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The impact of Alzheimer's disease medication on muscle relaxants.

With the aging of the population there are an increasing number of elderly people coming to surgery who are being treated for Alzheimer's disease. A very common treatment for Alzheimer's disease is an acetylcholine esterase inhibitor such as galantamine (Reminyl), rivastigmine (Exelon) and donepezil (Aricept). The first two have moderately short half-lives, but unfortunately the half-life of donezepil is three days or more. Thus, donezepil needs to be stopped about two weeks or more before surgery to ensure no interaction.

Extreme interactions with donezepil have been reported with muscle relaxants. One report documents a prolonged paralysis of 50 minutes after 1 mg/kg intravenous dose of suxamethonium and the recovery was characterised by fade on the train-of-four, indicating a phase 2 block (1). A similar acetyl cholinesterase interaction with competitive neuromuscular blockers has been reported. During a 45 minute anaesthetic, a 30 mg dose of atracurium in a 70-year-old man on 10 mg donezepil daily had no paralysing effect, as indicated by continued breathing and no fade on the train-of-four simulation (2).

If a patient requires relaxant anaesthesia, it seems that enormous amounts of a competitive agent will be necessary. Alternatively, if suxamethonium is used, an uncertain long duration of paralysis must be expected. This is one special situation where paralysis may be best achieved by a very large dose of a competitive agent, e.g. 2 to 5 mg/kg of rocuronium to overcome the increased competition. However, there then remains the problem of reversal. The addition of another anticholinesterase such as neostigmine may not achieve the usual reversal, especially as large doses have been given. One solution may be to use a very short acting competitive agent such as mivacurium with nerve twitch monitoring. Unfortunately, in the presence of an esterase inhibitor, its duration of action may also be extended. An alternative approach could be the use of sugammadex, which is specifically designed to reverse rocuronium by encapsulation (3). It has been shown that this agent can removed very high levels of rocuronium (4).

The use of rocuronium and then sugammadex in Alzheimer's patients on donepezil who need relaxant anaesthesia would seem an ideal solution. I understand that sugammadex is under consideration by the Therapeutic Goods Administration and should be available in Australia next year.

W. J. RUSSELL

Adelaide, South Australia

References

(1.) Crowe S, Collins L. Suxamethonium and donepezil: a cause of prolonged paralysis. Anesthesiology 2003; 98:574-575.

(2.) Baruaah J, Easby J, Kessell G. Effects of acetylcholinesterase inhibitor therapy for Alzheimer's disease on neuromuscular block. Br J Anaesth 2008; 100:420.

(3.) Naguib M. Sugammadex:another milestone in clinical neuromuscular pharmacology. Anesth Analg 2007; 104:575-581.

(4.) Groudine SB, Soto R, Lien C, Drover D, Roberts K. A randomised, dose-finding, phase II study of the selective relaxant binding drug, sugammadex, capable of safely reversing profound rocuronium-induced neuromuscular block. Anesth Analg 2007; 104:555-562.
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Title Annotation:Correspondence
Author:Russell, W.J.
Publication:Anaesthesia and Intensive Care
Geographic Code:8AUSA
Date:Jan 1, 2009
Words:477
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