 Welcome to the Overview Video in the video series The Medical Management of Chemical and Biological Casualties, sponsored by the United States Army Medical Research Institute of Chemical Defense. This course will introduce you to the different kinds of chemical agents, their physical chemical characteristics, and their effects on the body. Most importantly of all, though, we will talk about how casualties will present, how to evaluate them, and how to treat them. Now, what is a chemical agent? Well, there are several definitions. We could go to the Army Field Manual 8-285. That manual says that a chemical agent is a chemical substance which is intended for use in military operations to kill, seriously injure, or incapacitate humans or animals through its toxicological effects. When we talk about chemical agents or chemical warfare agents, it's important for us to understand how they are similar to and yet different from other substances that are noxious. Chemical agents are obviously chemicals of some sort that exert some toxicological effect. They're poisons. On the other hand, we have biological agents. Biological agents are organisms. They are living organisms such as bacteria or viruses or fungi. Well, if that's so, what are toxins? How do they fit in? A toxin is nothing more than a chemical compound produced by a biological organism. A toxin is usually so complex that it is not easily synthesized in the laboratory, but it can be synthesized and is synthesized by living organisms and extracted and then used for its poisonous effects. Although toxin is sometimes used synonymously in a general sense to refer to a poison, its restricted specific definition is this chemical compound that comes from a biological source. The word toxicant is sometimes also used as a general synonym for poison. The word sounds so close to toxin that it's probably best not used, but it is still technically correct. This definition specifically excludes three kinds of chemical agents. It excludes riot control agents, it excludes herbicides or weed killers, and it excludes smoke and flame materials, which have been around for thousands of years and which some people have presumed to act through a general mechanism of smoke inhalation rather than from specific toxicological mechanisms, although we'll see later that that's not an entirely true statement. Let's talk briefly about each of these agents. Riot control agents are agents that have an extremely high safety ratio. That is, the amount that it takes to kill someone is far and away greater than the amount that it takes to produce the desired physiological effect, which in the case of riot control agents is running of the nose, lacrimation or tearing, and irritation of the throat and upper airway. These agents can be divided into two general classes. There are the respiratory irritants and lacrimators or sternutators. A sternutator is another name for a sneezing agent. All of these agents produce the general symptoms of pain and irritation in the eyes, sneezing, irritation in the throat. They include such agents as CS, often called tear gas, CN, commercially known as MACE, DA, an older agent, and CR, actually a fairly new British agent. The other kind of riot control agent is a vomiting agent. This includes agents such as DM or Adamcite, DA, and DC. The designations CS, CN, and so forth are the NATO codes for these agents. The word for chloracetofinone, or CN, is different in English than it is in French or German, but all NATO countries understand that CN refers to this particular chemical compound. It's important to have at least a familiarity with the NATO codes used for the various agents that will be described in this course. Riot control agents have a short onset time. That is, within seconds of your entering a CS chamber or a CS tent and taking off your mask, your eyes begin to burn, you begin to have difficulty breathing, and you start to cough and maybe to sneeze. But the duration is also fairly short. Once you've left the tent, the symptoms go away within several minutes to a half an hour or so. Herbicides are the second main class of compounds specifically excluded by the definition in FM 8-285. They include compounds such as Agent White, Agent Blue, and Agent Orange, all names given to various weed killers. Agent Orange was the defoliant used extensively in Vietnam to clear forest areas. Health problems encountered by Vietnam veterans and described to Agent Orange come not from the compound itself, because Agent Orange is really only a mixture of a couple of common weed killers, 2-4-5-T and 2-4-D. The health problems from Agent Orange actually come from small quantities of TCDD or dioxin, which was a contaminant in the production process for Agent Orange. The third class of compounds specifically excluded by the definition in the field manual is smoke and flame. Smoke and flame have been used on the battlefield since at least 3000 B.C. And the impression may be that smoke and flame exert their effects in a general way having to do with inhaling hot, sooty particles rather than from a specific toxicological mechanism. But we'll see that that's not exactly true for all of these compounds. These compounds include fairly commonly encountered agents such as diesel oil, fog oil, HC smoke. HC smoke is the name given to standard white military obscure smoke. But we'll learn in this course that HC smoke can be just as deadly as any of the peripherally acting pulmonary compounds used in World War I. So we've talked about the general definition