Chemical Warfare

Chemical Warfare Agents

Risk of exposure to chemical warfare agents

Injury from CWAs may result from industrial accident, military stockpiling, war, or terrorist attack.

Industrial accidents are a significant potential source of exposure to the agents used in chemical weapons. Chemicals such as phosgene, cyanide, anhydrous ammonia, and chlorine are used widely and frequently are transported by industry. The accidental release of a methylisocyanate cloud (composed of phosgene and isocyanate) was implicated in the Bhopal disaster in 1984.

CWAs first were used in 1915, when the German military released 168 tons of chlorine gas at Ypres, Belgium, killing an estimated 5000 Allied troops. Two years later, the same battlefields saw the first deployment of sulfur mustard. Sulfur mustard was the major cause of chemical casualties in World War I. CWAs have been used in at least 12 conflicts since, including the first Persian Gulf War (Iraq-Iran War). The Iraqi military also used chemical weapons against the Iraqi Kurds during the second Persian Gulf War.

Civilians also have been exposed inadvertently to chemical weapons many years after weapon deployment during war. Approximately 50,000 tons of mustard shells were disposed of in the Baltic Sea following World War I. Since then, numerous fishermen have been burned accidentally while hauling leaking shells aboard boats. Leaking mustard shells also have injured collectors of military memorabilia and children playing in old battlefields.

Although a number of international treaties have banned the development, production, and stockpiling of CWAs, these agents reportedly still are being produced or stockpiled in several countries.

Within the last decade, terrorists deployed chemical weapons against civilian populations for the first time in history. The release of sarin in Matsumoto, Japan, in June 1994 by the extremist Aum Shinrikyo cult left 7 dead and 280 injured. The following year, in March 1995, the Aum Shinrikyo cult released sarin vapor in the Tokyo subway system during morning rush hour, leaving 12 dead and sending more than 5000 casualties to local hospitals.

Several characteristics of CWAs lend themselves to terrorist use. Chemical substrates used in CWAs are widely available, and recipes for CWA production may be found on the Internet. CWAs are transported easily and may be delivered by a variety of routes. Chemical agents often are difficult to protect against and quickly incapacitate the intended targets. Most civilian medical communities are inadequately prepared to deal with a chemical terrorist attack.

GENERAL CONSIDERATIONS

Types of chemical weapon agents

CWAs comprise a diverse group of hazardous substances. Major categories of CWAs include the following:

  • Nerve agents (eg, sarin, soman, cyclosarin, tabun, VX)

  • Vesicating or blistering agents (eg, mustards, lewisite)

  • Choking agents or lung toxicants (eg, chlorine, phosgene, diphosgene)

  • Cyanides

  • Incapacitating agents (eg, anticholinergic compounds)

  • Lacrimating or riot control agents (eg, pepper gas, cyanide, CS)

  • Vomiting agents (eg, adamsite)

    Physical properties

    CWAs generally are stored and transported as liquids and deployed as either liquid aerosols or vapors. Victims usually are exposed to agents via one or more of 3 routes: skin (liquid and high vapor concentrations), eyes (liquid or vapor), and respiratory tract (vapor inhalation).

    CWAs are characterized by 2 inversely related physical properties: volatility (ie, tendency of liquids to vaporize, which directly increases with temperature) and persistence (ie, tendency of liquids to remain in a liquid state).

    In general, volatile liquids pose the dual risk of dermal and inhalation exposure, while persistent liquids are more likely to be absorbed across the skin. The effects of vapors largely are influenced by ambient wind conditions; even a slight breeze can blow nerve agent vapor away from its intended target. Effects of vapor are enhanced markedly when deployed within an enclosed space.

    Clinical effects

    Depending on the agent and the type and amount (concentration) of exposure, CWA effects may be immediate or delayed. Large inhalation exposures to nerve agents or mustards are likely to be lethal immediately. Small dermal exposures to nerve agents and mustards are particularly insidious and generally require expectant observation for variable periods because of possible delayed effects. Specific clinical effects of CWAs are as varied as the agents.

