What is the best course of treatment for a patient experiencing a myasthenic crisis due to myasthenia gravis (MG)?

Myasthenic Crisis Management

Immediate Stabilization and ICU Admission

Myasthenic crisis requires immediate ICU admission with aggressive respiratory monitoring and rapid initiation of immunotherapy with either plasmapheresis (preferred) or IVIG, combined with high-dose corticosteroids. 1, 2

Critical Respiratory Assessment

• Perform immediate pulmonary function testing using the "20/30/40 rule" to identify imminent respiratory failure: vital capacity <20 ml/kg, maximum inspiratory pressure (NIF) <30 cmH₂O, or maximum expiratory pressure <40 cmH₂O 1, 2
• Measure forced vital capacity (FVC) and negative inspiratory force (NIF) at presentation and serially thereafter 1, 2
• The single breath count test (counting to ≥25 correlates with normal respiratory function) can supplement formal measurements 1
• Prepare for elective intubation before emergent respiratory arrest if FVC <20 ml/kg or NIF <30 cmH₂O 2

Critical pitfall: Do not wait for hypoxemia or hypercapnia on arterial blood gas—these are late findings and unreliable early indicators of respiratory failure 1. Pulse oximetry may remain normal until decompensation is imminent.

Acute Immunotherapy

First-Line Treatment Choice

Plasmapheresis is preferred over IVIG for myasthenic crisis with respiratory failure 2, 3, 4:

• Plasmapheresis regimen: 5 sessions over 5 days (standard) or 7 exchanges over 14 days for severe cases 1
• Alternative IVIG regimen: 2 g/kg total dose over 5 days (0.4 g/kg/day) 1, 2
• Plasmapheresis demonstrates superior efficacy in respiratory failure compared to IVIG, though both are acceptable 3, 4
• IVIG may be preferred in pregnant women due to fewer monitoring requirements 5

Important caveat: Sequential therapy (plasmapheresis followed by IVIG) provides no additional benefit and should be avoided 5. Choose one modality and proceed.

Corticosteroid Therapy

• Initiate high-dose corticosteroids immediately: methylprednisolone 1-2 mg/kg/day IV or prednisone 1-1.5 mg/kg/day orally 1, 2
• Continue corticosteroids throughout plasmapheresis or IVIG treatment 5
• Begin steroid taper 3-4 weeks after initiation based on symptom improvement 1

Pyridostigmine Management During Crisis

Discontinue or withhold pyridostigmine in intubated patients 1, 2:

• The FDA label warns that overdosage can cause cholinergic crisis, characterized by increasing muscle weakness that may be indistinguishable from myasthenic crisis 6
• For non-intubated patients with ongoing myasthenic symptoms, pyridostigmine may be continued at 30-600 mg daily orally 1
• If IV administration is necessary: 30 mg oral = 1 mg IV pyridostigmine = 0.75 mg neostigmine IM 1, 5

Critical distinction: Differentiating myasthenic crisis from cholinergic crisis may require edrophonium testing and clinical judgment, as both present with severe weakness 6. When in doubt during crisis, withhold anticholinesterase medications.

Medication Contraindications

Immediately discontinue these medications that worsen myasthenia gravis 1, 5, 2:

• IV magnesium (absolutely contraindicated) 1
• Beta-blockers 1, 2
• Fluoroquinolone antibiotics 1, 5, 2
• Aminoglycoside antibiotics 1, 5, 2
• Macrolide antibiotics 1, 5, 2
• Metoclopramide 5

If severe hypomagnesemia requires treatment, mandatory neurology consultation before any magnesium administration 1.

Diagnostic Workup During Crisis

While stabilizing the patient, obtain:

• Acetylcholine receptor (AChR) antibodies and anti-striated muscle antibodies 1, 5
• If AChR negative: muscle-specific kinase (MuSK) and lipoprotein-related protein 4 (LRP4) antibodies 1, 5
• CPK, aldolase, ESR, CRP to evaluate for concurrent myositis 1
• ECG and echocardiogram if respiratory insufficiency or elevated cardiac markers to exclude myocarditis 1

Monitoring Protocol

• Daily neurological evaluation throughout the crisis 1, 2
• Frequent pulmonary function assessments with NIF and VC measurements 1, 2
• Monitor for at least 24 hours in ICU even after apparent stabilization 1
• Median duration of mechanical ventilation is 12-14 days, though 20% remain ventilated after 1 month 7

Airway Management Considerations

• Early intubation is the most important intervention in myasthenic crisis 4
• Orotracheal intubation is preferred 4
• Consider small-bore duodenal feeding tubes to decrease aspiration risk 4
• Maximal expiratory pressure (Pemax) ≥40 cmH₂O predicts successful extubation 8
• Extubation failure (39% of cases) most commonly results from sputum impaction due to poor cough strength 8

Non-invasive positive pressure ventilation (NIPPV): May prevent intubation in select patients with APACHE II score <6 and serum bicarbonate <30 mmol/L 8. However, NIPPV should not be used prophylactically in stable patients 5. Success rate is approximately 57% when appropriately selected 8.

Prognosis

• Mortality in U.S. cohorts is <5%, driven primarily by age and medical comorbidities rather than the crisis itself 3, 7
• Most patients achieve good long-term MG control after crisis resolution 3
• Lifetime recurrence risk is approximately 30% 7
• Aggressive respiratory therapy correlates with shorter mechanical ventilation duration and fewer pulmonary complications 9