What are the dosage and administration guidelines for Physostigmine in treating anticholinergic poisoning?

Physostigmine Dosing and Administration for Anticholinergic Poisoning

For pediatric anticholinergic poisoning, administer physostigmine 0.02 mg/kg intramuscularly or by slow intravenous injection at no more than 0.5 mg per minute, with a maximum single dose of 0.5 mg, repeating at 5-10 minute intervals if needed up to a maximum total dose of 2 mg. 1

Pediatric Dosing Protocol

Initial Dose:

• 0.02 mg/kg administered intramuscularly or by slow IV injection 1
• Maximum rate: 0.5 mg per minute (never faster) 1
• Maximum single dose: 0.5 mg 1

Repeat Dosing:

• If toxic anticholinergic effects persist and there are no signs of cholinergic effects, repeat the dose at 5-10 minute intervals 1
• Maximum total cumulative dose: 2 mg 1

Adult Dosing Considerations

For hospital stocking purposes, guidelines recommend having 4 mg available for 8-hour treatment of one 100 kg patient, suggesting this represents the typical total dose needed 2

Administration Safety Requirements

Critical Rate Control:

• Rapid administration can cause bradycardia, hypersalivation leading to respiratory difficulties, and possible convulsions 1
• Always administer at a controlled rate not exceeding 1 mg per minute 1

Monitoring During Administration:

• Watch for excessive cholinergic symptoms: salivation, emesis, urination, and defecation—if these occur, terminate physostigmine immediately 1
• If excessive sweating or nausea occur, reduce the dosage 1
• Be prepared to provide respiratory support 1

Clinical Effectiveness

Response Rates by Agent:

• 100% response for non-diphenhydramine antihistamines, antipsychotics, and tricyclic antidepressants 3
• 68.7% response for anticholinergic plants 3
• 64.2% response for diphenhydramine 3
• Most patients (74.3%) required physostigmine alone without additional sedation 3

Time to Effect:

• Improvement in agitation typically occurs within 15-20 minutes of administration 4
• In cases where benzodiazepines failed to control violent agitation, physostigmine successfully decreased combative behavior 4

Indications and Patient Selection

Appropriate Use:

• Pure anticholinergic overdose with severe symptoms including pronounced delirium and violent agitation requiring physical restraint 5, 4
• Classic anticholinergic toxidrome: tachycardia, hot/dry/flushed skin, markedly dilated and fixed pupils, and delirium 4
• When benzodiazepines have failed to control severe agitation 4

Contraindications:

• Unknown ingestions or mixed overdoses 5
• Patients with cardiac conduction defects 5
• Tricyclic antidepressant overdose with cardiac conduction abnormalities (historical concern for asystole) 5
• Absence of anticholinergic symptoms 5

Safety Profile and Adverse Effects

Common Adverse Effects (from large retrospective study):

• 95.3% of patients had no documented adverse effects 3
• Emesis: 2.1% 3
• QTc prolongation: 1.0% 3
• Seizures: 1.0% 3

Sulfite Allergy Warning:

• Contains sodium bisulfite, which may cause allergic-type reactions including anaphylaxis or asthmatic episodes in susceptible individuals 1
• Sulfite sensitivity is more common in asthmatic patients 1

Cholinergic Crisis:

• Overdosage can cause a cholinergic crisis requiring immediate supportive care 1

Clinical Outcomes

Disposition:

• 18.8% of patients were discharged directly from the emergency department after physostigmine administration 3
• 8.4% of patients treated with physostigmine alone were discharged directly from the ED 3
• Most patients (57.6%) were admitted to ICU for observation 3

Key Clinical Pitfalls to Avoid

1. Never administer rapidly—this is the most common cause of serious complications including bradycardia and seizures 1
2. Do not use in unknown ingestions—toxicity occurs when used without confirmed anticholinergic symptoms 5
3. Do not continue if cholinergic symptoms develop—excessive salivation, emesis, urination, or defecation mandate immediate cessation 1
4. Do not exceed maximum doses—the 2 mg total pediatric dose limit exists for safety reasons 1
5. Always have atropine available—to reverse cholinergic crisis if overdosage occurs 1