There is No Crisis: Myasthenia Gravis

It’s a simple mechanism. People form antibodies to their own acetylcholine receptors which does two things:

First, it blocks endogenous acetylcholine from binding to their receptors, and if acetylcholine can’t bind, the patient’s muscles can’t contract. 

Second, like what happens when antibodies bind to most things, it causes complement-mediated destruction of acetylcholine receptors throughout the day, essentially depleting the number of receptors available as the day goes on. 

In sum, these people wake up in the morning as strong as they are going to be for the day, then become weaker as the day goes on. Their muscular weakness generally improves with rest and worsens with repetitive muscular activity.

A crisis is any worsening of baseline MG causing or threatening to cause respiratory failure (1). 

A myasthenic crisis usually presents with a shockingly varied array of complaints. You still remember the image on that slide entitled “Presentation”:

Diplopia, Drooling, Dyspnea, Dysphagia, Dysarthria, Opthomoplegia

A crisis usually starts out as bulbar muscular weakness, which can then spread to proximal muscles – deltoids, biceps, quadriceps. The weakness than can become general, even affecting the diaphragm and requiring intubation.

You need to choose one of two options. 

The first option, the blue pill if you will, is to use the patient’s history of MG to explain whatever the patient’s chief complaint is. This is easy and tempting because MG is notoriously good at mimicking a wide variety of other diseases. 

The second option, the red pill, is to think outside the box. What else can explain these patient’s chief complaints? Form a differential.

Why waste time though? Its most likely Myasthenic Crisis.

Maybe it is, but here’s the issue with relying on this: 

Not only does Myasthenic Crisis mimic multiple other diseases, but multiple other diseases can also trigger a Myasthenic Crisis (1-6). 

So you gain two things by going through a differential: first, peace of mind from crossing possibilities off your list; second, maybe you actually find whatever it is that was triggering this crisis to begin with, allowing you to treat it.

Common MG triggers are infectious, cardio-pulmonary and endocrine pathologies, physical pain, electrolyte abnormalities, hyperthermia, anemia, medications, and even emotional stress. 

So consider a broader work up: CMP, CBC, EKG, TFTs, Troponin, UA and chest X-ray. Ask about recent physical trauma or emotional stress, and importantly, get a current medication list.

There is one primary thing and two additional things you can do to assess impending respiratory failure. 

Primarily, of course, is ABCs. You may not have much experience with MG patients, but with your emergency medicine training, you should have plenty of experience with patients who look like they can’t breathe. Any sign that would concern you in any other patient, should concern you in an MG patient. 

The first additional evaluation is the Single Breath Count Test. It’s easy, just ask the patient to take a breath and count as high as they can without taking another breath. The lower the number they have to stop at, the higher your concern should be. Normal is over 30, under 20 is concerning (1,2).

The second additional evaluation is Pulmonary Function Testing (PFTs). It includes Vital Capacity (VC) and Negative Inspiratory Force (NIF), and they usually require a respiratory therapist to bring down equipment.  

To assess VC: the respiratory therapist is going to have the patient take a full inhalation followed by a full exhalation, and the volume of air moved is measured. Normal is greater than 60 ml/kg, or around 3 to 5 Liters. Any value under 20 ml/kg should make you more concerned, so set up airway stuff faster and get consultants involved quicker (1,2). 

To assess NIF: the respiratory therapist is going to have the patient inhale as hard as he or she can, and the amount of negative pressure generated is measured. Normal values are around 60 cmH2O. Any value under 30 cmH20 should also make you move faster (1,2).

Wait.

You start thinking more about PFTs, you start questioning, like the inquisitive ER doc you were trained to be. If MG worsens with repetitive muscular activity, should I really be asking these potential Myasthenic Crisis patients to be breathing as hard as they can repeatedly?

PFTs are incredibly effort and position-dependent, often generating values that vary widely (2). The more effort these patients put into it, the better the values will likely be, but also the more tired their muscles will likely get. If you’re concerned about impending respiratory failure, it’s probably prudent to not overdo these. 

The studies evaluating these tests are generally low quality, retrospective, and have no sensitivities or specificities reported. , In these studies, NIF was uniformly found to be less consistent and less informative than VC. It may be worth remembering that the studies were actually done on Guillain-Barre patients, not MG patients (7-13). 

Food for thought.

While there are medications for MG with cool, cutting edge mechanisms like acetylcholinesterases, pulse dose steroids, plasmapheresis, and IVIG; in the acute ED setting you have two simple principles of management:

First – Minimize Medications

You know that many medications, including corticosteroids, can trigger a crisis, so the fewer meds we add to the suspect list the better. Acetylcholinesterases seem intuitive but they are actually known to complicate the situation with increased airway secretions and cardiac dysrhythmias (1). Plasmapheresis and IVIG are typically the only useful medical therapy for a severe crisis, however, these medications should be given in conjunction with neurological consultation or within an ICU setting (1). 

Second – Reduce Work of Breathing

You know their respiratory muscles are getting weaker, so your goal is to make the act of breathing easier than it normally is so that these muscles are still effective. You can do this by not over-exerting these patients with things like frequently repeated PFTs, and by having a low threshold for starting NIPPV, like high flow nasal cannula or BIPAP (14-18).

Just make sure you’ve done everything you can prior because these patients are notoriously difficult to extubate which leads to longer ICU admissions and higher likelihood for in hospital complications. If you have to intubate, you have to intubate. Keep these two thoughts in mind:

First – Less Roc, More Sux

Non-depolarizing neuromuscular blockers just bind to acetylcholine receptors and prevent native acetylcholine from binding, causing paralysis. Since there are fewer acetylcholine receptors available, you can use less rocuronium– typically half the dose (1,2). 

Succinylcholine works by binding acetylcholine receptors and causing a massive muscular contraction with subsequent inability to repolarize, causing paralysis. Since there are fewer acetylcholine receptors available, you need to use more succinylcholine– typically 1.5x the dose (1,2).

Second – Sedate Appropriately

No matter which paralytic you use, you can count on the paralysis lasting 2-4 times longer in patients with MG. So don’t be cruel, sedate appropriately (1,2.

You took the blue pill.

You didn’t question the crisis.

You panicked.

You called Respiratory Therapy.

You consulted MICU.

You overhead paged Neurology.

You took the red pill.

You questioned the crisis.

You formed a differential. 

You found the 15 year old’s Peritonsillar Abscess.

You terminated the 25 year old’s Paroxysmal SVT. 

You still overhead paged neurology, but for a brainstem stroke.