Myasthenia gravis has appeared in the exam mainly as a foil for Guillain-Barre syndrome, but has more recently graduated to become an SAQ topic all of its own. Historical appearances have included:
So, it would seem it deserves its own summary note. Thus...
- Myasthenic crisis is an exacerbation of myasthenia gravis which requires mechanical ventilation
- Specific interventions include:
- First line:
- Plasmapheresis, or IV immunoglobulin
- High dose steroids (prednisolone 1.0-1.5mg/kg/day)
- Second line
- Pulse steroids (1g methylprednisolone)
- Steroid-sparing agents (azathioprine, mycophenolate)
- Immune suppression (rituximab, cyclophosphamide)
- Complement deactivation (eculizumab)
- Acetylcholinesterase inhibitors (pyridostigmine)
- Classes of drugs which exacerbate myasthenia gravis include:
- Immune checkpoint inhibitors (ipilimumab, pembrolizumab, atezolizumab, and nivolumab)
- Iodinated contrast media
- Live attenuated vaccines
- Challenges to the extubation of a myasthenia gravis patient (and methods to address them):
- Weakness (pyridostigmine)
- Cholinergic side effects, increased secretions (propantheline)
- Critical illness and steroid myopathy (dietary protein supplementation, physiotherapy, early mobility, use of steroid-sparing agents such as mycophenolate)
- Poor swallow or cough (tracheostomy as a bridge to future normal bulbar function)
- Slow weaning (so, extubate on to NIV)
- Marginal respiratory reserve (so, optimise VAP and CCF therapies before contemplating extubation)
The UpToDate entry by Bird is probably a definitive peer-reviewed source for the time-poor candidate who is either a paying customer or endowed with institutional access. The best free alternative would have to be Wendell & Levine (2011) or Schroeter et al (2018). For some excellent FOAM resources the reader is redirected to the IBCC and LITFL entries, as they are both rich in detail and free of pointless rambling.
The pathophysiology of things in general is really somewhat deemphasised in the CICM exams, and so only the shortest summary is offered here, as well as a link to redirect the interested reader to a great article by Baets & Stassen (2002). At the most basic level this thing is an autoimmune disease caused by IgG antibodies against the nicotinic acetylcholine receptor, and finding these antibodies is the most important step in the diagnostic process. These antibodies bind to a highly immunogenic epitope at the α-subunit of the receptor, and the result is the destruction of the receptor protein which is internalised into the myocyte and degraded. Obviously the binding of antibodies also has a significant immune effect, and produces the complement-mediated destruction of the postsynaptic membrane (though thankfully not the whole myocyte). The membrane grows back, but it has fewer folds and therefore a smaller surface area.
From Sanders & Massey (2008):
Other cranial nerve dysfunction
What else could it be?
Hehir & Sylvestri (2018) present a really helpful description of the natural history of this disease. Borrowing from their paper:
So, what is this "crisis" we speak of?
Though it might seem to a bit overdramatic to call something a "crisis" or "storm" (because why not "myasthenic conniption" instead), Bedlack & Sanders (2002) defend the term by pointing to the need to have definitions for standardise research and interventional guidelines. A myasthenic crisis is conventionally defined as any myasthenic exacerbation which results in intubation or non-invasive mechanical ventilation, or which prevents extubation following an elective procedure. It therefore depends on the decision to intubate or extubate, and therefore completely contingent on the subjective views of the intensivist and anaesthetist, of whom some might be cowards and others might be cowboys. And it might sound like life-threatening respiratory muscle failure is a good way to define severe disease, but one must be reminded that some of these patients might end up being intubated because of airway reflex problems. Still, the scientific community seems to have settled on this definition, and that is how it appears in UpToDate.
This section is a blend of the 2020 international myasthenia gravis consensus statement and the myasthenia crisis chapter from the Textbook of Neuroanesthesia and Neurocritical Care (2019).
Again from the 2020 international myasthenia gravis consensus statement:
So, with the worst of the myasthenia crisis now largely behind you, the time has come to think about weaning and extubation for your very borderline marginal patient who is probably still as weak as a kitten. It is weird that this aspect was apportioned only 30% of the total mark in Question 5 from the second paper of 2022, as this is probably the area that requires the most skill from the intensivist, whereas merely listing the interventions and classes of myasthenia-exacerbating drugs would be as easily accomplished by ChatGPT. Still, at least it was in there. Specifically, the question of extubation is asked in terms of "methods to address the challenges". It felt like it would be easier to manage this if it were a table:
|Challenge||Methods to address the challenge|
|Increased secretions (a side-effect of pyridostigmine)||"Propantheline is an antimuscarinic agent that counteracts many of the cholinergic side effects of pyridostigmine without reducing its action at the NMJ" - Farrugia et al, 2020|
|Slow fluctuating progress||Extubation to NIV is an option, particularly if bulbar function permits. Theoretically weaning could be facilitated by NAVA, but the evidence for that is fairly poor. There is some evidence that elective use of NIV immediately following extubation is better than waiting until the patient develops respiratory failure.|
|Difficult detection of readiness for extubation||Extubation success can be predicted by improving vital capacity on the ventilator, spontaneous mode, lack of fatuguabuility with sustained "sprints" of lower ventilator support|
|Concomitant respiratory compromise||It does not need to be said that these borderline patients should be as free as possible of any other reasons for extubation failure, such as pulmonary oedema or pneumonia.|
|Steroid and critical illness myopathy||Dietary protein supplementation, physiotherapy, early mobility, use of steroid-sparing agents such as mycophenolate|
|Poor bulbar function, weak cough||Tracheostomy as a bridge to future normal bulbar function following a course of therapy is a legitimate option|
An excellent paper on weaning the patient with neuromuscular disease was published by Torres-Castro et al in 2021, and likely served as the origin for this SAQ. Even though they did not find any papers that fit their inclusion criteria, they discuss the options in some detail, and the ideas in that paper were amalgamated into the table above.