What is the use and dosage of Neostigmine in patients with myasthenia gravis?

Neostigmine Use and Dosage in Myasthenia Gravis

For patients with myasthenia gravis, neostigmine should be administered at reduced doses (50-75% of standard dosing) with careful neuromuscular monitoring due to their increased sensitivity to non-depolarizing muscle relaxants. 1

Therapeutic Uses in Myasthenia Gravis

• Neostigmine is an acetylcholinesterase inhibitor used to treat muscle weakness in myasthenia gravis by increasing acetylcholine availability at the neuromuscular junction 2
• It can significantly improve respiratory muscle function, with studies showing increases in maximal inspiratory mouth pressure (33%), maximal expiratory mouth pressure (23.5%), and maximal voluntary ventilation (21%) 2
• Neostigmine can be used as an alternative to pyridostigmine when enteral administration is no longer possible, such as in end-of-life care 3

Dosing Considerations

• Patients with myasthenia gravis require a 50-75% reduction in the standard dose of neostigmine due to their increased sensitivity to non-depolarizing muscle relaxants 1
• Standard dosing for reversal of neuromuscular blockade is 0.03-0.07 mg/kg IV, but this should be reduced in myasthenic patients 4
• The dose reduction correlates with the severity of myasthenia gravis - more severe disease requires greater dose reduction 1
• Train-of-four (TOF) ratio monitoring prior to administration helps predict sensitivity - patients with TOF ratio <0.9 before neuromuscular blockade show greater sensitivity and require lower doses 1

Administration Routes

• Intravenous administration is most common for acute management and reversal of neuromuscular blockade 4
• Subcutaneous continuous infusion can be used when enteral administration of acetylcholinesterase inhibitors is no longer possible 3
• Intranasal administration has shown efficacy in clinical trials, with onset of action within 5-15 minutes and may be beneficial for:
  • Patients with irregular absorption of oral doses
  • When fast and temporary effect is needed
  • In bulbar impairment and emergencies 5

Monitoring Requirements

• Quantitative monitoring of neuromuscular blockade is strongly recommended after neostigmine administration until a TOF ratio of 0.9 has been obtained 1
• Assessment of neuromuscular function before administering neostigmine is essential to uncover impaired neuromuscular transmission 1
• Peripheral nerve stimulator should be used to determine whether neostigmine should be administered and to monitor recovery from neuromuscular blockade 4

Special Considerations and Precautions

• Patients on chronic pyridostigmine therapy may show variable responses to neuromuscular blocking agents depending on when the last dose was taken 6
• Continuing pyridostigmine until the day of surgery may prolong the onset time of neuromuscular blocking agents and require higher doses 6
• Omitting pyridostigmine before surgery may predispose patients to respiratory discomfort and increased sensitivity to neuromuscular blocking agents 6
• Administering neostigmine at high doses when TOF ratio is already >0.9 may impair neuromuscular transmission and induce TOF fade 1
• In cases of very slight residual blockade, reducing the neostigmine dose by half is recommended to avoid adverse effects 1

Potential Adverse Effects

• Muscarinic side effects (can be mitigated by administering atropine or glycopyrrolate) 4
• Administering neostigmine after full recovery (TOF ratio = 1.0) can decrease upper airway patency and reduce laryngeal dilation capacity 1
• When administered at high doses (40 μg/kg) with TOF ratio >0.9, neostigmine may impair neuromuscular transmission for 17-52 minutes 1

Remember that individual assessment is necessary as sensitivity to neostigmine varies greatly among patients with myasthenia gravis 1.