    Medical management

    To appropriately manage CWA exposures, emergency care personnel are required to protect themselves by performing the following:

  • Using PPE

  • Decontaminating patients immediately

  • Providing supportive care

  • Providing specific antidotes when indicated

    Personal protective equipment

    The primary responsibility of those who treat victims of CWAs is to protect themselves by wearing adequate PPE. First responders are at serious risk from the chemically contaminated environment (hot zone), either from direct contact with persistent liquid or from inhaling vapor. First responders and emergency care providers also are at risk from handling skin and clothing of victims contaminated with liquid CWAs (secondary skin and inhalation exposure). Conversely, providing care to those exposed only to vapor CWAs poses little risk to emergency care providers outside the hot zone. Unless a clear history of only vapor exposure is obtained, emergency medical personnel should assume that liquid contamination is present and wear PPE.

    Standard protective garments are inadequate for most CWAs. Double layers of latex gloves are useless against liquid nerve and blister agents, and surgical masks and air-purifying respirators are inadequate against nerve agent vapors.

    Levels of personal protective equipment

    US regulatory agencies mandate the use of appropriate levels of PPE.

  • Level A PPE is required for first responders and others working inside the hot zone, where vapor concentrations may be immediately dangerous to life and health. These suits are fully encapsulated, resistant to liquid and vapor chemical penetration, and include a self-contained breathing apparatus. Level A suits are also cumbersome, hot, and very difficult to wear for more than 30 minutes.

  • Level B PPE is required for hospital personnel involved in decontamination of unknown hazardous materials. These suits provide adequate protection against liquid and vapor chemicals when accompanied by a self-contained breathing apparatus or supplied air respirator.

  • Level C PPE is used when chemical agents have been identified and are amenable to removal by an air-purifying respirator. This suit also provides some protection against penetration by chemical liquids and vapors.

    Decontamination

  • Decontamination is the physical process of removing residual chemicals from persons, equipment, and the environment. Residual hazardous chemicals on those who have been exposed directly are a source of ongoing exposure to those persons and pose a risk of secondary exposure to first responders and emergency care personnel. Immediate decontamination is a major treatment priority for those with CWA exposure.

  • Initial decontamination involves removal from the contaminated environment, removal of all contaminated clothes and jewelry, and copious irrigation with water.

  • Rinse exposed persons with a 0.5% hypochlorite solution, which chemically neutralizes most CWAs (eg, nerve agents, mustards). A 0.5% hypochlorite solution conveniently is prepared by mixing 1 part 5% hypochlorite (household bleach) with 9 parts water.

  • Avoid hot water and vigorous scrubbing, as they may increase chemical absorption.

  • Vapor exposure alone does not require decontamination. Fully decontaminate patients with unclear exposure histories.

  • Ideally, decontaminate as close as possible to the site of exposure to minimize duration of exposure and prevent further spread. Hospitals receiving contaminated persons should establish an area outside the emergency department in which to perform decontamination before people and equipment are allowed in. Portable decontamination equipment with showers and run-off water collection systems are commercially available. All hospitals should have the capacity to safely decontaminate at least one person.

    Supportive and specific therapy

    Supportive therapy for victims of CWAs generally follows the universally accepted algorithm of first ensuring the adequacy of airway, breathing, and circulation, with one important exception. Severe nerve agent poisoning may require immediate administration of parenteral atropine. Many CWAs only can be treated supportively. Specific, well-established antidotes are available only for nerve agent and cyanide exposures. Since no laboratory tests are available to rapidly confirm exposure to CWAs, treatment is based on clinical criteria.

    NERVE AGENTS - PROPERTIES AND CLINICAL EFFECTS

    Mechanism of Action

     The 5 nerve agents, tabun (GA), sarin (GB), soman (GD), cyclosarin (GF), and VX, have chemical structures similar to the common organophosphate pesticide malathion. Like organophosphate insecticides, these agents phosphorylate and inactivate acetylcholinesterase (AChE). Acetylcholine accumulates at nerve terminals, initially stimulating and then paralyzing cholinergic neurotransmission throughout the body.

