What is the management approach for a patient with a history of myasthenia gravis (MG) experiencing an impending myasthenic crisis?

Diagnosis and Management of Impending Myasthenic Crisis

Immediate Recognition and Assessment

Patients with myasthenia gravis showing signs of impending crisis require immediate ICU admission with close respiratory monitoring, particularly when forced vital capacity falls below 20 ml/kg or negative inspiratory force drops below 30 cmH₂O. 1

Red Flag Symptoms Requiring Urgent Evaluation

• Monitor for rapidly progressive weakness of respiratory and bulbar muscles, including changes in speech or swallowing, respiratory difficulties, and increasing generalized weakness 2, 3
• Apply the "20/30/40 rule" to identify imminent respiratory failure: vital capacity <20 ml/kg, maximum inspiratory pressure <30 cmH₂O, or maximum expiratory pressure <40 cmH₂O 4, 1
• Perform immediate pulmonary function testing with negative inspiratory force (NIF) and vital capacity (VC) measurements 4
• Use the single breath count test as a bedside assessment: have the patient take a deep breath and count at two numbers per second while exhaling; counting to ≥25 correlates with normal respiratory muscle function 4

Diagnostic Workup

• Confirm diagnosis with acetylcholine receptor (AChR) antibodies and anti-striated muscle antibodies 4
• If AChR antibodies are negative, test for muscle-specific kinase (MuSK) and lipoprotein-related protein 4 (LRP4) antibodies 4
• Measure CPK, aldolase, ESR, and CRP to evaluate for concurrent myositis 4
• Perform cardiac evaluation with ECG and transthoracic echocardiogram if respiratory insufficiency or elevated CPK/troponin T is present to rule out concurrent myocarditis 4

Critical Medication Management

Medications to Immediately Discontinue

Immediately stop all medications that can precipitate or worsen myasthenic crisis, as these can trigger respiratory failure. 4, 1

• β-blockers - interfere with neuromuscular transmission 2, 4, 1
• IV magnesium - absolutely contraindicated 4, 1
• Fluoroquinolone antibiotics - can exacerbate muscle weakness 2, 4, 1
• Aminoglycoside antibiotics - worsen neuromuscular blockade 2, 4, 1
• Macrolide antibiotics - precipitate crisis 2, 4
• Metoclopramide - can trigger myasthenic crisis 2

Pyridostigmine Management

• Continue pyridostigmine (30-120 mg orally four times daily) in non-intubated patients with impending crisis 2
• Discontinue or withhold pyridostigmine if intubation becomes necessary 4, 1
• If IV administration is required: 30 mg oral pyridostigmine = 1 mg IV pyridostigmine = 0.75 mg neostigmine IM 2, 4

Important caveat: The FDA warns that distinguishing myasthenic crisis from cholinergic crisis (pyridostigmine overdose) can be extremely difficult, as both present with severe weakness. Increases in pyridostigmine during cholinergic crisis can have grave consequences, necessitating withdrawal of all anticholinesterase drugs and prompt atropine administration. 5

Acute Immunotherapy

For Grade 3-4 myasthenic exacerbations requiring hospitalization, initiate either plasmapheresis or IVIG immediately upon ICU admission. 2, 4

Treatment Options (Equally Effective)

Plasmapheresis (Preferred):

• Standard regimen: 5 sessions over 5 days 4, 1
• Alternative extended regimen: 7 exchanges over 14 days for severe cases 4
• Time to disease stabilization: median 8 days (range 7-12 days) 6
• Requires specialized equipment and expertise, often necessitating transfer to tertiary centers 4
• Risks include hemodynamic shifts, coagulation disorders, electrolyte imbalances, and line-related bacteremia 4

IVIG (Alternative):

• Dose: 2 g/kg total over 5 days (0.4 g/kg/day for 5 consecutive days) 2, 4, 1
• Time to disease stabilization: median 10 days (range 7-39 days) 6
• Preferred in pregnant women due to fewer monitoring requirements 2
• Easier administration with fewer complications compared to plasmapheresis 2

Critical point: Sequential therapy (plasmapheresis followed by IVIG) is no more effective than either treatment alone and should be avoided 2. Both modalities show equivalent efficacy in achieving disease stabilization 6.

Corticosteroid Therapy

• Initiate high-dose corticosteroids concurrently with plasmapheresis or IVIG 4, 1
• Dosing: Methylprednisolone 1-2 mg/kg/day IV or prednisone 1-1.5 mg/kg/day orally 2, 4, 1
• Begin steroid taper 3-4 weeks after initiation, based on symptom improvement 4

Respiratory Management

Intubation Criteria

Prepare for elective intubation before emergent respiratory arrest occurs when FVC <20 ml/kg or NIF <30 cmH₂O. 1

• Early intubation is essential to secure the airway due to bulbar symptoms with aspiration and/or respiratory insufficiency 3
• Median duration of mechanical ventilation: 12-14 days under sufficient treatment 3
• Approximately 20% of patients remain mechanically ventilated after 1 month due to comorbidities and complications 3

Monitoring Requirements

• Daily neurological evaluation throughout the crisis 2, 4, 1
• Frequent pulmonary function assessments with NIF and VC 2, 4
• Monitor for ventilator-associated pneumonia (VAP), the most common complication occurring in 30% of cases 6
• Pulse oximetry and arterial blood gases are not reliable early indicators of emerging respiratory failure 4

Common Precipitating Factors to Address

• Infection - most common precipitant, occurring in 65% of crisis episodes 6, 7
• Urinary tract infections represent a common infectious trigger 1
• Reduction in medication 7
• Menstruation 7
• Recent steroid administration 7

Prognosis and Expected Course

• Median duration of crisis: approximately 2 weeks (11-14 days) 3, 6
• Mortality rate: 2-8% with appropriate management 3, 6, 8
• Deaths are almost never caused by the crisis itself, but by comorbidities or complications (VAP, septicemia, cardiac failure, multiple organ failure) 3, 6, 7
• Lifetime risk of crisis recurrence: approximately 30% 3
• Complete resolution of admission symptoms is expected in survivors 6

Key Clinical Pitfalls

• Do not delay intubation - waiting for emergent respiratory arrest significantly worsens outcomes 1, 3
• Do not continue pyridostigmine in intubated patients - this can worsen outcomes and complicate differentiation from cholinergic crisis 4, 1, 5
• Do not use sequential immunotherapy (plasmapheresis then IVIG) - this provides no additional benefit 2
• Aggressively treat infections and complications - these determine ultimate outcomes more than the crisis itself 3, 6