Today, the thought of using a toxic chemical against a civilian population is considered barbaric, but many countries, including the United States once had chemical weapons programs. For many countries the chemical weapons programs began even before WWI and reached its intensity in the 1960s. These programs produced human toxic chemicals with the intent to both kill and incapacitate enemy soldiers.¹

Not until the last 10 years has there been significant concern about the use of these military chemical against civilian populations.² It should be noted that in 1993 most counties that had developed chemical weapons signed an agreement to destroy current stockpiles and stop future production. Both the United States and Russia signed the agreement. At the time Russia had approximately 40,000 tons of chemical weapons, followed by the United States with 31,000 tons. Both are in the process of destroying the weapons.³

Because much scientific study and practical application has gone into the use of chemicals as a weapon, there is speculation that terrorist groups could tap into this expertise to manufacture and disseminate toxic chemicals against civilians.

In March 1988, Saddam Hussein attacked the Kurds in Iraq using a chemical cocktail of mustard gas and various nerve agents. An estimated 5,000 Kurds died in the attack. Half of those living in the region of the attack have respiratory complications and on an average day, there are no normal births, mostly miscarriages. Those that survive have significant birth defects and mental retardation.⁴

Then in March 1995, a terrorist group, the Aum Shinrikyo, released sarin nerve agent into a Tokyo Subway station and perpetrated the largest non-wartime chemical attack on record against a civilian population. The attack resulted in more than 5,000 injuries, 12 deaths and 1,000 victims were hospitalized. This act of terrorism stimulated many of the efforts in this country to prepare for a chemical attack against our civilian population.¹

The chemical agents that could be used as a terrorist weapon fall under four major categories: neurotoxins, cyanides, respiratory irritants, and vesicants. These chemicals are both military and industrial based. Although American industries use and produce many toxic chemicals, most are not manufactured to intentionally cause harm to humans. In contrast, military anti-personnel chemicals are produced to both injure and kill.⁵

Neurotoxins (nerve agents)

Neurotoxins are organophosphate-based chemicals commonly common agents selected for use in wartime activities.² These agents are very effective because they can enter through virtually any route and cause severe incapacitation and death. Neurotoxins have been formulated to be extremely toxic to the intended target, but break down rapidly so that invading troops can inhabit the area within days after an attack. There are similar compounds used in industry, such as organophosphate insecticides; some of these possess extremely toxic qualities and could be used in place of military nerve agents.

Several commercially available organophosphate insecticides such as Parathion and tetraethylpyrophosphate (TEPP) are extremely toxic and may be easier to acquire than military-based nerve agents.² These insecticides trigger the same nervous system stimulation as a military nerve agent. Although these commercially available insecticides are very toxic, they do not have the extreme toxicity found in the military agents.³

Military nerve agents

Tabun (GA), sarin (GB), soman (GD), and VX (V-Agent) are the most widely known military neurotoxins. These agents are organophosphate compounds that can be sprayed in the air as a vaporizing mist or can be spread as a liquid that vaporizes through evaporation.³

G agents, developed in Germany during WWII, are volatile and evaporate slightly faster than water. This makes them very dangerous as an inhalation hazard. Although none of these agents are easy to make, tabun (GA) and sarin (GB) are easier to synthesized and therefore, may be more readily available. Soman is not easily formulated and is the most deadly of the G agents because of its ability to cause irreversible damage even with rapid use of antidotes.^3,2

VX (V for venom) is not as volatile as G agent, evaporating only as rapid as motor oil. This makes VX primarily a skin absorption hazard. For VX to become a respiratory hazard, it must be mechanically aerosolized or heated to increase volatility. Because of the viscosity of this agent, it will last longer on objects in the environment, causing injury or death days later.^3,2

The military nerve agents are odorless, so they can be used without easy detection. Terrorists, on the other hand, may not care so much about the odor generated by the chemical and may produce them without the additional synthesis needed to remove the odor. Typically, G agents produced without the removal of the aroma will have a fruity smell while VX will have a sulfur smell.³

Physiology of neurotoxins poisoning

In the synaptic junctions using acetylcholine as the neurotransmitter, the enzyme acetylcholinesterase functions to remove acetylcholine once a nerve impulse is transmitted across the junction.⁴ These nerve pathways are primarily located in the parasympathetic nervous system, but are also found in the central and somatic system. Nerve agents work by binding with the enzyme acetylcholinesterase, allowing acetylcholine to remain in the junction and over stimulate nerve pathways by sending continuous nerve impulses across the synapse. The bond between the nerve agent and acetylcholinesterase ages over time and eventually becomes a permanent bond that cannot be broken, even with the use of an antidote. Signs and symptoms of the over stimulation include excessive salivation, urination, diarrhea, excessive mucus production, muscle fasciculation, constricted pupils, and seizures. The acronym DUMBELS (diarrhea, urination, meiosis, bronchospasm, emesis, lacrimation, and salivation) abbreviates the most prevalent signs and symptoms.⁶