    Inhibition of AChE may not account for all of the toxic effects of nerve agents. These agents also are known to bind directly to nicotinic receptors and cardiac muscarinic receptors. They also antagonize gamma-aminobutyric acid (GABA) neurotransmission and stimulate glutamate N-methyl-d-aspartate (NMDA) receptors. These latter actions may partly mediate nerve agent–induced seizures and CNS neuropathology.

    Physical Properties

    Under temperate conditions, all nerve agents are volatile liquids. The most volatile agent, sarin, evaporates at approximately the same rate as water. The least volatile agent, VX, has the consistency of motor oil. This persistence and higher lipophilicity make VX 100-150 times more toxic than sarin when victims sustain dermal exposure. A 10-mg dose applied to the skin is lethal to 50% of unprotected individuals.

    All nerve agents rapidly penetrate skin and clothing. Nerve agent vapors are heavier than air and tend to sink into low places (eg, trenches, basements).

    Clinical Effects

    Nerve agents produce muscarinic, nicotinic, and direct CNS toxicity with a wide variety of effects on the respiratory tract, cardiovascular system, CNS, gastrointestinal (GI) tract, muscles, and eyes. Onset and severity of clinical effects vary widely, since numerous variables determine predominant effects. Agent identity, dose (determined by concentration and duration of exposure), and type of exposure primarily determine nerve agent toxicity. Toxic effects result from dermal exposure to liquid and ocular and inhalation exposure to vapor.

    Liquid exposure

    Liquid agents easily penetrate skin and clothing. Onset of symptoms occurs from 30 minutes to 18 hours following dermal exposure.

    Minimal liquid exposure (eg, a small droplet on the skin) may cause local sweating and muscle fasciculation, followed by nausea, vomiting, diarrhea, and generalized weakness. Even with decontamination, signs and symptoms may persist for hours.

    In contrast, persons with severe liquid exposures may be briefly asymptomatic (1-30 min) but rapidly may suffer abrupt loss of consciousness, convulsions, generalized muscular fasciculation, flaccid paralysis, copious secretions (nose, mouth, lungs), bronchoconstriction, apnea, and death.

    Vapor exposure

    Vapor inhalation produces clinical toxicity within seconds to several minutes. Effects may be local or systemic. Exposure to even a small amount of vapor usually results in at least one of the following categories of complaints: (1) ocular (miosis, blurred vision, eye pain, conjunctival injection), (2) nasal (rhinorrhea), or (3) pulmonary (bronchoconstriction, bronchorrhea, dyspnea).

    Exposure to a vapor concentration of 3.0 mg/m3 for 1 minute causes miosis and rhinorrhea. Inhalation of a high concentration of vapor results in loss of consciousness after only one breath, convulsions, respiratory arrest, and death. For example, breathing 10 mg /m3 of sarin vapor for only 10 minutes (100 mg/m3 for 1 min) causes death in approximately one half of exposed individuals. Severe vapor exposures also are characterized by generalized fasciculations, hypersecretions (mouth, lungs), and intense bronchoconstriction with respiratory compromise.

    Respiratory tract

    Nerve agents act on the upper respiratory tract to produce profuse watery nasal discharge, hypersalivation, and weakness of the tongue and pharynx muscles. Laryngeal muscles are paralyzed, resulting in stridor. In the lower respiratory tract, nerve agents produce copious bronchial secretions and intense bronchoconstriction. If untreated, the combination of hypersecretion, bronchoconstriction, respiratory muscle paralysis, and CNS depression rapidly progresses to respiratory failure and death. Nerve agents depress the central respiratory drive directly. Thus, early death following large vapor exposure likely results from primary respiratory arrest, not from neuromuscular blockade, bronchorrhea, or bronchoconstriction.

