Myasthenia Crisis

Authors:

Umair Hamid MD,

Danish Batti MD

Introduction

• Myasthenia crisis is a complication of myasthenia gravis

• Defined as worsening of myasthenic weakness requiring intubation or noninvasive ventilation

• Myasthenia crisis has a mortality rate of 5%

• 10 to 20% of myasthenia gravis patients experience myasthenic crisis at least once in their lifetime

Cholinergic crisis

• Paradoxical weakening with anticholinesterase medications is called "cholinergic crisis."

• It can be difficult to distinguish from worsening myasthenia gravis.

• Develops as a result of overstimulation of nicotinic and muscarinic receptors at the neuromuscular junctions and synapses

• It is a major side effect of excessive anticholinesterase medication if the dose limitation of pyridostigmine is exceeded above 120 mg every three hours. .

Precipitants

• concurrent infection

• post-surgical intervention (eg, thymectomy)

• pregnancy

• childbirth

• tapering of immunosuppressive medications

• Certain drugs

Table 1: Other causes of acute neuromuscular respiratory failure

Table 2: Drugs that precipitate myasthenia gravis

Management

• Admit in ICU for frequent monitoring of respiratory function

• Vital capacity (VC) and/or maximal inspiratory pressure (MIP) should be measured frequently, typically every four hours.

• Diaphragm thickness measurements by using ultrasound

• Elective intubation if suspecting impending respiratory failure

• Dyspnea on lying down that can be expressed as suffocation or drowning.

• Severe dysphagia with weak cough and difficulty clearing secretions.

• Signs of respiratory muscle weakness, such as hypophonia, pausing during speech to take a breath, poor respiratory effort, increased respiratory rate with shallow breaths, use of accessory muscles of respiration, and paradoxical abdominal breathing. However the signs of respiratory muscle weakness not always apparent.

• VC falls below 15 to 20 mL/kg

• MIP is less negative than -25 to -30 cmH20

• Decreased diaphragm thickening fraction

• Progressive respiratory acidosis despite therapy

• Arterial blood gases are insensitive tests to measure respiratory muscle weakness because they often develop only after the onset of life-threatening respiratory failure

• For patients with myasthenic crisis who are intubated, anticholinesterase medications used for myasthenia gravis (eg, pyridostigmine) should be withdrawn to reduce airway secretions. These medications can be restarted at a low dose after the patient has shown a response to plasma exchange (PLEX) or intravenous immune globulin (IVIG).

• Rapid therapy with PLEX or IVIG

• Expert consensus suggests that PLEX is more effective and works more quickly. The choice between the 2 therapies depends on patient comorbidity (e.g., PLEX cannot be used in sepsis and IVIg is contraindicated in hypercoagulable states, renal failure, or hypersensitivity to immunoglobulin) and other factors, including availability.

• Plasma exchange directly removes acetylcholine receptor antibodies from the circulation

• Generally the course of treatment consists of five exchanges (3 to 5 L of plasma each) over 7 to 14 days

• Dosage of IVIG is 2 g/kg, usually over 2-5 days.

• Concurrent initiation of chronic immunomodulating therapy with high-dose glucocorticoids; if glucocorticoids are contraindicated or less effective consider azathioprine, mycophenolate mofetil, or cyclosporine.

• Weaning from mechanical ventilation with spontaneous breathing trials considered after treatment with plasma exchange or IVIG has been started and respiratory muscle strength has been improved (VC >15 to 20 mL/kg and a MIP more negative than -25 to -30 cmH2O)

• Remove any precipitating factors such as drugs or infections exacerbating the disease.

• Workup for concurrent infections including CBC, UA, CXR and blood cultures.

• Treat any infection if present

• IV Magnesium added as allergy

Mechanical Ventilation in Myasthenia Crisis

• The key to the greatest chance of recovery in patients with neuromuscular disease is quick assessment and prompt treatment.

• Identifying patient with impending respiratory failure and prompt endotracheal intubation with positive pressure mechanical ventilation should be considered while managing myasthenia crisis

• Invasive mechanical ventilation has the advantage of adequate secretion clearance and full support for those suspected to have prolonged courses of crisis

• The mode of mechanical ventilation generally utilized for managing myasthenia crisis is assist control modes of volume controlled ventilation and low levels of positive end-expiratory pressure (PEEP) with subsequent adjustments.

• The median duration of mechanical ventilation is 14 days in myasthenia crisis

Complications of Myasthenia crisis

• Fever and infection, including pneumonia, bronchitis, urinary tract infection, colitis caused by Clostridium difficile, bacteremia, and sepsis.

• Increased risk for vascular complications including deep vein thrombosis, heart failure, acute myocardial infarction, cardiac arrhythmias, and cardiac arrest.

Further Reading

• Excellent Review Article - Getting Rid of Weakness in the ICU: An Updated Approach to the Acute Management of Myasthenia Gravis and Guillain-Barré Syndrome (Lizarraga, Lizarraga, & Benatar, 2016)

• Case Discussion - A 23-Year-Old Man With Dyspnea During Myasthenia Crisis (Weinberg, Cavalcante, Choy, & Ahmad, 2019)

Bibliography

• Boon, A. J., Harper, C.J., et al. Two-dimensional ultrasound imaging of the diaphragm: quantitative values in normal subjects. Muscle Nerve. 2013;47(6):884-889 https://doi.org/10.1002/mus.23702

• Sanders, D. B., Wolfe, G. I., Benatar, M., et al. International consensus guidance for management of myasthenia gravis: Executive summary. Neurology 2016; 87:419. https://doi.org/10.1212/WNL.0000000000002790

• Lizarraga, A. A., Lizarraga, K. J., & Benatar, M. (2016). Getting Rid of Weakness in the ICU: An Updated Approach to the Acute Management of Myasthenia Gravis and Guillain-Barré Syndrome. Seminars in Neurology, 36(6), 615–624. https://doi.org/10.1055/s-0036-1592106

• Weinberg, M., Cavalcante, J. A., Choy, T., & Ahmad, S. (2019). A 23-Year-Old Man With Dyspnea During Myasthenia Crisis. Chest, 155(6), e155–e157. https://doi.org/10.1016/j.chest.2018.10.054