A Primer on Chemical Weapons for EMS Personnel

Chemical weapons were first developed for use during World War I,1 but their actual use in war has been limited. Their development was met with a worldwide public outcry that they were inhumane and should be banned, and in April 1997 the Chemical Weapons Convention was signed. This treaty “prohibits the development, production, acquisition, stockpiling, retention or use of chemical weapons, as well as the transfer, directly or indirectly, of chemical weapons.”2 It now includes 145 signatories.

While most countries’ military establishments have abandoned chemical weapons (at least officially), such weapons have become items of great interest to terrorist groups like al Qaeda, Aum Shinrikyo and even some domestic groups.3 Chemical agents have been called “the poor man’s atomic bomb” because of their ease of acquisition, production and potential use.4 The Aum Shinrikyo religious cult’s 1995 nerve gas attack on the Tokyo subway system, using sarin, highlighted the destructive and chaotic power of these agents. The rush-hour attack killed 12 people, injured many others and sent more than 5,000 people to hospitals (though most were just worried they’d been exposed).5 Fortunately, the sarin preparation used was relatively weak, and the number of actual victims was comparatively small. However, the chaos that gripped the city demonstrated what could happen in a large chemical-weapon attack. Documents confiscated from Taliban and al Qaeda camps show that these groups also have procedures for making chemical weapons and have planned attacks using them in England and other locations.6

What Are Chemical Weapons?

Chemical weapons utilize chemical agents, compounds designed to kill or injure beyond reasonable functional recovery.7 Chemical warfare/terrorism weapons fall into four general classes based on their effects on the victim: Nerve agents, choking agents, blood agents and blister agents (see Table 1).

Nerve Agents—Nerve agents are the most likely candidates for use in a terrorist attack.1 Nerve agents, or nerve gases, are all similar in their chemical structure and mechanism of action. Nerve agents are organo-phosphate compounds, all of which have a phosphate group (PO4) in which one or more of the oxygen atoms has been replaced with another element like carbon, fluorine or sulfur. Organophosphate toxicity is due to the inhibition of acetylcholinesterase at cholinergic junctions of the nervous system.8 When the nerve agent enters a cell in the nervous system, it reacts with the enzyme acetylcholinesterase (also called RBC cholinesterase) and blocks its action. Acetylcholine is a neurotransmitter essential for the transmission of nerve impulses to muscles and organs. After an impulse is received, the acetylcholine must be destroyed and recycled in order for the muscle or organ to relax and the cycle to begin again. Acetylcholinesterase normally performs this function, but it cannot act when blocked by the nerve agent.9

Initially the blockage is reversible, but within a short time after exposure, the enzyme’s active site becomes phosphorylated and the block becomes irreversible, a process known as aging. Thus, acetylcholine continues to build up, and nerve impulses continue to be received by the muscles because the enzyme cannot hydrolyze the nerve agent due to the missing carbon-to-oxygen bond. Acetylcholine cannot bind to the enzyme because its binding site is blocked.8,9 Buildup of acetylcholine at the nerve endings mimics hyperactivity of the parasympathetic nervous system. This leads to a variety of clinical signs and symptoms including excess salivation, lacrimation, abdominal pain, vomiting and diarrhea. Effects are also seen at the parasympathetic neuroeffector junctions, sites of muscarinic activity, resulting in increased bronchial secretions and bronchoconstriction. At the neuromuscular junctions and autonomic ganglia (nicotinic activity sites) and also at certain synapses in the central nervous system, effects include weakness of voluntary muscles, irregular and violent contractions of involuntary muscles, twitching, paralysis and respiratory arrest.8,9

Atropine has historically been used as an antidote for nerve agents. However, atropine must be administered within minutes of exposure to be effective. Its effectiveness is dependent on the agent, the concentration received and a number of other factors. Atropine works by blocking the acetylcholine membrane receptors so that the excess acetylcholine resulting from nerve agent exposure can no longer work. It is most effective on the muscarinic receptors of the parasympathetic nervous system. Atropine has no direct effect on either acetylcholinesterase or the chemical nerve agent, so its action is not that of a true antidote.10 A second drug used with atropine is pralidoxime chloride, usually called 2-PAM chloride, which is also given by injection. This compound neutralizes the effect of the nerve agent by displacing the agent from, and competing for, the nerve agent binding site on the acetylcholinesterase enzyme.10

The first nerve agent, tabun, was developed by a German researcher in 1936 and was called GA for short. During World War II additional compounds were developed by the Nazis, including soman (GD), sarin (GB) and cyclosarin (GF). The British and Americans developed another set of nerve agents, designated VX, VE, VG and VM; however, only the VX agent was tested extensively.1,7 Agents GA, GF and VX block acetylcholinesterase activity at the nerve synapses, while agents GB and GD act on the same enzyme, RBC cholinesterase, in blood cells.7,12 Regardless of the mechanism of action, the end result and symptoms are the same for all agents. Nerve agents are most toxic through inhalation, and at lethal dose levels death occurs within seconds to minutes. While nerve agents are often called nerve gases, they are all liquids at room temperature. In an attack, they’re converted to a fine, stable aerosol which is easily dispersed and can penetrate to the deep part of the lungs on inhalation. These agents are also highly toxic through dermal exposure, since they are lipophilic and can readily penetrate the upper layers of the skin, eventually reaching the bloodstream. Percutaneous exposure requires higher levels of agent and occurs more slowly, but the end effects are the same.7

