 For the next hour or so, we're going to be talking about some toxic inhalation agents, and we're not going to confine ourselves to simply the classical chemical warfare agents, but we're going to expand the view a little bit, because there are some other agents out there that we understand that you folks as military physicians and nurses will be exposed to or have your patients exposed to. I'm going to give you a little bit of a historical perspective, not because I don't think Dr. Seidel's lecture was exhausted, but because it's a good lead-in to the discussion, and we'll talk about a couple of just general issues associated with toxic inhalation. And then I have five agents to discuss, and for each of those agents we'll talk about where they come from, how they hurt us, and what we can do to fix that. In 1899, the major nations of the world got together at a international peace convention and decided to ban then and forever chemical warfare agents. Unfortunately about 15 years later, all that went up in the smoke. When the First World War started, the Germans got the upper hand and swept across the lowlands of Belgium, but were stopped by the Allies the Battle of the Marn, and from then on stalemate ensued, trench warfare if you will. And when that stalemate began, both sides frantically looked for some way to achieve the initiative to break the stalemate. The Germans went to their chemical industry, the best in the world then and probably now. One of their chemical professors, Fritz Haber, suggested the use of chlorine gas, and the German High Command bought that. So in April of 1915, they used chlorine gas against the Allies at Ypres, Belgium. The photograph is two German troops positioning these chlorine gas cylinders, commercially produced cylinders, in the bunkers. They merely put the cylinder there, threaded a hose attached to the valve up over the top of the berm, pointed it toward the Allied lines. They took 6,000 cylinders and over a 10-minute period opened them all, and a large greenish cloud wafted over the Allied lines. The Allies say there were about 5,000 casualties that day, although we think maybe that was inflated a little bit for propaganda purposes. Nevertheless, there were very dramatic casualties from this, the first significant use of chemical agents on the modern battlefield. Unfortunately, both sides were unprepared. The Germans managed to cut a 4-mile swath in the French lines, but were unprepared to follow up. So they only managed to advance about 4 miles, and were stopped again, and transfer warfare continued. So from then on, it was a battle for the initiative. This grainy picture is a demonstration of the first mask that we used. There's a couple of German medics treating a casualty, a chemical agent and casualty with oxygen. You see, they're both wearing gauze masks, which were probably dipped in hypochlorite solution. The British and the rest of the Allies rapidly came up with protective masks like these after the attack at E-Belgium. And so the Germans were then obligated to find a more potent, more effective agent. And they did so with phosgene. So about a year later, or half a year later, they used phosgene, again at E-Belgium, and this time against the British. The important note here is that the mask casualties started not right after the exposure, but two days later. And we'll talk about that more in a little while. Kind of a historical footnote here. Once the British came up with a decent mask to protect themselves against phosgene, the Germans went back to the drawing board again and came up with this stuff called diphosgene, which when released converts into a mixture of phosgene and chloroform. The chloroform was intended to attack the filters of the masks, degenerate the filters, and then allow the phosgene to leak through. It didn't work too well, but once again a battle for the initiative. And eventually the British came up with an even better mask. The good news here is that with the masks you all have sitting next to you, we can defend ourselves against these kinds of agents. The bad news is that even though Mustard, the last agent that the Germans came up with, caused the most casualties, the most chemical casualties on the battlefield in World War I, chlorine and phosgene caused the most fatalities, about 80% of them. So if you're not protected, you're in a world of hurt. Why do we care about chlorine and phosgene anymore? After all, they're World War I gases and we'll probably never see them again on the battlefield. Well, we might, because the battlefield obviously has changed from that fixed piece kind of battle that we expected to see, but we have other concerns now as well. We're worried about industrial accidents, we're worried about terrorism, and both of these agents are ubiquitous in the chemical industry. Both chlorine and phosgene are used extensively as precursors for a lot of the high-tech materials that we use every day. All the plastics you see around you, the plastics that you're setting on in fact, are all produced using chlorine