Chemical Warfare By A Pratap Biology Essay

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The NATO definition of a chemical agent is : A chemical substance which is intended for use in military operations to kill , seriously injure or incapacitate targeted population because of it's physiological effects. From this definition, riot control agents, herbicides, smoke, flame and toxins are excluded. Chemical agents cause injuries, directly by irritation, burning or asphyxiation and indirectly by contaminating ground so that it can not be safely used by enemy.

Historical Perspective

It has been nearly 90 years when Armed Forces personnel overtly encountered threat of chemical weapon on the battle field. Chemical weapons are classical model of weapons of mass destruction resulting in not only large number of casualties, but also substantial contamination of personnel and equipment and thus adding an entirely different dimension to erstwhile conventional warfare.

The first recorded history from civilizations in Egypt, Babylon, India and China contain references to deadly poisons. The first pharaoh, Menes, cultivated, studied and accumulated poisons from plants, animals and minerals in 3,000 BC. Egyptians also studied lethal effects of hydrocyanic acid. Beginning 2,000 BC the great dynasties in India used smoke screen, toxic sleep inducing fumes and incendiary devices on large scale during battle. Chinese writings from 1,000 BC contain recipes for production of poisonous, noxious and irritant vapours for use in war.

However, chemical agents in modern sense were first used in World War 1, when on 10 March 1915 at Ypres, 35 Pioneer Regiment of Germany released 168 tons of chlorine gas along with favourable wind direction against allied troops consisting of Canadian, French and British personnel. Allies claimed that 5,000 troops fell victim to the gas attack. Subsequently great variety of chemicals were used by both the sides including use of Chlorine by allies in September 1915, Phosgene and Diphosgene in May 1916 by Germans, Hydrogen Cyanide and Cyanogen Chloride by French two months later and the most damaging being mustard agent producing Blisters agents by Germans in Jul 1917. Between February 1915 and November 1918. 113500 tons of chemical agents were used. These caused at least 1.3 million casualties, out of which 90,000were fatal. In the last 18 months of war one in six casualty was a chemical casualty with mustard accounting for 70%, although mortality from mustard gas attack was only 1.5%. Chemical agents were not used in World War II but at the end of war stockpiles of newer and deadlier Nerve Agents were discovered. The standard of training, degree of preparedness, fear of retaliation and Hitler's own distaste for chemicals because of having personally suffered in WW I are attributed as various reasons. [1]

Chemical weapons are cheap, can cause mass casualties, and are relatively easy to produce, even by developing nations. They have been used in many conflicts during the 20th century (box), most recently by Iraq during the Iran-Iraq war, as well as in terrorist attacks. The psychological impact of chemical weapons on society makes them ideal for terrorism, as shown by the release of nerve gas in the Tokyo subway system by members of the Aum Shinrikyo sect in 1995. In this review focus will be on the agents, that pose the greatest threat, recognising chemical weapons injuries, and the principles of management.

Use of chemical weapons in the 20th century

1914-8: Over 1 300 000 people received gas injuries in first world war, and over 90 000 of them died.

1935: Italy began conquest of Abyssinia (Ethiopia) using mustard gas delivered by aircraft spray

1936: Japan invaded China using chemical weapons (including mustard gas, phosgene, and hydrogen cyanide); German chemical laboratories produced first nerve agent-tabun

1963-7: Egypt used phosgene and mustard aerial bombs in support of South Yemen against the Yemeni royalist forces during the Yemeni civil war

1980-8: Iraq attacked Iran and Iraqi Kurds during Iran-Iraq war using mustard and nerve agents

1994-5: Japanese Aum Shinrikyo cult used sarin in terrorist attacks at Matsumoto in June 1994 and on the Tokyo underground in March 1995. [2]


For medical purposes, chemical agents are usually of chemical warfare have been classified into according to pharmacological principles, but for general use throughout all the Armed Forces it has been found more appropriate to classify them according to their overall combat efficiency. The two classification are given in Table 15.10

