Signs and Symptoms

• The order in which signs and symptoms appear and their relative severity depend on the route of exposure and whether the casualty has been exposed to liquid agent or vapour.

• The local effects of vapour and liquid exposure are described followed by a description of the systemic effects which occur after significant absorption of agent via any route.

Effects of Nerve Agent Vapour

• Absorption. The lungs and the eyes absorb nerve agents rapidly. Changes occur in the smooth muscle of the eye, resulting in miosis and in the smooth muscle and secretory glands of the bronchi, producing bronchial constriction and excessive secretions in the upper and lower airways. 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.

• Local Ocular Effects.

  • These effects begin within seconds or minutes after exposure, before there is any evidence of systemic absorption. The earliest ocular effect which follows minimal symptomatic exposure to vapour is miosis. This is an invariable sign of ocular exposure to enough vapour to produce symptoms. It is also the last ocular manifestation to disappear. 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 due to conjunctival hyperaemia, and a sensation of pressure with heaviness in and behind the eyes. Usually vision is not grossly impaired, although there may be a slight dimness especially in the peripheral fields or when in dim or artificial light.

  • Exposure to a level of a nerve agent vapour slightly above the minimal symptomatic dose results in miosis, pain in and behind the eyes attributable to ciliary spasm, especially on focusing, some difficulty of accommodation and frontal headache. The pain becomes worse when the casualty tries to focus the eyes or looks at a bright light. Some twitching of the eyelids may occur. Occasionally there is nausea and vomiting which, in the absence of systemic absorption, may be due to a reflex initiated by the ocular effects. These local effects may result in moderate discomfort and some loss of efficiency but may not necessarily produce casualties.

  • Following minimal symptomatic exposure, the miosis lasts from 24 to 72 hours. After exposure to at least the minimal symptomatic dose, miosis is well established within half an hour. Miosis remains marked during the first day after exposure and then diminishes gradually over 2 to 3 days after moderate exposure but may persist for as long as 14 days after severe exposure. The conjunctival erythema, eye pain, and headache may last from 2 to 15 days depending on the dose.

• Local Respiratory Effects. 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 expiration suggestive of bronchoconstriction or increased bronchial secretion. The rhinorrhoea usually lasts for several hours after minimal exposure and for about 1 day after more severe exposure. The respiratory symptoms are usually intermittent for several hours duration after mild exposure and may last for 1 or 2 days after more severe exposure.

Effects of Liquid Nerve Agent

• Local Ocular Effects. The local ocular effects are similar to the effects of nerve agent vapour. If the concentration of the liquid nerve agent contaminating the eye is high, the effects will be instantaneous and marked; and, if the exposure of the two eyes is unequal, the local manifestations may be unequal. Hyperaemia may occur but there is no immediate local inflammatory reaction such as may occur following ocular exposure to more irritating substances (for example, Lewisite).

• Local Skin Effects. Following cutaneous exposure, there is localised sweating at and near the site of exposure and localised muscular twitching and fasciculation. However, these may not be noticed causing the skin absorption to go undetected until systemic symptoms begin.

• Local Gastrointestinal Effects. Following the ingestion of substances containing a nerve agent, which is essentially tasteless, the initial symptoms include abdominal cramps, vomiting and diarrhoea.

Systemic Effects of Nerve Agent Poisoning

• 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. Following comparable degrees of exposure, respiratory manifestations are most severe after inhalation, and gastrointestinal symptoms may be most severe after ingestion. Otherwise, the systemic manifestations are, in general, similar after any exposure to nerve agent poisoning by any route. If local ocular exposure has not occurred, the ocular manifestations (including miosis) initially may be absent.

• The systemic effects may be considered to be nicotinic, muscarinic or by an action at receptors within the central nervous system. The predominance of muscarinic, nicotinic or central nervous system effects will influence the amount of atropine, oxime or anticonvulsant which must be given as therapy. These effects will be considered separately.

Muscarinic Effects of Nerve Agent Poisoning

• 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. After moderate or severe exposure, excessive bronchial and upper airway secretions occur and may become very profuse, causing coughing, airway obstruction and respiratory distress. Audible wheezing may occur, with prolonged expiration and difficulty in moving air into and out of the lungs, due to the increased bronchial secretion or to bronchoconstriction, or both. Some pain may occur in the lower thorax and salivation increases.