or phosgene as a precursor. And many rail cars full of both of these gases as liquid move through this country every day. We're also going to be talking about some related inhalation agents. And these are of particular importance to you folks as military health care professionals, because if you see a toxic inhalation exposure, it will probably more likely be one of these related agents before you see phosgene or chlorine. Remember that if you die from a chemical agent exposure, regardless of which agent we're talking about, it's going to be a respiratory death. And one of the big reasons is the data you see here on the screen. Obviously, percutaneous exposure is important, it's critical. That's why we have the suits that you're all sitting next to right now. And we make a big deal out of dotting them correctly and wearing them correctly. But certainly, when we're talking about simple surface area available for exposure, the lung is by far the greatest area of exposure. A little review and anatomy and physiology here just for a second. The nasopharynx is a wonderful organ, and it provides humidification and filtering for the gases that we take in every day. But remember that the nasopharynx is bypassed very easily as well. I don't know about you, but I can't pass my APFT by breathing through my nose. After about the first mile at least, I have to breathe through my mouth. And so the nasopharynx in a combat situation is bypassed quite quickly. Central airways, those airways from the mouth to about the level of 2 millimeter in diameter airways are important because they move the gases by bulk flow. And there's a lot of mixing of gases that goes on in these airways. Also remember that as you move from proximal to distal in these airways, that the surface area, the overall surface area increases dramatically. And that means that the flow is laminar through these airways, and it's normally very quiet. Turbulent flow is noisy flow. And we take advantage of that in the upper airway, particularly the level of the glottis. I'm producing turbulent flow, although not too well this morning, but I'm producing turbulent flow so that you can hear me. But turbulent flow in the central airways means trouble. What kind of symptoms do we pick up? What kind of signs do we pick up when we get turbulent flow in the central airways? What do we hear? Weasing, right? Weasing means turbulent flow in central airways. What about the upper airway? What about the level of the glottis? What kind of sign gives us an indication there's turbulent flow over and above the normal in the upper airway? Strider, the classic sign, right? And even before that, hoarseness. I'm a classic demonstrator of that this morning. I'm getting over my URI, so I have hoarseness. And that's one indication of partial upper airway obstruction. The peripheral airways, those airways from two millimeter size down to the alveoli, the flow of gases in these airways is by diffusion, very slow. That means a couple of things. First of all, that means that anything that gets down into these airways can stay there for a long period of time until it's absorbed. And secondly, it means that when we auscultate down in that area, we may not hear very much of anything at all, even though we're talking about a pathologic situation. So keep that in mind as we move on and talk about signs and symptoms of these agents. Remember the discussion we had about aerosols in the previous lectures? Aerosols are particles suspended in air, whether we're talking about liquid or solid. And aerosols tend to distribute themselves in the lungs when we take them in based upon their particle size. Aerosols are solid particles or droplets of liquid suspended in the air. These particles or droplets may become deposited in the airway. How far they travel into the airway will depend primarily on their size. Particles with a diameter of between five and 30 microns tend to become deposited in the upper airway. These larger particles fall out of the air and impact the mucus membranes of the nasopharynx due to the turbulent flow in this part of the airway. Particles of one to five microns in size reach the central airways and produce toxic effects in the tracheobronchial area of the lungs. Particles smaller than one micron in diameter will move throughout the lung by diffusion, easily reaching the peripheral airway and producing toxic effects in the alveoli. Unfortunately, we don't filter out gases too well. We need gases to live, obviously. So there aren't a lot of protective mechanisms that we have in place to guard against getting gases into the lungs. And gases distribute themselves in the lung based more upon their solubility and their reactivity. Very reactive gases and very soluble gases tend to distribute in the lung higher up in the upper airways and the central airways. Gases that are less soluble tend to reach the peripheral airways. Gases that are less reactive tend to reach the peripheral airways. But again, once they reach that area, can linger there long enough to cause disease. One of