of chemical warfare agents and we've talked about the three kinds of compounds that the definition in FM 8-285 specifically excludes. That is, riot control agents, herbicides, and smoke and flame. I should say at this time that the general name for these compounds in the public sector is poison gas. Poison gas because the first agents used in World War I on a large scale were in fact gases, chlorine, phosgene, chloropicrin, cyanide. Many of the subsequent agents, however, are not gases at all. They're liquids or in some cases even solids. So poison gas is really a misnomer in most cases and a better way to refer to these compounds in a general sense is to use the term chemical warfare agent. Let's return to the official chemical agents. What are they? How can we make sense of them so that when we hear one agent and another agent and another agent we don't get them mixed up? Well, let's develop a framework. Let's develop a skeleton, so to speak, on which we can then hang muscle and nerve and blood vessel and put all of the details onto this framework. Let's start by observing that of the official chemical agents there are only two main kinds. There are the toxic, sometimes called lethal agents. The agents that are designed specifically to seriously injure or to kill. Then there are the incapacitating agents. The agents that are designed not to produce any serious or long lasting injury. There are four main kinds of toxic agents, lung, blood blister and nerve. If you remember that, you will not only remember the four kinds of official chemical warfare agents but you will remember them in the order in which they were introduced into battle, which I think is a logical way of studying the agents themselves anyway. Let's talk briefly about each of these agents before we go on to talk about general concepts and some terms that I think are important for us to know. The lung agents include chlorine, which was the first agent used on a large scale in modern warfare. In 1915, the Germans released over 150 tons of chlorine on the battlefield against French and Algerian territorial troops near Ypres, Belgium. Chlorine acts both on the upper airways and the lower airways. And it's important to make a distinction for most of these agents between agents that irritate the upper airways. That is the central part of the airways and agents that affect the lower or peripheral parts of the airways. The anatomic and functional division of the respiratory tree into these two parts, central and peripheral, is an extremely important concept to understand. The respiratory tree begins obviously at the mouth and the nose, continues down through the throat, passed the windpipe into the trachea, and continues on into the two main stem bronchi, which divide and subdivide and subdivide again. After about 17 or so subdivisions, the bronchi, actually by now bronchioles, are no thicker than perhaps a couple of dimes. From the mouth to this point, air moves in a column with each breath that we take. And since there is bulk flow of air with each breath, there are clinical implications. Patients with damage to the central part of the respiratory tree are like a hose that's partially kinked. Because there's a moving column of air, any partial obstruction to the movement of that air will create noise. What does this mean in terms of the patient? It means that the patient will tell you that he or she has a problem. Not in so many words, but because of the noises that you'll hear coming from the patient. You'll hear the coughing or the sneezing or the inspiratory strider. Perhaps the laryngospasm, perhaps hoarseness or sneezing, but something to tell you that the bulk flow of air is being constricted at some point. That gives you an extremely important clinical clue to the diagnosis. There are some chemical compounds whose action is predominantly in the central part of the airways. They include acids, bases, the chemical warfare agents, mustard and lewisite, and to some extent chlorine, which seems to have equal effects centrally and peripherally. Now, you may know that mustard and lewisite aren't classified with the pulmonary or lung agents at all. They're considered to be vesicants or blister agents. That should not obscure the fact that these agents also have effects on the airways. However, when we talk about lung damaging agents, we mean especially the agents that act peripherally. The peripheral part of the respiratory tree is that part that extends distal to the 2 millimeter in diameter bronchioles. That is, we're talking about the respiratory bronchioles, the terminal bronchioles, and the alveoli or air sacs themselves. This is where gas transfer takes place between a gaseous medium and the blood. This is where oxygen gets into the blood. This is where carbon dioxide leaves the blood and gets back into the airway. Agents that attack the peripheral part of the airway typically damage the alveolar capillary membrane, leading to fluid leakage from the capillaries, first into the interstitium or parenchyma or lung substance of the lung itself, and then eventually into the air sacs themselves, which fill with fluid and create pulmonary edema or dryland drowning. The patient drowns in his or her own secretions. Phosgene, chloropicrin, diphosgene are examples of World War I agents that act peripherally. These agents typically have a latent period of several hours before the patient even develops symptoms. Seeing that the peripherally acting or pulmonary edematogenic agents affect the part of the airway where no bulk