What are the considerations for using succinylcholine (depolarizing neuromuscular blocker) in patients with myasthenia gravis?

Succinylcholine in Myasthenia Gravis: Clinical Considerations

Primary Recommendation

Avoid succinylcholine in patients with myasthenia gravis, particularly those taking pyridostigmine, due to the risk of prolonged neuromuscular blockade from reduced plasma cholinesterase activity. 1, 2

Mechanism of Concern

The interaction between myasthenia gravis treatment and succinylcholine creates a dangerous pharmacologic scenario:

• Pyridostigmine inhibits both acetylcholinesterase at the neuromuscular junction AND plasma cholinesterase (pseudocholinesterase) in the bloodstream, resulting in prolonged exposure to succinylcholine at the neuromuscular junction 2
• Patients with myasthenia gravis treated with cholinesterase inhibitors express reduced plasma cholinesterase activity, placing them at risk for experiencing prolonged neuromuscular blockade due to prolonged inactivation of succinylcholine 1, 2
• The combined effect produces excessive ligand accumulation at the neuromuscular junction, intensifying and prolonging depolarization 2

Preferred Alternative Approach

Use rocuronium at doses ≥0.6 mg/kg (preferably 0.9 mg/kg for rapid sequence intubation) as the preferred neuromuscular blocking agent in myasthenia gravis patients. 2

Rationale for Rocuronium:

• Rocuronium has a mild vagolytic effect and lacks cholinesterase-dependent metabolism, making it safer in patients receiving pyridostigmine 2
• Rocuronium acts as a competitive antagonist at nicotinic receptors without causing depolarization, unlike succinylcholine which causes sustained depolarization 3
• The duration of action is 30-60 minutes, which is longer than succinylcholine, but the safety benefit outweighs this disadvantage 4

Critical Dosing Considerations

If neuromuscular blockade is absolutely necessary in myasthenia gravis, use reduced doses of non-depolarizing agents with train-of-four (TOF) monitoring. 1

Specific Guidance:

• Patients with myasthenia gravis have reduced functional nicotinic receptors due to antibody targeting, resulting in higher sensitivity to non-depolarizing neuromuscular blocking agents 1
• Sensitivity to neuromuscular blocking agents varies greatly among myasthenia gravis patients depending on disease severity, requiring individual assessment with peripheral nerve stimulation before administering any neuromuscular blocking agent 1
• Assessment of neuromuscular function before administering a neuromuscular blocking agent may uncover impaired neuromuscular transmission, indicating the need for reduced dosing 1

Monitoring Requirements

Mandatory train-of-four monitoring is essential when any neuromuscular blocking agent is used in myasthenia gravis patients. 1, 4

• Monitor with peripheral nerve stimulation using train-of-four (TOF) to assess the response of innervated muscle to four stimuli at 0.5-second intervals 1
• A TOF ratio of 0.9 is the standard used to indicate return of muscle strength sufficient for patients to protect their airway and maintain spontaneous ventilation 1
• Neuromuscular monitoring allows precise neuromuscular blocking agent dosing in myasthenia gravis patients 5

Postoperative Complications and Management

Prolonged muscle weakness with breathing difficulties represents the most hazardous postoperative complication and requires extended monitoring. 2

Key Warnings:

• Patients must be fully awake, clear of secretions, and able to maintain upper airway reflexes before extubation to avoid postoperative complications such as upper airway obstruction 2
• Delayed muscle weakness can occur as late as 4 days after acute cholinesterase inhibitor exposure and may require supportive ventilation in an intensive care setting 2
• Rocuronium may exert paralytic effects for up to four hours in patients with myasthenia gravis if not properly dose-reduced 6

Common Pitfalls to Avoid

Never repeat dose succinylcholine in patients taking pyridostigmine, as the cumulative effect with ongoing cholinesterase inhibition becomes unpredictable. 2

Additional Cautions:

• Do not use neostigmine for reversal in patients with pyridostigmine treatment, as this adds further cholinesterase inhibition 2
• Pyridostigmine inhibits the metabolism of mivacurium, delaying recovery from this neuromuscular blocking agent 1, 2
• Discontinuing cholinesterase inhibitors on the day of surgery increases the risk of respiratory distress 1
• Avoid repeat dosing of succinylcholine and use non-depolarizing agents instead 5

Reversal Considerations

Sugammadex is associated with fewer postoperative myasthenic crises when reversing rocuronium-induced neuromuscular blockade. 5

• Sugammadex can reverse rocuronium by directly encapsulating and binding rocuronium molecules, removing them from the neuromuscular junction 3
• However, sugammadex reversal may be unpredictable in myasthenic patients, with case reports showing failure of complete reversal requiring neostigmine administration 7
• Neuromuscular blockade monitoring is mandatory during reversal in myasthenia gravis patients 7