Cholinergic

Cholinergic toxicity is almost always due to inhibition of the acetylcholinesterase enzyme, and so is also known as anticholinesterase toxicity.

Epidemiology and Risk Factors

Pathophysiology

ACh receptors are divided into:

  • Muscarinic
    May be excitatory or inhibitory, and typically slower than nicotinic receptors. Present in the:
    • PNS
      Modulate rather than drive activity.
      • Smooth muscle
        Not skeletal muscle.
    • SNS
      Sweat glands.
    • CNS
  • Nicotinic
    Are excitatory, and present in the:
    • Skeletal NMJ
    • Autonomic ganglia
    • CNS

Acetylcholine is normally cleaved by the acetylcholinesterase enzyme, inhibition of which leads to ↑ ACh. Acetylcholinesterase inhibitors can be classified into:

  • Reversible
    • Edrophonium
    • Neostigmine
    • Pyridostigmine
  • Irreversible
    Phosphorylates active site with the the bond becoming stronger over time.
    • Organophosphates

Aetiology

Clinical Features

Features of Cholinergic Toxicity
Muscarinic Nicotinic

Parasympathetic:

  • Bronchospasm
  • Bronchorrhoea
  • ↓ HR
  • Miosis
  • Diaphoresis
  • ↑ GI secretions
  • Urination
  • Diarrhoea

Neuromuscular effects:

  • Fasciculations → tremor
  • Weakness → paralysis

Adrenal stimulation:

  • ↑ HR
  • HTN
  • Mydriasis
    Overtakes muscarinic effects at ↑ dose.
  • Sweating
  • Urinary retention

The classic mnemonic for the muscarinic features of cholinergic toxicity is SLUDGEM:

  • Salivation
  • Lacrimation
  • Urination
  • Diarrhoea
  • Gastrointestinal upset
  • Emesis
  • Miosis

Assessment

History:

Exam:

Investigations

Bedside:

Laboratory:

  • Cholinesterase mixing study
    • Serum of patient, reference, and 1:1 mix are tested
    • Presence of free organophosphate will inhibit cholinesterase in the mixed sample

Imaging:

Other:

Diagnostic Approach and DDx

Management

  • Decontamination
  • Atropine to antagonise muscarinic effects
  • Pralidoxime to reactivate the receptor

Resuscitation:

Specific therapy:

  • Pharmacological
    • Activated charcoal
    • Atropine
      Muscarinic antagonist.
      • Very high (grams) doses may be required
      • Does not reverse nicotinic effects
    • Pralidoxime
      May be used for reversible or irreversible causes.
      • Reactivates phosphorylated cholinesterase
      • Early administration (ideally <24-48 hours) more effective
      • 2g Q6H until asymptomatic for 24 hours
  • Procedural
    • NG drainage
  • Physical
    • Remove clothing
    • Wash skin with water and soap

Supportive care:

  • A
    • Intubation
      Avoid suxamethonium.
  • B
    • Mechanical ventilation
  • C
    • Vasoactive support

Disposition:

Preventative:

Marginal and Ineffective Therapies

Anaesthetic Considerations

Complications

Prognosis

Key Studies

References