Methods of Dissemination of Chemical Agents

Chemical agents can be delivered by a host of simple mechanisms. During World War I, chemical agents were used only as land weapons and the resulting casualties were mainly due to vapor and largely confined to troops in the field. However, in any future war, chemical agents could be disseminated by various methods such as shells and missiles from land or sea, by aerial bombing or spraying and by clandestine aerosol attack by saboteurs. Accordingly selected targets, may far away from forward fighting lines such as cities, factories, dockyards and air bases. In the Tokyo subway attack by Aum Shinrikyo cult members in 1995, the terrorists left a plastic bag containing nerve agent Sarin on an underground train, piercing the plastic bag with umbrella tips before escaping. The released vapors of Sarin affected 3796 people and caused one dozen deaths. [2]

Nerve Agents


Nerve agents are the most toxic and deadliest known chemical agent causing severe morbidity and mortality even at extremely low dosage. They are a group of highly toxic organic esters of phosphoric acid derivatives and have physiological effects (inhibition of cholinesterase) resembling those of physostigmine and pyridostigmine. However, they are more potent, longer-acting, and tend to be irreversible after a time which varies with the agent. They include the G- and V-agents. Examples of G-agents are Tabun (GA), Sarin (GB), Soman (GD), and GF. A classical V-agent is VX. In some countries, "V" agents are known as "A" agents. The first Nerve Agent Tabun (GA) was discovered during research for insecticides in 1936 by German scientist Hans Kukenthal. Two years later Gerhard Schrader discovered Sarin (GB) and Soman (GD) was synthesized in 1944 by Richard Kuhn of Germany whereas VX was first synthesized by US in 1952. [1]

During WW Germany produced approximately 78,000 tons of chemical warfare agents including 12,000 tons of Tabun and smaller quantity 1000 lbs of Sarin were produced put in to munitions by Germans during WW II but never used.[1]

Physical and Chemical Properties

Nerve agents are colourless to pale yellow, but may become light brown due to impurities. Some are volatile, while others are relatively non-volatile at room temperature. Most nerve agents are essentially odourless; however, some have a faint fruity odour. In toxic amounts, aqueous solutions of nerve agents are tasteless. The G-agents tend to be non-persistent, whereas the V-agents are persistent. However, thickened non-persistent agents may present a hazard for an extended period of time. These agents are moderately soluble in water with slow hydrolysis but are highly soluble in lipids. Persistency is intricately related to climatic condition ie temperature and wind speed at the time of delivery on the target, higher the temperature and wind speed faster will they vaporize . They are rapidly inactivated by strong alkalis and chlorinating compounds (strong alkalis and chlorinating compounds are used for decontaminating equipment; in diluted formulas, chlorinating compounds are used for patient de-contamination). Details of physical properties of various nerve agents as per Table 15.11. [1]

Absorption Routes

Nerve agents may be absorbed through any body surface. When dispersed as a spray or aerosol, droplets can be absorbed through the skin, eyes, and respiratory tract. When dispersed as a vapour at expected field concentrations, the vapour is primarily absorbed through the respiratory tract. If enough agent is absorbed, local effects are followed by generalized systemic effects. The rapidity with which effects occur is directly related to the amount of agent absorbed in a given period of time. Liquid nerve agents may be absorbed through the skin, eyes, mouth, and membranes of the nose. Nerve agents may also be absorbed through the gastrointestinal tract when ingested with food or water. [3 & 5]

Mechanism of Action.

The effects of nerve agents are due to their ability to inhibit acetyl cholinesterase enzymes (AChE) throughout the body. Since the normal function of these enzymes 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 include the endings of the autonomic 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 accumulation of acetylcholine at these sites results in characteristic muscarinic signs and symptoms. The accumulation of acetylcholine at the endings of motor nerves to voluntary muscles and in some autonomic ganglia results in nicotinic signs and symptoms. Finally, the accumulation of excessive acetylcholine in the brain and spinal cord results in characteristic CNS symptoms. The inhibition of cholinesterase enzymes throughout the body by nerve agents may be irreversible and their effects prolonged; therefore, treatment should begin promptly before irreversibility occurs. [1&3]

Clinical Effects

The lungs and the eyes absorb nerve agents rapidly. Changes occur in the smooth muscle of the eye, resulting in miosis , also 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 and 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.