Physical properties and routes of entry

Neurotoxins are found in a liquid form and evaporate slowly having a viscosity ranging from water-like to motor oil thickness. The most volatile of the group is sarin, which can evaporate slightly faster than water.³ These agents can enter through all routes, but inhalation causes the most rapid effects. Because an enemy cannot guarantee that inhalation will occur, some nerve agents have thickeners, ensuring that the agents will remain on objects for long periods of time and, thus, be transmitted to the victim hours or days later. Once on the victim, the agent is absorbed through the skin, causing systemic poisoning.

An exposure to vapors usually generates mild to severe symptoms that occur within seconds to minutes. Mild symptoms include those defined in the acronym DUMBELS. Severe symptoms include all of the mild symptoms, with the addition of loss of consciousness, seizures, and apnea.² When there is a liquid exposure, the onset of symptoms is slower, ranging from five minutes to 18 hours, and is generally localized to the area of exposure during the onset of symptoms. As the poisoning become more systemic, effects will spread throughout the body.⁷

Decontamination

Decontamination is necessary for people exposed to neurotoxins. Victims’ clothing and skin can have enough chemical to cause harm to nurses trying to care for them. Those providing decontamination to victims must wear appropriate chemical personal protective equipment (PPE) including proper respiratory protection. Water has the ability to decontaminate nerve agents through a process of hydrolysis.¹ The process works well, but when thickening substances are added to the nerve agents, they are not easily soluble, and hydrolysis occurs slowly. The addition of soap to water will make the decontamination process more efficient by breaking down oil-based materials.¹ Hospital personnel participating in mass casualty decontamination efforts or those wearing chemical protective PPE to triage or treat patients must be trained under OSHA standards.

Chemically contaminated patients can present a secondary contamination hazard to health care providers. Appropriate PPE for chemically contaminated patients including airway protection may be necessary. Information about PPE is available from the American Hospital Association, the local emergency planning committee, or local fire department.

Treatment

The first treatment is to provide an open airway and support ventilation. Because patients are hypersecreting, the airways frequently become blocked and must be suctioned to ensure airway patency. If treatment is being provided in a health care setting, the first priority should be establishing a patent airway and starting oxygen before providing an antidote.⁸

Antidotes for nerve agent poisoning include atropine IM or IV, followed by pralidoxime chloride (protopam chloride, 2-PAM chloride). Atropine is administered rapidly in high doses under close cardiac and vital sign monitoring.⁹ Atropine blocks the release of acetylcholine in the synaptic junction and limits the need for acetylcholinesterase. Atropinization must be maintained until all the absorbed organophosphate has been metabolized and the body again produces sufficient quantities of acetylcholinesterase. The treatment could last from days to weeks, necessitating the use of huge quantities of atropine. The normal dosage is 2-6 mg every five minutes until the mucous membranes dry.⁹ The military provides an antidote kit for troops who are in danger of an attack with a nerve agent. The kit, called a Mark I, contains two auto injectors. One of the auto injectors contains 2 mg of atropine and the other 600 mg of pralidoxime for self-injection into intramuscular tissue. Many EMS agencies and even some hospitals in the U.S. have purchased these kits for treating mass casualties related to nerve agent poisoning.³

Pralidoxime is used as the second part of the nerve agent antidote. Pralidoxime has three desirable effects: frees and reactivates (breaks the bond) acetylcholinesterase; detoxifies the nerve agent; and has anticholinergic (atropine-like) effects. Pralidoxime’s ability to break the nerve agent/acetylcholinesterase bond lessens over time, so the faster this drug can be administered, the better the outcome.¹⁰

Valium should be considered any time that somatic system toxicity (seizures) is noted. If significant inhalation of a nerve agent occurred, it may be necessary to use Valium even before muscular involvement is witnessed.⁹

Cyanides (blood agents)

Terrorists can easily obtain and use cyanides and cyanide compounds to cause mass casualties in civilian populations. Not only have cyanides been used by militaries as anti-personnel chemical weapons, but these chemicals are common in industry. Cyanide is used in industry for heat treating and plating, fumigation, mineral extraction, dyeing, printing, photography, agriculture, and the manufacture of plastics, paper, and textiles. It is a chemical asphyxiant causing cellular suffocation. It is found as a gas, solid, or liquid.