the important protective mechanisms that we have against aerosols is the mucosiliary system, which can be easily damaged by some of the gases that we'll be looking at today along with gases that we get from cigarette smoke. So we can see, based upon where the gas affects the pulmonary system, different symptoms, different constellations of symptoms. And for different gases, they affect the lungs in different locations. So a classic example of a central airways kind of problem is mustard exposure. You already heard about that extensively. The kinds of gases we'll be talking about in the next half hour or so are more peripheral types of gases. Their effects are in the periphery like phosgene. Chlorine is an odd one because its effects are combined. We can see central and peripheral effects as well. Based upon the kind of gas we're dealing with, the kind of effects we expect to see, the symptoms and signs are going to be a little bit different. So if we have a gas that's affecting primarily the upper and the central airways, we're going to see things like wheezes, strider. We're going to have symptoms like coughing, like hoarseness and difficulty swallowing, complaint of substernal pain. Peripheral airway problems produce very few symptoms at first. Maybe a vague complaint of dysthymia, shortness of breath, and very few, if any, signs. Maybe a few crackles. For all the agents that we'll be talking about here, there are certain specific indications and problems that we see with all of these. First of all, the final common pathway for all these agents is pulmonary edema. We're talking about the classical ARDS syndrome. All of these agents cause, in one way or another, a leak in the alveolar capillary membrane. That membrane, which is thin by design, when it leaks, causes serous fluid to flow into the alveoli and eventually reduce diffusion of gases, the important ones like oxygen carbon dioxide. Exposures to all of the agents we'll be talking about can produce symptoms which have a latent period. Sometimes many hours pass before the patient, the casualty, complains at all of any symptoms. There may be many more hours that pass before you see any signs. Symptoms usually precede signs and even symptoms are delayed. Even though there's normally a latent period, high exposures to any of these agents can produce sudden death, principally by upper airway obstruction. Laryngeal spasm, bronchospasm, laryngeal edema. When the alveolar capillary membrane is damaged, that is an offering to the bacteria that exist that colonize the lungs to come on in and cause infection. So it's not unusual to see bacterial superinfection following exposure to any of these agents. It's important to note here that prophylactic antibiotics are not appropriate in this setting, however. All you manage to do if you treat prophylactically is select out the nastiest bug that the casualty has colonized already and you end up trying to treat that worst bug available. For all these exposures, they're exacerbated by exercise. This is an empirical finding from the First World War and from exposures beyond that. We know that with any of these agents, as bad as the exposure is, if the casualty exercises afterwards, the symptoms occur sooner and they're more intense. And unfortunately, there is no magic bullet for any of these exposures, unlike nerve agents which have true antidotes. There are no antidotes or specific prophylaxis for exposures to any of these agents. The first one we'll talk about is chlorine. The classical World War I chemical warfare agent, the agent upon which the name toxic gas is based. But as I said before, we're still worried about this agent. It's all around us every day. The tank cars full of this stuff move up and down our freeways daily. Remember that there were 60 rail cars full of this stuff moving through Atlanta every day during the Olympics. And it would not have taken a terrorist very much to figure out how to open one of the valves. And that's all we needed to do. We didn't need to blow up any of those tank cars, merely get one of the valves open, and it would have produced very serious results. It's used for a lot of things. Most importantly, it's used in the production of plastics. There are plastics all around us every day. Many large chemical plants across this country produce these plastics, and they use a lot of chlorine to do it. We can make it at home as well. I'm sure there's at least one person in this room who has made this stuff in their own kitchen or bathroom. Probably don't want to admit to it, but mixing household bleach and ammonia together gives you some nasty chloramine gas. It is a true gas at normal temperature and pressure, but it's heavier than air. So it tends to hug the ground, flow into low spaces like trenches. It does produce a greenish yellow color as a cloud. And its its fumes are very noxious, very pungent. There are two basic chemical reactions that go on at the tissue level that produce the symptoms and the signs that we see when a person is exposed to chlorine gas. One is the