Myasthenic Crisis

Myasthenic crisis is life threatening weakness of respiratory or bulbar muscles from myasthenia gravis, needing ventilatory support or intubation. It occurs in 15 to 20% of patients, usually within 2 years of onset, and often triggered by infection, surgery, drugs or rapid steroid or pyridostigmine change.

Pathophysiology. Antibody mediated loss of acetylcholine receptors (or MuSK or LRP4 function) reduces the safety margin of neuromuscular transmission, which fails with added stress.

Rapid onset of dyspnoea, orthopnoea, weak cough, bulbar weakness (dysphagia, dysarthria, secretion pooling), neck flexor weakness, ptosis and ophthalmoparesis. Rapid shallow breathing, paradoxical breathing and use of accessory muscles occur. Exclude cholinergic crisis (miosis, fasciculation, diarrhoea, bradycardia).

Red flags.

• Forced vital capacity under 20 mL/kg, or negative inspiratory pressure weaker than minus 30 cm H2O.
• Inability to count to 20 in one breath, or bulbar failure.
• Hypercapnia.

Diagnosis is clinical in known myasthenia gravis. Measure forced vital capacity and negative inspiratory pressure at the bedside every 2 to 4 hours, with arterial blood gas (hypercapnia is a late sign). Seek the trigger: infection (chest radiograph, cultures), drugs, thyroid and electrolytes (potassium, magnesium, phosphate). In new patients, check acetylcholine receptor, MuSK and LRP4 antibodies, repetitive stimulation, and CT thorax for thymoma.

Differential diagnosis.

• Cholinergic crisis, Guillain-Barre syndrome, botulism and Lambert-Eaton syndrome.
• Motor neuron disease, acute myopathy and critical illness weakness.

Airway and breathing. Admit to intensive care. Intubate for forced vital capacity under 15 to 20 mL/kg, rapidly falling values, hypercapnia, or bulbar failure. Non-invasive ventilation can avoid intubation in selected patients without bulbar failure. Avoid sedatives, and stop drugs that worsen myasthenia (aminoglycosides, fluoroquinolones, macrolides, magnesium, beta blockers).

Immunotherapy (start immediately).

• Plasma exchange: 5 exchanges of 1 to 1.5 plasma volumes on alternate days, with effect within days.
• Or intravenous immunoglobulin 0.4 g/kg daily for 5 days (2 g/kg total).

Corticosteroids. Prednisolone 1 mg/kg daily started after plasma exchange or immunoglobulin, because high doses can cause early worsening.

Anticholinesterases. Stop pyridostigmine in ventilated patients to reduce secretions, and restart at 30 mg every 6 hours at weaning.

Treat the trigger. Antibiotics for infection (avoid worsening agents), and correct electrolytes.

Long term. Thymectomy when appropriate, and steroid sparing agents (azathioprine 2 to 3 mg/kg daily, mycophenolate mofetil 1 g twice daily, rituximab 1 g twice).

Complications. Venous thromboembolism prophylaxis (enoxaparin 40 mg SC daily), nutrition and pressure care.

Monitoring. Forced vital capacity, bulbar function and arterial blood gas.

Referral and escalation. Admit to intensive care with neurology.

Special groups. In pregnancy, immunoglobulin or plasma exchange is used, and magnesium sulphate is avoided for eclampsia unless essential.