Military blood agents

Military cyanide compounds consist of two chemicals, hydrogen cyanide (military call this chemical AC) and cyanogen chloride (military CK). These agents are identical to their civilian counterparts used in industry. For this reason, terrorist may choose these agents to inflict harm.

Hydrogen cyanide is a liquid at less than 79 F, but vaporizes quickly. Cyanide gas is lighter than air, so when it is released, it rises and dissipates rapidly. For this reason, AC does not remain in surrounding areas. CK, is a liquid at less than 55 F, so it becomes a gas much quicker. CK gas is twice as heavy as air and therefore has a tendency to linger in low-lying areas and inflict harm for longer periods of time.¹¹

Physiology of cyanide poisoning

Cyanide has the odor of bitter almonds. The ability to detect this odor is a sex-linked recessive trait of only 60% to 80% of the population. The remaining population cannot detect the odor due to a sensory deficit that is greater in men than women by a ratio of 3-1.⁹

These agents work by inhibiting the ability of cells to use oxygen. Following an exposure, the cyanide ion enters the cells, binding with the mitochondrial enzyme cytochrome oxidase. This enzyme, in its original form, is necessary for electron transport needed for cellular respiration (the use of oxygen to convert glucose to energy). By binding to cytochrome oxidase, these ions cause a paralysis of the cells’ ability to carry out aerobic metabolism. The process eventually causes the cells to function under anaerobic metabolism. This anaerobic state ultimately causes decreased cellular energy production, metabolic acidosis, cellular suffocation, and death. The half-life of cyanide in the body is only about an hour, but during an exposure, death takes place well before the body starts to detoxify or excrete the chemical.¹¹

Physical properties, routes of entry

Cyanide is one of the most rapidly acting poisons. It most often gains access to the body through inhalation but can be ingested or absorbed through the skin and mucous membranes. Cyanide causes death within minutes to hours, depending on its concentration and route of entry as well as the exposure time and activity level of the victim.⁷

Patients present with a wide variety of symptoms because cyanide poisoning affects virtually all of the cells in the body. The most sensitive target organ is the central nervous system where the urgent need for oxygen is first sensed. Early effects can include headache, restlessness, dizziness, vertigo, agitation, and confusion. Later signs are seizures and coma.¹¹

Decontamination

Generally decontamination is not needed if a victim is only exposed to cyanide gas or vapor. The removal of a patient’s clothing is usually enough to remove any chemical hazard. If a victim is exposed to a liquid or solid, a soap and water wash is recommended.

Treatment

Treatment consists of establishing a patent airway then, as quickly as possible, begin advanced treatment using a cyanide antidote kit. The kit contains amyl nitrite, sodium nitrite, and sodium thiosulfate.⁷

The first step in the use of the cyanide antidote kit is to break a perle (similar to an ammonia capsule) of amyl nitrite. Allow the patient to inhale the amyl nitrite for 15 to 30 seconds of every minute while an IV is established.⁹ Once an IV is established, slowly administer 300mg (10ml) of sodium nitrite IVP over 10 minutes. Both of these nitrites are vasodilators and can cause a decrease in blood pressure that can usually be corrected with positioning and fluids.⁹

Last, infuse 50ml of a 25% solution of sodium thiosulfate, IV, over at least 10 minutes. Sodium thiosulfate acts as a clean-up agent by changing the remaining cyanide into a relatively harmless substance that is renally eliminated.⁹

The nitrites (amyl nitrite and sodium nitrite) convert hemoglobin into methemoglobin. Essentially, these chemicals change the iron ion in the hemoglobin from Fe++ (ferrous iron) into Fe+++ (ferric iron) converting hemoglobin into methemoglobin. Methemoglobin will not carry oxygen but has an affinity for (wants to bond with) the cyanide ion. Methemoglobin competes with cytochrome oxidase for the cyanide ion, actually attracting the cyanide away from the cytochrome oxidase. The cyanide antidote kit will convert about 20% of the hemoglobin into methemoglobin. This frees the cytochrome oxidase to participate again in aerobic cellular metabolism. Providing oxygen at a 100% concentration is necessary to reduce hypoxia related to the decreased hemoglobin.⁹

Respirator irritants (choking irritants)

Strong respiratory irritants have a long history of use by military forces. Even today, chlorine (CL) and phosgene (CG) remain in military arsenals around the world. When discussing terrorism, we cannot discount the possible use of these agents.¹

Many communities use chlorine gas in its pure form for chlorinating drinking water. It’s also used as an anti-mold and fungicide agent. Compounds containing chlorine are even used for chlorinating home swimming pools and cleaning toilets and showers. There is no doubt that this chemical is easily available to produce single exposures or mass casualty events.