Local respiratory effects. Following minimal exposure, the earliest effects on the respiratory tract are watery nasal discharge, nasal hyperaemia, sensation of tightness in the chest, and occasionally, prolonged wheezing expiration suggestive of bronchoconstriction and/ or increased bronchial secretion. The respiratory symptoms are usually intermittent for several hours duration after mild exposure; they may last for 1 or 2 days after more severe exposure.

Systemic effects. The sequence of symptoms varies with the route of exposure. While respiratory symptoms are generally the first to appear after inhalation of nerve agent vapor, 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 signs, symptoms, and their time course following exposure to nerve agent are given in. The systemic effects may be considered to be nicotinic, muscarinic, or by any action at receptors within the CNS. The predominance of muscarinic, nicotinic, or CNS effects will influence the amount of atropine, oxime, or anticonvulsant which must be given as therapy. These effects will be considered separately.

Muscarinic effects. The 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. The casualty may gasp for breath, froth at the mouth, and become cyanotic. If the upper airway becomes obstructed by secretions, laryngeal spasm, or hypo pharyngeal musculature collapse, or if the bronchial tree becomes obstructed by secretions or bronchoconstriction, little ventilation may occur despite respiratory movements.

As hypoxemia and cyanosis increase, the casualty will fall exhausted and become unconscious. Following inhalation of nerve agent vapor, 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 the 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, diarrhea, tenesmus, increased lacrimation, and urinary frequency. Cardiovascular effects are occasional early bradycardia, transient tachycardia and/or hypertension followed by 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 fatigability and mild generalized weakness which is increased by exertion. This is followed by involuntary muscular twitching, scattered muscular fasciculation, and occasional muscle cramps. The skin may be pale due to vasoconstriction and blood pressure moderately elevated (transitory) together with tachycardia, resulting from epinephrine response to excess acetylcholine. 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 generalized. Many rippling movements are seen under the skin and twitching movements appear in all parts of the body. This is followed by severe generalized muscular weakness, including the muscles of respiration. The respiratory movements become more labored, shallow, and rapid; then they become slow and finally intermittent. Later, respiratory muscle weakness may become profound and contribute to 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 liability, and giddiness. There may be insomnia or excessive dreaming, occasionally with nightmares. If the exposure is more marked, the symptoms which may be evident are ; headache, tremor, drowsiness, difficulty in concentration, memory impairment with slow recall of recent events, and slowing of reactions. In some casualties, there is apathy, withdrawal, and depression.. 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, generalized convulsions may ensue. With the appearance of severe CNS 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 promptly convulse without other obvious symptoms. Death is usually due to respiratory arrest and anoxia. Prompt initiation of assisted ventilation may prevent death. Depression of the circulatory centers 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, labored, and rapid, and the casualty may gasp and struggle for air. Cyanosis increases. Finally, respiration becomes slow and then ceases resulting in unconsciousness. The blood pressure (which may have been transitorily elevated) falls. Cardiac rhythm may become irregular and death may ensue. The individual may survive several lethal doses of a nerve agent if assisted ventilation is initiated via cricothyroidotomy or endotracheal tube, if airway secretions are cleared by postural drainage and suction, and if secretions and bronchial constrictions are diminished by the vigorous administration of atropine. However, if the exposure has been overwhelming, amounting to many times the lethal dose, death may occur as a result of respiratory arrest and cardiac arrhythmia despite treatment. When overwhelming doses of the agent arc absorbed quickly, death occurs rapidly without orderly progression of symptoms. [3,4 & 5)

General Principles of Treatment

The principles of treatment of nerve agent poisoning are the same as for any toxic substance exposure namely terminate the exposure, establish or maintain ventilation, administer an antidote if one is available and correct cardiovascular abnormalities. Most importantly, medical care providers must protect themselves from contamination.

Protection of rescuer/ medical care provider can be achieved by physical means, such as masks, gloves, and aprons or by ensuring that casualty has been thoroughly decontaminated.

