Are patients with Myasthenia Gravis (MG) at increased risk of sensitivity to non-depolarizing neuromuscular blockers?

Increased Sensitivity to Non-Depolarizing Neuromuscular Blockers in Myasthenia Gravis

Yes, patients with myasthenia gravis have significantly increased sensitivity to non-depolarizing neuromuscular blocking agents (NMBAs) due to reduced functional nicotinic receptors at the neuromuscular junction. 1

Pathophysiological Mechanism

• Myasthenia gravis is characterized by antibodies targeting nicotinic acetylcholine receptors, reducing the number of functional receptors at the neuromuscular junction 1
• This reduction in functional receptors leads to impaired neuromuscular transmission at baseline, causing increased sensitivity to non-depolarizing NMBAs 1
• Research in rat models confirms that the decreased number of acetylcholine receptors is the primary mechanism responsible for both increased sensitivity and prolonged effect of non-depolarizing NMBAs 2

Clinical Implications

• Patients with myasthenia gravis require significantly reduced doses of non-depolarizing NMBAs to achieve the desired neuromuscular blockade 1
• A 50-75% reduction in the recommended dose is common with agents like atracurium and cisatracurium 1
• The sensitivity to NMBAs correlates with the severity of myasthenia gravis 1
• Both seropositive and seronegative myasthenia gravis patients show equal sensitivity to non-depolarizing agents like vecuronium 3

Monitoring and Management Recommendations

• Peripheral nerve stimulation (PNS) with train-of-four (TOF) monitoring is essential when administering NMBAs to myasthenia gravis patients 1
• Assessment of neuromuscular function before administering NMBAs can help identify impaired transmission and guide appropriate dosing 1
• If TOF ratio is less than 0.9 before neuromuscular blockade, sensitivity to muscle relaxants is greater and doses must be reduced further 1
• Benzylisoquinoline muscle relaxants (atracurium/cisatracurium) are probably recommended due to their more predictable metabolism 1

Reversal Considerations

• Sugammadex is recommended for reversal of steroidal muscle relaxants (like rocuronium) in myasthenia gravis patients 1, 4
• Sugammadex avoids the need for acetylcholinesterase inhibitors, which can complicate management in patients already on cholinesterase inhibitors for myasthenia 4
• Patients on cholinesterase inhibitors (like pyridostigmine) have reduced plasma cholinesterase activity, which can further prolong the effect of certain NMBAs 1

Special Considerations

• Discontinuing cholinesterase inhibitors on the day of surgery increases the risk of respiratory distress 1
• Patients with primarily ocular disease may require higher doses of NMBAs than those with generalized disease 1
• Medications that can worsen myasthenia gravis (beta-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolides) should be avoided during the perioperative period 5, 6

Practical Approach to NMBA Use in Myasthenia Gravis

1. Assess baseline neuromuscular function with TOF monitoring 1
2. Reduce initial dose of non-depolarizing NMBA by 50-75% 1
3. Use PNS with TOF monitoring to guide additional dosing 1
4. Consider using benzylisoquinoline agents (atracurium/cisatracurium) 1
5. For steroidal NMBAs, use sugammadex for reversal when possible 1, 4
6. Maintain vigilant monitoring throughout the perioperative period 1