How should anticholinergics be managed in patients with pseudocholinesterase deficiency?

Pseudocholinesterase Deficiency and Anticholinergics

Anticholinergic medications can be used safely in patients with pseudocholinesterase deficiency, as these drugs do not require pseudocholinesterase for metabolism and their mechanism of action is unrelated to this enzyme deficiency.

Key Distinction: Anticholinergics vs. Cholinesterase-Dependent Drugs

Pseudocholinesterase deficiency specifically affects the metabolism of succinylcholine and mivacurium, which are neuromuscular blocking agents that require this enzyme for hydrolysis 1, 2. This deficiency leads to prolonged apnea and paralysis after administration of these specific drugs 1.

Anticholinergic agents work through an entirely different mechanism—they block muscarinic receptors rather than requiring enzymatic breakdown by pseudocholinesterase 3. Therefore, the presence of pseudocholinesterase deficiency does not contraindicate or alter the use of anticholinergic medications.

Clinical Management Algorithm

For Patients with Known Pseudocholinesterase Deficiency:

1. Anticholinergic Use:

• Proceed with standard anticholinergic dosing (atropine, glycopyrrolate, ipratropium, scopolamine) as clinically indicated 3
• No dose adjustments are required for pseudocholinesterase deficiency 3
• Monitor for typical anticholinergic side effects (dry mouth, urinary retention, tachycardia) but not for prolonged duration of action 3

2. Avoid Specific Neuromuscular Blockers:

• Absolutely avoid succinylcholine in patients with known pseudocholinesterase deficiency 1, 2, 4
• Avoid mivacurium, which also requires pseudocholinesterase for metabolism 1, 5
• Use alternative neuromuscular blocking agents (rocuronium, vecuronium, atracurium) that do not depend on pseudocholinesterase 3, 4

3. Cholinesterase Inhibitors Consideration:

• While cholinesterase inhibitors (donepezil, rivastigmine, galantamine) are not contraindicated by pseudocholinesterase deficiency, they should not be newly initiated perioperatively as they do not prevent or treat delirium and may increase adverse effects 3
• Patients already on chronic cholinesterase inhibitor therapy should continue their medications, as withholding may worsen symptoms 3

Important Clinical Pitfalls

Timing Considerations for Anesthesia:

• If succinylcholine is inadvertently given, expect prolonged neuromuscular blockade requiring sedation and mechanical ventilation until the block resolves spontaneously 1, 5
• The duration of prolonged blockade can be several hours; pharmacological reversal is not effective 1
• Peripheral nerve stimulator monitoring is essential to document recovery of neuromuscular function 1, 5

Preoperative Anticholinergic Use:

• Atropine and glycopyrrolate remain the drugs of choice for reducing secretions and minimizing vagal responses in patients with pseudocholinesterase deficiency 3
• In fact, larger doses of anticholinergics may be needed if the patient is also taking pyridostigmine (a cholinesterase inhibitor), as this increases parasympathetic activity 3

Specific Anticholinergic Applications

Respiratory Conditions:

• Ipratropium bromide can be used for exercise-induced bronchoconstriction, though its efficacy is inconsistent and variable between patients 3
• Anticholinergic bronchodilators are appropriate for acute asthma exacerbations when combined with beta-agonists 3

Perioperative Setting:

• Glycopyrrolate may be preferable to atropine for reducing secretions as it has less central nervous system penetration 3
• Scopolamine can be used for central anticholinergic effects but may prolong sedation when combined with general anesthetics 3

Postoperative Delirium:

• Avoid using anticholinergics as treatment for postoperative delirium, as they can worsen confusion through their anticholinergic effects 3

Evidence Quality Note

The guidelines clearly distinguish between drugs metabolized by pseudocholinesterase (succinylcholine, mivacurium) and those with anticholinergic mechanisms of action 3. The American Society of Anesthesiologists provides specific guidance on perioperative anticholinergic use, noting that these medications function independently of pseudocholinesterase activity 3.