If a nerve agent is used in an attack on a soft target like a subway, sporting event or shopping mall, it is likely that all exposed victims will be exhibiting the maximum toxic response by the time responders arrive. Table 2 lists the symptoms expected in victims. Those already dead will have died from respiratory arrest resulting from the constant contracting of the muscles of the lungs, while others may be in early stages of respiratory failure. Those exposed to lesser concentrations may exhibit a variety of symptoms including tightness in the chest, dim vision and myosis, runny nose, drooling, excessive sweating, labored breathing, uncontrolled urination and defecation, twitching, staggering, confusion and drowsiness.7,12 In the Tokyo sarin attack, the vast majority of patients showed little to no symptoms, and most were eventually discharged from the ED.

An agent’s ease of dispersal increases with its volatility, but its persistence after dispersal decreases as its volatility increases. GB (sarin) is the most volatile agent, readily evaporating at room temperature. Due to its high volatility, it is the easiest of all nerve agents to disperse as an aerosol. However, because it evaporates so readily, it does not persist for long periods on contaminated surfaces. VX, on the other hand, is not volatile and can persist in a contaminated area for months.7,11

The volatility of nerve agents presents a danger to EMS workers arriving at the scene of an attack. The danger results from a process called off-gassing, in which agents can be released from the clothes, hair or skin of contaminated victims. Unless proper PPE is employed, this can expose workers to sufficient levels of agent to cause symptoms. Sarin (GB) and soman (GD), which are highly volatile, can readily off-gas from victims’ clothing.13 For VX, the least volatile of the nerve agents, off-gassing is not a concern, but dermal exposure must be controlled because of its capacity to penetrate dermal and mucous membranes. In a clandestine attack where victims are not aware they’ve been exposed, off-gassing can also lead to exposure of additional individuals not in the primary attack zone. Contaminated individuals entering cars, buses, subways or buildings have the potential to transfer the agent to individuals with whom they come in close contact.

Choking Agents—Chlorine gas was the first choking agent used in warfare, by German troops in 1915. Diphosgene and phosgene gases were developed shortly thereafter. The mechanism of action of these agents is the same as nerve agents: On inhalation they react with moisture in the airway and decompose to produce hydrochloric acid (HCl) and oxygen free radicals. The HCl reacts with the tissues of the upper airways, causing tissue destruction and sloughing of tissue from the airway lining. The oxygen free radicals migrate to the smallest passageways, the alveolar-capillary membranes, causing cell damage and leaking of blood into the lungs.11,12

The boiling point of choking agents is low; thus, they exist as vapors at room temperature and are easily dispersed. Their persistence is generally dependent on atmo­spheric conditions. Agents released outdoors on a windy or rainy day would dissipate quickly, while agents released into a confined space (e.g., a building, subway or, as in WWI, a trench) could build up to toxic levels and persist longer. Both chlorine and phosgene are widely used by the chemical, pharmaceutical and other industries and are readily available from chemical supply houses. While these agents could be released by terrorists from some type of gas-generating device, they could also be dispersed in an explosion because they are nonflammable. There are no antidotes for choking agents.11,12

The signs and symptoms of exposure to choking agents include excessive coughing, sneezing, choking, severe pain in the chest and, on swallowing, tightness in the chest, difficulty breathing and coughing up of large amounts of frothy fluid (yellowish to bloody in color). Death results from pulmonary edema (adult respiratory distress syndrome, or ARDS) or spasms in the airways. Victims may remain asymptomatic for hours or days before pulmonary edema presents. In high-exposure scenarios, spasms in the airways usually result in rapid death, while extensive edema in the airways is indicative that death is near. Exposure to low concentrations can cause severe symptoms in victims with pre-existing lung disease. Victims exposed at lower doses may suffer latent health complications such as emphysema or COPD.11,12 As with the volatile nerve gases, the choking agents chlorine and phosgene can lead to EMS worker exposure as a result of off-gassing.

Blood Agents—Blood agents are cyanide-containing compounds that act on the enzyme cytochrome oxidase, which is essential for the exchange of carbon dioxide and oxygen between red blood cells and tissue cells. There are two compounds considered as blood agents: hydrogen cyanide (AC) and cyanogen chloride (CK). Both decompose to cyanide gas and produce an odor similar to that of bitter almonds. Blood agents require large, sustained doses to be lethal, as in some states’ gas chambers, where death occurs in as little as 15–20 seconds. AC is considerably more toxic than CK, and its toxic effects can occur through percutaneous exposure as well as by inhalation. There is no antidote for blood agents. Symptoms of blood agents are described in Table 2.11,12 Off-gassing from any cyanide-containing blood agent presents a real hazard to EMS and rescue personnel.