air movement is occurring with each breath has an extraordinarily important clinical implication. Air that enters the peripheral part of the respiratory tree enters only by brownian motion, only by diffusion. It does not enter more quickly at the end of a breath than it does in the middle of a breath or at the beginning of a breath. Therefore, when damage occurs to the alveolar capillary membrane, it is usually unaccompanied early on by any physical signs or noise. A patient exposed to a peripherally acting agent will notice usually after a latent period of several hours that he or she is having more difficulty breathing. There's stiffness in the chest. There's dyspnea. I just can't quite seem to catch my breath. A physical examination undertaken at this point is unlikely to show any signs of abnormality. There'll be no inspiratory crackles early on. There'll be no wrong eye or wheezes. A chest x-ray is unlikely to show curly B lines or an increase in fluid at this particular point. And the mistake would be to send this patient back to whatever he or she was doing before the exposure with the comment, I'm sorry, I can't find anything wrong on physical examination, laboratory, or x-ray, and therefore you must be fine. Because people in this situation go on to develop fulminant pulmonary edema and die, especially if they exert themselves after their exposure. The other thing that's important to know about lung agents, just as an introduction, is that apart from the vesicants that have lung effects, that is, mustard and lewiside, and apart from chlorine, which acts both centrally and peripherally, and apart from the classic World War I peripherally acting agents, such as phosgene, diphosgene, and chloropicrin, there are a variety of other compounds that, although not normally classified as chemical warfare agents, nevertheless, act in almost the same way and can be encountered in a civilian setting or in a military setting, but not on the battlefield. Examples include isocyanates, methyl isocyanate was responsible for the thousands of deaths that occurred in Bhopal, India. A compound called PFIB, or perfluoroisobutylene, is formed when teflon burns at high temperatures. Fires, including military fires, that involve the combustion of teflon can produce this compound, which is 10 times more toxic than phosgene. HC smoke was one of the smokes that I mentioned a little bit earlier. It's not an official chemical warfare agent, but it is a peripherally acting pulmonary adematogenic lung agent, as are oxides of nitrogen, a component of photochemical smog, and also a byproduct of the use of munitions. So let's see, where are we? Lung, blood, blister, nerve. We've covered the lung agents. Let's talk about the blood agents for a minute. To call an agent a blood agent, somehow, at least to me, implies that it must do its dirty work in the blood. That's actually not the case for hydrogen cyanide and cyanogen chloride, the two classical blood agents. An understanding of how cyanide acts at the subcellular level leads logically to an understanding of how the cyanide antidotes, sodium nitrite and sodium thiosulfate, work to remove cyanide from the body. All right, let's see. Lung, blood, blister. The next category must be blister agents or vesicants. There are three main categories of vesicants. There are the mustards, there's leucite, and there's phosgenoxin. The mustards can be further subdivided into sulfur mustard and the nitrogen mustards. By far, the most important of all of these compounds is sulfur mustard, which was introduced into battle in 1917, and which during the year or so of its use produced more casualties than all of the other chemicals used in World War I, and is still sometimes referred to as the king of gases, even though it's not really a gas. At usual temperatures and pressures, it's either a solid or a liquid, although that liquid can form a vapor. We'll talk about liquids and vapors in a few moments. Mustard damages not just the respiratory tract, but also the skin and the eyes. It can produce big blisters on the skin or it can lead simply to sloughing, to denudation of large areas of the skin. Mustard also is absorbed and distributed throughout the body and can have systemic effects on the body as a whole. Lung, blood, blister, nerve, nerve agents. Nerve agents are essentially pesticides against people. They are chemically related to some of the pesticides in common use, but they're extremely potent. They poison a very important enzyme that turns off nerve transmission. Transmission between a nerve and another nerve, between a nerve and a skeletal muscle, between a nerve and a smooth muscle, or between a nerve and a gland. When the enzyme normally responsible for turning off a nerve impulse is poisoned, it means that the end organ, whether it's another nerve, a skeletal muscle, a smooth muscle, or a gland, is hyper stimulated. And if this is a muscle, a skeletal muscle, we're talking about twitching articulations and eventually, once the muscle or other end organ becomes fatigued, failure of that end organ. The situation is analogous to spraying a fly. I don't know how many of you have watched what happens to a fly once you've sprayed it with a pesticide, but typically the fly is hyper excitable. It flies in circles and it's not very coordinated, but there's hyperactivity of the muscles. But then there's fatigue of the muscles, and the fly goes. That's what happens with people, okay? We've talked about the toxic agents, that is the lung agents, the blood agents, the