liberation of hydrochloric acid. The other is the production of oxygen-free radicals. The hydrochloric acid produces the central effects that we see from this agent. The irritation of the eyes and the nose, laryngeal symptoms that we see, obstruction, coughing, complaint of difficulty swallowing. In the peripheral airways, these oxygen-free radicals are the things that attack the alveolar capillary membrane and produce the pulmonary edema that we see. So that all the effects that we see from this gas and all the gases we'll be talking about are topical effects rather than systemic ones. With mild exposure, a kind of a pathonomonic symptom is complaint of suffocation. The patient feels like he's getting no air at all. And again, the central airway kinds of symptoms manifest themselves, irritation of the eyes and the throat, coughing. With higher exposures, we also see hoarseness in strider and the pulmonary edema comes on. With severe exposure, that pulmonary edema could come on very rapidly. And you see it produces copious airway secretions. And by copious, what we're talking about here is leaders of secretions. So you might expect that that leaky alveolar capillary membrane is not only filling up the lungs, but it's taking all of the fluid out of the intravascular space. So in addition to a pulmonary problem, we also have to deal in cases like this with probably hypotensive problems as well. Once again, there's no silver bullet here. Supportive care is what we need to use. And the hallmark of this care for pulmonary edema, of course, is positive pressure ventilation with positive end expiratory pressure or PEEP. Oxygen is always good. But until we get the patient to a ventilator, intubate him and use PEEP, we probably won't be able to maintain his oxygenation at a reasonable level. And that's the goal of therapy here, of course, is to keep him oxygenated, keep his PAO2 at least at 60. Bronchodiolators is there because remember that about 15% of the population has what we call hyperreactive airways disease or latent hyperreactive airways disease. And 15% of even this population does. Those folks that have a history of childhood asthma, eczema, hay fever, folks that are redheaded, they all have an increased risk for hyperactive airways, particularly in this setting. So you will have superimposed on the leaky capillary membrane, alveolar capillary membranes, bronchospasm, which is well treated with bronchodiolators. Again, that bacterial superinfection needs to be treated, not prophylactically, but with particular antibiotic that you choose based upon surveillance cultures that you need to do and sputum cultures. Interestingly, if bacterial superinfection doesn't follow, usually it's an uncomplicated course and there are no sequelae, no long term effects from these agents. Here's just one clinical example of an exposure to chlorine. This is a chemical factory worker, 36 year old female, and this is two hours after exposure. So this is a little bit unusual in the rapidity of the symptoms and the signs as well. Resting dyspnea, diffuse crackles, you see your PAO2 is dramatically affected and obviously that's not a good chest x-ray. This female did survive, however, and had no sequela, no long term effects from it. Phosgene is the other classical chemical warfare agent. And once again, it's ubiquitous. We use it in the chemical industry quite a lot. We use it to produce isocyanates and from that, herbicides and pesticides. A brief note, remember the Bhopal incident in 1984 that was produced by the liberation of isocyanates, methyl isocyanate along with Phosgene and chlorine and the death toll was about 8,000 people. So this is not an insignificant kind of exposure. Foam plastics, the seats that you folks are sitting on right now were produced using Phosgene as a precursor. And unfortunately, when you burn plastics, you get all those precursors back. So if we were to set your seat on fire right now, you'd get a good snoop full of Phosgene. Carbon tetrachloride, anybody remember what we used to use carbon tetrachloride for? Fire extinguishers, that's right. It was great stuff. It extinguished fires pretty well. But unfortunately, as they found, it also did a number on people. And so they got rid of that as a fire extinguisher. But it does liberate Phosgene when you set it on fire. It's a deceptively simple molecule. But those chlorine atoms are what the chemists in the plastic industry need to produce the chlorinated hydrocarbons that we depend on in high tech industry. Also, a true gas and even heavier than chlorine. It's not as pungent as chlorine, however. Some people describe its odor as that of pneumon hay or fresh cut grass. But by the time you smell that, you're probably in deep trouble already. Once again, it liberates two different species when it reacts with tissues. Just like chlorine, it liberates hydrochloric acid so we can expect to see with higher exposures, those kinds of symptoms associated with hydrochloric acid in the upper airways, irritation of the eyes, the nose, the throat. The acylation