What are the anesthetic implications for patients with myasthenia gravis?

Anesthetic Implications for Myasthenia Gravis

Neuromuscular Blocking Agents

Patients with myasthenia gravis require 50-75% dose reduction of non-depolarizing neuromuscular blocking agents (NMBAs) due to markedly increased sensitivity, and sugammadex is the preferred reversal agent. 1, 2

Non-Depolarizing NMBAs (Rocuronium, Vecuronium, Atracurium, Cisatracurium)

• Increased sensitivity and prolonged duration of action occur because antibodies reduce functional acetylcholine receptors at the neuromuscular junction 1, 2
• Reduce initial dose by 50-75% for atracurium and cisatracurium 1, 2
• The degree of sensitivity correlates directly with disease severity 1, 2
• Benzylisoquinoline agents (atracurium/cisatracurium) are preferred due to organ-independent elimination via Hofmann degradation, making them more predictable 1, 2
• Small test doses may be valuable in monitoring response, particularly in patients with known myasthenia 3, 4

Depolarizing NMBAs (Succinylcholine)

• Resistance to succinylcholine occurs requiring increased doses to achieve the same effect 1
• This paradoxical resistance is due to receptor down-regulation 1

Train-of-Four (TOF) Monitoring

• Mandatory neuromuscular monitoring with TOF is essential to avoid overdosing 1, 2
• If baseline TOF ratio is <0.9 before NMBA administration, sensitivity is greater and doses must be reduced further 1, 2
• Evaluation of TOF ratio by EMG in hypothenar hand muscles predicts sensitivity to non-depolarizing muscle relaxants 1

Reversal of Neuromuscular Blockade

Sugammadex is strongly recommended over neostigmine for reversal of rocuronium or vecuronium in myasthenia gravis patients. 1, 2, 5

• Sugammadex provides reliable, predictable, and rapid reversal (average 117 seconds to TOF >0.9) 6
• Neostigmine may interfere with long-term anticholinesterase treatment and is less predictable 1
• In a series of 117 MG patients, sugammadex resulted in zero cases of residual curarization, reintubation, or postoperative pneumonia 6
• The risks of residual neuromuscular blockade are significantly increased in myasthenia gravis 1

Preoperative Assessment and Optimization

Respiratory Function Testing

• Measure negative inspiratory force (NIF) and vital capacity (VC) in all patients preoperatively 7, 8
• Apply the "20/30/40 rule" to identify high-risk patients: VC <20 mL/kg, maximum inspiratory pressure <30 cmH₂O, or maximum expiratory pressure <40 cmH₂O 7, 8
• Patients with moderate to severe generalized weakness (MGFA class III-V) require frequent pulmonary function assessments 7, 8
• Respiratory insufficiency may develop without obvious dyspnea symptoms 7, 8

Medication Management

• Continue pyridostigmine on the day of surgery as discontinuation increases risk of respiratory distress 2, 9
• For non-intubated patients, pyridostigmine may be used from 30 mg orally up to 600 mg daily 7
• 30 mg oral pyridostigmine corresponds to 1 mg IV or 0.75 mg neostigmine IM 7

Medications to Avoid

Immediately discontinue or avoid these medications that can precipitate myasthenic crisis: 7, 8

• IV magnesium (absolutely contraindicated) 7
• Beta-blockers 7, 8
• Fluoroquinolones 7, 8
• Aminoglycosides 7, 8
• Macrolide antibiotics 7, 8

Intraoperative Management

Anesthetic Technique Options

• Volatile anesthetics (sevoflurane, isoflurane, enflurane) potentiate neuromuscular blockade and may allow avoidance of NMBAs entirely 1, 9
• Regional anesthesia (epidural, peripheral nerve blocks) is preferred when feasible to avoid NMBAs 5, 9
• If general anesthesia is required, consider avoiding NMBAs by using adequate volatile anesthetic depth 9

Special Intraoperative Considerations

• Rocuronium may increase pulmonary vascular resistance, requiring caution in patients with pulmonary hypertension or valvular disease 3
• Rocuronium and other NMBAs can prolong QTc interval when combined with general anesthetics 3
• Avoid mixing rocuronium with alkaline solutions (e.g., barbiturates) as it has acidic pH 3
• Tourniquet release may precipitate myasthenic crisis due to lactate release 10

Factors That Potentiate Neuromuscular Blockade

These conditions increase NMBA sensitivity and duration: 1, 3

• Inhalation anesthetics (especially enflurane and isoflurane) 1, 3
• Antibiotics (aminoglycosides, fluoroquinolones) 1, 3
• Magnesium salts 1, 3
• Lithium 1, 3
• Local anesthetics 1, 3
• Procainamide and quinidine 1, 3
• Acid-base abnormalities (metabolic acidosis and alkalosis enhance potency; respiratory acidosis prolongs recovery) 3

Extubation Criteria

Ensure absolutely no residual curarization before extubation with TOF ratio >0.9 and adequate spontaneous breathing. 5

• Confirm sufficient spontaneous ventilation parameters before extubation 5
• Monitor for minimum 24 hours in ICU, HDU, or recovery unit even after apparent stabilization 7
• Watch for signs of respiratory fatigue: difficulty holding up head, slurred speech, trouble chewing/swallowing 8

Postoperative Management

Pain Control

• Limit use of opioids and sedatives as they can precipitate respiratory depression 5
• Consider peripheral nerve blocks for adjunct pain control to minimize opioid requirements 5
• Avoid routine admission to ICU unless specific risk factors present 5

Monitoring

• Continue frequent respiratory function assessment postoperatively 7, 8
• Monitor for signs of myasthenic crisis requiring immediate intervention 7, 8
• For intubated patients, discontinue or withhold pyridostigmine 7

Risk Factors for Postoperative Complications

Higher risk patients include those with: 5, 9

• Severe generalized disease (MGFA class III-V) 7, 8
• Baseline respiratory compromise (abnormal NIF/VC) 7, 8
• Prolonged surgical procedures 5
• Use of high-dose NMBAs 5

Key Pitfalls to Avoid

• Never use standard NMBA doses - always reduce by 50-75% 1, 2
• Never extubate without confirming TOF >0.9 and adequate spontaneous ventilation 5
• Never administer IV magnesium - it is absolutely contraindicated 7
• Never discontinue anticholinesterase therapy preoperatively without careful consideration 2, 9
• Never assume normal respiratory function based on lack of dyspnea - objective testing is mandatory 7, 8
• Never mix rocuronium with alkaline solutions in the same syringe 3