blister agents, and the nerve agents. Let's talk briefly about the other major category of official chemical agents, the incapacitating agents. Incapacitating agents are designed not to cause serious or long term effects. There are several compounds that could theoretically be used as incapacitating agents. We could talk about hallucinogens such as LSD, we could talk about marijuana, we could talk about other agents that would induce some sort of temporary dysfunction. In fact, if riot control agents were considered by the United States to be official chemical warfare agents, they would be in this category. But normally when we talk about incapacitating agents, we talk about a kind of agent that is likely to exert its incapacitating effects by doing something to the central nervous system. The primary candidates are a group of compounds called glycolate anti-cholinergic. The most familiar example of which is atropine. Atropine by itself is not potent enough to be an effective chemical warfare incapacitant, but there are compounds that are more potent than atropine. One of them is a compound, the NATO code for which is BZ. The United States developed this compound, weaponized it, and then demilitarized it. It's importance for us today lies in the fact that Iraq developed its own mental incapacitant called Agent 15. What have we learned up to this point? We know what the general definition of a chemical warfare agent is. We know how a chemical agent differs from a biological agent and from a toxin. We know the three kinds of compounds that are excluded from consideration by the United States as official chemical warfare agents. That is, riot control agents, herbicides, and smoke and flame. We've learned what the two major kinds of official chemical warfare agents are, the toxic agents and the incapacitating agents. We've learned what the four major kinds of toxic agents are, lung, blood, blister, and nerve. And we've learned just a little bit about each one of these agents. Let's now talk about some general concepts. It's common to hear the expressions mustard gas and nerve gas as if these agents were in fact gases which they are not. So we'd better take a few minutes and decide exactly what we mean when we use the terms solid, liquid, gas, and vapor. There are three common states of matter, solid, liquid, and gas. So let's take an example, water. If I had solid water in my hand, what would I have? I'd have ice. That's pretty easy. If I had liquid water, I would have, of course, just a pool of water, a puddle of water in my hand. Now if I were to look up at a cloud, I suppose would that be gaseous water? No, clouds actually are aerosols. An aerosol is a suspension or a collection of small particles of solid or droplets of liquid suspended in another medium, usually a gas. In the case of clouds, we have small droplets of water that have coalesced around even tinier dust particles suspended in the atmosphere and visible as a cloud. Most gases and vapors, on the other hand, are not visible at all, unless the gas itself is inherently colored, for example, chlorine. So if a cloud is not gaseous water, what would be the form of water that would be encountered as gas? It would be steam. And once we heat water to its boiling point, water changes from a liquid form to a gas. And the gas itself is invisible. What we see coming from a teapot is actually a projection of small particles of liquid before they turn into gas. But water as steam, the gaseous form of water, is in fact invisible. There's one final form of matter that we've not yet addressed, and that's vapor. What is a vapor? A vapor is nothing more than the gaseous state of a substance at a temperature below the normal boiling point of that substance at a given pressure. For example, if I have a small quantity of water and leave it exposed to the air, eventually I will no longer see any liquid water. Where's it gone? Well, we know from the law of conservation of mass that the water hasn't actually disappeared, but it's changed into a gas. But since we did not heat the water to 212 degrees Fahrenheit at sea level first, the gas that we obtain is called a vapor. The application of this knowledge to chemical warfare agents lies in the fact that the clinical implications of chemical warfare agent exposure are different depending upon whether somebody has been exposed to a solid form of the agent, a liquid form, or agent in the form of a vapor or a gas. The state of an agent also has to do in a general way with how persistent the agent is. Now, persistence could mean a lot of things. It could mean how long the effects of an agent persist in the body. It could mean how long the agent itself stays around in the body. What it really means is how long the agent is likely to remain in the environment. Persistence in this sense is affected by a variety of factors. It's obviously affected by the chemical structure of the agent. If I have a quantity of water in this hand, I have a quantity of motor oil. On the other hand, the motor oil is obviously going to stay around longer. It will be more persistent because its chemical structure dictates that it will be more persistent than water. There are other things that obviously affect persistence as well. If I have a quantity of water in this hand and one in this hand, but blow on this hand, even though the chemical structure is the same, the water will disappear more rapidly. That is, it will be less persistent. So wind obviously has an effect on persistence. So does temperature. If I have a quantity