Myasthenic crisis

General information

  • Myasthenic crisis (MC) is a complication of myasthenia gravis (MG) characterized by worsening muscle weakness that may:
    1. Lead to respiratory failure and require intubation and mechanical ventilation
    2. Cause delayed extubation in post-operative patients
  • 15-20% of MG patients are affected by MC at least once in their lifetimes
  • The median time from onset of MG to first MC is 8-12 months
  • In 1/5 of MG patients MC is the initial presentation
  • Caution is warranted for patients with predominantly bulbar weakness. Impending airway compromise and respiratory failure may occur without signs of overt peripheral weakness. Not infrequently these patients are misdiagnosed as psychiatric when they do not have a preexisting MG diagnosis
  • Male:Female ratio is 1:4 before the age of 55 years and 1:1 after the age of 55 years
  • Average patient age for MC is 59 years
  • The most common precipitant of MC is infection, particularly bacterial pneumonia
  • 30-50% of admitted patients have no identifiable cause for their MC
  • Up to 90% of patients with MC require intubation and mechanical ventilation
  • 20% of patients require intubation during the initial evaluation at the emergency department
  • Patients requiring intubation spend a median of 17 days at the hospital
  • 18% of admitted patients will need rehabilitation after discharge
  • Thymoma is associated with worse prognosis in MC
  • Mortality rate of MC is 4%

Factors that may precipitate myasthenic crisis

  • Infection (most common)
  • Physical stress
  • Emotional stress
  • Pain
  • Perimenstrual state
  • Pregnancy
  • Sleep deprivation
  • Surgery
  • Aspiration pneumonitis
  • Extreme hyperthermia or hypothermia
  • Tapering of immunomodulating medications
  • Drugs (see Drug considerations in NMD section)

Rerspiratory management

See Respiratory management in NMD section.

Additional considerations when intubating MG patients:
  • Depolarizing agents (eg. succinylcholine) have decreased potency because of the depleted AChR
  • Non-depolarizing agents (eg. vecuronium) have increased potency and reduced doses are required for paralysis
Weaning from the ventilator
  • Should be attempted when clear signs of clinical improvement are seen. Typically when VC is > 15 ml/kg
  • Improvement in neck flexor and bulbar muscle strength correlates with improved respiratory function and can be used for clinical assessment
  • Transition to spontaneous mode of ventilation
  • 50% of patients are extubated at 13 days
  • Age >50 years, peak vital capacity <25 ml/kg on post-intubation days 1-6 and serum bicarbonate ≥30 mmol/L may predict prolongued intubation (>14 days)
  • Fluctuating weakness may confound the decision to extubate
  • 14-40% of patients will require tracheostomy
  • Over 1/4 of patients will require re-intubation
  • Non-invasive ventilation (eg. BiPAP) may be used to prevent intubation or re-intubation

Specific treatment

  • The two primary pharmacologic treatments available are IVIg and plasma exchange (PE)
  • The typical IVIg dosage regime is 0.4 g/kg body weight daily for 5 consecutive days
  • The typical PE regime is 5 exchanges (1 plasma volume or 3-4 L per exchange) usually performed every other day over 10 days. Replacement fluid is usually a solution of normal saline/5% albumin
  • Clinical response generally occurs after 2 days with PE and after 4-5 days with IVIg and usually lasts for several weeks
  • ~1/5 of patients may require a second treatment with PE or IVIg after the initial one
  • If there is insufficient response, PE can be given after IVIg and IVIg can be administered after PE
  • Some evidence suggests PE may be more effective than IVIg in the treatment of myasthenic crisis however PE carries a higher risk for complications
  • Corticosteroids can be initiated concurrently with IVIg and PE
  • High-dose prednisone 60-100 mg daily or 1-1.5 mg/kg/day is a commonly used scheme
  • Initial worsening following high-dose prednisone should be anticipated and might require continued ventilatory support
  • Mean time to improvement after prednisone was 13 days in one series of patients with MG exacerbation
  • Once the patient shows improvement the prednisone dose can be gradually reduced and converted to alternate-day dosing
  • Cyclosporine may be considered after the initial PE or IVIg therapy in patients with poor response or poor tolerance to corticosteroids.
  • Time to onset of action for cyclosporine is 1-2 months. Azathioprine and mycophentolate have even longer latencies
  • Acetylcholinesterase inhibitors:
    1. Increase bronchial secretions which may be detrimental in respiratory-compromised patients
    2. Confound clinical evaluation which is of paramount importance for correct management
    3. Offer only symptomatic relief without altering the course of the disease
    4. May worsen muscle weakness if used in excess
    5. Should be discontinued or their dose reduced in myasthenia crisis
    6. Can be reintroduced when primary treatment has been initiated and the patient shows good clinical response

Complications

  • Fever (most common)
  • Infections (pneumonia, bronchitis, urinary tract infections are most common)
  • Thromboembolic complications
  • Cardiac complications (congestive heart failure, arrhythmias, MI and cardiac arrest)
  • Atelectasis, C. difficile colitis, transfusion-dependent anemia and congestive heart failure have been found independently associated with longer duration of myasthenia crisis but not longer duration of intubation
  • Treatment related cholinergic crisis is uncommon in MC. Symptoms and signs include:
    • Increased salivation, perspiration, lacrimation
    • Increased pulmonary secretions
    • Nausea, vomiting, diarrhea
    • Bradycardia
    • Fasciculations