What to know about your patient with Myasthenia gravis

He/She likely has acetylcholine (ACh ) receptor antibodies. These bind to ACh receptors, which interferes with the ability of ACh to bind. Over time this leads to a decrease in the numbers of post-synaptic acetylcholine receptors at the neuromuscular junction

• Therefore, there is a decreased ability of the neuromuscular nerve-plate to transmit the signal, and an exaggerated fatigability of voluntary muscles
•  He/She is likely on an acetylcholinesterase inhibitor, which slows the breakdown of ACh so more ACh is available at the neuromuscular junction. (An example is pyridostigmine)

What to know about your paralytics

Agonist/Depolarizing agent (Ex: succinylcholine)

• Binds to the ACh receptor at the ACh site (has a similar structure to ACh)
• Depends on the functional status of receptors to work, which are decreased in the case of a patient with myasthenia gravis
• Metabolized by plasma acetylcholinesterase

Antagonist/Non-depolarizing agent (Ex: vecuronium, rocuronium, atracurium)

• Competitive antagonist that prevents ACh access to the receptor, preventing depolarization
• Depends on the quantity of receptors

Therefore, when using paralytics

A patient with myasthenia gravis requires a HIGHER dose of succinylcholine

• Whereas a “normal” patient will require 1.0-1.5mg/kg of succinylcholine, a patient with myasthenia will require 1.5-2.0mg/kg or approximately double the dose
• In general, there is a resistance to succinylcholine: a simple way to think about it is that the increased resistance is due to not having enough “normal” ACh receptors to cause a depolarization (defective receptors), so more drug is required to have an effective response
• Caveat: There are also case reports of myasthenic patients that demonstrated a typical response to a normal dose of drug.

A patient with myasthenia gravis requires a LOWER dose of non-depolarizing agents like rocuronium and vecuronium

• In general there is an increased sensitivity to non-depolarizing paralytics: this is attributed to there being a lower number of receptors. Studies show patients requiring only one-half the typical dose of a non-depolarizing agent.
• Caveat: studies show that the response to non-depolarizing drugs is highly variable – especially depending on the severity of the disease. Some patients with severe MG were found to require a very small dose of a non-
  depolarizing agent (even less than 50% of a “normal” dose), while some with minimal symptoms used doses that a patient without myasthenis gravis would require

Important to Remember!

Anticipate a longer duration of paralysis in myasthenia patients undergoing neuromuscular blockade. This is seen with both the depolarizing and non-depolarizing agents. In the case of succinylcholine, patients taking their prescribed acetylcholinesterase medications sometimes demonstrate prolonged paralysis, as they have decreased function of the enzyme that metabolizes succinylcholine

Current evidence from anesthesia literature shows that dosing of both depolarizing and non-depolarizing agents does not need to be changed depending on whether the patient is taking cholinesterase inhibitors

Sugammedex is a selective neuromuscular blocking agent that was designed to reverse rocuronium, and also has some effect on reversing vecuronium. It has been shown to be effective to reverse neuromuscular blockade in myasthenia patients.

References

• Abel M., Eisenkraft J.B.. Anesthetic implications of myasthenis gravis. Mt Sinai J Med, 2002; (69), pp.31-37
• Fujimoto M, Terasaki S, Nishi M, Yamamoto T. Response to rocuronium and its determinants in patients with myasthenia gravis: A case-control study. Eur J Anaesthesiol. 2015 Oct;(10):670-80
• Dillon FX. Anesthesia issues in the perioperative management of myasthenia gravis. Semin Neurol. 2004 Mar; 24(1):83-94. Review.
• Eisenkraft J, Book W, Mann S, Papatestas A, Hubbard M. Resistance to succinylcholine in myasthenia gravis: a dose-response study. Anesthesiology, 1988; 69:760-763
• Blichfeldt-Lauridsen L, Hansen BD. Anesthesia and myasthenia gravis. Acta Anaesthesiol Scand 2012; 56:17-22
• Lizarraga A, Lizarraga K, Benatar M. Getting rid of weakness in the ICU: An updated approach to the acute management of myasthenia gravis and guillain-barré syndrome. Semin Neurol 2016; (36):615-624