reaction, however, is the one that does the dirty work. This carbonyl chloride attacks many of the constituents of the capillary, the alveolar capillary membrane, nitrate groups, amine groups, oxygen, sulfur atoms. And because of that acylation reaction, we get the pulmonary edema effects that we see. With phosgene, unlike chlorine, the first symptoms of mild exposure may be very subtle, may be very difficult to notice even for the patient. Maybe a complaint of mild dyspnea at best or some chest tightness. Certainly nothing that would suggest to you that this patient is four plus sick and really needs intensive care. Moderate exposures also produce those hydrochloric acid associated symptoms, irritation of the eyes and the throat. And another historical footnote there, troops exposed to phosgene said that when they smoked cigarettes, the taste of the cigarette was particularly bad. I'm not a smoker, so I can imagine that cigarette smoke is bad anyway, but I guess it was different after you got hit with phosgene. With severe exposure, you can get pulmonary edema from this agent within four hours. And also sudden death may occur from laryngeal spasm. Remember the latent period. The onset of the symptoms from exposure, even from severe exposure, may be delayed four hours. And once again, exacerbated by exercise. Just like chlorine, we're talking about supportive care here. We need to maintain the patient's oxygenation, need to help him move the carbon dioxide in and out of the lungs. And so the best we can do for him is put him on a ventilator, giving positive pressure ventilation with positive end expiratory pressure to keep those alveoli open, hopefully keep that oxygen diffusing. And if there's an overlay of bronchospasm just like with chlorine, we'll treat with bronchodilators as well. Here's one example of a phosgene exposure, once again a chemical industry worker. 40 year old male, this is two hours after his exposure. He comes into the emergency room and this is what the physician sees. Only a mild complaint of shortness of breath. But when he does all the routine exam, he sees the guy's normal. Well, you look fine to me, go on back home and take the rest of the day off and rest. He comes back in a few hours later, and this is what he looks like. This is the same guy, seven hours after the same exposure. Now, even at rest, he's short of breath. And now we can hear crackles in the bases before we can hear nothing. Obviously his PAO2 is dramatically affected and this is not the chest x-ray of a normal adult. He too survived his exposure without sequela. Here's another example of phosgene exposure, obviously a much more severe exposure. You see the onset of symptoms dramatically quicker. This is two hours after exposure. Remember that with the first case, it took seven hours to develop these kinds of symptoms. This 40-year-old chemical worker saw these kinds of symptoms after two hours, died six hours after exposure. Now let's talk about three different toxic inelents. And these are not classical chemical warfare agents, but you are more likely to see exposures from these than from chlorine and phosgene. First is PFIB. Organofluoride polymers, once again, are used quite extensively in the plastics industry. And the classical organofluoride polymer that we're all familiar with is Teflon. Teflon is used not only to line skillets, but also in industry because of its slippery qualities because it has a lot of other very beneficial qualities that we use in the plastics industry. Unfortunately for us, they use this kind of polymer extensively in all military vehicles. All the electrical equipment, the wiring, etc., is insulated with these kinds of polymers. When you burn this stuff, you get nasty PFIB. Perfluoroisobutylene is 10 times more potent than phosgene. If you burn Teflon at relatively low temperatures, and obviously 450 degrees centigrade is not low by normal comparison, but relatively low, you get a very unusual syndrome. You liberate these polymers and you get what's described as polymer fume fever. The name comes from the fact that people exposed to these kinds of agents present with symptoms that look just like flu. Fever, malaise, high temperature, cough, and possible pulmonary infiltrates. Usually resolved spontaneously, like the flu, and there's usually no sequela. If you burn Teflon at much higher temperatures, and 800 degrees centigrade is certainly high temperature, then you get the nasty actor, you get PFIB. And the latent period that we talk about with all these agents could be very, very short with high exposures to PFIB. The outcome is the same, full pulmonary edema. And the treatment is the same as well. We're going to treat ARDS pulmonary edema the same way regardless of how we were exposed. Positive pressure ventilation and peep with oxygenation. HC smoke, I bet everybody has seen this stuff. This is white smoke, smoke grenades, okay? This is ubiquitous in the military. Anybody who's done any training exercise has probably been exposed to this stuff. And certainly our combat