of water at this temperature over here, but the same quantity of water just above a Bunsen burner and heat that water, even though I've not heated it to its boiling point, it will evaporate more quickly and therefore become less persistent. If I place a certain amount of water on my coat and the same amount of water in my hand, one of those quantities of water will evaporate more quickly than the other, depending upon the interaction of the water with the fabric in my coat. So it is with chemical agents. Persistence depends in part upon agent-surface interactions. Chemical agents differ in their persistence, depending upon their chemical structure. The G-nerve agents, GA or taboon, GB or sarin and GD or Solman, are liquids that evaporate at about the same rate that water evaporates or somewhat more slowly. They evaporate quickly enough that under usual temperatures and pressures, they will have disappeared within 24 hours of their deposition. Agents like this are called non-persistent. They include agents that are normally encountered as liquids, but that evaporate relatively quickly. Agents such as the G-nerve agents and hydrogen cyanide. They also include true gases such as chlorine and phosgene. Persistent agents, that is, agents that are likely still to be encountered in the environment after 24 hours, include the persistent nerve agent VX, mustard and lewisite. Agent present as a solid, a liquid of vapor or a gas contacts the body at certain sites. The concept of exposure deals with contact of the agent with an epithelial surface. Contact or exposure is not the same thing as absorption, which implies penetration of an epithelial barrier. The difference can also be expressed as the difference between external dose, which is the dose to which one has been exposed, and internal dose, the dose that actually penetrates an epithelial membrane to reach the interior of the body. It's important to recognize the various possible routes of exposure for any chemical agent. Exposure can occur through the skin, obviously. Exposure through intact skin is percutaneous absorption. Exposure can also occur through the eyes. So we have ocular exposure. The eyes are an excellent route of entry for chemical warfare agents. Exposure can occur via inhalation through the respiratory tract. Exposure can also occur via ingestion, so-called internal exposure. The converse of internal exposure is parenteral exposure, which in medicine normally implies penetration of an epithelial membrane via mechanical means. Normally, we're talking about an intramuscular injection, a subcutaneous injection, an intravenous injection. On the battlefield, that translates to penetration of an agent via a wound of some sort. Paracelsus once noted that all substances are poisons. It's only the dose that makes the difference. So it would be useful for us to have some way of comparing the toxicities or lethalities of chemical warfare agents. For liquids, this is a fairly familiar concept. You might think that an LD50 is the amount of poison that it would be necessary to give an individual to achieve a 50% probability that that individual would die. That's not precisely true. The LD50 is the amount of a chemical that would have to be administered to each person in a group in order for us to expect that 50% of that group would die. It's a population concept rather than an individual concept. Does that make a difference? It does because the name of the game in biology is variation. And there are individual variations in the biology of patients that render some patients more sensitive and other patients less sensitive to the effect of a chemical warfare agent. Since the dose response curve of chemical warfare agents is fairly steep, this may be a minor difference, but it's a difference that exists nonetheless. A related concept is the ED50, or effective dose 50. This is the dose to effect. We have to define an effect. If the effect of a given substance is to make people break out into, for instance, pink and yellow polka dots, the ED50 for production of pink and yellow polka dots is the amount of that substance that would have to be given to each person in a group in order for us to expect half the group to break out in pink and yellow polka dots. Another concept closely related to ED50 is the ID50, or incapacitating dose, for 50% of a population. This defines a particular effect, the effect of incapacitation. Since this term is an ambiguous one, I prefer personally the term ED50 defining the effect. It's relatively straightforward to compare the toxicities of agents that we encounter as liquids because we can express the LD50 as a weight or a mass. We can weigh out a certain quantity of the agent. But how do we weigh something that we encounter as a vapor or a gas? The answer is that we resort to using two concepts, concentration and time of exposure. We multiply the two values together to get a so-called CT product, which measures the external dose, the dose encountered by the external surfaces of the body. Let's see how that works. If I had a box that was one meter by one meter by one meter and I placed one milligram of liquid sarin inside that box, I could wait until the sarin has completely evaporated. At that point I can no longer weigh the sarin, but it doesn't make a difference because I know how much sarin is in the box, one milligram. The concentration of sarin in that box is one milligram per cubic meter. Suppose I now place my head inside the box and leave it there for eight minutes. The exposure time is eight