Terminating the Exposure The first and most important aspect of treating acute nerve agent poisoning is decontaminating the patient to prevent the casualty from further absorbing the agent, preventing the spread from spreading further, so that other personnel non chemical casualties and medical care providers de not get affected.

Decontamination's importance is obvious

Remove all the clothing immediately.

Wash the skin gently with soap and water.

Do not abrade the skin.

Flush the eyes with plenty of water or normal saline.

Decontamination of vapor is not necessary but some vapors get trapped into Clothing, hence clothing must be removed.

Decontamination of liquid exposure is done in military by using skin decontamination kit which contains active carbon impregnated with ion exchange resins which are capable of absorbing liquid off the skin.

Soap and large quantity of water can achieve the same aim in a hospital setting. It is important that decontamination is completed before the patient enters the hospital facility. This will avoid contamination of the hospital and its staff.

Ventilatory Support support is necessary aspect of therapy to save casualties with severe respiratory compromise. When the exposure is small, the casualty may have mild or severe dyspnea which may be reversed by administration if Atropine. If distress is severe and casualty is elderly the antidote may be supplemented by providing oxygen by inhalation.

Severely exposed casualties loose consciousness shortly after the onset of symptoms usually before signs of respiratory compromise. They have generalized muscular twitching or convulsive jerks and mat have initially spontaneous but impaired respiration. Assisted ventilation will be required to supplement gasping and infrequent attempts at respiration. Associated bronchospasm, and increased secretion further interfere with effective respiration. After the administration of Atropine, resistance decreases and secretions diminish. Thus in the unlikely but not an impossibility, a lone first responder must treat a severely poisoned casualty, first by IM Atropine administration and thereafter attempting intubation.

Atropine Therapy. Atropine has been the antidote of choice since nerve agents were first discovered and produced in World War II and was included in the German nerve agent first aid kits and was determined to be an effective antidote by British Scientists as well. Since 1940 Atropine has been adopted as the first line antidote to counter the effects of nerve agent poisoning by armed forces of most countries

A dose of 2 mg atropine was chosen for self / buddy administration through automatic Atropen injectors and three such injectors are included in the first aid kit.

When given to a normal individual without nerve agent intoxication, a dose of 2mg atropine causes heart rate increase of about 35 beats per minute, dry mouth, dry skin and mydriasis. When injected in an adequate amount, atropine reverses the effect of nerve agent in tissues that have muscarinic receptor sites. It decrease secretions and reverses spasm of smooth muscles. The amount of atropine to be administered is a matter of judgment depending upon clinical condition. The goal of therapy with atropine should be to minimize the effects of agent. However in acasualty with severe effects , it is better to administer too much atropine then too less.

Oxime Therapy. Oximes are nucleophilic substances that reactivate the organophosphate inhibited AChE. Oximes can be considered a more physiological method of treating nerve agent poisoning than atropine because they restore normal AChE enzyme function. Because oximes reactivate the AChE inhibited by a nerve agent, they might be expected to completely reverse the effects caused by nerve agent. However, because of reasons not understood, oximes are relatively ineffective in reversing effects in organs with muscarinic receptor sites and also they have limited penetration in to the CNS and therefore unable to reverse the central effects of intoxication.The dosage of 2-PAM Chloride has not been established but indirect evidences suggest that it is 15-20 mg/ Kg body weight. The effective dose depends on the nerve agent used and time lag between poisoning and oxime administration. The oxome administration through Combopen ie autojects containing 600mg oxime produces desirable clinical results.

Administration. An oxime should be initially administered with atropine. In cases of severe exposure, the contents of all the three autojects should be administered at 15 minutes interval. Additional atropine should be given to minimize secretions and reduce ventilator problems, the temptation to give more oxime with every dose of atropine to reduce muscular effects of the agent should be resisted and no more than 2.5 gm of oxime should be given within first 1 to 1.5 hours.

Anticonvulsive Therapy. Convulsions occur after severe nerve agent exposure. However, if they do not recur after atropine and oxime administration, no specific anticonvulsive therapy needs to be given. Diazepam has been shown to control nerve agent introduced seizures/ convulsions under experimental conditions. During Gulf War US Military issued autoinjectors containing 10 mg of Diazepam. However, this was intended not for self use but rather for use by buddy when soldier exhibited severe effects of nerve agent poisoning. First responders were provided with additional diazepam autoinjectors and could use two additional 10 mg doses at 10 minutes interval to convulsing casualty.