arms colleagues get into this stuff almost every day in training. Obscure smoke, white smoke, HC smoke is made from a mixture of zinc oxide and hydrochloroethane. When you burn the stuff, which you have to do to get the smoke, you get a lot of nasty actors. The zinc chloride is the thing that we think causes the pulmonary edema in this situation. But look at the list. There are a lot of other things on that list that we already know cause the same sorts of signs and symptoms. Our old friend, carbon tetrachloride, chlorine is on there, hydrochloric acid is on there, phosgene as well. Again with a mild exposure, the presenting symptoms may be very confusing. Just a vague complaint of shortness of breath and nothing more. No signs, just symptoms. After a more severe exposure, we may see severe dyspnea at first, but it may resolve fairly quickly. And then the latent period ensues, and then again we get those classical symptoms of pulmonary edema. One new little wrinkle here with HC smoke that we didn't see with the other agents, we can get long term sequela with exposure from this agent. We have seen empirically that patients exposed to this can get interstitial fibrosis as a long term problem. And that translates in the therapy. Another unusual event here, patient may present with coughing that produces bloody sputum in this situation. The pulmonary edema, the onset may be very quick with high exposures within 30 minutes. In addition to the same supportive care that we got, that we gave for the other agents, we may add steroids in this situation. And we're talking about steroids used acutely specifically for exposure to this agent to help avoid those classical long term sequela of interstitial fibrosis. And because those long term changes may occur, we may have to follow this patient over months with serial pulmonary function tests to make sure he's not having fibrotic changes. When you see white smoke on the battlefield, it's HC smoke. And under normal circumstances, and of course, the battlefield is not a normal place, but we're talking about an open battlefield, even that kind of obscured smoke that's produced off the back of a Humvee that literally coats the entire battlefield, covers the entire battlefield. The exposure to that is minimal. But when you're talking about an enclosed space, then it becomes critical. And the exposures that we've seen that produce this kind of pulmonary edema, we've seen with soldiers that have been exposed in enclosed areas. How many people have gone on field training exercises and had one of your buddies as a joke come into your tent in the middle of the night and pop one of these smoke grenades just to rest you out of bed? It goes on all the time, field training exercise in the combat arms. But it's a real nasty actor in enclosed spaces. One incident of a soldier who was tossing these smoke grenades out of the back of a Humvee without protection, obviously. One of those grenades got away from him and landed just momentarily in the bed of the truck. And he got it out fairly quickly, but obviously the cab of the truck filled with smoke. Pulmonary edema. He was in the hospital on a ventilator for weeks. Here's one example. Now, this is a 60-year-old male, but this is pretty classical. Eight hours after exposure, severe dyspnea. We hear now eight hours after exposure the signs as well. Crackles in the bases, depressed PAO2, and obviously dense infiltrates on the chest x-ray. Three and a half months later, that same patient still has signs and symptoms. He still complains of dyspnea at rest. His PAO2 is not normal even three months later. And they did a lung biopsy on this guy, open lung biopsy, and they found, sure enough, diffuse interstitial fibrosis. Here's another agent that your soldiers will be exposed to. Now, we've all been exposed to oxides of nitrogen. This is smog. But we can find nitrogen dioxide specifically in very specific situations associated with military functions. High temperature combustion. We're talking about things like arc welding. And arc welding goes on in military settings. Arc welding produces oxides of nitrogen. Nitrate-based explosives, ubiquitous in the military. Now, when you fire your M16 on the range, you produce oxides of nitrogen. Insignificant. You're standing in your foxhole, but it's wide open, and the round goes off and there's a little puff of smoke. Not to worry. But what about the crew of the self-propelled 155, who's buttoned up, you know, in the middle of a fire mission, loading rounds as fast as they can get them into the breach? And suppose, for instance, that their gas evacuator system isn't functioning up to par. Of course, that wouldn't happen in the modern military. But suppose the cab, the turret of that 155 self-propelled is going to fill up pretty quickly with oxides of nitrogen. And we have seen it in the past. Exposures like that can produce pulmonary edema. Even diesel exhausts produce a significant amount of oxides of nitrogen. And certainly there would be no situation where troops would be inside their garage