Makindo Medical Notes

Related Subjects: Acute Kidney Injury |Acute Rhabdomyolysis |Hyperkalaemia |Neuroleptic Malignant Syndrome |Malignant Hyperpyrexia (Malignant Hyperthermia) |Serotonin syndrome |Cholinergic crisis-syndrome

Cholinergic crisis is a life-threatening syndrome caused by overstimulation of acetylcholine (ACh) receptors. It is most often due to organophosphate insecticide poisoning, nerve agent exposure, or iatrogenic excess of acetylcholinesterase inhibitors in myasthenia gravis.

About

• Excess ACh stimulates both muscarinic and nicotinic receptors in the peripheral and central nervous system.
• Acetylcholinesterase (AChE) inhibition → ACh accumulation at neuromuscular junctions → sustained depolarisation → paralysis.
• Central effects (confusion, seizures, coma) add to life-threatening autonomic and neuromuscular dysfunction.

Aetiology

• Organophosphate insecticides: Malathion, parathion, diazinon (common agricultural poisonings).
• Nerve agents (chemical warfare): Sarin, Soman, Tabun, VX → irreversible AChE inhibition.
• Carbamate pesticides: Aldicarb, carbaryl → reversible AChE inhibitors, shorter duration.
• Iatrogenic: Excessive pyridostigmine/neostigmine in myasthenia gravis treatment.

Mechanism of Toxicity 🧬

• Muscarinic overstimulation → “DUMBELS” or “SLUDGE” mnemonic:
  • Diarrhoea
  • Urination
  • Miosis
  • Bronchorrhoea, bronchospasm, bradycardia
  • Emesis
  • Lacrimation
  • Salivation, sweating
• Nicotinic overstimulation → fasciculations, muscle cramps, weakness, flaccid paralysis, respiratory failure.
• CNS effects: Agitation, confusion, seizures, coma.

Nerve Agents Overview

Nerve agents are extremely potent AChE inhibitors developed for chemical warfare.

• Sarin (GB): Volatile, rapid-acting vapour → miosis, convulsions, death within minutes.
• Soman (GD): Highly toxic, “ages” AChE rapidly → antidotes less effective if delayed.
• Tabun (GA): Older agent, highly toxic by inhalation or contact.
• VX: Viscous, persistent oily liquid; lethal in tiny quantities via skin contact.

Clinical Features 🩺

• Muscarinic: Salivation, lacrimation, diarrhoea, vomiting, miosis, bronchorrhoea, bradycardia, hypotension.
• Nicotinic: Fasciculations, weakness, flaccid paralysis, respiratory failure.
• CNS: Anxiety, seizures, confusion, coma.
• Death: Respiratory paralysis, bronchospasm/secretions, pulmonary oedema, cardiac arrest.

Investigations 🔬

• Routine: FBC, U&E, ABG (often metabolic acidosis), lactate.
• CK (muscle breakdown from fasciculations/seizures).
• ECG (bradycardia, conduction block, QT changes).
• CXR (aspiration, pulmonary oedema).
• Plasma or RBC cholinesterase levels: confirm exposure (delayed result, not for acute management).

Management 💉

• Decontamination: PPE for staff! Remove clothing, wash skin with soap and water. Prevent secondary contamination.
• Airway & breathing: High-flow O₂. Intubation and ventilation often required. Suction copious secretions.
• Atropine (antimuscarinic):
  • Initial IV dose 1–2 mg, double every 5–10 min until secretions dry and bronchospasm/bradycardia resolve.
  • Large doses often required (tens of mg). Continue infusion as needed.
• Pralidoxime (2-PAM):
  • Oxime reactivates AChE if given before “aging” occurs (within hours for sarin, much faster for soman).
  • Dose: 30 mg/kg IV over 30 min, repeat or continuous infusion.
  • Ineffective in carbamate poisoning.
• Benzodiazepines: Diazepam or midazolam for seizures, also neuroprotective in nerve agent exposure.
• Supportive: IV fluids, ICU monitoring, prevent hypoxia and aspiration.

Clinical Pearls ✨

• 🧠 Differentiate from Myasthenic crisis: Both cause weakness, but cholinergic crisis has muscarinic features (salivation, diarrhoea, miosis), while myasthenic crisis does not.
• 🚨 Military/civil defence: Auto-injectors (atropine + pralidoxime) are carried by soldiers at risk of nerve agent attack.
• ⚡ Aging phenomenon: Organophosphates irreversibly bind AChE within hours — pralidoxime only works before aging.
• 💡 Massive atropine doses may be required; endpoint is drying of secretions, not heart rate.
• ❌ Atropine does not reverse nicotinic paralysis — only pralidoxime + ventilation do.