (25-50 mg/kg) may be beneficial in carbamate poisoning, while high doses may be harmful 4
Supportive Care Algorithm
1. Decontamination (Immediate Priority)
- Remove all contaminated clothing 1
- Wash skin and hair thoroughly with soap and water 1
- Healthcare provider protection: Use appropriate personal protective equipment to prevent secondary contamination 1
- Gastric lavage and activated charcoal if ingested 5
2. Airway Management
Early endotracheal intubation is recommended for life-threatening organophosphate or carbamate poisoning. 1
Intubation indications: 5
- Respiratory failure from any cause (bronchorrhea, bronchospasm, muscle paralysis, aspiration)
- Depressed level of consciousness with inability to protect airway
- Hemodynamic instability
- Increasing respiratory rate (e.g., 22 to 38 breaths/min indicates impending respiratory failure)
Critical warning: Avoid succinylcholine and mivacurium for intubation—these neuromuscular blockers are metabolized by cholinesterase and will have prolonged paralysis. 1, 2
3. Seizure Management
Administer benzodiazepines (diazepam first-line or midazolam) to treat seizures and agitation from organophosphate or carbamate poisoning. 1
4. Monitoring Requirements
- Continuous observation for at least 48-72 hours due to risk of relapse from continued absorption 1, 2
- Monitor for intermediate syndrome (occurs 24-96 hours post-exposure): neck flexor weakness, respiratory muscle weakness, proximal limb weakness 6
- Red blood cell acetylcholinesterase levels can approximate CNS toxicity severity 1
Clinical Manifestations by Receptor Type
Muscarinic Effects (Reversed by Atropine)
- Respiratory: Bronchorrhea, bronchospasm, laryngeal congestion 1
- Cardiovascular: Bradycardia, heart block, QT prolongation, hypotension 1
- Secretory: Excessive salivation, lacrimation, perspiration 1
- Gastrointestinal: Nausea, vomiting, diarrhea, abdominal cramps 1
- Urinary: Incontinence 1
- Ocular: Miosis 5
Nicotinic Effects (Reversed by Pralidoxime)
- Muscle fasciculations progressing to flaccid paralysis 1
- Respiratory muscle paralysis leading to respiratory failure 1
- Initial sympathetic hyperstimulation (tachycardia, hypertension) 1
Central Nervous System Effects
Common Pitfalls and Contraindications
Do not use atropine for bradycardia in the following situations: 1
- Type II second-degree or third-degree AV block with wide QRS (infranodal block)—atropine will be ineffective 1
- Post-cardiac transplant patients—may cause paradoxical bradycardia due to lack of vagal innervation 1
- Doses <0.5 mg may paradoxically worsen bradycardia 1, 7
Atropine cautions in acute coronary syndrome: Use cautiously as increased heart rate may worsen ischemia or increase infarct size. 1, 7
Pralidoxime timing: Effectiveness decreases after 36 hours due to "aging" of the organophosphate-enzyme complex. 2
Avoid these medications in organophosphate poisoning: Morphine, theophylline, aminophylline, reserpine, and phenothiazine tranquilizers. 2
Evidence Quality Note
The 2023 American Heart Association focused update provides the most current Class 1 recommendations for atropine and pralidoxime in organophosphate/carbamate poisoning. 1 However, meta-analyses of pralidoxime efficacy show conflicting results, with some studies suggesting no mortality benefit and possible harm. 6 Despite this, guideline recommendations support pralidoxime use, particularly when administered early via continuous infusion. 1, 8