What is the treatment for a 45mg neostigmine overdose?

Management of 45mg Neostigmine Overdose

Immediately administer atropine or glycopyrrolate to manage the cholinergic crisis, support ventilation artificially if respiratory muscles are compromised, and withdraw all anticholinesterase drugs. 1

Immediate Recognition and Differentiation

A 45mg absolute dose of neostigmine represents a massive overdose (typical therapeutic dosing is 0.04-0.05 mg/kg, meaning 45mg would be appropriate for a 900-1000kg patient). This will cause cholinergic crisis characterized by: 1

• Muscarinic symptoms: nausea, vomiting, diarrhea, excessive sweating, increased bronchial and salivary secretions, bradycardia 1
• Nicotinic symptoms: increasing muscle weakness progressing to respiratory muscle involvement and potential death 1
• Critical distinction: Must differentiate cholinergic crisis from myasthenic crisis, as they present similarly with extreme muscle weakness but require opposite treatments 1

Use edrophonium chloride testing and clinical judgment to differentiate between cholinergic crisis (which requires drug withdrawal) versus myasthenic crisis (which requires more anticholinesterase therapy). 1

Primary Treatment Algorithm

Step 1: Immediate Anticholinergic Administration

• Administer atropine immediately to counteract muscarinic effects (bradycardia, excessive secretions, gastrointestinal symptoms) 1
• Alternative: glycopyrrolate can be used instead of atropine 1
• Caution: While atropine treats muscarinic symptoms, it can mask signs of ongoing overdosage and inadvertently lead to deeper cholinergic crisis if you're not careful 1

Step 2: Respiratory Support

• Provide artificial ventilation support immediately if respiratory adequacy is compromised 1
• Continue ventilatory support until spontaneous respiration is adequate 1
• Monitor for respiratory muscle weakness, which can progress to respiratory failure and death 1

Step 3: Cardiac Monitoring

• Continuously monitor cardiac function throughout the overdose management 1
• Watch for severe bradycardia and dysrhythmias 1

Step 4: Withdraw All Anticholinesterase Drugs

• Immediately discontinue neostigmine and any other drugs in this class 1
• Do not administer additional anticholinesterase agents, as this will worsen the cholinergic crisis 1

Critical Pitfalls to Avoid

Never administer more neostigmine or other anticholinesterase drugs during suspected cholinergic crisis - this can have grave consequences including death. 1

Do not rely solely on atropine to mask symptoms - while it treats muscarinic effects, overuse can obscure the true severity of overdosage and prevent recognition of worsening cholinergic crisis. 1

Monitor for prolonged effects - neostigmine has a half-life of 15-30 minutes, but in massive overdose, effects may be prolonged and require extended monitoring and support. 2

Expected Clinical Course

• Muscle weakness will be the most dangerous manifestation, potentially progressing to involve respiratory muscles 1
• Research demonstrates that even therapeutic doses of neostigmine (2.5mg in adults, approximately 35 mcg/kg) can cause significant muscle weakness (-20% grip strength), depolarizing neuromuscular blockade, and restrictive spirometry patterns 3
• A 45mg dose represents roughly 18-fold higher than typical therapeutic dosing, making severe respiratory compromise highly likely 3
• High-dose neostigmine (>60 mcg/kg) is independently associated with post-operative respiratory complications with an odds ratio of 8.2 4

Monitoring Duration

Continue monitoring until all signs of cholinergic excess resolve and respiratory function is stable - given the massive overdose, this may require hours of intensive support. 1