    Cardiovascular system

    The cardiovascular effects of nerve agents vary and depend on the balance between their nicotinic receptor–potentiating effects at autonomic ganglia and their muscarinic receptor–potentiating effects at parasympathetic postganglionic fibers that innervate the heart.

    Sinus tachydysrhythmias with or without hypertension (sympathetic tone predomination) or bradydysrhythmias with or without variable atrioventricular blockade and hypotension (parasympathetic tone predomination) may occur.

    Superimposed hypoxia may produce tachycardia or precipitate ventricular tachydysrhythmias.

    Nerve agent–induced prolonged QT and torsades de pointes have been described in animals.

    In victims of the Tokyo sarin gas attack, sinus tachycardia and hypertension were common cardiovascular abnormalities, while sinus bradycardia was uncommon.

    Central nervous system

    Nerve agents produce a variety of neurologic signs and symptoms by acting on cholinergic receptors throughout the CNS. The most important clinical signs of neurotoxicity are a rapidly decreasing level of consciousness (sometimes within seconds of exposure) and generalized seizures. Symptoms such as headache, vertigo, paresthesias, anxiety, insomnia, depression, and emotional lability also have been reported.

    Musculoskeletal system

    Nerve agents initially stimulate and then paralyze neurotransmission at the neuromuscular junction. With minimal exposure, exposed persons may complain of vague weakness or difficulty walking. More significant exposures resemble the clinical effects that result from succinylcholine, with initial fasciculations followed by flaccid paralysis and apnea.

    Ocular

    Nerve agent liquid or vapor readily penetrates the conjunctiva and exerts direct muscarinic parasympathetic effects. This results in constriction of the iris (miosis, blurred and dim vision, headache), constriction of the ciliary muscle (pain, nausea, vomiting), and stimulation of the lacrimal glands (tearing, redness). Although miosis is the most consistent clinical finding after vapor exposure to nerve agents (occurred in 99% of persons exposed in Tokyo sarin attack), it may be absent or delayed in dermal exposure. Duration of miosis varies according to the extent of ocular exposure (up to 45 d).

    Laboratory Tests

    Routine toxicology testing does not identify nerve agents in serum or urine. Measurements of red blood cell (RBC) or plasma cholinesterase activity have been used as an index of the severity of nerve agent toxicity, but this approach is not always reliable. The reference range of RBC cholinesterase activity may vary widely, and mild exposures may be difficult to interpret without baseline measurement. In addition, RBC cholinesterase activity may not correlate with the severity of signs and symptoms following vapor exposure.

    In the Tokyo subway sarin attack, 27% of patients with clinical manifestations of moderate poisoning had plasma cholinesterase activity in the normal range. Moreover, different organophosphates variably inhibit RBC and plasma cholinesterase. For example, in mild-to-moderate exposures to sarin or VX, RBC cholinesterase activity is decreased to a much greater extent than plasma cholinesterase activity.

    Since plasma cholinesterase is produced by the liver, its activity also may be depressed in certain conditions (eg, liver disease, pregnancy, infections) or with certain drugs (eg, oral contraceptives). Conversely, a 20-25% reduction in RBC cholinesterase activity tends to correlate with severe clinical toxicity and, despite the exception noted above, activity of both enzymes approaches zero in most severely poisoned victims. Nevertheless, treatment decisions should be clinically based. Never withhold treatment from a symptomatic patient while awaiting laboratory confirmation. Conversely, decreased cholinesterase activity in the absence of clinical signs of toxicity is not an indication for treatment.

    MUSTARDS - MEDICAL MANAGEMENT

    Personal protective equipment

    Liquid mustard contamination poses a dermal contact risk for emergency care personnel. Specialized protective military garments containing a charcoal layer to absorb penetrating sulfur mustard provide protection for up to 6 hours. These protective garments (chemical protective overgarment, battle dress overgarment, mission-oriented protective posture) are not available outside the military. Level A PPE provides the best protection for civilian first responders, and hospital-based emergency care personnel involved in subsequent decontamination should wear level A PPE.

