Background

Nerve agents, or acetylcholinesterase inhibitors, are some of the most lethal substances ever to be weaponized. These agents exist in multiple forms from thick viscous liquids to highly dissolvable gases. They are chemically similar to organophosphates used for pesticides, and the syndromes they cause are much more common in farming communities than they are on the battlefield. The most lethal forms only require 1/1000th of an ounce to obtain a lethal dose in 50% of exposed population (LD50).

Nerve agents consist of mainly two classes, V agents and G agents. V agents are viscous in nature and can be spread in numerous ways. They are extremely dangerous if touched or ingested but can also pose a vapor hazard in close proximity. G agents are liquids at room temperature and are extremely effective as chemical weapons due to the ability to quickly expose a large number of people to lethal inhaled doses by vapor exposure.

Physiologically, these agents bind to acetylcholinesterase, thus inhibiting breakdown of acetylcholine. The two main types of cholinergic receptors where nerve agents interact are muscarinic and nicotinic. Muscarinic receptors are located in the smooth muscles and the glands. Symptoms caused by over-stimulation of muscarinic receptors can be recalled using the DUMBBELS mnemonic (Diarrhea, Urination, Miosis, Bronchorrhea/Bronchoconstriction, Bradycardia, Emesis, Lacrimation, Salivation). These symptoms can be countered by atropine (discussed later in the treatment section). Nicotinic receptors located in skeletal muscle and nerve ganglia are also affected by nerve agents. Symptoms caused by over-stimulation of nicotinic receptors can be remembered by using the first letter of the days of the week as a memory assist (Mydriasis, Tachycardia, Weakness, Hypertension, Fasciculations).  Administration of pralidoxime (2PAM) restores cholinesterase activity which typically results in improvement of the nicotinic symptoms.

Signs and Symptoms

Nerve agent poisoning can range from mild to severe; a severe exposure may quickly lead to death if not reversed. Rapid antidote treatment is extremely important since some nerve agents can irreversibly bind to acetylcholinesterase (for example, the half-life for irreversible binding, termed aging half-life, for soman/GD is two minutes).

For mildly affected individuals not wearing eye protection, miosis is commonly seen.  Other obvious muscarinic effects include severe lacrimation and profuse sweating, followed by nausea and vomiting, along with dyspnea and shortness of breath due to bronchorrhea and bronchoconstriction. More severely affected patients will have all of these signs and symptoms as well as profound weakness, fasciculations, seizures, loss of consciousness, apnea and death.

The speed of symptom onset depends on the route of exposure and dose of the agent. Inhalational exposure tends to result in faster onset of symptoms and can quickly cause death due to rapid systemic distribution. Dermal exposures, such as exposures with V agents, can cause delayed onset of symptoms.