The Pre-brief
What is myasthenia gravis (MG)?
MG is an autoimmune disease that stems from antibodies binding to acetylcholine (Ach) receptors and related molecules on the postsynaptic membrane of the neuromuscular junction. This leads to weakness of the skeletal muscles which can be generalized or localized with increases in weakness when muscles are used excessively (such as during exercise) or repeatedly (such as over the course of the day).
How to treat and how not to treat
Acetylcholinesterase inhibitors (ex: pyridostigmine) and immunosuppressive agents (ex: azathioprine, prednisolone) are the standard of care for stable patients with MG. For MG crises, more powerful treatments are needed such as intravenous immune globulin or plasma exchange.
However, in addition to knowing how to treat MG patients, it is equally important to know how not to treat them. In other words, you need to know which medications should be used with caution or avoided altogether when possible due to the risk of disease exacerbation.
The following medications have been confirmed to exacerbate MG, have been implicated in case reports, or have demonstrated strong culpability in in-vitro studies.
Note: This is not an all-inclusive list, but includes drugs that have been implicated repeatedly. Commonly used ICU medications have been bolded.
New case reports pop up all the time regarding more drugs implicated in worsening MG. However, banning the use of all drugs ever reported makes the pool of drugs left available for MG patients to use very small. Therefore, the best recommendation is to be cautious when using those drugs that have been reported in literature and to monitor patients for increasing weakness. An alternative agent should be utilized when possible.
What about paralytics?
Considering paralytics are neuromuscular blockers and MG patients have a disease process stemming from their neuromuscular junctions, it seems intuitive to believe that paralytics may not be safe to use in these patients.
Occasionally, some patients with MG will have their disease unmasked by the use of paralytics. The effects of paralytics can also be compounded by certain drugs including antibiotics and antiarrhythmics which may amplify their ability to cause weakness in MG patients.
However, paralytics can’t always be avoided such as when intubation is necessary, and they can still be used safely as long as you remember some key points.
- In MG, there is a decrease in the number of functional ACh receptors. Therefore, depolarizing neuromuscular blockers such as succinylcholine cannot effectively depolarize the endplate. To overcome this “resistance”, the dose of succinylcholine must be increased by 2x’s – 2.5x’s to have an adequate response.
- The opposite is true for nondepolarizing neuromuscular blockers such as rocuronium. MG patients experience increased sensitivity to these agents secondary to the reduced number of functional ACh receptors. For these patients, the dose of paralytic should be decreased to anywhere from 50% – 90%.
The Debrief
- Patients with MG may develop MG crisis in which admission to the ICU is typically necessary.
- Knowledge of medications/medication classes to avoid when possible is essential to prevent further disease damage in MG patients.
- When using paralytics in MG patients, remember to dose adjust accordingly. The dose of depolarizing paralytics such as succinylcholine should be increased by 2-2.5x’s. The dose of nondepolarizing paralytics such as rocuronium, should be decreased by 50-90%.
- Risk versus benefit should be considered carefully when using a medication that could worsen MG; alternative treatments should be considered.
References
- Gilhus N. Myasthenia Gravis. N Engl J Med. 2016; 375: 2570-81.
- Mehrizi M, Fontem R, Gearhart T, et al. Medications and Myasthenia Gravis: A Reference for Health Care Professionals. Myasthenia Gravis Foundation of America. Aug 2012.
- MyAware: Fighting Myasthenia Together. Contraindicated Drugs. Medical Professionals Resource Center. Available at: https://www.myaware.org/contraindicated-drugs
- Myasthenia Gravis Foundation of America. Cautionary Drugs. Available at: https://www.myaware.org/contraindicated-drugs
- Collins S, Roberts H, Hewer I. Anesthesia and Perioperative Considerations for Patients with Myasthenia Gravis. AANA J. 2020; 88(6): 485-91.
- Baraka A. Anaesthesia and Myasthenia Gravis. Can J Anaesth. 1992; 39(5) 476-86.