minutes. The concentration is one milligram per cubic meter. The CT product is eight milligram minutes per cubic meter. The beauty of this concept expressed as Haber's law is that it doesn't matter how I reach the product as long as the products are the same. I could place my head in a concentration of one milligram per cubic meter of sarin for eight minutes. Or in a separate box I could place eight milligrams of sarin and leave my head in for one minute. Since the CT products are the same, one would expect the effects to be roughly the same. Haber's law holds over a relatively wide range of concentrations and times with the notable exception of cyanide which is metabolized to a significant extent by the body. And just as we can speak of LD50s, so then can we speak of an LCT50, the CT product that would be fatal for 50% of a group, each member of which received that particular CT product. Note that because the CT product measures exposure rather than absorption, that is it measures external rather than internal dose. The internal dose can vary depending upon the root and conditions of exposure. For example, if I have a concentration of one milligram per cubic meter in this box and leave my head in for eight minutes but breathe like this, I would be exposing myself to the same external dose as if I were to put my head in this box with the same concentration of sarin for the same contact time and breathe like this. But because my respiratory rate and depth are greater in this box, my internal dose will be greater in this situation despite the fact that the CT products are the same in both cases. Let's now examine the sequence of events that would happen prior to, during and after exposure to chemical warfare agents. From a civilian perspective, the time between notification of an increased threat and actual exposure is a time in which certain preventive measures can be taken. It's called the crisis management phase. Once exposure has occurred, the time, the response after that point is called, appropriately enough, consequence management. From a medical perspective, the consequence management phase can be broken down into a latent period and a time after the appearance of clinically evident signs and symptoms. The time between exposure and the development of those symptoms is called the latent period. For some chemical agents, the latent period is on the order of a few seconds. For other chemical warfare agents, it may be up to several hours or even days. From a public health or preventive medicine standpoint, there are really only three ways in which someone can respond medically to an exposure, an illness, an injury, a disease. Those three phases are primary, secondary, and tertiary prevention. Those concepts work well with this diagram that we've established of temporal progression relating to chemical warfare agent exposure. Primary prevention corresponds to the crisis management phase in a civilian response. That is, primary prevention is what can be done before exposure occurs. To do what? To prevent exposure in the first place. Now, what could we do to prevent exposure to chemical warfare agents in the first place? Well, I suppose we could talk about demilitarization, disarmament. We could rid the planet of chemical warfare agents in the first place. That's not likely to happen despite our best efforts anytime soon. We could prevent exposure by having extraordinarily good intelligence that would tell us that the likelihood in a given area is low or high. And if we can depend upon that intelligence, that's an excellent primary preventive strategy. Having true pretreatments would be a primary preventive measure. That is, having compounds that could be administered to a soldier or to a civilian before exposure, that would protect him or her from a subsequent exposure. Mostly, in the military, we rely upon the primary preventive measures of personal protective equipment, including the chemical protective mask and personal protective clothing, the chemical protective overgarment, boots, and gloves. However, even more important than personal protective equipment is teaching a soldier or a civilian what to do. That is, training the individual to be able to respond appropriately so that upon exposure he or she does the right thing. Training by itself helps prepare for a chemical warfare event. But training can be supplemented by education, in the sense that training teaches someone what to do, whereas education teaches him or her why it has to be done. We hope that this series of videos will help teach not just what to do, but why it has to be done. However effective any of the preceding primary preventive measures will be, depends in large measure upon the organizational response to an incident. How well are people being prepared in the military or in the civilian sector? Is there appropriate command emphasis? Is there an appropriate structure being laid out in the civilian sector to respond to a chemical warfare event even before it takes place? All of that is primary prevention. Intervening in the space between exposure and the development of clinically evident signs and symptoms is what is called secondary prevention in public health. In this phase, early diagnosis can lead to a much better outcome for the patient, despite the failure of primary prevention to prevent the exposure itself with chemical warfare agents. In addition to early diagnosis, prompt decontamination can be lifesaving. Early evacuation to a medical treatment facility capable of administering appropriate medical