Issues for surgery
Increase in muscle weakness, potentially including respiratory muscles, if omitted.
Interaction with neuromuscular blockers if continued (see Interactions with common anaesthetic agents).
Advice in the perioperative period
Elective surgery
Continue.
The patient should be seen by the Anaesthetist pre-operatively to discuss the plan for surgery, including the potential effects of anaesthesia and associated medicines. The planning should involve the patient’s Neurologist to ensure the condition is fully optimised and stable before surgery and to plan post-operative care.
Ensure Anaesthetist is aware of the drug interactions (see Interactions with common anaesthetic agents).
Emergency surgery
Continue.
Ensure Anaesthetist is aware of the drug interactions (see Interactions with common anaesthetic agents).
Patients presenting with mechanical bowel or urinary obstruction should be urgently reviewed by a Neurologist since the UK Manufacturer of pyridostigmine states that it is contra-indicated in these
Perioperative considerations
Missed doses of pyridostigmine during long procedures may manifest as weakness at the end of surgery – consider treatment with neostigmine injection (subcutaneous / intramuscular) if enteral doses are going to be missed. See current product literature for equivalent doses.
Information can also be found on the Specialist Pharmacy Service website ‘Switching between neostigmine and pyridostigmine’.
Also see Neostigmine monograph for further information regarding its use perioperatively.
Post-operative advice
Restart once next dose is due.
Medication for myasthenia gravis should not be missed. If patients are unable to take their regular oral medication post-operatively, convert to neostigmine injection (subcutaneous / intramuscular) – see current product literature for dose conversion and seek Specialist advice.
Information can also be found on the Specialist Pharmacy Service website ‘Switching between neostigmine and pyridostigmine'.
Also see Neostigmine (injection) drug monograph for further information regarding its use perioperatively.
Patients undergoing thymectomy
The dose of pyridostigmine may need to be reviewed post-operatively since requirements can reduce – seek specialist advice.
Interactions 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 treatment.
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 prolonged.
Pyridostigmine antagonises the effect of NMBDs and neostigmine is routinely used for reversal. 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 (see Further information).
Suxamethonium
Suxamethonium has decreased efficacy at usual doses in patients with myasthenia gravis due to a reduced number of acetylcholine receptors. Higher doses or repeated doses of suxamethonium may produce a dual block (non-depolarising block following the initial depolarising block) resulting in delayed recovery.
Unlike non-depolarising NMBDs, administration of pyridostigmine increases the concentration of acetylcholine at the neuromuscular junction and thus prolongs the action of suxamethonium. Ideally suxamethonium should be avoided in patients with myasthenia gravis.
Bradycardia
Pyridostigmine can increase the risk of bradycardia when used concomitantly with the following: -
- alfentanil, fentanyl or remifentanil
- neostigmine
- propofol
- suxamethonium (see also Neuromuscular blocking drugs above)
Interactions with other common medicines used in the perioperative period
Antimicrobials
Aminoglycoside antibiotics (e.g. amikacin, gentamicin, neomycin, streptomycin, tobramycin) should be used with caution, and only if no alternative treatment available, in patients with myasthenia gravis as they impair neuromuscular transmission.
Fluoroquinolone (e.g. ciprofloxacin) and macrolide (e.g. erythromycin) antimicrobials have been seen to increase the muscular weakness associated with myasthenia gravis and might, therefore, antagonise the actions of pyridostigmine. While the clinical significance of this interaction is unknown, bear it in mind in case of an unexpected response to treatment. Ideally consider an alternative antimicrobial.
Corticosteroids
Corticosteroids may cause a transient worsening of symptoms; monitor for muscle weakness if used.
Magnesium supplementation
Magnesium inhibits the release of acetylcholine which can cause deterioration of myasthenia gravis. It should only be used if necessary; monitor for worsening of symptoms.
Further information
Reversal of NMBD blockade
Reversal with neostigmine can be unpredictable and there is a risk of triggering cholinergic crisis, hence the dose should be carefully titrated to effect. Sugammadex is an option for NMBD blockade reversal since it is not affected by anticholinesterases. It has been shown to be superior to neostigmine for reversing moderate-to-deep neuromuscular block and may reduce the risk of perioperative myasthenic crises and post-operative pneumonia.
References
Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 19th September 2024]
Brambrink, A. & Kirsch, J. Perioperative Care of Patients with Neuromuscular Disease and Dysfunction. Anesthesiology Clinics. 2007; 25(3): 483-509
Daum P, Smelt J, Ibrahim IR. Perioperative management of myasthenia gravis. BJA Educ. 2021 Nov;21(11):414-419. Doi: 10.1016/j.bjae.2021.07.001
Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 19th September 2024]
Specialist Pharmacy Service. Switching between neostigmine and pyridostigmine. Published 25th October 2022. Accessed via www.sps.nhs.uk on 19th September 2024
Summary of Product Characteristics – Mestinon® (pyridostigmine). Mylan products limited. Accessed via www.medicines.org.uk 19/09/2024 [date of revision of the text July 2023]