Pyridostigmine Bromide as Pre Treatment. Pyridostigmine is one of the known drugs, which act as competitive ChE inhibitor with that of Nerve Agents. The drug in larf=ge doses mimics the peripheral toxic effects of organophosphate nerve agents. The suggestion of using these carbamates as pre treatment may seem paradoxical. But critical characteristics of carbamates-enzyme bonding contribute to it's usefulness. Firstly, the bonding between carbamates and AChE is freely and spontaneously reversible, unlike that of irreversible inhibition of Ache by nerve agent. The second characteristic is that carbamate bound AChE id fully protected from effects of nerve agents because of already in bound form. Functionally sufficient excess 20% - 40% of the enzyme bound with pyridostigmine does not significantly impair neurotransmission. Pyridostigmine maintains a good safety record following it's administration in myasthenia gravis cases and approved by FDA USA. The recommended dose for nerve agent Pre-treatment is 30 mg 8 hourly. This recommended regime when followed, no significant decrements have been found in the performance of a variety of military tasks

Wartime Use. Pyridostigmine was used to protect soldiers from likely use of nerve agent in Gulf War in 1991 during Operation Desert Storm. The drug in 30 mg 8 hourly dosage was taken by all US and allied troops. Data on safety and possible adverse responses were collected from unit medical officers of 41,650 soldiers of XVIII Air Borne Corps. They were able to perform their mission without any noticeable impairment. In some cases gastrointestinal changes included flatus, loose stools and abdominal cramps were noticeable but not disabling.

Recommended therapy for casualties occurring from exposure to nerve agent is given at Table15.12 [1]

Summary of Management of Nerve Agent Casualties

First Aid/ Buddy Aid using Nerve Agent First Aid Kit

Injection Atropine should be given before other measures.

If available give Inj Pralidoxime chloride.

Specific Management at Medical facility

Respiratory Support

Respiratory failure is the cause of death in almost all cases of nerve agent poisoning. Intubation and ventilation should be done to deliver oxygen. Bronchial spasm and bronchial secretions complicate the issue and should be tackled. Atropine should always be given before ventilation to make it easier.

Antidote Therapy


Atropine is the drug of choice worldwide because of its wide temperatures stability, easy availability, rapid effectiveness, intramuscular or intravenous ease of administration and low toxicity. Atropine produces rapid effects at muscarnic synapses but has little effect at nicotinic synapses. This means that atropine can quickly reverse the respiratory effects of nerve agents but it will not help neuromuscular and possibly sympathetic effects. Intravenous route is preferred in a hospital care setting. Average requirement of atropine in an adult exposed to nerve agent is usually in the range of 20 to 30 mg.


Oximes reactivate the cholinestrase whose active site has been bound to nerve agent. Oxime therapy is limited by a phenomenon called 'aging'. In aging, a side chain on nerve agents fall off the complex at a characteristic rate. Oximes cannot reactivate negatively charged aged complexes. In a hospital setting PAM is given intravenously. The usual dose in an adult is 1000mg slowly IV over 20-30 minutes; not more than 2500mg to be given over a period of 1 to 1½ hrs.


Benzodiazepines are effective in stopping status epilepticus caused by nerve agents. Diazepam is the approved drug for such seizures. US forces have been provided with diazepam 10mg autoinjectors for IM use. An adult will need 30-40mg diazepam IM to control nerve agent induced status epilepticus. In a hospital setting IV route is preferred. Midazolam has been found to be most effective benzodiazepine recently but is yet to be approved by FDA. [3 &4]

Blister Agents (Vesicants)

Vesicants are agents that produce chemical burns. Sulphur Mustard, the first vesicant was initially synthesized by Desperetz in 1822 but it's vesicant properties were discovered in the middle of nineteenth century, first used as a chemical weapon in WW 1 and accounted for 160970 casualties out of total of 180983 casualties attributed to chemical agents. Thereafter mustard has been used on numerous occasions and still is considered a major chemical agent. [1]

Mustard (H and HD)

Physical Properties.

