The nerve agents, sometimes also called nerve gases, are a group of particularly toxic chemical warfare agents that were initially developed just before and during World War II.

The first compounds to be synthesised are known as the G agents (“G” stands for German, as they were discovered and synthesised by German scientists). These are:

  • GA – Tabun
  • GB – Sarin
  • GD – Soman

 

The V agents (“V” stands for venomous) were first synthesised in the 1950s and are approximately 10-times more poisonous than sarin. These include:

  • VX – Venomous agent X
  • VE – Venomous agent E
  • VG – Venomous agent G
  • VM – Venomous agent M

 

One of the most famous events involving the use of a nerve agent was the March 1995 Tokyo subway sarin attack. During this attack, Sarin was released into the Tokyo subway system during rush hour. As a result, over 5,000 people sought medical attention, of which, 984 were moderately poisoned, 54 were severely poisoned and 12 died.

 

Toxic mechanism

The nerve agents are organophosphorus esters that are chemically related to organophosphorus insecticides. They act by inhibiting acetylcholinesterase (AChE), an enzyme that catalyses the breakdown of the neurotransmitter acetylcholine (ACh), resulting in an accumulation of ACh at both muscarinic and nicotinic cholinergic receptors.

Nerve agents can be absorbed across any body surface. When dispersed as a spray or an aerosol, they can be absorbed through the skin, eyes and respiratory tract. When dispersed as a vapour, they are primarily absorbed through the respiratory tract and the eyes. If enough agent is absorbed, local effects are followed by generalised systemic effects.

 

Clinical presentation

The clinical features seen after exposure occur due to a combination of muscarinic, nicotinic and central nervous system effects:

Muscarinic effects (DUMBBELS):

  • Diarrhoea
  • Urination
  • Miosis
  • Bronchorrhoea
  • Bronchospasm
  • Emesis
  • Lacrimation
  • Salivation
  • Plus bradycardia and hypotension

 

Nicotinic effects:

  • Sweating
  • Tremor
  • Fasciculations
  • Muscle weakness
  • Flaccid paralysis

 

Central nervous system effects:

  • Agitation and irritability
  • Amnesia
  • Ataxia
  • Respiratory depression
  • Seizures
  • Coma

 

 

Investigations

Although no laboratory test exists to directly measure nerve agent levels in the serum or urine, red cell and plasma cholinesterase activity can be used to make a definitive diagnosis (although this is usually made clinically) and to monitor the response to treatment.

Arterial blood gases should be assessed as nerve agent intoxication generally produces significant respiratory impairment.

Chest X-rays may be helpful when treating patients with significant pulmonary symptoms.

ECGs can also be helpful as a number of electrocardiographic changes have been reported in nerve agent intoxication, including:

  • Bradycardia
  • Atrioventricular block
  • QT prolongation
  • Torsades de pointes
  • Ventricular arrhythmias

 

 

Prehospital management

Healthcare workers should wear adequate personal protective equipment when dealing with contaminated casualties as secondary contamination may occur. Ventilation should be maximised and breathing equipment used if working in contaminated areas. This should be the first priority for the healthcare workers responding, as without ensuring their safety, they cannot help the casualties involved in the event.

Early skin decontamination is of the utmost importance. Casualties should be moved to an area of safety, and all contaminated clothing should be removed to reduce further exposure. The skin should be copiously irrigated with water to physically remove the nerve agent and then washed with an alkaline solution of soap and water or 0.5% hypochlorite solution to chemically neutralise the nerve agent. Contact lenses should be removed and the eyes irrigated to prevent ongoing absorption through the eyes.

Initial resuscitation should occur using an ABCDE approach, and casualties should be supported and transferred to hospital as quickly as possible. Ventilation may be necessary. Nerve agent antidote autoinjectors can be used, and pre-hospital personnel should be guided by local policy when using these. Antidotes are discussed in more detail below.

 

Hospital management

The mainstay of pharmacological management of nerve gas exposure is the repeated administration of antidotes. The two antidotes used are atropine and pralidoxime.

Atropine is the standard anticholinergic used to manage the symptoms of nerve agent poisoning. It acts as a muscarinic acetylcholine receptor antagonist, blocking the effects of excess acetylcholine. It is given as an initial 1.2 mg intravenous bolus. This is then repeated and doubled every 2-3 minutes until excessive bronchial secretion ceases and miosis resolves. Up to 100 mg of atropine may be required.

Pralidoxime (2-PAMCl) is the standard oxime used to treat nerve agent poisoning. This works by reactivating acetylcholinesterase by scavenging the phosphoryl group attached to the functional hydroxyl group of the enzyme, counteracting the nerve agent itself. Moderately or severely poisoned patients should be given pralidoxime 30 mg/kg body weight (2 g in an adult) intravenously over four minutes.

Antidote administration should be continued for at least 24 hours or longer until the patient is asymptomatic, and there is no reduction in serial red cell cholinesterase activity assays.

Intravenous benzodiazepines can also be helpful useful in controlling apprehension, agitation, fasciculation and seizures. There is evidence that benzodiazepines can improve long-term prognosis and reduce the risk of brain damage.

Observation should be continued for a minimum of 12 hours. Follow-up for intermediate or delayed syndromes may be required.

 

Header image used on licence from Shutterstock


Thank you to the joint editorial team of www.frcemexamprep.co.uk for this article.

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