Pharmacotherapy

The pharmacotherapy for myasthenic crisis focuses on providing ventilatory support, optimizing underlying myasthenia gravis treatment, and avoiding medications that may exacerbate neuromuscular weakness.

Ventilatory Support

• Endotracheal intubation and mechanical ventilation are required in myasthenic crisis to maintain airway patency and support respiratory function.
• Non-invasive positive pressure ventilation may be trialed in milder cases without immediate need for intubation.
• Careful patient selection is necessary to avoid delaying intubation when required.
• Medication selection requires careful consideration during intubation and mechanical ventilation in myasthenic crisis patients to avoid exacerbating neuromuscular weakness.

Intubation Medications

Induction Agents

• Propofol 1-2 mg/kg IV

• Rapid onset anesthetic induction
  • Dose-dependent hypotension and respiratory depression

• Ketamine 1-2 mg/kg IV

• Maintains respiratory drive and airway reflexes
  • Sympathomimetic – less hypotension

• Etomidate 0.3 mg/kg IV

• Minimal hemodynamic effects
  • May cause myoclonus – negative impact on endotracheal intubation

Paralytic Agents

• Propofol 1-2 mg/kg IV

• Rapid onset anesthetic induction
  • Dose-dependent hypotension and respiratory depression

• Ketamine 1-2 mg/kg IV

• Maintains respiratory drive and airway reflexes
  • Sympathomimetic – less hypotension

• Etomidate 0.3 mg/kg IV

• Minimal hemodynamic effects
  • May cause myoclonus – negative impact on endotracheal intubation

• Rocuronium 0.6-1 mg/kg IV

• Reduced dose of 0.6 mg/kg due to enhanced neuromuscular blockade
  • Onset of action 1-2 minutes
  • Duration 30-60 minutes

• Cisatracurium 0.1-0.2 mg/kg IV

• Lower dose of 0.1-0.2 mg/kg
  • Onset 3-5 minutes
  • Duration 45-75 minutes

• Succinylcholine is avoided

• Depolarizing agent – triggers extensive depolarization
  • May fail to achieve adequate intubation conditions due to reduced acetylcholine receptors
  • Prolonged paralysis and inability to ventilate possible

Managing myasthenic crisis requires a multifaceted pharmacological approach beyond just airway protection with intubation. Key treatment modalities include immunomodulating agents, immunosuppressants, and avoidance of medications exacerbating neuromuscular weakness.

Glucocorticoids

• High dose intravenous glucocorticoids form the cornerstone of treatment.
• Agents: Methylprednisolone or Dexamethasone
• Dosing:

• Methylprednisolone 500-1000 mg IV daily for 3-5 days
  • Dexamethasone 40 mg IV daily for 3-5 days

• Transition to high dose oral prednisone 1-1.5 mg/kg/day after pulse.
• Effects may take several weeks – bridge with plasmapheresis/IVIG.
• Monitor glucose, electrolytes, mental status.
• Never discontinue abruptly – taper gradually.

Plasmapheresis

• Mode of action: Filters and removes pathogenic antibodies.
• Dosing: Exchange 1-1.5 plasma volumes on alternate days. Total of 5-6 exchanges.
• Replacement with albumin or plasma to maintain oncotic pressure.
• Adverse effects: Hypotension, hypocalcemia, bleeding, infections.
• Provides passive immunomodulation until steroids/immunosuppressants effective.

IV Immunoglobulin (IVIG)

• Mechanism: Provides IgG antibodies for immunomodulation.
• Dosing: 2 g/kg ideal body weight divided over 2-5 days.
• Onset within 3-7 days, effects last 3-6 weeks.
• Adverse effects: Headache, fever, renal dysfunction, thrombotic events.
• Provides passive immunomodulation until steroids/immunosuppressants effective.

Immunosuppressants

• Initiate steroid-sparing immunosuppressants like azathioprine, mycophenolate mofetil, or cyclosporine.
• Do NOT rely solely on immunosuppressants in acute setting due to slow onset.
• Tailor regimen based on prior MG treatment history.
• Monitor for bone marrow suppression, hepatic toxicity.

Avoid Exacerbating Medications

• Prevent worsening of neuromuscular blockade:

• Aminoglycosides, magnesium, fluoroquinolones
  • Anticholinesterase inhibitors if cholinergic crisis
  • Beta-blockers, calcium channel blockers

• Use peripheral nerve stimulation monitoring with paralytics.