What are the treatment recommendations for an oral overdose of 45mg of neostigmine (acetylcholinesterase inhibitor)?

Oral Neostigmine Overdose: Treatment Recommendations

For an oral overdose of 45mg neostigmine, immediately administer atropine to counteract cholinergic crisis (muscarinic symptoms), provide supportive care with airway management and cardiac monitoring, and be prepared for potential respiratory failure requiring mechanical ventilation. 1

Understanding the Clinical Context

The 45mg oral dose represents a significant overdose:

• Standard IV dosing for neuromuscular blockade reversal is only 0.04-0.05 mg/kg (approximately 2.5-5mg total for an adult) 2, 3
• For myasthenia gravis, the conversion is 30mg oral pyridostigmine = 1mg IV neostigmine, suggesting oral neostigmine bioavailability is much lower than IV 4
• However, 45mg orally still represents a substantial cholinergic load that will cause toxicity 1

Immediate Management Algorithm

Step 1: Recognize Cholinergic Crisis

Monitor for muscarinic symptoms that characterize overdosage 1:

• Gastrointestinal: Nausea, vomiting, diarrhea, abdominal cramping
• Respiratory: Increased bronchial secretions, bronchospasm, respiratory muscle weakness
• Cardiac: Bradycardia, AV block 5
• Other: Excessive salivation, sweating, miosis

Step 2: Administer Atropine Immediately

• Atropine is the antidote for cholinergic crisis and should be given promptly 1
• Atropine counteracts the muscarinic effects (bradycardia, secretions, bronchospasm) 1
• Titrate atropine to control secretions and maintain adequate heart rate 1

Step 3: Secure Airway and Ventilation

• Cholinergic crisis can progress to respiratory failure and death through involvement of respiratory muscles 1
• Ventilation should be supported by artificial means until adequacy of spontaneous respiration is assured 1
• The combination of increased secretions, bronchospasm, and muscle weakness creates high aspiration risk 1

Step 4: Cardiac Monitoring

• Continuous cardiac monitoring is essential as neostigmine can cause bradycardia and AV block 1, 5
• Be prepared to administer additional atropine for symptomatic bradycardia 1

Critical Pitfall: Distinguishing Cholinergic Crisis from Myasthenic Crisis

This distinction is life-or-death important but only applies if the patient has underlying myasthenia gravis 1:

• Cholinergic crisis (from neostigmine overdose): Requires WITHDRAWAL of all anticholinesterase drugs and administration of atropine 1
• Myasthenic crisis (from undertreated myasthenia): Requires MORE anticholinesterase therapy 1
• Both present with extreme muscle weakness, making clinical differentiation difficult 1
• Edrophonium chloride testing can help differentiate, but clinical judgment is paramount 1
• In an overdose scenario without known myasthenia gravis, assume cholinergic crisis 1

Important Caveats About Atropine Use

While atropine is essential for managing cholinergic crisis, be aware that 1:

• Atropine masks gastrointestinal and other muscarinic side effects
• This masking can lead to inadvertent continuation or escalation of cholinesterase inhibitor dosing in chronic settings
• However, in acute overdose, this concern is secondary to the immediate need to counteract life-threatening cholinergic effects

Supportive Care Measures

Beyond the immediate interventions 1:

• Monitor oxygen saturation continuously
• Suction secretions as needed to maintain airway patency
• Consider benzodiazepines if seizures develop (though not commonly reported with neostigmine overdose)
• Monitor for at least 24 hours given the potential for delayed or prolonged effects with oral ingestion