treatment would also be a secondary preventive measure if executed during the time between exposure and the development of clinical signs or symptoms. Once those symptoms have arisen, by definition primary prevention has failed and secondary prevention has failed. Tertiary prevention means medical treatment if both primary and secondary prevention has failed. And a casualty presents with clinically observable signs or symptoms of a chemical agent exposure. A person's life can still be saved by prompt and appropriate medical treatment to include decontamination even at this stage, administration of antidotes, supportive care as necessary, and continued evacuation. If I were viewing this video course I wanted to learn as much as I could about chemical warfare agents and how to manage chemical agent exposure. I would try to break this down into two segments. Two questions. A, how do I learn about chemical agents? And B, how do I approach a patient who's been exposed to chemical agents? For the first question, how to learn about chemical agents? I think that it would be good to have a framework where possible. The videos that comprise this video series will take what seems to me to be the logical approach of first introducing a given agent by talking a little bit about the history and background of the agent. How does it fit in? How does it fit into the framework that we've already discussed? It's then important to know something about the physical chemical properties of the chemical agent. Is it a solid? Is it a liquid? Is it a vapor? Does it vaporize relatively quickly? What does it smell like? Are there any warning symptoms? What are their detectors available? Once we have a handle on the physical chemical properties of the chemical agent in question, we can then examine the question of what the agent does once it contacts the body and enters the body. That is, how does the body handle the agent? We're talking here about the pharmacologists or toxicologists' alphabet of ADBE. That is, absorption, distribution, biotransformation or metabolism, and elimination. What happens to the agent once it gets into the body? How is it distributed? If in fact it is distributed systemically, and how is it eliminated from the body? That's a different question from asking how does the agent handle the body? How does it exert its effects? What are the toxicodynamics of the agent? What is its mechanism of action? If we know how the agent affects the body, how it causes the pathological lesions, we can then ask ourselves the next question, how does the patient manifest those pathological changes? What's the clinical presentation of the patient? Once we know what the patient will look like and act like, we have a handle on a diagnosis, and we can assess the patient. Once we've assessed the patient, we can proceed to patient management. How do we treat the patient? What are the secondary and tertiary preventive strategies available to us once exposure has occurred? These measures almost always include, as a first principle, protecting ourselves. It does the casualty no good if we become casualties ourselves in attempting to treat. If general supportive care is available, general supportive care is administered. Specific antidotes are available. Specific antidotes are given. Another principle of patient management applicable to almost all agents is decontamination. Separating the patient from the agent and appropriate evacuation is also a part of the management of chemical casualties. It's important to keep the various elements of this process in perspective. Knowing about the history and background of a chemical agent may not seem particularly important, but it helps fix information about the chemical in our minds. Knowing about the agent's physical chemical properties, toxicokinetics, and toxicodynamics is not important in and of itself. It's a means to an end, but it's a very important means because without knowing that, we will not be nearly so effective at assessing the patient. Let's now proceed to how we assess a patient, a casualty of a chemical agent. In normal medical practice, we use the problem-oriented medical record, which of course has the four components of SOA and P. The subjective component is eliciting a patient history, taking the symptoms. The O stands for objective, of course, and here we're talking about signs. We're talking about physical examination, laboratory studies, blood tests, radiological studies, and everything that will give us objective, independently verifiable information about the condition of a patient. We then go to the assessment stage after which we can proceed to the P or the plan, the management plan. In normal medical practice, the assessment phase ends once we have reached a diagnosis. It can then proceed to the plan part of the problem-oriented medical record. But with chemical warfare agents, getting a diagnosis is only the first step of a slightly expanded evaluation or assessment phase. An easy way to systematize this process is to use a mnemonic such as asbestos. With asbestos, A stands for the agent and is equivalent to a general diagnosis. But it's not enough just to say that we now have a nerve agent casualty. We've identified the agent, but there are several other things that we need to know before we can progress to managing that patient. We need to know the S in asbestos. What's the state of the agent? Is it solid? Is it liquid? Is it vapor? Is it a gas? Does that make a difference to the patient? It certainly does, because the clinical