August, 2008
Definition

any MG exacerbation necessitating mechanical ventilation
Epidemiology
 incidence of MG is 3-4 per million per year

2F:1M; peak in females in childbearing years

15-20% of MG patients will experience a MG Crises; majority (75%) occur within first 2 years after diagnosis of MG
Risk Factors
 no triggering factor in 30-40%
PTE

August, 2008 PTE
 patient who have a MGC are at higher risk for having a thymoma (up to 30% of such patients)
Pathophysiology

MG is autoimmune disease of the nicotinic acetylcholine receptor of skeletal muscle at the neuromuscular junction; this results in destruction of the postsynaptic membrane and reduced number of available binding sites for acetylcholine and thus inconsistent generation of muscle fiber action potentials occur, which manifests as skeletal weakness

Acetylcholine receptor antibodies are detected in 90% of patients with generalized symptoms, and only in 70% with predominant involvement of the ocular muscles
 in the 10% who have a negative assay, other protein-antibodies have been implicated: MuSK, titin, ryanodine
Clinical Presentation

MG present in one of three different forms: o ocular o bulbar o generalized

Characteristically the weakness worsens by prolonged or repetitive activity and improves with rest
 patients with MGC typically present with acute respiratory failure

Physical Examination o may appear anxious o rapid/shallow breathing o paradoxical chest movements due to diaphragmatic weakness

Consider other differential diagnoses

August, 2008 PTE
 respiratory failure due to weakness of respiratory and bulbar musculature o weak cough
 secretion accumulation
 hypoxia
 shunting of pulmonary blood flow o hypoventilation
 hypercarbia
 acidosis

Indications for mechanical ventilation in MG patients: o FVC <15mL/kg (normal >60/kg) o NIF <20cm H2O (normal >70 cm/H2O) o PEF <40cm H2O (normal >100cm H2O)
 use serial bedside PFTs to assess patient’s course
 bulbar muscle dysfunction (oropharynx & laryngeal musclulature) may contribute to respiratory failure by loss of upper airway diameter/patency; swallowing function and cough reflex may become impaired leading to inability to clear secretions and/or protect airway
Management
 once MGC identified
 intubate patients via RSI but avoid paralytic (patients are very sensitive to these)
 initial ventilator settings should allow rest of fatigued patient and promotion of lung recruitment/expansion (AC, PEEP 5, Vt 6mL/kg ideal body weight, RR12-
16)

Search for the trigger of the MGC (and/or make the diagnosis)

Institute therapies:

August, 2008 PTE
 no role for acetylcholinesterase inhibitors in the acute setting of MGC o although work quickly to improve neuromuscular transmission they may promote excessive secretions which can lead to mucous plugging o cardiac arrhythmias—especially common in patients with MGC—may be triggered by IV acetylcholinesterease inhibitors

Plasma Exchange efficacious in 75% of patients

Monitor for cardiac arrhythmias—can occur in up to 17%

Long-term treatment o prednisone may have a transient worsening of muscle strength in the first few week of initiation o usually started at 1mg/kg/day x4weeks then tapered slowly

All patients should have imaging to assess for thymoma
 presence of such should mandate resection

Start ventilator weaning when patient free of crises triggers, VC >10mL/kg, NI >-
20cm H2O, positive expiratory force >40cm H2O; do trials early in day; wean to
PSV and gradually decrease PSV by 1-2cm H2O per day

When patient ready for ventilator weaning, anticholinesterase medication restart at ½ previous dose
Outcome
 extubation rates: o 25% at 7 days o 50% at 13 days o 75% at 31 days

Risk factors for prolonged intubation o age >50y o pre-intubation CO2 >30mg/dL o highest VC <25mL/kg during first week of intubation

Mean hospitalization time is one month

August, 2008 PTE

77% of those intubated >2weeks had functional dependence at hospital discharge compared with 26% of those intubated <2weeks in one study

Mortality for MGC is 4-8%

1/3 of patients with MGC will have a recurrent episode
References

Bershad EM et al. Myasthenia Gravis Crisis. Southern Medical Journal. Vol
101, No1, Jan 2008. p63-69.

Green, DM. Weakness in the ICU. The Neurologist. 2005;11: 338–347.
