Donepezil-related inadequate neuromuscular blockade during laparoscopic surgery: A case report

Abstract

BACKGROUND Donepezil is an acetylcholinesterase inhibitor used to improve cognition and delay disease progression in dementia patients by increasing acetylcholine levels. This drug may potentially interact with neuromuscular blocking agents (NMBAs) that act on muscular acetylcholine receptors during general anesthesia. Herein, we present a case of inadequate neuromuscular blockade with rocuronium, a nondepolarizing NMBA, in a dementia patient who had taken donepezil. CASE SUMMARY A 71-year-old man was scheduled for laparoscopic gastrectomy. He had been taking donepezil 5 mg for dementia. General anesthesia was induced with propofol and remifentanil. The depth of neuromuscular blockade was monitored by train-of-four (TOF) stimulation. After the administration of rocuronium, the TOF ratio decreased at an unusually slow rate, and a TOF count of 0 was detected 7 min later. After intubation, a TOF count of 1 was detected within 1 min, and a TOF ratio of 12% was detected within 2 min. The TOF count remained at 4 even with an additional bolus and continuous infusion of rocuronium, suggesting resistance to this NMBA. Instead of propofol, an inhalation anesthetic was administered alongside another NMBA (cisatracurium). Then, the quality of neuromuscular blockade improved, and the TOF count remained at 0-1 for the next 70 min. No further problems were encountered with respect to surgery or anesthesia. CONCLUSION Donepezil may be responsible for inadequate neuromuscular blockade during anesthesia, especially when total intravenous anesthesia is used.

Donepezil inhibits neuromuscular junctional acetylcholinesterase and enhances synaptic transmission and function in isolated skeletal muscle

“…Donepezil, a piperidine anti‐AChE, is widely prescribed for treatment of AD, but relatively little consideration has been given to its effects on peripheral cholinergic synaptic function. Several clinical case studies have reported complications when administration of neuromuscular blockers had been required in patients who were already being treated with donepezil (Baruah et al, 2008 ; Bhardwaj et al, 2011 ; Jang et al, 2020 ). In addition, there have been proposals to extend administration of donepezil, for example, to elderly patients presenting for orthopaedic surgery, in order to mitigate postoperative cognitive dysfunction (Zhu et al, 2021 ).…”

“…We found in a recent study that endplate contractions and prolonged Ca 2+ transients (‘calcium bombs’) induced by an organophosphorus anti‐AChE were mitigated by modest (1–4 mM) increases in extracellular Mg 2+ ionic concentration, both in vivo and in vitro (Dissanayake, Chou, et al, 2021 ). Further investigation may indicate whether prophylactic or therapeutic administration of MgSO 4 , as utilised, for example, in the treatment of eclampsia (Duley et al, 2003 ), might also mitigate muscle cramps reported as a side effect elderly patients on standard medication with donepezil (Birks & Harvey, 2006 ), or the requirement for higher doses of non‐depolarising neuromuscular blockers in such patients when muscle relaxation may be required during surgery (Baruah et al, 2008 ; Bhardwaj et al, 2011 ; Jang et al, 2020 ).…”

“…In addition, patients receiving donepezil who undergo surgical procedures for unrelated conditions show enhanced neuromuscular block when depolarising antagonists of nicotinic acetylcholine receptor s (nAChRs) such as suxamethonium are administered (Crowe & Collins, 2003 ; Sprung et al, 1998 ). Conversely, higher concentrations of non‐depolarising neuromuscular blockers may be required to achieve prolonged muscle relaxation in anaesthetised patients, who are already receiving donepezil (Baruah et al, 2008 ; Bhardwaj et al, 2011 ; Jang et al, 2020 ).…”