Mustard is an oily liquid ranging from colourless, when pure, to dark brown when impure. Mustard is heavier than water, but small droplets float on water surfaces and present a special hazard in contaminated areas. It smells like garlic or horseradish. Distilled HD, the most common form of mustard, freezes at 57 degree F boils at 442 degree F. It is only slightly soluble in water, which gradually destroys it, but un-dissolved mustard may persist in water for long periods. It is most soluble in fats and oils. It is freely soluble in acetone, carbon tetrachloride, alcohol and liquid fuels (gasoline, kerosene, and diesel); however, these solvents do not destroy mustard. Mustard disappears from contaminated ground or materials through evaporation or through hydrolysis. It is rapidly destroyed by decontaminating chemicals or by boiling in water. The primary use of mustard is to cause delayed casualties by the liquid and vapour effects on the skin and the eyes and by the vapour effects through the respiratory system. The persistence of hazard from mustard vapour or liquid depends on the degree of contamination by the liquid, type of mustard, nature of the terrain and soil, type of munitions used, and weather conditions. Mustard may persist much longer in wooded areas than in the open. Mustard persists two to five times longer in winter than in summer. The hazard from the vapour is many times greater under hot conditions than under cool conditions. Standard chemical agent detector kits should be used to detect the presence of HD vapour in the field. Even very small repeated exposures to mustard are cumulative in effect. For example, repeated exposures to vapours from spilled mustard can kill or I produce 100 percent disability by irritating the lungs and causing a chronic cough and pain in the chest. [3]

Mechanism of Action

Mustards are by-functional alkylating agents, containing two reactive chloroethyl functions. The binding of reactive with DNA produces a range of effects :-

Due to instability of alkylated guanine residues these may be released from DNA thus changing the original DNA molecule, inability to provide proper template of information resulting in erroneous incorporation of nucleotides, ultimately leading to mutation and synthesis of non-functional proteins.

Damage to DNA can include cellular repair mechanism which may not be error free, leading to erroneous DNA replication.

Alkylation of guanines inhibits DNA replication process and impaired protein synthesis.

In general three distinct levels of biological action can be discerned following exposure ti mustard ie cytostatic, mutagenic and cytotoxic. These actions of mustard resembling those produced by ionising radiation have labelled them as radiomimetic compounds. [1]

Another hypothesis postulates that mustard reacts with intracellular free radical scavenger Glutathione thereby depleting it allowing oxygen derived free radicals. The oxidizing compounds thus formed would react with membrane phospholipids to form free peroxides that could, in turn, lead to membrane alterations, change in membrane fluidity , and eventual breakdown of cellular membranes. [1] still is considered a major chemical agent and [1]

Effects of HD on the Eyes

Symptoms, and Prognosis. In a single exposure, the eyes are more susceptible to mustard than either the respiratory tract or the skin. Conjunctivitis follows an exposure time of about 1 hour to a concentration barely perceptible by odour. This exposure does not affect the respiratory tract or the skin significantly. A latent period of 4 to 12 hours follows mild exposure, after which there is lacrimation and a sensation of grit in the eyes. The conjunctivae and the lids become red and oedematous. Heavy exposure irritates the eyes after 1 to 3 hours and produces some severe lesions. Although temporary blindness may occur, permanent blindness is very rare. Casualties should therefore be reassured and a positive attitude taken. Care must be exercised to avoid transferring liquid agent from the hands to the eyes. Mustard burns of the eyes may be divided as follows:

Mild conjunctivitis (75 percent of cases in World War I). Recovery takes 1 to 2 weeks.

Severe conjunctivitis with minimal corneal involvement (15 percent of the cases in World War 1). Blepharospasm, oedema of the lids, and conjunctivae occur, as may orange-peel roughening of the cornea. Recovery takes 2 to 5 weeks.

(Mild corneal involvement (10 percent of the cases in World War I). Areas of corneal erosion stain green with fluorescein. Superficial corneal scarring and vascularization occurs as does iritis. Temporary relapses occur and convalescence may take 2 to 3 months. Hospital care is indicated for casualties of this type.

