Anticholinergic toxicity

Introduction

• Agitated delirium with variable signs of peripheral muscarinic blockade
• No reliable symptoms or signs make a definitive diagnosis
• Focal neurological signs DO NOT occur
• May be mixed with other toxidromes depending on agent taken
• Mad as a hatter, red as a beet, dry as a bone
• Peripheral signs may resolve with ongoing central delirium

Clinical features

• Central
  • Agitated delirium characterised by:
    • Fluctuating mental status
    • Confusion
    • Restlessness
    • Fidgeting
    • Visual hallucinations
    • Picking at objects in the air
    • Mumbling slurred speech
    • Disruptive behaviour
  • Tremor
  • Myoclonus
  • Coma
  • Seizures (rare)

Clinical features

• Peripheral
  • Mydriasis (NOT UNIVERSAL)
  • Tachycardia
  • Dry mouth
  • Dry skin
  • Flushing
  • Hyperthermia
  • Sparse or absence bowel sounds
  • Urinary retention

Agents

• Antiparkinsonian – Amantadine, benztropine, benzhexol
• Antihistamines
• Antitussives – Dextromethorphan
• TCA
• Typical antipsychotics – Chlorpromazine, droperidol, haloperidol, thioridazine
• Atypical antipsychotics – Olanzapine, quetiapine
• Anticonvulsants – Carbamazepine
• Motion sickness agents – Hyoscine-scopolamine, meclizine
• Antimuscarinics – Atropine, hyoscine, glycopyrrolate
• Topical ophthalmological – Cyclopentolate, homatropine, tropicamide
• Urinary antispasmodics – Oxybutynin
• Muscles relaxants – Cyclobenzaprine, Orphenadrine
• Plants – Selected mushrooms, Datura species

Orphenadrine

• Muscle relaxant that is highly toxic in overdose
• Anticholinergic + Na channel blockade
• Risk of seizure, myocardial depression and arrhythmia
• Sodium channel blockade responds to bicarbonate
• Death has been reported following a 1g ingestion

Buscopan

• Smoking buscopan results in scopolamine and subsequent anticholinergic toxicity

Benztropine

• Anticholinergic delirium can last up to 5 days

Differential

• Encephalitis
• Hypoglycaemia
• Hyponatraemia
• Atypical seizures
• Neuroleptic malignant syndrome
• Serotonin syndrome
• Neurotrauma
• Sepsis
• Subarachnoid haemorrhage
• Wenicke’s encephalopathy

Complications

• Injury to selves or others
• Dehydration
• Hyperthermia
• Rhabdomyolysis
• Acute kidney injury
• Pulmonary aspiration

Management

• Resuscitation
• Anticholinergic syndrome usually manifests within hours of ingestion and can persist for up to 5 days (e.g benztropine, carbamazepine)
• Fluid resuscitation/maintenance, IDC if any evidence of retention
• Agitation – Diazepam 5-10mg PO or IV q10-15min until resting
• Avoid drugs with known anticholinergic effects e.g. haloperidol, chlorpromazine
• Screening ECG, BSL, serum paracetamol
• Specific drug levels e.g Carbamazepine
• FBC, Chem20, CK, VBG
• Offer AC within 2 hours of immediate release and 4 hours of SR preparations

Antidotes

• Physostigmine
  • Centrally acting acetylcholinesterase inhibitor that can reverse delirium
  • Useful if benzo’s not adequate and can confirm diagnosis
  • 400-800mcg IV as slow push and repeat q10 min until desired effect
  • Up to 2mg trial dose
  • If no benefit, can cease
  • If beneficial, consider rivastigmine patch (esp. SR agents) and repeated loading of physostigmine hourly if required
  • Risk of cholinergic toxicity so cardiac monitoring for bradycardia advised
  • Small risk of seizure through direct nicotinic receptor agonism

Antidotes

• Physostigmine (Dawson and Buckley 2016)
  • 52 patient retrospective review of physo vs. benzo vs. both
  • Physostigmine alone controlled agitation in 96% and reversed delirium in 87%
  • Benzos controlled agitation in 24% but ineffective at reversing delirium
  • Equal rates of side effects and lower rates of intubation
  • Elimination half-life of 22 minutes and therefore needs repeat dosing

Antidotes

• Rivastigmine
  • 9.6mg/24 hour patch effective at more prolonged cholinergic therapy
  • After 24 hours, release of medication from patch is extremely slow
  • Once removed, short half-life of rivastigmine ensures rapid reduction in plasma levels (3.4 hours for 17.4mg patch)

Last Updated on October 13, 2020 by Andrew Crofton