Overview
Definition
A toxic hyper-cholinergic state caused by the inhibition of acetylcholinesterase.
Epidemiology
Common in agricultural areas (farmers exposed to pesticides) and as a method of attempted suicide in developing countries.
Etiology & Risk Factors
- Organophosphates (found in pesticides and nerve agents like Sarin) irreversibly bind and inhibit Acetylcholinesterase.
- This leads to massive accumulation of Acetylcholine (ACh) at muscarinic and nicotinic receptors.
Clinical Symptoms
- Muscarinic symptoms (DUMBELS): Diarrhea, Urination, Miosis (pinpoint pupils), Bronchospasm/Bradycardia, Emesis, Lacrimation, Salivation/Sweating
- Nicotinic symptoms: Muscle fasciculations (twitching) followed by profound weakness and paralysis (including the diaphragm)
- CNS symptoms: Seizures, coma
Clinical Approach
Diagnosis
- Clinical diagnosis based on the classic 'wet' presentation (excessive secretions)
- Red Blood Cell (RBC) Acetylcholinesterase activity: Can be measured to confirm the diagnosis, but treatment should not be delayed
Management
- Decontamination: Remove clothing and wash the skin (protect healthcare workers!)
- Atropine: A competitive muscarinic antagonist. Reverses the DUMBELS symptoms (especially bronchospasm and bradycardia). Titrate until respiratory secretions dry up.
- Pralidoxime (2-PAM): Reactivates acetylcholinesterase by removing the organophosphate. Must be given early before the enzyme 'ages' (permanently binds). Reverses the NICOTINIC muscle weakness.
- Benzodiazepines for seizures
Complications
- Respiratory failure (from both bronchospasm and diaphragmatic paralysis)
- Seizures