Nerve Agents

The nerve agents are a group of particularly toxic chemical warfare agents. They were developed just before and during World War II and are related chemically to the organophosphorus insecticides. The principle agents in this group are:

• GA (Tabun)
• GB (Sarin)
• GD (Soman)
• GF
• VX (methylphosphonothioic acid)

The "G" agents tend to be non-persistent whereas the "V" agents are persistent. Some "G" agents may be thickened with various substances in order to increase their persistence, and therefore the total amount penetrating intact skin. At room temperature GB is a comparatively volatile liquid and therefore non-persistent. GD is also significantly volatile, as is GA though to a lesser extent. VX is a relatively non-volatile liquid and therefore persistent. It is regarded as presenting little vapour hazard to people exposed to it. In the pure state nerve agents are colorless and mobile liquids. In an impure state nerve agents may be encountered as yellowish to brown liquids. Some nerve agents have a faint fruity odour.

The effects of the nerve agents are mainly due to their ability to inhibit acetylcholinesterase throughout the body. Since the normal function of this enzyme is to hydrolyse acetylcholine wherever it is released, such inhibition results in the accumulation of excessive concentrations of acetylcholine at its various sites of action. These sites include the endings of the parasympathetic nerves to the smooth muscle of the iris, ciliary body, bronchial tree, gastrointestinal tract, bladder and blood vessels; to the salivary glands and secretory glands of the gastrointestinal tract and respiratory tract; and to the cardiac muscle and endings of sympathetic nerves to the sweat glands.

The sequence of symptoms varies with the route of exposure. While respiratory symptoms are generally the first to appear after inhalation of nerve agent vapour, gastrointestinal symptoms are usually the first after ingestion. Tightness in the chest is an early local symptom of respiratory exposure. This symptom progressively increases as the nerve agent is absorbed into the systemic circulation, whatever the route of exposure. Following comparable degrees of exposure, respiratory manifestations are most severe after inhalation, and gastrointestinal symptoms may be most severe after ingestion.

The lungs and the eyes absorb nerve agents rapidly. In high vapour concentrations, the nerve agent is carried from the lungs throughout the circulatory system; widespread systemic effects may appear in less than 1 minute.

• The earliest ocular effect which follows minimal symptomatic exposure to vapour is miosis. The pupillary constriction may be different in each eye. Within a few minutes after the onset of exposure, there also occurs redness of the eyes. Following minimal exposure, the earliest effects on the respiratory tract are a watery nasal discharge, nasal hyperaemia, sensation of tightness in the chest and occasionally prolonged wheezing
• Exposure to a level of a nerve agent vapour slightly above the minimal symptomatic dose results in miosis, pain in and behind the eyes and frontal headache. Some twitching of the eyelids may occur. Occasionally there is nausea and vomiting.
• In mild exposures, the systemic manifestations of nerve agent poisoning usually include tension, anxiety, jitteriness, restlessness, emotional lability, and giddiness. There may be insomnia or excessive dreaming, occasionally with nightmares.
• If the exposure is more marked, the following symptoms may be evident: headache, tremor, drowsiness, difficulty in concentration, impairment of memory with slow recall of recent events, and slowing of reactions. In some casualties there is apathy, withdrawal and depression.
• With the appearance of moderate systemic effects, the casualty begins to have increased fatiguability and mild generalised weakness which is increased by exertion. This is followed by involuntary muscular twitching, scattered muscular fasciculations and occasional muscle cramps. The skin may be pale due to vasoconstriction and blood pressure moderately elevated.
• If the exposure has been severe, the cardiovascular symptoms will dominate and twitching (which usually appear first in the eyelids and in the facial and calf muscles) becomes generalised. Many rippling movements are seen under the skin and twitching movements appear in all parts of the body. This is followed by severe generalised muscular weakness, including the muscles of respiration. The respiratory movements become more laboured, shallow and rapid; then they become slow and finally intermittent.
• After moderate or severe exposure, excessive bronchial and upper airway secretions occur and may become very profuse, causing coughing, airway obstruction and respiratory distress. Bronchial secretion and salivation may be so profuse that watery secretions run out of the sides of the mouth. The secretions may be thick and tenacious. If the exposure is not so overwhelming as to cause death within a few minutes, other effects appear. These include sweating, anorexia, nausea and heartburn. If absorption of nerve agent has been great enough, there may follow abdominal cramps, vomiting, diarrhoea, and urinary frequency. The casualty perspires profusely, may have involuntary defecation and urination and may go into cardiorespiratory arrest followed by death.
• If absorption of nerve agent has been great enough, the casualty becomes confused and ataxic. The casualty may have changes in speech, consisting of slurring, difficulty in forming words, and multiple repetition of the last syllable. The casualty may then become comatose, reflexes may disappear and generalised convulsions may ensue. With the appearance of severe central nervous system symptoms, central respiratory depression will occur and may progress to respiratory arrest.
• After severe exposure the casualty may lose consciousness and convulse within a minute without other obvious symptoms. Death is usually due to respiratory arrest requires prompt initiation of assisted ventilation to prevent death. If assisted ventilation is initiated , the individual may survive several lethal doses of a nerve agent.
• If the exposure has been overwhelming, amounting to many times the lethal dose, death may occur despite treatment as a result of respiratory arrest and cardiac arrhythmia. When overwhelming doses of the agent are absorbed quickly, death occurs rapidly without orderly progression of symptoms.

Nerve agent poisoning may be identified from the characteristic signs and symptoms. If exposure to vapour has occurred, the pupils will be very small, usually pin-pointed. If exposure has been cutaneous or has followed ingestion of a nerve agent in contaminated food or water, the pupils may be normal or, in the presence of severe systemic symptoms, slightly to moderately reduced in size. In this event, the other manifestations of nerve agent poisoning must be relied on to establish the diagnosis. No other known chemical agent produces muscular twitching and fasciculations, rapidly developing pin-point pupils, or the characteristic train of muscarinic, nicotinic and central nervous system manifestations.

The rapid action of nerve agents call for immediate self treatment. Unexplained nasal secretion, salivation, tightness of the chest, shortness of breath, constriction of pupils, muscular twitching, or nausea and abdominal cramps call for the immediate intramuscular injection of 2 mg of atropine, combined if possible with oxime.

• GB and VX doses which are potentially life-threatening may be only slightly larger than those producing least effects. Death usually occurs within 15 minutes after absorption of a fatal VX dosage.
• Although only about half as toxic as GB by inhalation, GA in low concentrations is more irritating to the eyes than GB. Symptoms appear much more slowly from a skin dosage than from a respiratory dosage. Although skin absorption great enough to cause death may occur in 1 to 2 minutes, death may be delayed for 1 to 2 hours. Respiratory lethal dosages kill in 1 to 10 minutes, and liquid in the eye kills almost as rapidly.

The values are estimates of the doses which have lethal effects on man. LD50 expresses the dose at which 50 per cent of the exposed population will die as a result of their injuries. A different measure is used for inhalation, the product of the concentration (C) and the length of exposure (t). Again, L stands for lethal and 50 for 50 per cent effect. Effective dosages for vapor are estimated for exposure durations of 2-10 minutes.