Phosgene, although not as common as chlorine, is found in industry and used for organic synthesis during the production of polyurethane, insecticides, and dyes.It is also a by-product of burning Freon, which has lead to many injuries among firefighters.^1,9

Military choking agents

Chlorine and Phosgene are typically stored as liquids but rapidly become gases once released into the atmosphere. Their expansion ratios allow them to be transported in smaller containers, and, once released the fill a large area.¹

These agents were used on the battlefield to incapacitate an enemy force so that it could be overtaken by advancing troops. This strategy worked well, because both of these gases dispersed rapidly into the environment, leaving no contaminated objects behind to cause injury.

Once exposed, victims are overcome with severe, uncontrollable coughing, gagging, and tightness in the chest.¹² Bronchospasms and laryngeal spasms are common, causing apnea and unconsciousness. Other injuries include tissue sloughing, localized edema, and pulmonary edema, all contributing to obstruction of the airways. Because chlorine is water soluble, injury begins in the upper airways, where the chemical combines with the water-based mucous lining the airways.

Phosgene is not easily soluble in water and therefore directly attacks the alveoli, where tissue destruction at this level can be severe. The breakdown of these cells allows fluid from the bloodstream to advance into the airways, a condition called noncardiogenic pulmonary edema. This form of pulmonary edema is very difficulty to treat. When the injury is not fatal, many times the victim is left with destroyed lung tissue and a lifetime of respiratory disease ranging from chronic obstructed pulmonary disease to chronic pneumonia.¹³

Physiology of respiratory irritant injury

Injuries to the upper respiratory areas are usually a result of exposure to water-soluble chemicals that readily dissolve into the moisture-coated airways. In the case of chlorine, this results in the production of hydrochloric acid and chemical burns at the site. Laryngeal edema and laryngeal spasms should be expected and treated aggressively.^7,9

Injuries to the lower regions of the respiratory tract usually result when the chemical inhaled is not water-soluble, is in a high concentration, or is inhaled over an extended period of time. This deeper injury causes swelling of the finer bronchioles, sloughing of damaged tissue, and damage to the alveoli. Cilia that may be damaged are unable to rid the fine bronchioles of the sloughed cells and increased mucous production caused by the damaged airways. The lower airways obstruction caused by this exposure adds to the complexity of the injury and increases the chance of death.^7,9

Noncardiogenic pulmonary edema is the result of a chemical irritant reaching the alveoli and causing damage. The damage interferes with the alveoli’s natural ability to keep fluids out of the alveolar space, which results in fluids filling injured alveoli and fine bronchioles, eventually advancing into the upper airways. If the exposure causes severe alveolar damage, the end result will be death.⁷

Physical properties, routes of entry

Both chlorine and phosgene are heavier than air and are able to seek out low-lying areas and persist for long periods of time. Although these chemicals are considered respiratory hazards, chlorine has additional effects on both mucous membranes and moist skin. Exposed patients will present with burning eyes, nose, and possibly burning skin in areas that are moist (under arms and groin areas).¹⁰

Decontamination

Chlorine will combine with any moisture on the skin and form a solution of hydrochloric acid causing skin burns. Decontamination consists of removing clothing and rinsing/washing with soap and water.⁶

Treatment

The treatment for respiratory irritant is twofold. Initial treatment is to open the airways to allow the free movement of air into the alveoli. The second part of the treatment is to reduce the fluid in the alveoli to allow gas exchange with the blood. Getting oxygen to the alveoli is vitally important.⁸

In upper respiratory injury, oxygen must pass through narrowed passageways to gain access to the lower system. Bronchodilators like albuterol given in an updraft will provide some dilation of the airways. Brethine (terbutaline sulfate) and epinephrine given subcutaneously may also assist in making the bronchioles larger to allow for the passage of air and oxygen. However, care must be taken with any of these drugs as their side effects, high blood pressure and rapid heart rate, will be with hypoxia.⁹

When lower airway injury results, the outcome is usually pulmonary edema (PE). Reducing pulmonary pressure with the use of Lasix, Morphine, or Nitroglycerine may produce a positive effect but will usually not stop the progression of chemically induced PE. Because the alveolar tissue is injured causing the infusion of fluid from the bloodstream. Definitive treatment will involve positive pressure ventilation using a volume-cycled ventilator. This will serve to both reduce the infusion of fluid from the blood stream and assist oxygen exchange in alveoli that have been injured from the chemical exposure.⁷