(Severe corneal involvement (about 0.1 percent of mustard casualties in World War I). Ischemic necrosis of conjunctivae may be seen. Dense corneal °pacification with deep Ulceration and vascularization occurs. Convalescence may take several months. Patients, may be predisposed to late relapses.



The risk of leaving liquid vesicant in the eyes is much greater than the risk from exposure of the eyes to vesicant vapours during the short period of decontamination. Decontamination must, therefore, be done despite the presence of vapour. (b) Speed in decontaminating the eyes is absolutely essential. This self-aid procedure is very effective for mustard within the first few seconds after exposure but is of less value after 2 minutes. Decontamination is done the same as for other vesicants (app D).

Treatment of mustard conjunctivitis.

Mild lesions require little treatment. Although the lesions may become infected, a steroid antibiotic eye ointment, such as dexamethasone sodium phosphate-neomycin ophthalmic ointment, can be applied. Ophthalmic ointments, such as 5 percent boric acid ointment, will provide lubrication and minimal antibacterial effects. The application of sterile petroleum jelly between the eyelids will provide additional lubrication and prevent sealing of the eyelids.

More severe injuries will cause enough oedema of the lids, photophobia, and blepharospasm to obstruct vision. This obstruction of vision alarms patients. To allay their fears, the lids may be gently forced open to assure them that they are not blind.

The pain is controlled best by systemic narcotic analgesics. Patients with severe photophobia and blepharospasm should have one drop of atropine sulphate solution (1 percent) instilled in the eye three times a day. To prevent infection, a few drops of 15 percent solution of sodium sulphacetamide should be instilled every 4 hours. Other antibacterial ophthalmic preparations may be substituted for sodium sulphacetamide.

The eye must not be bandaged or the lids allowed to stick together. Sealing of the lids may be prevented as described in a above. The accumulation of secretions in the conjunctival sac or pressure on the eye predisposes to corneal ulceration. To prevent complications, the patient should be treated by an ophthalmologist as soon as possible. When possible, the patient should be kept in a darkened room, given dark sunglasses, oil given an eyeshade to help his photophobia.

Treatment of infected mustard burns of the eye.

Secondary infection is a serious complication and increases the amount of permanent scarring of the cornea. If infection develops, initial treatment should be carried out with several drops of 15 percent solution of sodium sulphacetamide every 2 hours. After appropriate cultures, specific antibacterial preparation may be applied. Irrigation should he gentle and employed only to remove accumulated exudate. Pain is controlled as described in (2) (c) above, Patients with secondary infection or other complications should be referred to an Ophthalmologist. Local anaesthetics should not be used

Effects of HD on the Skin

The severity of the lesions and the rapidly with which they develop are greatly influenced by weather conditions as well as by the degree of exposure. Hot, humid weather strikingly increases the action of mustard. Even under temperate conditions, the warm, moist skin of the perineum, external genitalia, axillae, ante -cubital fossae, and neck are particularly susceptible.

Latent period. Exposure is followed by a latent period which varies with the degree, of exposure. It may be as short as an hour after liquid contamination, when the weather is hot and humid, or as long as several days after mild vapor exposures. With most vapor exposures in temperate weather, the latent period is usually 6 to 12 hours.

Erythema. Erythema gradually appears (2 to 48 hours post exposure) and becomes brighter, resembling sunburn. Slight edema of the skin may occur. In severe burns, the edema may limit motion of the limb. Itching is common and may be intense. As the erythema fades, areas of increased pigmentation are left (this sequence is reminiscent of that seen in sunburn).

Vesication. Except with mild vapour burns, erythema is followed by vesication. This is caused by progressive development of liquefaction necrosis of the cells in the lower layers of the epidermis. Exudation of tissue fluid into the spaces so formed results in an intraepidermal vesicle. Clinically, multiple pinpoint lesions may arise within the erythematous skin; these enlarge and coalesce to form the typical blister (which is unusually large, domed, thin-walled, yellowish, and may be surrounded by erythema). The blister is filled with a clear or slightly yellow liquid that tends to coagulate. The blister fluid does not contain mustard and is not a vesicant. Liquid contamination of the skin usually results in a ring of vesicles surrounding a gray-white area of skin which, although necrotic, does not vesicate. Unhydrolyzed vesicant on contaminated patients may pose a hazard to other individuals coming in contact with them.

