Effects of acetylcholinesterase inhibitor therapy for Alzheimer's disease on neuromuscular block
Dundee and Middlesbrough, UK
* E-mail: gareth.kessell{at}stees.nhs.uk
Editor—Acetylcholinesterase inhibitors (donepezil, rivastigmine, and galantamine) are now currently recommended in the management of moderately severe Alzheimer's disease.1 Therefore, it is likely that over time, an increasing number of anaesthetists will encounter patients taking this type of medication yet there is sparse literature on interactions with anaesthetic drugs nor is there guidance regarding perioperative management. We would like to draw the readers' attention to a case which illustrates the difficulties which can be experienced with this group of patients when undergoing anaesthesia requiring muscle relaxation.
A 70-yr-old gentleman was being anaesthetized before a hemiarthroplasty for a fractured left neck of femur. His regular medications consisted of donepezil 10 mg, alfuzosin 10 mg, beclometasone 200 µg, Combivent 2 puffs, ferrous sulphate 200 mg, and Co-careldopa 12.5/50 mg. After induction with propofol, he was given atracurium 30 mg. A train-of-four (TOF) stimulus with a peripheral nerve stimulator produced four twitches with no evidence of fade. Intubation was achieved, but the patient coughed due to the lack of neuromuscular block. The patient breathed throughout the 45 min operation; a further 10 mg of atracurium was given during surgery, but there remained a full response to further TOF stimulation. He was extubated successfully 45 min post-induction without the use of reversal agents.
Reference to the British National Formulary supports the suspicion that donepezil was the agent most likely to be responsible for the lack of neuromuscular block as it ‘possibly antagonizes the effects of non-depolarizing muscle relaxants’. The patient's other medications do not share this property. Rivastigmine is also known to antagonize the effect of non-depolarizing neuromuscular blocking agents.2
As previously mentioned, there is currently little literature on the subject. A study in rats found that tacrine (a centrally acting anticholinesterase) administered chronically caused resistance to neuromuscular block with d-tubocurarine. This would add weight to the hypothesis that donepezil antagonized the atracurium in our patient's case. In this animal study, resistance decreased with time, possibly due to Ach-receptor down-regulation.3
Depolarizing neuromuscular blocking agents can also be affected by anticholinesterases. Donepezil may, and galantamine and rivastigmine are, known to enhance the effect of suxemethonium.2 Prolonged relaxation in a patient taking donepezil who was paralysed with suxemethonium has been described in the literature.4
An abstract from a Spanish article describes prolonged relaxation with succinylcholine and inadequate response to high doses of atracurium in a patient taking donepezil, demonstrating both of the aforementioned phenomena in one patient.5
We think it important and timely that these significant interactions are brought to the attention of other anaesthetists as we expect that patients on anticholinesterases requiring anaesthesia with neuromuscular blocking agents will present with increasing frequency in the future. We would also recommend the cessation of anticholinesterases 3–4 weeks before anaesthesia wherever possible. This should not have a detrimental effect on the patient's overall cognitive function, as anticholinesterases may have no disease modifying action.6
References
1 National Institute for Health and Clinical Excellence. Donepezil, galantamine, rivastigmine (review) and memantine for the treatment of Alzheimer's disease (amended). (2007) London: NICE.
2 British National Formulary. Appendix 1 Interactions. Available from www.bnf.org/bnf/current/41001.646.htm (accessed October 29, 2007).
3 Ibebunjo C, Donati F, Fox GS, Eshelby D, Tchervenkov JI. The effects of chronic tacrine therapy on d-tubocurarine blockade in the soleus and tibialis muscles of the rat. Anesth Analg (1997) 85:431–6.[Abstract]
4 Crowe S, Collins L. Suxamethonium and donepezil: a cause of prolonged paralysis. Anesthesiology (2003) 98:574–5.[CrossRef][Web of Science][Medline]
5 Sanchez MJ, Demartini FA, Roca de Togores LA. Interaction of donepezil and muscular blockers in Alzheimer's disease [abstract]. Rev Esp Anestesiol Reanim (2003) 50:97–100.[Medline]
6 British Geriatrics Society. Communications to the Autumn Meeting of the British Geriatrics Society. Programme of Abstracts (2007) Harrogate, Yorkshire: Harrogate International Centre. October.
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||