Vesicants (blister agents)

Vesicants were originally developed by the military to be used both as area contaminants to severely injure exposed skin and as a respiratory and eye irritant when vaporized. Many chemicals in industry are capable of causing skin irritation, but none to the degree that military blister agents can.¹

Military blister agents

Three types of blister agents are primarily used by the military. These agents include mustard (H), phosgene oxime (CX), and lewisite (L). These agents are all liquids that vaporize slowly. Skin and eye exposure is the most common effect that results from direct contact with the liquid.¹

Physiology of blister agent exposure

These agents are capable of causing extreme pain and large blisters on contact. If the vapors are inhaled, the lung tissue will form large obstructing blisters. Once the blisters break, a large open wound results that allows the establishment of infections that can eventually cause death.

After blister agents gain access into the body, the chemical cycles in the extracellular fluid forming an extremely reactive substance binding with both intracellular and extracellular enzymes and proteins causing extensive tissue damage. Once exposed, a victim may manifest a latent period when no symptoms are present. Two to 24 hours later, the reaction appears with the formation of blisters on the skin and necrosis of the mucosa of the airways with progressive involvement of the airway musculature, and severe irritation to the eyes including swelling in the cornea and related tissues that leads to permanent scarring. Injuries from blister agents are considered radiomimetic in nature as these agents have the ability to alter DNA, similar to radiation poisoning.¹⁴

Lewisite acts similarly to mustard but has additional effects that are systemic. Symptoms beyond the blistering effects may include pulmonary edema, diarrhea, vomiting, weakness, and low blood pressure. The irritation lewisite causes to the eyes is devastating. If a victim is not decontaminated within one minute, damage will probably be permanent.¹

Physical properties and routes of entry

Mustard has a freezing point of 57 F, so it solidifies at temperatures less than this. For this reason it does not readily vaporize unless it is heated to above 100 F and, therefore, is not a significant respiratory hazard. Lewisite and phosgene oxime vaporize more readily than mustard, making them more of a respiratory hazard. All of the blister agent vapors are heavier than air, allowing them to stay near the ground and not dissipate quickly.^5,9

Decontamination

Decontamination for all blister agents must be immediate and involve the removal of all contaminated clothing. Caution must be exercised in removing victims’ clothing as secondary contamination could take place. Clothing must be handled using chemical protective gloves and other appropriate PPE.⁵ The decontamination solution of choice is soap and water.

Each vesicant harms tissues on contact. Mustard differs from the other agents, as it does not produce symptoms for several hours, leaving the victim without a clue that an exposure has taken place. Both phosgene oxime and Lewisite cause irritation almost immediately, which alerts the victim to the exposure and allows earlier decontamination.⁸

Treatment

Treatment after exposure to blister agents is mostly supportive. The skin damage is similar to that seen in thermal burns and could be as simple as treating a sun burn to total management of a severely ill person with burns and the challenges of controlling fluid and electrolyte balance. Burns to the eyes are treated with ophthalmic ointment and topical antibiotics. Respiratory involvement may require intubation and ventilation utilizing PEEP or CPAP to maintain oxygenation.³

Health care issues

Although there have been no significant acts of terrorism using chemicals in the U.S., state and local governments are busy preparing for chemical terrorism. Fire and police departments have training programs that teach emergency responders how to respond safely if chemicals are involved in an incident.⁵ The military has shared its experience with training centers and has helped develop programs to teach health care providers how to treat casualties of chemical exposures.

Special chemical protective equipment has been developed for hospitals if mass casualties arrive and are contaminated with hazardous chemicals. Nurses, especially those working in emergency rooms, must know how to both protect themselves from contaminated patient and know how to treat those exposed.⁵ If an act of terrorism involving chemicals occurs, the FBI will respond and will be the lead agency in charge of the incident. The Environmental Protection Agency will have oversight of environmental clean-up and the Department of Homeland Security will coordinate overall federal actions. Health departments will stay in contact throughout the nation using the Health Alert Network (HAN), one of the means of communicating information about the event. The HAN is an Internet-based communication program that can be used to alert other areas of the county about an attack and share experiences in dealing with the event.

When mass casualties involving a chemical exposure occur, supplies and equipment needed to treat the victims can be rapidly depleted. When a shortage of supplies and equipment is predicted, local emergency management can be contacted for help. Local emergency management can contact the state (governor’s office) and request the Strategic National Stockpile. Once requested, the SNS will be in a community within 12 hours and provide large quantities of antidotes and equipment to supply hospitals that are treat mass casualty victims.¹⁵