Resorption. If the blister does not rupture, resorption takes place in about a week. The roof forms a crust beneath which re-epidermisation takes place. However, because of their thinness and tenseness, the blisters are fragile and usually break. If the roof becoms lagged, the burn may be considered an open wound. Once the blister has broken, it is bet to remove its ragged roof to decrease the possibility of secondary infection.

Healing. Since the damage to the corium is relatively superficial, healing occurs with formation little scar tissue formation, except in more extensive or infected burns where scarring is more severe.

Pigmentation. Mustard burns usually are followed by a persistent brown pigmentation except at the site of actual vesication, where there may be a temporary & pigmentation due to exfoliation of the pigmented lavers of the skin.

Hypersensitivity. Repeated burns may lead to hypersensitivity of the skin to mustard.

Symptoms and Prognosis.

An outstanding characteristic of the action of mustard is its insidiousness. Exposures to mustard are not accompanied by immediate symptoms, nor do any local manifestations occur until erythema develops. At this time there may be itching and mild burning. This pruritus may last several days and persist after healing. The blisters may be painful.

Mustard erythema heals at about the same rate as sunburn of like severity. Areas of multiple pinpoint vesication usually heal, with desquamation, in 1 to 2 weeks. Healing times for mustard blisters vary widely with both severity and anatomical location. In general, blisters of the face heal in 1 to 2 weeks. Blisters located in other areas may take slightly longer to heal; but if protected from infection, they will heal in 2 to 4 weeks. If cutaneous injury results in full-thickness coagulation necrosis, skin grafting may ultimately be necessary. However, a mustard burn of the skin is usually limited to the epidermis and does not require grafting.

Moderate contamination of mustard skin lesions with saprophytic bacteria, which causes no appreciable inflammatory reaction, does not seem to delay the healing of mustard burns. Active infection, with inflammation and purulent exudation, may increase the severity of the lesions and delay healing greatly.

Diagnosis of Skin Lesions Due to Mustard.

Similar skin burns are produced by mustard and the nitrogen mustards. Mustard burns are also similar in appearance to those caused by arsenical vesicants. Differentiation of mustard lesions from those produced by arsenicals is based upon:

Treatment of Mustard Erythema. Mustard erythema in mild cases requires no treatment. If an annoying itch is present, considerable relief may be obtained with topical steroid creams or sprays. Severe erythema around the genitalia may become quite painful and associated weeping and maceration may ensue. Often, treatment with exposure of the area is desirable and care must be taken so that secondary infection of tissue does not occur.

Treatment of Mustard Blisters.

Once blisters have broken, it is best to remove its ragged roof to decrease the possibility of secondary infection. Cleanse the area with tap water or saline, then apply sterile petrolatum gauze when the areas are small. Dressings should be changed and the wound inspected every 3 to 4 days. Small blisters on the face are opened and best left uncovered. Large blisters may best be treated by open methods. Apply about one-eighth of an inch thick layer of 10 percent mafenide acetate or silver sulfadiazine burn cream to the blisters as a topical antibiotic agent. A casualty with widespread vesication caused by mustard burns.

If the dressing sticks to the wound, care will be necessary to avoid pulling off the top of the blister. It is good practice to trim the edges of adherent gauze, leave it in place, and put a fresh dressing over it. If the wound needs to be examined, the dressing may be soaked off with sterile saline.

Treatment of Denuded Areas.

Contamination of mustard burns with saprophytic bacteria is common and unless careful wound care is given, serious infection may result. If there is no inflammatory reaction, the treatment is the same as for uncontaminated burns. Figure 4-16 shows burns produced by the reaction of mustard vapour with sweat.

Wounds which become infected must be treated with appropriate antibiotics after 'adequate cultures have been obtained. The medical officer must evaluate the infection and make the appropriate decision regarding further care