Treatment of Anticholinergic Poisoning
For anticholinergic poisoning, immediately discontinue the offending agent, provide supportive care with IV fluids and benzodiazepines for agitation, and administer physostigmine (1-2 mg IV in adults, 0.02 mg/kg IV in children) for severe toxicity with significant CNS effects or life-threatening peripheral manifestations. 1, 2
Initial Stabilization and Assessment
- Secure airway, breathing, and circulation as the first priority 2
- Obtain vital signs including temperature, heart rate, blood pressure, and perform focused neurological assessment to evaluate level of consciousness and agitation 2
- Obtain an ECG to assess for QRS prolongation or dysrhythmias 2
- Recognize the classic anticholinergic presentation: delirium, hot and dry skin with erythema, mydriasis, tachycardia, mild hyperthermia, tachypnea, and decreased or absent bowel sounds 1
- The dry, erythematous skin distinguishes anticholinergic toxicity from sympathomimetic toxicity which presents with diaphoresis 1
First-Line Treatment Approach
Discontinue and Decontaminate
- Immediately discontinue the precipitating anticholinergic agent 1, 2
- Consider activated charcoal if recent oral ingestion occurred and the airway is protected 2
Supportive Care
- Administer IV fluids for hydration 1, 2
- Provide benzodiazepines for agitation and seizure control 1, 2, 3
- Benzodiazepines are the first-line treatment for agitation, though they may not fully resolve combative behavior in severe cases 3
Physostigmine: The Definitive Antidote
Physostigmine is indicated for severe anticholinergic toxicity with significant CNS effects (severe delirium, hallucinations, seizures) or life-threatening peripheral manifestations. 1, 2
Dosing and Administration
- Adult dosing: 1-2 mg IV slowly over 5 minutes, may repeat after 10-30 minutes if needed 2
- Pediatric dosing: 0.02 mg/kg IV (maximum 0.5 mg/dose) 1, 2
- Physostigmine works by reversibly inhibiting acetylcholinesterase, increasing acetylcholine concentration at cholinergic transmission sites 4
- Dramatic reversal of anticholinergic symptoms occurs within 15-20 minutes after IV administration 4, 3
- Duration of action is relatively short (45-60 minutes), so repeat dosing may be necessary 4
Evidence Supporting Physostigmine Use
- Patients receiving physostigmine alone have significantly lower intubation rates (1.9% vs. 8.4%) compared to other treatments 5
- In case series, physostigmine decreased agitation within 15-20 minutes without untoward effects 3
- Despite its efficacy, toxicologists use physostigmine in only 12.4% of anticholinergic toxicity cases as sole therapy, with benzodiazepines being more commonly used (28.7%) 5
Contraindications to Physostigmine
Do not administer physostigmine in patients with: 1, 2
- Cardiovascular disease
- Asthma
- Gangrene
- Diabetes
- Mechanical obstruction of the intestine or urinary tract
Common Pitfall
- Underdosing of physostigmine is common; larger doses than standard may be required in severe cases 2
Management of Specific Complications
Hyperthermia
Urinary Retention
- Manage with bladder catheterization 2
QRS Prolongation or Dysrhythmias
Severe Agitation Not Responsive to Benzodiazepines
- This is a specific indication for physostigmine administration 2
Special Considerations and Caveats
- Avoid succinylcholine in patients with anticholinergic crisis as it may cause prolonged paralysis 1, 2
- Physostigmine readily crosses the blood-brain barrier (unlike neostigmine, a quaternary ammonium compound), allowing it to reverse both central and peripheral anticholinergic effects 4
- In cases of national physostigmine shortage, rivastigmine (3 mg orally or via nasogastric tube, repeated hourly until symptom resolution, or transdermal patch) may serve as an alternative, though this is based on limited case reports 6