This monograph does not cover the use of the combination product of neostigmine metilsulfate and glycopyrronium bromide injection indicated for the reversal of residual non-depolarising neuromuscular block.
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 prior to 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 neostigmine states that it is contra-indicated in these conditions.
Perioperative Considerations
Missed doses of neostigmine during long procedures may manifest as weakness at the end of surgery. Doses due during surgery should be administered as appropriate.
Post-operative advice
Restart once next dose is due.
If the patient was switched to neostigmine perioperatively, they should be restarted on their usual medication regimen as soon as they are able to tolerate oral doses.
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 neostigmine 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.
Neostigmine antagonises the effect of NMBDs and intravenous 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 neostigmine 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
Neostigmine can increase the risk of bradycardia when used concomitantly with the following: -
- alfentanil, fentanyl or remifentanil
- 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 neostigmine. 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 symptoms1; 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 is superior to neostigmine for reversing moderate-to-deep neuromuscular block and may reduce the risk of perioperative myasthenic crises and postoperative 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 DOI: 10.1016/j.anclin.2007.05.005
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]
Summary of Product Characteristics – Neostigmine Methylsulfate Injection BP 2.5mg in 1ml. hameln pharma ltd. Accessed via www.medicines.org.uk 19/09/2024 [date of revision of the text May 2021]