What is the treatment for anticholinergic (anticholinergic syndrome) confusion?

Treatment of Anticholinergic Confusion

For anticholinergic-induced confusion and delirium, physostigmine is the definitive antidote and should be administered intravenously at 0.5-1 mg (0.01-0.02 mg/kg in children) with a minimum 10-15 minute interval before re-dosing if needed. 1, 2

Immediate Recognition and Assessment

The anticholinergic syndrome presents with both central and peripheral manifestations that must be identified before treatment 3, 1:

Central effects include:

• Agitated delirium, confusion, and disorientation 3
• Hallucinations and anxiety 3
• Seizures in severe cases 3

Peripheral effects include:

• Tachycardia and mild hyperthermia 3
• Mydriasis (dilated pupils) and dry mucous membranes 3
• Hot, dry, flushed skin 3
• Urinary retention and decreased bowel sounds 3

The classic mnemonic is "Red as a beet, dry as a bone, hot as a hare, blind as a bat, mad as a hatter, full as a flask" 3

Primary Treatment Algorithm

Step 1: Discontinue Offending Agents

Immediately stop all anticholinergic medications that may be contributing to the syndrome 3. Common culprits include first-generation antihistamines (diphenhydramine), muscle relaxants (cyclobenzaprine), overactive bladder agents (oxybutynin), tricyclic antidepressants, phenothiazines, and anticholinergics used to manage antipsychotic side effects 4, 1.

Step 2: Physostigmine Administration (For Severe Cases)

Physostigmine is the antidote of choice for severe anticholinergic toxicity with pronounced delirium and agitation 1, 5:

• Dosing: 0.5-1 mg IV in adults (0.01-0.02 mg/kg in children) 2
• Timing: Dramatic reversal occurs within 15-20 minutes of IV administration 1, 6
• Re-dosing: Wait minimum 10-15 minutes before considering repeat dose 2
• Duration: Effects last approximately 45-60 minutes 1

Physostigmine works by inhibiting acetylcholinesterase, thereby increasing acetylcholine concentrations at cholinergic synapses and reversing both central and peripheral anticholinergic effects 1.

Step 3: Alternative Management When Physostigmine Unavailable

If physostigmine is unavailable due to supply shortages, rivastigmine can be used as an alternative 7:

• Oral/NG dosing: 3 mg hourly until symptom resolution 7
• Transdermal patch: Provides consistent 24-hour drug absorption 7

Benzodiazepines are less effective than physostigmine for anticholinergic delirium but may be used for agitation when physostigmine is contraindicated 5, 6. However, patients receiving only physostigmine have significantly lower intubation rates (1.9% vs 8.4%) compared to those receiving benzodiazepines 8.

Critical Safety Considerations

Contraindications to physostigmine include 5, 2:

• Cardiac conduction defects or arrhythmias
• Unknown ingestions (particularly tricyclic antidepressants with cardiac toxicity)
• Absence of clear anticholinergic symptoms

Potential adverse effects include 2:

• Seizures (reported in up to 2.5% of cases) 2
• Cholinergic toxicity with excessive dosing 2
• Cardiac arrhythmias when used inappropriately 5

The key to safety is using lower doses with longer re-dosing intervals, as pharmacokinetic studies show a longer latency to maximal brain acetylcholine increase than previously assumed 2.

Supportive Care

While awaiting antidote effect, provide 3:

• Benzodiazepines for severe agitation requiring physical restraint 3
• Standard supportive measures including airway protection if needed 3
• Continuous cardiac monitoring 5

Special Population Considerations

In elderly patients, anticholinergic medications are particularly problematic 4:

• Older adults have baseline cognitive impairment and reduced physiologic reserve 3
• Strongly anticholinergic medications (diphenhydramine, cyclobenzaprine, oxybutynin) should be avoided entirely 4
• In elderly patients with Alzheimer's disease on antipsychotics, avoid benztropine or trihexyphenidyl entirely 3

Common Pitfalls to Avoid

• Do not use benzodiazepines as first-line treatment when physostigmine is available and appropriate, as physostigmine is more effective and safer for pure anticholinergic toxicity 5, 6
• Do not re-dose physostigmine too quickly (wait at least 10-15 minutes) to avoid cholinergic toxicity 2
• Do not use physostigmine in mixed overdoses or when tricyclic antidepressant toxicity cannot be excluded 5
• Do not continue anticholinergic medications used solely to manage side effects of other drugs when treating anticholinergic syndrome 3