Should acetylcholinesterase inhibitors (e.g., donepezil, rivastigmine patch, galantamine) be continued on the day of surgery, and how do they affect the dosing and response to non‑depolarizing neuromuscular blockers and succinylcholine?

Acetylcholinesterase Inhibitors and Surgery

Acetylcholinesterase inhibitors should be discontinued 24-48 hours before elective surgery due to their significant risk of exaggerating neuromuscular blockade from both succinylcholine and non-depolarizing neuromuscular blockers, which can lead to inadequate muscle relaxation, prolonged paralysis, and delayed recovery requiring postoperative ventilatory support.

Critical Drug Interaction

The FDA explicitly warns that galantamine (and by extension, all acetylcholinesterase inhibitors including donepezil and rivastigmine) "is likely to exaggerate the neuromuscular blocking effects of succinylcholine-type and similar neuromuscular blocking agents during anesthesia" 1. This is a class effect applicable to all acetylcholinesterase inhibitors.

Mechanism and Clinical Impact

Acetylcholinesterase inhibitors increase acetylcholine levels at the neuromuscular junction by preventing its breakdown. This creates two opposing problems:

With Non-Depolarizing Blockers (Rocuronium, Atracurium, Cisatracurium, Vecuronium)

• Resistance to blockade: Excess acetylcholine competes with the blocker at nicotinic receptors
• Inadequate muscle relaxation during surgery despite higher-than-normal doses 2, 3, 4
• Train-of-four monitoring shows persistently elevated counts (3-4) even with repeated dosing 3
• May require 2-3 times the standard dose to achieve adequate surgical conditions 4

With Succinylcholine (Depolarizing Blocker)

• Prolonged paralysis: Acetylcholinesterase inhibitors potentiate and extend the depolarizing block 5
• Risk of Phase II block (paradoxical prolongation) 6
• Unpredictable duration of action

Perioperative Management Algorithm

Preoperative (Preferred Approach)

1. Discontinue acetylcholinesterase inhibitors 24-48 hours before elective surgery 7

   • Donepezil: 48 hours (longer half-life)
   • Rivastigmine patch: Remove 24 hours prior
   • Galantamine: 24-48 hours

2. Document baseline cognitive status to guide postoperative resumption

If Surgery Cannot Be Delayed

Anesthetic strategy adjustments:

• Avoid succinylcholine entirely due to unpredictable prolongation 5

• For non-depolarizing blockers:

  • Anticipate requiring 1.5-2× standard intubating dose 3, 4
  • Use mandatory quantitative neuromuscular monitoring (train-of-four) 8
  • Consider switching to inhalational anesthesia if total intravenous anesthesia fails to provide adequate conditions 3
  • Have sugammadex immediately available for rapid reversal of rocuronium/vecuronium 8

• Dosing strategy:

  • Rocuronium: Start with 1.0-1.2 mg/kg (vs. standard 0.6 mg/kg)
  • Monitor TOF continuously; expect slower onset (7+ minutes vs. 2-3 minutes) 3
  • Maintain with continuous infusion rather than boluses for better control

Reversal Considerations

Critical point: The presence of acetylcholinesterase inhibitors complicates reversal with neostigmine (which is also an acetylcholinesterase inhibitor), creating additive cholinergic effects and unpredictable outcomes 8.

Preferred reversal strategy:

• Use sugammadex for rocuronium/vecuronium (dose per standard guidelines based on TOF monitoring) 8

  • Moderate block (TOF count 2-4): 2.0 mg/kg
  • Deep block (PTC 1-2): 4.0 mg/kg
  • Very deep block: 8.0 mg/kg

• Avoid neostigmine if possible due to compounding cholinergic effects

• Continue TOF monitoring post-reversal to detect recurarization 8

Postoperative Management

• Extended monitoring in PACU for respiratory depression
• Assess for residual weakness before extubation (TOF ratio ≥0.9 mandatory) 8
• Resume acetylcholinesterase inhibitor only after full neuromuscular recovery documented
• Typically safe to restart 24 hours postoperatively if no residual blockade

Common Pitfalls

1. Assuming standard neuromuscular blocker doses will work: They won't. Multiple case reports document failed intubation conditions and inadequate surgical relaxation 2, 3, 4

2. Not using quantitative monitoring: Visual/tactile TOF assessment is inadequate in this population 8

3. Using neostigmine for reversal: This adds more acetylcholinesterase inhibition on top of the patient's chronic medication 6

4. Premature extubation: Residual blockade risk is substantially higher; confirm TOF ratio ≥0.9 objectively 8, 4

Emergency Surgery Scenario

If the patient has taken their acetylcholinesterase inhibitor the morning of emergency surgery:

• Proceed with rapid sequence induction using rocuronium 1.2 mg/kg (not succinylcholine)
• Have sugammadex 16 mg/kg available for immediate reversal if cannot intubate/cannot ventilate
• Plan for potential difficult intubation due to inadequate relaxation
• Consider awake fiberoptic intubation if airway concerns exist

The evidence consistently demonstrates that continuing acetylcholinesterase inhibitors through surgery creates significant anesthetic complications with potential for serious morbidity from inadequate muscle relaxation, failed intubation, or prolonged postoperative paralysis requiring mechanical ventilation 2, 3, 4.