Cholinergic toxicity

Introduction

• Due to increased ACh activity at central and peripheral muscarinic and nicotinic receptors
• Acts at pre- and post-synaptic parasympathetic, pre-ganglionic sympathetic and somatic nerves
• Occurs due to inhibition of acetylcholinesterase or direct agonism
• Most cases are due to organophosphate or carbamate pesticides

Clinical features

• Acetylcholinesterase inhibitors
  • Organophosphates
  • Carbamates
  • Nerve agents: Tabun, Sarin, Soman, VX
  • Dementia agents: Donepezil, galantamine, rivastigmine, tacrine
  • Myaesthenia gravis agents: Edrophonium, neostigmine, physostigmine, pyridostigmine
• Acetylcholine agonists
  • Muscarinic: Acetylcholine, bethanechol, carbachol, pilocarpine
  • Nicotinic: Nicotine
  • Mushrooms

Clinical presentation

• Classically copious secretions, vomiting, diarrhoea and altered mental status
• Fasciculation and muscle weakness may be evident
• Death can occur from respiratory failure secondary to copious secretions and weakness of ventilatory muscles
• Bradycardia is common and expected but tachycardia can also occur due to hypoxia, peripheral vasodilation and the effects of nicotinic stimulation

Clinical features

• CNS – Agitation, central respiratory depression, coma, confusion, lethargy, seizures
• Neuromuscular – Fasciculations, weakness
• Parasympathetic muscarinic – Abdominal cramping, bradycardia, bronchoconstriction, bronchorrhoea, diarrhoea, lacrimation, miosis, salivation, urinary incontinence, vomiting
• Sympathetic nicotinic – Hypertension, mydriasis, sweating, tachycardia
• Nerve agents seem to cause miosis predictably

Differential

• Weakness – Snakebite, GBS, myaesthenic crisis, botulism
• Bradycardia and vomiting – Cardiotropic intoxication (digoxin, oleander, beta-blockers, CCB)
• Gastroenteritis and abdominal emergencies
• Atypical seizures
• Mushroom ingestion
• Respiratory disorders e.g. CCF, asthma
• Salicylate intoxication
• Serotonin syndrome
• Sympathomimetic intoxication
• Theophylline intoxication

Complications

• Respiratory failure
• Dehydration
• AKI
• Seizures
• Intermediate syndrome
  • 24-96 hours after acute cholinergic crisis
  • Proximal muscle weakness and cranial nerve palsies
  • Lasts days to weeks
• Organophosphate-induced delayed polyneuropathy (ODIDP)
  • Distal axonal-type polyneuropathy
  • Both motor and sensory deficits
  • Potentially permanent
• Chronic organophosphate-induced neuropsychiatric disorder
  • Non-specific personality/behavioural changes following organophosphate poisoning

Management

• Decontamination should not delay resuscitation – PPE is crucial
• ABC
• Atropine 1.2mg IV bolus then double dose every 2-3 minutes until drying of secretions
• Control seizures with benzos
• Ongoing fluid maintenance + IDC
• Pralidoxime
  • 2g in 100mL N/S over 15 minutes then 500mg/hr infusion

Last Updated on June 25, 2021 by Andrew Crofton