Nerve agents, sometimes called nerve gases, are among the most toxic chemical warfare agents known. Originally developed during and after World War II, they are potent inhibitors of acetylcholinesterase and can cause rapid systemic collapse if not promptly managed.
Classification of Nerve Agents
Nerve agents fall into two main families based on their history and potency:
G Agents – Developed by German scientists (hence the “G”):
- GA (Tabun)
- GB (Sarin)
- GD (Soman)
V Agents – Discovered later and significantly more potent:
- VX (Venomous Agent X)
- VE
- VG
- VM
Note: V agents are up to 10 times more toxic than sarin. Even microscopic quantities can cause severe poisoning through skin contact or inhalation.
Mechanism of Toxicity
Nerve agents are organophosphorus compounds that irreversibly inhibit acetylcholinesterase (AChE). This leads to the accumulation of acetylcholine (ACh) at synapses, causing continuous stimulation of muscarinic, nicotinic, and central nervous system (CNS) receptors.
They are rapidly absorbed via:
- Inhalation (vapour or aerosol)
- Skin and eye contact
- Ingestion (less common)
Systemic symptoms depend on the dose and route of exposure.
Clinical Features
Symptoms result from overstimulation of:
- Muscarinic receptors
- Nicotinic receptors
- Central cholinergic pathways
Muscarinic (DUMBBELS):
- Diarrhoea
- Urination
- Miosis (pinpoint pupils)
- Bronchorrhoea, bronchospasm
- Emesis
- Lacrimation
- Salivation
- Plus: bradycardia and hypotension
Nicotinic:
- Sweating
- Fasciculations
- Tremors
- Muscle weakness
- Flaccid paralysis
CNS:
- Agitation, confusion, amnesia
- Ataxia
- Seizures
- Coma
- Respiratory depression
Investigations
Diagnosis is primarily clinical, but supportive investigations include:
- Plasma and red cell cholinesterase activity — decreased levels confirm poisoning and can guide treatment response
- Arterial blood gases (ABG) — to assess respiratory compromise
- Chest X-ray — for pulmonary oedema or aspiration
- ECG — may show bradyarrhythmias, QT prolongation, AV block, or ventricular arrhythmias
Pre-Hospital Management
Scene safety is critical. Secondary exposure is a real risk:
- Ensure responders wear appropriate PPE
- Remove patients from contaminated areas
Immediate decontamination:
- Remove clothing (can eliminate 80–90% of exposure)
- Irrigate skin with water or saline
- Use soap or 0.5% hypochlorite solution where available
- Remove contact lenses and irrigate eyes thoroughly
Initiate ABCDE resuscitation. Provide oxygen and ventilatory support as needed.
Autoinjector antidotes (e.g. atropine + pralidoxime) may be available depending on local emergency protocols.
Hospital Management
- Atropine:
- First-line agent
- Competitive antagonist at muscarinic receptors
- Dose: Start with 1.2 mg IV, double every 2–3 minutes until bronchial secretions are controlled and pupils dilate
- Massive doses (up to 100 mg) may be needed
- Pralidoxime (2-PAM):
- Reactivates AChE by cleaving the phosphorylated enzyme complex
- Dose: 30 mg/kg IV over 4–5 minutes (approx. 2 g in adults)
- Should be started as early as possible
- Continue treatment for at least 24 hours or until symptoms and cholinesterase levels normalise
- Benzodiazepines:
- Use to control seizures, agitation, and fasciculations
- Shown to reduce long-term neurological damage
Monitoring and Follow-Up
Continuous monitoring is required for at least 12–24 hours
Watch for intermediate syndrome (delayed respiratory and neuromuscular complications)
Longer-term follow-up may be needed for CNS or peripheral nervous system sequelae
Key Historical Example: Tokyo Subway Attack
In 1995, a sarin gas attack on the Tokyo subway system resulted in:
- Over 5,000 individuals seeking medical care
- 54 severely poisoned, 12 deaths
- This highlighted both the lethality of nerve agents and the need for rapid public health response
Takeaway Points
Nerve agents are highly lethal but treatable with rapid action
Atropine and pralidoxime are cornerstone antidotes
Early decontamination, PPE use, and ventilation save lives
Seizures and respiratory failure are key drivers of mortality — act fast
Header image used on licence from Shutterstock.
Thank you to the joint editorial team of MRCEM Exam Prep for this article.