manifestations of chemical agent poisoning depend in large part upon the state of the agent when it contacts the body. Knowing the state of the agent and thinking about contact with the body naturally leads us to consider the B question in asbestos, the body site. Where did exposure to the agent occur? What's the root of entry of the agent? Is it ocular? Is it percutaneous? Is it parenteral through wounds? Is it some other way? Is it a combination of the above? Once we've addressed the root of entry question, which speaks to the issue of exposure and absorption, we then need to ask ourselves whether distribution has occurred. That is, we ask ourselves an effects question. The E in asbestos stands for effects in the sense that effects can be either local or systemic. We need to ask ourselves that question. Once we've determined whether systemic distribution has occurred, we can then ask ourselves something about the severity of the effects. Are they mild? Are they moderate? Are they severe? And we can then progress to the T in asbestos, which stands for time course or temporal progression and consists of three related questions. One about the past, one about the present, and one about the future. When we ask about the past, we need to consider the latent period. Was there one? If there was, how long was it? Does it make a difference? Yes, it does because for many of the agents, the shorter the latent period, the higher the dose. Knowing something about the latent period also tells us what the patient is likely to do in the future. When we ask a question about the present condition of the patient, we recognize the fact that patients are not static. Patients are not like snapshots. They're more like videos. They progress through time. Patients can get better. They can stay the same. They can be getting worse. And it's important to assess how the patient is doing at this moment. Is he or she getting better? Is he or she getting worse? Is he or she fluctuating in status? Knowing the answer to that question would then let us know what the patient is likely to do in the future. That is, what is his or her prognosis? If we make an estimate of what the patient is likely to do in the future and the patient does not do that, we have to ask ourselves whether there are other diagnoses that need to be considered. In fact, we always need to ask ourselves the O in asbestos, other diagnoses. And we need to ask this question from two perspectives. The first perspective is, is there an alternate diagnosis that should have been made? That is, was I wrong the first time? Do I need to go back to the A of asbestos and make another diagnosis? Do I need to pick another element from my differential diagnosis? Once we are confident that we have reached a correct diagnosis, after having considered the other elements in the differential, we then have to ask ourselves whether there are additional diagnoses. So the second question in the old phase of asbestos is, are there other diagnoses? In addition to the one that I already made, a person can be exposed not just to one chemical agent, but to a variety of chemical agents at the same time. We know that this happened in World War I, when the Germans used so-called Bruntkeites techniques to saturate an area with up to three different kinds of chemical agents at the same time. A person could be exposed to a chemical agent and a biological agent at the same time. A person could have conventional injuries, conventional wounds at the same time that he or she carries a diagnosis of chemical agent exposure. Patients have pre-existing medical conditions. Patients who are at least semi-conscious almost always have a psychological overlay, in addition to whatever other diagnoses they may be carrying. And finally, if there is more than one diagnosis, and there usually is, we have to ask ourselves the last question, the S question in asbestos. Is there synergism or interaction between the diagnoses that we've made? Although initial management of the patient may have to occur within seconds of seeing the patient, going through the asbestos mnemonic should form part of the secondary survey of any patient exposed to a chemical warfare agent. So to review, we have learned what a chemical warfare agent is. We've learned three agents that are not considered to be official chemical warfare agents, and we've learned that the agents that the United States considers to be official chemical agents fall under the category of toxic agents, of which there are four kinds, lung, blood, blister, and nerve, and incapacitating agents. We've learned a little bit about each agent, and we've learned some important information about terms that are likely to be encountered in any perusal of the chemical warfare agent literature. We've learned what a vapor is. We've learned something about the states of chemical warfare agents. We've learned about persistence. We've learned how to compare the toxicities of chemical warfare agents encountered as liquids or as gases and vapors. And finally, we've discussed the idea of medical response to chemical warfare agents, the various phases of response, crisis management and consequence management, the idea of a latent period, the role of primary, secondary, and tertiary prevention in the management of chemical warfare agents. And we've discussed a framework for learning about chemical warfare agents themselves and a framework exemplified by the mnemonic asbestos for approaching the assessment of a patient in connection with ongoing management of that patient.