    Decontamination

    Decontamination within 2 minutes of exposure is the most important intervention for patients with dermal exposure, since mustard rapidly becomes fixed to tissues, and its effects are irreversible. The classic description is an initial lack of signs and symptoms, which does not lessen the urgency to decontaminate patients as soon as possible.

    Remove clothing immediately and wash the underlying skin with soap and water. Ocular exposure requires immediate copious irrigation with saline or water. Next, decontaminate the skin with 0.5% hypochlorite solution or with alkaline soap and water, which chemically inactivates sulfur mustard. Because mustard is relatively insoluble in water, water alone has limited value as a decontaminant. Decontamination after the first few minutes of exposure does not prevent subsequent damage but at least protects emergency care personnel from further contact exposure.

    Supportive care

    Treatment of mustard exposure proceeds according to symptoms. Since the effects of mustards typically are delayed, persons with complaints immediately after exposure may have an additional injury. Patients with signs of upper airway obstruction require endotracheal intubation or the creation of a surgical airway. Also consider endotracheal intubation for persons with severe exposures. Use the largest endotracheal tube that can pass through, since sloughing epithelium may obstruct smaller tubes. Have patients inhale moist air. Mucolytics also are recommended for those with respiratory complaints.

    Avoid overhydration, since fluid losses generally are less than with thermal burns. Monitor fluid and electrolyte status and replace losses accordingly. Mustard-induced burns are especially painful, warranting the liberal use of narcotic analgesia. Adequate burn care is essential, since skin lesions heal slowly and are prone to infection. Severe burns may require debridement, irrigation, and topical antibiotics, such as silver sulfadiazine. Address tetanus toxoid immunity.

    Severe ocular burns require ophthalmologic consultation. Eye care typically includes daily irrigation, topical antibiotic solutions, topical corticosteroids, and mydriatics. Treat minor corneal injuries similarly to corneal abrasions. Apply petroleum jelly to prevent eyelid margins from sticking together. More severe corneal injuries may take as long as 2-3 months to heal. Permanent visual defects are rare.

    Specific therapy

    Although no antidotes currently are available to treat mustard toxicity, several agents are under investigation, including antioxidants (vitamin E), anti-inflammatory drugs (corticosteroids), mustard scavengers (glutathione, N-acetylcysteine), and nitric oxide synthase inhibitors (L-nitroarginine methyl ester).

    Administer granulocyte colony-stimulating factor to patients with bone marrow suppression following mustard exposure.

    Disposition

    Patients with significant respiratory tract burns usually require ICU admission and aggressive pulmonary care. Admit patients with significant dermal burns to a burn unit for aggressive wound management, analgesia, and supportive care. Arrange to monitor blood cell counts for 2 weeks following significant exposures. For 12 hours prior to discharge, observe patients who are initially asymptomatic following mustard exposure.

    Most patients recover completely. Only a small fraction have chronic ocular or pulmonary damage. Approximately 2% of those exposed to sulfur mustard in World War I died, mostly due to burns, respiratory tract damage, and bone marrow suppression. Sulfur mustard is a known carcinogen, yet a single exposure causes only minimal risk.

    CONCLUSION

    CWAs comprise a diverse group of extremely hazardous materials. Emergency physicians should be familiar with the pathophysiology and various clinical presentations produced by CWAs as well as the principles and practices of appropriate medical management. Since deployment of CWAs also places emergency care providers at serious risk of exposure, emergency physicians must be familiar with PPE and decontamination.

    As potential weapons of mass destruction, CWAs are capable of causing a catastrophic medical disaster, which would overwhelm any healthcare system. Since civilian victims exposed to CWAs are likely to flee to the nearest hospital, emergency physicians play a key role in preparing emergency departments for the treatment of persons exposed to CWAs.

     

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