Cholinergic Toxidrome
Cholinergic Toxidromes: Recognition, Assessment and Prehospital Management
Cholinergic toxidromes are uncommon presentations, particularly in the UK and Western healthcare systems. However, when they do occur, they can rapidly become life-threatening.
The challenge with these patients is that the exposure may not always be obvious. Clinicians may arrive at a scene without knowing a poisoning has occurred, with recognition only developing once the clinical features become apparent.
Understanding the causes, recognising the toxidrome and maintaining good scene safety awareness are therefore essential when managing suspected cholinergic toxicity.
What causes cholinergic toxicity?
The main causes of cholinergic toxidromes include:
Organophosphates
Carbamates
Mushrooms containing muscarine
Nerve agents such as sarin and Novichok
Acetylcholinesterase inhibitors (drugs ending “stigmine”
Although some of these exposures are now rare, they remain important because of the severity of illness they can cause.
Organophosphates and carbamates
Organophosphates and carbamates are pesticides that produce their effects by interfering with acetylcholine metabolism.
Organophosphates contain a phosphate molecule bound to a carbon ring structure. They are effective insecticides because insects rely heavily on acetylcholine within their nervous system.
Many of these agents have now been withdrawn or banned across the UK and Western world. A large number were removed during the 2000s, with further withdrawals occurring after Brexit during the 2020s.
Most pesticides currently used in Western countries are now different agents, including pyrethroids, which produce sodium channel effects, and neonicotinoids, which do not produce the same cholinergic effects.
Reviewing the UK Health and Safety Executive approvals register, the only organophosphates that appear to remain approved for use are Fosthiazate and Pirimiphos-methyl. These are heavily restricted and alternative agents are preferentially used.
Therefore, while exposure is likely to be very rare, it is not impossible.
Mushrooms containing muscarine
Mushroom-related cholinergic toxicity can be particularly challenging to recognise.
Exposure may occur when:
Foragers mistake toxic mushrooms for edible species
Individuals seeking psilocybin-containing mushrooms accidentally consume a toxic species
A potential difficulty is the timing of symptoms. Psilocybin effects may occur within around 30 minutes, whereas muscarinic symptoms may not appear until around two hours after exposure.
The toxic effects occur due to muscarine within certain mushrooms.
Unlike many other cholinergic agents, muscarine does not cross the blood-brain barrier. This means patients are unlikely to develop central nervous system acetylcholine effects and will primarily demonstrate peripheral features.
Sarin and Novichok nerve agents
Sarin is a nerve agent developed during World War II.
These agents act by binding to acetylcholinesterase, preventing the enzyme from breaking down acetylcholine. This results in acetylcholine accumulation at synapses.
Examples of sarin use include the Tokyo subway attacks in 1995 and use against civilians during the Syrian civil war.
Novichok agents were developed later and have a slightly different chemical structure, but for understanding cholinergic toxicity they can be considered to produce similar effects.
Understanding the pathophysiology
Cholinergic toxicity occurs because of excessive stimulation of both muscarinic and nicotinic receptors.
The most common mechanism is inhibition of acetylcholinesterase, the enzyme responsible for breaking down acetylcholine within the synaptic cleft.
When this enzyme is inhibited, acetylcholine accumulates, causing excessive parasympathetic activity and producing the clinical toxidrome.
The effects depend on the level of exposure and can involve multiple body systems.
Clinical features of cholinergic toxicity
Muscarinic effects
SLUDGE
Salivation
Lacrimation
Urination
Defecation
Gastrointestinal upset
Emesis
Patients may also develop:
Bradycardia and hypotension
Excess acetylcholine activity affects the heart through vagal stimulation and M2 muscarinic receptors, reducing sinoatrial node firing and atrioventricular conduction.
This can result in:
Bradycardia
AV block
ST changes
Peaked T waves
QT prolongation
Respiratory effects
Excess acetylcholine causes bronchospasm and bronchoconstriction through M3 muscarinic receptor stimulation.
Patients may develop:
Wheeze
Shortness of breath
Bronchorrhoea
Excess respiratory secretions
Combined with sialorrhoea, these secretions can produce the characteristic frothing or foaming appearance seen in severe poisoning.
Fatality is often related to respiratory failure caused by a combination of respiratory muscle failure, bronchospasm and excessive secretions.
Miosis and sweating
Parasympathetic stimulation causes pupil constriction, producing pinpoint pupils.
Muscarinic receptors are also involved in sweating, with excessive stimulation resulting in diaphoresis.
Nicotinic and central effects
Nicotinic receptor stimulation causes:
Fasciculations
Myoclonic jerking
Muscle weakness
Flaccid paralysis
Excess acetylcholine activity within the central nervous system can cause:
Confusion
Reduced conscious level
Seizures
Coma
Scene safety and CBRN considerations
Scene safety is critical because clinicians may not recognise the exposure until they are already present.
Possible indicators include:
Multiple unexplained casualties
Skin, eye or airway irritation
Vomiting, sweating, twitching, pinpoint pupils or breathing difficulties
Unusual materials or equipment
Vapour or mist clouds
Oily droplets or films
Withered vegetation
Unusual smells or tastes
Management may include moving away from the scene, ideally uphill and upwind, followed by appropriate decontamination.
Dry decontamination involves blotting and rubbing contaminated areas using paper towels or blankets, working from top to bottom and leaving the face until last.
Wet decontamination may involve water bottles or saline bags, prioritising the face and hands if resources are limited.
Specialist advice should be sought early, including discussion with HART where appropriate.
Prehospital treatment
Management begins with:
Scene assessment
Identification of possible poisoning
Recognition of toxidromes
Appropriate PPE
Decontamination where required
Specialist resources such as HART, Fire and Rescue Service and critical care teams should be considered depending on the situation.
Treatment follows a standard A–E approach.
Airway protection is essential due to reduced conscious level, vomiting risk and excessive secretions. Some patients may require advanced airway management.
Breathing management may include:
High-flow oxygen
Ventilatory support if respiratory failure occurs
Bronchodilators such as salbutamol and ipratropium
Antidotal treatment
Atropine
Atropine works by competitively blocking muscarinic receptors, preventing excess acetylcholine from causing further stimulation.
The aim of atropinisation is:
Reduced secretions
Clear lungs on auscultation
Heart rate greater than 80 bpm
Systolic blood pressure greater than 80 mmHg
Miosis may persist for several days and should not be used as an endpoint.
Pralidoxime
Pralidoxime is an acetylcholinesterase reactivator. It restores acetylcholinesterase activity, particularly at nicotinic receptors, improving symptoms such as muscle weakness, fasciculations and paralysis.
Timing is important because pralidoxime is most effective before irreversible binding occurs.
It should currently be avoided in carbamate poisoning due to concerns regarding worsening toxicity.
Ongoing management
Further treatment includes:
IV fluids for hypotension
Benzodiazepines for seizures or agitation
Rapid transfer to hospital
An early pre-alert should be provided to the receiving emergency department, including the suspected exposure, patient condition and treatments given.
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References:
JESIP. CBRN Initial Operational Response Guidance.
https://www.jesip.org.uk/uploads/media/pdf/CBRN%20JOPs/IOR_Guidance_V2_July_2015.pdfStatPearls. Cholinergic Crisis. NCBI Bookshelf.
StatPearls. Pralidoxime. NCBI Bookshelf.
LITFL. Cholinergic Syndrome – CCC Toxicology.
British National Formulary. Pralidoxime chloride.
The Human Medicines Regulations 2012.
JRCALC Clinical Practice Guidelines 2026. CBRNE Atropine guidance.