in the middle of winter with the Humvee idling in, you know, in the corner. Similar to exposure to H.C. smoke. Similar symptoms, similar signs. The latent period may be very long-term. Patient may have symptoms acutely, which may resolve spontaneously, and have a very long, latent period of two to five weeks, and then present, again, in the hospital with pulmonary edema. Like H.C. smoke, exposures to oxides of nitrogen can produce long-term fibrotic changes in the lungs. So once again, we may suggest the use of acutely, the use of steroids to help avoid that, along with the other supportive care that we've already talked about. This is an account, again, from World War I, but it gives wrapped up, all in one package, the basic tenets of exposure to any of these agents. This is a chemist working in his lab, carrying what amounts to a beaker of liquid phosgene, and it breaks. He gets a big snoot full of this stuff, but manages to get out the door pretty quickly. That happens at one o'clock in the afternoon. He gets out of the room and his only symptom at that point is he's coughing a little bit. Once again, remember, with large exposures, that hydrochloric acid may produce some upper airway irritation initially. Now, an hour and a half later, he's in the hospital. They put him in the car and drive him straight to the hospital. He's at rest the whole time. They gave him the hospital, he's kept at rest. And his symptoms are so mild, they don't even call the resident to see him at first. Now it's four and a half hours after his exposure. Now he's in a world of hurt. Coughing, frothy expectoration, cyanosis, and he's rapidly deteriorating. Look at this here. Every fit of coughing brings up large quantities of clear yellowish frothy liquid, 80 ounces over an hour and a half. That's bigger than a big gulp. That's a lot of fluid. Where's it coming from? The intravascular space, right? Into the lungs and then out the mouth. So you need to replete that. This guy is going to be intravascularly depleted. Six hours and 50 minutes after his exposure, this man is dead. Without any great struggle for breath, the symptoms of irritation were very slighted onset. There was then a delay of at least four hours. Again, almost pathodermonic here. And the final development of serious edema up to death took a little more than an hour though the patient was continually rested in bed. Pretty dramatic stuff. And that's not an unusual experience. That's usual in this kind of exposure. Once again from World War One, this is a sort of a graphic demonstration of that exacerbation with exercise that we talked about. Men who have passed through a gas attack and have subsequently complained of only slight cough, nausea and tightness of chest, while resting in the trenches have collapsed and even died abruptly some hours later on attempting to perform some vigorous muscular effort. So what does that mean to you on the battlefield or any place you get exposures from any of these agents? This is the guy that presents to your battalion aid station to your medical treatment facility with very vague complaints. And how many people have we seen over the course of a normal duty day with vague complaints? Maybe because oh they're they're coming up to an APFT they don't want to take. Their unit is about to deploy. They're being PCS'd, ETS'd, whatever. They present with vague complaints. You can't find anything wrong with them and maybe you give them some acetaminophen and send them on their way. This guy, if you tell him to put his ruck back on and send him back to his unit, is going to come back to you two, four, six hours later in form of a pulmonary edema. So this is the guy that you want to watch. Observe for at least four hours and make sure that he's not going to develop those signs and symptoms. These exposures could produce central problems, peripheral problems, or both. We've already seen that. Remember the latent period and it's dependent upon the severity of the exposure. More severe the exposure, shorter the latent period, both for symptoms and signs. And remember that the signs occur sometimes much later than the symptoms. General rule of thumb here. If the symptoms occur less than four hours after the exposure, we can say that this is a very severe exposure and it's often lethal. Greater than four hours, he's got a good chance of survival if he gets the proper care, which is to say an ICU ventilator with positive pressure ventilation, maybe for days, maybe for weeks. Pretty simple. Getting him out of the exposure, ABCs, does he have an airway, is he breathing, is he circulating properly. Maintain bed rest, a critical one. One that's very difficult to do sometimes in a battlefield scenario. Look at him when he comes in and then if there's any suggestion of exposure to any of these agents, observe him for at least four hours. And if he shows you anything at all within those four hours, then you treat what you see. If after four hours, no symptoms, no signs, then you can feel pretty confident that this guy's going to do pretty well.