Anticholinesterases for Myasthenia Gravis

Neostigmine, Pyridostigmine 

  Issues for Surgery

Increase in muscle weakness, potentially including respiratory muscles, if omitted.

Interaction with neuromuscular blockers if continued (see Interaction(s) with Common Anaesthetic Agents).

  Advice in the Perioperative period

Elective and Emergency Surgery

Continue.

Ensure Anaesthetist is aware of the drug interactions.

  Interaction(s) with Common Anaesthetic Agents

Local anaesthetics

Local or regional anaesthesia is often preferred in myasthenia gravis; however, the dose of ester local anaesthetics may need to be reduced due to concomitant pyridostigmine or neostigmine treatment¹.

Neuromuscular Blocking Drugs (NMBDs)

Non-depolarising NMBDs
Patients with myasthenia gravis have a reduced number of acetylcholine receptors; this leads to high sensitivity to non-depolarising NMBDs and patients may only require 10% of a normal dose. Medium-acting drugs e.g. atracurium or vecuronium are preferred to long-acting drugs e.g. pancuronium and rocuronium but, even with dose reduction; the duration of the block can be prolonged¹.

Pyridostigmine and neostigmine antagonise the effect of NMBDs and neostigmine is routinely used for reversal^{1, 2, 3}. However, in patients with myasthenia gravis reversal can be unpredictable, partially due to chronic anticholinesterase treatment. Excessive administration of reversal agents could precipitate cholinergic crisis^{1, 4, 5}.

Suxamethonium
Suxamethonium has decreased efficacy at usual doses in patients with myasthenia gravis due to a reduced number of acetylcholine receptors¹. Higher doses or repeated doses of suxamethonium may produce a dual block (non-depolarising block following the initial depolarising block) resulting in delayed recovery⁶.

Unlike non-depolarising NMBDs, administration of pyridostigmine or neostigmine increases the concentration of acetylcholine at the neuromuscular junction and thus prolongs the action of suxamethonium ^{1, 4, 5}. Ideally suxamethonium should be avoided in patients with myasthenia gravis.

Bradycardia

Pyridostigmine and neostigmine can increase the risk of bradycardia when used concomitantly with the following⁶: -

• alfentanil, fentanyl or remifentanil
• propofol
• suxamethonium (see also Neuromuscular Blocking Drugs above)

  Interaction(s) with other Common Medicines used in the Perioperative Period

Aminoglycoside antibiotics (e.g. amikacin, gentamicin, neomycin, streptomycin, tobramycin) are contraindicated in patients with myasthenia gravis as they impair neuromuscular transmission⁶.

  Further Information

The stress of surgery and potential exposure to exacerbating drugs can trigger a myasthenia crisis⁵.

  References

1. Brambrink, A. & Kirsch, J. Perioperative Care of Patients with Neuromuscular Disease and Dysfunction. Anesthesiology Clinics. 2007; 25(3): 483-509
2. Summary of Product Characteristics – Neostigmine Bromide Tablets15mg. Alliance pharmaceuticals. Accessed via www.medicines.org.uk 10/05/2019 [date of revision of the text February 2015]
3. Summary of Product Characteristics – Mestinon^® (pyridostigmine). Mylan products limited. Accessed via www.medicines.org.uk 10/05/2019 [date of revision of the text February 2018]
4. Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 10^th May 2019]
5. Myaware (registered charity 1046443). http://www.myaware.org [Accessed on 10^th May 2019]
6. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 10^th May 2019]