• 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 postural drainage or suction is not employed, these secretions may add to the airway obstruction. Laryngeal spasm and collapse of the hypopharyngeal musculature may also obstruct the airway. The casualty may gasp for breath, froth at the mouth, and become cyanotic.

• If the upper airway becomes obstructed by secretions, laryngeal spasm or hypopharyngeal musculature collapse, or if the bronchial tree becomes obstructed by secretions or bronchoconstriction, little ventilation may occur despite respiratory movements. As hypoxaemia and cyanosis increase, the casualty will fall exhausted and become unconscious.

• Following inhalation of nerve agent vapour, the respiratory manifestations predominate over the other muscarinic effects; they are likely to be most severe in older casualties and in those with a history of respiratory disease, particularly bronchial asthma. However, if the exposure is not so overwhelming as to cause death within a few minutes, other muscarinic effects appear. These include sweating, anorexia, nausea and epigastric and substernal tightness with heartburn and eructation. If absorption of nerve agent has been great enough (whether due to a single large exposure or to repeated smaller exposures), there may follow abdominal cramps, increased peristalsis, vomiting, diarrhoea, tenesmus, increased lachrymation and urinary frequency. Cardiovascular effects are a bradycardia, hypotension and cardiac arrhythmias. The casualty perspires profusely, may have involuntary defecation and urination and may go into cardiorespiratory arrest followed by death.

Nicotinic Effects

• With the appearance of moderate muscarinic 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 (transitory) together with a tachycardia, resulting from cholinergic stimulation of sympathetic ganglia and possibly from the release of epinephrine. If the exposure has been severe, the muscarinic cardiovascular symptoms will dominate and the fascicular 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. Later, respiratory muscle weakness may become profound and contribute to the respiratory depression. Central respiratory depression may be a major cause of respiratory failure.

Central Nervous System Effects

• 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 symptoms, abnormalities of the electroencephalogram occur, characterised by irregularities in rhythm, variations in potential, and intermittent bursts of abnormally slow waves of elevated voltage similar to those seen in patients with epilepsy. These abnormal waves become more marked after one or more minutes of hyperventilation which, if prolonged, may occasionally precipitate a generalised convulsion.

• 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 respiration may become Cheyne-Stokes in character. Finally, generalised convulsions may ensue.

• With the appearance of severe central nervous system symptoms, central respiratory depression will occur (adding to the respiratory embarrassment that may already be present) and may progress to respiratory arrest. However, after severe exposure the casualty may lose consciousness and convulse within a minute without other obvious symptoms. Death is usually due to respiratory arrest and anoxia, and requires prompt initiation of assisted ventilation to prevent death. Depression of the circulatory centres may also occur, resulting in a marked reduction in heart rate with a fall of blood pressure some time before death.

Cumulative Effects of Repeated Exposure

• Daily exposure to concentrations of a nerve agent insufficient to produce symptoms following a single exposure may result in the onset of symptoms after several days. Continued daily exposure may be followed by increasingly severe effects.

• After symptoms subside, increased susceptibility may persist for up to 3 months. The degree of exposure required to produce recurrence of symptoms and the severity of these symptoms depend on the dose received and the time interval since the last exposure. Increased susceptibility is not limited to the particular nerve agent initially absorbed.

Cause of Death

• In the absence of treatment, death is caused by anoxia resulting from airway obstruction, weakness of the muscles of respiration and central depression of respiration.

• Airway obstruction is due to pharyngeal muscular collapse, upper airway and bronchial secretions, bronchial constriction and occasionally laryngospasm and paralysis of the respiratory muscles.

• Respiration is shallow, laboured, and rapid and the casualty may gasp and struggle for air. Cyanosis increases. Finally, respiration becomes slow and then ceases. Unconsciousness ensues. The blood pressure (which may have been transitorily elevated) falls. Cardiac rhythm may become irregular and death may ensue.

• If assisted ventilation is initiated via cricothyroidotomy or endotracheal tube and airway secretions are removed by postural drainage and suction and diminished by the administration of atropine, the individual may survive several lethal doses of a nerve agent. However, 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.