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Donepezil: Anesthetic interactions

Pharmacologically, donepezil (Aricept®) is an acetylcholinesterase inhibitor. It is most active in the central nervous system, where it is used to increase levels of acetylcholine in patients with Alzheimer’s type dementia. While donepezil is most active in the CNS, it also has some level of peripheral activity that can lead to interactions with the commonly used neuromuscular blocking agents (NMBAs). Unfortunately, this interaction with NMBAs has not been well studied, and the majority of literature is composed of case studies.

When combined with a depolarizing NMBA (succinylcholine), the effects of donepezil can lead to prolonged blockade. In 2003, Crowe and Collins presented a case wherein a patient taking donepezil was paralyzed with a standard dose of succinylcholine given after induction. After 20 minutes, the patient still did not have any twitches on train of four monitoring. 4 twitches with fade were finally noted 50 min following administration of the single dose of succinylcholine. Upon review of records, it was discovered that the same patient had undergone an anesthetic with succinylcholine in the past (prior to being started on donepezil), with no prolonged blockade noted.

With regard to non-depolarizing NMBAs, the opposite effect has been reported. In 2011, Bhardwaj et al reported a case wherein the patient was given a 0.6 mg/kg dose of rocuronium upon induction. The patient’s respiratory efforts reappeard during direct laryngoscopy and an additional 10 mg was given. Assuming that the rocuronium was ineffective, the decision was made to transition to vecuronium. Unexpectedly, the patient continued to require much higher doses than expected to maintain paralysis throughout the duration of the case.

When anesthetizing a patient taking donepezil, two strategies exist with regard to perioperative management. Under most circumstances, patient care will not be compromised if the risk of altered blockade is anticipated and balanced against the need to provide optimal intubating conditions. When succinylcholine is administered, it appears that there is minimal actual prolongation of neuromuscular blockade (likely lasting less than an hour). With that in mind, succinylcholine may not be a suitable NMBA for a short case if the patient is taking donepezil. By contrast, if a non-depolarizing NMBA is used, a shorter than usual duration of blockade should be anticipated. If the risk of altered neuromuscular blockade outweighs the benefits of remaining on the drug, then the donepezil can be held prior to surgery. The half-life of donepezil is reported at 70 hours and withholding the medication for a period of at least 2 weeks prior to scheduled operations is recommended in the manufacturer’s package insert.

Other References

  1. Suzanne Crowe, Linda Collins; Suxamethonium and Donepezil: A Cause of Prolonged Paralysis. Anesthesiology 2003;98(2):574-575. Link
  2. Bhardwaj A, Dharmavaram S, Wadhawan S, Sethi A, Bhadoria P. Donepezil: A cause of inadequate muscle relaxation and delayed neuromuscular recovery. J Anaesthesiol Clin Pharmacol 2011;27:247-8 Link