Blister Agents (Vesicants)—Blister agents were widely employed on Allied troops in WWI. They are chemically dissimilar, but their mechanism of action and symptoms are essentially the same. They cause itching and large, painful, incapacitating blisters on the skin. These chemicals can also cause respiratory symptoms like cough, sore throat, chest tightness, nasal pain and dyspnea. Ocular symptoms may include lacrimation, severe eye pain, blurred vision and corneal ulceration.12

Blister agents include mustard gases, lewisite and phosgene oxime. The mustard class includes two agents, nitrogen mustard (HN) and mustard gas (HD), which contain nitrogen and sulfur, respectively. HN has a slightly fishy odor, while HD smells like garlic. Lewisite (agent L) is an arsenic-containing organic chemical, while phosgene oxime (CX) contains two chlorine atoms and is highly reactive with components of living tissue. Lewisite has an odor described as fruity or like geraniums, and CX has a very strong disagreeable odor. The eyes are the most vulnerable part of the body to these agents. Low concentrations that may not cause skin blistering will cause rapid eye inflammation. The respiratory symptoms of mustards and lewisite are similar and outlined in Table 2. There is no specific treatment for mustard gas. For systemic symptoms of exposure to lewisite, the compound dimercaprol (British anti-Lewisite, or BAL) was developed during WWII.11

Detecting Chemical Agents at the Scene

Early detection of chemical agents in a terrorist attack is essential in order to determine what level of PPE is required to protect EMS personnel and to initiate appropriate decontamination procedures for victims. In such cases final confirmation of the agent usually comes from samples sent to a certified laboratory for analysis, a process often requiring 1–3 days. However, a wide variety of handheld devices is available for detection of organic chemical vapors on-site within seconds. These detectors, which are generally carried by hazmat teams, can detect volatile organic compounds (VOCs), explosives and most chemical agents. Such devices vary in their ability to detect all agents and are semi-quantitative in determining the actual concentration present; however, they are adequate for making first-response determinations.14

Protecting EMS at the Scene

In a terrorist attack, a major concern for EMS personnel is how to deliver appropriate emergency care while protecting themselves from secondary contamination. EMS responders must understand how to select and don appropriate PPE based upon a rapid assessment of the scene and consultation with hazmat experts.15 Four levels of protection have been defined and are described in Table 3. A review of PPE requirements for EMS workers is available in the August 2004 issue of EMS Magazine.16 EMS workers must also be aware of their surroundings in the event of a secondary attack occurring after their arrival.

EMS providers deliver medical attention to victims in the warm zone (decon area) or cold zone (contamination-free area). PPE requirements may be dictated by lack of knowledge of the agent involved or by direct order from Incident Command, the safety or hazmat officer or other authorized individual within the incident command system.15

References

1. Mitretek Systems. History of Chemical Warfare, www.mitretek.org/home.nsf/homelandsecurity/HistChemWar.
2. Text of Chemical Weapons Convention, April 29, 1997.
3. Council on Foreign Relations. Q&A on Terrorist Groups, https://cfrterror ism.org/groups.
4. Testimony of Rep. Glen Browder (D-AL) before U.S. House of Representatives, Congressional Record, March 21, 1995.
5. Council on Foreign Relations. Q&A on Terrorist Groups, https://cfrterror ism.org/groups/aumshinrikyo.html.
6. www.lib.ecu.edu/govdoc/terrorism.html#wmd.
7. U.S. Army Technical Guide 218, General & detailed fact sheet on chemical agents, 1995. Sheets 218-(02–05)-1096. https://chppm-www.apgea.army.mil/doc uments/TG/TECHGUID/Tg218.pdf.
8. Furtado NC, Chan L. Toxicity, Organophosphates. www.emedicine.com/med/topic1677.htm.
9. Arnold JL. CBRNE—Nerve Agents; G series. www.emedicine.com/emerg/topic898.htm.
10. Chemical Weapons: Nerve Agents. https://faculty.washington.edu/chudler/weap.html.
11. Adams R. Homeland Defense Info Kit, Part 1: Chemical Weapons. National Fire & Rescue, May/June 2002, pp. 23–26, 45–47.
12. Medical Aspects of Chemical, Biological and Radiological Warfare. www.tpub.com/content/medical/14295/css/14295_301.htm.
13. Arnold JL. Personal Protective Equipment. www.emedicine.com/emerg/ topic894.htm.
14. Hanson D. Sniffing out explosives. Law Enforcement Tech Feb. 2005, pp. 68–79.
15. National Academies Press. Personal Protective Equipment. www.nap.edu/html/terrorism/ch3.html.
16. Hanson D. Under attack: Protecting EMS personnel. Emerg Med Serv 33(8): 99–104, Aug. 2004.